FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Fairley, KJ Howell, MD Tomazic-Jezic, VJ Leakakos, T Truscott, W Meade, BJ AF Fairley, KJ Howell, MD Tomazic-Jezic, VJ Leakakos, T Truscott, W Meade, BJ TI Augmented latex-specific IGE antibody response in BALB/c mice upon concurrent exposure to natural rubber latex proteins with glutaraldehyde SO JOURNAL OF TOXICOLOGY-CUTANEOUS AND OCULAR TOXICOLOGY LA English DT Article DE latex proteins; IgE; glutaraldehyde ID ALLERGIC CONTACT-DERMATITIS; DIESEL EXHAUST PARTICLES; HEALTH-CARE WORKERS; OCCUPATIONAL ASTHMA; IMMUNOLOGICAL RESPONSES; AIRWAY INFLAMMATION; ADJUVANT ACTIVITY; MITE ALLERGEN; RISK-FACTORS; PREVALENCE AB Health care workers are exposed to numerous agents that are known to induce hypersensitivity-mediated diseases. Yet, little is known regarding the role of coexposure to these agents on the development of hypersensitivity responses. The present studies were conducted to evaluate the immunomodulatory role of dermal exposure to glutaraldehyde (Glut) on the induction of IgE antibodies to natural rubber latex (NRL) proteins. Female BALB/c mice were dermally exposed to Glut (0.05-1 ppm; 0.1-1%) and nonammoniated latex (NAL; 25 mug) 5 days/week for up to 86 days. The NAL alone at concentrations up to 1% did not induce significantly elevated levels of total serum or latex-specific IgE. In contrast, both total and NAL-specific serum IgE were dose-dependently (p < 0.01 and p < 0.05, respectively) elevated in mice concurrently exposed to 25 mug NAL and increasing concentrations of Glut up to 0.75 ppm. Further testing was performed to investigate the mechanism by which Glut augmented the latex-specific response. Barrier integrity tests demonstrated that Glut did not induce sufficient disruption of the strateum corneum (less than 1% (H2O)-H-3 penetration was observed in a guinea pig model) to allow for increased penetration of the latex proteins. However, coexposure to 25 mug NAL and 0.75 ppm Glut for 2 days as compared to the vehicle control was shown to induce a 15-fold increase in MHC II positive Langerhans' cells in the epidermis. Additional experiments confirmed the upregulation of a Th2 response. Upon sacrifice following 86 days of exposure, animals exposed to 25 mug NAL and 0.75 ppm Glut demonstrated a significant increase (p < 0.01) in CD40 + (3.95 +/- 0.38 x 10(6)), B220+ (7.67 +/- 1.18 x 10(6)), and IgE+B220+ (3.28 +/- 0.75 x 10(6)) cells as compared to the vehicle control groups (2.29 +/- 0.18 x 10(6), 3.31 +/- 0.18 x 10(6), and 0.82 +/- 0.15 x 10(6) cells), respectively. These studies demonstrate the potential for mixed exposures in the health care environment to modulate the development of IgE-mediated responses to natural rubber latex proteins, underscoring the importance of environmental factors in the development of allergies to foreign antigens. C1 NIOSH, Agr & Immunotoxicol Grp, Morgantown, WV 26505 USA. US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. FeRX Inc, Preclin Dev, San Diego, CA USA. Kimberly Clark Inc, Sci Affairs & Clin Educ, Roswell, GA USA. RP Meade, BJ (reprint author), 1095 Willowdale Rd,MS 4020, Morgantown, WV 26505 USA. EM bhm8@cdc.gov NR 62 TC 0 Z9 0 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0731-3829 J9 J TOXICOL-CUTAN OCUL JI J. Toxicol.-Cutan. Ocul. Toxicol. PY 2004 VL 23 IS 4 BP 303 EP 320 DI 10.1081/CUS-200037220 PG 18 WC Ophthalmology; Toxicology SC Ophthalmology; Toxicology GA 884XO UT WOS:000226120200007 ER PT J AU Cardwell, KF Henry, SH AF Cardwell, KF Henry, SH TI Risk of exposure to and mitigation of effect of aflatoxin on human health: A West African example SO JOURNAL OF TOXICOLOGY-TOXIN REVIEWS LA English DT Article DE aflatoxin; West Africa; aspergillus flavus; hepatocellular carcinoma; hepatitis B virus; agro-ecology; child growth development; nutritional status ID ASPERGILLUS-SECTION FLAVI; 4 AGROECOLOGICAL-ZONES; REPUBLIC-OF-BENIN; LIVER-CANCER; HEPATOCELLULAR-CARCINOMA; DIETARY AFLATOXIN; INSECT INFESTATION; GAMBIAN CHILDREN; PREHARVEST MAIZE; UNITED-STATES AB The purpose of this chapter is to examine the relative risk of exposure of different human populations to food-borne aflatoxins; the types of health impact that may be incurred by dietary exposure to aflatoxins; and possible strategies likely to mitigate risks to human health. Risk of exposure is examined in a global context comparing risk of toxin exposure by levels of national socioeconomic development. Then risk of exposure is reexamined in the context of agro-ecology, distribution of toxigenicity of Aspergillus flavus, and social factors that influence food management practices. The effects of aflatoxin exposure on human health are explored in three sections: human disease and nutritional status, carcinogenicity, and child growth and development. The section concerning mitigation of the effects of aflatoxin on human health contrasts efficacy of regulation, food basket modification, and production-side agriculture intervention. It is concluded that risk of hepatocellular carcinoma in developing countries, such as West Africa, may be addressed by vaccination for hepatitis B virus (HBV) and other public health options. Young children in West Africa who are chronically exposed to aflatoxin in foods and who consume nutritionally deficient diets have been shown to be stunted and underweight, as measured by World Health Organization (WHO) Z-scores. C1 USDA, CSREES, Washington, DC 20024 USA. US FDA, CSREES, Washington, DC 20024 USA. RP USDA, CSREES, Washington, DC 20024 USA. EM kcardwell@csrees.usda.gov NR 72 TC 18 Z9 19 U1 2 U2 14 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 0731-3837 J9 J TOXICOL-TOXIN REV JI J. Toxicol.-Toxin Rev. PY 2004 VL 23 IS 2-3 BP 217 EP 247 DI 10.1081/TXR-200027817 PG 31 WC Toxicology SC Toxicology GA 860VW UT WOS:000224372900004 ER PT S AU Waynant, RW Ilev, IK AF Waynant, RW Ilev, IK BE Longo, L Hofstetter, AG Pascu, ML Waidelich, WRA TI Light sources and their role in laser therapy SO LASER FLORENCE 2003: A WINDOW ON THE LASER MEDICINE WORLD SE Proceedings of SPIE LA English DT Proceedings Paper CT Annual Laser Florence 2003 Conference CY NOV 06-08, 2003 CL Florence, ITALY SP Int Acad Laser Med & Surg, Inst Laser Med, MURST, Italian Univ, Res Off, Italian Hlth Off, European Community, USUHS Bethesta, Florence Med Assoc, Reg Toscana, Comune Firenze, Int Soc Laser Med & Surg, SPIE, SPIE Romania Chapter, Opt Soc Amer, European Opt Soc, Romanian Soc Laser Med & Biol, N Amer Assoc Laser Therapy, European Soc Laser Aesthet Surg, E European Confederat Natl Soc Plast Surg & Aesthet Med, Forum Venoso Latino Americano, World Assoc Laser Therapy, Italian Soc Day Surg, Soc Italiana Ottica & Foton DE laser therapy; lasers; LEDs broadband thermal sources; luminescence studies; breath analysis AB Further research in laser therapy has resulted in the introduction of sources such as LEDs, and filtered and unfiltered broadband thermal sources. While well-controlled studies and comparisons of these devices have not yet been done, such studies should include the same well-documented description of the sources and other parameters of the studies. C1 US FDA, Ctr Devices & Radiol Hlth, Electroopt Branch, Rockville, MD 20857 USA. RP Waynant, RW (reprint author), US FDA, Ctr Devices & Radiol Hlth, Electroopt Branch, HFZ-134,12725 Twinbrook Pkwy, Rockville, MD 20857 USA. NR 8 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-5563-6 J9 PROC SPIE PY 2004 VL 5610 BP 96 EP 101 DI 10.1117/12.584390 PG 6 WC Engineering, Biomedical; Optics SC Engineering; Optics GA BBA75 UT WOS:000224432500017 ER PT S AU Waynant, RW Ilev, IK Mitra, K AF Waynant, RW Ilev, IK Mitra, K BE Bartels, KE Bass, LS DeRiese, WTW Gregory, KW Hirschberg, H Katzir, A Kollias, N Madsen, SJ Malek, RS McNallyHeintzelman, KM Paulsen, KD Robinson, DS Tate, LP Trowers, EA Wong, BJ TI Are ultrashort x-ray pulses likely to be less carcinogenic? SO LASERS IN SURGERY: ADVANCED CHARACTERIZATION, THERAPEUTICS, AND SYSTEMS XIV SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Conference on Lasers in Surgery - Advanced Characterization, Therapeutics and Systems XIV CY JAN 24-27, 2004 CL San Jose, CA SP SPIE DE ultrashort; x-ray; carcinogenisis; breath analysis ID HUMAN BREATH; SPECTROSCOPY; ETHANE AB With the development of femtosecond and shorter pulsewidth lasers and the ability to amplify these pulses to incredibly high pulsed power has come the ability to produce ultrashort pulses of x-rays. In previous years sessions of this conference we have proposed use of these ultrashort pulses of x-rays to produce high resolution, high image quality three dimensional x-ray images of breast and other areas of the body. Theoretical studies of the impact of increasing higher power of UV and X-Ray sources for sterilization lead us to question whether very short pulses of extremely high power (but low dose, i.e. J/cm2) may have less carcinogenic effect. If this is true, it could potentially allow greater use of such x-ray systems for breast cancer surveillance as well as other areas such as deep body inspection. In addition, it could allow for creation of better images by use of higher resolution, noise reduction and higher repetition rates. Better images should improve detection. C1 US FDA, Ctr Devices & Radiol Hlth, Electroopt Branch, Rockville, MD 20857 USA. RP Waynant, RW (reprint author), US FDA, Ctr Devices & Radiol Hlth, Electroopt Branch, HFZ-134,12725 Twinbrook Pkwy, Rockville, MD 20857 USA. RI Mitra, Kunal/C-6560-2016 OI Mitra, Kunal/0000-0002-7277-4908 NR 13 TC 0 Z9 0 U1 0 U2 1 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-5220-3 J9 P SOC PHOTO-OPT INS PY 2004 VL 5312 BP 267 EP 272 DI 10.1117/12.528234 PG 6 WC Medicine, Research & Experimental; Optics; Physics, Applied; Surgery SC Research & Experimental Medicine; Optics; Physics; Surgery GA BAR78 UT WOS:000223294600036 ER PT J AU Zharov, VP Ferguson, S Eidt, JF Howard, PC Fink, LM Waner, M AF Zharov, VP Ferguson, S Eidt, JF Howard, PC Fink, LM Waner, M TI Infrared Imaging of subcutaneous veins SO LASERS IN SURGERY AND MEDICINE LA English DT Article DE infrared imaging; subcutaneous veins; diagnosis; vascular pathology ID ELECTRONIC ENDOSCOPY; POLARIZED-LIGHT; PHOTOGRAPHY; TISSUE; SKIN; TRANSILLUMINATION; FEASIBILITY; CONTRAST; VESSELS; INJURY AB Background and Objectives: Imaging of subcutaneous veins is important in many applications, such as gaining venous access and vascular surgery. Despite a long history of medical infrared (IR) photography and imaging, this technique is not widely used for this purpose. Here we revisited and explored the capability of near-IR imaging to visualize subcutaneous structures, with a focus on diagnostics of superficial veins. Study Design/Materials and Methods: An IR device comprising a head-mounted IR LED array (880 nm), a small conventional CCD camera (Toshiba Ik-mui, Tokyo, Japan), virtual-reality optics, polarizers, filters, and diffusers was used in vivo to obtain images of different subcutaneous structures. The same device was used to estimate the IR image quality as a function of wavelength produced by a tunable xenon lamp-based monochrometer in the range of 500-1,000 nm and continuous-wave Nd:YAG (1.06 mum) and diode (805 nm) lasers. Results: The various modes of optical illumination were compared in vivo. Contrast of the IR images in the reflectance mode was measured in the near-IR spectral range of 650-1,060 nm. Using the LED array, various IR images were obtained in vivo, including images of vein structure in a pigmented, fatty forearm, varicose leg veins, and vascular lesions of the tongue. Conclusion: Imaging in the near-IR range (880-930 nm) provides relatively good contrast of subcutaneous veins, underscoring its value for diagnosis. This technique has the potential for the diagnosis of varicose veins with a diameter of 0.5-2 mm at a depth of 1-3 mm, guidance of venous access, podiatry, phlebotomy, injection sclerotherapy, and control of laser interstitial therapy. (C) 2004 Wiley-Liss, Inc. C1 Univ Arkansas Med Sci, Philips Classic Laser Biomed Lab, Little Rock, AR 72205 USA. Univ Arkansas Med Sci, Div Vasc & Gen Surg, Little Rock, AR 72205 USA. US FDA, Natl Ctr Toxicol Res, Natl Toxicol Program, Ctr Phototoxicol, Jefferson, AR USA. Cent Arkansas Vet Healthcare Syst, Little Rock, AR USA. Arkansas Childrens Hosp, Little Rock, AR 72202 USA. RP Zharov, VP (reprint author), Univ Arkansas Med Sci, Philips Classic Laser Biomed Lab, 4301 W Markham St,Slot 543, Little Rock, AR 72205 USA. EM ZharovVladimir@uams.edu RI Zharov, Vladimir/J-9728-2013 NR 34 TC 49 Z9 50 U1 4 U2 16 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0196-8092 EI 1096-9101 J9 LASER SURG MED JI Lasers Surg. Med. PY 2004 VL 34 IS 1 BP 56 EP 61 DI 10.1002/lsm.10248 PG 6 WC Dermatology; Surgery SC Dermatology; Surgery GA 765DY UT WOS:000188252900008 PM 14755425 ER PT J AU Satchithanandam, S Oles, CJ Spease, CJ Brandt, MM Yurawecz, MP Rader, JI AF Satchithanandam, S Oles, CJ Spease, CJ Brandt, MM Yurawecz, MP Rader, JI TI Trans, saturated, and unsaturated fat in foods in the united states prior to mandatory trans-fat labeling SO LIPIDS LA English DT Article AB On July 11, 2003, the U.S. Food and Drug Administration published a final rule amending its food-labeling regulations to require that trans FA be declared in the nutrition label of conventional foods and dietary supplements. The effective date of this final rule is January 1, 2006. This places some urgency on increasing the number and types of currently available foods for which there are trans-fat data. Compositional databases on trans fat content of food are currently limited. The purpose of this study was to determine the trans-fat content of a wide range of foods prior to the effective date of the new regulation. AOAC Official Method of Analysis 996.01 was modified for the analysis of trans fat in noncereal products. Food products for analysis were selected on the basis of market share and data from the USDA's 1994-1996 Continuing Survey of Food Intake by Individuals. Foods were purchased from local supermarkets, weighed, hydrolyzed, converted to FAME, and analyzed by GC. The results showed that trans fat (g/100 g fat) ranged from 0.0 to 48.8 in bread, cake, and related products; from 14.9 to 27.7 in margarines; from 7.7 to 35.3 in cookies and crackers; from 24.7 to 38.2 in frozen potatoes; from 0.0 to 17.1 in salty snacks; from 0.0 to 13.2 in vegetable oils and shortenings; from 0.0 to 2.2 in salad dressings and mayonnaises; and from 0.0 to 2.0 in dry breakfast cereals. Serving sizes for the foods included in this survey ranged from 12 to 161 g, and trans-fat levels ranged from 0.0 to 7.2 g/serving. The significant differences in trans-fat content in products within each food category are due to differences in the type of fats and oils used in the manufacturing processes. C1 Food & Drug Adm, Off Nutr Prod Labeling & Dietary Supplements, Div Res & Appl Technol, College Pk, MD 20740 USA. RP Satchithanandam, S (reprint author), Food & Drug Adm, Off Nutr Prod Labeling & Dietary Supplements, Div Res & Appl Technol, HFS-840,5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM Ssubrama@cfsan.fda.gov NR 14 TC 33 Z9 35 U1 1 U2 5 PU AMER OIL CHEMISTS SOC A O C S PRESS PI CHAMPAIGN PA 221 W BRADLEY AVE, CHAMPAIGN, IL 61821-1827 USA SN 0024-4201 J9 LIPIDS JI Lipids PD JAN PY 2004 VL 39 IS 1 BP 11 EP 18 DI 10.1007/s11745-004-1195-5 PG 8 WC Biochemistry & Molecular Biology; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Nutrition & Dietetics GA 800XM UT WOS:000220061000002 PM 15055229 ER PT J AU Schiffenbauer, J Simon, LS AF Schiffenbauer, J Simon, LS TI Randomized controlled trials in systemic lupus erythematosus: what has been done and what do we need to do? SO LUPUS LA English DT Article DE disease activity indices (DAIs); flare; health related quality of life (HRQOL); lupus; noninferiority trials; randomized controlled trials (RCTs) ID QUALITY-OF-LIFE; SLE CLINICAL-TRIALS; DISEASE-ACTIVITY MEASURES; IMMUNOSUPPRESSIVE THERAPY; DAMAGE INDEX; DOUBLE-BLIND; MOS SF-36; NEPHRITIS; CYCLOPHOSPHAMIDE; RECOMMENDATIONS AB The study of systemic lupus erythematosus (SLE) is a challenging undertaking. It is difficult to assess outcomes in SLE randomized controlled trials (RCTs), and this is illustrated by the lack of new therapies approved for use in lupus. In a disease that is waxing and waning, and requires constantly changing medications, identifying treatment effects of new therapies may be difficult, and the use of potentially toxic therapies requires a rigorous understanding of the benefit to risk ratio. Some issues that need to be considered by the investigator in designing these studies include: 1) should the trial focus on patients with active or inactive disease; 2) which of the measures of disease activity should be used or should prevention of flares be examined; 3) should the study focus on defined organ specific endpoints or utilize one of the available disease activity indices to identify changes in disease activity; 4) should the trial be a superiority trial or an equivalence trial. This review summarizes the critical issues involving the design of studies in lupus and provides the reader with suggestions and recommendations for consideration before embarking on trials in this area. C1 CDER, Food & Drug Adm, Rockville, MD 20850 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Schiffenbauer, J (reprint author), CDER, Food & Drug Adm, 9201 Corp Blvd, Rockville, MD 20850 USA. EM schiffenbaue@cder.fda.gov NR 27 TC 20 Z9 21 U1 0 U2 0 PU ARNOLD, HODDER HEADLINE PLC PI LONDON PA 338 EUSTON ROAD, LONDON NW1 3BH, ENGLAND SN 0961-2033 J9 LUPUS JI Lupus PY 2004 VL 13 IS 5 BP 398 EP 405 DI 10.1191/0961203303lu1033oa PG 8 WC Rheumatology SC Rheumatology GA 830VS UT WOS:000222152800020 PM 15230299 ER PT J AU Kapoor, GS Zhan, Y Johnson, GR O'Rourke, DM AF Kapoor, GS Zhan, Y Johnson, GR O'Rourke, DM TI Distinct domains in the SHP-2 phosphatase differentially regulate epidermal growth factor receptor/NF-kappa B activation through Gab1 in glioblastoma cells SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; PROTEIN-KINASE-B; EPITHELIAL MORPHOGENESIS DOWNSTREAM; TYROSINE-PHOSPHATASE; PHOSPHATIDYLINOSITOL 3-KINASE; GRB2-ASSOCIATED BINDER-1; SIGNAL-TRANSDUCTION; ADAPTER PROTEINS; DOCKING PROTEIN; NOONAN-SYNDROME AB The transcription factor nuclear factor kappaB (NF-kappaB) plays an important role in inflammation and cancer, is activated by a variety of stimuli including tumor necrosis factor alpha, interleukin-1, UV irradiation, and viruses, as well as receptor tyrosine kinases, such as epidermal growth factor receptor (EGFR). Although previous studies suggest that EGFR can induce NF-kappaB, the mechanism of this activation remains unknown. In this study, we identify the components of the EGFR-induced signalosome in human glioblastoma cells required to regulate NF-kappaB activation. Immunoprecipitation analyses with ErbB-modulated cells indicate that association between SHP-2 and Grb2-associated binder 1 (Gab1) is the critical step in the formation of the signalosome linking EGFR to NF-kappaB activation. We also show that EGFR-induced NF-kappaB activation is mediated by the PI3-kinase/Akt activation loop. Overexpression of SHP-2, Gab1, and myristoylated Akt significantly upregulated NF-kappaB transcriptional activity and DNA binding activity in glioblastoma cells. Interestingly, overexpression of either one of the two SH2 domain mutants of SHP-2, R32E or R138E, slightly reduced NF-kappaB activity relative to that of wild-type SHP-2, indicating that the SH2 domains of SHP-2 are required for EGFR-induced NF-kappaB activation. On the other hand, ectopic overexpression of either a Gab1 mutant incapable of binding to SHP-2 (Y627F) or a phosphatase-inactive SHP-2 mutant (C459S) caused a significant increase in NF-kappaB activity. Moreover, SHP-2 C459S-expressing cells displayed higher Gab1 phosphotyrosine content, suggesting that SHP-2 regulates Gab1 phosphoryllation through its phosphatase domain, which confers a negative regulatory effect on NF-kappaB activity. These results indicate that SHP-2/Gab1 association is critical for linking EGFR to NF-kappaB transcriptional activity via the PI3-kinase/Akt signaling axis in glioblastoma cells and that SHP-2 acts as a dual regulator of NF-kappaB activation. C1 Univ Penn, Sch Med, Dept Neurosurg, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP O'Rourke, DM (reprint author), Univ Penn, Sch Med, Dept Neurosurg, 502 Stemmler Hall,36th & Hamilton Walk, Philadelphia, PA 19104 USA. EM orourked@mail.med.upenn.edu FU NCI NIH HHS [R01 CA090586, R01 CA 90586] NR 89 TC 43 Z9 47 U1 0 U2 2 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 JAN PY 2004 VL 24 IS 2 BP 823 EP 836 DI 10.1128/MCB.24.2.823-836.2004 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 764MT UT WOS:000188211200030 PM 14701753 ER PT J AU Wang, LH Yang, XY Zhang, XH Mihalic, K Fan, YX Xiao, WH Howard, OMZ Appella, E Maynard, AT Farrar, WL AF Wang, LH Yang, XY Zhang, XH Mihalic, K Fan, YX Xiao, WH Howard, OMZ Appella, E Maynard, AT Farrar, WL TI Suppression of breast cancer by chemical modulation of vulnerable zinc fingers in estrogen receptor SO NATURE MEDICINE LA English DT Article ID CELL-CYCLE PROGRESSION; DNA-BINDING DOMAIN; NUCLEOCAPSID PROTEIN; MOLECULAR-MECHANISMS; ANTITUMOR-ACTIVITY; GENE-EXPRESSION; TRICHOSTATIN-A; TUMOR-GROWTH; MCF-7 CELLS; NUDE-MICE AB Current antiestrogen therapy for breast cancer is limited by the mixed estrogenic and antiestrogenic activity of selective estrogen receptor modulators. Here we show that the function of zinc fingers in the estrogen receptor DNA-binding domain (DBD) is susceptible to chemical inhibition by electrophilic disulfide benzamide and benzisothiazolone derivatives, which selectively block binding of the estrogen receptor to its responsive element and subsequent transcription. These compounds also significantly inhibit estrogen-stimulated cell proliferation, markedly reduce tumor mass in nude mice bearing human MCF-7 breast cancer xenografts, and interfere with cell-cycle and apoptosis regulatory gene expression. Functional assays and computational analysis support a molecular mechanism whereby electrophilic agents preferentially disrupt the vulnerable C-terminal zinc finger, thus suppressing estrogen receptor-mediated breast carcinoma progression. Our results provide the proof of principle for a new strategy to inhibit breast cancer at the level of DNA binding, rather than the classical antagonism of estrogen binding. C1 NCI, Basic Res Program, SAIC Frederick, NIH, Frederick, MD 21702 USA. NCI, Cytokine Mol Mech Sect, NIH, Frederick, MD 21702 USA. US FDA, Div Therapeut Prot, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. NCI, Mol Immunoregulat Lab, NIH, Frederick, MD 21702 USA. NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Wang, LH (reprint author), NCI, Basic Res Program, SAIC Frederick, NIH, POB B, Frederick, MD 21702 USA. RI Xiao, Weihua/N-2775-2013; Howard, O M Zack/B-6117-2012 OI Xiao, Weihua/0000-0001-9102-6326; Howard, O M Zack/0000-0002-0505-7052 FU NCI NIH HHS [N01-CO-12400] NR 45 TC 61 Z9 62 U1 2 U2 9 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 JAN PY 2004 VL 10 IS 1 BP 40 EP 47 DI 10.1038/nm969 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 759NK UT WOS:000187743600037 PM 14702633 ER PT J AU Benjamin, RK Hochberg, FH Fox, E Bungay, PM Elmquist, WF Stewart, CF Gallo, JM Collins, JM Pelletier, RP de Groot, JF Hickner, RC Cavus, I Grossman, SA Colvin, OM AF Benjamin, RK Hochberg, FH Fox, E Bungay, PM Elmquist, WF Stewart, CF Gallo, JM Collins, JM Pelletier, RP de Groot, JF Hickner, RC Cavus, I Grossman, SA Colvin, OM TI Review of microdialysis in brain tumors, from concept to application: First Annual Carolyn Frye-Halloran Symposium SO NEURO-ONCOLOGY LA English DT Review ID ANGIOGENESIS INHIBITOR TNP-470; IN-VIVO MICRODIALYSIS; HEAD-INJURED PATIENTS; CEREBRAL BLOOD-FLOW; INTRACEREBRAL MICRODIALYSIS; MALIGNANT GLIOMA; EXTRACELLULAR GLUTAMATE; CEREBROSPINAL-FLUID; DRUG TRANSPORT; GRADE GLIOMAS AB In individuals with brain tumors, pharmacodynamic and pharmacokinetic studies of therapeutic agents have historically used analyses of drug concentrations in serum or cerebrospinal fluid, which unfortunately do not necessarily reflect concentrations within the tumor and adjacent brain. This review article introduces to neurological and medical oncologists, as well as pharmacologists, the application of microdialysis in monitoring drug metabolism and delivery within the fluid of the interstitial space of brain tumor and its surroundings. Microdialysis samples soluble molecules from the extracellular fluid via a semipermeable membrane at the tip of a probe. In the past decade, it has been used predominantly in neurointensive care in the setting of brain trauma, vasospasm, epilepsy, and intracerebral hemorrhage. At the first Carolyn Frye-Halloran Symposium held at Massachusetts General Hospital in March 2002, the concept of microdialysis was extended to specifically address its possible use in treating brain tumor patients. In doing so we provide a rationale for the use of this technology by a National Cancer Institute consortium, New Approaches to Brain Tumor Therapy, to measure levels of drugs in brain tissue as part of phase 1 trials. C1 Massachusetts Gen Hosp, Brain Tumor Ctr, Boston, MA 02114 USA. NCI, Bethesda, MD 20892 USA. NIH, Bethesda, MD 20892 USA. Univ Minnesota, Dept Pharmaceut, Minneapolis, MN 55455 USA. St Jude Childrens Res Hosp, Memphis, TN 38105 USA. Fox Chase Canc Ctr, Dept Pharmacol, Philadelphia, PA 19111 USA. US FDA, Ctr Drug Evaluat & Res, Lab Clin Pharmacol, Rockville, MD 20857 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. CMA Microdialysis, N Chelmsford, MA 01863 USA. E Carolina Univ, Human Performance Lab, Greenville, NC 27858 USA. Yale Univ, Dept Psychiat, New Haven, CT 06519 USA. Johns Hopkins, Sidney Kimmel Comprehens Canc Ctr, Dept Neurooncol, Baltimore, MD 21231 USA. Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. RP Benjamin, RK (reprint author), Carolina Neurosurg & Spine Associates, Neurooncol Ctr, 1628 E Morehead Rd,Suite 200, Charlotte, NC 28207 USA. EM Ramsis.benjamin@cnsa.co NR 66 TC 25 Z9 27 U1 2 U2 6 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JAN PY 2004 VL 6 IS 1 BP 65 EP 74 DI 10.1215/S1152.8517.03.00010.3 PG 10 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 757WE UT WOS:000187583800011 PM 14769143 ER PT J AU Itzhak, Y Achat-Mendes, CN Ali, SF Anderson, KL AF Itzhak, Y Achat-Mendes, CN Ali, SF Anderson, KL TI Long-lasting behavioral sensitization to psychostimulants following p-chloroamphetamine-induced neurotoxicity in mice SO NEUROPHARMACOLOGY LA English DT Article DE MDMA (ecstasy); cocaine; p-chloroaniphetamine; neurotoxicity; locomotor activity ID INDUCED DOPAMINERGIC NEUROTOXICITY; RAT NUCLEUS-ACCUMBENS; NITRIC-OXIDE SYNTHASE; LOCOMOTOR-ACTIVITY; EXTRACELLULAR DOPAMINE; SEROTONIN TRANSPORTER; REPEATED COCAINE; DEFICIENT MICE; AMPHETAMINE; BRAIN AB Amphetamine analogs such as p-chloroamphetamine (PCA) cause serotonergic and dopaminergic neurotoxicity. The behavioral consequences and the responsiveness to psychostimulants following the neurotoxic insult are unclear. The present study was undertaken to investigate the outcome of neurotoxic and non-neurotoxic PCA pre-treatments on the sensitivity of Swiss Webster mice to the psychomotor stimulating effects of PCA, 3,4-methylenedioxymethamphetamine (MDMA) and cocaine. PCA (15 mg/kg x 2; i.p.) caused 37-70% depletion of dopaminergic and serotonergic markers in mouse brain. Saline and PCA (15 mg/kg x 2) mice were challenged on days 5, 12, 40 and 74 with one of the following drugs: PCA (5 mg/kg), MDMA (10 mg/kg) and cocaine (20 mg/kg). The PCA pre-exposed mice showed marked locomotor sensitization from days 5-74 to all three drugs tested. The time course of the sensitized response coincided with the time course of the neurotoxic insult as determined by reduced densities of striatal dopamine transporter and frontal cortex serotonin transporter binding sites. A single injection of PCA (5 mg/kg) caused neither neurotoxicity nor sensitization to the locomotor stimulating effects of PCA, MDMA and cocaine. Repeated administration of a low non-neurotoxic dose of PCA (5 mg/kg/day; 6 days) caused a transient locomotor sensitization to PCA that dissipated after one month. Results of the present study suggest that PCA-induced serotonergic and dopaminergic neurotoxicity coincides with long-lasting locomotor sensitization to psychostimulants. These findings may be relevant to the psychopathology of amphetamines-induced neurotoxicity. (C) 2003 Elsevier Ltd. All rights reserved. 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. EM yitzhak@med.miami.edu FU NIDA NIH HHS [DA12867] NR 43 TC 16 Z9 16 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3908 J9 NEUROPHARMACOLOGY JI Neuropharmacology PD JAN PY 2004 VL 46 IS 1 BP 74 EP 84 DI 10.1016/S0028-3908(03)00316-2 PG 11 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 774EC UT WOS:000188965900008 PM 14654099 ER PT J AU Pereira, FC Macedo, TR Imam, SZ Ribeiro, CF Ali, SF AF Pereira, FC Macedo, TR Imam, SZ Ribeiro, CF Ali, SF TI Lack of hydroxyl radical generation upon central administration of methamphetamine in rat caudate nucleus: a microdialysis study SO NEUROTOXICITY RESEARCH LA English DT Article DE methamphetamine; dopaminergic neurotoxicity; hydroxyl radicals; caudate nucleus; microdialysis; salicylic acid; 2,3-dihydroxybenzoic acid ID DOPAMINE; NEUROTOXICITY; DEGENERATION; INHIBITION; MECHANISMS; SALICYLATE; GLUTAMATE; RELEASE AB The most widely accepted concept of oxidative damage centers on the formation of hydroxyl radical ('OH) which has an extremely short-life and is the major damaging free radical. It was suggested that methamphetamine (METH) toxicity is mediated via production of 'OH, as measured by 2,3-dihydroxybenzoic acid (2,3-DHBA). In this study we compared the effects of local caudate nucleus perfusion of METH with systemic administration of METH on (OH)-O-' generation in relation to DA release. Local perfusion of METH (5 mM, 140 min) induced a higher level of dopamine (DA) release compared to the first METH injection (10 mg/kg, 3 times, i.p.). No significant correlation was found between changes in extracellular DA levels and 'OH generation when perfusing METH locally; however, both increased after systemic METH administration. C1 Natl Ctr Toxicol Res, FDA, Div Neurotoxicol, Neurochem Lab, Jefferson, AR 72079 USA. Univ Coimbra, Fac Med, Inst Pharmacol & Therapeut, Coimbra, Portugal. RP Ali, SF (reprint author), Natl Ctr Toxicol Res, FDA, Div Neurotoxicol, Neurochem Lab, HFT-132, Jefferson, AR 72079 USA. EM sali@nctr.fda.gov OI Pereira, Frederico/0000-0002-9381-3320; Fontes Ribeiro, Carlos/0000-0002-9707-4895 NR 16 TC 9 Z9 9 U1 2 U2 2 PU F P GRAHAM PUBLISHING CO PI MOUNTAIN HOME PA PO BOX 370, MOUNTAIN HOME, TN 37684 USA SN 1029-8428 J9 NEUROTOX RES JI Neurotox. Res. PY 2004 VL 6 IS 2 BP 149 EP 152 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 848PY UT WOS:000223480800005 PM 15325967 ER PT J AU Ferguson, SA Cada, AM AF Ferguson, SA Cada, AM TI Developmental treatment with difluoromethylornithine has few effects on behavior or body weight in Sprague-Dawley rats SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Article DE treatment; DFMO; behavior ID ACOUSTIC STARTLE RESPONSE; ALPHA-DIFLUOROMETHYLORNITHINE; ORNITHINE DECARBOXYLASE; CEREBELLAR CORTEX; IRREVERSIBLE INHIBITOR; NEONATAL RAT; BRAIN; POLYAMINES; EXPOSURE; FEMALE AB Developmental difluoromethylornithine (DFMO) treatment reduces cerebellar weight [Neuroscience 17 (1986) 399, Neurotoxicol. Teratol. 22 (2000) 415, Behav. Brain Res. 126 (2001) 135], but the functional alterations resulting from this have been little investigated. Here, Sprague-Dawley rats were subcutaneously injected with 500 mg/kg DFMO on postnatal days (PNDs) 5-12 and a comprehensive set of behavioral assessments measured early developmental behaviors (righting reflex, negative geotaxis), motor coordination, acoustic startle, short- and long-term activity, social behaviors, anxiety, and spatial learning and memory. DFMO treatment appeared to cause a decreased latency to perform the negative geotaxis behavior on PNDs 8-10 and increased latency to hang by the forelimbs on PNDs 12-14. Our previous study did not indicate similar effects, but age at testing differed between the two studies. DFMO treatment caused a decreased latency to maximum acoustic startle response in both the acoustic startle paradigm and in the pulse-alone trials of the prepulse inhibition test. This DFMO treatment paradigm induced a 10% decrease in adult cerebellar weight [Behav. Brain Res. 126 (2001) 135], but the results here imply that such developmental stunting has few functional alterations. (C) 2003 Elsevier Inc. All rights reserved. C1 Natl Ctr Toxicol Res, Div Neurotoxicol, FDA, Jefferson, AR 72079 USA. RP Ferguson, SA (reprint author), Natl Ctr Toxicol Res, Div Neurotoxicol, FDA, HFT-132,3900 NCTR Rd, Jefferson, AR 72079 USA. EM sferguson@nctr.fda.gov NR 56 TC 7 Z9 7 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0892-0362 J9 NEUROTOXICOL TERATOL JI Neurotoxicol. Teratol. PD JAN-FEB PY 2004 VL 26 IS 1 BP 83 EP 93 DI 10.1016/j.ntt.2003.08.001 PG 11 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA 803NG UT WOS:000220237200009 PM 15001217 ER PT J AU Al-Khaldi, SF Mossoba, MM AF Al-Khaldi, SF Mossoba, MM TI Gene and bacterial identification using high-throughput technologies: Genomics, proteomics, and phonemics SO NUTRITION LA English DT Article ID TRANSFORM INFRARED-SPECTROSCOPY; MICROARRAY ANALYSIS; DNA MICROARRAYS; VIBRATIONAL SPECTROSCOPY; HAEMOPHILUS-INFLUENZAE; LISTERIA-MONOCYTOGENES; FOODBORNE PATHOGENS; VIRULENCE FACTOR; CHIP TECHNOLOGY; PROTEIN CHIP C1 US FDA, Ctr Food Safety & Appl Nutr, Div Microbiol Studies, Microarray Lab 3E014 DNA,OPDFB, College Pk, MD 20740 USA. US FDA, Ctr Food Safety & Appl Nutr, OSAS, Div Gen Sci Support, College Pk, MD 20740 USA. RP Al-Khaldi, SF (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Div Microbiol Studies, Microarray Lab 3E014 DNA,OPDFB, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM sufian.al-khaldi@cfsan.fda.gov NR 47 TC 28 Z9 28 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0899-9007 J9 NUTRITION JI Nutrition PD JAN PY 2004 VL 20 IS 1 BP 32 EP 38 DI 10.1016/j.nut.2003.09.006 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 763KD UT WOS:000188083300007 PM 14698011 ER PT J AU Ibrahim, A Hirschfeld, S Cohen, MH Griebel, DJ Williams, GA Pazdur, R AF Ibrahim, A Hirschfeld, S Cohen, MH Griebel, DJ Williams, GA Pazdur, R TI FDA drug approval summaries: Oxaliplatin SO ONCOLOGIST LA English DT Article DE oxaliplatin; metastatic colorectal cancer; second-line treatment ID METASTATIC COLORECTAL-CANCER; FOLINIC ACID; PHASE-II; 5-FLUOROURACIL; REGIMEN AB The purpose of this report is to summarize information on oxaliplatin, a drug recently approved by the U.S. Food and Drug Administration. Information provided includes regulatory history, study design, efficacy and safety results, and pertinent literature references. A single, multicenter, randomized trial, enrolling 463 patients with metastatic colorectal carcinoma whose disease had recurred or progressed during or within 6 months of completion of therapy with the combination of bolus 5-fluorouracil (FU)/leucovorin (LV) and irinotecan, was submitted. Study arms included infusional 5-FU/LV alone (arm A), oxaliplatin alone (arm B), and the combination of oxaliplatin and infusional 5-FU/LV(arm C). Oxaliplatin, at a dose of 85 mg/m(2), was administered to patients in arms B and C intravenously over 2 hours in 250-500 ml of dextrose 5% in water (D5W) on day 1 only. A 200-mg/m(2) dose of LV was administered simultaneously to arm C patients, in a separate bag using a Y-line, or alone to arm A patients, by i.v. infusion, Over 2 hours. 5-FU was then administered to arms A and C patients, first as a bolus injection over 2-4 minutes at a dose of 400 mg/m(2), then as a continuous infusion in 500 ml of D5W over 22 hours at a dose of 600 mg/m(2). LV was repeated on day 2 of the cycle (arms A and C) followed by a 400-mg/m(2) 5-FU bolus and a 600-mg/m(2) 22-hour infusion. Treatment was repeated every 2 weeks. Response rate was the prespecified end point for accelerated approval. Time to progression (TTP) was a secondary end point. The prespecified primary comparison was between the 5-FU/LV regimen and the 5-FU/LV/oxaliplatin combination regimen. The three arms were well balanced for patient prognostic factors. There were no complete responders. The partial response rates were 0%, 1%, and 9% for the 5-FU/LV, oxaliplatin, and oxaliplatin plus 5-FU/LV treatments, respectively (p = 0.0002, arm C versus arm A). The median times to radiographic tumor progression, based on available radiographs, were 2.7 months, 1.6 months, and 4.6 months, respectively (p < 0.0001, arm C versus arm A). Common adverse events associated with the combination treatment included peripheral neuropathy, fatigue, diarrhea, nausea, vomiting, stomatitis, and abdominal pain. Neutropenia was the major hematologic toxicity. Adverse events were similar in men and women and in patients <65 and greater than or equal to65 years of age, but older patients may have been more susceptible to dehydration, diarrhea, hypokalemia, and fatigue. Oxaliplatin in combination with infusional 5-FU/LV was approved for the treatment of patients with metastatic carcinoma of the colon or rectum whose disease has recurred or progressed during or within 6 months of completion of first-line therapy with the combination of bolus 5-FU/LV and irinotecan. Approval was based on response rate and on an interim analysis of TTP. No results are available, at this time, that demonstrate a clinical benefit, such as improvement in disease-related symptoms or survival. C1 US FDA, Div Oncol Drug Prod, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Ibrahim, A (reprint author), US FDA, Div Oncol Drug Prod, Ctr Drug Evaluat & Res, HFD-150,5600 Fishers Lane, Rockville, MD 20857 USA. EM IbrahimA@cder.fda.gov RI Hirschfeld, Steven/E-2987-2016 OI Hirschfeld, Steven/0000-0003-0627-7249 NR 7 TC 75 Z9 82 U1 0 U2 5 PU ALPHAMED PRESS PI MIAMISBURG PA ONE PRESTIGE PLACE, STE 290, MIAMISBURG, OH 45342-3758 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2004 VL 9 IS 1 BP 8 EP 12 DI 10.1634/theoncologist.9-1-8 PG 5 WC Oncology SC Oncology GA 767ZK UT WOS:000188503600003 PM 14755010 ER PT J AU Hazarika, M White, RM Johnson, JR Pazdur, R AF Hazarika, M White, RM Johnson, JR Pazdur, R TI FDA drug approval summaries: Pemetrexed (Alimta (R)) SO ONCOLOGIST LA English DT Editorial Material DE pemetrexed; Alimta (R); malignant pleural mesothelioma ID MALIGNANT PLEURAL MESOTHELIOMA; LEUKEMIA GROUP-B; PHASE-II TRIAL; CISPLATIN; GEMCITABINE; THERAPY; CANCER AB The purpose of this report is to summarize information on pemetrexed (LY231514; MTA; Alimta(R); Eli Lilly and Company; Indianapolis, IN), a drug recently approved by the U.S. Food and Drug Administration (FDA). The review of the efficacy and safety of pemetrexed is summarized below. Pemetrexed is a pyrrolopyrimidine antifolate. It inhibits thymidylate synthase, glycinamide ribonucleotide formyltransferase, and dihydrofolate reductase. In a single, randomized, single-blind, multicenter phase III trial, the efficacy and safety of pemetrexed combined with cisplatin (Platinol(R); Bristol-Myers Squibb; Princeton, NJ) were compared with those of single-agent cisplatin in 448 patients with malignant pleural mesothelioma. Two hundred twenty-six patients were randomized to receive pemetrexed and cisplatin, while 222 patients were randomized to receive cisplatin alone. The primary study end point was survival. Median survival times were 12.1 months for the pemetrexed plus cisplatin treated arm and 9.3 months for the cisplatin alone arm. Pemetrexed causes myelosuppression. The most common adverse events were neutropenia, fatigue, leukopenia, nausea, dyspnea, and vomiting. On February 4, 2004, pemetrexed was approved by the FDA in combination with cisplatin for the treatment of patients with malignant pleural mesothelioma whose disease is unresectable or who are otherwise not candidates for curative surgery. The recommended dose of pemetrexed is 500 mg/m(2) administered as an i.v. infusion over 10 minutes on day 1 of each 21-day cycle together with cisplatin at a dose of 75 mg/m(2) infused over 2 hours beginning 30 minutes after the pemetrexed infusion. Patients must receive oral folic acid and vitamin B-12 injections prior to the start of therapy and continue these during therapy to reduce severe toxicities. Patients should also receive corticosteroids with chemotherapy to reduce the risk of skin rashes. Approval was based on superior survival as a clinical benefit. C1 US FDA, Ctr Drug Evaluat & Res, Div Oncol Drug Prod, Rockville, MD 20857 USA. RP Hazarika, M (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Oncol Drug Prod, HFD-150,5600 Fishers Lane, Rockville, MD 20857 USA. EM HazarikaM@cder.fda.gov NR 16 TC 57 Z9 65 U1 1 U2 3 PU ALPHAMED PRESS PI MIAMISBURG PA ONE PRESTIGE PLACE, STE 290, MIAMISBURG, OH 45342-3758 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2004 VL 9 IS 5 BP 482 EP 488 DI 10.1634/theoncologist.9-5-482 PG 7 WC Oncology SC Oncology GA 860NH UT WOS:000224349800001 PM 15477632 ER PT S AU Ilev, IK Waynant, RW Byrnes, KR Anders, J AF Ilev, IK Waynant, RW Byrnes, KR Anders, J BE Gannot, I TI A fiber-optic approach for in vivo minimally-invasive study of tissue optical properties SO OPTICAL FIBERS AND SENSORS FOR MEDICAL APPLICATIONS IV SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Conference on Optical Fibers and Sensors for Medical Applictions IV CY JAN 24-25, 2004 CL San Jose, CA SP SPIE DE optical fibers; minimally invasive optical techniques; tissue properties ID UNCOATED HOLLOW TAPER; LASER DELIVERY AB Based on a fiber-optic approach, we present a fundamental in vivo study of optical properties and light transmission characteristics of single and multiple tissue layers and blood in a Sprague Dawley rat model. In our experiments, we utilize either coherent laser sources with various energy and spectral characteristics or incoherent light sources in a broadband spectral range covering the visible and near-infrared (from 400 nm to 1200 nm). The measurement techniques are based on a simple minimally invasive fiber-optic light delivery system that provides an effective method for homogeneously and precisely controlling the light irradiation of the tissue medium as well as being a highly sensitive detector of the tissue's scattered light. The delivery-sensor probes are placed into different tissue layers (skin, subcutaneous connective and deep connective tissue, back muscle, bone and spinal cord) and blood, and broadband spectral transmission characteristics of these media are measured in vivo. The transmission spectra are analyzed in order to determine the specificity of interaction of different tissues with light. The main goal is to determine the most effective coherent or incoherent light sources and their optimal parameters that might be used for minimally invasive therapeutic and optical diagnostics techniques. C1 US FDA, Ctr Devices & Radiol Hlth, Off Sci & Technol, Rockville, MD 20857 USA. RP Ilev, IK (reprint author), US FDA, Ctr Devices & Radiol Hlth, Off Sci & Technol, HFZ-134, Rockville, MD 20857 USA. OI Byrnes, Kimberly/0000-0002-7501-7734 NR 7 TC 1 Z9 1 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-5225-4 J9 P SOC PHOTO-OPT INS PY 2004 VL 5317 BP 147 EP 150 DI 10.1117/12.529159 PG 4 WC Engineering, Biomedical; Instruments & Instrumentation; Optics SC Engineering; Instruments & Instrumentation; Optics GA BAN19 UT WOS:000222939100019 ER PT S AU Pfefer, TJ Agrawal, A Drezek, RA AF Pfefer, TJ Agrawal, A Drezek, RA BE Gannot, I TI Computational analysis of beveled-tip fiber probes for selective detection of subsurface fluorophores in turbid media SO OPTICAL FIBERS AND SENSORS FOR MEDICAL APPLICATIONS IV SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Conference on Optical Fibers and Sensors for Medical Applictions IV CY JAN 24-25, 2004 CL San Jose, CA SP SPIE DE fluorescence spectroscopy; light-tissue interaction; computational modeling; fiberoptics; optical diagnostics ID FLUORESCENCE SPECTROSCOPY; TISSUE FLUORESCENCE; SINGLE-FIBER; DESIGNS; MODEL; DEPTH AB Optimization of illumination-collection parameters may lead to an improvement in the efficacy of fluorescence spectroscopy devices for minimally invasive disease detection. While device-tissue interface geometry has been shown to have a strong influence on the origin of detected fluorescence, prior studies have tended to focus on systems which deliver and collect light at approximately normal incidence to the tissue surface. Optical fibers with beveled surfaces enable the delivery and/or collection of light at a range of angles. This feature may make it possible to interrogate subsurface tissue regions with a greater degree of spatial selectivity. In this study, simulations were performed using a Monte Carlo model of fluorescent light propagation in order to estimate the behavior and potential limitations of this approach. The effect of tissue optical properties, illumination angle, collection angle and illumination-collection fiber separation distance were investigated. Results indicated that beveled fiber probes may significantly improve the ability of fiberoptic probes to selectively interrogate specific tissue regions or layers, however, the advantage over flat fibers is reduced as tissue attenuation increases. C1 US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Pfefer, TJ (reprint author), US FDA, Ctr Drug Evaluat & Res, HFZ-134,12725 Twinbrook Pkwy, Rockville, MD 20857 USA. NR 11 TC 1 Z9 1 U1 0 U2 1 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-5225-4 J9 P SOC PHOTO-OPT INS PY 2004 VL 5317 BP 206 EP 213 DI 10.1117/12.546520 PG 8 WC Engineering, Biomedical; Instruments & Instrumentation; Optics SC Engineering; Instruments & Instrumentation; Optics GA BAN19 UT WOS:000222939100027 ER PT S AU Wood, JM Webster, RG Webby, RJ Robertson, JS Katz, J Levandowski, RA Grohmann, G Cox, N Hay, AJ Tashiro, M Hampson, A Gust, I Stohr, K AF Wood, JM Webster, RG Webby, RJ Robertson, JS Katz, J Levandowski, RA Grohmann, G Cox, N Hay, AJ Tashiro, M Hampson, A Gust, I Stohr, K BE Kawaoka, Y TI Influenza pandemic vaccines: the imminent challenges from a technical and regulatory perspective SO OPTIONS FOR THE CONTROL OF INFLUENZA V SE INTERNATIONAL CONGRESS SERIES LA English DT Proceedings Paper CT 5th International Conference on Options for the Control of Influenza CY OCT 07-11, 2003 CL Okinawa, JAPAN SP Pharmaceut Manufacturers Assoc Tokyo, Pharmaceut Assoc Osaka, Wyeth Vaccine, MedImmune, Fujirebio, Nagoya City Univ, Takara Bio, Rikaken, Japan Bio Sci Lab, Japanese Soc Control Influenza, Japanese Fdn Promot Int Med Res Corp, Japanese Soc Virol, Japanese Soc Clin Virol, NPO Biomed Sci Assoc, WHO, Minist Hlth, Labor & Welfare Japan DE pandemic influenza; vaccines; reverse genetics ID A VIRUS; REVERSE GENETICS; GENERATION AB In 1997, we were ill prepared to produce vaccines in response to the sudden emergence of highly pathogenic H5N1 influenza. This experience stimulated efforts to improve technical and regulatory procedures for pandemic vaccine virus development and, in February 2003, when highly pathogenic H5N1 influenza re-appeared in man, we were able to produce H5N1 vaccine strains by reverse genetics within the space of 3 months. The technical and regulatory progress which made this possible is reviewed and newly developed WHO biosafety risk assessment for vaccine production is described. Recommendations are made for the significant challenges that lie ahead. (C) 2004 Elsevier B.V. All rights reserved. C1 Natl Inst Biol Stand & Controls, Div Virol, Potters Bar EN6 3QG, Herts, England. St Jude Childrens Res Hosp, Div Virol, Dept Infect Dis, Memphis, TN 38105 USA. Ctr Dis Control, WHO Collaborating Ctr Influenza, Atlanta, GA 30333 USA. US FDA, Ctr Biol Evaluat & Res, Lab Pediat & Resp Viral Dis, Div Viral Prod,Off Vaccines Res & Review, Bethesda, MD USA. Therapeut Goods Adm Labs, Woden, ACT, Australia. Natl Inst Med Res, WHO Collaborating Ctr Influenza, London NW7 1AA, England. Natl Inst Infect Dis, WHO Collaborating Ctr Influenza, Tokyo, Japan. WHO Collaborating Ctr Influenza, Parkville, Vic, Australia. WHO, WHO Global Influenza Programme, CH-1211 Geneva, Switzerland. RP Wood, JM (reprint author), Natl Inst Biol Stand & Controls, Div Virol, Blanche Lane S Mimms, Potters Bar EN6 3QG, Herts, England. EM jwood@nibsc.ac.uk NR 6 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0531-5131 BN 0-444-51639-5 J9 INT CONGR SER JI Int. Congr. Ser. PY 2004 VL 1263 BP 51 EP 54 DI 10.1016/j.ics.2004.01.049 PG 4 WC Infectious Diseases; Virology SC Infectious Diseases; Virology GA BAU81 UT WOS:000223655000010 ER PT S AU Liu, T Ye, ZP AF Liu, T Ye, ZP BE Kawaoka, Y TI Alteration of the basic amino acid domain of wild-type matrix protein reduced influenza virus replication at non-permissive temperature SO OPTIONS FOR THE CONTROL OF INFLUENZA V SE INTERNATIONAL CONGRESS SERIES LA English DT Proceedings Paper CT 5th International Conference on Options for the Control of Influenza CY OCT 07-11, 2003 CL Okinawa, JAPAN SP Pharmaceut Manufacturers Assoc Tokyo, Pharmaceut Assoc Osaka, Wyeth Vaccine, MedImmune, Fujirebio, Nagoya City Univ, Takara Bio, Rikaken, Japan Bio Sci Lab, Japanese Soc Control Influenza, Japanese Fdn Promot Int Med Res Corp, Japanese Soc Virol, Japanese Soc Clin Virol, NPO Biomed Sci Assoc, WHO, Minist Hlth, Labor & Welfare Japan DE alteration; protein; influenza virus ID RNA-BINDING DOMAINS; M1 PROTEIN; A VIRUS; VIRAL RIBONUCLEOPROTEINS; NUCLEAR TRANSPORT; INFECTED-CELLS; MEMBRANE; LOCALIZATION; EXPORT; HEMAGGLUTININ AB The matrix protein (M1) of influenza virus plays an essential role in viral assembly and a variety of functions, including association with influenza virus ribonucleoprotein (RNP). Our previous studies show that the association of M I with viral RNA and NP protein not only promotes formation of helical RNP, but also is required for export of RNP from the nucleus during viral replication. The RNA-binding domains of M1 have been mapped to two independent regions, a zinc-finger motif at amino acid positions 148 to 162, and a series of basic amino acids (RKLKR) at amino acid positions 10 1 to 105, which is also involved in RNP-binding activity. To further understand the role of the RNP-binding domain of M1 on viral assembly and replication, mutations in the coding sequences of RKLKR and zinc-finger motif of M1 were constructed using a PCR technique and introduced into wild-type influenza virus by reverse genetics. Altering the zinc-finger motif of M1 only slightly affected viral growth. Substitution of Arg with Ser at position 101 or 105 of RKLKR did not have a major impact on nuclear export of RNP or viral replication. In contrast, deletion of RKLKR or substitution of Lys with Asn at position 102 or 104 of RKLKR resulted in a lethal mutation. These results indicate that RKLKR domain of M1 protein plays an important role in viral replication. (C) 2004 Elsevier B.V. All rights reserved. C1 US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Lab Pediat & Resp Viral Dis, Bethesda, MD 20982 USA. RP Ye, ZP (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Lab Pediat & Resp Viral Dis, Blgd 29A,Rm 2B17,8800 Rockville Pike, Bethesda, MD 20982 USA. NR 42 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0531-5131 BN 0-444-51639-5 J9 INT CONGR SER PY 2004 VL 1263 BP 83 EP 89 DI 10.1016/j.ics.2004.02.146 PG 7 WC Infectious Diseases; Virology SC Infectious Diseases; Virology GA BAU81 UT WOS:000223655000017 ER PT J AU Myers, MJ Farrell, DE Snider, TGR Post, LO AF Myers, MJ Farrell, DE Snider, TGR Post, LO TI Inflammatory cytokines, pleuropneumonia infection and the effect of dexamethasone SO PATHOBIOLOGY LA English DT Article DE swine; Actinobacillus pleuropneumoniae; pneumonia; TNF-alpha; IL-1 beta; IL-6; IL-8; IL-10 ID NECROSIS-FACTOR-ALPHA; PORCINE ACTINOBACILLUS-PLEUROPNEUMONIA; IN-VIVO; HUMAN MONOCYTES; SWINE; ENDOTOXIN; PATHOGENESIS; EXPRESSION; CORTISOL; LIPOPOLYSACCHARIDE AB Objectives: Actinobacillus pleuropneumoniae causes an often fatal infection of swine due to pleuropneumonia. To determine if inflammatory cytokines are associated with A. pleuropneumoniae-induced pneumonia, infected and noninfected animals were concomitantly administered saline or dexamethasone. Methods: Twenty-four swine were treated with saline, A. pleuropneumoniae, dexamethasone, or A. pleuropneumoniae and dexamethasone (n=6). The plasma levels of TNF-alpha, IL-1beta, IL-6, IL-8, and IL-10 were examined through time of necropsy (72 h). Gross pathology and histopathology was performed on all animals. Results: Dexamethasone had no effect on A. pleuropneumoniae-induced increases in lung/body weight ratios. Gross pathology of the infected pigs included fibrinous pleuropneumonia with necrosis and hemorrhage in a focal to a multifocal pattern. Histopathology of infected pig lungs revealed necrotizing extensive, fibrinopurulent pneumonia with edema and fibrinopurulent pleuritis. Plasma IL-6 levels were elevated in A. pleuropneumoniae-infected animals beginning 6 h after infection. Dexamethasone treatment did not alter A. pleuropneumoniae-induced plasma IL-6 levels. A. pleuropneumoniae infection did not elicit plasma levels of TNF-alpha, IL-1beta, IL-8, or IL-10. Conclusion: These results suggest that the pneumonia caused by A. pleuropneumoniae infection is not due to the release of systemic inflammatory cytokines. Copyright (C) 2004 S. Karger AG, Basel. C1 US FDA, Div Anim Res, Ctr Vet Med, Laurel, MD 20708 USA. Louisiana State Univ, Sch Vet Med, Dept Pathobiol Sci, Baton Rouge, LA 70803 USA. US FDA, Div Surveillance, Ctr Vet Med, Rockville, MD 20857 USA. RP Myers, MJ (reprint author), US FDA, Div Anim Res, Ctr Vet Med, 8401 Muirkirk Rd, Laurel, MD 20708 USA. NR 46 TC 4 Z9 5 U1 0 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-2008 J9 PATHOBIOLOGY JI Pathobiology PY 2004 VL 71 IS 1 BP 35 EP 42 DI 10.1159/000072960 PG 8 WC Cell Biology; Pathology SC Cell Biology; Pathology GA 740TR UT WOS:000186418100005 PM 14555843 ER PT S AU Farshid, M AF Farshid, M BE Robertson, JS TI Viral safety evaluation of plasma-derived therapeutic products SO PDA/EMEA EUROPEAN VIRUS SAFETY FORUM SE DEVELOPMENTS IN BIOLOGICALS LA English DT Proceedings Paper CT PDA/EMEA European Virus Safety Forum 2003 CY SEP 29-OCT 01, 2003 CL Paul-Ehrlich Inst, Langen, GERMANY SP PDA, European Agcy Evaluat Med Prod HO Paul-Ehrlich Inst AB The viral safety of plasma-derived products, in the U.S., is ensured by a complementary approach consisting of donor screening for high-risk activities or history, donor testing for relevant blood-borne viruses, and the inclusion of viral clearance steps in the manufacturing process. Thus, any manufacturing process for the production of plasma-derived products should be validated for its capacity to clear viruses. This validation is performed by using small-scale laboratory models that mimic the actual manufacturing process with regard to its critical operating parameters and performance characteristics. In addition, there are a number of validation components that are deemed essential for obtaining reliable viral validation data. These include: (i) validation of the small-scale model to establish its relevance to the actual process; (ii) choice of viruses in performing spiking experiments; (iii) reliability and validity of the assays used to determine viral titer in the test articles and (iv) calculation of total log reductions in the validated steps. C1 CBER FDA, Div Hematol, Rockville, MD 20852 USA. RP Farshid, M (reprint author), CBER FDA, Div Hematol, HFM-345,Suite 200N,1401 Rockville Pike, Rockville, MD 20852 USA. EM farshidm@cber.fda.gov NR 5 TC 4 Z9 5 U1 0 U2 0 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 1424-6074 BN 3-8055-7873-3 J9 DEV BIOLOGICALS JI Dev. Biols PY 2004 VL 118 BP 11 EP 15 PG 5 WC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy; Virology SC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy; Virology GA BDW88 UT WOS:000235894400002 PM 15645668 ER PT S AU Brorson, K Norling, L Hamilton, E Lute, S Lee, K Curtis, S Xu, Y AF Brorson, K Norling, L Hamilton, E Lute, S Lee, K Curtis, S Xu, Y BE Robertson, JS TI Current and future approaches to ensure the viral safety of biopharmaceuticals SO PDA/EMEA EUROPEAN VIRUS SAFETY FORUM SE DEVELOPMENTS IN BIOLOGICALS LA English DT Proceedings Paper CT PDA/EMEA European Virus Safety Forum 2003 CY SEP 29-OCT 01, 2003 CL Paul-Ehrlich Inst, Langen, GERMANY SP PDA, European Agcy Evaluat Med Prod HO Paul-Ehrlich Inst ID REVERSE-TRANSCRIPTASE ASSAY; TIME QUANTITATIVE PCR; MAB CELL-CULTURE; PROTEIN-PURIFICATION; MONITOR RETROVIRUS; CLEARANCE; SIMIAN-VIRUS-40; QUANTIFICATION; PERFORMANCE; SIGNALS C1 CDER FDA, Div Monoclonal Antibodies, Bethesda, MD 20892 USA. RP Brorson, K (reprint author), CDER FDA, Div Monoclonal Antibodies, Bldg 29B,Rm 5E16,29 Lincoln Dr, Bethesda, MD 20892 USA. EM kurt.brorson@fda.hhs.gov NR 31 TC 20 Z9 22 U1 0 U2 0 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 1424-6074 BN 3-8055-7873-3 J9 DEV BIOLOGICALS JI Dev. Biols PY 2004 VL 118 BP 17 EP 29 PG 13 WC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy; Virology SC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy; Virology GA BDW88 UT WOS:000235894400003 PM 15645669 ER PT J AU Weiss, KD AF Weiss, KD TI Safety, pharmacokinetics, and pharmacodynamics of drotrecogin alfa (activated) in children with severe sepsis SO PEDIATRICS LA English DT Editorial Material C1 US FDA, Off Drug Evaluat 6, Off New Drugs, Ctr Drug Evaluat & Res, Rockville, MD 20852 USA. RP Weiss, KD (reprint author), US FDA, Off Drug Evaluat 6, Off New Drugs, Ctr Drug Evaluat & Res, 1401 Rockville Pike,Ste 380, Rockville, MD 20852 USA. EM weissk@cber.fda.gov NR 3 TC 3 Z9 3 U1 0 U2 0 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 JAN PY 2004 VL 113 IS 1 BP 134 EP 134 DI 10.1542/peds.113.1.134 PG 1 WC Pediatrics SC Pediatrics GA 762XX UT WOS:000188010600039 PM 14702464 ER PT J AU Pool, V Mootrey, G Chen, RT Gargiullo, PM Braun, MM Kelso, JM Yunginger, JW AF Pool, V Mootrey, G Chen, RT Gargiullo, PM Braun, MM Kelso, JM Yunginger, JW TI Gelatin allergy - Reply SO PEDIATRICS LA English DT Letter C1 Ctr Dis Control & Prevent, Immunizat Safety Branch, Atlanta, GA 30333 USA. Ctr Dis Control & Prevent, Viral Vaccine Preventable Dis Branch, Epidemiol & Surveillance Div, Natl Immunizat Program, Atlanta, GA 30333 USA. US FDA, Div Epidemiol, Off Biostat & Epidemiol, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. USN, Med Ctr, Div Allergy, San Diego, CA 92134 USA. Mayo Clin Coll Med, Dept Pediat & Adolescent Med, Rochester, MN 55905 USA. RP Pool, V (reprint author), Ctr Dis Control & Prevent, Immunizat Safety Branch, Atlanta, GA 30333 USA. NR 6 TC 2 Z9 2 U1 0 U2 0 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 JAN PY 2004 VL 113 IS 1 BP 170 EP 171 PG 3 WC Pediatrics SC Pediatrics GA 762XX UT WOS:000188010600049 ER PT J AU Powers, JH Johann-Liang, R AF Powers, JH Johann-Liang, R TI Tubes and ear infections SO PEDIATRICS LA English DT Letter C1 US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20850 USA. RP Powers, JH (reprint author), US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20850 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 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 JAN PY 2004 VL 113 IS 1 BP 178 EP 179 DI 10.1542/peds.113.1.178 PG 3 WC Pediatrics SC Pediatrics GA 762XX UT WOS:000188010600065 PM 14702480 ER PT J AU Manda, B Drinkard, CR Shatin, D Graham, DJ AF Manda, B Drinkard, CR Shatin, D Graham, DJ TI The risk of esophageal obstruction associated with an anti-allergy medication (Claritin-D-(R) 24-hour - Original formulation) SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Article DE pharmacoepidemiology; post-marketing drug surveillance; adverse drug events; anti-allergy medication ID EXTENDED-RELEASE TABLETS AB Purpose To investigate a possible increased risk of esophageal obstruction among users of loratadine and pseudoephedrine (Claritin-D-(R) 24-Hour [C-D 24], the original, round, extended-release formulation) compared to two other tablet formulations of loratadine. Methods Pharmacy data of 12 managed care plans were screened to identify users in the three groups from 1 September 1996 to 31 December 1998. Users with a medical claim following their first loratadine prescription (Index prescription) indicating an esophageal obstruction or endoscopic procedure were considered claims-identified cases. Medical records were reviewed to validate case status. Results There were 233 901 users (61% female) and 245 claims-identified cases occurring within 30 days after the first prescription. The incidence rate per 10000 users of claims-identified cases occurring on the Index prescription date was higher among C-D 24 users (IR = 1.4) than Claritin((R)) Regular (C-R) users (IR = 0.07; p < 0.002) or Claritin-D-(R) 12-Hour (C-D 12) users (IR = 0.3; p > 0.05). Medical record review of 15 claims-identified cases confirmed two cases of acute esophageal obstruction, both among C-D 24 users. Conclusions Claims-based analysis suggested an increased risk of endoscopic procedures on the Index date among C-D 24 users compared to C-R users. However, after medical record review, the study did not provide conclusive evidence of an association between C-D 24 use and esophageal obstruction. This study highlights the importance of validating findings from claims data using medical records. Copyright (C) 2003 John Wiley Sons, Ltd. C1 Ctr Hlth Care Policy & Evaluat, UnitedHlth Grp, Minneapolis, MN 55344 USA. US FDA, Off Drug Safety, Rockville, MD 20857 USA. RP Manda, B (reprint author), Ctr Hlth Care Policy & Evaluat, UnitedHlth Grp, 12125 Technol Dr,MN002-0260, Minneapolis, MN 55344 USA. EM bharati_s_manda@uhc.com FU FDA HHS [FD-U-001643-01/02] NR 4 TC 4 Z9 4 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD JAN PY 2004 VL 13 IS 1 BP 29 EP 34 DI 10.1002/pds.816 PG 6 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 768GW UT WOS:000188536100004 PM 14971120 ER PT J AU Ning, BT Wang, C Morel, F Nowell, S Ratnasinghe, DL Carter, W Kadlubar, FF Coles, B AF Ning, BT Wang, C Morel, F Nowell, S Ratnasinghe, DL Carter, W Kadlubar, FF Coles, B TI Human glutathione S-transferase A2 polymorphisms: variant expression, distribution in prostate cancer cases/controls and a novel form SO PHARMACOGENETICS LA English DT Article DE glutathione S-transferase; polymorphism; prostate cancer; expression; linkage disequilibrium ID I105V POLYMORPHISM; GENE; SUSCEPTIBILITY; CARCINOGENS; PROMOTER; GSTP1; P1; DETOXIFICATION; ASSOCIATION; GENOTYPES AB Variability of expression of the major glutathione S-transferases (GSTs) of liver, GSTA1 and GSTA2, is thought to affect the efficiency of detoxification of xenobiotics, including chemical carcinogens. Polymorphism of the GSTA1 regulatory sequence determines some of the variation of hepatic GSTA1 expression, but the polymorphisms in GSTA2 (exons 5 and 7) were not thought to affect GSTA2 activity. By examining GST protein expression for a set of human liver and pancreas samples (coupled with a cloning/polymerase chain reaction-restriction fragment length polymorphism strategy), we identified a novel substitution Prol(110)Ser (328C>T) and the corresponding novel variant GSTA2*E (Ser(110)Ser(112)Lys(196)Glu(210)), and confirmed the presence of variants GSTA2*A (Pro(110)Ser(112)Lys(196)Glu(210)), GSTA2*B (Pro(110)Ser(112)Lys(196)Ala(210)) and GSTA2*C (Pro(110)Thr(112)Lys(196)Glu(210)). GSTA2*C occurred at 30-60% (i.e. approximately 100-fold more frequent than previously reported) and GSTA2*E occurred (heterozygous) at approximately 11%. Hepatic expression of the Ser(112) variants (GSTA2*A, GSTA2*B or GSTA2*E) was approximately four-fold higher than that of the Thr(112) variant (GSTA2* C). Compared to any other variant, GSTA2E had lower rates of catalysis towards 1-chloro-2,4-dinitrobenzene (CDNB), 4-vinylpyridine, and cumene-, t-butyl- and arachidonic acid hydroperoxides, although K-cat/K-m for CDNB were similar for all four variants. Using a kc prostate cancer case-control population, it was found that GSTA1 *A/GSTA2 C335 and GSTA1 * B/GSTA2 G335 were in linkage disequilibrium in Caucasians but not in African-Americans. However, there were no significant differences in the distribution of these polymorphisms or resultant haplotypes by case status. Nevertheless, the rare genotypes, GSTA2*E/*E and GSTA1*B/*B + GSTA2*C/ * C (potential low GSTA2 activity and low hepatic GSTA1 and GSTA2 expression, respectively) could increase the risk of adverse effects of xenobiotics via compromised efficiency of detoxification. Pharmacogenetics 14:35-44 (C) 2004 Lippincott Williams Wilkins. C1 Natl Ctr Toxicol Res, Div Mol Epidemiol HFT100, Jefferson, AR 72079 USA. Univ Rennes 1, INSERM, U456, Rennes, France. RP Coles, B (reprint author), Natl Ctr Toxicol Res, Div Mol Epidemiol HFT100, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM bcoles@nctr.fda.gov NR 29 TC 32 Z9 35 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0960-314X J9 PHARMACOGENETICS JI Pharmacogenetics PD JAN PY 2004 VL 14 IS 1 BP 35 EP 44 DI 10.1097/01.fpc.0000054149.92680.ae PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy GA 779HG UT WOS:000189288800004 PM 15128049 ER PT J AU Zineh, I Gerhard, T Aquilante, CL Beitelshees, AL Beasley, BN Hartzema, AG AF Zineh, I Gerhard, T Aquilante, CL Beitelshees, AL Beasley, BN Hartzema, AG TI Availability of pharmacogenomics-based prescribing information in drug package inserts for currently approved drugs SO PHARMACOGENOMICS JOURNAL LA English DT Article ID FACTOR-IX; GENOTYPING ASSAY; HEMOPHILIA-B; THERAPY; CYP2C9; GENE; WARFARIN; POLYMORPHISMS; ASSOCIATION; CANCER C1 Univ Florida, Coll Pharm, Dept Pharm Practice, Gainesville, FL 32610 USA. Univ Florida, Ctr Pharmacogenom, Gainesville, FL USA. Univ Florida, Coll Pharm, Dept Pharm Hlth Care Adm, Gainesville, FL USA. Univ Colorado, Sch Pharm, Dept Clin Pharm, Denver, CO 80202 USA. US FDA, Off Clin Pharmacol & Biopharmaceut, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Zineh, I (reprint author), Univ Florida, Coll Pharm, Dept Pharm Practice, POB 100486, Gainesville, FL 32610 USA. EM zineh@cop.ufl.edu NR 41 TC 27 Z9 28 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1470-269X J9 PHARMACOGENOMICS J JI Pharmacogenomics J. PY 2004 VL 4 IS 6 BP 354 EP 358 DI 10.1038/sj.tpj.6500284 PG 5 WC Genetics & Heredity; Pharmacology & Pharmacy SC Genetics & Heredity; Pharmacology & Pharmacy GA 879QB UT WOS:000225731200003 PM 15483659 ER PT J AU Schlesser, J AF Schlesser, J. TI Survival of a five strain cocktail of Escherichia coli O157 : H7 during thermalization and the 60 day aging period of hard cheese made from unpasteurized SO POULTRY SCIENCE LA English DT Meeting Abstract DE thermalization; Escherichia coli O157 : H7; raw milk cheese C1 [Schlesser, J.] NCFST, Food & Drug Adm, Summit Argo, IL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU POULTRY SCIENCE ASSOC INC PI SAVOY PA 1111 N DUNLAP AVE, SAVOY, IL 61874-9604 USA SN 0032-5791 J9 POULTRY SCI JI Poult. Sci. PY 2004 VL 83 SU 1 BP 122 EP 123 PG 2 WC Agriculture, Dairy & Animal Science SC Agriculture GA V45UO UT WOS:000203095400490 ER PT J AU Schlesser, J Gerdes, R AF Schlesser, J. Gerdes, R. TI Incidence of Escherichia coli O157 : H7 in raw milk and survival of a five strain cocktail of E. coli O157 : H7 during the 60 days aging period of hard cheese made from unpasteurized milk SO POULTRY SCIENCE LA English DT Meeting Abstract DE raw milk cheese; Escherichia coli O157 : H7; E. coli O157 : H7 in raw milk C1 [Schlesser, J.] US FDA, NCFST, Summit Argo, IL USA. [Gerdes, R.] IIT, Summit Argo, IL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU POULTRY SCIENCE ASSOC INC PI SAVOY PA 1111 N DUNLAP AVE, SAVOY, IL 61874-9604 USA SN 0032-5791 J9 POULTRY SCI JI Poult. Sci. PY 2004 VL 83 SU 1 BP 383 EP 384 PG 2 WC Agriculture, Dairy & Animal Science SC Agriculture GA V45UO UT WOS:000203095401577 ER PT J AU Baumgard, LH Sanders, SR Mendivill, OB Kay, JK Marchellol, JA Delmonte, P Griinari, JM Yurawecz, MP AF Baumgard, L. H. Sanders, S. R. Mendivill, O. B. Kay, J. K. Marchellol, J. A. Delmonte, P. Griinari, J. M. Yurawecz, M. P. TI Subcutaneous and abdominal fatty acid composition and CLA profiles in grain finished steers SO POULTRY SCIENCE LA English DT Meeting Abstract DE beef; CLA; adipose depot C1 [Baumgard, L. H.; Sanders, S. R.; Mendivill, O. B.; Kay, J. K.; Marchellol, J. A.] Univ Arizona, Tucson, AZ USA. [Delmonte, P.; Yurawecz, M. P.] US FDA, Washington, DC 20204 USA. [Griinari, J. M.] Univ Helsinki, FIN-00014 Helsinki, Finland. NR 0 TC 0 Z9 0 U1 0 U2 0 PU POULTRY SCIENCE ASSOC INC PI SAVOY PA 1111 N DUNLAP AVE, SAVOY, IL 61874-9604 USA SN 0032-5791 J9 POULTRY SCI JI Poult. Sci. PY 2004 VL 83 SU 1 BP 422 EP 422 PG 1 WC Agriculture, Dairy & Animal Science SC Agriculture GA V45UO UT WOS:000203095401730 ER PT J AU Petricoin, EF Liotta, LA AF Petricoin, EF Liotta, LA TI Clinical proteomics: Application at the bedside SO PROTEOMICS IN NEPHROLOGY SE CONTRIBUTIONS TO NEPHROLOGY LA English DT Article ID ARTIFICIAL NEURAL-NETWORKS; OVARIAN-CANCER; MASS-SPECTROMETRY; BIOMARKER; CLASSIFICATION; IDENTIFICATION; PREDICTION; DISCOVERY; PROSTATE; DISEASE C1 US FDA, Ctr Biol Evaluat & Res, Off Director, FDA NCI Clin Proteom Program, Bethesda, MD 20892 USA. NCI, Canc Res Ctr, Pathol Lab, FDA NCI Clin Proteom Program, Bethesda, MD 20892 USA. RP Petricoin, EF (reprint author), US FDA, Ctr Biol Evaluat & Res, Off Director, FDA NCI Clin Proteom Program, Bldg 29A 2D12,8800 Rockville Pike, Bethesda, MD 20892 USA. NR 33 TC 10 Z9 12 U1 0 U2 0 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0302-5144 J9 CONTRIB NEPHROL JI Contrib.Nephrol. PY 2004 VL 141 BP 93 EP 103 PG 11 WC Urology & Nephrology SC Urology & Nephrology GA BY13L UT WOS:000187846000007 PM 14650227 ER PT S AU Inn, KGW Lin, ZC Schultz, M Wu, ZG McMahon, C Outola, I Kurosaki, H Nour, S Selvig, L Karam, L Hutchinson, JMR AF Inn, KGW Lin, ZC Schultz, M Wu, ZG McMahon, C Outola, I Kurosaki, H Nour, S Selvig, L Karam, L Hutchinson, JMR BE Laue, CA Nash, KL TI Interface of environmental, bioassay, and radioanalytical Standard Reference Materials and traceability evaluations SO RADIOANALYTICAL METHODS IN INTERDISCIPLINARY RESEARCH: FUNDAMENTALS IN CUTTING-EDGE APPLICATIONS SE ACS SYMPOSIUM SERIES LA English DT Article; Proceedings Paper CT Symposium on Radioanalytical Methods at the Frontier of Interdisciplinary Science held at the 223rd National Meeting of the American-Chemical-Society CY APR 08-10, 2002 CL ORLANDO, FLORIDA SP Amer Chem Soc, Div Nucl Chem & Technol ID BONE ASH STANDARD; ACTINIDES; OCEAN AB Radiochemistry is the cornerstone for certifying environmental natural-matrix Standard Reference Materials (SRMs), and for verifying environmental and radiobioassay test samples for the National Institute of Standards and Technology (NIST) traceability evaluation programs. Natural-matrix SRMs provide the basis for radiochemical methods validation, demonstration of traceability for environmental radionuclide measurements, and the basis for measurement comparison over time within and among laboratories. The certifications of eight natural-matrix radionuclide SRMs are conducted through the efforts of intercomparisons, of experienced laboratories from around the world. While the SRM program has been successful in certifying many radionuclides in environmental matrices, there have also been several unresolved radiochemical issues left to future efforts. The evaluation programs provide the program participants with a direct and unambiguous evaluation of the traceability of their radioanalytical capabilities by NIST. Because the participants in the evaluation programs depend on absolute confidence in the results of the evaluation to assess their radioanalytical methods for bias from the national physical standard, Bq, NIST must verify the production of the test samples to approximately 1 percent (relative combined standard uncertainty) with radiochemical measurements that depend on extraordinary laboratory practices. C1 NIST, Ionizing Radiat Div, Gaithersburg, MD 20899 USA. US FDA, WEAC, Winchester, MA 01890 USA. Ametek, Oak Ridge, TN 37831 USA. Radiol Protect Inst Ireland, Dublin 14, Ireland. RP Inn, KGW (reprint author), NIST, Ionizing Radiat Div, Gaithersburg, MD 20899 USA. NR 23 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 SIXTEENTH ST NW, WASHINGTON, DC 20036 USA SN 0097-6156 BN 0-8412-3837-5 J9 ACS SYM SER PY 2004 VL 868 BP 38 EP 49 PG 12 WC Chemistry, Multidisciplinary; Chemistry, Analytical; Chemistry, Inorganic & Nuclear SC Chemistry GA BY28F UT WOS:000188742000004 ER PT J AU Samei, E Seibert, JA Andriole, K Badano, A Crawford, J Reiner, B Flynn, MJ Chang, P AF Samei, E Seibert, JA Andriole, K Badano, A Crawford, J Reiner, B Flynn, MJ Chang, P TI AAPM/RSNA tutorial on equipment selection: PACS equipment overview - General guidelines for purchasing and acceptance testing of PACS equipment SO RADIOGRAPHICS LA English DT Article; Proceedings Paper CT Annual Meeting of the Radiological-Society-of-North-America CY DEC, 2002 CL CHICAGO, ILLINOIS SP Radiolog Soc North Amer DE computers; images, storage and retrieval; picture archiving and communication system (PACs) ID COMPUTED RADIOGRAPHY SYSTEMS; DETECTOR PERFORMANCE; DIGITAL RADIOGRAPHY AB A picture archiving and communication system (PACS) is a comprehensive computer system that is responsible for the electronic storage and distribution of medical images in the medical enterprise. The system is highly integrated with digital acquisition and display devices and is often related closely to other medical information systems, such as the radiology information system or hospital information system. In the past few years, there has been continuous growth in clinical implementation of PACS to reduce costs and improve patient care, a trend that is expected to continue. However, a PACS is complex and costly to acquire, replace, maintain, and repair. To select a system that best meets their requirements, purchasers of PACS equipment need to be aware of the key characteristics and differing features of the various products. After the PACS has been installed, the user should perform technical and clinical acceptance testing to ensure that the system meets expectations. (C)RSNA, 2004. C1 Duke Univ, Dept Radiol, Durham, NC 27710 USA. Duke Univ, Dept Phys, Durham, NC 27710 USA. Duke Univ, Dept Biomed Engn, Durham, NC 27710 USA. Univ Calif Davis, Dept Radiol, Sacramento, CA 95817 USA. Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94143 USA. US FDA, Ctr Devices & Radiol Hlth, Med Imaging & Comp Applicat Branch, Off Sci & Technol, Rockville, MD 20857 USA. Med Univ S Carolina, Dept Radiol, Charleston, SC 29425 USA. Vet Affairs Maryland Healthcare Syst, Dept Radiol, Baltimore, MD USA. Univ Maryland, Sch Med, Dept Radiol, Baltimore, MD 21201 USA. Henry Ford Hlth Syst, Detroit, MI USA. Univ Pittsburgh, Med Ctr, Dept Radiol Informat, Pittsburgh, PA 15260 USA. RP Samei, E (reprint author), Duke Univ, Dept Radiol, DUMC Box 3302, Durham, NC 27710 USA. EM samei@duke.edu NR 21 TC 21 Z9 23 U1 0 U2 5 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0271-5333 J9 RADIOGRAPHICS JI Radiographics PD JAN-FEB PY 2004 VL 24 IS 1 BP 313 EP 334 DI 10.1148/rg.241035137 PG 22 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 763DH UT WOS:000188058400028 PM 14730055 ER PT J AU Interewicz, B Olszewski, WL Leak, LV Petricoin, EF Ross, S Liotta, LA AF Interewicz, B Olszewski, WL Leak, LV Petricoin, EF Ross, S Liotta, LA TI Low-molecular weight proteins in normal subjects and patients wiyh inflammatory lymph stasis SO SHOCK LA English DT Meeting Abstract CT 6th World Congress on Trauma, Shock, Inflammation and Sepsis - Pathophysiology, Immune Consequences and Therapy CY MAR 02-06, 2004 CL Munich, GERMANY C1 Polish Acad Sci, Med Res Ctr, PL-02106 Warsaw, Poland. US FDA, Ctr Biol Evaluat & Res, Clin Proteom Program Therapeut Prot, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1073-2322 J9 SHOCK JI Shock PY 2004 VL 21 SU 1 MA 431 BP 108 EP 108 PG 1 WC Critical Care Medicine; Hematology; Surgery; Peripheral Vascular Disease SC General & Internal Medicine; Hematology; Surgery; Cardiovascular System & Cardiology GA 810FF UT WOS:000220689500432 ER PT B AU Banks, DL Olszewski, RT AF Banks, DL Olszewski, RT BE Bozdogan, H TI Data mining in federal agencies SO STATISTICAL DATA MINING AND KNOWLEDGE DISCOVERY LA English DT Proceedings Paper CT C Warren Neel International Conference on Statistical Data Mining and Knowledge Discovery CY JUN 22-25, 2002 CL Knoxville, TN SP Dept Statist, Coll Business Adm, SAS Inst, Univ Tennessee Sci Alliance, Off Res Adm, Oak Ridge Natl Lab, Ctr Informat Technol & Res, Statist Innovat Inc, Classificat Soc N Amer ID REGRESSION AB Federal agencies in the United States collect enormous quantities of data. Recently, they have begun to attempt to apply data mining to extract additional insights from their collections. This paper examines four areas that particularly affect data mining in the U.S. government: data quality, mathematical ways to find representative cases, methods to screen out datasets for which data mining efforts are unlikely to be successful, and estimation of risk in databases of spontaneous reports. These are non-trivial problems, but progress on any of these fronts could significantly improve the quality of data analysis for the benefit of the public. C1 US FDA, Rockville, MD 20857 USA. RP Banks, DL (reprint author), US FDA, Rockville, MD 20857 USA. NR 24 TC 1 Z9 1 U1 0 U2 1 PU CHAPMAN & HALL/CRC PRESS PI BOCA RATON PA 6000 BROKEN SOUND PKWY, NW, STE 300, BOCA RATON, FL 33487 USA BN 1-58488-344-8 PY 2004 BP 529 EP 548 PG 20 WC Computer Science, Artificial Intelligence; Statistics & Probability SC Computer Science; Mathematics GA BY55X UT WOS:000189408200032 ER PT J AU Zeng, XM Miura, T Luo, YQ Bhattacharya, B Condie, B Chen, J Ginis, I Lyons, I Mejido, J Puri, RK Rao, MS Freed, WJ AF Zeng, XM Miura, T Luo, YQ Bhattacharya, B Condie, B Chen, J Ginis, I Lyons, I Mejido, J Puri, RK Rao, MS Freed, WJ TI Properties of pluripotent human embryonic stem cells BG01 and BG02 SO STEM CELLS LA English DT Article DE embryonic stem cells; differentiation; microarray ID NEURAL PRECURSORS; GENE-EXPRESSION; LINES; DIFFERENTIATION; ESTABLISHMENT; CULTURE; GROWTH; CARDIOMYOCYTES; BLASTOCYSTS; ENRICHMENT AB Human ES (hES) cell lines have only recently been generated, and differences between human and mouse ES cells have been identified. In this manuscript we describe the properties of two human ES cell lines, BG01 and BG02. By immunocytochemistry and reverse transcription polymerase chain reaction, undifferentiated cells expressed markers that are characteristic of ES cells, including SSEA-3, SSEA-4, TRA-1-60, TRA-181, and OCT-3/4. Both cell lines were readily maintained in an undifferentiated state and could differentiate into cells of all three germ layers, as determined by expression of beta-tubulin III neuron-specific molecule (ectoderm), cardiac troponin I (cardiomyocytes, mesoderm), and alpha-fetoprotein (endoderm). A large-scale microarray (16,659 genes) analysis identified 373 genes that were expressed at three-fold or higher levels in undifferentiated BG01 and BG02 cells as compared with pooled human RNA. Ninety-two of these genes were also highly expressed in four other hES lines (TE05, GE01, GE09, and pooled samples derived from GE01, GE09, and GE07). Included in the list are genes involved in cell signaling and development, metabolism, transcription regulation, and many hypothetical proteins. Two focused arrays designed to examine transcripts associated with stem cells and with the transforming growth factor-beta superfamily were employed to examine differentially expressed genes. Several growth factors, receptors, and components of signaling pathways that regulate embryonic development, in particular the nodal signaling pathway, were detected in both BG01 and BG02. These data provide a detailed characterization and an initial gene expression profile for the BG01 and BG02 human ES cell lines. C1 NIDA, Dev & Plast Sect, Cellular Neurobiol Res Branch, DHHS, Baltimore, MD 21224 USA. BresaGen Inc, Athens, GA USA. US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Lab Mol Tumor Biol, Bethesda, MD USA. NIA, Neurosci Lab, DHHS, Baltimore, MD 21224 USA. RP Zeng, XM (reprint author), NIDA, Dev & Plast Sect, Cellular Neurobiol Res Branch, DHHS, 333 Cassell Dr, Baltimore, MD 21224 USA. EM xzeng@intra.nida.nih.gov; raomah@grc.nia.nih.gov FU NIDDK NIH HHS [R24DK063689] NR 36 TC 104 Z9 114 U1 0 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1066-5099 J9 STEM CELLS JI Stem Cells PY 2004 VL 22 IS 3 BP 292 EP 312 DI 10.1634/stemcells.22-3-292 PG 21 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA 827AC UT WOS:000221869600010 PM 15153607 ER PT S AU Kaplan, DS AF Kaplan, DS BE Schutte, E Picciolo, GL Kaplan, D TI Development of standards for the characterization of natural materials used in Tissue Engineered Medical Products (TEMPs) SO TISSUE ENGINEERED MEDICAL PRODUCTS (TEMPS) SE AMERICAN SOCIETY FOR TESTING AND MATERIALS SPECIAL TECHNICAL PUBLICATION LA English DT Proceedings Paper CT Symposium on Tissue Engineered Medical Products CY NOV 04-05, 2002 CL Miami Beach, FL SP Amer Soc Testing & Mat, Int Comm F4 AB ASTM Committee on F4 Medical and Surgical Materials and Devices, Division IV, Tissue Engineered Medical Products (TEMPs), Biomaterials and Biomolecules for TEMPs Subcommittee (F4.42) has been developing standards for characterizing natural materials used in TEMPs. Natural materials include alginate, chitosan, collagen and hyaluronate. These materials support cell growth and differentiation on TEMPs substrates and scaffolds. Natural materials have been used in a variety of applications, including encapsulation, cell seeding, development of "memory" biomaterials, as well as degradable scaffolds, growth factor/nucleic acid delivery vehicles, and as a carrier to improve product handling characteristics. These materials have typically been very poorly characterized as to their chemical, physical and biological properties. This has resulted in variability in the products produced from these starting materials. The development of Standard Guides and Test Methods for characterizing natural materials is anticipated to reduce the variability of these starting materials and to aid in the assessment of the safety of the subsequent TEMPs. C1 US FDA, Ctr Devices & Radiol Hlth, Off Sci & Technol, Rockville, MD 20852 USA. RP Kaplan, DS (reprint author), US FDA, Ctr Devices & Radiol Hlth, Off Sci & Technol, 12725 Twinbrook Pkwy, Rockville, MD 20852 USA. NR 4 TC 0 Z9 0 U1 0 U2 1 PU AMERICAN SOCIETY TESTING AND MATERIALS PI W CONSHOHOCKEN PA 100 BARR HARBOR DRIVE, W CONSHOHOCKEN, PA 19428-2959 USA SN 1040-1695 BN 0-8031-3471-1 J9 AM SOC TEST MATER PY 2004 VL 1452 BP 172 EP 175 DI 10.1520/STP11644S PG 4 WC Cell Biology; Engineering, Biomedical; Materials Science, Biomaterials SC Cell Biology; Engineering; Materials Science GA BAH88 UT WOS:000222328400016 ER PT J AU Wallace, KB Hausner, E Herman, E Holt, GD MacGregor, JT Metz, AL Murphy, E Rosenblum, IY Sistare, FD York, MJ AF Wallace, KB Hausner, E Herman, E Holt, GD MacGregor, JT Metz, AL Murphy, E Rosenblum, IY Sistare, FD York, MJ TI Serum troponins as biomarkers of drug-induced cardiac toxicity SO TOXICOLOGIC PATHOLOGY LA English DT Review ID CREATINE-KINASE-MB; ANTHRACYCLINE-INDUCED CARDIOTOXICITY; LEFT-VENTRICULAR DYSFUNCTION; ACUTE MYOCARDIAL-INFARCTION; JOINT EUROPEAN-SOCIETY; HUMAN SKELETAL-MUSCLE; AMINO-ACID-SEQUENCE; HEART-FAILURE; SUBARACHNOID HEMORRHAGE; RELEASE KINETICS C1 Univ Minnesota, Sch Med, Dept Biochem & Mol Biol, Duluth, MN 55812 USA. US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20852 USA. US FDA, Ctr Drug Evaluat & Res, Laurel, MD 20708 USA. Oxford GlycoSci, Montgomery Village, MD 20886 USA. US FDA, Natl Ctr Toxicol Res, Rockville, MD 20857 USA. Pfizer Inc, Ann Arbor Labs, Drug Safety Evaluat, Global Res & Dev, Ann Arbor, MI 48105 USA. NIEHS, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. Schering Plough Corp, Res Inst, Gen Toxicol, Drug Safety & Metab, Lafayette, NJ 07848 USA. GlaxoSmithKline, Clin Pathol Lab, Preclin Safety Sci, Ware SG12 0DP, Herts, England. RP Wallace, KB (reprint author), Univ Minnesota, Sch Med, Dept Biochem & Mol Biol, 1035 Univ Dr, Duluth, MN 55812 USA. EM kwallace@d.umn.edu NR 144 TC 81 Z9 89 U1 1 U2 5 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 JAN-FEB PY 2004 VL 32 IS 1 BP 106 EP 121 DI 10.1080/01926230490261302 PG 16 WC Pathology; Toxicology SC Pathology; Toxicology GA 763GU UT WOS:000188067200015 PM 14713555 ER PT J AU Crissman, JW Goodman, DG Hildebrandt, PK Maronpot, RR Prater, DA Riley, JH Seaman, WJ Thake, DC AF Crissman, JW Goodman, DG Hildebrandt, PK Maronpot, RR Prater, DA Riley, JH Seaman, WJ Thake, DC TI Best practices guideline: T6oxicologic histopathology SO TOXICOLOGIC PATHOLOGY LA English DT Article DE toxicology; histopathology; methods; best practice; pathology; microscopy; guideline ID TOXICOLOGIC PATHOLOGY; RECOMMENDATIONS; PERSPECTIVE C1 Pfizer Inc, Kalamazoo, MI 49001 USA. Dow Corning Corp, Hlth & Environm Sci, Midland, MI 48686 USA. Covance Labs Inc, Vienna, VA 22182 USA. Pathco Inc, Frederick, MD 21702 USA. NIEHS, Lab Expt Pathol, Res Triangle Pk, NC 27709 USA. US FDA, Ctr Vet Med, Rockville, MD 20855 USA. Estuary Pharmaceut, Cambridge, MA 02139 USA. RP Seaman, WJ (reprint author), Pfizer Inc, 301 Henrietta St, Kalamazoo, MI 49001 USA. EM william.j.seaman@pfizer.com NR 20 TC 134 Z9 144 U1 1 U2 3 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD JAN-FEB PY 2004 VL 32 IS 1 BP 126 EP 131 DI 10.1080/0192623049026875 PG 6 WC Pathology; Toxicology SC Pathology; Toxicology GA 763GU UT WOS:000188067200018 PM 14713558 ER PT B AU Brennan, MJ AF Brennan, MJ BE DeQuadros, CA TI A new generation of tuberculosis vaccines SO VACCINES: PREVENTING DISEASE AND PROTECTING HEALTH SE PAN AMERICAN HEALTH ORGANIZATION SCIENTIFIC PUBLICATION LA English DT Proceedings Paper CT Conference on Vaccines, Prevention and Public Health CY NOV 25-27, 2002 CL Pan Amer Hlth Org, Washington, DC HO Pan Amer Hlth Org ID MYCOBACTERIUM-BOVIS BCG; T-CELL RESPONSES; ENVIRONMENTAL MYCOBACTERIA; PROTECTIVE IMMUNITY; EFFICACY; VACCINATION; PREVENTION; PROTEIN; IMPACT; MALAWI C1 US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. RP Brennan, MJ (reprint author), US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. NR 23 TC 5 Z9 5 U1 0 U2 0 PU PAN AMERICAN HEALTH ORGANIZATION PI WASHINGTON PA 525 TWENTY-THIRD ST NW, WASHINGTON, DC 20037 USA BN 92-75-11596-6 J9 PAHO SCI P PY 2004 IS 596 BP 177 EP 182 PG 6 WC Public, Environmental & Occupational Health; Immunology; Infectious Diseases SC Public, Environmental & Occupational Health; Immunology; Infectious Diseases GA BAE77 UT WOS:000221907000023 ER PT J AU Sahagun-Ruiz, A Sierra-Honigmann, AM Krause, P Murphy, PM AF Sahagun-Ruiz, A Sierra-Honigmann, AM Krause, P Murphy, PM TI Simian cytomegalovirus encodes five rapidly evolving chemokine receptor homologues SO VIRUS GENES LA English DT Article DE chemokine; cytomegalovirus; genomics; herpesvirus; inflammation; receptor ID PROTEIN-COUPLED RECEPTOR; KAPOSIS-SARCOMA; MOLECULAR MIMICRY; US28; GENE; IDENTIFICATION; PATHOGENESIS; EXPRESSION; DELETION; SYSTEM AB Many herpesviruses, poxviruses and retroviruses encode proteins related to chemokines and chemokine receptors. The first one discovered, US28 of human cytomegalovirus ( HCMV), is a 7-transmembrane domain G protein-coupled chemokine receptor able to activate diverse cellular responses, including cell migration and gene expression. A related ORF named US27 is adjacent to US28, but no functions have been defined yet. Recently ORFs 3-7, a cluster of five concatenated ORFs with highest homology to US28 and mammalian chemokine receptors, were sequenced from a prototype "stealth virus'', an African green monkey simian CMV (SCMV)-related entity with unusual fungal, bacterial and mammalian gene homologues. Stealth viruses have not yet been independently replicated in tissue culture, and therefore their biological significance remains unclear. ORF3, ORF4, ORF5 and ORF6 are complete ORFs whereas the sequence of ORF7 is incomplete. In the present study, we identified five corresponding ORFs in the genome of a clinical isolate of bona. de simian CMV ( SCMV), strain 9610. We found substantial differences between the SCMV and "stealth virus'' ORFs, especially for ORF5 where there are 31% nonidentities at the amino acid level. Four conserved genes unrelated to chemokines (64K/CAP, DNBI, UL32, and IE2) in SCMV and HCMV had on average 52% identity at the deduced amino acid level, whereas the corresponding values for the SCMV ORFs versus US28 ranged from 21% to 30%, suggesting rapid gene diversification in this cluster. Consistent with this, the amino acid identity for any pairwise comparison among the SCMV ORFs is only 21 - 52%. The chemokine receptor homologues are estimated to comprise similar to 2 - 3% of the SCMV genome. HCMV US27 and US28 homologues have also been identified in the chimpanzee CMV genome, whereas mouse and rat CMV lack chemokine receptor homologues. This genomic analysis indicates that SCMV has an unusually high concentration of US28-related chemokine receptor homologues that have arisen by gene duplication and have diverged extensively from their closest relatives in mammals and other beta herpesviruses. The rate of divergence appears to be very rapid compared to other known SCMV genes, suggesting strong positive selection. C1 NIAID, Mol Signalling Sect, Host Def Lab, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Murphy, PM (reprint author), NIAID, Mol Signalling Sect, Host Def Lab, NIH, Bethesda, MD 20892 USA. EM pmm@nih.gov NR 27 TC 17 Z9 19 U1 0 U2 2 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0920-8569 J9 VIRUS GENES JI Virus Genes PD JAN PY 2004 VL 28 IS 1 BP 71 EP 83 DI 10.1023/B:VIRU.0000012265.33168.b5 PG 13 WC Genetics & Heredity; Virology SC Genetics & Heredity; Virology GA 764NU UT WOS:000188213600006 PM 14739653 ER PT J AU Fleming-Jones, ME Smith, RE AF Fleming-Jones, ME Smith, RE TI Volatile organic compounds in foods: A five year study SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE volatile organic compound (VOC); gas chromatography-mass spectrometry (GC-MS); food analysis ID PURGE-AND-TRAP; DRINKING-WATER; GAS-CHROMATOGRAPHY; CANCER MORTALITY; DAIRY-PRODUCTS; TOTAL DIET; CHLOROFORM; EXPOSURE; STYRENE; BENZENE AB A purge and trap procedure was used with gas chromatography-mass spectrometry determination to analyze 70 foods for volatile organic compounds (VOCs). The results from analyses over a 5 year period (1996-2000) are reported. VOCs were found in at least one sample of all foods tested, although no single compound was found in each of the foods. The total amount of VOCs found in a single food item over the 5 year period ranged from 24 to 5328 ppb, with creamed corn (canned) the lowest and cheddar cheese the highest. Benzene was found in all foods except American cheese and vanilla ice cream. Benzene levels ranged from 1 to 190 ppb, with the highest level found in fully cooked ground beef. Benzene was found in 12 samples of cooked ground beef, with an average of 40 ppb. Benzene levels above 100 ppb were also seen in at least one sample each of a cola (138 ppb), raw bananas (132 ppb), and cole slaw (102 ppb). This compares to a maximum contaminant level of 5 ppb set by the U.S. EPA for drinking water. C1 US FDA, Lenexa, KS 66214 USA. RP Smith, RE (reprint author), US FDA, 11510 W 80th St, Lenexa, KS 66214 USA. NR 64 TC 65 Z9 69 U1 1 U2 39 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 DEC 31 PY 2003 VL 51 IS 27 BP 8120 EP 8127 DI 10.1021/jf0303159 PG 8 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 757MG UT WOS:000187565600046 PM 14690406 ER PT J AU Lachenbruch, PA AF Lachenbruch, PA TI Proper metrics for clinical trials: transformations and other procedures to remove non-normality effects SO STATISTICS IN MEDICINE LA English DT Article; Proceedings Paper CT 23rd Scientific Meeting of the International-Society-for-Clinical-Biostatistics CY 2002 CL PARIS, FRANCE SP Int Soc Clin Biostatist DE size and power of t-test; rank sum and Box-Cox likelihood ratio test; non-normality AB A simulation study was performed to study the effects of non-normality and to examine procedures to ameliorate possible loss of power when data are incorrectly assumed to be normally distributed. It was found that only distributions with high asymmetry or heavy tails seriously affect the t-test. The Box-Cox likelihood ratio test appears to have some advantages over the others, but this must be offset by the greater complexity in making the results understandable to non-statisticians. The variability in outcomes with the different procedures demonstrates the importance of specifying such procedures a priori. Published in 2003 by John Wiley Sons, Ltd. RP Lachenbruch, PA (reprint author), FDA, CBER, Off Biostat & Epidemiol, 1401 Rockville Pike,HFM 215, Rockville, MD 20852 USA. NR 12 TC 5 Z9 5 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD DEC 30 PY 2003 VL 22 IS 24 BP 3823 EP 3842 DI 10.1002/sim.1675 PG 20 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 754VM UT WOS:000187352900010 PM 14673941 ER PT J AU Chmielewski, MK Marchan, V Cieslak, J Grajkowski, A Livengood, V Munch, U Wilk, A Beaucage, SL AF Chmielewski, MK Marchan, V Cieslak, J Grajkowski, A Livengood, V Munch, U Wilk, A Beaucage, SL TI Thermolytic carbonates for potential 5 '-hydroxyl protection of deoxyribonucleosides SO JOURNAL OF ORGANIC CHEMISTRY LA English DT Article ID SOLID-PHASE SYNTHESIS; LIGHT-DIRECTED SYNTHESIS; OLIGONUCLEOTIDE SYNTHESIS; DEOXYNUCLEOSIDE PHOSPHORAMIDITES; DNA-SYNTHESIS; OLIGODEOXYRIBONUCLEOTIDE SYNTHESIS; OLIGORIBONUCLEOTIDE SYNTHESIS; NUCLEOTIDE CHEMISTRY; MICROARRAYS; NUCLEOSIDES AB Thermolytic groups structurally related to well-studied heat-sensitive phosphate/thiophosphate protecting groups have been evaluated for 5'-hydroxyl protection of deoxyribonucleosides as carbonates and for potential use in solid-phase oligonucleotide synthesis. The spatial arrangement of selected functional groups forming an asymmetric nucleosidic 5'-O-carbonic acid ester has been designed to enable heat-induced cyclodecarbonation reactions, which would result in the release of carbon dioxide and the generation of a nucleosidic 5'-hydroxyl group. The nucleosidic 5'-O-carbonates 3-8, 10-15, and 19-21 were prepared and were isolated in yields ranging from 45 to 83%. Thermolytic deprotection of these carbonates is preferably performed in aqueous organic solvent at 90 degreesC under near neutral conditions. The rates of carbonate deprotection are dependent on the nucleophilicity of the functional group involved in the postulated cyclodecarbonation reaction and on solvent polarity. Deprotection kinetics increase according to the following order: 4 < 5 < 10 < 6 < 12 < 7 < 13 < 8 < 14 congruent to 19-21 and CCl4 < dioxane < MeCN < t-BuOH < MeCN:phosphate buffer (3:1 v/v, pH 7.0) < EtOH:phosphate buffer (1:1 v/v, pH 7.0). Complete thermolytic deprotection of carbonates 7, 8, 13, and 14 is achieved within 20 min to 2 h under optimal conditions in phosphate buffer-MeCN. The 2-(2-pyridyl)amino-1-phenylethyl and 2-[N-methyl-N-(2-pyridyl)]aminoethyl groups are particularly promising for 5'-hydroxyl protection of deoxyribonucleosides as thermolytic carbonates. C1 US FDA, Ctr Biol Evaluat & Res, Div Therapeut Prot, Bethesda, MD 20892 USA. NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Beaucage, SL (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Therapeut Prot, 8800 Rockville Pike, Bethesda, MD 20892 USA. EM beaucage@cber.fda.gou RI Marchan, Vicente/K-9751-2014 OI Marchan, Vicente/0000-0002-1905-2156 NR 49 TC 20 Z9 21 U1 2 U2 7 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-3263 J9 J ORG CHEM JI J. Org. Chem. PD DEC 26 PY 2003 VL 68 IS 26 BP 10003 EP 10012 DI 10.1021/jo035089g PG 10 WC Chemistry, Organic SC Chemistry GA 755TL UT WOS:000187427500017 PM 14682694 ER PT J AU Cieslak, J Beaucage, SL AF Cieslak, J Beaucage, SL TI Thermolytic properties of 3-(2-pyridyl)-1-propyl and 2-[N-methyl-N-(2-pyridyl)]aminoethyl phosphate/thiophosphate protecting groups in solid-phase synthesis of oligodeoxyribonucleotides SO JOURNAL OF ORGANIC CHEMISTRY LA English DT Article ID SULFUR-TRANSFER REAGENT; 3H-1,2-BENZODITHIOL-3-ONE 1,1-DIOXIDE; PHOSPHATE; MONOMERS AB Thermolytic groups may serve as alternatives to the conventional 2-cyanoethyl group for phosphate/thiophosphate protection in solid-phase oligonucleotide synthesis to prevent DNA alkylation by acrylonitrile generated under the basic conditions used for oligonucleotide deprotection. Additionally, thermolytic groups are attractive in the context of engineering a "heat-driven" process for the synthesis of oligonucleotides on diagnostic microarrays. In these regards, the potential application of pyridine derivatives as thermolytic phosphate/thiophosphate protecting groups has been investigated. Specifically, 2-pyridinepropanol and 2-[N-methyl-N-(2-pyridyl)]aminoethanol were incorporated into deoxyribonucleoside phosphoramidites 7a-d and 9, which were found as efficient as 2-cyanoethyl deoxyribonucleoside phosphoramidites in solid-phase oligonucleotide synthesis. Whereas the removal of 3-(2-pyridyl)-1-propyl phosphate/thiophosphate protecting groups from oligonucleotides is effected within 30 min upon heating at 55 degreesC in concentrated NH4OH or in an aqueous buffer at pH 7.0, cleavage of 2-[N-methyl-N-(2-pyridyl)]aminoethyl groups occurs spontaneously when their phosphate or phosphorothioate esters are formed during oligonucleotide synthesis. The deprotection of these groups follows a cyclodeesterification process generating the bicyclic salts 13 and 14 as side products. These salts do not alkylate or otherwise modify any DNA nucleobases and do not desulfurize a phosphorothioate diester model under conditions mimicking large-scale oligonucleotide deprotection. C1 US FDA, Ctr Biol Evaluat & Res, Div Therapeut Prot, Bethesda, MD 20892 USA. RP Beaucage, SL (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Therapeut Prot, 8800 Rockville Pike, Bethesda, MD 20892 USA. EM beaucage@cber.fda.gov NR 16 TC 18 Z9 18 U1 1 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-3263 J9 J ORG CHEM JI J. Org. Chem. PD DEC 26 PY 2003 VL 68 IS 26 BP 10123 EP 10129 DI 10.1021/jo0354490 PG 7 WC Chemistry, Organic SC Chemistry GA 755TL UT WOS:000187427500032 PM 14682709 ER PT J AU Dato, V Weltman, A Waller, K Highbaugh-Battle, A Hembree, C Evenson, S Wheeler, C Vogt, T AF Dato, V Weltman, A Waller, K Highbaugh-Battle, A Hembree, C Evenson, S Wheeler, C Vogt, T CA CDC TI Hepatitis A outbreak associated with green onions at a restaurant - Monaca, Pennsylvania, 2003 (Reprinted from MMWR, vol 52, pg 1155-1157, 2003) SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Reprint C1 Penn Dept Hlth, Bur Epidemiol, Harrisburg, PA 17108 USA. US FDA, Ohio Dept Hlth, Rockville, MD 20857 USA. CDC, Atlanta, GA 30333 USA. RP Dato, V (reprint author), Penn Dept Hlth, Bur Epidemiol, Harrisburg, PA 17108 USA. NR 6 TC 3 Z9 3 U1 0 U2 1 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 DEC 24 PY 2003 VL 290 IS 24 BP 3187 EP + PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 756TR UT WOS:000187499300007 ER PT J AU Brown, EW Mammel, MK LeClerc, JE Cebula, TA AF Brown, EW Mammel, MK LeClerc, JE Cebula, TA TI Limited boundaries for extensive horizontal gene transfer among Salmonella pathogens SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ESCHERICHIA-COLI; NATURAL-POPULATIONS; RECOMBINATION; EVOLUTION; SEQUENCE; BACTERIA; STRAINS; MUTS; INCONGRUENCE; CONSEQUENCES AB Recombination is thought to be rare within Salmonella, as evidenced by absence of gene transfer among SARC strains that represent the broad genetic diversity of the eight primary subspecies of this common facultative intracellular pathogen. We adopted a phylogenetic approach to assess recombination within the mutS gene of 70 SARB strains, a genetically homogeneous population of Salmonella enterica subspecies I strains, which have in common the ability to infect warm-blooded animals. We report here that SARB strains show evidence for widespread recombinational exchange in contrast to results obtained with strains exhibiting species-level genetic variation. Besides extensive allele shuffling, SARB strains showed notably larger recombinagenic patch sizes for mutS (at least approximate to1.1 kb) than previously reported for S. enterica SARC strains. Explaining these experimental dichotomies provides important insight for understanding microbial evolution, because they suggest likely ecologic and genetic barriers that limit extensive gene transfer in the feral setting. C1 US FDA, Div Mol Biol, Off Appl Res & Safety Assessment, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. RP Cebula, TA (reprint author), US FDA, Div Mol Biol, Off Appl Res & Safety Assessment, Ctr Food Safety & Appl Nutr, HFS-025, Laurel, MD 20708 USA. NR 33 TC 31 Z9 31 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 23 PY 2003 VL 100 IS 26 BP 15676 EP 15681 DI 10.1073/pnas.2634406100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 757GL UT WOS:000187554600071 PM 14671318 ER PT J AU Roach, JAG Andrzejewski, D Gay, ML Nortrup, D Musser, SM AF Roach, JAG Andrzejewski, D Gay, ML Nortrup, D Musser, SM TI Rugged LC-MS/MS survey analysis for acrylamide in foods SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE acrylamide; exploratory; FDA; food survey; liquid chromatography-tandem mass spectrometry; LC-MS/MS; method ID MASS-SPECTROMETRY; LIQUID-CHROMATOGRAPHY; GAS-CHROMATOGRAPHY; HEATED FOODS; CONFIRMATION AB The described liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the detection of acrylamide in food entails aqueous room temperature extraction, SPE cleanup, and analysis by LC-MS/MS. The method is applicable to a wide variety of foods. [C-13(3)]acrylamide is the internal standard. The limit of quantitation is 10 ppb (mug/kg). Data were obtained in duplicate from >450 products representing >35 different food types. The variability in analyte levels in certain food types suggests that it may be possible to reduce acrylamide levels in those foods. C1 USDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Roach, JAG (reprint author), USDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. NR 22 TC 103 Z9 106 U1 4 U2 16 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 DEC 17 PY 2003 VL 51 IS 26 BP 7547 EP 7554 DI 10.1021/jf0346354 PG 8 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 753ZP UT WOS:000187278500005 PM 14664505 ER PT J AU Fu, X Blaydes, BS Weis, CC Latendresse, JR Muskhelishvili, L Sutter, TR Delclos, KB AF Fu, X Blaydes, BS Weis, CC Latendresse, JR Muskhelishvili, L Sutter, TR Delclos, KB TI Effects of dietary soy and estrous cycle on adrenal cytochrome P4501B1 expression and DMBA metabolism in adrenal glands and livers in female Sprague-Dawley rats SO CHEMICO-BIOLOGICAL INTERACTIONS LA English DT Article DE CYP1B1; estrous cycle; soy; adrenal gland; DMBA; metabolism ID POLYCYCLIC AROMATIC-HYDROCARBONS; PROTEIN ISOLATE; MAMMARY-GLAND; LIQUID-CHROMATOGRAPHY; TISSUE DISTRIBUTION; MESSENGER-RNA; WHEY PROTEINS; CYP1B1; GENISTEIN; OVARY AB Cytochrome P450 1B01 (CYP1B1) has been shown to be important in the bioactivation of 7,12-dimethylbenz[a]anthracene (DMBA) to an adrenal toxin in rats. We investigated the effects of diet and stage of estrous cycle on CYP1B1 expression in rat adrenal glands and on DMBA metabolism by rat adrenal and hepatic microsomes. Female Sprague-Dawley (SD) rats were placed on either standard soy-containing NIH-31 rat chow or soy- and alfalfa-free 5K96 diet from postnatal day (PND) 21 until sacrifice at PND50+/-5. Stage of estrous at sacrifice was assessed by vaginal cytology and confirmed by histological examination of the vagina. Dietary soy at the level present in NIH-31 diet did not affect serum estrogen and progesterone levels. Immunohistochemical analysis confirmed that CYP1B1 was exclusively expressed in the zona fasciculata and zona reticularis in adrenal cortex, which are the regions vulnerable to DMBA-induced adrenal necrosis. Adrenal CYP1B1 protein expression, (3)H-DMBA depletion. and formation of DMBA-3,4-, and -8,9-dihydrodiols by adrenal microsomes were greater in animals fed. 5K96 diet, and the stage of the estrous cycle affected these parameters only in the soy-free 5K96 diet. In hepatic microsomes, the formation of DMBA-3,4-dihydrodiol, 7-hydroxy- and 12-hydroxy-DMBA were lower in animals fed NIH-31 diet than in those fed 5K96 diet. Thus, dietary soy and the estrous cycle appear to regulate adrenal CYP1B1 expression and DMBA metabolism by both adrenal and hepatic microsomes. The use of different basal diets containing variable levels of soy components may affect certain toxicity assessments. (C) 2003 Elsevier Ireland Ltd. All rights reserved. C1 US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. Pathol Associates Int Inc, Jefferson, AR 72079 USA. Univ Memphis, W Harry Feinstone Ctr Genom Res, Memphis, TN 38152 USA. RP Delclos, KB (reprint author), US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, 3900 NCTR Rd,HFT-110, Jefferson, AR 72079 USA. EM bdelclos@nctr.fda.gov RI Latendresse, John/A-9215-2009 NR 53 TC 11 Z9 11 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0009-2797 J9 CHEM-BIOL INTERACT JI Chem.-Biol. Interact. PD DEC 15 PY 2003 VL 146 IS 3 BP 273 EP 284 DI 10.1016/j.cbi.2003.09.004 PG 12 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology GA 753TF UT WOS:000187246100006 PM 14642739 ER PT J AU Kawakami, M Kawakami, K Kasperbauer, JL Hinkley, LL Tsukuda, M Strome, SE Puri, RK AF Kawakami, M Kawakami, K Kasperbauer, JL Hinkley, LL Tsukuda, M Strome, SE Puri, RK TI Interleukin-13 receptor alpha 2 chain in human head and neck cancer serves as a unique diagnostic marker SO CLINICAL CANCER RESEARCH LA English DT Article ID SQUAMOUS-CELL CARCINOMA; IN-SITU HYBRIDIZATION; PSEUDOMONAS EXOTOXIN; CYTOTOXIN; PROTEIN; EXPRESSION; THERAPY; PATHWAY; MODEL; IL-13 AB Previous studies have demonstrated that approximately 30% of squamous cell carcinoma of the head and neck (SCCHN) cell lines express high levels of interleukin-13 receptor(s) (IL-13R). However, the incidence, expression level, and significance of IL-13R expression in human tumor specimens is not known. In addition, it is not known whether normal head and neck tissues express IL-13R. In this study, we evaluated the expression of IL-13R subunits (IL-13alpha1, IL-13Ralpha2, and IL-4Ralpha) in 337 surgically excised specimens of SCCHN and normal head and neck tissues. Specimens were obtained from 139 patients with SCCHN and 16 patients with benign tonsil disorders from two centers in the United States and Japan and evaluated with immunohistochemistry and in situ hybridization. Extensive analysis demonstrated that the majority of SCCHN tumors uniformly expressed low levels of IL-13Ralpha1 chain; however, 77% of the tumors expressed moderate to high levels of IL-4Ralpha, which forms a signaling complex with IL-13Ralpha1 chain. On the other hand, 33% of SCCHN tumors expressed moderate to high levels of IL-13Ralpha2 chain. Using tissue array from 99 patients, we observed that the expression levels of IL-13Ralpha2 and IL-4Ralpha were significantly higher in SCCHN than in normal head and neck tissues (P < 0.005). Detailed analysis of clinicopathological features demonstrated a positive statistically significant correlation between IL-13Ralpha2 expression and clinically advanced primary SCCHN tumor (T-4; Tumor-Node-Metastasis classification; P < 0.05). However, there was no correlation among IL-13R expression and sex, age of patients, stage of lymph node metastasis, squamous cell carcinoma grade, or allergic history. Taken together, this study suggests that IL-13R may be involved in SCCHN tumor progression, and 33% of IL-13Ralpha2-positive SCCHN cases may be targeted by IL-13 cytotoxin and IL-13R-targeted agent. C1 US FDA, Ctr Biol Evaluat & Res, Lab Mol Tumor Biol, Div Cell & Gene Therapies, Bethesda, MD 20892 USA. Mayo Clin, Dept Otolaryngol, Rochester, MN USA. Mayo Clin, Dept Head & Neck Surg, Rochester, MN USA. Yokohama City Univ, Sch Med, Dept Otolaryngol, Yokohama, Kanagawa 232, Japan. RP Puri, RK (reprint author), US FDA, Ctr Biol Evaluat & Res, Lab Mol Tumor Biol, Div Cell & Gene Therapies, NIH Bldg 29B,Room 2NN10,29 Lincoln Dr MSC 4555, Bethesda, MD 20892 USA. NR 24 TC 34 Z9 38 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 15 PY 2003 VL 9 IS 17 BP 6381 EP 6388 PG 8 WC Oncology SC Oncology GA 758QH UT WOS:000187661300011 PM 14695138 ER PT J AU Ishii, KJ Kawakami, K Gursel, I Conover, J Joshi, BH Klinman, DM Puri, RK AF Ishii, KJ Kawakami, K Gursel, I Conover, J Joshi, BH Klinman, DM Puri, RK TI Antitumor therapy with bacterial DNA and toxin: Complete regression of established tumor induced by liposomal CpG oligodeoxynucleotides plus interleukin-13 cytotoxin SO CLINICAL CANCER RESEARCH LA English DT Article ID RECEPTOR ALPHA-2 CHAIN; IMMUNOSTIMULATORY DNA; PSEUDOMONAS EXOTOXIN; CANCER-THERAPY; IMMUNE THERAPY; NECK-CANCER; CELLS; MOTIFS; HEAD; IMMUNOSURVEILLANCE AB Despite urgent need, no single strategy has been widely effective at controlling the growth of rapidly progressive solid tumors. We demonstrate here a potent antitumor therapy using modified bacterial DNA and toxin. Treatment of human head and neck cancer established as xenografts in athymic mice with immunostimulatory CpG oligodeoxynucleotides encapsulated in sterically stabilized cationic liposome [(CpG ODN)(SSCL)] and recombinant interleukin-13 Pseudomonas exotoxin (IL13-PE) significantly reduced the tumor growth followed by complete regression in most animals. The antitumor activity of (CpG ODN)(SSCL) was dependent on natural killer cells that infiltrated within tumors. Interestingly, IL13-PE enhanced (CpG ODN)(SSCL)-induced natural killer cell activity and cytokine production in vivo and in vitro. These data strongly suggest that a combination of innate immune activation by (CpG ODN)(SSCL) and tumor-directed targeting by IL13-PE is a novel approach for human cancer immunotherapy. C1 US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Bethesda, MD 20014 USA. US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Bethesda, MD 20014 USA. RP Ishii, KJ (reprint author), Osaka Univ, Res Inst Microbial Dis, Dept Host Def, 3-1 Yomadaoka, Suita, Osaka 5650871, Japan. RI Ishii, Ken/B-1685-2012; OI Ishii, Ken/0000-0002-6728-3872; Gursel, Ihsan/0000-0003-3761-1166 NR 40 TC 19 Z9 21 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 15 PY 2003 VL 9 IS 17 BP 6516 EP 6522 PG 7 WC Oncology SC Oncology GA 758QH UT WOS:000187661300029 PM 14695156 ER PT J AU Sivapalasingam, S Barrett, E Kimura, A Van Duyne, S De Witt, W Ying, M Frisch, A Phan, Q Gould, E Shillam, P Reddy, V Cooper, T Hoekstra, M Higgins, C Sanders, JP Tauxe, RV Slutsker, L AF Sivapalasingam, S Barrett, E Kimura, A Van Duyne, S De Witt, W Ying, M Frisch, A Phan, Q Gould, E Shillam, P Reddy, V Cooper, T Hoekstra, M Higgins, C Sanders, JP Tauxe, RV Slutsker, L TI A multistate outbreak of Salmonella enterica serotype Newport infection linked to mango consumption: Impact of water-dip disinfestation technology SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID UNITED-STATES; SURVEILLANCE; TOMATOES AB Fresh produce increasingly is recognized as an important source of salmonellosis in the United States. In December 1999, the Centers for Disease Control and Prevention detected a nationwide increase in Salmonella serotype Newport ( SN) infections that had occurred during the previous month. SN isolates recovered from patients in this cluster had indistinguishable pulsed- field gel electrophoresis ( PFGE) patterns ( which identified the outbreak strain), suggesting a common source. Seventy- eight patients from 13 states were infected with the outbreak strain. Fifteen patients were hospitalized; 2 died. Among 28 patients enrolled in the matched case- control study, 14 ( 50%) reported they ate mangoes in the 5 days before illness onset, compared with 4 ( 10%) of the control subjects during the same period ( matched odds ratio, 21.6; 95% confidence interval, 3.53 - infinity; P = .0001). Traceback of the implicated mangoes led to a single Brazilian farm, where we identified hot water treatment as a possible point of contamination; this is a relatively new process to prevent importation of an agricultural pest, the Mediterranean fruit fly. This is the first reported outbreak of salmonellosis implicating mangoes. PFGE was critical to the timely recognition of this nationwide outbreak. This outbreak highlights the potential global health impact of foodborne diseases and newly implemented food processes. C1 Ctr Dis Control & Prevent, Foodborne & Diarrheal Branch, Natl Ctr Infect Dis, Natl Ctr Environm Hlth, Decatur, GA 30030 USA. Ctr Dis Control & Prevent, Epidem Intelligence Serv, Epidemiol Program Off, Decatur, GA 30030 USA. Ctr Dis Control & Prevent, Biostat & Informat Management Branch, Decatur, GA 30030 USA. Virginia Dept Hlth, Richmond, VA USA. Calif Dept Hlth Serv, Gardena, CA USA. Connecticut Dept Hlth, Hartford, CT USA. Massachusetts Dept Hlth, Jamaica Plain, MS USA. Colorado Dept Hlth, Denver, CO 80220 USA. New York City Dept Hlth & Mental Hyg, New York, NY USA. Rhode Isl Dept Hlth, Providence, RI 02908 USA. US FDA, Rockville, MD 20857 USA. RP Tauxe, RV (reprint author), Ctr Dis Control & Prevent, Foodborne & Diarrheal Branch, Natl Ctr Infect Dis, Natl Ctr Environm Hlth, 1600 Clifton Rd,MS A-38, Decatur, GA 30030 USA. NR 24 TC 81 Z9 84 U1 3 U2 15 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD DEC 15 PY 2003 VL 37 IS 12 BP 1585 EP 1590 DI 10.1086/379710 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 749VJ UT WOS:000186949300009 PM 14689335 ER PT J AU Fleischer, R Laessig, K AF Fleischer, R Laessig, K TI Safety and efficacy evaluation of pleconaril for treatment of the common cold SO CLINICAL INFECTIOUS DISEASES LA English DT Letter C1 US FDA, Ctr Drug Evaluat & Res, Div Antiviral Drug Prod, Rockville, MD 20157 USA. RP Fleischer, R (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Antiviral Drug Prod, HFD-530,5600 Fishers Ln, Rockville, MD 20157 USA. NR 2 TC 16 Z9 17 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD DEC 15 PY 2003 VL 37 IS 12 BP 1722 EP 1722 PG 1 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 749VJ UT WOS:000186949300035 PM 14689362 ER PT J AU Mathew, AG Arnett, DB Cullen, P Ebner, PD AF Mathew, AG Arnett, DB Cullen, P Ebner, PD TI Characterization of resistance patterns and detection of apramycin resistance genes in Escherichia coli isolated from swine exposed to various environmental conditions SO INTERNATIONAL JOURNAL OF FOOD MICROBIOLOGY LA English DT Article DE Escherichia coli; antibiotic resistance; swine; apramycin; stress ID FIELD GEL-ELECTROPHORESIS; ANTIBIOTIC-RESISTANCE; PIGS; COLIBACILLOSIS; GENTAMICIN AB Weaned pigs were separated into eight treatments including a control without exposure to apramycin; a control with exposure to apramycin; and apramycin plus either cold stress, heat stress, overcrowding, intermingling, poor sanitation, or intervention with oxytetracycline, to determine the effects of management and environmental conditions on antibiotic resistance among indigenous Escherichia coli. Pigs exposed to apramycin sulfate received that antibiotic in the feed at a concentration of 150 g/ton for 14 days. Environmental treatments were applied 5 days following initial antibiotic administration and maintained throughout the study. Fecal samples were obtained on day 0 (prior to antibiotic treatment) and on days 2, 7, 14, 28, 64, 148, and 149. E. coli were isolated and tested for resistance to apramycin using a minimum inhibitory concentration (MIC) broth microdilution method. Macrorestriction profiling, arbitrarily primed PCR, PCR targeting a gene coding for apramycin resistance, and DNA hybridization were used to characterize genetic elements of resistance. Increased (P < 0.0001) resistance to apramycin was noted in E. coli from all treatment groups administered apramycin. MICs of isolates from control pigs receiving apramycin returned to pretreatment levels following removal of the antibiotic, whereas isolates from cold stress, overcrowding, and oxytetracycline groups expressed greater (P < 0.05) MICs through day 64, before returning to pretreatment levels. Genetic analysis indicated that all resistant isolates carried the aac(3)IV gene sequence and this sequence was found in a variety of E. coli isotypes. Our data indicate that E. coli resistance to apramycin is increased upon exposure to various stressors. (C) 2003 Elsevier Science B.V. All rights reserved. C1 Univ Tennessee, Dept Anim Sci, Knoxville, TN 37996 USA. Louisiana State Univ, Hlth Sci Ctr, Shreveport, LA 71130 USA. US FDA, Rockville, MD 20857 USA. Oak Ridge Natl Lab, Oak Ridge, TN 37831 USA. RP Mathew, AG (reprint author), Univ Tennessee, Dept Anim Sci, 2505 River Dr, Knoxville, TN 37996 USA. NR 25 TC 25 Z9 30 U1 2 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-1605 J9 INT J FOOD MICROBIOL JI Int. J. Food Microbiol. PD DEC 15 PY 2003 VL 89 IS 1 BP 11 EP 20 DI 10.1016/S0168-1605(03)00124-7 PG 10 WC Food Science & Technology; Microbiology SC Food Science & Technology; Microbiology GA 743CW UT WOS:000186555700002 PM 14580969 ER PT J AU Hashemi, RR Young, JF AF Hashemi, RR Young, JF TI The prediction of methylmercury elimination half-life in humans using animal data: A neural network/rough sets analysis SO JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A LA English DT Article ID INTERSPECIES PHARMACOKINETIC COMPARISONS; METHYL MERCURY; GUINEA-PIG; ALLOMETRIC RELATIONSHIPS; MACACA-FASCICULARIS; TISSUE DISTRIBUTION; SPECIES-DIFFERENCES; BLOOD; METABOLISM; EXPOSURE AB Artificial neural networks and Rough Sets methodology have been utilized to predict human pharmacokinetic elimination half-life data based on animal data training sets. Methylmercury (Hg) pharmacokinetic data was obtained from 3 7 literature references, which provided data on species, gender, age, weight, route of administration, dose, dose frequency, and elimination half-life based on either whole-body Hg analysis or blood Hg analysis. Data were categorized into various formats for analysis comparisons. Rough Sets methodology was utilized to identify and remove redundant independent variables. Artificial neural networks were used to produce models based on the animal data, which were in turn used to predict and compare to the human elimination half-life values. These neural network predictions were compared to allometric graphical plots of the same data. The best artificial neural network prediction was based on a "thermometer" categorical representation of the data. C1 Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Ctr Toxicol Res, Jefferson, AR 72079 USA. Armstrong Atlantic State Univ, Dept Comp Sci, Savannah, GA USA. RP Young, JF (reprint author), Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Ctr Toxicol Res, 3900 NCTR Rd,HFT-20, Jefferson, AR 72079 USA. NR 85 TC 4 Z9 6 U1 0 U2 3 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1528-7394 J9 J TOXICOL ENV HEAL A JI J. TOXICOL. ENV. HEALTH PT A PD DEC 12 PY 2003 VL 66 IS 23 BP 2227 EP 2252 DI 10.1080/15287390390241277 PG 26 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 750PL UT WOS:000187004900004 PM 14612335 ER PT J AU Chou, MW Wang, YP Yan, J Yang, YC Beger, RD Williams, LD Doerge, DR Fu, PP AF Chou, MW Wang, YP Yan, J Yang, YC Beger, RD Williams, LD Doerge, DR Fu, PP TI Riddelliine N-oxide is a phytochemical and mammalian metabolite with genotoxic activity that is comparable to the parent pyrrolizidine alkaloid riddelliine SO TOXICOLOGY LETTERS LA English DT Article DE riddelliine N-oxide; riddelline; pyrrolizidine alkaloid; DHP-derived DNA adducts; P-32-postlabeling/HPLC analysis ID DNA ADDUCT FORMATION; IN-VITRO; RATS; DEHYDRORETRONECINE; CONVERSION; MICE; VIVO AB Pyrrolizidine alkaloids (PAs) and their N-oxide derivatives are naturally-formed genotoxic phytochemicals that are widely distributed throughout the world. Although, the quantities of PAs and PA N-oxides in plants are nearly equal, the biological and genotoxic activities of PA N-oxides have not been studied extensively. PA N-oxides are major metabolites of PAs and are generally regarded as detoxification products. However, in this study, we report that rat liver microsomes converted riddelliine N-oxide to the genotoxic 6.7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine (DHP) metabolite. Metabolism of riddellime N-oxide by rat liver microsomes under hypoxic conditions (argon) generated predominantly the parent PA, riddellime. The reduction of riddelliine N-oxide to riddelliine was diminished, when the metabolism of riddelliine N-oxide with rat liver microsomes was conducted aerobically. Rat liver microsomal incubations of riddelliine N-oxide in the presence of calf thymus DNA produced a set of DHP-derived DNA adducts as detected and quantified by P-32-postlabeling/HPLC. The same DHP-derived DNA adducts were also found in liver DNA of F344 rats fed riddelliine N-oxide or riddelliine. When rats received doses of 1.0 mg/kg riddellime N-oxide for three consecutive days, the level of DNA adducts was 39.9 +/- 0.6 adducts/10(7) nucleotides, which was 2.6-fold less than that measured in rats treated with riddellime at the same dose. We have previously shown that these DHP-derived DNA adducts are produced by chronic feeding of riddellime and that the adduct levels correlated with liver tumor formation. Results presented in this paper indicate that riddellime N-oxide, through its conversion to riddellime, is also a potential genotoxic hepatocarcinogen. (C) 2003 Elsevier Ireland Ltd. All rights reserved. C1 Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Chou, MW (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. NR 30 TC 52 Z9 54 U1 2 U2 9 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0378-4274 J9 TOXICOL LETT JI Toxicol. Lett. PD DEC 10 PY 2003 VL 145 IS 3 BP 239 EP 247 DI 10.1016/S0378-4274(03)00293-5 PG 9 WC Toxicology SC Toxicology GA 750TH UT WOS:000187013800004 PM 14580895 ER PT J AU Parsons, BL AF Parsons, BL TI MED1: A central molecule for maintenance of genome integrity and response to DNA damage SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Editorial Material ID N-GLYCOSYLASE; CPG SITES; REPAIR; MBD4; TUMORIGENESIS; INTERACTS; PROTEINS; DOMAIN; MICE C1 US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. RP Parsons, BL (reprint author), US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. NR 16 TC 18 Z9 20 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 9 PY 2003 VL 100 IS 25 BP 14601 EP 14602 DI 10.1073/pnas.2637169100 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 753JA UT WOS:000187227200001 PM 14657347 ER PT J AU Sung, K Khan, SA Nawaz, MS Khan, AA AF Sung, K Khan, SA Nawaz, MS Khan, AA TI A simple and efficient Triton X-100 boiling and chloroform extraction method of RNA isolation from Gram-positive and Gram-negative bacteria SO FEMS MICROBIOLOGY LETTERS LA English DT Article DE RNA; electrophoresis; hybridization ID ESCHERICHIA-COLI; HYBRIDIZATION; MYCOBACTERIA; PROBES; PCR; DNA AB A fast, reliable, and inexpensive Triton X-100 boiling procedure for RNA isolation from both the Gram-positive and Gram-negative bacteria was developed. The yield of RNA was 0.2-2 mg per 10 ml bacterial culture. The method was tested on Gram-positive and Gram-negative bacteria of eight genera and nine species and yielded reproducible results. In parallel experiments, the Qiagen and hot phenol extraction methods both yielded RNA that contained contaminating 16S and 23S rRNA. The Triton X-100 boiling method reported here yielded RNA that was free from 16S and 23S rRNA, contained full-length transcripts and did not require additional purification. The presence of specific mRNA in one of the RNA samples obtained by this procedure was demonstrated by partial amplification of a 732 by vancomycin resistance gene, vanA, by reverse transcription-polymerase chain reaction (RT-PCR). The presence of a full-length transcript (1031 bases) of the vanA gene was verified by Northern hybridization and probing with a digoxigenin (DIG)-labeled vanA PCR partial product. The method provides a rapid, reliable, and simple tool for the isolation of good quality RNA suitable for various molecular biology experiments. (C) 2003 Federation of European Microbiological Societies. Published by Elsevier B.V. All rights reserved. C1 US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. RP Khan, SA (reprint author), US FDA, Natl Ctr Toxicol Res, Div Microbiol, 3900 NCTR Rd, Jefferson, AR 72079 USA. NR 17 TC 30 Z9 31 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1097 J9 FEMS MICROBIOL LETT JI FEMS Microbiol. Lett. PD DEC 5 PY 2003 VL 229 IS 1 BP 97 EP 101 DI 10.1016/S0378-1097(03)00791-2 PG 5 WC Microbiology SC Microbiology GA 754YY UT WOS:000187362100014 PM 14659548 ER PT J AU Williams, LD Von Tungeln, LS Beland, FA Doerge, DR AF Williams, LD Von Tungeln, LS Beland, FA Doerge, DR TI Liquid chromatographic-mass spectrometric determination of the metabolism and disposition of the anti-retroviral nucleoside analogs zidovudine and lamivudine in C57BL/6N and B6C3F1 mice SO JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES LA English DT Article DE zidovudine; lamivudine ID 3'-AZIDO-3'-DEOXYTHYMIDINE; PHARMACOKINETICS; GENOTOXICITY; MONKEYS; CELLS; AZT AB Transmission of HIV from mother to infant can be effectively prevented by zidovudine (3'-azido-3'-deoxythymidine; AZT) alone or in combination with other anti-retroviral drugs; however, significant evidence for genotoxicity, including transplacental carcinogenicity in mice, has been reported for AZT. A method, based upon solid phase extraction (SPE) in the 96-well format, gradient liquid chromatography (LC), and electrospray mass spectrometry (MS), was developed and validated to measure serum concentrations in maternal C57BL/6N and fetal 1360171 mice of the nucleoside analogs AZT, lamivudine ((-)2,3'-dideoxy-3'-thiacytidine; 3TC), and several metabolites selected based on importance in detoxification and bioactivation reactions. After intravenous (IV) and oral dosing with either 400 mg/kg AZT or 200 mg/kg 3TC, pharmacokinetics were determined for AZT, AZT-5-glucuronide, 3-amino-3'-deoxythymidine (AMT), AZT-5'-phosphate, 3TC, and 3TC-5'-phosphate in serum of adult female mice. Pharmacokinetics were also determined in spleen for AZT-5-phosphate and 3TC-5'-phosphate following IV dosing. In addition, a preliminary assessment was made of placental transfer of AZT and 3TC and the presence of metabolites in the fetal compartment. The method described provides a means to evaluate thoroughly metabolism and disposition of anti-retroviral nucleoside analogs in maternal and fetal mice for comprehensive studies of genotoxicity. (C) 2003 Elsevier B.V. All rights reserved. C1 US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Doerge, DR (reprint author), US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, HFT-110,3900 NCTR Rd, Jefferson, AR 72079 USA. FU PHS HHS [224-93-0001] NR 13 TC 22 Z9 23 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1570-0232 J9 J CHROMATOGR B JI J. Chromatogr. B PD DEC 5 PY 2003 VL 798 IS 1 BP 55 EP 62 DI 10.1016/j.jchromb.2003.08.051 PG 8 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 748CN UT WOS:000186844800008 PM 14630359 ER PT J AU Lou, H Choi, YH LaVoy, JE Major, ME Hagedorn, CH AF Lou, H Choi, YH LaVoy, JE Major, ME Hagedorn, CH TI Analysis of mutant NS5B proteins encoded by isolates from chimpanzees chronically infected following clonal HCV RNA inoculation SO VIROLOGY LA English DT Article DE hepatitis C virus; plus-strand RNA viruses; RNA replication; nonstructural protein 5B; NS5B; RNA-dependent RNA polymerase ID HEPATITIS-C VIRUS; DE-NOVO INITIATION; 3' NONTRANSLATED REGION; RIBOSOME ENTRY SITE; CRYSTAL-STRUCTURE; CELL-CULTURE; UNTRANSLATED REGION; POLYMERASE ACTIVITY; ESCHERICHIA-COLI; SERINE-PROTEASE AB We hypothesized that mutations in the HCV NS5B polymerase, which occur during infection, may affect RNA-dependent RNA polymerase (RdRp) activity. NS5B proteins corresponding to a genotype la infectious clone and mutants identified in chimpanzees following inoculation with the clone were expressed and purified and their in vitro RdRp activity was compared to a NS5B genotype 1b control. A Gln-65-to-His mutation increased RdRp activity by 1.8-fold as compared to the infectious clone. Moreover, this NS5B1 a protein had RdRp activity similar to the NS5B1b control. Three NS5B proteins representing mutations found in another animal had no in vitro RdRp activity. All mutations were maintained in the majority circulating virus for at least 216 weeks. The results demonstrate that some in vivo mutations of NS5B directly enhance in vitro RdRp activity. In addition, they suggest that the in vitro RdRp activity of NS5B may not always reflect in vivo activity within replication complexes. (C) 2003 Elsevier Inc. All rights reserved. C1 Emory Univ, Sch Med, Dept Med, Atlanta, GA 30322 USA. Emory Univ, Sch Med, Genet Program, Winship Canc Ctr, Atlanta, GA 30322 USA. US FDA, CBER, Lab Hepatitis Viruses, Bethesda, MD 20892 USA. RP Hagedorn, CH (reprint author), Univ Kansas, Med Ctr, Winship Canc Ctr, 4035 Delp Pavilion,Mail Stop 1023,3901 Rainbow, Kansas City, KS 66160 USA. FU NCI NIH HHS [CA63640]; NIAID NIH HHS [AI41424] NR 43 TC 3 Z9 4 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD DEC 5 PY 2003 VL 317 IS 1 BP 65 EP 72 DI 10.1016/j.virol.2003.08.038 PG 8 WC Virology SC Virology GA 755UX UT WOS:000187430800006 PM 14675625 ER PT J AU Lewis, SM Johnson, ZJ Mayhugh, MA Duffy, PH AF Lewis, SM Johnson, ZJ Mayhugh, MA Duffy, PH TI Nutrient intake and growth characteristics of male Sprague-Dawley rats fed AIN-93M purified diet or NIH-31 natural-ingredient diet in a chronic two-year study SO AGING CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article ID CALORIC RESTRICTION; FISCHER-344 RATS; CHRONIC DISEASE; SURVIVAL; PROTEIN; AGE; BIOMARKERS; LONGEVITY; RODENTS; RETARDATION AB Background and aims: Daily nutrient intake and growth of male Sprague-Dawley (SD) rats fed compositionally different diets were monitored over 114 weeks to determine whether rats fed ad libitum (AL) or diet restricted (DR) followed normal growth parameters. A second objective was to evaluate the usefulness of the American Institutes of Nutrition's AIN-93M (maintenance formulation) diet for aging and DR studies. Methods: Rats were fed NIH-31 cereal-based diet AL, or a vitamin-fortified modification of the NIH-31 diet at 10, 25, or 40% DR. Other SD rats were fed AIN-93M diet AL or 31% DR; daily nutrient intake and growth response were reported. Results: At all intervals up to 36 weeks of age, rats fed AL the NIH-31 diet consumed significantly (p<0.001) more than rats fed AL the AIN-93M diet, and required more diet per unit of gain than AIN-93M AL rats. However, body weight (BW) gain in rats AL-fed the AIN-93M diet demonstrated that energy components were more efficiently metabolized than in those fed the NIH-31 diet. Whereas diet restriction decreased BW, the rate of maturation, i.e., the rate of reaching a mature BW, increased as intake level decreased. Growth response showed all growth curves were normal, but intake level effects on mature BW and maturation rate differed significantly (p<0.001). Curves for rats AL- and DR-fed the AIN-93M diets were similar to those of rats AL- and DR-fed NIH-31 diet formulations, suggesting that diets adequately met growth requirements and supported normal growth parameters of male SD rats when fed AL or DR. Conclusions: A modification in the AIN-93M energy components to reduce total calories and an evaluation of other nutrient profiles could improve its usefulness as a maintenance and aging diet. (C) 2003, Editrice Kurtis. C1 US FDA, Bionet Corp, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. US FDA, Div Genet & Reprod Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Univ Arkansas, Dept Anim Sci, Fayetteville, AR 72701 USA. RP Lewis, SM (reprint author), US FDA, Bionet Corp, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM smlewis@nctr.fda.gov NR 40 TC 11 Z9 11 U1 0 U2 0 PU EDITRICE KURTIS S R L PI MILAN PA VIA LUIGI ZOJA 30, 20153 MILAN, ITALY SN 1594-0667 J9 AGING CLIN EXP RES JI Aging Clin. Exp. Res. PD DEC PY 2003 VL 15 IS 6 BP 460 EP 468 PG 9 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 769MC UT WOS:000188653000004 PM 14959948 ER PT J AU Holleran, JL Egorin, MJ Zuhowski, EG Parise, RA Musser, SM Pan, SS AF Holleran, JL Egorin, MJ Zuhowski, EG Parise, RA Musser, SM Pan, SS TI Use of high-performance liquid chromatography to characterize the rapid decomposition of wortmannin in tissue culture media SO ANALYTICAL BIOCHEMISTRY LA English DT Article DE wortmannin; PI-3 kinase; HPLC ID PHOSPHOINOSITIDE 3-KINASE; PHOSPHATIDYLINOSITOL 3-KINASE; LIPIDS; CELLS AB Although wortmannin is extensively used in molecular signaling studies, its stability in tissue culture medium has not been assessed precisely. Therefore, we used high-performance liquid chromatography (HPLC) and mass spectrometry (MS) to characterize the decomposition of wortmannin in five commonly used media. Wortmannin was added to medium alone or to medium supplemented with 10% unheated or heat-in activated fetal bovine serum and incubated at 37degreesC. After 0, 5, 10, 20, 35, and 60 min, wortmannin remaining in the medium was quantified, and its decay constant and half-life were calculated. In all media, wortmannin decomposed monoexponentially, with half-lives between 8 and 13 min. HPLC/MS indicated that wortmannin decomposed to materials with m/z 447, 433, 373, and 313. Acidification of material produced by incubation of wortmannin in tissue culture medium or 1 muM NaOH converted the material with m/z 447 back to one that cochromatographed with and had an m/z (429) identical to that of wortmannin. Therefore wortmannin is much less stable in tissue culture medium than previously thought although some apparent loss of wortmannin reflects reversible, pH-dependent opening of the lactone ring of wortmannin. This rapid and complex decomposition of wortmannin argues for care being taken in how it is used in in vitro studies. (C) 2003 Elsevier Inc. All rights reserved. C1 Univ Pittsburgh, Inst Canc, Mol Therapeut Drug Discovery Program, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Sch Med, Dept Med, Div Hematol Oncol, Pittsburgh, PA 15213 USA. US FDA, Ctr Food Safety & Appl Nutr, Instrumentat & Biophys Branch, College Pk, MD 20740 USA. RP Egorin, MJ (reprint author), Univ Pittsburgh, Inst Canc, Mol Therapeut Drug Discovery Program, Pittsburgh, PA 15213 USA. NR 26 TC 31 Z9 34 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 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD DEC 1 PY 2003 VL 323 IS 1 BP 19 EP 25 DI 10.1016/j.ab.2003.08.030 PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 747UF UT WOS:000186822700004 PM 14622954 ER PT J AU Li, W Backlund, PS Boykins, RA Wang, GY Chen, HC AF Li, W Backlund, PS Boykins, RA Wang, GY Chen, HC TI Susceptibility of the hydroxyl groups in serine and threonine to beta-elimination/Michael addition under commonly used moderately high-temperature conditions SO ANALYTICAL BIOCHEMISTRY LA English DT Article DE beta-elimination/Michael addition reaction; phosphoserine; phosphothreonine; phosphopeptide; MALDI-TOF; LC-MS/MS ID PHOSPHORYLATION SITES; MASS-SPECTROMETRY; CHEMICAL MODIFICATION; SUBSTITUTED SERYL; SEQUENCE-ANALYSIS; PROTEINS; PEPTIDES; PHOSPHOPEPTIDES; IDENTIFICATION; RESIDUES AB The beta-elimination/Michael addition reaction has been employed for the modification of O-acylated and phosphorylated Ser and Thr residues in a variety of derivatives. The modified Ser and Thr can be analyzed by amino acid composition analysis, N-terminal Edman degradation sequence analysis, and tandem mass spectrometric sequencing which generally allows the identification and localization of the phosphorylation or glycosylation sites. However, the reactivity of the free hydroxyl group on serine and threonine by sodium hydroxide-induced beta-elimination has not been critically examined. In this study, two analogous phosphopeptides, KMpSTLSYR and KMSpTLSYR, were subjected to beta-elimination under the widely used conditions previously reported, followed by sulfite or ethanethiol addition. After treatment of the phosphopeptides in 0.1 N NaOH/0.6 M Na2SO3 at 37 degreesC for 24 h, matrix-assisted laser desorption ionization-time of flight mass spectrometric analyses of the products revealed an appreciable mass peak with an additional observed mass of 64 compared to the expected mass from the conversion of phosphate to sulfite. Similarly, treatment of the phosphopeptides in 0.52 N NaOH/1.36 M ethanethiol at 50degreesC for 18 h or for even as short as I h also yielded additional 44 mass of ethylthiogroup in excess of the expected mass for the modified phosphopeptide. Electrospray ionization tandem mass spectrometric analysis confirms that the modification occurred on the hydroxyl group of Ser and Thr in addition to P-Ser and P-Thr. On the other hand, modification on the free hydroxyl group of Ser or Thr was not detected under the mild condition of 0.1 N NaOH/0.6 M Na2SO3 at 25 degreesC for 24 h as previously reported (Li et al., Anal. Chem. 74:5701-5710, 2002). This finding suggests that temperatures above 25 degreesC and excessive alkalinity should be avoided to prevent the O-elimination of the hydroxyl group of Ser and Thr in peptides. This is of particular concern when employing highly sensitive tandem mass spectrometric methods for the identification and localization of Ser and Thr as modification sites by the P-elimination/Michael addition reaction. The additional modification site(s) may complicate the interpretation of data and lead to an erroneous conclusion. Published by Elsevier Inc. C1 NICHHD, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA. NICHHD, Lab Cellular & Mol Biophys, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Bacterial Parasit & Allegen Prod, Biophys Lab, Bethesda, MD 20892 USA. RP Chen, HC (reprint author), NICHHD, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA. NR 27 TC 31 Z9 32 U1 1 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD DEC 1 PY 2003 VL 323 IS 1 BP 94 EP 102 DI 10.1016/j.ab.2003.08.015 PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 747UF UT WOS:000186822700013 PM 14622963 ER PT J AU Shieh, YC Baric, RS Woods, JW Calci, KR AF Shieh, YC Baric, RS Woods, JW Calci, KR TI Molecular surveillance of enterovirus and Norwalk-like virus in oysters relocated to a municipal-sewage-impacted gulf estuary SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID ROUND-STRUCTURED VIRUSES; HUMAN ENTERIC VIRUSES; UNITED-STATES; MULTISTATE OUTBREAK; HEPATITIS-A; MOLLUSCAN SHELLFISH; GASTROENTERITIS; EPIDEMIOLOGY; STRAIN; DIVERSITY AB An 18-month survey was conducted to examine the prevalence of enteric viruses and their relationship to indicators in environmentally polluted shellfish. Groups of oysters, one group per 4 weeks, were relocated to a coastal water area in the Gulf of Mexico that is impacted by municipal sewage and were analyzed for enteroviruses, Norwalk-like viruses (NLV), and indicator microorganisms (fecal coliform, Escherichia coli, and male-specific coliphages). The levels of indicator microorganisms were consistent with the expected continuous pollution of the area. Fourteen of the 18 oyster samples were found by reverse transcription (RT)-PCR to harbor NLV and/or enterovirus sequences. Of the four virus-negative oysters, three had exposure to water temperatures of >29degreesC. Concomitant with these findings, two of these four oysters also accumulated the lowest levels of coliphages. PCR primers targeting pan-enteroviruses and the NLV 95/96-US common subset were utilized; NLV sequences were detected more frequently than those of enteroviruses. Within the 12-month sampling period, NLV and enterovirus sequences were detected in 58 and 42%, respectively, of the oysters (67% of the oysters tested were positive for at least one virus) from a prohibited shellfish-growing area approximately 30 In away from a sewage discharge site. Eight (4.6%) of the 175 NLV capsid nucleotide sequences were heterogeneous among the clones derived from naturally polluted oysters. Overall, enteric viral sequences were found in the contaminated oysters throughout all seasons except hot summer, with a higher prevalence of NLV than enterovirus. Although a high percentage of the oysters harbored enteric viruses, the virus levels were usually less than or equal to 2 logs of RT-PCR-detectable units per gram of oyster meat. C1 US FDA, Gulf Coast Seafood Lab, Dauphin Isl, AL 36528 USA. Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27599 USA. RP Shieh, YC (reprint author), US FDA, Gulf Coast Seafood Lab, POB 158, Dauphin Isl, AL 36528 USA. NR 41 TC 45 Z9 47 U1 2 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 DEC PY 2003 VL 69 IS 12 BP 7130 EP 7136 DI 10.1128/AEM.69.12.7130-7136.2003 PG 7 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 753LZ UT WOS:000187234000022 PM 14660358 ER PT J AU Hayes, JR English, LL Carter, PJ Proescholdt, T Lee, KY Wagner, DD White, DG AF Hayes, JR English, LL Carter, PJ Proescholdt, T Lee, KY Wagner, DD White, DG TI Prevalence and antimicrobial resistance of Enterococcus species isolated from retail meats SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID INTENSIVE-CARE-UNIT; GLYCOPEPTIDE RESISTANCE; ANTIBIOTIC-RESISTANCE; QUINUPRISTIN-DALFOPRISTIN; MOLECULAR CHARACTERIZATION; VANCOMYCIN RESISTANCE; HOSPITALIZED-PATIENTS; INTESTINAL BACTERIA; NORWEGIAN POULTRY; GROWTH PROMOTION AB From March 2001 to June 2002, a total of 981 samples of retail raw meats (chicken, turkey, pork, and beef) were randomly obtained from 263 grocery stores in Iowa and cultured for the presence of Enterococcus spp. A total of 1,357 enterococcal isolates were recovered from the samples, with contamination rates ranging from 97% of pork samples to 100% of ground beef samples. Enterococcus faecium was the predominant species recovered (61%), followed by E. faecalis (29%), and E. hirae (5.7%). E. faecium was the predominant species recovered from ground turkey (60%), ground beef (65%), and chicken breast (79%), while E. faecalis was the predominant species recovered from pork chops (54%). The incidence of resistance to many production and therapeutic antimicrobials differed among enterococci recovered from retail meat samples. Resistance to quinupristin-dalfopristin, a human analogue of the production drug virginiamycin, was observed in 54, 27, 9, and 18% of E. faecium isolates from turkey, chicken, pork, and beef samples, respectively. No resistance to linezolid or vancomycin was observed, but high-level gentamicin resistance was observed in 4% of enterococci, the majority of which were recovered from poultry retail meats. Results indicate that Enterococcus spp. commonly contaminate retail meats and that dissimilarities in antimicrobial resistance patterns among enterococci recovered from different meat types may reflect the use of approved antimicrobial agents in each food animal production class. C1 US FDA, Ctr Vet Med, Laurel, MD 20708 USA. Univ Maryland, Dept Cell Biol & Mol Genet, College Pk, MD 20742 USA. RP White, DG (reprint author), US FDA, Ctr Vet Med, Laurel, MD 20708 USA. NR 58 TC 117 Z9 130 U1 1 U2 22 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0099-2240 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD DEC PY 2003 VL 69 IS 12 BP 7153 EP 7160 DI 10.1128/AEM.69.12.7153-7160.2003 PG 8 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 753LZ UT WOS:000187234000025 PM 14660361 ER PT J AU Tall, BD Fall, S Pereira, MR Ramos-Valle, M Curtis, SK Kothary, MH Chu, DMT Monday, SR Kornegay, L Donkar, T Prince, D Thunberg, RL Shangraw, KA Hanes, DE Khambaty, FA Lampel, KA Bier, JW Bayer, RC AF Tall, BD Fall, S Pereira, MR Ramos-Valle, M Curtis, SK Kothary, MH Chu, DMT Monday, SR Kornegay, L Donkar, T Prince, D Thunberg, RL Shangraw, KA Hanes, DE Khambaty, FA Lampel, KA Bier, JW Bayer, RC TI Characterization of Vibrio fluvialis-like strains implicated in limp lobster disease SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID FIELD GEL-ELECTROPHORESIS; ANTIBIOTIC-RESISTANCE; ENVIRONMENTAL SOURCES; HOMARUS AMERICANUS; FLUID ACCUMULATION; VIRULENCE PLASMID; BACTERIAL DISEASE; R-PLASMIDS; SP-NOV; VULNIFICUS AB Studies were undertaken to characterize and determine the pathogenic mechanisms involved in a newly described systemic disease in Homarus americanus (American lobster) caused by a Vibrio fluvialis-like microorganism. Nineteen isolates were obtained from eight of nine lobsters sampled. Biochemically, the isolates resembled V. fluvialis, and the isolates grew optimally at 20degreesC; none could grow at temperatures above 23degreesC. The type strain (1AMA) displayed a thermal reduction time (D value) of 5.77 min at 37degreesC. All of the isolates required at least 1% NaCl for growth. Collectively, the data suggest that these isolates may embody a new biotype. Pulsed-field gel electrophoresis (PFGE) analysis of the isolates revealed five closely related subgroups. Some isolates produced a sheep hemagglutinin that was neither an outer membrane protein nor a metalloprotease. Several isolates possessed capsules. The isolates were highly susceptible to a variety of antibiotics tested. However, six isolates were resistant to erythromycin. Seventeen isolates harbored plasmids. Lobster challenge studies revealed that the 50% lethal dose of a plasmid-positive strain was 100-fold lower than that of a plasmid-negative strain, suggesting that the plasmid may enhance the pathogenicity of these microorganisms in lobsters. Microorganisms that were recovered from experimentally infected lobsters exhibited biochemical and PFGE profiles that were indistinguishable from those of the challenge strain. Tissue affinity studies demonstrated that the challenge microorganisms accumulated in heart and midgut tissues as well as in the hemolymph. Culture supernatants and polymyxin B lysates of the strains caused elongation of CHO cells in tissue culture, suggesting the presence of a hitherto unknown enterotoxin. Both plasmid-positive and plasmid-negative strains caused significant dose-related intestinal fluid accumulations in suckling mice. Absence of viable organisms in the intestinal contents of mice suggests that these microorganisms cause diarrhea in mice by intoxication rather than by an infectious process. Further, these results support the thermal reduction data at 37degreesC and suggest that the mechanism(s) that led to fluid accumulation in mice differs from the disease process observed in lobsters by requiring neither the persistence of viable microorganisms nor the presence of plasmids. In summary, results of lobster studies satisfy Koch's postulates at the organismal and molecular levels; the findings support the hypothesis that these V. fluvialis-like organisms were responsible for the originally described systemic disease, which is now called limp lobster disease. C1 US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. Univ Maine, Lobster Inst, Orono, ME 04469 USA. RP Tall, BD (reprint author), US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. OI Tall, Ben/0000-0003-0399-3629 NR 70 TC 26 Z9 28 U1 1 U2 11 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0099-2240 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD DEC PY 2003 VL 69 IS 12 BP 7435 EP 7446 DI 10.1128/AEM.69.12.7435-7446.2003 PG 12 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 753LZ UT WOS:000187234000060 PM 14660396 ER PT J AU Tsai, CA Hsueh, HM Chen, JJ AF Tsai, CA Hsueh, HM Chen, JJ TI Estimation of false discovery rates in multiple testing: Application to gene microarray data SO BIOMETRICS LA English DT Article DE Bayesian Type I error; comparison-wise error rate (CWE); false discovery rate (FDR); number of rejections; number of true null hypotheses; q-value ID COMPLEX TRAITS; STATISTICS; DISSECTION AB Testing for significance with gene expression data from DNA microarray experiments involves simultaneous comparisons of hundreds or thousands of genes. If R denotes the number of rejections (declared significant genes) and V denotes the number of false rejections, then VIR, if R > 0, is the proportion of false rejected hypotheses. This paper proposes a model for the distribution of the number of rejections and the conditional distribution of V given R, V/ R. Under the independence assumption, the distribution of R is a convolution of two binomials and the distribution of V/R has a noncentral hypergeometric distribution. Under an equicorrelated model, the distributions are more complex and are also derived. Five false discovery rate probability error measures are considered: FDR = E(V/R), pFDR = E(V/R/R > 0) (positive FDR), cFDR = E(V/R\R = r) (conditional FDR), mFDR = E(V)/E(R) (marginal FDR), and eFDR = E(V)/r (empirical FDR). The pFDR, cFDR, and mFDR are shown to be equivalent under the Bayesian framework, in which the number of true null hypotheses is modeled as a random variable. We present a parametric and a bootstrap procedure to estimate the FDRs. Monte Carlo simulations were conducted to evaluate the performance of these two methods. The bootstrap procedure appears to perform reasonably well, even when the alternative hypotheses are correlated (rho=.25). An example from a toxicogenomic microarray experiment is presented for illustration. C1 US FDA, Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. Natl Chengchi Univ, Dept Stat, Taipei 11623, Taiwan. RP Tsai, CA (reprint author), US FDA, Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. OI Tsai, Chen-An/0000-0002-7490-4331; HSUEH, HUEY-MIIN/0000-0003-0536-9440 NR 20 TC 97 Z9 100 U1 1 U2 13 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0006-341X J9 BIOMETRICS JI Biometrics PD DEC PY 2003 VL 59 IS 4 BP 1071 EP 1081 DI 10.1111/j.0006-341X.2003.00123.x PG 11 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 756UE UT WOS:000187501100037 PM 14969487 ER PT J AU Herold, KE Rasooly, A AF Herold, KE Rasooly, A TI Oligo Design: a computer program for development of probes for oligonucleotide microarrays SO BIOTECHNIQUES LA English DT Article ID NEAREST-NEIGHBOR THERMODYNAMICS; DOT-T MISMATCHES; MELTING TEMPERATURE; PREDICT STABILITY; DNA; HYBRIDIZATION; PARAMETERS; SEQUENCE; DUPLEXES; DEPENDENCE AB Oligonucleotide microarrays have demonstrated potential for the analysis of gene expression, genotyping, and mutational analysis. Our work focuses primarily on the detection and identification of bacteria based on known short sequences of DNA. Oligo Design, the software described here, automates several design aspects that enable the improved selection of oligonucleotides for use with microarrays for these applications. Two major features of the program are: (i) a tiling algorithm for the design of short overlapping temperature-matched oligonucleotides of variable length, which are useful for the analysis of single nucleotide polymorphisms and (ii) a set of tools for the analysis of multiple alignments of gene families and related short DNA sequences, which allow for the identification of conserved DNA sequences for PCR primer selection and variable DNA sequences for the selection of unique probes for identification. Note that the program does not address the full genome perspective but, instead, is focused on the genetic analysis of short segments of DNA. The program is Internet-enabled and includes a built-in browser and the automated ability to download sequences from GenBank(R) by specifying the GI number. The program also includes several utilities, including audio recital of a DNA sequence (useful for verifying sequences against a written document), a random sequence generator that provides insight into the relationship between melting temperature and GC content, and a PCR calculator. C1 Univ Maryland, Dept Mech Engn, College Pk, MD 20742 USA. US FDA, Rockville, MD 20857 USA. RP Herold, KE (reprint author), Univ Maryland, Dept Mech Engn, College Pk, MD 20742 USA. NR 26 TC 13 Z9 15 U1 0 U2 0 PU EATON PUBLISHING CO PI NATICK PA 154 E. CENTRAL ST, NATICK, MA 01760 USA SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD DEC PY 2003 VL 35 IS 6 BP 1216 EP + PG 5 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 753UX UT WOS:000187249900015 PM 14682056 ER PT J AU Papaconstantinou, AD Brown, KM Noren, BT McAlister, T Fisher, BR Goering, PL AF Papaconstantinou, AD Brown, KM Noren, BT McAlister, T Fisher, BR Goering, PL TI Mercury, cadmium, and arsenite enhance heat shock protein synthesis in chick embryos prior to embryotoxicity SO BIRTH DEFECTS RESEARCH PART B-DEVELOPMENTAL AND REPRODUCTIVE TOXICOLOGY LA English DT Article DE arsenite; cadmium; mercury; chick embryo; heat shock proteins; teratogenicity; embryotoxicity ID SODIUM ARSENITE; STRESS PROTEINS; RAT EMBRYOS; MOUSE EMBRYOS; DEVELOPMENTAL TOXICITY; INDUCED TOLERANCE; INDUCTION; TERATOGENICITY; EXPRESSION; CHLORIDE AB yBACKGROUND: Cells respond to adverse environmental stimuli by enhancing the expression of specific genes, the products of which include a suite of proteins known as heat shock proteins (hsps), a response often attributed to cellular protection. METHODS: In this study, we characterized alterations in hsp expression in chick embryos (Hamburger-Hamilton stage 17, 72 h) exposed in ovo to arsenite (As), mercury (Hg), and cadmium (Cd), known developmental toxicants. Embryos were incubated for 2 h following exposure to 3, 10, 30, or 100 nmol metal, or for 2, 4, 12, or 24 h following treatment with 10 nmol metal. RESULTS: An enhanced de novo synthesis of 24-, 70-, and 90-kD, 70- and 90-kD, and 70-kD proteins was observed with As, Hg, and Cd treatments, respectively. These responses were transient; apparent rates of protein synthesis were maximal 2-4 h after exposure and returned to control rates by 24 h. Actinomycin D experiments demonstrated that arsenite-induced expression of these proteins is transcriptionally regulated. Immunoblotting experiments identified the 24-, 70-, and 90-kD proteins as the heat shock proteins hsp24, hsp70, and hsp90, respectively. Exposure duration-related abnormalities were noted in the neural tube with all metals and in the ganglia and somites with Cd and As. Retina, allantois, and limb defects were specific to Cd-treated embryos, and branchial arch defects were specific to As-treated embryos. CONCLUSIONS: The data support metal-induced developmental abnormalities, which are preceded by synthesis of stress proteins. Published 2003 Wiley-Liss, Inc. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20852 USA. George Washington Univ, Dept Biol Sci, Washington, DC 20052 USA. RP Goering, PL (reprint author), US FDA, Ctr Devices & Radiol Hlth, HFZ-112,12709 Twinbrook Pkwy, Rockville, MD 20852 USA. EM plg@cdrh.fda.gov NR 47 TC 28 Z9 29 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 1542-9733 J9 BIRTH DEFECTS RES B JI Birth Defects Res. Part B-Dev. Reprod. Toxicol. PD DEC PY 2003 VL 68 IS 6 BP 456 EP 464 DI 10.1002/bdrb.10044 PG 9 WC Oncology; Genetics & Heredity; Toxicology SC Oncology; Genetics & Heredity; Toxicology GA 760YA UT WOS:000187861800002 PM 14745979 ER PT J AU Wolins, N Lozier, J Eggerman, TL Jones, E Aguilar-Cordova, E Vostal, JG AF Wolins, N Lozier, J Eggerman, TL Jones, E Aguilar-Cordova, E Vostal, JG TI Intravenous administration of replication-incompetent adenovirus to rhesus monkeys induces thrombocytopenia by increasing in vivo platelet clearance SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE thrombocytopenia; adenovirus; toxicity; platelet survival; primates ID AGGREGATION; TOXICITY; VECTORS AB A replication-incompetent adenovirus vector was administered to rhesus macaques at 1, 3 and 6 x 10(12) particles/kg doses to investigate its toxicity. Platelet count decrements of 28%, 82% and 90%, respectively, were observed, with corresponding platelet half-lives of 69.0, 25.2 and 22.2 h (compared with 111 h in untreated animals). The platelet decline was equivalent for all three doses for 8 h, and platelet count recovery began as early as 8 h after infusion for low-dose recipients, or as late as 24 h for the medium and high dose recipients. These observations suggest that thrombocytopenia is a saturable, reversible consumptive process. C1 US FDA, Ctr Biol Evaluat & Res, OBRR, Div Hematol,Lab Cellular Hematol, Bethesda, MD 20892 USA. NIDDKD, NIH, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Vostal, JG (reprint author), US FDA, Ctr Biol Evaluat & Res, OBRR, Div Hematol,Lab Cellular Hematol, Bldg 29,Room 321,8800 Rockville Pike, Bethesda, MD 20892 USA. NR 11 TC 33 Z9 33 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD DEC PY 2003 VL 123 IS 5 BP 903 EP 905 DI 10.1046/j.1365-2141.2003.04719.x PG 3 WC Hematology SC Hematology GA 745NX UT WOS:000186695700016 PM 14632782 ER PT J AU Hingorani, SR Petricoin, EF Maitra, A Rajapakse, V King, C Jacobetz, MA Ross, S Conrads, TP Veenstra, TD Hitt, BA Kawaguchi, Y Johann, D Liotta, LA Crawford, HC Putt, ME Jacks, T Wright, CVE Hruban, RH Lowy, AM Tuveson, DA AF Hingorani, SR Petricoin, EF Maitra, A Rajapakse, V King, C Jacobetz, MA Ross, S Conrads, TP Veenstra, TD Hitt, BA Kawaguchi, Y Johann, D Liotta, LA Crawford, HC Putt, ME Jacks, T Wright, CVE Hruban, RH Lowy, AM Tuveson, DA TI Preinvasive and invasive ductal pancreatic cancer and its early detection in the mouse SO CANCER CELL LA English DT Article ID K-RAS ONCOGENE; TRANSGENIC MICE; METALLOPROTEINASE MATRILYSIN; CYCLOOXYGENASE-2 EXPRESSION; PROTEOMIC PATTERNS; PROGRESSION MODEL; PROSTATE-CANCER; TGF-ALPHA; CARCINOMA; TUMORIGENESIS AB To evaluate the role of oncogenic RAS mutations in pancreatic tumorigenesis, we directed endogenous expression of KRAS(G12D) to progenitor cells of the mouse pancreas. We find that physiological levels of Kras(G12D) induce ductal lesions that recapitulate the full spectrum of human pancreatic intraepithelial neoplasias (PanINs), putative precursors to invasive pancreatic cancer. The PanINs are highly proliferative, show evidence of histological progression, and activate signaling pathways normally quiescent in ductal epithelium, suggesting potential therapeutic and chemopreventive targets for the cognate human condition. At low frequency, these lesions also progress spontaneously to invasive and metastatic adenocarcinomas, establishing PanINs as definitive precursors to the invasive disease. Finally, mice with PanINs have an identifiable serum proteomic signature, suggesting a means of detecting the preinvasive state in patients. C1 Univ Penn, Abramson Family Canc Res Inst, Abramson Canc Ctr, Dept Med, Philadelphia, PA 19104 USA. Univ Penn, Abramson Family Canc Res Inst, Abramson Canc Ctr, Dept Canc Biol, Philadelphia, PA 19104 USA. US FDA, NCI Clin Proteom Program, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Sidney Kimmel Canc Ctr, Dept Pathol, Baltimore, MD 21287 USA. Johns Hopkins Univ, Sch Med, Sidney Kimmel Canc Ctr, Dept Oncol, Baltimore, MD 21287 USA. NCI, Canc Res Ctr, Pathol Lab, FDA,Clin Proteom Program, Bethesda, MD 20892 USA. SAIC Frederick Inc, NCI, Biomed Proteom program, Analyt Chem Lab,Mass Spectrometry Ctr, Ft Detrick, MD 21702 USA. Correlog Syst Inc, Bethesda, MD 20892 USA. Vanderbilt Univ, Dept Cell & Dev Biol, Sch Med, Nashville, TN 37232 USA. SUNY Stony Brook, Dept Pharmacol Sci, Stony Brook, NY 11794 USA. Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. MIT, Dept Biol, Cambridge, MA 02139 USA. Ctr Canc Res, Howard Hughes Med Inst, Cambridge, MA 02139 USA. Univ Cincinnati, Coll Med, Dept Surg, Div Surg Oncol, Cincinnati, OH 45219 USA. RP Tuveson, DA (reprint author), Univ Penn, Abramson Family Canc Res Inst, Abramson Canc Ctr, Dept Med, Philadelphia, PA 19104 USA. RI Crawford, Howard/A-2874-2008; Tang, Amy/L-3226-2016 OI Tang, Amy/0000-0002-5772-2878 FU NCI NIH HHS [P50-CA-62924, R25-CA87812]; NIDDK NIH HHS [P30 DK050306] NR 60 TC 981 Z9 1001 U1 15 U2 79 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD DEC PY 2003 VL 4 IS 6 BP 437 EP 450 DI 10.1016/S1535-6108(03)00309-X PG 14 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 757VY UT WOS:000187583200007 PM 14706336 ER PT J AU Esfandiari, F Green, R Cotterman, RF Pogribny, IP James, SJ Miller, JW AF Esfandiari, F Green, R Cotterman, RF Pogribny, IP James, SJ Miller, JW TI Methyl deficiency causes reduction of the methyl-CpG-binding protein, MeCP2, in rat liver SO CARCINOGENESIS LA English DT Article ID DNA METHYLATION; ALTERNATIVE POLYADENYLATION; FOLATE/METHYL DEFICIENCY; GENE-EXPRESSION; P53 GENE; CHROMATIN; REGION; CANCER AB MeCP2 is a member of a family of proteins [methyl- (cytosine-guanine)CpG-binding proteins] that bind specifically to methylated DNA and induce chromatin remodeling and gene silencing. Dietary deficiency of folate, choline and methionine causes decreased tissue S-adenosylmethionine concentrations (methyl deficiency), global DNA hypomethylation, hepatic steatosis, cirrhosis and ultimately hepatic tumorigenesis in rodents. We investigated the effects of this diet on expression of MeCP2 during pre-neoplastic transformation of liver tissue. After 9 weeks, MeCP2 mRNA level was slightly higher in methyl-deficient rats compared with replete controls, while after 36 weeks, a difference in MeCP2 mRNA level was no longer observed. In contrast, MeCP2 protein level was reduced almost 2-fold in the deficient rats compared with replete controls at both 9 and 36 weeks. Conversely, a second methyl-CpG-binding protein, MBD2, showed increased levels of both message and protein at the two time points. Low MeCP2 protein in the deficient rats was associated with a low level of the co-repressor protein, Sin3a, at 36 weeks. Moreover, a known gene target of MeCP2, the tumor suppressor gene metallothionein-I, was over-expressed in the deficient rat livers at both 9 and 36 weeks, suggesting that reduction in MeCP2 may have functional consequences. Methyl deficiency also caused an increase in the ratio of long to short variants of MeCP2 transcripts. This finding suggests that reduced MeCP2 protein level is the result of a reduced rate of translation. Reduction of MeCP2 protein expression may influence the initiation and/or progression of hepatic cancer induced by methyl deficiency and may provide a useful marker of pre-neoplastic change. C1 Univ Calif Davis, Sch Med, Dept Med Pathol, Sacramento, CA 95817 USA. Natl Ctr Toxicol Res, Dept Biochem Toxicol, Jefferson, AR 72079 USA. RP Miller, JW (reprint author), Univ Calif Davis, Sch Med, Dept Med Pathol, Room 3200A,4645 2nd Ave, Sacramento, CA 95817 USA. NR 17 TC 20 Z9 21 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD DEC PY 2003 VL 24 IS 12 BP 1935 EP 1940 DI 10.1093/carcin/bgg163 PG 6 WC Oncology SC Oncology GA 753EL UT WOS:000187219100010 PM 12949043 ER PT J AU Xu, LL Heinze, T Pogge, A Slikker, W Schmued, L AF Xu, LL Heinze, T Pogge, A Slikker, W Schmued, L TI Chemical characterization of fluoro-Jade B, a high affinity histochemical marker of toxicant-induced neuronal degeneration. SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Meeting Abstract CT 226th National Meeting of the American-Chemical-Society CY SEP 07-11, 2003 CL NEW YORK, NEW YORK SP Amer Chem Soc C1 US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. US FDA, Natl Ctr Toxicol Res, Div Chem, Jefferson, AR 72079 USA. EM LXu@NCTR.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 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD DEC PY 2003 VL 16 IS 12 MA 52 BP 1673 EP 1673 PG 1 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 755AM UT WOS:000187365700073 ER PT J AU Wang, YP Xia, QS Yang, YC Yan, J Fu, PP Chou, MW AF Wang, YP Xia, QS Yang, YC Yan, J Fu, PP Chou, MW TI Human liver microsomal reduction of pyrrolizidine alkaloid N-oxides to form the corresponding carcinogenic parent compounds. SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Meeting Abstract CT 226th National Meeting of the American-Chemical-Society CY SEP 07-11, 2003 CL NEW YORK, NEW YORK SP Amer Chem Soc C1 Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. EM ywang@nctr.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 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD DEC PY 2003 VL 16 IS 12 MA 72 BP 1678 EP 1678 PG 1 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 755AM UT WOS:000187365700093 ER PT J AU Di Paolo, OA Plaxco, JR Coles, BF Macleod, SL Kadlubar, FF AF Di Paolo, OA Plaxco, JR Coles, BF Macleod, SL Kadlubar, FF TI Molecular pathology of cyclooxygenase-2, e-cadherin and retinoic acid receptor beta in benign prostatic hyperplastic (bph) tissue. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics CY NOV 17-21, 2003 CL BOSTON, MASSACHUSETTS SP AACR, NCI, EORTC C1 Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Arkansas Canc Res Ctr, Little Rock, AR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 1 PY 2003 VL 9 IS 16 SU S BP 6250S EP 6250S PN 2 PG 1 WC Oncology SC Oncology GA 756LU UT WOS:000187467300736 ER PT J AU Kalluri, P Crowe, C Reller, M Gaul, L Hayslett, J Barth, S Eliasberg, S Ferreira, J Holt, K Bengston, S Hendricks, K Sobel, J AF Kalluri, P Crowe, C Reller, M Gaul, L Hayslett, J Barth, S Eliasberg, S Ferreira, J Holt, K Bengston, S Hendricks, K Sobel, J TI An outbreak of foodborne botulism associated with food sold at a salvage store in Texas SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID CHEESE AB Foodborne botulism is caused by potent neurotoxins of Clostridium botulinum. We investigated a large outbreak of foodborne botulism among church supper attendees in Texas. We conducted a cohort study of attendees and investigated the salvage store that sold the implicated foods. We identified 15 cases of botulism (40%) among 38 church supper attendees. Nine patients (60%) had botulinum toxin type A detected in stool specimens. The diagnosis was delayed in 3 cases. Fifteen (63%) of 24 attendees who ate a chili dish developed botulism (relative risk, undefined; P<.001). The chili dish was prepared with "brand X" or "brand Y" frozen chili, "brand Z" canned chili, and hot dogs. An unopened container of brand X chili yielded type A toxin. Brand X chili was purchased at a salvage store where perishable foods were inadequately refrigerated. Our investigation highlights the need to improve clinicians' awareness of botulism. More rigorous and more unannounced inspections may be necessary to detect food mishandling at salvage stores. C1 Ctr Dis Control & Prevent, Foodborne & Diarrheal Dis Branch, Div Bacterial & Mycot Dis, Natl Ctr Infect Dis, Atlanta, GA 30030 USA. Ctr Dis Control & Prevent, Epidem Intelligence Serv, Epidemiol Program Off, Atlanta, GA 30030 USA. Texas Dept Hlth, Austin, TX 78756 USA. US FDA, Off Regulatory Affairs, Rockville, MD 20857 USA. Food Safety & Inspect Serv, USDA, Washington, DC 20250 USA. RP Kalluri, P (reprint author), Ctr Dis Control & Prevent, Foodborne & Diarrheal Dis Branch, Div Bacterial & Mycot Dis, Natl Ctr Infect Dis, MS A-38,1600 Clifton Rd, Atlanta, GA 30030 USA. NR 14 TC 23 Z9 23 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD DEC 1 PY 2003 VL 37 IS 11 BP 1490 EP 1495 DI 10.1086/379326 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 743LD UT WOS:000186572500010 PM 14614672 ER PT J AU Hall, SD Wang, ZQ Huang, SM Hamman, MA Vasavada, N Adigun, AQ Hilligoss, JK Miller, M Gorski, JC AF Hall, SD Wang, ZQ Huang, SM Hamman, MA Vasavada, N Adigun, AQ Hilligoss, JK Miller, M Gorski, JC TI The interaction between St John's wort and an oral contraceptive SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID HYPERICUM-PERFORATUM; HORMONAL CONTRACEPTION; X RECEPTOR; ETHINYLESTRADIOL; METABOLISM; PHARMACOKINETICS; DEPRESSION; BIOAVAILABILITY; RIFAMPICIN; RIFABUTIN AB Objectives. The popular herbal remedy St John's wort is an inducer of cytochrome P450 (CYP) 3A enzymes and may reduce the efficacy of oral contraceptives. Therefore we evaluated the effect of St John's wort on the disposition and efficacy of Ortho-Novum 1/35 (Ortho-McNeil Pharmaceutical, Inc, Raritan, NJ), a popular combination oral contraceptive pill containing ethinyl estradiol (INN, ethinylestradiol) and norethindrone (INN, norethisterone). Methods: Twelve healthy premenopausal women who were using oral contraception (>3 months) received a combination oral contraceptive pill (Ortho-Novum 1/35) for 3 consecutive 28-day menstrual cycles. During the second and third cycles, the participants received 300 mg St John's wort 3 times a day. The serum concentrations of ethinyl estradiol (day 7), norethindrone (day 7), follicle-stimulating hormone (days 1216), luteinizing hormone (days 12-16), progesterone (day 21), and intravenous and oral midazolam (days 22 and 23) were determined in serial blood samples. The incidence of breakthrough bleeding was quantified during the first and third cycles. Results: Concomitant use of St John's wort was associated with a significant (P <.05) increase in the oral clearance of norethindrone (8.2 +/- 2.7 L/h to 9.5 +/- 3.4 L/h, P =.042) and a significant reduction in the half-life of ethinyl estradiol (23.4 +/- 19.5 hours to 12.2 +/- 7.1 hours, P =.023). The oral clearance of midazolam was significantly increased (109.2 +/- 47.9 L/h to 166.7 +/- 81.3 L/h, P =.007) during St John's wort administration, but the systemic clearance of midazolam was unchanged (37.7 +/- 11.3 L/h to 39.0 +/- 10.3 L/h, P =.567). Serum concentrations of follicle-stimulating hormone, luteinizing hormone, and progesterone were not significantly affected by St John's wort dosing (P >.05). Breakthrough bleeding occurred in 2 of 12 women in the control phase compared with 7 of 12 women in the St John's wort phase. The oral clearance of midazolam after St John's wort dosing was greater in women who had breakthrough bleeding (215.9 +/- 66.5 L/h) than in those who did not (97.5 +/- 37.2 L/h) (P =.005). Conclusion: St John's wort causes an induction of ethinyl estradiol-norethindrone metabolism consistent with increased CYP3A activity. Women taking oral contraceptive pills should be counseled to expect breakthrough bleeding and should consider adding a barrier method of contraception when consuming St Johns wort. C1 Schering Plough Corp, Kenilworth, NJ 07033 USA. Indiana Univ, Sch Med, Indianapolis, IN 46204 USA. US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. US FDA, Off Commissioner, Rockville, MD 20857 USA. RP Hall, SD (reprint author), Wishard Mem Hosp, Dept Med, Div Clin Pharmacol, 1001 W 10Th St,Myers Bldg W7123, Indianapolis, IN 46202 USA. FU FDA HHS [FD-T-001756-01]; NCRR NIH HHS [MO1-RR00750]; NIGMS NIH HHS [T32GM08425]; PHS HHS [T00224402D] NR 33 TC 133 Z9 138 U1 0 U2 20 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD DEC PY 2003 VL 74 IS 6 BP 525 EP 535 DI 10.1016/j.clpt.2003.08.009 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 752BC UT WOS:000187125700004 PM 14663455 ER PT J AU Powers, JH AF Powers, JH TI Development of drugs for anti microbial-resistant pathogens SO CURRENT OPINION IN INFECTIOUS DISEASES LA English DT Review DE antimicrobial agents; drug development; resistance ID UNITED-STATES AB Purpose of review Clinicians have noted an association between antimicrobial resistance and antimicrobial use since the introduction of these agents over 50 years ago. The problem of resistance becomes more pressing, however, when organisms acquire resistance mechanisms to multiple antimicrobial agents. Treatment options are limited for some multidrug-resistant organisms. Antimicrobial resistance is a driving force for the need for new antimicrobial agents, especially for these multidrug-resistant pathogens. At the same time, large pharmaceutical companies have indicated that they are devoting fewer resources to antimicrobial drug development. Recent findings This article will review initiatives by the US Food and Drug Administration to identify problem pathogens for which drug development is of most public health importance, and to streamline the drug development process for antimicrobial agents. This article will also touch upon initiatives by federal agencies to implement programs to educate clinicians and the public on the appropriate use of antimicrobial agents to preserve the usefulness of currently marketed drugs. Summary The most effective way to address the issues of antimicrobial resistance appears to be striking a balance between promoting new drug development and the prudent use of older agents to preserve the usefulness of currently marketed products. C1 US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Powers, JH (reprint author), 9201 Corp Blvd,HFD-104, Rockville, MD 20850 USA. EM powersjoh@cder.fda.gov NR 19 TC 22 Z9 24 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0951-7375 J9 CURR OPIN INFECT DIS JI Curr. Opin. Infect. Dis. PD DEC PY 2003 VL 16 IS 6 BP 547 EP 551 DI 10.1097/01.qco.0000104294.87920.b4 PG 5 WC Infectious Diseases SC Infectious Diseases GA 809YD UT WOS:000220671100006 PM 14624104 ER PT J AU Flurer, CL AF Flurer, CL TI Analysis of antibiotics by capillary electrophoresis SO ELECTROPHORESIS LA English DT Review DE antibiotics; capillary electrophoresis; review ID INDUCED FLUORESCENCE DETECTION; MICELLAR ELECTROKINETIC CHROMATOGRAPHY; SOLID-PHASE EXTRACTION; ZONE-ELECTROPHORESIS; PHARMACEUTICAL-PREPARATIONS; UV DETECTION; ALTERNATIVE METHOD; OXOLINIC ACID; HUMAN SERUM; DERIVATIZATION AB Recent developments in the characterization of antibiotics are reviewed. Many capillary electrophoretic techniques have been utilized in their analyses, addressing various aspects of quantifying, profiling, and monitoring. Laser-induced fluorescence detection systems demonstrated their usefulness in clinical settings and in the monitoring of residue levels in food matrices. Different sample introduction methods have been explored, enhancing detection sensitivity, or reducing or eliminating sample manipulation prior to injection. C1 US FDA, Forens Chem Ctr, Cincinnati, OH USA. RP Flurer, CL (reprint author), US FDA, Forens Chem Ctr, 6751 Steger Dr, Cincinnati, OH USA. NR 44 TC 29 Z9 29 U1 5 U2 13 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 0173-0835 J9 ELECTROPHORESIS JI Electrophoresis PD DEC PY 2003 VL 24 IS 22-23 BP 4116 EP 4127 DI 10.1002/elps.200305639 PG 12 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 755TX UT WOS:000187428500019 PM 14661238 ER PT J AU Xu, L Tsuji, K Mostowski, H Candotti, F Rosenberg, A AF Xu, L Tsuji, K Mostowski, H Candotti, F Rosenberg, A TI Evidence that the mouse 3 ' kappa light chain enhancer confers position-independent transgene expression in T- and B-lineage cells SO HUMAN GENE THERAPY LA English DT Article ID LOCUS-CONTROL REGION; BETA-GLOBIN GENE; MURINE LEUKEMIA-VIRUS; HUMAN CD2 GENE; LONG TERMINAL REPEAT; KAPPA 3 ENHANCER; ERYTHROLEUKEMIA-CELLS; TRANSCRIPTION FACTOR; RETROVIRAL VECTORS; HIGH-LEVEL AB One of the major obstacles for successful application of murine leukemia virus (MLV) vectors to genetic therapy of lymphocyte disorders is low levels of transgene expression or the eventual loss of expression. To overcome this problem, an improved retroviral vector was constructed utilizing the myeloproliferative sarcoma virus (MPSV) long terminal repeat (LTR), which provided a significantly higher level of transgene expression in human lymphoid cells than did MLV vectors. Nevertheless, transgene expression remained low in a large percentage of transduced cells. To address whether lymphocyte enhancer elements might improve transgene expression mediated by retroviral vectors in lymphocytes, we cloned the mouse immunoglobulin 3' kappa light chain enhancer gene (mE3') into the MPSV vector. We found that the mE3' conferred a higher, more uniform and sustained level of expression in transduced T- and B-cell lines, and in primary T cells, than did the control vector lacking this element. Integration sites were diverse and a single copy of the proviral genome was present in all examined transduced cells. The mE3' failed to enhance transgene expression in most nonlymphoid cells, indicating it is relatively lineage-specific. Taken together, these results provide strong evidence that the mE3' functions as a locus control region (LCR) in conferring enhanced integration-site-independent expression of a retroviral transgene. C1 NHGRI, Div Therapeut Prot, NIH, Bethesda, MD 20892 USA. NHGRI, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, US FDA,NIH, Bethesda, MD 20892 USA. NHGRI, Disorders Immun Sect, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. RP Rosenberg, A (reprint author), NHGRI, Div Therapeut Prot, NIH, Bethesda, MD 20892 USA. NR 49 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 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD DEC PY 2003 VL 14 IS 18 BP 1753 EP 1764 DI 10.1089/104303403322611764 PG 12 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 753RX UT WOS:000187245300006 PM 14670126 ER PT J AU Beiden, SV Maloof, MA Wagner, RF AF Beiden, SV Maloof, MA Wagner, RF TI A general model for finite-sample effects in training and testing of competing classifiers SO IEEE TRANSACTIONS ON PATTERN ANALYSIS AND MACHINE INTELLIGENCE LA English DT Article DE pattern recognition; classifier design and evaluation; discriminant analysis; ROC analysis; components-of-variance models; bootstrap methods ID STATISTICAL PATTERN-RECOGNITION; OF-VARIANCE MODELS; ROC ANALYSIS; CROSS-VALIDATION; COMPONENTS; PERFORMANCE; BOOTSTRAP; DESIGN; SIZE; INDEX AB The conventional wisdom in the field of statistical pattern recognition (SPR) is that the size of the finite test sample dominates the variance in the assessment of the performance of a classical or neural classifier. The present work shows that this result has only narrow applicability. In particular, when competing algorithms are compared, the finite training sample more commonly dominates this uncertainty. This general problem in SPR is analyzed using a formal structure recently developed for multivariate random-effects receiver operating characteristic (ROC) analysis. Monte Carlo trials within the general model are used to explore the detailed statistical structure of several representative problems in the subfield of computer-aided diagnosis in medicine. The scaling laws between variance of accuracy measures and number of training samples and number of test samples are investigated and found to be comparable to those discussed in the classic text of Fukunaga, but important interaction terms have been neglected by previous authors. Finally, the importance of the contribution of finite trainers to the uncertainties argues for some form of bootstrap analysis to sample that uncertainty. The leading contemporary candidate is an extension of the 0.632 bootstrap and associated error analysis, as opposed to the more commonly used cross-validation. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. Georgetown Univ, Dept Comp Sci, Washington, DC 20057 USA. RP Beiden, SV (reprint author), US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. NR 29 TC 23 Z9 23 U1 0 U2 2 PU IEEE COMPUTER SOC PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1314 USA SN 0162-8828 J9 IEEE T PATTERN ANAL JI IEEE Trans. Pattern Anal. Mach. Intell. PD DEC PY 2003 VL 25 IS 12 BP 1561 EP 1569 DI 10.1109/TPAMI.2003.1251149 PG 9 WC Computer Science, Artificial Intelligence; Engineering, Electrical & Electronic SC Computer Science; Engineering GA 746UA UT WOS:000186765000006 ER PT J AU Gammell, PM Harris, GR AF Gammell, PM Harris, GR TI IGBT-based kilovoltage pulsers for ultrasound measurement applications SO IEEE TRANSACTIONS ON ULTRASONICS FERROELECTRICS AND FREQUENCY CONTROL LA English DT Article ID ECHO APPLICATIONS; GENERATOR AB Two high-voltage pulser designs are presented that offer advantages in some ultrasound measurement applications, such as driving thick ultrasonic source transducers used for broadband measurements of attenuation or hydrophone frequency response and directivity. The pulsers use integrated gate bipolar transistors (IGBTs) as the switching devices, and in one design an output voltage pulse is produced that has a peak amplitude nearly twice that of the supply voltage. The pulsers are inexpensive and relatively easy to construct. The power supply need only provide the average current to charge the capacitors, as opposed to the much higher peak pulse current. With a 1200 V supply and a pulse repetition frequency of 200 Hz, the non-doubling and doubling pulsers provided peak voltages of greater than 1100 V and 2200 V, respectively, into loads ranging from 50 Omega to 500 Omega. For a 50 Omega load, slewing rates of 38 V/ns and 23 V/ns were measured for the non-doubling and doubling pulsers, respectively. For a 500 Omega load these values were 56 V/ns and 36 V/ns. C1 Gammell Appl Technol, Exmore, VA 23350 USA. US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. RP Gammell, PM (reprint author), Gammell Appl Technol, Exmore, VA 23350 USA. EM pgammell@ieee.org; grh@cdrh.fda.gov NR 14 TC 8 Z9 8 U1 0 U2 2 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 0885-3010 J9 IEEE T ULTRASON FERR JI IEEE Trans. Ultrason. Ferroelectr. Freq. Control PD DEC PY 2003 VL 50 IS 12 BP 1722 EP 1728 DI 10.1109/TUFFC.2003.1256313 PG 7 WC Acoustics; Engineering, Electrical & Electronic SC Acoustics; Engineering GA 769AM UT WOS:000188604100012 PM 14761043 ER PT J AU Price, WD AF Price, WD TI Symposium on analytical method challenges for measuring nutrients and antinutrients in plants: Introduction to the symposium SO JOURNAL OF ANIMAL SCIENCE LA English DT Editorial Material C1 US FDA, Ctr Vet Med, Off Surveillance & Compliance, Rockville, MD 20855 USA. RP Price, WD (reprint author), US FDA, Ctr Vet Med, Off Surveillance & Compliance, 7500 Standish Pl, Rockville, MD 20855 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC ANIMAL SCIENCE PI SAVOY PA 1111 NORTH DUNLAP AVE, SAVOY, IL 61874 USA SN 0021-8812 J9 J ANIM SCI JI J. Anim. Sci. PD DEC PY 2003 VL 81 IS 12 BP 3216 EP 3217 PG 2 WC Agriculture, Dairy & Animal Science SC Agriculture GA 748UH UT WOS:000186879100033 PM 14677878 ER PT J AU Kunkle, CA Schmitt, MP AF Kunkle, CA Schmitt, MP TI Analysis of the Corynebacterium diphtheriae DtxR regulon: Identification of a putative siderophore synthesis and transport system that is similar to the Yersinia high-pathogenicity island-encoded yersiniabactin synthesis and uptake system SO JOURNAL OF BACTERIOLOGY LA English DT Article ID TOXIN REPRESSOR DTXR; FERRIC UPTAKE REGULATOR; ESCHERICHIA-COLI; FUR REGULON; IRON-UPTAKE; PSEUDOMONAS-AERUGINOSA; STREPTOCOCCUS-PYOGENES; BACILLUS-SUBTILIS; OXIDATIVE STRESS; GENE-EXPRESSION AB The diphtheria toxin repressor, DtxR, is a global iron-dependent regulatory protein in Corynebacterium diphtheriae that controls gene expression by binding to 19-bp operator sequences. To further define the DtxR regulon in C. diphtheriae, a DtxR repressor titration assay (DRTA) was developed and used to identify 10 previously unknown DtxR binding sites. Open reading frames downstream from seven of the newly identified DtxR binding sites are predicted to encode proteins associated with iron or heme transport. Electrophoretic mobility shift assays indicated that DtxR was able to bind to DNA fragments carrying the 19-bp operator regions, and transcriptional analysis of putative promoter elements adjacent to the binding site sequences revealed that most of these regions displayed iron- and DtxR-regulated activity. A putative siderophore biosynthesis and transport operon located downstream from one of the DtxR binding sites, designated sid, is similar to the yersiniabactin synthesis and uptake genes encoded on the Yersinia pestis high pathogenicity island. The siderophore biosynthetic genes in the sid operon contained a large deletion in the C. diphtheriae C7 strain, but the sid genes were unaffected in four clinical isolates that are representative of the dominant strains from the recent diphtheria epidemic in the former Soviet Union. Mutations in the siderophore biosynthetic genes in a clinical strain had no effect on siderophore synthesis or growth in low-iron conditions; however, a mutation in one of the putative transport proteins, cdtP, resulted in reduced growth in iron-depleted media, which suggests that this system may have a role in iron uptake. The findings from this study indicate that C. diphtheriae contains at least, 18 DtxR binding sites and that DtxR may affect the expression of as many as 40 genes. C1 US FDA, CBER, DBPAP, Lab Bacterial Toxins, Bethesda, MD 20892 USA. RP Schmitt, MP (reprint author), US FDA, CBER, DBPAP, Lab Bacterial Toxins, 8800 Rockville Pike,Bldg 29,Room 108, Bethesda, MD 20892 USA. NR 59 TC 40 Z9 42 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD DEC PY 2003 VL 185 IS 23 BP 6826 EP 6840 DI 10.1128/JB.185.23.6826-6840.2003 PG 15 WC Microbiology SC Microbiology GA 745BY UT WOS:000186669500010 PM 14617647 ER PT J AU Merkel, TJ Boucher, PE Stibitz, S Grippe, VK AF Merkel, TJ Boucher, PE Stibitz, S Grippe, VK TI Analysis of bvgR expression in Bordetella pertussis SO JOURNAL OF BACTERIOLOGY LA English DT Article ID RESPONSE REGULATOR BVGA; RNA-POLYMERASE; FHA PROMOTER; VIRULENCE FACTORS; TOXIN PROMOTER; DNA-BINDING; ACTIVATION; PROTEIN; LOCUS; GENE AB Bordetella pertussis, the causative agent of whooping cough, produces a wide array of factors that are associated with its ability to cause disease. The expression and regulation of these virulence factors are dependent upon the bvg locus, which encodes three proteins: BvgA, a 23-kDa cytoplasmic protein; BvgS, a 135-kDa transmembrane protein; and BvgR, a 32-kDa protein. It is hypothesized that BvgS responds to environmental signals and interacts with BvgA, a transcriptional regulator, which upon modification by BvgS binds to specific promoters and activates transcription. An additional class of genes is repressed by the products of the bvg locus. The repression of these genes is dependent upon the third gene, bvgR. Expression of bvgR is dependent upon the function of BvgA and BvgS. This led to the hypothesis that the binding of phosphorylated BvgA to the bvgR promoter activates the expression of bvgR. We undertook an analysis of the transcriptional activation of bvgR expression. We identified the bvgR transcript by Northern blot analysis and identified the start site of transcription by primer extension. We determined that transcriptional activation of the bvgR promoter in an in vitro transcription system requires the addition of phosphorylated BvgA. Additionally, we have identified cis-acting regions that are required for BvgA activation of the bvgR promoter by in vitro footprinting and in vivo deletion and linker scanning analyses. A model of BvgA binding to the bvgR promoter is presented. C1 US FDA, Lab Resp & Special Pathogens, DBPAP, CBER, Bethesda, MD 20892 USA. RP Merkel, TJ (reprint author), US FDA, Lab Resp & Special Pathogens, DBPAP, CBER, Bldg 29,Room 418,29 Lincoln Dr, Bethesda, MD 20892 USA. NR 47 TC 22 Z9 24 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD DEC PY 2003 VL 185 IS 23 BP 6902 EP 6912 DI 10.1128/JB.185.23.6902-6912.2003 PG 11 WC Microbiology SC Microbiology GA 745BY UT WOS:000186669500017 PM 14617654 ER PT J AU Zhao, S Qaiyumi, S Friedman, S Singh, R Foley, SL White, DG McDermott, PF Donkar, T Bolin, C Munro, S Baron, EJ Walker, RD AF Zhao, S Qaiyumi, S Friedman, S Singh, R Foley, SL White, DG McDermott, PF Donkar, T Bolin, C Munro, S Baron, EJ Walker, RD TI Characterization of Salmonella enterica serotype Newport isolated from humans and food animals SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID TYPHIMURIUM DT104 INFECTIONS; AMPC BETA-LACTAMASE; MULTIDRUG-RESISTANT; ESCHERICHIA-COLI; ANTIBIOTIC-RESISTANCE; UNITED-STATES; IDENTIFICATION; EMERGENCE; BACTERIA; CATTLE AB Salmonella enterica serotype Newport isolates resistant to at least nine antimicrobials (including extended-spectrum cephalosporins), known as serotype Newport MDR-AmpC isolates, have been rapidly emerging as pathogens in both animals and humans throughout the United States. Resistance to extended-spectrum cephalosporins is associated with clinical failures, including death, in patients with systemic infections. In this study, 87 Salmonella serotype Newport strains were characterized by pulsed-field gel electrophoresis (PFGE) and antimicrobial susceptibility testing and examined for the presence of class 1 integrons and bla(CMY) genes. Thirty-five PFGE patterns were observed with XbaI, and three of these patterns were indistinguishable among isolates from humans and animals. Fifty-three (60%) Salmonella serotype Newport isolates were identified as serotype Newport MDR-AmpC, including 16 (53%) of 30 human isolates, 27 (93%) of 29 cattle isolates, 7 (70%) of 10 swine isolates, and 3 (30%) of 10 chicken isolates. However, 28 (32%) Salmonella serotype Newport isolates were susceptible to all 16 antimicrobials tested. The bla(CMY) gene was present in all serotype Newport MDR-AmpC isolates. Furthermore, the plasmid-mediated bla(CMY) gene was transferable via conjugation to an Escherichia coli strain. The transconjugant showed the MDR-AmpC resistance profile. Thirty-five (40%) of the isolates possessed class I integrons. Sequence analyses of the integrons showed that they contained aadA, which confers resistance to streptomycin, or aadA and dhfr, which confer resistance to trimethoprim-sulfamethoxazole. One integron from a swine isolate contained the sat-1 gene, which encodes resistance to streptothricin, an antimicrobial agent that has never been approved for use in the United States. In conclusion, Salmonella serotype Newport MDR-AmpC was commonly identified among Salmonella serotype Newport isolates recovered from humans and food animals. These findings support the possibility of transmission of this organism to humans through the food chain. C1 US FDA, Ctr Vet Med, Res Off, Div Anim & Food Microbiol, Laurel, MD 20708 USA. US FDA, Ctr Food Safety & Appl Nutr, Div Microbiol Studies, College Pk, MD 20740 USA. Michigan State Univ, Anim Hlth Diagnost Lab, E Lansing, MI 48824 USA. Stanford Univ, Ctr Med, Stanford, CA 94305 USA. RP Zhao, S (reprint author), US FDA, Ctr Vet Med, Res Off, Div Anim & Food Microbiol, Laurel, MD 20708 USA. NR 23 TC 121 Z9 136 U1 0 U2 13 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 DEC PY 2003 VL 41 IS 12 BP 5366 EP 5371 DI 10.1128/JCM.41.12.5366-5371.2003 PG 6 WC Microbiology SC Microbiology GA 753JT UT WOS:000187228800002 PM 14662912 ER PT J AU Booth, BP Gobburu, JVS AF Booth, BP Gobburu, JVS TI Considerations in analyzing single-trough concentrations using mixed-effects modeling SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article DE population pharmacokinetics; bias; trough concentrations; Bayesian estimates AB The purpose of this study was to assess the effect of trial design and data analysis choices on the bias and precision of pharmacokinetic (PK) parameter estimation, NONMEM was used to simulate and analyze plasma concentrations collected according to a dense (five samples) or sparse (single-trough samples) sampling scheme for a one-compartment open model with intravenous administration. The results indicated that the bias on estimates of CL with only single-trough data was 17% compared to less than 1% for only dense data. The estimates of CL were improved by fixing all other parameters and estimating only mean and variance of CL (-11% to 1.4%, depending on the estimation method). Adding dense data led to further improvements (-2.3% to 0.3%, depending on further improvements). In these cases, first-order conditional estimation (FOCE) methods resulted in better estimates of CL than first-order (FO) methods. These steps also improved the Bayesian estimates of CL. These studies support the following recommendations: (1) avoid collecting single-trough concentrations unless there is reasonable knowledge about the PK of the drug; (2) if collecting single-trough concentrations is inevitable, avoid estimating all parameters when modeling single-trough concentration data; (3) use prior information by modeling the single-trough concentration data along with dense data from other studies; and (4) use Bayes estimates if the PK model and its parameters are known with reasonable certainty. C1 US FDA, Ctr Drug Evaluat & Res, Off Clin Pharmacol & Biopharmaceut, Div Pharmaceut Evaluat 1, Rockville, MD 20857 USA. RP Booth, BP (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Clin Pharmacol & Biopharmaceut, Div Pharmaceut Evaluat 1, HFD-860,WOC 2,5600 Fishers Lane, Rockville, MD 20857 USA. NR 14 TC 17 Z9 18 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD DEC PY 2003 VL 43 IS 12 BP 1307 EP 1315 DI 10.1177/0091270003258670 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 743MD UT WOS:000186574800002 PM 14615466 ER PT J AU Chakrabarti, K Kaczmarek, RV Thomas, JA Romanyukha, A AF Chakrabarti, K Kaczmarek, RV Thomas, JA Romanyukha, A TI Effect of room illuminance on monitor black level luminance and monitor calibration SO JOURNAL OF DIGITAL IMAGING LA English DT Article DE black level; luminance; illuminance; image contrast; diffuse reflection; image surround ID DIGITAL MAMMOGRAPHY SYSTEM; VIEWING CONDITIONS; DISPLAY DEVICES; IMAGES; CRT AB In this article we demonstrate the effect of room illuminance and surrounding monitor black level luminance on image quality for soft copy interpretation. Luminance values of a 10% central target and image quality evaluations and observer performance using a contrast-detail mammography (CDMAM) phantom demonstrate these effects. Our results indicate that high room illuminance has a more damaging effect on image quality when the surrounding monitor luminance is 0% to 5% of the maximum monitor luminance. The effect of room illuminance is less obvious when the surrounding monitor luminance is 20% of the maximum. C1 US FDA, Radiol Devices Branch,DRARD, ODE, CDRH, Rockville, MD 20850 USA. OHIP, Div Mammog Qual & Radiat Program, CDRH, Rockville, MD 20850 USA. Uniformed Serv Univ Hlth Sci, Dept Radiol, Bethesda, MD 20814 USA. RP Chakrabarti, K (reprint author), US FDA, Radiol Devices Branch,DRARD, ODE, CDRH, HFZ-470,9200 Corp Blvd, Rockville, MD 20850 USA. EM KXC@CDRH.FDA.GOV NR 15 TC 18 Z9 18 U1 0 U2 1 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0897-1889 J9 J DIGIT IMAGING JI J. Digit. Imaging PD DEC PY 2003 VL 16 IS 4 BP 350 EP 355 DI 10.1007/s10278-003-1720-5 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 802UV UT WOS:000220189300007 PM 14747935 ER PT J AU Jang, EB Holler, T Cristofaro, M Lux, S Raw, AS Moses, AL Carvalho, LA AF Jang, EB Holler, T Cristofaro, M Lux, S Raw, AS Moses, AL Carvalho, LA TI Improved attractants for Mediterranean fruit fly, Ceratitis capitata (Wiedemann): Responses of sterile and wild flies to (-) enantiomer of ceralure B1 SO JOURNAL OF ECONOMIC ENTOMOLOGY LA English DT Article ID TEPHRITIDAE; DIPTERA; TRIMEDLURE AB Tests were conducted on wild Mediterranean fruit flies, Ceratitis capiata (Wiedemann), in Hawaii, Italy, and Kenya, and on sterile released flies in Florida and California with a new male attractant, (-)-ceralure B1. Compared on an equal dosage basis, Mediterranean fruit fly males were significantly more attracted to the (-)-ceralure B1 than to trimedlure in each of the sites tested except for California. Compared with the standard commercial 2 g trimedlure plug, 10 mg applied on cotton wicks (Kauai) was as attractive to wild males as trimedlure after the first 2 d of the test but not after 7 d. At a dose of 40 mg (50 times less than in the 2-g plug), the (-)-ceralure B1 was significantly more attractive to male flies than the 2-g trimedlure plug for the first week of service (Florida) but not after 2 wk. Studies using released sterile flies in Florida confirm our previous work on the improved attraction of (-)-ceralure B1 (40 mg) over trimedlure. However, this trend did not hold up in a single test conducted in a residential area in California that did not show a significant difference in attraction using 20 mg of compound. Future refinements in synthesis and costs of this compound and increased availability and testing will be needed before any final evaluation in the field can be carried out. C1 USDA ARS, US Pacific Basin Agr Res Ctr, Hilo, HI 96720 USA. USDA APHIS PPQ, Ctr Plant Hlth & Technol, Gainesville, FL 32608 USA. ENEA, CR Casaccia, BIOTEC, I-00060 Rome, Italy. Int Ctr Insect Physiol & Ecol, Nairobi, Kenya. US FDA, CDER, Rockville, MD 20857 USA. RP Jang, EB (reprint author), USDA ARS, US Pacific Basin Agr Res Ctr, POB 4459, Hilo, HI 96720 USA. EM ejang@pbarc.ars.usda.gov RI Lux, Slawomir/G-1731-2012 OI Lux, Slawomir/0000-0001-5978-1145 NR 17 TC 9 Z9 10 U1 0 U2 3 PU ENTOMOL SOC AMER PI LANHAM PA 9301 ANNAPOLIS RD, LANHAM, MD 20706 USA SN 0022-0493 J9 J ECON ENTOMOL JI J. Econ. Entomol. PD DEC PY 2003 VL 96 IS 6 BP 1719 EP 1723 DI 10.1603/0022-0493-96.6.1719 PG 5 WC Entomology SC Entomology GA 767RY UT WOS:000188467500013 PM 14977108 ER PT J AU Lamont, WH AF Lamont, WH TI Concentration of inorganic arsenic in samples of white rice from the United States SO JOURNAL OF FOOD COMPOSITION AND ANALYSIS LA English DT Article DE inorganic arsenic; white rice ID FLOODED CONDITIONS; ELEMENTAL CONTENT; VIETNAMESE RICE; SOIL SOLUTION AB Concentrations of inorganic arsenic were determined by ion-trap, electrospray, mass spectrometry in 40 samples of white rice, which were collected in the United States. Inorganic arsenic was qualitatively present in all samples. The quantitative range of concentrations of inorganic arsenic extended from <0.025 to 0.271 mug/g (wet-mass basis). The extremes of the range were validated with acceptable analytical recoveries of fortifications. Statistical bounds of the range were established and assessed. The distribution of concentrations over the observed range was characterized statistically with an empirical lognormal probability distribution function. For the samples of white rice, a geometric mean corresponding to 0.112 mug/g and a geometric standard deviation equivalent to 0.055 mug/g of inorganic arsenic were derived from the empirical lognormal function. Published by Elsevier Ltd. C1 Elemental Res Branch, Food & Drug Adm, College Pk, MD 20740 USA. RP Lamont, WH (reprint author), Elemental Res Branch, Food & Drug Adm, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. NR 23 TC 26 Z9 26 U1 2 U2 7 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 DEC PY 2003 VL 16 IS 6 BP 687 EP 695 DI 10.1016/S0889-1575(03)00097-8 PG 9 WC Chemistry, Applied; Food Science & Technology SC Chemistry; Food Science & Technology GA 743QW UT WOS:000186585900006 ER PT J AU Senkel, IA Jolbitado, B Zhang, YF White, DG Ayers, S Meng, JH AF Senkel, IA Jolbitado, B Zhang, YF White, DG Ayers, S Meng, JH TI Isolation and characterization of Escherichia coli recovered from Maryland apple cider and the cider production environment SO JOURNAL OF FOOD PROTECTION LA English DT Article ID HEMOLYTIC UREMIC SYNDROME; CRITICAL CONTROL POINT; ANTIBIOTIC-RESISTANCE; ANTIMICROBIAL RESISTANCE; O157-H7; SURVIVAL; EFFICACY; CATTLE; JUICE; SANITATION AB Contaminated apple cider has been implicated in several Escherichia coli O157:H7 outbreaks. In an attempt to investigate sources and modes of entry of E. coli into apple cider, samples of fresh apple, pomace, and cider and equipment and mill floor swabs were analyzed for standard plate counts (SPC), total coliforms (TC), fecal coliforms (FC), and E coli. E. coli was isolated from 14 (33%) of 42 samples of bottled fresh cider, from food equipment in 6 (67%) of 9 mills, and from apples, pomace, or cider in 7 (78%) of 9 mills. Seventy-five E. coli isolates were further characterized for Shiga toxin-producing E. coli (STEC)-associated virulence factors, antimicrobial susceptibility, and pulsed-field gel electrophoresis (PFGE) type. No E. coli O157:H7 or other STEC was identified. Serotyping and PFGE revealed 64 distinct profiles, suggesting that recovered E. coli arose from multiple independent sources. However, on one occasion, E. coli isolated from the source apple sample was closely related to the E. coli identified in the finished cider sample. E. coli isolates were further tested for antimicrobial susceptibility to 17 antimicrobial agents of human and veterinary importance. Fourteen (19%) of the 75 isolates were resistant to at least one of the antimicrobial agents tested, and 9 (12%) were resistant to at least two of these agents. Of the resistant isolates recovered, 64% were resistant to tetracycline and 57% were resistant to streptomycin. Overall, the level of E. coli contamination in source apple samples did not differ significantly from those in samples of pomace, cider at the press, and cider entering the bottling tank; therefore, source apples cannot be dismissed as a potential contributor of E. coli to the cider-making process. C1 Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA. Maryland Dept Hlth & Mental Hyg, Div Food Control, Baltimore, MD 21203 USA. Maryland Dept Hlth & Mental Hyg, Div Publ Hlth Environm Microbiol, Baltimore, MD 21203 USA. US FDA, Div Anim & Food Microbiol, Ctr Vet Med, Laurel, MD 20708 USA. RP Meng, JH (reprint author), Univ Maryland, Dept Nutr & Food Sci, 0112 Skinner Bldg, College Pk, MD 20742 USA. NR 32 TC 5 Z9 5 U1 0 U2 2 PU INT ASSOC FOOD PROTECTION PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD DEC PY 2003 VL 66 IS 12 BP 2237 EP 2244 PG 8 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 750XM UT WOS:000187023800007 PM 14672219 ER PT J AU Cook, DW AF Cook, DW TI Sensitivity of Vibrio species in phosphate-buffered saline and in oysters to high-pressure processing SO JOURNAL OF FOOD PROTECTION LA English DT Article ID HIGH HYDROSTATIC-PRESSURE; RAW OYSTERS; PARAHAEMOLYTICUS; VULNIFICUS; GULF; TEMPERATURE; INFECTIONS; ATLANTIC AB Multiple strains of Vibrio, vulnificus, Vibrio parahaemolyticus, and Vibrio cholerae non-O1 were tested in phosphate-buffered saline for their sensitivity to high-pressure processing (HPP). Variability in sensitivity among strains was observed for all species; this variability decreased at higher pressures. V. vulnificus was the species that was most sensitive to treatment at 200 MPa (decimal reduction time [D] = 26 s), and V. cholerae was the species that was most resistant to treatment at 200 MPa (D = 149 s). The O3:K6 serotype of V. parahaemolyticus was more resistant to pressure than other serotypes of V. parahaemolyticus were. The results of studies involving V. vulnificus naturally occurring in oysters revealed that a pressure treatment of 250 MPa for 120 s achieved a >5-log reduction in the levels of this bacterium. V. parahaemolyticus serotype O3:K6 in oysters required a pressure of 300 MPa for 180 s for a comparable 5-log reduction. When properly applied, HPP can be effective in improving the safety of shellfish with respect to Vibrio spp. C1 US FDA, Gulf Coast Seafood Lab, Dauphin Isl, AL 36528 USA. RP Cook, DW (reprint author), 111 White Ave, Ocean Springs, MS 39564 USA. NR 21 TC 53 Z9 59 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 DEC PY 2003 VL 66 IS 12 BP 2276 EP 2282 PG 7 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 750XM UT WOS:000187023800012 PM 14672224 ER PT J AU Muskhelishvili, L Latendresse, JR Kodell, RL Henderson, EB AF Muskhelishvili, L Latendresse, JR Kodell, RL Henderson, EB TI Evaluation of cell proliferation in rat tissues with BrdU, PCNA, Ki-67(MIB-5) immunohistochemistry and in situ hybridization for histone mRNA SO JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY LA English DT Article DE proliferation; immunohistochemistry; in situ hybridization; labeling indices ID NUCLEAR ANTIGEN PCNA; MONOCLONAL-ANTIBODY; LIVER-REGENERATION; GROWTH FRACTION; DNA-REPAIR; GASTRIC-CARCINOMA; PARAFFIN SECTIONS; PROGNOSTIC VALUE; EXPRESSION; KI-67 AB The standard method for assessment of cell proliferation in paraffin-embedded tissue sections is 5-bromodeoxyuridine (BrdU) immunohistochemistry (IHC). BrdU can be administered to laboratory animals via IP injections, is readily incorporated into nuclei during the DNA synthetic phase of the cell cycle, and is detected with an anti-BrdU antibody. This method has several disadvantages, and an accurate method for evaluation of proliferative activity that can substitute for BrdU IHC, when necessary, is of great interest to investigators. Alternative methods for detection of proliferating cells in tissue sections are proliferating cell nuclear antigen (PCNA) IHC, Ki-67 IHC, and in situ hybridization (ISH) for histone mRNA. To determine the optimal choice, we analyzed the correlation of anti-PCNA, anti-Ki-67(MIB-5), and histone mRNA labeling indices (LIs) with anti-BrdU LI in rat highly replicative (renewing) tissues. The correlation between anti-BrdU and histone mRNA Lis, as well as the correlation between anti-BrdU and anti-Ki-67 Lis, was statistically significant. There was no significant correlation between anti-BrdU and anti-PCNA Lis. These results suggest that both ISH for histone mRNA and IHC with MIB-5 are preferable techniques for assessment of cell proliferation in rat paraffin-embedded renewing tissues compared to PCNA IHC. They can substitute for BrdU IHC when necessary. C1 Natl Ctr Toxicol Res, Charles River Labs, Jefferson, AR 72079 USA. Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. RP Muskhelishvili, L (reprint author), Natl Ctr Toxicol Res, Charles River Labs, 3900 NCTR Rd,MC 923, Jefferson, AR 72079 USA. EM lmuskhelishvili@nctr.fda.gov RI Latendresse, John/A-9215-2009; Messier, Claude/A-2322-2008 OI Messier, Claude/0000-0002-4791-1763 NR 59 TC 137 Z9 144 U1 1 U2 14 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0022-1554 J9 J HISTOCHEM CYTOCHEM JI J. Histochem. Cytochem. PD DEC PY 2003 VL 51 IS 12 BP 1681 EP 1688 PG 8 WC Cell Biology SC Cell Biology GA 748UA UT WOS:000186878400012 PM 14623936 ER PT J AU Navarro, A Frevel, M Gamero, AM Williams, BRG Feldman, G Larner, AC AF Navarro, A Frevel, M Gamero, AM Williams, BRG Feldman, G Larner, AC TI Thrombomodulin RNA is destabilized through its 3 '-untranslated element in cells exposed to IFN-gamma SO JOURNAL OF INTERFERON AND CYTOKINE RESEARCH LA English DT Article ID PROTEIN-KINASE P38; MESSENGER-RNA; GENE-EXPRESSION; INTERFERON-GAMMA; BINDING PROTEIN; STABILITY; STABILIZATION; MACROPHAGES; ADHESION; LEVEL AB Interferon-gamma (IFN-gamma) is a potent activator of mononuclear phagocytes, allowing them to play a prominent role in acute and chronic inflammatory responses. IFN-gamma binding to its cell surface receptor initiates changes in the steady-state levels of cellular RNAs, permitting the proteins encoded by these RNAs to exert its biologic actions. Hundreds of cellular RNAs have been identified whose rates of transcription are altered by incubation of cells with IFNs. The rates of transcription of many of the genes encoding these RNAs are enhanced by IFN-gamma-mediated activation of the Stat1 transcription factor that is tyrosine phosphorylated and translocates to the nucleus, where it binds enhancers present in IFN-stimulated genes (ISGs). IFN-gamma can also modify the concentrations of some RNAs by posttranscriptional mechanisms. However, very little is understood about the molecular mechanisms regulating this phenomenon. We have identified the RNA encoding thrombomodulin (TM), a physiologic receptor for thrombin, that is downregulated in primary human monocytes incubated with IFN-gamma. Using actinomycin D as a transcriptional inhibitor, we show that the mRNA half-life is rapidly shortened by IFN-gamma. The TM transcript contains a large 3'-untranslated region (UTR), with several AU-rich elements (AREs), elements that have been implicated in the regulation of mRNA decay. Using a tetrcycline-regulatory promoter system, we analyzed RNA levels in the absence of transcription of TM. Results from these experiments indicate that incubation of cells with IFN-gamma accelerates the decay of TM RNA through its 3'-UTR. This is the first report describing a clear posttranscriptional downregulation of an mRNA by IFN-gamma that identifies the 3'-UTR as a target of IFN-gamma-stimulated destabilization. C1 Cleveland Clin Fdn, Lerner Res Inst, Dept Immunol, Cleveland, OH 44195 USA. Cleveland Clin Fdn, Lerner Res Inst, Dept Canc Biol, Cleveland, OH 44195 USA. Ctr Biol Evaluat & Res, Div Monoclonal Antibodies, Bethesda, MD 20892 USA. RP Larner, AC (reprint author), Cleveland Clin Fdn, Dept Immunol NB30, 9500 Euclid Ave, Cleveland, OH 44195 USA. EM larnera@ccf.org RI Williams, Bryan/A-5021-2009 OI Williams, Bryan/0000-0002-4969-1151 NR 26 TC 11 Z9 11 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1079-9907 J9 J INTERF CYTOK RES JI J. Interferon Cytokine Res. PD DEC PY 2003 VL 23 IS 12 BP 723 EP 728 DI 10.1089/107999003772084833 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 761QZ UT WOS:000187925700015 PM 14769148 ER PT J AU Whittaker, P Mossoba, MM Al-Khaldi, S Fry, FS Dunkel, VC Tall, BD Yurawecz, MP AF Whittaker, P Mossoba, MM Al-Khaldi, S Fry, FS Dunkel, VC Tall, BD Yurawecz, MP TI Identification of foodborne bacteria by infrared spectroscopy using cellular fatty acid methyl esters SO JOURNAL OF MICROBIOLOGICAL METHODS LA English DT Article DE bacteria; infrared; principal component analysis (PCA); soft independent modeling of class analogy (SIMCA) ID CHROMATOGRAPHY-MASS-SPECTROMETRY; GAS-CHROMATOGRAPHY; TRIMETHYLSULFONIUM HYDROXIDE; VIBRATIONAL SPECTROSCOPY; RELEVANT MICROORGANISMS; CLASSIFICATION; PYROLYSIS; PROFILES; STRAINS AB Identification of bacterial species by profiling fatty acid methyl esters (FAMEs) has commonly been carried out by using a 20-min capillary gas chromatographic procedure followed by library matching of FAME profiles using commercial MIDI databases and proprietary pattern recognition software. Fast GC (5 min) FAME procedures and mass spectrometric methodologies that require no lipid separation have also been reported. In this study, bacterial identification based on the rapid (2 min) infrared measurement of FAME mixtures was demonstrated. The microorganisms investigated included Gram positive bacteria Staphylococcus aureus, Listeria monocytogenes, Bacillus anthracis, and Bacillus cereus, and Gram negative bacteria from the family Enterobacteriacae: Yersinia enterocolitica, Salmonella typhimurium, Shigella sonnei, and Escherichia coli (four strains of E. coli), and non-Enterobacteriacae: Vibrio cholerae, Vibrio vulnificus, and Vibrio parahemolyticus. Foodborne bacterial mixtures of FAMEs were measured by using an attenuated total reflection (ATR)-Fourier transform infrared (FTIR) spectroscopic procedure and discriminated by multivariate analysis. Results showed that the Enterobacteriacae could be discriminated from the vibrios. The identification was at the level of species (for the Bacillus and Hibrio genera) or strains (for the E. coli species). A series of bacterial FAME test samples were prepared and analyzed for accuracy of identification, and all were correctly identified. Our results suggest that this infrared strategy could be used to identify foodborne pathogens. Published by Elsevier B.V. C1 OSAS, Div Gen Sci Support, FDA, CFSAN, College Pk, MD 20740 USA. ONPLDS, Div Res & Appl Technol, FDS, CFSAN, College Pk, MD 20740 USA. OPDFB, Div Microbiol Studies, FDA, CFSAN, College Pk, MD 20740 USA. FDS, CFSAN, OSCI, College Pk, MD 20740 USA. RP Mossoba, MM (reprint author), OSAS, Div Gen Sci Support, FDA, CFSAN, 5100 Paint Branch Pkwy,Mail Stop HFS 717,Room BE-, College Pk, MD 20740 USA. OI Tall, Ben/0000-0003-0399-3629 NR 26 TC 23 Z9 27 U1 0 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-7012 J9 J MICROBIOL METH JI J. Microbiol. Methods PD DEC PY 2003 VL 55 IS 3 BP 709 EP 716 DI 10.1016/j.mimet.2003.07.005 PG 8 WC Biochemical Research Methods; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 747UP UT WOS:000186823500016 PM 14607413 ER PT J AU Ali, SF Itzhak, Y AF Ali, SF Itzhak, Y TI Acute and repeated administration of gamma-hydroxybutyrate (GBH) produces neurobehavioral and neurochemical alterations in mice SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT Joint Meeting of the International-Society-for-Neurochemistry/Asian-Pacific-Society-for-Neuro chemistry CY AUG 03-08, 2003 CL WANCHAI, PEOPLES R CHINA SP Int soc Neurochem, Asian Pacific Soc Neurochem DE CPP; dopamine; GBL; GHB; neurotoxicity; tolerance C1 US FDA, Natl Ctr Toxicol Res, Neurochem Lab, Div Neurotoxicol, Jefferson, AR 72079 USA. Univ Miami, Sch Med, Dept Psychiat & Behav Sci, Miami, FL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD DEC PY 2003 VL 87 SU 1 BP 69 EP 69 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 753PR UT WOS:000187240200237 ER PT J AU Sloan, E O'Neill, M Kaysner, C DePaola, A Nordstrom, JL Sofosi, J AF Sloan, E O'Neill, M Kaysner, C DePaola, A Nordstrom, JL Sofosi, J TI Evaluation of two nonradioactive gene probes for the enumeration of Vibrio parahaemolyticus in crabmeat SO JOURNAL OF RAPID METHODS AND AUTOMATION IN MICROBIOLOGY LA English DT Article ID THERMOLABILE HEMOLYSIN; CHESAPEAKE BAY; OYSTERS; MEDIA; WASHINGTON; WATERS; TDH AB This study evaluated two nonradioactive DNA probe procedures for the detection and enumeration of Vibrio parahaemolyticus in crabmeat by comparing counts obtained by direct plating and by most probable number (MPN) procedures. The nonradioactive probes evaluated were an alkaline phosphatase-labeled thermolabile direct hemolysin (AP-tlh) and a digoxigenin-labeled thermostable direct hemolysin (DG-tdh) for detection and enumeration of total and pathogenic V. parahaemolyticus, respectively. Inoculated samples (50 g each) of steamed crabmeat were analyzed by nine analysts in seven laboratories. Samples were inoculated with various Vibrio strains and combinations of strains at different levels of inoculation (0 to 92, 000 cells/g). The results indicated that the AP-tlh probe was reliable for identification and enumeration of total V. parahaemolyticus and the DG-tdh probe was specific for the pathogenic strains. Both probes required less effort and expense than the biochemical testing and hemolysin assays that have previously been used. ne MPN and direct plating procedures using the nonradioactive probes were both effective for enumeration of total and pathogenic V. parahaemolyticus in the absence of competing microflora, but direct plating was preferable to MPN for enumeration of V. parahaemolyticus, especially pathogenic strains, in the presence of competitors. C1 US FDA, Denver Fed Ctr, Denver Dist Lab, Denver, CO 80225 USA. US FDA, Pacific Reg Lab NW, Bothell, WA 98021 USA. US FDA, Seafood Prod Res Ctr, Bothell, WA 98021 USA. US FDA, Gulf Coast Seafood Lab, Dauphin Isl, AL 36528 USA. Colorado State Univ, Dept Anim Sci, Ft Collins, CO 80523 USA. RP Nordstrom, JL (reprint author), US FDA, Denver Fed Ctr, Denver Dist Lab, POB 25087, Denver, CO 80225 USA. EM jessica.nordstrom@cfsan.fda.gov NR 29 TC 2 Z9 2 U1 0 U2 2 PU FOOD NUTRITION PRESS INC PI TRUMBULL PA 6527 MAIN ST, P O BOX 374, TRUMBULL, CT 06611 USA SN 1060-3999 J9 J RAPID METH AUT MIC JI '. Rapid Methods Autom. Microbiol. PD DEC PY 2003 VL 11 IS 4 BP 297 EP 311 DI 10.1111/j.1745-4581.2003.tb00269.x PG 15 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 807NW UT WOS:000220509200004 ER PT J AU Li, L Chiarelli, MP Branco, PS Antunes, AM Marques, MM Goncalves, LL Beland, FA AF Li, L Chiarelli, MP Branco, PS Antunes, AM Marques, MM Goncalves, LL Beland, FA TI Differentiation of isomeric C8-substituted alkylaniline adducts of guanine by electrospray ionization and tandem quadrupole ion trap mass spectrometry SO JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY LA English DT Article; Proceedings Paper CT 15th Sanibel Conference on Mass Spectrometry CY 2003 CL SANIBEL ISLAND, FL ID METHYLATED ANILINES PRESENT; FAST-ATOM-BOMBARDMENT; TOBACCO-SMOKE; DNA-ADDUCTS; IDENTIFICATION; SPECTRA AB Product ion spectra from thirteen C8-substituted alkylaniline adducts of guanine and deoxyguanosine were generated using electrospray ionization and quadrupole ion trap mass spectrometry and studied to investigate the possibility of differentiating isomeric adduct structures based upon the relative abundances of fragment ions derived from the alkylaniline-modified guanine bases (BH2+ ions). The structural discrimination of the BH2+ ions formed by attachment of isomeric alkylanilines to the C8 position of guanine is a challenging problem because the ions tend to yield product ion spectra that are qualitatively identical upon collisional activation. In this study, a statistical method, referred to as a similarity index, was used to compare the product ion spectra of isomeric BH2+ ions and differentiate their structures. All the adducts investigated could be distinguished from SIs calculated using 5-6 product ions. These results suggest that a searchable database of product ion spectra may be created and used to characterize DNA adducts from aromatic amines whenever they are detected at levels amenable to mass spectral analysis. (C) 2003 American Society for Mass Spectrometry. C1 Loyola Univ, Dept Chem, Chicago, IL 60626 USA. Univ Nova Lisboa, Fac Ciencias & Tecnol, Ctr Quim Fina & Biotechnol, Dept Quim, Caparica, Portugal. Inst Super Tecn, Ctr Quim Estrutural, Lisbon, Portugal. Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR USA. RP Chiarelli, MP (reprint author), Loyola Univ, Dept Chem, 1068 W Sheridan Rd, Chicago, IL 60626 USA. EM mchiare@luc.edu RI Branco, Paula/I-6567-2012; REQUIMTE, ORG/M-4578-2013; REQUIMTE, LAQV/N-9835-2013; Marques, M. Matilde/E-2535-2012; Antunes, Alexandra/B-7871-2009; Goncalves, Luisa/A-4120-2016; OI Branco, Paula/0000-0002-7312-8596; Marques, M. Matilde/0000-0002-7526-4962; Antunes, Alexandra/0000-0003-1827-7369; Goncalves, Luisa/0000-0002-3654-8612; Goncalves, Luisa/0000-0002-2385-7395 NR 18 TC 9 Z9 9 U1 1 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1044-0305 J9 J AM SOC MASS SPECTR JI J. Am. Soc. Mass Spectrom. PD DEC PY 2003 VL 14 IS 12 BP 1488 EP 1492 DI 10.1016/j.jasms.2003.08.009 PG 5 WC Biochemical Research Methods; Chemistry, Analytical; Chemistry, Physical; Spectroscopy SC Biochemistry & Molecular Biology; Chemistry; Spectroscopy GA 755UH UT WOS:000187429500015 PM 14652195 ER PT J AU Shaikh, B Rummel, N Gieseker, C Serfling, S Reimschuessel, R AF Shaikh, B Rummel, N Gieseker, C Serfling, S Reimschuessel, R TI Metabolism and residue depletion of albendazole and its metabolites in rainbow trout, tilapia and Atlantic salmon after oral administration SO JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS LA English DT Article ID PHARMACOKINETICS; SHEEP; CATTLE; FENBENDAZOLE; ANTHELMINTICS AB Metabolic and residue depletion profiles of albendazole (ABZ) and its major metabolites in three fish species, rainbow trout, tilapia and Atlantic salmon are reported. Based on these profiles, similarities (or dissimilarities) between species will determine the potential to group fish species. ABZ at 10 mg/kg body weight was incorporated into fish food formulated in a gelatin base or in gel capsule and fed as a single dose to six fish from each species. Rainbow trout were held three each in a partitioned 600-L tank. Tilapia and Atlantic salmon were housed in separate 20-L tanks. Samples of muscle with adhering skin were collected at 8, 12, 18, 24, 48, 72, and 96 h postdose from trout kept at 12 degreesC, at 4, 8, 12, 24, 48, 72, 96, 120, and 144 h postdose from tilapia kept at 25 degreesC and at 8, 14, 24, 48, 72, and 96 h postdose from Atlantic salmon kept at 15 degreesC. The samples were homogenized in dry ice and subjected to extraction and cleanup procedures. The final extracts were analyzed for parent drug ABZ and its major metabolites, albendazole sulfoxide (ABZ-SO), albendazole sulfone (ABZ-SO2) and albendazole aminosulfone using high-performance liquid chromatography with fluorescence detection. ABZ was depleted by 24 h in trout and tilapia and by 48 h in salmon; ABZ-SO, a pharmacologically active metabolite, was depleted by 48 h in tilapia, by 72 h in rainbow trout and was present until 96 h in salmon; and low levels of ABZ-SO2 and albendazole aminosulfone, both inactive metabolites, were detectable at least till 96 h in all three fish species. C1 US FDA, Ctr Vet Med, Res Off, Laurel, MD 20708 USA. RP Shaikh, B (reprint author), US FDA, Ctr Vet Med, Res Off, 8401 Muirkirk Rd, Laurel, MD 20708 USA. NR 22 TC 11 Z9 11 U1 0 U2 7 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0140-7783 J9 J VET PHARMACOL THER JI J. Vet. Pharmacol. Ther. PD DEC PY 2003 VL 26 IS 6 BP 421 EP 427 DI 10.1046/j.0140-7783.2003.00534.x PG 7 WC Pharmacology & Pharmacy; Veterinary Sciences SC Pharmacology & Pharmacy; Veterinary Sciences GA 757FL UT WOS:000187550100004 PM 14962053 ER PT J AU Korotkova, EA Park, R Cherkasova, EA Lipskaya, GY Chumakov, KM Feldman, EV Kew, OM Agol, VI AF Korotkova, EA Park, R Cherkasova, EA Lipskaya, GY Chumakov, KM Feldman, EV Kew, OM Agol, VI TI Retrospective analysis of a local cessation of vaccination against poliomyelitis: a possible scenario for the future SO JOURNAL OF VIROLOGY LA English DT Article ID IMMUNODEFICIENT PATIENT; POLIOVIRUS STRAINS; WILD POLIOVIRUS; ERADICATION; EVOLUTION; CIRCULATION; PERSISTENCE; RECOMBINANT; DELIVERY; VACCINES AB The global eradication of poliomyelitis will require substantial changes in immunization practices. One of the proposed scenarios includes cessation of vaccination with live oral poliovirus vaccine (OPV) and the creation of an OPV stockpile for emergency response in case of the reintroduction of poliovirus into circulation. We describe here a retrospective analysis of the cessation of OPV usage in a region of the Byelorussian Republic of the former Soviet Union in 1963 to 1966. During this period, a widespread circulation and evolution of independent lineages of vaccine-derived polioviruses took place in the region. Some of these lineages appeared to originate from OPV given to 40 children in the community during this period of essentially no vaccinations. The data demonstrate very high risks associated with both the local cessation of OPV vaccination and the proposed use of OPV to control a possible reemergence of poliovirus in the postvaccination period. The high transmissibility of Off-derived viruses in nonimmune population, documented here, and the known existence of long-term OPV excretors should be also considered in assessing risks of the synchronized global cessation of OPV usage. C1 Russian Acad Med Sci, Inst Poliomyelitis & Viral Encephalitis, Moscow 142782, Russia. Res Inst Epidemiol & Microbiol, Minsk 220050, Byelarus. Ctr Dis Control & Prevent, Natl Ctr Infect Dis, Atlanta, GA 30333 USA. Ctr Biol Evaluat & Res Food & Drug Adm, Rockville, MD 20852 USA. European Reg Off World Hlth Org, DK-2100 Copenhagen, Denmark. RP Agol, VI (reprint author), Inst Poliomyelitis, Kievskoye Shosse 27 Km, Moscow 142782, Russia. RI Agol, Vadim/E-1941-2013 NR 32 TC 41 Z9 41 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 2003 VL 77 IS 23 BP 12460 EP 12465 DI 10.1128/JVI.77.23.12460-12465.2003 PG 6 WC Virology SC Virology GA 744DM UT WOS:000186612700009 PM 14610170 ER PT J AU Prince, GA Mond, JJ Porter, DD Yim, KC Lan, SJ Klinman, DM AF Prince, GA Mond, JJ Porter, DD Yim, KC Lan, SJ Klinman, DM TI Immunoprotective activity and safety of a respiratory syncytial virus vaccine: Mucosal delivery of fusion glycoprotein with a CpG oligodeoxynucleotide adjuvant SO JOURNAL OF VIROLOGY LA English DT Article ID COTTON RATS; SIGMODON-HISPIDUS; IMMUNE GLOBULIN; INFECTION; DISEASE; IMMUNIZATION; PATHOGENESIS; INFANTS; HOSPITALIZATION; PNEUMONIA AB CpG oligodeoxynucleotides (ODN) were identified that stimulated immunoglobulin production and cell proliferation in cotton rat cells in vitro. Three of these ODN were used as a mucosall adjuvant in the noses of cotton rats immunized via this route with respiratory syncytial virus fusion (F) protein. The CpG ODN markedly increased the cotton rat humoral neutralizing-antibody response to respiratory syncytial virus. Such immunized animals had a marked reduction in the production of infectious virus after a live-virus challenge. Animals immunized with the combination of F protein and CpG developed enhanced pulmonary pathology consisting of alveolitis and interstitial pneumonitis after a live-virus challenge. Similar enhanced disease has been seen in cotton rats and children immunized with formalin-inactivated respiratory syncytial virus. C1 Vir Syst Inc, Rockville, MD 20850 USA. US FDA, Ctr Biol Evaluat & Res, Sect Retroviral Immunol, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA. Biosynexus Inc, Gaithersburg, MD 20877 USA. RP Prince, GA (reprint author), Vir Syst Inc, 9610 Med Ctr Dr,Suite 100, Rockville, MD 20850 USA. FU PHS HHS [MM8929] NR 29 TC 35 Z9 38 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 2003 VL 77 IS 24 BP 13156 EP 13160 DI 10.1128/JVI.77.24.13156-13160.2003 PG 5 WC Virology SC Virology GA 750YF UT WOS:000187025500024 PM 14645572 ER PT J AU Rubin, SA Amexis, G Pletnikov, M Li, ZQ Vanderzanden, J Mauldin, J Sauder, C Malik, T Chumakov, K Carbone, KA AF Rubin, SA Amexis, G Pletnikov, M Li, ZQ Vanderzanden, J Mauldin, J Sauder, C Malik, T Chumakov, K Carbone, KA TI Changes in mumps virus gene sequence associated with variability in neurovirulent phenotype (vol 77, pg 11616, 2003) SO JOURNAL OF VIROLOGY LA English DT Correction C1 US FDA, Ctr Biol Evaluat & Res, DVP, Off Vaccines Res & Rev, Bethesda, MD 20892 USA. Johns Hopkins Univ, Dept Psychiat, Baltimore, MD 21205 USA. Johns Hopkins Univ, Dept Med, Baltimore, MD 21205 USA. RP Rubin, SA (reprint author), US FDA, Ctr Biol Evaluat & Res, DVP, Off Vaccines Res & Rev, Bethesda, MD 20892 USA. NR 1 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 2003 VL 77 IS 24 BP 13456 EP 13456 DI 10.1128/JVI.77.24.13456.2003 PG 1 WC Virology SC Virology GA 750YF UT WOS:000187025500056 ER PT J AU Yoshitomi, KJ Jinneman, KC Weagant, SD AF Yoshitomi, KJ Jinneman, KC Weagant, SD TI Optimization of a 3 '-minor groove binder-DNA probe targeting the uidA gene for rapid identification of Escherichia coli O157 : H7 using real-time PCR SO MOLECULAR AND CELLULAR PROBES LA English DT Article DE Escherichia coli O157 : H7; uidA; minor groove binder probe ID POLYMERASE-CHAIN-REACTION; HEMOLYTIC UREMIC SYNDROME; MULTIPLEX PCR; VIRULENCE FACTORS; MOLECULAR BEACONS; SEROTYPE O157-H7; BOVINE FECES; TOXIN GENES; ASSAY; AMPLIFICATION AB Enterohemorrhagic Escherichia coli are harmful human pathogens capable of causing bloody diarrhea and vomiting. An important serotype commonly associated with human illness is the E. coli O157:H7 serotype. Unlike other real-time polymerase chain reaction (PCR) methods for identifying E. coli O157:H7, this study describes the development and optimization of a real-time PCR method targeting a conserved point mutation at +93 in the uidA (gusA) gene that is unique to O157:H7, distinguishing it from non-O15TH7 serotypes. A TET-labeled Minor Groove Binder (MGB) DNA probe was designed for use in a 5' nuclease PCR assay. Using a panel of two E. coli O157:H7 strains, three E. coli non-O157:H7 strains, and one non-E. coli species, the assay was optimized for the specific detection of the E. coli O15TH7 strains. Optimal conditions were identified at high anneal/extend temperatures, low magnesium concentrations, and low probe concentrations, resulting in correct identification of E. coli O15TH7 and non-O157:H7 strains. The improved specificity of MGB probes for single base pair mismatches such as the +93 uidA mutation provides a novel approach towards rapid identification of E. coli O157:H7. Published by Elsevier Ltd. C1 US FDA, Seafood Prod Res Ctr, Bothell, WA 98021 USA. US FDA, Pacific Reg Lab NW, Bothell, WA 98021 USA. RP Yoshitomi, KJ (reprint author), US FDA, Seafood Prod Res Ctr, 22201 23rd Dr SE, Bothell, WA 98021 USA. EM ken.yoshitomi@fda.gov NR 43 TC 26 Z9 26 U1 0 U2 1 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0890-8508 J9 MOL CELL PROBE JI Mol. Cell. Probes PD DEC PY 2003 VL 17 IS 6 BP 275 EP 280 DI 10.1016/j.mcp.2003.07.001 PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Cell Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Cell Biology GA 746GA UT WOS:000186737600002 PM 14602477 ER PT J AU Nawaz, MS Wang, RF Khan, SA Khan, AA AF Nawaz, MS Wang, RF Khan, SA Khan, AA TI Detection of galE gene by polymerase chain reaction in campylobacters associated with Guillain-Barre syndrome SO MOLECULAR AND CELLULAR PROBES LA English DT Article DE galE gene; polymerase chain reaction; Guillain-Barre syndrome ID FISHERS-SYNDROME; JEJUNI; VIRULENCE AB Guillain-Barre Syndrome (GBS) is a neuromuscular disorder and campylobacteriosis is known to trigger the onset of the disorder. A polymerase chain reaction (PCR) protocol was developed that could specifically amplify a 497-bp region of the UDP-galactose 4-epimerase (gal E) gene sequence in campylobacters responsible for triggering the onset of GBS. The identity of the PCR product was confirmed by HindIII endonuclease restriction digestion, which produced the predicted 430 and 67-bp DNA fragments. The assay could detect the presence of the gene in Campylobacter suspensions containing as few as 5 cells ml(-1). The assay detected the presence of the gene in 17 of the 20 campylobacters isolated from chicken, 9 of the 13 campylobacters isolated from turkey and 7 of the 7 campylobacters isolated from human stools. All Campylobacter strains isolated from chicken, turkey and clinical samples were resistant to multiple antibiotics. The assay failed to detect the presence of the gene in five different microaerophilic strains of Helicobacter spp., E. coli and Salmonella spp. The entire diagnostic assay, including template preparation, amplification and electrophoresis, can be completed within 6 h. (C) 2003 Published by Elsevier Ltd. C1 US FDA, Natl Ctr Toxicol Res, Dept Microbiol, Jefferson, AR 72079 USA. RP Nawaz, MS (reprint author), US FDA, Natl Ctr Toxicol Res, Dept Microbiol, Jefferson, AR 72079 USA. NR 19 TC 2 Z9 2 U1 1 U2 1 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0890-8508 J9 MOL CELL PROBE JI Mol. Cell. Probes PD DEC PY 2003 VL 17 IS 6 BP 313 EP 317 DI 10.1016/j.mcp.2003.08.002 PG 5 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Cell Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Cell Biology GA 746GA UT WOS:000186737600008 PM 14602483 ER PT J AU Mohammad, RM Al-Katib, A Aboukameel, A Doerge, DR Sarkar, F Kucuk, O AF Mohammad, RM Al-Katib, A Aboukameel, A Doerge, DR Sarkar, F Kucuk, O TI Genistein sensitizes diffuse large cell lymphoma to CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID NF-KAPPA-B; STANDARD REGIMEN CHOP; NON-HODGKINS-LYMPHOMA; JAPANESE MEN; TNF-ALPHA; PROTEINS; ACTIVATION; INHIBITOR; CANCER; ANGIOGENESIS AB The incidence of non-Hodgkin's lymphoma (NHL) has been increasing and is now the leading cause of death in males aged 15-54. Diffuse large cell lymphoma (DLCL) is the most common subtype of NHL. These cells are notable for the high expression of the transcription factor nuclear factor kappa beta (NF-kappaB), raising the possibility that constitutive activation of the NF-kappaB pathway may contribute to the poor prognosis of DLCL patients. Soy isoflavone genistein promotes apoptosis by decreasing NF-kappaB activity. The combination of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) remains the standard therapy for DLCL with a cure rate of -40%. The WSU-DLCL2 cell line and its severe combined immunodeficient (SCID) xenograft have constitutively active NF-kappaB which provides us with an excellent model in which to study NFr,B modulation and CHOP sensitization by genistein. The antitumor activity of CHOP with or without a genistein was evaluated in our WSU-DLCL2 model. In vivo, WSU-DLCL2-bearing SCID mice received genistein alone (800 mug kg(-1) 1 day(-1), p.o. as gavages for 5 days), CHOP alone ("C", 40 mg/kg, Lv.; "H", 3.3 mg/kg, Lv.; "0", 0.5 mg/kg, Lv.; and "P", 0.2 mg/kg, every day for 5 days, p.o.), or genistein for 5 days followed by CHOP. Tumor growth inhibition (T/C), tumor growth delay (T - C), and log(10) kill for genistein, CHOP, and genistein followed by CHOP were 33.6%, 19.2%, and 5.2%; 7, 8, and 17 days; and 1.0, 1.2, and 2.6, respectively. To begin elucidating the mechanism of genistein-induced sensitization of WSU-DLCL2 cells to CHOP chemotherapy in this xenograft mouse model, we studied the in vitro effect of genistein on WSU-DLCL2 growth inhibition, cell cycle, Bax:Bcl-2 ratio, NF-kappaB DNA binding, and apoptosis in vitro. At 30 muM, genistein inhibited the growth significantly, induced G(2)-M arrest, increased Bax:Bcl-2 ratio, decreased NF-kappaB DNA binding, and induced apoptosis. Genistein also inhibited NF-kappaB DNA binding in vivo, whereas CHOP enhanced it. Our results show that genistein has growth modulatory effects on `WSU-DLCL2 cells and enhances the antitumor activity of CHOP. Because soy isoflavone genistein is a widely available nutritional supplement, its use in combination with CHOP chemotherapy should be further explored in a clinical trial in patients with NHL. C1 Wayne State Univ, Sch Med, Div Hematol & Oncol, Karmanos Canc Inst, Detroit, MI 48201 USA. Wayne State Univ, Sch Med, Dept Internal Med, Detroit, MI 48201 USA. Wayne State Univ, Sch Med, Dept Pathol, Detroit, MI 48201 USA. Wayne State Univ, Sch Med, Dept Internal Med, Detroit, MI 48201 USA. US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Mohammad, RM (reprint author), Wayne State Univ, Sch Med, Div Hematol & Oncol, Karmanos Canc Inst, 724 HWCRC,4100 John R St, Detroit, MI 48201 USA. FU NCI NIH HHS [P30 CA33453-20] NR 33 TC 42 Z9 48 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD DEC PY 2003 VL 2 IS 12 BP 1361 EP 1368 PG 8 WC Oncology SC Oncology GA 759PW UT WOS:000187746900012 PM 14707277 ER PT J AU LoPachin, RM Jones, RC Patterson, TA Slikker, W Barber, DS AF LoPachin, RM Jones, RC Patterson, TA Slikker, W Barber, DS TI Application of proteomics to the study of molecular mechanisms in neurotoxicology SO NEUROTOXICOLOGY LA English DT Review DE proteome; neurotoxicant; protein adduction; mass spectroscopy ID ALZHEIMERS-DISEASE BRAIN; OXIDATIVELY MODIFIED PROTEINS; CREATINE-KINASE BB; MASS-SPECTROMETRY; 2-DIMENSIONAL ELECTROPHORESIS; TOP-DOWN; IDENTIFICATION; ELECTROSPRAY; TECHNOLOGY; COMPLEX AB The proteome is the protein compliment of the genome and is the result of genetic expression, ribosomal synthesis and proteolytic degradation. Proteins participate in most major cell processes and their function is highly regulated by post-translational modifications such as phosphorylation and glycosylation. As a result, neurotoxicant-induced changes in protein levels, function or regulation could have a negative impact on neuronal viability. At the molecular level, direct oxidative or covalent modifications of individual proteins by various chemicals or drugs is likely to lead to perturbation of tertiary structure and a loss of function. The proteome and the functional determinants of its individual protein components are, therefore, likely targets of neurotoxicant action and resulting characteristic disruptions could be critically involved in corresponding mechanisms of neurotoxicity. Clearly, investigating changes in the proteome can provide important clues for deciphering mechanisms of toxicant action and, therefore, proteomics, the study of the proteome, is currently, and will likely remain, a significant experimental approach for mechanistic research in neurotoxicology. The purpose of this review is to discuss proteomics as a tool for neurotoxicological investigations. A variety of classic proteomic techniques (e.g. liquid chromatography (LC)/tandem mass spectroscopy, two-dimensional gel image analysis) as well as more recently developed approaches (e.g. two-hybrid systems, antibody arrays, protein chips, isotope-coded affinity tags, ICAT) are available to determine protein levels, identify components of multiprotein complexes and to detect post-translational changes. Proteomics, therefore, offers a comprehensive overview of cell proteins, and in the case of neurotoxicant exposure, can provide quantitative data regarding changes in corresponding expression levels and/or post-translational modifications that might be associated with neuron injury. (C) 2003 Elsevier Inc. All rights reserved. C1 Albert Einstein Coll Med, Monash Med Ctr, Dept Anesthesiol, Bronx, NY 10467 USA. US FDA, Natl Ctr Toxicol Res, Div Chem, Jefferson, AR 72079 USA. Univ Florida, Ctr Environm & Human Technol, Gainesville, FL USA. RP LoPachin, RM (reprint author), Albert Einstein Coll Med, Monash Med Ctr, Dept Anesthesiol, Moses 7,111 E,210th St, Bronx, NY 10467 USA. FU NIEHS NIH HHS [R01 ES03830-17, ES07912-07] NR 50 TC 20 Z9 22 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0161-813X J9 NEUROTOXICOLOGY JI Neurotoxicology PD DEC PY 2003 VL 24 IS 6 BP 761 EP 775 DI 10.1016/j.neuro.2003.08.003 PG 15 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA 751NV UT WOS:000187074600001 PM 14637371 ER PT J AU Xu, ZJ Seidler, FJ Tate, CA Garcia, SJ Slikker, W Slotkin, TA AF Xu, ZJ Seidler, FJ Tate, CA Garcia, SJ Slikker, W Slotkin, TA TI Sex-selective hippocampal alterations after adolescent nicotine administration: Effects on neurospecific proteins SO NICOTINE & TOBACCO RESEARCH LA English DT Article ID RAT-BRAIN REGIONS; FIBRILLARY ACIDIC PROTEIN; NERVOUS-SYSTEM; DENTATE GYRUS; POSTNATAL-DEVELOPMENT; GENE-EXPRESSION; UP-REGULATION; ADULT-RATS; EXPOSURE; NEURONS AB Nicotine is a neuroteratogen that targets cell development and synaptic function into adolescence, when smoking typically commences. We used a rat model of adolescent nicotine exposure to characterize the types of cells involved in hippocampal alterations. Nicotine was given to adolescent rats by minipump infusions from postnatal day (PN) 30 to PN47.5, using a dose rate (6 mg/kg/day) that replicates the plasma nicotine levels found in smokers. We examined specific neuronal and astrocyte proteins in the posttreatment period (PN50, PN60), when deficits in neurotransmission first appear: glial fibrillary acidic protein (GFAP), a marker for astrocytes; neurofilament 68-kDa protein (NF68), which is:concentrated in the neuronal perikaryon and proximal neurites; and neurofilament 200-kDa protein (NF200), which is found in axonal projections distal to the perikaryon. Adolescent nicotine treatment evoked a significant decrease across all three markers, with the effect restricted to females and showing intensification between PN50 and PN60. These changes correspond to the sex-selectivity and temporal course over which other biomarkers indicate hippocampal cell damage and alterations in synaptic function. We conclude that administration of nicotine to adolescent rats alters neuroproteins in the female hippocampus during withdrawal, effects that could contribute to neurobehavioral deficits. C1 Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Durham, NC 27710 USA. Univ Arkansas Med Sci, Dept Pharmacol & Toxicol, Little Rock, AR USA. Natl Ctr Toxicol Res, US FDA, Div Neurotoxicol, Jefferson, AR USA. RP Slotkin, TA (reprint author), Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Box 3813 DUMC, Durham, NC 27710 USA. EM t.slotkin@duke.edu FU NIDA NIH HHS [DA14247] NR 58 TC 19 Z9 20 U1 0 U2 1 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1462-2203 J9 NICOTINE TOB RES JI Nicotine Tob. Res. PD DEC PY 2003 VL 5 IS 6 BP 955 EP 960 DI 10.1080/14622200310001615321 PG 6 WC Substance Abuse; Public, Environmental & Occupational Health SC Substance Abuse; Public, Environmental & Occupational Health GA 764ZL UT WOS:000188241000019 PM 14668080 ER PT J AU Turk, DC Dworkin, RH Allen, RR Bellamy, N Brandenburg, N Carr, DB Cleeland, C Dionne, R Farrar, JT Galer, BS Hewitt, DJ Jadad, AR Katz, NP Kramer, LD Manning, DC McCormick, CG McDermott, MP McGrath, P Quessy, S Rappaport, BA Robinson, JP Royal, MA Simon, L Stauffer, JW Stein, W Tollett, J Witter, J AF Turk, DC Dworkin, RH Allen, RR Bellamy, N Brandenburg, N Carr, DB Cleeland, C Dionne, R Farrar, JT Galer, BS Hewitt, DJ Jadad, AR Katz, NP Kramer, LD Manning, DC McCormick, CG McDermott, MP McGrath, P Quessy, S Rappaport, BA Robinson, JP Royal, MA Simon, L Stauffer, JW Stein, W Tollett, J Witter, J TI Core outcome domains for chronic pain clinical trials: IMMPACT recommendations SO PAIN LA English DT Article DE chronic pain; clinical trials; assessment; outcomes; quality of life; physical functioning; emotional functioning; adverse events; global ratings ID QUALITY-OF-LIFE; LOW-BACK-PAIN; CONSORT STATEMENT; HEALTH-STATUS; IMPACT; RESPONSIVENESS; OSTEOARTHRITIS; MANAGEMENT; DISTRESS; SOCIETY AB Objective. To provide recommendations for the core outcome domains that should be considered by investigators conducting clinical trials of the efficacy and effectiveness of treatments for chronic pain. Development of a core set of outcome domains would facilitate comparison and pooling of data, encourage more complete reporting of outcomes, simplify the preparation and review of research proposals and manuscripts, and allow clinicians to make informed decisions regarding the risks and benefits of treatment. Methods. Under the auspices of the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT), 27 specialists from academia. governmental agencies, and the pharmaceutical industry participated in a consensus meeting and identified core outcome domains that should be considered in clinical trials of treatments for chronic pain. Conclusions. There was a consensus that chronic pain clinical trials should assess outcomes representing six core domains: (1) pain, (2) physical functioning, (3) emotional functioning, (4) participant ratings of improvement and satisfaction with treatment, (5) symptoms and adverse events, (6) participant disposition (e.g. adherence to the treatment regimen and reasons for premature withdrawal from the trial). Although consideration should be given to the assessment of each of these domains, there may be exceptions to the general recommendation to include all of these domains in chronic pain trials. When this occurs, the rationale for not including domains should be provided. It is not the intention of these recommendations that assessment of the core domains should be considered a requirement for approval of product applications by regulatory agencies or that a treatment must demonstrate statistically significant effects for all of the relevant core domains to establish evidence of its efficacy. (C) 2003 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved. C1 Univ Washington, Dept Anesthesiol, Seattle, WA 98195 USA. Univ Rochester, Rochester, NY USA. AstraZeneca, Wilmington, DE USA. Univ Queensland, St Lucia, Qld 4067, Australia. Pfizer Pharmaceut Grp, New York, NY USA. Tufts Univ, Dept Anesthesiol, Medford, MA 02155 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Natl Inst Dent & Craniofacial Res, Bethesda, MD USA. Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. Endo Pharmaceut Inc, Chadds Ford, PA USA. Ortho McNeil Pharmaceut Inc, Raritan, NJ USA. Univ Toronto, Toronto, ON, Canada. Univ Hlth Network, Toronto, ON, Canada. Harvard Univ, Cambridge, MA 02138 USA. Purdue Pharma, Stamford, CT USA. Novartis Pharmaceut Corp, E Hanover, NJ USA. NIH, Bethesda, MD 20892 USA. Dalhousie Univ, Dept Psychol, Halifax, NS, Canada. GlaxoSmithKline, Res Triangle Pk, NC USA. US FDA, Rockville, MD 20857 USA. Univ Washington, Dept Phys Med & Rehabil, Seattle, WA 98195 USA. Elan Pharmaceut, San Diego, CA USA. Abbott Labs, Lake Forest, IL USA. Univ Calif San Diego, La Jolla, CA 92093 USA. US Dept Vet Affairs, Washington, DC USA. RP Turk, DC (reprint author), Univ Washington, Dept Anesthesiol, Seattle, WA 98195 USA. EM turkdc@u.washington.edu RI Farrar, John/A-1037-2007; Bellamy, Nicholas/G-3631-2010; OI Farrar, John/0000-0001-8656-5157; McGrath, Patrick/0000-0002-9568-2571 NR 48 TC 483 Z9 491 U1 3 U2 27 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD DEC PY 2003 VL 106 IS 3 BP 337 EP 345 DI 10.1016/j.pain.2003.08.001 PG 9 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 753AR UT WOS:000187209600014 PM 14659516 ER PT J AU Abramson, JS Baker, CJ Baltimore, RS Bocchini, JA Long, SS McMillan, JA Meissner, HC Powell, KR Prober, CG Rennels, MB Saari, TN Weiner, LB Blackmon, L Batton, DG Bell, EF Denson, SE Engle, WA Kanto, WP Martin, GI Stark, AR AF Abramson, JS Baker, CJ Baltimore, RS Bocchini, JA Long, SS McMillan, JA Meissner, HC Powell, KR Prober, CG Rennels, MB Saari, TN Weiner, LB Blackmon, L Batton, DG Bell, EF Denson, SE Engle, WA Kanto, WP Martin, GI Stark, AR CA Comm Infect Dis Comm Fetus Newborn TI Revised indications for the use of Palivizumab and Respiratory Syncytial Virus Immune Globulin Intravenous for the prevention of respiratory syncytial virus infections SO PEDIATRICS LA English DT Article AB Palivizumab and Respiratory Syncytial Virus Immune Globulin Intravenous ( RSV- IGIV) are licensed by the Food and Drug Administration for use in preventing severe lower respiratory tract infections caused by respiratory syncytial virus ( RSV) in high- risk infants, children younger than 24 months with chronic lung disease ( formerly called bronchopulmonary dysplasia), and certain preterm infants. This statement provides revised recommendations for administering RSV prophylaxis to infants and children with congenital heart disease, for identifying infants with a history of preterm birth and chronic lung disease who are most likely to benefit from immunoprophylaxis, and for reducing the risk of RSV exposure and infection in high- risk children. On the basis of results of a recently completed clinical trial, prophylaxis with palivizumab is appropriate for infants and young children with hemodynamically significant congenital heart disease. RSV- IGIV should not be used in children with hemodynamically significant heart disease. Palivizumab is preferred for most high-risk infants and children because of ease of intramuscular administration. Monthly administration of palivizumab during the RSV season results in a 45% to 55% decrease in the rate of hospitalization attributable to RSV. Because of the large number of infants born after 32 to 35 weeks' gestation and because of the high cost, immunoprophylaxis should be considered for this category of preterm infants only if 2 or more risk factors are present. High- risk infants should not attend child care during the RSV season when feasible, and exposure to tobacco smoke should be eliminated. C1 Amer Acad Pediat, Comm Infect Dis, Elk Grove Village, IL 60007 USA. Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. Natl Vaccine Program Off, Atlanta, GA USA. Amer Acad Pediat, Infect Dis Sect, Elk Grove Village, IL USA. Amer Acad Family Phys, Leawood, KS 66211 USA. NIH, Bethesda, MD 20892 USA. US FDA, Rockville, MD 20857 USA. Amer Thorac Soc, New York, NY 10019 USA. Amer Acad Pediat, Comm Fetus & Newborn, Elk Grove Village, IL USA. Amer Coll Obstetricians & Gynecologists, Washington, DC 20090 USA. Natl Assoc Neonatal Nurses, Glenview, IL 60025 USA. RP Abramson, JS (reprint author), Amer Acad Pediat, Comm Infect Dis, Elk Grove Village, IL 60007 USA. NR 5 TC 122 Z9 127 U1 0 U2 2 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD DEC PY 2003 VL 112 IS 6 BP 1442 EP 1446 PG 5 WC Pediatrics SC Pediatrics GA 749YK UT WOS:000186957500039 ER PT J AU Tabacova, S Little, R Tsong, Y Vega, A Kimmel, CA AF Tabacova, S Little, R Tsong, Y Vega, A Kimmel, CA TI Adverse pregnancy outcomes associated with maternal enalapril antihypertensive treatment SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Article DE anti-hypertensive drugs; ACE inhibitors; enalapril maternal exposure; adverse pregnancy outcomes; oligohydramnios; congenital abnormalities; neonatal renal failure ID CONVERTING ENZYME-INHIBITORS; NEONATAL RENAL-FAILURE; ACE-INHIBITORS; INDUCED HYPERTENSION; RISK-FACTORS; FETAL; PREECLAMPSIA; GROWTH; FETOPATHY; DISTRESS AB Background Adverse pregnancy outcomes following the use of angiotensin-converting enzyme (ACE) inhibitors, including enalapril, have been reported in descriptive studies. However, no analytical studies on the relationship between the adverse outcomes and enalapril gestational exposures are available. Objectives To explore the association between enalapril exposure and adverse outcomes in pregnancy, taking into account other possible risk factors. Methods We analyzed a series of all usable cases reported to the FDA between 1986 and 2000 in which enalapril was a suspect drug for the observed adverse outcomes (N = 110). Parameters of exposure and reported outcomes as well as information on potentially confounding variables were systematically abstracted from this series by a single physician. Because exposure to ACE inhibitors after the first trimester of pregnancy had been associated with adverse outcomes in the existing literature, we divided the cases into those exposed in the first trimester only (considered as the baseline group) and cases exposed beyond or after this time. Frequency of reported adverse outcomes in the second group was compared with those in the baseline group; odds ratios were computed, taking account of potentially confounding variables by logistic regression where appropriate. Results Exposure to enalapril after the first trimester of pregnancy was strongly associated with oligohydramnios and specific adverse outcomes thought to be secondary to reduced amniotic fluid volume (limb deformities, cranial ossification deficits, lung hypoplasia), as well as with neonatal renal failure. The relationship did not change after taking numerous potential confounders into account, including duration of exposure, concomitant drug use, maternal age, concurrent disease, neonatal gender, and gestational age at birth. Such a pattern of abnormalities is considered to be a consequence of the effect of ACE inhibition on fetal renal function that develops after the first trimester. Conclusion The specificity and temporality of the observed adverse manifestations suggest a causal relationship to enalapril exposure. Copyright (C) 2003 John Wiley Sons, Ltd. C1 US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. US FDA, Natl Ctr Toxicol Res, Rockville, MD USA. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. US EPA, Natl Ctr Environm Assesment, Off Res & Dev, Washington, DC 20460 USA. RP Tabacova, S (reprint author), US FDA, Ctr Drug Evaluat & Res, Dndp,Hfd-120,5600 Fishers Lane, Rockville, MD 20857 USA. NR 42 TC 49 Z9 56 U1 0 U2 2 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD DEC PY 2003 VL 12 IS 8 BP 633 EP 646 DI 10.1002/pds.796 PG 14 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 757GH UT WOS:000187554300001 PM 14762979 ER PT J AU Spiridonov, NA Arkhipov, VV Foigel, AG Shipulina, LD Fomkina, MG AF Spiridonov, NA Arkhipov, VV Foigel, AG Shipulina, LD Fomkina, MG TI Protonophoric and uncoupling activity of royleanones from Salvia officinalis and euvimals from Eucalyptus viminalis SO PHYTOTHERAPY RESEARCH LA English DT Article DE royleanone; Salvia officinalis; euvimal; Eucalyptus viminalis; protonophoric activity; cytotoxicity ID OXIDATIVE-PHOSPHORYLATION AB The mechanism of action of quinones from the roots of Salvia officinalis L. (royleanones) and terpenoid phenolahlehydes from the leaves of Eucalyptus viminalis Labill. (euvimals) was studied. Royleanones and euvimals displayed marked protonophoric activity on artificial bilayer lipid membranes in vitro, and exerted an uncoupling action on oxidative phosphorylation in isolated rat liver mitochondria. The results suggest that biological membranes are the primary targets of royleanones and euvimals, and the protonophoric activity may contribute to the cytotoxicity and antimicrobial properties of these compounds. Copyright (C) 2003 John Wiley Sons, Ltd. C1 US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. Russian Acad Sci, Inst Theoret & Expt Biophys, Pushchino 142292, Moscow Region, Russia. All Russian Med & Aromat Plants Res Inst, Moscow, Russia. RP Spiridonov, NA (reprint author), US FDA, Ctr Biol Evaluat & Res, HFM-541,Bldg 29A,Room 3B-20,29 Lincoln Dr, Bethesda, MD 20892 USA. RI Spiridonov, Nikolay/B-6287-2014 NR 14 TC 10 Z9 10 U1 0 U2 3 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0951-418X J9 PHYTOTHER RES JI Phytother. Res. PD DEC PY 2003 VL 17 IS 10 BP 1228 EP 1230 DI 10.1002/ptr.1403 PG 3 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 758TK UT WOS:000187666100021 PM 14669263 ER PT J AU Contrera, JF Matthews, EJ Benz, RD AF Contrera, JF Matthews, EJ Benz, RD TI Predicting the carcinogenic potential of pharmaceuticals in rodents using molecular structural similarity and E-state indices SO REGULATORY TOXICOLOGY AND PHARMACOLOGY LA English DT Article DE quantitative structure-activity relationship (QSAR); electrotopological; E-state descriptors; carcinogenicity; predictive modeling; computational toxicology; in silico ID FALSE-POSITIVE RATES; ELECTROTOPOLOGICAL STATE; VARIABLE SELECTION; DRUG DESIGN; QSAR; TOXICITY; INFORMATION; DESCRIPTORS; COMBINATION; TOXICOLOGY AB MDL QSAR (formerly SciVision QSAR IS) software is one of the several software systems under evaluation by the Informatics and Computational Safety Analysis Staff (ICSAS) of the FDA Center for Drug Evaluation and Research for regulatory and scientific decision support applications. MDL QSAR software contains an integrated set of tools for similarity searching, compound clustering, and modeling molecular structure related parameters that includes 240 electrotopological E-state, connectivity, and other descriptors. These molecular descriptors can be statistically correlated with toxicological or biological endpoints. The goal of this research was to evaluate the feasibility of using MDL QSAR software to develop structure-activity relationship (SAR) models that can be used to predict the carcinogenic potential of pharmaceuticals and organic chemicals. A validation study of 108 compounds that include 86 pharmaceuticals and 22 chemicals that were not present in a control rodent carcinogenicity data set of 1275 compounds demonstrated that MDL QSAR models had excellent coverage (93%) and good sensitivity (72%) and specificity (72%) for rodent carcinogenicity. The software correctly predicted 72% of non-carcinogenic compounds and compounds with carcinogenic findings. E-state descriptors contributed to more than half of the SAR models used to predict carcinogenic activity. We believe that electrotopological E-state descriptors and QSAR IS (MDL QSAR) software are promising new in silico approaches for modeling and predicting rodent carcinogenicity and may have application for other toxicological endpoints. Published by Elsevier Inc. C1 US FDA, Ctr Drug Evaluat & Res, Off Pharmaceut Sci, ICSAS, Rockville, MD 20857 USA. RP Contrera, JF (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Pharmaceut Sci, ICSAS, HFD-901,5600 Fishers Lane, Rockville, MD 20857 USA. NR 40 TC 68 Z9 68 U1 2 U2 12 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0273-2300 J9 REGUL TOXICOL PHARM JI Regul. Toxicol. Pharmacol. PD DEC PY 2003 VL 38 IS 3 BP 243 EP 259 DI 10.1016/S0273-2300(03)00071-0 PG 17 WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology SC Legal Medicine; Pharmacology & Pharmacy; Toxicology GA 747LU UT WOS:000186806600001 PM 14623477 ER PT J AU Middaugh, LD Dow-Edwards, D Li, AA Sandler, JD Seed, J Sheets, LP Shuey, DL Slikker, W Weisenburger, WP Wise, LD Selwyn, MR AF Middaugh, LD Dow-Edwards, D Li, AA Sandler, JD Seed, J Sheets, LP Shuey, DL Slikker, W Weisenburger, WP Wise, LD Selwyn, MR TI Neurobehavioral assessment: A survey of use and value in safety assessment studies SO TOXICOLOGICAL SCIENCES LA English DT Article DE developmental toxicology; neurobehavioral toxicology; F1 generation assessment; perinatal drug exposure ID COLLABORATIVE BEHAVIORAL TERATOLOGY; CHARACTERIZE DEVELOPMENTAL NEUROTOXICITY; HEALTH RISK ASSESSMENT; TESTING PROCEDURES; IDENTIFY; RATS; ALCOHOL; DESIGN; PERIOD; ISSUES AB This report describes the results of a survey designed to evaluate the contribution of F-1 neurobehavioral testing to hazard identification and characterization in safety assessment studies. (To review the details of the distributed survey, please see the supplementary data for this article on the journal's Web site.) The survey provided information about studies completed in industrial laboratories in the United States, Europe, and Japan since 1990 on 174 compounds. The types of compounds included were pharmaceutical (81% agricultural (7%), industrial (M), or were undefined (10%). Information collected included the intended use of the test agent, general study design and methodology, the types and characteristics of F-1 behavioral evaluations, and the frequency with which agents affected neurobehavioral parameters in comparison to other F-0 and F-1 generation parameters, F-1 general toxicology parameters such as mortality, pre- and postweaning body weight, and food intake were assessed in most studies and were affected more frequently than other parameters by the test agents. F-1 behavioral parameters were assessed less consistently across studies, and were less frequently affected by the agents tested. Although affected by agents less often than general toxicology parameters, F-1 behavioral parameters along with other parameters defined the no-observed-effect level (NOEL) in 17/113 (15%) of studies and solely defined the NOEL in 3/113 (2.6%) of studies. Thus, F-1 behavioral parameters sometimes improved on the standard toxicological measures of hazard identification. While not detecting agent effects as readily as some measures, the F-1 behavioral parameters provide information about agent effects on specialized functions of developing offspring not provided by other standard measures of toxicity. The survey results emphasize the need for further research into the methods of behavioral assessment as well as the mechanisms underlying the neurobehavioral alterations. C1 Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. SUNY Brooklyn, Dept Physiol & Pharmacol, Brooklyn, NY 11203 USA. Exponent Inc, San Francisco, CA 94114 USA. Hlth & Environm Sci Inst, Int Life Sci Inst, Washington, DC 20005 USA. US EPA, Washington, DC 20460 USA. Endo Pharmaceut Inc, Chadds Ford, PA 19317 USA. Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. Pfizer Inc, Div Cent Res, Drug Safety Evaluat, Groton, CT 06340 USA. Merck Res Labs, W Point, PA 19486 USA. PAREXEL Int, Durham, NC 27713 USA. RP Middaugh, LD (reprint author), Med Univ S Carolina, Dept Psychiat & Behav Sci, 171 Ashley Ave, Charleston, SC 29425 USA. NR 38 TC 26 Z9 26 U1 1 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 DEC PY 2003 VL 76 IS 2 BP 250 EP 261 DI 10.1093/toxsci/kfg211 PG 12 WC Toxicology SC Toxicology GA 752NF UT WOS:000187173500002 PM 12915715 ER PT J AU Weaver, JL Staten, D Swann, J Armstrong, G Bates, M Hastings, KL AF Weaver, JL Staten, D Swann, J Armstrong, G Bates, M Hastings, KL TI Detection of systemic hypersensitivity to drugs using standard guinea pig assays SO TOXICOLOGY LA English DT Article DE drug allergy; hypersensitivity; guinea pig; drug ID MODELS; PHARMACEUTICALS; ANAPHYLAXIS; ANTIBIOTICS AB The most commonly used assays designed to detect either skin or systemic immune-based hypersensitivity reactions are those using guinea pigs (GP). We obtained data from various FDA records to evaluate the correlation between GP assay results and reported post-marketing systemic hypersensitivity reactions. We examined the new drug application (NDA) reviews of approved drugs for the results of GP assays. Post-marketing human data were extracted from the FDA adverse event reporting system (AERS). Drug usage data were obtained from a commercial database maintained by IMS Health Inc. We found 83 (21%) of 396 drugs approved between 1978 and 1998 had reported GP test results. Among these 83 drugs, 14 (17%) were found to have positive results in at least one GP assay. Simple reporting index (RI) values for systemic hypersensitivity reactions were calculated from AERS data and usage to produce the index of adverse event reports per million shipping units of drug. A variety of definitions of positive human response were examined. A statistically significant association was seen for rash between post-marketing and clinical trials adverse event reports. No statistically significant associations between human data and GP test results were observed. These data suggest that standard GP assays have limited ability to predict human systemic hypersensitivity potential for pharmaceuticals. Published by Elsevier Ireland Ltd. C1 Ctr Drug Evaluat & Res, Off Testing & Res, Div Appl Pharmacol Res, Laurel, MD 20708 USA. Ctr Biol Evaluat & Res, Div Vaccines & Related Prod Applicat, Rockville, MD USA. CDER, Off Drug Safety, Rockville, MD USA. US FDA, CDER, Div Special Pathogen & Immunol Drug Prod, Rockville, MD 20857 USA. RP Weaver, JL (reprint author), Ctr Drug Evaluat & Res, Off Testing & Res, Div Appl Pharmacol Res, MOD-1,8301 Muirkirk Rd, Laurel, MD 20708 USA. NR 17 TC 16 Z9 20 U1 1 U2 2 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0300-483X J9 TOXICOLOGY JI Toxicology PD DEC 1 PY 2003 VL 193 IS 3 BP 203 EP 217 DI 10.1016/S0300-483X(03)00267-1 PG 15 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 745DP UT WOS:000186674100002 PM 14599760 ER PT J AU Leakey, JEA Seng, JE Allaben, WT AF Leakey, JEA Seng, JE Allaben, WT TI Body weight considerations in the B6C3F(1) mouse and the use of dietary control to standardize background tumor incidence in chronic bioassays SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE dietary restriction; chloral hydrate; mouse liver tumors; body weight ID RESPONSE TREND TESTS; DAWLEY RAT SURVIVAL; CALORIC RESTRICTION; INCREASED CARCINOGENICITY; RISK-ASSESSMENT; F344 RATS; MICE; TOXICITY; TOXICOLOGY; TUMORIGENESIS AB In B6C3F(1) mice, the rate of body growth influences susceptibility to liver neoplasia and large variations in body weight can complicate the interpretation of bioassay data. The relationship between body weight and liver tumor incidence was calculated for historical control populations of male and female ad libitum-fed mice (approx. 2750 and 2300 animals, respectively) and in populations of male and female mice which had been subjected to forced body weight reduction due to either dietary restriction or exposure to noncarcinogenic chemicals (approx. 1600 and 1700, respectively). Resulting tumor risk data were then used to construct idealized weight curves for male and female B6C3F(1) mice; these curves predict a terminal background liver tumor incidence of 15-20%. Use of dietary control to manipulate body growth of male B6C3F(1) mice to fit the idealized weight curve was evaluated in a 2-year bioassay of chloral hydrate. Cohorts of mice were successfully maintained at weights approximating their idealized target weights throughout the study. These mice exhibited less body weight variation than their ad libitum-fed counterparts (e.g., standard deviations of body weight were 1.4 and 3.4 g for respective control groups at 36 weeks). Historical control body weight and tumor risk data from the two male mouse populations were utilized to predict background liver tumor rates for each experimental group of the chloral hydrate study. The predicted background tumor rates closely matched the observed rates for both the dietary controlled and ad libitum-fed chloral hydrate control groups when each mouse was evaluated according to either its weekly food consumption or its weekly change in body weight. (C) 2003 Elsevier Inc. All rights reserved. C1 Natl Ctr Toxicol Res, Div Chem, Jefferson, AR 72079 USA. RP Leakey, JEA (reprint author), Natl Ctr Toxicol Res, Div Chem, 3900 NCTR Rd, Jefferson, AR 72079 USA. FU PHS HHS [224-86-001, 224-933-0001] NR 59 TC 12 Z9 12 U1 1 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD DEC 1 PY 2003 VL 193 IS 2 BP 237 EP 265 DI 10.1016/j.taap.2003.07.006 PG 29 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 753GL UT WOS:000187223600011 PM 14644626 ER PT J AU Leakey, JEA Seng, JE Latendresse, JR Hussain, N Allen, LJ Allaben, WT AF Leakey, JEA Seng, JE Latendresse, JR Hussain, N Allen, LJ Allaben, WT TI Dietary controlled carcinogenicity study of chloral hydrate in male B6C3F(1) mice SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE dietary restriction; chloral hydrate; mouse liver tumors; body weight ID MALE FISCHER-344 RAT; TRICHLOROACETIC-ACID; CALORIC RESTRICTION; DICHLOROACETIC ACID; PEROXISOME PROLIFERATION; MOUSE-LIVER; LIPID-PEROXIDATION; DRINKING-WATER; BODY-WEIGHT; TRICHLOROETHYLENE AB Chloral hydrate, which is used as a sedative in pediatric medicine and is a by-product of water chlorination, is hepatocarcinogenic in B6C3F(1) mice, a strain that can exhibit high rates of background liver tumor incidence, which are associated with increased body weight. In this study, dietary control was used to manipulate body growth in male B6C3F(1) mice in a 2-year bioassay of chloral hydrate. Male B6C3F(1) mice were treated with water or 25, 50, or 100 mg/kg chloral hydrate by gavage. The study compared ad libitum-fed mice with dietary controlled mice. The latter received variably restricted feed allocations to maintain their body weights on a predetermined "idealized" weight curve predictive of a terminal background liver tumor incidence of 15-20%. These mice exhibited less individual body weight variation than did their ad libitum-fed counterparts. This was associated with a decreased variation in liver to body weight ratios, which allowed the demonstration of a statistically significant dose response to chloral hydrate in the dietary controlled, but not the ad libitum-fed, test groups. Chloral hydrate increased terminally adjusted liver tumor incidence in both dietary controlled (23.4, 23.9, 29.7, and 38.6% for the four dose groups, respectively) and ad libitum-fed mice (33.4, 52.6, 50.6, and 46.2%), but a statistically significant dose response was observed only in the dietary controlled mice. This dose response positively correlated with markers of peroxisomal proliferation in the dietary controlled mice only. The study suggests that dietary control not only improves terminal survival and decreases interassay variation, but also can increase assay sensitivity by decreasing intra-assay variation. (C) 2003 Elsevier Inc. All rights reserved. C1 Natl Ctr Toxicol Res, Div Chem, Jefferson, AR 72079 USA. RP Leakey, JEA (reprint author), Natl Ctr Toxicol Res, Div Chem, 3900 NCTR Rd, Jefferson, AR 72079 USA. RI Latendresse, John/A-9215-2009 FU PHS HHS [224-933-0001, 224-86-001] NR 91 TC 17 Z9 17 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 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD DEC 1 PY 2003 VL 193 IS 2 BP 266 EP 280 DI 10.1016/j.taap.2003.07.007 PG 15 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 753GL UT WOS:000187223600012 PM 14644627 ER PT J AU Seng, JE Agrawal, N Horsley, ETM Leakey, TI Scherer, EM Xia, SJ Allaben, WT Leakey, JEA AF Seng, JE Agrawal, N Horsley, ETM Leakey, TI Scherer, EM Xia, SJ Allaben, WT Leakey, JEA TI Toxicokinetics of chloral hydrate in ad libitum-fed, dietary-controlled, and calorically restricted male B6C3F(1) mice following short-term exposure SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE chloral hydrate; dietary restriction; metabolism ID TRICHLOROACETIC-ACID; RAT-LIVER; DICHLOROACETIC ACID; PEROXISOME PROLIFERATION; REDUCING ENZYMES; MESSENGER-RNA; MOUSE-LIVER; METABOLISM; TRICHLOROETHYLENE; INDUCTION AB Chloral hydrate is widely used as a sedative in pediatric medicine and is a by-product of water chlorination and a metabolic intermediate in the biotransformation of trichloroethylene. Chloral hydrate and its major metabolite, trichloroacetic acid, induce liver tumors in B6C3F(1) mice, a strain that can exhibit high rates of background liver tumor incidence, which is associated with increased body weight. This report describes the influence of diet and body weight on the acute toxicity, hepatic enzyme response, and toxickinetics of chloral hydrate as part of a larger study investigating the carcinogenicity of chloral hydrate in ad libitum-fed and dietary controlled mice. Dietary control involves moderate food restriction to maintain the test animals at an idealized body weight. Mice were dosed with chloral hydrate at 0, 50, 100, 250, 500, and 1000 mg/kg daily, 5 days/week, by aqueous gavage for 2 weekly dosing cycles. Three diet groups were used: ad libitum, dietary control, and 40% caloric restriction. Both dietary control and caloric restriction slightly reduced acute toxicity of high doses of chloral hydrate and potentiated the induction of hepatic enzymes associated with peroxisome proliferation. Chloral hydrate toxicokinetics were investigated using blood samples obtained by sequential tail clipping and a microscale gas chromatography technique. It was rapidly cleared from serum within 3 h of dosing. Trichloroacetate was the major metabolite in serum in all three diet groups. Although the area under the curve values for serum trichloroacetate were slightly greater in the dietary controlled and calorically restricted groups than in the ad libitum-fed groups, this increase did not appear to completely account for the potentiation of hepatic enzyme induction by dietary restriction. (C) 2003 Elsevier Inc. All rights reserved. C1 Natl Ctr Toxicol Res, Div Chem, Jefferson, AR 72079 USA. RP Leakey, JEA (reprint author), Natl Ctr Toxicol Res, Div Chem, 3900 NCTR Rd, Jefferson, AR 72079 USA. FU PHS HHS [224-86-001, 224-933-0001] NR 38 TC 14 Z9 14 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 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD DEC 1 PY 2003 VL 193 IS 2 BP 281 EP 292 DI 10.1016/j.taap.2003.07.008 PG 12 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 753GL UT WOS:000187223600013 PM 14644628 ER PT J AU Nishizuka, S Charboneau, L Young, L Major, S Reinhold, WC Waltham, M Kouros-Mehr, H Bussey, KJ Lee, JK Espina, V Munson, PJ Petricoin, E Liotta, LA Weinstein, JN AF Nishizuka, S Charboneau, L Young, L Major, S Reinhold, WC Waltham, M Kouros-Mehr, H Bussey, KJ Lee, JK Espina, V Munson, PJ Petricoin, E Liotta, LA Weinstein, JN TI Proteomic profiling of the NCI-60 cancer cell lines using new high-density reverse-phase lysate microarrays SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ANTICANCER DRUG SCREEN; MOLECULAR PHARMACOLOGY; MESSENGER-RNA; EXPRESSION DATABASE; PROTEIN MICROARRAYS; GENE; DIFFERENTIATION; FEASIBILITY; PATTERNS; VILLIN AB Because most potential molecular markers and targets are proteins, proteomic profiling is expected to yield more direct answers to functional and pharmacological questions than does transcriptional profiling. To aid in such studies, we have developed a protocol for making reverse-phase protein lysate microarrays with larger numbers of spots than previously feasible. Our first application of these arrays was to profiling of the 60 human cancer cell lines (NCl-60) used by the National Cancer Institute to screen compounds for anticancer activity. Each glass slide microarray included 648 lysate spots representing the NCl-60 cell lines plus controls, each at 10 two-fold serial dilutions to provide a wide dynamic range. Mouse monoclonal antibodies and the catalyzed signal amplification system were used for immunoquantitation. The signal levels from the >30,000 data points for our first 52 antibodies were analyzed by using P-SCAN and a quantitative dose interpolation method. Clustered image maps revealed biologically interpretable patterns of protein expression. Among the principal early findings from these arrays were two promising pathological markers for distinguishing colon from ovarian adenocarcinomas. When we compared the patterns of protein expression with those we had obtained for the same genes at the mRNA level by using both cDNA and oligonucleoticle arrays, a striking regularity appeared: cell-structure-related proteins almost invariably showed a high correlation between mRNA and protein levels across the NCl-60 cell lines, whereas non-cell-structure-related proteins showed poor correlation. C1 NCI, Genom & Bioinformat Grp, Mol Pharmacol Lab, NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. NIH, Math & Stat Comp Lab, Ctr Informat Technol, Bethesda, MD 20892 USA. Univ Virginia, Sch Med, Dept Hlth Evaluat Sci, Charlottesville, VA 22908 USA. US FDA, Ctr Biol Evaluat & Res, Div Therapeut Prot, Tissue Proteom Unit, Bethesda, MD 20892 USA. RP Weinstein, JN (reprint author), NCI, Genom & Bioinformat Grp, Mol Pharmacol Lab, NIH, Room 5056,Bldg 37,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Waltham, Mark/A-1728-2009; OI Bussey, Kimberly/0000-0003-1001-8207; Espina, Virginia/0000-0001-5080-5972 NR 31 TC 320 Z9 340 U1 4 U2 18 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 NOV 25 PY 2003 VL 100 IS 24 BP 14229 EP 14234 DI 10.1073/pnas.2331323100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 747KN UT WOS:000186803800086 PM 14623978 ER PT J AU Lehr, GJ Barry, TL Franolic, JD Petzinger, G Scheiner, P AF Lehr, GJ Barry, TL Franolic, JD Petzinger, G Scheiner, P TI LC determination of impurities in methoxsalen drug substance: isolation and identification of isopimpinellin as a major impurity by atmospheric pressure chemical ionization LC/MS and NMR SO JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS LA English DT Article DE furanocoumarins; methoxsalen; isopimpinellin; bergapten; ammidin; impurities; liquid chromatography; atmospheric ionization mass spectrometry; NMR spectroscopy ID PERFORMANCE LIQUID-CHROMATOGRAPHY; MASS-SPECTROMETRY; FUROCOUMARINS; SPECTROSCOPY; SEPARATION; PROFILES; MS AB A gradient elution LC method was developed to separate methoxsalen from three of its known impurities: isopimpinellin, bergapten, and ammidin. The method employs a methanol-6%THF (aq) mobile phase, phenyl column, and detection at 254 nm. The gradient LC procedure was applied to seven lots of methoxsalen from five different manufacturers. Six of the seven lots tested contained isopimpinellin as the major impurity at a concentration range of 0.2-2.5%. Identification of the impurity as isopimpinellin was accomplished by a combination of analytical and preparative LC atmospheric pressure chemical ionization liquid chromatography/mass spectrometry, and NMR. Published by Elsevier B.V. C1 US FDA, Dept Hlth & Human Serv, NE Reg Lab, Jamaica, NY 11433 USA. US FDA, Dept Hlth & Human Serv, Ctr Drug Evaluat & Res, Off Gener Drugs, Rockville, MD 20855 USA. CUNY, York Coll, Dept Chem, Jamaica, NY 11451 USA. RP Lehr, GJ (reprint author), US FDA, Dept Hlth & Human Serv, NE Reg Lab, 158-15 Liberty Ave, Jamaica, NY 11433 USA. NR 21 TC 10 Z9 11 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0731-7085 J9 J PHARMACEUT BIOMED JI J. Pharm. Biomed. Anal. PD NOV 24 PY 2003 VL 33 IS 4 BP 627 EP 637 DI 10.1016/S0731-7085(03)00353-4 PG 11 WC Chemistry, Analytical; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 747PD UT WOS:000186812400012 PM 14623588 ER PT J AU Virata, MLA Yu, MYW AF Virata, MLA Yu, MYW TI Anti-D levels in commercial intravenous immunoglobulin products: A safety issue. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 US FDA, Ctr Biol Evaluat & Res, Office Blood Res & Review, Div Hematol, 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 NOV 16 PY 2003 VL 102 IS 11 MA 4240 BP 133B EP 133B PN 2 PG 1 WC Hematology SC Hematology GA 742UU UT WOS:000186537100531 ER PT J AU Lozier, JN AF Lozier, JN TI The mouse MHC locus is the major genetic factor that controls the antibody response to human factor IX in mice. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 568 BP 163A EP 164A PN 1 PG 2 WC Hematology SC Hematology GA 742UP UT WOS:000186536700568 ER PT J AU Niu, Y Murata, T Watanabe, K Kawakami, K Puri, R Inoue, JI Yoshimura, A Kobayashi, N AF Niu, Y Murata, T Watanabe, K Kawakami, K Puri, R Inoue, JI Yoshimura, A Kobayashi, N TI MIP-T3 associates with IL-13R alpha 1 and suppresses STAT6 activation in response to IL-13 stimulation. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Nagasaki Univ, Grad Sch Biomed Sci, Div Mol Pharmacol Infect Agents, Nagasaki, Japan. FDA, Ctr Biol Evaluat & Res, Lab Mol Tumor Biol, Bethesda, MD USA. Univ Tokyo, Inst Med Sci, Div Cellular & Mol Biol, Minato Ku, Tokyo, Japan. Kyushu Univ, Med Inst Bioregulat, Div Mol & Cellular Immunol, Fukuoka, Japan. RI Yoshimura, Akihiko/K-5515-2013 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 1264 BP 349A EP 349A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536701264 ER PT J AU Zivny, JH Holada, K Simak, J Vostal, JG AF Zivny, JH Holada, K Simak, J Vostal, JG TI Increased apoptosis of erythroid cells during anemia recovery in prion protein deficient (Prnp-/-) mice. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 US FDA, Ctr Biol Evaluat & Res, Lab Cellular Hematol, Bethesda, MD 20014 USA. Charles Univ, Sch Med 1, Prague, Czech Republic. RI Simak, Jan/C-1153-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 1862 BP 510A EP 511A PN 1 PG 2 WC Hematology SC Hematology GA 742UP UT WOS:000186536701861 ER PT J AU Tsujimura, H Tamura, T Kong, HJ Nishiyama, A Ishii, KJ Klinman, DM Ozato, K AF Tsujimura, H Tamura, T Kong, HJ Nishiyama, A Ishii, KJ Klinman, DM Ozato, K TI Cytokine induction by toll-like receptor 9 depends on the transcription factor IRF-8/ICSBP in dendritic cells SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 NICHHD, Lab Mol Growth Regulat, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. RI Ishii, Ken/B-1685-2012 OI Ishii, Ken/0000-0002-6728-3872 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 1914 BP 523A EP 523A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536701913 ER PT J AU Aurran-Schleinitz, TM Telford, W Perfetto, S Wilson, WH Marti, GE AF Aurran-Schleinitz, TM Telford, W Perfetto, S Wilson, WH Marti, GE TI Comparative multicolor flow cytometry of blood from normal donors and chronic lymphocytic leukemia to assess normal and aberrant B-cell subsets. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 US FDA, CBER, OCTGT, DCGT,Lab Stem Cell Biol, Bethesda, MD 20014 USA. NCI, Flow Cytometry Core Facil, NIH, Bethesda, MD 20892 USA. NIAIS, Vaccine Res Ctr, NIH, Bethesda, MD USA. NCI, MOCRU, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 2489 BP 672A EP 672A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536702487 ER PT J AU Simak, J Novak, J AF Simak, J Novak, J TI Ceramide mediated release of membrane microparticles from endothelial cells is controlled by caspase 1 activity and in contrast to executive apoptotic blebbing is kinase independent. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 US FDA, Ctr Biol Evaluat & Res, Lab Cellular Hematol, Rockville, MD 20857 USA. RI Simak, Jan/C-1153-2011 NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 2980 BP 805A EP 805A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536702980 ER PT J AU Daniels, JT Fusaro, V Rosenblatt, K Ross, S Igarashi, T Srinivasan, R Petricoin, EF Liotta, L Childs, RW AF Daniels, JT Fusaro, V Rosenblatt, K Ross, S Igarashi, T Srinivasan, R Petricoin, EF Liotta, L Childs, RW TI Serologic methods to diagnose acute GVHD based on protein patterns using surface-enhanced-laser-desorption-ionization-time of flight (SELDI-TOF) mass spectrometry. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Walter Reed Army Med Ctr, Washington, DC 20307 USA. US FDA, Ctr Biol Evaluat & Res, Div Therapeut Prot, NIH, Bethesda, MD 20014 USA. NCI, NIH, Bethesda, MD 20892 USA. NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NCI, Urol Oncol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 3536 BP 949A EP 950A PN 1 PG 2 WC Hematology SC Hematology GA 742UP UT WOS:000186536703536 ER PT J AU O'Neill, RT AF O'Neill, RT TI Sam Greenhouse: his contributions as a consultant to the Food and Drug Administration SO STATISTICS IN MEDICINE LA English DT Article DE statistical advice; clinical trials; observational studies; consultant; Food and Drug Administration; Sam Greenhouse AB This paper recounts contributions made by Sam Greenhouse to the Food and Drug Administration during his tenure as an advisory committee member and as chair of the committee. The events and topics are taken from available recollections and minutes and selectively describe a range of topic areas and issues about which Sam Greenhouse played a substantial leadership role. Published in 2003 by John Wiley Sons, Ltd. C1 Ctr Drug Evaluat & Res, Food & Drug Adm, Off Biostat, Rockville, MD 20857 USA. RP O'Neill, RT (reprint author), Ctr Drug Evaluat & Res, Food & Drug Adm, Off Biostat, Room 15B45,5600 Fishers Lane, Rockville, MD 20857 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD NOV 15 PY 2003 VL 22 IS 21 BP 3285 EP 3289 DI 10.1002/sim.1629 PG 5 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 737RK UT WOS:000186245400005 PM 14566912 ER PT J AU Chan, TC Jiang, J Temenak, JJ Richards, AL AF Chan, TC Jiang, J Temenak, JJ Richards, AL TI Development of a rapid method for determining the infectious dose (ID)(50) of Orientia tsutsugamushi in a scrub typhus mouse model for the evaluation of vaccine candidates SO VACCINE LA English DT Article DE scrub typhus; Orientia tsutsugumushi; infectious dose ID RICKETTSIA-TSUTSUGAMUSHI; HOST DEFENSES; DISEASES; THAILAND AB The infectious dose (ID) of an inoculum for which 50% of susceptible mice will become infected (ID50) with Orientia tsutsugamushi is usually determined by rechallenging mice that have already been challenged with O. tsutsugamushi to determine the lethal dose (LD)(50) titer of the inoculum. Those mice not killed by the initial challenge and which survived a rechallenge with 1000 LD50 were considered immune and to have been initially infected with O. tsutsugamushi. Mice that succumbed to the rechallenge were considered not to have been initially infected. We have developed a more rapid method of determining the ID50 of inocula for use in our vaccine studies based upon the observation that mice surviving initial challenge and that go on to survive rechallenge produced detectable IgG to O. tsutsugamushi antigens by enzyme-linked immunosorbent assay (ELISA). Mice that did not survive rechallenge, and therefore did not receive an initial infectious inoculum did not produce detectable IgG to O. tsutsugamushi antigens. Both original LD50 and ID50 titers determinations require observation of mice for 21 days post-challenge. Our new ID50 determination does not require mice or the additional 21-day observation period for rechallenge and therefore is more rapid and cost-effective than the previous standard method of determining ID50 titer necessary for the evaluation of vaccine candidates. Published by Elsevier Ltd. C1 USN, Rickettsial Dis Dept, IDD, Med Res Ctr, Silver Spring, MD 20910 USA. US FDA, Bacterial Vaccines & Allergen Prod Branch, Div Vaccines & Related Prod Applicat, OVRR,CBER, Rockville, MD 20852 USA. RP Richards, AL (reprint author), USN, Rickettsial Dis Dept, IDD, Med Res Ctr, 3A-9,503 Robert Grant Ave, Silver Spring, MD 20910 USA. NR 24 TC 11 Z9 11 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD NOV 7 PY 2003 VL 21 IS 31 BP 4550 EP 4554 DI 10.1016/S0264-410X(03)00505-X PG 5 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 747XG UT WOS:000186830900009 PM 14575767 ER PT J AU Busch, M Pietrelli, L Caglioti, S Sazama, K Schuermann, J Betz, T Perrotta, D Sambol, AR Safranek, T Stramer, SL Dodd, R Strong, DM Dickey, W Kleinman, S Nakhasi, H Epstein, J Goodman, J Chamberland, M Kuehnert, M Petersen, L Roehrig, J Crall, N Marfin, A Montgomery, S de Oliveira, AM AF Busch, M Pietrelli, L Caglioti, S Sazama, K Schuermann, J Betz, T Perrotta, D Sambol, AR Safranek, T Stramer, SL Dodd, R Strong, DM Dickey, W Kleinman, S Nakhasi, H Epstein, J Goodman, J Chamberland, M Kuehnert, M Petersen, L Roehrig, J Crall, N Marfin, A Montgomery, S de Oliveira, AM CA CDC TI Update: Detection of West Nile virus in blood donations - United States, 2003 (Reprinted from MMWR, vol 52, pg 916-919, 2003) SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Reprint C1 Blood Syst Res Inst, San Francisco, CA USA. Roche Mol Syst, Alameda, CA USA. Blood Syst Labs, Tempe, AZ USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Texas Dept Hlth, Austin, TX 78756 USA. Nebraska Publ Hlth Lab, Omaha, NE USA. Nebraska Hlth & Human Serv, Lincoln, NE USA. Amer Red Cross, Gaithersburg, MD USA. Puget Sound Blood Ctr, Seattle, WA 98104 USA. Belle Bonfils Mem Blood Ctr, Denver, CO USA. Amer Assoc Blood Banks, Victoria, BC, Canada. US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. CDC, Div Viral & Rickettsial Dis, Atlanta, GA 30333 USA. CDC, Div Vector Borne Infect Dis, Natl Ctr Infect Dis, Atlanta, GA 30333 USA. RP Busch, M (reprint author), Blood Syst Res Inst, San Francisco, CA USA. NR 4 TC 0 Z9 0 U1 1 U2 1 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 NOV 5 PY 2003 VL 290 IS 17 BP 2248 EP 2250 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 739PZ UT WOS:000186356800006 ER PT J AU Peterson, ED Kaul, P Kaczmarek, RG Hammill, BG Armstrong, PW Bridges, CR Ferguson, TB AF Peterson, ED Kaul, P Kaczmarek, RG Hammill, BG Armstrong, PW Bridges, CR Ferguson, TB CA Soc Thoracic Surgeons TI From controlled trials to clinical practice: Monitoring transmyocardial revascularization use and outcomes SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID REFRACTORY ANGINA-PECTORIS; LASER REVASCULARIZATION; RANDOMIZED-TRIAL; MEDICAL THERAPY; MORTALITY; RISK; MORBIDITY; CHANNELS AB OBJECTIVES We sought to examine trends in the use and outcomes of transmyocardial revascularization (TMR) in community practice. We also identified important risk factors for TMR and compared outcomes of TMR combined with coronary artery bypass graft surgery (TMR + CABG) versus bypass alone in patients receiving incomplete revascularization. BACKGROUND Although it is approved for use as a stand-alone procedure, there are limited data on the outcomes of (TMR + CABG). METHODS We identified 3,717 patients receiving TMR at 173 U.S. hospitals participating in the Society of Thoracic Surgeons (STS) National Cardiac Database. Baseline characteristics and outcomes in these patients were compared with those from six published randomized TMR trials. Multivariable logistic regression was used to identify clinical risk factors for mortality with TMR. Risk-adjusted mortality was also compared for TMR + CABG relative to CABG only in patients not amenable to complete traditional revascularization. RESULTS Between January 1998 and December 2001, the number of STS hospitals performing TMR and total procedural counts increased markedly, driven predominately by more TMR + CABG cases. Overall mortality rates for TMR-alone and TMR + CABG were 6.4% and 4.2%, respectively. Operative risks were significantly higher in those patients with recent myocardial infarction, unstable angina, and depressed ventricular function. Among patients receiving incomplete revascularization, TMR + CABG was not associated with decreased mortality risk compared with CABG alone, adjusted odds ratio 1.11 (95% confidence interval 0.74 to 1.67). CONCLUSIONS The use of TMR, and in particular, TMR + CABG, is expanding in community practice. Although procedural risks are high, there is room for optimization through improved patient selection and timing of the procedure. Further studies of TMR + CABG are needed given its growing use and unclear benefits. (C) 2003 by the American College of Cardiology Foundation. C1 Louisiana State Univ, Hlth Sci Ctr, New Orleans, LA USA. Univ Penn, Philadelphia, PA 19104 USA. US FDA, Rockville, MD 20857 USA. Univ Alberta, Edmonton, AB, Canada. Duke Clin Res Inst, Durham, NC USA. RP Peterson, ED (reprint author), Duke Univ, Med Ctr, Box 3236, Durham, NC 27710 USA. FU AHRQ HHS [U18HS10548] NR 19 TC 35 Z9 36 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD NOV 5 PY 2003 VL 42 IS 9 BP 1611 EP 1616 DI 10.1016/S0735-1097(03)01121-5 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 739LU UT WOS:000186348600015 PM 14607448 ER PT J AU Gann, PH Khachik, F AF Gann, PH Khachik, F TI Tomatoes or lycopene versus prostate cancer: Is evolution anti-reductionist? SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID BETA-CAROTENE; RISK; ASSOCIATION; PRODUCTS; HUMANS; JUICE; CELLS C1 Northwestern Univ, Dept Prevent Med, Chicago, IL 60611 USA. Northwestern Univ, Feinberg Sch Med, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA. Univ Maryland, Joint Inst Food Safety & Appl Nutr, Dept Chem & Biochem, College Pk, MD 20742 USA. RP Gann, PH (reprint author), Northwestern Univ, Dept Prevent Med, 680 N Lakeshore Dr,Suite 1102, Chicago, IL 60611 USA. RI Khachik, Frederick/C-5055-2009 NR 12 TC 27 Z9 27 U1 0 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 NOV 5 PY 2003 VL 95 IS 21 BP 1563 EP 1565 DI 10.1093/jnci/djg112 PG 3 WC Oncology SC Oncology GA 739DW UT WOS:000186327800001 PM 14600081 ER PT J AU Gardner, JD Gallo-Torres, H Sloan, S Robinson, M Miner, PB AF Gardner, JD Gallo-Torres, H Sloan, S Robinson, M Miner, PB TI The basis for the decreased response to proton pump inhibitors in gastro-oesophageal reflux disease patients without erosive oesophagitis SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS LA English DT Article ID GASTRIC-ACID-SECRETION; SPHINCTER RELAXATIONS; ENDOGENOUS CHOLECYSTOKININ; INTEGRATED ACIDITY; OPTIMAL THRESHOLDS; OMEPRAZOLE; DISTENSION; HUMANS; PH; INVOLVEMENT AB Background: The reason why heartburn in gastro-oesophageal reflux disease subjects without oesophagitis is less responsive to proton pump inhibitors than heartburn in those with erosive oesophagitis is not known. Methods: Gastric and oesophageal pH were,determined in 26 subjects with gastro-oesophageal reflux disease at baseline and on days 1, 2 and 8 of treatment with 20 mg omeprazole or 20 mg rabeprazole in, a randomized, two-way cross-over fashion. The presence or absence of erosive oesophagitis at baseline was documented by upper gastrointestinal endoscopy. Results: At a given value of the integrated gastric acidity during treatment with a proton pump inhibitor, the probability of pathological oesophageal reflux was significantly higher in subjects with no oesophagitis than in those with erosive oesophagitis. This occurred because the post-prandial gastric acidity in subjects with no oesophagitis showed a decreased response to the antisecretory agent. Conclusions: Compared with gastro-oesophageal reflux disease subjects with erosive oesophagitis, those with no oesophagitis are relatively refractory to the pharmacodynamic effects of proton pump inhibitors on the postprandial integrated gastric acidity. C1 Sci Org Inc, Chatham, NJ 07928 USA. US FDA, Rockville, MD 20857 USA. Janssen Pharmaceut Inc, Titusville, NJ USA. Univ Oklahoma, Hlth Sci Ctr, Oklahoma Fdn Digest Res, Oklahoma City, OK USA. RP Gardner, JD (reprint author), Sci Org Inc, 156 Terrace Dr, Chatham, NJ 07928 USA. NR 30 TC 16 Z9 17 U1 0 U2 1 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0269-2813 J9 ALIMENT PHARM THERAP JI Aliment. Pharmacol. Ther. PD NOV 1 PY 2003 VL 18 IS 9 BP 891 EP 905 DI 10.1046/j.1365-2036.2003.01777.x PG 15 WC Gastroenterology & Hepatology; Pharmacology & Pharmacy SC Gastroenterology & Hepatology; Pharmacology & Pharmacy GA 743HM UT WOS:000186566400004 PM 14616153 ER PT J AU Brusic, V Petrovsky, N Gendel, SM Millot, M Gigonzac, O Stelman, SJ AF Brusic, V Petrovsky, N Gendel, SM Millot, M Gigonzac, O Stelman, SJ TI Computational tools for the study of allergens SO ALLERGY LA English DT Review DE allergen; molecular modelling; prediction of allergenicity; prediction of cross-reactivity; sequence analysis ID DUST MITE ALLERGEN; JAPANESE ENCEPHALITIS-VIRUS; MULTIPLE SEQUENCE ALIGNMENT; GENETICALLY-MODIFIED FOODS; MAJOR CHERRY ALLERGEN; IGE-BINDING EPITOPES; B-CELL EPITOPES; CROSS-REACTIVITY; SECONDARY STRUCTURE; DERMATOPHAGOIDES-PTERONYSSINUS AB Allergy is a major cause of morbidity worldwide. The number of characterized allergens and related information is increasing rapidly creating demands for advanced information storage, retrieval and analysis. Bioinformatics provides useful tools for analysing allergens and these are complementary to traditional laboratory techniques for the study of allergens. Specific applications include structural analysis of allergens, identification of B- and T-cell epitopes, assessment of allergenicity and cross-reactivity, and genome analysis. In this paper, the most important bioinformatic tools and methods with relevance to the study of allergy have been reviewed. C1 Inst Infocomm Res, Singapore 119631, Singapore. Univ Canberra, Ctr Med Informat, Canberra, ACT, Australia. US FDA, Biotechnol Studies Branch, Natl Ctr Food Safety & Technol, Summit Argo, IL USA. Commiss European Communities, Joint Res Ctr, IHCP, I-21020 Ispra, Italy. Aventis CropSci, Evry, France. Dow AgroSci, San Diego, CA USA. RP Brusic, V (reprint author), Inst Infocomm Res, 21 Heng Mui Keng Terrace, Singapore 119631, Singapore. FU FDA HHS [FD-000431] NR 103 TC 32 Z9 34 U1 1 U2 5 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0105-4538 J9 ALLERGY JI Allergy PD NOV PY 2003 VL 58 IS 11 BP 1083 EP 1092 DI 10.1034/j.1398-9995.2003.00224.x PG 10 WC Allergy; Immunology SC Allergy; Immunology GA 739BQ UT WOS:000186322700001 PM 14616117 ER PT J AU Brusic, V Millot, M Petrovsky, N Gendel, SM Gigonzac, O Stelman, SJ AF Brusic, V Millot, M Petrovsky, N Gendel, SM Gigonzac, O Stelman, SJ TI Allergen databases SO ALLERGY LA English DT Review DE allergen data; bioinformatics; data management; molecular databases ID DATA-BANK; PROTEIN; IDENTIFICATION; IMMUNOTHERAPY; FOODS AB Allergies represent a significant medical and industrial problem. Molecular and clinical data on allergens are growing exponentially and in this article we have reviewed nine specialized allergen databases and identified data sources related to protein allergens contained in general purpose molecular databases. An analysis of allergens contained in public databases indicates a high level of redundancy of entries and a relatively low coverage of allergens by individual databases. From this analysis we identify current database needs for allergy research and, in particular, highlight the need for a centralized reference allergen database. C1 Inst Infocomm Res, Singapore 119631, Singapore. Univ Canberra, Med Informat Ctr, Canberra, ACT, Australia. Commiss European Communities, Joint Res Ctr, IHCP, I-21020 Ispra, Italy. US FDA, Biotechnol Studies Branch, Natl Ctr Food Safety & Technol, Summit Argo, IL USA. Bayer CropSci, Evry, France. Dow AgroSci, San Diego, CA USA. RP Brusic, V (reprint author), Inst Infocomm Res, 21 Heng Mui Keng Terrace, Singapore 119631, Singapore. FU FDA HHS [FD-000431] NR 32 TC 43 Z9 45 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0105-4538 J9 ALLERGY JI Allergy PD NOV PY 2003 VL 58 IS 11 BP 1093 EP 1100 DI 10.1034/j.1398-9995.2003.00248.x PG 8 WC Allergy; Immunology SC Allergy; Immunology GA 739BQ UT WOS:000186322700002 PM 14616118 ER PT J AU Chang, N Simone, A Schultheis, L Rappaport, B AF Chang, N Simone, A Schultheis, L Rappaport, B TI Reviewing case reports and the droperidol warning: FDA response SO ANESTHESIA AND ANALGESIA LA English DT Letter ID QT INTERVAL; PROLONGATION C1 US FDA, Ctr Drug Evaluat & Res, Div Anesthet Crit Care & Addict Drug Prod, Rockville, MD 20857 USA. RP Chang, N (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Anesthet Crit Care & Addict Drug Prod, Rockville, MD 20857 USA. NR 7 TC 6 Z9 6 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD NOV PY 2003 VL 97 IS 5 BP 1542 EP 1542 PG 1 WC Anesthesiology SC Anesthesiology GA 735YZ UT WOS:000186143600061 PM 14570686 ER PT J AU Chen, TH Small, DA McDermott, MK Bentley, WE Payne, GF AF Chen, TH Small, DA McDermott, MK Bentley, WE Payne, GF TI Enzymatic methods for in situ cell entrapment and cell release SO BIOMACROMOLECULES LA English DT Article ID GREEN FLUORESCENT PROTEIN; ESCHERICHIA-COLI; GELATIN MATRICES; CROSS-LINKING; TRANSGLUTAMINASE; TISSUE; PHOTOPOLYMERIZATION; HYDROGELS; GEL; IMMOBILIZATION AB We report an enzyme-based method for the in situ entrapment of cells within a biopolymeric hydrogel matrix. Specifically, we used a calcium-independent microbial transglutaminase that is known to cross-link proteins and observed that it catalyzes the formation of gels from a pre-gel solution containing 10% gelatin and E. coli cells. Hydrogel formation occurs 2-3 h after adding transglutaminase, and no additional external intervention is required to initiate gel formation. The in situ entrapped cells grow rapidly and to high cell densities within the gelatin hydrogel. Additionally, the entrapped cells respond to isopropylthiogalactoside induction. The cross-linked gelatin network can be rapidly hydrolyzed (within 1 h) by the protease, proteinase K. Treatment of the network by this protease releases the entrapped E. coli cells. These cells appear unharmed by proteinase K; they can grow and be induced after protease treatment. The ability to in situ entrap, grow, and release cells under mild conditions provides unique opportunities for a range of applications and should be especially useful for microfluidic biosensor systems. C1 Univ Maryland, Inst Biotechnol, Ctr Biosyst Res, College Pk, MD 20742 USA. Univ Maryland Baltimore Cty, Dept Chem & Biochem Engn, Baltimore, MD 21250 USA. Univ Maryland, Dept Chem Engn, College Pk, MD 20742 USA. US FDA, Off Sci & Technol, Div Mech & Mat Sci, Rockville, MD 20850 USA. RP Payne, GF (reprint author), Univ Maryland, Inst Biotechnol, Ctr Biosyst Res, 5115 Plant Sci Bldg, College Pk, MD 20742 USA. NR 33 TC 49 Z9 50 U1 0 U2 12 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1525-7797 J9 BIOMACROMOLECULES JI Biomacromolecules PD NOV-DEC PY 2003 VL 4 IS 6 BP 1558 EP 1563 DI 10.1021/bm034145k PG 6 WC Biochemistry & Molecular Biology; Chemistry, Organic; Polymer Science SC Biochemistry & Molecular Biology; Chemistry; Polymer Science GA 746CV UT WOS:000186729700013 PM 14606880 ER PT J AU Haverkos, HW Battula, N Drotman, DP Rennert, OM AF Haverkos, HW Battula, N Drotman, DP Rennert, OM TI Enteroviruses and type 1 diabetes mellitus SO BIOMEDICINE & PHARMACOTHERAPY LA English DT Review DE enterovirus; type 1 diabetes mellitus; cofactors ID COXSACKIE-B-VIRUS; MOLECULAR MIMICRY; JUVENILE-ONSET; ENCEPHALOMYOCARDITIS VIRUS; CELL AUTOIMMUNITY; IDENTICAL-TWINS; IGM RESPONSES; RISK-FACTOR; HLA-DQ; CHILDREN C1 US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. Ctr Dis Control & Prevent, Natl Ctr Infect Dis, Atlanta, GA USA. NICHHD, NIH, Bethesda, MD 20892 USA. RP Haverkos, HW (reprint author), US FDA, Ctr Drug Evaluat & Res, HFD-530,5600 Fishers Lane, Rockville, MD 20857 USA. NR 90 TC 24 Z9 24 U1 0 U2 0 PU EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS PA 23 RUE LINOIS, 75724 PARIS, FRANCE SN 0753-3322 J9 BIOMED PHARMACOTHER JI Biomed. Pharmacother. PD NOV PY 2003 VL 57 IS 9 BP 379 EP 385 DI 10.1016/j.biopha.2003.03.001 PG 7 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 746CC UT WOS:000186728100001 PM 14652163 ER PT J AU Golding, H Aliberti, J King, LR Manischewitz, J Andersen, J Valenzuela, J Landau, NR Sher, A AF Golding, H Aliberti, J King, LR Manischewitz, J Andersen, J Valenzuela, J Landau, NR Sher, A TI Inhibition of HIV-1 infection by a CCR5-binding cyclophilin from Toxoplasma gondii SO BLOOD LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; CHEMOKINE RECEPTOR CCR5; SMALL-MOLECULE INHIBITOR; CELL-LINE; STRUCTURAL DETERMINANTS; MONOCLONAL-ANTIBODIES; PRIMARY MACROPHAGES; CORECEPTOR ACTIVITY; CXCR4 CORECEPTOR; DENDRITIC CELLS AB The activation of murine dendritic cells by Toxoplasma gondii has recently been shown to depend on a parasite protein that signals through the chemokine receptor CCR5. Here we demonstrate that this molecule, cyclophilin-18 (C-18), is an inhibitor of HIV-1 cell fusion and infection with cell-free virus. T gondii C-18 efficiently blocked syncytium formation between human T cells and effector cells expressing R5 but not X4 envelopes. Neither human nor Plasmodium falciparum cyclophilins possess such inhibitory activity. Importantly, C-18 protected peripheral blood leukocytes from infection with multiple HIV-1 R5 primary isolates from several clades. C-18 bound directly to human CCR5, and this interaction was partially competed by the beta-chemokine macrophage inflammatory protein 1beta (MIP-1beta) and by HIV-1 R5 gp120. In contrast to several other antagonists of HIV coreceptor function, C-18 mediated inhibition did not induce beta-chemokines or cause CCR5 down-modulation, suggesting direct blocking of envelope binding to the receptor. These data support the further development of C-18 derivatives as HIV-1 inhibitors for preventing HIV-1 transmission and for postexposure prophylaxis. (C) 2003 by The American Society of Hematology. C1 US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Bethesda, MD 20892 USA. NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. Salk Inst Biol Studies, Infect Dis Lab, La Jolla, CA 92037 USA. RP Golding, H (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Bldg 29A,Rm 1A21,8800 Rockville Pike, Bethesda, MD 20892 USA. RI Aliberti, Julio/G-4565-2012; Aliberti, Julio/I-7354-2013 OI Aliberti, Julio/0000-0003-3420-8478 NR 44 TC 26 Z9 28 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 1 PY 2003 VL 102 IS 9 BP 3280 EP 3286 DI 10.1182/blood-2003-04-1096 PG 7 WC Hematology SC Hematology GA 736BA UT WOS:000186149400037 PM 12855560 ER PT J AU Stolzenberg-Solomon, RZ Qiao, YL Abnet, CC Ratnasinghe, DL Dawsey, SM Dong, ZW Taylor, PR Mark, SD AF Stolzenberg-Solomon, RZ Qiao, YL Abnet, CC Ratnasinghe, DL Dawsey, SM Dong, ZW Taylor, PR Mark, SD TI Esophageal and gastric cardia cancer risk and folate- and vitamin B-12-related polymorphisms in Linxian, China SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID NUTRITION INTERVENTION TRIALS; DISEASE-SPECIFIC MORTALITY; CASE-COHORT; METHYLENETETRAHYDROFOLATE REDUCTASE; MINERAL SUPPLEMENTATION; PERNICIOUS-ANEMIA; POPULATION; VITAMIN; ADENOCARCINOMA; DYSPLASIA AB Linxian, a rural county in North Central China, has among the highest rates of esophageal squamous cell carcinoma (ESCC) and gastric cardia adenocarcinoma (GCA) in the world. Its inhabitants have documented chronic nutritional inadequacies, including folate and vitamin B-12 deficiencies. Using a cohort we have been studying in Linxian since 1985, we examined the relationship between incident ESCC and GCA cancers and three polymorphisms in two genes that code for enzymes that require folate and B-12 as cofactors: methionine synthase reductase (MTRR) A66G and methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C. We conducted a case-cohort study among 4005 individuals in our cohort who were alive and cancer free in 1991 and had blood samples adequate for DNA extraction. Polymorphisms were measured on all 219 incident cancers (129 ESCCs and 90 GCAs) that developed through May 1996 and on 398 controls. Cox proportional hazard models were used to estimate relative risks (RRs) and 95% confidence intervals (CIs). Individuals with the MTHFR 677TT genotype had significantly higher combined ESCC/GCA risks (RR, 1.45; 95% CI, 1.02-2.05) than those with CC or CT genotypes. The only subjects to have MTHFR 1298CC were three ESCC cases (P = 0.03). Compared with subjects with the MTRR 66AA genotype, subjects with the AG or GG genotypes had significantly higher risk of ESCC (RR, 1.59; 95% CI, 1.04-2.42). No association was observed for GCA. Our results suggest that the MTHFR C677T and MTRR A66G polymorphisms influence the risk of ESCC and GCA in this population. C1 NCI, Nutrit Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. NCI, Biostat Branch, Div Canc Epidemiol & Genet, Rockville, MD USA. US FDA, Ctr Populat Genomics, Natl Ctr Toxicol Res, Jefferson, AR USA. NCI, Canc Prevent Studies Branch, Ctr Canc Res, Rockville, MD USA. Chinese Acad Med Sci, Inst Canc, Beijing 100021, Peoples R China. NCI, Div Canc Prevent, Rockville, MD USA. RP Stolzenberg-Solomon, RZ (reprint author), NCI, Nutrit Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Suite 320 MSC 7232, Rockville, MD 20852 USA. RI Qiao, You-Lin/B-4139-2012; Abnet, Christian/C-4111-2015 OI Qiao, You-Lin/0000-0001-6380-0871; Abnet, Christian/0000-0002-3008-7843 NR 24 TC 88 Z9 95 U1 1 U2 18 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 NOV PY 2003 VL 12 IS 11 BP 1222 EP 1226 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 750NB UT WOS:000187001700016 PM 14652285 ER PT J AU Martinez, ME Lanza, E Alberts, DS Schatzkin, A Jacobs, E Einspahr, J Green, S Reid, ME Ratnasinghe, L Gunter, EW AF Martinez, ME Lanza, E Alberts, DS Schatzkin, A Jacobs, E Einspahr, J Green, S Reid, ME Ratnasinghe, L Gunter, EW TI Blood selenium and colorectal adenoma recurrence; Pooled analyses from the wheat bran fiber trial and the polyp prevention trial. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 2nd Annual AACR International Conference on Frontiers in Cancer Prevention Research CY OCT 26-30, 2003 CL PHOENIX, ARIZONA SP Amer Assoc Canc Res, Pfizer, AstraZeneca, Canc Res & Prevent Fdn, SuperGen, AFLAC Inc, Avon Fdn, Bristol Myers Squibb, Eli Lilly & Co, NCI, Takeda Pharmaceut N Amer Inc, Calif Breast Canc Res Program C1 Univ Arizona, Tucson, AZ USA. NCI, Bethesda, MD 20892 USA. Roswell Pk Canc Inst, Buffalo, NY 14263 USA. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Ctr Dis Control & Prevent, Atlanta, GA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2003 VL 12 IS 11 SU S BP 1280S EP 1280S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 752GT UT WOS:000187153300017 ER PT J AU Magnuson, B Francke-Carroll, S AF Magnuson, B Francke-Carroll, S TI Comparison of the growth and pathology of colonic preneoplastic lesions in young and adult F344 rats fed various diets. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 2nd Annual AACR International Conference on Frontiers in Cancer Prevention Research CY OCT 26-30, 2003 CL PHOENIX, ARIZONA SP Amer Assoc Canc Res, Pfizer, AstraZeneca, Canc Res & Prevent Fdn, SuperGen, AFLAC Inc, Avon Fdn, Bristol Myers Squibb, Eli Lilly & Co, NCI, Takeda Pharmaceut N Amer Inc, Calif Breast Canc Res Program C1 Univ Maryland, College Pk, MD 20742 USA. US FDA, Pathol Branch, Ctr Food Safety & Appl Nutr, College Pk, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2003 VL 12 IS 11 SU S BP 1282S EP 1282S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 752GT UT WOS:000187153300024 ER PT J AU Lyn-Cook, B Maddox, N Word, B Taylor, S Goobsy, N Hammons, G AF Lyn-Cook, B Maddox, N Word, B Taylor, S Goobsy, N Hammons, G TI COX-2 and NQO1 are potential chemopreventive targets of isothiocynates in pancreatic cancer SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 2nd Annual AACR International Conference on Frontiers in Cancer Prevention Research CY OCT 26-30, 2003 CL PHOENIX, ARIZONA SP Amer Assoc Canc Res, Pfizer, AstraZeneca, Canc Res & Prevent Fdn, SuperGen, AFLAC Inc, Avon Fdn, Bristol Myers Squibb, Eli Lilly & Co, NCI, Takeda Pharmaceut N Amer Inc, Calif Breast Canc Res Program C1 US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2003 VL 12 IS 11 SU S BP 1321S EP 1321S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 752GT UT WOS:000187153300176 ER PT J AU Dorgan, JE Boayke, NA Fears, TR Schleicher, RL Helsel, W Anderson, C Robinson, J Guin, JD Lessin, S Ratnasinghe, LD Tangrea, JA AF Dorgan, JE Boayke, NA Fears, TR Schleicher, RL Helsel, W Anderson, C Robinson, J Guin, JD Lessin, S Ratnasinghe, LD Tangrea, JA TI Serum carotenoids and alpha-tocopherol and risk of non-melanoma skin cancer. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 2nd Annual AACR International Conference on Frontiers in Cancer Prevention Research CY OCT 26-30, 2003 CL PHOENIX, ARIZONA SP Amer Assoc Canc Res, Pfizer, AstraZeneca, Canc Res & Prevent Fdn, SuperGen, AFLAC Inc, Avon Fdn, Bristol Myers Squibb, Eli Lilly & Co, NCI, Takeda Pharmaceut N Amer Inc, Calif Breast Canc Res Program C1 Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Temple Univ, Sch Med, Philadelphia, PA 19122 USA. NCI, Bethesda, MD 20892 USA. Ctr Dis Control, Atlanta, GA 30333 USA. Informat Management Serv Inc, Silver Spring, MD USA. Loyola Univ, Chicago, IL 60611 USA. 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 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 NOV PY 2003 VL 12 IS 11 SU S BP 1339S EP 1339S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 752GT UT WOS:000187153300245 ER PT J AU Romero-Steiner, S Frasch, C Concepcion, N Goldblatt, D Kayhty, H Cakevainen, M Laferriere, C Wauters, D Nahm, MH Schinsky, MF Plikaytis, BD Carlone, GM AF Romero-Steiner, S Frasch, C Concepcion, N Goldblatt, D Kayhty, H Cakevainen, M Laferriere, C Wauters, D Nahm, MH Schinsky, MF Plikaytis, BD Carlone, GM TI Multilaboratory evaluation of a viability assay for measurement of opsonophagocytic antibodies specific to the capsular polysaccharides of Streptococcus pneumoniae SO CLINICAL AND DIAGNOSTIC LABORATORY IMMUNOLOGY LA English DT Article ID PNEUMOCOCCAL CONJUGATE VACCINE; LINKED-IMMUNOSORBENT-ASSAY; PHAGOCYTIC CAPACITY; EFFICACY; FORMULATION; SEROGROUPS; DISEASE; ADULTS; SERA AB Opsonophagocytosis is a correlate of protection that measures the functional activity of vaccine-induced antibodies. A standardized opsonophagocytosis assay (OPA) should be used as part of the evaluation of current and future pneumococcal (Pnc) pollysaccharide (Ps)-based vaccines. We enrolled five laboratories to evaluate a previously standardized viability OPA. Each laboratory was provided with a detailed OPA protocol, seven target Pnc strains (serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F), two quality control sera and 12 paired sera (blinded) from adult donors who received one dose of the 23-valent Pnc Ps vaccine. Laboratories sent their results to the Centers for Disease Control and Prevention for analysis. Sera were tested in duplicate (single run), and the results were averaged to yield a single OPA titer (greater than or equal to50% killing) for each serum sample. The percentage of sera within one or two dilutions of the calculated median OPA titer was determined for each laboratory and for each serotype. In general, laboratories were capable of detecting OPA titers within one or two dilutions of the median for at least 75 and 88%, respectively, of the sera tested. The level of agreement with the median OPA titers varied depending on the participating laboratory (overall agreement = 0.8 [99% confidence interval = 0.75 to 0.85]). All OPA median titers reported for quality control sera were within one dilution of the expected titer. We conclude that this OPA can be done in multiple laboratories with a high degree of interlaboratory reproducibility. C1 Ctr Dis Control & Prevent, Resp Dis Immunol Sect, Res Dis Branch, Div Bacterial & Mycot Dis, Atlanta, GA 30333 USA. US FDA, Bethesda, MD 20014 USA. Univ London, London WC1E 7HU, England. Natl Publ Hlth Inst, Helsinki, Finland. Glaxo SmithKline Biol, Rixensart, Belgium. Univ Rochester, Rochester, NY 14627 USA. RP Romero-Steiner, S (reprint author), Ctr Dis Control & Prevent, Resp Dis Immunol Sect, Res Dis Branch, Div Bacterial & Mycot Dis, 1600 Clifton Rd,MS A-36, Atlanta, GA 30333 USA. RI Goldblatt, David/C-5972-2008; OI Goldblatt, David/0000-0002-0769-5242; Romero-Steiner, Sandra/0000-0003-4128-7768; Nahm, Moon/0000-0002-6922-1042 NR 26 TC 42 Z9 45 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1071-412X J9 CLIN DIAGN LAB IMMUN JI Clin. Diagn. Lab. Immunol. PD NOV PY 2003 VL 10 IS 6 BP 1019 EP 1024 DI 10.1128/CDLI.10.6.1019-1024.2003 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 745PX UT WOS:000186698000007 PM 14607861 ER PT J AU Reed, GF Lynn, F Meade, BD AF Reed, GF Lynn, F Meade, BD TI Use of coefficient of variation in assessing variability of quantitative assays (vol 9, pg 1235, 2003) SO CLINICAL AND DIAGNOSTIC LABORATORY IMMUNOLOGY LA English DT Correction C1 NEI, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. RP Reed, GF (reprint author), NEI, NIH, Bethesda, MD 20892 USA. NR 1 TC 1 Z9 1 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1071-412X J9 CLIN DIAGN LAB IMMUN JI Clin. Diagn. Lab. Immunol. PD NOV PY 2003 VL 10 IS 6 BP 1162 EP 1162 DI 10.1128/CDLI.10.6.1162.2003 PG 1 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 745PX UT WOS:000186698000033 ER PT J AU Fusaro, VA Stone, JH AF Fusaro, VA Stone, JH TI Mass spectrometry-based proteomics and analyses of serum: A primer for the clinical investigator SO CLINICAL AND EXPERIMENTAL RHEUMATOLOGY LA English DT Review DE proteomics; vasculitis; mass spectrometry ID PEPTIDES; CANCER; ELECTROPHORESIS; IDENTIFICATION; PATTERNS; PLASMA AB The vocabulary of proteomics and the swiftly-developing, technological nature of the field constitute substantial barriers to clinical investigators. In recent years, mass spectrometry has emerged as the most promising technique in this field. The purpose of this review is to introduce the field of mass spectrometry-based proteomics to clinical investigators, to explain Many of the relevant terms, to introduce the equipment employed in this field, and to outline approaches to asking clinical questions using a proteomic approach. Examples of clinical applications of proteomic techniques are provided from the fields of cancer and vasculitis research, with an emphasis on a pattern recognition approach. C1 US FDA, Natl Canc Inst, Clin Proteom Program, Rockville, MD 20857 USA. Johns Hopkins Univ, Sch Med, Div Rheumatol, Baltimore, MD 21218 USA. RP Stone, JH (reprint author), Johns Hopkins Vasculitis Ctr, 5501 Hopkins Bayview Circle, Baltimore, MD 21224 USA. NR 21 TC 9 Z9 10 U1 0 U2 3 PU CLINICAL & EXPER RHEUMATOLOGY PI PISA PA VIA SANTA MARIA 31, 56126 PISA, ITALY SN 0392-856X J9 CLIN EXP RHEUMATOL JI Clin. Exp. Rheumatol. PD NOV-DEC PY 2003 VL 21 IS 6 SU 32 BP S3 EP S14 PG 12 WC Rheumatology SC Rheumatology GA 758HC UT WOS:000187627400002 PM 14740422 ER PT J AU Momosaki, S Hsia, CC Nakashima, Y Kojiro, M Tabor, E AF Momosaki, S Hsia, CC Nakashima, Y Kojiro, M Tabor, E TI Integration of hepatitis B virus containing mutations in the core promoter/X gene in patients with hepatocellular carcinoma SO DIGESTIVE AND LIVER DISEASE LA English DT Article DE core promoter; hepatitis B virus; hepatocellular carcinoma; integration; mutation ID TOPOISOMERASE-I; DNA; TRANSACTIVATION; EXPRESSION; SEQUENCES; SITES AB Integration of hepatitis B virus is thought to bean essential step in hepatitis B virus associated hepatocarcinogenesis. Mutations at nucleotides 1762 and 1764 in the hepatitis B virus, within a sequence encoding both the core promoter gene and the X gene, have been found frequently in patients with hepatocellular carcinoma. However, integration of these mutant sequences has not been reported to date. Methods. A 228-base pair segment of the hepatitis B virus core promoter gene was amplified from hepatocellular carcinomas and adjacent non-tumourous liver tissue by nested PCR and sequenced. Integration of hepatitis B virus into human genomic DNA was investigated using the 'genome walking' method. Results. Point mutations were found in both hepatitis B virus nucleotides 1762 and 1764 in 8 of 14 hepatocellular carcinoma tissues (57%) and in 11 of 14 adjacent non-tumourous liver tissues (79%). Three patients were evaluated using the 'genome walking' method; all were found to have hepatitis B virus DNA integrated in their hepatocellular carcinoma (two patients) and/or in their non-tumourous liver tissue (three patients). Integration occurred in all tissues near host genomic sites that are prone to integration. Hepatitis B virus was integrated at or near the hepatitis B virus DR1 site in all samples, and all contained truncated X gene sequences that have been reported to be capable of producing fusion transcripts with transactivation potential. Conclusions. Integrated hepatitis B virus DNA containing core promoter mutations at nucleotides 1762 and 1764 was found in hepatocellular carcinoma and/or adjacent non-tumourous liver tissue of three patients. These findings leave open the possibility that insertional mutagenesis or transactivation by fusion transcripts resulting from hepatitis B virus integration could play a role in hepatocarcinogenesis in some patients. (C) 2003 Editrice Gastroenterologica Italiana S.r.l, Published by Elsevier Ltd. All rights reserved. C1 US FDA, Ctr Biol Evaluat & Res, Div Emerging & Transfus Transmitted Dis, Rockville, MD 20852 USA. Kurume Univ, Dept Pathol, Kurume, Fukuoka 830, Japan. RP Tabor, E (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Emerging & Transfus Transmitted Dis, 1401 Rockville Pike,HFM-300, Rockville, MD 20852 USA. NR 21 TC 5 Z9 6 U1 0 U2 2 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 NOV PY 2003 VL 35 IS 11 BP 795 EP 800 DI 10.1016/S1590-8658(03)00462-6 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 751AF UT WOS:000187030100009 PM 14674670 ER PT J AU Fraunfelder, FW AF Fraunfelder, FW TI Ocular side effects associated with bisphosphonates SO DRUGS OF TODAY LA English DT Review ID INDUCED UVEITIS; PAMIDRONATE; INFLAMMATION; ALENDRONATE; IRITIS; CANCER AB Bisphosphonates are used to inhibit bone resorption in postmenopausal women and in the management of hypercalcemia of malignancy. Recently, some drugs within this class of medicines have been proven to cause scleritis. Prior to this, bisphosphonates had been reported to cause a variety of ocular side effects, most of which are inflammatory. This review discusses the many different medicines called bisphosphonates and highlights the ocular side effect profile of each. In cases where information on dechallenge is provided, all the ocular side effects resolved after discontinuation of the medication. Recognition of adverse ocular events in association with bisphosphonate therapy should alert clinicians to the need for ophthalmic evaluation and the consideration of discontinuation of therapy in all cases of scleritis. (C) 2003 Prous Science. All rights reserved. C1 Oregon Hlth Sci Univ, Casey Eye Inst, Natl Registry Drug Induced Ocular Side Effects, Portland, OR 97201 USA. WHO, Collaborating Ctr Int Drug Monitorings, Uppsala, Sweden. US FDA, Rockville, MD 20857 USA. RP Fraunfelder, FW (reprint author), Oregon Hlth Sci Univ, Casey Eye Inst, Natl Registry Drug Induced Ocular Side Effects, 3375 SW Terwilliger Blvd, Portland, OR 97201 USA. EM eyedrug@ohsu.edu NR 25 TC 16 Z9 17 U1 0 U2 3 PU PROUS SCIENCE, SA PI BARCELONA PA PO BOX 540, PROVENZA 388, 08025 BARCELONA, SPAIN SN 0025-7656 J9 DRUGS TODAY JI Drugs Today PD NOV PY 2003 VL 39 IS 11 BP 829 EP 835 DI 10.1358/dot.2003.39.11.799461 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 779BJ UT WOS:000189275500001 PM 14702129 ER PT J AU Tong, WD Cao, XX Harris, S Sun, HM Fang, H Fuscoe, J Harris, A Hong, HX Xie, Q Perkins, R Shi, LM Casciano, D AF Tong, WD Cao, XX Harris, S Sun, HM Fang, H Fuscoe, J Harris, A Hong, HX Xie, Q Perkins, R Shi, LM Casciano, D TI ArrayTrack - Supporting toxicogenomic research at the US Food and Drug Administration national Center for Toxicological Research SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Editorial Material DE bioinformatics; data analysis; database; genomics; infrastructure; MIAME; microarray; systems toxicology; toxicogenomics; toxicology ID SCIENTIFIC JOURNALS; GENE-EXPRESSION; MICROARRAY DATA; DNA CHIPS; TECHNOLOGIES; BIOLOGY; INFORMATION; REPOSITORY; STANDARDS; DATABASE AB The mapping of the human genome and the determination of corresponding gene functions, pathways, and biological mechanisms are driving the emergence of the new research fields of toxicogenomics and systems toxicology. Many technological advances such as microarrays are enabling this paradigm shift that indicates an unprecedented advancement in the methods of understanding the expression of toxicity at the molecular level. At the National Center for Toxicological Research (NCTR) of the U.S. Food and Drug Administration, core facilities for genomic, proteomic, and metabonomic technologies have been established that use standardized experimental procedures to support centerwide toxicogenomic research. Collectively, these facilities are continuously producing an unprecedented volume of data. NCTR plans to develop a toxico-informatics integrated system (TIS) for the purpose of fully integrating genomic, proteomic, and metabonomic data with the data in public repositories as well as conventional in vitro and in vivo toxicology data. The TIS will enable data curation in accordance with standard ontology and provide or interface a rich collection of tools for data analysis and knowledge mining. In this article the design, practical issues, and functions of the TIS are discussed through presenting its prototype version, ArrayTrack, for the management and analysis of DNA microarray data. ArrayTrack is logically constructed of three linked components: a) a library (LIB) that mirrors critical data in public databases; b) a database (MicroarrayDB) that stores microarray experiment information that is Minimal Information About a Microarray Experiment (MIAME) compliant; and c) tools (TOOL) that operate on experimental and public data for knowledge discovery. Using ArrayTrack, we can select an analysis method from the TOOL and apply the method to selected microarray data stored in the MicroarrayDB; the analysis results can be linked directly to gene information in the LIB. C1 NCTR, Ctr Toxicoinformat, Div Biometry & Risk Assessment, US FDA, Jefferson, AR 72079 USA. Northrop Grumman Informat Technol, Jefferson, AR USA. Ctr Funct Genom, Div Reprod & Genet Toxicol, Jefferson, AR USA. Div Reprod & Genet Toxicol, Jefferson, AR USA. Ctr Hepatotox, Jefferson, AR USA. US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Tong, WD (reprint author), NCTR, Ctr Toxicoinformat, Div Biometry & Risk Assessment, US FDA, 3900 NCTR Rd,HFT-020, Jefferson, AR 72079 USA. EM wrong@nctr.fda.gov NR 30 TC 142 Z9 149 U1 2 U2 11 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 NOV PY 2003 VL 111 IS 15 BP 1819 EP 1826 DI 10.1289/ehp.6497 PG 8 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 760ZD UT WOS:000187864400010 PM 14630514 ER PT J AU Andreishcheva, EN Kunkel, JP Gemmill, TR Trimble, RB AF Andreishcheva, EN Kunkel, JP Gemmill, TR Trimble, RB TI Five genes involved in biosynthesis of the pyruvylated Gal beta 1,3-Epitope in Schizosaccharomyces pombe N-linked glycans SO GLYCOBIOLOGY LA English DT Meeting Abstract CT 8th Annual Conference of the Society-for-Glycobiology CY DEC 03-06, 2003 CL SAN DIEGO, CALIFORNIA SP Soc Glycobiol C1 New York State Dept Hlth, Wadsworth Ctr, Albany, NY USA. SUNY Albany, Sch Publ Hlth, Dept Biomed Sci, Albany, NY USA. US FDA, CBER, Lab Bacteriol Toxins, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD NOV PY 2003 VL 13 IS 11 MA 118 BP 858 EP 858 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 735WU UT WOS:000186138200121 ER PT J AU Day, JB Lee, CA AF Day, JB Lee, CA TI Secretion of the orgC gene product by Salmonella enterica serovar typhimurium SO INFECTION AND IMMUNITY LA English DT Article ID HOST-CELLS; EPITHELIAL-CELLS; INVASION GENES; BACTERIAL INTERNALIZATION; DEPENDENT MECHANISM; ACTIN CYTOSKELETON; EFFECTOR PROTEINS; EUKARYOTIC CELLS; NEEDLE COMPLEX; IDENTIFICATION AB HilA activates the transcription of genes on Salmonella pathogenicity island 1 (SPI1), which encodes a type III secretion system (TTSS). Previous studies showed that transposon insertions in orgC, a gene located on SPI1, increase hil4 expression. We characterize the orgC gene product and show that it is secreted via the SPI1 TTSS. We propose a model whereby OrgC functions as a secreted repressor of the SPI1 virulence genes. C1 Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. RP Day, JB (reprint author), US FDA, Ctr Food Safety & Appl Nutr, HFS-300,5100 Paint Branch Pkwy, College Pk, MD 20740 USA. FU NIAID NIH HHS [AI3344] NR 40 TC 8 Z9 8 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD NOV PY 2003 VL 71 IS 11 BP 6680 EP 6685 DI 10.1128/IAI.71.11.6680-6685.2003 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 736VR UT WOS:000186194300073 PM 14573697 ER PT J AU Mahmood, I AF Mahmood, I TI Center specificity in the limited sampling model (LSM): can the LSM developed from healthy subjects be extended to disease states? SO INTERNATIONAL JOURNAL OF CLINICAL PHARMACOLOGY AND THERAPEUTICS LA English DT Article DE center specificity; limited sampling model; renal and hepatic impairment ID MAXIMUM PLASMA-CONCENTRATION; UNDER-THE-CURVE; C-MAX; PHARMACOKINETICS; AREA; AUC; CARBAMAZEPINE; POPULATION; DESIGN AB Background and objectives: Area under the curve (AUC) can be related to the therapeutic or toxic effect of a drug. In order to accurately measure AUC, multiple blood samples are required, but in a clinical setting, frequent blood sampling from the patients is time-consuming and expensive. The limited sampling model (LSM) is one of the approaches that is gaining popularity due to its simplicity for the estimation of AUC using 1 - 3 samples. Despite its simplicity, the LSM has some shortcomings. One of the major drawbacks of the LSM is that the LSM developed under a given condition may not be extended to other conditions. For example, the LSM developed from healthy subjects may not be extended to disease states such as renal or hepatic impairment or vice versa. This characteristic of the LSM can be referred to as "center-specific". In this investigation, the LSM developed from the healthy subjects was used to predict AUC in patients with renal or hepatic impairment. Methods: Two sets of simulated plasma concentration versus time data for 2 antihypertensive drugs and measured plasma concentration versus time data for 2 representative drugs (A and B) were used in the analysis. Results and conclusion: The results of the study indicate that the LSM developed from healthy subjects is inadequate to predict AUC in patients with hepatic or renal impairment, indicating center specificity of the LSM. C1 US FDA, Off Therapeut Res & Review, Div Clin Trial Design & Anal,Woodmont Off,Ctr 1, Clin Pharmacol & Toxicol Branch,Ctr Biol Evaluat, Rockville, MD 20852 USA. RP Mahmood, I (reprint author), US FDA, Off Therapeut Res & Review, Div Clin Trial Design & Anal,Woodmont Off,Ctr 1, Clin Pharmacol & Toxicol Branch,Ctr Biol Evaluat, HFD-579,Suite 200N,1401 Rockville Pike, Rockville, MD 20852 USA. NR 21 TC 9 Z9 11 U1 0 U2 0 PU DUSTRI-VERLAG DR KARL FEISTLE PI OBERHACHING PA BAJUWARENRING 4, D-82041 OBERHACHING, GERMANY SN 0946-1965 J9 INT J CLIN PHARM TH JI Int. J. Clin. Pharmacol. Ther. PD NOV PY 2003 VL 41 IS 11 BP 517 EP 523 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 739RC UT WOS:000186359400003 PM 14651035 ER PT J AU Brock, WJ Rodricks, JV Rulis, A Dellarco, VL Gray, GM Lane, RW AF Brock, WJ Rodricks, JV Rulis, A Dellarco, VL Gray, GM Lane, RW TI Food safety: Risk assessment methodology and decision-making criteria SO INTERNATIONAL JOURNAL OF TOXICOLOGY LA English DT Article; Proceedings Paper CT 23rd Annual Meeting of the American-College-of-Toxicology CY NOV 10-13, 2002 CL HERSHEY, PENNSYLVANIA SP Amer Coll Toxicol DE ADI; food safety; pesticides; risk assessment AB As our scientific technology grows, risk assessment methods become more complex and, therefore, open to greater scientific debate. Risk assessment has always been a part of the regulatory notification and approval process for foods. However, the methodologies applied to risk assessment and decision- making have become diverse, dependent on a number of features, including the areas of the world in which one operates, the need to use cumulative risk assessment for pesticides and other ingredients or alternative risk assessment considerations for evaluating nontraditional or bioengineered foods. Diverse institutional structures within a single federal regulatory authority may tend to lead to diversity in risk outcomes that creates policy decisions that complicate and confuse the risk management process. On top of this challenge, decisions become more complicated by the need to examine beneficial factors of foods rather than the adverse effects of foods and food additives. Foods are a complex mixture of ingredients. Regulatory groups recognize the need to use new approaches for evaluating the safety and risks associated with foods and food additives, and to do so in a timely manner. The United States Food and Drug Administration ( US FDA) in its need to ensure standards of " reasonable certainty of no harm" continues to explore alternative means to be responsive to petitioners as well as continue to examine scientifically validated means, e. g., quantitative structure- activity relationship ( QSAR), and computer- assisted programs, within the approval process to assist in the evaluation of risks. Another means to improve the risk management process would include the cumulative risk assessment of pesticides that will, no doubt, be the beginning of more intensive efforts to understand cumulative exposures and the inherent risks from multiple pathways of exposure. The passage of the Food Quality Protection Act ( FQPA) resulted in developing additional risk assessment methodologies and approaches to assess the potential for multiple exposures and risks. Addressing the international criteria used in decision- making related to foods safety assessment has resulted in acceptable intake values for food ingredients for carcinogens and noncarcinogens that, in general, tend to be more stringent in the United States compared to Europe. Clearly, the need for harmonization of risk assessment criteria and the impact of the decision process on regulatory approvals and safety assessment is a future need for the continued assurances of food safety. The topics presented in this paper are based on a symposium held in November 2002 at the annual meeting of the American College of Toxicology. C1 ENVIRON Inst Hlth Sci, Arlington, VA 22203 USA. US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. US EPA, Off Pesticide Program, Washington, DC 20460 USA. Harvard Univ, Sch Publ Hlth, Ctr Risk Anal, Boston, MA 02115 USA. Unilever Bestfoods, Englewood Cliffs, NJ USA. RP Brock, WJ (reprint author), ENVIRON Inst Hlth Sci, 4350 N Fairfax Dr,Suite 300, Arlington, VA 22203 USA. NR 27 TC 7 Z9 8 U1 0 U2 17 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 NOV-DEC PY 2003 VL 22 IS 6 BP 435 EP 451 DI 10.1080/10915810390251438 PG 17 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 754PQ UT WOS:000187326800005 PM 14680991 ER PT J AU White, DG Datta, A McDermott, P Friedman, S Qaiyumi, S Ayers, S English, L McDermott, S Wagner, DD Zhao, S AF White, DG Datta, A McDermott, P Friedman, S Qaiyumi, S Ayers, S English, L McDermott, S Wagner, DD Zhao, S TI Antimicrobial susceptibility and genetic relatedness of Salmonella serovars isolated from animal-derived dog treats in the USA SO JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY LA English DT Article DE antimicrobial resistance; integrons; PFGE ID UNITED-STATES; RESISTANCE; HUMANS; EPIDEMIOLOGY; TYPHIMURIUM AB Objectives: The objectives of this study were to determine the potential risk of dog treats in transmitting Salmonella to humans in the USA, and to characterize genetic relatedness and antimicrobial resistance among the isolates. Methods: A total of 158 dog treats derived from pig ears and other animal parts were randomly collected nationwide and assayed for the presence of Salmonella. The Salmonella isolates were characterized using serotyping, pulsed-field gel electrophoresis (PFGE) and antimicrobial susceptibility testing. Results: Forty-one percent (65/158) of samples were positive for Salmonella. Eighty-four Salmonella isolates, comprising 24 serotypes, were recovered from the 65 positive samples. Fourteen samples were contaminated with more than one Salmonella serotype. PFGE analysis of 78 Salmonella isolates yielded 64 patterns. S. Infantis with PFGE patterns indistinguishable from those of strains identified in Canadian outbreaks in 1999 were recovered in several dog treat products. The majority of Salmonella isolates were susceptible to the antimicrobials tested; however, resistance was observed to tetracycline (26%), streptomycin (23%), sulfamethoxazole (19%), chloramphenicol (8%) and ampicillin (8%). Twenty-eight (36%) Salmonella isolates were resistant to at least one antimicrobial and 10 (13%) isolates displayed resistance to four or more antimicrobials. Two isolates were identified as S. Typhimurium DT104 with the characteristic penta-resistance phenotype (ampicillin, chloramphenicol, streptomycin, sulfamethoxazole and tetracycline). One S. Brandenburg isolate was resistant to eight antimicrobials. Seven Salmonella isolates also contained class I integrons encoding resistance genes to aminoglycosides, beta-lactam and streptothricin antimicrobials. Conclusions: The study indicates that animal-derived dog treats in the USA could be a potential source of animal and human infections with Salmonella, including multidrug-resistant Salmonella strains. C1 US FDA, Div Anim & Food Microbiol, Res Off, Ctr Vet Med, Laurel, MD 20708 USA. US FDA, Div Field Sci, Off Regulatory Affairs, Laurel, MD 20708 USA. RP Zhao, S (reprint author), US FDA, Div Anim & Food Microbiol, Res Off, Ctr Vet Med, Laurel, MD 20708 USA. NR 10 TC 39 Z9 44 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-7453 J9 J ANTIMICROB CHEMOTH JI J. Antimicrob. Chemother. PD NOV PY 2003 VL 52 IS 5 BP 860 EP 863 DI 10.1093/jac/dkg441 PG 4 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA 741EQ UT WOS:000186446100020 PM 14519678 ER PT J AU Asafu-Adjaye, EB Wong, SK AF Asafu-Adjaye, EB Wong, SK TI Determination of ginsenosides (ginseng saponins) in dry root powder from Panax ginseng, Panax quinquefolius, and selected commercial products by liquid chromatography: Interlaboratory study SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID LIGHT-SCATTERING DETECTION; MASS-SPECTROMETRY; DRUG PREPARATIONS; SEPARATION; EXTRACTS; HPLC AB Twelve collaborating laboratories assayed 4 products, namely, Panax ginseng, Panax quinquefolius, and 2 ginseng products, for 6 ginsenosides: R-b1, R-b2, R-c, R-d, R-e, and R-g1. Collaborators also received a negative control for the recovery study. Pure ginsenosides were provided as reference standards for the liquid chromatography (LC) analysis and the system suitability tests. The LC analyses were performed on the methanol extract using UV detection at 203 nm. For P. ginseng, individual ginsenosides were consistent in their means; repeatability standard deviations (RSDr) ranged from 4.17 to 5.09% and reproducibility standard deviations (RSDR) ranged from 7.27 to 11.3%. For P. quinquefolius, the Rb-1 and Rb-2 ginsenosides were higher and lower in concentration than P ginseng, with RSDR values of 3.44 and 6.60% and RSDR values of 5.91 and 12.6% respectively, and other analytes at intermediate precisions. For ginseng commercial products, RSDr values ranged from 3.39 to 8.12%, and RSDR values ranged from 7.65 to 16.5%. A recovery study was also conducted for 3 ginsenosides: R-g1, R-e, and R-bl. The average recoveries were 99.9, 96.2, and 92.3%, respectively. The method is not applicable for the determination of R-g1 and R-e in ginseng product at levels <300 mg/kg. C1 US FDA, CDER, Prod Qual Res Lab, Rockville, MD 20857 USA. Hong Kong Govt Lab, Homantin Govt Off, Hong Kong, Hong Kong, Peoples R China. RP Asafu-Adjaye, EB (reprint author), US FDA, CDER, Prod Qual Res Lab, HFD-941,NLRC Ste 2400, Rockville, MD 20857 USA. EM asafue@cder.fda.gov NR 19 TC 11 Z9 11 U1 2 U2 5 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD NOV-DEC PY 2003 VL 86 IS 6 BP 1112 EP 1123 PG 12 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 770EW UT WOS:000188711100004 PM 14979691 ER PT J AU Cieri, UR AF Cieri, UR TI Determination of atropine (hyoscyamine) sulfate in commercial products by liquid chromatography with UV absorbance and fluorescence detection: Multilaboratory study SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article AB A liquid chromatographic (LC) method with 2 detection systems for determining atropine (hyoscyamine) sulfate in commercial products was tested in a multilaboratory study. Depending on the type of product, sample solutions are prepared in methanol or methanol-water (1 + 1). The standard solution contains about 1.0 mg atropine sulfate/100 mL and is prepared in the same solvent used in sample preparation. LC separations are performed on a 7.5 cm Novapak silica column. The mobile phase is prepared by mixing 970 mL methanol with 30 mL of a 1% aqueous solution of 1-pentanesulfonic acid, sodium salt. Detection is by 2 systems, UV absorbance detection at 220 nm and fluorescence detection with excitation at 255 nm and emission at 285 nm. The injection volume is 100 or 200 muL. The following materials were used for the study: 2 separate samples of tablets labeled to contain 0.4 mg atropine sulfate, 2 separate samples of extended-re lease tablets labeled to contain 0.375 mg hyoscyamine sulfate, one sample of atropine sulfate injection labeled to contain 2 mg/mL, and one sample of 1% (v/v) atropine sulfate ophthalmic. Eight participants analyzed 2 separate portions of the 6 samples by both detection systems. A ninth participant analyzed the samples in duplicate but only by UV absorbance detection because of the unavailability of a fluorescence detector. The relative standard deviation (RSD) between laboratories ranged from 1.4 to 3.3% for samples of tablets and injections but higher for ophthalmic solutions (5.1-5.2%). A linearity study was conducted in the originating laboratory before the multilaboratory study with 5 solutions ranging in concentration from 0.80 to 1.20 mg atropine sulfate in 100 mL. Average recoveries were 100.0% by UV absorbance detection and 99.9% by fluorescence detection; the RSDs were 1.1 and 1.2%, respectively. C1 US FDA, Philadelphia, PA 19106 USA. RP Cieri, UR (reprint author), US FDA, 2nd & Chestnut Sts, Philadelphia, PA 19106 USA. EM ucieri@ora.fda.gov NR 7 TC 4 Z9 4 U1 1 U2 4 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD NOV-DEC PY 2003 VL 86 IS 6 BP 1128 EP 1134 PG 7 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 770EW UT WOS:000188711100006 PM 14979693 ER PT J AU Hammack, W Carson, MC Neuhaus, BK Hurlbut, JA Nochetto, C Stuart, JS Brown, A Kilpatrick, D Youngs, K Ferbos, K Heller, DN AF Hammack, W Carson, MC Neuhaus, BK Hurlbut, JA Nochetto, C Stuart, JS Brown, A Kilpatrick, D Youngs, K Ferbos, K Heller, DN TI Multilaboratory validation of a method to confirm chloramphenicol in shrimp and crabmeat by liquid chromatography-tandem mass spectrometry SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID RESIDUES AB An existing method for chloramphenicol (CAP) determination in shrimp using a gas chromatograph with electron capture detector was adapted for confirmation of CAP with a liquid chromatograph intgrfaced to a triple quadrupole mass spectrometer. CAP residues are extracted from tissue with ethyl acetate, isolated via liquid-liquid extraction, and concentrated by evaporation. Extracts are chromatographed by using a reversed-phased column and analyzed by electrospray negative mode tandem mass spectrometry. Four product ions (m/z 152, 176, 194, and 257) of precursor m/z 321 were monitored. Moving from, gas chromatography to liquid chromatography-tandem mass spectrometry improved the sensitivity of the method greatly, enabling reliable confirmation of CAP residues at 0.3. mug/kg (ppb). The method meets confirmation criteria recommended by the U.S. Food and Drug Administration and 4-point identification criteria established by the European Union. With slight modifications to accommodate different equipment, the method was validated in 3 laboratories. C1 US FDA, Ctr Vet Med, Res Off, Laurel, MD 20708 USA. Florida Dept Agr & Consumer Serv, Chem Residue Lab, Tallahassee, FL 32399 USA. US FDA, Off Regulatory Affairs, Pacific Reg Lab NW, Bothell, WA 98021 USA. RP Carson, MC (reprint author), US FDA, Ctr Vet Med, Res Off, 8401 Muirkirk Rd, Laurel, MD 20708 USA. EM mcarson@cvm.fda.gov NR 22 TC 21 Z9 22 U1 0 U2 3 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD NOV-DEC PY 2003 VL 86 IS 6 BP 1135 EP 1143 PG 9 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 770EW UT WOS:000188711100007 PM 14979694 ER PT J AU Rogers, PL Staruszkiewicz, WF Benner, RA AF Rogers, PL Staruszkiewicz, WF Benner, RA TI Gas chromatographic method for putrescine and cadaverine in shrimp SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID DECOMPOSITION; INDOLE; STORAGE; FOODS AB A gas-liquid chromatographic method developed for the determination of putrescine and cadaverine in fishery products was modified for application to the determination of diamines in shrimp. Addition of potassium chloride and hydrochloric acid to the methanol-water extraction solvent resulted in increased recovery of the diamines and minimized gel formation. The recovery of putrescine increased on average from 64 to 98%, and the recovery of cadaverine increased from 85 to 93%. The chromatographic separation of the derivatized diamines was significantly improved with a change from an OV-225 column (cyanopropyl methyl phenyl methyl silicone) to a more polar HP-Innowax column (crosslinked polyethylene glycol). Background levels of putrescine and cadaverine in known high-quality shrimp ranged from 0 to 0.7 ppm. Shrimp that failed sensory examination generally contained putrescine at levels >4.8 ppm and cadaverine at levels >1.3 ppm. C1 US FDA, Ctr Food Safety & Appl Nutr, Washington Seafood Lab, Beltsville Res Facil, Laurel, MD 20708 USA. RP Rogers, PL (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Washington Seafood Lab, Beltsville Res Facil, HFS-426,8301 Muirkirk Rd, Laurel, MD 20708 USA. EM PRogers@cfsan.fda.gov NR 13 TC 7 Z9 7 U1 1 U2 2 PU AOAC INT PI GAITHERSBURG PA 481 N FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 EI 1944-7922 J9 J AOAC INT JI J. AOAC Int. PD NOV-DEC PY 2003 VL 86 IS 6 BP 1172 EP 1178 PG 7 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 770EW UT WOS:000188711100012 PM 14979699 ER PT J AU Tortorello, ML AF Tortorello, ML TI Indicator organisms for safety and quality - Uses and methods for detection: Minireview SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID LISTERIA-MONOCYTOGENES; ESCHERICHIA-COLI; DRINKING-WATER; FOODS; SALMONELLA; OUTBREAK AB Indicator organisms have been used for nearly a century to assess the microbiological status of water and foods. Beginning with their use in water sanitation programs, their applications have been extended over the years to other products, and they have become important components of the microbiological testing programs of both industry and regulatory agencies. Functionally, they may be viewed as safety or quality indicators. Safety indicators suggest the presence of conditions associated with increased risk of exposure to a pathogen. Quality indicators assess conditions of importance to product manufacture or consumer acceptability. This minireview summarizes the history, use, and analytical methods for the most commonly used indicator organisms, including the aerobic plate count, yeasts and molds, the coliform groups, Escherichia coli, Enterobacteriaceae, and Listeria. C1 US FDA, Natl Ctr Food Safety & Technol, Summit Argo, IL 60501 USA. RP Tortorello, ML (reprint author), US FDA, Natl Ctr Food Safety & Technol, 6502 S Archer Rd, Summit Argo, IL 60501 USA. EM mlt@cfsan.fda.gov NR 44 TC 26 Z9 26 U1 3 U2 25 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD NOV-DEC PY 2003 VL 86 IS 6 BP 1208 EP 1217 PG 10 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 770EW UT WOS:000188711100017 PM 14979704 ER PT J AU Phelan, KM Mosholder, AD Lu, S AF Phelan, KM Mosholder, AD Lu, S TI Lithium interaction with the cyclooxygenase 2 inhibitors rofecoxib and celecoxib and other nonsteroidal anti-inflammatory drugs SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID BLOOD-CELL CONCENTRATIONS; INCREASES PLASMA LITHIUM; ION LEVELS; TOXICITY; SERUM; INDOMETHACIN; PIROXICAM; SULINDAC; ASPIRIN; IBUPROFEN AB Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) have been reported to increase serum lithium concentrations. We sought to determine whether NSAIDs that selectively inhibit cyclooxygenase (COX) 2 also elevate serum lithium concentrations. Method. The U.S. Food and Drug Administration's Adverse Event Reporting System (AERS) database was searched in January 2003 for reports of interactions between lithium and rofecoxib or celecoxib, the selective COX-2 inhibitors marketed in the United States. Additionally, a literature search was performed using PubMed with the MeSH terms anti-inflammatory agents, nonsteroidal and lithium. Reports of interactions between NSAIDs and lithium were selected for review based on titles of retrieved citations. Results: Eighteen cases of increased serum lithium concentrations after the addition of one of the COX-2 inhibitors to stable lithium therapy were retrieved from AERS, 13 with rofecoxib and 5 with celecoxib. Serum lithium concentration increases of up to 99% and 448% with concomitant celecoxib and rofecoxib use, respectively, were reported. Thirty-six English-language literature articles report interactions between lithium and various NSAIDs. Although some articles report no effect or decreased serum lithium concentrations with concomitant aspirin or sulindac, increased serum lithium concentration reports exist for aspirin, sulindac, and 14 other NSAIDs, including celecoxib and rofecoxib. Conclusion: Clinicians should consider NSAID use in the differential diagnosis of lithium toxicity, monitor patients' serum lithium concentrations during the initiation or discontinuation of NSAID therapy, and be aware that the selective COX-2 inhibitors can increase serum lithium concentrations leading to toxicity. C1 US FDA, Off Drug Safety, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Mosholder, AD (reprint author), US FDA, Off Drug Safety, Ctr Drug Evaluat & Res, 5600 Fishers Lane,HFD-430, Rockville, MD 20857 USA. NR 43 TC 42 Z9 43 U1 1 U2 5 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD NOV PY 2003 VL 64 IS 11 BP 1328 EP 1334 PG 7 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 747RX UT WOS:000186819700008 PM 14658947 ER PT J AU Cowley, SC Elkins, KL AF Cowley, SC Elkins, KL TI CD4(+) T cells mediate IFN-gamma-independent control of Mycobacterium tuberculosis infection both in vitro and in vivo SO JOURNAL OF IMMUNOLOGY LA English DT Article ID BACILLUS-CALMETTE-GUERIN; INTERFERON-GAMMA; IMMUNE-RESPONSE; B-CELL; MICE DEFICIENT; HOST-DEFENSE; LYMPHOTOXIN; RESISTANCE; GENE; SUSCEPTIBILITY AB Although IFN-gamma, is necessary for survival of Mycobacterium tuberculosis infection in people and animal models, it may not be sufficient to clear the infection, and IFN-gamma is not a reliable correlate of protection. To determine whether IFN-gamma-independent mechanisms of immunity exist, we developed a murine ex vivo culture system that directly evaluates the ability of splenic or lung lymphocytes to control the growth of M. tuberculosis within infected macrophages, and that models in vivo immunity to tuberculosis. Surprisingly, CD4(+) T cells controlled >90% of intracellular M. tuberculosis growth in the complete absence of IFN-gamma stimulation of macrophages, via a NO-dependent mechanism. Furthermore, bacillus Calmette-Guerin-vaccinated IFN-gamma-deficient mice exhibited significant protection against M. tuberculosis challenge that was lost upon depletion of CD4(+) T cells. These findings, demonstrate that CD4(+) T cells possess IFN-gamma-independent mechanisms that can limit the growth of an intracellular pathogen and are dominant in secondary responses to M. tuberculosis. C1 FDA, CBER, DBPAP, LMDCI, Rockville, MD 20852 USA. RP Cowley, SC (reprint author), FDA, CBER, DBPAP, LMDCI, 1401 Rockville Pike,HFM 431, Rockville, MD 20852 USA. NR 43 TC 69 Z9 69 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 1 PY 2003 VL 171 IS 9 BP 4689 EP 4699 PG 11 WC Immunology SC Immunology GA 735WD UT WOS:000186136800026 PM 14568944 ER PT J AU Kawakami, K Kawakami, M AF Kawakami, K Kawakami, M TI Interleukin-13 Pseudomonas exotoxin therapy in animal model of breast cancer SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 18th Annual Scientific Meeting of the International-Society-for-Biological-Therapy-of-Cancer CY OCT 31-NOV 02, 2003 CL BETHESDA, MARYLAND C1 US FDA, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20014 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 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2003 VL 26 IS 6 BP S35 EP S35 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 736UG UT WOS:000186191100111 ER PT J AU Villalba, S Salvucci, O Aoki, Y Sierra, MD Gupta, G Davis, D Wyvill, K Little, R Yarchoan, R Tosato, G AF Villalba, S Salvucci, O Aoki, Y Sierra, MD Gupta, G Davis, D Wyvill, K Little, R Yarchoan, R Tosato, G TI Serum inactivation contributes to the failure of stromal-derived factor-1 to block HIV-1 infection in vivo SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE chemokine; cytokine; chemokine processing; AIDS; anti-HIV therapy ID CHEMOKINE RECEPTOR CXCR4; HEMATOPOIETIC PROGENITOR CELLS; HUMAN ENDOTHELIAL-CELLS; BONE-MARROW; LYMPHOCYTE CHEMOATTRACTANT; MOLECULAR-CLONING; B-LYMPHOPOIESIS; FLOW CONDITIONS; GENE VARIANT; SDF-1 AB The chemokine stromal-derived factor-1 (SDF-1) can block human immunodeficiency virus type I (HIV-1) infection in vitro by binding to the CXC chemokine receptor, CXCR-4, which serves as a coreceptor for T cell tropic HIV-1. In spite of being constitutively expressed in vivo, SDF-1 does not appear to block HIV-1 infection and spread in vivo. We report that SDF-1 is consistently measured in normal serum (15.4 +/- 3.0 ng/ml; mean +/- SD) and in serum from AIDS patients (16.6 +/- 3.7 ng/ml). However, we find that circulating SDF-1 is modified to an inactive form. When exposed to serum, recombinant SDF-1 is specifically and rapidly altered to yield an apparently smaller chemokine that does not bind to SDF-1 receptor-expressing cells, does not have chemoattractive or pre-B cell stimulatory activity, and does not block HIV-1 infection. Thus, serum modification and inactivation contribute to the failure of SDF-1 to block HIV-1 infection and spread in man. The inactivation of circulating SDF-1 may be critical in permitting local gradients to develop and direct cell trafficking. C1 NCI, Ctr Canc Res, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA. NCI, HIV & AIDS Malignancy Branch, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Biostat, Rockville, MD USA. RP Villalba, S (reprint author), NCI, Ctr Canc Res, Expt Transplantat & Immunol Branch, NIH, Bldg 10,Room 12N226,MSC 1907, Bethesda, MD 20892 USA. NR 55 TC 24 Z9 25 U1 0 U2 0 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 NOV PY 2003 VL 74 IS 5 BP 880 EP 888 DI 10.1189/jlb.0403149 PG 9 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 755FG UT WOS:000187392400028 PM 12960279 ER PT J AU James, SJ Pogribny, IP Pogribna, M Miller, BJ Jernigan, S Melnyk, S AF James, SJ Pogribny, IP Pogribna, M Miller, BJ Jernigan, S Melnyk, S TI Mechanisms of DNA damage, DNA hypomethylation, and tumor progression in the folate/methyl-deficient rat model of hepatocarcinogenesis SO JOURNAL OF NUTRITION LA English DT Article; Proceedings Paper CT International Research Conference on Food, Nutrition and Cancer CY JUL 17-18, 2003 CL WASHINGTON, D.C. SP Amer Inst Canc Res, World Canc Res Fund Int, Balchem Corp, BASF Aktiengesell, Calif Dried Plum Board, Campbell Soup Co, Danisco USA Inc, Hills Pet Nutrit Inc, IP 6 Int Inc, Mead Johnson Nutrit, Roche Vitamins Inc, Ross Prod Div, Abbot Labs, Solae Co DE folate deficiency; methyl deficiency; DNA methylation; hepatocarcinogenesis; DNA strand breaks; uracil; deoxynucleotides ID PERICENTROMERIC SATELLITE REGIONS; CHOLINE-DEVOID DIET; FOLATE-DEFICIENCY; P53 GENE; URACIL MISINCORPORATION; METHYLATION PATTERNS; HUMAN-LYMPHOCYTES; POOL IMBALANCE; MESSENGER-RNA; STRAND BREAKS AB Using the folate/methyl-deficient rat model of hepatocarcinogenesis, we obtained evidence that may provide new insights into a major unresolved paradox in DNA methylation and cancer research: the mechanistic basis for genome-wide hypomethylation despite an increase in DNA methyltransferase activity and gene-specific regional hypermethylation. Previous studies revealed that the methyltransferase binds with higher affinity to DNA strand breaks, gaps, abasic sites, and uracil than it does to its cognate hemimethylated CpG sites, consistent with its ancestral function as a DNA repair enzyme. These same DNA lesions are an early occurrence in models of folate and methyl deficiency and are often present in human preneoplastic cells. We hypothesized that the high-affinity binding of the maintenance DNA methyltransferase to unrepaired lesions in DNA could sequester available enzyme away from the replication fork and promote passive replication-dependent demethylation. In support of this possibility, we found that lesion-containing DNA is less efficiently methylated than lesion-free DNA from folate/methyl-deficient rats and that an increase in DNA strand breaks precedes DNA hypomethylation. Despite an adaptive increase in DNA methyltransferase activity, hemimethylated DNA from folate/methyl-deficient rats is progressively replaced by double-stranded unmethylated DNA that is resistant to remethylation with dietary methyl repletion. In promoter regions, the inappropriate binding of the DNA methyltransferase to unrepaired lesions or mispairs may promote local histone deacetylation, methylation, and regional hypermethylation associated with tumor suppressor gene silencing. These insights in an experimental model are consistent with the possibility that DNA lesions may be a necessary prerequisite for the disruption of normal DNA methylation patterns in preneoplastic and neoplastic cells. C1 Univ Arkansas Med Sci, Dept Pediat, Little Rock, AR 72202 USA. Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP James, SJ (reprint author), Univ Arkansas Med Sci, Dept Pediat, Little Rock, AR 72202 USA. NR 64 TC 80 Z9 84 U1 0 U2 4 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD NOV PY 2003 VL 133 IS 11 SU 1 BP 3740S EP 3747S PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 745UP UT WOS:000186708400003 PM 14608108 ER PT J AU Kadlubar, FF AF Kadlubar, FF TI Molecular epidemiology of cancer. SO JOURNAL OF NUTRITION LA English DT Meeting Abstract CT International Research Conference on Food, Nutrition and Cancer CY JUL 17-18, 2003 CL WASHINGTON, D.C. SP Amer Inst Canc Res, World Canc Res Fund Int, Balchem Corp, BASF Aktiengesell, Calif Dried Plum Board, Campbell Soup Co, Danisco USA Inc, Hills Pet Nutrit Inc, IP 6 Int Inc, Mead Johnson Nutrit, Roche Vitamins Inc, Ross Prod Div, Abbot Labs, Solae Co C1 Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD NOV PY 2003 VL 133 IS 11 SU 1 BP 3849S EP 3850S PG 2 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 745UP UT WOS:000186708400031 ER PT J AU Rodriguez, WJ Roberts, R Murphy, D AF Rodriguez, WJ Roberts, R Murphy, D TI Current regulatory policies regarding pediatric indications and exclusivity SO JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION LA English DT Article; Proceedings Paper CT Conference on Treatment of Pediatric Gastroesophageal Reflux Disease CY DEC 06-08, 2000 CL WASHINGTON, D.C. DE food and drug administration modernization act of 1997 (FDAMA); pediatric exclusivity; 1998 pediatric rule AB Pediatric studies have resulted in changes in the dose of many medications given to children and an increased awareness of safety issues. An additional 6 months of pediatric exclusivity legislated under the Food and Drug Administration (FDA) Modernization Act of 1997 for pediatric studies undertaken in response to written requests from the FDA have stimulated the conduct of a large number of studies. C1 Food & Drug Adm, CDER, Rockville, MD USA. RP Rodriguez, WJ (reprint author), Off Counter Terrorism & Pediat Drug Dev OCTAP, 5600 Fisher Lane,HFD-960, Rockville, MD 20857 USA. NR 0 TC 7 Z9 7 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-2116 J9 J PEDIATR GASTR NUTR JI J. Pediatr. Gastroenterol. Nutr. PD NOV-DEC PY 2003 VL 37 SU 1 BP S40 EP S45 DI 10.1097/00005176-200311001-00009 PG 6 WC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics SC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics GA 739YW UT WOS:000186368100009 PM 14685077 ER PT J AU Chaput, MP Teixeira, JC Boivin, WS Kerr, LN Mailhot, SA O'Malley, LG AF Chaput, MP Teixeira, JC Boivin, WS Kerr, LN Mailhot, SA O'Malley, LG TI A method for assessing the durability of medical examination gloves SO JOURNAL OF TESTING AND EVALUATION LA English DT Article DE medical gloves; vinyl; latex; durability; donning method; abrasion ID LATEX; VINYL; INTEGRITY; BARRIER; PERFORATIONS; QUALITY; SURGERY AB A method was developed to test the durability of medical examination gloves. Target failure rate ranges were established for the method by analysis of published failure rates for gloves tested after clinical use. The method consists of two parts: a Simulated Donning Test Procedure and a Shaker Table Abrasion Procedure. FDA water leak testing was performed to detect defects after stressing the gloves. In the donning procedure, a donning apparatus is used to simulate the stresses of donning medical gloves. In the abrasion procedure, a hand phantom is placed inside the glove; the glove is placed into a Fleaker(TM) beaker containing an abrasive material; and a shaker table agitates the setup and stresses the glove. Failure rates were 4% for vinyl gloves and 0% for latex gloves after simulated donning alone and 41% for vinyl and 11% for latex after combined donning and abrasion testing. The measured failure rates were within the established target rate ranges. C1 US FDA, Winchester Engn & Analyt Ctr, Winchester, MA 01890 USA. RP Chaput, MP (reprint author), US FDA, Winchester Engn & Analyt Ctr, 109 Holton St, Winchester, MA 01890 USA. NR 17 TC 1 Z9 1 U1 0 U2 1 PU AMER SOC TESTING MATERIALS PI W CONSHOHOCKEN PA 100 BARR HARBOR DR, W CONSHOHOCKEN, PA 19428-2959 USA SN 0090-3973 J9 J TEST EVAL JI J. Test. Eval. PD NOV PY 2003 VL 31 IS 6 BP 472 EP 478 PG 7 WC Materials Science, Characterization & Testing SC Materials Science GA 742KP UT WOS:000186516200004 ER PT J AU Rubin, SA Amexis, G Pletnikov, M Vanderzanden, J Mauldin, J Sauder, C Malik, T Chumakov, K Carbone, KM AF Rubin, SA Amexis, G Pletnikov, M Vanderzanden, J Mauldin, J Sauder, C Malik, T Chumakov, K Carbone, KM TI Changes in mumps virus gene sequence associated with variability in neurovirulent phenotype SO JOURNAL OF VIROLOGY LA English DT Article ID NEWCASTLE-DISEASE VIRUS; CENTRAL-NERVOUS-SYSTEM; YELLOW-FEVER VIRUS; INFLUENZA-A VIRUS; HEMAGGLUTININ-NEURAMINIDASE; AQUEDUCTAL STENOSIS; INDUCED HYDROCEPHALUS; NEUROADAPTED STRAIN; VACCINE STRAIN; HEARING-LOSS AB Mumps virus is highly neurotropic and, prior to widespread vaccination programs, was the major cause of viral meningitis in the United States. Nonetheless, the genetic basis of mumps virus neurotropism and neurovirulence was until recently not understood, largely due to the lack of an animal model. Here, nonneurovirulent (Jeryl Lynn vaccine) and highly neurovirulent (88-1961 wild type) mumps virus strains were passaged in human neural cells or in chicken fibroblast cells with the goal of neuroadapting or neuroattenuating the viruses, respectively. When tested in our rat neurovirulence assay against the respective parental strains, a Jeryl Lynn virus variant with an enhanced propensity for replication (neurotropism) and damage (neurovirulence) in the brain and an 88-1961 wild-type virus variant with decreased neurotropic and neurovirulent properties were recovered. To determine the molecular basis for the observed differences in neurovirulence and neuroattenuation, the complete genomes of the parental strains and their variants were fully sequenced. A comparison at the nucleotide level associated three amino acid changes with enhanced neurovirulence of the neuroadapted vaccine strain: one each in the nucleoprotein, matrix protein, and polymerase and three amino acid changes with reduced neurovirulence of the neuroattenuated wild-type strain: one each in the fusion protein, hemagglutinin-neuraminidase protein, and polymerase. The potential role of these amino acid changes in neurotropism, neurovirulence, and neuroattenuation is discussed. C1 US FDA, Ctr Biol Evaluat & Res, OVRR, DVP, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Dept Psychiat, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. RP Rubin, SA (reprint author), US FDA, Ctr Biol Evaluat & Res, OVRR, DVP, Bldg 29A,Room 1A-21,8800 Rockville Pike, Bethesda, MD 20892 USA. NR 60 TC 27 Z9 28 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 NOV PY 2003 VL 77 IS 21 BP 11616 EP 11624 DI 10.1128/JVI.77.21.11616-11624.2003 PG 9 WC Virology SC Virology GA 733HY UT WOS:000185995300032 PM 14557647 ER PT J AU Mohan, KVK Muller, J Atreya, CD AF Mohan, KVK Muller, J Atreya, CD TI The N- and C-terminal regions of rotavirus NSP5 are the critical determinants for the formation of viroplasm-like structures independent of NSP2 SO JOURNAL OF VIROLOGY LA English DT Article ID IN-VIVO; PHOSPHOPROTEIN NSP5; SEQUENCE-ANALYSIS; PHOSPHORYLATION; PROTEIN; LOCALIZATION; MUTATIONS; DOMAIN; RNA AB Molecular events and the interdependence of the two rotavirus nonstructural proteins, NSP5 and NSP2, in producing viroplasm-like structures (VLS) were previously evaluated by using transient cellular coexpression of the genes for the two proteins, and VLS domains as well as the NSP2-binding region of NSP5 were mapped in the context of NSP2. Review of the previous studies led us to postulate that NSP2 binding of NSP5 may block the N terminus of NSP5 or render it inaccessible and that any similar N-terminal blockage may render NSP5 alone capable of producing VLS independent of NSP2. This possibility was addressed in this report by using two forms of NSP5-green fluorescent protein (GFP) chimeras wherein GFP is fused at either the N or the C terminus of NSP5 (GFP-NSP5 and NSP5-GFP) and evaluating their VLS-forming capability (by light and electron microscopy) and phosphorylation and multimerization potential independent of NSP2. Our results demonstrate that NSP5 alone can form VLS when the N terminus is blocked by fusion with a nonrotavirus protein (GFP-NSP5) but the C terminus is unmodified. Only GFP-NSP5 was able to undergo hyperphosphorylation and multimerization with the native form of NSP5, emphasizing the importance of an unmodified C terminus for these events. Deletion analysis of NSP5 mapped the essential signals for VLS formation to the C terminus and clearly suggested that hyperphosphorylation of NSP5 is not required for VLS formation. The present study emphasizes in general that when fusion proteins are used for functional studies, constructs that represent fusions at both the N and the C termini of the protein should be evaluated. C1 US FDA, Ctr Biol Evaluat & Res, Div Viral Prod,Lab Pediat & Resp Viral Dis, Sect Viral Pathogenesis & Vaccine Adverse React, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Lab Vector Borne Viral Dis, Bethesda, MD 20892 USA. RP Atreya, CD (reprint author), NIH, CBER, FDA, Bldg 29A,Room 2C-11,HFM-460,8800 Rockville Pike, Bethesda, MD 20892 USA. NR 23 TC 33 Z9 35 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 NOV PY 2003 VL 77 IS 22 BP 12184 EP 12192 DI 10.1128/JVI.77.22.12184-12192.2003 PG 9 WC Virology SC Virology GA 738NG UT WOS:000186294300033 PM 14581555 ER PT J AU Kaczmarek, RG Liu, CHK Gross, TP AF Kaczmarek, RG Liu, CHK Gross, TP TI Medical device surveillance: Gender differences in pulmonary artery rupture after pulmonary artery catheterization SO JOURNAL OF WOMENS HEALTH LA English DT Article ID SWAN-GANZ CATHETER; MANAGEMENT; PERFORATION; DIAGNOSIS AB Background: Pulmonary artery (PA) rupture is a rare but often fatal complication of PA catheterization. Methods: An analysis was performed of all the case reports of PA rupture after PA catheterization that were submitted to the Food and Drug Administration's Medical Device Reporting (MDR) system between the years 1991 and 2001. The MDR system is a national passive surveillance system that includes adverse event reports from such sources as manufacturers and healthcare professionals. The Nationwide Inpatient Sample (NIS), a massive, nationally representative database maintained by the Agency for Healthcare Research and Quality, was examined to study patterns of PA catheter use. Results: A total of 71 PA rupture cases were identified from the MDR data. The most likely outcome following PA rupture was death. These PA ruptures were associated with 47 deaths and 24 injuries. The range of reported ages of the cases was between 40 and 91 years, with a mean age of 74 years. Of the 71 PA rupture cases, 52 were in women and 10 were in men, with gender not reported in 9 of the cases. There were significantly more cases in women than expected (Mantel-Haenszel common odds ratio estimate = 5.84, 95% confidence interval 2.97 - 11.46, p < 0.001). Conclusions: These data suggest that women may be at significantly greater risk of PA rupture after PA catheterization than men. Clinicians must be aware of the potential for this complication of PA catheterization. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. RP Kaczmarek, RG (reprint author), US FDA, Ctr Devices & Radiol Hlth, HFZ-541,1350 Piccard Dr, Rockville, MD 20850 USA. EM rxk@cdrh.fda.gov NR 11 TC 3 Z9 3 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1540-9996 J9 J WOMENS HEALTH JI J. Womens Health PD NOV PY 2003 VL 12 IS 9 BP 931 EP 935 DI 10.1089/154099903770948168 PG 5 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA 768FJ UT WOS:000188532700013 PM 14670173 ER PT J AU Hicks, JM AF Hicks, JM TI An overview of terrorism and its impact on biomedical research facilities SO LAB ANIMAL LA English DT Article AB Since the '9/11' and anthrax-contaminated-letter events of 2001, American society has given the term "bioterrorism" much attention. The author clarifies the definitions associated with bioterrorism and terrorism, provides an historical perspective regarding bioweapons, defines and characterizes the types of agents used as bioweapons, reviews pertinent bioterrorism legislation, and concludes by assessing the impact of these elements on biomedical research facilities. C1 US FDA, Ctr Food Safety & Appl Nutr, Off Sci, College Pk, MD 20740 USA. Johns Hopkins Bloomberg Sch Publ Hlth, Dept Environm Hlth Sci & Hlth Policy & Management, Baltimore, MD USA. RP Hicks, JM (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Sci, College Pk, MD 20740 USA. NR 26 TC 1 Z9 1 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0093-7355 J9 LAB ANIMAL JI Lab Anim. PD NOV PY 2003 VL 32 IS 10 BP 41 EP 48 DI 10.1038/laban1103-41 PG 8 WC Veterinary Sciences SC Veterinary Sciences GA 744WJ UT WOS:000186655600009 PM 15235681 ER PT J AU Sahu, SN Acharya, S Tuminaro, H Patel, I Dudley, K LeClerc, JE Cebula, TA Mukhopadhyay, S AF Sahu, SN Acharya, S Tuminaro, H Patel, I Dudley, K LeClerc, JE Cebula, TA Mukhopadhyay, S TI The bacterial adaptive response gene, barA, encodes a novel conserved histidine kinase regulatory switch for adaptation and modulation of metabolism in Escherichia coli SO MOLECULAR AND CELLULAR BIOCHEMISTRY LA English DT Article DE Escherichia coli stress response; barA; histidine kinase; DNA microarray analysis ID ENTERICA SEROVAR TYPHIMURIUM; III SECRETION SYSTEM; SALMONELLA-TYPHIMURIUM; BIOFILM FORMATION; 2-COMPONENT SYSTEM; HYDROGEN-PEROXIDE; STRESS-RESPONSE; VIRULENCE; EXPRESSION; IDENTIFICATION AB Histidine kinases are important prokaryotic determinants of cellular adaptation to environmental conditions, particularly stress. The highly conserved histidine kinase, BarA, encoded by the bacterial adaptive response gene, barA, is a member of the family of tripartite histidine kinases, and is involved in stress adaptation. BarA has been implicated to play a role during infection of epithelial cells. Homologues and orthologues of BarA have been found in pathogenic yeast, fungi, mould and in plants. The primary aim of this review is to assimilate evidence present in the current literature linking the role of BarA in stress response, and to support it with preliminary experimental evidence indicating that, it is indeed a global response regulator. In particular, the review focuses on the unusual domain structure of the BarA protein, its role in oxidative, weak acid, and osmotic stress responses and its role in biofilm formation. A preliminary genomic approach to identify downstream genes regulated by the BarA signaling pathway, using DNA microarray, is reported. The results demonstrate that BarA plays a global response regulatory role in cell division, carbon metabolism, iron metabolism and pili formation. The evolutionary significance of these types of histidine kinase sensors is reviewed in light of their roles in pathogenesis. C1 Univ Maryland, Virginia Maryland Reg Coll Vet Med, College Pk, MD 20742 USA. Univ Maryland, Inst Biotechnol, Ctr Biosyst Res, College Pk, MD 20742 USA. Univ Maryland, Dept Anim & Avian Sci, College Pk, MD 20742 USA. US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. RP Mukhopadhyay, S (reprint author), 8075 Greenmead Dr, College Pk, MD 20742 USA. NR 57 TC 17 Z9 17 U1 1 U2 7 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 NOV PY 2003 VL 253 IS 1-2 BP 167 EP 177 DI 10.1023/A:1026028930203 PG 11 WC Cell Biology SC Cell Biology GA 727LN UT WOS:000185660200019 PM 14619967 ER PT J AU Lathers, CM AF Lathers, CM TI Challenges and opportunities in animal drug development: a regulatory perspective SO NATURE REVIEWS DRUG DISCOVERY LA English DT Article ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; INHIBITORS AB Veterinary drugs are important in maintaining the health and productivity of agricultural animals, and the health of companion animals. Although there are many parallels between the development of animal drugs and human drugs, there are also important differences. This article focuses on some key challenges and opportunities for veterinary drug development in the light of the regulatory framework for animal healthcare. C1 US FDA, Ctr Vet Med, Off Director, HFV 1, Rockville, MD 20855 USA. RP Lathers, CM (reprint author), US FDA, Ctr Vet Med, Off Director, HFV 1, 7519 Standish Pl, Rockville, MD 20855 USA. NR 16 TC 4 Z9 4 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-1776 J9 NAT REV DRUG DISCOV JI Nat. Rev. Drug Discov. PD NOV PY 2003 VL 2 IS 11 BP 915 EP 918 DI 10.1038/nrd1229 PG 4 WC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA 744TX UT WOS:000186649900019 PM 14560318 ER PT J AU Wulfkuhle, JD Aquino, JA Calvert, VS Fishman, DA Coukos, G Liotta, LA Petricoin, EF AF Wulfkuhle, JD Aquino, JA Calvert, VS Fishman, DA Coukos, G Liotta, LA Petricoin, EF TI Signal pathway profiling of ovarian cancer from human tissue specimens using reverse-phase protein microarrays SO PROTEOMICS LA English DT Article DE ovarian cancer; protein microarrays; signal transduction profiling ID HUMAN-BREAST; ONCOGENE; TUMORS; CARCINOMAS; ACTIVATION; AKT2 AB Defects in cell signaling pathways play a central role in cancer cell growth, survival, invasion and metastasis. An important goal of proteomics is to characterize and develop "circuit maps" of these signaling pathways in normal and diseased cells. We have used reverse-phase protein array technology coupled with laser capture microdissection and phospho-specific antibodies to examine the activation status of several key molecular "gates" involved in cell survival and proliferation signaling in human ovarian tumor tissue. The levels of activated extracellular-regulated kinase (ERK1/2) varied considerably in tumors of the same histotype, but no significant differences between histotypes were observed. Advanced stage tumors had slightly higher levels of phosphorylated ERK1/2 compared to early stage tumors. The activation status of Akt and glycogen synthase kinase 3beta, key proteins and indicators of the state of the phosphatidylinositol 3-kinase/Akt pro-survival pathway also showed more variation within each histotype than between the histoypes studied. Our results demonstrate the utility of reverse phase protein microarrays for the multiplexed analysis of signal transduction from discreet cell populations of cells procured directly from human ovarian tumor specimens and suggest that patterns in signal pathway activation in ovarian tumors may be patient-specific rather than type or stage specific. C1 NCI, Ctr Canc Res, Bethesda, MD 20892 USA. Food & Drug Adm, Bethesda, MD USA. Northwestern Univ, Sch Med, Chicago, IL 60611 USA. Univ Penn, Philadelphia, PA 19104 USA. RP Wulfkuhle, JD (reprint author), NCI, Ctr Canc Res, Bldg 29A Room 2B20,8800 Rockville Pike, Bethesda, MD 20892 USA. NR 18 TC 167 Z9 175 U1 1 U2 9 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 NOV PY 2003 VL 3 IS 11 BP 2085 EP 2090 DI 10.1002/pmic.200300591 PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 743PJ UT WOS:000186582500003 PM 14595806 ER PT J AU Espina, V Mehta, AI Winters, ME Calvert, V Wulfkuhle, J Petricoin, EF Liotta, LA AF Espina, V Mehta, AI Winters, ME Calvert, V Wulfkuhle, J Petricoin, EF Liotta, LA TI Protein microarrays: Molecular profiling technologies for clinical specimens SO PROTEOMICS LA English DT Review DE catalyzed reporter deposition; individual targeted therapy; laser capture microdissection; molecular profiling; protein microarray; review ID CATALYZED REPORTER DEPOSITION; LASER CAPTURE MICRODISSECTION; SIGNAL AMPLIFICATION; PROTEOMICS; CANCER; IMMUNOASSAY; MICROENVIRONMENT; DISEASE AB Proteomics, the study of protein function within biologic systems, will further our understanding of cancer pathogenesis. Coupled with transcript profiling, proteomics can herald the advent of molecular therapy tailored to the individual patient's neoplasm. Protein microarrays, one emerging class of proteomic technologies, have broad applications for discovery and quantitative analysis. This technology is uniquely suited to gather information about the post-translational modifications of proteins reflecting the activity state of signal pathways and networks. Protein microarrays now make it feasible to conduct signal network profiling within cellular samples. Nevertheless, to be successful, design and use of protein microarrays must take into consideration enormous analytical challenges. A subclass of protein microarrays, Reverse Phase Arrays, created to meet these challenges, has been optimized for use with tissue specimens, and is now in use for the analysis of biopsy samples for clinical trial research. C1 NCI, Pathol Lab, Ctr Canc Res,Food & Drug Adm, FDA,Clin Proteom Program,Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. Howard Hughes Med Inst, Bethesda, MD 20817 USA. RP Espina, V (reprint author), NCI, Pathol Lab, Ctr Canc Res,Food & Drug Adm, FDA,Clin Proteom Program,Ctr Biol Evaluat & Res, Bldg 10 Room B1B53,9000 Rockville Pike, Bethesda, MD 20892 USA. OI Espina, Virginia/0000-0001-5080-5972 NR 58 TC 163 Z9 172 U1 0 U2 15 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 NOV PY 2003 VL 3 IS 11 BP 2091 EP 2100 DI 10.1002/pmic.200300592 PG 10 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 743PJ UT WOS:000186582500004 PM 14595807 ER PT J AU Grubb, RL Calvert, VS Wulkuhle, JD Paweletz, CP Linehan, WM Phillips, JL Chuaqui, R Valasco, A Gillespie, J Emmert-Buck, M Liotta, LA Petricoin, EF AF Grubb, RL Calvert, VS Wulkuhle, JD Paweletz, CP Linehan, WM Phillips, JL Chuaqui, R Valasco, A Gillespie, J Emmert-Buck, M Liotta, LA Petricoin, EF TI Signal pathway profiling of prostate cancer using reverse phase protein arrays SO PROTEOMICS LA English DT Article DE prostate cancer; protein microarrays; signal transduction profiling AB Reverse phase protein arrays represent a new proteomics microarray technology with which to study the fluctuating state of the proteome in minute quantities of cells. The activation status of cell signaling pathways controls cellular fate and deregulation of these pathways underpins carcinogenesis. Changes in pathway activation that occur between early stage prostatic epithelial lesions, prostatic stroma and the extracellular matrix can be analyzed by obtaining pure populations of cell types by laser capture microdissection (LCM) and analyzing the relative states of several key phosphorylation points within the cellular circuitry. We have applied reverse phase protein array technology to analyze the status of key points in cell signaling involved in pro-survival, mitogenic, apoptotic and growth regulation pathways in the progression from normal prostate epithelium to invasive prostate cancer. Using multiplexed reverse phase protein arrays coupled with LCM, the states of signaling changes during disease progression from prostate cancer study sets were analyzed. Focused analysis of phosphospecific endpoints revealed changes in cellular signaling events through disease progression and, between patients. We have used a new protein array technology to study specific molecular pathways believed to be important in cell survival and progression from normal epithelium to invasive carcinoma directly from human tissue specimens. With the advent of molecular targeted therapeutics, the identification, characterization and monitoring of the signaling events within actual human biopsies will be critical for patient-tailored therapy. C1 US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. NCI, Urol Oncol Branch, Bethesda, MD 20892 USA. NCI, Ctr Canc Res, Pathol Lab, FDA Clin Proteom Program, Bethesda, MD 20892 USA. NCI, Pathol Lab, Clin Pathogenet Unit, Bethesda, MD 20892 USA. Catholic Univ Chile, Dept Urol, Santiago, Chile. RP Petricoin, EF (reprint author), US FDA, Ctr Biol Evaluat & Res, Bldg 29A Room 2D12,8800 Rockville Pike, Bethesda, MD 20892 USA. NR 19 TC 143 Z9 155 U1 0 U2 5 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 NOV PY 2003 VL 3 IS 11 BP 2142 EP 2146 DI 10.1002/pmic.200300598 PG 5 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 743PJ UT WOS:000186582500010 PM 14595813 ER PT J AU Tong, WD Fang, H Hong, HX Xie, Q Perkins, R Anson, J Sheehan, DM AF Tong, WD Fang, H Hong, HX Xie, Q Perkins, R Anson, J Sheehan, DM TI Regulatory application of SAR/QSAR for priority setting of endocrine disruptors: A perspective SO PURE AND APPLIED CHEMISTRY LA English DT Article; Proceedings Paper CT Symposium on Implications of Endocrine Active Substances for Humans and Wildlife CY NOV 17-21, 2002 CL YOKOHAMA, JAPAN ID RECEPTOR-BINDING-AFFINITY; LARGE DIVERSE SET; IN-VITRO ASSAYS; ESTROGEN-RECEPTOR; ENVIRONMENTAL ESTROGENS; CONFORMATIONAL COVERAGE; RISK ASSESSMENT; CHEMICALS; TOXICOLOGY; QSAR AB Some seven years have passed since the U.S. legislature mandated the Environmental Protection Agency (EPA) to develop and implement a screening and testing program for chemicals that may disrupt the delicate endocrine system. The envisioned EPA program has evolved to incorporate a tiered scheme of in vitro and in vivo assays, and considered QSAR as a viable method to set testing priorities. At the U.S. Food and Drug Administration's (FDA) National Center for Toxicological Research (NCTR), the Endocrine Disruptor Knowledge Base Project has developed models to predict estrogen and androgen receptor binding. Our approach rationally integrates various QSAR models into a sequential "Four-Phase" scheme according to the strength of each type of model. In four hierarchical phases, models predict the inactive chemicals that are then eliminated from the pool of chemicals to which increasingly precise but more time-consuming models are subsequently applied. Each phase employs different models selected to work complementarily in representing key activity-determining structure features in order to absolutely minimize the rate of false negatives, an outcome we view as paramount for regulatory use. In this paper, the QSAR models developed at NCTR, and particularly how we integrated these models into the "Four-Phase" system will be discussed for a number of datasets, including 58 000 chemicals identified by the U.S. EPA. C1 US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Logicon ROW Sci, Jefferson, AR 72079 USA. RP Tong, WD (reprint author), US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 45 TC 26 Z9 27 U1 0 U2 4 PU INT UNION PURE APPLIED CHEMISTRY PI RES TRIANGLE PK PA 104 TW ALEXANDER DR, PO BOX 13757, RES TRIANGLE PK, NC 27709-3757 USA SN 0033-4545 J9 PURE APPL CHEM JI Pure Appl. Chem. PD NOV-DEC PY 2003 VL 75 IS 11-12 BP 2375 EP 2388 DI 10.1351/pac200375112375 PG 14 WC Chemistry, Multidisciplinary SC Chemistry GA 764YG UT WOS:000188233800057 ER PT J AU Lamb, JC Koeter, HBWM Becker, R Gies, A Davies, L Inoue, T Jacobs, A Lyons, G Matsumoto, M Timm, G AF Lamb, JC Koeter, HBWM Becker, R Gies, A Davies, L Inoue, T Jacobs, A Lyons, G Matsumoto, M Timm, G TI Risk management options for endocrine disruptors in national and international programs SO PURE AND APPLIED CHEMISTRY LA English DT Article; Proceedings Paper CT Symposium on Implications of Endocrine Active Substances for Humans and Wildlife CY NOV 17-21, 2002 CL YOKOHAMA, JAPAN AB This workshop was convened to address common issues and concerns associated with risk management of endocrine-disrupting chemicals (EDCs). The talks described the tools and policies for key Japanese, Australian, German, and U.S. regulatory agencies. The agencies participating in the workshop were responsible for the regulation of various substances including: chemicals, pesticides, environmental contamination, pharmaceuticals, and food additives. The panel also described the role of the Organization for Economic Cooperation and Development (OECD) in standardizing the tools and validation of testing and screening methods. The panel also included nongovernmental organizations presenting the views of the World Wildlife Fund, and the chemical industry from industrialized nations; each organization described its concerns and proposed approaches to risk management of EDCs. This summary highlights the most important areas of common points of view of government, industry, and environmentalists. We also try to identify issues upon which viewpoints diverge. C1 BBL Inc, BBL Sci, Reston, VA USA. Org Econ Cooperat & Dev, Paris, France. US FDA, Rockville, MD 20857 USA. Minist Econ Trade & Ind, Chem Management Policy Div, Chiyoda Ku, Tokyo 1008901, Japan. RP Matsumoto, M (reprint author), BBL Inc, BBL Sci, Reston, VA USA. NR 1 TC 1 Z9 1 U1 0 U2 1 PU INT UNION PURE APPLIED CHEMISTRY PI RES TRIANGLE PK PA 104 TW ALEXANDER DR, PO BOX 13757, RES TRIANGLE PK, NC 27709-3757 USA SN 0033-4545 J9 PURE APPL CHEM JI Pure Appl. Chem. PD NOV-DEC PY 2003 VL 75 IS 11-12 BP 2549 EP 2553 DI 10.1351/pac200375112549 PG 5 WC Chemistry, Multidisciplinary SC Chemistry GA 764YG UT WOS:000188233800081 ER PT J AU Jacobs, A Brown, P Farrelly, J Fisher, JE Morse, D AF Jacobs, A Brown, P Farrelly, J Fisher, JE Morse, D TI Endocrine disruption and the USFDA's Center for Drug Evaluation and Research SO PURE AND APPLIED CHEMISTRY LA English DT Article; Proceedings Paper CT Symposium on Implications of Endocrine Active Substances for Humans and Wildlife CY NOV 17-21, 2002 CL YOKOHAMA, JAPAN AB Drugs may have intended or unintended endocrine effects. Drug evaluation may include both in vitro and in vivo evaluations of toxicity and developmental/reproductive effects. After a signal is identified, human relevance is of utmost concern. An integration "tool" that formalizes a weight-of-evidence approach has been developed to assess concern about reproductive/developmental toxicity to humans. This approach can be used to assess concern about an endocrine disruption signal. A signal alone does not mean a concern for humans. An effect needs to have biologic relevance, and exposure thresholds for effects may exist. Risk/benefit for a particular drug is a clinical decision and may vary by the drug indication. Risk management for an identified concern could include wording in patient communications, tracking distribution or limited distribution, and patient or pregnancy registries. C1 US FDA, Rockville, MD 20857 USA. RP Jacobs, A (reprint author), US FDA, HFD-540 5600 Fishers Lane, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU INT UNION PURE APPLIED CHEMISTRY PI RES TRIANGLE PK PA 104 TW ALEXANDER DR, PO BOX 13757, RES TRIANGLE PK, NC 27709-3757 USA SN 0033-4545 J9 PURE APPL CHEM JI Pure Appl. Chem. PD NOV-DEC PY 2003 VL 75 IS 11-12 BP 2605 EP 2607 DI 10.1351/pac200375112605 PG 3 WC Chemistry, Multidisciplinary SC Chemistry GA 764YG UT WOS:000188233800086 ER PT J AU Pomper, GJ Rick, ME Epstein, JS Read, EJ Leitman, SE AF Pomper, GJ Rick, ME Epstein, JS Read, EJ Leitman, SE TI Management of severe VWD with cryoprecipitate collected by repeated apheresis of a single dedicated donor SO TRANSFUSION LA English DT Article ID PLASMA-EXCHANGE DONATION; VON-WILLEBRAND-DISEASE; SEVERE VONWILLEBRAND DISEASE; FACTOR-VIII; DDAVP AB BACKGROUND: Rare and severe forms of VWD are associated with trace or absent VWF. The feasibility of supporting a child with severe VWD from birth through age 12 with cryoprecipitate derived from DDAVP-stimulated plasma exchange of a single dedicated donor is reported. STUDY DESIGN AND METHODS: An infant with excessive hemorrhage at circumcision was found to have Type 3 VWD. His father carried an allele with a mutation at the level of VWF mRNA expression but did not have a history of bleeding. Cryoprecipitate was prepared from serial DDAVP-stimulated plasma exchanges of the father RESULTS: Repeated plasma-exchange donations were performed to provide all of the VWF needed for his son. An average of 14 cryoprecipitate units was prepared from each donation, and the units contained markedly elevated levels of FVIII:C. The cryoprecipitate was stored for up to 102 months. Components tested after more than 8 years of storage showed 48 to 130 percent of original FVIII:C activity. Ninety-seven percent of the bleeding episodes, such as epistaxis, tongue-biting accidents, and other minor lacerations, were successfully managed with a single 50- to 100-percent replacement dose of FVIII. The patient experienced normal growth and development and is free of any long-term sequelae attributable to his disease. CONCLUSIONS: Cryoprecipitate prepared by repeated plasma exchange of a VWD carrier provided excellent hemostatic function, even after storage intervals of more than a year. Plasma exchange of a committed donor was a cost-effective and safe option for long-term management of VWD. C1 US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. NIH, Warren Grant Magnuson Clin Ctr, Dept Transfus Med, Bethesda, MD 20892 USA. NIH, Warren Grant Magnuson Clin Ctr, Dept Lab Med, Bethesda, MD 20892 USA. RP Pomper, GJ (reprint author), Wake Forest Univ, Sch Med, Dept Pathol, Winston Salem, NC 27157 USA. NR 19 TC 3 Z9 4 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD NOV PY 2003 VL 43 IS 11 BP 1514 EP 1521 DI 10.1046/j.1537-2995.2003.00550.x PG 8 WC Hematology SC Hematology GA 737TG UT WOS:000186247400003 PM 14617308 ER PT J AU Herman, BA Harris, GR AF Herman, BA Harris, GR TI Response to "An extended commentary on 'models and regulatory considerations for transient temperature rise during diagnostic ultrasound pulses' by Herman and Harris (2002)" by Miller and Dewey (2003) SO ULTRASOUND IN MEDICINE AND BIOLOGY LA English DT Editorial Material C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. RP Herman, BA (reprint author), US FDA, Ctr Devices & Radiol Hlth, 9200 Corp Blvd,HFZ-132, Rockville, MD 20850 USA. NR 6 TC 3 Z9 3 U1 0 U2 1 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 NOV PY 2003 VL 29 IS 11 BP 1661 EP 1662 DI 10.1016/j.ultrasmedbio.2003.09.001 PG 2 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA 748RA UT WOS:000186873800014 ER PT J AU Liotta, LA Ferrari, M Petricoin, E AF Liotta, LA Ferrari, M Petricoin, E TI Written in blood SO NATURE LA English DT Article C1 NCI, Bethesda, MD 20892 USA. Ohio State Univ, Dorothy M Davis Heart & Lung Res Inst, Dept Internal Med, Columbus, OH 43210 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Liotta, LA (reprint author), NCI, 10 Ctr Dr, Bethesda, MD 20892 USA. NR 5 TC 341 Z9 375 U1 6 U2 28 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD OCT 30 PY 2003 VL 425 IS 6961 BP 905 EP 905 DI 10.1038/425905a PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 737KY UT WOS:000186230600022 PM 14586448 ER PT J AU Reefhuis, J Mann, EA Whitney, CG AF Reefhuis, J Mann, EA Whitney, CG TI Bacterial meningitis in children with cochlear implants - Reply SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID RECURRENT MENINGITIS; DYSPLASIA; MALFORMATION C1 Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. US FDA, Rockville, MD 20857 USA. RP Reefhuis, J (reprint author), Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. RI Reefhuis, Jennita/E-1793-2011 OI Reefhuis, Jennita/0000-0002-4747-4831 NR 5 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 OCT 30 PY 2003 VL 349 IS 18 BP 1772 EP 1773 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 737FJ UT WOS:000186219500019 ER PT J AU Sankoh, AJ D'Agostino, RB Huque, MF AF Sankoh, AJ D'Agostino, RB Huque, MF TI Efficacy endpoint selection and multiplicity adjustment methods in clinical trials with inherent multiple endpoint issues SO STATISTICS IN MEDICINE LA English DT Article DE closed tests; composite endpoints; decision-making scenario; endpoint-specific conclusions; multiple endpoints ID CLEAR STATISTICAL SIGNIFICANCE; BONFERRONI PROCEDURE; TESTS; ALPHA; DRUG; IF AB The ideal approach for the design and analysis of clinical trials is to select a single primary endpoint that provides a complete characterization of the disease under study and pen-nits an efficient evaluation of the effect of a test drug. However, this is often not possible for a number of diseases or clinical trials. This paper examines some practical clinical decision-making scenarios for the selection and analysis of efficacy outcome measures in clinical trials with inherent multiplicity components. Copyright (C) 2003 John Wiley Sons, Ltd. C1 Aventis Pharmaceut, Global Biostat, Bridgewater, NJ 08807 USA. Boston Univ, Dept Math, Boston, MA 02215 USA. US FDA, Div Biometr 3, CDER, Rockville, MD 20857 USA. RP Sankoh, AJ (reprint author), Aventis Pharmaceut, Global Biostat, POB 6890,200 Crossing Blvd,BX2-300E, Bridgewater, NJ 08807 USA. NR 35 TC 61 Z9 62 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD OCT 30 PY 2003 VL 22 IS 20 BP 3133 EP 3150 DI 10.1002/sim.1557 PG 18 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 727JV UT WOS:000185655600002 PM 14518019 ER PT J AU Bektas, M Barak, LS Jolly, PS Liu, H Lynch, KR Lacana, E Suhr, KB Milstien, S Spiegel, S AF Bektas, M Barak, LS Jolly, PS Liu, H Lynch, KR Lacana, E Suhr, KB Milstien, S Spiegel, S TI The G protein-coupled receptor GPR4 suppresses ERK activation in a ligand-independent manner SO BIOCHEMISTRY LA English DT Article ID MULTIPLE SIGNALING PATHWAYS; GROWTH-FACTOR RECEPTOR; BETA-ARRESTIN; SPHINGOSINE 1-PHOSPHATE; KINASE ACTIVATION; BETA(2)-ADRENERGIC RECEPTOR; LYSOPHOSPHATIDIC ACID; CA2+ SENSITIZATION; ADENYLATE-CYCLASE; TYPE-2 RECEPTORS AB The lysophospholipids, lysophosphatidic acid, sphingosine-1-phosphate, and sphingosylphosphorylcholine (SPC), are bioactive lipid molecules that regulate diverse biological processes. Although the specific G protein-coupled receptors for lysophosphatidic acid and sphingosine-1-phosphate have been well-characterized, much less is known of the SPC receptors. It has been reported that ovarian cancer G protein-coupled receptor 1 (OGR1) is a high affinity receptor for SPC, and its closely related homologue GPR4 is a high affinity receptor for SPC with low affinity for lysophosphatidylcholine (LPC). However, in a functional assay to examine the specificity of ligand binding, we found that neither SPC nor LPC, or other related lysophospholipids, induced internalization of GPR4 from the plasma membrane. In agreement, these lysolipids also did not induce translocation of beta-arrestin2-GFP from the cytosol to the plasma membrane in GPR4 expressing cells. However, when these cells were cotransfected with G protein-coupled receptor kinase 2. in the absence of added ligands, beta-arrestin2-GFP accumulated in cytoplasmic vesicles, reminiscent of vesicular labeling usually observed after agonist stimulation of GPCRs. In addition, neither SPC nor LPC stimulated the binding of GTPgammaS to membranes prepared from GPR4 expressing cells and did not activate ERK1/2. Surprisingly, enforced expression of GPR4 inhibited activation of ERK1/2 induced by several stimuli, including SPC, sphingosine-1-phosphate, and even EGF. Collectively, our results suggest that SPC and LPC are not the ligands for GPR4 and that this receptor may constitutively inhibit ERK1/2 activation. C1 Virginia Commonwealth Univ, Sch Med, Dept Biochem, Richmond, VA 23298 USA. Duke Univ, Med Ctr, Dept Cell Biol, Durham, NC 27710 USA. Univ Virginia, Sch Med, Dept Pharmacol, Charlottesville, VA 22908 USA. US FDA, Immunol Lab, Bethesda, MD 20892 USA. Chungnam Natl Univ, Sch Med, Dept Dermatol, Taejon 301040, South Korea. NIMH, Lab Cellular & Mol Regulat, Bethesda, MD 20892 USA. RP Spiegel, S (reprint author), Virginia Commonwealth Univ, Sch Med, Dept Biochem, Med Coll Virginia Campus, Richmond, VA 23298 USA. FU NCI NIH HHS [CA61774]; NHLBI NIH HHS [HL61365] NR 70 TC 48 Z9 49 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD OCT 28 PY 2003 VL 42 IS 42 BP 12181 EP 12191 DI 10.1021/bi035051y PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 735UX UT WOS:000186133900007 PM 14567679 ER PT J AU Lipicky, RJ DeFelice, A Gordon, MA Hung, J Karkowsky, A Lawrence, J Pelayo, JC Targum, S Throckmorton, D Willard, J Girton, J Hsu, P Mangano, D Stertz, B Glasser, S Sherpa, TY Fenichel, RR AF Lipicky, RJ DeFelice, A Gordon, MA Hung, J Karkowsky, A Lawrence, J Pelayo, JC Targum, S Throckmorton, D Willard, J Girton, J Hsu, P Mangano, D Stertz, B Glasser, S Sherpa, TY Fenichel, RR TI Placebo in hypertension adverse reaction meta-analysis (PHARM) SO CIRCULATION LA English DT Meeting Abstract CT 76th Annual Scientific Session of the American-Heart-Association CY NOV 07-12, 2003 CL ORLANDO, FLORIDA SP Amer Heart Assoc C1 Independent, Gaithersburg, MD USA. US FDA, Div Cardiorenal Drug Prod, Rockville, MD 20857 USA. Ischemia Rsch & Educ Fdn, San Francisco, CA USA. Univ Minnesota, Minneapolis, MN USA. Harlem Hosp Med Ctr, New York, NY 10037 USA. Independent, Washington, DC 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2003 VL 108 IS 17 SU S MA 2076 BP 452 EP 452 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 739RQ UT WOS:000186360602133 ER PT J AU Koelle, DM Liu, Z McClurkan, CL Cevallos, RC Vieira, J Hosken, NA Meseda, CA Snow, DC Wald, A Corey, L AF Koelle, DM Liu, Z McClurkan, CL Cevallos, RC Vieira, J Hosken, NA Meseda, CA Snow, DC Wald, A Corey, L TI Immunodominance among herpes simplex virus-specific CD8 T cells expressing a tissue-specific homing receptor SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE cytotoxic T lymphocytes; cutaneous lymphocyte-associated antigen; lymphocyte homing receptors ID COMPLETE DNA-SEQUENCE; CLASS-I ALLELES; GENITAL HERPES; LYMPHOCYTE CYTOTOXICITY; GENE-PRODUCT; IFN-GAMMA; TYPE-2; EPITOPE; ANTIGEN; CTL AB The study of immunodominance within microbe-specific CD8 T cell responses has been challenging. We used a previously undescribed approach to create unbiased panels of CD8 cytotoxic T lymphocyte clones specific for herpes simplex virus type 2, a pathogen with a complex genome encoding at least 85 polypeptides. Circulating herpes simplex virus type 2-specific cells were enriched and cloned after sorting for expression of the skin homing-associated receptor, cutaneous lymphocyte-associated antigen, bypassing restimulation with antigen. The specificity of the resultant cytotoxic clones was determined. Clonal frequencies were compared with each other and with the total number of cytotoxic clones. For each subject within the homing receptor-positive compartment, the CD8 cytotoxic response was dominated by T cells specific for only a few peptides. Previously undescribed antigens and epitopes in viral tegument, capsid, or scaffold proteins were immunodominant in some subjects. Clone enumeration analyses were confirmed in some subjects with dominance studies by using herpes simplex mutants, vaccinia recombinants, and/or enzyme-linked immune spots. We conclude that among circulating cells expressing a homing-associated receptor, during chronic herpes type 2 infection, the CD8 T cell response becomes quite focused despite the presence of many potential antigenic peptides. C1 Univ Washington, Dept Lab Med, Seattle, WA 98195 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. Univ Washington, Dept Pathobiol, Seattle, WA 98195 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. US FDA, Rockville, MD 20852 USA. Corixa Inc, Seattle, WA 98104 USA. Virginia Mason Res Ctr, Seattle, WA 98101 USA. RP Koelle, DM (reprint author), Univ Washington, Dept Lab Med, Seattle, WA 98195 USA. RI Wald, Anna/B-6272-2012; OI Wald, Anna/0000-0003-3486-6438; Koelle, David/0000-0003-1255-9023 FU NIAID NIH HHS [AI 50132, R01 AI050132, P01 AI030731, AI 48135, AI 30731, R21 AI050132] NR 47 TC 41 Z9 43 U1 0 U2 0 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 OCT 28 PY 2003 VL 100 IS 22 BP 12899 EP 12904 DI 10.1073/pnas.2131705100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 738RF UT WOS:000186301100071 PM 14566059 ER PT J AU Chowdhury, BA AF Chowdhury, BA TI Bed covers and dust mites SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 US FDA, Rockville, MD 20857 USA. RP Chowdhury, BA (reprint author), US FDA, Rockville, MD 20857 USA. NR 1 TC 2 Z9 3 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 OCT 23 PY 2003 VL 349 IS 17 BP 1668 EP 1669 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 734ZT UT WOS:000186088400016 PM 14575054 ER PT J AU Chang, JT Green, L Beitz, J AF Chang, JT Green, L Beitz, J TI Renal failure with the use of zoledronic acid SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 US FDA, Rockville, MD 20857 USA. RP Chang, JT (reprint author), US FDA, Rockville, MD 20857 USA. NR 4 TC 217 Z9 222 U1 1 U2 3 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 OCT 23 PY 2003 VL 349 IS 17 BP 1676 EP 1678 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 734ZT UT WOS:000186088400033 PM 14573746 ER PT J AU Curtis, S Lee, K Blank, GS Brorson, K Xu, Y AF Curtis, S Lee, K Blank, GS Brorson, K Xu, Y TI Generic/matrix evaluation of SV40 clearance by anion exchange chromatography in flow-through mode SO BIOTECHNOLOGY AND BIOENGINEERING LA English DT Article DE anion exchange chromatography; SV40; virus clearance; monoclonal antibodies; generic validation ID TIME QUANTITATIVE PCR; MONOCLONAL-ANTIBODIES; PURIFICATION; VIRUS; SIMIAN-VIRUS-40; PARTICLES; VACCINE; CULTURE; CELLS AB The potential of viral contamination is a regulatory concern for continuous cell line-derived pharmaceutical proteins. Complementary and redundant safety steps, including an evaluation of the viral clearance capacity of unit operations in the purification process, are performed prior to registration and marketing of biotechnology pharmaceuticals. Because process refinement is frequently beneficial, CBER/FDA has published guidance facilitating process improvement by delineating specific instances where the bracketing and generic approaches are appropriate for virus removal validation. In this study, a generic/matrix study was performed using Q-Sepharose Fast Flow (QSFF) chromatography to determine if bracketing and generic validation can be applied to anion exchange chromatography. Key operational parameters were varied to upper and lower extreme values and the impact on viral clearance was assessed using simian virus 40 (SV40) as the model virus. Operational ranges for key chromatography parameters were identified where an SV40 log,0 reduction value (LRV) of greater than or equal to4.7 log(10) is consistently achieved. On the basis of the apparent robustness of SV40 removal by Q-anion exchange chromatography, we propose that the concept of "bracketed generic" validation can be applied to this and potentially other chromatography unit operations. (C) 2003 Wiley Periodicals, Inc. C1 Genentech Inc, Proc Sci, San Francisco, CA 94080 USA. US FDA, Ctr Biol Evaluat & Res, Div Monoclonal Antibodies, Bethesda, MD 20892 USA. Glaxo Smith Kline Inc, Biopharmaceut Proc Dev, King Of Prussia, PA 19406 USA. RP Xu, Y (reprint author), Genentech Inc, Proc Sci, 1 DNA Way, San Francisco, CA 94080 USA. NR 25 TC 51 Z9 53 U1 4 U2 9 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 OCT 20 PY 2003 VL 84 IS 2 BP 179 EP 186 DI 10.1002/bit.10746 PG 8 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 723RC UT WOS:000185444500006 PM 12966574 ER PT J AU Rathore, D Hrstka, SCL Sacci, JB De la Vega, P Linhardt, RJ Kumar, S McCutchan, TF AF Rathore, D Hrstka, SCL Sacci, JB De la Vega, P Linhardt, RJ Kumar, S McCutchan, TF TI Molecular mechanism of host specificity in Plasmodium falciparum infection - Role of circumsporozoite protein SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN MALARIA PARASITE; SPOROZOITES; HEPARIN; GENE; THROMBOSPONDIN; KNOWLESI; VACCINE; DNA; GLYCOSAMINOGLYCANS; MITOCHONDRIAL AB Plasmodium falciparum sporozoites invade liver cells in humans and set the stage for malaria infection. Circumsporozoite protein ( CSP), a predominant surface antigen on sporozoite surface, has been associated with the binding and invasion of liver cells by the sporozoites. Although CSP across the Plasmodium genus has homology and conserved structural organization, infection of a non-natural host by a species is rare. We investigated the role of CSP in providing the host specificity in P. falciparum infection. CSP from P. falciparum, P. gallinaceum, P. knowlesi, and P. yoelii species representing human, avian, simian, and rodent malaria species were recombinantly expressed, and the proteins were purified to homogeneity. The recombinant proteins were evaluated for their capacity to bind to human liver cell line HepG2 and to prevent P. falciparum sporozoites from invading these cells. The proteins showed significant differences in the binding and sporozoite invasion inhibition activity. Differences among proteins directly correlate with changes in the binding affinity to the sporozoite receptor on liver cells. P. knowlesi CSP (PkCSP) and P. yoelii CSP (PyCSP) had 4,790- and 17,800-fold lower affinity for heparin in comparison to P. falciparum CSP (PfCSP). We suggest that a difference in the binding affinity for the liver cell receptor is a mechanism involved in maintaining the host specificity by the malaria parasite. C1 NIAID, Growth & Dev Sect, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. Virginia Polytech Inst & State Univ, Virginia Bioinformat Inst, Blacksburg, VA 24061 USA. Univ Iowa, Dept Med, Iowa City, IA 52242 USA. Univ Iowa, Dept Nat Prod Chem, Iowa City, IA 52242 USA. Univ Iowa, Dept Chem, Iowa City, IA 52242 USA. Univ Iowa, Dept Chem & Biochem Engn, Iowa City, IA 52242 USA. Univ Maryland, Sch Med, Dept Microbiol & Immunol, Baltimore, MD 21201 USA. USN, Med Res Ctr, Malaria Program, Silver Spring, MD 20910 USA. US FDA, Bacterial & Parasit Dis Sect, Div Emerging TRansfus & Transmitted Dis, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP McCutchan, TF (reprint author), NIAID, Growth & Dev Sect, Lab Malaria & Vector Res, NIH, Rm 126,Bldg 4,4 Ctr Dr,MSC 0425, Bethesda, MD 20892 USA. NR 33 TC 32 Z9 35 U1 1 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 17 PY 2003 VL 278 IS 42 BP 40905 EP 40910 DI 10.1074/jbc.M306250200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 730TX UT WOS:000185847200061 PM 12904297 ER PT J AU de Jong, MC Scheffer, GL Broxterman, HJ Hooijberg, JH Slootstra, JW Meloen, RH Kreitman, RJ Husain, SR Joshi, BH Puri, RK Scheper, RJ AF de Jong, MC Scheffer, GL Broxterman, HJ Hooijberg, JH Slootstra, JW Meloen, RH Kreitman, RJ Husain, SR Joshi, BH Puri, RK Scheper, RJ TI Multidrug-resistant tumor cells remain sensitive to a recombinant interleukin-4-Pseudomonas exotoxin, except when overexpressing the multidrug resistance protein MRP1 SO CLINICAL CANCER RESEARCH LA English DT Article ID PERMUTED INTERLEUKIN 4-TOXIN; FIBROBLAST-GROWTH-FACTOR; BREAST-CARCINOMA CELLS; P-GLYCOPROTEIN; DRUG-RESISTANCE; CANCER-CELLS; ANTITUMOR-ACTIVITY; MEMBRANE-VESICLES; ATPASE ACTIVITY; IL-4 RECEPTORS AB Tumor cells may become resistant to conventional anticancer drugs through the occurrence of transmembrane transporter proteins such as P-glycoprotein (ABCB1), breast cancer resistance protein (ABCG2), or members of the multidrug resistance-associated protein family (MRP1-MRP5; ABCC1-ABCC5). In this report, we studied whether tumor cells that are cytostatic drug resistant because of overexpression of one of the above mentioned proteins are sensitive to a new anticancer agent, interieukin-4 toxin (IL-4 toxin). IL-4 toxin is a fusion protein composed of circularly permuted IL-4 and a truncated form of Pseadomonas exotoxin (PE) [IL-4(38-37)-PE38KDEL]. Ninety-six-h cytotoxicity assays and 10-day clonogenic assays showed that drug-selected multidrug resistant (MDR) tumor cells that overexpress P-glycoprotein or breast cancer resistance proteins are still sensitive to IL-4 toxin. Also, tumor cells transfected with cDNA for MRP2-5 showed no resistance, or marginal resistance, only to the toxin as compared with the parent cells. In contrast, MRP1-overexpressing cells, both drug selected and MRP1 transfected, are clearly resistant to IL-4 toxin with resistance factors of 4.3 to 8.4. MRP1-overexpressing cells were not resistant to PE itself. IL-4 toxin resistance in MRP1-overexpressing cells could be reversed by the MRP1 inhibitors probenecid or MK571 and were not affected by glutathione depletion by DL-buthionine-S,R-sulfoximine. In a transport assay using plasma membrane vesicles prepared from MRP1-overexpressing cells, IL-4 toxin and IL-4, but not PE, inhibited the translocation of the known MRP1 substrate 17beta-estradiol 17-(beta-D-glucuronide) (E(2)17betaG). These data suggest that MRP1-overexpressing cells are resistant to IL-4 toxin because of extrusion of this agent by MRP1. Still, the results of this study demonstrate that IL-4 toxin effectively kills most MDR tumor cells and, therefore, represents a promising anticancer drug. C1 Free Univ Amsterdam, Med Ctr, Dept Pathol, NL-1081 HV Amsterdam, Netherlands. Free Univ Amsterdam, Med Ctr, Dept Med Oncol, NL-1081 HV Amsterdam, Netherlands. Free Univ Amsterdam, Med Ctr, Dept Pediat Hematol Oncol, NL-1081 HV Amsterdam, Netherlands. ID DLO, Inst Anim Sci & Hlth, Dept Mol Recognit, NL-8200 AB Lelystad, Netherlands. NCI, Mol Biol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. US FDA, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Scheper, RJ (reprint author), Free Univ Amsterdam, Med Ctr, Dept Pathol, De Boelelaan 1117, NL-1081 HV Amsterdam, Netherlands. NR 47 TC 8 Z9 8 U1 1 U2 3 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD OCT 15 PY 2003 VL 9 IS 13 BP 5009 EP 5017 PG 9 WC Oncology SC Oncology GA 737CW UT WOS:000186212000044 PM 14581376 ER PT J AU Seo, KH Holt, PS Stone, HD Gast, RK AF Seo, KH Holt, PS Stone, HD Gast, RK TI Simple and rapid methods for detecting Salmonella enteritidis in raw eggs SO INTERNATIONAL JOURNAL OF FOOD MICROBIOLOGY LA English DT Article DE Salmonella enteritidis; rapid detection; egg ID POOLS AB The Centers for Disease Control and Prevention estimates there were 300,000 cases of Salmonella enteritidis (SE) in 1997. Egg products were associated with many of the cases. To address this problem, many producers implemented flock surveillance of the SE situation at their facilities. A rapid and simple method for detecting SE from poultry samples is critical for the effective implementation of such testing strategies. A lateral flow device for the detection of SE utilized in this study was manufactured by Neogen, Lansing, MI. The test panel is a presumptive qualitative test system that detects only members of Group D I Salmonella species. A series of studies were conducted to optimize the test procedure for raw eggs with different sample preparations. A novel antigen extraction method was developed for use with the test panel kit. The detection limit of the test panel kit was increased approximately tenfold when the extraction method was used. Detection of SE was 100% in raw egg pools inoculated with 10 SE cells per in] of egg and incubated at a 1:10 ratio in buffered peptone water (BPW) or tetrathionate brilliant green broth (TBG) for 24 It at 37 degreesC. The developed lateral flow test kit could provide a simple, rapid, and inexpensive method for egg producers and processors to test specifically for Salmonella group D I serovars, such as SE, in egg samples. (C) 2003 Elsevier Science B.V. All rights reserved. C1 ARS, USDA, SE Poultry Res Lab, Athens, GA 30605 USA. US FDA, CFSAN, College Pk, MD 20740 USA. RP Holt, PS (reprint author), ARS, USDA, SE Poultry Res Lab, 934 Coll Stn Rd, Athens, GA 30605 USA. NR 10 TC 24 Z9 26 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-1605 J9 INT J FOOD MICROBIOL JI Int. J. Food Microbiol. PD OCT 15 PY 2003 VL 87 IS 1-2 BP 139 EP 144 DI 10.1016/S0168-1605(03)00053-9 PG 6 WC Food Science & Technology; Microbiology SC Food Science & Technology; Microbiology GA 724QY UT WOS:000185499300015 PM 12927716 ER PT J AU Edghill-Smith, Y Venzon, D Karpova, T McNally, J Nacsa, J Tsai, WP Tryniszewska, E Moniuszko, M Manischewitz, J King, LR Snodgrass, SJ Parrish, J Markham, P Sowers, M Martin, D Lewis, MG Berzofsky, JA Belyakov, IM Moss, B Tartaglia, J Bray, M Hirsch, V Golding, H Franchini, G AF Edghill-Smith, Y Venzon, D Karpova, T McNally, J Nacsa, J Tsai, WP Tryniszewska, E Moniuszko, M Manischewitz, J King, LR Snodgrass, SJ Parrish, J Markham, P Sowers, M Martin, D Lewis, MG Berzofsky, JA Belyakov, IM Moss, B Tartaglia, J Bray, M Hirsch, V Golding, H Franchini, G TI Modeling a safer smallpox vaccination regimen, for human immunodeficiency virus type 1-infected patients, in immunocompromised Macaques SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID VACCINIA VIRUS; INFECTION; AIDS; RECOMBINANT; THERAPY; COMPLICATIONS; PROTECTION; EXPRESSION; CHALLENGE; SIVMAC251 AB We have modeled smallpox vaccination with Dryvax (Wyeth) in rhesus macaques that had depletion of CD4(+) T cells induced by infection with simian immunodeficiency virus or simian/human immunodeficiency virus. Smallpox vaccination induced significantly larger skin lesions in immunocompromised macaques than in healthy macaques. Unexpectedly, "progressive vaccinia" was infrequent. Vaccination of immunocompromised macaques with the genetically-engineered, replication-deficient poxvirus NYVAC, before or after retrovirus infection, was safe and lessened the severity of Dryvax-induced skin lesions. Neutralizing antibodies to vaccinia were induced by NYVAC, even in macaques with severe CD4(+) T cell depletion, and their titers inversely correlated with the time to complete resolution of the skin lesions. Together, these results provide the proof of concept, in macaque models that mirror human immunodeficiency virus type 1 infection, that a prime-boost approach with a highly attenuated poxvirus followed by Dryvax increases the safety of smallpox vaccination, and they highlight the importance of neutralizing antibodies in protection against virulent poxvirus. C1 NCI, Basic Res Lab, Bethesda, MD 20892 USA. NCI, Biostat & Data Management Sect, Bethesda, MD 20892 USA. NCI, Fluorescence Imaging Facil, Lab Receptor Biol & Gene Express, Bethesda, MD 20892 USA. NCI, Metab Branch, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Bethesda, MD USA. NIAID, Viral Dis Lab, Bethesda, MD 20892 USA. NIAID, Biodef Clin Res Branch, Off Clin Res, Bethesda, MD 20892 USA. NIAID, Mol Microbiol Lab, Rockville, MD USA. NIAID, Bioqual, Rockville, MD USA. Adv BioSci Labs, Kensington, NSW, Australia. So Res Inst, Frederick, MD USA. Med Acad Bialystok, Dept Pediat 3, Bialystok, Waszyngtona, Poland. Aventis Pasteur, Toronto, ON, Canada. RP Franchini, G (reprint author), NCI, Basic Res Lab, 41-D804, Bethesda, MD 20892 USA. RI Venzon, David/B-3078-2008 FU NIAID NIH HHS [N01-AI-15451] NR 31 TC 23 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 OCT 15 PY 2003 VL 188 IS 8 BP 1181 EP 1191 DI 10.1086/378518 PG 11 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 730VD UT WOS:000185850100014 PM 14551889 ER PT J AU Hsu, T Hingley-Wilson, SM Chen, B Chen, M Dai, AZ Morin, PM Marks, CB Padiyar, J Goulding, C Gingery, M Eisenberg, D Russell, RG Derrick, SC Collins, FM Morris, SL King, CH Jacobs, WR AF Hsu, T Hingley-Wilson, SM Chen, B Chen, M Dai, AZ Morin, PM Marks, CB Padiyar, J Goulding, C Gingery, M Eisenberg, D Russell, RG Derrick, SC Collins, FM Morris, SL King, CH Jacobs, WR TI The primary mechanism of attenuation of bacillus Calmette-Guerin is a loss of secreted lytic function required for invasion of lung interstitial tissue SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID MYCOBACTERIUM-TUBERCULOSIS H37RV; EPITHELIAL-CELLS; BOVIS BCG; VIRULENCE; PATHOGENESIS; SMEGMATIS; INFECTION; DELETION; GENOMICS; DELIVERY AB Tuberculosis remains a leading cause of death worldwide, despite the availability of effective chemotherapy and a vaccine. Bacillus Calmette-Guerin (BCG), the tuberculosis vaccine, is an attenuated mutant of Mycobacterium bovis that was isolated after serial subcultures, yet the functional basis for this attenuation has never been elucidated. A single region (RD1), which is absent in all BCG substrains, was deleted from virulent M. bovis and Mycobacterium, tuberculosis strains, and the resulting DeltaRD1 mutants were significantly attenuated for virulence in both immunocompromised and immunocompetent mice. The M. tuberculosis DeltaRD1 mutants were also shown to protect mice against aerosol challenge, in a similar manner to BCG. Interestingly, the DeltaRD1 mutants failed to cause cytolysis of pneumocytes, a phenotype that had been previously used to distinguish virulent M. tuberculosis from BCG. A specific transposon mutation, which disrupts the Rv3874 Rv3875 (cfp-10 esat-6) operon of RD1, also caused loss of the cytolytic phenotype in both pneumocytes and macrophages. This mutation resulted in the attenuation of virulence in mice, as the result of reduced tissue invasiveness. Moreover, specific deletion of each transcriptional unit of RD1 revealed that three independent transcriptional units are required for virulence, two of which are involved in the secretion of ESAT-6 (6-kDa early secretory antigenic target). We conclude that the primary attenuating mechanism of bacillus Calmette-Guerin is the loss of cytolytic activity mediated by secreted ESAT-6, which results in reduced tissue invasiveness. C1 Yeshiva Univ Albert Einstein Coll Med, Howard Hughes Med Inst, Dept Pathol, Bronx, NY 10461 USA. Yeshiva Univ Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10461 USA. Yeshiva Univ Albert Einstein Coll Med, Analyt Imaging Facil, Bronx, NY 10461 USA. Univ Calif Los Angeles, UCLA DOE Inst Genom & Proteom, Los Angeles, CA 90095 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. Emory Univ, Sch Med, Ctr Dept Med, Atlanta, GA 30303 USA. RP Jacobs, WR (reprint author), Yeshiva Univ Albert Einstein Coll Med, Howard Hughes Med Inst, Dept Pathol, Bronx, NY 10461 USA. FU NIAID NIH HHS [AI 26170, AI 52356, R01 AI026170, R37 AI026170]; NIGMS NIH HHS [GM 62410, P50 GM062410] NR 31 TC 397 Z9 413 U1 3 U2 19 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 OCT 14 PY 2003 VL 100 IS 21 BP 12420 EP 12425 DI 10.1073/pnas.1635213100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 733WU UT WOS:000186024300087 PM 14557547 ER PT J AU Yazwinski, TA Chapman, HD Davis, RB Letonja, T Pote, L Maes, L Vercruysse, J Jacobs, DE AF Yazwinski, TA Chapman, HD Davis, RB Letonja, T Pote, L Maes, L Vercruysse, J Jacobs, DE TI World Association for the Advancement of Veterinary Parasitology (WAAVP) guidelines for evaluating the effectiveness of anthelmintics in chickens and turkeys SO VETERINARY PARASITOLOGY LA English DT Article DE anthelmintics; chicken; turkey; WAAVP guidelines ID RAILLIETINA-CESTICILLUS MOLIN; ASCARIDIA-GALLI EGGS; RUMINANTS BOVINE; EFFICACY; INFECTIONS; POULTRY; FENBENDAZOLE; POPULATIONS; PREVALENCE; HELMINTHS AB These guidelines have been prepared to assist in the planning, operation and interpretation of studies designed to assess the effectiveness of drugs against helminth parasites of chickens and turkeys. They are the first to be compiled under the auspices of the World Association for the Advancement of Veterinary Parasitology (WAAVP) for these parasites. The advantages and disadvantages of the widely used critical and controlled tests are discussed. Information is provided on the selection of animals for experiments, animal housing, feed, dose determination studies, confirmatory and field trials, record keeping and necropsy procedures. This document should help investigators and those involved in product approval and registration in conducting and evaluating studies concerned with determining the effectiveness and safety of anthelmintic drugs. (C) 2003 Elsevier B.V. All rights reserved. C1 Univ Ghent, Fac Vet Med, Dept Virol Parasitol & Immunol, B-9820 Merelbeke, Belgium. Univ London Royal Vet Coll, Dept Pathol & Infect Dis, Hatfield AL9 7TA, Herts, England. Univ Instelling Antwerp, Fac Pharmaceut Sci, Dept Microbiol, B-2610 Antwerp, Belgium. Mississippi State Univ, Coll Vet Med, Mississippi State, MS 39762 USA. US FDA, Ctr Vet Med, ONADE, HFV135, Rockville, MD 20855 USA. Univ Georgia, Coll Vet Med, Avian Med Res Ctr, Athens, GA 30602 USA. Univ Arkansas, Dept Poultry Sci, Fayetteville, AR 72701 USA. Univ Arkansas, Dept Anim Sci, Fayetteville, AR 72701 USA. RP Vercruysse, J (reprint author), Univ Ghent, Fac Vet Med, Dept Virol Parasitol & Immunol, Salisburylaan 133, B-9820 Merelbeke, Belgium. EM jozef.vercruysse@ugent.be RI Maes, Louis/A-2384-2017 OI Maes, Louis/0000-0002-2324-9509 NR 45 TC 35 Z9 36 U1 0 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-4017 EI 1873-2550 J9 VET PARASITOL JI Vet. Parasitol. PD OCT 8 PY 2003 VL 116 IS 2 BP 159 EP 173 DI 10.1016/S0304-4017(03)00264-4 PG 15 WC Parasitology; Veterinary Sciences SC Parasitology; Veterinary Sciences GA 729LP UT WOS:000185775300007 PM 14519320 ER PT J AU Kirkland, DJ Hayashi, M MacGregor, JT Muller, L Schechtman, LM Sofuni, I AF Kirkland, DJ Hayashi, M MacGregor, JT Muller, L Schechtman, LM Sofuni, I TI Summary of major conclusions SO MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS LA English DT Editorial Material ID GENOTOXICITY TEST PROCEDURES; INTERNATIONAL WORKSHOP C1 Covance Labs Ltd, Harrogate HG3 1PY, N Yorkshire, England. Natl Inst Hlth Sci, Setagaya Ku, Tokyo 1588501, Japan. US FDA, Natl Ctr Toxicol Res, Rockville, MD 20857 USA. Novartis Pharma AG, CH-4002 Basel, Switzerland. NovusGene Inc, Tokyo 1928512, Japan. RP Kirkland, DJ (reprint author), Covance Labs Ltd, Otley Rd, Harrogate HG3 1PY, N Yorkshire, England. NR 5 TC 1 Z9 2 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 OCT 7 PY 2003 VL 540 IS 2 BP 123 EP 125 DI 10.1016/j.mrgentox.2003.07.002 PG 3 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 733PX UT WOS:000186010800002 PM 14550496 ER PT J AU Moore, MM Honma, M Clements, J Bolcsfoldi, G Cifone, M Delongchamp, R Fellows, M Gollapudi, B Jenkinson, P Kirby, P Kirchner, S Muster, W Myhr, B O'Donovan, M Oliver, J Omori, T Ouldelhkim, MC Pant, K Preston, R Riach, C San, R Stankowski, LF Thakur, A Wakuri, S Yoshimura, I AF Moore, MM Honma, M Clements, J Bolcsfoldi, G Cifone, M Delongchamp, R Fellows, M Gollapudi, B Jenkinson, P Kirby, P Kirchner, S Muster, W Myhr, B O'Donovan, M Oliver, J Omori, T Ouldelhkim, MC Pant, K Preston, R Riach, C San, R Stankowski, LF Thakur, A Wakuri, S Yoshimura, I TI Mouse lymphoma thymidine kinase gene mutation assay: International Workshop on Genotoxicity Tests Workgroup Report - Plymouth, UK 2002 SO MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS LA English DT Article; Proceedings Paper CT International Workshop on Genotoxicity Testing CY JUN 28-29, 2002 CL PLYMOUTH, ENGLAND DE mouse lymphoma; genotoxicity; mutant frequency ID MICROWELL METHOD; PROTOCOL ISSUES; CELLS; AGAR AB The Mouse Lymphoma Assay (MLA) Workgroup of the International Workshop on Genotoxicity Tests (IWGT) met on June 28th and 29th, 2002, in Plymouth, England. This meeting of the MLA group was devoted to discussing the criteria for assay acceptance and appropriate approaches to data evaluation. Prior to the meeting, the group conducted an extensive analysis, of data from both the microwell and soft agar versions of the assay. For the establishment of criteria for assay acceptance, 10 laboratories (6 using the microwell method and 4 using soft agar) provided data on their background mutant frequencies plating, efficiencies of the negative/vehicle control, cell suspension growth, and positive control mutant frequencies. Using the distribution curves generated from this data, the Workgroup reached consensus on the range of values that should be used to determine whether an individual experiment is acceptable. In order to establish appropriate approaches for data evaluation, the group used a number of statistical methods to evaluate approximately 400 experimental data sets from 10 laboratories entered into a database created for the earlier MLA Workshop held in New Orleans [Environ. Mol. Mutagen. 40 (2002) 292]. While the Workgroup could not, during this meeting, make a final recommendation for the evaluation of data, a general strategy was developed and the Workgroup members agreed to evaluate this new proposed approach using their own laboratory data. This evaluation should lead to a consensus global approach for data evaluation in the near future. (C) 2003 Elsevier B.V. All rights reserved. C1 US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Natl Inst Hlth Sci, Div Genet & Mutagenesis, Tokyo 158, Japan. Covance Labs Ltd, Harrogate, N Yorkshire, England. AstraZeneca R&D, Safety Assessment, Sodertalje, Sweden. Covance Labs Inc, Vienna, VA USA. AstraZeneca R&D, Safety Assessment UK, Macclesfield, Cheshire, England. Dow Chem Co USA, TERC, Midland, MI 48674 USA. Safepharm Labs Ltd, Shardlow, Derby, England. Sitek Res Labs, Rockville, MD USA. F Hoffmann La Roche & Co Ltd, CH-4002 Basel, Switzerland. GlaxoSmithKline, Ware, Herts, England. Natl Inst Hlth Sci, Pharmaceut & Med Devices Evaluat Ctr, Tokyo 158, Japan. Aventis Pharma, Paris, France. Johnson & Johnson Pharmaceut Res & Dev, Spring House, PA USA. Inveresk Res, Tranent, Scotland. BioReliance Corp, Rockville, MD USA. Food & Drug Safety Ctr, Hatano Res Inst, Kanagawa, Japan. Sci Univ Tokyo, Fac Engn, Shinjuku Ku, Tokyo 162, Japan. RP Moore, MM (reprint author), US FDA, Natl Ctr Toxicol Res, HFT-120,3900 NCTR Rd, Jefferson, AR 72079 USA. NR 13 TC 41 Z9 49 U1 0 U2 4 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 OCT 7 PY 2003 VL 540 IS 2 BP 127 EP 140 DI 10.1016/j.mrgentox.2003.07.003 PG 14 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 733PX UT WOS:000186010800003 PM 14550497 ER PT J AU Thybaud, W Dean, S Nohmi, T de Boer, J Douglas, GR Glickman, BW Gorelick, NJ Heddle, JA Heflich, RH Lambert, L Martus, HJ AF Thybaud, W Dean, S Nohmi, T de Boer, J Douglas, GR Glickman, BW Gorelick, NJ Heddle, JA Heflich, RH Lambert, L Martus, HJ TI In vivo transgenic mutation assays SO MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS LA English DT Article; Proceedings Paper CT International Workshop on Genotoxicity Testing CY JUN 28-29, 2002 CL PLYMOUTH, ENGLAND ID ETHYL-N-NITROSOUREA; GENE-MUTATIONS; CELL-PROLIFERATION; MOLECULAR CHARACTERISTICS; GENOTYPIC SELECTION; MOUSE LYMPHOCYTES; SPI(-) SELECTION; MUTANT FREQUENCY; LACI TRANSGENE; MUTA(TM) MOUSE AB Transgenic rodent gene-mutation models provide relatively quick and statistically reliable assays for gene mutations in the DNA from any tissue. This report summarizes those issues that have been agreed upon at a previous IWGT meeting [Environ. Mol. Mutagen. 35 (2000) 253], and discusses in depth those issues for which no consensus was reached before. It was previously agreed that for regulatory applications, assays should be based upon neutral genes, be generally available in several laboratories, and be readily transferable. For phage-based assays, five to ten animals per group should be analyzed, assuming a spontaneous mutant frequency (MF) of similar to3 x 10(-5) mutants/locus and 125,000-300,000 plaque or colony forming units (pfu or cfu) per tissue per animal. A full set of data should be generated for a vehicle control and two dose groups. Concurrent positive control animals are only necessary during validation, but positive control DNA must be included in each plating. Tissues should be processed and analyzed in a blocked design, where samples from negative control, positive control and each treatment group are processed together. The total number of pfus or cfus and the MF for each tissue and animal are reported. Statistical tests should consider the animal as the experimental unit. Nonparametric statistical tests are recommended. A positive result is a statistically significant dose-response and/or statistically significant increase in any dose group compared to concurrent negative controls using an appropriate statistical model. A negative result is a statistically non-significant change, with all mean MFs within two standard deviations of the control. During the current workshop, a general protocol was agreed in which animals are treated daily for 28 consecutive days and tissues sampled 3 days after the final treatment. This recommendation could be modified by reducing or increasing the number of treatments or the length of the treatment period, when scientifically justified. Normally male animals alone are sufficient and normally at least one rapidly proliferating and one slowly proliferating tissue should be sampled. Although, as agreed previously, sequencing data are not normally required, they might provide useful additional information in specific circumstances, mainly to identify and correct for clonal. expansion and in some cases to determine a mechanism associated with a positive response. (C) 2003 Elsevier B.V All rights reserved. C1 Aventis Pharma, Drug Safety Evaluat, Vitry Sur Seine, France. Huntingdon Life Sci, Huntingdon, Cambs, England. Natl Inst Hlth Sci, Div Genet & Mutagenesis, Tokyo 158, Japan. Univ Victoria, Ctr Biomed Res, Victoria, BC, Canada. Hlth Canada, Ctr Environm Hlth, Mutagenesis Sect, Ottawa, ON K1A 0L2, Canada. York Univ, Dept Biol, Toronto, ON M3J 2R7, Canada. US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Novartis Pharma AG, Genet Toxicol& Funct Validat, Basel, Switzerland. SRI Int, Toxicol Lab, Menlo Pk, CA 94025 USA. Natl Inst Hlth, Div Cellular & Gene Therapy Prod, Tokyo 141, Japan. Snow Brand Labio Co Ltd, Inst Res & Dev, Aichi, Japan. RP Thybaud, W (reprint author), Aventis Pharma, Drug Safety Evaluat, Vitry Sur Seine, France. NR 61 TC 5 Z9 5 U1 0 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1383-5718 J9 MUTAT RES-GEN TOX EN JI Mutat. Res. Genet. Toxicol. Environ. Mutagen. PD OCT 7 PY 2003 VL 540 IS 2 BP 141 EP 151 DI 10.1016/j.mrgentox.2003.07.004 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 733PX UT WOS:000186010800004 ER PT J AU Storer, RD French, JE Donehower, LA Gulezian, D Mitsumori, K Recio, L Schiestl, RH Sistare, FD Tamaoki, N Usui, T van Steeg, H AF Storer, RD French, JE Donehower, LA Gulezian, D Mitsumori, K Recio, L Schiestl, RH Sistare, FD Tamaoki, N Usui, T van Steeg, H CA IWGT Working Grp TI Transgenic tumor models for carcinogen identification: the heterozygous Trp53-deficient and RasH2 mouse lines SO MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS LA English DT Article; Proceedings Paper CT International Workshop on Genotoxicity Testing CY JUN 28-29, 2002 CL PLYMOUTH, ENGLAND DE carcinogen; genetically altered mouse model; rodent ID INDUCE INTRACHROMOSOMAL RECOMBINATION; SHORT-TERM CARCINOGENICITY; EYED UNSTABLE MUTATION; P53-DEFICIENT MICE; THYMIC LYMPHOMAS; TG.AC MOUSE; NONRESPONDER PHENOTYPE; KNOCKOUT MICE; MESSENGER-RNA; XPA AB Genetically altered mouse models (GAMM) for human cancers have been critical to the investigation and characterization of oncogene and tumor suppressor gene expression and function and the associated cancer phenotype. Similarly, several of the mouse models with defined genetic alterations have shown promise for identification of potential human carcinogens and investigation of mechanisms of carcinogen-gene interactions and tumorigenesis. In particular, both the B6.129N5-Trp53 mouse, heterozygous for a p53 null allele, and the CB6F(1)-RasH2 mouse, hemizygous for the human H-ras transgene, have been extensively investigated. Using 26-week exposure protocols at or approaching the maximum tolerated dose, the summary results to date indicate the potential for GAMM to identify and, possibly, classify chemicals of potential risk to humans using short-term carcinogenicity experiments. This IWGT session focused on: (1) the development of recommendations for genetic/molecular characterization required in animals, tissues, and tumors before and after treatment for identification of presumptive human carcinogens based on the current state of knowledge, (2) identification of data gaps in our current state of knowledge, and (3) development of recommendations for research strategies for further development of our knowledge base of these particular models. By optimization of protocols and identification of significant outcomes and responses to chemical exposure in appropriate short-term mechanism-based genetically altered rodent models, strategies for prevention and intervention may be developed and employed to the benefit of public health. Published by Elsevier B.V. C1 Merck Res Labs, Dept Genet & Cellular Toxicol, W Point, PA 19486 USA. NIEHS, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA. Baylor Coll Med, Dept Mol Virol & Microbiol, Houston, TX 77030 USA. Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA. Tacon Farms Inc, Germantown, NY 12526 USA. Tokyo Univ Agr & Technol, Fac Agr, Tokyo 1838509, Japan. Merck Res Labs, Dept Genet & Cellular Toxicol, W Point, PA 19486 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol Environm Hlth & Radiat Oncol, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. US FDA, Ctr Drug Evaluat & Res, Laurel, MD 20708 USA. Cent Inst Expt Anim, Kawasaki, Kanagawa 2160001, Japan. Natl Inst Publ Hlth & Environm, RIVM, Lab Toxicol Pathol & Genet, Bilthoven, Netherlands. RP Storer, RD (reprint author), Merck Res Labs, Dept Genet & Cellular Toxicol, WP45-311, W Point, PA 19486 USA. OI MITSUMORI, KUNITOSHI/0000-0002-0754-572X NR 52 TC 4 Z9 4 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1383-5718 J9 MUTAT RES-GEN TOX EN JI Mutat. Res. Genet. Toxicol. Environ. Mutagen. PD OCT 7 PY 2003 VL 540 IS 2 BP 165 EP 176 DI 10.1016/j.mrgentox.2003.07.006 PG 12 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 733PX UT WOS:000186010800006 PM 14550500 ER PT J AU Muller, L Blakey, D Dearfield, KL Galloway, S Guzzie, P Hayashi, M Kasper, P Kirkland, D MacGregor, JT Parry, JM Schechtman, L Smith, A Tanaka, N Tweats, D Yamasaki, H AF Muller, L Blakey, D Dearfield, KL Galloway, S Guzzie, P Hayashi, M Kasper, P Kirkland, D MacGregor, JT Parry, JM Schechtman, L Smith, A Tanaka, N Tweats, D Yamasaki, H TI Strategy for genotoxicity testing and stratification of genotoxicity test results - report on initial activities of the IWGT Expert Group SO MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS LA English DT Article; Proceedings Paper CT International Workshop on Genotoxicity Testing CY JUN 28-29, 2002 CL PLYMOUTH, ENGLAND DE genotoxicity C1 Novartis Pharma AG, CH-4002 Basel, Switzerland. Hlth Canada, Safe Environm Programme, Ottawa, ON K1A 0L2, Canada. US EPA, Off Res & Dev, Washington, DC 20460 USA. Merck Res Labs, W Point, PA 19486 USA. Natl Inst Hlth Sci, Div Genet & Mutagenesis, Tokyo 158, Japan. Fed Inst Drugs & Med Devices, Bonn, Germany. Covance Labs Ltd, Harrogate, England. US FDA, Natl Ctr Toxicol Res, Rockville, MD 20857 USA. Univ Coll Swansea, Ctr Mol Genet & Toxicol, Swansea, W Glam, Wales. Hlth & Safety Execut, Bootle, Merseyside, England. Food & Drug Safety Ctr, Hatano Res Inst, Kanagawa, Japan. GlaxoSmithKline, Ware, Herts, England. Kwansei Gakuin Univ, Sch Sci & Technol, Dept Biosci, Sanda, Japan. RP Muller, L (reprint author), Novartis Pharma AG, CH-4002 Basel, Switzerland. NR 20 TC 24 Z9 24 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 OCT 7 PY 2003 VL 540 IS 2 BP 177 EP 181 DI 10.1016/j.mrgentox.2003.07.007 PG 5 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 733PX UT WOS:000186010800007 PM 14550501 ER PT J AU Machuca, A Hewlett, I AF Machuca, A Hewlett, I TI Residual risk of human immunodeficiency virus infection in blood banks. Impact of screening with nucleic acid tests SO MEDICINA CLINICA LA Spanish DT Review DE HIV; transfusion; transmission; blood banks; NATs ID HIV-1 GENETIC SUBTYPES; NON-B SUBTYPES; UNITED-STATES; WINDOW-PERIOD; DONORS; TRANSFUSION; TRANSMISSION; TYPE-1; DIVERSITY; DONATION AB Residual risk of human immunodeficiency virus infection in blood banks. Impact of screening with nucleic acid tests. In most developed countries of the world, the risk of human immunodeficiency virus (HIV) transmission by transfusion of blood and blood products is extraordinarily small. This level of blood safety has been accomplished by successive refinement in donor screening and testing procedures for the detection and inactivation of different infectious agents in blood and blood products. In USA, the recent introduction of nucleic acid techniques (NAT) in blood banks for the detection of HIV and hepatitis C virus (HCV) has meant a great advance in decreasing the residual risk of HIV/HCV transmission by blood transfusion. In general, after analyzing the first four-years of NATs experience in US blood banks, the introduction of NATs in European blood centers could be considered, since this technique has shown improved output to detect donations from individuals in the very early stages of infection before detectable serologic response has been developed. C1 FDA, CBER, Mol Virol Lab, Bethesda, MD 20892 USA. RP Machuca, A (reprint author), FDA, CBER, Mol Virol Lab, Bldg 29B,Rm 4E16,HFM 315,8800 Rockville Pike, Bethesda, MD 20892 USA. NR 64 TC 0 Z9 1 U1 0 U2 1 PU EDICIONES DOYMA S/L PI BARCELONA PA TRAV DE GRACIA 17-21, 08021 BARCELONA, SPAIN SN 0025-7753 J9 MED CLIN-BARCELONA JI Med. Clin. PD OCT 4 PY 2003 VL 121 IS 11 BP 418 EP 425 DI 10.1157/13052320 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 738TL UT WOS:000186303900007 PM 14563274 ER PT J AU Temple, RJ AF Temple, RJ TI Choice of treatment: Outcomes,and treatment goals SO AMERICAN HEART JOURNAL LA English DT Editorial Material ID CALCIUM-ANTAGONISTS; CONTROLLED TRIALS; HYPERTENSION; INHIBITORS C1 US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Temple, RJ (reprint author), US FDA, Ctr Drug Evaluat & Res, 5600 Fisher Lane HFD-101, Rockville, MD 20857 USA. NR 6 TC 2 Z9 2 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD OCT PY 2003 VL 146 IS 4 BP 565 EP 567 DI 10.1016/S0002-8703(03)00362-4 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 733UN UT WOS:000186019200003 PM 14564306 ER PT J AU Lineback, DR Jones, JM AF Lineback, DR Jones, JM TI Sugars and Health Workshop, held in Washington, DC, September 18-20, 2002 SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Editorial Material C1 Univ Maryland, Joint Inst Food Safety & Appl Nutr, College Pk, MD 20742 USA. Coll St Catherine, St Paul, MN USA. RP Lineback, DR (reprint author), Univ Maryland, Joint Inst Food Safety & Appl Nutr, 0220 Symons Hall, College Pk, MD 20742 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD OCT PY 2003 VL 78 IS 4 BP 814S EP 814S PG 1 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 722XQ UT WOS:000185403700025 ER PT J AU Lineback, DR Jones, JM AF Lineback, DR Jones, JM TI Sugars and health workshop: summary and conclusions SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Editorial Material C1 Univ Maryland, Joint Inst Food Safety & Appl Nutr, College Pk, MD 20742 USA. Coll St Catherine, St Paul, MN USA. RP Lineback, DR (reprint author), Univ Maryland, Joint Inst Food Safety & Appl Nutr, 0220 Symons Hall, College Pk, MD 20742 USA. NR 9 TC 3 Z9 3 U1 0 U2 0 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD OCT PY 2003 VL 78 IS 4 BP 893S EP 897S PG 5 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 722XQ UT WOS:000185403700035 PM 14522754 ER PT J AU Myers, MR Porter, JM AF Myers, MR Porter, JM TI Impulsive-motion model for computing the closing motion of mechanical heart-valve leaflets SO ANNALS OF BIOMEDICAL ENGINEERING LA English DT Article DE heart-valve model; occluder closing motion; occluder velocity; cavitation ID DYNAMICS; PROSTHESIS; BEHAVIOR AB The speed of mechanical heart-valve leaflets is known to be an important quantity for predicting cavitation, yet no simple computational means exists for predicting the leaflet speed. In this study, a model for simulating the motion of heart-valve leaflets in rigid test systems is presented. The input for the simulations is the ventricular pressure trace, readily measured in heart-valve tests. The model is based upon an impulsive-motion approximation, wherein the motion within the system is produced by rapid acceleration at the boundary, e.g., by a moving piston. A set of quasisteady, linear equations for the pressure field that are decoupled from the leaflet equation of motion is derived. The pressure field and leaflet moment are computed without the need to treat moving boundaries. Model predictions of closing time compared favorably with those measured in a 1994 cavitation study. Computed values of leaflet tip speed were also compared with those of a previous study, at the same value of average pressure slope. The model values were in agreement with measured speeds, given the limitations of using the average pressure slope as a metric for comparison. (C) 2003 Biomedical Engineering Society. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20852 USA. RP Myers, MR (reprint author), US FDA, Ctr Devices & Radiol Hlth, HFZ-132,21725 Twinbrook Pkwy, Rockville, MD 20852 USA. NR 17 TC 5 Z9 5 U1 0 U2 1 PU BIOMEDICAL ENGINEERING SOC AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0090-6964 J9 ANN BIOMED ENG JI Ann. Biomed. Eng. PD OCT PY 2003 VL 31 IS 9 BP 1031 EP 1039 DI 10.1114/1.1603750 PG 9 WC Engineering, Biomedical SC Engineering GA 731WE UT WOS:000185908800002 PM 14582606 ER PT J AU Bhabu, P Poletto, C Mann, E Bielamowicz, S Ludlow, CL AF Bhabu, P Poletto, C Mann, E Bielamowicz, S Ludlow, CL TI Thyroarytenoid muscle responses to air pressure stimulation of the laryngeal mucosa in humans SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article; Proceedings Paper CT Meeting of the American-Laryngological-Association CY MAY 02-03, 2003 CL NASHVILLE, TENNESSEE SP Amer Laryngolog Assoc DE air pressure; laryngeal adductor reflex; larynx; sensation; thyroarytenoid muscle ID LONG-LATENCY RESPONSES; BRAIN-STEM REFLEXES; SENSORY DISCRIMINATION; SPASMODIC DYSPHONIA; NERVE-STIMULATION; CAT AB Others have observed glottic adduction in response to air puff stimuli and suggested that this is a reliable indicator of laryngeal sensation. We undertook to determine whether the same thresholds are found if one uses either thyroarytenoid (TA) muscle responses or subjects' reports of laryngeal sensation. We also studied the characteristics of TA responses to unilateral air pressure stimulation of the mucosa overlying the arytenoid cartilages. Ten normal volunteers provided button press responses to air pressure stimuli during bilateral TA electromyography. Similar thresholds were determined by reports of sensation as by electromyographic responses (p < .0005). The early TA responses occurred either around 80 ms or around 125 ms after onset of the air puff, with equal frequency on the ipsilateral and contralateral sides. The TA muscle responses to air pressure stimulation differ in physiological characteristics from the laryngeal adductor reflex that occurs in response to electrical stimulation of the superior laryngeal nerve. C1 Natl Inst Neurol Disorders & Stroke, Laryngeal & Speech Sect, NIH, Bethesda, MD USA. US FDA, Div Ophthalm & Ear Nose & Throat Dev, Rockville, MD USA. George Washington Univ, Ctr Med, Div Otolaryngol Head & Neck Surg, Washington, DC USA. RP Ludlow, CL (reprint author), 10 Ctr Dr,MSC 1416,Bldg 10,Rm 5D38, Bethesda, MD 20892 USA. OI Ludlow, Christy/0000-0002-2015-6171 NR 18 TC 16 Z9 16 U1 1 U2 4 PU ANNALS PUBL CO PI ST LOUIS PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 USA SN 0003-4894 J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD OCT PY 2003 VL 112 IS 10 BP 834 EP 840 PG 7 WC Otorhinolaryngology SC Otorhinolaryngology GA 731PM UT WOS:000185895700002 PM 14587972 ER PT J AU Altekruse, SF Elvinger, F Wang, Y Ye, K AF Altekruse, SF Elvinger, F Wang, Y Ye, K TI A model to estimate the optimal sample size for microbiological surveys SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID SALMONELLA-ENTERITIDIS; CAMPYLOBACTER; INFECTION; POULTRY; FLOCKS AB Estimating optimal sample size for microbiological surveys is a challenge for laboratory managers. When insufficient sampling is conducted, biased inferences are likely; however, when excessive sampling is conducted valuable laboratory resources are wasted. This report presents a statistical model for the estimation of the sample size appropriate for the accurate identification of the bacterial subtypes of interest in a specimen. This applied model for microbiology laboratory use is based on a Bayesian mode of inference, which combines two inputs: (ii) a prespecified estimate, or prior distribution statement, based on available scientific knowledge and (ii) observed data. The specific inputs for the model are a prior distribution statement of the number of strains per specimen provided by an informed microbiologist and data from a microbiological survey indicating the number of strains per specimen. The model output is an updated probability distribution of strains per specimen, which can be used to estimate the probability of observing all strains present according to the number of colonies that are sampled. In this report two scenarios that illustrate the use of the model to estimate bacterial colony sample size requirements are presented. In the first scenario, bacterial colony sample size is estimated to correctly identify Campylobacter amplified restriction fragment length polymorphism types on broiler carcasses. The second scenario estimates bacterial colony sample size to correctly identify Salmonella enterica serotype Enteritidis phage types in fecal drag swabs from egg-laying poultry flocks. An advantage of the model is that as updated inputs from ongoing surveys are incorporated into the model, increasingly precise sample size estimates are likely to be made. C1 US FDA, Ctr Vet Med, Rockville, MD 20857 USA. Virginia Polytech & State Univ, Virginia Maryland Reg Coll Vet Med, Blacksburg, VA USA. Virginia Polytech & State Univ, Dept Stat, Blacksburg, VA USA. RP Altekruse, SF (reprint author), Food Safety Inspect Serv, Off Policy, Program Dev & Evaluat, 300 12th St,SW,Rm 402, Washington, DC 20250 USA. RI Tast Lahti, Elina/R-8664-2016 NR 12 TC 8 Z9 8 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0099-2240 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD OCT PY 2003 VL 69 IS 10 BP 6174 EP 6178 DI 10.1128/AEM.69.10.6174-6178.2003 PG 5 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 731JV UT WOS:000185881300056 PM 14532078 ER PT J AU Jinneman, KC Yoshitomi, KJ Weagant, SD AF Jinneman, KC Yoshitomi, KJ Weagant, SD TI Multiplex real-time PCR method to identify Shiga toxin genes stx1 and stx2 and Escherichia coli O157 : H7/H- serotype SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID POLYMERASE-CHAIN-REACTION; RAPID DETECTION; MOLECULAR BEACONS; ASSAYS; O157; QUANTIFICATION; IDENTIFICATION; AMPLIFICATION; EXPRESSION; INFECTION AB A multiplex real-time PCR method to simultaneously detect the stx1 and stx2 genes of Shiga toxin-producing Escherichia coli and a unique conserved single-nucleotide polymorphism in the E. coli O157:H7/H- uidA gene has been developed. There is more than 98.6% sensitivity and 100% specificity for all three gene targets based on a panel of 138 isolates. The PCR efficiencies were greater than or equal to1.89, and as few as 6 CFU/reaction could be detected. C1 US FDA, Seafood Prod Res Ctr, Pacific Reg Lab NW, Bothell, WA 98021 USA. RP Jinneman, KC (reprint author), US FDA, Seafood Prod Res Ctr, Pacific Reg Lab NW, 22201 23rd Dr SE, Bothell, WA 98021 USA. NR 36 TC 67 Z9 70 U1 0 U2 8 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0099-2240 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD OCT PY 2003 VL 69 IS 10 BP 6327 EP 6333 DI 10.1128/AEM.69.10.6327-6333.2003 PG 7 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 731JV UT WOS:000185881300079 PM 14532101 ER PT J AU Okamura, M Lillehoj, HS Raybourne, RB Babu, U Heckert, R AF Okamura, M Lillehoj, HS Raybourne, RB Babu, U Heckert, R TI Antigen-specific lymphocyte proliferation and interleukin production in chickens immunized with killed salmonella enteritidis vaccine or experimental subunit vaccines SO AVIAN DISEASES LA English DT Article DE chicken; Salmonella; cell-mediated immunity; interleukin; flagella ID LINKED-IMMUNOSORBENT-ASSAY; LAYING HENS; FUNCTIONAL-CHARACTERIZATION; MONOCLONAL-ANTIBODIES; MURINE INTERLEUKIN-6; EGG TRANSMISSION; PHAGE TYPE-4; B-CELLS; INFECTION; TYPHIMURIUM AB Lymphocyte proliferation and interleukin (IL)-2 and IL-6 levels in serum were measured as indicators of cell-mediated immunity after immunization of chickens with a commercial killed Salmonella enteritidis (SE) vaccine or experimental subunit vaccines of crude protein (CP) extract or the outer membrane protein (OMP). Significantly increased proliferative responses to SE flagella, but not lipopolysaccharide, porin, CP, or OMP, were observed at 1 wk postimmunization in the three vaccination groups. The responses to flagella were specific because flagella-induced proliferation was not seen in chickens immunized with adjuvant alone. Of the three immunization protocols, use of the killed SE vaccine appeared most effective because it induced higher flagella-Stimulated lymphocyte proliferation at 1 and 2 wk postvaccination compared with the CP- and OMP-vaccinated groups. Significantly increased IL-2 and IL-6 levels in serum were seen at 1 wk postimmunization in the three vaccination groups compared with adjuvant alone, but there were no differences between the killed vaccine and the subunit vaccines at this time, and the levels of both lymphokines returned to baseline at 2 wk postimmunization. We conclude that cell-mediated immunity to SE after vaccination with the killed bacterial vaccine or subunit vaccines is transient and mainly limited to flagella. C1 USDA ARS, Anim & Nat Resources Inst, Parasite Biol Epidemiol & Systemat Lab, Beltsville, MD 20705 USA. US FDA, Ctr Food Safety & Appl Nutr, Immunobiol Branch, Laurel, MD 20708 USA. Univ Maryland, Coll Vet Med, VA MD Reg, College Pk, MD 20742 USA. RP Lillehoj, HS (reprint author), USDA ARS, Anim & Nat Resources Inst, Parasite Biol Epidemiol & Systemat Lab, Beltsville, MD 20705 USA. NR 60 TC 17 Z9 17 U1 1 U2 2 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 OCT-DEC PY 2003 VL 47 IS 4 BP 1331 EP 1338 DI 10.1637/6096 PG 8 WC Veterinary Sciences SC Veterinary Sciences GA 751KF UT WOS:000187065200007 PM 14708979 ER PT J AU da Costa, GG Churchwell, MI Hamilton, LP Von Tungeln, LS Beland, FA Marques, MM Doerge, DR AF da Costa, GG Churchwell, MI Hamilton, LP Von Tungeln, LS Beland, FA Marques, MM Doerge, DR TI DNA adduct formation from acrylamide via conversion to glycidamide in adult and neonatal mice SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID TANDEM MASS-SPECTROMETRY; HEMOGLOBIN ADDUCTS; LIQUID-CHROMATOGRAPHY; MAILLARD REACTION; IN-VITRO; 3-METHYLADENINE; MOUSE; RATS; ACRYLONITRILE; ONCOGENICITY AB Acrylamide (AA) is a high production volume chemical with many industrial uses; however, recent findings of ppm levels in starchy foods cooked at high temperature have refocused worldwide attention on the neurotoxicity, germ cell mutagenicity, and carcinogenicity of AA. Oxidative metabolism of AA to its epoxide metabolite, glycidamide (GA), has been observed in experimental animals and humans and may be associated with many of the toxic effects of AA exposure, including formation of N7-(2-carbamoyl-2-hydroxyethyl)guanine (N7-GA-Gua) in vivo. This paper describes the characterization of two new GA-derived DNA adducts formed in vitro, N3-(2-carbamoyl-2-hydroxyethyl)adenine (N3-GA-Ade) and N1-(2-carboxy-2-hydroxyethyl)-2'-deoxyadenosine. A sensitive method for quantification of N7-GA-Gua and N3-GA-Ade, based on LC with tandem mass spectrometry and isotope dilution, was developed and validated for use in measuring DNA adduct formation in selected tissues of adult and whole body DNA of 3 day old neonatal mice treated with AA and GA. In adult mice, DNA adduct formation was observed in liver, lung, and kidney with levels of N7-GA-Gua around 2000 adducts/10(8) nucleotides and N3-GA-Ade around 20 adducts/10(8) nucleotides. Adduct levels were modestly higher in adult mice dosed with GA as opposed to AA; however, treatment of neonatal mice with GA produced 5-7-fold higher whole body DNA adduct levels than with AA, presumably reflective of lower oxidative enzyme activity in newborn mice. DNA adduct formation from AA treatment in adult mice showed a supralinear dose-response relationship, consistent with saturation of oxidative metabolism at higher doses. These results increase our understanding of the mutagenic potential of GA and provide further evidence for a genotoxic mechanism in AA carcinogenesis. C1 Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. Univ Tecn Lisboa, Ctr Quim Estruct, Inst Super Tecn, P-1049001 Lisbon, Portugal. RP Doerge, DR (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. EM ddoerge@nctr.fda.gov RI Marques, M. Matilde/E-2535-2012 OI Marques, M. Matilde/0000-0002-7526-4962 NR 36 TC 139 Z9 140 U1 1 U2 17 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD OCT PY 2003 VL 16 IS 10 BP 1328 EP 1337 DI 10.1021/tx034108e PG 10 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 735GC UT WOS:000186103200016 ER PT J AU Fang, H Tong, WD Branham, WS Moland, CL Dial, SL Hong, HX Xie, Q Perkins, R Owens, W Sheehan, DM AF Fang, H Tong, WD Branham, WS Moland, CL Dial, SL Hong, HX Xie, Q Perkins, R Owens, W Sheehan, DM TI Study of 202 natural, synthetic, and environmental chemicals for binding to the androgen receptor SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID ALTERS SEXUAL-DIFFERENTIATION; IN-UTERO EXPOSURE; REPRODUCTIVE DEVELOPMENT; ESTROGEN-RECEPTOR; PROSTATIC-CARCINOMA; CYPROTERONE-ACETATE; STEROID-RECEPTORS; NUCLEAR RECEPTOR; ESCHERICHIA-COLI; RISK-ASSESSMENT AB A number of environmental and industrial chemicals are reported to possess androgenic or antiandrogenic activities. These androgenic endocrine disrupting chemicals may disrupt the endocrine system of humans and wildlife by mimicking or antagonizing the functions of natural hormones. The present study developed a low cost recombinant androgen receptor (AR) competitive binding assay that uses no animals. We validated the assay by comparing the protocols and results from other similar assays, such as the binding assay using prostate cytosol. We tested 202 natural, synthetic, and environmental chemicals that encompass a broad range of structural classes, including steroids, diethylstilbestrol and related chemicals, antiestrogens, flutamide derivatives, bisphenol A derivatives, alkylphenols, parabens, alkyloxyphenols, phthalates, siloxanes, phytoestrogens, DDTs, PCBs, pesticides, organophosphate insecticides, and other chemicals. Some of these chemicals are environmentally persistent and/or commercially important, but their AR binding affinities have not been previously reported. To the best of our knowledge, these results represent the largest and most diverse data set publicly available for chemical binding to the AR. Through a careful structure-activity relationship (SAR) examination of the data set in conjunction with knowledge of the recently reported ligand-AR crystal structures, we are able to define the general structural requirements for chemical binding to AR. Hydrophobic interactions are important for AR binding. The interaction between ligand and AR at the 3- and 17-positions of testosterone and R1881 found in other chemical classes are discussed in depth. The SAR studies of ligand binding characteristics for AR are compared to our previously reported results for estrogen receptor binding. C1 Northrop Grumman Informat Technol, Jefferson, AR 72079 USA. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Procter & Gamble Co, Cincinnati, OH 45253 USA. RP Tong, WD (reprint author), Northrop Grumman Informat Technol, Jefferson, AR 72079 USA. NR 63 TC 193 Z9 201 U1 5 U2 46 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 OCT PY 2003 VL 16 IS 10 BP 1338 EP 1358 DI 10.1021/tx030011g PG 21 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 735GC UT WOS:000186103200017 PM 14565775 ER PT J AU Purucker, ME Rosebraugh, CJ Zhou, F Meyer, RJ AF Purucker, ME Rosebraugh, CJ Zhou, F Meyer, RJ TI Inhaled fluticasone propionate by Diskus in the treatment of asthma - A comparison of the efficacy of the same nominal dose given either once or twice a day SO CHEST LA English DT Article DE asthma; Diskus; dose regimen; Flovent; fluticasone propionate; multidose powder inhaler; pediatric study ID MODERATE ASTHMA; CORTICOSTEROIDS; SAFETY AB Study objective: In September 2000, the US Food and Drug Administration (FDA) approved the use of Flovent Diskus (FD) [fluticasone propionate; GlaxoSmithKline; Research Triangle Park, NC], which is an orally inhaled, dry-powder corticosteroid, for the maintenance treatment of asthma at dosages of 50 to 1,000 mug administered twice-daily. Once-daily dosage regimens did not receive approval. This article will detail six clinical trials, five of which incorporated comparative once-daily and twice-daily treatment arms of the same nominal dose of FD. Design: Six 12-week, randomized, double-blind, placebo-controlled studies in patients with mild-to-moderate asthma, including two pediatric asthma trials (patient age, 4 to 11 years) of total daily doses of fluticasone propionate (FP) of 100 or 200 mug, and four adult and adolescent studies of total daily doses of FP of 100, 200, or 500 mug. Results: Twice-daily dosing was numerically superior to once-daily dosing at the same nominal dose in all comparative studies for the primary end point, change in predose FEV1. In five trials, the results of the once-daily dosage of FP were statistically indistinguishable from those with placebo. One trial demonstrated the superiority of FP, 500 mug once-daily, over placebo; however, the effect size was half that observed with twice-daily dosing. Once-daily FP dosing showed no advantage in safety or in patient adherence to medication. Conclusions: In the FDA review of once-daily dosing of the FD regimen, 100 or 200 mug once-daily dosing was not shown to be significantly better than placebo. FP 500 mug once-daily was found to be superior to placebo, but at about one half the effect size as the same nominal dose given bid. No advantage in patient safety or adherence was demonstrated for once-daily administration over twice-daily administration, and once-daily administration is not currently recommended. C1 US FDA, Div Pulm & Allergy Drug Prod, Rockville, MD 20857 USA. US FDA, Div Biometr, Rockville, MD 20857 USA. US FDA, CDER, Off Drug Evaluat 2, Rockville, MD 20857 USA. RP Rosebraugh, CJ (reprint author), Div Counter Drug Prod, 5600 Fisher Ln,HFD-560, Rockville, MD 20857 USA. NR 15 TC 29 Z9 30 U1 0 U2 2 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD OCT PY 2003 VL 124 IS 4 BP 1584 EP + DI 10.1378/chest.124.4.1584 PG 10 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 733LU UT WOS:000186002500054 PM 14555594 ER PT J AU Bross, PF Baird, A Chen, G Jee, JM Lostritto, RT Morse, DE Rosario, LA Williams, GM Yang, PL Rahman, A Williams, G Pazdur, R AF Bross, PF Baird, A Chen, G Jee, JM Lostritto, RT Morse, DE Rosario, LA Williams, GM Yang, PL Rahman, A Williams, G Pazdur, R TI Fulvestrant in postmenopausal women with advanced breast cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID ENDOCRINE THERAPY; TAMOXIFEN; ANASTROZOLE; TRIAL AB Purpose: Patients with hormone-sensitive breast cancer who have responded to tamoxifen (TAM) may receive additional benefit from a second endocrine agent after progression or relapse after TAM therapy. Fulvestrant (FVT; Faslodex; i.m. injection, ICI 182,780; AstraZeneca Pharmaceuticals, Wilmington, DE) was developed as a selective antagonist of estrogen. In postmenopausal women, FVT is reported to inhibit the proliferative effects of estrogen on sensitive tissues and has no apparent measurable estrogenic activity. In this report, we describe the data and analyses supporting marketing approval for FVT by the United States Food and Drug Administration (FDA). Experimental Design: The FDA review of 16 clinical trials and 6 pharmacokinetic trials, as well as preclinical pharmacology and chemistry data, are described. The bases for marketing approval are summarized. Results: Toxicology studies in the mouse, rat, and dog showed minimal toxicity except for antiestrogenic effects. Because of FVT aqueous insolubility, an i.m. formulation, given at monthly intervals, was selected for clinical studies. Pharmacokinetic studies demonstrated sustained concentrations with monthly injection. In in vitro studies FVT was extensively metabolized, primarily by hepatic cytochrome P450 3A4. Phase I studies showed minimal toxicity, and the maximal dose (250 mg) was limited by FVT solubility. In two Phase III trials, 851 patients were randomized to either 250 mg FVT i.m. monthly or to anastrozole (ANZ) 1 mg p.o. daily. Ninety-six percent of patients had received TAM previously for early (adjuvant treatment) or advanced breast cancer. Response rates (RR) were 17% for both FVT and ANZ study arms in the North American trial, and were 20% versus 15% for FVT versus ANZ, respectively, in the European trial. There were no observed differences between study arms with respect to time to progression or survival. The most common FVT adverse events reported as potentially treatment-related were injection site reactions and hot flashes. Conclusions: FVT was approved on April 25, 2002 by the FDA for the treatment of hormone receptor-positive metastatic breast cancer in postmenopausal women with disease progression after antiestrogen therapy. The recommended dose is 250 mg i.m. monthly as a single 5 ml injection or as two concurrent 2.5 ml injections into the buttocks. Approval was based on results of two randomized trials comparing response rates and time to progression of FVT- and ANZ-treated patients. Complete prescribing information is available on the FDA website. C1 US FDA, Div Oncol Drug Prod, Ctr Drug Evaluat & Res, HFD 150, Rockville, MD 20852 USA. RP Bross, PF (reprint author), US FDA, Div Oncol Drug Prod, Ctr Drug Evaluat & Res, HFD 150, 1451 Rockville Pike, Rockville, MD 20852 USA. NR 21 TC 28 Z9 29 U1 2 U2 7 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 OCT 1 PY 2003 VL 9 IS 12 BP 4309 EP 4317 PG 9 WC Oncology SC Oncology GA 730KV UT WOS:000185830700004 PM 14555500 ER PT J AU Verthelyi, D Klinman, DM AF Verthelyi, D Klinman, DM TI Immunoregulatory activity of CpG oligonucleotides in humans and nonhuman primates SO CLINICAL IMMUNOLOGY LA English DT Article DE innate immunity; CpG ODN; primates; human; vaccines; immunoprotection; allergies; cancer; safety ID TOLL-LIKE RECEPTOR-9; SYSTEMIC LUPUS-ERYTHEMATOSUS; CELL DNA METHYLATION; HUMAN IMMUNE CELLS; BACTERIAL-DNA; IN-VITRO; DENDRITIC CELLS; IMMUNOSTIMULATORY OLIGODEOXYNUCLEOTIDES; SYNTHETIC OLIGODEOXYNUCLEOTIDES; CUTANEOUS LEISHMANIASIS AB Oligodeoxynucleotides (ODN) containing CpG motifs mimic the ability of microbial DNA to activate the innate immune system. The resultant response limits the early spread of infectious organisms while promoting the development of adaptive immunity. CpG ODN show promise as vaccine adjuvants and in the treatment of asthma, allergy, infection, and cancer. Due to evolutionary divergence in CpG recognition between species, CpG ODN that are most active in rodents are poorly immunostimulatory in primates. Thus, evidence that CpG ODN have therapeutic activity in mice must be confirmed in primates. Two distinct types of CpG ODN were identified that stimulate primate PBMC. D-type ODN trigger plasmacytoid DC to secrete IFNalpha, monocytes to mature into functionally active DC, and NK cells to secrete IFNgamma. K-type ODN stimulate B cells and monocytes to proliferate and secrete IgM, IL-10, and/or IL-6. In vivo studies in nonhuman primates indicate that proinflammatory or humoral immune responses can be selectively facilitated by judicious use of these distinct types of ODN. C1 US FDA, Ctr Biol Evaluat & Res, Sect Retroviral Immunol, Bethesda, MD 20892 USA. US FDA, Div Therapeut Prot, Bethesda, MD 20892 USA. RP Klinman, DM (reprint author), US FDA, Ctr Biol Evaluat & Res, Sect Retroviral Immunol, Bldg 29A,Room 3B19,8800 Rockville Pike, Bethesda, MD 20892 USA. EM Klinman@cber.fda.gov NR 70 TC 54 Z9 58 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 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PD OCT PY 2003 VL 109 IS 1 BP 64 EP 71 DI 10.1016/S1521-6616(03)00202-X PG 8 WC Immunology SC Immunology GA 739AA UT WOS:000186319000009 PM 14585277 ER PT J AU Vandermeeren, Y Bastings, E Fadiga, L Olivier, E AF Vandermeeren, Y Bastings, E Fadiga, L Olivier, E TI Long-latency motor evoked potentials in congenital hemiplegia SO CLINICAL NEUROPHYSIOLOGY LA English DT Article DE corticospinal tract; functional recovery; cerebral palsy; transcranial magnetic stimulation ID TRANSCRANIAL MAGNETIC STIMULATION; SINGLE SPINAL MOTONEURONS; LATE MUSCULAR RESPONSES; TIME FOLLOWING STROKE; CEREBRAL-PALSY; MULTIPLE-SCLEROSIS; BRAIN-STIMULATION; FUNCTIONAL ORGANIZATION; CORTICAL ORGANIZATION; MIRROR MOVEMENTS AB Objective: To investigate long-latency motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation in congenital hemiplegia (CH) and to seek for correlation with paretic hand movement deficits. Methods: MEPs were recorded from the first dorsal interosseous of both hands in 12 CH patients and 12 age-matched controls; dexterity and upper limb function were quantitatively assessed in both groups. Results: In CH patients, long-latency MEPs, occurring much later than the commonly reported MEPs, were frequently observed in the paretic and non-paretic hands. Four distinct groups of long-latency MEPs were found, each cluster being identified by its mean latency, namely 35, 85, 160 and 225 ms. The residual dexterity of the paretic hand was correlated with the presence of contralateral MEPs with a 20 and 225 ms latency and was negatively correlated with ipsilateral MEPs, irrespective of their latency. In controls, only few MEPs with a latency of 225 ms were found in 4 out of 12 subjects. Conclusions: The pattern of MEPs found in CH patients differs dramatically from that reported in adult stroke patients, suggesting that long-latency MEPs are a rather distinctive consequence of early corticospinal lesions. The hypothesis that a given cluster of long-latency MEPs is mediated by a particular pathway appears very unlikely. Rather, we suggest that an exacerbation of cortical and/or spinal excitability is at the origin of these long-latency MEPs. (C) 2003 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. C1 Univ Catholique Louvain, Neurophysiol Lab, B-1200 Brussels, Belgium. US FDA, Ctr Drug Evaluat & Res, Div Neuropharmacol Drug Prod, Rockville, MD 20857 USA. Univ Ferrara, Fac Med, Dept Biomed Sci, Sect Human Physiol, I-44100 Ferrara, Italy. RP Olivier, E (reprint author), Univ Catholique Louvain, Neurophysiol Lab, 54 Ave Hippocrate, B-1200 Brussels, Belgium. OI fadiga, luciano/0000-0001-5691-5080 NR 59 TC 9 Z9 9 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 1388-2457 J9 CLIN NEUROPHYSIOL JI Clin. Neurophysiol. PD OCT PY 2003 VL 114 IS 10 BP 1808 EP 1818 DI 10.1016/S1388-2457(03)00161-5 PG 11 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 733CL UT WOS:000185982300005 PM 14499742 ER PT J AU Ellenberg, SS AF Ellenberg, SS TI Are all monitoring boundaries equally ethical? SO CONTROLLED CLINICAL TRIALS LA English DT Editorial Material ID RANDOMIZED CLINICAL-TRIALS; DEVELOPING-COUNTRIES; PLACEBO ORTHODOXY; PRACTICAL ISSUES; DESIGNS; PROTECTION; COMMITTEES; MYTHS C1 US FDA, Off Biostat & Epidemiol, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Ellenberg, SS (reprint author), US FDA, Off Biostat & Epidemiol, Ctr Biol Evaluat & Res, 1401 Rockville Pike,Suite 200 S, Rockville, MD 20852 USA. NR 41 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 0197-2456 J9 CONTROL CLIN TRIALS JI Controlled Clin. Trials PD OCT PY 2003 VL 24 IS 5 BP 585 EP 588 DI 10.1016/S0197-2456(03)00090-4 PG 4 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 728JG UT WOS:000185713600007 PM 14500055 ER PT J AU Xie, H Raybourne, RB Babu, US Lillehoj, HS Heckert, RA AF Xie, H Raybourne, RB Babu, US Lillehoj, HS Heckert, RA TI CpG-induced immunomodulation and intracellular bacterial killing in a chicken macrophage cell line SO DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY LA English DT Article DE chicken; macrophages; phagocytosis; apoptosis ID TOLL-LIKE RECEPTORS; CUTTING EDGE; SYNTHETIC OLIGONUCLEOTIDES; IMMUNE-RESPONSES; B-CELLS; DNA; OLIGODEOXYNUCLEOTIDES; MOTIFS; ANTIGEN; ACTIVATION AB The immunostimulatory properties of synthetic CpG oligodeoxynucleotides (ODNs) have been studied in various mammalian models including humans and mice. However, little was known about effects of CpG ODNs on immune responses of chickens, a common avian species with important economical value in the poultry industry. In the present study, two CpG ODNs, 2006 and 1826, which show immunomodutating properties for humans and mice were tested using a chicken macrophage cell line (HD11). ODN 2006, which has been reported to be an optimal stimulatory sequence for humans, showed strong immunomodulatory effects on HD11 cells, whereas ODN 1826, a CpG sequence with optimal immunostimulatory effects on mice, had weak influences on HD11 cells. ODN 2006 also induced strong IL-6 and nitric oxide secretion by HD11 cells in both dose-and time-dependent manners. Intracellular killing of Salmonella enteritidis (SE) was also increased in ODN 2006-activated HD11 cells. Furthermore, HD11 cells had reduced proliferation and underwent apoptosis, which is contradictory to the effects of ODN 2006 on human and murine cells. N-G-monomethyl L-arginine(L-NMMA), an iNOS inhibitor, inhibited apoptosis of HD11 cells induced by ODN 2006, suggesting that this effect was likely mediated through an iNOS-dependent pathway. These results indicate that the differences in the responses of chicken HID I I macrophage cells to CpG ODNs compared to those of mammalian macrophages are species-related, and the potential of CpG ODNs as immunomodulators in poultry needs to be further explored. (C) 2003 Elsevier Science Ltd. All rights reserved. C1 Univ Maryland, Virginia Maryland Reg Coll Vet Med, College Pk, MD 20742 USA. US FDA, Ctr Food Safety & Nutr, Immunol Branch, Laurel, MD 20708 USA. USDA ARS, Anim & Nat Resource Inst, Parasite Biol Epidemiol & Systemat Lab, Beltsville, MD 20705 USA. RP Heckert, RA (reprint author), Univ Maryland, Virginia Maryland Reg Coll Vet Med, 8075 Greenmead Dr, College Pk, MD 20742 USA. NR 40 TC 57 Z9 61 U1 0 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0145-305X J9 DEV COMP IMMUNOL JI Dev. Comp. Immunol. PD OCT PY 2003 VL 27 IS 9 BP 823 EP 834 DI 10.1016/S0145-305X(03)00079-X PG 12 WC Immunology; Zoology SC Immunology; Zoology GA 706ZE UT WOS:000184484300007 PM 12818639 ER PT J AU Mei, N Lee, J Sun, XJ Xing, JZ Hanson, J Le, XC Weinfeld, M AF Mei, N Lee, J Sun, XJ Xing, JZ Hanson, J Le, XC Weinfeld, M TI Genetic predisposition to the cytotoxicity of arsenic: the role of DNA damage and ATM SO FASEB JOURNAL LA English DT Article DE DNA double-strand breaks; p53; cell cycle ID DOUBLE-STRAND BREAKS; PROTEIN CROSS-LINKS; NUCLEOTIDE EXCISION-REPAIR; HAMSTER V79 CELLS; ATAXIA-TELANGIECTASIA; HUMAN FIBROBLASTS; FANCONI-ANEMIA; IONIZING-RADIATION; OXIDATIVE DAMAGE; DEFECTIVE REPAIR AB Arsenic is a pervasive cytotoxin and carcinogen in the environment. Although its mode of action has yet to be fully elucidated, oxidative DNA damage has been suggested. A series of DNA repair-defective human and hamster cell lines associated with sensitivity to oxidative agents were examined for their response to arsenic-induced cytotoxicity. Only the Ataxia telangiectasia (AT) cells displayed a marked hypersensitive response (greater than twofold). The protective role of the ATM protein was confirmed by the normal response to arsenic displayed by AT cells expressing wild-type ATM. Although the ATM protein plays a pivotal role in response to DNA double-strand breakage, none of the other cell lines with defects in double-strand break repair displayed a similar hypersensitivity. Further examination indicated that concentrations of sodium arsenite as high as 1 mg/l do not generate significant levels of double-strand breaks. Our data suggest that the ATM protein functions in an important but different capacity in the cellular response to arsenic toxicity than it does in response to agents that generate double-strand breaks, such as ionizing radiation. Furthermore, the lack of hypersensitivity to arsenic displayed by the other cell lines calls into question the hypothesis that DNA damage is a significant factor in arsenic cytotoxicity. C1 Cross Canc Inst, Dept Expt Oncol, Edmonton, AB T6G 1Z2, Canada. Univ Alberta, Fac Med & Dent, Dept Publ Hlth Sci, Edmonton, AB T6G 2G3, Canada. Cross Canc Inst, Div Epidemiol, Edmonton, AB T6G 1Z2, Canada. RP Le, XC (reprint author), US FDA, Natl Ctr Toxicol Res, Div genet & Reprod Toxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM xc.le@ualberta.ca; michaelw@cancerboard.ab.ca RI mei, nan/E-8915-2011; Le, X. Chris/O-4947-2015 OI mei, nan/0000-0002-3501-9014; Le, X. Chris/0000-0002-7690-6701 NR 63 TC 18 Z9 19 U1 0 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD OCT PY 2003 VL 17 IS 13 BP 2310 EP + DI 10.1096/fj.02-0093fje PG 21 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 739KH UT WOS:000186343300020 PM 14563695 ER PT J AU Nyman, PJ Diachenko, GW Perfetti, GA AF Nyman, PJ Diachenko, GW Perfetti, GA TI Determination of 1,3-dichloropropanol in soy and related sauces by using gas chromatography/mass spectrometry SO FOOD ADDITIVES AND CONTAMINANTS LA English DT Article DE chloropropanols; 1,3-dichloro-2-propanol; soy sauce; acid-hydrolysed vegetable protein AB A gas chromatography/mass spectrometry method for 3-MCPD in foods and food ingredients was modified for the determination of 1,3-DCP in soy and related sauces. The method was validated by using a blank soy sauce. The detection limit, quantitation limit and recoveries were determined, and identities were confirmed by mass spectrometry on the basis of analyses of test portions spiked with 1,3-DCP at 10, 25, 50 and 100 ng g -1 . The spiked test portions were quantitated by using an internal standard calibration curve. For the spiked test portions, the mean internal standard-corrected recovery for 1,3-DCP was 100% with a relative standard deviation of 1.32%. The limits of detection and quantitation were determined as 0.055 and 0.185 ng g -1 , respectively. The method also was compared with a headspace GC/MS method recently developed by the UK's Central Science Laboratory. Results from the method comparison showed that the recoveries for the spiked test portions, as well as the amounts of 1,3-DCP found in the retail products, were comparable. C1 US FDA, Div Chem Res & Environm Review, Off Food Addit Safety, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Nyman, PJ (reprint author), US FDA, Div Chem Res & Environm Review, Off Food Addit Safety, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. NR 14 TC 13 Z9 14 U1 0 U2 11 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 OCT PY 2003 VL 20 IS 10 BP 903 EP 908 DI 10.1080/02652030310001603783 PG 6 WC Chemistry, Applied; Food Science & Technology; Toxicology SC Chemistry; Food Science & Technology; Toxicology GA 738PC UT WOS:000186296200002 PM 14594674 ER PT J AU Nyman, PJ Diachenko, GW Perfetti, GA AF Nyman, PJ Diachenko, GW Perfetti, GA TI Survey of chloropropanols in soy sauces and related products SO FOOD ADDITIVES AND CONTAMINANTS LA English DT Article DE soy sauce; acid-hydrolysed vegetable protein; chloropropanols; 3-monochloropropane-1,2-diol; 1,3-dichloro-2-propanol ID GAS-CHROMATOGRAPHY AB A survey of soy sauces and related products available in the USA was conducted to determine the levels of 3-monochloropropane-1,2-diol (3-MCPD) and 1,3-dichloro-2-propanol (1,3-DCP) in these products. Fifty-five retail samples were purchased and analysed for 3-MCPD. 3-MCPD determinations were made according to a gas chromatography/mass spectrometry method validated by a collaborative trial. Eighty-five per cent of the samples analysed contained greater than the detection limit of 0.005 ppm (mug g -1 ) for 3-MCPD. Thirty-three per cent contained greater than 1 ppm; the highest level was 876 ppm 3-MCPD. Thirty-nine of the samples analysed for 3-MCPD also were analysed for 1,3-DCP by using a modified method developed and validated in-house. Fifty-six per cent of the samples analysed for 1,3-DCP contained greater than the detection limit of 0.055 ppb (ng g -1 ) for 1,3-DCP; the highest level was 9.8 ppm 1,3-DCP. Products manufactured in Asia contained the highest chloropropanol levels. C1 US FDA, Div Chem Res & Environm Review, Off Food Addit Safety, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Nyman, PJ (reprint author), US FDA, Div Chem Res & Environm Review, Off Food Addit Safety, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. NR 16 TC 24 Z9 26 U1 1 U2 7 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 OCT PY 2003 VL 20 IS 10 BP 909 EP 915 DI 10.1080/02652030310001603792 PG 7 WC Chemistry, Applied; Food Science & Technology; Toxicology SC Chemistry; Food Science & Technology; Toxicology GA 738PC UT WOS:000186296200003 PM 14594675 ER PT J AU Song, YS Al-Taher, F Sadler, G AF Song, YS Al-Taher, F Sadler, G TI Migration of volatile degradation products into ozonated water from plastic packaging materials SO FOOD ADDITIVES AND CONTAMINANTS LA English DT Article DE ozone; ozonation; drinking water; degradation; migration; plastic polymers ID HDPE BOTTLES; OFF-FLAVOR; POLYETHYLENE; OZONE; ANTIOXIDANTS; OXIDATION; RELEASE AB Migration of volatile degradation products from poly(ethylene terephthalate) (PET) and high-density polyethylene (HDPE) bottles, polypropylene (PP) caps and ethyl vinyl acetate (EVA) liners into ozonated water was measured. Polymer strips were immersed in deionized and distilled water with ozone concentrations of 0.5, 2.5 and/or 5 mg kg(-1) inside 35-ml vials, which were clamp-sealed and stored at 40degreesC for 10 days. A purge-and-trap unit was developed to extract volatile products from the ozonated water in vials. The extractables were trapped in an adsorbent tube and analysed using a GC-MS coupled with an automated thermal desorber (ATD). Mass spectra were interpreted by comparison with a NIST mass spectral library, and an internal standard method was used to quantify the extractables of interest. Several volatile compounds found in ozonated water that had been in contact with PP, EVA and HDPE polymers included butanal, pentanal, hexanal, heptanal, octanal, nonanal, 2,2-dimethyl propanal, 3-hexanone, 2-hexanone and heptanone. These compounds could cause off-taste and off-odour with a low organoleptic threshold. In general, the concentrations of these volatile compounds increased with an increased exposure to ozone. The highest concentration found was 14.1 +/- 0.6 mug kg(-1) for hexanal with a 5 mg kg(-1) ozone treatment of PP caps. Even at a treatment level of 5 mg kg -1 ozone, which is greater than 10 times the current regulatory limits for bottled water, the extractables migrating from those polymers were within the levels permitted by the FDA. For the PET sample, no significant peaks were observed before or after ozonation. These results imply that PP caps containing EVA liners may be major sources of off-odour and taste in ozonated bottled water. C1 US FDA, Div Food Proc & Packaging, Summit Argo, IL 60501 USA. IIT, Natl Ctr Food Safety & Technol, Summit Argo, IL 60501 USA. RP Song, YS (reprint author), US FDA, Div Food Proc & Packaging, 6502 S Archer Rd, Summit Argo, IL 60501 USA. NR 17 TC 7 Z9 7 U1 2 U2 14 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 OCT PY 2003 VL 20 IS 10 BP 985 EP 994 DI 10.1080/02652030310001606014 PG 10 WC Chemistry, Applied; Food Science & Technology; Toxicology SC Chemistry; Food Science & Technology; Toxicology GA 738PC UT WOS:000186296200011 PM 14594682 ER PT J AU Lou, H LaVoy, J Choi, YKH Major, ME Hagedorn, CH AF Lou, H LaVoy, J Choi, YKH Major, ME Hagedorn, CH TI High activity mutant of HCVNS5B polymerase identified in chronically infected chimpanzees. SO HEPATOLOGY LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Association-for-the-Study-of-Liver-Disease CY OCT 24-28, 2003 CL BOSTON, MASSACHUSETTS SP Amer Assoc Study Liver Diseases C1 Emory Univ, Sch Med, Atlanta, GA 30322 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2003 VL 38 IS 4 SU 1 MA 303 BP 301A EP 301A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 730ER UT WOS:000185816700304 ER PT J AU Senior, JR Tipping, RW AF Senior, JR Tipping, RW TI Serum transaminase elevations alone lack specificity for detecting rare serious liver disease. SO HEPATOLOGY LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Association-for-the-Study-of-Liver-Disease CY OCT 24-28, 2003 CL BOSTON, MASSACHUSETTS SP Amer Assoc Study Liver Diseases C1 US FDA, Rockville, MD 20857 USA. Merck Res Labs, Blue Bell, PA USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2003 VL 38 IS 4 SU 1 MA 1132 BP 701A EP 701A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 730ER UT WOS:000185816701131 ER PT J AU Shahverdi, AR Fazeli, MR Kakavand, M Jamalifar, H Hamedi, J AF Shahverdi, AR Fazeli, MR Kakavand, M Jamalifar, H Hamedi, J TI Inhibition of nitrofurantoin reduction by menthol leads to enhanced antimicrobial activity SO JOURNAL OF CHEMOTHERAPY LA English DT Article DE nitrofurantoin; nitroreduction; menthol; enterobacteria ID LIVER; NITROREDUCTASE; RESISTANCE; ACTIVATION; MECHANISM AB Nitrofurantoin is a nitroaromatic compound used for the treatment of urinary tract infections. Nitrofurantoin activity is regulated by a nitroreduction process. It is first reduced by bacterial nitroreductases to active short-life intermediates, which are further converted to non-toxic molecules, which negatively affect its antibacterial activity. In this study we have shown that resistant strains of Klebsiella sp. inactivate the bactericidal activity of nitrofurantoin. Also we demonstrated a synergistic effect between menthol and nitrofurantoin bactericidal activities against nitrofurantoin susceptible Enterobacteriaceae. C1 Univ Tehran Med Sci, Fac Pharm, Dept Phamaceut Biotechnol, Tehran, Iran. US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Univ Tehran, Fac Sci, Dept Biol, Tehran, Iran. RP Shahverdi, AR (reprint author), Univ Tehran Med Sci, Fac Pharm, Dept Phamaceut Biotechnol, Postal Code 14174, Tehran, Iran. EM shahver@sina.tums.ac.ir NR 16 TC 11 Z9 11 U1 1 U2 2 PU ESIFT SRL PI FLORENCE PA VIA CARLO DEL GRECO 36, 50141 FLORENCE, ITALY SN 1120-009X J9 J CHEMOTHERAPY JI J. Chemother. PD OCT PY 2003 VL 15 IS 5 BP 449 EP 453 PG 5 WC Oncology; Infectious Diseases; Pathology; Pharmacology & Pharmacy SC Oncology; Infectious Diseases; Pathology; Pharmacology & Pharmacy GA 736RR UT WOS:000186187400004 PM 14598936 ER PT J AU Levin, MJ Dahl, KM Weinberg, A Giller, R Patel, A Krause, PR AF Levin, MJ Dahl, KM Weinberg, A Giller, R Patel, A Krause, PR TI Development of resistance to acyclovir during chronic infection with the oka vaccine strain of varicella-zoster virus, in an immunosuppressed child SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; THYMIDINE KINASE GENES; HERPES-ZOSTER; SYNDROME AIDS; WILD-TYPE; THERAPY; IDENTIFICATION; TRANSPLANTS; LESIONS; CANCER AB A 1-year-old boy was vaccinated with the Oka strain of varicella just prior to the discovery of a tumor that required intensive antitumor therapy. Three months later he developed herpes zoster, which developed into chronic verrucous lesions that were refractory to treatment with acyclovir and which subsequently disseminated. DNA from a biopsy specimen of a chronic herpes-zoster lesion indicated that the Oka vaccine strain of the the virus caused this severe complication. Analysis of this viral DNA demonstrated a mutation in the viral thymidine kinase gene. Plasmids containing this altered gene were unable to produce functional thymidine kinase in an in vitro translation system. The presence of this mutation would explain the clinical resistance to acyclovir. This is the first report of Oka-strain varicella virus causing severe disease after reactivation and of resistance to acyclovir during an infection caused by this virus. C1 Univ Colorado, Hlth Sci Ctr, Sect Pediat Infect Dis, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Sect Pediat Hematol Oncol & Bone Marrow Transplan, Denver, CO 80262 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. RP Levin, MJ (reprint author), Univ Colorado, Hlth Sci Ctr, Sect Pediat Infect Dis, 4200 E 9th Ave,C-227, Denver, CO 80262 USA. NR 36 TC 59 Z9 61 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 OCT 1 PY 2003 VL 188 IS 7 BP 954 EP 959 DI 10.1086/378502 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 726HV UT WOS:000185593900003 PM 14513413 ER PT J AU Mossoba, MM Al-Khaldi, SF Jacobson, A Crowe, LIS Fry, FS AF Mossoba, MM Al-Khaldi, SF Jacobson, A Crowe, LIS Fry, FS TI Application of a disposable transparent filtration membrane to the infrared spectroscopic discrimination among bacterial species SO JOURNAL OF MICROBIOLOGICAL METHODS LA English DT Article DE bacteria; identification; transparent membrane filter; infrared spectroscopy; multivariate analysis ID VIBRATIONAL SPECTROSCOPY; FOODBORNE PATHOGENS; IDENTIFICATION; CLASSIFICATION AB This study describes the application of filtration, infrared spectroscopy, and multivariate analysis to the identification of 10 foodborne bacterial species. The bacteria were applied by filtration to a disposable optical membrane that is transparent to infrared radiation. The filtration step was rapid (2 min). Observed cellular infrared spectra were unique and were used to discriminate among the different species. A dataset for the 10 bacterial species investigated was successfully used to correctly identify unknowns included in the dataset. Published by Elsevier Science B.V. C1 US FDA, DGSS, OSAS, CFSAN, College Pk, MD 20740 USA. US FDA, Div Microbiol Studies, OPDFB, CFSAN, College Pk, MD 20740 USA. RP Mossoba, MM (reprint author), US FDA, DGSS, OSAS, CFSAN, 5100 Paint Branch Pkwy,Mail Stop HFS 717,Room BE-0, College Pk, MD 20740 USA. NR 18 TC 21 Z9 21 U1 1 U2 6 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 OCT PY 2003 VL 55 IS 1 BP 311 EP 314 DI 10.1016/S0167-7012(03)00114-3 PG 4 WC Biochemical Research Methods; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 732QA UT WOS:000185956000034 PM 14500023 ER PT J AU Puri, RK AF Puri, RK TI Introduction to special issue: targeted toxins for glioma therapy SO JOURNAL OF NEURO-ONCOLOGY LA English DT Editorial Material C1 US FDA, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. RP Puri, RK (reprint author), US FDA, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-594X J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD OCT PY 2003 VL 65 IS 1 BP 1 EP 2 DI 10.1023/A:1026258013992 PG 2 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 735DE UT WOS:000186096500001 PM 14649880 ER PT J AU Kawakami, M Kawakami, K Puri, RK AF Kawakami, M Kawakami, K Puri, RK TI Interleukin-4-Pseudomonas exotoxin chimeric fusion protein for malignant glioma therapy SO JOURNAL OF NEURO-ONCOLOGY LA English DT Review DE clinical trials; cpIL-4PE; cytotoxin therapy; malignant glioma; preclinical experimental therapy ID COMMON GAMMA-CHAIN; IL-13 RECEPTOR ALPHA-2; BREAST-CARCINOMA CELLS; INTERLEUKIN-13 RECEPTOR; PSEUDOMONAS EXOTOXIN; IN-VIVO; FUNCTIONAL COMPONENT; SIGNAL-TRANSDUCTION; CANCER-CELLS; ANTITUMOR-ACTIVITY AB Human malignant glioma cell lines, primary cell cultures, and tumor specimens derived from surgical samples have been shown to overexpress high-affinity receptors (R) for interleukin-4 (IL-4) in vitro and in situ. The significance of IL-4R expression on malignant glioma cells is still unclear. However, IL-4 has been reported to mediate functional effects in several solid tumor cell lines. These activities include inhibition of cell proliferation, regulation of adhesion molecules, and induction of signal transduction through the JAK/STAT pathway. To target IL-4Rs on tumor cells, we have produced a chimeric recombinant fusion protein consisting of a binding ligand, circularly permuted IL-4 and a mutated form of Pseudomonas exotoxin. This molecule is termed IL4(38 - 37)-PE38KDEL, cpIL4-PE, or IL-4 cytotoxin. Recombinant cpIL4-PE is highly and specifically cytotoxic to glioma cell lines in vitro, while it is not cytotoxic or less cytotoxic to hematopoietic and normal brain cells. In a nude mouse model, cpIL4-PE showed significant antitumor activity and partial or complete regression of small or large established human glioblastoma tumors. Encouraging preclinical efficacy, safety, and tolerability studies lead to testing of this agent in patients with recurrent glioblastoma. Based on these pilot studies, an extended Phase I/II clinical trial is currently ongoing to determine safety, tolerability, and efficacy of cpIL4-PE when injected stereotactically directly into the recurrent glioma by convection enhanced delivery. Preliminary clinical results suggest that cpIL4-PE can cause pronounced necrosis of recurrent glioma tumors without systemic toxicity. The central nervous system toxicities observed were attributed to the volume of infusion and/or nonspecific toxicity. Ongoing clinical trials will reveal antitumor activities of IL-4 cytotoxin in recurrent malignant glioma. 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 51 TC 50 Z9 53 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-594X J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD OCT PY 2003 VL 65 IS 1 BP 15 EP 25 DI 10.1023/A:1026294416718 PG 11 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 735DE UT WOS:000186096500003 PM 14649882 ER PT J AU Husain, SR Puri, RK AF Husain, SR Puri, RK TI Interleukin-13 receptor-directed cytotoxin for malignant glioma therapy: from bench to bedside SO JOURNAL OF NEURO-ONCOLOGY LA English DT Review DE anti-tumor activity; brain tumor; fusion protein; glioblastoma; IL-13 cytotoxin clinical trial; IL-13-PE38; IL-13 receptor; nude mice; receptor targeting; tumor regression ID GROWTH-FACTOR-RECEPTOR; COMMON GAMMA-CHAIN; PSEUDOMONAS EXOTOXIN; IL-13 RECEPTOR; ALPHA CHAIN; SIGNAL-TRANSDUCTION; CHIMERIC PROTEIN; GENE-THERAPY; GLIOBLASTOMA-MULTIFORME; MONOCLONAL-ANTIBODY AB Central nervous system malignant neoplasias, in particular, glioblastoma multiforme (GBM) have defied all current therapeutic modalities. New therapies involving tumor targeting approach are being explored. This approach relies on the identification of unique or over-expressed cell surface receptors or antigens on tumor cells. In that regard, we have identified receptor for an immune regulatory cytokine, interleukin-13 (IL-13), which is over-expressed on human malignant glioma cell lines and primary tumor cell cultures. To target IL-13 receptors (IL-13R) for cancer therapy, we have developed a recombinant fusion protein composed of IL-13 and a mutated form of Pseudomonas exotoxin ( IL13-PE38QQR or IL-13 cytotoxin). The IL-13 cytotoxin was found to be highly selective and potent in killing human GBM cells in vitro while normal cells including immune cells, endothelial cells and normal brain cells were generally spared the cytotoxic effect of IL-13 cytotoxin. This is because these cells either expressed none or expressed low levels of IL-13R. Consistent with in vitro cytotoxic activity, IL-13 cytotoxin mediated remarkable anti-tumor activity to human glioma in animal xenograft models. The direct injection of IL-13 cytotoxin into subcutaneous human GBM tumors grown in nude mice produced complete and durable regression of established tumors. Intravenous and intraperitoneal administration of IL-13 cytotoxin also reduced tumor burden significantly with fewer complete responders. All animals tolerated therapy well with minimal toxicity to vital organs. Pre-clinical safety and toxicity studies were performed in mice, rats and monkeys. Systemic administration of IL-13 cytotoxin appeared to be well tolerated at high doses (up to 50 mug/kg). Intrabrain parenchyma administration of IL-13 cytotoxin at doses up to 100 mug/ml was very well tolerated without any evidence of gross or microscopic necrosis, whereas at 500 mug/ml dose, localized necrosis was observed in normal rat brain. Based on these encouraging pre-clinical studies, three Phase I/II clinical trials in adults with malignant glioma have been initiated. The first clinical trial involves convection-enhanced delivery (CED) of IL-13 cytotoxin into recurrent malignant glioma. This route of IL-13 cytotoxin administration appears to be fairly well tolerated with no neurotoxicity. The second clinical trial involves infusion of IL-13 cytotoxin by CED following tumor resection. The initial stage of the second study assessed histologic effect of drug administered prior to resection. In third one, IL-13 cytotoxin is infused by CED followed by tumor resection. All three clinical trials are currently ongoing. 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, Natl Inst Hlth Bldg 29B,Room 2NN10,29 Lincoln Dr, Bethesda, MD 20892 USA. NR 64 TC 79 Z9 86 U1 1 U2 5 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-594X J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD OCT PY 2003 VL 65 IS 1 BP 37 EP 48 DI 10.1023/A:1026242432647 PG 12 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 735DE UT WOS:000186096500005 PM 14649884 ER PT J AU Liu, TF Cohen, KA Willingham, MC Tatter, SB Puri, RK Frankel, AE AF Liu, TF Cohen, KA Willingham, MC Tatter, SB Puri, RK Frankel, AE TI Combination fusion protein therapy of refractory brain tumors: demonstration of efficacy in cell culture SO JOURNAL OF NEURO-ONCOLOGY LA English DT Review DE diphtheria toxin; epidermal growth factor; gliomas; interleukin-13; Pseudomonas exotoxin ID GROWTH-FACTOR RECEPTOR; GLIOBLASTOMA-MULTIFORME CELLS; HIGH-GRADE GLIOMA; MALIGNANT GLIOMAS; DIPHTHERIA-TOXIN; MONOCLONAL-ANTIBODIES; CHAIN; IMMUNOTOXINS; CANCER; RICIN AB Primary brain tumors including anaplastic astrocytomas and glioblastoma multiforme are difficult to treat because of their locally invasive nature and relative resistance to chemotherapy and radiation therapy. Novel agents that can kill multi-drug resistant tumor cells and reach tumor cells at distant sites in the brain are needed. One such class of agents is fusion proteins which consist of brain-tumor-selective peptide ligands fused to peptide toxins. The ligand directs the protein to the glioma cell surface; the peptide toxin is then internalized into the cell, translocates to the cytosol and catalytically inactivates protein synthesis leading to cell death. Fusion proteins are toxic to multi-drug resistant brain tumor cells. Because of the large molecular weight of these molecules, a unique delivery system has been developed - convection- enhanced delivery (CED). The method creates a bulk flow which supplements diffusion and achieves drug concentrations in the brain parenchyma orders of magnitude greater than by systemic administration. Patients with recurrent glioma treated with individual fusion protein CED have obtained clinical remissions lasting years. However, toxicities to normal brain have been observed and relapses ultimately occurred. To address the clinical need of these patients and improve upon the therapeutic index observed to date with single fusion protein CED, we generated a novel fusion proteinDAB(389)EGF and tested it in combination with another active fusion protein, IL13PE38QQR. We observed potent glioma cytotoxicity with each fusion protein and synergistic toxicity with the combination. Further, brain tumor cells showed heterogeneous expression of individual receptors suggesting that the combination - DAB(389)EGF and IL13PE38QQR may show improved efficacy and should undergo further preclinical development for therapy of patients with relapsed high-grade gliomas. C1 Wake Forest Univ, Bowman Gray Sch Med, Dept Med, Winston Salem, NC 27157 USA. Wake Forest Univ, Bowman Gray Sch Med, Dept Surg, Winston Salem, NC 27157 USA. Wake Forest Univ, Bowman Gray Sch Med, Dept Pathol, Winston Salem, NC 27157 USA. Wake Forest Univ, Bowman Gray Sch Med, Dept Comparat Med, Winston Salem, NC 27157 USA. US FDA, Bethesda, MD 20014 USA. RP Frankel, AE (reprint author), Wake Forest Univ, Bowman Gray Sch Med, Dept Med, Hanes 4046,Med Ctr Blvd, Winston Salem, NC 27157 USA. FU NCI NIH HHS [R01CA76178, R21CA090550, R01CA090263] NR 40 TC 8 Z9 10 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-594X J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD OCT PY 2003 VL 65 IS 1 BP 77 EP 85 PG 9 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 735DE UT WOS:000186096500008 PM 14649887 ER PT J AU Itzhak, Y Ali, SF Anderson, KL AF Itzhak, Y Ali, SF Anderson, KL TI Fenfluramine-induced serotonergic neurotoxicity in mice: lack of neuroprotection by inhibition/ablation of nNOS SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE 7-nitroindazole; fenfluramine; methamphetamine; nitric oxide; serotonergic and dopaminergic neurotoxicity ID NEURONAL NITRIC-OXIDE; INDUCED DOPAMINERGIC NEUROTOXICITY; RAT-BRAIN; TRYPTOPHAN-HYDROXYLASE; METHAMPHETAMINE; SYNTHASE; 7-NITROINDAZOLE; INHIBITOR; OXIDATION; MOUSE AB Previous studies have implicated a role for nitric oxide ( NO) and peroxynitrite in methamphetamine-induced dopaminergic neurotoxicity. The present study was undertaken to investigate whether NO is involved in serotonergic neurotoxicity caused by fenfluramine. In the first experiment, the effect of the neuronal nitric oxide synthase (nNOS) inhibitor 7-nitroindazole (7-NI; 25 mg/kg x 4) on fenfluramine ( 25 mg/kg x 4)-induced serotonergic neurotoxicity in Swiss Webster mice was investigated. In the second experiment, the effect of fenfluramine ( 25 mg/kg x 4) on nNOS (-/-) and wild-type (WT) mice was investigated. Fenfluramine induced hypothermia in all three mouse strains, and 7-NI had no thermoregulatory effect. Selective depletion of 5-HT and 5-HT transporter binding sites in the striatum, frontal cortex and hippocampus in all three mouse strains was observed, with no evidence of dopaminergic neurotoxicity. In the first experiment, 7-NI did not attenuate serotonergic neurotoxicity in Swiss Webster mice. In the second experiment, nNOS( -/-) and WT mice were equally sensitive to serotonergic neurotoxicity. These findings suggest that NO and peroxynitrite do not mediate fenfluramine-induced serotonergic neurotoxicity, and that NO is a selective mediator of amphetamines-induced dopaminergic neurotoxicity. C1 Univ Miami, Sch Med, Dept Psychiat & Behav Sci, 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, Gautier Bldg Room 503,1011 NW 15 St, Miami, FL 33136 USA. FU NIDA NIH HHS [R01 DA12867] NR 26 TC 9 Z9 9 U1 0 U2 1 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD OCT PY 2003 VL 87 IS 1 BP 268 EP 271 DI 10.1046/j.1471-4159.2003.02023.x PG 4 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 721KY UT WOS:000185316600028 PM 12969273 ER PT J AU Yu, H Srauss, KI Rossi, L Borenstein, MR Jansen, SA AF Yu, H Srauss, KI Rossi, L Borenstein, MR Jansen, SA TI Liquid chromatography/mass spectrometric method for the simultaneous determination of twenty four eicosanoids extracted from rodent brain tissue SO JOURNAL OF NEUROTRAUMA LA English DT Meeting Abstract CT 21st Annual National-Neurotrauma-Society Symposium CY NOV 06-07, 2003 CL BILOXI, MISSISSIPPI SP Natl Neurotrama Soc C1 Univ Cincinnati, Cincinnati, OH 45221 USA. US FDA, Philadelphia, PA USA. Temple Univ, Philadelphia, PA 19122 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 0897-7151 J9 J NEUROTRAUM JI J. Neurotrauma PD OCT PY 2003 VL 20 IS 10 MA P156 BP 1066 EP 1066 PG 1 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA 734RX UT WOS:000186072300069 ER PT J AU Ishibe, N Goldin, LR Caporaso, NE Sgambati, MT Dean, M Albitar, M Manshouri, T Gerrard, B Marti, GE AF Ishibe, N Goldin, LR Caporaso, NE Sgambati, MT Dean, M Albitar, M Manshouri, T Gerrard, B Marti, GE TI ATM mutations and protein expression are not associated with familial B-CLL cases SO LEUKEMIA RESEARCH LA English DT Article ID CHRONIC LYMPHOCYTIC-LEUKEMIA; MANTLE CELL LYMPHOMA; ATAXIA-TELANGIECTASIA; GENE; INACTIVATION; KINASE C1 NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. NCI, Div Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. NCI, Lab Genome Divers, FCRDS, Ft Detrick, MD 21702 USA. Univ Texas, MD Anderson Canc Ctr, Hematopathol Dept, Sect Leukemia, Houston, TX 77030 USA. NCI, FCRDC, Intramural Res Support Program, Ft Detrick, MD 21702 USA. US FDA, Flow & image Cytometry Sect, Div Cell & Gene Therapies, Bethesda, MD 20892 USA. RP Ishibe, N (reprint author), NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, 6120 Exectu Blvd,MSC 7236, Bethesda, MD 20892 USA. RI Dean, Michael/G-8172-2012 OI Dean, Michael/0000-0003-2234-0631 FU NCI NIH HHS [N01-CO-12400] NR 18 TC 8 Z9 9 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0145-2126 J9 LEUKEMIA RES JI Leuk. Res. PD OCT PY 2003 VL 27 IS 10 BP 973 EP 975 DI 10.1016/S0145-2126(03)00067-5 PG 3 WC Oncology; Hematology SC Oncology; Hematology GA 702WL UT WOS:000184247700019 PM 12860021 ER PT J AU Zaslavsky, BG McDonald, JJ AF Zaslavsky, BG McDonald, JJ TI A characterization of Jordan canonical forms which are similar to eventually nonnegative matrices with the properties of nonnegative matrices SO LINEAR ALGEBRA AND ITS APPLICATIONS LA English DT Article DE nonnegative matrices; eventually nonnegative matrices; Jordan form; Weyr characteristic; level characteristic ID SYSTEMS; POWERS; CONE; RANK AB In this paper we give necessary and sufficient conditions for a matrix in Jordan canonical form to be similar to an eventually nonnegative matrix whose irreducible diagonal blocks satisfy the conditions identified by Zaslavsky and Tam, and whose subdiagonal blocks (with respect to its Frobenius normal form) are nonnegative. These matrices are referred to as semi-nonnegative matrices, and we show that they exhibit many of the same combinatorial spectral properties as nonnegative matrices. This paper extends the work on Jordan forms of irreducible eventually nonnegative matrices to the reducible case. (C) 2003 Elsevier Inc. All rights reserved. C1 Washington State Univ, Dept Math, Pullman, WA 99164 USA. US FDA, CBER, OBE, Rockville, MD 20852 USA. RP McDonald, JJ (reprint author), Washington State Univ, Dept Math, POB 643113, Pullman, WA 99164 USA. NR 26 TC 15 Z9 15 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0024-3795 J9 LINEAR ALGEBRA APPL JI Linear Alg. Appl. PD OCT 1 PY 2003 VL 372 BP 253 EP 285 DI 10.1016/S0024-3795(03)00534-2 PG 33 WC Mathematics, Applied; Mathematics SC Mathematics GA 716WV UT WOS:000185053300014 ER PT J AU Badano, A Flynn, MJ Martin, S Kanicki, J AF Badano, A Flynn, MJ Martin, S Kanicki, J TI Angular dependence of the luminance and contrast in medical monochrome liquid crystal displays SO MEDICAL PHYSICS LA English DT Article DE liquid crystal display; medical display; luminance response; display contrast; viewing angle AB Active-matrix liquid crystal displays (AMLCDs) are light-modulating devices that generate images by differentially transmitting a nearly uniform luminous field provided by a backlight. While emissive displays exhibit a quasi-Lambertian emission with almost constant contrast at off-normal viewing, the anisotropy of the electro-optic effect that controls light transmission in AMLCDs causes a pixel luminance that varies, sometimes strongly, with viewing angle. These variations are not identical for all gray levels and can eventually cause grayscale inversions. In this paper, we measured the luminance emission of a monochrome medical AMLCD, a medical cathode-ray tube monitor, and a color desktop AMLCD, using a collimated photopic probe positioned on a manual rotation arm, and a research radiometer with automatic readout. The probe measures luminance with a small acceptance angle and provides optical shielding from emissions at other viewing directions that contaminate the readings. We obtained luminance response curves versus angle in the vertical, horizontal and at 45degrees diagonal directions. The display systems were calibrated to reflect the DICOM Part 3.14 standard grayscale display function (GDF) when measured using the manufacturer's probe and software tools. We analyzed the measurements at different viewing directions with respect to their departure from the GDF by computing the non-nalized contrast (DeltaL/L) as a function of the DICOM just-noticeable difference index. Although cathode-ray tubes are known to be quasi-Lambertian emitters, the luminance at normal viewing is higher than the luminance observed at large angles. This decrease in luminance is however proportionally similar for all gray levels, resulting in a relatively flat contrast response for all angles. In addition to being more pronounced, the angular variation in AMLCDs does not follow the same profile at different intensities with the subsequent variation in the achieved display contrast. The changes due to off-normal viewing are substantial at large angles in the horizontal and vertical directions, and much worse in the diagonal viewing directions. (C) 2003 American Association of Physicists in Medicine. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. Henry Ford Hlth Syst, Dept Radiol, Detroit, MI 48202 USA. Univ Michigan, Dept Elect Engn & Comp Sci, Ann Arbor, MI 48109 USA. RP Badano, A (reprint author), US FDA, Ctr Devices & Radiol Hlth, 12720 Twinbrook Pkwy, Rockville, MD 20857 USA. RI Kanicki, Jerzy/E-2753-2016; OI Kanicki, Jerzy/0000-0002-3649-8360; badano, aldo/0000-0003-3712-6670 NR 21 TC 29 Z9 29 U1 0 U2 5 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 OCT PY 2003 VL 30 IS 10 BP 2602 EP 2613 DI 10.1118/1.1606449 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 732PA UT WOS:000185953700005 PM 14596296 ER PT J AU Nakayama, S Kushiro, A Asahara, T Tanaka, R Hu, L Kopecko, DJ Watanabe, H AF Nakayama, S Kushiro, A Asahara, T Tanaka, R Hu, L Kopecko, DJ Watanabe, H TI Activation of hilA expression at low pH requires the signal sensor CpxA, but not the cognate response regulator CpxR, in Salmonella enterica serovar Typhimurium SO MICROBIOLOGY-SGM LA English DT Article ID INVASION GENE-EXPRESSION; SONNEI VIRF GENE; ESCHERICHIA-COLI; PLASMID VECTORS; VIRULENCE; PROTEIN; SEQUENCE; SYSTEM; MEMBER; IDENTIFICATION AB A two-component regulatory system, cpxR-cpxA, plays an important role in the pH-dependent regulation of virF, a global activator for virulence determinants including invasion genes, in Shigella sonnei. The authors examined whether the cpxR-cpxA homologues have some function in the expression of Salmonella enterica serovar Typhimurium invasion genes via the regulation of hilA, an activator for these genes. In a Salmonella cpxA mutant, the hilA expression level was reduced to less than 10% of that in the parent strain at pH 6(.)0. This mutant strain also showed undetectable synthesis of an invasion gene product, SipC, at pH 6(.)0 and reduced cell invasion capacity - as low as 20% of that of the parent. In this mutant, the reduction in hilA expression was much less marked at pH 8(.)0 than at pH 6(.)0 - no less than 50% of that in the parent, and no significant reduction was observed in either SipC synthesis or cell invasion rate, compared to the parent. Unexpectedly, a Salmonella cpxR mutant strain and the parent showed no apparent difference in all three characteristics described above at either pH. These results indicate that in Salmonella, the sensor kinase CpxA activates hilA, and consequently, invasion genes and cell invasion capacity at pH 6(.)0. At pH 8(.)0, however, CpxA does not seem to have a large role in activation of these factors. Further, the results show that this CpxA-mediated activation does not require its putative cognate response regulator, CpxR. This suggests that CpxA may interact with regulator(s) other than CpxR to achieve activation at low pH. C1 Natl Inst Infect Dis, Dept Bacteriol, Shinjuku Ku, Toyama 1628640, Japan. Yakult Cent Inst Microbiol Res, Kunitachi, Tokyo 1868650, Japan. US FDA, Ctr Biol Evaluat & Res, Lab Enter & Sexually Transmitted Dis, Bethesda, MD 20892 USA. RP Watanabe, H (reprint author), Natl Inst Infect Dis, Dept Bacteriol, Shinjuku Ku, 1-23-1, Toyama 1628640, Japan. NR 36 TC 36 Z9 36 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 OCT PY 2003 VL 149 BP 2809 EP 2817 DI 10.1099/mic.0.26229-0 PN 10 PG 9 WC Microbiology SC Microbiology GA 733NU UT WOS:000186008200013 PM 14523114 ER PT J AU Johann-Liang, R Zalkikar, J Powers, JH AF Johann-Liang, R Zalkikar, J Powers, JH TI Correlation between bacteriologic and clinical endpoints in trials of acute otitis media SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Letter DE acute otitis media; bacteriologic outcome; clinical outcome; double tympanocentesis C1 US FDA, Ctr Drug Evaluat & Res, Div Special Pathogen & Immunol Drug Prod, Rockville, MD 20857 USA. US FDA, Ctr Drug Evaluat & Res, Off Biostat, Rockville, MD 20857 USA. US FDA, Ctr Drug Evaluat & Res, Off Drug Evaluat, Rockville, MD 20857 USA. RP Johann-Liang, R (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Special Pathogen & Immunol Drug Prod, Rockville, MD 20857 USA. NR 7 TC 13 Z9 14 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0891-3668 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD OCT PY 2003 VL 22 IS 10 BP 936 EP 937 DI 10.1097/01.inf.0000092637.66762.c6 PG 2 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA 733XH UT WOS:000186025600025 PM 14551499 ER PT J AU Bohlke, K Davis, RL Marcy, SM Braun, MM DeStefano, F Black, SB Mullooly, JP Thompson, RS AF Bohlke, K Davis, RL Marcy, SM Braun, MM DeStefano, F Black, SB Mullooly, JP Thompson, RS CA Vaccine Safety Datalink Team TI Risk of anaphylaxis after vaccination of children and adolescents SO PEDIATRICS LA English DT Article DE anaphylaxis; vaccination; vaccine adverse reactions ID HEPATITIS-B VACCINATION; TETANUS AB Objective. To quantify the risk of anaphylaxis after vaccination of children and adolescents. Methods. The study population consisted of children and adolescents who were enrolled at 4 health maintenance organizations that participated in the Vaccine Safety Datalink Project. For the period 1991-1997, we identified potential cases by searching for occurrences of International Classification of Diseases, Ninth Revision (ICD-9) code 995.0 (anaphylactic shock), E948.0 through E948.9 (adverse reaction from bacterial vaccines), and E949.0 through E949.9 (adverse reaction from other vaccines and biological substances). At 1 study site, we also included a range of other allergy codes. We restricted to diagnoses on days 0 to 2 after vaccination (ICD-9 995.0) or day 0 (all other ICD-9 codes). We then reviewed the medical record to confirm the diagnosis. Results. We identified 5 cases of potentially vaccine-associated anaphylaxis after administration of 7 644 049 vaccine doses, for a risk of 0.65 cases/million doses (95% confidence interval: 0.21-1.53). None of the episodes resulted in death. Vaccines that were administered before the anaphylactic episodes were generally given in combination and included measles-mumps-rubella, hepatitis B, diphtheria-tetanus, diphtheria-tetanus-pertussis, Haemophilus influenzae type b, and oral polio vaccine. One case of anaphylaxis followed measles-mumps-rubella vaccine alone. At the site at which we reviewed additional allergy codes, we identified 1 case after 653 990 vaccine doses, for a risk of 1.53 cases/million doses (95% confidence interval: 0.04-8.52). Conclusions. Patients and health care providers can be reassured that vaccine-associated anaphylaxis is a rare event. Nevertheless, providers should be prepared to provide immediate medical treatment should it occur. C1 Grp Hlth Cooperat Puget Sound, Ctr Hlth Studies, Seattle, WA 98101 USA. Grp Hlth Cooperat Puget Sound, Dept Prevent Care, 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 Epidemiol, Seattle, WA 98195 USA. Univ Washington, Sch Publ Hlth, Dept Pediat, Seattle, WA 98195 USA. Kaiser Fdn Hosp, Panorama City, CA USA. US FDA, Div Epidemiol, Off Biostat & Epidemiol, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. Ctr Dis Control & Prevent, Natl Immunizat Program, Atlanta, GA USA. No Calif Kaiser Permanente, Pediat Vaccine Study Ctr, Oakland, CA USA. NW Kaiser Permanente, Ctr Hlth Res, Portland, OR USA. RP Bohlke, K (reprint author), Grp Hlth Cooperat Puget Sound, Ctr Hlth Studies, 1730 Minor Ave,Ste 1600, Seattle, WA 98101 USA. NR 21 TC 150 Z9 163 U1 1 U2 17 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 OCT 1 PY 2003 VL 112 IS 4 BP 815 EP 820 DI 10.1542/peds.112.4.815 PG 6 WC Pediatrics SC Pediatrics GA 727NV UT WOS:000185665700023 PM 14523172 ER PT J AU LaPointe, NMA Pamer, CA Kramer, JM AF LaPointe, NMA Pamer, CA Kramer, JM TI New antiarrhythmic agents for atrial fibrillation and atrial flutter: United States drug market response as an indicator of acceptance SO PHARMACOTHERAPY LA English DT Article ID DOFETILIDE; MANAGEMENT AB Objective. To determine how well dofetilide and Betapace AF (sotalol, approved solely for atrial fibrillation and atrial flutter), with their detailed dosing and monitoring guidelines for safety, were accepted into clinical practice during the 2 calendar years after their introduction. Methods and Results. We reviewed the number of new, refill, and total prescriptions of all antiarrhythmic agents in the United States from April 2000-December 2001 to assess use of dofetilide and Betapace AF in the drug market. Both were prescribed very infrequently throughout the study period. In addition, the infrequent reported use of these drugs for patients with atrial fibrillation and flutter indicated poor acceptance of these agents by prescribing physicians. We speculated that the restricted distribution and required educational program for dofetilide, as well as the availability of generic sotalol products, may have discouraged physicians from prescribing both dofetilide and Betapace AF. Conclusion. A common goal for both the dofetilide risk-management program and the creation of a sotalol product indicated solely for atrial fibrillation and atrial flutter was to provide safer treatment for patients with these arrhythmias. Unfortunately, limited penetration of dofetilide and Betapace AF into the U.S. market suggests that drugs without a risk-management program or detailed dosing guidelines were more likely than dofetilide or Betapace AF to be selected for treatment of atrial fibrillation and atrial flutter. C1 Duke Ctr Educ & Res Therapeut, Duke Clin Res Inst, Durham, NC 27715 USA. US FDA, Off Drug Safety, Div Drug Risk Evaluat, Rockville, MD 20857 USA. RP LaPointe, NMA (reprint author), Duke Ctr Educ & Res Therapeut, Duke Clin Res Inst, POB 17969, Durham, NC 27715 USA. FU AHRQ HHS [U18HS10548] NR 8 TC 1 Z9 1 U1 0 U2 0 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 OCT PY 2003 VL 23 IS 10 BP 1316 EP 1321 DI 10.1592/phco.23.12.1316.32703 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 728ZX UT WOS:000185747200010 PM 14594348 ER PT J AU Ferguson, SA Gough, BJ Cada, AM AF Ferguson, SA Gough, BJ Cada, AM TI In vivo basal and amphetamine-induced striatal dopamine and metabolite levels are similar in the spontaneously hypertensive, Wistar-Kyoto and Sprague-Dawley male rats SO PHYSIOLOGY & BEHAVIOR LA English DT Article DE spontaneously hypertensive rat; Wistar-Kyoto; amphetamine; microdialysis; striatum; dopamine ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT HYPERACTIVITY DISORDER; CENTRAL-NERVOUS-SYSTEM; ANIMAL-MODEL; BEHAVIORAL-RESPONSES; LOCOMOTOR-ACTIVITY; CAUDATE-NUCLEUS; H-3 DOPAMINE; BRAIN; RELEASE AB Nigrostriatal alterations are proposed to partially underlie the hypertension and hyperactivity exhibited by the spontaneously hypertensive rat (SHR). Here, in vivo microdialysis was used to measure baseline and d-amphetamine (AMPH)-stimulated striatal dopamine (DA) and metabolite levels in adult male SHR, Wistar-Kyoto (WKY), and Sprague-Dawley (SD) rats. At approximately 19 weeks of age, baseline levels of DA, 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA) were measured after which time, each rat was injected intraperitoneally with 2 mg/kg AMPH and samples were collected for the subsequent 200 min. There were no significant strain differences in baseline levels of DA, HVA, and 5-HIAA. The baseline level of DOPAC was decreased in the WKY relative to the SD. AMPH treatment altered DA, DOPAC, HVA, and 5-HIAA to a similar extent in all strains; thus, there were no significant strain differences, nor did the area under the curve (AUC) for DA levels differ between strains. AUC for DOPAC was significantly smaller for the WXY relative to the SD strain, likely due to the lower baseline level. At the single dose of amphetamine used here, the results indicate that in vivo DA levels in the SHR are similar to the WKY and SD strains. Published by Elsevier Inc. C1 Natl Ctr Toxicol Res FDA, Div Neurotoxicol, HFT 132, Jefferson, AR 72079 USA. RP Ferguson, SA (reprint author), Natl Ctr Toxicol Res FDA, Div Neurotoxicol, HFT 132, 3900 NCTR Rd, Jefferson, AR 72079 USA. NR 43 TC 12 Z9 12 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0031-9384 J9 PHYSIOL BEHAV JI Physiol. Behav. PD OCT PY 2003 VL 80 IS 1 BP 109 EP 114 DI 10.1016/S0031-9384(03)00214-2 PG 6 WC Psychology, Biological; Behavioral Sciences SC Psychology; Behavioral Sciences GA 737ZV UT WOS:000186263000014 PM 14568315 ER PT J AU Desta, AB Owen, RD Cress, LW AF Desta, AB Owen, RD Cress, LW TI Non-thermal exposure to radiofrequency energy from digital wireless phones does not affect ornithine decarboxylase activity in L929 cells SO RADIATION RESEARCH LA English DT Article ID HZ MAGNETIC-FIELDS; IN-VITRO; MICROWAVES AB L929 murine fibroblast cells were exposed to radiofrequency (RF) radiation from a time division multiple access wireless phone operating at 835 MHz frequency to determine the effect of RF-radiation energy emitted by wireless phones on ornithine decarboxylase (ODC) activity in cultured cells. Exposure was for 8 h to an average specific absorption rate (SAR) from <1 W/kg up to 15 W/kg. After exposure, cells were harvested and ODC activity was measured. No statistically significant difference in ODC activity was found between RF-radiation-exposed and sham-exposed cells at non-thermal specific absorption rates. At SARs which resulted in measurable heating of the medium, a dose-dependent decrease in enzymatic activity was observed and was shown to be consistent with a comparable decrease caused by non-RF-radiation heating. Thus we observed only the well-known enzyme inhibition due to heating, rather than the previously reported enhancement attributed to RF-radiation exposure. (C) 2003 by Radiation Research Society. C1 US FDA, Rockville, MD 20850 USA. RP Cress, LW (reprint author), HFZ-114,9200 Corporate Blvd, Rockville, MD 20850 USA. NR 12 TC 15 Z9 15 U1 0 U2 1 PU RADIATION RESEARCH SOC PI OAK BROOK PA 820 JORIE BOULEVARD, OAK BROOK, IL 60523 USA SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD OCT PY 2003 VL 160 IS 4 BP 488 EP 491 DI 10.1667/RR3054 PG 4 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA 723GL UT WOS:000185424300011 PM 12968926 ER PT J AU Hong, H Fang, H Xie, Q Perkins, R Sheehan, DM Tong, W AF Hong, H Fang, H Xie, Q Perkins, R Sheehan, DM Tong, W TI Comparative Molecular Field Analysis (CoMFA) model using a large diverse set of natural, synthetic and environmental chemicals for binding to the androgen receptor SO SAR AND QSAR IN ENVIRONMENTAL RESEARCH LA English DT Article; Proceedings Paper CT Conference on Computational Methods in Toxicology and Pharmacology Integrating Internet Resources CY SEP 17-19, 2003 CL THESSALONIKI, GREECE DE QSAR; CoMFA; androgen receptor; endocrine disrupting chemicals; androgen; environmental chemicals ID ESTROGEN-RECEPTOR; QSAR MODELS; ENDOCRINE DISRUPTORS; 3D QSAR; PREDICTION; INHIBITORS; DISCOVERY AB A large number of natural, synthetic and environmental chemicals are capable of disrupting the endocrine systems of experimental animals, wildlife and humans. These so-called endocrine disrupting chemicals (EDCs), some mimic the functions of the endogenous androgens, have become a concern to the public health. Androgens play an important role in many physiological processes, including the development and maintenance of male sexual characteristics. A common mechanism for androgen to produce both normal and adverse effects is binding to the androgen receptor (AR). In this study, we used Comparative Molecular Field Analysis (CoMFA), a three-dimensional quantitative structure-activity relationship (3D-QSAR) technique, to examine AR-ligand binding affinities. A CoMFA model with r(2) = 0.902 and q(2) = 0.571 was developed using a large training data set containing 146 structurally diverse natural, synthetic, and environmental chemicals with a 10(6)-fold range of relative binding affinity (RBA). By comparing the binding characteristics derived from the CoMFA contour map with these observed in a human AR crystal structure, we found that the steric and electrostatic properties encoded in this training data set are necessary and sufficient to describe the RBA of AR ligands. Finally, the CoMFA model was challenged with an external test data set; the predicted results were close to the actual values with average difference of 0.637 logRBA. This study demonstrates the utility of this CoMFA model for real-world use in predicting the AR binding affinities of structurally diverse chemicals over a wide RBA range. C1 Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Ctr Toxicoinformat, Jefferson, AR 72079 USA. Daniel M Sheehan & Assoc, Little Rock, AR 72202 USA. Northrop Grumman Informat Technol, Jefferson, AR 72079 USA. RP Tong, W (reprint author), Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Ctr Toxicoinformat, Jefferson, AR 72079 USA. NR 31 TC 39 Z9 39 U1 0 U2 3 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1062-936X J9 SAR QSAR ENVIRON RES JI SAR QSAR Environ. Res. PD OCT-DEC PY 2003 VL 14 IS 5-6 BP 373 EP 388 DI 10.1080/10629360310001623962 PG 16 WC Chemistry, Multidisciplinary; Computer Science, Interdisciplinary Applications; Environmental Sciences; Mathematical & Computational Biology; Toxicology SC Chemistry; Computer Science; Environmental Sciences & Ecology; Mathematical & Computational Biology; Toxicology GA 746ZN UT WOS:000186779100006 PM 14758981 ER PT J AU MacGregor, JT AF MacGregor, JT TI The future of regulatory toxicology: Impact of the biotechnology revolution SO TOXICOLOGICAL SCIENCES LA English DT Editorial Material DE toxicity; biomarkers; microarray; proteomics; genomics; metabonomics; polymorphism; haplotype; validation ID POSITRON-EMISSION-TOMOGRAPHY; LINKAGE DISEQUILIBRIUM MAP; GLUTATHIONE-S-TRANSFERASE; TRANSGENIC ANIMAL-MODELS; IN-VIVO; GENE-EXPRESSION; MASS-SPECTROMETRY; DNA-REPAIR; QUALITY-CONTROL; LIVING SUBJECTS AB The molecular biology revolution and the advent of genomic and proteomic technologies are facilitating rapid advances in our understanding of the molecular details of cell and tissue function. These advances have the potential to transform toxicological and clinical practice, and are likely to lead to the supplementation or replacement of traditional biomarkers of cellular integrity, cell and tissue homeostasis, and morphological alterations that result from cell damage or death. New technologies that permit simultaneous monitoring of many hundreds, or thousands, of macro- and small molecules ("-omics" technologies) promise to allow functional monitoring of multiple (or perhaps all) key cellular pathways simultaneously. Elucidation of cellular responses to molecular damage, including evolutionarily conserved inducible molecular defense systems, suggests the possibility of new biomarkers based on molecular responses to functional perturbations and cellular damage. Our improved understanding of the molecular basis of various pathologies suggests that monitoring specific molecular responses may provide improved prediction of human outcomes. Responses that can be monitored directly in the human should provide "bridging biomarkers" that may eliminate much of the current uncertainty in extrapolating from laboratory models to human outcome. Another aspect of genomics is our enhanced ability to associate DNA sequence variations with biological outcomes and individual sensitivity. The human genome sequence has revealed that sequence variations are very common, and may be an important determinant of variation in biological outcomes. The impending availability of a complete human haplotype map linked to standard genetic markers greatly facilitates identification of genetic variations that convey sensitivity or resistance to chemical exposures. Genetic approaches have already linked a large number of genetic variants (polymorphisms) with human diseases and adverse reactions from exposure to drugs or toxicants, suggesting an important role in sensitivity to drugs and environmental agents, disease susceptibilities, and therapeutic responses. As these opportunities are transformed into reality, regulatory toxicological practice is likely to be shaped in the future by the combination of, conventional pathology, toxicology, molecular genetics, biochemistry, cell biology, and computational bioinformatics-resulting in the broad application of molecular approaches to monitoring functional disturbances. 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 103 TC 31 Z9 36 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 OCT PY 2003 VL 75 IS 2 BP 236 EP 248 DI 10.1093/toxsci/kfg197 PG 13 WC Toxicology SC Toxicology GA 724KG UT WOS:000185486300003 PM 12883082 ER PT J AU Epstein, JS Vostal, JG AF Epstein, JS Vostal, JG TI FDA approach to evaluation of pathogen reduction technology SO TRANSFUSION LA English DT Editorial Material ID BACTERIAL-CONTAMINATION; TRANSFUSION C1 FDA, Ctr Biol Evaluat & Res, Off Blood Res & Review, Rockville, MD USA. RP Epstein, JS (reprint author), FDA, Ctr Biol Evaluat & Res, Off Blood Res & Review, Rockville, MD USA. NR 13 TC 25 Z9 25 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD OCT PY 2003 VL 43 IS 10 BP 1347 EP 1350 DI 10.1046/j.1537-2995.2003.00584.x PG 4 WC Hematology SC Hematology GA 726NY UT WOS:000185606800002 PM 14507263 ER PT J AU Pierce, LR Jain, N AF Pierce, LR Jain, N TI Risks associated with the use of intravenous immunoglobulin SO TRANSFUSION MEDICINE REVIEWS LA English DT Review ID HEPATITIS-C VIRUS; IMMUNE THROMBOCYTOPENIC PURPURA; ACUTE-RENAL-FAILURE; ACUTE LUNG INJURY; ASEPTIC-MENINGITIS; GLOBULIN TREATMENT; GAMMA-GLOBULIN; IVIG THERAPY; COMPLICATIONS; NEUTROPENIA AB Although US immune globulin intravenous (human) (IGIV) products have been regarded as safe, it is important to recognize that many of the controlled clinical studies of IGIVs have been of modest size and have limited power to define the incidence of only the most common adverse events (AEs). A significant number of "postmarketing" serious AEs affecting renal, cardiovascular, CNS, integumentary, and hematologic organ systems have been reported. Variables potentially affecting the risk and intensity of adverse events associated with administration of IGIV include patient age, underlying condition, history of migraine, cardiovascular or renal disease, dose, concentration, rate of infusion, specific brand/formulation/excipients, and lot(s) of the particular IGIV product being administered. Each manufacturer's IGIV preparation is a unique product carrying its own specific evidence-based indications and safety profile. In view of the seriousness of potential adverse effects of IGIV products, and current lack of data surrounding their frequency, clinicians are advised to limit their prescription of these products for conditions for which efficacy is supported by adequate and well-controlled clinical trials. Prescribers should pay close attention to patient selection; consider the potential risk/benefit ratio vis-a-vis alternate therapies; and familiarize themselves with the identification, management, and proposed strategies to minimize the risks of IGIV. (C) 2003 Elsevier Inc. All rights reserved. C1 US FDA, Clin Review Branch, Div Hematol, Off Blood Res & Review,Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Pierce, LR (reprint author), US FDA, Clin Review Branch, Div Hematol, Off Blood Res & Review,Ctr Biol Evaluat & Res, 1401 Rockville Pike,HFM-392, Rockville, MD 20852 USA. NR 53 TC 103 Z9 107 U1 1 U2 4 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0887-7963 J9 TRANSFUS MED REV JI Transf. Med. Rev. PD OCT PY 2003 VL 17 IS 4 BP 241 EP 251 DI 10.1053/S0887-7963(03)00038-5 PG 11 WC Hematology SC Hematology GA 737AQ UT WOS:000186206600001 PM 14571392 ER PT J AU Verthelyi, D Zeuner, RA AF Verthelyi, D Zeuner, RA TI Differential signaling by CpG DNA in DCs and B cells: not just TLR9 SO TRENDS IN IMMUNOLOGY LA English DT Article ID TOLL-LIKE RECEPTORS; PLASMACYTOID DENDRITIC CELLS; HUMAN IMMUNE CELLS; PROTEIN-KINASE; BACTERIAL-DNA; ACTIVATION; OLIGODEOXYNUCLEOTIDES; SUBSETS; OLIGONUCLEOTIDES; PRECURSORS AB CpG-containing oligodeoxynucleotides (CpG ODNs) act on Toll-like receptor 9 (TLR9) that is expressed on B cells and plasmacytoid dendritic cells (pDCs) to stimulate the innate immune system, however, different types of CpG ODNs induce distinct responses. Recent papers suggest some CpG ODNs could require a second receptor or cofactor to signal. The different signaling complexes assembled might impact on the affinity with which CpG ODNs signal to TLR9 or activate additional pathways that lead to distinct immune responses. C1 US FDA, Ctr Biol Evaluat & Res, Div Therapeut Proteins, Bethesda, MD 20892 USA. Univ Kiel, Klinikum Schleswig Holstein, Dept Med 2, D-24116 Kiel, Germany. RP Verthelyi, D (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Therapeut Proteins, Bldg 29A Rm 3B19,8800 Rockville Pike, Bethesda, MD 20892 USA. NR 24 TC 73 Z9 79 U1 0 U2 1 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 OCT PY 2003 VL 24 IS 10 BP 519 EP 522 DI 10.1016/S1471-4906(03)00243-6 PG 4 WC Immunology SC Immunology GA 734LY UT WOS:000186058500001 PM 14552833 ER PT J AU Brown, EW LeClerc, JE Cebula, TA AF Brown, EW LeClerc, JE Cebula, TA TI Searching for keys under the devil's lamppost SO TRENDS IN MICROBIOLOGY LA English DT Letter ID SALMONELLA-ENTERICA; ESCHERICHIA-COLI; TYPHI; RECOMBINATION; SEQUENCE; REARRANGEMENTS; GENOME C1 US FDA, Ctr Food Safety & Appl Nutr, Div Mol Biol, Laurel, MD 20708 USA. RP Cebula, TA (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Div Mol Biol, Laurel, MD 20708 USA. NR 19 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0966-842X J9 TRENDS MICROBIOL JI Trends Microbiol. PD OCT PY 2003 VL 11 IS 10 BP 454 EP 456 DI 10.1016/j.tim.2003.08.005 PG 3 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 737AU UT WOS:000186206900003 PM 14557027 ER PT J AU Woodhouse, EC Fisher, A Bandle, RW Bryant-Greenwood, B Charboneau, L Petricoin, EF Liotta, LA AF Woodhouse, EC Fisher, A Bandle, RW Bryant-Greenwood, B Charboneau, L Petricoin, EF Liotta, LA TI Drosophila screening model for metastasis: Semaphorin 5c is required for I(2)gl cancer phenotype SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID GROWTH-FACTOR-BETA; TUMOR-SUPPRESSOR PROTEIN; II HEAVY-CHAIN; LETHAL(2)GIANT LARVAE; GENE; ACTIVATION; DPP; THROMBOSPONDIN-1; EMBRYOGENESIS; PROGRESSION AB Cancer metastasis is a complex process involving many genes and pathways. This complexity hinders the identification of molecules functionally required for this process. We have developed and used a Drosophila screening system to identify genes that are functionally important for tumorigenicity and metastasis. Deletion of Drosophila lethal giant larvae (1(2)gl) leads to highly invasive and widely metastatic tumors on transplantation into adult flies. Random homozygous P element insertions were screened for the ability to modulate the 1(2)gl phenotype. Analysis of metastasis patterns of the lines containing P element insertions and lacking wild-type l(2)gl expression identified three homozygous mutations that dramatically alter tumorigenesis and/or metastasis. Semaphorin Sc (Sema 5c) is required for tumorigenicity, apontic overexpression suppresses metastasis but not tumorigenicity, and pointed up-regulation accelerates lethality of 1(2)gl tumors. Furthermore, class 5 semaphorins are shown to be expressed in cancer cells and localized to the membrane. Drosophila Sema-5c and the mammalian homologs are transmembrane proteins with extracellular thrombospondin type I (Tspl) repeats. Tspl repeats are known in some proteins to bind and activate transforming growth factor (TGF)-beta ligand. Phospho-Mad and the downstream target gene vestigial were elevated in 1(2)gl tumors, thus linking Drosophila neoplasia to the Dpp (TGF-beta-like) signal pathway. The activation of the Dpp pathway in 1(2)gl tumors occurred only in the presence of Sema-5c. This study demonstrates that the power of Drosophila genetics can be applied to screen, identify, and characterize molecules that are functionally required for invasion and metastasis. C1 NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Off Director, Bethesda, MD 20892 USA. RP Liotta, LA (reprint author), NCI, Pathol Lab, Ctr Canc Res, NIH, Bldg 10,Room 2A33,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 41 TC 48 Z9 52 U1 1 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 30 PY 2003 VL 100 IS 20 BP 11463 EP 11468 DI 10.1073/pnas.2031202100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 727XG UT WOS:000185685700053 PM 14500904 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-1 transcription in B6C3F1 mice by beta-estradiol and bisphenol A: involvement of the estrogen receptor and protein kinase C SO TOXICOLOGY LETTERS LA English DT Article DE bisphenol A; beta-estradiol; estrogen receptor; uterus; heat shock protein; protein kinase C ID HEAT-SHOCK FACTOR; MESSENGER-RIBONUCLEIC-ACID; FACTOR-I GENE; PROGESTERONE-RECEPTOR; MOUSE UTERUS; CELL-LINES; 72 KDA; EXPRESSION; RATS; ANTIESTROGEN AB We have previously demonstrated that bisphenol A (BPA)- and beta-estradiol (E-2)-induced increases in uterine weight and heat shock protein (hsp) 90alpha and hsp72 levels are mediated through the estrogen receptor (ER). It is not, however, clear if BPA and E-2 regulation of hsps is at the transcriptional or post-transcriptional level. Therefore, in this study we examined the ability of BPA and E-2 to increase uterine weight and regulate transcription of these hsps and of heat shock factor (HSF)-1 in ovariectomized B6C3F1 mice at 6 or 24 h after a single subcutaneous injection of E-2 (1 mug/kg) or BPA (100 mg/kg). The role of the ER and protein kinase C (PKC) in these E-2 and BPA effects was evaluated by co-administration of the antiestrogen ICI 182,780 (5 mg/kg) or the PKC inhibitor GF 109203X (0.5 mg/kg), respectively. The results demonstrated ER involvement in uterine weight increases. Uterine hsp mRNA levels are increased by E-2 and BPA through a direct effect on their transcription and/or, in the case of E-2, through an increase in HSF-1 mRNA. PKC is involved in the BPA-induced increases in hsp90alpha mRNA levels. We conclude that E-2 and BPA regulate hsp90alpha and hsp72alpha transcription via similar and distinct pathways. (C) 2003 Elsevier Ireland Ltd. All rights reserved. C1 George Washington Univ, Dept Biol Sci, Washington, DC 20052 USA. US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Brown, KM (reprint author), George Washington Univ, Dept Biol Sci, 332 Lisner Hall,2023 G St NW, Washington, DC 20052 USA. NR 52 TC 25 Z9 26 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0378-4274 J9 TOXICOL LETT JI Toxicol. Lett. PD SEP 30 PY 2003 VL 144 IS 2 BP 257 EP 270 DI 10.1016/S0378-4274(03)00215-7 PG 14 WC Toxicology SC Toxicology GA 725LJ UT WOS:000185544400012 PM 12927369 ER PT J AU Wang, L Yan, J Fu, PP Parekh, KA Yu, HT AF Wang, L Yan, J Fu, PP Parekh, KA Yu, HT TI Photomutagenicity of cosmetic ingredient chemicals azulene and guaiazulene SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article DE azulene; guaiazulene; photomutagenicity; light irradiation; Ames test; TA102 ID POLYCYCLIC AROMATIC-HYDROCARBONS; ASSAYS; PHOTOCHEMISTRY; BACTERIAL; LIGHT AB The photomutagenicity of the popular skin conditioning agents azulene and guaiazulene were tested in Salmonella typhimurium TA98, TA100 and TA102. Following irradiation with UVA and/or visible light, both azulene and guaiazulene exhibited mutagenicity 4-5-fold higher than the spontaneous background mutation. In contrary, naphthalene, a structural isomer of azulene, was not photomutagenic under the same conditions. Azulene was photomutagenic when irradiated with UVA light alone, visible light alone, or a combination of UVA and visible light. Azulene and guaiazulene are not mutagenic when the experiment is conducted with the exclusion of light. Therefore, extreme care must be taken when using cosmetic products with azulene/guaiazulene as ingredients since after applying these products on the skin, exposure to sunlight is inevitable. (C) 2003 Elsevier B.V. All rights reserved. C1 Jackson State Univ, Dept Chem, Jackson, MS 39217 USA. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Yu, HT (reprint author), Jackson State Univ, Dept Chem, Jackson, MS 39217 USA. FU NCRR NIH HHS [G12RR13459]; NIGMS NIH HHS [S06 GM008047-290048, S06 GM008047, S06 GM08047] NR 22 TC 23 Z9 23 U1 1 U2 9 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 SEP 29 PY 2003 VL 530 IS 1-2 BP 19 EP 26 DI 10.1016/S0027-5107(03)00131-3 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 733UM UT WOS:000186019100003 PM 14563527 ER PT J AU Pealer, LN Marfin, AA Petersen, LR Lanciotti, RS Page, PL Stramer, SL Stobierski, MG Signs, K Newman, B Kapoor, H Goodman, JL Chamberland, ME AF Pealer, LN Marfin, AA Petersen, LR Lanciotti, RS Page, PL Stramer, SL Stobierski, MG Signs, K Newman, B Kapoor, H Goodman, JL Chamberland, ME CA W Nile Virus Transmission Investig TI Transmission of West Nile virus through blood transfusion in the United States in 2002 SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID NEW-YORK-CITY; ENCEPHALITIS; EPIDEMIC; INFECTION; RISK AB BACKGROUND: During the 2002 West Nile virus epidemic in the United States, patients were identified whose West Nile virus illness was temporally associated with the receipt of transfused blood and blood components. METHODS: Patients with laboratory evidence of recent West Nile virus infection within four weeks after receipt of a blood component from a donor with viremia were considered to have a confirmed transfusion-related infection. We interviewed the donors of these components, asking them whether they had had symptoms compatible with the presence of a viral illness before or after their donation; blood specimens retained from the time of donation and collected at follow-up were tested for West Nile virus. RESULTS: Twenty-three patients were confirmed to have acquired West Nile virus through transfused leukoreduced and nonleukoreduced red cells, platelets, or fresh-frozen plasma. Of the 23 recipients, 10 (43 percent) were immunocompromised owing to transplantation or cancer and 8 (35 percent) were at least 70 years of age. Immunocompromised recipients tended to have longer incubation periods than nonimmunocompromised recipients and infected persons in mosquito-borne community outbreaks. Sixteen donors with evidence of viremia at donation were linked to the 23 infected recipients; of these donors, 9 reported viral symptoms before or after donation, 5 were asymptomatic, and 2 were lost to follow-up. Fever, new rash, and painful eyes were independently associated with being an implicated donor with viremia rather than a donor without viremia. All 16 donors were negative for West Nile virus-specific IgM antibody at donation. CONCLUSIONS: Transfused red cells, platelets, and fresh-frozen plasma can transmit West Nile virus. Screening of potential donors with the use of nucleic acid-based assays for West Nile virus may reduce this risk. C1 Ctr Dis Control & Prevent, Epidem Intelligence Serv, Div Appl Publ Hlth Training, Epidemiol Program Off, Atlanta, GA 30333 USA. Ctr Dis Control & Prevent, Div Viral & Rickettsial Dis, Natl Ctr Infect Dis, Atlanta, GA 30333 USA. CDC, Div Vector Borne Infect Dis, Natl Ctr Infect Dis, Ft Collins, CO USA. Amer Red Cross, Blood Serv, Biomed Headquarters, Washington, DC 20006 USA. Amer Red Cross, Blood Serv, Sci Support Off, Gaithersburg, MD USA. Michigan Dept Community Hlth, Bur Labs, Lansing, MI USA. Amer Red Cross, Blood Serv, Detroit, MI USA. US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. RP Pealer, LN (reprint author), Ctr Dis Control & Prevent, Epidem Intelligence Serv, Div Appl Publ Hlth Training, Epidemiol Program Off, 1600 Clifton Rd,D-18, Atlanta, GA 30333 USA. NR 23 TC 308 Z9 334 U1 1 U2 15 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 SEP 25 PY 2003 VL 349 IS 13 BP 1236 EP 1245 DI 10.1056/NEJMoa030969 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 724LJ UT WOS:000185488800006 PM 14500806 ER PT J AU Motiwala, T Ghoshal, K Das, A Majumder, S Weichenhan, D Wu, YZ Holman, K James, SJ Jacob, ST Plass, C AF Motiwala, T Ghoshal, K Das, A Majumder, S Weichenhan, D Wu, YZ Holman, K James, SJ Jacob, ST Plass, C TI Suppression of the protein tyrosine phosphatase receptor type O gene (PTPRO) by methylation in hepatocellular carcinomas SO ONCOGENE LA English DT Article DE DNA methylation; DNA amplification; folate deficiency; hepatocellular carcinoma; PTPRO; 5-azacytidine ID COMPARATIVE GENOMIC HYBRIDIZATION; ACUTE LYMPHOBLASTIC-LEUKEMIA; DNA METHYLTRANSFERASE GENE; ACUTE MYELOID-LEUKEMIA; RNA POLYMERASE-I; RAT HEPATOMA; COLORECTAL-CANCER; IMMUNODEFICIENCY SYNDROME; DEFICIENT DIETS; SOLID TUMORS AB A diet lacking folic acid and choline and low in methionine (folate/methyl deficient diet, FMD diet) fed to rats is known to produce preneoplastic nodules (PNNs) after 36 weeks and hepatocellular carcinomas (tumors) after 54 weeks. FMD diet-induced tumors exhibit global hypomethylation and regional hypermethylation. Restriction landmark genome scanning analysis with methylation-sensitive enzyme NotI (RLGS-M) of genomic DNA isolated from control livers, PNNs and tumor tissues was performed to identify the genes that are differentially methylated or amplified during multistage hepatocarcinogenesis. Out of the 1250 genes analysed, 2 to 5 genes were methylated in the PNNs, whereas 5 to 45 genes were partially or completely methylated in the tumors. This analysis also showed amplification of 3 to 12 genes in the primary tumors. As a first step towards identifying the genes methylated in the PNNs and primary hepatomas, we generated a rat NotI-EcoRV genomic library in the pBluescriptKS vector. Here, we describe identification of one methylated and downregulated gene as the rat protein tyrosine phosphatase receptor type O ( PTPRO) and one amplified gene as rat C-MYC. Methylation of PTPRO at the NotI site located immediate upstream of the trancription start site in the PNNs and tumors, and amplification of C-MYC gene in the tumors were confirmed by Southern blot analyses. Bisulfite genomic sequencing of the CpG island encompassing exon 1 of the PTPRO gene revealed dense methylation in the PNNs and tumors, whereas it was methylation free in the livers of animals on normal diet. Reverse transcription-polymerase chain reaction (RT-PCR) analysis showed significant decrease in the expression of PTPRO in the tumors and in a transplanted rat hepatoma. The expression of PTPRO mRNA in the transplanted hepatoma after demethylation with 5-azacytidine, a potent inhibitor of DNA methyltransferases, further confirmed the role of methylation in PTPRO gene expression. These results demonstrate alteration in methylation pro. le and expression of specific genes during tumor progression in the livers of rats in response to folate/methyl deficiency, and further implicate the potential role of PTPRO as a novel growth regulatory gene at least in the hepatocellular carcinomas. C1 Ohio State Univ, Dept Mol & Cellular Biochem, Columbus, OH 43210 USA. Med Univ Lubeck, Inst Biol, D-23538 Lubeck, Germany. Ohio State Univ, Coll Med, Div Human Canc Genet, Columbus, OH 43210 USA. US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Jacob, ST (reprint author), Ohio State Univ, Dept Mol & Cellular Biochem, Columbus, OH 43210 USA. RI Das, Anindita/K-8003-2013; Plass, Christoph/H-7192-2014; OI Das, Anindita/0000-0003-4422-7277 FU NCI NIH HHS [R01 CA086978, CA86978, R01 CA086978-01A2]; NIEHS NIH HHS [ES10874, R01 ES010874, R01 ES010874-01] NR 70 TC 74 Z9 82 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 SEP 25 PY 2003 VL 22 IS 41 BP 6319 EP 6331 DI 10.1038/sj.onc.1206750 PG 13 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 725GK UT WOS:000185535300002 PM 14508512 ER PT J AU Ahmad, SR Graham, DJ AF Ahmad, SR Graham, DJ TI Pneumonitis with antiandrogens SO ANNALS OF INTERNAL MEDICINE LA English DT Letter C1 US FDA, Rockville, MD 20857 USA. RP Ahmad, SR (reprint author), US FDA, Rockville, MD 20857 USA. NR 4 TC 1 Z9 1 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD SEP 16 PY 2003 VL 139 IS 6 BP 528 EP 529 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 721PE UT WOS:000185324100015 PM 13679336 ER PT J AU Michaud, AL Yurawecz, MP Delmonte, P Corl, BA Bauman, DE Brenna, JT AF Michaud, AL Yurawecz, MP Delmonte, P Corl, BA Bauman, DE Brenna, JT TI Identification and characterization of conjugated fatty acid methyl esters of mixed double bond geometry by acetonitrile chemical ionization tandem mass spectrometry SO ANALYTICAL CHEMISTRY LA English DT Article ID LINOLEIC-ACID; GAS-CHROMATOGRAPHY; ISOMERS; SEPARATION; MECHANISMS; CHEESE AB Fatty acids with conjugated double bonds have attracted great interest because of their reported potent bioactivities. However, there are currently no rapid methods for their structural characterization. We report here a convenient mass spectrometry-based strategy to establish double bond geometry by analysis of collisional dissociation products of cis/trans and trans/cis conjugated linoleic acids (CLAs), as methyl esters, and to distinguish CLAs from homoallylic (methylene-interrupted) fatty acids in a single-stage mass spectrum. A series of CLA standards with double bond positions 6,8; 7,9; 8,10; 9,11; 10,12; 11,13; 12,14; and 13,15, with all four possible geometries (cis/trans; trans/cis; cis/cis; trans/trans) were analyzed. The m/z 54 (1-methyleneimino)-1-ethenylium ion, generated by self-reaction of acetonitrile under chemical ionization conditions, reacts with unsaturated fatty acids to yield an [M + 54](+) ion, which decomposes in the single-stage mass spectrum by loss of neutral methanol to form [M + 54 - 32](+). The ratio of [M + 54](+)/[M + 54 - 32](+) in the single-stage mass spectra of CIA isomers is 1 order of magnitude less than for homoallylic diene FAME. Collisional dissociation of the [M + 54](+) ion yields two diagnostic ions that contain the alpha- and omega-carbon atoms and is characteristic of double bond position in the analyte. The fragment vinylic to the trans double bond is significantly more abundant than that for the cis double bond, revealing double bond geometry. The ratio of a to omega diagnostic ion abundances is >4.8 for cis/trans isomers, <0.5 for trans/cis isomers, and 0.7-3.2 for cis/cis and trans/trans isomers. This method provides a rapid alternative to conventional conjugated fatty acid analysis and, together with complementary elution time information provided by gas chromatography, enables rapid, positive identification of double bond position and geometry in most CIA FAME. C1 Cornell Univ, Div Nutr Sci, Ithaca, NY 14853 USA. US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. Cornell Univ, Dept Anim Sci, Ithaca, NY 14853 USA. RP Brenna, JT (reprint author), Cornell Univ, Div Nutr Sci, Ithaca, NY 14853 USA. RI Brenna, James/A-4167-2008; Corl, Benjamin/P-3150-2016 OI Corl, Benjamin/0000-0002-6495-3279 FU NIGMS NIH HHS [GM49209] NR 20 TC 47 Z9 48 U1 1 U2 19 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0003-2700 J9 ANAL CHEM JI Anal. Chem. PD SEP 15 PY 2003 VL 75 IS 18 BP 4925 EP 4930 DI 10.1021/ac034221+ PG 6 WC Chemistry, Analytical SC Chemistry GA 723NW UT WOS:000185439300029 PM 14674473 ER PT J AU Schild, LJ Divi, RL Beland, FA Churchwell, MI Doerge, DR da Costa, GG Marques, MM Poirier, MC AF Schild, LJ Divi, RL Beland, FA Churchwell, MI Doerge, DR da Costa, GG Marques, MM Poirier, MC TI Formation of tamoxifen-DNA adducts in multiple organs of adult female cynomolgus monkeys dosed with tamoxifen for 30 days SO CANCER RESEARCH LA English DT Article ID BREAST-CANCER PATIENTS; ENDOMETRIAL SAMPLES; MASS-SPECTROMETRY; LIVER; RATS; GENOTOXICITY; TOREMIFENE; MICE; 4-HYDROXYTAMOXIFEN; IDENTIFICATION AB The use of the antiestrogen tamoxifen (TAM) is associated with an increase in endometrial cancer. TAM-induced endometrial carcinogenesis may proceed through a genotoxin-mediated pathway, although the detection of endometrial TAM-DNA adducts in exposed women is still controversial. In this study, a monkey model has been used to investigate the question of TAM-DNA adduct formation in primates. Two methods have been used to determine TAM-DNA adducts: a TAM-DNA chemiluminescence immunoassay (TAM-DNA CIA), using an antiserum that has specificity for (E)-alpha-(deoxyguanosin-N-2-yl)-tamoxifen (dG-TAM) and (E)-alpha-(deoxyguanosin-N-2-yl)-N-desmethyltamoxifen (dG-desmethyl-TAM) and electrospray ionization tandem mass spectrometry (ES-MS/MS) coupled with on-line sample preparation and high-performance liquid chromatography (HPLC). Mature (19 year old) cynomolgus monkeys were given either vehicle control (n = 1) or TAM (n = 3) twice daily for a total dose of 2 mg of TAM/kg body weight (bw)/day for 30 days by naso-gastric intubation. Tissues were harvested, and DNA was isolated from uterus, ovary, liver, brain cortex, and kidney. By TAM-DNA CIA, values for uterine TAM-DNA adducts in two monkeys were 0.9 and 1.7 adducts/10(8) nucleotides, whereas values for ovarian TAM-DNA adducts in the same animals were 0.4 and 0.5 adducts/10(8) nucleotides. Liver, brain cortex, and kidney DNA samples from the three exposed monkeys had TAM-DNA levels of 2.1-4.2 adducts/108 nucleotides, 0.4-5.0 adducts/10(8) nucleotides, and 0.7-2.1 adducts/10(8) nucleotides, respectively. By HPLC-ES-MS/MS, the levels of TAM-DNA adducts detected in all tissues were comparable with those observed by TAM-DNA CIA. Thus, values for uterine DNA adducts ranged from 0.5 to 1.4 adducts/10(8) nucleotides, whereas values for ovarian TAM-DNA adducts, measurable in two monkeys, were 0.2 and 0.3 adducts/10(8) nucleotides. Liver DNA contained the highest TAM-DNA adduct levels (7.0-11.1 adducts/10(8) nucleotides), whereas brain cortex DNA contained lower adduct levels (0.6-4.8 adducts/10(8) nucleotides) and the lowest levels were measured in the kidney (0.2-0.4 adducts/10(8) nucleotides). This study indicates that cynomolgus monkeys are capable of metabolizing TAM to genotoxic intermediates that form TAM-DNA adducts in multiple tissues. C1 NCI, Carcinogen DNA Interact Sect, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. Univ Tecn Lisboa, Ctr Quim Estrutural, Inst Super Tecn, P-1049001 Lisbon, Portugal. RP Poirier, MC (reprint author), NCI, Carcinogen DNA Interact Sect, Canc Res Ctr, NIH, Bldg 37,Room 4032,37 Convent Dr, Bethesda, MD 20892 USA. EM poirierm@exchange.iiih.gov RI Marques, M. Matilde/E-2535-2012 OI Marques, M. Matilde/0000-0002-7526-4962 NR 44 TC 28 Z9 28 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 15 PY 2003 VL 63 IS 18 BP 5999 EP 6003 PG 5 WC Oncology SC Oncology GA 727RN UT WOS:000185672600049 PM 14522927 ER PT J AU Rabin, RL Alston, MA Sircus, JC Knollmann-Ritschel, B Moratz, C Ngo, D Farber, JM AF Rabin, RL Alston, MA Sircus, JC Knollmann-Ritschel, B Moratz, C Ngo, D Farber, JM TI CXCR3 is induced early on the pathway of CD4(+) T cell differentiation and bridges central and peripheral functions SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CHEMOKINE RECEPTOR EXPRESSION; DENDRITIC CELLS; IFN-GAMMA; IN-VIVO; B-CELLS; CHEMOTACTIC RESPONSIVENESS; LYMPHOID ORGANS; TH2 CELLS; LYMPHOCYTES; MEMORY AB Chemokine receptors on T cells are frequently categorized as functioning either in immune system homeostasis within lymphoid organs, or in peripheral inflammation. CXCR3 is in the latter category and is reported to be expressed selectively on Th1 cells. We found that CXCR3 was expressed in vivo on newly activated tonsillar CD4(+) T cells. Using CD4(+) T cells from cord blood, we found that CXCR3 was induced by cellular activation in vitro independently of the cytokine milieu, although on resting cells, expression was maintained preferentially on those that had been activated in type 1 conditions. In inflamed tonsils, CXCR3(+)CD4(+) T cells were localized around and within germinal centers. The inference that CXCR3 has a role in germinal center reactions was supported by the finding that the CXCR3 ligand CXC chemokine ligand 9 was expressed in a pattern demarcating a subset of germinal centers both in tonsil and in lymph nodes from an HIV-infected individual. We next investigated the role of CXCR3 on peripheral effector/memory CD4(+) T cells by comparing its pattern of expression with that of CCR5, another Th1-cell associated chemokine receptor. Analysis of cells directly from peripheral blood and after activation in vitro suggested that CXCR3 expression preceded that of CCR5, supporting a model of sequential induction of chemokine receptors during CD4(+) T cell differentiation. Taken together, our data show that CXCR3 can be expressed at all stages of CD4(+) T cell activation and differentiation, bridging central function in lymphoid organs and effector function in peripheral tissues. C1 NIAID, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. USN, Med Ctr, Dept Pathol, Bethesda, MD 20814 USA. RP Farber, JM (reprint author), NIAID, Clin Invest Lab, NIH, Bldg 10,Room 11N228,MSC 1888,10 Ctr Dr, Bethesda, MD 20892 USA. NR 51 TC 52 Z9 54 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 15 PY 2003 VL 171 IS 6 BP 2812 EP 2824 PG 13 WC Immunology SC Immunology GA 720DY UT WOS:000185247300012 PM 12960302 ER PT J AU Limaye, PB Apte, UM Shankar, K Bucci, TJ Warbritton, A Mehendale, HM AF Limaye, PB Apte, UM Shankar, K Bucci, TJ Warbritton, A Mehendale, HM TI Calpain released from dying hepatocytes mediates progression of acute liver injury induced by model hepatotoxicants SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article; Proceedings Paper CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol DE acetaminophen; Ca2+; calpain; CCl4; death proteins; inhibitor of calpain; liver injury progression; N-CBZ-Val-Phe-methyl ester ID TISSUE-REPAIR; CELL INJURY; INHIBITION; ACTIVATION; MECHANISMS; APOPTOSIS; NECROSIS; DISEASE; RATS; THIOACETAMIDE AB Liver injury is known to progress even after the hepatotoxicant is long gone and the mechanisms of progressive injury are not understood. We tested the hypothesis that hydrolytic enzymes such as calpain, released from dying hepatocytes, destroy the surrounding cells causing progression of injury. Calpain inhibitor, N-CBZ-VAL-PHE-methyl ester (CBZ), administered I h after a toxic but nonlethal dose of CCl4 (2 ml/kg, ip) to male Sprague Dawley rats substantially mitigated the progression of liver injury (6 to 48 h) and also led to 75% protection against CCl4-induced lethality following a lethal dose (LD75) of CCl4 (3 ml/kg). Calpain leakage in plasma and in the perinecrotic areas increased until 48 h and decreased from 72 It onward paralleling progression and regression of liver injury, respectively, after CCl4 treatment. Mitigation of progressive injury was accompanied by substantially low calpain in perinecrotic areas and in plasma after CBZ treatment. Normal hepatocytes incubated with the plasma collected from CCl4-treated rats (collected at 12 It when most of the CCl4 is eliminated) resulted in extensive cell death prevented by CBZ. Cell-impermeable calpain inhibitor E64 also protected against progression of CCl4-induced liver injury, thereby confirming the role of released calpain in progression of liver injury. Following CCl4 treatment, calpain-specific breakdown of a-fodrin increased, while it was negligible in rats receiving CBZ after CCl4. Hepatocyte cell death in incubations containing calpain was completely prevented by CBZ. Eighty percent of Swiss Webster mice receiving a lethal dose (LD80) of acetarainophen (600 mg/kg, ip) survived if CBZ was administered I h after acetaminophen, suggesting that calpain-mediated progression of liver injury is neither species nor chemical specific. These findings suggest the role of calpain in progression of liver injury. (C) 2003 Elsevier Inc. All rights reserved. C1 NE Louisiana Univ, Coll Hlth Sci, Sch 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 Hlth Sci, Sch Pharm, Dept Toxicol, 700 Univ Ave,Sugar Hill 306 B, Monroe, LA 71209 USA. NR 43 TC 73 Z9 77 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 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD SEP 15 PY 2003 VL 191 IS 3 BP 211 EP 226 DI 10.1016/S0041-008X(03)00250-3 PG 16 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 725EU UT WOS:000185531500003 PM 13678654 ER PT J AU Rellahan, BL Graham, LJ Tsygankov, AY DeBell, KE Veri, MC Noviello, C Bonvini, E AF Rellahan, BL Graham, LJ Tsygankov, AY DeBell, KE Veri, MC Noviello, C Bonvini, E TI A dynamic constitutive and inducible binding of c-Cbl by PLC gamma 1 SH3 and SH2 domains (negatively) regulates antigen receptor-induced PLC gamma l activation in lymphocytes SO EXPERIMENTAL CELL RESEARCH LA English DT Article ID GROWTH-FACTOR RECEPTOR; PROTEIN-TYROSINE KINASES; JURKAT T-CELLS; PHOSPHOLIPASE C-GAMMA-1; SIGNAL-TRANSDUCTION; PROTOONCOGENE PRODUCT; CSF-1 RECEPTOR; RING FINGER; ASSOCIATION; PHOSPHORYLATION AB We investigated the structural requirements for c-Cbl-mediated inhibition of Ag receptor-induced PLCgamma1 activation. Analysis of site-specific c-Cbl mutants indicated that tyrosine phosphorylation of c-Cbl was required for down-regulation of the PLCgamma1/Ca2+ pathway. Coprecipitation experiments indicated that c-Cbl and PLCgamma1 constitutively interact through a PLCgamma1 SH3 domain-dependent mechanism and that c-Cbl and PLCgamma1 can inducibly interact through the SH2(C) domain of PLCgamma1. Additional data indicate that the SH3 domain of PLCgamma1 binds to both canonical and noncanonical SH3 domain-binding sites in the proline-rich region of c-Cbl. Overexpression of c-Cbl in a PLCgamma-deficient B cell line, P10-14, stably reconstituted with wild-type PLCgamma1 led to a significant decrease in B cell receptor-induced NF-AT-dependent transcription, a PLCgamma- and Ca2+-dependent event. In contrast, c-Cbl overexpression in P10-14 cells reconstituted with a PLCgamma1 SH3 domain mutant had little effect on receptor-induced NF-AT activation. These data suggest that c-Cbl-mediated regulation of PLCgamma1 requires an interaction between c-Cbl and PLCgamma1 that is primarily mediated by the SH3 domain of PLCgamma1. The interaction of c-Cbl with PLCgamma1 may negatively effect events required for PLCgamma1 activation. (C) 2003 Elsevier Science (USA). All rights reserved. C1 CBER, Div Monoclonal Antibodies, Immunobiol Lab, Bethesda, MD 20892 USA. Temple Univ, Sch Med, Dept Microbiol & Immunol, Philadelphia, PA 19140 USA. RP Rellahan, BL (reprint author), CBER, Div Monoclonal Antibodies, Immunobiol Lab, NIH Campus,29B-4G03,8800 Rockville Pike, Bethesda, MD 20892 USA. EM rellahan@cber.fda.gov NR 53 TC 9 Z9 9 U1 0 U2 0 PU ELSEVIER INC PI SAN DIEGO PA 525 B STREET, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4827 EI 1090-2422 J9 EXP CELL RES JI Exp. Cell Res. PD SEP 10 PY 2003 VL 289 IS 1 BP 184 EP 194 DI 10.1016/S0014-4827(03)00260-X PG 11 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 718VL UT WOS:000185167100018 PM 12941616 ER PT J AU Niemann, RA Gay, ML AF Niemann, RA Gay, ML TI Determination of ephedrine alkaloids and synephrine in dietary supplements by column-switching cation exchange high-performance liquid chromatography with scanning-wavelength ultraviolet and fluorescence detection SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE ephedra; ephedrine alkaloids; synephrine; dietary supplements; cation exchange; HPLC; analysis; determination; UV spectra; fluorescence ID CITRUS-AURANTIUM L.; HERBAL PRODUCTS AB An HPLC method with on-line cleanup coupled to the separation column is described for determination of (-)-norephedrine, (+)-norpseudoephedrine, (-)-ephedrine, (+)-pseudoephedrine, (-)-N-methyl-ephedrine, (+)-N-methylpseudoephedrine, and (+/-)-synephrine in finished dietary supplement products. Test portions were extracted in acidified aqueous acetone. A filtered aliquot was cleaned up on a strong cation exchange (SCX) precolumn that later was automatically coupled to the SCX analytical column. Measurement was by full-scan UV spectra for confirmation of identity by spectral matching and real-time integration of three wavelength signals for multiple quantitation. (+/-)-Synephrine was also quantitated by native fluorescence. Recovery averaged 95-100%. Determination of the major ingredients (-)-ephedrine, (+)-pseudoephedrine, and (+/-)-synephrine compared favorably to findings by an independent LC-MS analysis for a set of 25 samples. The results of a survey were reported for total ephedrine alkaloid and synephrine content and were compared to content declaration, for similar to48 finished products. C1 US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Niemann, RA (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. NR 12 TC 46 Z9 52 U1 1 U2 8 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 SEP 10 PY 2003 VL 51 IS 19 BP 5630 EP 5638 DI 10.1021/jf0302052 PG 9 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 719NQ UT WOS:000185210100008 PM 12952412 ER PT J AU Lloyd, JC Haber, P Mootrey, GT Braun, AM Rhodes, PH Chen, RT AF Lloyd, JC Haber, P Mootrey, GT Braun, AM Rhodes, PH Chen, RT CA VAERS Working Grp TI Adverse event reporting rates following tetanus-diphtheria and tetanus toxoid vaccinations: data from the Vaccine Adverse Event Reporting System (VAERS), 1991-1997 SO VACCINE LA English DT Article DE vaccines; adverse events; postmarketing surveillance ID NEWLY INDEPENDENT STATES; UNITED-STATES; IMMUNITY; POPULATION; SITUATION; SAFETY AB Since 1966, the Advisory Committee on Immunization Practices (ACIP) has recommended tetanus-diphtheria toxoid (Td) be used instead of single antigen tetanus toxoid (TT) because, while both vaccines protect against tetanus, only Td protects against diphtheria. Despite this recommendation, approximately 2.5 million doses of TT were distributed annually from 1991 to 1997. One possible explanation for the continued use of TT is concern about the relative safety of Td. Small clinical trials found Td to be associated with a higher rate of local vaccine-associated adverse events (VAEs) than TT. To determine if the findings from the trials would hold up on a larger scale, we compared the rate of reporting to the Vaccine Adverse Event Reporting System (VAERS), a passive reporting system, after either vaccine from 1991 to 1997. There were 40 reports per million doses of Td, and 27 reports per million doses of TT, for a reporting rate ratio of 1.4. Reporting rates to VAERS are lower than the rates of VAEs identified in the clinical trials, but the magnitude of the difference in VAEs following TT versus Td is similar. While reporting rates are lower after TT than Td, rates of reported VAEs after both vaccines are low. (C) 2003 Elsevier Science Ltd. All rights reserved. C1 Utah Dept Hlth, Off Epidemiol, Bur Children Special Hlth Care Needs, Salt Lake City, UT 84114 USA. Ctr Dis Control & Prevent, Natl Immunizat Program, Vaccine Safety & Dev Branch, Atlanta, GA 30333 USA. US FDA, Off Biostat & Epidemiol, Div Epidemiol, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. RP Lloyd, JC (reprint author), Utah Dept Hlth, Off Epidemiol, Bur Children Special Hlth Care Needs, POB 144640, Salt Lake City, UT 84114 USA. NR 31 TC 17 Z9 22 U1 1 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD SEP 8 PY 2003 VL 21 IS 25-26 BP 3746 EP 3750 DI 10.1016/S0264-410X(03)00404-3 PG 5 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 719YY UT WOS:000185233700033 PM 12922107 ER PT J AU Vodeiko, GM McInnis, J Chizhikov, V Levandowski, RA AF Vodeiko, GM McInnis, J Chizhikov, V Levandowski, RA TI Genetic and phenotypic analysis of reassortants of high growth and low growth strains of influenza B virus SO VACCINE LA English DT Article DE influenza B; reassortants; growth; phenotype; sequence ID A VIRUS; NS1 PROTEIN; NEURAMINIDASE; HEMAGGLUTININ; LINEAGES; BINDING; ACID; HA AB The yield of influenza virus in eggs is critical to influenza vaccine production and availability, but the contribution of specific genes to the growth properties of influenza B viruses is not well understood. Influenza B/Beijing/184/93 and B/Shangdong/7/97 were chosen for study because B/Shangdong/7/97 replicated to several fold higher titers in eggs than B/Beijing/184/93 as demonstrated by hemagglutination titers and EID50. A reassortant with the HA, NP and PB2 genes from B/Beijing/184/93 and all other genes from B/Shangdong/7/97 had the high growth phenotype of B/Shangdong/7/97 in eggs, which suggests that NS, M, NA, PBIor PA, or a combination of these genes derived from B/Shangdong/7/97 were needed for the high growth phenotype of the reassortants. A high degree of homology was found among the genetic sequences of B/Beijing/184/93, B/Shangdong/7/97, and other influenza B viruses. However, differences potentially related to growth characteristics were suggested by analysis of the deduced amino acid (AA) sequences of four genes: NS (NS1, NS2), M (BM2). NA (NA, NB) and PB1. The studies identify multiple genes that may affect growth of influenza B viruses in eggs. Published by Elsevier Science Ltd. C1 US FDA, Ctr Biol & Evaluat & Res, Off Vaccines Res & Review, Div Viral Prod,Lab Pediat & Resp Viral Dis, Bethesda, MD 20892 USA. US FDA, Ctr Biol & Evaluat & Res, Off Vaccines Res & Review, Div Viral Prod,Lab Methods Dev, Bethesda, MD 20892 USA. RP Vodeiko, GM (reprint author), US FDA, Ctr Biol & Evaluat & Res, Off Vaccines Res & Review, Div Viral Prod,Lab Pediat & Resp Viral Dis, Rm 1D22,Bldg 29A,8800 Rockville Pike, Bethesda, MD 20892 USA. NR 27 TC 16 Z9 16 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 SEP 8 PY 2003 VL 21 IS 25-26 BP 3867 EP 3874 DI 10.1016/S0264-410X(03)00312-8 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 719YY UT WOS:000185233700047 PM 12922121 ER PT J AU Ruggera, PS Witters, DM von Maltzahn, G Bassen, HI AF Ruggera, PS Witters, DM von Maltzahn, G Bassen, HI TI In vitro assessment of tissue heating near metallic medical implants by exposure to pulsed radio frequency diathermy SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID SEVERE CNS DAMAGE; DBS AB A patient with bilateral implanted neurostimulators suffered significant brain tissue damage, and subsequently died, following diathermy treatment to hasten recovery from teeth extraction. Subsequent MRI examinations showed acute deterioration of the tissue near the deep brain stimulator (DBS) lead's electrodes which was attributed to excessive tissue heating induced by the diathermy treatment. Though not published in the open literature, a second incident was reported for a patient with implanted neurostimulators for the treatment of Parkinson's disease. During a diathermy treatment for severe kyphosis, the patient had a sudden change in mental status and neurological deficits. The diathermy was implicated in causing damage to the patient's brain tissue. To investigate if diathermy induced excessive heating was possible with other types of implantable lead systems, or metallic implants in general, we conducted a series of in vitro laboratory tests. We obtained a diathermy unit and also assembled a controllable laboratory exposure system. Specific absorption rate (SAR) measurements were performed using fibre optic thermometry in proximity to the implants to determine the rate of temperature rise using typical diathermy treatment power levels. Comparisons were made of the SAR measurements for a spinal cord stimulator (SCS) lead, a pacemaker lead and three types of bone prosthesis (screws, rods and a plate). Findings indicate that temperature changes of 2.54 and 4.88 degreesC s(-1) with corresponding SAR values of 9129 and 17 563 W kg(-1) near the SCS and pacemaker electrodes are significantly higher than those found in the proximity of the other metallic implants which ranged from 0.04 to 0.69 degreesC s(-1) (129 to 2471 W kg(-1)). Since the DBS leads that were implanted in the reported human incidents have one-half the electrode surface area of the tested SCS lead, these results imply that tissue heating at rates at least equal to or up to twice as much as those reported here for the SCS lead could occur for the DBS leads. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. RP Ruggera, PS (reprint author), US FDA, Ctr Devices & Radiol Hlth, HFZ-133,9200 Corp Blvd, Rockville, MD 20850 USA. NR 14 TC 35 Z9 36 U1 0 U2 5 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 SEP 7 PY 2003 VL 48 IS 17 BP 2919 EP 2928 AR PII S0031-9155(03)64304-6 DI 10.1088/0031-9155/48/17/312 PG 10 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 725ZT UT WOS:000185573300012 PM 14516109 ER PT J AU Bennett, RW AF Bennett, RW TI Serological inactivation/chemical reactivation behavior of staphylococcal enterotoxin. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 226th National Meeting of the American-Chemical-Society CY SEP 07-11, 2003 CL NEW YORK, NY SP Amer Chem Soc C1 US FDA, Microbiol Methods Res Branch, Div Microbiol Studies, College Pk, MD 20740 USA. EM Reginaid.Bennett@fda.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP PY 2003 VL 226 MA 102-AGFD BP U67 EP U67 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 751JF UT WOS:000187062400217 ER PT J AU Feng, P AF Feng, P TI Development, validation and impact of rapid methods for testing for pathogens and their toxins in foods. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 226th National Meeting of the American-Chemical-Society CY SEP 07-11, 2003 CL NEW YORK, NY SP Amer Chem Soc C1 US FDA, Div Microbiol Studies, College Pk, MD 20870 USA. EM pfeng@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 SEP PY 2003 VL 226 MA 099-AGFD BP U66 EP U66 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 751JF UT WOS:000187062400214 ER PT J AU Ferreira, JL Sharma, SK Eblen, BS Andreadis, JD Matlanka, SE AF Ferreira, JL Sharma, SK Eblen, BS Andreadis, JD Matlanka, SE TI Evaluation of the DIG-ELISA for the detection of type A, B, E, and F clostridium botulinum toxins. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 226th National Meeting of the American-Chemical-Society CY SEP 07-11, 2003 CL NEW YORK, NY SP Amer Chem Soc C1 US FDA, ORA SE Reg Lab, Atlanta, GA 30309 USA. US FDA, CFSAN, Rockville, MD 20857 USA. CDC, Natl Botulism Surveillance & Reference Lab, Atlanta, GA 30333 USA. EM jferreir@ora.fda.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP PY 2003 VL 226 MA 101-AGFD BP U67 EP U67 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 751JF UT WOS:000187062400216 ER PT J AU Hawryluk, TP AF Hawryluk, TP TI Marine toxin detection at the FDA Northeast Regional Laboratory. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 226th National Meeting of the American-Chemical-Society CY SEP 07-11, 2003 CL NEW YORK, NY SP Amer Chem Soc C1 US FDA, NE Reg Lab, Jamaica, NY 11433 USA. EM Timothy.Hawryluk@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 SEP PY 2003 VL 226 MA 116-AGFD BP U69 EP U69 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 751JF UT WOS:000187062400231 ER PT J AU Hungerford, JM AF Hungerford, JM TI Rapid methods for marine toxins and toxic decomposition products in seafoods. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 226th National Meeting of the American-Chemical-Society CY SEP 07-11, 2003 CL NEW YORK, NY SP Amer Chem Soc C1 US FDA, Seafood Prod Res Ctr, PRL NW, Bothell, WA 98021 USA. EM jhungerf@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 SEP PY 2003 VL 226 MA 120-AGFD BP U70 EP U70 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 751JF UT WOS:000187062400235 ER PT J AU Manger, RM Woodle, D Berger, A Hungerford, JM AF Manger, RM Woodle, D Berger, A Hungerford, JM TI Sensitive and rapid detection of marine toxins using mouse neuroblastoma cells and voltage sensitive dyes. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 226th National Meeting of the American-Chemical-Society CY SEP 07-11, 2003 CL NEW YORK, NY SP Amer Chem Soc C1 Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. US FDA, Seafood Prod Res Ctr, PRL NW, Rockville, MD 20857 USA. EM rmanger@fred.fhcrc.org 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 SEP PY 2003 VL 226 MA 118-AGFD BP U69 EP U69 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 751JF UT WOS:000187062400233 ER PT J AU Payne, GF Chen, TH McDermott, MK Small, DA Bentley, WE AF Payne, GF Chen, TH McDermott, MK Small, DA Bentley, WE TI Amino acid-residue-specific enzymes for protein grafting and crosslinking. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 226th National Meeting of the American-Chemical-Society CY SEP 07-11, 2003 CL NEW YORK, NEW YORK SP Amer Chem Soc C1 Univ Maryland, Inst Biotechnol, Ctr Biosyst Res, College Pk, MD 20742 USA. US FDA, Off Sci & Technol, Div Mech & Mat Sci, Rockville, MD 20857 USA. Univ Maryland, UMBI, Ctr Biosyst Res, Dept Chem Engn, College Pk, MD 20742 USA. EM payne@umbi.umd.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 SEP PY 2003 VL 226 MA 471-POLY BP U426 EP U426 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 751JG UT WOS:000187062502235 ER PT J AU Wang, YP Xia, QS Yang, YC Yan, J Fu, PP Chou, MW AF Wang, YP Xia, QS Yang, YC Yan, J Fu, PP Chou, MW TI Human liver micromsomal reduction of pyrrolizidine alkaloid N-oxides to form the corresponding carcinogenic parent compounds. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 226th National Meeting of the American-Chemical-Society CY SEP 07-11, 2003 CL NEW YORK, NY SP Amer Chem Soc C1 Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. EM ywang@nctr.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 SEP PY 2003 VL 226 MA 074-TOXI BP U329 EP U329 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 751JF UT WOS:000187062401519 ER PT J AU Xu, LL Heinze, T Pogge, A Slikker, W Schmued, L AF Xu, LL Heinze, T Pogge, A Slikker, W Schmued, L TI Chemical characterization of Fluoro-Jade B, a high affinity histochemical marker of toxicant-induced neuronal degeneration. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 226th National Meeting of the American-Chemical-Society CY SEP 07-11, 2003 CL NEW YORK, NY SP Amer Chem Soc C1 Natl Ctr Toxicol Res FDA, Div Neurotoxicol, Jefferson, AR 72079 USA. Natl Ctr Toxicol Res FDA, Div Chem, Jefferson, AR 72079 USA. EM LXu@NCTR.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 SEP PY 2003 VL 226 MA 053-TOXI BP U325 EP U325 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 751JF UT WOS:000187062401499 ER PT J AU Battisti, PL Daher, A Bannwarth, S Voortman, J Peden, KWC Hiscott, J Mouland, AJ Benarous, R Gatignol, A AF Battisti, PL Daher, A Bannwarth, S Voortman, J Peden, KWC Hiscott, J Mouland, AJ Benarous, R Gatignol, A TI Additive activity between the trans-activation response RNA-binding protein, TRBP2, and cyclin T1 on HIV type 1 expression and viral production in murine cells SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; CARBOXYL-TERMINAL DOMAIN; TAT-ASSOCIATED KINASE; IN-VIVO; POLYMERASE-II; P-TEFB; HUMAN CHROMOSOME-12; RODENT CELLS; SPECIFICALLY ASSOCIATE; MOLECULAR CLONE AB Tat-mediated trans-activation of the HIV-1 long terminal repeat (LTR) occurs through the phosphorylation of the carboxy-terminal domain of the RNA polymerase II. The kinase complex, pTEFb, composed of cyclin T1 (CycT1) and CDK9, mediates this process. The trans-activation response ( TAR) RNA-binding protein 2 (TRBP2) increases HIV-1 LTR expression through TAR and protein kinase R (PKR) binding, but not through interactions with the Tat-CycT1-CDK9 complex. TRBP2 and the Tat-CycT1-CDK9 complex have overlapping binding sites on TAR RNA. TRBP2 and CycT1 increased Tat trans-activation in NIH 3T3 cells with additive effects. Upon transfection of HIV-1 pLAI, pNL4-3, pMAL, and pAD molecular clones, reverse transcriptase (RT) activity and p24 concentration were decreased 200- to 900-fold in NIH 3T3 cells compared with HeLa cells in both cells and supernatants. In murine cells, cotransfection of the HIV clones with CycT1 or TRBP2 increased modestly the expression of RT activity in cell extracts. The analysis of Gag expression in murine cells transfected with CycT1 compared with human cells showed a 20-fold decrease in expression and a strong processing defect. The expression of both CycT1 and TRBP2 had a more than additive activity on RT function in cell extracts and on viral particle production in supernatant of murine cells. These results suggest an activity of CycT1 and TRBP2 at different steps in HIV-1 expression and indicate the requirement for another posttranscriptional factor in murine cells for full HIV replication. C1 McGill Univ, Lady Davis Inst Med Res, McGill AIDS Ctr, Mol Oncol Grp, Montreal, PQ H3T 1E2, Canada. Inst Cochin Genet Mol, INSERM, U529, F-75014 Paris, France. US FDA, Lab Retrovirus Res, Bethesda, MD 20892 USA. McGill Univ, Dept Med & Microbiol & Immunol, Montreal, PQ H3A 2B4, Canada. RP Gatignol, A (reprint author), McGill Univ, Lady Davis Inst Med Res, McGill AIDS Ctr, Mol Oncol Grp, 3755 Cote St Catherine, Montreal, PQ H3T 1E2, Canada. NR 71 TC 14 Z9 14 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. PD SEP PY 2003 VL 19 IS 9 BP 767 EP 778 DI 10.1089/088922203769232566 PG 12 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 727TF UT WOS:000185675200006 PM 14585207 ER PT J AU Avigan, M Justice, R Mackey, AC Nair, N AF Avigan, M Justice, R Mackey, AC Nair, N TI Re: Brandt et al. - An evidence-based approach to the management of irritable bowel syndrome in North America SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Letter C1 US FDA, Ctr Drug Evaluat & Res, Off New Drugs, Div Gastrointestinal & Coagulat Drug Prod, Rockville, MD 20857 USA. US FDA, Div Drug Risk Evaluat, Off Drug Safety, Rockville, MD 20857 USA. RP Mackey, AC (reprint author), US FDA, Ctr Drug Evaluat & Res, Off New Drugs, Div Gastrointestinal & Coagulat Drug Prod, 15B-18,HFD-430,5600 Fishers Lane, Rockville, MD 20857 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 EI 1572-0241 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD SEP PY 2003 VL 98 IS 9 BP 2105 EP 2106 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 726CR UT WOS:000185581000036 PM 14499800 ER PT J AU Kawalek, JC Howard, KD Farrell, DE Derr, J Cope, CV Jackson, JD Myers, MJ AF Kawalek, JC Howard, KD Farrell, DE Derr, J Cope, CV Jackson, JD Myers, MJ TI Effect of oral administration of low doses of pentobarbital on the induction of cytochrome P450 isoforms and cytochrome P450-mediated reactions in immature Beagles SO AMERICAN JOURNAL OF VETERINARY RESEARCH LA English DT Article; Proceedings Paper CT 11th North-American-International-Society-for-the-Study-of-Xenobiotics Meeting CY OCT 27-31, 2002 CL ORLANDO, FLORIDA SP N Amer Int Soc Study Xenobiot ID MICROSOMAL-ENZYME INDUCTION; DRUG-METABOLIZING-ENZYMES; MONOXIDE-BINDING PIGMENT; LIVER-MICROSOMES; DOG LIVER; CHROMATOGRAPHY/MASS SPECTROMETRY; COUMARIN 7-HYDROXYLASE; HISTOLOGICAL CHANGE; B6C3F1 MOUSE; IDENTIFICATION AB Objective-To determine the effect of oral administration of low doses of pentobarbital on cytochrome P450 (CYP) isoforms and CYP-mediated reactions in immature Beagles. Animals-42 immature (12-week-old) Beagles. Procedure-Dogs were grouped and treated orally as follows for 8 weeks: low-dose pentobarbital (50 mug/d; 4 males, 4 females), mid-dose pentobarbital (150 mug/d; 4 males, 4 females), high-dose pentobarbital (500 mug/d; 4 males, 4 females), positive-pentobarbital control 10 mg/kg/d; 2 males, 2 females), positive-phenobarbital control (10 mg/kg/d; 2 males, 2 females), and negative control (saline [0.9% NaCl] solution; 5 males, 5 females). Serum biochemical and hematologic values were monitored. On necropsy examination, organ weights were determined, and histologic evaluation of tissue sections of liver, kidney, small intestine, testes, epididymis, and ovaries was performed. Hepatic and intestinal drug-metabolizing enzyme activities were measured, and relative amounts of CYP isoforms were determined by western blot analysis. Results-The amount of a hepatic CYP2A-related isoform in dogs from the high-dose pentobarbital treatment group was twice that of dogs from the negative control group. CYP2C was not detectable in small intestinal mucosa of dogs from the negative control group; measurable amounts of CYP2C were found in dogs from the various (low-, mid-, and high-dose) pentobarbital treatment groups and from positive-pentobarbital and positive phenobarbital control groups. Several CYP-mediated reactions increased in a dose-dependent manner. The lowest calculated effective dose of pentobarbital ranged from 200 to 450 mug/d. Conclusions and Clinical Relevance-Several CYP isoforms and their associated reactions were induced in dogs by oral administration of low amounts of pentobarbital. C1 US FDA, Ctr Vet Med, Res Off, Laurel, MD 20708 USA. Food & Drug Adm, Ctr Vet Med, New Anim Drug Evaluat, Rockville, MD 20855 USA. RP Kawalek, JC (reprint author), US FDA, Ctr Vet Med, Res Off, 8401 Muirkirk Rd, Laurel, MD 20708 USA. NR 38 TC 3 Z9 3 U1 1 U2 2 PU AMER VETERINARY MEDICAL ASSOC PI SCHAUMBURG PA 1931 N MEACHAM RD SUITE 100, SCHAUMBURG, IL 60173-4360 USA SN 0002-9645 J9 AM J VET RES JI Am. J. Vet. Res. PD SEP PY 2003 VL 64 IS 9 BP 1167 EP 1175 DI 10.2460/ajvr.2003.64.1167 PG 9 WC Veterinary Sciences SC Veterinary Sciences GA 716PZ UT WOS:000185038700016 PM 13677397 ER PT J AU Artlett, CM O'Hanlon, TP Lopez, AM Song, YW Miller, FW Rider, LG AF Artlett, CM O'Hanlon, TP Lopez, AM Song, YW Miller, FW Rider, LG TI HLA-DQA1 is not an apparent risk factor for microchimerism in patients with various autoimmune diseases and in healthy individuals SO ARTHRITIS AND RHEUMATISM LA English DT Article ID SYSTEMIC-SCLEROSIS; JUVENILE DERMATOMYOSITIS; PERIPHERAL-BLOOD; MATERNAL PLASMA; T-LYMPHOCYTES; FETAL DNA; CELLS; HLA-DQA1-ASTERISK-0501; WOMEN; PCR AB Objective. Microchimeric cells have been identified in lesions and peripheral blood of patients with systemic sclerosis (SSc) and idiopathic inflammatory myopathies (IIM), and HLA-DQA1*0501 is a risk factor for these diseases in some populations. Furthermore, DQA1*0501 has been associated with T lymphocyte microchimerism in SSc. To better define the strength of this association, we assessed the relationship among DQA1 alleles and microchimerism. Methods. DNA from whole peripheral blood or magnetically sorted T cells was tested for microchimeric cells by polymerase chain reaction of the Y chromosome or of HLA-Cw in 87 SSc patients, 28 juvenile IIM patients, and 88 healthy controls. Thirty-seven mother-son pairs were also analyzed for microchimerism and DQA1*0501. Results. We were unable to demonstrate that DQA1*0501 is associated with microchimerism in T lymphocytes or in whole peripheral blood DNA in patients with SSc or juvenile IIM or in healthy individuals. In the 37 mother-son pairs, we were unable to demonstrate an association of DQA1*0501 with microchimerism in peripheral blood DNA or T lymphocytes, and compatibility between the donor's and recipient's HLA alleles did not influence microchimerism in the recipient. Conclusion. These data suggest that HLA-DQA1 alleles do not appear to play a role in the persistence of microchimerism in the peripheral blood or T lymphocytes of patients with selected autoimmune diseases or in healthy individuals. C1 Thomas Jefferson Univ, Div Rheumatol, Philadelphia, PA 19107 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. NIAMSD, Arthrit & Rheumatism Branch, NIH, Bethesda, MD USA. Seoul Natl Univ Hosp, Seoul 110744, South Korea. RP Artlett, CM (reprint author), Thomas Jefferson Univ, Div Rheumatol, 233 S 10th St, Philadelphia, PA 19107 USA. RI Song, Yeong Wook/J-2765-2012; OI Rider, Lisa/0000-0002-6912-2458; Miller, Frederick/0000-0003-2831-9593 NR 19 TC 22 Z9 22 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 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2003 VL 48 IS 9 BP 2567 EP 2572 DI 10.1002/art.11235 PG 6 WC Rheumatology SC Rheumatology GA 723KQ UT WOS:000185431900021 PM 13130476 ER PT J AU Curtis, J Shatin, D Rawson, NSB Braun, MM Manda, B Moreland, L Allison, J Saag, KG AF Curtis, J Shatin, D Rawson, NSB Braun, MM Manda, B Moreland, L Allison, J Saag, KG TI Impact of risk communication on tuberculin skin testing for infliximab and etanercept users. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 67th Annual Scientific Meeting of the American-College-of-Rheumatology/38th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 23-28, 2003 CL ORLANDO, FLORIDA C1 Univ Alabama, Birmingham, AL USA. Ctr Hlth Care Policy & Evaluat, Minneapolis, MN USA. US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 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 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2003 VL 48 IS 9 SU S MA 1584 BP S610 EP S610 PG 1 WC Rheumatology SC Rheumatology GA 723LA UT WOS:000185432801625 ER PT J AU Siegel, JN Zhen, B Siegel, A Chauhan, N Keystone, E Landewe, R Wolfe, F van der Heijde, D Steven, F AF Siegel, JN Zhen, B Siegel, A Chauhan, N Keystone, E Landewe, R Wolfe, F van der Heijde, D Steven, F TI Evidence of effects of a TNF blocking agent in ACR20 non-responders. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 67th Annual Scientific Meeting of the American-College-of-Rheumatology/38th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 23-28, 2003 CL ORLANDO, FLORIDA C1 FDA, Rockville, MD USA. Univ Washington, Seattle, WA 98195 USA. NIH, Bethesda, MD 20892 USA. Univ Toronto, Toronto, ON, Canada. Univ Hosp Maastricht, Maastricht, Netherlands. Natl Data Bank Rheumat Dis, Wichita, KS USA. Abbott Labs, Parsippany, NJ 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 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2003 VL 48 IS 9 SU S MA 221 BP S127 EP S128 PG 2 WC Rheumatology SC Rheumatology GA 723LA UT WOS:000185432800266 ER PT J AU Bruckner, L Cussler, K Halder, M Barrat, J Castle, P Duchow, K Gatewood, DM Gibert, R Groen, J Knapp, B Levis, R Milne, C Parker, S Stunkel, K Visser, N Volkers, P AF Bruckner, L Cussler, K Halder, M Barrat, J Castle, P Duchow, K Gatewood, DM Gibert, R Groen, J Knapp, B Levis, R Milne, C Parker, S Stunkel, K Visser, N Volkers, P TI Three Rs approaches in the quality control of inactivated rabies vaccines SO ATLA-ALTERNATIVES TO LABORATORY ANIMALS LA English DT Article ID SINGLE RADIAL IMMUNODIFFUSION; MONOCLONAL-ANTIBODY; POTENCY TEST; VIRUS GLYCOPROTEIN; ABNORMAL TOXICITY; QUANTITATION; ELISA C1 Inst Viruskrankheiten & Immunpropphylaxe, CH-3147 Mittelhausern, Switzerland. AGAATI, NL-3584 CL Utrecht, Netherlands. European Commiss, Joint Res Ctr, ECVAM, Inst Hlth & Consumer Protect, I-21020 Ispra, VA, Italy. AFSSA, Lab Etudes & Rech Rage & Pathol Anim Sauvage, F-54220 Malzeville, France. Council Europe, European Dept Qual Med, F-67029 Strasbourg, France. Paul Ehrlich Inst, D-63207 Langen, Germany. Ctr Vet Biol, Licensing & Policy Dev, Ames, IA 50010 USA. AFSSAPS, F-69007 Lyon, France. Univ Rotterdam Hosp, Inst Virol, NL-3015 GD Rotterdam, Netherlands. Chiron Behring GmbH & Co, D-35041 Marburg, Germany. Ctr Biol Evaluat & review, Div Viral Prod, Rockville, MD 20852 USA. Natl Inst Biol Stand & Controls, Div Virol, Potters Bar EN6 3QG, Herts, England. Essex Anim Hlth, D-30938 Burgwedel, Germany. Intervet Int BV, NL-5831 AN Boxmeer, Netherlands. RP Bruckner, L (reprint author), Inst Viruskrankheiten & Immunpropphylaxe, CH-3147 Mittelhausern, Switzerland. NR 53 TC 22 Z9 22 U1 0 U2 0 PU FRAME PI NOTTINGHAM PA RUSSELL & BURCH HOUSE 96-98 NORTH SHERWOOD ST, NOTTINGHAM NG1 4EE, NOTTS, ENGLAND SN 0261-1929 J9 ATLA-ALTERN LAB ANIM JI ATLA-Altern. Lab. Anim. PD SEP PY 2003 VL 31 IS 4 BP 429 EP 454 PG 26 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 734UB UT WOS:000186075400009 PM 15601248 ER PT J AU Chudy, M Hewlett, I Saldanha, J Bianco, C Conrad, AJ Gierman, T Heldebrant, C Rautmann, GG Roth, WK Stramer, S Weimer, T Whitaker, B Zerlauth, G AF Chudy, M Hewlett, I Saldanha, J Bianco, C Conrad, AJ Gierman, T Heldebrant, C Rautmann, GG Roth, WK Stramer, S Weimer, T Whitaker, B Zerlauth, G TI Technical considerations for the performance of Nucleic acid Amplification Technology (NAT) - The NAT Task Force Group SO BIOLOGICALS LA English DT Article DE NAT; plasma; blood; viral testing minimum requirements ID INTERNATIONAL STANDARD; PLASMA POOLS; ASSAYS; RNA; ESTABLISHMENT AB The complexity of Nucleic acid Amplification Technology (NAT(1)), comprising sample preparation, amplification and detection methods, requires specific design considerations for both the laboratory and the procedures utilized in such testing. The purpose of this paper is to establish technical considerations for the performance of NAT. These include the collection, handling and assay of specimens and the design of laboratories to routinely and reliably detect low levels of nucleic acid sequences. The sensitivity of NAT due to the exponential amplification of nucleic acids makes contamination a major concern from specimen collection to sample detection. Therefore, laboratories need to be designed to prevent and control contamination through adequate equipment and appropriate workflow. These technical considerations should provide a basis for establishing a robust and reproducible NAT system. (C) 2003 The International Association for Biologicals. Published by Elsevier Ltd. All rights reserved. C1 Plasma Prot Therapeut Assoc, Annapolis, MD 21401 USA. Paul Ehrlich Inst, D-6070 Langen, Germany. US FDA, CBER, Rockville, MD 20857 USA. Natl Inst Biol Stand, Potters Bar, Herts, England. Amer Blood Ctr, Washington, DC USA. Natl Inst Genet, Los Angeles, CA USA. Bayer Corp, Res Triangle Pk, NC USA. Alpha Therapeut Corp, Los Angeles, CA USA. European Directorate Qual Med, Strasbourg, France. German Red Cross, Frankfurt, Germany. Amer Red Cross, Blood Serv, Gaithersburg, MD USA. Aventis Behring, Marburg, Germany. Baxter BioSci, Vienna, Austria. RP Whitaker, B (reprint author), Plasma Prot Therapeut Assoc, 147 Old Solomons Isl Rd,Suite 100, Annapolis, MD 21401 USA. NR 10 TC 5 Z9 5 U1 0 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 SEP PY 2003 VL 31 IS 3 BP 153 EP 159 DI 10.1016/S1045-1056(03)00020-4 PG 7 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA 721NR UT WOS:000185322900001 PM 12935802 ER PT J AU Ebrahimi, N Molefe, D Ying, ZL AF Ebrahimi, N Molefe, D Ying, ZL TI Identifiability and censored data SO BIOMETRIKA LA English DT Article DE censored observation; constant-sum condition; Greenwood's formula; identifiability; Kaplan-Meier estimator; survival function ID VARIABLE-SUM MODELS; SURVIVAL ANALYSIS; CONSTANT-SUM AB It is well known that, without the assumption of independence between two nonnegative random variables X and Y, the survival function of X is not identifiable on the basis of the joint distribution function of Z = min(X, Y) and delta = I(Z = Y). In this paper, we provide a simple condition in the form of conditional distribution of Y given X. We show that our condition is equivalent to the constant-sum condition proposed by Williams & Lagakos (1977). As a result the survival function of X can be identified from the joint distribution of Z and delta and the Kaplan-Meier estimator with Greenwood's formula for its variance remains valid. Examples which satisfy the condition are given. C1 No Illinois Univ, Div Stat, De Kalb, IL 60115 USA. US FDA, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. Columbia Univ, Dept Stat, New York, NY 10027 USA. RP Ebrahimi, N (reprint author), No Illinois Univ, Div Stat, De Kalb, IL 60115 USA. NR 8 TC 5 Z9 5 U1 0 U2 0 PU BIOMETRIKA TRUST PI LONDON PA UNIV COLLEGE LONDON GOWER ST-BIOMETRIKA OFFICE, LONDON WC1E 6BT, ENGLAND SN 0006-3444 J9 BIOMETRIKA JI Biometrika PD SEP PY 2003 VL 90 IS 3 BP 724 EP 727 DI 10.1093/biomet/90.3.724 PG 4 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 723XL UT WOS:000185456800017 ER PT J AU Nishizuka, S Chen, ST Gwadry, FG Alexander, J Major, SM Scherf, U Reinhold, WC Waltham, M Charboneau, L Young, L Bussey, KJ Kim, SY Lababidi, S Lee, JK Pittaluga, S Scudiero, DA Sausville, EA Munson, PJ Petricoin, EF Liotta, LA Hewitt, SM Raffeld, M Weinstein, JN AF Nishizuka, S Chen, ST Gwadry, FG Alexander, J Major, SM Scherf, U Reinhold, WC Waltham, M Charboneau, L Young, L Bussey, KJ Kim, SY Lababidi, S Lee, JK Pittaluga, S Scudiero, DA Sausville, EA Munson, PJ Petricoin, EF Liotta, LA Hewitt, SM Raffeld, M Weinstein, JN TI Diagnostic markers that distinguish colon and ovarian adenocarcinomas: identification by genomic, proteomic, and tissue array profiling SO CANCER RESEARCH LA English DT Article ID UNKNOWN PRIMARY SITE; NATIONAL-CANCER-INSTITUTE; TUMOR-CELL-LINES; MOLECULAR PHARMACOLOGY; EXPRESSION DATABASE; DRUG DISCOVERY; VILLIN; PROTEIN; GENE; CARCINOMA AB Colon and ovarian cancers can be difficult to distinguish in the abdomen, and the distinction is important because it determines which drugs will be used for therapy. To identify molecular markers for that differential diagnosis, we developed a multistep protocol starting with the 60 human cancer cell lines used by the National Cancer Institute to screen for new anticancer agents. The steps included: (a) identification of candidate markers using cDNA microarrays; (b) verification of clone identities by resequencing; (e) corroboration of transcript levels using Affymetrix oligonucleotide chips; (d) quantitation of protein expression by "reverse-phase" protein microarray; and (e) prospective validation of candidate markers on clinical tumor sections in tissue microarrays. The two best candidates identified were villin for colon cancer cells and moesin for ovarian cancer cells. Because moesin stained stromal elements in both types of cancer, it would probably not have been identified as a marker if we had started with mRNA or protein profiling of bulk tumors. Villin appears at least as useful as the currently used colon cancer marker cytokeratin 20, and moesin also appears to have utility. The multistep process introduced here has the potential to produce additional markers for cancer diagnosis, prognosis, and therapy. C1 NCI, Lab Mol Pharmacol, Genom & Bioinformat Grp, NIH, Bethesda, MD 20892 USA. Ctr Informat Technol, Math & Stat Comp Lab, Analyt Biostat Sect, NCI, Bethesda, MD 20814 USA. Dev Therapeut Program, Div Canc Treatment & Diagnosis, Bethesda, MD 20814 USA. Sci Applicat Int Corp, NCI, Frederick Canc Res & Dev Ctr, Ft Detrick, MD 21702 USA. Food & Drug Adm, Ctr Biol Evaluat & Res, Tissue Proteom Unit, Div Therapeut Prot, Bethesda, MD 20814 USA. RP Weinstein, JN (reprint author), NCI, Lab Mol Pharmacol, Genom & Bioinformat Grp, NIH, Bldg 37,Rm 5056, Bethesda, MD 20892 USA. RI Waltham, Mark/A-1728-2009; OI Hewitt, Stephen/0000-0001-8283-1788; Kim, Sohyoung/0000-0002-6140-7918 NR 47 TC 150 Z9 155 U1 1 U2 8 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 1 PY 2003 VL 63 IS 17 BP 5243 EP 5250 PG 8 WC Oncology SC Oncology GA 722XD UT WOS:000185402600015 PM 14500354 ER PT J AU Chen, JJZ Gokden, N Greene, GF Green, B Kadlubar, FF AF Chen, JJZ Gokden, N Greene, GF Green, B Kadlubar, FF TI Simultaneous generation of multiple mitochondrial DNA mutations in human prostate tumors suggests mitochondrial hyper-mutagenesis SO CARCINOGENESIS LA English DT Article ID MUTATOR PHENOTYPE; CARCINOMA-CELLS; HIGH-FREQUENCY; CANCER; PROGRESSION; POLYMERASE; DAMAGE; PATHOGENESIS; MALIGNANCY; SEQUENCE AB Multiple somatic mitochondrial DNA mutations are frequently reported in human tumors, but the process leading to homoplasmic transformation and accumulation of multiple mutations in the same tumor cell lineage remains a mystery. We address possible mechanisms responsible for the generation of multiple mitochondrial (mt)DNA mutations observed in a high frequency of prostate tumors using sensitive mutant-specific PCR coupled with laser capture microdissection. Analysis of prostate tumors with multiple mtDNA mutations in the control region indicates that the mutations are locally confined, that the multiple mutations exist on the same molecules and that more than one mtDNA mutant species co-exists in the same neoplastic lesion. These results suggest an unusually rapid process in mtDNA mutagenesis during tumor progression. On the basis of prostate tumor cell kinetics, we propose a unique process of mitochondrial hyper-mutagenesis, probably mediated by cellular oxidative stress, to account for a burst of multiple mtDNA mutations in human prostate tumors. C1 Natl Ctr Toxicol Res, Div Mol Epidemiol, Jefferson, AR 72079 USA. Univ Arkansas Med Sci, Dept Pathol, Little Rock, AR 72205 USA. Univ Arkansas Med Sci, Dept Urol, Little Rock, AR 72205 USA. RP Chen, JJZ (reprint author), Natl Ctr Toxicol Res, Div Mol Epidemiol, Jefferson, AR 72079 USA. FU PHS HHS [E07113.01] NR 34 TC 31 Z9 34 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD SEP PY 2003 VL 24 IS 9 BP 1481 EP 1487 DI 10.1093/carcin/bgg102 PG 7 WC Oncology SC Oncology GA 721HB UT WOS:000185310000007 PM 12869417 ER PT J AU da Costa, GG Marques, MM Freeman, JP Beland, FA AF da Costa, GG Marques, MM Freeman, JP Beland, FA TI Synthesis and investigation of alpha-hydroxy-N,N-didesmethyltamoxifen as a proximate carcinogen in the metabolic activation of tamoxifen SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID DNA-ADDUCTS; BREAST-CANCER; ALPHA-HYDROXYTAMOXIFEN; RAT-LIVER; N-DESMETHYLTAMOXIFEN; IDENTIFICATION; SULFOTRANSFERASE; PREVENTION; CELLS; ACETOXYTAMOXIFEN AB Tamoxifen is an adjuvant chemotherapeutic agent for the treatment of breast cancer and a chemoprotective agent for breast cancer prevention. Despite being beneficial in regard to breast cancer, tamoxifen is known to increase the risk of endometrial cancer and thromboembolic events in women; in addition, it induces liver tumors in rats and endometrial tumors in rats and mice. Tamoxifen and its metabolite, N-desmethyltamoxifen, are metabolically activated to DNA binding electrophiles through alpha-hydroxylation, followed by O-esterification, primarily via sulfation. In the present study, we have investigated whether a second desmethylated metabolite of tamoxifen, N,N-didesmethyltamoxifen, is also involved in the metabolic activation of this antiestrogen to a genotoxic species. alpha-Hydroxy-N,N-didesmethyltamoxifen was synthesized, further activated by sulfation, and then reacted with DNA. After enzymatic hydrolysis to deoxynucleosides, HPLC analysis indicated the formation of one major DNA adduct, which was characterized as (E)-alpha-(deoxyguanosin-N-2-yl)-N,N-didesmethyltamoxifen. Using P-32-postlabeling, in combination with HPLC, the same adduct was detected in liver DNA from rats treated intraperitoneally with alpha-hydroxy-N,N-didesmethyltamoxifen. In contrast, only a low extent of adduct formation could be found in rats administered N,N-didesmethyltamoxifen. These data indicate that although alpha-hydroxy-N,N-didesmethyltamoxifen can be converted to a genotoxin in rat liver, this pathway is a minor one in the metabolic activation of tamoxifen. C1 Univ Tecn Lisboa, Ctr Quim Estrutural, Inst Super Tecn, P-1049001 Lisbon, Portugal. Natl Ctr Toxicol Res, Div Chem, Jefferson, AR 72079 USA. Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Marques, MM (reprint author), Univ Tecn Lisboa, Ctr Quim Estrutural, Inst Super Tecn, Complexo 1,Av Rovisco Pais, P-1049001 Lisbon, Portugal. EM matilde.marques@ist.utl.pt; fbeland@nctr.fda.gov RI Marques, M. Matilde/E-2535-2012 OI Marques, M. Matilde/0000-0002-7526-4962 NR 49 TC 7 Z9 7 U1 0 U2 2 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 SEP PY 2003 VL 16 IS 9 BP 1090 EP 1098 DI 10.1021/tx030010o PG 9 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 723AR UT WOS:000185410700007 ER PT J AU Chou, MW Jian, Y Williams, LD Xia, Q Churchwell, M Doerge, DR Fu, PP AF Chou, MW Jian, Y Williams, LD Xia, Q Churchwell, M Doerge, DR Fu, PP TI Identification of DNA adducts derived from riddelliine, a carcinogenic pyrrolizidine alkaloid SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID IN-VITRO; DIHYDROPYRROLIZINE DERIVATIVES; RAT-LIVER; N-OXIDES; DEHYDRORETRONECINE; METABOLITES; ALKYLATION; TUMORS; MONOCROTALINE; TOXICITY AB Riddelliine is a naturally occurring carcinogenic pyrrolizidine alkaloid that produces liver tumors in experimental animals. Riddelliine requires metabolic activation to dehydroriddelliine and 6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine (DHP) to exert its toxicity. Previously, P-32-postlabeling HPLC was used to detect a set of eight DHP-derived adduct peaks from DNA modified both in vitro and in vivo. Among these DHP-derived DNA adducts, two were identified as epimers of DHP-2'-deoxyguanosine X-monophosphate. In this study, the remaining adducts have been characterized as DHP-modified dinucleotides. A series of dinucleotides, TpGp, ApGp, TpCp, ApCp, TpAp, ApAp, TpTp, and ApTp, were obtained by enzymatic digestion of calf thymus DNA with micrococcal nuclease (MN) and spleen phosphodiesterase (SPD) followed by HPLC separation and structural identification by negative ion electrospray tandem mass spectrometry (ES/MS/MS). Incubation of individual dinucleotides with DHP produced DHP-modified dinucleotide adducts that were also characterized using LC-ES/MS/MS. A parallel analysis of the isolated DHP-modified dinucleotides using P-32-postlabeling recapitulated the series of unidentified adduct peaks that we previously reported from DHP-modified calf thymus DNA in vitro and rat liver DNA in vivo. Intact calf thymus DNA was also reacted with DHP and then digested by MN/SPD under the same conditions'. The adduct profile obtained from LC-ES/MS/MS analysis was similar to that observed from the isolated dinucleotides. Structural analysis using LC-ES/MS/MS showed that DHP bound covalently to both 3'- and 5'-guanine, -adenine, and -thymine bases (but not cytosine) of dinucleotides to produce two or more isomers of each DHP-dinucleotide adduct. By comparing adduct formation at dissimilar bases within individual dinucleotides, the relative reactivity of DHP with individual bases was determined to be guanine > adenine similar to thymine. Identification of the entire set of DHP-derived DNA adducts further validates the conclusion that riddelliine is a genotoxic carcinogen and enhances the applicability of these biomarkers for assessing carcinogenic risks from exposure to pyrrolizidine alkaloids. C1 Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Fu, PP (reprint author), Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 40 TC 33 Z9 33 U1 0 U2 9 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 SEP PY 2003 VL 16 IS 9 BP 1130 EP 1137 DI 10.1021/tx030018y PG 8 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 723AR UT WOS:000185410700012 PM 12971801 ER PT J AU Turesky, RJ Freeman, JP Holland, RD Nestorick, DM Miller, DW Ratnasinghe, DL Kadlubar, FF AF Turesky, RJ Freeman, JP Holland, RD Nestorick, DM Miller, DW Ratnasinghe, DL Kadlubar, FF TI Identification of aminobiphenyl derivatives in commercial hair dyes SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID BLADDER-CANCER RISK; AROMATIC-AMINES; PERCUTANEOUS PENETRATION; MASS-SPECTROMETRY; CIGARETTE-SMOKE; TOBACCO-SMOKE; AZO DYES; REDUCTION; GAS; CHROMATOGRAPHY AB A recent epidemiological study suggested that aromatic amines present in hair dyes may contribute to an increased risk of bladder cancer (Gago-Dominguez, et al. (2003) Carcinogenesis 24, 483-489). Moreover, a preliminary study linked frequent hair dye usage with elevated levels of DNA adducts of 4-aminobiphenyl (4-ABP) in human epithelial breast cells (Gorlewska, et al. Proc. Am. Assoc. Cancer Res. 43, 1018 -1019). Therefore, we sought to determine if 4-ABP, a recognized human urinary bladder carcinogen, is present in commercial hair dyes. 4-ABP was isolated from dyes by solvent extraction with hexane, followed by silica gel chromatography, either with or without chemical treatment of the extract with Zinc/HCl, and a final purification with a mixed cation exchange reversed-phase resin. The identity of 4-ABP was confirmed by both HPLC with electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS) and gas chromatography with negative ion chemical ionization mass spectrometry (GC-NICI-MS) following chemical derivatization with pentafluoropropionic anhydride (PFPA). The levels of 4-ABP ranged from not detectable (<0.29 parts per billion (ppb)) up to 12.8 ppb. The noncarcinogenic isomer 2-aminobiphenyl (2-ABP) was also found at quantities up to 310 ppb. 4-ABP was detected in eight of the 11 hair dyes and found in black, red, and blonde hair dyes but not in brown hair dyes. 1,4-Phenylenediamine (PPD) is a key constituent for color development of many permanent hair dyes. Some batches of chemical research grade PPD were contaminated with 4-ABP (up to 500 ppb) and 2-ABP (up to 70 parts per million) and may be a source of ABP contamination in hair dyes. These analytical data demonstrate that 4-ABP is present in some hair dyes. Studies on dermal absorption and bioavailability of 4-ABP from hair dyes are required to determine if this aromatic amine contributes to the increased risk of bladder cancer reported in frequent users of hair dyes. C1 Natl Ctr Toxicol Res, Div Chem, Jefferson, AR 72079 USA. Natl Ctr Toxicol Res, Div Mol Epidemiol, Jefferson, AR 72079 USA. RP Turesky, RJ (reprint author), Natl Ctr Toxicol Res, Div Chem, 3900 NCTR Rd, Jefferson, AR 72079 USA. NR 54 TC 82 Z9 83 U1 1 U2 11 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 SEP PY 2003 VL 16 IS 9 BP 1162 EP 1173 DI 10.1021/tx030029r PG 12 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 723AR UT WOS:000185410700016 PM 12971805 ER PT J AU Marti, GE AF Marti, GE TI B cell moncolonal lyphocytosis (BCML) and B cell abormalities in the setting of familial B cell chronic lymphocytic leukemia (vol 52B, pg 1, 2003) SO CYTOMETRY PART B-CLINICAL CYTOMETRY LA English DT Correction C1 US FDA, CBER, Div Gene & Cell Therapy, Bethesda, MD 20892 USA. RP Marti, GE (reprint author), US FDA, CBER, Div Gene & Cell Therapy, NIH Bldg,29B,Room 2NN08,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 1 TC 1 Z9 1 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0196-4763 J9 CYTOM PART B-CLIN CY JI Cytom. Part B-Clin. Cytom. PD SEP PY 2003 VL 55B IS 1 BP 63 EP 63 DI 10.1002/cyto.b.10045 PG 1 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 718VR UT WOS:000185167600010 ER PT J AU Gutman, S Feigal, D AF Gutman, S Feigal, D TI Decision making in pharmacogenomic diagnosis: is there anything new under the sun? SO DRUG DISCOVERY TODAY LA English DT Editorial Material C1 US FDA, Off Vitro Diagnost Devices, Rockville, MD 20850 USA. RP Gutman, S (reprint author), US FDA, Off Vitro Diagnost Devices, HFZ 440,2098 Gaither Rd, Rockville, MD 20850 USA. NR 6 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1359-6446 J9 DRUG DISCOV TODAY JI Drug Discov. Today PD SEP 1 PY 2003 VL 8 IS 17 BP 765 EP 766 AR PII S1359-6446(03)02715-6 DI 10.1016/S1359-6446(03)02715-6 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 718MZ UT WOS:000185151700001 PM 12946630 ER PT J AU Song, YS Begley, T Paquette, K Komolprasert, V AF Song, YS Begley, T Paquette, K Komolprasert, V TI Effectiveness of polypropylene film as a barrier to migration from recycled paperboard packaging to fatty and high-moisture food SO FOOD ADDITIVES AND CONTAMINANTS LA English DT Article DE polypropylene; film barrier; recycled paperboard; contaminant(s); food packaging for reheating and cooking ID POTENTIAL FUNCTIONAL BARRIERS; MOLECULAR-WEIGHT PERMEANTS; COMPOSITIONAL ANALYSIS; CONTACT; CONTAMINANTS; BENZOPHENONE; TESTS AB The capability of a polypropylene (PP) film barrier to prevent migration of residual contaminants from recycled paperboard into food simulants was studied. Anthracene, benzophenone, methyl stearate and pentachlorophenol were chosen as chemical surrogates to represent classes of contaminants likely to be found in recycled paper/paperboard. Each surrogate was spiked into a test specimen made of seven thin virgin paper layers at concentrations of 1-50 mg kg(-1) . Test specimen were dried, stacked and sandwiched with PP films, laminated with PP film and then subjected to migration experiments using a compression cell maintained at 100degreesC for 2 h. The concentration of the surrogates in the test specimen and in 95% ethanol, isopropanol and 10% ethanol food-simulating solvents was determined by gas chromatography with flame ionization and electron capture detection. The results show that although the concentrations of the surrogates in the food simulants decreased with an increase in PP film thickness, they were still high and generally resulted in dietary concentrations >0.5 mug kg(-1) , the level that US Food and Drug Administration would equate with negligible risk for a contaminant migrating from food packaging. Only at the lowest spiking level (1 mg kg(-1) benzophenone) did migration from the paperboard through a 0.127-mm PP film result in a dietary concentration of less than or equal to0.5 mug kg(-1) . Therefore, it can be concluded that for an extended time at 100degreesC, PP would not be an acceptable barrier to migration of contaminants that are expected to be in post-consumer paper/paperboard. C1 US FDA, Div Food Proc & Packaging, Natl Ctr Food Safety& Technol, Summit Argo, IL 60501 USA. US FDA, OFAS, College Pk, MD 20740 USA. US FDA, OFAS, Washington, DC 20502 USA. RP Song, YS (reprint author), US FDA, Div Food Proc & Packaging, Natl Ctr Food Safety& Technol, 6502 S Archer Rd, Summit Argo, IL 60501 USA. FU FDA HHS [FD-000431] NR 28 TC 21 Z9 26 U1 2 U2 16 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 SEP PY 2003 VL 20 IS 9 BP 875 EP 883 DI 10.1080/02652030310001597592 PG 9 WC Chemistry, Applied; Food Science & Technology; Toxicology SC Chemistry; Food Science & Technology; Toxicology GA 722QB UT WOS:000185386600012 PM 13129783 ER PT J AU Mendez, S Tabbara, K Belkaid, Y Bertholet, S Verthelyi, D Klinman, D Seder, RA Sacks, DL AF Mendez, S Tabbara, K Belkaid, Y Bertholet, S Verthelyi, D Klinman, D Seder, RA Sacks, DL TI Coinjection with CpG-containing immunostimulatory oligodeoxynucleotides reduces the pathogenicity of a live vaccine against cutaneous leishmaniasis but maintains its potency and durability SO INFECTION AND IMMUNITY LA English DT Article ID SUSCEPTIBLE BALB/C MICE; CD8(+) T-CELLS; PROTECTIVE IMMUNITY; MAJOR INFECTION; INTERFERON-GAMMA; CONTROLLED TRIAL; DNA VACCINATION; NATURAL MODEL; DOUBLE-BLIND; PLUS BCG AB The inoculation of live, nonattenuated Leishmania major to produce a lesion in a selected site that heals, referred to as leishmanization, is to date the only vaccine against leishmaniasis that has proven to be effective in humans. Its use has been restricted or abandoned entirely, however, due to safety concerns. In an attempt to develop a leishmanization protocol that minimizes pathology while maintaining long-term protection, live parasites were coinjected with CpG-containing immunostimulatory oligodeoxynucleotides (CpG ODNs) alone or in combination with whole-cell lysates of heat-killed L. major promastigotes bound to alum (ALM). C57BL/6 mice infected intradermally by using L. major plus CpG ODN with or without ALM developed few or no dermal lesions and showed an early containment of parasite growth, while mice infected with L. major with or without ALM developed sizable dermal lesions that required up to 10 weeks to heal. The CpG ODNs provoked a transient inflammation that included an early recruitment and accumulation of gamma interferon-producing CD4(+) lymphocytes in the site. Attenuation of the live vaccine did not compromise its ability to confer long-term immunity, as mice receiving L. major and CpG ODN plus ALM were totally protected against reinfection with L. major for up to 6 months. By comparison, the immunity elicited by two efficient nonlive vaccines began to wane by 6 months. Our results suggest that immune modulation using CpG ODNs might be a practical approach to improving the safety of a highly effective live vaccine that has already been widely applied. C1 NIAID, Parasit Dis Lab, Bethesda, MD 20892 USA. NIAID, Vaccine Res Ctr, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. US FDA, Cellular Immunol Sect, Sect Retroviral Immunol, Bethesda, MD 20892 USA. RP Sacks, DL (reprint author), NIAID, Parasit Dis Lab, Bldg 4,Rm 126,Ctr Dr MSC 0425, Bethesda, MD 20892 USA. NR 52 TC 55 Z9 56 U1 0 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 SEP PY 2003 VL 71 IS 9 BP 5121 EP 5129 DI 10.1128/IAI.71.9.5121-5129.2003 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 715WR UT WOS:000184996600034 PM 12933855 ER PT J AU Mahmood, I AF Mahmood, I TI Impact of random and fixed (optimal) sampling approach on the Bayesian estimation of clearance SO INTERNATIONAL JOURNAL OF CLINICAL PHARMACOLOGY AND THERAPEUTICS LA English DT Article DE sparse sampling; Bayesian estimation; clearance ID MAXIMUM PLASMA-CONCENTRATION; CONCENTRATION C-MAX; UNDER-THE-CURVE; COMPUTER-SIMULATION; PHARMACOKINETICS; POPULATION; MODEL; AREA; AUC; CARBAMAZEPINE AB Background and objective: The population pharmacokinetic approach is based on sparse sampling. In sparse sampling approaches, the selection of the time point(s) is very critical for the prediction of pharmacokinetic parameters. Several investigators have shown that the predictive performance of the Bayesian approach is influenced by the initial estimates of pharmacokinetic parameters as well as the time of blood sampling. The objective of this study is to evaluate the impact of random and fixed sparse sampling approach on the Bayesian estimation of clearance. Methods: Three drugs were selected for this study. Two sparse sampling methods (random or fixed) using Bayesian approach were used to assess clearance in healthy subjects following a single oral dose. The initial estimates of the model parameters and interand intra-subject variabilities were obtained from the previous pharmacokinetic studies conducted in healthy volunteers. The predicted clearance values using sparse sampling (1, 2 or 3 blood samples per subject) were compared with the clearance values obtained by extensive sampling. Results and conclusion: The results indicated that both random and fixed sampling approaches, irrespective of number of blood samples, can be used to estimate mean population as well as post hoc predicted individual clearance (Bayesian) with accuracy. However, the precision of the prediction of clearance was found to be better with fixed rather random blood sampling approach. C1 US FDA, Off Therapeut Res & Review,Ctr Biol Evaluat & Res, Div Clin Trial Design & Anal, Clin Pharmacol & Toxicol Branch,Woodmont Off Ctr, Rockville, MD 20852 USA. RP Mahmood, I (reprint author), US FDA, Off Therapeut Res & Review,Ctr Biol Evaluat & Res, Div Clin Trial Design & Anal, Clin Pharmacol & Toxicol Branch,Woodmont Off Ctr, Suite 200N,1401 Rockville Pike,HFD-579, Rockville, MD 20852 USA. NR 18 TC 3 Z9 3 U1 0 U2 1 PU DUSTRI-VERLAG DR KARL FEISTLE PI OBERHACHING PA BAJUWARENRING 4, D-82041 OBERHACHING, GERMANY SN 0946-1965 J9 INT J CLIN PHARM TH JI Int. J. Clin. Pharmacol. Ther. PD SEP PY 2003 VL 41 IS 9 BP 392 EP 396 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 717UW UT WOS:000185110000003 PM 14526763 ER PT J AU Osterberg, RE See, NA AF Osterberg, RE See, NA TI Toxicity of excipients - A food and drug administration perspective SO INTERNATIONAL JOURNAL OF TOXICOLOGY LA English DT Article DE excipients; guidance; regulatory AB Excipients are essential components of drug products. They are also potential toxicants. Examples of known excipient-induced toxicities include renal failure and death from diethylene glycol, osmotic diarrhea caused by ingested mannitol, hypersensitivity reactions from lanolin, and cardiotoxicity induced by propylene glycol. Proposals to test or market new drug products in the United States should adequately address the safety of the proposed exposure to the excipients in those products. The specific safety data that may be needed will vary depending upon the clinical situation, including such factors as the duration, level, and route of exposure, but may include acute, repeat-dose, reproductive, and genetic toxicity data, carcinogenicity data, and specialized toxicology information, such as sensitization or local irritation data. Many guidances exist to aid in the development of pharmaceuticals, including the International Conference on Harmonization (ICH) documents and various Food and Drug Administration/Center for Drug Evaluation and Research (FDA/CDER) pharmacology and toxicology guidances. The FDA/CDER has recently adopted a new guidance for industry, "Nonclinical Studies for Development of Pharmaceutical Excipients," which focuses on issues associated with development of safety databases that will support clinical use of excipients in drug products. The new guidance document is introduced and discussed in this article. C1 US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20850 USA. RP Osterberg, RE (reprint author), US FDA, Ctr Drug Evaluat & Res, 9201 Corp Blvd, Rockville, MD 20850 USA. NR 16 TC 25 Z9 25 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 SEP-OCT PY 2003 VL 22 IS 5 BP 377 EP 380 DI 10.1080/10915810390232330 PG 4 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 730HL UT WOS:000185825000007 PM 14555410 ER PT J AU Christopher, D Curry, P Doub, B Furnkranz, K Lavery, M Lin, K Lyapustina, S Mitchell, J Rogers, B Strickland, H Tougas, T Tsong, Y Wyka, B AF Christopher, D Curry, P Doub, B Furnkranz, K Lavery, M Lin, K Lyapustina, S Mitchell, J Rogers, B Strickland, H Tougas, T Tsong, Y Wyka, B CA PQRI Prt Siz Dis Mas Bal Wk Grp TI Considerations for the development and practice of cascade impaction testing, including a mass balance failure investigation tree SO JOURNAL OF AEROSOL MEDICINE-DEPOSITION CLEARANCE AND EFFECTS IN THE LUNG LA English DT Article ID SIZE DISTRIBUTION; CALIBRATION; ANDERSEN C1 Trudell Med Int, London, ON N5V 5G4, Canada. Gardner Carton & Douglas, Washington, DC USA. US FDA, Rockville, MD 20857 USA. US FDA, St Louis, MO USA. Boehringer Ingelheim Pharmaceut Inc, Ridgefield, CT 06877 USA. Schering Plough Res Inst, Kenilworth, NJ USA. RP Mitchell, J (reprint author), Trudell Med Int, 725 3rd St, London, ON N5V 5G4, Canada. NR 19 TC 34 Z9 34 U1 0 U2 2 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0894-2684 J9 J AEROSOL MED JI J. Aerosol Med.-Depos. Clear. Eff. Lung PD FAL PY 2003 VL 16 IS 3 BP 235 EP 247 DI 10.1089/089426803769017604 PG 13 WC Public, Environmental & Occupational Health; Respiratory System SC Public, Environmental & Occupational Health; Respiratory System GA 725ZG UT WOS:000185572000002 PM 14572321 ER PT J AU Roybal, JE Pfenning, AP Storey, JM Gonzales, SA Turnipseed, SB AF Roybal, JE Pfenning, AP Storey, JM Gonzales, SA Turnipseed, SB TI Liquid chromatographic determination of diminazene diaceturate (Berenil (TM)) in raw bovine milk SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID PAIRED-ION EXTRACTION; PLASMA AB A simple liquid chromatographic (LC) method is presented for the determination of diminazene (DZ) in raw bovine milk. DZ is extracted from raw milk by chilled aqueous centrifugation and is isolated from milk components on a cyano solid-phase extraction column. DZ is eluted by using a methanol-ion pairing reagent. A Phenomenex LUNA CN column and an acetonitrile-buffered mobile phase with a counter ion are used for gradient LC. The LC effluent is monitored at a detection wavelength of 372 nm by using a deuterium lamp. Under the parameters described, the retention time of DZ is 8-10 min with a peak area response of 6.5 mAU/ng. The method demonstrated excellent precision over all levels tested (25-400 ppb) with an overall average recovery of 90.4 +/- 14.5%. The method is applicable to the monitoring of milk for DZ residues at the 25 ppb level with a limit of quantitation of 10 ppb. C1 US FDA, Anim Drugs Res Ctr, Denver Fed Ctr, Denver, CO 80225 USA. RP Roybal, JE (reprint author), US FDA, Anim Drugs Res Ctr, Denver Fed Ctr, POB 25087, Denver, CO 80225 USA. NR 8 TC 2 Z9 4 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 SEP-OCT PY 2003 VL 86 IS 5 BP 930 EP 934 PG 5 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 738LK UT WOS:000186289000009 PM 14632393 ER PT J AU McClure, FD Lee, JK Wilson, DB AF McClure, FD Lee, JK Wilson, DB TI Validity of the percent reduction in standard deviation outlier test for screening laboratory means from a collaborative study SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID OUTLYING OBSERVATIONS; POINTS AB AOAC INTERNATIONAL recommends an outlier test that is based on the "percent reduction in standard deviation" (PRSD) for screening the highest or lowest and 2-highest or 2-lowest laboratory means from a collaborative study. The original critical values that were developed to assess the significance of the test statistics associated with the PRSD test were obtained by simulation. In this paper, we answer several questions relative to the validity of the simulated critical values and develop formulas, based on the Student's t-distribution, to compare the simulated and formula-based critical values. Assumptions and derivations of formulas are provided along with selected tabular critical values that are used to test hypotheses at various levels of significance. C1 US FDA, Ctr Food Safety & Appl Nutr, Off Sci Anal & Support, Div Math, College Pk, MD 20740 USA. RP McClure, FD (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Sci Anal & Support, Div Math, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. NR 19 TC 4 Z9 4 U1 1 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 SEP-OCT PY 2003 VL 86 IS 5 BP 1045 EP 1055 PG 11 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 738LK UT WOS:000186289000024 PM 14632408 ER PT J AU McClure, FD Lee, JK AF McClure, FD Lee, JK TI Computation of HORRAT values SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article AB The formula for the Horwitz ratio (HORRAT) as presented in the Study Director's Manual of AOAC INTERNATIONAL is applicable only when the concentration is in the unit/unit form (e.g., mug/mug, g/g, etc.). When the analyte concentration is a trace or mass fraction amount (e.g., mug/g), the formula generates incorrect HORRAT values. Alternative calculation procedures are presented to circumvent such problems. C1 US FDA, Ctr Food Safety & Appl Nutr, Off Sci Anal & Support, Div Math, College Pk, MD 20740 USA. RP McClure, FD (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Sci Anal & Support, Div Math, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. NR 0 TC 20 Z9 20 U1 1 U2 3 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD SEP-OCT PY 2003 VL 86 IS 5 BP 1056 EP 1058 PG 3 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 738LK UT WOS:000186289000025 PM 14632409 ER PT J AU McClure, FD Graves, QF AF McClure, FD Graves, QF TI Determination of sample size for validation of allergen-screening methods SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article AB For various levels of confidence (i.e., 80 and 90%) and ratios (K = sigma(p)(2)/sigma(N)(2), where sigma(p)(2) and sigma(N)(2) are the analyte variances for the positive and negative distributions, respectively), sample sizes sufficient to test the requirements that a given method detects greater than or equal to90% of the positives (greater than or equal to5 ppm of a given analyte) while misclassifying less than or equal to10% of the negatives (implying a specificity rate, true negatives that will be correctly classified, of 90%) were estimated by using a rationale that minimizes the cost of sampling. C1 US FDA, Ctr Food Safety & Appl Nutr, Off Sci Anal & Support, Div Math, College Pk, MD 20740 USA. RP McClure, FD (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Sci Anal & Support, Div Math, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. NR 0 TC 0 Z9 0 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 SEP-OCT PY 2003 VL 86 IS 5 BP 1059 EP 1062 PG 4 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 738LK UT WOS:000186289000026 PM 14632410 ER PT J AU Volokhov, D Chizhikov, V Chumakov, K Rasooly, A AF Volokhov, D Chizhikov, V Chumakov, K Rasooly, A TI Microarray-based identification of thermophilic Campylobacter jejuni, C-coli, C-lari, and C-upsaliensis SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID POLYMERASE-CHAIN-REACTION; FIELD GEL-ELECTROPHORESIS; LINKED-IMMUNOSORBENT-ASSAY; PCR ASSAY; MULTIPLEX PCR; ARCOBACTER-BUTZLERI; SAMPLES; DIFFERENTIATION; SPP.; PREVALENCE AB DNA microarrays are an excellent potential tool for clinical microbiology, since this technology allows relatively rapid identification and characterization of microbial and viral pathogens. In the present study, an oligonucleotide microarray was developed and used for the analysis of thermophilic Campylobacter spp., the primary food-borne pathogen in the United States. We analyzed four Campylobacter species: Campylobacter jejuni, C coli, C lari, and C. upsaliensis. Our assay relies on the PCR amplification of specific regions in five target genes (fur, glyA, cdtABC, ceuB-C, and fliY) as a first step, followed by microarray-based analysis of amplified DNAs. Alleles of two genes, fur and glyA, which are found in all tested thermophilic Campylobacter spp., were used for identification and discrimination among four bacterial species, the ceuB-C gene was used for discrimination between C. jejuni and C. coli, and the fliY and cdt genes were used as additional genetic markers specific either for C upsaliensis and C lari or for C jejuni. The array was developed and validated toy using 51 previously characterized Campylobacter isolates. All isolates were unambiguously identified on the basis of hybridization patterns with 72 individual species-specific oligoprobes. Microarray identification of C. jejuni and C. coli was confirmed by PCR amplification of other genes used for identification (hipO and ask). Our results demonstrate that oligonucleotide microarrays are suitable for rapid and accurate simultaneous differentiation among C. jejuni, C. coli, C. lari, and C upsaliensis. 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, 5100 Plant Branch Pkwy, College Pk, MD 20740 USA. NR 39 TC 81 Z9 91 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 SEP PY 2003 VL 41 IS 9 BP 4071 EP 4080 DI 10.1128/JCM.41.9.4071-4080.2003 PG 10 WC Microbiology SC Microbiology GA 720DT UT WOS:000185246800011 PM 12958228 ER PT J AU Miller, RA Walker, RD Baya, A Clemens, K Coles, M Hawke, JP Henricson, BE Hsu, HM Mathers, JJ Oaks, JL Papapetropoulou, M Reimschuessel, R AF Miller, RA Walker, RD Baya, A Clemens, K Coles, M Hawke, JP Henricson, BE Hsu, HM Mathers, JJ Oaks, JL Papapetropoulou, M Reimschuessel, R TI Antimicrobial susceptibility testing of aquatic bacteria: Quality control disk diffusion ranges for Escherichia coli ATCC 25922 and Aeromonas salmonicida subsp salmonicida ATCC 33658 at 22 and 28C SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article AB Quality control (QC) ranges for disk diffusion susceptibility testing of aquatic bacterial isolates were proposed as a result of a multilaboratory study conducted according to procedures established by the National Committee for Clinical Laboratory Standards (NCCLS). Ranges were proposed for Escherichia coli ATCC 25922 and Aeromonas salmonicida subsp. salmonicida ATCC 33658 at 22 and 28degreesC for nine different antimicrobial agents (ampicillin, enrofloxacin, erythromycin, florfenicol, gentamicin, oxolinic acid, oxytetracycline, ormetoprim-sulfadimethoxine, and trimethoprim-sulfamethoxazole). All tests were conducted on standard Mueller-Hinton agar. With greater than or equal to95% of all data points fitting within the proposed QC ranges, the results from this study comply with NCCLS guidelines and have been accepted by the NCCLS Subcommittee for Veterinary Antimicrobial Susceptibility Testing. These QC guidelines will permit greater accuracy in interpreting results and, for the first time, the ability to reliably compare susceptibility test data between aquatic animal disease diagnostic laboratories. C1 US FDA, Ctr Vet Med, Div Anim & Food Microbiol, Laurel, MD 20708 USA. Maryland Dept Agr, Anim Hlth Diagnost Lab, College Pk, MD 20740 USA. Idaho Fish Hlth Ctr, US Fish & Wildlife Serv, Ahsahka, ID 83520 USA. Univ Prince Edward Isl, Atlantic Vet Coll, Aquat Diagnost Serv, Charlottetown, PE C1A 4P3, Canada. Louisiana State Univ, Sch Vet Med, Baton Rouge, LA 70803 USA. Virginia Dept Agr & Comsumer Serv, Warrenton, VA USA. Univ Wisconsin, Wisconsin Vet Diagnost Lab, Madison, WI 53705 USA. Alpharma, Div Anim Hlth, Chicago Hts, IL 60411 USA. Washington State Univ, Washington Anim Dis Diagnost Lab, Pullman, WA 99164 USA. Univ Patras, Publ Hlth Lab, Patras 26500, Greece. RP Miller, RA (reprint author), US FDA, Ctr Vet Med, Div Anim & Food Microbiol, HFV530,8401 Muirkirk Rd, Laurel, MD 20708 USA. NR 15 TC 30 Z9 34 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 SEP PY 2003 VL 41 IS 9 BP 4318 EP 4323 DI 10.1128/JCM.41.9.4318-4323.2003 PG 6 WC Microbiology SC Microbiology GA 720DT UT WOS:000185246800046 PM 12958263 ER PT J AU Nilsson, WB Paranjpye, RN DePaola, A Strom, MS AF Nilsson, WB Paranjpye, RN DePaola, A Strom, MS TI Sequence polymorphism of the 16S rRNA gene of Vibrio vulnificus is a possible indicator of strain virulence (vol 41, pg 442, 2003) SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Correction C1 US Dept Commerce, NOAA, Natl Marine Fisheries Serv, NW Fisheries Sci Ctr, Seattle, WA 98112 USA. US FDA, Gulf Coast Seafood Lab, Dauphin Isl, AL 36528 USA. RP Nilsson, WB (reprint author), US Dept Commerce, NOAA, Natl Marine Fisheries Serv, NW Fisheries Sci Ctr, Seattle, WA 98112 USA. NR 1 TC 1 Z9 1 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD SEP PY 2003 VL 41 IS 9 BP 4496 EP 4496 DI 10.1128/JCM.41.9.4496.2003 PG 1 WC Microbiology SC Microbiology GA 720DT UT WOS:000185246800091 ER PT J AU Lathers, CM Ferguson, B Wang, S Yuan, T Zhang, XC AF Lathers, CM Ferguson, B Wang, S Yuan, T Zhang, XC TI Terahertz-rays: New technique to image bone? SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Meeting Abstract CT 32nd Annual Meeting of the American-College-of-Clinical-Pharmacology CY SEP 21-23, 2003 CL TAMPA, FLORIDA SP Amer Coll Clin Pharmacol C1 US FDA, Ctr Vet Med, Rockville, MD 20857 USA. Rensselaer Polytech Inst, Dept Phys, Troy, NY 12180 USA. RI Zhang, Xi-Cheng/G-1306-2016 OI Zhang, Xi-Cheng/0000-0003-3721-1357 NR 0 TC 0 Z9 0 U1 1 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 SEP PY 2003 VL 43 IS 9 MA 10 BP 1017 EP 1017 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 714PA UT WOS:000184921600016 ER PT J AU Lathers, CM Drusano, GL AF Lathers, CM Drusano, GL TI Individual bioequivalence to predict drug levels. SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Meeting Abstract CT 32nd Annual Meeting of the American-College-of-Clinical-Pharmacology CY SEP 21-23, 2003 CL TAMPA, FLORIDA SP Amer Coll Clin Pharmacol C1 Albany Med Coll, Albany, NY 12208 USA. US FDA, Ctr Vet Med, Rockville, MD 20857 USA. RI Zhang, Xi-Cheng/G-1306-2016 OI Zhang, Xi-Cheng/0000-0003-3721-1357 NR 0 TC 0 Z9 0 U1 1 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 SEP PY 2003 VL 43 IS 9 MA 8 BP 1017 EP 1017 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 714PA UT WOS:000184921600015 ER PT J AU Lathers, CM Koehler, SA Wecht, CW Schraeder, PL AF Lathers, CM Koehler, SA Wecht, CW Schraeder, PL TI Antiepileptic drug (AED) levels in autopsy cases of sudden, unexpected deaths in persons with epilepsy (SUDEP) in Allegheny County Pennsylvania in 2001. SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Meeting Abstract CT 32nd Annual Meeting of the American-College-of-Clinical-Pharmacology CY SEP 21-23, 2003 CL TAMPA, FLORIDA SP Amer Coll Clin Pharmacol C1 US FDA, Ctr Vet Med, Rockville, MD 20857 USA. Allegheny Cty, Off Coroner, Pittsburgh, PA USA. Albert Einstein Med Ctr, Dept Neurol, Philadelphia, PA 19141 USA. Thomas Jefferson Univ, Jefferson Med Coll, Philadelphia, PA 19107 USA. RI Zhang, Xi-Cheng/G-1306-2016 OI Zhang, Xi-Cheng/0000-0003-3721-1357 NR 0 TC 0 Z9 0 U1 1 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 SEP PY 2003 VL 43 IS 9 MA 5 BP 1017 EP 1017 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 714PA UT WOS:000184921600014 ER PT J AU Lathers, CM AF Lathers, CM TI Veterinary medicine and drug development. SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Meeting Abstract CT 32nd Annual Meeting of the American-College-of-Clinical-Pharmacology CY SEP 21-23, 2003 CL TAMPA, FLORIDA SP Amer Coll Clin Pharmacol C1 US FDA, Ctr Vet Med, Rockville, MD 20857 USA. RI Zhang, Xi-Cheng/G-1306-2016 OI Zhang, Xi-Cheng/0000-0003-3721-1357 NR 0 TC 0 Z9 0 U1 1 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 SEP PY 2003 VL 43 IS 9 MA 4 BP 1017 EP 1017 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 714PA UT WOS:000184921600013 ER PT J AU Lathers, CM AF Lathers, CM TI Renal disease and head-out water immersion: Insights for space flight. SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Meeting Abstract CT 32nd Annual Meeting of the American-College-of-Clinical-Pharmacology CY SEP 21-23, 2003 CL TAMPA, FLORIDA SP Amer Coll Clin Pharmacol C1 US FDA, Ctr Vet Med, Off Director, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 SEP PY 2003 VL 43 IS 9 MA 12 BP 1018 EP 1018 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 714PA UT WOS:000184921600018 ER PT J AU Lathers, CM Lohr, JW AF Lathers, CM Lohr, JW TI Head-out water immersion. Lessons learned for hypertension and space flight. SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Meeting Abstract CT 32nd Annual Meeting of the American-College-of-Clinical-Pharmacology CY SEP 21-23, 2003 CL TAMPA, FLORIDA SP Amer Coll Clin Pharmacol C1 US FDA, Ctr Vet Med, Rockville, MD 20857 USA. VA Med Ctr, Buffalo Inst Med Res, Buffalo, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 SEP PY 2003 VL 43 IS 9 MA 11 BP 1018 EP 1018 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 714PA UT WOS:000184921600017 ER PT J AU Koehler, SA Wecht, CH Schraeder, PL Lathers, CM AF Koehler, SA Wecht, CH Schraeder, PL Lathers, CM TI One-year postmortem examination of epilepsy deaths in Allegheny County Pennsylvania in 2001. SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Meeting Abstract CT 32nd Annual Meeting of the American-College-of-Clinical-Pharmacology CY SEP 21-23, 2003 CL TAMPA, FLORIDA SP Amer Coll Clin Pharmacol C1 Allegheny Cty, Off Coroner, Pittsburgh, PA USA. Drexel Univ, Dept Neurol, Philadelphia, PA 19104 USA. US FDA, Ctr Vet Med, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 SEP PY 2003 VL 43 IS 9 MA 45 BP 1025 EP 1025 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 714PA UT WOS:000184921600047 ER PT J AU Kenna, L Jarugula, V Sun, H Parekh, A Chatterjee, D AF Kenna, L Jarugula, V Sun, H Parekh, A Chatterjee, D TI QT interval correction methods: Experience with two clinical trials using active controls. SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Meeting Abstract CT 32nd Annual Meeting of the American-College-of-Clinical-Pharmacology CY SEP 21-23, 2003 CL TAMPA, FLORIDA SP Amer Coll Clin Pharmacol C1 US FDA, CDER, Off Clin Pharm & Biopharm, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 SEP PY 2003 VL 43 IS 9 MA 99 BP 1037 EP 1037 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 714PA UT WOS:000184921600093 ER PT J AU Al-Fayoumi, SI Sun, H AF Al-Fayoumi, SI Sun, H TI Pharmacokinetic/pharmacodynamic modeling & simulation in opiate-induced respiratory depression SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Meeting Abstract CT 32nd Annual Meeting of the American-College-of-Clinical-Pharmacology CY SEP 21-23, 2003 CL TAMPA, FLORIDA SP Amer Coll Clin Pharmacol C1 US FDA, Ctr Drug Evaluat & Res, Off Clin Pharmacol & Biopharmaceut, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 SEP PY 2003 VL 43 IS 9 MA 105 BP 1039 EP 1039 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 714PA UT WOS:000184921600099 ER PT J AU De Jesus, AJ Whiting, RC AF De Jesus, AJ Whiting, RC TI Thermal inactivation, growth, and survival studies of Listeria monocytogenes strains belonging to three distinct genotypic lineages SO JOURNAL OF FOOD PROTECTION LA English DT Article ID MULTILOCUS ENZYME ELECTROPHORESIS; FRAGMENT-LENGTH-POLYMORPHISM; HEAT-RESISTANCE AB Twenty-one Listeria monocytogenes strains belonging to three different genotypic lineages were evaluated for differences between lineages and between individual strains with respect to thermal inactivation, growth, and survival. Three sets of heat inactivation conditions (60degreesC, pH 6.0, and 0.5 M lactate; 55degreesC, pH 6.0, and 0.5 M lactate; and 50degreesC, pH 4.0, and 0.5 M lactate) were used on strains grown in modified brain heart infusion (BHI) broth with and without glucose. Two sets of growth conditions (35degreesC, pH 6.5, and 0.1 M lactate and 5degreesC, pH 6.5, and 0.1 M lactate) were used with modified BHI broths to determine lag phases and exponential growth rates. Two sets of conditions (28degreesC, pH 4.0, and I M lactate and 28degreesC, pH 4.5, and 0.5 M lactate) were used with modified BHI broth to determine survival times (D-values). Thermal inactivation D-values were consistently lowest for lineage 111, but differences were not significant for any set of conditions tested. Some significant differences were observed between lineages with respect to some of the growth and survival conditions tested. Extensive strain-to-strain variation was observed for all parameters tested. Average coefficients of variation for the thermal inactivation, growth, and survival studies were 0.31, 0.18, and 0.26, respectively. Strain-to-strain variations were approximately equal to the uncertainties associated with the analytical procedures. The results obtained indicate a diversity among strains encountered in food processing that must be accounted for in process calculations and risk assessments. C1 US FDA, Ctr Safety & Appl Nutr, College Pk, MD 20740 USA. RP De Jesus, AJ (reprint author), US FDA, Ctr Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. NR 19 TC 51 Z9 52 U1 1 U2 4 PU INT ASSOC FOOD PROTECTION PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD SEP PY 2003 VL 66 IS 9 BP 1611 EP 1617 PG 7 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 719PV UT WOS:000185213000015 PM 14503714 ER PT J AU Seo, KH Brackett, RE Valentin-Bon, IE Holt, PS AF Seo, KH Brackett, RE Valentin-Bon, IE Holt, PS TI Comparison of homogenization methods for recovering Salmonella enteritidis from eggs SO JOURNAL OF FOOD PROTECTION LA English DT Article ID IRON SUPPLEMENTATION; RAPID DETECTION; POOLS; HENS AB For Salmonella Enteritidis (SE) detection, shell eggs have been homogenized with stomachers, with electric blenders, and by hand massaging. However, to date, there have been no published reports addressing whether the method of homogenization affects the recovery of SE from raw eggs. Three inoculum levels (10, 126, and 256 SE cells per pool of 10 eggs) were used to conduct three experiments. The 10-egg pools were homogenized by one of four homogenization methods-mechanical stomaching, electric blending, hand massaging, and hand stirring-for 30 s. The homogenized eggs were then incubated at 37degreesC, and SE colonies were enumerated after 24 and 48 h of incubation. After 24 h of incubation, no SE was recovered from egg samples from stomached or electrically blended pools inoculated with <10 cells, while levels of 10(6) CFU/ml were found for samples from whipped or hand-massaged pools inoculated with <10 cells. Similarly, after 24 h of incubation, the numbers of SE cells recovered from hand-massaged or hand-stirred egg pools inoculated with 126 cells were significantly larger than the numbers recovered from stomached or electrically blended egg pools inoculated with 126 cells. The number of SE cells recovered from samples homogenized with a blender was still significantly smaller than the numbers recovered from samples homogenized by the other three methods when the inoculum level was increased to 256 CFU per pool. However, the SE count for all samples approached 9 log(10) CFU/ml after 48 h of incubation. It is concluded that the detection of small SE populations in shell egg samples could be improved with the use hand massaging and hand stirring for homogenization. C1 US FDA, Ctr Food Safety & Appl Nutr, Off Plant & Dairy Foods & Beverages, College Pk, MD 20740 USA. USDA ARS, SE Poultry Res Lab, Athens, GA 30605 USA. RP Seo, KH (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Plant & Dairy Foods & Beverages, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. NR 16 TC 6 Z9 6 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 SEP PY 2003 VL 66 IS 9 BP 1666 EP 1669 PG 4 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 719PV UT WOS:000185213000023 PM 14503722 ER PT J AU Valentin-Bon, IE Brackett, RE Seo, KH Hammack, TS Andrews, WH AF Valentin-Bon, IE Brackett, RE Seo, KH Hammack, TS Andrews, WH TI Preenrichment versus direct selective agar plating for the detection of Salmonella enteritidis in shell eggs SO JOURNAL OF FOOD PROTECTION LA English DT Article ID RELATIVE EFFECTIVENESS; CONTAMINATED EGGS; GROWTH; HENS; RECOVERY; ALBUMIN; POOLS; STRAINS; MULTIPLICATION; STORAGE AB The relative effectiveness of two methods for the recovery of Salmonella Enteritidis (SE) from jumbo and medium shell eggs was compared. The first method used in the comparison consisted of a preenrichment of the sample, and the second method was developed by the U.S. Department of Agriculture's Animal and Plant Health Inspection Service (APHIS). Three bulk lots of blended, pooled eggs, each containing 220 liquid whole eggs that were thoroughly mixed manually were artificially inoculated with different levels of SE cells between approximately 10(0) and 10(3) CFU/ml. Twenty samples containing the contents of approximately 10 eggs each (by weight) were withdrawn from each of the inoculated bulk lots and incubated for 4 days at room temperature (ca. 23degreesC). For the APHIS method, each sample was cultured by direct plating onto brilliant green (BG), brilliant green with novobiocin (BGN), xylose lysine desoxycholate (XLD), and xylose lysine agar Tergitol 4 (XLT4) agars. For the preenrichment method, 25-g portions from each pool were enriched in modified tryptic soy broth with 30 mg/liter of FeSO4. After 24 h of incubation, the preenrichments were subcultured to tetrathionate and Rappaport-Vassiliadis broths, and streaked to 13G, BGN, bismuth sulfite, XLD, and XLT4 agar plates. SE isolates were confirmed biochemically and serologically. In all of the experiments, the preenrichment method recovered significantly more SE isolates (P < 0.05) of all the phage types and inoculum levels than did the APHIS method. From a total of 539 jumbo egg test portions analyzed, 381 (71%) were SE-positive by the preenrichment method and 232 (43%) were positive by the APHIS method. From a total of 360 medium egg test portions analyzed, 223 (62%) were SE-positive by the preenrichment method and 174 (48%) were positive by the APHIS method. The preenrichment method provided greater sensitivity for the isolation of SE in contaminated egg slurries than did the APHIS method. C1 US FDA, Ctr Food Safety & Appl Nutr, Off Plant & Dairy Food & Beverages, College Pk, MD 20740 USA. RP Valentin-Bon, IE (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Plant & Dairy Food & Beverages, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. NR 29 TC 11 Z9 14 U1 1 U2 8 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 SEP PY 2003 VL 66 IS 9 BP 1670 EP 1674 PG 5 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 719PV UT WOS:000185213000024 PM 14503723 ER PT J AU Benner, RA Staruszkiewicz, WF Rogers, PL Otwell, WS AF Benner, RA Staruszkiewicz, WF Rogers, PL Otwell, WS TI Evaluation of putrescine, cadaverine, and indole as chemical indicators of decomposition in Penaeid shrimp SO JOURNAL OF FOOD SCIENCE LA English DT Article DE putrescine; cadaverine; indole; shrimp; decomposition ID TEMPERATURE; STORAGE AB Putrescine, cadaverine, and indole were evaluated as chemical indicators of decomposition for wild and aquacultured Penaeid shrimp decomposed under controlled conditions at 0, 12, 24, and 36 degreesC and for commercial shrimp samples collected and evaluated by Food and Drug Administration experts. Putrescine, cadaverine, and indole levels increased with time as the temperatures of decomposition increased. Putrescine, at a reject level of 3 ppm, confirmed sensory evidence of decomposition more frequently than did cadaverine or indole at reject levels of 3 ppm or 25 mug/100 g, respectively. Based on this research, putrescine appears to be the most comprehensive chemical indicator for decomposition in fresh or frozen Penaeid shrimp studied to date. C1 US FDA, Washington Seafood Lab, Beltsville Res Facil, Laurel, MD 20708 USA. Univ Florida, Aquat Food Prod Lab, Gainesville, FL USA. RP Benner, RA (reprint author), US FDA, Washington Seafood Lab, Beltsville Res Facil, 8501 Muirkirk Rd,HFS-426, Laurel, MD 20708 USA. NR 12 TC 8 Z9 8 U1 1 U2 3 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 SEP PY 2003 VL 68 IS 7 BP 2178 EP 2185 DI 10.1111/j.1365-2621.2003.tb05743.x PG 8 WC Food Science & Technology SC Food Science & Technology GA 725BY UT WOS:000185523900008 ER PT J AU Jakubzick, C Choi, ES Joshi, BH Keane, MP Kunkel, SL Puri, RK Hogaboam, CM AF Jakubzick, C Choi, ES Joshi, BH Keane, MP Kunkel, SL Puri, RK Hogaboam, CM TI Therapeutic attenuation of pulmonary fibrosis via targeting of IL-4- and IL-13-responsive cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID INDUCED LUNG FIBROSIS; MONOCYTE CHEMOATTRACTANT PROTEIN-1; INTERLEUKIN-13 RECEPTOR ALPHA-2; ALLERGIC AIRWAY DISEASE; GENE-EXPRESSION; ALVEOLAR MACROPHAGES; SIGNAL-TRANSDUCTION; GROWTH-FACTOR; KNOCKOUT MICE; PERIBRONCHIAL FIBROSIS AB Severe forms of idiopathic interstitial pneumonia (IIP), such as usual interstitial pneumonia, can be impervious to modern steroid and immunosuppressive treatment regimens, thereby emphasizing the need for novel effective therapies. Consequently, research attention has been directed toward understanding the cytokine networks that may affect fibroblast activation and, hence, the progression of certain IIPs. This led us to investigate whether the specific targeting of resident lung cells responsive to IL-4 and IL-13 exerted a therapeutic effect in an experimental model of IIP, namely the bleomycin-induced model of pulmonary fibrosis. IL-4, IL-13, and their corresponding receptor subunits, IL-4Ralpha, IL-13Ralpha1, and IL-13Ralpha2, were maximally expressed at the mRNA and protein levels in whole lung samples on day 21 or 28 after an intratracheal bleomycin challenge. The intranasal administration of an IL-13 immunotoxin chimeric molecule (IL13-PE) from days 21-28, but not for 1-wk periods at earlier times, after bleomycin challenge had a significant therapeutic effect on histological and biochemical parameters of bleomycin-induced pulmonary fibrosis compared with the control group. The intranasal IL13-PE therapy significantly reduced the numbers of IL-4 and IL-13 receptor-positive mononuclear cells and macrophages and the levels of profibrotic cytokine and chemokine in the lungs of bleomycin-challenged mice on day 28. Thus, this study demonstrates that IL-4- and/or IL-13-binding cells are required for the maintenance of pulmonary fibrosis induced by bleomycin and highlights the importance of further investigation of antifibrotic therapeutics that target these cells during pulmonary fibrosis. C1 Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI 48109 USA. Univ Calif Los Angeles, Dept Med, Div Pulm & Crit Care Med, Sch Med, Los Angeles, CA 90095 USA. US FDA, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Hogaboam, CM (reprint author), Univ Michigan, Sch Med, Dept Pathol, Room 5214,Med Sci 1,1301 Catherine Rd, Ann Arbor, MI 48109 USA. RI hogaboam, cory /M-3578-2014 FU NHLBI NIH HHS [P50 HL 56402-04] NR 77 TC 76 Z9 78 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 1 PY 2003 VL 171 IS 5 BP 2684 EP 2693 PG 10 WC Immunology SC Immunology GA 715KM UT WOS:000184970900063 PM 12928422 ER PT J AU He, Y Imam, SZ Dong, ZJ Jankovic, J Ali, SF Appel, SH Le, WD AF He, Y Imam, SZ Dong, ZJ Jankovic, J Ali, SF Appel, SH Le, WD TI Role of nitric oxide in rotenone-induced nigro-striatal injury SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE dopamine; nigro-striatum; nitric oxide; Parkinson's disease; rotenone ID PARKINSONS-DISEASE; DOPAMINERGIC-NEURONS; ELECTRON-TRANSPORT; SYNTHASE PROTECTS; MPTP TOXICITY; DEGENERATION; INHIBITION; EXPOSURE; PEROXYNITRITE; EXPRESSION AB Rotenone, a widely used pesticide, causes a syndrome in rats that mimics, both behaviorally and pathologically, the symptoms of Parkinson's disease. The present study evaluated the role of nitric oxide in rotenone-induced nigro-striatal injury. After administration of rotenone in rats for 40 days, there was a moderate but significant injury of the nigro-striatal pathway indicated by a 47% decrease in striatal dopamine levels and a 28% loss of substantia nigra tyrosine hydroxylase-immunopositive neurons. Furthermore, a significant (37%) increase in the number of cells positive for nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) in the striatum was observed, accompanied by a 83% increase in nitric oxide synthase (NOS) activity and a significant increase in the production of 3-nitrotyrosine (3-NT). There was a significant increase (45%) in the optical density of NADPH-d staining and an increase (72%) in NOS activity in the substantia nigra. Moreover, administration of the neuronal NOS inhibitor 7-nitroindazole significantly attenuated the increased NOS activity and 3-NT production, and provided significant protection against rotenone-induced nigro-striatal injury. Our data suggest that chronic rotenone administration can lead to significant injury to the nigro-striatal system, mediated by increased generation of nitric oxide. C1 Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA. US FDA, Natl Ctr Toxicol Res, Neurochem Lab, Div Neurotoxicol, Jefferson, AR 72079 USA. Third Mil Med Univ, Dept Toxicol, Chongqing, Peoples R China. RP Le, WD (reprint author), Baylor Coll Med, Dept Neurol, 1 Baylor Plaza, Houston, TX 77030 USA. EM weidongl@bcm.tmc.edu FU NINDS NIH HHS [NS 40370-01] NR 40 TC 89 Z9 96 U1 0 U2 4 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD SEP PY 2003 VL 86 IS 6 BP 1338 EP 1345 DI 10.1046/j.1471-4159.2003.01938.x PG 8 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 764ZQ UT WOS:000188241400003 PM 12950443 ER PT J AU Blakely, S Herbert, A Collins, M Jenkins, M Mitchell, G Grundel, E O'Neill, KR Khachik, F AF Blakely, S Herbert, A Collins, M Jenkins, M Mitchell, G Grundel, E O'Neill, KR Khachik, F TI Lutein interacts with ascorbic acid more frequently than with alpha-tocopherol to alter biomarkers of oxidative stress in female Zucker obese rats SO JOURNAL OF NUTRITION LA English DT Article; Proceedings Paper CT Experimental Biology 2002 Meeting CY APR 20-24, 2002 CL NEW ORLEANS, LOUISIANA DE obesity; antioxidants; carotenoids; lutein; ascorbic acid; alpha-tocopherol ID BETA-CAROTENE; MACULAR PIGMENT; VITAMIN-C; ANTIOXIDANT; ZEAXANTHIN; SERUM; DIET; TISSUES; PLASMA; BIOAVAILABILITY AB The influence of dietary lutein, with and without moderate amounts of vitamin C (VC) or vitamin E (VE), on biomarkers of oxidative stress was examined in rats. Nine groups of immature Zucker obese (fa/fa) and lean female rats (8/group) consumed ad libitum for 8 wk the AIN-93G diet (Control) to which was added either dl-alpha-tocopherol acetate (VE) at 0.60 mg/kg or ascorbic acid (VC) at 0.75 mg/kg diet. Each of these diets contained lutein oil (FloraGlo) at 0.5 (Lut0.5) or 1.0 (Lut1.0) mg/kg diet. Weight gain, food efficiency and relative liver weight were higher in obese than in lean rats. Although liver malondialdehyde (MDA) concentrations were significantly higher in obese than in lean rats, levels were significantly lower in obese rats fed VE, VE-Lut and VC-Lut0.5 compared with other obese groups. The accumulation of alpha-tocopherol in liver was 6- and 3-times; greater in the VE and VE-Lut1.0 groups, respectively, compared with the obese and lean control groups. Lutein reduced the activity of superoxide dismutase (SOD) in obese rats, independent of VC or VE, and raised the activity of glutathione peroxidase to higher levels in lean rats when combined with VC. Plasma insulin levels were dramatically higher in obese compared with lean rats, but significantly lower in obese rats fed VC-Lut0.5, VE-Lut1.0 and Lut1.0 compared with the Control group. These results suggest that lutein independently reduces the activity of SOD and alters more biomarkers of oxidative stress when combined with vitamin C than with vitamin E, and that vitamin E reduces liver lipid peroxidation in obese rats when the accumulation of liver alpha-tocopherol is very high. C1 US FDA, College Pk, MD 20740 USA. Ctr Dis Control & Prevent, Atlanta, GA 30341 USA. Univ Calif Berkeley, Dept Mol & Biochem Nutr, Berkeley, CA 94704 USA. Univ Maryland, Dept Chem, College Pk, MD 20742 USA. RP Blakely, S (reprint author), US FDA, College Pk, MD 20740 USA. RI Khachik, Frederick/C-5055-2009 NR 44 TC 14 Z9 15 U1 0 U2 3 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD SEP PY 2003 VL 133 IS 9 BP 2838 EP 2844 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 720KC UT WOS:000185259100024 PM 12949374 ER PT J AU Innis, SM Davidson, AGF Chen, A Dyer, R Melnyk, S James, SJ AF Innis, SM Davidson, AGF Chen, A Dyer, R Melnyk, S James, SJ TI Increased plasma homocysteine and S-adenosylhomocysteine and decreased methionine is associated with altered phosphatidylcholine and phosphatidylethanolamine in cystic fibrosis SO JOURNAL OF PEDIATRICS LA English DT Article ID FATTY-ACID DEFICIENCY; CHOLINE DEFICIENCY; N-METHYLTRANSFERASE; ADENOSYLMETHIONINE; BIOSYNTHESIS; REQUIREMENT; NUTRITION; SECRETION; LIVER; RATS AB Objective We used a novel approach based on the intersection of phospholipid and methionine metabolism at the S-adenosylmethionine (SAM)-dependent methylation of phosphatidylethanolamine (PE) to study potential alterations in phospholipid metabolism in children with cystic fibrosis (CF). Methyl groups from methionine via SAM are used for sequential methylation of PE to form phosphatidylcholine (PC) with the generation of S-adenosylhomocysteine (SAH) and homocysteine. Study design Plasma phospholipids and methionine metabolites and plasma and red blood cell phospholipid fatty acids were determined in 53 children with CF and 18 control children. Results Plasma methionine and the PC/PE ratio was lower and homocysteine, SAH, and PE were higher in children with CF than in control children (P < .001). Plasma methionine was inversely (P < .05) and SAH and homocysteine were positively (P < .001) correlated with the plasma PE. Docosahexaenoic acid (22:6n-3) was significantly lower in plasma phospholipids and triglycerides and in red blood cell PC and PE of children with CF than in control children (P < .05). Conclusions These studies demonstrate that methionine metabolism is altered and associated with alteration of the plasma PC/PE ratio in CF. Altered phospholipid and methionine metabolism may contribute to the clinical complications associated with CF. C1 Univ British Columbia, Dept Pediat, Vancouver, BC V6T 1W5, Canada. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Innis, SM (reprint author), British Colombia Res Inst Childrens & Womens Hlth, Room 179,950 W 28th Ave, Vancouver, BC V5Z 4H4, Canada. EM sinnis@interchange.ubc.ca NR 33 TC 30 Z9 31 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD SEP PY 2003 VL 143 IS 3 BP 351 EP 356 DI 10.1067/S0022-3476(03)00326-3 PG 6 WC Pediatrics SC Pediatrics GA 728GV UT WOS:000185710200015 PM 14517519 ER PT J AU Drum, BA AF Drum, BA TI Aberration analyses needed for FDA evaluation of safety and effectiveness of wavefront-guided refractive surgical devices SO JOURNAL OF REFRACTIVE SURGERY LA English DT Article; Proceedings Paper CT 4th International Congress of the Wavefront Sensing and Aberration Free Refractive Correction CY FEB 14-16, 2003 CL SAN FRANCISCO, CALIFORNIA AB PURPOSE: Manufacturers of refractive surgical lasers are seeking Food and Drug Administration (FDA) approval for refractive surgery based on wavefront measurements rather than manifest refractions. This article draws attention to the need for better understanding of the relationship between aberrations and visual function and better testing methods for evaluating safety and effectiveness of wavefront-guided refractive surgery. METHODS: Before U.S. market approval for a new medical device, the FDA must determine whether the manufacturer has provided reasonable assurance that the device is safe and effective for its intended use, based on valid scientific evidence. The issues discussed here are based on FDA reviewers' experiences in evaluating Investigational Device Exemption (IDE) and Premarket Approval (PMA) applications for wavefront-guided refractive lasers. RESULTS: Even an optimal wavefront correction can provide only a marginally greater visual function benefit than a conventional spherocylindrical correction in a normal eye. Actual benefits are even smaller or nonexistent because variability from uncontrollable sources (eg, healing, aging, accommodation, pupil size, or ocular biomechanical effects) are typically larger than the errors treated. The effects of higher order aberrations and aberration changes on visual function are complex and poorly understood. CONCLUSIONS: The FDA's need for better tools to assess safety and effectiveness of wavefront-guided refractive surgery has stimulated major research efforts within the vision, ophthalmic, and optometric research communities. More research is needed to better understand the relationship between aberrations and visual function, and to be able to predict the visual effects of specific aberration changes in individual eyes. This research would have been more appropriately done before rather than after clinical trials for wavefront-guided refractive lasers. C1 US FDA, CDRH, ODE, DOED, Rockville, MD 20850 USA. RP Drum, BA (reprint author), US FDA, CDRH, ODE, DOED, 9200 Corp Blvd,HFZ-460, Rockville, MD 20850 USA. NR 3 TC 6 Z9 6 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 1081-597X J9 J REFRACT SURG JI J. Refractive Surg. PD SEP-OCT PY 2003 VL 19 IS 5 BP S588 EP S591 PG 4 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 725WH UT WOS:000185565000014 PM 14518749 ER PT J AU Gallas, BD Barrett, HH AF Gallas, BD Barrett, HH TI Validating the use of channels to estimate the ideal linear observer SO JOURNAL OF THE OPTICAL SOCIETY OF AMERICA A-OPTICS IMAGE SCIENCE AND VISION LA English DT Article ID DETECTION PERFORMANCE; IMAGE QUALITY; OBJECTIVE ASSESSMENT; HOTELLING-OBSERVER; 2-COMPONENT NOISE; SYSTEMS; MODEL; DISCRIMINATION; VARIABILITY; EFFICIENCY AB Image quality can be objectively defined according to how well an observer can perform a task of practical interest given the image. We review a practical model observer for the signal-detection task. The ideal observer for this task is a function of the image probability distributions, which are multidimensional and complicated. This observer is often too difficult to derive or estimate. An alternative to the ideal observer is the ideal linear observer, which can still be unmanageable. Our alternative is the ideal linear observer constrained to a small set of channels: the channelized-Hotelling observer. (C) 2003 Optical Society of America. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. Univ Arizona, Dept Radiol, Tucson, AZ 85724 USA. Univ Arizona, Ctr Opt Sci, Tucson, AZ 85724 USA. RP Gallas, BD (reprint author), US FDA, Ctr Devices & Radiol Hlth, HFZ-142,12720 Twinbrook Pkwy, Rockville, MD 20857 USA. OI Gallas, Brandon/0000-0001-7332-1620 FU NIBIB NIH HHS [P41 EB002035, R37 EB000803] NR 48 TC 86 Z9 86 U1 0 U2 3 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 0740-3232 J9 J OPT SOC AM A JI J. Opt. Soc. Am. A-Opt. Image Sci. Vis. PD SEP PY 2003 VL 20 IS 9 BP 1725 EP 1738 DI 10.1364/JOSAA.20.001725 PG 14 WC Optics SC Optics GA 716EV UT WOS:000185016600005 PM 12968645 ER PT J AU Laassri, M Chizhikov, V Mikheev, M Shchelkunov, S Chumakov, K AF Laassri, M Chizhikov, V Mikheev, M Shchelkunov, S Chumakov, K TI Detection and discrimination of orthopoxviruses using microarrays of immobilized oligonucleotides SO JOURNAL OF VIROLOGICAL METHODS LA English DT Article DE rapid identification; nucleic acids diagnostics; variola virus; monkeypox virus; chickenpox virus; vaccinia; biodefense ID VARICELLA-ZOSTER VIRUS; HUMAN MONKEYPOX; SMALLPOX; IDENTIFICATION; PROTEINS; DNA; DIFFERENTIATION; PCR; TRANSACTIVATOR; POLYMORPHISM AB Variola virus (VARV), causing smallpox, is a potential biological weapon. Methods to detect VARV rapidly and to differentiate it from other viruses causing similar clinical syndromes are needed urgently. We have developed a new micro array-based method that detects simultaneously and discriminates four orthopoxvirus (OPV) species pathogenic for humans (variola, monkeypox, cowpox, and vaccinia viruses) and distinguishes them from chickenpox virus (varicella-zoster virus or VZV). The OPV gene C23L/B29R, encoding the CC-chemokine binding protein, was sequenced for 41 strains of seven species of orthopox viruses obtained from different geographical regions. Those C23L/B29R sequences and the ORF 62 sequences from 13 strains of VZV (selected from GenBank) were used to design oligonucleotide probes that were immobilized on an aldehyde-coated glass surface (a total of 57 probes). The microchip contained several unique 13-21 bases long oligonucleotide probes specific to each virus species to ensure redundancy and robustness of the assay. A region approximately 1100 bases long was amplified from samples of viral DNA and fluorescently labeled with Cy5-modified dNTPs, and single-stranded DNA was prepared by strand separation. Hybridization was carried out under plastic coverslips, resulting in a fluorescent pattern that was quantified using a confocal laser scanner. 49 known and blinded samples of OPV DNA, representing different OPV species, and two VZV strains were tested. The oligonucleotide microarray hybridization technique identified reliably and correctly all samples. This new procedure takes only 3 h, and it can be used for parallel testing of multiple samples. (C) 2003 Published by Elsevier B.V. C1 US FDA, Lab Method Dev, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. State Res Ctr Virol & Biotechnol Vector, Dept Mol Biol Genomes, Koltsov 630559, Novosibirsk Reg, Russia. RP Chumakov, K (reprint author), US FDA, Lab Method Dev, Ctr Biol Evaluat & Res, 1401 Rockville Pike,HFM-470, Rockville, MD 20852 USA. NR 36 TC 60 Z9 64 U1 3 U2 4 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 SEP PY 2003 VL 112 IS 1-2 BP 67 EP 78 DI 10.1016/S0166-0934(03)00193-9 PG 12 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Virology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Virology GA 723HL UT WOS:000185426900008 PM 12951214 ER PT J AU Koller, EA Cross, JT Doraiswamy, PM Malozowski, SN AF Koller, EA Cross, JT Doraiswamy, PM Malozowski, SN TI Pancreatitis associated with atypical antipsychotics: From the Food and Drug Administration's MedWatch surveillance system and published reports SO PHARMACOTHERAPY LA English DT Review ID CLOZAPINE; OLANZAPINE; SEVERITY AB Study Objective. To investigate the relative numbers and clinical characteristics of pancreatitis in patients treated with the atypical antipsychotic agents, clozapine, olanzapine, and risperidone, versus the conventional neuroleptic, haloperidol. Design. Pharmacovigilance study of pooled, spontaneously reported adverse events. Setting. Government-affiliated drug evaluation center. Patients. One hundred ninety-two patients who developed pancreatitis during treatment with one or more antipsychotic agents. Intervention. Patients were identified with the Food and Drug Administration's MedWatch surveillance program and a MEDLINE search. Measurements and Main Results. Most cases of pancreatitis occurred within 6 months after the start of therapy with one or more antipsychotic agents. Of the reports of pancreatitis occurring in conjunction with these drugs, 40%, 33%, 16%, and 12% were in patients receiving treatment with clozapine, olanzapine, risperidone, and haloperidol, respectively In 50% of the patients receiving haloperidol, an atypical antipsychotic was listed as a concomitant drug. Valproate was administered concomitantly in 23% of patients. Hyperglycemia and acidosis, although uncommon, developed with all the drugs except haloperidol. Twenty-two patients died. In contrast to patients who developed pancreatitis while receiving an atypical antipsychotic, those who developed the disease while receiving haloperidol were women and tended to be older. Conclusion. The number of reports involving the three atypical antipsychotic agents and the relative paucity of reports involving haloperidol, despite its more extensive patient exposure, suggest that atypical antipsychotics may precipitate pancreatitis. However, the risk may not be the same with all agents; pancreatitis was reported most frequently with clozapine, followed by olanzapine, and then risperidone. The temporal relationship of the onset of pancreatitis with the start of drug therapy further supports a cause-and-effect relationship. C1 Ctr Drug Evaluat & Review Food & Drug Adm, Div Metab & Endocrine Drug Prod, Rockville, MD USA. Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Psychiat, Durham, NC 27710 USA. Natl Inst Diabet & Digest Dis, Clin Trials & Diabet Translat, NIH, Bethesda, MD USA. RP Doraiswamy, PM (reprint author), Duke Univ, Med Ctr, Dept Psychiat, Box 3018, Durham, NC 27710 USA. NR 32 TC 43 Z9 44 U1 0 U2 1 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 SEP PY 2003 VL 23 IS 9 BP 1123 EP 1130 DI 10.1592/phco.23.10.1123.32759 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 718KL UT WOS:000185144200006 PM 14524644 ER PT J AU Monday, SR Weagant, SD Feng, P AF Monday, SR Weagant, SD Feng, P TI Use of endogenous host plasmids for generation of Escherichia coli O157 : H7 and Shigella sonnei strains that stably express the green fluorescent protein SO PLASMID LA English DT Article DE GFR; transposon insertion; plasmids; control strains ID GENE-EXPRESSION; SEROTYPES; MARKER AB The gfp gene was manipulated from a commercially available, high copy vector into endogenous plasmids of Escherichia coli O15:H7 and Shigella sonnei to yield stable GFP strains that required neither high copy number for visualization nor antibiotics for stable maintenance of the phenotype. The GFP phenotype of these strains remained stable after repeated passages in media and conditions that enhance plasmid instability and loss from bacterial cells. These results demonstrate the utility of the endogenous plasmids in selectively marking bacteria without altering host cellular function or biochemical properties. Published by Elsevier Inc. C1 US FDA, Div Microbiol Studies, College Pk, MD 20740 USA. US FDA, Pacific Reg Lab, Bothell, WA 98021 USA. RP Monday, SR (reprint author), US FDA, Div Microbiol Studies, HFS-516,5100 Paint Branch Pkwy, College Pk, MD 20740 USA. NR 21 TC 2 Z9 2 U1 1 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0147-619X J9 PLASMID JI Plasmid PD SEP PY 2003 VL 50 IS 2 BP 161 EP 167 DI 10.1016/S0147-619X(03)00057-x PG 7 WC Genetics & Heredity; Microbiology SC Genetics & Heredity; Microbiology GA 717YV UT WOS:000185119100008 PM 12932742 ER PT J AU Herrmann, PC Gillespie, JW Charboneau, L Bichsel, VE Paweletz, CP Calvert, VS Kohn, EC Emmert-Buck, MR Liotta, LA Petricoin, EF AF Herrmann, PC Gillespie, JW Charboneau, L Bichsel, VE Paweletz, CP Calvert, VS Kohn, EC Emmert-Buck, MR Liotta, LA Petricoin, EF TI Mitochondrial proteome: Altered cytochrome c oxidase subunit levels in prostate cancer SO PROTEOMICS LA English DT Article DE cancer; cytochrome c oxidase; mitochondrial proteome; oxidative phosphorylation; prostate ID CELLS; ASSIGNMENT; SEQUENCE; TISSUE; GENES; RESPIRATION; PROGRESSION; EXPRESSION; METABOLISM AB to quantitatively analyze the ratios of mitochondrial encoded cytochrome c oxidase subunits to nuclear encoded cytochrome c oxidase subunits, and to correlate the ratios with malignant progression in human prostate tissue specimens. Cytochrome c oxidase subunits I-III comprise the catalytic core of the enzyme and are all synthesized from mitochondrial DNA. The remaining subunits (IV-VIII) are synthesized from cellular nuclear DNA. A significant (P < 0.001, 30/30 prostate cases) shift in the relative concentrations of nuclear encoded cytochrome c oxidase subunits IV, Vb, and Vic compared to mitochondrial encoded cytochrome c oxidase subunits I and II was noted during the progression of prostate cancer from normal epithelium through premalignant lesions to invasive carcinoma. Significantly, this shift was discovered to begin even in the premalignant stage. Reverse phase protein lysate array-based observations were corroborated with immunohistochemistry, and extended to a few human carcinomas in addition to prostate. This analysis points to a role for nuclear DNA encoded mitochondrial proteins in carcinogenesis; underscoring their potential as targets for therapy while highlighting the need for full characterization of the mitochondrial proteome. C1 NCI, US FDA, Clin Prote Program, Lab Pathol,NIH, Bethesda, MD 20892 USA. NCI, US FDA, Clin Prote Program, Div Therapeut Prod, Bethesda, MD 20892 USA. RP Herrmann, PC (reprint author), NCI, US FDA, Clin Prote Program, Lab Pathol,NIH, 10 Ctr Dr,Bldg 10,Room 2N212, Bethesda, MD 20892 USA. NR 32 TC 95 Z9 107 U1 0 U2 10 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 SEP PY 2003 VL 3 IS 9 BP 1801 EP 1810 DI 10.1002/pmic.200300461 PG 10 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 722YB UT WOS:000185404700020 PM 12973739 ER PT J AU Jacobs, A El Hage, J Hastings, K Jacobson-Kram, D Leighton, J Morse, D AF Jacobs, A El Hage, J Hastings, K Jacobson-Kram, D Leighton, J Morse, D TI Recommended tissue list for histopathologic examination SO TOXICOLOGIC PATHOLOGY LA English DT Letter C1 US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Jacobs, A (reprint author), US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. NR 1 TC 1 Z9 1 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD SEP-OCT PY 2003 VL 31 IS 5 BP 571 EP 571 DI 10.1080/01926230390229219 PG 1 WC Pathology; Toxicology SC Pathology; Toxicology GA 712GG UT WOS:000184789300014 PM 14692627 ER PT J AU Rios, M Srinivasan, K Wood, O Daniel, S Tomioka, K Williams, A Hewlett, I AF Rios, M Srinivasan, K Wood, O Daniel, S Tomioka, K Williams, A Hewlett, I TI West Nile Virus: Correlation between infectivity and RNA copy number SO TRANSFUSION LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Association-of-Blood-Banks CY NOV 01-14, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Assoc Blood Banks C1 CBER FDA, Bethesda, MD USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 2003 VL 43 IS 9 SU S BP 3A EP 3A PG 1 WC Hematology SC Hematology GA 716TT UT WOS:000185045700010 ER PT J AU Castilho, L Rios, M Rodrigues, A Pellegrino, J Costa, FF AF Castilho, L Rios, M Rodrigues, A Pellegrino, J Costa, FF TI Molecular study of partial D in polytransfused patients: Implications for transfusion practice SO TRANSFUSION LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Association-of-Blood-Banks CY NOV 01-14, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Assoc Blood Banks C1 UNICAMP, Hemocentro, Campinas, SP, Brazil. US FDA, DETTD, CBER, Bethesda, MD USA. UNICAMP, Hemocentro, Campinas, SP, Brazil. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 2003 VL 43 IS 9 SU S BP 95A EP 96A PG 2 WC Hematology SC Hematology GA 716TT UT WOS:000185045700324 ER PT J AU Rodrigues, A Rios, M Rosa, KA Toledo, RS Zanelli, AP Castilho, L AF Rodrigues, A Rios, M Rosa, KA Toledo, RS Zanelli, AP Castilho, L TI Molecular studies of weak D types in Brazilian blood donors SO TRANSFUSION LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Association-of-Blood-Banks CY NOV 01-14, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Assoc Blood Banks C1 US FDA, DETTD, CBER, Bethesda, MD USA. UNICAMP, Hemocentro, Campinas, SP, Brazil. Fdn Hemocentro Ribeirao Preto, Ribeirao Preto, Brazil. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 2003 VL 43 IS 9 SU S BP 96A EP 96A PG 1 WC Hematology SC Hematology GA 716TT UT WOS:000185045700326 ER PT J AU Bloom, E Arcidiacono, JA AF Bloom, E Arcidiacono, JA TI Role of adhesion molecules in human natural killer cell-mediated killing of porcine endothelial cells and their modulation by oxidation-reduction SO XENOTRANSPLANTATION LA English DT Meeting Abstract CT 7th Congress of the International-Xenotransplantation-Association CY 2003 CL GLASGOW, SCOTLAND SP Int Xenotransplantat Assoc C1 US FDA, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD SEP PY 2003 VL 10 IS 5 BP 511 EP 511 PG 1 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 717FB UT WOS:000185074800140 ER PT J AU Moon, H Ahn, H Kodell, RL Lee, JJ AF Moon, H Ahn, H Kodell, RL Lee, JJ TI Estimation of k for the poly-k test with application to animal carcinogenicity studies SO STATISTICS IN MEDICINE LA English DT Article DE bioassay; dose response; sacrifice; trend test; tumour incidence rate ID TUMOR-INCIDENCE RATE; TUMORIGENICITY EXPERIMENTS; FISCHER-344 RATS; TREND TEST; TIME; MORTALITY; MODELS; ONSET AB This paper extends the survival-adjusted Cochran-Armitage test in order to achieve improved robustness to a variety of tumour onset distributions. The Cochran-Armitage test is routinely applied for detecting a linear trend in the incidence of a tumour of interest across dose groups. To improve the robustness to the effects of differential mortality across groups, Bailer and Portier introduced the poly-3 test by a survival adjustment using a fractional weighting scheme for subjects not at full risk of tumour development. The performance of the poly-3 test depends on how closely it represents the correct specification of the time-at-risk weight in the data. Bailer and Portier further suggested that this test can be improved by using a general k reflecting the shape of the tumour onset distribution. In this paper, we propose a method to estimate k by equating the empirical lifetime tumour incidence rate obtained from the data based on the fractional weighting scheme to a separately estimated cumulative lifetime tumour incidence rate. This poly-k test with the statistically estimated k appears to perform better than the poly-3 test which is conducted without prior knowledge of the tumour onset distribution. Our simulation shows that the proposed method improves the robustness to various tumour onset distributions in addition to the robustness to the effects of mortality achieved by the poly-3 test. Large sample properties are shown via simulations to illustrate the consistency of the proposed method. The proposed methods are applied to analyse two real data sets. One is to find a dose-related linear trend on animal carcinogenicity, and the other is to test an effect of calorie restriction on experimental animals. Copyright (C) 2003 John Wiley Sons, Ltd. C1 US FDA, Div Biometry & Risk Assessment, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. SUNY Stony Brook, Dept Appl Math & Stat, Stony Brook, NY 11794 USA. Univ Texas, MD Anderson Canc Ctr, Dept Biostat, Houston, TX 77030 USA. RP Moon, H (reprint author), US FDA, Div Biometry & Risk Assessment, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. FU NCI NIH HHS [CA 77289-05, CA 91844] NR 20 TC 8 Z9 9 U1 1 U2 5 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD AUG 30 PY 2003 VL 22 IS 16 BP 2619 EP 2636 DI 10.1002/sim.1444 PG 18 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 708BJ UT WOS:000184546400006 PM 12898548 ER PT J AU Rafii, F Wynne, R Heinze, TM Paine, DD AF Rafii, F Wynne, R Heinze, TM Paine, DD TI Mechanism of metronidazole-resistance by isolates of nitroreductase-producing Enterococcus gallinarum and Enterococcus casseliflavus from the human intestinal tract SO FEMS MICROBIOLOGY LETTERS LA English DT Article DE metronidazole; Enterococcus; intestinal bacteria; nitroreductase ID GASTROINTESTINAL-TRACT; NITROIMIDAZOLE DRUGS; RISK-FACTORS; REDUCTION; STRAINS; METABOLISM; BACTEREMIA; SEQUENCE; FAECIUM AB Enterococcus casseliflavus and Enterococcus gallinarum strains resistant to metronidazole, nitrofurantoin and nitrofurazone were isolated from fecal samples of a patient with recurrent ulcerative colitis treated with metronidazole. Unlike other metronidazole-resistant bacteria, these strains produced nitroreductase but metabolized metronidazole to compounds that could not be detected by liquid chromatography with UV or mass spectral analysis. Metronidazole-susceptible Clostridium perfringens grew equally well in spent cultures of Enterococcus spp. incubated with or without metronidazole. These data indicate that the nitroreductases produced by these Enterococcus strains did not activate metronidazole to bactericidal metabolites and these bacteria may reduce the effectiveness of metronidazole. We have indirect evidence for an alternative pathway that results in metronidazole resistance. These strains of enterococcus had nitroreductase so resistance should not have occurred. (C) 2003 Federation of European Microbiological Societies. Published by Elsevier B.V. All rights reserved. C1 US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. US FDA, Natl Ctr Toxicol Res, Div Chem, Jefferson, AR 72079 USA. RP Rafii, F (reprint author), US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. NR 19 TC 23 Z9 24 U1 2 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1097 J9 FEMS MICROBIOL LETT JI FEMS Microbiol. Lett. PD AUG 29 PY 2003 VL 225 IS 2 BP 195 EP 200 DI 10.1016/S0378-1097(03)00513-5 PG 6 WC Microbiology SC Microbiology GA 720CR UT WOS:000185244400005 PM 12951241 ER PT J AU Niu, Y Murata, T Watanabe, K Kawakami, K Yoshimura, A Inoue, J Puri, RK Kobayashi, N AF Niu, Y Murata, T Watanabe, K Kawakami, K Yoshimura, A Inoue, J Puri, RK Kobayashi, N TI MIP-T3 associates with IL-13R alpha 1 and suppresses STAT6 activation in response to IL-13 stimulation SO FEBS LETTERS LA English DT Article DE interleukin-13 receptor-alpha 1binding protein-1; microtubule interacting protein that associates with tumor necrosis factor receptor associating factor-3; interleukin-13; interleukin-4; signal transducer and activator of transcription-6 ID REED-STERNBERG CELLS; SIGNAL-TRANSDUCTION; HODGKIN LYMPHOMA; INTERLEUKIN-13 RECEPTOR; AIRWAY HYPERREACTIVITY; B-CELLS; CYTOKINE; ASTHMA; IL-4R-ALPHA; EXPRESSION AB To unravel the mechanism of interleukin-13 (IL-13)specific functions, we sought to identify IL-13 receptor (IL-13R) binding molecules. A novel human IL-13Ralpha1 binding protein (IL13RBP1) has been identified using yeast tri-hybrid system, which was found to encode the same protein as MIP-T3 (microtubule interacting protein that associates with tumor necrosis factor (TNF) receptor associating factor-3 (TRAF3)). It constitutively associates with IL-13Ralpha1 and suppresses IL-4/13-induced signal transducer and activator of transcription-6 (STAT6) phosphorylation. IL-13-induced STAT6 activation was also inhibited as determined by dual luciferase assay and electrophoretic mobility shift assay (EMSA). These results suggest that MIP-T3 is a novel inhibitor of IL-13 signaling and may be a useful molecule in ameliorating various conditions in which IL-13 plays a central role. (C) 2003 Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies. C1 Nagasaki Univ, Grad Sch Biomed Sci, Div Mol Pharmacol Infect Agents, Nagasaki 8528521, Japan. US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Lab Mol Tumor Biol, Bethesda, MD 20892 USA. Kyushu Univ, Med Inst Bioregulat, Div Mol & Cellular Immunol, Higashi Ku, Fukuoka 8128582, Japan. Univ Tokyo, Inst Med Sci, Dept Canc Biol, Div Cell & Mol Biol, Tokyo 1088639, Japan. RP Murata, T (reprint author), Nagasaki Univ, Grad Sch Biomed Sci, Div Mol Pharmacol Infect Agents, Nagasaki 8528521, Japan. RI Yoshimura, Akihiko/K-5515-2013 NR 22 TC 11 Z9 12 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD AUG 28 PY 2003 VL 550 IS 1-3 BP 139 EP 143 DI 10.1016/S0014-5793(03)00860-3 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 716XM UT WOS:000185055000025 PM 12935900 ER PT J AU Kovalchuk, O Burke, P Arkhipov, A Kuchma, N James, SJ Kovalchuk, I Pogribny, I AF Kovalchuk, O Burke, P Arkhipov, A Kuchma, N James, SJ Kovalchuk, I Pogribny, I TI Genome hypermethylation in Pinus silvestris of Chernobyl - a mechanism for radiation adaptation? SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article DE Chernobyl; radiation; pine; stress response; global genome methylation ID TRANSGENIC PLANTS; METHYLATION; DNA; ARABIDOPSIS; IRRADIATION; ACCIDENT AB Adaptation is a complex process by which populations of organisms respond to long-term environmental stresses by permanent genetic change. Here we present data from the natural "open-field" radiation adaptation experiment after the Chernobyl accident and provide the first evidence of the involvement of epigenetic changes in adaptation of a eukaryote-Scots pine (Pinus silvestris), to chronic radiation exposure. We have evaluated global genome methylation of control and radiation-exposed pine trees using a method based on cleavage by a methylation-sensitive HpaII restriction endonuclease that leaves a 5' guanine overhang and subsequent single nucleotide extension with labeled [H-3] dCTP. We have found that genomic DNA of exposed pine trees was considerably hypermethylated. Moreover, hypermethylation appeared to be dependent upon the radiation dose absorbed by the trees. Such hypermethylation may be viewed as a defense strategy of plants that prevents genome instability and reshuffling of the hereditary material, allowing survival in an extreme environment. Further studies are clearly needed to analyze in detail the involvement of DNA methylation and other epigenetic mechanisms in the complex process of radiation stress and adaptive response. (C) 2003 Elsevier Science B.V. All rights reserved. C1 Univ Lethbridge, Dept Biol Sci, Lethbridge, AB T1K 3M4, Canada. Chernobyl Sci & Tech Ctr Int Res, UA-255620 Chernobyl, Ukraine. Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Kovalchuk, O (reprint author), Univ Lethbridge, Dept Biol Sci, 4401 Univ Dr, Lethbridge, AB T1K 3M4, Canada. NR 22 TC 89 Z9 112 U1 6 U2 36 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 AUG 28 PY 2003 VL 529 IS 1-2 BP 13 EP 20 DI 10.1016/S0027-5107(03)00103-9 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 720ED UT WOS:000185247800002 PM 12943916 ER PT J AU Yaron, S White, DG Matthews, KR AF Yaron, S White, DG Matthews, KR TI Characterization of an Escherichia coli O157 : H7 marR mutant SO INTERNATIONAL JOURNAL OF FOOD MICROBIOLOGY LA English DT Article DE E. coli O157 : H7; antibiotic resistance; mar operon ID MULTIPLE-ANTIBIOTIC-RESISTANCE; TYPHIMURIUM DT104; SALMONELLA; EFFLUX; LOCUS; EXPRESSION; REPRESSOR; OPERON; GENES; TETRACYCLINE AB One mechanism for generation of multiple antibiotic resistance in enteric bacteria involves the global regulatory system marRAB. The operon, when induced, encodes for resistance to structurally and functionally unrelated antibiotics. Exposure of Escherichia coli O157:H7 to increasing levels of chloramphenicol (CHL) resulted in survival of mutants that were resistant to the inducing agent and to tetracycline (TET), nalidixic acid (NAL), and ciprofloxacin (CIP). A mutant (RU122) that lacks MarR, the transcriptional repressor of the multiple antibiotic resistance (mar) operon, served as a genetic tool to study the role of MarR in growth of E. coli O157:H7. No significant difference (P>0.05) was observed in growth curves of the wild-type or the mutant under the conditions examined (rich and minimal media, acidic conditions, and temperatures from 24 to 42 C). A preconditioned mutant (indRU122; cultured for 17 h in Luria-Bertani (LB) containing chloramphenicol and then examined) exhibited greater growth under all treatments tested compared to the mutant. marCRAB of E. coli O157:H7 was sequenced and compared to other known mar sequences to determine divergence from other bacteria (Salmonella, Klebsiella, and Enterobacter). (C) 2003 Elsevier Science B.V. All rights reserved. C1 Rutgers State Univ, Dept Food Sci, Cook Coll, New Brunswick, NJ 08901 USA. US FDA, Ctr Vet Med, Div Anim & Food Microbiol, Laurel, MD 20708 USA. RP Matthews, KR (reprint author), Rutgers State Univ, Dept Food Sci, Cook Coll, 65 Dudley Rd, New Brunswick, NJ 08901 USA. EM matthews@aesop.rutgers.edu NR 30 TC 12 Z9 13 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-1605 J9 INT J FOOD MICROBIOL JI Int. J. Food Microbiol. PD AUG 25 PY 2003 VL 85 IS 3 BP 281 EP 291 DI 10.1016/S0168-1605(02)00547-0 PG 11 WC Food Science & Technology; Microbiology SC Food Science & Technology; Microbiology GA 709MU UT WOS:000184629600007 PM 12878386 ER PT J AU Dehouck, P Heyden, YV Smeyers-Verbeke, J Massart, DL Marini, RD Chiap, P Hubert, P Crommen, J Van de Wauw, W De Beer, J Cox, R Mathieu, G Reepmeyer, JC Voigt, B Estevenon, O Nicolas, A Van Schepdael, A Adams, E Hoogmartens, J AF Dehouck, P Heyden, YV Smeyers-Verbeke, J Massart, DL Marini, RD Chiap, P Hubert, P Crommen, J Van de Wauw, W De Beer, J Cox, R Mathieu, G Reepmeyer, JC Voigt, B Estevenon, O Nicolas, A Van Schepdael, A Adams, E Hoogmartens, J TI Interlaboratory study of a liquid chromatography method for erythromycin: determination of uncertainty SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article DE interlaboratory study; uncertainty; reproducibility; validation; erythromycin ID ACIDIC AQUEOUS-SOLUTIONS; DECOMPOSITION; SUBSTANCES AB Erythromycin is a mixture of macrolide antibiotics produced by Saccharopolyspora erythreas during fermentation. A new method for the analysis of erythromycin by liquid chromatography has previously been developed. It makes use of an Astec C-18 polymeric column. After validation in one laboratory, the method was now validated in an interlaboratory study. Validation studies are commonly used to test the fitness of the analytical method prior to its use for routine quality testing. The data derived in the interlaboratory study can be used to make an uncertainty statement as well. The relationship between validation and uncertainty statement is not clear for many analysts and there is a need to show how the existing data, derived during validation, can be used in practice. Eight laboratories participated in this interlaboratory study. The set-up allowed the determination of the repeatability variance, S-r(2) and the between-laboratory variance, S-L(2) Combination of S-r(2) and S-L(2) results in the reproducibility variance S-R(2). It has been shown how these data can be used in future by a single laboratory that wants to make an uncertainty statement concerning the same analysis. (C) 2003 Elsevier B.V. All rights reserved. C1 Katholieke Univ Leuven, Lab Farmaceut Chem & Anal Geneesmiddelen, B-3000 Louvain, Belgium. Free Univ Brussels, Brussels, Belgium. Univ Liege, Inst Pharm, Dept Pharmaceut Analyt Chem, Liege, Belgium. Wetenschappelijk Inst Volksgezondheid Louis Paste, Brussels, Belgium. Abbott Fermentat Prod, N Chicago, IL USA. Abbott Fermentat Prod, Barcelonata, PR USA. US FDA, Div Pharmaceut Anal, St Louis, MO USA. US Pharmacopeia, Res & Dev Lab, Rockville, MD USA. Univ Henri Poincare, Fac Pharm, Chim Analyt Lab, Nancy, France. RP Hoogmartens, J (reprint author), Katholieke Univ Leuven, Lab Farmaceut Chem & Anal Geneesmiddelen, Van Evenstr 4, B-3000 Louvain, Belgium. NR 15 TC 17 Z9 19 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR A JI J. Chromatogr. A PD AUG 22 PY 2003 VL 1010 IS 1 BP 63 EP 74 DI 10.1016/S0021-9673(03)01023-9 PG 12 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 715HX UT WOS:000184966900007 PM 14503816 ER PT J AU Roberts, R Rodriguez, W Murphy, D Crescenzi, T AF Roberts, R Rodriguez, W Murphy, D Crescenzi, T TI Pediatric drug labeling - Improving the safety and efficacy of pediatric therapies SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID CHILDREN AB Context Approximately 50% to 75% of drugs used in pediatric medicine have not been studied adequately to provide appropriate labeling information. In 1997, Congress passed the Food and Drug Administration Modernization Act (FDAMA), which encouraged pediatric drug development by providing an incentive in the form of additional marketing exclusivity. Objective To identify new drug labeling information from pediatric studies submitted to the FDA in response to written requests. Design and Setting Between July 1998 and April 1, 2002, the FDA requested studies on 242 drugs, and 53 drugs were granted exclusivity. As of January 2003, 49 drugs have dew labels. Data from the studies of the first 33 drugs with new pediatric information on the label as of April 2002 are included. Significant labeling information was analyzed along with baseline data and types of studies requested. Main Outcome Measures Safety data and pediatric information for labeled drugs. Results There were 53 studies for 33 drug products, 12 (23%)were evaluated for safety only; 23 (43%), safety and efficacy; and 18 (34%), pharmacokinetics and/or pharmacodynamics. Significant new dosing and/or safety information was identified for 12 (36%) drugs. New dosing information was determined for 7 of these drugs. Safety information was defined for gabapentin, propofol, sevoflurane, the combination of ribavirin and interferon alfa-2b, and various betamethasone-containing dermatologic preparations. There was a higher percentage of deaths reported with patients who received propofol compared with controls in the pediatric intensive care unit. Seizures were seen in patients administered sevoflurane. Patients receiving a combination of ribavirin and interferon alfa-2b experienced an increased incidence of suicidal ideation when compared with adults. An unexpectedly high percentage of those receiving betamethasone-containing dermatologic preparations had documented hypopituitary-ad renal axis suppression. Conclusion The FDAMA has stimulated pediatric clinical studies resulting in improved understanding of the pharmacokinetics of drugs prescribed in pediatric medicine, important dose changes, and improved safety for children taking certain drugs. C1 US FDA, Off Counter Terrorism & Pediat Drug Dev, Ctr Drug Evaluat & Res, Rockville, MD 20855 USA. RP Roberts, R (reprint author), US FDA, Off Counter Terrorism & Pediat Drug Dev, Ctr Drug Evaluat & Res, Metro Pk N 1,7520 Standish Pl,Room 220, Rockville, MD 20855 USA. NR 19 TC 162 Z9 171 U1 0 U2 4 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 AUG 20 PY 2003 VL 290 IS 7 BP 905 EP 911 DI 10.1001/jama.290.7.905 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 712ZE UT WOS:000184828800027 PM 12928467 ER PT J AU Kim, YH Engesser, KH Cerniglia, CE AF Kim, YH Engesser, KH Cerniglia, CE TI Two polycyclic aromatic hydrocarbon o-quinone reductases from a pyrene-degrading Mycobacterium SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE degradation; Mycobacterium; PAH o-quinone reductase; polycyclic aromatic hydrocarbons ID SP STRAIN PYR-1; DIHYDRODIOL DEHYDROGENASE; DEGRADATION; IDENTIFICATION; MUTAGENICITY; METABOLISM; OXIDATION; OXIDOREDUCTASE; BENZOPYRENE; CYTOTOXICITY AB Polycyclic aromatic hydrocarbon (PAH) o-quinone reductase (PQR) plays a crucial role in the detoxification of PAH o-quinones by reducing them to catechols. Two constitutive PQRs were found in cell extracts of a pyrene-degrading Mycobacterium sp. strain PYR100. The enzymes had an activity towards 9,10-phenanthrenequinone (PQ) and/or 4,5-pyrenequinone (PyQ), and the relative amounts varied with the pH of the culture media. PQR1, containing an FAD cofactor, was a monomer (20.1 kDa), and PQR2, with no flavin cofactor, was a homodimer (26.5 kDa subunits). There was no homology between the N-terminal sequences of PQR1 and PQR2. Dicumarol and quercetin inhibited PQR2 more strongly than PQR1. PQR1 had much lower specificity constants (k(cat)/K-m, 10(5) M-1 s(-1)) for menadione (0.80) and PQ (5.19) than PQR2 (13.9 for menadione and 176 for PQ). Additionally, PQR2 exhibited a broad substrate specificity with high specificity constants for 1,4-naphthalenequinone, 1,2-naphthalenequinone, and PyQ. (C) 2003 Elsevier Science (USA). All rights reserved. C1 US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Univ Stuttgart, Abt Biol Abluftreinigung, ISWA, D-7000 Stuttgart, Germany. RP Cerniglia, CE (reprint author), US FDA, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. NR 36 TC 38 Z9 38 U1 2 U2 10 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD AUG 15 PY 2003 VL 416 IS 2 BP 209 EP 217 DI 10.1016/S0003-9861(03)00297-2 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 712HY UT WOS:000184793300011 PM 12893299 ER PT J AU Slotkin, TA Freibaum, BD Tate, CA Thillai, I Ferguson, SA Cada, AM Seidler, FJ AF Slotkin, TA Freibaum, BD Tate, CA Thillai, I Ferguson, SA Cada, AM Seidler, FJ TI Long-lasting CNS effects of a short-term chemical knockout of ornithine decarboxylase during development: nicotinic cholinergic receptor upregulation and subtle macromolecular changes in adulthood SO BRAIN RESEARCH LA English DT Article DE alpha-difluoromethylornithine; cholinergic receptor; DNA, in developing brain; glial fibrillary acidic protein; nicotinic receptor; ornithine decarboxylase; polyamine ID FIBRILLARY ACIDIC PROTEIN; DEVELOPING RAT-BRAIN; ALPHA-DIFLUOROMETHYLORNITHINE; ACETYLCHOLINE-RECEPTOR; IRREVERSIBLE INHIBITOR; ADENYLYL-CYCLASE; IMPAIRED DEVELOPMENT; CEREBELLAR CORTEX; EXPOSURE; CHLORPYRIFOS AB Ornithine decarboxylase (ODC) and the polyamines play an essential role in brain cell replication and differentiation and polyamines also regulate the function of nicotinic acetylcholine receptors (nAChRs). We administered alpha-difluoromethylornithine (DFMO), an irreversible inhibitor of ODC, to neonatal rats on postnatal days 5-12, during the mitotic peak of the cerebellum, a treatment regimen that achieves a chemical knockout of ODC activity and polyamine depletion limited to the treatment period. Although growth inhibition and gross dysmorphology were limited to the cerebellum, both alpha7 and alpha4beta2 nAChRs were upregulated in adulthood in the frontal cortex, hippocampus and thalamus, with the largest effect in the latter region, primarily in females. Receptor upregulation was accompanied by abnormalities in macromolecular indices of cell packing density and cell membrane surface area, but the generalized cellular alterations did not share the regional or sex selectivity shown by the effects on nAChRs. Elevated DNA concentration was most notable in the hippocampus and was associated with augmented levels of glial fibrillary acidic protein, thus implying gliosis as the cause of the increased number of cells. DFMO's effects on both nAChR expression and cellular biomarkers resembled those of developmental exposure to nicotine. Accordingly, some of the effects may represent a specific alteration in nAChR signaling evoked by polyamine depletion during a critical developmental window. Alterations in polyamine gating of cholinergic synaptic signaling may thus contribute to the adverse neurobehavioral effects of numerous neuroteratogens that directly or indirectly disrupt the ODC/polyamine pathway. (C) 2003 Elsevier B.V. All rights reserved. C1 Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Durham, NC 27710 USA. US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Slotkin, TA (reprint author), Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Box 3813 DUMC, Durham, NC 27710 USA. FU NICHD NIH HHS [R01 HD 09713]; NIDA NIH HHS [R01 DA 14247]; NIEHS NIH HHS [T32 ES 07031] NR 58 TC 12 Z9 12 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD AUG 15 PY 2003 VL 981 IS 1-2 BP 118 EP 125 DI 10.1016/S0006-8993(03)02993-7 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 713NN UT WOS:000184864700013 PM 12885432 ER PT J AU Schroeder, CM White, DG Ge, BL Zhang, YF McDermott, PF Ayers, S Zhao, SH Meng, JH AF Schroeder, CM White, DG Ge, BL Zhang, YF McDermott, PF Ayers, S Zhao, SH Meng, JH TI Isolation of antimicrobial-resistant Escherichia coli from retail meats purchased in Greater Washington, DC, USA SO INTERNATIONAL JOURNAL OF FOOD MICROBIOLOGY LA English DT Article DE isolation; Escherichia coli; retail meats ID ANTIBIOTIC-RESISTANCE; FOOD ANIMALS; SALMONELLA; HUMANS; GENES; IDENTIFICATION; O157; BEEF AB Four hundred and seventy-two generic Escherichia coli isolates were recovered from ground and whole retail beef, chicken, pork, and turkey obtained from Greater Washington, DC, USA during the years 1998 to 2000. Many of the isolates displayed resistance to tetracycline (59%), sulfamethoxazole (45%), streptomycin (44%), cephalothin (38%) and ampicillin (35%). Resistance was also observed, but to a lesser extent, to gentamicin (12%), nalidixic acid (8%), chloramphenicol (6%), ceftiofur (4%) and ceftriaxone (1%). Sixteen percent of the isolates displayed resistance to one antimicrobial, followed by 23% to two, 23% to three, 12% to four, 7% to five, 3% to six, 2% to seven and 2% to eight. Three E. coli isolates were shown to possess Shiga toxin genes (stx2) via PCR; all were O non-typeable and were recovered from ground beef samples purchased on the same day at the same supermarket. One of the Shiga toxin-producing E. coli (STEC) isolates was susceptible to each of the antimicrobials tested, whereas one displayed resistance to cephalothin and sulfamethoxazole, and one displayed resistance to ampicillin, cephalothin, gentamicin, streptomycin, sulfamethoxazole and tetracycline. Findings from this study indicate that retail raw meats may often be contaminated with antimicrobial-resistant E. coli. Crown Copyright (C) 2002 Published by Elsevier Science B.V. All rights reserved. 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 26 TC 75 Z9 80 U1 2 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-1605 J9 INT J FOOD MICROBIOL JI Int. J. Food Microbiol. PD AUG 15 PY 2003 VL 85 IS 1-2 BP 197 EP 202 DI 10.1016/S0168-1605(02)00508-1 PG 6 WC Food Science & Technology; Microbiology SC Food Science & Technology; Microbiology GA 706VF UT WOS:000184475200018 PM 12810283 ER PT J AU Lucas, AD Merritt, K Hitchins, VM Woods, TO McNamee, SG Lyle, DB Brown, SA AF Lucas, AD Merritt, K Hitchins, VM Woods, TO McNamee, SG Lyle, DB Brown, SA TI Residual ethylene oxide in medical devices and device material SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS LA English DT Article DE ethylene oxide; medial device; polymer; bioavailable; toxicity ID FLOW-CYTOMETRY; CELL-DEATH; STERILIZATION; APOPTOSIS; IMMEDIATE AB Ethylene oxide (EO) gas is commonly used to sterilize medical devices. The amount of residual EO remaining in a device depends partly on the type and size of polymeric material. A major concern is the amount of residue that may be available in the body. With the use of the method described by AAMI for headspace analysis of EO residues, different polymers and medical devices subjected to different numbers of sterilization cycles were examined. Next, the effect of various extraction conditions and extraction solutions on these polymers and medical devices was evaluated. The results showed different polymers desorb EO differently. One polyurethane (PU 75D) had much higher EO residue than a different polyurethane (PU 80A). Repeated extraction of the PU 75D was necessary to quantify total EO residue levels. Different extraction solutions influence the amount and reproducibility of EO detected, whereas multiple resterilizations showed no difference in amount of residual EO. Bioavaillability of EO was estimated by extracting the devices and polymers in water. Comparison of total EO residues to EO that was bioavailable showed no difference for some polymers and devices, while others had an almost eightfold difference. Some standard biocompatibility tests were run on extracts and devices, but no significant effects were observed. (C) 2003 Wiley Periodicals, Inc. C1 US FDA, Off Sci & Technol, Ctr Devices & Radiol Hlth, Rockville, MD 20852 USA. RP Lucas, AD (reprint author), US FDA, Off Sci & Technol, Ctr Devices & Radiol Hlth, HFZ 112,12709 Twinbrook Pkwy, Rockville, MD 20852 USA. NR 21 TC 29 Z9 30 U1 1 U2 5 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0021-9304 J9 J BIOMED MATER RES B JI J. Biomed. Mater. Res. Part B PD AUG 15 PY 2003 VL 66B IS 2 BP 548 EP 552 DI 10.1002/jbm.b.10036 PG 5 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 707TE UT WOS:000184525300008 PM 12861606 ER PT J AU Twaddle, NC Churchwell, MI Newbold, RR Delclos, KB Doerge, DR AF Twaddle, NC Churchwell, MI Newbold, RR Delclos, KB Doerge, DR TI Determination using liquid-chromatography-electrospray tandem mass spectroscopy of ethinylestradiol serum pharmacokinetics in adult Sprague-Dawley rats SO JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES LA English DT Article DE pharmacokinetics; ethinylestradiol ID SPECTROMETRIC DETERMINATION; TISSUE DISTRIBUTION; ETHINYL-ESTRADIOL; RHESUS-MONKEY; IN-VITRO; PHYTOESTROGENS; METABOLISM; BETA; GENISTEIN; EXPOSURE AB The pharmacokinetics of ethinylestradiol (EE2), a potent synthetic estrogen, was investigated in male and female Sprague-Dawley rats as part of a series of endocrine-active compounds, including genistein and nonylphenol. A method based on solid-phase extraction and LC with negative ion electrospray tandem mass spectrometric detection was developed and validated. The limit of detection in untreated rat serum was below 0.01 ng/ml (0.03 nM), the limit of quantification was 0.03 ng/ml (0.10 W), the intra- and inter-day precision was 2-9%, and the intra- and inter-day accuracy was 89-94%. This method was used to determine the serum pharmacokinetics of EE2 in rats following oral gavage administration of 1 mg/kg body weight. EE2 was present in serum primarily in the unconjugated form at concentrations below 0.5 ng/ml. The maximal serum concentration was proportional to dose over the range of 0.04-0.5 mg/kg body weight and pharmacokinetic parameters were determined using model-independent analysis. Significant sex differences were observed for elimination half-times and volumes of distribution, but not for total serum clearance or maximal concentrations. The pharmacokinetic analysis of EE2 will be useful for comparing the toxicological effects of EE2 to those of other environmental estrogens in related rodent endocrine disruptor studies. (C) 2003 Elsevier B.V. All rights reserved. C1 Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. NIEHS, Dev Endocrinol Sect, Mol Toxicol Lab, Environm Toxicol Program, Res Triangle Pk, NC 27709 USA. RP Doerge, DR (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. NR 18 TC 19 Z9 21 U1 1 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1570-0232 J9 J CHROMATOGR B JI J. Chromatogr. B PD AUG 15 PY 2003 VL 793 IS 2 BP 309 EP 315 DI 10.1016/S1570-0232(03)00331-3 PG 7 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 711KK UT WOS:000184739200011 PM 12906905 ER PT J AU Altekruse, SF Tollefson, LK AF Altekruse, SF Tollefson, LK TI Human campylobacteriosis: a challenge for the veterinary profession SO JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION LA English DT Review ID GUILLAIN-BARRE-SYNDROME; JEJUNI-COLI ENTERITIS; RISK-FACTORS; BROILER FLOCKS; THERMOPHILIC CAMPYLOBACTERS; UNITED-STATES; COMPETITIVE-EXCLUSION; CROSS-CONTAMINATION; ESCHERICHIA-COLI; FEED WITHDRAWAL C1 NCI, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. US FDA, Ctr Vet Med, Rockville, MD 20895 USA. RP Altekruse, SF (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd MSC 7234, Rockville, MD 20852 USA. NR 109 TC 27 Z9 28 U1 0 U2 7 PU AMER VETERINARY MEDICAL ASSOC PI SCHAUMBURG PA 1931 N MEACHAM RD SUITE 100, SCHAUMBURG, IL 60173-4360 USA SN 0003-1488 J9 J AM VET MED ASSOC JI J. Am. Vet. Med. Assoc. PD AUG 15 PY 2003 VL 223 IS 4 BP 445 EP 452 DI 10.2460/javma.2003.223.445 PG 8 WC Veterinary Sciences SC Veterinary Sciences GA 710RB UT WOS:000184692300026 PM 12930081 ER PT J AU Fu, TJ Abbott, UR Hatzos, C AF Fu, TJ Abbott, UR Hatzos, C TI Rebuttal on digestibility of food allergens and nonallergenic proteins in simulated gastric fluid and simulated intestinal fluid - A comparative study SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Letter ID GENETICALLY-MODIFIED FOODS; IN-VITRO; STORAGE PROTEINS; PEANUT ALLERGEN; STABILITY; IDENTIFICATION; BIOTECHNOLOGY; PROTEOLYSIS; CHALLENGE; SAFETY C1 US FDA, Summit Argo, IL 60501 USA. IIT, Natl Ctr Food Safety & Technol, Summit Argo, IL 60501 USA. RP Abbott, UR (reprint author), US FDA, Summit Argo, IL 60501 USA. NR 40 TC 3 Z9 3 U1 0 U2 4 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 AUG 13 PY 2003 VL 51 IS 17 BP 5185 EP 5187 DI 10.1021/jf0303767 PG 3 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 709QH UT WOS:000184635500057 ER PT J AU Goyard, S Segawa, H Gordon, J Showalter, M Duncan, R Turco, SJ Beverley, SM AF Goyard, S Segawa, H Gordon, J Showalter, M Duncan, R Turco, SJ Beverley, SM TI An in vitro system for developmental and genetic studies of Leishmania donovani phosphoglycans SO MOLECULAR AND BIOCHEMICAL PARASITOLOGY LA English DT Article DE protozoan parasites; in vitro differentiation; axenic amastigotes; transfection; phosphoglycan molecules (PG); lipophosphoglycan (LPG); virulence ID PROTOZOAN PARASITE LEISHMANIA; AXENIC AMASTIGOTES; FUNCTIONAL COMPLEMENTATION; PENTAVALENT ANTIMONY; ACID-PHOSPHATASES; GROWN AMASTIGOTES; VIRULENCE GENES; PROMASTIGOTES; LIPOPHOSPHOGLYCAN; IDENTIFICATION AB Glycoconjugates have been shown to play important roles in Leishmania development. However, the ability to study these molecules and other processes would benefit greatly from improved methods for genetic manipulation and analysis of the amastigote stage. This is especially challenging for L. donovani, the agent of the most severe form of leishmaniasis, which can rapidly lose virulence during in vitro culture. Here we report on a clonal subline of an L. donovani 1S2D (LdBob or LdB), which differentiates readily from promastigotes to amastigotes in axenic culture, and maintains this ability during extended parasite cultivation in vitro. This derivative can be plated and transfected efficiently while grown as promastigotes or amastigotes. Importantly, LdB maintains the ability to differentiate while undergoing genetic alterations required for creation of gene knockouts and complemented lines. Like virulent L. donovani, LdB exhibits down-regulation of lipophosphoglycan (LPG) synthesis and up-regulation of A2 protein synthesis in amastigotes. We showed that knockouts of LPG2, encoding a Golgi GDP-mannose transporter, eliminated phosphoglycan synthesis in LdB axenic amastigotes. These and other data suggest that LdB axenic amastigotes will be generally useful as a differentiation model in Studies of gene expression, virulence, glycoconjugate function and drug susceptibility in L. donovani. (C) 2003 Elsevier B.V. All rights reserved. C1 Washington Univ, Sch Med, Dept Mol Microbiol, St Louis, MO 63110 USA. Univ Kentucky, Med Ctr, Dept Mol & Cellular Biochem, Lexington, KY 40536 USA. US FDA, Lab Bacterial Parasit & Unconvent Agents, CBER, Bethesda, MD 20892 USA. RP Beverley, SM (reprint author), Washington Univ, Sch Med, Dept Mol Microbiol, 600 S Euclid Ave,Campus Box 8230, St Louis, MO 63110 USA. RI Duncan, Robert/I-8168-2015; OI Duncan, Robert/0000-0001-8409-2501; Beverley, Stephen/0000-0001-5319-0811 FU NIAID NIH HHS [AI030178] NR 52 TC 105 Z9 107 U1 0 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-6851 J9 MOL BIOCHEM PARASIT JI Mol. Biochem. Parasitol. PD AUG 11 PY 2003 VL 130 IS 1 BP 31 EP 42 DI 10.1016/S0166-6851(03)00142-7 PG 12 WC Biochemistry & Molecular Biology; Parasitology SC Biochemistry & Molecular Biology; Parasitology GA 719VC UT WOS:000185224900004 PM 14550894 ER PT J AU Badano, A AF Badano, A TI Optical blur and collection efficiency in columnar phosphors for X-ray imaging SO NUCLEAR INSTRUMENTS & METHODS IN PHYSICS RESEARCH SECTION A-ACCELERATORS SPECTROMETERS DETECTORS AND ASSOCIATED EQUIPMENT LA English DT Article DE phosphor screens; optical blur; optical gain; resolution; modulation transfer function; line-spread function ID DETECTIVE QUANTUM EFFICIENCY; RADIATION DETECTORS; MODULATION TRANSFER; PHOTOGRAPHIC EMULSIONS; LIGHT COLLECTION; SCREENS; SCINTILLATORS; CRYSTAL; SYSTEMS; MODEL AB Columnar phosphors are common in modern indirect X-ray digital imaging systems. However, a comprehensive description of the light scattering processes within such structures has not yet been reported. We present a Monte Carlo analysis of the depth-depenclent optical blur and collection efficiency of columnar phosphor screens. We present line-spread (LSF) and modulation transfer (MTF) functions, and optical collection efficiencies for screens with transparent phosphors and different back-layer reflectance. Our phosphor model consists of a uniformly spaced columnar array (9 pm diameter with 1 mum gaps). We present data for single X-ray interactions occurring at varying depths (99, 90, 40, 30 20 10, and 1 mum) for a given screen thickness of 100 mum, and for screens of varying thicknesses (10, 20, 40, 100, 200, and 300 mum) with exponentially absorbed X-ray beams corresponding to typical mammography spectra. We show quantitatively that depth of interaction and phosphor thickness have a strong effect on LSF and MTF. Our Monte Carlo results are in agreement with published experimentally measured MTF results. The depth-dependent collection efficiency is affected by optical absorption, while being independent of interaction depth and thickness for transparent phosphors. (C) 2003 Elsevier B.V. All rights reserved. C1 US FDA, Off Sci & Technol, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Badano, A (reprint author), US FDA, Off Sci & Technol, Ctr Devices & Radiol Hlth, 12720 Twinbrook Pkwy,Mail Shop,HFZ 142,Room 167, Rockville, MD 20857 USA. OI badano, aldo/0000-0003-3712-6670 NR 40 TC 23 Z9 24 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-9002 J9 NUCL INSTRUM METH A JI Nucl. Instrum. Methods Phys. Res. Sect. A-Accel. Spectrom. Dect. Assoc. Equip. PD AUG 11 PY 2003 VL 508 IS 3 BP 467 EP 479 DI 10.1016/S0168-9002(03)01651-6 PG 13 WC Instruments & Instrumentation; Nuclear Science & Technology; Physics, Nuclear; Physics, Particles & Fields SC Instruments & Instrumentation; Nuclear Science & Technology; Physics GA 710BG UT WOS:000184660500028 ER PT J AU Kainz, W Chan, DD Casamento, JP Bassen, HI AF Kainz, W Chan, DD Casamento, JP Bassen, HI TI Calculation of induced current densities and specific absorption rates (SAR) for pregnant women exposed to hand-held metal detectors SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID RADIOFREQUENCY RADIATION; DIELECTRIC-PROPERTIES; BIOLOGICAL TISSUES; ELECTROMAGNETIC-FIELDS; LIMITING EXPOSURE; 300 GHZ; TERATOGENICITY; FREQUENCIES; GUIDELINES; HUMANS AB The finite difference time domain (FDTD) method in combination with a well established frequency scaling method was used to calculate the internal fields and current densities induced in a simple model of a pregnant woman and her foetus, when exposed to hand-held metal detectors. The pregnant woman and foetus were modelled using a simple semi-heterogeneous model in 10 mm resolution, consisting of three different types of tissue. The model is based on the scanned shape of a pregnant woman in the 34th gestational week. Nine different representative models of hand-held metal detectors operating in the frequency range from 8 kHz to 2 MHz were evaluated. The metal detectors were placed directly on the abdomen of the computational model with a spacing of 1 cm. Both the induced current density and the specific absorption rate (SAR) are well below the recommended limits for exposure of the general public published in the ICNIRP Guidelines and the IEEE C95.1 Standard. The highest current density is 8.3 mA m(-2) and the highest SAR is 26.5 muW kg(-1). Compared to the limits for the induced current density recommended in the ICNIRP Guidelines, a minimum safety factor of 3 exists. Compared to the IEEE C95.1 Standard, a safety factor of 60000 for the specific absorption rate was found. Based on the very low specific absorption rate and an induced current density below the recommended exposure limits, significant temperature rise or nerve stimulation in the pregnant woman or in the foetus can be excluded. C1 CDRH, Food Drug Adm, Rockville, MD 20852 USA. RP CDRH, Food Drug Adm, 12725 Twinbrook Pkwy, Rockville, MD 20852 USA. EM wxk@cdrh.fda.gov NR 23 TC 24 Z9 25 U1 1 U2 4 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 EI 1361-6560 J9 PHYS MED BIOL JI Phys. Med. Biol. PD AUG 7 PY 2003 VL 48 IS 15 BP 2551 EP 2560 AR PII S0031-9155(03)63078-2 DI 10.1088/0031-9155/48/15/319 PG 10 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 717NZ UT WOS:000185097400019 PM 12953914 ER PT J AU Cherkasova, E Laassri, M Chizhikov, V Korotkova, E Dragunsky, E Agol, VI Chumakov, K AF Cherkasova, E Laassri, M Chizhikov, V Korotkova, E Dragunsky, E Agol, VI Chumakov, K TI Microarray analysis of evolution of RNA viruses: Evidence of circulation of virulent highly divergent vaccine-derived polioviruses SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE molecular evolution; recombination; population heterogeneity; mutation screening; live vaccine ID QUANTITATIVE MUTANT ANALYSIS; QUALITY-CONTROL; GENETIC STABILITY; SABIN-1 STRAIN; POLIOMYELITIS; POPULATIONS; SEQUENCE; FITNESS; IDENTIFICATION; MICROEVOLUTION AB Two approaches based on hybridization of viral probes with oligonucleotide microarrays were developed for rapid analysis of genetic variations during microevolution of RNA viruses. Microarray analysis of viral recombination and microarray for resequencing and heterogeneity analysis were able to generate instant genetic maps of vaccine-derived polioviruses (VDPVs) and reveal the degree of their evolutionary divergence. Unlike conventional methods based on cDNA sequencing and restriction fragment length polymorphism, the microarray approaches are better suited for analysis of heterogeneous populations and mixtures of different strains. The microarray hybridization profile is very sensitive to the cumulative presence of small quantities of different mutations, including those that cannot be revealed by sequencing, making this approach useful for characterization of profiles of nucleotide sequence diversity in viral populations. By using these methods, we identified a type-3 VDPV isolated from a healthy person and missed by conventional methods of screening. The mutational profile of the polio strain was consistent with > 1 yr of circulation in human population and was highly virulent in transgenic mice, confirming the ability of VDPV to persist in communities despite high levels of immunity. The proposed methods for fine genotyping of heterogeneous viral populations can also have utility for a variety of other applications in studies of genetic changes in viruses, bacteria, and genes of higher organisms. C1 US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. Moscow MV Lomonosov State Univ, AN Belozersky Inst Phys Chem Biol, Moscow 119899, Russia. Russian Acad Med Sci, MP Chumakov Inst Poliomyelitis & Viral Encephalit, Moscow 142782, Russia. RP Chumakov, K (reprint author), US FDA, Ctr Biol Evaluat & Res, 1401 Rockville Pike,HFM 470, Rockville, MD 20852 USA. RI Agol, Vadim/E-1941-2013 NR 48 TC 69 Z9 76 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 5 PY 2003 VL 100 IS 16 BP 9398 EP 9403 DI 10.1073/pnas.1633511100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 709HP UT WOS:000184620000055 PM 12878723 ER PT J AU Cowley, SC Elkins, KL AF Cowley, SC Elkins, KL TI Multiple T cell subsets control Francisella tularensis LVS intracellular growth without stimulation through macrophage interferon gamma receptors SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE protective immunity; Francisella tularensis LVS; interferon gamma; TNF-alpha; T cells alpha ID NECROSIS-FACTOR-ALPHA; LIVE VACCINE STRAIN; PROTECTIVE IMMUNITY; LISTERIA-MONOCYTOGENES; LYMPHOTOXIN-ALPHA; MEDIATED-IMMUNITY; DEFICIENT MICE; SECRETED TNF; IFN-GAMMA; INFECTION AB A variety of data suggest that in vivo production of interferon (IFN)-gamma is necessary, but not sufficient, for expression of secondary protective immunity against intracellular pathogens. To discover specific IFN-gamma-independent T cell mediated mechanisms, we took advantage of an in vitro culture system that models in vivo immune responses to the intracellular bacterium Francisclla tularensis live vaccine strain (LVS). LVS-immune lymphocytes specifically controlled 99% of the growth of LVS in wild-type murine bone marrow-derived macrophages. Surprisingly, LVS-immune lymphocytes also inhibited LVS intracellular growth by as much as 95% in macrophages derived from IFN-gamma receptor knockout (IFNgammaP KO) mice. CD8(+) T cells, and to a lesser degree CD4(+) T cells, controlled LVS intracellular growth in both wild-type and IFNgammaR KO macrophages. Further, a unique population of Thy1(+)alphabeta(+)CD4(-)CD4(-)CD8(-) cells that was previously suggested to operate during secondary immunity to LVS in vivo strongly controlled LVS intracellular growth in vitro. A large proportion of the inhibition of LVS intracellular growth in IFNgammaR KO macrophages by all three T cell subsets could be attributed to tumor necrosis factor (TNF) alpha. Thus, T cell mechanisms exist that control LVS intracellular growth without acting through the IFN-gamma receptor; such control is due in large part to TNF-alpha, and is partially mediated by a unique double negative T cell subpopulation. C1 US FDA, LMDCI, DBPAP, CBER, Rockville, MD 20852 USA. RP Cowley, SC (reprint author), US FDA, LMDCI, DBPAP, CBER, 1401 Rockville Pike,HFM 431, Rockville, MD 20852 USA. NR 33 TC 69 Z9 69 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD AUG 4 PY 2003 VL 198 IS 3 BP 379 EP 389 DI 10.1084/jem.20030687 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 712TQ UT WOS:000184813700002 PM 12885873 ER PT J AU Nicklas, RA Chowdhury, BA AF Nicklas, RA Chowdhury, BA TI Effect of anti-IgE therapy in patients with food allergy SO ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY LA English DT Editorial Material ID PEANUT ALLERGY; ANAPHYLACTIC REACTIONS; CHILDREN; IMMUNOTHERAPY; CROMOLYN C1 US FDA, Ctr Drug Evaluat & Res, Div Pulm Allergy & Drug Prod, Rockville, MD 20857 USA. RP Nicklas, RA (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Pulm Allergy & Drug Prod, Rockville, MD 20857 USA. NR 20 TC 3 Z9 3 U1 0 U2 1 PU AMER COLL ALLERGY ASTHMA IMMUNOLOGY PI ARLINGTON HTS PA 85 WEST ALGONQUIN RD SUITE 550, ARLINGTON HTS, IL 60005 USA SN 1081-1206 J9 ANN ALLERG ASTHMA IM JI Ann. Allergy Asthma Immunol. PD AUG PY 2003 VL 91 IS 2 BP 119 EP 120 PG 2 WC Allergy; Immunology SC Allergy; Immunology GA 714DN UT WOS:000184897200005 PM 12952103 ER PT J AU Orlandi, PA Carter, L Brinker, AM da Silva, AJ Chu, DM Lampel, KA Monday, SR AF Orlandi, PA Carter, L Brinker, AM da Silva, AJ Chu, DM Lampel, KA Monday, SR TI Targeting single-nucleotide polymorphisms in the 18S rRNA gene to differentiate Cyclospora species from Eimeria species by multiplex PCR SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID IMPORTED RASPBERRIES; TEMPLATE PREPARATION; MOLECULAR CHARACTERIZATION; ENZYMATIC AMPLIFICATION; INTESTINAL PATHOGEN; OUTBREAK; CAYETANENSIS; MUTATION; HUMANS; DNA AB Cyclospora cayetanensis is a coccidian parasite that causes protracted diarrheal illness in humans. C. cayetanensis is the only species of this genus thus far associated with human illness, although Cyclospora species from other primates have been named. The current method to detect the parasite uses a nested PCR assay to amplify a 294-bp region of the small subunit rRNA gene, followed by restriction fragment length polymorphism (RFLP) or DNA sequence analysis. Since the amplicons generated from C. cayetanensis and Eimetia species are the same size, the latter step is required to distinguish between these different species. The current PCR-RFLP protocol, however, cannot distinguish between C. cayetanensis and these new isolates. The differential identification of such pathogenic and nonpathogenic parasites is essential in assessing the risks to human health from microorganisms that may be potential contaminants in food and water sources. Therefore, to expand the utility of PCR to detect and identify these parasites in a multiplex assay, a series of genus- and species-specific forward primers were designed that are able to distinguish sites of limited sequence heterogeneity in the target gene. The most effective of these unique primers were those that identified single-nucleotide polymorphisms (SNPs) at the 3' end of the primer. Under more stringent annealing and elongation conditions, these SNP primers were able to differentiate between C. cayetanensis, nonhuman primate species of Cyclospora, and Eimeria species. As a diagnostic tool, the SNP PCR protocol described here presents a more rapid and sensitive alternative to the currently available PCR-RFLP detection method. In addition, the specificity of these diagnostic primers removes the uncertainty that can be associated with analyses of foods or environmental sources suspected of harboring potential human parasitic pathogens. C1 US FDA, Div Virulence Assessment, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. US FDA, Div Microbiol Studies, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. Ctr Dis Control & Prevent, Div Parasit Dis, Natl Ctr Infect Dis, Atlanta, GA 30341 USA. RP Orlandi, PA (reprint author), US FDA, CFSAN, OARSA, DVA,MOD Res Facil 1, Rm 3603,HFS-025,8301 Muirkirk Rd, Laurel, MD 20708 USA. NR 32 TC 27 Z9 31 U1 2 U2 9 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 AUG PY 2003 VL 69 IS 8 BP 4806 EP 4813 DI 10.1128/AEM.69.8.4806-4813.2003 PG 8 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 710GM UT WOS:000184672500061 PM 12902274 ER PT J AU Okada, S Weatherhead, E Targoff, IN Wesley, R Miller, FW AF Okada, S Weatherhead, E Targoff, IN Wesley, R Miller, FW CA Int Myositis Collab Study Grp TI Global surface ultraviolet radiation intensity may modulate the clinical and immunologic expression of autoimmune muscle disease SO ARTHRITIS AND RHEUMATISM LA English DT Article ID IDIOPATHIC INFLAMMATORY MYOPATHY; MYOSITIS-SPECIFIC AUTOANTIBODIES; UVB-RADIATION; IMMUNE-SYSTEM; DERMATOMYOSITIS; MICE; IMMUNOSUPPRESSION; POLYMYOSITIS; IRRADIATION; AUTOANTIGEN AB Objective. To determine if geoclimatic factors may influence the nature and frequency of dermatomyositis (DM), polymyositis, and associated autoantibodies around the world. Methods. We assessed, in the first global evaluation of these conditions, the relationship between 13 geoclimatic variables that may modulate disease and the relative proportion of DM and its associated autoantibody anti-Mi-2, directed against an SNF2-superfamily helicase associated with the nucleosome remodeling and histone acetylation and deacetylation complex, in a global myositis population. Altogether, 919 consecutive patients from populations at 15 locations were studied. Results. Univariate and multivariate analyses demonstrated that of the variables evaluated, surface ultraviolet (UV) radiation intensity (irradiance) most strongly contributed to the relative proportion of DM and was strongly related to the proportion of anti-Mi-2 autoantibodies (weighted r = 0.939, P < 4 x 10(-7) and weighted r = 0.69, P = 0.02, respectively). Published ethnogeographic immunogenetic allele frequencies imply that the striking differences in the proportion of DM- and DM-specific autoantibodies observed around the world are not the result of inherent global variations in known genetic risk factors. Conclusion. These data suggest that UV radiation exposure may modulate the clinical and immunologic expression of an autoimmune disease in different populations around the world. C1 NIEHS, Off Clin Res, NIH, DHHS, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. Univ Colorado, Cooperat Inst Res Environm Sci, Boulder, CO 80309 USA. Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USA. NIH, Ctr Clin, Bethesda, MD 20892 USA. RP Miller, FW (reprint author), NIEHS, Off Clin Res, NIH, DHHS, 9 Mem Dr,NIH Bldg 9,Room 1W107,MSC 0958, Bethesda, MD 20892 USA. EM millerf@mail.nih.gov RI Song, Yeong Wook/J-2765-2012; Weatherhead, Elizabeth/I-7091-2015; OI Weatherhead, Elizabeth/0000-0002-9252-4228; Miller, Frederick/0000-0003-2831-9593 NR 45 TC 74 Z9 76 U1 0 U2 3 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 AUG PY 2003 VL 48 IS 8 BP 2285 EP 2293 DI 10.1002/art.11090 PG 9 WC Rheumatology SC Rheumatology GA 708TG UT WOS:000184585000025 PM 12905483 ER PT J AU Witter, J Simon, LS AF Witter, J Simon, LS TI Chronic pain and fibromyalgia: the regulatory perspective SO BEST PRACTICE & RESEARCH IN CLINICAL RHEUMATOLOGY LA English DT Article DE chronic pain; fibromyalgia; analgesia; osteoarthritis; Food and Drug Administration; labels; clinical trials AB Chronic pain is an important clinical entity that represents a currently unmet medical need. Relief of pain is an important public health goal for patients of all ages, from perinatal to geriatric. This article will describe some of the current regulatory issues in developing and approving drugs to treat chronic pain. It will also begin to familiarize the reader with the importance of the so-called 'label' and some of its roles to enable the best 'risk-benefit' decisions be made for, and by, patients with chronic pain. C1 US FDA, Ctr Drug Evaluat & Res, Div Analges, Rockville, MD 20857 USA. US FDA, Ctr Drug Evaluat & Res, Div Antiinflammatory Analges & Ophthalm Drug Prod, Rockville, MD 20857 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Rheumatol,Lowry Med Off, Boston, MA 02215 USA. RP Simon, LS (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Analges, Rockville, MD 20857 USA. NR 1 TC 3 Z9 3 U1 0 U2 1 PU BAILLIERE TINDALL PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1521-6942 J9 BEST PRACT RES CL RH JI Best Pract. Res. Clin. Rheumatol. PD AUG PY 2003 VL 17 IS 4 BP 541 EP 546 DI 10.1016/S1521-6942(03)00045-7 PG 6 WC Rheumatology SC Rheumatology GA 702TG UT WOS:000184239300002 PM 12849710 ER PT J AU Calvert, RJ Tepper, S Diwan, BA Anderson, LM Kritchevsky, D AF Calvert, RJ Tepper, S Diwan, BA Anderson, LM Kritchevsky, D TI Treatment with lovastatin, cholestyramine or niacin alters K-ras membrane association in mouse lung in a strain-dependent manner: results in females SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE cholesterol; cholestyramine; K-ras; lovastatin; lung; mouse; niacin; sex difference ID CORONARY ATHEROSCLEROSIS PREVENTION; ESTROGEN-RECEPTOR-ALPHA; LONG-TERM TREATMENT; CANCER RISK; SERUM-CHOLESTEROL; GENE-EXPRESSION; SEX-DIFFERENCES; TUMOR FORMATION; NICOTINIC-ACID; GUINEA-PIG AB Hypocholesterolemic drugs may themselves increase (cholestyramine, CS) or decrease (lovastatin, Lov) peripheral tissue de novo cholesterol biosynthesis. This will alter the abundance of prenyl groups and potentially increase (CS) or decrease (Lov) K-ras membrane localization, with possible pro- or anti-carcinogenic effects (K-ras is a proto-oncogene frequently mutated in lung cancer). Female A/J, Swiss, and C57BL/6 mice were fed 2 or 4% CS, 1% niacin, or injected with Lov three (Lov-3x) or five (Lov-5x) times per week. After three weeks, serum cholesterol and triglycerides were determined enzymatically. Total, membrane, and cytoplasmic K-ras proteins were determined in lung homogenates by immunoprecipitation followed by Western blotting with a K-ras specific antibody. CS feeding increased membrane K-ras as hypothesized in A/J and C57BL/6 mice, but had no effect in Swiss mice. Lov failed in all three strains to reduce membrane K-ras. and resulted in an increase in total K-ras in A/J and C57BL/6 mice, while again lacking effect in Swiss mice. Niacin had no effect on K-ras protein in any mouse strain. These results differ from our published results for male mice of the same strains, particularly for A/J mice. Increased amounts of K-ras protein in the membrane fraction of A/J females (but not males) treated with either Lov or CS imply that if K-ras were to become mutated, CS could result in increased lung tumorigenesis and Lov would be less likely to be protective in females. In the light of these data, both sexes should be included in future animal and human chemoprevention trials. (C) 2003 Elsevier Science Inc. All rights reserved. C1 US FDA, Ctr Food Safety & Appl Nutr, Div Res & Appl Technol, Off Nutr Prod Labeling & Dietary Supplements, College Pk, MD 20740 USA. NCI, Frederick Canc Res & Dev Ctr, Basic Res Program, Frederick, MD 21702 USA. Wistar Inst Anat & Biol, Philadelphia, PA 19104 USA. NCI, Lab Comparat Carcinogenesis, Frederick, MD 21702 USA. RP Calvert, RJ (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Div Res & Appl Technol, Off Nutr Prod Labeling & Dietary Supplements, College Pk, MD 20740 USA. FU NHLBI NIH HHS [HL00735]; ODCDC CDC HHS [N01-CD-12400] NR 49 TC 3 Z9 3 U1 2 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD AUG 1 PY 2003 VL 66 IS 3 BP 393 EP 403 DI 10.1016/S0006-2952(03)00211-9 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 713NL UT WOS:000184864500005 PM 12907238 ER PT J AU Laughren, TP AF Laughren, TP TI Comorbid mood disorders and medical illness: A food and drug administration perspective SO BIOLOGICAL PSYCHIATRY LA English DT Editorial Material ID DEPRESSION C1 US FDA, HFD 120, Rockville, MD 20857 USA. RP Laughren, TP (reprint author), US FDA, HFD 120, 1451 Rockville Pike, Rockville, MD 20857 USA. NR 6 TC 8 Z9 8 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD AUG 1 PY 2003 VL 54 IS 3 BP 195 EP 199 DI 10.1016/S0006-3223(03)00529-8 PG 5 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 706KA UT WOS:000184451800006 PM 12893095 ER PT J AU Dixon, AM Venable, R Widmalm, G Bull, TE Pastor, RW AF Dixon, AM Venable, R Widmalm, G Bull, TE Pastor, RW TI Application of NMR, molecular simulation, and hydrodynamics to conformational analysis of trisaccharides SO BIOPOLYMERS LA English DT Article DE carbohydrate; conformational; flexibility; M-GOESY; rotational relaxation; translational diffusion ID NUCLEAR-MAGNETIC-RESONANCE; ANOMERIC METHYL GLYCOSIDES; DYNAMICS SIMULATION; SPECTROSCOPY; OLIGOSACCHARIDES; DISACCHARIDE; FLEXIBILITY; RELAXATION; WATER; DIFFUSION AB The preferred conformations and conformational flexibilities of the trisaccharides alpha-D-Glcp-(1-->2)-beta-D-Glcp-(1-->3)-alpha-D-Glcp-OMe (I) and alpha-D-Glcp-(1-->3)[beta-D-Glcp-(1-->4)]-alpha-D-Glcp-OMe (II) in aqueous solution were determined using nuclear magnetic resonance (NMR) spectroscopy, molecular dynamics (MD) and Langevin dynamics (LD) simulations, and hydrodynamics calculations. Both trisaccharides have a vicinal substitution pattern in which long range (nonsequential) interactions may play an important role. LD simulation at 600 K indicated that the all-syn conformation predominated, though other conformations were apparent. NOE data and MD and LD simulations at 298 K all indicated that trisaccharide I is a single all-syn conformer in solution. Given that previous studies showed evidence of anti-conformers in beta-D-Glcp-(1-->2)-beta-D-Glcp-(1-->3)-alpha-D-Glcp-OMe, this result provides an example of how changing the anomeric configuration of one residue from beta to alpha can make an oligosaccharide more rigid. Discrepancies in inter-ring distances obtained by experiment and by simulation of the all-syn conformer suggest presence of an anti-psi conformation at the beta-(1-->4)-linkage for II. A combined analysis of measured and calculated translational diffusion constants and C-13 T-1 relaxation times yield order parameters of 0.9 for each trisaccharide. This implies that any interconversion among conformations is significantly slower than tumbling. Anisotropies of approximately 1.6 and 1.3 calculated for I and II, respectively, are consistent with the observed relatively flat T-1 profiles because the tumbling is not in the motional narrowing regime. (C) 2003 Wiley Periodicals, Inc.* C1 US FDA, Biophys Lab, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. Univ Stockholm, Arrhenius Lab, Dept Organ Chem, S-10691 Stockholm, Sweden. RP Pastor, RW (reprint author), US FDA, Biophys Lab, Ctr Biol Evaluat & Res, 1401 Rockville Pike, Rockville, MD 20852 USA. RI Dixon, Ann/I-3696-2012 OI Dixon, Ann/0000-0002-5261-304X NR 41 TC 22 Z9 22 U1 2 U2 6 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0006-3525 J9 BIOPOLYMERS JI Biopolymers PD AUG PY 2003 VL 69 IS 4 BP 448 EP 460 DI 10.1002/bip.10421 PG 13 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 709AK UT WOS:000184602400004 PM 12879491 ER PT J AU Krieg, RC Paweletz, CP Liotta, LA Petricoin, EF AF Krieg, RC Paweletz, CP Liotta, LA Petricoin, EF TI Dilution of protein gel stain results in retention of staining capacity SO BIOTECHNIQUES LA English DT Article ID POLYACRYLAMIDE-GELS; ELECTROPHORESIS C1 NCI, Clin Proteom Program, Pathol Lab, NIH, Bethesda, MD 20892 USA. US FDA, Bethesda, MD 20014 USA. RP Krieg, RC (reprint author), NCI, Clin Proteom Program, Pathol Lab, NIH, Bethesda, MD 20892 USA. NR 9 TC 9 Z9 11 U1 0 U2 1 PU EATON PUBLISHING CO PI NATICK PA 154 E. CENTRAL ST, NATICK, MA 01760 USA SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD AUG PY 2003 VL 35 IS 2 BP 376 EP + PG 2 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 711VV UT WOS:000184762500018 PM 12951779 ER PT J AU Delston, RB Kothary, MH Shangraw, KA Tall, BD AF Delston, RB Kothary, MH Shangraw, KA Tall, BD TI Isolation and characterization of a zinc-containing metalloprotease expressed by Vibrio tubiashii SO CANADIAN JOURNAL OF MICROBIOLOGY LA English DT Article DE Vibrio tubiashii; metalloprotease; hemagglutinin ID ELASTOLYTIC PROTEASE; BACILLARY NECROSIS; PURIFICATION; VULNIFICUS; CHOLERAE; CLONING AB A Vibrio tubiashii hemagglutinin, a protease, was purified by ammonium sulfate precipitation, gel filtration, and hydrophobic interaction chromatography. It agglutinates sheep, chicken, bovine, rabbit, guinea pig, and human erythrocytes. It has a molecular mass of 35 kDa, isoelectric points of 3.5 and 3.7, and is inhibited by ortho-phenanthro line, phosphoramidon, and Zincov. The N-terminal amino acid sequence (Ala-Gln-Ala-Thr-Gly-Thr-Gly- Pro-Gly-Gly-Asn-Gln-Lys-Thr-Gly-Gln- Tyr-Asn-Phe-Gly) has strong homology to other Vibrio proteases. C1 US FDA, Ctr Food Safety & Appl Nutr, Div Microbiol Studies, College Pk, MD 20740 USA. US FDA, Ctr Food Safety & Appl Nutr, Div Virulence Assessment, Laurel, MD 20708 USA. RP Tall, BD (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Div Microbiol Studies, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. OI Tall, Ben/0000-0003-0399-3629 NR 20 TC 16 Z9 18 U1 0 U2 1 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 AUG PY 2003 VL 49 IS 8 BP 525 EP 529 DI 10.1139/W03-067 PG 5 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Immunology; Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Immunology; Microbiology GA 739VX UT WOS:000186368400006 PM 14608388 ER PT J AU Musser, SM Egorin, MJ Zuhowski, EG Hamburger, DR Parise, RA Covey, JM White, KD Eiseman, JL AF Musser, SM Egorin, MJ Zuhowski, EG Hamburger, DR Parise, RA Covey, JM White, KD Eiseman, JL TI Biliary excretion of 17-(allylamino)-17-demethoxygeldanamycin (NSC 330507) and metabolites by Fischer 344 rats SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE geldanamycin; ansamycin; HSP90; biliary excretion ID GLUCOCORTICOID RECEPTOR FUNCTION; GENE-PRODUCT P185; BENZOQUINOID ANSAMYCINS; ANTITUMOR AGENT; ANTIPROLIFERATIVE ACTIVITY; GELDANAMYCIN DERIVATIVES; TISSUE DISTRIBUTION; TYROSINE KINASES; CELL-LINES; IN-VIVO AB Purpose. 17-(Allylamino)-17-demethoxygeldanamycin (17AAG), an analogue of the benzoquinone ansamycin geldanamycin, has been extensively studied preclinically and is being evaluated clinically. Studies were performed to define the biliary excretion of 17AAG after i.v. delivery to rats, and to characterize the metabolites of 17AAG observed in rat bile. Materials and methods. In vivo studies were performed in bile-duct-cannulated Fischer 344 rats given a 10 mg/kg i.v. bolus dose of 17AAG. In vitro studies were performed with cloned human CYPs and microsomal epoxide hydrolase. Biliary excretion of 17AAG and metabolites was quantified by HPLC and followed for 4 h after drug delivery. 17AAG metabolites in bile and in in vitro reaction mixtures were identified with LC/MS/MS.Results. By 15 min after i.v. delivery of 17AAG, bile contained at least 15 biotransformation products with absorbance spectra similar to that of 17AAG. Of these, metabolites eluting at 2.7, 2.9, and 8.6 min were present in sufficient concentrations to be quantified, although the lack of authentic standards resulted in their being expressed as 17AAG equivalents. Within the first 4 h after drug delivery, biliary excretion accounted for 28.9+/-6.1% of the 10-mg/kg 17AAG dose. 17AAG and 17-(amino)-17-demethoxygeldanamycin (17AG) accounted for 4.1+/-1.0% of the delivered dose, with 17AAG accounting for 2.0+/-0.5% and 17AG accounting for 2.1+/-0.5%. The metabolites eluting at 2.7, 2.9, and 8.6 min accounted for 10.6+/-2.0%, 9.8+/-1.2%, and 1.0+/-0.2%, respectively, of the administered dose. LC/MS/MS analysis of bile demonstrated major metabolites with molecular weights of 545 and 619, corresponding to 17AG and the diol previously described as resulting from metabolism of 17AAG by CYP3A and microsomal epoxide hydrolase. Of the remaining proposed metabolites, ten had a mass and MS/MS spectrum consistent with mono-oxygenated 17AAG metabolites. One of these metabolites has been identified as the epoxide previously described as resulting from CYP3A oxidation of the allyl double bond. Two other proposed metabolites had a mass and MS/MS spectrum consistent with demethylated 17AAG metabolites, and one had a mass and MS/MS spectrum consistent with a di-demethylated 17AAG metabolite. An analogous series of demethylated and oxidized metabolites was also observed for the 17AG metabolite. Conclusions. Biliary excretion of 17AAG represents a major route of elimination, although most of the material excreted is in the form of metabolites. Bile of rats dosed with 17AAG contained a number of metabolites not previously identified in the plasma or urine of mice treated with 17AAG, but analogous to metabolites described in bile of rats treated with 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin (17DMAG, NSC 707545), another geldanamycin analogue undergoing preclinical evaluation in preparation for subsequent clinical trials. C1 US FDA, Instrumentat & Biophys Branch, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. Univ Pittsburgh, Inst Canc, Mol Therapeut Drug Discovery Program, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Div Hematol Oncol, Dept Med, Sch Med, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Dept Pharmacol, Sch Med, Pittsburgh, PA 15213 USA. NCI, Toxicol & Pharmacol Branch, Dev Therapeut Program, Div Canc Treatment & Daig, Bethesda, MD 20892 USA. RP Egorin, MJ (reprint author), Univ Pittsburgh, Inst Canc, Mol Therapeut Drug Discovery Program, Room G27E,Hillman Res Pavil,5117 Ctr Ave, Pittsburgh, PA 15213 USA. FU NCI NIH HHS [N01-CM07106, 2P30CA47904] NR 44 TC 8 Z9 8 U1 0 U2 2 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD AUG PY 2003 VL 52 IS 2 BP 139 EP 146 DI 10.1007/s00280-003-0630-z PG 8 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 703TV UT WOS:000184297800008 PM 12761648 ER PT J AU Klinman, DM Currie, D AF Klinman, DM Currie, D TI Hierarchical recognition of CpG motifs expressed by immunostimulatory oligodeoxynucleotides SO CLINICAL AND EXPERIMENTAL IMMUNOLOGY LA English DT Article DE CpG oligonucleotides; human; PBMC; immune response; innate immunity; cytokine; Ig ID HUMAN IMMUNE CELLS; BACTERIAL-DNA; SYNTHETIC OLIGONUCLEOTIDES; IN-VITRO; B-CELL; ADJUVANTS; RESPONSES; ACTIVATION; SEQUENCES; ANTIGEN AB Synthetic oligodeoxynucleotides (ODN) containing unmethylated CpG motifs trigger human PBMC to proliferate and secrete 19, cytokines and chemokines. CpG ODN have entered clinical trials, and show promise as vaccine adjuvants, antiallergens, and for the treatment of infectious diseases and cancer. ODNs under consideration for human use vary in the sequence, number and location of the CpG motifs they contain. Yet little is known of the magnitude of the immune response elicited by these diverse ODNs, or the rules governing their interaction with immune cells. This work compares the proliferative, IgM, IL-6 and IP-10 response of PBMC from normal donors to a diverse panel of CpG ODNs. Results indicate that ODNs expressing 3-4 different CpG motifs are strongly stimulatory. The location of these motifs is important, with those at the 5' end exerting the greatest influence on ODN activity. These findings provide a basis for the rational design of ODNs optimized for clinical use. C1 US FDA, Ctr Biol Evaluat & Res, Sect Retroviral Immunol, Bethesda, MD 20892 USA. RP Klinman, DM (reprint author), US FDA, Ctr Biol Evaluat & Res, Sect Retroviral Immunol, Bldg 29 A,Rm 3D10, Bethesda, MD 20892 USA. NR 26 TC 16 Z9 18 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0009-9104 J9 CLIN EXP IMMUNOL JI Clin. Exp. Immunol. PD AUG PY 2003 VL 133 IS 2 BP 227 EP 232 DI 10.1046/j.1365-2249.2003.02216.x PG 6 WC Immunology SC Immunology GA 706TZ UT WOS:000184472300012 PM 12869028 ER PT J AU Petricoin, E Liotta, LA AF Petricoin, E Liotta, LA TI Counterpoint - The vision for a new diagnostic paradigm SO CLINICAL CHEMISTRY LA English DT Editorial Material ID PROTEOMIC PATTERNS; PROSTATE-CANCER; OVARIAN-CANCER; SERUM; BIOMARKER; IDENTIFICATION C1 NCI, NCI FDA Clin Proteom Program, Pathol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. NCI, FDA Clin Proteom Program, Off Direct, Ctr Biol Evaluat & Res Food & Drug Adm, Bethesda, MD 20892 USA. RP Liotta, LA (reprint author), NCI, NCI FDA Clin Proteom Program, Pathol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. NR 12 TC 59 Z9 61 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 AUG PY 2003 VL 49 IS 8 BP 1276 EP 1278 DI 10.1373/49.8.1276 PG 3 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 705CR UT WOS:000184378900007 PM 12881442 ER PT J AU Woo, EJ Burwen, DR Gatumu, SNM Ball, R AF Woo, EJ Burwen, DR Gatumu, SNM Ball, R CA Vaccine Adverse Event Reporting TI Extensive limb swelling after immunization: Reports to the vaccine adverse event reporting system SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID ACELLULAR PERTUSSIS VACCINES; INJECTION SITE REACTIONS; TETANUS TOXOIDS; UNITED-STATES; DIPHTHERIA; IMMUNOGENICITY; SAFETY; REACTOGENICITY; CHILDREN; JAPAN AB Extensive limb swelling (ELS) has been reported after vaccination with a limited number of vaccine types. We sought to describe vaccine types involved in and the clinical characteristics of ELS cases reported to the Vaccine Adverse Event Reporting System (VAERS). A case of ELS was defined as any report of edema extending at least to the elbow or knee of a vaccinated extremity. Four hundred ninety-seven cases were identified, with some describing swelling from the shoulder to the hand or the hip to the foot. Patient age ranged from 0.1 to 91 years. The proportion of reports of ELS associated with a given vaccine, among all VAERS reports received for that vaccine, varied substantially among vaccines. Most reactions began within 1 day after vaccination and involved other signs of inflammation. Postvaccination ELS can involve both the proximal and distal segments of the extremity, affects all age groups, and occurs after vaccination with a broad range of vaccines. C1 US FDA, Vaccine Safety Branch, Div Epidemiol, Off Biostat & Epidemiol,Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Woo, EJ (reprint author), US FDA, Vaccine Safety Branch, Div Epidemiol, Off Biostat & Epidemiol,Ctr Biol Evaluat & Res, 1401 Rockville Pike, Rockville, MD 20852 USA. NR 20 TC 40 Z9 43 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 AUG 1 PY 2003 VL 37 IS 3 BP 351 EP 358 DI 10.1086/375820 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 705RE UT WOS:000184407900006 PM 12884159 ER PT J AU Joshi, BH Leland, P Puri, RK AF Joshi, BH Leland, P Puri, RK TI Identification and characterization of interleukin-13 receptor in human medulloblastoma and targeting these receptors with interleukin-13-pseudomonas exotoxin fusion protein SO CROATIAN MEDICAL JOURNAL LA English DT Article; Proceedings Paper CT Mayo Clinic Course in Advanced Cellular and Molecular Medicine CY SEP 01-05, 2003 CL ZAGREB, CROATIA DE bacterial toxins; fluorescent antibody technique; interleukin-13; medulloblastoma; pseudomonas aeruginosa; receptors; interleukin; reverse transcriptase polymerase chain reaction ID CELL CARCINOMA-CELLS; CIRCULARLY PERMUTED INTERLEUKIN-4; HIGH-AFFINITY INTERLEUKIN-4; COMMON GAMMA-CHAIN; HUMAN GLIOMA-CELLS; PSEUDOMONAS EXOTOXIN; IL-13 RECEPTOR; CHIMERIC PROTEIN; SIGNAL-TRANSDUCTION; BRAIN-TUMORS AB Aim. To identify and characterize the subunit structure of interleukin-13 receptor (IL-13R) in human medulloblastoma cell lines and target them with a chimeric fusion protein consisting of interleukin-13 and Pseudomonas exotoxin (termed as IL-13 cytotoxin). Methods. Five human medulloblastoma cell lines were examined for the expression of IL-13R subunits at the mRNA and protein levels by reverse transcriptase-polymerase chain reaction (RT-PCR) and indirect immunofluorescence studies, respectively. In addition, IL-13 cytotoxin-induced cytotoxicity was examined in these medulloblastoma cell lines by measuring protein synthesis inhibition. Results. All five medulloblastoma cell lines expressed mRNA and proteins for IL-4Ralpha and IL-13Ralpha1 chains, whereas three of the cell lines also showed the presence of IL-13Ralpha2. mRNA or protein for IL-2gammac chain was not detected in any of the cell lines. Consistent with the expression of IL-13Ralpha2 chain, IL-13 cytotoxin was highly and specifically cytotoxic to three of five medulloblastoma cell lines. The sensitivity of medulloblastoma cell lines to IL-13 cytotoxin could be completely eliminated by concurrent incubation with excess of IL-13, but not with IL-2 or IL-4. Conclusion. These studies establish IL-13R, in particular IL-13Ralpha2, as a medulloblastoma-associated target for IL-13 cytotoxin therapy. IL-13 cytotoxin may be useful for medulloblastoma therapy. Alternatively, IL-13Ralpha2 may serve as a tumor-specific antigen for active immunotherapy. C1 US FDA, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. RP Puri, RK (reprint author), NIH Bldg 29B,Room 2NN10,29 Lincoln Dr, Bethesda, MD 20892 USA. NR 62 TC 16 Z9 18 U1 0 U2 0 PU MEDICINSKA NAKLADA PI ZAGREB PA VLASKA 69, HR-10000 ZAGREB, CROATIA SN 0353-9504 J9 CROAT MED J JI Croat. Med. J. PD AUG PY 2003 VL 44 IS 4 BP 455 EP 462 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 718HB UT WOS:000185138100012 PM 12950150 ER PT J AU Katzman, SM Wikstrom, J Chenault, M Harel, T Grossman, A Khawaled, R Smith, PJS Shirihai, OS AF Katzman, SM Wikstrom, J Chenault, M Harel, T Grossman, A Khawaled, R Smith, PJS Shirihai, OS TI The effect of diabetes on metabolic heterogeneity and oscillatory behavior of individual cells in intact Islets of Langerhans SO DIABETOLOGIA LA English DT Meeting Abstract CT 18th Congress of the International-Diabetes-Federation CY AUG 24-29, 2003 CL PARIS, FRANCE SP Int Diabetes Fed C1 Marine Biol Lab, Biocurrents Res Ctr, Woods Hole, MA 02543 USA. Karolinska Inst, S-10401 Stockholm, Sweden. US FDA, Washington, DC 20204 USA. Impulse Dynam, Haifa, Israel. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD AUG PY 2003 VL 46 SU 2 MA 489 BP A172 EP A172 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 720BX UT WOS:000185242100489 ER PT J AU Naaz, A Yellayi, S Zakroczymski, MA Bunick, D Doerge, DR Lubahn, DB Helferich, WG Cooke, PS AF Naaz, A Yellayi, S Zakroczymski, MA Bunick, D Doerge, DR Lubahn, DB Helferich, WG Cooke, PS TI The soy isoflavone genistein decreases adipose deposition in mice SO ENDOCRINOLOGY LA English DT Article ID ESTROGEN-RECEPTOR-ALPHA; LIPOPROTEIN-LIPASE; SOYBEAN ISOFLAVONES; TISSUE DISTRIBUTION; WEIGHT-REDUCTION; PHYTO-ESTROGENS; PLASMA-LIPIDS; OBESE MICE; SHORT-TERM; WOMEN AB Adipose tissue is responsive to estrogen and expresses both estrogen receptor alpha and beta. To test the hypothesis that the estrogenic soy isoflavone genistein can have effects on adipose tissue, juvenile or adult C57/BL6 mice were ovariectomized and given daily injections of vehicle, 17beta-estradiol (5 mug/kg.d) or genistein (8-200 mg/kg.d) sc for 21-28 d. To test effects of dietary genistein, 25- to 27-d-old mice were fed diets containing 0-1500 parts per million (ppm) genistein for 12 d. Mice were killed and fat pads weighed. Parametrial fat pads were used for morphometric and Northern analysis. Genistein injections decreased adipose weight and adipocyte circumference at higher doses; effects in adult and juvenile mice were similar. Genistein decreased lipoprotein lipase mRNA, which may be a critical aspect of its adipose effects. Juveniles fed 500-1500 ppm dietary genistein had dose-responsive decreases in fat pad weights of 37-57%, compared with controls; 300 ppm genistein did not cause decreases. Genistein doses of 300, 500, 1000, and 1500 ppm produced serum genistein concentrations of 1.02 +/- 0.14 muM, 1.79 +/- 0.32 muM, 2.55 +/- 0.18 muM, and 3.81 +/- 0.39 muM, respectively. These results indicate dietary genistein at 500-1500 ppm produces antilipogenic effects in mice at serum levels that humans are realistically exposed to. C1 Univ Illinois, Dept Vet Biosci, Urbana, IL 61802 USA. Univ Illinois, Dept Food Sci & Nutr, Urbana, IL 61802 USA. Univ Illinois, Div Nutr Sci, Urbana, IL 61802 USA. Univ Missouri, Dept Biochem, Columbia, MO 65211 USA. Univ Missouri, Dept Child Hlth, Columbia, MO 65211 USA. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Cooke, PS (reprint author), Univ Illinois, Dept Vet Biosci, 2001 S Lincoln Ave, Urbana, IL 61802 USA. NR 50 TC 155 Z9 165 U1 0 U2 10 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD AUG PY 2003 VL 144 IS 8 BP 3315 EP 3320 DI 10.1210/en.2003-0076 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 703AW UT WOS:000184258700008 PM 12865308 ER PT J AU Perkins, R Fang, H Tong, WD Welsh, WJ AF Perkins, R Fang, H Tong, WD Welsh, WJ TI Quantitative structure-activity relationship methods: Perspectives on drug discovery and toxicology SO ENVIRONMENTAL TOXICOLOGY AND CHEMISTRY LA English DT Review DE quantitative structure-activity relationship toxicology; drug design; chemoinformatics; chemometric ID MOLECULAR-FIELD ANALYSIS; ATOMIC PHYSICOCHEMICAL PARAMETERS; ELECTROTOPOLOGICAL STATE INDEXES; STRUCTURE-PROPERTY RELATIONSHIP; ESTROGEN-RECEPTOR LIGANDS; ARTIFICIAL NEURAL-NETWORK; ALPHA BINDING-AFFINITY; 3D QSAR; PARTITION-COEFFICIENTS; GENETIC ALGORITHMS AB Quantitative structure-activity relationships (QSARs) attempt to correlate chemical structure with activity using statistical approaches. The QSAR models are useful for various purposes including the prediction of activities of untested chemicals. Quantitative structure-activity relationships and other related approaches have attracted broad scientific interest, particularly in the pharmaceutical industry for drug discovery and in toxicology and environmental science for risk assessment. An assortment of new QSAR methods have been developed during the past decade, most of them focused on drug discovery. Besides advancing our fundamental knowledge of QSARs, these scientific efforts have stimulated their application in a wider range of disciplines, such as toxicology, where QSARs have not yet gained full appreciation. In this review, we attempt to summarize the status of QSAR with emphasis on illuminating the utility and limitations of QSAR technology. We will first review two-dimensional (2D) QSAR with a discussion of the availability and appropriate selection of molecular descriptors. We will then proceed to describe three-dimensional (3D) QSAR and key issues associated with this technology, then compare the relative suitability of 2D and 3D QSAR for different applications. Given the recent technological advances in biological research for rapid identification of drug targets, we mention several examples in which QSAR approaches are employed in conjunction with improved knowledge of the structure and function of the target receptor. The review will conclude by discussing statistical validation of QSAR models, a topic that has received sparse attention in recent years despite its critical importance. C1 Logicon ROW Sci, Jefferson, AR 72079 USA. US FDA, Natl Ctr Toxicol Res, Ctr Tox Informat, Jefferson, AR 72079 USA. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Pharmacol, Piscataway, NJ 08854 USA. RP Perkins, R (reprint author), Logicon ROW Sci, 3900 NCTR Rd,MC 910, Jefferson, AR 72079 USA. NR 131 TC 134 Z9 137 U1 2 U2 31 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 AUG PY 2003 VL 22 IS 8 BP 1666 EP 1679 DI 10.1897/01-171 PG 14 WC Environmental Sciences; Toxicology SC Environmental Sciences & Ecology; Toxicology GA 727CT UT WOS:000185639300003 PM 12924569 ER PT J AU Tong, W Welsh, WJ Shi, LM Fang, H Perkins, R AF Tong, W Welsh, WJ Shi, LM Fang, H Perkins, R TI Structure-activity relationship approaches and applications SO ENVIRONMENTAL TOXICOLOGY AND CHEMISTRY LA English DT Review DE structure-activity relationship; predictive toxicology; computational toxicology; chemometrics ID ESTROGEN-RECEPTOR-BINDING; ATOMIC PHYSICOCHEMICAL PARAMETERS; DIRECTED QUANTITATIVE STRUCTURE; ARTIFICIAL NEURAL NETWORKS; MOLECULAR-FIELD ANALYSIS; OPTIMAL FRAGMENTATION PRINCIPLE; SOLVATION ENERGY RELATIONSHIPS; CHEMICAL-STRUCTURE DATABASES; DRUG DISCOVERY DATABASES; LARGE DIVERSE SET AB New techniques and software have enabled ubiquitous use of structure-activity relationships (SARs) in the pharmaceutical industry and toxicological sciences. We review the status of SAR technology by using examples to underscore the advances as well as the unique technical challenges. Applying SAR involves two steps: Characterization of the chemicals under investigation, and application of chemometric approaches to explore data patterns or to establish the relationships between structure and activity. We describe generally but not exhaustively the SAR methodologies popular use in toxicology, including representation of chemical structure, and chemometric techniques where models are both unsupervised and supervised. The utility of SAR technology is most evident when supervised methods are used to predict toxicity of untested chemicals based only on chemical structure. Such models can predict on both an ordinal scale (e.g., active vs inactive) or a continuous scale (e.g., median lethal dose [LD50] dose). The reader is also referred to a companion paper in this issue that discusses quantitative structure-activity relationship (QSAR) methods that have advanced markedly over the past decade. C1 Logicon ROW Sci, Jefferson, AR 72079 USA. US FDA, Natl Ctr Toxicol Res, Ctr Toxiconinformat, Jefferson, AR 72079 USA. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Pharmacol, Piscataway, NJ 08854 USA. BASF Corp, Princeton, NJ 08543 USA. RP Perkins, R (reprint author), Logicon ROW Sci, 3900 NCTR Rd,MC 910, Jefferson, AR 72079 USA. NR 151 TC 35 Z9 36 U1 1 U2 19 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 AUG PY 2003 VL 22 IS 8 BP 1680 EP 1695 DI 10.1897/01-198 PG 16 WC Environmental Sciences; Toxicology SC Environmental Sciences & Ecology; Toxicology GA 727CT UT WOS:000185639300004 PM 12924570 ER PT J AU Cordoba-Rodriguez, R Frucht, DM AF Cordoba-Rodriguez, R Frucht, DM TI IL-23 and IL-27: new members of the growing family of IL-12 related cytokines with important implications for therapeutics SO EXPERT OPINION ON BIOLOGICAL THERAPY LA English DT Review DE CD4+T cell; human; IL-12; IL-23; IL-27; mouse; Th1 differentiation ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; CENTRAL-NERVOUS-SYSTEM; HUMAN DENDRITIC CELLS; CHRONIC HEPATITIS-B; LINEAGE COMMITMENT; INTERFERON-GAMMA; T-CELLS; TYROSINE PHOSPHORYLATION; MYCOBACTERIAL INFECTION; INTERLEUKIN-12 THERAPY AB The recent discoveries of the two interleukin (IL)-12-related cytokines, IL-23 and IL-27, reveal that the regulation of cellular immunity is more complex than originally thought. Until these discoveries, the role of IL-12 in modulating cellular immune responses had been overestimated due to the belief that the IL-12 p40 subunit was unique to IL-12. However, because p40 is shared between IL-12 and IL-23, it would be expected that p40(-/-) mice are doubly deficient in IL-12 and IL-23. Indeed, the essential role previously attributed to IL-12 in experimental autoimmune encephalitis during studies of p40(-/-) mice has been shown to be due to IL-23 instead. The newest addition to the IL-12 cytokine family, IL-27, has unique features as well. Its specific action on naive CD4+ T cells in both mice and humans appears to distinguish it from the other IL-12 family members. Although related, the IL-12 family of cytokines and their receptors have distinct patterns of expression and unique effects on developing immune responses. This review summarises much of the pertinent literature on the IL-12 cytokine family and provides predictions regarding their potential therapeutic roles based on what has been learned about their functions in vitro and in vivo in gene-deficient mice. C1 US FDA, Ctr Biol Evaluat & Res, Div Monoclonal Antibodies, Cell Biol Lab, Bethesda, MD 20892 USA. RP Frucht, DM (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Monoclonal Antibodies, Cell Biol Lab, Bethesda, MD 20892 USA. NR 61 TC 22 Z9 24 U1 0 U2 1 PU ASHLEY PUBLICATIONS LTD PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1471-2598 J9 EXPERT OPIN BIOL TH JI Expert Opin. Biol. Ther. PD AUG PY 2003 VL 3 IS 5 BP 715 EP 723 DI 10.1517/14712598.3.5.715 PG 9 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 708BB UT WOS:000184545600003 PM 12880372 ER PT J AU Lee, HS Kim, JG AF Lee, HS Kim, JG TI Effects of debittering on red grapefruit juice concentrate SO FOOD CHEMISTRY LA English DT Article DE clear grapefruit juice concentrate; vitamin C; color; debitter ID ORANGE JUICE; CITRUS JUICE; VITAMIN-C; LIMONIN; NARINGIN; STORAGE; RESINS AB Clarified, debittered grapefruit juice concentrate (64.2 degreesBx) was produced by membrane filtration, debittering, and an evaporation process. Debittering by an XAD-16 adsorption column removed more than 78% of bitterness in grapefruit juice, based on naringin content. Also, some of the non-bitter flavonoids, such as narirutin and hesperidin, were nearly completely removed. Other values, such as vitamin C, and total phenolics, based on absorbance at 325 run, were also reduced (P < 0.05) after debittering. The vitamin C loss can probably be attributed to juice handling during processing. Absorption spectra in the 200-450 nm region showed characteristic absorption maxima around 280 and 322 nm in the control but no spectral fine structure in debittered concentrate. Besides differences in flavonoid profile, there was a slight difference in colour. Debittered concentrate had less chroma (CIE C*) and more lightness (CIE L*) than the control. Thus, the colour of debittered concentrate could be described as slightly paler than that of the control. (C) 2003 Published by Elsevier Science Ltd. C1 Florida Dept Citrus, Ctr Citrus Res & Educ, Lake Alfred, FL 33850 USA. Natl Hort Res Inst, Suwon 440310, South Korea. RP Lee, HS (reprint author), US FDA, CFSAN, OFAS, College Pk, MD 20740 USA. NR 20 TC 21 Z9 33 U1 1 U2 21 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 AUG PY 2003 VL 82 IS 2 BP 177 EP 180 DI 10.1016/S0308-8146(02)00280-7 PG 4 WC Chemistry, Applied; Food Science & Technology; Nutrition & Dietetics SC Chemistry; Food Science & Technology; Nutrition & Dietetics GA 693ZG UT WOS:000183747800001 ER PT J AU Garthright, WE Blodgett, RJ AF Garthright, WE Blodgett, RJ TI FDA's preferred MPN methods for standard, large or unusual tests, with a spreadsheet SO FOOD MICROBIOLOGY LA English DT Article DE MPN; most probable number; serial dilution; fermentation tubes; microbial concentration ID SERIAL DILUTIONS; DENSITY; BIAS AB The US Food and Drug Administration (FDA) presents its preferred methods for statistical interpretation of serial dilution tests for microbes in the Bacteriological Analytical Manual (BAM) of the FDA and the AOAC. This article explains why the particular methods in the manual were selected and describes the adjustments chosen to create a new, flexible method for calculating most probable numbers (MPNs), confidence intervals, and measures of improbability for up to 18 dilutions and up to 1020 tubes per dilution. The methods have been put into a spreadsheet for easy use, and are offered free in the interest of promoting the microbial safety of food and water. The FDA prefers the MPN, not adjusted for bias, for its point estimate of concentration, with the improbability standards and confidence intervals of De Man for standard three-dilution tables with up to 10 tubes per dilution. For large or unusual test designs, the FDA also prefers the MPN but with a new improbability index and the confidence intervals of Haldane. Some other methods in recent literature are discussed briefly, and reasons are given why they are not preferred. Published by Elsevier Science Ltd. C1 US FDA, Ctr Food Safety & Appl Nutr, Div Math, College Pk, MD 20740 USA. RP Blodgett, RJ (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Div Math, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. NR 21 TC 65 Z9 65 U1 3 U2 15 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0740-0020 J9 FOOD MICROBIOL JI Food Microbiol. PD AUG PY 2003 VL 20 IS 4 BP 439 EP 445 AR PII S0740-0020(02)00144-2 DI 10.1016/S0740-0020(02)00144-2 PG 7 WC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology SC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology GA 678TQ UT WOS:000182882900009 ER PT J AU Wear, KA Laib, A AF Wear, KA Laib, A TI The dependence of ultrasonic backscatter on trabecular thickness in human calcaneus: Theoretical and experimental results SO IEEE TRANSACTIONS ON ULTRASONICS FERROELECTRICS AND FREQUENCY CONTROL LA English DT Article ID BONE-MINERAL DENSITY; BOVINE CANCELLOUS BONE; QUANTITATIVE ULTRASOUND; HIP FRACTURE; FREQUENCY-DEPENDENCE; CORTICAL BONE; OS CALCIS; MECHANICAL-PROPERTIES; IN-VITRO; ATTENUATION AB Trabecular thickness within cancellous bone is an important determinant of osteoporotic fracture risk. Noninvasive assessment of trabecular thickness potentially could yield useful diagnostic information. Faran's theory of elastic scattering from a cylindrical object immersed in a fluid has been used to predict the dependence of ultrasonic backscatter on trabecular thickness. The theory predicts that, in the range of morphological and material properties expected for trabecular bone, the backscatter coefficient at 500 kHz should be approximately proportional to trabecular thickness to the power of 2.9. Experimental measurements of backscatter coefficient were performed on 43 human calcaneus samples in vitro. Mean trabecular thicknesses on the 43 samples were assessed using micro computed tomography (CT). A power law fit to the data showed that the backscatter coefficient empirically varied as trabecular thickness to the 2.8 power. The 95% confidence interval for this exponent was 1.7 to 3.9. The square of the correlation coefficient for the linear regression to the log transformed data was 0.40. This suggests that 40% of variations in backscatter may be attributed to variations in trabecular thickness. These results reinforce previous studies that offered validation for the Faran cylinder model for prediction of scattering properties of cancellous bone, and provide added evidence for the potential diagnostic utility of the backscatter measurement. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20852 USA. SCANCO Med AG, CH-8303 Bassersdorf, Switzerland. RP US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20852 USA. EM kaw@cdrh.fda.gov NR 73 TC 33 Z9 38 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 AUG PY 2003 VL 50 IS 8 BP 979 EP 986 DI 10.1109/TUFFC.2003.1226542 PG 8 WC Acoustics; Engineering, Electrical & Electronic SC Acoustics; Engineering GA 713BW UT WOS:000184836400005 PM 12952089 ER PT J AU Semper, AE Heron, K Woollard, ACS Kochan, JP Friedmann, PS Church, MK Reischl, IG AF Semper, AE Heron, K Woollard, ACS Kochan, JP Friedmann, PS Church, MK Reischl, IG TI Surface expression of Fc epsilon RI on Langerhans' cells of clinically uninvolved skin is associated with disease activity in atopic dermatitis, allergic asthma, and rhinitis SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE Fc epsilon RI; Langerhans' cell; IgE; IgE receptor; skin; atopic dermatitis; epidermal sheet; atopic disease ID ANTIGEN-PRESENTING CELLS; HIGH-AFFINITY RECEPTOR; DENDRITIC CELLS; IGE RECEPTOR; NASAL-MUCOSA; ALPHA-SUBUNIT; LESIONAL SKIN; BINDING; MICROSCOPY; ACTIVATION AB Background: FcepsilonRI expressed on the surface of human epidermal Langerhans' cells facilitates uptake of IgE-associated allergens and plays a pivotal role in the pathogenesis of atopic dermatitis. Seminal results from studies investigating Langerhans' cell FcepsilonRI in skin biopsy sections or epidermal cell suspensions demonstrate the highest receptor expression in lesional skin of patients with active atopic dermatitis. Objective: We sought to investigate and localize FcepsilonRI expression on Langerhans' cells within a minimally disturbed tissue environment in clinically uninvolved skin and to compare receptor expression between healthy donors and patients with atopic dermatitis or other allergic diseases. Methods: Intact epidermal sheets from skin suction blisters, immunofluorescently stained with Langerhans' cell markers and anti-FeepsilonRIalpha (mAbs 15E5 and 22E7) or anti-IgE, were examined by means of confocal microscopy. Samples incubated with anti-FcepsilonRIalpha before or after cell fixation-permeabilization were compared to discriminate between cytoplasmic and membrane localization. Results: Cytoplasmic FcepsilonRI alpha chain was found in Langerhans' cells from all donors, irrespective of atopic status. Surface FeepsilonRI-bound IgE was detected in the skin of individuals with active atopic dermatitis and in the skin of those with active asthma or rhinitis. No surface FcepsilonRI was expressed in the skin of patients with a clinical history of atopic dermatitis, asthma, or rhinitis whose disease was in remission or in the skin of nonatopic individuals. Conclusion: In clinically uninvolved skin, Langerhans' cell-surface FcepsilonRI expression is not only linked to atopic dermatitis but is also generally associated with allergic disease. This supports the concept of a systemic regulatory mechanism associated with active allergic disease, which is further aggravated by local inflammation in atopic skin lesions. C1 Univ Southampton, Sch Med, Div Infect Inflammat & Repair, Southampton, Hants, England. Hoffmann La Roche Inc, Nutley, NJ USA. RP Reischl, IG (reprint author), US FDA, Ctr Biol Evaluat & Res, Off Therapeut Review & Res, Div Monoclonal Antibodies, Bldg 29B,HFM 564,29 Lincoln Dr,MSC 4555, Bethesda, MD 20892 USA. NR 39 TC 37 Z9 39 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD AUG PY 2003 VL 112 IS 2 BP 411 EP 419 DI 10.1067/mai.2003.1626 PG 9 WC Allergy; Immunology SC Allergy; Immunology GA 709WY UT WOS:000184650600028 PM 12897750 ER PT J AU Collins, JM AF Collins, JM TI Functional imaging in phase I studies: Decorations or decision making? SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID RECOMBINANT HUMAN ENDOSTATIN; COMBRETASTATIN A-4 PHOSPHATE; VASCULAR-TARGETING AGENT; ADVANCED SOLID TUMORS C1 US FDA, Lab Clin Pharmacol, Rockville, MD 20857 USA. RP Collins, JM (reprint author), US FDA, Lab Clin Pharmacol, Rockville, MD 20857 USA. NR 10 TC 30 Z9 31 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 AUG 1 PY 2003 VL 21 IS 15 BP 2807 EP 2809 DI 10.1200/JCO.2003.05.100 PG 3 WC Oncology SC Oncology GA 706PJ UT WOS:000184461800001 PM 12807933 ER PT J AU Fleischman, GJ Napier, CL Stewart, D Palumbo, SA AF Fleischman, GJ Napier, CL Stewart, D Palumbo, SA TI Effect of temperature on the growth response of Salmonella enteritidis inoculated onto the vitelline membranes of fresh eggs SO JOURNAL OF FOOD PROTECTION LA English DT Article ID SHELL EGGS; HENS; CONTAMINATION AB The growth response of Salmonella Enteritidis (SE) on the vitelline membrane in vitro was studied with the use of a special tube devised specifically for the inoculation of SE onto the vitelline membrane and for the sampling of the yolk near the inoculation site. This latter ability allowed the detection of the movement of SE into the yolk. The growth of SE on the membrane was compared with that of SE inoculated into yolk and albumen in vitro and in ovo in fresh in-shell eggs. The incubation time was 2 days, and the incubation temperatures were 4, 8, 15, 27, and 37degreesC. Comparison of the results obtained for in vitro growth showed that at 4, 8, and 15degreesC, SE behaved as if it were in the albumen, with its numbers decreasing over time. At 27 and 37degreesC, SE grew as if it were in yolk, with a maximum increase of 4.5 log CFU after 2 days at 37degreesC. In no experiments involving growth on the vitelline membrane did SE appear in the yolk. Comparisons between in vitro and in ovo growth responses of SE in yolk and albumen indicate that SE growth on the membrane parallels that in the in-shell egg. C1 US FDA, Summit Argo, IL 60501 USA. IIT, Natl Ctr Food Safety & Technol, Summit Argo, IL 60501 USA. RP Fleischman, GJ (reprint author), US FDA, 6502 S Archer Rd, Summit Argo, IL 60501 USA. FU FDA HHS [FD-000431] NR 13 TC 9 Z9 9 U1 0 U2 1 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 AUG PY 2003 VL 66 IS 8 BP 1368 EP 1373 PG 6 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 708NN UT WOS:000184574500004 PM 12929821 ER PT J AU Reddy, NR Solomon, HM Tetzloff, RC Rhodehamel, EJ AF Reddy, NR Solomon, HM Tetzloff, RC Rhodehamel, EJ TI Inactivation of Clostridium botulinum type A spores by high-pressure processing at elevated temperatures SO JOURNAL OF FOOD PROTECTION LA English DT Article ID HIGH HYDROSTATIC-PRESSURE; PHOSPHATE-BUFFERED SALINE; LISTERIA-MONOCYTOGENES; ESCHERICHIA-COLI; BACTERIAL-SPORES; FOODBORNE PATHOGENS; SPOROGENES SPORES; ORANGE JUICE; EWES MILK; HEAT AB The effects of high-pressure treatments at various temperature-time combinations on the inactivation of spores of Clostridium botulinum type A strains 62-A and BS-A in phosphate buffer (0.067 M, pH 7.0) and in a crabmeat blend were investigated. The log unit reduction of strain 62-A spores increased significantly as the processing pressure increased from 417 to 827 MPa (from 60,000 to 120,000 lb/in(2)) at 75degreesC. The reduction of BS-A and 62-A spores in either medium increased as processing temperatures increased from 60 to 75degreesC and processing times increased from 5 to 15 or 20 min at a maximum pressure of 827 MPa. Approximately 2- and 3-log reductions of BS-A and 62-A spores, respectively, in phosphate buffer were obtained at the maximum pressure-maximum temperature combination of 827 MPa and 75degrees for a processing time of 20 min. Processing for 15 min at the maximum pressure-maximum temperature combination resulted in maximum reductions of 3.2 and 2.7 log units for BS-A and 62-A spores, respectively, in the crabmeat blend. Results obtained in this study indicate that the crabmeat blend did not protect BS-A and 62-A spores against inactivation by high-pressure processing. C1 US FDA, Summit Argo, IL 60501 USA. IIT, Natl Ctr Food Safety & Technol, Summit Argo, IL 60501 USA. US FDA, Div Microbiol Studies, Washington, DC 20204 USA. Sealed Air Corp, Duncan, SC 29334 USA. RP Reddy, NR (reprint author), US FDA, 6502 S Archer Rd, Summit Argo, IL 60501 USA. EM rukma.reddy@cfsan.fda.gov FU FDA HHS [FD-000431] NR 47 TC 63 Z9 67 U1 1 U2 13 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 AUG PY 2003 VL 66 IS 8 BP 1402 EP 1407 PG 6 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 708NN UT WOS:000184574500009 PM 12929826 ER PT J AU Yoon, KS Burnette, CN Whiting, RC AF Yoon, KS Burnette, CN Whiting, RC TI Effects of pH and agitation on the growth of Listeria monocytogenes Scott A in brain heart infusion broth containing combined potassium lactate and sodium diacetate during storage at 4 or 10 degrees C SO JOURNAL OF FOOD PROTECTION LA English DT Article ID COLD-SMOKED SALMON; VACUUM PACKAGES; INHIBITION; BEEF; MEAT; ANTIMICROBIALS; CONTAMINATION; FRANKFURTERS; TEMPERATURE; ATMOSPHERE AB The objective of this study was to compare the effects of pH on the growth kinetics of Listeria monocytogenes Scott A in static and agitated broths stored at 4 and 10degreesC with and without a combination of 1.85% potassium lactate (PL) and 0.13% sodium diacetate (SDA) (3.3% of a 60% commercial solution, PURASAL P Opti.Form 4). The pH of brain heart infusion broth without (control) or with 1.85% PL + 0.13% SDA was adjusted to 5.5, 6.0, 6.5, and 7.5. L. monocytogenes Scott A was inoculated (at 10(2)-CFU/ml) into pH-adjusted broth, which was stored at 4 or 10degreesC with or without agitation. At pH 5.5, a listeriostatic effect was observed for the broth containing 1.85% PL + 0.13% SDA at 4 and 10degreesC both with and without agitation. At pH 6.0, 1.85% PL + 0.13% SDA fully controlled the growth of L. monocytogenes Scott A in static broth at 4degreesC for up to 20 days and significantly slowed the growth of the pathogen in agitated broth. At 10degreesC, the growth of L. monocytogenes Scott A was significantly reduced by 1.85% PL + 0.13% SDA in agitated and unagitated broths. At pH 6.5, 1.85% PL + 0.13% SDA significantly suppressed the growth of L. monocytogenes Scott A at both 4degreesC (P < 0.001) and 10degreesC (P < 0.01). At pH 7.5, 1.85% PL + 0.13% SDA had a limited effect on the growth of L. monocytogenes Scott A in broth stored at 4 and 10degreesC. At 4degreesC, agitation decreased the lag time and increased the growth rate of L. monocytogenes Scott A at all tested pHs. A similar but less obvious trend was observed for broths stored at 10degreesC. These results indicate that lactate-diacetate combinations effectively acted with low pH and temperature to inhibit the growth of L. monocytogenes Scott A. C1 Univ Maryland Eastern Shore, Dept Human Ecol, Prince Anne, MD 21853 USA. US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20470 USA. RP Yoon, KS (reprint author), Univ Maryland Eastern Shore, Dept Human Ecol, Prince Anne, MD 21853 USA. NR 26 TC 10 Z9 10 U1 0 U2 2 PU INT ASSOC FOOD PROTECTION PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD AUG PY 2003 VL 66 IS 8 BP 1469 EP 1473 PG 5 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 708NN UT WOS:000184574500022 PM 12929839 ER PT J AU Gursel, I Gursel, M Yamada, H Ishii, KJ Takeshita, F Klinman, DM AF Gursel, I Gursel, M Yamada, H Ishii, KJ Takeshita, F Klinman, DM TI Repetitive elements in mammalian telomeres suppress bacterial DNA-induced immune activation SO JOURNAL OF IMMUNOLOGY LA English DT Article ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; STIMULATORY CPG MOTIFS; IN-VIVO; INHIBITORY RECEPTORS; CUTTING EDGE; CELLS; OLIGODEOXYNUCLEOTIDES; OLIGONUCLEOTIDES; ARTHRITIS; SEQUENCE AB Bacterial DNA contains immunostimulatory CpG motifs that trigger an innate immune response capable of promoting host survival following infectious challenge. Yet CpG-driven immune activation may also have deleterious consequences, ranging from autoinumme disease to death. We find that repetitive elements present at high frequency in mammalian telomeres, but rare in bacteria, down-regulate CpG-induced immune activation. Suppressive activity correlates with the ability of telomeric TTAGGG repeats to form G-tetrads. Colocalization of CpG DNA with Toll-like receptor 9 in endosomal vesicles is disrupted by these repetitive elements, although cellular binding and uptake remain unchanged. These findings are the first to establish that specific host-derived molecules can down-regulate the innate immune response elicited by a TLR ligand. C1 US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. US FDA, Sect Retroviral Immunol, Bethesda, MD 20892 USA. RP Klinman, DM (reprint author), US FDA, 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, Ihsan/0000-0003-3761-1166 NR 45 TC 147 Z9 156 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD AUG 1 PY 2003 VL 171 IS 3 BP 1393 EP 1400 PG 8 WC Immunology SC Immunology GA 704FG UT WOS:000184327600035 PM 12874230 ER PT J AU Huang, LY Aliberti, J Leifer, CA Segal, DM Sher, A Golenbock, DT Golding, B AF Huang, LY Aliberti, J Leifer, CA Segal, DM Sher, A Golenbock, DT Golding, B TI Heat-killed Brucella abortus induces TNF and IL-12p40 by distinct MyD88-dependent pathways: TNF, unlike IL-12p40 secretion, is toll-like receptor 2 dependent SO JOURNAL OF IMMUNOLOGY LA English DT Article ID INNATE IMMUNE-SYSTEM; CELL WALL COMPONENTS; CUTTING EDGE; SIGNAL-TRANSDUCTION; BACTERIAL-DNA; PATTERN-RECOGNITION; DENDRITIC CELLS; T-CELLS; LIPOPOLYSACCHARIDE; MICE AB Cattle and humans are susceptible to infection with the Gram-negative intracellular bacterium Brucella abortus. Heat-killed B. abortus (HKBA) is a strong Th1 adjuvant and carrier. Previously, we have demonstrated that dendritic cells produce IL-12 in response to HKBA stimulation. In the present study, we use knockout mice and in vitro reconstitution assays to examine the contribution of signaling by Toll-like receptors (TLRs) and their immediate downstream signaling initiator, myeloid differentiation protein MyD88, in the activation following stimulation by HKBA. Our results show that HKBA-mediated induction of IL-12p40 and TNF is dependent on the adapter molecule MyD88. To identify the TLR involved in HKBA recognition, we examined HKBA responses in TLR2- and TLR4-deficient animals. TNF responses to HKBA were TLR4 independent; however, the response in TLR2-deficient mice was significantly delayed and reduced, although not completely abolished. Studies using Chinese hamster ovary/CD14 reporter cell lines stably transfected with either human TLR2 or human TLR4 confirmed the results seen with knockout mice, namely TLR2, but not TLR4, can mediate cellular activation by HKBA. In addition, human embryonic kidney 293 cells, which do not respond to HKBA, were made responsive by transfecting TLR2, but not TLR4 or TLR9. Taken together, our data demonstrate that MyD88-dependent pathways are crucial for activation by HKBA and that TLR2 plays a role in TNF, but not IL-12p40 pathways activated by this microbial product. C1 US FDA, Ctr Biol Evaluat & Res, Div Hematol, Lab Plasma Derivat, Bethesda, MD 20892 USA. NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. Univ Massachusetts, Sch Med, Dept Med, Worcester, MA 01605 USA. RP Golding, B (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Hematol, Lab Plasma Derivat, Bldg 29,Room 328,8800 Rockville Pike HFM-345, Bethesda, MD 20892 USA. RI Aliberti, Julio/G-4565-2012; Aliberti, Julio/I-7354-2013 OI Aliberti, Julio/0000-0003-3420-8478 NR 47 TC 50 Z9 52 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD AUG 1 PY 2003 VL 171 IS 3 BP 1441 EP 1446 PG 6 WC Immunology SC Immunology GA 704FG UT WOS:000184327600041 PM 12874236 ER PT J AU Manischewitz, J King, LR Bleckwenn, NA Shiloach, J Taffs, R Merchlinsky, M Eller, N Mikolajczyk, MG Clanton, DJ Monath, T Weltzin, RA Scott, DE Golding, H AF Manischewitz, J King, LR Bleckwenn, NA Shiloach, J Taffs, R Merchlinsky, M Eller, N Mikolajczyk, MG Clanton, DJ Monath, T Weltzin, RA Scott, DE Golding, H TI Development of a novel vaccinia-neutralization assay based on reporter-gene expression SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID SMALLPOX VACCINATION; VIRUS; COMPLICATIONS; RESPONSES AB In anticipation of large-scale smallpox vaccination, clinical trials of new vaccine candidates with improved safety profiles, and new vaccinia immune globulin (VIG) products, there is an immediate need to develop new assays to measure vaccinia-specific immune responses. The classical assay to measure vaccinia neutralization, the plaque-reduction neutralization test (PRNT), is slow, labor intensive, and difficult to validate and transfer. Here we describe the development of a novel vaccinia-neutralization assay based on the expression of a reporter gene, beta-galactosidase (beta-Gal). Using a previously constructed vaccinia-beta-Gal recombinant virus, vSC56, we developed a neutralization assay that is rapid, sensitive, and reproducible. The readout is automated. We show that the neutralizing titers, ID50, for several VIG products measured by our assay were similar to those obtained by PRNTs. A new Food and Drug Administration VIG standard was established for distribution to other laboratories. The new assay will serve as an important tool both for preclinical and clinical trials of new smallpox vaccines and for evaluation of therapeutic agents to treat vaccine-associated adverse reactions. C1 US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. US FDA, Div Emerging Transfus Dis, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. US FDA, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. Dynport Vaccine Co, Frederick, MD USA. Acambis, Cambridge, MA USA. NIDDKD, Biotechnol Unit, NIH, Bethesda, MD 20892 USA. RP Golding, H (reprint author), US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, HFM-454,Bldg 29A,Rm 1A21,8800 Rockville Pike, Bethesda, MD 20892 USA. NR 17 TC 51 Z9 51 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 AUG 1 PY 2003 VL 188 IS 3 BP 440 EP 448 DI 10.1086/376557 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 704BB UT WOS:000184316900014 PM 12870127 ER PT J AU Weber, F Asher, A Bucholz, R Berger, M Prados, M Chang, S Bruce, J Hall, W Rainov, NG Westphal, M Warnick, RE Rand, RW Floeth, F Rommel, F Pan, H Hingorani, VN Puri, RK AF Weber, F Asher, A Bucholz, R Berger, M Prados, M Chang, S Bruce, J Hall, W Rainov, NG Westphal, M Warnick, RE Rand, RW Floeth, F Rommel, F Pan, H Hingorani, VN Puri, RK TI Safety, tolerability, and tumor response of IL4-Pseudomonas exotoxin (NBI-3001) in patients with recurrent malignant glioma SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article DE astrocytoma; glioblastoma multiforme; immunotoxin; intratumoral therapy; malignant glioma ID PERMUTED INTERLEUKIN 4-TOXIN; BRAIN-TUMORS; IL-4 RECEPTORS; EGF RECEPTOR; THERAPY; TOXIN; EXPRESSION; PROTEIN; CELLS; REGRESSION AB Purpose: This was an open-label, dose-escalation trial of intratumoral administration of IL-4 Pseudomonas exotoxin (NBI-3001) in patients with recurrent malignant glioma. Patients and methods: A total of 31 patients with histologically verified supratentorial grades 3 and 4 astrocytoma were studied. Of these, 25 patients were diagnosed with glioblastoma multiforme (GBM) while six were diagnosed with anaplastic astrocytoma. Patients were over 18 years of age and had Karnofsky performance scores greater than or equal to 60. Patients were assigned to one of four dose groups in a dose-escalation fashion: 6 mug/ml x 40 ml, 9 mug/ml x 40 ml, 15 mug/ml x 40 ml, or 9 mug/ml x 100 ml of NBI-3001 administered via convection-enhanced delivery intratumorally using stereotactically placed catheters. Patients were followed with serial MRI scans and clinical assessments every four weeks for the first 16 weeks and then every eight weeks until week 26. Results: No drug-related systemic toxicity, as evident by lack of hematological or serum chemical changes, was apparent in any patients; treatment-related adverse effects were limited to the central nervous system. No deaths were attributable to treatment. Drug-related grade 3 or 4 toxicity was seen in 39% of patients in all dose groups and 22% of patients at the maximum tolerated dose of 6 mug/ml x 40 ml. The overall median survival was 8.2 months with a median survival of 5.8 months for the GBM patients. Six-month survival was 52% and 48%, respectively. Gadolinium-enhanced magnetic resonance imaging of the brain showed areas of decreased signal intensity within the tumor consistent with tumor necrosis following treatment in many patients. Conclusions: NBI-3001 appears to have an acceptable safety and toxicity profile when administered intratumorally in patients with recurrent malignant glioma. C1 Neurocrine Biosci Inc, San Diego, CA 92121 USA. Univ Dusseldorf, Dept Neurol Surg, D-4000 Dusseldorf, Germany. Carolina Neurosurg & Spine Associates, Charlotte, NC USA. St Louis Univ, Sch Med, St Louis, MO USA. Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA 94143 USA. Columbia Univ, New York, NY USA. Univ Minnesota, Minneapolis, MN USA. Univ Halle Wittenberg, Neurochirurg Klin, Halle Saale, Germany. Univ Hamburg, Krankenhaus Eppendorf, Neurochirurg Klin, D-2000 Hamburg, Germany. Univ Cincinnati, Cincinnati, OH USA. John Wayne Canc Inst, Santa Monica, CA USA. NIH, Lab Mol Tumor Biol,Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, US FDA, Bethesda, MD 20892 USA. RP Pan, H (reprint author), Neurocrine Biosci Inc, 10555 Sci Ctr Dr, San Diego, CA 92121 USA. NR 25 TC 111 Z9 114 U1 1 U2 4 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-594X J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD AUG-SEP PY 2003 VL 64 IS 1 BP 125 EP 137 DI 10.1007/BF02700027 PG 13 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 706TL UT WOS:000184471100014 PM 12952293 ER PT J AU Mock, DM Mock, NI Stewart, CW LaBorde, JB Hansen, DK AF Mock, DM Mock, NI Stewart, CW LaBorde, JB Hansen, DK TI Marginal biotin deficiency is teratogenic in ICR mice SO JOURNAL OF NUTRITION LA English DT Article; Proceedings Paper CT North American Pediatric Gastroenterology and Nutrition Meeting CY OCT, 1999 CL DENVER, COLORADO DE biotin deficiency; mice; birth defects; nutrition ID 3-HYDROXYISOVALERIC ACID; URINARY-EXCRETION; NORMAL-PREGNANCY; MOUSE EMBRYOS; INDICATORS; ETHANOL; PROTEIN; RAT AB The incidence of marginal biotin deficiency in normal human gestation is approximately one in three. In ICR mice, maternal biotin deficiency results in cleft palate, micrognathia, microglossia and limb hypoplasia. However, the relationships among the severity of maternal biotin deficiency, fetal biotin status and malformations have not been reported. This study utilized validated indices of biotin status to investigate the relationships among maternal biotin status, fetal biotin status and the rate of fetal malformations in ICR mice. Biotin status was controlled by feeding diets with varying egg white concentration. In dams and fetuses, biotin status was assessed by hepatic biotin content and hepatic activity of the biotin-dependent enzyme propionyl-CoA carboxylase; in dams, status was also assessed by urinary excretion of biotin and 3-hydroxyisovaleric acid. Malformations were assessed morphologically. Biotin was measured by HPLC/avidin-binding assay. Propionyl-CoA carboxylase (PCC) activity was determined by (HCO3)-C-14 incorporation. 3-Hydroxyisovaleric acid concentration was determined by GC/MS. Although no overt signs of deficiency appeared, metabolic disturbances caused by biotin deficiency were detectable in dams and fetuses. These disturbances increased with increasing egg white. Fetal biotin status correlated significantly with maternal biotin status (fetal vs. dam hepatic biotin, r = 0.671; fetal vs. dam PCC activity, r = 0.70). The incidences of malformations were strikingly dependent on egg white concentration. We conclude that in ICR mice, marginal maternal biotin deficiency causes fetal biotin deficiency. We speculate that the fetal malformations are primarily the consequence of fetal biotin deficiency. Because murine malformations appeared at degrees of biotin deficiency that are similar to those in human gestation, we speculate that some human fetal malformations may be caused by biotin deficiency. C1 Univ Arkansas Med Sci, Dept Biochem & Mol Biol, Little Rock, AR 72205 USA. Univ Arkansas Med Sci, Dept Pediat, Little Rock, AR 72205 USA. Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. RP Mock, DM (reprint author), Univ Arkansas Med Sci, Dept Biochem & Mol Biol, Little Rock, AR 72205 USA. FU NIDDK NIH HHS [DK36823, R01 DK036823, R37 DK036823] NR 35 TC 44 Z9 53 U1 1 U2 5 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD AUG PY 2003 VL 133 IS 8 BP 2519 EP 2525 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 709BC UT WOS:000184604000003 PM 12888630 ER PT J AU Miller, DL Balter, S Cole, PE Lu, HT Berenstein, A Albert, R Schueler, BA Georgia, JD Noonan, PT Russell, EJ Malisch, TW Vogelzang, RL Geisinger, M Cardella, JF St George, J Miller, GL Anderson, J AF Miller, DL Balter, S Cole, PE Lu, HT Berenstein, A Albert, R Schueler, BA Georgia, JD Noonan, PT Russell, EJ Malisch, TW Vogelzang, RL Geisinger, M Cardella, JF St George, J Miller, GL Anderson, J TI Radiation doses in interventional radiology procedures: The RAD-IR study - Part II: Skin dose SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article ID AREA PRODUCT; ABLATION PROCEDURES; PATIENT DOSIMETRY; EXPOSURE; FLUOROSCOPY; INJURIES; NEURORADIOLOGY; FILTRATION; RISK AB PURPOSE: To determine peak skin dose (PSD), a measure of the likelihood of radiation-induced skin effects, for a variety of common interventional radiology and interventional neuroradiology procedures, and to identify procedures associated with a PSD greater than 2 Gy. MATERIALS AND METHODS: An observational study was conducted at seven academic medical centers in the United States. Sites prospectively contributed demographic and radiation dose data for subjects undergoing 21 specific procedures in a fluoroscopic suite equipped with built-in dosimetry capability. Comprehensive physics evaluations and periodic consistency checks were performed on each unit to verify the stability and consistency of the dosimeter. Seven of 12 fluoroscopic suites in the study were equipped with skin dose mapping software. RESULTS: Over a 3-year period, skin dose data were recorded for 800 instances of 21 interventional radiology procedures. Wide variation in PSD was observed for different instances of the same procedure. Some instances of each procedure we studied resulted in a PSD greater than 2 Gy, except for nephrostomy, pulmonary angiography, and inferior vena cava filter placement. Some instances of transjugular intrahepatic portosystemic shunt (TIPS) creation, renal/visceral angioplasty, and angiographic diagnosis and therapy of gastrointestinal hemorrhage produced PSDs greater than 3 Gy. Some instances of hepatic chemoembolization, other tumor embolization, and neuroembolization procedures in the head and spine produced PSDs greater than 5 Gy. In a subset of 709 instances of higher-dose procedures, there was good overall correlation between PSD and cumulative dose (r = 0.86; P < .000001) and between PSD and dose-area-product (r = 0.85, P < .000001), but there was wide variation in these relationships for individual instances. CONCLUSIONS: There are substantial variations in PSD among instances of the same procedure and among different procedure types. Most of the procedures observed may produce a PSD sufficient to cause deterministic effects in skin. It is suggested that dose data be recorded routinely for TIPS creation, angioplasty in the abdomen or pelvis, all embolization procedures, and especially for head and spine embolization procedures. Measurement or estimation of PSD is the best method for determining the likelihood of radiation-induced skin effects. Skin dose mapping is preferable to a single-point measurement of PSD. C1 Natl Naval Med Res Inst, Dept Radiol, Bethesda, MD 20889 USA. Uniformed Serv Univ Hlth Sci, F Edward Hebert Sch Med, Dept Radiol & Nucl Med, Bethesda, MD 20814 USA. NCI, Ctr Canc Res, Med Oncol Clin Res Unit, Bethesda, MD 20892 USA. US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. Lenox Hill Hosp, Dept Med, New York, NY 10021 USA. Beth Israel Med Ctr, Ctr Endovasc Surg, Hyman Newman Inst Neurol & Neurosurg, 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. NW Mem Hosp, Feinberg Sch Med, Dept Radiol, Chicago, IL 60611 USA. Univ Texas, SW Med Ctr, Dallas, TX 75230 USA. RP Miller, DL (reprint author), Natl Naval Med Res Inst, Dept Radiol, 8901 Wisconsin Ave, Bethesda, MD 20889 USA. EM dm72v@nih.gov NR 44 TC 143 Z9 153 U1 0 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1051-0443 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD AUG PY 2003 VL 14 IS 8 BP 977 EP 990 PG 14 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA 708MY UT WOS:000184572800005 PM 12902555 ER PT J AU Argaw, T Ritzhaupt, A Wilson, CA AF Argaw, T Ritzhaupt, A Wilson, CA TI Development of a real time quantitative PCR assay for detection of porcine endogenous retrovirus (vol 97, pg 106, 2002) SO JOURNAL OF VIROLOGICAL METHODS LA English DT Correction C1 US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Lab Immunol & Virol, Bethesda, MD 20892 USA. RP Wilson, CA (reprint author), Bldg 29B,Room,2NN11,8800 Rockville Pike, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 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 AUG PY 2003 VL 111 IS 2 BP 165 EP 165 DI 10.1016/S0166-0934(03)00168-X PG 1 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Virology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Virology GA 710ED UT WOS:000184667100012 ER PT J AU Silberstein, E Xing, L de Beek, WV Lu, JH Cheng, H Kaplan, GG AF Silberstein, E Xing, L de Beek, WV Lu, JH Cheng, H Kaplan, GG TI Alteration of hepatitis A virus (HAV) particles by a soluble form of HAV cellular receptor 1 containing the immunoglobulin- and mucin-like regions SO JOURNAL OF VIROLOGY LA English DT Article ID MONOCLONAL-ANTIBODY 190/4; MONKEY KIDNEY-CELLS; CELLULAR RECEPTOR 1; POLIOVIRUS RECEPTOR; RICH REGION; CULTURE; ADAPTATION; NEUTRALIZATION; INFECTION; GROWTH AB Hepatitis A virus (HAV) infects African green monkey kidney cells via HAV cellular receptor I (haver-1). The ectodomain of havcr-1 contains an N-terminal cysteine-rich immunoglobulin-like region (D1), followed by a mucin-like region that extends D1 well above the cell surface. D1 is required for binding of HAV, and a soluble construct containing D1 fused to the hinge and Fc portions of human immunoglobulin G1 (IgG1), D1-Fc, bound and neutralized HAV inefficiently. However, D1-Fc did not alter the virions. To determine whether additional regions of havcr-1 are required to trigger uncoating of HAV, we constructed D1muc-Fc containing D1 and two-thirds of the mucin-like region fused to the Fc and hinge portions of human IgG1. D1muc-Fc neutralized 10 times more HAV than did D1-Fc. Sedimentation analysis in sucrose gradients showed that treatment of HAV with 20 to 200 nM D1muc-Fc disrupted the majority of the virions, whereas treatment with 2 nM D1muc-Fc had no effect on the sedimentation of the particles. Treatment of HAV with 100 nM D1muc-Fc resulted in low-level accumulation of 100- to 125S particles. Negative-stain electron microscopy analysis revealed that the 100- to 125S particles had the characteristics of disrupted virions, such as internal staining and diffuse edges. Quantitative PCR analysis showed that the 100- to 125S particles contained viral RNA. These results indicate that D1 and the mucin-like region of havcr-1 are required to induce conformational changes leading to HAV uncoating. C1 FDA, CBER, DETTD, Lab Hepatitis & Related Emerging Agents, Bethesda, MD 20892 USA. Karolinska Inst, Dept Biosci, S-14157 Huddinge, Sweden. RP Kaplan, GG (reprint author), FDA, CBER, DETTD, Lab Hepatitis & Related Emerging Agents, Bethesda, MD 20892 USA. NR 40 TC 46 Z9 48 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 AUG PY 2003 VL 77 IS 16 BP 8765 EP 8774 DI 10.1128/JVI.77.16.8765-8774.2003 PG 10 WC Virology SC Virology GA 706PU UT WOS:000184462800018 PM 12901378 ER PT J AU Gagne, RM Boswell, JS Myers, KJ AF Gagne, RM Boswell, JS Myers, KJ TI Signal detectability in digital radiography: Spatial domain figures of merit SO MEDICAL PHYSICS LA English DT Article DE detectability; detective quantum efficiency; digital radiography; matched filter; observer model; signal-to-noise ratio (SNR) ID OBSERVER DETECTION PERFORMANCE; IMAGING-SYSTEMS; AMORPHOUS SELENIUM; NOISE; OPTIMIZATION; DETECTORS; RADIOLOGY; IMAGES; MODEL AB The usefulness of Fourier-based measures of imaging performance has come into question for the evaluation of digital imaging systems. Figures of merit such as detective quantum efficiency (DQE) based on Fourier domain parameters are relevant for linear, shift-invariant systems with stationary noise. However, no digital imaging system is shift invariant, and realistic images do not satisfy the stationarity condition. Our methods for the task-based evaluation of imaging systems, based on signal detectability in the spatial domain, do not require such assumptions. We have computed the performance of ideal and quasi-ideal observers for the task of signal detection in digital radiography. Signal detectability in terms of an observer signal-to-noise-ratio (SNR) has been compared to results obtained from a Monte Carlo simulation of the digital image-acquisition process. The simulation incorporates the effects of random amplification and secondary quantum blur, integration over pixel area, and electronic noise. The observer figures of merit that have been previously shown to bracket human performance directly specify the usefulness of the images for the stated diagnostic task. In addition, the observer figures of merit give a task-dependent measure of imaging system efficiency in terms of the ratio of an output SNR2 to an input SNR2. Thus, the concept of "detective quantum efficiency" reappears in a natural way but based in the spatial domain and not dependent on shift invariance and stationarity assumptions. With respect to the optimum amount of system blur, our simulations indicate that under certain task-dependent conditions, large signals are fairly insensitive to blur in the x-ray transducer, while an optimum blur is found for small signals. (C) 2003 American Association of Physicists in Medicine. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Gagne, RM (reprint author), US FDA, Ctr Devices & Radiol Hlth, 12720 Twinbrook Pkwy, Rockville, MD 20857 USA. OI Boswell, Jonathan/0000-0003-4552-7490 NR 43 TC 33 Z9 33 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 AUG PY 2003 VL 30 IS 8 BP 2180 EP 2193 DI 10.1118/1.1578485 PG 14 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 713BE UT WOS:000184834600025 PM 12945984 ER PT J AU Zhang, BL Zhang, YQ Shacter, E AF Zhang, BL Zhang, YQ Shacter, E TI Caspase 3-mediated inactivation of rac GTPases promotes drug-induced apoptosis in human lymphoma cells SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID FAS-INDUCED APOPTOSIS; MEDIATED CLEAVAGE; MORPHOLOGICAL-CHANGES; ACTIVATING PROTEINS; DEPENDENT PATHWAY; BREAST-CANCER; RHO GTPASES; CDC42; SUBSTRATE; TRANSFORMATION AB The Rac members of the Rho family GTPases control signaling pathways that regulate diverse cellular activities, including cytoskeletal organization, gene transcription, and cell transformation. Rac is implicated in apoptosis, but little is known about the mechanism by which it responds to apoptotic stimuli. Here we demonstrate that endogenous Rac GTPases are caspase 3 substrates that are cleaved in human lymphoma cells during drug-induced apoptosis. Cleavage of Rac1 occurs at two unconventional caspase 3 sites, VVGD11/G and VMVD47/G, and results in inactivation of the GTPase and effector functions of the protein (binding to the p21-activated protein kinase PAK1). Expression of caspase 3-resistant Rac1 mutants in the cells suppresses drug-induced apoptosis. Thus, proteolytic inactivation of Rac GTPases represents a novel, irreversible mechanism of Rac downregulation that allows maximal cell death following drug treatment. C1 US FDA, Ctr Biol Evaluat & Res, Div Therapeut Prot, Biochem Lab, Bethesda, MD 20892 USA. RP Zhang, BL (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Therapeut Prot, Biochem Lab, HFM-535,29 Lincoln Dr,Bldg 29A,Room 2B-24, Bethesda, MD 20892 USA. NR 47 TC 34 Z9 35 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD AUG PY 2003 VL 23 IS 16 BP 5716 EP 5725 DI 10.1128/MCB.23.16.5716-5725.2003 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 707TZ UT WOS:000184527100020 PM 12897143 ER PT J AU Riegel, AC Ali, SF French, ED AF Riegel, AC Ali, SF French, ED TI Toluene-induced locomotor activity is blocked by 6-hydroxydopamine lesions of the nucleus accumbens and the mGluR2/3 agonist LY379268 SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE 6-hydroxydopamine; inhalant abuse; toluene; nucleus accumbens; dopamine; metabotropic glutamate receptors ID METABOTROPIC GLUTAMATE RECEPTORS; VENTRAL TEGMENTAL AREA; FREELY MOVING RATS; EXTRACELLULAR DOPAMINE; PREFRONTAL CORTEX; REWARD PATHWAYS; ABUSED SOLVENT; CHO-CELLS; MICRODIALYSIS; EXPOSURE AB The abuse of volatile inhalants remains a prominent, yet poorly understood, form of substance abuse among youth. Nevertheless, the identification of a mechanism underlying the reinforcing properties of inhalants has been hampered by the lack of a clearly identifiable neural substrate upon which these chemicals act. One ingredient that is common to many abused inhalants is toluene, an organic solvent that is self-administered by nonhuman primates and rodents. Most drugs of abuse have been found to elicit forward locomotion in rats, an effect owing to the activation of mesoaccumbal dopamine (DA) pathways. Thus, the present study was undertaken using two different approaches to determine whether toluene-induced locomotor hyperactivity is also ultimately dependent upon DA neurotransmission in the mesolimbic nucleus accumbens (NAC). Here we report on the effects of 6-hydroxydopamine (6-OHDA) lesions of the NAC or pretreatment with the metabotropic mGlu2/3 receptor agonist LY379268 on toluene-induced locomotor activity. Both procedures, which are known to alter neurotransmission within the NAC, significantly attenuated toluene's locomotor stimulatory effects. These results provide strong support for a central mechanism of action of inhalants, which in the past has been more typically attributed to general nonspecific mechanisms throughout the brain. Moreover, as with other drugs of abuse, the NAC may be the final common pathway subserving toluene's abuse liability. C1 Univ Arizona, Coll Med, Dept Pharmacol, Tucson, AZ 85724 USA. US FDA, Natl Ctr Toxicol Res, Neurochem Lab, Div Neurotoxicol, Jefferson, AR 72079 USA. RP French, ED (reprint author), Univ Arizona, Coll Med, Dept Pharmacol, Tucson, AZ 85724 USA. FU NIDA NIH HHS [DA T-334180] NR 64 TC 39 Z9 40 U1 1 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD AUG PY 2003 VL 28 IS 8 BP 1440 EP 1447 DI 10.1038/sj.npp.1300193 PG 8 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 704DD UT WOS:000184321700006 PM 12784113 ER PT J AU Thompson, KL Sistare, FD AF Thompson, KL Sistare, FD TI Selection of drugs to test the specificity of the Tg.AC assay by screening for induction of the gadd153 promoter in vitro SO TOXICOLOGICAL SCIENCES LA English DT Article DE Tg.AC; gadd153; c-fos; zeta-globin; HepG2; K562 ID GREEN FLUORESCENT PROTEIN; MULTIDRUG-RESISTANCE; TRANSGENIC MICE; CYPROTERONE-ACETATE; LYMPHOCYTE-CULTURES; MICRONUCLEUS TEST; GROWTH-FACTOR; CELL-LINES; MOUSE SKIN; PYRIMETHAMINE AB Short-term assays for carcinogenicity testing of chemicals that use transgenic mice designed to have altered expression of genes mechanistically relevant to carcinogenesis are attractive alternatives to two-year dosing studies in rodents. The models that have been the received the greatest level of performance evaluation include p53(+/-), rasH2, Xpa/p53(+/-), and Tg.AC mice. For use of these models in a regulatory setting to evaluate the carcinogenic potential of pharmaceuticals, it is important to establish an assurance of assay specificity and positive predictivity based on studies using drugs with a wide spectrum of pharmacologic activity. For this purpose, 99 noncarcinogenic drugs were prioritized based on their activity in an in vitro induction assay correlative with a positive response in the Tg.AC assay (induction of the gadd153 promoter in HepG2 cells). Activities in two assays less predictive of Tg.AC activity (induction of c-fos and zeta-globin gene promoters) were also measured. Nine percent of the screened drugs induced the gadd153 promoter by at least fourfold. Several criteria were used to select candidates for subsequent in vivo testing in the Tg.AC assay: (1) sufficient drug solubility in appropriate skin paint vehicles to elicit systemic toxicity, (2) the level of induction of the gadd153 promoter by the drug, (3) the in vitro potency of the drug, and (4) the cost of the drug required for a 6-month study. Based on these criteria, amiloride, dipyridamole, and pyrimethamine were selected from 99 rodent noncarcinogens in a drug database for testing the specificity of the Tg.AC assay. C1 US FDA, Div Appl Pharmacol Res, Off Testing & Res,Off Pharmaceut Sci, Ctr Drug Evaluat & Res, Laurel, MD 20708 USA. RP Thompson, KL (reprint author), 8301 Muirkirk Rd, Laurel, MD 20708 USA. NR 38 TC 6 Z9 7 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 AUG PY 2003 VL 74 IS 2 BP 260 EP 270 DI 10.1093/toxsci/kfg113 PG 11 WC Toxicology SC Toxicology GA 705LU UT WOS:000184397200007 PM 12730611 ER PT J AU Thompson, KL Rosenzweig, BA Weaver, JL Zhang, J Lin, KK Sistare, FD AF Thompson, KL Rosenzweig, BA Weaver, JL Zhang, J Lin, KK Sistare, FD TI Evaluation of the Tg.AC assay: Specificity testing with three noncarcinogenic pharmaceuticals that induce selected stress gene promoters in vitro and the inhibitory effects of solvent components SO TOXICOLOGICAL SCIENCES LA English DT Article DE Tg.AC; gadd153; TPA; DMSO; solvent ID MOUSE SKIN; TRANSGENIC MOUSE; MICE; CARCINOGENICITY; RESPONSIVENESS; TUMORIGENESIS; PYRIMETHAMINE; PAPILLOMAS AB Understanding the strengths and limitations of alternative models, such as the Tg.AC assay, for evaluation of the potential carcinogenicity of pharmaceuticals requires assessment of assay specificity through studies that specifically target biologically active compounds that are known to not be carcinogens in rodents. To identify drugs that might provoke a false positive response in the Tg.AC assay, we screened pharmaceuticals for in vitro induction of the gadd153 promoter and the zeta-globin promoter. We have previously found a high correlation between induction of the gadd153 promoter in HepG2 cells and activity in the Tg.AC assay. The three drugs selected through screening 99 noncarcinogenic pharmaceuticals were amiloride, dipyridamole, and pyrimethamine. A 26-week skin paint study was conducted in hemizygous Tg.AC mice with the three drugs at two doses selected by a 4-week dose range finding study. Evidence of systemic toxicity was observed in animals dosed chronically with pyrimethamine or amiloride, but no skin papillomas were observed in mice treated with amiloride, dipyridamole, or pyrimethamine for 26 weeks. All male mice and 80% of female mice treated with 12-O-tetradecanoylphorbol-13-acetate (TPA) in acetone developed a maximal tumor burden. However, mice treated with TPA in a vehicle containing 2.4% DMSO had greatly reduced incidences of papillomas. In summary, the correct negative response was shown in the Tg.AC assay for three noncarcinogenic pharmaceuticals, which adds further favorable evidence of appropriate specificity of this model system. However, vehicle composition must be carefully selected because the outcome of this assay can be confounded by certain commonly used solvents. C1 US FDA, Div Appl Pharmacol Res, Off Testing & Res, Off Pharmaceut Sci, Laurel, MD 20708 USA. US FDA, Div Biometrt 2, Off Biostat,Off Pharmacoepidemiol & Stat Sci, Ctr Drug Evaluat & Res, Laurel, MD 20708 USA. RP Thompson, KL (reprint author), US FDA, Div Appl Pharmacol Res, Off Testing & Res, Off Pharmaceut Sci, Laurel, MD 20708 USA. NR 23 TC 3 Z9 3 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 AUG PY 2003 VL 74 IS 2 BP 271 EP 278 DI 10.1093/toxsci/kfg141 PG 8 WC Toxicology SC Toxicology GA 705LU UT WOS:000184397200008 PM 12773758 ER PT J AU David, LS Plakas, SM El Said, KR Jester, ELE Dickey, RW Nicholson, RA AF David, LS Plakas, SM El Said, KR Jester, ELE Dickey, RW Nicholson, RA TI A rapid assay for the brevetoxin group of sodium channel activators based on fluorescence monitoring of synaptoneurosomal membrane potential SO TOXICON LA English DT Article DE NSP toxin assay; brevetoxins; mouse brain synaptoneurosomes; voltage-sensitive sodium channels; membrane potential; rhodamine 6G ID FORMERLY GYMNODINIUM-BREVE; RAT-BRAIN SYNAPTOSOMES; PTYCHODISCUS-BREVIS; RED TIDE; TOXINS; SHELLFISH; RECEPTOR; EXTRACTS; PBTX-3; SITES AB A functional pharmacologically-based assay for the brevetoxin group of sodium channel activators was developed using synaptoneurosomes isolated from the brains of CD1 mice. The assay can detect the depolarizing effect of brevetoxin congeners PbTx-2 and PbTx-3 as enhancements of the veratridine-dependent increase in fluorescence of the voltage-sensitive fluorescent probe rhodamine 6G. The assay is relatively rapid and can detect brevetoxin activity in the nanomolar range. The synaptoneurosomal assay has been used to analyse mussel tissue extracts spiked with PbTx-2, and composite toxicity, expressed as PbTx-3 equivalents in extracts of oysters naturally exposed to brevetoxins. In this latter context, the synaptoneurosomal technique was shown to compare favorably with the cytotoxicity assay, the receptor binding assay and HPLC/MS. Our results support the concept that this membrane potential assay detects brevetoxins based on their interaction with sodium channels. (C) 2003 Elsevier Ltd. All rights reserved. C1 Simon Fraser Univ, Dept Biol Sci, Burnaby, BC V5A 1S6, Canada. US FDA, Gulf Coast Seafood Lab, Dauphin Isl, AL 36528 USA. RP Nicholson, RA (reprint author), Simon Fraser Univ, Dept Biol Sci, 8888 Univ Dr, Burnaby, BC V5A 1S6, Canada. EM nicholso@sfu.ca NR 42 TC 19 Z9 20 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0041-0101 J9 TOXICON JI Toxicon PD AUG PY 2003 VL 42 IS 2 BP 191 EP 198 DI 10.1016/S0041-0101(03)00133-8 PG 8 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 711RD UT WOS:000184754100008 PM 12906890 ER PT J AU Reefhuis, J Honein, MA Whitney, CG Chamany, S Mann, EA Biernath, KR Broder, K Manning, S Avashia, S Victor, M Costa, P Devine, O Graham, A Boyle, C AF Reefhuis, J Honein, MA Whitney, CG Chamany, S Mann, EA Biernath, KR Broder, K Manning, S Avashia, S Victor, M Costa, P Devine, O Graham, A Boyle, C TI Risk of bacterial meningitis in children with cochlear implants SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID RECURRENT MENINGITIS; OTITIS-MEDIA; INNER-EAR; DYSPLASIA; MALFORMATION AB BACKGROUND: In June 2002, the Food and Drug Administration received reports of bacterial meningitis in patients with cochlear implants for treatment of hearing loss. Implants that included a positioner (a wedge inserted next to the implanted electrode to facilitate transmission of the electrical signal by pushing the electrode against the medial wall of the cochlea) were voluntarily recalled in the United States in July 2002. METHODS: We identified patients with meningitis and conducted a cohort study and a nested case-control investigation involving 4264 children who had received cochlear implants in the United States between January 1, 1997, and August 6, 2002, and who were less than six years of age when they received the implants. We calculated the incidence of meningitis in the cohort and assessed risk factors for meningitis among patients and among 199 controls, using data from interviews with parents and abstracted from medical records. RESULTS: We identified 26 children with bacterial meningitis. The incidence of meningitis caused by Streptococcus pneumoniae was 138.2 cases per 100,000 person-years - more than 30 times the incidence in a cohort of the same age in the general U.S. population. Postimplantation bacterial meningitis was strongly associated with the use of an implant with a positioner (odds ratio, 4.5 [95 percent confidence interval, 1.3 to 17.9], with adjustment for medical, surgical, and environmental factors) and with the joint presence of radiographic evidence of a malformation of the inner ear and a cerebrospinal fluid leak (adjusted odds ratio, 9.3 [95 percent confidence interval, 1.2 to 94.5]). The incidence of meningitis among patients who had received an implant with a positioner remained higher than the incidence among those whose implants did not have a positioner for the duration of follow-up (24 months from the time of implantation). CONCLUSIONS: Parents and health care providers should ensure that all children who receive cochlear implants are appropriately vaccinated and are then monitored and treated promptly for any bacterial infections after receiving the implant. C1 Ctr Dis Control & Prevent, Natl Ctr Birth Defects & Dev Disabil, Atlanta, GA 30333 USA. Ctr Dis Control & Prevent, Epidemiol Program Off, Atlanta, GA 30333 USA. Ctr Dis Control & Prevent, Natl Ctr Infect Dis, Atlanta, GA 30333 USA. Ctr Dis Control & Prevent, Natl Immunizat Program, Atlanta, GA 30333 USA. US FDA, Rockville, MD 20857 USA. New York City Dept Hlth & Mental Hyg, New York, NY USA. Texas Dept Hlth, Austin, TX 78756 USA. RP Reefhuis, J (reprint author), Ctr Dis Control & Prevent, Natl Ctr Birth Defects & Dev Disabil, 1600 Clifton Rd NE,MS E-86, Atlanta, GA 30333 USA. RI Reefhuis, Jennita/E-1793-2011 OI Reefhuis, Jennita/0000-0002-4747-4831 NR 26 TC 130 Z9 138 U1 1 U2 8 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 JUL 31 PY 2003 VL 349 IS 5 BP 435 EP 445 DI 10.1056/NEJMoa031101 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 706FV UT WOS:000184443700005 PM 12890842 ER PT J AU Gans, H DeHovitz, R Forghani, B Beeler, J Maldonado, Y Arvin, AM AF Gans, H DeHovitz, R Forghani, B Beeler, J Maldonado, Y Arvin, AM TI Measles and mumps vaccination as a model to investigate the developing immune system: passive and active immunity during the first year of life SO VACCINE LA English DT Article; Proceedings Paper CT International Symposium on Protection of Newborns through Maternal Immunization CY DEC 08-11, 2002 CL VEYRIER DU LAC, FRANCE SP Fdn Merieux, WHO DE measles; mumps; antiviral; cellular immunity; developmental immunology ID UNITED-STATES; INFANTS; CHILDREN; MECHANISM; ANTIBODY; MOTHERS AB Evaluations of neutralizing antibody responses in 6, 9- and 12-month-old infants given measles or mumps vaccine indicated that 6-month-old infants had diminished humoral immune responses associated with passive antibody effects, but also had an intrinsic deficiency in antiviral antibody production, which was independent of passive antibody effects. In contrast, lower neutralizing antibody titers in 9-month-olds were related only to passive antibody effects. Measles and mumps-specific T-cell proliferation and interferon-gamma (IFNgamma) production were induced by vaccination at 6, 9 or 12 months, regardless of passive neutralizing antibodies or age. These observations suggest a need to refine concepts about passive antibody interference and primary vaccine failure, taking into account the sensitization of antiviral T-cells, which occurs in the presence of passive antibodies and is observed in infants who do not develop active Immoral immunity. A second dose of measles vaccine given at 12-15 months enhanced antiviral T-cell responses to measles in infants who were vaccinated at 6 or 9 months, and produced higher seroconversion rates. Since T-cell immunity is elicited under the cover of passive antibodies, the youngest infants benefit from the synergistic protection mediated by maternal antibodies and their own capacity to develop sensitized antiviral T-cells, which prime for subsequent exposures to the viral antigens. Conceptually, maternal immunization approaches with vaccines that can be given to women of child-bearing age before pregnancy, or that are safe for administration during pregnancy, should enhance passive antibody protection. Rather than being detrimental to infant adaptive immune responses, maternal vaccination can be coupled effectively with vaccine regimens that elicit priming of antiviral immune responses in infants during the first year of life. (C) 2003 Elsevier Science Ltd. All rights reserved. C1 Stanford Univ, Sch Med, Dept Pediat, Stanford, CA 94305 USA. Palo Alto Med Fdn, Dept Pediat, Palo Alto, CA USA. Dept Hlth Serv, Viral & Rickettsial Dis Lab, Richmond, CA USA. US FDA, Div Viral Prod, Bethesda, MD 20014 USA. RP Arvin, AM (reprint author), Stanford Univ, Sch Med, Dept Pediat, 300 Pasteur Dr,Rm G312, Stanford, CA 94305 USA. FU NICHD NIH HHS [HD01310, HD33698]; PHS HHS [A137127] NR 19 TC 71 Z9 73 U1 0 U2 5 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 JUL 28 PY 2003 VL 21 IS 24 BP 3398 EP 3405 DI 10.1016/S0264-410X(03)00341-4 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 705NZ UT WOS:000184402300012 PM 12850348 ER PT J AU Gruber, MF AF Gruber, MF TI Maternal immunization: USFDA regulatory considerations SO VACCINE LA English DT Article; Proceedings Paper CT International Symposium on Protection of Newborns through Maternal Immunization CY DEC 08-11, 2002 CL VEYRIER DU LAC, FRANCE SP Fdn Merieux, WHO DE maternal immunization; vaccine; developmental toxicity; pregnancy; prenatal immunization; regulatory consideration ID NONSPECIFIC STIMULATION; POLYSACCHARIDE VACCINE; IMMUNE-SYSTEM; PREGNANCY AB Vaccination of pregnant women provides important health benefits to both, mother and infant, and has been an important disease prevention strategy in these two groups. While most vaccines Currently licensed in the US are not indicated for use during pregnancy, depending on the vaccine, vaccination programs do frequently include pregnant women. In addition, recent emphasis has been placed on maternal immunization strategies to protect young infants from severe infections. Currently, unless the vaccine is specifically indicated four maternal immunization, no data are collected regarding the vaccine's safety in pregnant women prior to licensure. However, more females of childbearing age participate in clinical trials and a broad range of novel vaccine products are in development indicated for adolescents and adults. Thus, there is increasing concern for the unintentional exposure of an embryo/fetus before information is available regarding the potential risk versus benefit of the vaccine. Since pregnant women are usually excluded from participation in clinical trials, conclusions regarding developmental risk at the time of licensure are frequently based solely on data derived from developmental toxicity studies in animal models. This paper will review regulatory, preclinical and clinical issues as they pertain to development programs for vaccines intended for vaccination during pregnancy. Published by Elsevier Science Ltd. C1 US FDA, CBER, Rockville, MD 20852 USA. RP Gruber, MF (reprint author), US FDA, CBER, Woodmont Off Complex 1 Rockville Pike, Rockville, MD 20852 USA. NR 21 TC 18 Z9 19 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 JUL 28 PY 2003 VL 21 IS 24 BP 3487 EP 3491 DI 10.1016/S0264-410X(03)00357-8 PG 5 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 705NZ UT WOS:000184402300030 PM 12850366 ER PT J AU Ramirez, T Garcia-Montalvo, V Wise, C Cea-Olivares, R Poirier, LA Herrera, LA AF Ramirez, T Garcia-Montalvo, V Wise, C Cea-Olivares, R Poirier, LA Herrera, LA TI S-adenosyl-L-methionine is able to reverse micronucleus formation induced by sodium arsenite and other cytoskeleton disrupting agents in cultured human cells SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article DE SAW; micronucleus; NMR; fibroblasts; lymphocytes ID PERFORMANCE LIQUID-CHROMATOGRAPHY; DNA METHYLATION; BREAST-CANCER; FOLATE-DEFICIENCY; MAMMALIAN-CELLS; GENE-EXPRESSION; RAT-LIVER; ADENOSYLMETHIONINE; DAMAGE; ADENOSYLETHIONINE AB Deficiencies of folic acid and methionine, two of the major components of the methyl metabolism, correlate with an increment of chromosome breaks and micronuclei. It has been proposed that these effects may arise from a decrease of S-adenosyl-L-methionine (SAM), the universal methyl donor. Some xenobiotics, such as arsenic, originate a reduction of SAM levels, and this is believed to alter some methylation processes (e.g. DNA methylation). The aim of the present work was to analyze the effects of exogenous SAM on the micronucleus (MN) frequency induced by sodium arsenite in human lymphocytes treated in vitro and to investigate whether these effects are related to DNA methylation. Results showed a reduction in the MN frequency in cultures treated with sodium arsenite and SAM compared to those treated with arsenite alone. To understand the mechanism by which SAM reduced the number of micronucleated cells, its effect on MN induced by other xenobiotics was also analyzed. Results showed that SAM did not have any effect on the increase in MN frequency caused by alkylating (mitomycin C or cisplatin) or demethylating agents (5-azacytidine, hydralazine, ethionine and procainamide), but it reduced the number of micronucleated cells in those treated with agents that inhibit microtubule polymerization (albendazole sulphoxide and colcemid). Since albenclazole sulphoxide and colcemid inhibit microtubule polymerization, we decided to evaluate the effect of SAM on microtubule integrity. Data obtained from these evaluations showed that sodium arsenite, albendazole sulphoxide, and colcemid affect the integrity and organization of microtubules and that these effects are significantly reduced when cultures were treated at the same time with SAM. The data taken all together point out that the positive effects of SAM could be due to its ability to protect microtubules through an unknown mechanism. (C) 2003 Elsevier Science B.V. All rights reserved. C1 Univ Nacl Autonoma Mexico, Inst Nacl Cancerol, Inst Invest Biomed, Unidad Invest Biomed & Canc, Mexico City, DF, Mexico. Univ Nacl Autonoma Mexico, Inst Quim, Mexico City, DF, Mexico. Natl Ctr Toxicol Res, Little Rock, AR USA. RP Herrera, LA (reprint author), Univ Nacl Autonoma Mexico, Inst Invest Biomed, Dept Med Genom & Toxicol Ambiental, Ciudad Univ,POB 70-228, Mexico City 04510, DF, Mexico. EM metil@hotmail.com OI Garcia-Montalvo, Veronica/0000-0002-6220-9702 NR 52 TC 37 Z9 37 U1 1 U2 5 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 JUL 25 PY 2003 VL 528 IS 1-2 BP 61 EP 74 DI 10.1016/S0027-5107(03)00099-X PG 14 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 707XL UT WOS:000184535200007 PM 12873724 ER PT J AU Shvartsburg, AA AF Shvartsburg, AA TI Aromatic ring destruction in complexes of dipositive metal cations SO CHEMICAL PHYSICS LETTERS LA English DT Article ID GAS-PHASE; ELECTROSPRAY-IONIZATION; CHARGE-TRANSFER; DMSO COMPLEXES; IONS; ACETONITRILE; COORDINATION; CHEMISTRY; FRAGMENTATION; TRICATIONS AB Singly charged metal cations do not normally activate the pi-ring in monoaromatic ligands. Here pyridine complexes of six dipositive metal cations (Ca, Mg, Mn, Fe, Co, and Cu) are probed using collisional dissociation. Except for Cu, species with one-three ligands (depending on the metal) exhibit two significant aromaticity-destroying ligand cleavage processes. One proceeds with charge reduction yielding singly charged bare or ligated metal cyanide cations and C4H5+, and the other retains the double charge eliminating one or two small neutrals such as NH2 or CH3. The previously reported cluster-to-metal charge transfer producing charged ligand clusters is shown to not occur. Published by Elsevier Science B.V. C1 Natl Ctr Toxicol Res, Div Chem, Jefferson, AR 72079 USA. RP Shvartsburg, AA (reprint author), Pacific NW Nalt Lab, MSIN K8-98,3335 Q Ave, Richland, WA 99352 USA. NR 28 TC 11 Z9 11 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0009-2614 J9 CHEM PHYS LETT JI Chem. Phys. Lett. PD JUL 17 PY 2003 VL 376 IS 1-2 BP 6 EP 10 DI 10.1016/S0009-2614(03)00815-7 PG 5 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 704AM UT WOS:000184315600002 ER PT J AU Wilkin, JK Pappas, EG DeCamp, WH AF Wilkin, JK Pappas, EG DeCamp, WH TI Peanut allergy SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID ALLERGENICITY; OILS C1 US FDA, Rockville, MD 20857 USA. RP Wilkin, JK (reprint author), US FDA, Rockville, MD 20857 USA. NR 4 TC 0 Z9 0 U1 1 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 JUL 17 PY 2003 VL 349 IS 3 BP 302 EP 302 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 701KA UT WOS:000184165700021 ER PT J AU Zhao, SH Datta, AR Ayers, S Friedman, S Walker, RD White, DG AF Zhao, SH Datta, AR Ayers, S Friedman, S Walker, RD White, DG TI Antimicrobial-resistant Salmonella serovars isolated from imported foods SO INTERNATIONAL JOURNAL OF FOOD MICROBIOLOGY LA English DT Article DE Salmonella; antimicrobial resistance; imported foods ID ANTIBIOTIC-RESISTANCE; UNITED-STATES; ANIMALS; SEROTYPES; INTEGRONS; ORIGINS; FISH AB A total of 187 Salmonella isolates representing 82 serotypes recovered from 4072 imported foods in the year 2000 by the U.S. Food and Drug Administration field laboratories were tested for their susceptibility to 17 antimicrobials of human and veterinary importance. Fifteen (8%) isolates were resistant to at least one antimicrobial, and five (2.7%) were resistant to three or more antimicrobials. Most of the isolates (n=9) exhibited resistance to tetracycline. Four isolates from catfish or tilapia from Taiwan or Thailand also demonstrated resistance to nalidixic acid. These nalidixic acid-resistant Salmonella isolates possessed a point mutation at the Ser83 or Asp87 position in DNA gryase, resulting in amino acid substitutions to phenylalanine, tyrosine, or asparagine. One Salmonella Derby isolated from frozen anchovies imported from Cambodia was resistant to six antimicrobials including ampicillin, amoxicillin/clavulanic acid, chloramphenicol, sulfamethoxazole, tetracycline, and trimethoprim/sulfamethoxazole. Of seven isolates displaying resistance to sulfonamides, only one S. Derby and one Salmonella Agona contained class 1 integrons that were further shown to possess the aadA and pse-1 genes conferring resistance to streptomycin and ampicillin, respectively. This study indicates that antimicrobial-resistant Salmonella are present in imported foods, primarily of seafood origin, and stresses the need for continued surveillance of foodborne zoonotic bacterial pathogens from imported foods entering the United States. (C) 2002 Elsevier Science B.V All rights reserved. C1 US FDA, Ctr Vet Med, Res Off, Div Anim & Food Microbiol, Laurel, MD 20708 USA. US FDA, Div Field Sci, Rockville, MD 20857 USA. RP Zhao, SH (reprint author), US FDA, Ctr Vet Med, Res Off, Div Anim & Food Microbiol, 8401 Muirkirk Rd, Laurel, MD 20708 USA. NR 23 TC 61 Z9 63 U1 2 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-1605 J9 INT J FOOD MICROBIOL JI Int. J. Food Microbiol. PD JUL 15 PY 2003 VL 84 IS 1 BP 87 EP 92 DI 10.1016/S0168-1605(02)00402-6 PG 6 WC Food Science & Technology; Microbiology SC Food Science & Technology; Microbiology GA 691JJ UT WOS:000183602600011 PM 12781958 ER PT J AU Zaitseva, M Peden, K Golding, H AF Zaitseva, M Peden, K Golding, H TI HIV coreceptors: role of structure, posttranslational modifications, and internalization in viral-cell fusion and as targets for entry inhibitors SO BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES LA English DT Review DE HIV envelope; HIV receptor/coreceptor; viral-cell fusion; entry-inhibitor ID IMMUNODEFICIENCY-VIRUS TYPE-1; GP120 ENVELOPE GLYCOPROTEIN; CHEMOKINE RECEPTOR CXCR4; PROTEIN-COUPLED RECEPTOR; 2ND EXTRACELLULAR LOOP; SELECTIVE ANTI-HIV-1 ACTIVITY; CARBOXYL-TERMINAL DOMAIN; SMALL-MOLECULE INHIBITOR; 5 CCR5 PHOSPHORYLATION; HIGH-AFFINITY BINDING AB The human immunodeficiency virus (HIV) envelope glycoprotein forms trimers on the virion surface, with each monomer consisting of two subunits, gp120 and gp41. The gp120 envelope component binds to CD4 on target cells and undergoes conformational changes that allow gp120 to interact with certain G-protein-coupled receptors (GPCRs) on the same target membranes. The GPCRs that function as HIV coreceptors were found to be chemokine receptors. The primary coreceptors are CCR5 and CXCR4, but several other chemokine receptors were identified as "minor coreceptors", indicating their ability support entry of some HIV strains in tissue cultures. Formation of the trimolecular complexes stabilizes virus binding and triggers a series of conformational changes in gp41 that facilitate membrane fusion and viral cell entry. Concerted efforts are underway to decipher the specific interactions between gp120/CD4, gp120/coreceptors, and their contributions to the subsequent membrane fusion process. It is hoped that some of the transient conformational intermediates in gp120 and gp41 would serve as targets for entry inhibitors. In addition, the CD4 and coreceptors are primary targets for several classes of inhibitors currently under testing. Our review summarizes the current knowledge on the interactions of HIV gp 120 with its receptor and coreceptors, and the important properties of the chemokine receptors and their regulation in primary target cells. We also summarize the classes of coreceptor inhibitors under development. (C) 2003 Elsevier B.V. All rights reserved. C1 US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Bethesda, MD 20892 USA. RP Golding, H (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, 8800 Rockville Pike, Bethesda, MD 20892 USA. NR 140 TC 56 Z9 61 U1 1 U2 15 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0005-2736 J9 BBA-BIOMEMBRANES JI Biochim. Biophys. Acta-Biomembr. PD JUL 11 PY 2003 VL 1614 IS 1 BP 51 EP 61 DI 10.1016/S0005-2736(03)00162-7 PG 11 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 706ZA UT WOS:000184483900006 PM 12873765 ER PT J AU Weisz, A Andrzejewski, D AF Weisz, A Andrzejewski, D TI Identification of 2-bromo-3,4,5,6-tetrachloroaniline and its quantification in the color additives D&C Red Nos. 27 and 28 (phloxine B) using solid-phase microextraction and gas chromatography-mass spectrometry SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article DE hunsdiecker reaction; bromotetrachloroanilines; anilines; D&C Red No. 27; D&C Red No. 28; phloxines; dyes ID POLYCHLORINATED-BIPHENYLS; AROMATIC-AMINES; WATER; HYDROCARBONS; EXTRACTION AB The present work describes (a) the identification and characterization of a contaminant, 2-bromo-3,4,5,6-tetrachloroaniline (2BTCA), in the color additives D&C Red Nos. 27 and 28 (phloxine 13) and (b) the determination of the extent and level of 2BTCA contamination in certified lots of these colors. For these purposes, 213TCA (a compound not previously reported in the literature) and its positional isomer 4-bromo-2,3,5,6-tetrachloroaniline (4BTCA) were synthetically prepared. 4BTCA was used as the internal standard for the quantification of 213TCA in the colors. Test portions from 35 certified lots of D&C Red Nos. 27 and 28 were analyzed for 213TCA using a solid-phase microextraction-GC-MS method. Those lots were submitted for certification by both domestic (seven) and foreign (four) manufacturers during the past 4 years. Of the test portions analyzed, 22 (62.9%) contained 213TCA in amounts ranging from 0.15 to 435.7 ppm with an average value of 131.7 ppm. The remaining 13 (37.1%) test portions contained no detectable 213TCA or less than 0.01 ppm, which is the limit of quantification of the present method. The analyses revealed substantial differences in the level of 213TCA across lots from the same manufacturer as well as among different manufacturers. The wide range of 213TCA levels found in the analyzed lots suggests that the presence of 2BTCA in D&C Red Nos. 27 and 28 may be avoided or significantly reduced during the manufacturing process. A direct correlation was observed between the presence of 213TCA and that of 3,4,5,6-tetrachlorophthalic acid in analyzed batches of D&C Red Nos. 27 and 28. A chemical pathway that could explain the presence of 2BTCA in these color additives, and ways to avoid its formation, are also proposed. Published by Elsevier B.V. C1 US FDA, Ctr Food Safety & Appl Nutr, Off Cosmet & Colors, College Pk, MD 20151 USA. US FDA, Ctr Food Safety & Appl Nutr, Off Sci Anal & Support, College Pk, MD 20740 USA. RP Weisz, A (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Cosmet & Colors, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. NR 20 TC 9 Z9 9 U1 0 U2 5 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 JUL 11 PY 2003 VL 1005 IS 1-2 BP 143 EP 153 DI 10.1016/S0021-9673(03)00917-8 PG 11 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 703TJ UT WOS:000184296800012 PM 12924789 ER PT J AU Nussbaum, JM Major, M Gunnery, S AF Nussbaum, JM Major, M Gunnery, S TI Transcriptional upregulation of interferon-induced protein kinase, PKR, in breast cancer SO CANCER LETTERS LA English DT Article DE PKR promoter; interferon stimulation response element; interferon; ISGF3; breast cancer ID NF-KAPPA-B; CONSTITUTIVE ACTIVATION; NUCLEAR FACTOR-90; CARCINOMA CELLS; KCS ELEMENT; T-CELLS; RNA; STAT3; GROWTH; GENE AB PKR (double-stranded RNA activated protein kinase) is overexpressed and overactive in human breast carcinoma (BC) cells. Here, we report that BC cells also have higher PKR mRNA levels and exhibit increased transcription from the PKR promoter. Mutational analysis of the PKR promoter indicated that the interferon stimulation response element (ISRE) is responsible for the increased transcription in BC cells. By gel retardation assay, ISRE-protein complexes formed by BC and non-transformed nuclear extracts were compared. A BC-specific ISRE-protein complex resembles the multimeric factor, ISGF3. (C) 2003 Elsevier Science Ltd. All rights reserved. C1 Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Biochem & Mol Biol, MSB, Newark, NJ 07103 USA. US FDA, Ctr Biol Evaluat & Res, DVP, Bethesda, MD 20892 USA. RP Gunnery, S (reprint author), Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Biochem & Mol Biol, MSB, E609,185 S Orange Ave, Newark, NJ 07103 USA. FU PHS HHS [AL34522] NR 37 TC 21 Z9 21 U1 0 U2 0 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 JUL 10 PY 2003 VL 196 IS 2 BP 207 EP 216 DI 10.1016/S0304-3835(03)00276-3 PG 10 WC Oncology SC Oncology GA 706FG UT WOS:000184442300011 PM 12860279 ER PT J AU Beard, BB Chang, IA AF Beard, BB Chang, IA TI An alternative method for determination of low-frequency specific absorption rate patterns in homogeneous phantoms SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID RESOLUTION MEASUREMENTS AB We propose a new application of voltage gradient measurements to determine specific absorption rate (SAR) at low frequencies where quasi-static electromagnetic conditions apply. This method, which we call the voltage gradient method, relies on direct measurement of the voltage field rather than measurement of the electric field or thermal transients. The voltage gradient method is fast and can be implemented with voltmeters of moderate cost. We tested the voltage gradient method using normal saline, in a phantom with simple geometry, and a sine wave voltage source at 5, 10, 20 and 50 kHz. Compared to the SAR measured thermally in the same phantom, the voltage gradient method produced almost identical curves when normalized. When the results of the voltage gradient method were scaled to the same power level used for the thermal SAR, the agreement was compatible with typical thermal SAR accuracy. C1 US FDA, Ctr Devices & Radiol Hlth, Electrophys Branch, Rockville, MD 20850 USA. RP Beard, BB (reprint author), US FDA, Ctr Devices & Radiol Hlth, Electrophys Branch, HFZ-133,9200 Corp Blvd, Rockville, MD 20850 USA. OI Beard, Brian/0000-0001-6480-0857 NR 6 TC 1 Z9 1 U1 0 U2 3 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 JUL 7 PY 2003 VL 48 IS 13 BP 2013 EP 2022 AR PII S0031-9155(03)60758-X DI 10.1088/0031-9155/48/13/312 PG 10 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 706LA UT WOS:000184454100013 PM 12884932 ER PT J AU Averbuch, M Katzper, M AF Averbuch, M Katzper, M TI Severity of baseline pain and degree of analgesia in the third molar post-extraction dental pain model SO ANESTHESIA AND ANALGESIA LA English DT Article AB The purpose of this study was to determine whether different levels of pain would respond similarly to analgesia. We compared the analgesic response to ibuprofen in subjects with moderate versus severe baseline pain in clinical trials using the third molar post-extraction dental pain model. We performed a pooled raw data analysis of 517 subjects included in the ibuprofen treatment arm of 11 similar studies submitted to the Food and Drug Administration. The inclusion and exclusion criteria were similar in all studies. All studies used the same metrics and recorded pain at the same times. As expected, the well established analgesic effect of ibuprofen was confirmed. More intense baseline pain was initially associated with a larger decrease and greater fractional decreasing in pain intensity after medication. A larger percentage of those with milder baseline pain obtained relief compared with those with severe baseline pain. Reduction in pain intensity occurred mainly in the first 2 h. At later time points, the association of baseline conditions with a reduction in pain level diminished. We conclude that the intensity of initial pain is not correlated with the need for larger doses of analgesic. C1 US FDA, Ctr Drug Evaluat & Res, Div Analges Antiinflammatory & Ophthalm Drug Prod, Rockville, MD 20854 USA. Tel Aviv Univ, Fac Med, IL-69978 Tel Aviv, Israel. RP Katzper, M (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Analges Antiinflammatory & Ophthalm Drug Prod, 2 Locks Pond Court,HFD-550, Rockville, MD 20854 USA. NR 7 TC 14 Z9 15 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD JUL PY 2003 VL 97 IS 1 BP 163 EP 167 DI 10.1213/01.ANE.0000063827.97392.5E PG 5 WC Anesthesiology SC Anesthesiology GA 695CZ UT WOS:000183814700029 PM 12818960 ER PT J AU Li, JT Lockey, RF Bernstein, L Portnoy, JM Nicklas, RA AF Li, JT Lockey, RF Bernstein, L Portnoy, JM Nicklas, RA TI Untitled - Response SO ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY LA English DT Letter ID IMMUNOTHERAPY C1 Mayo Clin & Mayo Fdn, Rochester, MN 55905 USA. Univ S Florida, Tampa, FL USA. Univ Cincinnati, Med Ctr, Cincinnati, OH 45267 USA. Childrens Mercy Hosp, Kansas City, MO 64108 USA. George Washington Med Ctr, Washington, DC USA. US FDA, Rockville, MD 20857 USA. RP Li, JT (reprint author), Mayo Clin & Mayo Fdn, 200 1st St SW, Rochester, MN 55905 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU AMER COLL ALLERGY ASTHMA IMMUNOLOGY PI ARLINGTON HTS PA 85 WEST ALGONQUIN RD SUITE 550, ARLINGTON HTS, IL 60005 USA SN 1081-1206 J9 ANN ALLERG ASTHMA IM JI Ann. Allergy Asthma Immunol. PD JUL PY 2003 VL 91 IS 1 BP 97 EP 98 PG 2 WC Allergy; Immunology SC Allergy; Immunology GA 702EJ UT WOS:000184206200021 ER PT J AU Zuckerman, BD Sapirstein, W AF Zuckerman, BD Sapirstein, W TI Mismatching of annular sizers and cardiac prosthetic valve sewing cuff sizes SO ANNALS OF THORACIC SURGERY LA English DT Letter C1 US FDA, Ctr Devices & Radiol Hlth, MDUS Food & Drug Adm, Rockville, MD 20850 USA. RP Zuckerman, BD (reprint author), US FDA, Ctr Devices & Radiol Hlth, MDUS Food & Drug Adm, 9200 Corp Blvd,HFZ 450, Rockville, MD 20850 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD JUL PY 2003 VL 76 IS 1 BP 337 EP 337 AR PII S0003-4975(02)00181-4 DI 10.1016/S0003-4975(02)04682-9 PG 1 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 697XK UT WOS:000183968400083 PM 12842579 ER PT J AU Moody, JD Fu, PP Freeman, JP Cerniglia, CE AF Moody, JD Fu, PP Freeman, JP Cerniglia, CE TI Regio- and stereoselective metabolism of 7,12-dimethylbenz[a]anthracene by Mycobacterium vanbaalenii PYR-1 SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID POLYCYCLIC AROMATIC-HYDROCARBONS; SP STRAIN PYR-1; ABSOLUTE-CONFIGURATION; MICROBIAL-METABOLISM; FUNGAL METABOLISM; 7,12-DIMETHYLBENZANTHRACENE; DEGRADATION; IDENTIFICATION; STEREOCHEMISTRY; CYTOCHROME-P450 AB The degradation of 7,12-dimethylbenz[a]anthracene (DMBA), a carcinogenic polycyclic aromatic hydrocarbon, by cultures of Mycobacterium vanbaalenii PYR-1 was studied. When M. vanbaalenii PYR-1 was grown in the presence of DMBA for 136 h, high-pressure liquid chromatography (HPLC) analysis showed the presence of four ethyl acetate-extractable compounds and unutilized substrate. Characterization of the metabolites by mass and nuclear magnetic resonance spectrometry indicated initial attack at the C-5 and C-6 positions and on the methyl group attached to C-7 of DMBA. The metabolites were identified as cis-5,6-dihydro-5,6-dihydroxy-7,12-dimethylbenz[a]anthracene (DMBA cis-5,6-dihydrodiol), trans-5,6-dihydro-5,6-dihydroxy-7,12-dimethylbenz[a]anthracene (DMBA trans-5,6-dihydrodiol), and 7-hydroxymethyl-12-methylbenz[a]anthracene, suggesting dioxygenation and monooxygenation reactions. Chiral stationary-phase HPLC analysis of the dihydrodiols showed that DMBA cis-5,6-dihydrodiol had 95% 5S,6R and 5% 5R,6S absolute stereochemistry. On the other hand, the DMBA trans-5,6-dihydrodiol was a 100% 5S,6S enantiomer. A minor photooxidation product, 7,12-epidioxy-7,12-dimethylbenz[a]anthracene, was also formed. The results demonstrate that M. vanbaalenii PYR-1 is highly regio- and stereoselective in the degradation of DMBA. C1 US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. US FDA, Natl Ctr Toxicol Res, Div Chem, Jefferson, AR 72079 USA. RP Cerniglia, CE (reprint author), US FDA, Natl Ctr Toxicol Res, Div Microbiol, HFT-250, Jefferson, AR 72079 USA. NR 40 TC 30 Z9 30 U1 0 U2 3 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 JUL PY 2003 VL 69 IS 7 BP 3924 EP 3931 DI 10.1128/AEM.69.7.3924-3931.2003 PG 8 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 699XM UT WOS:000184082100030 PM 12839762 ER PT J AU DePaola, A Ulaszek, J Kaysner, CA Tenge, BJ Nordstrom, JL Wells, J Puhr, N Gendel, SM AF DePaola, A Ulaszek, J Kaysner, CA Tenge, BJ Nordstrom, JL Wells, J Puhr, N Gendel, SM TI Molecular, serological, and virulence characteristics of Vibrio parahaemolyticus isolated from environmental, food, and clinical sources in north America and Asia SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID THERMOSTABLE DIRECT HEMOLYSIN; UNITED-STATES; PANDEMIC SPREAD; O3-K6 CLONE; TDH GENE; OYSTERS; STRAINS; UREASE; TRH; EMERGENCE AB Potential virulence attributes, serotypes, and ribotypes were determined for 178 pathogenic Vibrio parahaemolyticus isolates from clinical, environmental, and food sources on the Pacific, Atlantic, and Gulf Coasts of the United States and from clinical sources in Asia. The food and environmental isolates were generally from oysters, and they were defined as being pathogenic by using DNA probes to detect the presence of the thermostable direct hemolysin (tdh) gene. The clinical isolates from the United States were generally associated with oyster consumption, and most were obtained from outbreaks in Washington, Texas, and New York. Multiplex PCR was used to confirm the species identification and the presence of tdh and to test for the tdh-related hemolysin trh. Most of the environmental, food, and clinical isolates from the United States were positive for tdh, trh, and urease production. Outbreak-associated isolates from Texas, New York, and Asia were predominantly serotype O3:K6 and possessed only tdh. A total of 27 serotypes and 28 ribogroups were identified among the isolates, but the patterns of strain distribution differed between the serotypes and ribogroups. All but one of the O3:K6 isolates from Texas were in a different ribogroup from the O3:K6 isolates from New York or Asia. The O3:K6 serotype was not detected in any of the environmental and food isolates from the United States, and none of the food or environmental isolates belonged to any of the three ribogroups that contained all of the O3:K6 and related clinical isolates. The combination of serotyping and ribotyping showed that the Pacific Coast V. parahaemolyticus population appeared to be distinct from that of either the Atlantic Coast or Gulf Coast. The fact that certain serotypes and ribotypes contained both clinical and environmental isolates while many others contained only environmental isolates implies that certain serotypes or ribotypes are more relevant for human disease. C1 US FDA, Gulf Coast Seafood Lab, Dauphin Isl, AL 36528 USA. US FDA, Natl Ctr Food Safety & Technol, Summit Argo, IL 60501 USA. US FDA, Seafood Prod Res Ctr, Bothell, WA 98021 USA. Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. RP DePaola, A (reprint author), US FDA, Gulf Coast Seafood Lab, Dauphin Isl, AL 36528 USA. FU FDA HHS [U01 FD000431] NR 41 TC 121 Z9 129 U1 0 U2 8 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 JUL PY 2003 VL 69 IS 7 BP 3999 EP 4005 DI 10.1128/AEM.69.7.3999-4005.2003 PG 7 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 699XM UT WOS:000184082100042 PM 12839774 ER PT J AU DePaola, A Nordstrom, JL Dalsgaard, A Forslund, A Oliver, J Bates, T Bourdage, KL Gulig, PA AF DePaola, A Nordstrom, JL Dalsgaard, A Forslund, A Oliver, J Bates, T Bourdage, KL Gulig, PA TI Analysis of Vibrio vulnificus from market oysters and septicemia cases for virulence markers SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID FIELD GEL-ELECTROPHORESIS; UNITED-STATES; PLASMID DNA; STRAINS; PATHOGENESIS; EPIDEMIOLOGY; INFECTIONS; RETAIL; COAST AB Representative encapsulated strains of Vibrio vulnificus from market oysters and oyster-associated primary septicemia cases (25 isolates each) were tested in a blinded fashion for potential virulence markers that may distinguish strains from these two sources. These isolates were analyzed for plasmid content, for the presence of a 460-bp amplicon by randomly amplified polymorphic DNA PCR, and for virulence in subcutaneously (s.c.) inoculated, iron-dextran-treated mice. Similar percentages of market oyster and clinical isolates possessed detectable plasmids (24 and 36%, respectively), produced the 460-bp amplicon (45 and 50%, respectively), and were judged to be virulent in the mouse s.c. inoculation-iron-dextran model (88% for each). Therefore, it appears that nearly all V vulnificus strains in oysters are virulent and that genetic tests for plasmids and specific PCR size amplicons cannot distinguish between fully virulent and less virulent strains or between clinical and environmental isolates. The inability of these methods to distinguish food and clinical V. vulnificus isolates demonstrates the need for alternative subtyping approaches and virulence assays. C1 US FDA, Gulf Coast Seafood Lab, Dauphin Isl, AL 36528 USA. Royal Vet & Agr Univ, Dept Vet Microbiol, DK-1870 Frederiksberg, Denmark. Univ N Carolina, Dept Biol, Charlotte, NC 28223 USA. Univ Florida, Coll Med, Dept Mol Genet & Microbiol, Gainesville, FL 32610 USA. RP DePaola, A (reprint author), US FDA, Gulf Coast Seafood Lab, Dauphin Isl, AL 36528 USA. NR 24 TC 49 Z9 50 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0099-2240 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD JUL PY 2003 VL 69 IS 7 BP 4006 EP 4011 DI 10.1128/AEM.69.7.4006-4011.2003 PG 6 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 699XM UT WOS:000184082100043 PM 12839775 ER PT J AU Rafii, F Davis, C Park, M Heinze, TM Beger, RD AF Rafii, F Davis, C Park, M Heinze, TM Beger, RD TI Variations in metabolism of the soy isoflavonoid daidzein by human intestinal microfloras from different individuals SO ARCHIVES OF MICROBIOLOGY LA English DT Article DE isoflavonoids; daidzein; equol; intestinal bacteria; soybean ID SOYBEAN ISOFLAVONES; GUT MICROFLORA; BREAST-CANCER; C-RING; GENISTEIN; EQUOL; PHYTOESTROGENS; WOMEN; RISK; BACTERIA AB Isoflavonoids found in legumes, such as soybeans, are converted by intestinal bacteria to metabolites that might have increased or decreased estrogenic activity. Variation in the effects of dietary isoflavonoids among individuals has been attributed to differences in their metabolism by intestinal bacteria. To investigate this variation, the metabolism of the isoflavonoid daidzein by bacteria from ten fecal samples, provided at different times by six individuals on soy-containing diets, was compared. After anaerobic incubation of bacteria with daidzein for 2 weeks, four samples had metabolized daidzein and six samples had not. Three of the positive samples were from individuals whose microflora had not metabolized daidzein in previous samples. Dihydrodaidzein was observed in one sample, dihydrodaidzein and equol in another sample, and equol and O-desmethylangolensin in two other samples. These results corroborate the hypothesis that the microflora of the gastrointestinal tract of an individual influences the particular isoflavone metabolites produced following consumption. C1 US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. Dollarway High Sch, Pine Bluff, AR 71602 USA. US FDA, Natl Ctr Toxicol Res, Div Chem, Jefferson, AR 72079 USA. RP Rafii, F (reprint author), US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. NR 28 TC 50 Z9 57 U1 1 U2 5 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0302-8933 J9 ARCH MICROBIOL JI Arch. Microbiol. PD JUL PY 2003 VL 180 IS 1 BP 11 EP 16 DI 10.1007/s00203-003-0551-6 PG 6 WC Microbiology SC Microbiology GA 695GM UT WOS:000183822800002 PM 12783157 ER PT J AU Dhariwal, K Jackson, A AF Dhariwal, K Jackson, A TI Effect of length of sampling schedule and washout interval on magnitude of drug carryover from period 1 to period 2 in two-period, two-treatment bioequivalence studies and its attendant effects on determination of bioequivalence SO BIOPHARMACEUTICS & DRUG DISPOSITION LA English DT Article DE bioequivalence; washout interval; AUC; carryover AB The relationships between post-dosing blood sampling schedules and length of washout interval on the percent of drug carryover into period 2, in a two-treatment, two-period, crossover bioequivalence study was investigated. Observed simulations were done using a two-compartment model with a beta half-life of 100h, sampling to 200 and 300h, followed by 1 to 4 washout half-lives. These data were compared with simulations with sampling for 200 and 300h and no carryover between periods (i.e. true data) and used to establish the per cent carryover. Pseudo-observed concentration period 2 data were also generated for an experimental amiodarone bioequivalence study by adding either 5%, 10% or 50% of the period 2 C-max, value to the observed concentrations of selected subjects (i.e. those with longest half-lives) to give a pseudo-plasma concentration profile. Further investigation via simulation was done by including or excluding subjects with time 0 concentrations of 1%-10% of period 2 C-max. The simulated data indicated that up to a 3% carryover of AUC into the second period of a bioequivalence study had no effect on the power of the 90% Cl for AUC and C-max. For amiodarone, second period pre-dose drug concentrations equal to as much as 50% of the observed period 2 C-max value had less effect on the 90% Cl (i.e. compared with the true data) for AUC and C-max than did subject deletion. Copyright (C) 2003 John Wiley Sons, Ltd. C1 US FDA, Off Clin Pharmacol & Biopharmaceut, Rockville, MD 20857 USA. RP Jackson, A (reprint author), US FDA, Off Clin Pharmacol & Biopharmaceut, Rockville, MD 20857 USA. NR 9 TC 6 Z9 6 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0142-2782 J9 BIOPHARM DRUG DISPOS JI Biopharm. Drug Dispos. PD JUL PY 2003 VL 24 IS 5 BP 219 EP 228 DI 10.1002/bdd.359 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 706YL UT WOS:000184482600006 PM 12784322 ER PT J AU Hansen, DK Streck, RD Antony, AC AF Hansen, DK Streck, RD Antony, AC TI Antisense modulation of the coding or regulatory sequence of the folate receptor (Folate binding protein-1) in mouse embryos leads to neural tube defects SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Article DE folic acid; folate receptor; neural tube defects; mouse; rodent whole embryo culture; gene expression; antisense ID METHYLENETETRAHYDROFOLATE REDUCTASE GENE; FOLIC-ACID SUPPLEMENTATION; PERICONCEPTIONAL MULTIVITAMIN SUPPLEMENTATION; CONOTRUNCAL HEART-DEFECTS; SPINA-BIFIDA; 5,10-METHYLENETETRAHYDROFOLATE REDUCTASE; RISK FACTOR; MESSENGER-RNA; METHIONINE SYNTHASE; 677C->T MUTATION AB BACKGROUND: Although folic acid decreases the incidence of neural tube defects (NTDs) in humans, the mechanism for this protection is unknown. We have employed antisense technology to alter expression of the gene for the folate receptor (folate binding protein-1 [Folbp1]) in mouse embryos cultured in vitro. METHODS: Embryos were explanted on day 8 of gestation and cultured for 44 hr. Several oligodeoxyribonucleotides designed to modulate the coding region or a regulatory sequence in the 5'-untranslated region of Folbp1 were microinjected into the amniotic sac of embryos at the beginning of the culture period. RESULTS: Two different antisense sequences to the 5' and 3' coding region in Folbp1 produced concentration-dependent increases in the number of embryos with NTDs. Coinjection of 5-methyltetrahydrofolate with these sequences decreased the frequency of abnormal embryos. A semi-quantitative RT-PCR technique used to measure the amount of Folbp1 mRNA in treated and control embryos confirmed that the mRNA level was decreased by treatment with the antisense sequences. An antisense oligodeoxyribonucleotide to a 17 base cis regulatory element also generated a concentration-dependent increase in the frequency of embryos with NTDs, and a decrease in the level of Folbp1 mRNA. CONCLUSIONS: These results demonstrate that alterations in expression of Folbp1 by perturbing either the coding sequence or a critical regulatory cis-element can play a role in NTDs. Published 2003 Wiley-Liss, Inc. C1 Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Food & Drug Adm, Jefferson, AR 72079 USA. Indiana Univ, Sch Med, Dept Med, Indianapolis, IN USA. Roudebush Vet Affairs Med Ctr, Indianapolis, IN USA. RP Hansen, DK (reprint author), Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Food & Drug Adm, Jefferson, AR 72079 USA. FU NICHD NIH HHS [R01 HD39295] NR 63 TC 14 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 1542-0752 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD JUL PY 2003 VL 67 IS 7 BP 475 EP 487 DI 10.1002/bdra.10072 PG 13 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 720XH UT WOS:000185287200001 PM 14565618 ER PT J AU Xin, KQ Hoshino, Y Toda, Y Igimi, S Kojima, Y Jounai, N Ohba, K Kushiro, A Kiwaki, M Hamajima, K Klinman, D Okuda, K AF Xin, KQ Hoshino, Y Toda, Y Igimi, S Kojima, Y Jounai, N Ohba, K Kushiro, A Kiwaki, M Hamajima, K Klinman, D Okuda, K TI Immunogenicity and protective efficacy of orally administered recombinant Lactococcus lactis expressing surface-bound HIV Env SO BLOOD LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; GP120 ENVELOPE GLYCOPROTEIN; DNA VACCINE VECTOR; CD8(+) T-CELLS; CHOLERA-TOXIN; MUCOSAL IMMUNITY; DENDRITIC CELLS; RESPONSES; IMMUNIZATION; LYMPHOCYTES AB This study investigates whether genetically modified orally administered Lactococcus lactis (L lactis) could be used as an HIV vaccine. L lactis is immunogenic and extremely safe when delivered orally. We created a recombinant L lactis vector expressing the envelope protein of HIV on its cell surface. Oral immunization with this vector induced high levels of HIV-specific serum IgG and fecal IgA antibodies. Cell-mediated immune responses also were generated in both the regional lymph nodes and the spleen. Dendritic cells are readily infected by L lactis and appear to play a potential role in mediating the development of these immune responses. The protective efficacy of this vaccine strategy was demonstrated by challenging mice intraperitoneally with an HIV Env-expressing vaccinia virus. Their viral loads were 350-fold lower than those of control mice. These findings support the further development of L lactis-based HIV vaccines. (C) 2003 by The American Society of Hematology. C1 Yokohama City Univ, Sch Med, Dept Bacteriol, Kanazawa Ku, Yokohama, Kanagawa 2360004, Japan. Food & Drug Adm Natl Hlth Inst, Rockville, MD USA. Yakult Cent Inst Microbiol Res, Tokyo, Japan. US FDA, Bethesda, MD 20014 USA. Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. RP Okuda, K (reprint author), Yokohama City Univ, Sch Med, Dept Bacteriol, Kanazawa Ku, 3-9 Fukuura, Yokohama, Kanagawa 2360004, Japan. RI Ohba, Kenji/D-8072-2015 OI Ohba, Kenji/0000-0002-4936-8186 NR 37 TC 83 Z9 89 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 JUL 1 PY 2003 VL 102 IS 1 BP 223 EP 228 DI 10.1182/blood-2003-01-0110 PG 6 WC Hematology SC Hematology GA 695FK UT WOS:000183820300040 PM 12649143 ER PT J AU Zivny, J Jelinek, J Pospisilova, D Plasilova, M Necas, E Stopka, T AF Zivny, J Jelinek, J Pospisilova, D Plasilova, M Necas, E Stopka, T TI Diamond Blackfan anemia stem cells fail to repopulate erythropoiesis in NOD/SCID mice SO BLOOD CELLS MOLECULES AND DISEASES LA English DT Article DE diamond Blackfan anemia; hematopoiesis; erythropiesis; stem cells; NOD/SCID mice; colony-forming assay ID RIBOSOMAL-PROTEIN S19; IN-VITRO RESPONSE; ERYTHROID PROGENITORS; LONG-TERM; GENE; MUTATIONS; THERAPY; DEFECT; GROWTH AB Diamond Blackfan Anemia (DBA) is a congenital disorder characterized by decreased red blood cell production and developmental abnormalities. We herein show that DBA progenitors produced lower numbers of phenotypically normal erythroid colonies in vitro, whereas nonerythroid colonies were normally abundant and developed. To determine whether DBA stem cells are capable of producing early erythroid, monocyto-granulocytic, and lymphoid progenitors in vivo we used a mouse xenotransplantation model. We demonstrate that DBA stem cells poorly repopulated erythroid progeny in NOD/SCID mice, whereas the monocyto-granulocytic and lymphoid progenies were repopulated normally. Therefore, we conclude that disordered DBA erythropoiesis may be a result of defective erythroid-lineage commitment and maintenance of early erythroid progenitors. (C) 2003 Elsevier Science (USA). All rights reserved. C1 Charles Univ, Fac Med 1, Dept Pathophysiol, Prague, Czech Republic. Inst Hematol & Blood Transfus, CR-12820 Prague, Czech Republic. Palacky Univ, Gen Pediat Hosp, CR-77147 Olomouc, Czech Republic. RP Zivny, J (reprint author), US FDA, OBRR, DH, 8800 Rockville Pike,HFM-335, Bethesda, MD 20892 USA. RI Jelinek, Jaroslav/A-8476-2008; Jelinek, Jaroslav/D-2282-2012; Stopka, Tomas/D-5864-2017 OI Jelinek, Jaroslav/0000-0002-2533-0220; Stopka, Tomas/0000-0001-7236-6894 NR 19 TC 4 Z9 4 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1079-9796 J9 BLOOD CELL MOL DIS JI Blood Cells Mol. Dis. PD JUL-AUG PY 2003 VL 31 IS 1 BP 93 EP 97 DI 10.1016/S1079-9796(03)00115-3 PG 5 WC Hematology SC Hematology GA 700FF UT WOS:000184101400016 PM 12850491 ER PT J AU Mann, M Chowdhury, B Sullivan, E Nicklas, R Anthracite, R Meyer, RJ AF Mann, M Chowdhury, B Sullivan, E Nicklas, R Anthracite, R Meyer, RJ TI Serious asthma exacerbations in asthmatics treated with high-dose formoterol SO CHEST LA English DT Article DE asthma; forn-ioterol; long-acting beta-agonist ID LONG-TERM TREATMENT; INHALED FORMOTEROL; PERSISTENT ASTHMA; DOUBLE-BLIND; DRY POWDER; SALMETEROL; SUBSENSITIVITY; ALBUTEROL; BUDESONIDE; SALBUTAMOL AB Objective: To review three prospective, randomized, placebo-controlled, double-blind clinical studies of formoterol (Foradil Aerolizer;, Novartis Pharmaceuticals; Basel, Switzerland) at dosages of 12 mug and 24 mug bid for the treatment of patients with asthma. Data sources: Clinical studies submitted to the US Food and Drug Administration in support of the approval of Foradil Aerolizer for marketing in the United States. Results: More patients treated regularly with formoterol, 24 mug bid, had a serious asthma exacerbation than did patients who had been treated with placebo. In the first study, 4 of 135 adult patients (3%) who had been treated with formoterol, 24 mug bid, had a serious asthma exacerbation compared to none of 136 placebo-treated patients. In the second study, 5 of 136 patients (3.7%) treated with formoterol, 24 mug bid, had a serious asthma exacerbation compared to 2 of 141 placebo-treated patients (1.4%). In the third study, I I of 171 pediatric patients (6.4%) treated with formoterol, 24 mug bid, had a serious asthma exacerbation compared to none of 176 placebo-treated patients. Conclusion: Regular use of high-dose inhaled formoterol (24 mug bid) may be associated with more frequent serious asthma exacerbations. C1 US FDA, Div Pulm & Allergy Drug Prod, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Mann, M (reprint author), US FDA, Div Pulm & Allergy Drug Prod, Ctr Drug Evaluat & Res, 5600 Fishers Ln, Rockville, MD 20857 USA. NR 20 TC 104 Z9 109 U1 0 U2 2 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD JUL PY 2003 VL 124 IS 1 BP 70 EP 74 DI 10.1378/chest.124.1.70 PG 5 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 701KP UT WOS:000184167000014 PM 12853504 ER PT J AU Wernette, CM Frasch, CE Madore, D Carlone, G Goldblatt, D Plikaytis, B Benjamin, W Quataert, SA Hildreth, S Sikkema, DJ Kayhty, H Jonsdottir, I Nahm, MH AF Wernette, CM Frasch, CE Madore, D Carlone, G Goldblatt, D Plikaytis, B Benjamin, W Quataert, SA Hildreth, S Sikkema, DJ Kayhty, H Jonsdottir, I Nahm, MH TI Enzyme-linked immunosorbent assay for quantitation of human antibodies to pneumococcal polysaccharides SO CLINICAL AND DIAGNOSTIC LABORATORY IMMUNOLOGY LA English DT Article ID INFLUENZAE TYPE-B; CONJUGATE VACCINE FORMULATION; CROSS-REACTIVE ANTIBODIES; STREPTOCOCCUS-PNEUMONIAE; CAPSULAR POLYSACCHARIDE; INTRANASAL IMMUNIZATION; MONOCLONAL-ANTIBODIES; C-POLYSACCHARIDE; OPSONOPHAGOCYTIC ACTIVITY; ANTICAPSULAR ANTIBODIES C1 Univ Alabama, Dept Pathol & Microbiol, Birmingham, AL 35249 USA. US FDA, Bethesda, MD 20014 USA. Wyeth Vaccines, W Henrietta, NY USA. Ctr Dis Control & Prevent, Atlanta, GA USA. Inst Child Hlth, London, England. Natl Publ Hlth Inst, Helsinki, Finland. Landspitali Univ Hosp, Dept Immunol, Reykjavik, Iceland. RP Nahm, MH (reprint author), Univ Alabama, Dept Pathol & Microbiol, Birmingham, AL 35249 USA. RI Goldblatt, David/C-5972-2008; OI Goldblatt, David/0000-0002-0769-5242; Nahm, Moon/0000-0002-6922-1042 FU NIAID NIH HHS [AI-85334] NR 73 TC 197 Z9 202 U1 1 U2 7 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1071-412X J9 CLIN DIAGN LAB IMMUN JI Clin. Diagn. Lab. Immunol. PD JUL PY 2003 VL 10 IS 4 BP 514 EP 519 DI 10.1128/CDLI.10.4.514-519.2003 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 703MU UT WOS:000184284100003 PM 12853378 ER PT J AU Sheela, RR Babu, U Mu, J Elankumaran, S Bautista, DA Raybourne, RB Heckert, RA Song, WX AF Sheela, RR Babu, U Mu, J Elankumaran, S Bautista, DA Raybourne, RB Heckert, RA Song, WX TI Immune responses against Salmonella enterica serovar enteritidis infection in virally immunosuppressed chickens SO CLINICAL AND DIAGNOSTIC LABORATORY IMMUNOLOGY LA English DT Article ID PHAGE TYPE-4 INFECTION; ANEMIA VIRUS-INFECTION; LYMPHOCYTE SUBPOPULATIONS; AGENT; MICE; PATHOGENESIS; TYPHIMURIUM; HENS; EGGS; PATHOGENICITY AB To understand the role of immune mechanisms in protecting chickens from Salmonella infections, we examined the immune responses of Salmonella enterica serovar Enteritidis-infected chickens and the effect of chicken anemia virus (CAV), a T-cell-targeted virus, on S. enterica serovar Enteritidis-induced immune responses. One-day-old chicks were orally inoculated with S. enterica serovar Enteritidis with or without intramuscular injection of CAV. The bacterial infection, pathology, and immune responses of chickens were evaluated at 14, 28, and 56 days postinoculation. The infection increased the levels of S. enterica serovar Enteritidis-specific mucosal immunoglobulin A (IgA), the number of gut-associated T cells, and the titer of serum IgG specific for S. enterica serovar Enteritidis surface antigens. CAV infection depressed these immune responses, especially the mucosal immune responses, but did not increase the number of S. enterica serovar Enteritidis-infected cells in the intestine. The severity of pathological lesions appeared to be reciprocal to the level of immune responses, but the S. enterica serovar Enteritidis infection persisted. These results suggest that oral infection of S. enterica serovar Enteritidis in chickens induces both mucosal and systemic immune responses, which have a limited effect on the S. enterica serovar Enteritidis infection under conditions designed to mimic the field situation. C1 Univ Maryland, Dept Cell Biol & Mol Genet, College Pk, MD 20742 USA. Univ Maryland, Coll Vet Med, College Pk, MD 20742 USA. US FDA, Laurel, MD 20707 USA. RP Song, WX (reprint author), Univ Maryland, Dept Cell Biol & Mol Genet, College Pk, MD 20742 USA. RI Subbiah, Elankumaran/E-9277-2010 OI Subbiah, Elankumaran/0000-0003-4135-9477 NR 48 TC 36 Z9 37 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1071-412X J9 CLIN DIAGN LAB IMMUN JI Clin. Diagn. Lab. Immunol. PD JUL PY 2003 VL 10 IS 4 BP 670 EP 679 DI 10.1128/CDLI.10.4.670-679.2003 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 703MU UT WOS:000184284100028 PM 12853403 ER PT J AU Dezzutti, CS Guenthner, PC Daniel, S Utz, U Cabrera, T Marshall, JH Bianco, C Lal, RB Cowan, EP AF Dezzutti, CS Guenthner, PC Daniel, S Utz, U Cabrera, T Marshall, JH Bianco, C Lal, RB Cowan, EP TI Detection of human T-lymphotropic virus (HTLV) tax sequences in New York City blood donors seronegative for HTLV types 1 and 2 SO CLINICAL AND DIAGNOSTIC LABORATORY IMMUNOLOGY LA English DT Article ID I-ASSOCIATED MYELOPATHY; VIRAL-INFECTIONS; TRANSFUSION; PREVALENCE; PROVIRUSES; PRODUCTS; DISEASE; RISK AB A potential public health concern is the reported detection of the human T-lymphotropic virus (HTLV) tax gene in the lymphocytes of up to 11% of a low-risk group of New York City blood donors (NYBD). This study aimed to independently confirm the prevalence of HTLV tax sequences in 293 NYBD. All NYBD tested negative for antibodies to HTLV types 1 and 2 and HTLV Tax. HTLV tax sequences were not detected in the NYBD lymphocytes. These data demonstrate the lack of HTLV-1 tax in this group of NYBD at low risk for HTLV infection. C1 Ctr Dis Control & Prevent, Div AIDS STD & TB Lab Res, Atlanta, GA 30333 USA. US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20850 USA. Amer Blood Ctr, Washington, DC 20005 USA. RP Dezzutti, CS (reprint author), Ctr Dis Control & Prevent, Div AIDS STD & TB Lab Res, 1600 Clifton Rd NE,Mailstop G19, Atlanta, GA 30333 USA. NR 19 TC 5 Z9 6 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1071-412X J9 CLIN DIAGN LAB IMMUN JI Clin. Diagn. Lab. Immunol. PD JUL PY 2003 VL 10 IS 4 BP 715 EP 717 DI 10.1128/CDLI.10.4.715-717.2003 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 703MU UT WOS:000184284100035 PM 12853410 ER PT J AU Ibrahim, A Scher, N Williams, G Sridhara, R Li, N Chen, G Leighton, J Booth, B Gobburu, JVS Rahman, A Hsieh, Y Wood, R Vause, D Pazdur, R AF Ibrahim, A Scher, N Williams, G Sridhara, R Li, N Chen, G Leighton, J Booth, B Gobburu, JVS Rahman, A Hsieh, Y Wood, R Vause, D Pazdur, R TI Approval summary for zoledronic acid for treatment of multiple myeloma and cancer bone metastases SO CLINICAL CANCER RESEARCH LA English DT Article ID BREAST-CANCER; BISPHOSPHONATES; PAMIDRONATE AB Purpose: This article summarizes data submitted to the United States Food and Drug Administration for marketing approval of zoledronic acid (Zol; Novartis Pharmaceuticals, East Hanover, NJ), a bisphosphonate drug for treating patients with bone metastases. Experimental Design: We review the chemistry, toxicology, pharmacology, and clinical study results submitted to support the supplemental New Drug Application for Zol for treatment of patients with bone metastases. Four- and 8-mg Zol doses were selected for Phase III trials based on bone resorption markers and clinical efficacy parameters. Patients with bone metastases were randomized in three Phase III studies (prostate cancer, solid tumors, and multiple myeloma or breast cancer) to receive 4 or 8 mg of Zol or to a control arm. The control was a placebo in the prostate cancer study and the other solid tumor study and was 90 mg of pamidronate (Pam) in the study of breast cancer and multiple myeloma. Studies were amended twice because of renal toxicity, initially to increase Zol infusion time from 5 to 15 min and later to decrease the dose in the Zol 8-mg arm to 4 mg. The efficacy end point was skeletal-related events (SREs), a composite end point consisting of pathologic fracture, radiation therapy to bone, changes in antineoplastic therapy for bone pain (prostate cancer only), surgery to bone, or spinal cord compression. This end point was analyzed either as the proportion of patients with SRE or time to first SRE. The breast cancer and myeloma study used a noninferiority statistical analysis methods to determine efficacy. Results: In prostate cancer, both the proportions analysis and time-to-SRE analysis showed significantly less bone morbidity on Zol (4 mg) than placebo, but no significant difference between Zol (8 mg) and placebo in either analysis. In the solid tumor study, the time to SRE analysis but not the proportions analysis showed significantly less skeletal morbidity on Zol (4 mg) than placebo, and Zol (8 mg) was significantly better than placebo in both analyses. The breast cancer and myeloma study demonstrated noninferiority of Zol compared with Pam, with Zol retaining at least 49.3% of the Pam treatment effect previously demonstrated in placebo-controlled trials. Zol was approved on February 22, 2002, by the United States Food and Drug Administration for the "treatment of patients with multiple myeloma and documented bone metastases from solid tumors, in conjunction with standard antineoplastic therapy. Prostate cancer should have progressed after treatment with at least one hormonal therapy." The recommended dose and schedule is 4 mg of Zol infused over 15 min every 3-4 weeks. Increased Zol doses and shorter infusions are not recommended because of potential renal toxicity. C1 Ctr Drug Evaluat & Res, Div Oncol Drug Prod, Rockville, MD 20857 USA. RP Ibrahim, A (reprint author), Ctr Drug Evaluat & Res, Div Oncol Drug Prod, 5600 Fishers Lane,HFD-150, Rockville, MD 20857 USA. NR 10 TC 95 Z9 97 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUL PY 2003 VL 9 IS 7 BP 2394 EP 2399 PG 6 WC Oncology SC Oncology GA 700JK UT WOS:000184108700003 PM 12855610 ER PT J AU Petricoin, EF Liotta, LA AF Petricoin, EF Liotta, LA TI Mass spectrometry-based diagnostics: The upcoming revolution in disease detection has already arrived - Response SO CLINICAL CHEMISTRY LA English DT Letter C1 US FDA, Bethesda, MD 20892 USA. NIH, Pathol Lab, Bethesda, MD 20892 USA. RP Petricoin, EF (reprint author), US FDA, Bldg 29A,Room 2D12,8800 Rockville Pike, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 JUL PY 2003 VL 49 IS 7 BP 1228 EP 1229 PG 2 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 694TD UT WOS:000183789600043 ER PT J AU Hotchkiss, CE Paule, MG AF Hotchkiss, CE Paule, MG TI Effect of pair-housing on operant behavior task performance by rhesus monkeys SO CONTEMPORARY TOPICS IN LABORATORY ANIMAL SCIENCE LA English DT Article ID CYNOMOLGUS MONKEYS; BATTERY AB This study evaluated the effects of pair-housing on several operant (trained) behaviors in rhesus macaques (Macaca mulatta). Sixteen young, male, individually housed rhesus monkeys (age, 2.5 to 5.5 years) performed a battery of behaviors consisting of motivation (progressive ratio, PR), short-term memory and attention (delayed matching-to-sample, DMTS), color and position discrimination (conditioned position responding, CPR), and learning (incremental repeated acquisition, IRA) tasks. Behavioral assessments occurred 5 days/week, with the PR, IRA, and CPR tasks presented on one test day, and the DMTS task presented on the next test day. Thus, each task was performed two or three days/week. Eight subjects then were pair-housed, while eight age-matched controls remained individually housed. Pair-housed monkeys were separated for behavior testing and feeding but allowed access to each other approximately 20 h/day. The performance of the two groups of monkeys were compared for the 2 months prior to pairing, for a 2-month transition period as the pairs adjusted to the new housing situation, and for a 2-month period after the pairs had been established. Performance of the CPR and IRA tasks did not change over time in either group. For the PR and DMTS tasks, the number of trials completed increased over the course of the study in the controls but not in the pair-housed monkeys. In conclusion, pair-housing monkeys is feasible for studies involving operant behavior testing as a model for a variety of complex brain functions. However, housing condition may affect some test parameters, and this must be taken into consideration during experimental design. C1 Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Hotchkiss, CE (reprint author), Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 14 TC 8 Z9 9 U1 1 U2 6 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1060-0558 J9 CONTEMP TOP LAB ANIM JI Contemp. Top. Lab. Anim. Sci. PD JUL PY 2003 VL 42 IS 4 BP 38 EP 41 PG 4 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 710LB UT WOS:000184680700008 PM 12906400 ER PT J AU Conrods, TP Zhou, M Petricoin, EF Liotta, L Veenstra, TD AF Conrods, TP Zhou, M Petricoin, EF Liotta, L Veenstra, TD TI Cancer diagnosis using proteomic patterns SO EXPERT REVIEW OF MOLECULAR DIAGNOSTICS LA English DT Review DE bioinformatics; biomarkers; cancer; early diagnosis; mass spectrometry; proteomic patterns ID OVARIAN-CANCER; PROSTATE-CANCER; MASS-SPECTROMETRY; SERUM; BIOMARKERS; MEN AB The advent of proteomics has brought with it the hope of discovering novel biomarkers that can be used to diagnose diseases, predict susceptibility and monitor progression. Much of this effort has focused upon the mass spectral identification of the thousands of proteins that populate complex biosystems such as serum and tissues. A revolutionary approach in proteomic pattern analysis has emerged as an effective method for the early diagnosis of diseases such as ovarian cancer. Proteomic pattern analysis relies on the pattern of proteins observed and does not rely on the identification of a traceable biomarker. Hundreds of clinical samples per day can be analyzed utilizing this technology, which has the potential to be a novel, highly sensitive diagnostic tool for the early detection of cancer. C1 SAIC Frederick Inc, Biomed Proteom Program, NCI, Mass Spectrometry Ctr, Frederick, MD 21702 USA. NCI, Clin Proteom Program, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. NCI, Clin Proteom Program, Pathol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. SAIC Frederick Inc, Biomed Proteom Program, NCI, Analyt Chem Lab, Frederick, MD 21702 USA. RP Veenstra, TD (reprint author), SAIC Frederick Inc, Biomed Proteom Program, NCI, Mass Spectrometry Ctr, POB B, Frederick, MD 21702 USA. EM conrads@ncifcrf.gov; mzhou@ncifcrf.gov; petricoin@cber.FDA.gov; liottal@nih.gov; veenstra@ncifcrf.gov FU NCI NIH HHS [N01-CO-12400] NR 35 TC 97 Z9 107 U1 0 U2 9 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 JUL PY 2003 VL 3 IS 4 BP 411 EP 420 DI 10.1586/14737159.3.4.411 PG 10 WC Pathology SC Pathology GA 767KC UT WOS:000188437900002 PM 12877381 ER PT J AU Shankar, K Vaidya, VS Corton, JC Bucci, TJ Liu, J Waalkes, MP Mehendale, HM AF Shankar, K Vaidya, VS Corton, JC Bucci, TJ Liu, J Waalkes, MP Mehendale, HM TI Activation of PPAR-alpha in streptozotocin-induced diabetes is essential for resistance against acetaminophen toxicity SO FASEB JOURNAL LA English DT Article DE cell proliferation; microarray; real-time PCR; tissue repair ID PEROXISOME PROLIFERATOR CIPROFIBRATE; HEAT-SHOCK-PROTEIN; CARBON-TETRACHLORIDE HEPATOTOXICITY; ANTIMITOTIC AGENT COLCHICINE; AMELIORATES LIVER-INJURY; RECEPTOR-ALPHA; THIOACETAMIDE HEPATOTOXICITY; N-ACETYLCYSTEINE; COVALENT BINDING; MAP KINASE AB Diabetic (DB) mice exhibit significant resistance to hepatotoxicants. The role of peroxisome proliferator receptor (PPAR)-alpha activation in diabetes, in protection against lethal acetaminophen (APAP) challenge, was investigated. Upon treatment with APAP (600 mg/kg, i.p., a LD100 dose in wild-type [WT] non-DB mice), WT-DB mice showed only 30% mortality and 40% less liver injury as measured by alanine aminotransferase and histopathology. In contrast, diabetes in PPAR knockout (PPAR-alpha(-/-)) mice failed to protect against APAP toxicity, suggesting the importance of PPAR-alpha in diabetes-induced protection. S-phase DNA synthesis and PCNA immunohistochemical staining after injury showed early and robust tissue repair in WT-DB mice, but not in the PPAR-alpha(-/-) DB mice. Microarray analyses were performed on livers from non-DB and DB (WT and PPAR-alpha(-/-)) mice at 0 and 12 h after APAP. Microarray data were confirmed via real-time polymerase chain reaction analysis of several genes, including stress response, immediate early genes, DNA damage, heat shock proteins, and cell cycle regulators, followed by Western analyses of selected proteins. Gel shift assays revealed higher activation of nuclear factor-kappaB in WT-DB mice after APAP treatment. These findings suggest PPAR-alpha activation as a hepatoprotective adaptive response mediating protection against APAP in diabetes. C1 Univ Louisiana Monroe, Dept Toxicol, Sch Pharm, Coll Hlth Sci, Monroe, LA 71209 USA. Toxicogenomics, Chapel Hill, NC USA. Natl Ctr Toxicol Res, Pathol Associates Int, Jefferson, AR 72079 USA. NIEHS, Inorgan Carcinogenesis Sect, NCI, Res Triangle Pk, NC 27709 USA. RP Mehendale, HM (reprint author), Univ Louisiana Monroe, Dept Toxicol, Sch Pharm, Coll Hlth Sci, 700 Univ Ave,Sugar Hall 306, Monroe, LA 71209 USA. EM mehendale@ulm.edu NR 61 TC 38 Z9 38 U1 1 U2 5 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 JUL PY 2003 VL 17 IS 10 BP 1748 EP + DI 10.1096/fj.02-1186fje PG 33 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 706TR UT WOS:000184471600016 PM 12958197 ER PT J AU Kawakami, K Kawakami, M Husain, SR Puri, RK AF Kawakami, K Kawakami, M Husain, SR Puri, RK TI Potent antitumor activity of IL-13 cytotoxin in human pancreatic tumors engineered to express IL-13 receptor alpha 2 chain in vivo SO GENE THERAPY LA English DT Article DE tumor antigen; gene transfer; nitric oxide; innate immunity; orthotopic model ID INTERLEUKIN (IL)-13 BINDING; HIGH-AFFINITY INTERLEUKIN-4; CELL CARCINOMA-CELLS; PSEUDOMONAS EXOTOXIN; SIGNAL-TRANSDUCTION; CHIMERIC PROTEIN; CANCER-CELLS; HUMAN BREAST; MONOCLONAL-ANTIBODY; TARGETED CYTOTOXIN AB Interleukin-13 receptor (IL-13R) alpha2 chain plays a key role in ligand binding and internalization. We have recently demonstrated that this cytokine receptor chain has unique characteristics in tumor biology: it inhibits tumorigenicity of breast and pancreatic cancer in animal models. In this study, we have exploited IL-13Ralpha2 chain and established a novel approach for pancreatic cancer therapy. For this, a plasmid encoding the IL-13Ralpha2 chain gene was mixed with liposomes and injected into subcutaneously or orthotopically xenografted human pancreatic tumors in immunodeficient mice, followed by systemic or local therapy by a recombinant IL-13 cytotoxin. Only tumors forced to express IL-13Ralpha2 chain acquired extreme susceptibility to the antitumor effect of IL-13 cytotoxin. There was a dominant infiltration of cells including macrophages and natural killer cells in the regressing tumors. Since macrophages were found to produce nitric oxide, IL-13Ralpha2-targeted cancer therapy involved not only a direct tumor cell killing by IL-13 cytotoxin but also activation of innate immune response at the tumor site. Therefore, this approach may be a new powerful tool for pancreatic cancer or other localized cancer therapy. C1 US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Lab Mol Tumor Biol, Bethesda, MD 20892 USA. RP Puri, RK (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Lab Mol Tumor Biol, NIH Bldg,29B,Room 2NN10,29 Lincoln Dr,MSC 4555, Bethesda, MD 20892 USA. NR 50 TC 16 Z9 16 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0969-7128 J9 GENE THER JI Gene Ther. PD JUL PY 2003 VL 10 IS 13 BP 1116 EP 1128 DI 10.1038/sj.gt.3301956 PG 13 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 689ZZ UT WOS:000183524000006 PM 12808442 ER PT J AU Pavelka, MS Chen, B Kelley, CL Collins, FM Jacobs, WR AF Pavelka, MS Chen, B Kelley, CL Collins, FM Jacobs, WR TI Vaccine efficacy of a lysine auxotroph of Mycobacterium tuberculosis SO INFECTION AND IMMUNITY LA English DT Article AB The in vivo growth phenotype and vaccine efficacy of a lysine auxotrophic mutant of Mycobacterium tuberculosis strain H37Rv are described. An immunization experiment using a mouse model with an aerosol challenge showed that two doses of the M. tuberculosis mutant were required to generate protection equivalent to that of the Mycobacterium bovis BCG vaccine. C1 Yeshiva Univ Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10461 USA. Yeshiva Univ Albert Einstein Coll Med, Howard Hughes Med Inst, Bronx, NY 10461 USA. US FDA, Ctr Biol Evaluat & Res, Lab Mycobacterial Dis, Bethesda, MD 20892 USA. RP Jacobs, WR (reprint author), Yeshiva Univ Albert Einstein Coll Med, Dept Microbiol & Immunol, 1300 Morris Pk Ave, Bronx, NY 10461 USA. FU NIAID NIH HHS [AI33969, AI26170, N01 AI045244, N01-AI45244, R01 AI026170, R37 AI026170] NR 10 TC 54 Z9 57 U1 0 U2 5 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 JUL PY 2003 VL 71 IS 7 BP 4190 EP 4192 DI 10.1128/IAI.71.7.4190-4192.2003 PG 3 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 694WB UT WOS:000183797200070 PM 12819116 ER PT J AU Hammack, TS Amaguana, RM Johnson, ML Andrews, WH AF Hammack, TS Amaguana, RM Johnson, ML Andrews, WH TI Effectiveness of universal pre-enrichment broth for recovery of Salmonella from selected dairy foods SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID INJURED SALMONELLA; ENRICHMENT; MICROFLORA; PRODUCTS; MEDIA; JUICE; MILK AB The relative efficiencies of 2 Bacteriological Analytical Manual (BAM) pre-enrichments, lactose broth (LAC) and brilliant green water (BGW), were compared with Universal Pre-enrichment (UP) broth for the recovery of individual Salmonella serovars from instant nonfat dry milk (NFDM), dry whole milk (DWM), lactic casein (LC), and liquid whole milk (LWM). BGW was compared with UP broth for the analysis of NFDM and DWM but not with the other 2 matrixes. LAC was compared with UP broth for the analysis of LC and LWM. UP broth was made both from a commercial dehydrated preparation (UPC) and from individual ingredients (UPI). Bulk quantities of the selected dairy foods were inoculated with Salmonella serovars at levels intended to produce fractionally positive results, where at least half of the test portions analyzed, with one of the methods being evaluated, would be shown to be Salmonella-positive. For NFDM, in 6 of 9 experiments, with 2 different Salmonella serovars, BGW was significantly more productive than either UPI or UPC broth (p < 0.05). Salmonella was recovered from 118 of 180 test portions with BGW, from 25 of 180 test portions with UPC, and from 14 of 180 test portions with UPI. For DWM, in 2 of 4 experiments, with 2 different Salmonella serovars, BGW was significantly more productive than either UPI or UPC broth (p < 0.05). Salmonella was recovered from 67 of 80 test portions with BGW, from 36 of 80 test portions with UPC, and from 37 of 80 test portions with UPI. For LWM, in 9 of 9 experiments, with 3 different Salmonella serovars, there were no significant differences among the broths. Salmonella was recovered from 120 of 180 test portions with LAC, from 135 of 180 test portions with UPC, and from 129 of 180 test portions with UPI. For LC, in 5 of 7 experiments, with 2 different Salmonella serovars, both UPI and UPC broth were significantly more productive than LAC (p < 0.05). Salmonella was recovered from 42 of 140 test portions with LAC, from 114 of 140 test portions with U PC, and from 114 of 140 test portions with UPI. In addition, overall results showed that UPC and UPI broths were equivalent for the recovery of Salmonella from the foods tested, without regard to their performance in comparison with either LAC or BGW. C1 US FDA, Ctr Food Safety & Appl Nutr, Div Microbiol Studies, College Pk, MD 20740 USA. RP Hammack, TS (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Div Microbiol Studies, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. NR 16 TC 7 Z9 7 U1 0 U2 4 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 JUL-AUG PY 2003 VL 86 IS 4 BP 714 EP 718 PG 5 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 717HH UT WOS:000185081300021 PM 14509429 ER PT J AU Mahmood, I Green, MD Fisher, JE AF Mahmood, I Green, MD Fisher, JE TI Selection of the first-time dose in humans: Comparison of different approaches based on interspecies scaling of clearance SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article DE interspecies scaling; first-time dose; drug development; allometric scaling; predicted human clearance; toxicity ID LABORATORY-ANIMALS; PHARMACOKINETICS; DISPOSITION; MORPHINE; DOG; TOXICOKINETICS; MOXIFLOXACIN; VENLAFAXINE; TOPIRAMATE; METABOLISM AB The authors describe four approaches to selecting a safe starting dose for humans in clinical drug trials based on interspecies scaling of clearance. Human clearance was predicted by scaling for 10 example drugs for which animal clearance values were available in the literature. The predicted human clearance values were then used to select the estimated starting dose in humans. These doses were then compared with the actual doses given to humans during clinical trials. All four approaches used to estimate the first-time dose in humans provided values that were within the dose range given to humans from Phases I to II. This work demonstrates that animal pharmacokinetic data can be used to estimate a suitable human starting dose, provided the data have been obtained from a dose that produces no adverse effects. C1 US FDA, Div Clin Trial Design & Anal, Off Therapeut Res & Review, Clin Pharmacol & Toxicol Branch,Ctr Biol Evaluat, Rockville, MD 20852 USA. US FDA, Div Neuropharmacol Drug Prod, Ctr Drug Evaluat & Res, Rockville, MD 20852 USA. RP Mahmood, I (reprint author), US FDA, Div Clin Trial Design & Anal, Off Therapeut Res & Review, Clin Pharmacol & Toxicol Branch,Ctr Biol Evaluat, HFD-579,Woodmont Off Ctr 1,Suite 200N,1401 Rockvi, Rockville, MD 20852 USA. NR 35 TC 30 Z9 32 U1 0 U2 7 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 JUL PY 2003 VL 43 IS 7 BP 692 EP 697 DI 10.1177/0091270003254631 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 694AV UT WOS:000183751300002 PM 12861964 ER PT J AU Jung, YS Frank, JF Brackett, RE AF Jung, YS Frank, JF Brackett, RE TI Evaluation of antibodies for immunomagnetic separation combined with flow cytometry detection of Listeria monocytogenes SO JOURNAL OF FOOD PROTECTION LA English DT Article ID ESCHERICHIA-COLI O157-H7; RAPID DETECTION; MONOCLONAL-ANTIBODIES; DAIRY-PRODUCTS; SALMONELLA; BEEF; IMS; SAMPLES; CHEESE; LIQUID AB Four polyclonal anti-Listeria antibodies were evaluated for the detection of Listeria monocytogenes in direct and indirect assays using immunomagnetic separation with flow cytometry. The efficiency of immunocapturing using magnetic beads was also determined. None of the tested antibodies exhibited sufficient specificity or avidity to allow sufficient separation and detection of L. monocytogenes for a useful test that differentiated between negative (without cell) and positive (with cell) samples. Plating results confirmed that cells were captured with Dynabeads anti-Listeria and magnetic beads coated with goat anti-Listeria antibody with recovery ranging from 7 to 23%. Fluorescent-labeled polyclonal antibodies used in this study were not sufficiently specific to allow the detection of L. monocytogenes cells captured by the beads. C1 Univ Georgia, Ctr Food Safety, Dept Food Sci & Technol, Athens, GA 30602 USA. US FDA, Off Plant Dairy Foods & Beverages, Washington, DC 20204 USA. RP Frank, JF (reprint author), Univ Georgia, Ctr Food Safety, Dept Food Sci & Technol, Athens, GA 30602 USA. NR 24 TC 19 Z9 21 U1 1 U2 5 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 JUL PY 2003 VL 66 IS 7 BP 1283 EP 1287 PG 5 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 699BH UT WOS:000184035700024 PM 12870765 ER PT J AU Jounai, N Okuda, K Kojima, Y Toda, Y Hamajima, K Ohba, K Klinman, D Xin, KQ AF Jounai, N Okuda, K Kojima, Y Toda, Y Hamajima, K Ohba, K Klinman, D Xin, KQ TI Contribution of the rev gene to the immunogenicity of DNA vaccines targeting the envelope glycoprotein of HIV SO JOURNAL OF GENE MEDICINE LA English DT Article DE HIV; env and rev genes; vaccine; animal model ID HUMAN-IMMUNODEFICIENCY-VIRUS; CYTOTOXIC T-LYMPHOCYTES; VIRAL MESSENGER-RNA; IMMUNE-RESPONSES; EFFECTIVE INDUCTION; RHESUS-MONKEYS; CODON USAGE; TYPE-1; EXPRESSION; VACCINATION AB Background The Rev protein of HIV plays a critical role in the export of viral mRNA from the nucleus to the cytoplasm of infected cells. This work examines the effect of introducing rev into a DNA vaccine encoding the Env protein of HIV, and compares the activity of env genes regulated by CMV versus CAG promoters. Methods The HIV Env gp160 encoding gene with or without the rev gene was subcloned into a CMV promoter or a CAG promoter-driven expression plasmid. The Env protein expression of the plasmids was examined in vitro and the HIV-specific immunity was explored in BALB/c mice by an intramuscular route. The immune mice were intraperitoneally challenged with an HIV Env-expression vaccinia virus. Results Results indicate that the CAG promoter induces significantly higher levels of Env expression, and better immune responses, than the CMV promoter. Incorporating the rev gene into these plasmids further boosts antigen expression and immunogenicity. Indeed, vaccination with the pCAGrev/env or pCMVrev/env plasmid resulted in 1000-fold lower viral load than that with pCMVenv when the mice were challenged with an Env-expressing vaccinia virus. Conclusions Incorporating rev into a DNA vaccine significantly increases the level of expression and immunogenicity of a co-expressed env gene, and that protective efficacy is further improved by utilizing a pCAG promoter. Copyright (C) 2003 John Wiley Sons, Ltd. C1 Yokohama City Univ, Sch Med, Dept Bacteriol, Kanazawa Ku, Yokohama, Kanagawa 2360004, Japan. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Xin, KQ (reprint author), Yokohama City Univ, Sch Med, Dept Bacteriol, Kanazawa Ku, 3-9 Fukuura, Yokohama, Kanagawa 2360004, Japan. RI Ohba, Kenji/D-8072-2015 OI Ohba, Kenji/0000-0002-4936-8186 NR 46 TC 18 Z9 18 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 JUL PY 2003 VL 5 IS 7 BP 609 EP 617 DI 10.1002/jgm.391 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 706WW UT WOS:000184478900008 PM 12825200 ER PT J AU Leifer, CA Verthelyi, D Klinman, DM AF Leifer, CA Verthelyi, D Klinman, DM TI Heterogeneity in the human response to immunostimulatory CpG oligodeoxynucleotides SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE CpG oligonucleotides; human PBMC; immune response; heterogeneity; cytokines; immunoglobulin ID BACTERIAL-DNA; SYNTHETIC OLIGONUCLEOTIDES; IMMUNE ADJUVANTS; CUTTING EDGE; IN-VITRO; B-CELLS; MOTIFS; ACTIVATION; ANTIGEN; INFLAMMATION AB Synthetic oligodeoxynucleotides (ODNs) containing unmethylated CpG motifs trigger an immune response characterized by proliferation, B-cell activation, and cytokine production. CpG ODNs show promise in animal models as vaccine adjuvants and anti-allergens and for the treatment of infectious diseases and cancer. Several different CpG motifs capable of stimulating human cells have been identified, and several CpG-containing ODNs are now in various stages of clinical trials. However, little is known of the comparative magnitude or breadth of the immune responses these CpG ODNs elicit. This work compares the proliferative, IgM, and IL-6 response of PBMCs from 100 normal donors to a panel of I I ODNs selected as highly active from over 100 phosphorothioate ODNs. While PBMCs from every donor responded to at least one member of the ODN panel, no single ODN was optimally stimulatory in all subjects or for all responses. A mixture of ODNs with complementary activities induced significantly broader stimulation of donor PBMCs than any single ODN, providing a rational basis for proceeding into clinical trials with such a mixture. C1 US FDA, Ctr Biol Evaluat & Res, Sect Retroviral Immunol, Bethesda, MD 20892 USA. RP Klinman, DM (reprint author), US FDA, Ctr Biol Evaluat & Res, Sect Retroviral Immunol, Bldg 29A,Rm 3D10, Bethesda, MD 20892 USA. NR 25 TC 28 Z9 30 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD JUL-AUG PY 2003 VL 26 IS 4 BP 313 EP 319 DI 10.1097/00002371-200307000-00003 PG 7 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 698EV UT WOS:000183985400003 PM 12843793 ER PT J AU Bacot, SM Lenz, P Frazier-Jessen, MR Feldman, GM AF Bacot, SM Lenz, P Frazier-Jessen, MR Feldman, GM TI Activation by prion peptide PrP106-126 induces a NF-kappa B-driven proinflammatory response in human monocyte-derived dendritic cells SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE TSE; cell signaling; inflammation ID CENTRIFUGAL ELUTRIATION CCE; CENTRAL-NERVOUS-SYSTEM; SCRAPIE-INFECTED MICE; NECROSIS-FACTOR-ALPHA; PROTEIN-FRAGMENT; MICROGLIAL CELLS; NEUROLOGICAL DISEASE; ENRICHED FRACTIONS; IL-4 RECEPTOR; IN-VITRO AB Specific prion peptides have been shown to mimic the pathologic isoform of the prion protein (PrP) and to induce a neurotoxic effect in vitro and in vivo. As monocytic cells are thought to play a role in the transmission and pathogenesis of prion disease, the use of these peptides in regulating monocytic cell function is under intense investigation. In the current study, we characterize the ability of prion peptide PrP106-126 to activate specific signaling pathways in human monocyte-derived dendritic cells (DCs). Electrophoretic mobility shift assays establish the activation of transcription factor nuclear factor-kappaB within 15 min of exposure, with as little as 25 muM peptide. This signaling cascade results in the up-regulation of inflammatory cytokines interleukin (IL)-1beta, IL-6, and tumor necrosis factor alpha (TNF-alpha) at the mRNA and protein levels. Phenotypic activation of DCs exposed to PrP106-126 is partly a result of an antocrine TNF-alpha response and results in an increased ability of these cells to induce lymphocyte proliferation. The effects of PrP106-126 on DCs were elicited through a receptor complex distinct from that used by human monocytes, demonstrating the ability of this peptide to interact with a multiplicity of receptors on various cell types. Together, these data suggest an involvement of DCs in prion disease pathogenesis. C1 US FDA, Div Monoclonal 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 Monoclonal Antibodies, Ctr Biol Evaluat & Res, HFB-564,Bldg 29A,Rm 3C24,29 Lincoln Dr, Bethesda, MD 20892 USA. NR 53 TC 17 Z9 18 U1 0 U2 0 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 JUL PY 2003 VL 74 IS 1 BP 118 EP 125 DI 10.1189/jlb.1102521 PG 8 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 755FB UT WOS:000187367800016 PM 12832450 ER PT J AU Santamaria, A Salvatierra-Sanchez, R Vazquez-Roman, B Santiago-Lopez, D Villeda-Hernandez, J Galvan-Arzate, S Jimenez-Capdeville, ME Ali, SF AF Santamaria, A Salvatierra-Sanchez, R Vazquez-Roman, B Santiago-Lopez, D Villeda-Hernandez, J Galvan-Arzate, S Jimenez-Capdeville, ME Ali, SF TI Protective effects of the antioxidant selenium on quinolinic acid-induced neurotoxicity in rats: in vitro and in vivo studies SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE antioxidant defense; excitotoxin; neurotoxicity; N-methyl-D-aspartate receptor; quinolinic acid; selenium ID INDUCED LIPID-PEROXIDATION; NF-KAPPA-B; MAMMALIAN THIOREDOXIN REDUCTASE; INDUCED HIPPOCAMPAL DAMAGE; NITRO-L-ARGININE; HUNTINGTONS-DISEASE; OXIDATIVE STRESS; CORPUS STRIATUM; NEURODEGENERATIVE DISORDERS; GLUTATHIONE PEROXIDASE AB Quinolinic acid (QUIN), a well known excitotoxin that produces a pharmacological model of Huntington's disease in rats and primates, has been shown to evoke degenerative events in nerve tissue via NMDA receptor (NMDAr) overactivation and oxidative stress. In this study, the antioxidant selenium (as sodium selenite) was tested against different markers of QUIN-induced neurotoxicity under both in vitro and in vivo conditions. In the in vitro experiments, a concentration-dependent effect of selenium was evaluated on the regional peroxidative action of QUIN as an index of oxidative toxicity in rat brain synaptosomes. In the in vivo experiments, selenium (0.625 mg per kg per day, i.p.) was administered to rats for 5 days, and 2 h later animals received a single unilateral striatal injection of QUIN (240 nmol/muL). Rats were killed 2 h after the induction of lesions with QUIN to measure lipid peroxidation and glutathione peroxidase (GPx) activity in striatal tissue. In other groups, the rotation behavior, GABA content, morphologic alterations, and the corresponding ratio of neuronal damage were all evaluated as additional markers of QUIN-induced striatal toxicity 7 days after the intrastriatal injection of QUIN. Selenium decreased the peroxidative action of QUIN in synaptosomes both from whole rat brain and from the striatum and hippocampus, but not in the cortex. A protective concentration-dependent effect of selenium was observed in QUIN-exposed synaptosomes from whole brain and hippocampus. Selenium pre-treatment decreased the in vivo lipid peroxidation and increased the GPx activity in QUIN-treated rats. Selenium also significantly attenuated the QUIN-induced circling behavior, the striatal GABA depletion, the ratio of neuronal damage, and partially prevented the morphologic alterations in rats. These data suggest that major features of QUIN-induced neurotoxicity are partially mediated by free radical formation and oxidative stress, and that selenium partially protects against QUIN toxicity. C1 US FDA, Div Neurotoxicol, HFT 132, Natl Ctr Toxicol Res,Neurochem Lab, Jefferson, AR 72079 USA. Inst Nacl Neurol & Neurocirug Manuel Velasco Suar, Dept Neuroquim, Mexico City, DF, Mexico. RP Ali, SF (reprint author), US FDA, Div Neurotoxicol, HFT 132, Natl Ctr Toxicol Res,Neurochem Lab, Jefferson, AR 72079 USA. NR 78 TC 76 Z9 76 U1 3 U2 4 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD JUL PY 2003 VL 86 IS 2 BP 479 EP 488 DI 10.1046/j.1471-4159.2003.01857.x PG 10 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 696RE UT WOS:000183900300022 PM 12871589 ER PT J AU Petricoin, EF Liotta, LA AF Petricoin, EF Liotta, LA TI Clinical applications of proteomics SO JOURNAL OF NUTRITION LA English DT Article; Proceedings Paper CT Conference on Nutritional Genomics and Proteomics in Cancer Prevention CY SEP 05-06, 2002 CL BETHESDA, MARYLAND SP NCI, Ctr Canc Res, NCI, Div Canc Prevent, Natl Ctr Complementary & Alternat Med, Amer Soc Nutr Sci DE proteomics; pattern diagnostics; SELDI; protein microarrays; cell signaling ID PROTEIN IDENTIFICATION TECHNOLOGY; LASER CAPTURE MICRODISSECTION; ARTIFICIAL NEURAL NETWORKS; TYROSINE KINASE INHIBITOR; IMMOBILIZED PH GRADIENTS; HUMAN PROSTATE-CANCER; B-CELL LYMPHOMA; OVARIAN-CANCER; MASS-SPECTROMETRY; BREAST-CANCER AB Proteomics, the systematic evaluation of changes in the protein constituency of a cell, is more than just the generation of lists of proteins that increase or decrease in expression as a cause or consequence of disease. The ultimate goal is to characterize the information flow through protein pathways that interconnect the extracellular microenvironment with the control of gene transcription. The nature of this information can be a cause or a consequence of disease processes. Clinical applications of proteomics involve the use of proteomic technologies at the bedside. The analysis of human cancer as a model for how proteomics can have an impact at the bedside is now employing several new proteomic technologies that are being developed for early detection, therapeutic targeting and finally, patient-tailored therapy. C1 US FDA, Natl Canc Inst, Ctr Biol Evaluat & Res, Clin Proteom Program, Rockville, MD 20852 USA. NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Petricoin, EF (reprint author), US FDA, Natl Canc Inst, Ctr Biol Evaluat & Res, Clin Proteom Program, Rockville, MD 20852 USA. NR 82 TC 61 Z9 62 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 JUL PY 2003 VL 133 IS 7 SU S BP 2476S EP 2484S PG 9 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 701HY UT WOS:000184163200014 PM 12840227 ER PT J AU Derr, J Goldsmith, LJ AF Derr, J Goldsmith, LJ TI How to report nonsignificant results: Frequently asked questions SO JOURNAL OF ORTHOPAEDIC & SPORTS PHYSICAL THERAPY LA English DT Editorial Material C1 US FDA, Rockville, MD 20857 USA. Univ Louisville, Sch Publ Hlth & Informat Sci, Dept Bioinformat & Biostat, Louisville, KY 40292 USA. RP Derr, J (reprint author), US FDA, Rockville, MD 20857 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU J O S P T, PI ALEXANDRIA PA 1111 NORTH FAIRFAX ST, STE 100, ALEXANDRIA, VA 22314-1436 USA SN 0190-6011 J9 J ORTHOP SPORT PHYS JI J. Orthop. Sports Phys. Ther. PD JUL PY 2003 VL 33 IS 7 BP 367 EP 368 PG 2 WC Orthopedics; Rehabilitation; Sport Sciences SC Orthopedics; Rehabilitation; Sport Sciences GA 738AQ UT WOS:000186264900001 ER PT J AU Adler, M Shafer, HF Manley, HA Hackley, BE Nicholson, JD Keller, JE Goodnough, MC AF Adler, M Shafer, HF Manley, HA Hackley, BE Nicholson, JD Keller, JE Goodnough, MC TI A capillary electrophoresis technique for evaluating botulinum neurotoxin B light chain activity SO JOURNAL OF PROTEIN CHEMISTRY LA English DT Article DE botulinum neurotoxin B; Clostridium botulinum; capillary electrophoresis; VAMP/synaptobrevin; enzymatic cleavage ID CLOSTRIDIAL NEUROTOXINS; TETANUS; SYNAPTOBREVIN; CLEAVAGE; PROTEASE; RELEASE AB Botulinum neurotoxin B (BoNT/B) produces muscle paralysis by cleaving synaptobrevin/vesicle-associated membrane protein (VAMP), an 18-kDa membrane-associated protein located on the surface of small synaptic vesicles. A capillary electrophoresis (CE) assay was developed to evaluate inhibitors of the proteolytic activity of BoNT/B with the objective of identifying suitable candidates for treatment of botulism. The assay was based on monitoring the cleavage of a peptide that corresponds to residues 44 - 94 of human VAMP-2 (V51) following reaction with the catalytic light chain (LC) of BoNT/B. Cleavage of V51 generated peptide fragments of 18 and 33 amino acids by scission of the bond between Q76 and F77. The fragments and parent peptide were clearly resolved by CE, allowing accurate quanti. cation of the BoNT/B LC-mediated reaction rates. The results indicate that CE is suitable for assessing the enzymatic activity of BoNT/B LC. C1 USA, Neurotoxicol Branch, Div Pharmacol, Med Res Inst Chem Def,MCMR UV PN, Aberdeen Proving Ground, MD 21010 USA. USA, Off Commander, Med Res Inst Chem Def, Aberdeen Proving Ground, MD 21010 USA. US FDA, Lab Bacterial Toxins, CEBER, Rockville, MD 20852 USA. Univ Wisconsin, Food Res Inst, Dept Food Microbiol, Madison, WI 53706 USA. RP Adler, M (reprint author), USA, Neurotoxicol Branch, Div Pharmacol, Med Res Inst Chem Def,MCMR UV PN, 3100 Ricketts Point Rd, Aberdeen Proving Ground, MD 21010 USA. EM Michael.Adler@amedd.army.mil NR 22 TC 10 Z9 10 U1 0 U2 0 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0277-8033 J9 J PROTEIN CHEM JI J. Protein Chem. PD JUL PY 2003 VL 22 IS 5 BP 441 EP 448 DI 10.1023/B:JOPC.0000005459.00492.60 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 748MM UT WOS:000186865700006 PM 14690246 ER PT J AU Wear, KA AF Wear, KA TI The effect of trabecular material properties on the frequency dependence of backscatter from cancellous bone SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID BAND ULTRASOUND ATTENUATION; MINERAL DENSITY; HUMAN CALCANEUS; CORTICAL BONE; OS CALCIS; MECHANICAL-PROPERTIES; WOMEN; OSTEOPOROSIS; PREDICTION; FRACTURES AB Previous experimental studies indicate that backscatter coefficient for human calcaneal trabecular bone varies approximately as frequency cubed. This frequency dependence has been shown to be consistent with a model in which trabeculae are thought of as long thin cylinders composed of a substance with the same material properties as hydroxyapatite. The true material properties of human trabecular bone are not known however. Based on reported measurements of material properties of many bones and bonelike substances, it is possible that the density and longitudinal sound speed of trabecular bone material are far lower than the hydroxyapatite model would suggest. In this letter, it is shown that the frequency dependence of backscatter is still expected to be approximately cubic for wide ranges for density and longitudinal sound speed (encompassing the conceivable ranges for trabecular bone). C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20852 USA. RP US FDA, Ctr Devices & Radiol Hlth, HFZ-142,12720 Twinbrook Pkwy, Rockville, MD 20852 USA. EM kaw@cdrh.fda.gov NR 33 TC 13 Z9 13 U1 0 U2 1 PU ACOUSTICAL SOC AMER AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0001-4966 EI 1520-8524 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD JUL PY 2003 VL 114 IS 1 BP 62 EP 65 DI 10.1121/1.15546921 PG 4 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA 699ZF UT WOS:000184087100006 PM 12880019 ER PT J AU Chanmugam, P Guthrie, JF Cecilio, S Morton, JF Basiotis, PP Anand, R AF Chanmugam, P Guthrie, JF Cecilio, S Morton, JF Basiotis, PP Anand, R TI Did fat intake in the United States really decline between 1989-1991 and 1994-1996? SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Article ID DIETARY-FAT; TRENDS AB The objectives of this study were to determine changes in fat and energy intakes in the United States between 1989-1991 and 1994-1996, and to examine the implications of expressing fat intake in grams vs as a percent of total energy intake. The source of data was the Continuing Survey of Food Intake by Individuals. The results suggest that intake of energy rose between the 2 time periods, primarily due to higher carbohydrate intake. There was also a modest increase in fat intake. However fat intake, as a percent of total energy, declined. The higher energy intakes were primarily from beverages, especially soft drinks, food mixtures, grain snacks, and pastries. The primary sources of higher fat intakes were meat mixtures, vegetables, and some categories of the grain group. Similar trends in the Food Supply Series suggested that the changes observed were not entirely due to changes in survey methodology. Because the increase in fat intake was masked by the increase in energy intake, we conclude that assessing trends in fat intake as a percent of energy consumption can be misleading, unless information on total energy and fat intake, in grams, is also provided. These preliminary findings should be interpreted cautiously until they are confirmed by formal secular trend analyses. C1 Louisiana State Univ, Sch Human Ecol, Baton Rouge, LA 70803 USA. USDA, Econ Res Serv, Washington, DC USA. Food & Drug Adm, Ctr Food Safety & Appl Nutr, Washington, DC USA. Dept Vet Affairs, Vet Hlth Adm, Washington, DC USA. USDA, Ctr Nutr Policy & Promot, Washington, DC USA. RP Chanmugam, P (reprint author), Louisiana State Univ, Sch Human Ecol, Baton Rouge, LA 70803 USA. NR 31 TC 38 Z9 38 U1 0 U2 0 PU AMER DIETETIC ASSOC PI CHICAGO PA 216 W JACKSON BLVD #800, CHICAGO, IL 60606-6995 USA SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD JUL PY 2003 VL 103 IS 7 BP 867 EP 872 DI 10.1053/jada.2003.50166 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 697DF UT WOS:000183926400019 PM 12830026 ER PT J AU Sobotka, TJ Harper, S Hanig, J Robl, M AF Sobotka, TJ Harper, S Hanig, J Robl, M TI Strategy for controlling noise and vibration during renovation of an animal facility SO LAB ANIMAL LA English DT Article ID LABORATORY-ANIMALS; RAT AB The noise level in an animal facility is an important environmental variable that can adversely affect animal welfare, as well as experimental data. The authors describe the strategy they used to record, evaluate, and control excess noise and vibration during a period of renovation, while maintaining the operation of a research facility. C1 US FDA, Ctr Food Safety & Appl Nutr, Off Appl Res & Safety Assessment, Laurel, MD 20708 USA. US FDA, Ctr Drug Evaluat & Res, Off Pharmaceut Sci OPS, Laurel, MD 20708 USA. RP Sobotka, TJ (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Appl Res & Safety Assessment, 8301 Muirkirk Rd, Laurel, MD 20708 USA. NR 11 TC 0 Z9 0 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0093-7355 J9 LAB ANIMAL JI Lab Anim. PD JUL-AUG PY 2003 VL 32 IS 7 BP 34 EP 40 DI 10.1038/laban0803-34 PG 7 WC Veterinary Sciences SC Veterinary Sciences GA 697RC UT WOS:000183956200009 PM 19760848 ER PT J AU Brown, AT Smith, TP Cruz, CP Poirier, LA Simmons, D Williams, DK Wang, YF Eidt, JF Moursi, MM AF Brown, AT Smith, TP Cruz, CP Poirier, LA Simmons, D Williams, DK Wang, YF Eidt, JF Moursi, MM TI Intimal hyperplasia following carotid endarterectomy in an insulin-resistant rat model SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article; Proceedings Paper CT 35th Annual Meeting of the Association-for-Academic-Surgery CY NOV 15-17, 2001 CL MILWAUKEE, WISCONSIN SP Assoc Acad Surg ID TOTAL HOMOCYSTEINE LEVELS; PLASMA HOMOCYSTEINE; SUCROSE DIET; HIGH-FAT; DISEASE; INCREASES; SERUM; HYPERINSULINEMIA; MECHANISMS; RESTENOSIS AB Hyperhomocysteinemia, a known risk factor for cardiovascular disease, results in an elevation of intimal hyperplasia (IH) following a carotid endarterectomy (CEA) in a rat model. An exaggerated IH response following CEA has been observed in rats with dietary induced hyperhomocysteinemia. Type 2 diabetics often present with hyperhomocysteinemia and are at higher risk for developing vascular blockage following surgical procedures. To determine if insulin resistance increases IH risks following endarterectomy, the 3 goals of this study were: (1) to establish plasma homocysteine concentrations in dietary induced insulin-resistant rats and their controls, (2) to investigate whether a positive correlation of IH and plasma homocysteine response occurs following CEA in the insulin-resistant rat model, and (3) if so, to attempt to decrease IH by supplementation with folic acid, a known enzymatic cofactor in the homocysteine metabolic pathway. To achieve these aims, male rats (275 to 300 g) were fed 1 of 4 diets for a 4-month period: (1) high-fat sucrose (HFS), (2) low-fat complex carbohydrate (LFCC), (3) HFS + 25 mg/kg folic acid (HFS+F), or (4) LFCC + 25 mg/kg folic acid (LFCC+F). At the end of the 4-month period the rats underwent an open (non-balloon) unilateral CEA. Two weeks post-endarterectomy, blood, liver and carotid tissue were removed to measure plasma insulin, folic acid, and homocysteine, 2 key enzymes of homocysteine metabolism-methylenetetrahydrofolate reductase (MTHFR) and cystathionine P-synthase (CBS)-and percent lumenal stenosis (IH%). Computer-assisted morphometric analysis was used to measure the percentage of IH in the carotid artery. Plasma homocysteine was significantly higher in the HFS group when compared with the LFCC group (11.3 +/- 1.3 mumol/L v 7.4 +/- 0.6 mumol/L, P = .008) as was post-endarterectomy IH producing lumenal stenosis (30.7% +/- 4.2% v 14.0% +/- 4.3%, P = .008). Plasma insulin in the HFS group was higher than the LFCC (control) group and was significant (36.3 +/- 3.0 muU/mL v 21.1 +/- 0.8 muU/mL, P = .0004). Folic acid supplementation in the HFS group resulted in reductions of plasma homocysteine (HFS v HFS+F, 11.3 +/- 1.3 mumol/L v 7.95 +/- 1.0 mumol/L, P = .02) and post-endarterectomy IH (HFS v HFS+F, 30.7% +/- 4.2 % v 10.4% +/- 1.6%, P =.0001). The control or LFCC group was not statistically different from the HFS+F group in homocysteine or IH. Folate supplementation did not decrease insulin concentrations in the HFS+F group compared to the LFCC group. We conclude that the HFS diet produced an insulin-resistant state with an elevated plasma homocysteine and an exaggerated lH response following carotid endarterectomy in this rat model. Dietary folate supplementation reduced plasma homocysteine concentrations in the HFS diet, which implicates hyperhomocysteinemia as an etiologic factor in the development of post-CEA IH in this insulin-resistant rat model. (C) 2003 Elsevier Inc. All rights reserved. C1 Univ Arkansas Med Sci, Dept Surg, Div Vasc Surg, Dept Biometry, Little Rock, AR 72205 USA. Cent Arkansas Vet Healthcare Syst, Div Vasc Surg, Dept Surg, Little Rock, AR USA. Cent Arkansas Vet Healthcare Syst, Div Endocrinol, Dept Med, Little Rock, AR USA. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Moursi, MM (reprint author), Univ Arkansas Med Sci, Dept Surg, Div Vasc Surg, Dept Biometry, Slot 520,4301 W Markham St, Little Rock, AR 72205 USA. NR 25 TC 7 Z9 7 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD JUL PY 2003 VL 52 IS 7 BP 834 EP 839 DI 10.1016/S0026-0495(03)00097-0 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 701YX UT WOS:000184197500006 PM 12870157 ER PT J AU Dobrovolsky, VN McKinzie, PB Shaddock, JG Mittelstaedt, RA Heflich, RH Parsons, BL AF Dobrovolsky, VN McKinzie, PB Shaddock, JG Mittelstaedt, RA Heflich, RH Parsons, BL TI Pms2 deficiency results in increased mutation in the Hprt gene but not the Tk gene of Tk(+/-) transgenic mice SO MUTAGENESIS LA English DT Article ID DNA MISMATCH REPAIR; MOUSE LYMPHOCYTES; CROSSING-OVER; N-NITROSOUREA; APRT LOCUS; HETEROZYGOSITY; CELLS; CHROMOSOME; APOPTOSIS; MEIOSIS AB The effects of deficiency in the DNA mismatch repair (MMR) protein Pms2 were investigated using the endogenous mouse Hprt and Tk genes as reporters of intragenic mutation and loss of heterozygosity (LOH). Pms2(-/-)Tk(+/-), Pms2(+/+)Tk(+/-), Pms2(+/-)Tk(+/-) and Pms2(-/-)Tk(-/-) mice were bred from Pms2(+/-)Tk(+/-) mice. At 2 months of age, the body weight and splenic T lymphocyte yields were significantly lower in Pms2(-/-)Tk(-/-) mice than in littermates of the other genotypes. The mice were evaluated for their spontaneous mutant frequencies in the Hprt and Tk genes of splenic lymphocytes and their frequency of micronuclei in polychromatic erythrocytes from bone marrow. The cloning efficiency of lymphocytes derived from Pms2(-/-)Tk(-/-) animals was 12-fold lower than that of animals of the other genotypes. Compared with Pms2(+/+) and Pms2(+/-) mice, Pms2(-/-) mice had a 21- to 69-fold increase in the Hprt mutant frequency. The Hprt mutant frequency was equally high in Pms2-deficient, Tk(+/-) and Tk(-/-) mice. No significant Pms2-dependent change in mutant frequency was detected using the Tk mutational target. When individual Tk mutants were analyzed for LOH mutation by allele-specific genotyping, the fraction of LOH mutants was lower in Pms2-deficient than in Pms2-proficient mice (29.2 and 43.6%, respectively). The frequency of bone marrow micronuclei was significantly higher in Pms2(-/-)Tk(-/-) mice than in Pms2(-/-)Tk(+/-) mice. These observations suggest that the simultaneous occurrence of Tk and Pms2 deficiencies may cause a decrease in cell viability that diminishes the Tk mutational response, making it impossible to discern clearly the effect of Pms2 deficiency on LOH-type mutation using the Tk reporter system. The interaction between Tk deficiency and a component of the MMR system suggests that Tk-deficient cells may have higher levels of DNA polymerase misincorporation or endogenous DNA damage than Tk-proficient cells. C1 Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. RP Parsons, BL (reprint author), Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, HFT-120,3900 NCTR Rd, Jefferson, AR 72079 USA. NR 28 TC 11 Z9 11 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0267-8357 J9 MUTAGENESIS JI Mutagenesis PD JUL PY 2003 VL 18 IS 4 BP 365 EP 370 DI 10.1093/mutage/geg007 PG 6 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA 697PC UT WOS:000183951400006 PM 12840110 ER PT J AU Hackett, JL Lesko, LJ AF Hackett, JL Lesko, LJ TI Microarray data - the USFDA, industry and academia SO NATURE BIOTECHNOLOGY LA English DT Editorial Material C1 US FDA, Off In Vitro Diagnost Device Evaluat & Safety, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. US FDA, Off Clin Pharmacol & Biopharmaceut, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Hackett, JL (reprint author), US FDA, Off In Vitro Diagnost Device Evaluat & Safety, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. NR 2 TC 29 Z9 29 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD JUL PY 2003 VL 21 IS 7 BP 742 EP 743 DI 10.1038/nbt0703-742 PG 2 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 696KL UT WOS:000183886000019 PM 12833089 ER PT J AU Chelonis, JJ Gillam, MP Paule, MG AF Chelonis, JJ Gillam, MP Paule, MG TI The effects of prenatal cocaine exposure on reversal learning using a simple visual discrimination task in rhesus monkeys SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Article DE reversal; discrimination; prenatal cocaine; adult; monkeys ID EXTRADIMENSIONAL SHIFT TASKS; OPERANT TEST BATTERY; INFANT OUTCOMES; ADULT-RABBITS; PREGNANCY; FETAL; PERFORMANCE; ATTENTION; ABUSE; BRAIN AB The purpose of this research was to determine if adult animals that were exposed to cocaine prenatally would be able to adapt to changes in the rules of reinforcement for a simple discrimination task. Treatment groups included 0.0, 1.0, and 3.0 mg cocaine/kg/day and an escalating-dose group that began treatment at 3.0 mg cocaine/kg/day, after which the dose was increased by 0.5 mg cocaine/kg/day every 2 weeks throughout the pregnancy. All animals performed a color and position discrimination task for food reinforcers for approximately 6 years before the present study. For this task, subjects were presented with colored stimuli that determined the correctness of subsequent position choices: left for red or yellow and right for blue or green. At 7 years of age, the rules for obtaining reinforcement were reversed. Animals exposed to all doses of cocaine showed impaired reversal performance. Further, animals exposed to the escalating doses of cocaine continued to show this impairment for over 285 sessions (about 2 1/2 years). The number of sessions required by subjects to master these contingency changes indicated that, using a task with which they have an extensive history, cocaine-exposed animals have greater difficulty in adapting to important changes in their environment. (C) 2003 Elsevier Science Inc. All rights reserved. C1 Univ Arkansas, Dept Psychol, Little Rock, AR 72204 USA. Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. RP Chelonis, JJ (reprint author), Univ Arkansas, Dept Psychol, 2801 S Univ Ave, Little Rock, AR 72204 USA. FU NIDA NIH HHS [DA12901, DA13919] NR 81 TC 18 Z9 18 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0892-0362 J9 NEUROTOXICOL TERATOL JI Neurotoxicol. Teratol. PD JUL-AUG PY 2003 VL 25 IS 4 BP 437 EP 446 DI 10.1016/S0892-0362(03)00017-5 PG 10 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA 693AU UT WOS:000183693100003 PM 12798961 ER PT J AU Ferguson, SA Delclos, KB Newbold, RR Flynn, KM AF Ferguson, SA Delclos, KB Newbold, RR Flynn, KM TI Dietary ethinyl estradiol exposure during development causes increased voluntary sodium intake and mild maternal and offspring toxicity in rats SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Article DE ethinyl estradiol; endocrine disrupter; sodium intake; locomotor activity; play behavior; saccharin intake ID SEXUALLY DIMORPHIC BEHAVIOR; ESTROGEN-RECEPTORS-ALPHA; DOSE ORAL-CONTRACEPTIVES; FEMALE GUINEA-PIG; PRENATAL EXPOSURE; DIETHYLSTILBESTROL DES; SEX-DIFFERENCES; AGGRESSIVE-BEHAVIOR; GONADAL-HORMONES; ENDOCRINE DISRUPTORS AB Exogenous estrogen exposure during development often results in behavioral masculinization and/or defeminization of genetic females. Genetic males may be defeminized, hypermasculinized or even demasculinized after similar treatment. Here, pregnant Sprague-Dawley rats consumed phytoestrogen-free diets containing 0, 1, 5 or 200 ppb EE2 beginning on gestational day (GD) 7. Offspring were weaned to the same maternal diet and maintained gonadally intact. There were mild effects on body weight and food consumption in dams of the 200 ppb group and their offspring weighed less at birth than those of the control group; however, gross assessments of nursing behavior were normal in all dietary groups. Postweaning, offspring of the 200 ppb group weighed less and consumed less food than controls. There were no EE2-related effects on open-field activity (tested at postnatal days (PND) 22-24, 43-45 and 64-66), play behavior (tested at PND 35), running wheel activity (PND 63-77) or intake of a 0.3% saccharin-flavored solution (PND 69-71). Intake of a 3.0% sodium chloride-flavored solution on PND 73-75 was increased in both male and female offspring of the 200 ppb group relative to same-sex controls, an effect that is reportedly estrogen mediated. Sodium chloride-flavored solution intake is a sexually dimorphic behavior for which female rats consume more than males. Here, while EE2 exposure had few effects on the conventional tests of sexually dimorphic behaviors, exposure to 200 ppb in the diet appeared to feminize genetic males and hyperfeminize genetic females with regard to sodium intake. (C) 2003 Elsevier Science Inc. All rights reserved. C1 US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. NIEHS, Environm Toxicol Program, Toxicol Lab, Res Triangle Pk, NC 27709 USA. RP Ferguson, SA (reprint author), US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, 3900 NCTR Rd,HFT-132, Jefferson, AR 72079 USA. NR 71 TC 17 Z9 17 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0892-0362 J9 NEUROTOXICOL TERATOL JI Neurotoxicol. Teratol. PD JUL-AUG PY 2003 VL 25 IS 4 BP 491 EP 501 DI 10.1016/S0892-0362(03)00015-1 PG 11 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA 693AU UT WOS:000183693100008 PM 12798966 ER PT J AU Saari, TN AF Saari, TN CA Comm Infect Dis TI Immunization of preterm and low birth weight infants SO PEDIATRICS LA English DT Article ID HEPATITIS-B VACCINE; INACTIVATED POLIOVIRUS VACCINE; PNEUMOCOCCAL CONJUGATE VACCINE; EXTREMELY PREMATURE-INFANTS; HAEMOPHILUS-INFLUENZAE; ANTIBODY-RESPONSE; ACELLULAR PERTUSSIS; COMBINED DIPHTHERIA; IMMUNE-RESPONSES; FOLLOW-UP AB Preterm (PT) infants are at increased risk of experiencing complications of vaccine-preventable diseases but are less likely to receive immunizations on time. Medically stable PT and low birth weight (LBW) infants should receive full doses of diphtheria, tetanus, acellular pertussis, Haemophilus influenzae type b, hepatitis B, poliovirus, and pneumococcal conjugate vaccines at a chronologic age consistent with the schedule recommended for full-term infants. Infants with birth weight less than 2000 g may require modification of the timing of hepatitis B immunoprophylaxis depending on maternal hepatitis B surface antigen status. All PT and LBW infants benefit from receiving influenza vaccine beginning at 6 months of age before the beginning of and during the influenza season. All vaccines routinely recommended during infancy are safe for use in PT and LBW infants. The occurrence of mild vaccine-attributable adverse events are similar in both full-term and PT vaccine recipients. Although the immunogenicity of some childhood vaccines may be decreased in the smallest PT infants, antibody concentrations achieved usually are protective. C1 AAP, Practice Action Grp, Elk Grove Village, IL 60007 USA. Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. Amer Acad Family Physicians, Leawood, KS 66211 USA. NIH, Bethesda, MD 20892 USA. Natl Vaccine Program Off, Atlanta, GA USA. Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. US FDA, Rockville, MD 20857 USA. Amer Thorac Soc, New York, NY 10019 USA. RP Saari, TN (reprint author), AAP, Practice Action Grp, Elk Grove Village, IL 60007 USA. NR 44 TC 80 Z9 86 U1 0 U2 0 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 JUL PY 2003 VL 112 IS 1 BP 193 EP 198 DI 10.1542/peds.112.1.193 PG 6 WC Pediatrics SC Pediatrics GA 696WR UT WOS:000183911000046 PM 12837889 ER PT J AU Ibia, EO Imoisili, M Pikis, A AF Ibia, EO Imoisili, M Pikis, A TI Group A beta-hemolytic streptococcal osteomyelitis in children SO PEDIATRICS LA English DT Article; Proceedings Paper CT Annual Meeting of the Pediatric-Academic-Societies CY APR 29-MAY 13, 2001 CL BALTIMORE, MARYLAND SP Pediatr Acad Soc DE acute hematogenous osteomyelitis; group A beta-hemolytic streptococcus; varicella ID ACUTE HEMATOGENOUS OSTEOMYELITIS; ERYTHROCYTE SEDIMENTATION-RATE; C-REACTIVE PROTEIN; INFLUENZAE TYPE-B; BLOOD-CELL COUNT; SEPTIC ARTHRITIS; JOINT INFECTIONS; VARICELLA; EPIDEMIOLOGY; INFANTS AB Objective Little attention has been given to acute hematogenous osteomyelitis (AHO) caused by group A beta-hemolytic Streptococcus (GABHS), although up to 10% of cases are caused by this microorganism. The objective of this study was to define the clinical and laboratory characteristics of AHO caused by GABHS. Methods. Between January 1983 and June 1999, 29 patients were treated at Children's National Medical Center with AHO caused by GABHS. The characteristics of these patients were compared with those of 28 patients with AHO caused by Streptococcus pneumoniae and those of a matched sample of 45 patients with AHO caused by Staphylococcus aureus. Results. Median ages of children with GABHS, S pneumoniae, and S aureus AHO were 36.0, 13.7, and 96.0 months, respectively. On admission, patients with GABHS AHO had a mean temperature of 38.9 +/- 1.3degreesC and a mean white blood cell count of 17 000 +/- 7800/mm(3), findings similar to those from patients with S pneumoniae AHO. Patients with S aureus AHO had significantly lower admission temperature (38.1 +/- 1.1degreesC) and white blood cell count (10 600 +/- 4900/mm(3)). Varicella infection was the risk factor in 5 cases (17%) of GABHS AHO, whereas none of the cases of AHO caused by S pneumoniae and S aureus was associated with varicella infection. Adjacent septic arthritis occurred in 22%, 28%, and 61% of children with GABHS, S aureus, and S pneumoniae AHO, respectively. Admission erythrocyte sedimentation rate and frequency of bacteremia were similar in all groups. However, time to normalization of erythrocyte sedimentation rate was longer for GABHS and S aureus than for S pneumoniae AHO. GABHS, like S pneumoniae, affected fewer nonextremity bones compared with S aureus. Conclusions. GABHS should be considered in pre-school- and early school-aged children who are suspected of having AHO and whose clinical and laboratory features are characterized by high fever and marked leukocytosis. It should also be highly considered in any child with AHO associated with varicella infection. C1 US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. Childrens Natl Med Ctr, Dept Infect Dis, Washington, DC 20010 USA. Natl Inst Dent & Craniofacial Res, Oral Infect & Immun Branch, NIH, Bethesda, MD USA. RP Pikis, A (reprint author), US FDA, Ctr Drug Evaluat & Res, 5600 Fishers Lane,HFD-530, Rockville, MD 20857 USA. NR 22 TC 30 Z9 31 U1 0 U2 0 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 JUL PY 2003 VL 112 IS 1 BP E22 EP E26 DI 10.1542/peds.112.1.e22 PG 5 WC Pediatrics SC Pediatrics GA 696WR UT WOS:000183911000005 PM 12837901 ER PT J AU Repique, CJ Li, A Brickey, WJ Ting, JPY Collins, FM Morris, SL AF Repique, CJ Li, A Brickey, WJ Ting, JPY Collins, FM Morris, SL TI Susceptibility of mice deficient in the MHC class II transactivator to infection with Mycobacterium tuberculosis SO SCANDINAVIAN JOURNAL OF IMMUNOLOGY LA English DT Article ID IFN-GAMMA; GENE-EXPRESSION; MESSENGER-RNA; GRANULOMA-FORMATION; TGF-BETA; T-CELLS; INTERFERON; COMPLEX; MACROPHAGES; INDUCTION AB Major histocompatibility complex (MHC) class II antigen presentation and subsequent CD4(+) T-cell activation are critical for acquired immunity to Mycobacterium tuberculosis infection. MHC class 11 gene expression is primarily controlled by the master transactivator CIITA protein. Without functional CIITA protein, MHC class II expression is lost, impairing immune responses and increasing susceptibility to infection. In this study, we compared protective immune responses of CIITA-deficient mice and wild-type C57BL/6 controls with low dose aerosol M tuberculosis infection. After aerogenic challenge, CIITA(-/-) mice failed to limit mycobacterial growth (2-5 and 2.0 log(1-) > WT lung and spleen CFUs, respectively, at day 58). Lung histopathology involved extensive necrosis, severe pneumonitis and overwhelming inflammation in the gene knockout mice. Mean survival time for CIITA(-/-) mice was significantly reduced (57 versus >300 days for WT). This extreme sensitivity to tuberculous infection was largely attributed to the absence of CD4(+) cells. Flow cytometric studies detected virtually no CD4(+) cells in CIITA(-/-) mouse spleens after infection versus elevated numbers in WT spleens. Failed CD4(+) T-cell expansion markedly reduced interferon-gamma (IFN-gamma production in CIITA(-/-) mice versus WT controls. These results suggest the necessity of a functional CIITA pathway for controlling tuberculous infections and that interventions targeting CIITA expression may be useful antimycobacterial therapeutics. C1 US FDA, Lab Mycobacterial Dis & Cellular Immunol, OVRR, CBER, Bethesda, MD 20892 USA. Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. Univ N Carolina, Dept Microbiol & Immunol, Chapel Hill, NC USA. RP Morris, SL (reprint author), US FDA, Lab Mycobacterial Dis & Cellular Immunol, OVRR, CBER, HFM-431,Bldg 29,Room 502,29 Lincoln Dr, Bethesda, MD 20892 USA. NR 33 TC 14 Z9 14 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0300-9475 J9 SCAND J IMMUNOL JI Scand. J. Immunol. PD JUL PY 2003 VL 58 IS 1 BP 15 EP 22 DI 10.1046/j.1365-3083.2003.01266.x PG 8 WC Immunology SC Immunology GA 698NY UT WOS:000184006700003 PM 12828554 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 Role of tissue repair in survival from S-(1,2-dichlorovinyl)-(L)-cysteine-induced acute renal tubular necrosis in the mouse 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 DE beta-lyase; DCVC; mercuric chloride; protection; renal injury; tissue repair ID CONJUGATE BETA-LYASE; MERCURIC-CHLORIDE; RAT-KIDNEY; S-(1,2-DICHLOROVINYL)-L-CYSTEINE; NEPHROTOXICITY; TOXICITY; MICE; AUTOPROTECTION; METABOLISM; MECHANISM AB S-(1,2-Dichlorovinyl)-(L)-cysteine (DCVC), a model nephrotoxicant in mice, causes acute tubular necrosis and death at high doses. Our earlier studies revealed that renal tissue repair was critical for survival in mice with DCVC nephrotoxicity. The objective of this study was to investigate if increasing renal tissue repair could protect mice from the lethal outcome of DCVC. Male Swiss Webster (SW) mice were administered a low dose of DCVC (15 mg/kg, ip) 72 h before injection of a normally lethal dose of DCVC (75 mg/kg, ip); this resulted in 100% protection against the lethal effect of DCVC. Because DCVC caused similar totwofold decrease in cytosolic and mitochondrial beta-lyase activity, the possibility that DCVC protection may be caused by decreased bioactivation was examined. Mercuric chloride (HgCl2, 6 mg/kg), a nephrotoxicant with no effect on beta-lyase activity, was administered 96 h before a lethal dose of DCVC. This also resulted in 100% protection from the lethal effect of DCVC. In both studies total glutathione was unchanged at any time after the lethal dose of DCVC was administered, obviating the role of glutathione in protection. In both cases the augmented and sustained tissue repair induced by priming dose and documented by H-3-thymidine pulse labeling and immunocytochemistry for proliferating cell nuclear antigen resulted in 100% survival in spite of the extensive renal injury. These findings suggest that stimulation of renal tubular repair by the priming dose, through augmented cell division, and the resistance of new cells to mechanisms of progression of injury, underlies auto- and heteroprotection against DCVC. The molecular mechanisms may have potential application in pharmacotherapeutic intervention for treatment of acute renal failure. C1 NE Louisiana Univ, Sch Pharm, Dept Toxicol, Monroe, LA 71209 USA. Syngenta, Cent Toxicol Lab, Macclesfield SK10 4TJ, Cheshire, England. Natl Ctr Toxicol Res, Pathol Associates Int, Jefferson, AR 72079 USA. RP Mehendale, HM (reprint author), NE Louisiana Univ, Sch Pharm, Dept Toxicol, 700 Univ Ave,Sugar Hall,Room 306, Monroe, LA 71209 USA. FU NIDDK NIH HHS [DK-61650] NR 41 TC 30 Z9 31 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 JUL PY 2003 VL 74 IS 1 BP 215 EP 227 DI 10.1093/toxsci/kfg111 PG 13 WC Toxicology SC Toxicology GA 692NG UT WOS:000183666700023 PM 12730612 ER PT J AU Hastings, KL El-Hage, J Jacobs, A Leighton, J Morse, D Osterberg, RE AF Hastings, KL El-Hage, J Jacobs, A Leighton, J Morse, D Osterberg, RE TI Letter to the Editor SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Letter ID LIVER C1 US FDA, Ctr Drug Evaluat & Res, Off New Drugs, Rockville, MD 20857 USA. RP Hastings, KL (reprint author), US FDA, Ctr Drug Evaluat & Res, Off New Drugs, Rockville, MD 20857 USA. NR 8 TC 38 Z9 41 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 JUL 1 PY 2003 VL 190 IS 1 BP 91 EP 92 DI 10.1016/S0041-008X(03)00150-9 PG 2 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 699EJ UT WOS:000184042700012 PM 12831788 ER PT J AU Woodcock, J AF Woodcock, J TI Risk management: Issues for outcomes research SO VALUE IN HEALTH LA English DT Editorial Material C1 US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20855 USA. RP Woodcock, J (reprint author), US FDA, Ctr Drug Evaluat & Res, Pk Lawn Bldg,HFD-001,5600 Fisher Lane, Rockville, MD 20855 USA. NR 0 TC 1 Z9 1 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 JUL-AUG PY 2003 VL 6 IS 4 BP 420 EP 424 DI 10.1046/j.1524-4733.2003.64004.x PG 5 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 707BD UT WOS:000184488800005 PM 12859582 ER PT J AU Tibbetts, RJ White, DG Dyer, NW Giddings, CW Nolan, LK AF Tibbetts, RJ White, DG Dyer, NW Giddings, CW Nolan, LK TI Characterization of Escherichia coli isolates incriminated in colisepticaemia in mink SO VETERINARY RESEARCH COMMUNICATIONS LA English DT Article DE antimicrobial resistance; colisepticaemia; Escherichia coli; mink; plasmid; serotype; virulence factors ID POLYMERASE-CHAIN-REACTION; VIRULENCE FACTORS; STRAINS; RESISTANCE; PLASMIDS; CHICKENS; PATHOGENICITY; SALMONELLA; HEALTHY; GENES AB Colisepticaemia is a major health and economic concern for the mink industry, yet little information is available about the Escherichia coli that cause this disease. In this study, 40 E. coli, isolated from mink clinically diagnosed with colisepticaemia that had been submitted to the North Dakota State University Veterinary Diagnostic Laboratory, were randomly selected for characterization. These isolates were serotyped and screened for resistance to 18 antimicrobials, possession of transmissible R plasmids, and the presence of several virulence traits or genes using bioassays or the polymerase chain reaction. Several serotypes were identified that have previously been associated with septicaemia in other animal species. The majority of the isolates exhibited multiple antimicrobial resistance phenotypes. Common resistance phenotypes observed included those to tetracycline, sulfamethoxazole, streptomycin, ampicillin and kanamycin. Several of the isolates that could be studied by conjugation contained transmissible R plasmids coding for multiple antimicrobial resistance phenotypes. About half of the isolates produced colicin; all produced enterobactin; and all but one-quarter produced aerobactin. None of the isolates tested produced enterohaemolysin, and one-fifth were considered to be beta haemolytic. About half appeared to contain the gene encoding cytotoxic necrotizing factor-L three contained the gene encoding EAE, but none appeared to contain the genes coding for LT, Sta/b, SLT-I/II or CNF-II toxins or K99 antigen. Approximately one-third of the isolates elaborated capsule. The results show that the E. coli isolates implicated in mink colisepticaemia possess similar virulence traits and antimicrobial resistance phenotypes to those associated with diarrhoeal diseases in food animals. C1 N Dakota State Univ, Dept Vet & Microbiol Sci, Fargo, ND 58105 USA. Purdue Univ, Sch Vet Med, Dept Vet Pathol, Anim Dis Diagnost Lab 1175, W Lafayette, IN 47907 USA. US FDA, Ctr Vet Med, Res Off, Laurel, MD 20708 USA. N Dakota State Univ, N Dakota Vet Diagnost Lab, Fargo, ND 58105 USA. RP Nolan, LK (reprint author), N Dakota State Univ, Dept Vet & Microbiol Sci, Fargo, ND 58105 USA. NR 40 TC 5 Z9 6 U1 1 U2 4 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0165-7380 J9 VET RES COMMUN JI Vet. Res. Commun. PD JUL PY 2003 VL 27 IS 5 BP 341 EP 357 DI 10.1023/A:1024741719361 PG 17 WC Veterinary Sciences SC Veterinary Sciences GA 701PV UT WOS:000184176700001 PM 14509449 ER PT J AU Chapman, LE Wilson, CA AF Chapman, LE Wilson, CA TI Implications of the advent of homozygous alpha 1,3-galactosyltransferase gene-deficient pigs on transmission of infectious agents SO XENOTRANSPLANTATION LA English DT Editorial Material ID HUMAN SERUM; RETROVIRUS INACTIVATION; ANTIBODY; SENSITIZATION; CELLS C1 Ctr Dis Control & Prevent, Natl Ctr Infect Dis, Atlanta, GA 30333 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. RP Chapman, LE (reprint author), Ctr Dis Control & Prevent, Natl Ctr Infect Dis, Atlanta, GA 30333 USA. NR 16 TC 7 Z9 7 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD JUL PY 2003 VL 10 IS 4 BP 287 EP 288 DI 10.1034/j.1399-3089.2003.00074.x PG 2 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 688NY UT WOS:000183443200001 PM 12795676 ER PT J AU McIntyre, MC Kannan, B Solano-Aguilar, GI Wilson, CA Bloom, ET AF McIntyre, MC Kannan, B Solano-Aguilar, GI Wilson, CA Bloom, ET TI Detection of porcine endogenous retrovirus in cultures of freshly isolated porcine bone marrow cells SO XENOTRANSPLANTATION LA English DT Article DE bone marrow; human; pig; retrovirus; xenotransplantation ID GROWTH-FACTORS; ENGRAFTMENT; INFECTION; TRANSPLANTATION; INTERFERENCE; EXPRESSION; CYTOKINES; TROPISM; SWINE; PIGS AB Pigs are under consideration as possible sources of organs for xenotransplantation in humans. The induction of hematopoietic microchimerism through xenotransplantation of source animal hematopoietic cells has been suggested as a means to induce tolerance in potential recipients. Because all porcine cells contain genetic information for porcine endogenous retrovirus (PERV), coculture techniques, reverse transcriptase (RT) and reverse transcriptase-polymerase chain reaction assays were used to determine whether infectious PERV is released from fresh porcine bone marrow cells cultured in the presence or absence of porcine cytokines. Human embryonic kidney cell line, HEK-293 cells cocultured with porcine bone marrow cells were positive for PERV RNA but never became positive for viral RT activity, suggesting the PERV infection was not productive. In contrast, high levels of RT activity was detected in porcine ST-IOWA cells after coculture, demonstrating that these cells became productively infected. PERV was released from cultured porcine bone marrow cells without stimulation, and combinations of the porcine hematopoietic cytokines, interleukin-3, granulocyte macrophage-colony stimulating factor and stem cell factor had no additional effect on the infectivity or in vitro tropism of released PERV virions. C1 US FDA, Lab Immunol & Virol HFM518, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. US FDA, Div Inspect & Surveillance, CBER, Rockville, MD 20857 USA. ARS, Nutrient & Funct Requirement Lab, Beltsville Human Nutr Res Inst, USDA, Beltsville, MD USA. RP Bloom, ET (reprint author), US FDA, Lab Immunol & Virol HFM518, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, 8800 Rockville Pike,Bldg 29B,Room 2NN04, Bethesda, MD 20892 USA. NR 17 TC 14 Z9 14 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD JUL PY 2003 VL 10 IS 4 BP 337 EP 342 DI 10.1034/j.1399-3089.2003.02044.x PG 6 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 688NY UT WOS:000183443200007 PM 12795682 ER PT J AU Brezna, B Khan, AA Cerniglia, CE AF Brezna, B Khan, AA Cerniglia, CE TI Molecular characterization of dioxygenases from polycyclic aromatic hydrocarbon-degrading Mycobacterium spp. SO FEMS MICROBIOLOGY LETTERS LA English DT Article DE polycyclic aromatic hydrocarbon degradation; dioxygenase; Mycobacterium; DNA sequence; diversity ID SP STRAIN PYR-1; NAPHTHALENE DIOXYGENASE; DEGRADATION GENES; PYRENE; EXPRESSION; BACTERIUM; PHENANTHRENE; METABOLISM; BIPHENYL; BENZOPYRENE AB Polycyclic aromatic hydrocarbon (PAH)-degrading genes nidA and nidB that encode the alpha and beta subunits of the aromatic ring-hydroxylating dioxygenase have been cloned and sequenced from Mycobacterium vanbaalenii PYR-1 [Khan et al., Appl. Environ Microbiol. 67 (2001) 3577-3585]. In this study, the presence of nidA and nidB in 12 other Mycobacterium or Rhodococcus strains was investigated. Initially, all strains were screened for their ability to degrade PAHs by a spray plate method, and for the presence of the dioxygenase Rieske center region by polymerase chain reaction (PCR). Only Mycobacterium sp. PAH 2.135 (RJGII-135), M. flavescens PYR-GCK (ATCC 700033), M. gilvum BB1 (DSM 9487) and M. frederiksbergense FAn9T (DSM 44346), all previously known PAH degraders. were positive in both tests. From the three positive strains, complete open reading frames of the nidA and nidB genes were amplified by PCR, using primers designed according to the known nidA and nidB sequences from PYR-1, cloned in the pBAD/Thio-TOPO vector and sequenced. The sequences showed >98% identity with the M. vanbaalenii PYR-1 nidA and nidB genes. Southern DNA-DNA hybridization using nidA and nidB probes from PYR-1 revealed that there is more than one copy of nidA and nidB genes in the strains PYR-1. BB1, PYR-GCK and FAn9T. However, only one copy of each gene was observed in PAH2.135. (C) 2003 Federation of European Microbiological Societies. Published by Elsevier Science B.V. All rights reserved. C1 US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. Slovak Acad Sci, Inst Mol Biol, Bratislava 84551, Slovakia. RP Khan, AA (reprint author), US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. NR 46 TC 56 Z9 62 U1 0 U2 17 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1097 J9 FEMS MICROBIOL LETT JI FEMS Microbiol. Lett. PD JUN 27 PY 2003 VL 223 IS 2 BP 177 EP 183 DI 10.1016/S0378-1097(03)00328-8 PG 7 WC Microbiology SC Microbiology GA 697VV UT WOS:000183964700005 PM 12829283 ER PT J AU Aidoo, A Mittelstaedt, RA Bishop, ME Lyn-Cook, LE Chen, YJ Duffy, P Heflich, RH AF Aidoo, A Mittelstaedt, RA Bishop, ME Lyn-Cook, LE Chen, YJ Duffy, P Heflich, RH TI Effect of caloric restriction on Hprt lymphocyte mutation in aging rats SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article DE ad libitum; caloric restriction; Hprt mutation; aging; reactive oxygen species ID OXIDATIVE DNA-DAMAGE; ETHYL-N-NITROSOUREA; DIETARY RESTRICTION; FISCHER-344 RATS; MUTANT FREQUENCY; FOOD RESTRICTION; REACTIVE OXYGEN; IN-VIVO; CELL-PROLIFERATION; P53-DEFICIENT MICE AB Caloric restriction (CR) reduces tumor incidence and retards aging in laboratory animals, including non-human primates. Because of the relationships among mutation, disease susceptibility, and aging, we investigated whether or not CR affects the accumulation of somatic cell mutations in aging animals. Starting at approximately 2 months of age, male CD rats (Harlan Sprague-Dawley-derived) were placed on different levels of dietary intake: ad libitum (AL) feeding, and 90% (10% CR), 75% (25% CR) and 60% (40% CR) of the total calories consumed by AL animals. At 3, 6, 12, and 24 months after the beginning of CR, Hprt mutant frequencies (MFs) were determined. The MFs measured in spleen lymphocytes from AL and CR rats sacrificed at 3 months of dietary restriction were similar for all dietary groups. However, the MFs at 6, 12, and 24 months of CR were significantly higher in AL-fed rats compared with animals on 40% CR: (4.5 +/- 0.4) x 10(-6) versus (3.3 +/- 0.3) x 10(-6) (P = 0.032) in 6 months CR rats; (10.3 +/- 2.3) x 10(-6) versus (7.3 +/- 1.2) x 10(-6) in 12 months CR rats (P = 0.04), and (18.3 +/- 3.2) x 10(-6) versus (7.8 +/- 1.0) x 10(-6) (p = 0.001) in 24 months CR rats. In addition, rats receiving 25% CR for 24 months had a MF, (10.7 +/- 2.0) x 10(-6), between the 40% CR and AL rats. Multiplex PCR of the Hprt gene in mutant clones from 12 and 24 months 40% CR rats and the corresponding AL rats detected deletions in 42% of CR mutants and 19% of AL mutants. Because of the difference in Hprt MF in the two groups, the estimated MF associated with deletions in CR rats was similar to the deletion MF in AL rats. This observation implies that the lower MF in CR rats is due to a reduction in smaller Hprt mutations (i.e. base substitutions and frameshifts). The pattern of smaller Hprt mutations from AL rats suggests that many were produced by reactive oxygen species (ROS). The results indicate that CR reduces the accumulation of spontaneous somatic cell mutation in aging rats, especially those caused by base substitutions and frameshifts. Published by Elsevier Science B.V. C1 US FDA, Jefferson Labs, Div Genet & Reproduct Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. US FDA, Jefferson Labs, Div Biometry & Risk Assessment, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Aidoo, A (reprint author), US FDA, Jefferson Labs, Div Genet & Reproduct Toxicol, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. NR 66 TC 23 Z9 24 U1 0 U2 5 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 JUN 19 PY 2003 VL 527 IS 1-2 BP 57 EP 66 DI 10.1016/S0027-5107(03)00072-1 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 690WL UT WOS:000183573400007 PM 12787914 ER PT J AU Uhl, K Kennedy, DL Kweder, SL AF Uhl, K Kennedy, DL Kweder, SL TI Information on medication use in pregnancy SO AMERICAN FAMILY PHYSICIAN LA English DT Editorial Material C1 US FDA, Ctr Drug Evaluat & Res, Off New Drugs, Pregnancy Labeling Task Force, Rockville, MD 20852 USA. RP Uhl, K (reprint author), US FDA, Ctr Drug Evaluat & Res, Off New Drugs, Pregnancy Labeling Task Force, 1351 Rockville Pike,HFD-020, Rockville, MD 20852 USA. NR 10 TC 3 Z9 5 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 JUN 15 PY 2003 VL 67 IS 12 BP 2476 EP + PG 2 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA 694CU UT WOS:000183756900002 PM 12825839 ER PT J AU Wiestner, A Rosenwald, A Barry, TS Wright, G Davis, RE Henrickson, SE Zhao, H Ibbotson, RE Orchard, JA Davis, Z Stetler-Stevenson, M Raffeld, M Arthur, DC Marti, GE Wilson, WH Hamblin, TJ Oscier, DG Staudt, LM AF Wiestner, A Rosenwald, A Barry, TS Wright, G Davis, RE Henrickson, SE Zhao, H Ibbotson, RE Orchard, JA Davis, Z Stetler-Stevenson, M Raffeld, M Arthur, DC Marti, GE Wilson, WH Hamblin, TJ Oscier, DG Staudt, LM TI ZAP-70 expression identifies a chronic lymphocytic leukemia subtype with unmutated immunoglobulin genes, inferior clinical outcome, and distinct gene expression profile SO BLOOD LA English DT Article ID V-H GENES; CD38 EXPRESSION; B-CELLS; GENOMIC ABERRATIONS; PROGNOSTIC-FACTORS; MUTATIONAL STATUS; ANTIGEN; CHAIN; PHENOTYPE; SURVIVAL AB The presence or absence of somatic mutations in the expressed immunoglobulin heavy chain variable regions (IgVH) of chronic lymphocytic leukemia (CLL) cells provides prognostic information. Patients whose leukemic cells express unmutated IgVH regions (Ig-unmutated CLL) often have progressive disease, whereas patients whose leukemic cells express mutated IgVH regions (Ig-mutated CLL) more often have an indolent disease. Given the difficulty in performing IgVH sequencing in a routine diagnostic laboratory, this prognostic distinction is currently unavailable to most patients. Pilot gene expression profiling studies in patients with CLL identified genes that were differentially expressed between the Ig-unmutated and Ig-mutated CLL subtypes. Here, we have profiled an expanded cohort of 107 patients and show that ZAP-70 is the gene that best distinguishes the CLL subtypes. Ig-unmutated CLL expressed ZAP-705.54-fold more highly than Ig-mutated CLL (P < 10(-21)). ZAP-70 expression correctly predicted IgVH mutation status in 93% of patients. ZAP-70 expression and IgVH mutation status were comparable in their ability to predict time to treatment requirement following diagnosis. In 7 patients, ZAP-70 expression and IgVH mutation status were discordant: 4 Ig-mutated CLLs had high ZAP-70 expression and 3 Ig-unmutated CLLs had low ZAP-70 expression. Among these ZAP-70 "outliers," those with Ig-mutated CLL had clinical features that are uncharacteristic of this CLL subtype: 2 required early treatment and 2 used a mutated VH3-21 gene, an IgVH gene that has been associated with progressive disease. We developed reverse transcriptase-polymerase chain reaction and immunohistochemical assays for ZAP-70 expression that can be applied clinically and would yield important prognostic information for patients with CLL. (Blood. 2003;101:4944-4951). C1 NCI, Metab Branch, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. NCI, Div Canc Treatment & Diag, Biometr Res Branch, NIH, Bethesda, MD USA. Royal Boumemouth Hosp, Dept Hematol, Bournemouth, Dorset, England. US FDA, Ctr Biol Evaluat & Res, Off Cellular Tissue & Gene Therapies, Bethesda, MD USA. NCI, Div Clin Sci, Med Branch, NIH, Bethesda, MD USA. RP Staudt, LM (reprint author), NCI, Metab Branch, Canc Res Ctr, NIH, Bldg 10,Rm 4N114, Bethesda, MD 20892 USA. EM lstaudt@mail.nih.gov NR 48 TC 507 Z9 531 U1 0 U2 8 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 JUN 15 PY 2003 VL 101 IS 12 BP 4944 EP 4951 DI 10.1182/blood-2002-10-3306 PG 8 WC Hematology SC Hematology GA 689FV UT WOS:000183481700053 PM 12595313 ER PT J AU Aleman, C Annereau, JP Liang, XJ Cardarelli, CO Taylor, B Yin, JJ Aszalos, A Gottesman, MM AF Aleman, C Annereau, JP Liang, XJ Cardarelli, CO Taylor, B Yin, JJ Aszalos, A Gottesman, MM TI P-glycoprotein, expressed in multidrug resistant cells, is not responsible for alterations in membrane fluidity or membrane potential SO CANCER RESEARCH LA English DT Article ID TUMOR-CELLS; MOTIONAL FREEDOM; CARCINOMA-CELLS; TRANSPORTER; DEPOLYMERIZATION; INHIBITORS; ADRIAMYCIN; APOPTOSIS; PROTEINS; PACKING AB Expression of P-glycoprotein (P-gp), the multidrug resistance (MDR) 1 gene product, can lead to MDR in tumors. However, the physiological role of P-gp in normal tissues is not well understood. Previous studies on multidrug-resistant cells have suggested changes in membrane fluidity and membrane potential associated with P-gp expression, but interpretation of these studies is difficult, because most experimental cells have been selected for long periods in the presence of cytotoxic drugs and may have other host alterations. Therefore, we created two cell lines in which a transfected human MDR1 cDNA is repressed by tetracycline and induced in the absence of tetracycline. One cell line was derived from a mouse embryonic fibroblast cultured from a double (mdr1a/1b) knockout mouse, and the other was from a human HeLa cell line. Analysis of the kinetics of expression of P-gp showed that the mRNA had a half-life of similar to4 h, and the protein had a half-life of similar to16 h. P-gp cell surface expression (measured with monoclonal antibody MRK-16) and P-gp function (measured with a fluorescent substrate, rhodamine 123) was characterized by using fluorescence-activated cell sorting. No differences in membrane potential using the fluorescent probe oxonol or in membrane "fluidity" using fluorescent anisotropy probe or electron spin resonance probe were observed in the tet-repressible P-gp-expressing cells. In contrast, several drug-selected cells that express P-gp showed an increase in membrane fluidity and membrane potential. These results suggest that expression of P-gp per se has little effect on membrane fluidity or membrane potential, and it does not have H+ pump activity. The changes. in these parameters observed in drug-selected cells must reflect other host adaptations to drug selection. C1 NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. NCI, FACS Core Facil, NIH, Bethesda, MD 20892 USA. Ctr Food Safety & Appl Nutr, Instrumentat & Biophys Branch, College Pk, MD 20740 USA. RP Gottesman, MM (reprint author), NCI, Cell Biol Lab, NIH, Bldg 37, Bethesda, MD 20892 USA. RI Yin, Jun Jie /E-5619-2014 NR 38 TC 51 Z9 52 U1 0 U2 5 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUN 15 PY 2003 VL 63 IS 12 BP 3084 EP 3091 PG 8 WC Oncology SC Oncology GA 691CG UT WOS:000183586800016 PM 12810633 ER PT J AU Cook, JL Miura, TA Ikle, DN Lewis, AM Routes, JM AF Cook, JL Miura, TA Ikle, DN Lewis, AM Routes, JM TI E1A oncogene-induced sensitization of human tumor cells to innate immune defenses and chemotherapy-induced apoptosis in vitro and in vivo SO CANCER RESEARCH LA English DT Article ID NATURAL-KILLER-CELLS; HUMAN BREAST-CANCER; SYSTEMIC GENE-THERAPY; NECROSIS FACTOR-ALPHA; ADENOVIRUS E1A; CYTOLYTIC SUSCEPTIBILITY; CELLULAR-SUSCEPTIBILITY; P53-DEPENDENT APOPTOSIS; ACTIVATED MACROPHAGES; MEDIATED APOPTOSIS AB Expression of the adenoviral E1A oncogene induces susceptibility of neoplastic cells from different species to both immune-mediated and chemotherapy-induced cell death. These effects of E1A are easily measured in vitro using cytotoxicity assays. However, conventional in vivo assays of tumor development lack similar precision for measurement of oncogene-induced changes in tumor cell traits. E1A expression in p53 mutant human breast carcinoma cells sensitized them in vitro to diverse immunological injuries and apoptosis triggered by chemotherapeutic agents, as predicted from studies of rodent tumor cells. Nude mice, which possess innate cellular immune defenses against E1A-expressing tumor cells, were used in a quantitative tumor induction assay to test the in vivo correlations of E1A-induced immunosensitivity and chemosensitivity of human tumor cells. Two distinct, E1A-induced breast cancer cell traits could be measured in nude mice: (a) increased tumor latency and (b) reduced efficiency of tumor induction. These results were confirmed in studies of E1A-expressing human fibrosarcoma cells. The results demonstrate that E1A-induced conversion of human cells from a cytolytic resistant to a cytolytic susceptible phenotype, as detected in vitro, translates into reduced tumorigenicity of cells confronted with innate immune defenses and exposed to chemotherapeutic agents in nude mice. However, the data also show that E1A expression does not completely eliminate the tumorigenicity of either established human tumor cells or of cells immortalized by E1A. This experimental approach should be useful for studies of the effects of other oncogene-related tumor cell traits on tumorigenicity and could be used for preclinical studies of different treatment strategies for human tumors. C1 Univ Illinois, Dept Med, Infect Dis Sect, Chicago Coll Med, Chicago, IL 60612 USA. Univ Illinois, Dept Immunol Microbiol, Chicago Coll Med, Chicago, IL 60612 USA. Univ Illinois, Ctr Canc, Chicago, IL 60612 USA. Natl Jewish Med & Res Ctr, Dept Med, Denver, CO 80206 USA. Univ Colorado, Dept Hlth Sci, Dept Med, Denver, CO 80206 USA. Univ Colorado, Dept Hlth Sci, Dept Immunol, Denver, CO 80206 USA. Univ Colorado, Dept Hlth Sci, Ctr Canc, Denver, CO 80206 USA. City Hope Natl Med Ctr, Dept Biostat, Duarte, CA 91010 USA. Beckman Res Inst, Duarte, CA 91010 USA. US FDA, Lab DNA Viruses, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20812 USA. RP Cook, JL (reprint author), Univ Illinois, Dept Med, Infect Dis Sect, Chicago Coll Med, MC-735,808 S Wood St, Chicago, IL 60612 USA. FU NCI NIH HHS [CA86727, CA76491] NR 72 TC 15 Z9 16 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUN 15 PY 2003 VL 63 IS 12 BP 3435 EP 3443 PG 9 WC Oncology SC Oncology GA 691CG UT WOS:000183586800065 PM 12810682 ER PT J AU Turesky, RJ Richoz, J Constable, A Curtis, KD Dingley, KH Turteltaub, KW AF Turesky, RJ Richoz, J Constable, A Curtis, KD Dingley, KH Turteltaub, KW TI The effects of coffee on enzymes involved in metabolism of the dietary carcinogen 2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine in rats SO CHEMICO-BIOLOGICAL INTERACTIONS LA English DT Article DE heterocyclic aromatic amines; coffee; caffeine; metabolism; chemoprotection ID HETEROCYCLIC AROMATIC-AMINES; NATURALLY-OCCURRING ANTIOXIDANTS; GLUTATHIONE-S-TRANSFERASE; DIGESTIVE-TRACT CANCERS; DNA ADDUCT FORMATION; FEMALE F344 RATS; BLACK TEA; GREEN TEA; UDP-GLUCURONOSYLTRANSFERASES; DITERPENES CAFESTOL AB The effects of coffee on the metabolism and genotoxicity of the dietary carcinogen 2-amino-l-methyl-6-phenylimidazo[4.5-b]pyridine (PhIP) were investigated. Coffee diminished the bacterial mutagenicity of PhIP in the Ames reversion assay through inhibition of cytochrome P450 1A2 (CYP1A2), a key enzyme involved in the metabolic activation of PhIP. When given as part of the diet (0, 1 or 5% w/w) to male Fischer-344 rats for 2 weeks, coffee affected the expression of hepatic enzymes involved in PhIP metabolism. Coffee increased the expression of CYP1A2 by 16-fold in the 5% coffee-treated group, and approximately half of this inductive effect was attributed to caffeine. Coffee also increased the expression of enzymes involved in the detoxication of PhIP. A 2-fold increase in expression of glutathione S-transferase alpha was observed, UDP-glucuronosyl transferase (UGTs) activities of p-nitrophenol increased 2-fold, while N-2-and N3-glucuronidation of the genotoxic metabolite 2-hydroxyamino-1-methyl-6-phenylimidazo[4,5-b]pyridine (HONH-PhIP) increased by 1.3-fold in the 5% coffee-treated over the control group. The amount of PhIP (0.75 mg/kg, 24 h) eliminated in urine as the N-2-and N3-glucuronide conjugates of HONH-PhIP increased by 1.8- and 2.5-fold. respectively, in the 5% coffee-treated group over control rats, suggesting either increased rates of N-oxidation of PhIP or N-glcuronidation of HONH-PhIP. Despite the strong induction of CYP1A2, there was no increase in PhIP-DNA adduct formation in colon and pancreas while liver adducts decreased by 50% over control animals. These data suggest that the effect of coffee on inhibition of PhIP N-oxidation and ensuing DNA damage is more important in vivo than its effect on induction of PhIP N-hydroxylation. (C) 2003 Elsevier Science Ireland Ltd. All rights reserved. C1 Natl Ctr Toxicol Res, Div Chem, Jefferson, AR 72079 USA. Nestec Ltd, Nestle Res Ctr, CH-1000 Lausanne 26, Switzerland. Lawrence Livermore Natl Lab, Biol & Biotechnol Res Program, Livermore, CA 94551 USA. RP Turesky, RJ (reprint author), Natl Ctr Toxicol Res, Div Chem, 3900 NCTR Rd, Jefferson, AR 72079 USA. FU NCRR NIH HHS [RR13461] NR 55 TC 21 Z9 21 U1 3 U2 7 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0009-2797 J9 CHEM-BIOL INTERACT JI Chem.-Biol. Interact. PD JUN 15 PY 2003 VL 145 IS 3 BP 251 EP 265 DI 10.1016/S0009-2797(03)00022-X PG 15 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology GA 681BF UT WOS:000183016200002 PM 12732453 ER PT J AU Johann-Liang, R Albrecht, R AF Johann-Liang, R Albrecht, R TI Safety evaluations of drugs containing artemisinin derivatives for the treatment of malaria SO CLINICAL INFECTIOUS DISEASES LA English DT Letter C1 US FDA, Div Special Pathogen & Immunol Drug Prod, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Johann-Liang, R (reprint author), 9201 Corp Blvd,HFD590, Rockville, MD 20850 USA. NR 4 TC 10 Z9 11 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 JUN 15 PY 2003 VL 36 IS 12 BP 1626 EP 1627 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 688WJ UT WOS:000183460000025 PM 12802771 ER PT J AU Fay, MP Pfeiffer, R Cronin, KA Le, CX Feuer, EJ AF Fay, MP Pfeiffer, R Cronin, KA Le, CX Feuer, EJ TI Age-conditional probabilities of developing cancer SO STATISTICS IN MEDICINE LA English DT Article DE competing risks; gamma confidence interval; hypothetical cohort; lifetime risk; surveillance; vital rates ID RATES AB We propose an estimator of the probability of developing a disease in a given age range, conditional on never having developed the disease prior to the beginning of the age range. Our estimator improves the one described by Wun, Merrill and Feuer (Lifetime Data Analysis 1998; 4, 169-186) that is currently used by the U.S. National Cancer Institute for the SEER Cancer Statistics Review. Both estimators use cross-sectional disease rates and provide an interpretation of these rates in terms of the age-conditional probability of developing disease in a hypothetical cohort. The difficulty of this problem is that rates are not available per person-years alive and disease free, but only per person-years alive. Wun et al. used ad hoc methods to handle this problem which did not properly account for competing risks, did not provide a measure of variability, and only allowed age ranges using prespecified 5-year age intervals. Here we solve the problem under a unified competing risks framework, which allows the calculation of the age-conditional probabilities for any age range. We generalize gamma confidence intervals to apply to our new statistic. Although our new method provides estimates which are numerically similar to that of Wun et al., this paper provides a comprehensive theoretical basis for estimation and inference about the age-conditional probability of developing a disease. Published in 2003 by John Wiley Sons, Ltd. C1 NCI, Bethesda, MD 20892 USA. US FDA, CDER, Div Biometr 3, Rockville, MD 20850 USA. RP Fay, MP (reprint author), NCI, 6116 Execut Blvd,Suite 504,MSC 8317, Bethesda, MD 20892 USA. RI Fay, Michael/A-2974-2008; Pfeiffer, Ruth /F-4748-2011; OI Fay, Michael P./0000-0002-8643-9625 FU Intramural NIH HHS [Z99 AI999999] NR 9 TC 58 Z9 58 U1 0 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 JUN 15 PY 2003 VL 22 IS 11 BP 1837 EP 1848 DI 10.1002/sim.1428 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 679AP UT WOS:000182899100005 PM 12754719 ER PT J AU Morris, SM Akerman, GS Warbritton, AR Patton, RE Doerge, DR Ding, XH Chen, JJ AF Morris, SM Akerman, GS Warbritton, AR Patton, RE Doerge, DR Ding, XH Chen, JJ TI Effect of dietary genistein on cell replication indices in C57BL6 mice SO CANCER LETTERS LA English DT Article DE genistein; feeding trial; C57BL6; cell replication ID ELECTROSPRAY MASS-SPECTROMETRY; KINASE INHIBITOR GENISTEIN; LIQUID-CHROMATOGRAPHY; ISOFLAVONE GENISTEIN; SOY ISOFLAVONES; APOPTOSIS; ARREST; INDUCTION; LEUKEMIA; CANCER AB The phytoestrogen and isoflavone, genistein, inhibited the activity of the DNA synthesis-related enzyme, topoisomerase-II (topo-II), altered cell-cycle traverse and produced cell death in cell culture models. In order to examine the potential effects of genistein on cell replication and cell death in an animal model, 8-week-old C57BL6 mice were fed either a control diet or one containing one of five doses (100-2000 ppm) of genistein for 28 days. At the end of the feeding period, both male and female mice were sacrificed and the serum isoflavone and aglycone levels determined by liquid chromatography with electrospray tandem mass spectrometry (LC-ES/MS/MS). Immunohistochemistry was utilized to measure the cell replication and cell death rates in the small intestine. Total isoflavone concentration increased from below the limits of detection (0.001 muM) in control animals to 0.28 muM in male and 0.54 muM in female mice fed the 2000 ppm diet. A decrease in the percentage of cells in G(0) and an increase in the percentage of cells in S-phase, consistent with topo-II-induced S-phase arrest, was found in the duodenum and jejunum of the small intestine. Thus, genistein appears to accumulate to a sufficient level to affect topo-II activity in the small intestine. Published by Elsevier Science Ireland Ltd. C1 US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. Charles River Labs, Jefferson, AR 72079 USA. US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. Northrup Grumman IT, Jefferson, AR 72079 USA. US FDA, Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. RP Morris, SM (reprint author), US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, HFT-120,3900 NCTR Rd, Jefferson, AR 72079 USA. NR 22 TC 8 Z9 9 U1 0 U2 0 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 JUN 10 PY 2003 VL 195 IS 2 BP 139 EP 145 DI 10.1016/S0304-3835(03)00155-1 PG 7 WC Oncology SC Oncology GA 691WD UT WOS:000183628200002 PM 12767521 ER PT J AU Barbaro, V Bartolini, P Calcagnini, G Censi, F Beard, B Ruggera, P Witters, D AF Barbaro, V Bartolini, P Calcagnini, G Censi, F Beard, B Ruggera, P Witters, D TI On the mechanisms of interference between mobile phones and pacemakers: parasitic demodulation of GSM signal by the sensing amplifier SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID ELECTROMAGNETIC-INTERFERENCE; CELLULAR TELEPHONES; RISK AB The aim of this study was to investigate the mechanisms by which the radiated radiofrequency (RF) GSM (global system for mobile communication) signal may affect pacemaker (PM) function. We measured the signal at the output of the sensing amplifier of PMs with various configurations of low-pass filters. We used three versions of the same PM model: one with a block capacitor which short circuits high-frequency signals; one with a ceramic feedthrough capacitor, a hermetically sealed mechanism connecting the internal electronics to the external connection block, and one with both. The PMs had been modified to have an electrical shielded connection to the output of the sensing amplifier. For each PM, the output of the sensing amplifier was monitored under exposure to modulated and non-modulated RF signals, and to GSM signals (900 and 1800 MHz). Non-modulated RF signals did not alter the response of the PM sensing amplifier. Modulated RF signals showed that the block capacitor did not succeed in short circuiting the RF signal, which is somehow demodulated by the PM internal non-linear circuit elements. Such a demodulation phenomenon poses a critical problem because digital cellular phones use extremely low-frequency modulation (as low as 2 Hz), which can be mistaken for normal heartbeat. C1 Ist Super Sanita, Biomed Engn Lab, I-00161 Rome, Italy. US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Calcagnini, G (reprint author), Ist Super Sanita, Biomed Engn Lab, Viale Regina Elena 299, I-00161 Rome, Italy. RI CALCAGNINI, GIOVANNI/E-3711-2015; CENSI, FEDERICA/E-3712-2015; BARTOLINI, PIETRO/E-4619-2015; OI Beard, Brian/0000-0001-6480-0857 NR 12 TC 16 Z9 16 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 JUN 7 PY 2003 VL 48 IS 11 BP 1661 EP 1671 AR PII S0031-9155(03)59460-X DI 10.1088/0031-9155/48/11/312 PG 11 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 690RD UT WOS:000183562000012 PM 12817944 ER PT J AU Schmued, LC AF Schmued, LC TI Demonstration and localization of neuronal degeneration in the rat forebrain following a single exposure to MDMA SO BRAIN RESEARCH LA English DT Article DE methylenedioxymethamphetamine; ecstasy; Fluoro-Jade B; pathology; neuronal degeneration ID CENTRAL SEROTONERGIC NEURONS; BRAIN; 3,4-METHYLENEDIOXYMETHAMPHETAMINE; NEUROTOXICITY; TERMINALS; MDA AB Methylenedioxymethamphetamine (MDMA, Ecstasy) is a powerful releaser of serotonin. Increasing recreational use of this stimulant and hallucinogenic drug has raised concerns about its potential to produce brain damage. The vast majority of previous research studies have focused on the compound's ability to deplete serotonin (5-hydroxytryptamine, 5-HT) from axon terminals. Despite extensive research on this '5-HT terminal neurotoxicity', a much less studied aspect of MDMA toxicity involves its ability to actually kill nerve cells. Only two prior studies mention the existence of MDMA-induced neuronal degeneration, as reflected by a limited number of argyrophylic neurons within the somatosensory cortex, following very high doses of MDMA. The development of Fluoro-Jade B as a simple and reliable marker of neuronal degeneration has allowed us to conduct the first comprehensive localization of MDMA induced neuronal degeneration throughout the entire rat forebrain. In addition to the previously reported neuronal degeneration within parietal cortex, degenerating neurons were also observed in the insular/perirhinal cortex, the ventromedial/ventrolateral thalamus, and the tenia tecta. The extent of neuronal degeneration observed generally correlated with the degree of hyperthermia achieved. Published by Elsevier Science B.V. C1 US FDA, Natl Ctr Toxicol Res, Dept Neurotoxicol, Jefferson, AR 72079 USA. RP Schmued, LC (reprint author), US FDA, Natl Ctr Toxicol Res, Dept Neurotoxicol, Jefferson, AR 72079 USA. NR 31 TC 76 Z9 76 U1 2 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD JUN 6 PY 2003 VL 974 IS 1-2 BP 127 EP 133 DI 10.1016/S0006-8993(03)02563-0 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 684NV UT WOS:000183214200012 PM 12742630 ER PT J AU Prival, MJ AF Prival, MJ TI The unusual effect of pKM101 on the mutagenicity of acetaldehyde oxime in Salmonella typhimurium SO MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS LA English DT Article DE acetaldehyde oxime; Salmonella typhimurium; mucAB ID ESCHERICHIA-COLI; MUTAGENESIS AB Acetaldehyde oxime was found to induce more revertants in Salmonella typhimurium strain TA1535 than in TA100 in the absence of S9 metabolic activation. TA 100 was originally constructed from TA1535 by the addition of the plasmid pKM101, carrying mucAB which generally enhances sensitivity to the mutagenic effects of chemicals. The role of pKM101 in lowering the sensitivity to acetaldehyde oxime was explored by: (1) increasing the incubation time of the selective agar plates from 2 to 3 days; (2) using a new strain, isogenic to TA100, constructed by introducing pKM101 into the TA1535 isolate used in these experiments; (3) by testing a strain constructed by inserting into TA1535 a plasmid carrying mucAB but otherwise unrelated to pKM101. Each of these alterations increased the number of revertants per plate in the presence of acetaldehyde oxime, indicating that the apparent nonmutagenicity of this chemical in TA100 is due to multiple factors. Published by Elsevier Science B.V. C1 US FDA, Div In Vitro & Biochem Toxicol, Laurel, MD 20708 USA. RP Prival, MJ (reprint author), 4117 Jenifer St NW, Washington, DC 20015 USA. NR 17 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1383-5718 J9 MUTAT RES-GEN TOX EN JI Mutat. Res. Genet. Toxicol. Environ. Mutagen. PD JUN 6 PY 2003 VL 537 IS 2 BP 201 EP 208 DI 10.1016/S1383-5718(03)00087-1 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 689ZR UT WOS:000183523300007 PM 12787823 ER PT J AU King, KE Ponnamperuma, RM Yamashita, T Tokino, T Lee, LA Young, MF Weinberg, WC AF King, KE Ponnamperuma, RM Yamashita, T Tokino, T Lee, LA Young, MF Weinberg, WC TI Delta Np63 alpha functions as both a positive and a negative transcriptional regulator and blocks in vitro differentiation of murine keratinocytes SO ONCOGENE LA English DT Article DE Delta Np63 alpha; p63; p53 homologues; keratinocytes; epidermal differentiation ID SQUAMOUS-CELL CARCINOMAS; P53 GENE DOSAGE; MALIGNANT PROGRESSION; P53-RELATED PROTEIN; SPONTANEOUS TUMORS; P63 EXPRESSION; CORE DOMAIN; P73; HOMOLOG; APOPTOSIS AB DeltaNp63 is overexpressed in squamous carcinomas where it is associated with proliferation and is believed to enhance cell growth by blocking p53-mediated transactivation. In normal epithelium, DeltaNp63alpha protein expression is abundant in basal cells and decreases with differentiation. To explore the biological consequences of DeltaNp63alpha overexpression in relation to squamous carcinogenesis, we evaluated its effect on normal squamous differentiation and p53 transactivation function in keratinocytes. Forced overexpression of DeltaNp63alpha in primary murine keratinocytes in vitro inhibits morphological differentiation induced by elevated extracellular [Ca2+], abrogates Ca2+-induced growth arrest, and blocks expression of maturation-specific proteins keratin 10 and filaggrin. This suggests that DeltaNp63 overexpression in squamous carcinomas may serve to maintain the basal cell phenotype and promote cell survival. DeltaNp63alpha blocks transactivation of p53 responsive reporter constructs mediated by endogenous or exogenous p53 at 17 h postinfection, as expected. However, at 41 h, when p53-mediated transactivation is diminished, DeltaNp63alpha: enhances transactivation of these reporter constructs by 2.2-12-fold over control. Maximal DeltaNp63alpha-induced transactivation requires intact p53 responsive elements, but is independent of cellular p53 status. This positive transcriptional function of DeltaNp63alpha appears to be cell-type specific, as it is not observed in primary dermal fibroblasts or Saos-2 cells. These findings support DeltaNp63alpha as a master regulator of keratinocyte differentiation, and suggest a novel function of this protein in the maintenance of epithelial homeostasis. C1 US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. Sapporo Med Univ, Sch Med, Sapporo, Hokkaido 0608556, Japan. Univ Colorado, Sch Med, Denver, CO 80262 USA. Denver Hlth Med Ctr, Denver, CO 80262 USA. Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20892 USA. RP Weinberg, WC (reprint author), US FDA, Ctr Biol Evaluat & Res, 29 Lincoln Dr,HFM-564,Bldg 29B,Room 3NN04, Bethesda, MD 20892 USA. RI Weinberg, Wendy/A-8920-2009 NR 49 TC 103 Z9 108 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD JUN 5 PY 2003 VL 22 IS 23 BP 3635 EP 3644 DI 10.1038/sj.onc.1206536 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 687WD UT WOS:000183399200014 PM 12789272 ER PT J AU Mendell, MJ Naco, GM Wilcox, TG Sieber, WK AF Mendell, MJ Naco, GM Wilcox, TG Sieber, WK TI Environmental risk factors and work-related lower respiratory symptoms in 80 office buildings: An exploratory analysis of NIOSH data SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE indoor environmental quality; indoor air quality; sick building syndrome; nonspecific symptoms; respiratory symptoms; respiratory disease; ventilation systems; building-related illness; asthma ID HYPERSENSITIVITY PNEUMONITIS; OUTBREAK; DAMPNESS; HEALTH; ASTHMA; DUST AB Background We evaluated relationships between lower respiratory symptoms and risk factors or microbiological contamination in office buildings. Methods The National Institute for Occupational Safety and Health collected data from 80 office buildings during standardized indoor environmental-health hazard evaluations. Present analyses included lower respiratory symptom-based outcome definitions and risk factors for potential microbiologic contamination. Multivariate logistic regression models for selected outcomes identified key risk factors. Results Adjusted odds ratios (95% confidence intervals) for "at least three of four work-related lower respiratory symptoms" were, for debris in ventilation air intake, 2.0 (1.0-3.9), and for poor drainage in air-conditioning drip pans, 2.6 (1.3-5.2). Adjusted associations with risk factors were consistently stronger for outcomes requiring both multiple symptoms and improvement away from work, and somewhat stronger among diagnosed asthmatics. Conclusions Moisture and debris in ventilation systems, possibly by supporting microbiologic growth, may increase adverse respiratory effects, particularly among asthmatics. Data from more representative buildings are needed to confirm these findings. Published 2003 Wiley-Liss, Inc. C1 Univ Calif Berkeley, Lawrence Berkeley Lab, Indoor Environm Dept, Environm Energy Technol Div, Berkeley, CA 94720 USA. US FDA, Off Field Programs, Ctr Food Safety & Appl Nutr, Rockville, MD USA. NIOSH, Div Surveillance Hazard Evaluat & Field Surveys, Cincinnati, OH USA. RP Mendell, MJ (reprint author), Univ Calif Berkeley, Lawrence Berkeley Lab, Indoor Environm Dept, Environm Energy Technol Div, 1 Cyclotron Rd,MS 90-3058, Berkeley, CA 94720 USA. NR 24 TC 25 Z9 26 U1 3 U2 5 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD JUN PY 2003 VL 43 IS 6 BP 630 EP 641 DI 10.1002/ajim.10211 PG 12 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 682GF UT WOS:000183082800008 PM 12768613 ER PT J AU Brown, SA Merritt, K AF Brown, SA Merritt, K TI Use of containment pans and lids for autoclaving caustic solutions SO AMERICAN JOURNAL OF INFECTION CONTROL LA English DT Article ID CREUTZFELDT-JAKOB-DISEASE; SPONGIFORM ENCEPHALOPATHY; SCRAPIE AB As a means of decontaminating instruments possibly exposed to Creutzfeldt-Jakob disease, the World Health Organization has recommended immersion and autoclaving in sodium hydroxide. However, this recommendation has raised concerns of possible damage to autoclaves, and hazards to operators as a result of the caustic vapors. A series of experiments has been conducted that demonstrate that there are containment pan-and-lid combinations in which instruments can be autoclaved in sodium hydroxide without risk to the autoclave or the operator. C1 Ctr Devices & Radiol Hlth Food & Drug Adm, Div Mech & Mat Sci, Off Sci & Technol, Rockville, MD 20852 USA. Ctr Devices & Radiol Hlth Food & Drug Adm, Div Life Sci, Off Sci & Technol, Rockville, MD 20852 USA. RP Brown, SA (reprint author), Ctr Devices & Radiol Hlth Food & Drug Adm, Div Mech & Mat Sci, Off Sci & Technol, 9200 Corp Blvd, Rockville, MD 20852 USA. NR 8 TC 8 Z9 8 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0196-6553 J9 AM J INFECT CONTROL JI Am. J. Infect. Control PD JUN PY 2003 VL 31 IS 4 BP 257 EP 260 DI 10.1067/mic.2003.51 PG 4 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 687EM UT WOS:000183363200010 PM 12806365 ER PT J AU Chen, JZ Kadlubar, FF AF Chen, JZ Kadlubar, FF TI A new clue to glaucoma pathogenesis SO AMERICAN JOURNAL OF MEDICINE LA English DT Editorial Material ID GLUTATHIONE-S-TRANSFERASE; OXIDATIVE STRESS; OXIDANTS; PATHWAY; TISSUE; EYE C1 Natl Ctr Toxicol Res, Div Mol Epidemiol, Jefferson, AR 72079 USA. RP Kadlubar, FF (reprint author), Natl Ctr Toxicol Res, Div Mol Epidemiol, 3900 Natl Ctr Toxicol Res Rd, Jefferson, AR 72079 USA. NR 11 TC 26 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 0002-9343 J9 AM J MED JI Am. J. Med. PD JUN 1 PY 2003 VL 114 IS 8 BP 697 EP 698 DI 10.1016/S0002-9343(03)00199-2 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 685ZQ UT WOS:000183295400012 PM 12798460 ER PT J AU Schroeder, CM Parlor, KW Marsh, TL Ames, NK Goeman, AK Walker, RD AF Schroeder, CM Parlor, KW Marsh, TL Ames, NK Goeman, AK Walker, RD TI Characterization of the predominant anaerobic bacterium recovered from digital dermatitis lesions in three Michigan dairy cows SO ANAEROBE LA English DT Article; Proceedings Paper CT 6th Biennial Congress of the Anaerobe-Society-of-the-Americas CY JUN 29-JUL 02, 2002 CL PARK CITY, UTAH SP Anarobe Soc Americas DE digital dermatitis; Bacteroides; CFB phylum; cow ID BACTEROIDES-NODOSUS; CATTLE; DNA AB Digital dermatitis is a superficial epidermatitis of the feet of cattle. Data from previous work suggest that spirochaetes, Campylobacter spp., and Bacteroides spp. may be important in the disease, but the etiology of this disease is not entirely clear. Tissue samples collected from digital dermatitis lesions in three Holstein-Friesian cows from a Michigan dairy yielded a predominant colony type when incubated anaerobically on blood agar at 35degreesC for 24-48 h. The isolate was a non-flagellated Gram-negative rod, 7 muM long and < 0.5 muM wide; its growth was strictly anaerobic and resulted in slight beta-hemolysis on blood agar; 16S rRNA gene sequence analysis indicated it belonged to the cytophoga-flexibacter-bacteroides phylum. The finding that this bacterium was the predominant anaerobe recovered from digital dermatitis lesions suggests it may be involved in the digital dermatitis disease process. Published by Elsevier Science Ltd. C1 US FDA, Ctr Vet Med, Res Off, Div Anim & Food Microbiol, Laurel, MD 20708 USA. Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA. Michigan State Univ, Coll Vet Med, Lansing, MI 48909 USA. Michigan State Univ, Dept Microbiol, Lansing, MI 48909 USA. RP Walker, RD (reprint author), US FDA, Ctr Vet Med, Res Off, Div Anim & Food Microbiol, Laurel, MD 20708 USA. NR 27 TC 11 Z9 11 U1 0 U2 7 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1075-9964 J9 ANAEROBE JI Anaerobe PD JUN PY 2003 VL 9 IS 3 BP 151 EP 155 DI 10.1016/S1075-9964(03)00084-2 PG 5 WC Microbiology SC Microbiology GA 719TQ UT WOS:000185221300008 PM 16887703 ER PT J AU Zaidi, MB Zamora, E Diaz, P Tollefson, L Fedorka-Cray, PJ Headrick, ML AF Zaidi, MB Zamora, E Diaz, P Tollefson, L Fedorka-Cray, PJ Headrick, ML TI Risk factors for fecal quinolone-resistant Escherichia coli in Mexican children SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID ANTIBIOTIC-RESISTANCE; FLORA; EMERGENCE; FLUOROQUINOLONES; TRIMETHOPRIM; COMMUNITY; ANIMALS; HUMANS AB We determined the prevalence of, and risk factors for, fecal quinolone-resistant Escherichia coli (QREC) in 324 children from Yucatan, Mexico. QREC was higher in children with recent Salmonella infection (100%) than in children with diarrhea (61%) or healthy children (54%) (P = 0.007). Multivariate analysis identified recent hospitalization of a family member (P = 0.011, odds ratio [OR] = 5.1) and carriage of Salmonella (P = 0.004, OR = 3.7) as independent risk factors for QREC. C1 Hosp Gen O Horan, Lab Invest, Merida 97000, Yucatan, Mexico. US FDA, Ctr Vet Med, Rockville, MD 20857 USA. ARS, Antimicrobial Resistance Res Unit, USDA, Russell Res Ctr, Atlanta, GA USA. RP Zaidi, MB (reprint author), Hosp Gen O Horan, Lab Invest, Av Itzaes Jacinto Canek, Merida 97000, Yucatan, Mexico. NR 21 TC 20 Z9 21 U1 0 U2 0 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 JUN PY 2003 VL 47 IS 6 BP 1999 EP 2001 DI 10.1128/AAC.47.6.1999-2001.2003 PG 3 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 684BD UT WOS:000183184800037 PM 12760884 ER PT J AU Hammond, MEH Barker, P Taube, S Gutman, S AF Hammond, MEH Barker, P Taube, S Gutman, S TI Standard reference material for Her2 testing - Report of a National Institute of Standards and Technology-sponsored Consensus Workshop SO APPLIED IMMUNOHISTOCHEMISTRY & MOLECULAR MORPHOLOGY LA English DT Article DE Her2; manufactured materials; immunohistochemistry; cancer drug tests ID IN-SITU HYBRIDIZATION; BREAST-CANCER; IMMUNOHISTOCHEMICAL ASSAY; HER-2/NEU; CARCINOMA AB A workshop was sponsored by the National Institute of Standards and Technology, the Cancer Diagnosis Program of the National Cancer Institute, the Food and Drug Administration, and the College of American Pathologists to address the need for a reference material for Her2 gene protein testing. It was agreed that such a standard was desirable and necessary to ensure the reliability of Her2 testing to qualify patients for trastuzumab therapy. Two standards consisting of well characterized cell lines will be produced, 1 that will be a National Institute of Standards and Technology-certifiable standard, and 1 that will be a commercially developed standard for use in all Her2 testing. It was also agreed that all Her2 testing must be performed on samples fixed only in 10% buffered formalin, as specified in the Food and Drug Administration-approved testing methods. Participants agreed to plan strategies to educate pathologists, clinicians, and laboratories about the need and use of such a standard. A National Committee for Clinical Laboratory Standards guideline for the use of the standard reference material will be created to facilitate this process. C1 Latter Day St Hosp, Dept Pathol, Salt Lake City, UT 84143 USA. Univ Utah, Sch Med, Salt Lake City, UT USA. Natl Inst Stand & Technol, Gaithersburg, MD 20899 USA. NCI, Div Canc Treatment & Diagnosis, Canc Diagnosis Program, Rockville, MD USA. US FDA, Div Clin Lab Devices, Rockville, MD 20857 USA. RP Hammond, MEH (reprint author), Latter Day St Hosp, Dept Pathol, 8th Ave & C St, Salt Lake City, UT 84143 USA. NR 14 TC 25 Z9 29 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1062-3345 J9 APPL IMMUNOHISTO M M JI Appl. Immunohistochem. PD JUN PY 2003 VL 11 IS 2 BP 103 EP 106 PG 4 WC Anatomy & Morphology; Medical Laboratory Technology; Pathology SC Anatomy & Morphology; Medical Laboratory Technology; Pathology GA 687FX UT WOS:000183366700001 PM 12777990 ER PT J AU Kulka, M Chen, A Ngo, D Bhattacharya, SS Cebula, TA Goswami, BB AF Kulka, M Chen, A Ngo, D Bhattacharya, SS Cebula, TA Goswami, BB TI The cytopathic 18f strain of Hepatitis A virus induces RNA degradation in FrhK4 cells SO ARCHIVES OF VIROLOGY LA English DT Article ID DOUBLE-STRANDED-RNA; 5 NONTRANSLATED REGION; FAST-GROWING STRAIN; PROTEIN-KINASE-R; INFECTED CELLS; IN-VITRO; GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE; ENCEPHALOMYOCARDITIS VIRUS; CONSTITUTIVE EXPRESSION; RIBOSOMAL-RNA AB The mechanism responsible for the induction of apoptosis by the rapidly replicating HM175/18f strain of Hepatitis A virus (HAV) was investigated. Full length HAV RNA and viral capsid protein VP1 were detected in 18f infected cells at earlier times post-infection than in HM175/clone 1 infected cells. Analysis of total cellular RNA from HM175/18f infected FrhK4 cells by denaturing agarose gel electrophoresis and Northern blot hybridization revealed extensive degradation of both the 28S and 18S ribosomal RNA (rRNA) molecules. Similar degradation was observed when these cells were infected with Human coxsackievirus B1, a fast replicating enterovirus. In contrast, the parental strain of 18f, HM175/clone 1 did not induce RNA degradation. Inhibition of RNA degradation correlated with inhibition of virus replication. The pattern of rRNA degradation resembled degradation of rRNAs by RNase L, an enzyme activated in interferon-treated cells following infection with certain viruses. Ribosomal RNA degradation was accompanied by the reduction in the levels of several cellular RNAs including those for beta-actin and glyceraldehyde-3-phosphate dehydrogenase, while the levels of c-myc and c-jun were higher. Interferon mRNAs could not be detected in either infected or mock-infected control cells, and STAT1, a key regulator of interferon action was not phosphorylated following virus infection. These results reveal a heretofore-undescribed pathway that involves the regulation of RNA degradation and apoptosis following HAV/18f replication in FrhK4 cells. C1 US FDA, Div Mol Biol, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. RP Goswami, BB (reprint author), US FDA, Div Mol Biol, Ctr Food Safety & Appl Nutr, HFS-025,8301 Muirkirk Rd, Laurel, MD 20708 USA. NR 66 TC 13 Z9 14 U1 0 U2 1 PU SPRINGER-VERLAG WIEN PI VIENNA PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 VIENNA, AUSTRIA SN 0304-8608 J9 ARCH VIROL JI Arch. Virol. PD JUN PY 2003 VL 148 IS 7 BP 1275 EP 1300 DI 10.1007/s00705-003-0110-0 PG 26 WC Virology SC Virology GA 694MZ UT WOS:000183779500003 PM 12827461 ER PT J AU Zeuner, RA Verthelyi, D Gursel, M Ishii, KJ Klinman, DM AF Zeuner, RA Verthelyi, D Gursel, M Ishii, KJ Klinman, DM TI Influence of stimulatory and suppressive DNA motifs on host susceptibility to inflammatory arthritis SO ARTHRITIS AND RHEUMATISM LA English DT Article ID 4TH INTERNATIONAL-WORKSHOP; NF-KAPPA-B; BACTERIAL-DNA; CPG MOTIFS; REACTIVE ARTHRITIS; IMMUNOSTIMULATORY DNA; IMMUNE ACTIVATION; TNF-ALPHA; OLIGODEOXYNUCLEOTIDES; CELLS AB Objective. To examine whether systemic administration of immunostimulatory and immunosuppressive oligodeoxynucleotides (ODNs) alter host susceptibility to inflammatory arthritis. Methods. Normal BALB/c mice were treated systemically with CpG ODNs or suppressive ODNs, and then challenged intraarticularly with CpG DNA. The onset and magnitude of the resulting inflammatory response was monitored. Results. Systemic delivery of CpG ODNs significantly increased susceptibility to local inflammation, whereas systemic treatment with suppressive ODNs reduced this susceptibility. CD11c+ cells played a key role in mediating host sensitivity to arthritis. These cells were the dominant source of tumor necrosis factor a production in CpG-stimulated animals and transferred resistance to arthritis from mice treated with suppressive ODNs. Conclusion. Systemic exposure to immunostimulatory and immunosuppressive DNA influences host susceptibility to local inflammatory challenge. Current findings raise the possibility that suppressive ODNs may be useful in the prevention/treatment of proinflammatory diseases. C1 US FDA, Ctr Biol Evaluat & Res, Sect Retroviral Immunol, Bethesda, MD 20892 USA. Univ Kiel, Med Clin 2, Kiel, Germany. US FDA, Sect Retroviral Immunol, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. RP Klinman, DM (reprint author), US FDA, Ctr Biol Evaluat & Res, Sect Retroviral Immunol, 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 NR 34 TC 46 Z9 48 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 JUN PY 2003 VL 48 IS 6 BP 1701 EP 1707 DI 10.1002/art.11035 PG 7 WC Rheumatology SC Rheumatology GA 688AQ UT WOS:000183410300030 PM 12794839 ER PT J AU McFarland, HI Hansal, SA Morris, DI McVicar, DW Love, PE Rosenberg, AS AF McFarland, HI Hansal, SA Morris, DI McVicar, DW Love, PE Rosenberg, AS TI Signaling, through MHC in transgenic mice generates a population of memory phenotype cytolytic cells that lack TCR SO BLOOD LA English DT Article ID NAIVE T-CELLS; CLASS-I MHC; ZETA-CHAIN; ANTIGEN RECEPTOR; LYMPHOCYTES-T; CUTTING EDGE; HEMATOPOIETIC-CELLS; PRECURSOR CELLS; GAMMA-CHAIN; TUMOR-CELLS AB We constructed a chimeric molecule, composed of the T-cell receptor (TCR)-zeta chain fused to the extracellular domains of a prototypical allogeneic major histocompatibility complex (MHC) class I molecule, D-d, to assess whether such a construct could affect Dd allospecific responses in vitro and in vivo. To generate cytotoxic T lymphocytes (CTLs) expressing the construct, D-d-zeta was targeted to lymphocyte populations in transgenic mice by placing its expression under control of the CD2 promoter. In response to ligation of D-d, lymphocytes from transgenic mice expressing high levels of D-d-zeta are activated to proliferate and kill cells binding to Dd, despite the near total loss of CD8(+) T cells in these mice. Thus, the D-d-zeta cytolytic cell was found not to be a conventional CD8(+) CTL, but rather an unusual T lineage cell (CD3(-)CD5(+)Thy1.1(+)) that lacked alphabeta or gammadelta TCRs, as well as CD4 and CD8 coreceptors, but expressed surface markers strikingly similar to memory CTLs, including CD44, Ly-6C, and CD122. These cells originate in the thymus and potently veto responses to D-d in vitro. Lacking TCRs, these veto cells are unlikely to mediate graft-versus-host disease (GVHD) and thus may be useful as a cellular therapy for therapeutic deletion of alloreactive T cells in the settings of graft rejection and GVHD. (C) 2003 by The American Society of Hematology. C1 US FDA, Ctr Biol Evaluat & Res, Div Therapeut Prot, Bethesda, MD 20014 USA. NCI, Expt Immunol Lab, Div Basic Sci, NIH, Frederick, MD 21701 USA. NICHHD, Lab Mammalian Gene & Dev, NIH, Bethesda, MD 20892 USA. RP McFarland, HI (reprint author), 29A-2B12,8800 Rockville Pike, Bethesda, MD 20892 USA. RI McVicar, Daniel/G-1970-2015; McFarland, Hugh/K-1503-2016 OI McFarland, Hugh/0000-0002-3322-038X NR 62 TC 5 Z9 5 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JUN 1 PY 2003 VL 101 IS 11 BP 4520 EP 4528 DI 10.1182/blood-2002-10-3265 PG 9 WC Hematology SC Hematology GA 682CJ UT WOS:000183072800052 PM 12586613 ER PT J AU Goldin, LR Ishibe, N Sgambati, M Marti, GE Fontaine, L Lee, MP Kelley, JM Scherpbier, T Buetow, KH Caporaso, NE AF Goldin, LR Ishibe, N Sgambati, M Marti, GE Fontaine, L Lee, MP Kelley, JM Scherpbier, T Buetow, KH Caporaso, NE TI A genome scan of 18 families with chronic lymphocytic leukaemia SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE chronic lymphocytic leukaemia; genetics; family studies; linkage mapping; candidate genes ID LINKAGE ANALYSIS; LOD SCORES; GENETIC DISSECTION; COMPLEX TRAITS; ATM MUTATIONS; LEUKEMIA; CANCER; ANTICIPATION; GUIDELINES AB Chronic lymphocytic leukaemia (CLL) accounts for about 30% of all leukaemias and is most prevalent in older individuals. Significant familial aggregation has been demonstrated but the mode of inheritance is unknown. Recurrent cytogenetic abnormalities are frequently found in CLL tumour cells but no susceptibility genes have been confirmed. We have collected clinical data and biospecimens on families ascertained for having at least two living patients with CLL. The current study included DNA samples from 94 individuals (38 affected patients) in 18 families. We have carried out a genome scan using the ABI 28-panel medium density linkage mapping set (average spacing of 10 cM and average heterozygosity of 80%). Genotypes for 359 markers were scored. Multipoint limit of detection (lod) scores were calculated, assuming both dominant and recessive inheritance and allowing for increased penetrance with age and genetic heterogeneity. Non-parametric linkage scores were also calculated. Lod scores of 1.0 or greater were found on regions of chromosomes 1, 3, 6, 12, 13 and 17, but none of these loci achieved statistical significance. Four of these six regions (6q, 13q, 12 and 17p) coincide with areas where cytogenetic abnormalities are frequently observed in CLL tumour cells and are, therefore, strong candidate regions for containing germ line changes. C1 NCI, Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Cell & Gene Therapies, Flow & Image Cytometry Sect, Bethesda, MD USA. NCI, Lab Populat Genet, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Goldin, LR (reprint author), NCI, Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd,Room 7008,MSC 7236, Bethesda, MD 20892 USA. NR 34 TC 42 Z9 42 U1 1 U2 1 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD JUN PY 2003 VL 121 IS 6 BP 866 EP 873 DI 10.1046/j.1365-2141.2003.04372.x PG 8 WC Hematology SC Hematology GA 686DK UT WOS:000183305700006 PM 12786797 ER PT J AU Fang, GC Chang, CN Chu, CC Wu, YS Fu, PPC Chang, SC Yang, IL AF Fang, GC Chang, CN Chu, CC Wu, YS Fu, PPC Chang, SC Yang, IL TI Fine (PM2.5), coarse (PM2.5-10), and metallic elements of suspended particulates for incense burning at Tzu Yun Yen temple in central Taiwan SO CHEMOSPHERE LA English DT Article DE fine particle; coarse particle; incense; temple; metallic elements ID DRY DEPOSITION; HEAVY-METAL; MATTER; PM10; AEROSOLS; DUST; TSP; AIR AB Ambient suspended particulate concentrations were measured at Tzu Yun Yen temple (120degrees, 34', 10" E; 24degrees, 16', 12" N) in this study. This is representative of incense burning and semi-open sampling sites. The Universal-sampler collected fine and coarse particle material was used to measure suspended particulate concentrations, and sampling periods were from 16/08/2001 to 2/1/2002 at Tzu Yun Yen temple. In addition, metallic element concentrations, compositions of PM2.5 and PM2.5-10 for incense burning at Tzu Yun Yen temple were also analyzed in this study. The PM2.5/PM10 ratios ranged between 31% and 87% and averaged 70 +/- 11% during incense the burning period, respectively. The median metallic element concentration order for these elements is Fe > Zn > Cr > Cd > Pb > Mn > Ni > Cu in fine particles (PM2.5) at the Tzu Yun Yen temple sampling site. The median metallic element concentration order for these elements is Fe > Zn > Cr > Pb > Cd > Ni > Mn > Cu in coarse particle (PM2.5-10) at the Tzu Yun Yen temple sampling site. Fine particulates (PM2.5) are the main portion of PM10 at Tzu Yun Yen temple in this study. From the point of view of PM10, these data reflect that the elements Fe, Zn, and Cr were the major elements distributed at Tzu Yun Yen temple in this study. (C) 2003 Elsevier Science Ltd. All rights reserved. C1 Hungkuang Univ, Air Tox & Environm Anal Lab, Dept Environm Engn, Hungkuang Inst Technol, Taichung 433, Taiwan. Tunghai Univ, Dept Environm Sci, Taichung 407, 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, Dept Environm Engn, Hungkuang Inst Technol, Taichung 433, Taiwan. NR 18 TC 32 Z9 32 U1 4 U2 15 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0045-6535 J9 CHEMOSPHERE JI Chemosphere PD JUN PY 2003 VL 51 IS 9 BP 983 EP 991 DI 10.1016/S0045-6535(03)00124-3 PG 9 WC Environmental Sciences SC Environmental Sciences & Ecology GA 674KY UT WOS:000182637000019 PM 12697189 ER PT J AU Johnson, JR Bross, P Cohen, M Rothmann, M Chen, G Zajicek, A Gobburu, J Rahman, A Staten, A Pazdur, R AF Johnson, JR Bross, P Cohen, M Rothmann, M Chen, G Zajicek, A Gobburu, J Rahman, A Staten, A Pazdur, R TI Approval summary: Imatinib mesylate capsules for treatment of adult patients with newly diagnosed Philadelphia chromosome-positive chronic myelogenous leukemia in chronic phase SO CLINICAL CANCER RESEARCH LA English DT Article ID CHRONIC MYELOID-LEUKEMIA; INTERFERON-ALPHA; BUSULFAN; TRIAL AB Purpose: The purpose is to describe the Food and Drug Administration (FDA) review and approval of imatinib (Gleevec; Novartis Pharmaceuticals, East Hanover, NJ) for treatment of adult patients with newly diagnosed Philadelphia chromosome-positive chronic myelogenous leukemia (CML) in chronic phase. Experimental Design: The FDA reviewed data in electronic format from a randomized controlled clinical trial of 1106 adult patients with newly diagnosed Philadelphia chromosome-positive CML in chronic phase, comparing imatinib with the combination of IFN-alpha and cytarabine. Results: Imatinib showed clinically and statistically significantly better results for time-to-progression to accelerated phase or blast crisis, progression-free survival, complete hematological response rate, and cytogenetic response rate. With a median follow-up of 14 months, a maximum follow-up of 19.5 months, and an expected median survival of 5-6 years on the IFN-alpha/cytarabine control arm, few of the expected progressions to accelerated or blast phase or deaths have occurred. Imatinib was also better tolerated. Edema, nausea, rigors, neutropenia, and headache were more frequent in women. Only 57% of the IFN-alpha target dose was administered, and only 68% of patients received any cytarabine. However, this does not appear to adequately explain the superiority of imatinib observed in this trial. Results of a population pharmacokinetic study in a subgroup of 371 patients and a separate rifampin-imatinib drug-drug interaction study in healthy volunteers are presented. Conclusions: On December 20, 2002, imatinib was granted accelerated approval under subpart H, rather than regular approval. Follow-up is short compared with the natural history of chronic phase CML or more mature results with established therapies such as IFN-alpha or transplantation. If imatinib should stop working after 1.5-2 years, the results could be importantly different from the present analysis. As a Phase IV postmarketing commitment, the applicant has agreed to provide follow-up reports on this imatinib study annually for the next 6 years. C1 US FDA, Ctr Drug Evaluat & Res, Div Oncol Drug Prod, Rockville, MD 20857 USA. RP Johnson, JR (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Oncol Drug Prod, HFD-150,5600 Fishers Lane, Rockville, MD 20857 USA. NR 17 TC 62 Z9 63 U1 2 U2 4 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUN PY 2003 VL 9 IS 6 BP 1972 EP 1979 PG 8 WC Oncology SC Oncology GA 687PP UT WOS:000183386000003 PM 12796358 ER PT J AU Campbell, G AF Campbell, G TI The design and analysis of diagnostic imaging clinical studies with multiple readers SO CONTROLLED CLINICAL TRIALS LA English DT Meeting Abstract CT Joint International Conference of the International-Society-for-Clinical-Biostatistics/Society-for-Clinical-Tr ials CY JUL 20-24, 2003 CL LONDON, ENGLAND SP Int Soc Clin Biostat, Soc Clin Trials C1 US FDA, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-2456 J9 CONTROL CLIN TRIALS JI Controlled Clin. Trials PD JUN PY 2003 VL 24 SU 3 MA 59 BP 71S EP 72S PG 2 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 686TP UT WOS:000183337300061 ER PT J AU Chen, G Wang, YC Chi, GYH AF Chen, G Wang, YC Chi, GYH TI Hypotheses, type I error and fraction retention in active control non-inferiority trials SO CONTROLLED CLINICAL TRIALS LA English DT Meeting Abstract CT Joint International Conference of the International-Society-for-Clinical-Biostatistics/Society-for-Clinical-Tr ials CY JUL 20-24, 2003 CL LONDON, ENGLAND SP Int Soc Clin Biostat, Soc Clin Trials C1 US FDA, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-2456 J9 CONTROL CLIN TRIALS JI Controlled Clin. Trials PD JUN PY 2003 VL 24 SU 3 MA 87 BP 85S EP 85S PG 1 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 686TP UT WOS:000183337300089 ER PT J AU Lachenbruch, PA Kou, J Rida, W AF Lachenbruch, PA Kou, J Rida, W TI Lot consistency as an equivalence problem SO CONTROLLED CLINICAL TRIALS LA English DT Meeting Abstract CT Joint International Conference of the International-Society-for-Clinical-Biostatistics/Society-for-Clinical-Tr ials CY JUL 20-24, 2003 CL LONDON, ENGLAND SP Int Soc Clin Biostat, Soc Clin Trials C1 US FDA, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 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 JUN PY 2003 VL 24 SU 3 MA 88 BP 86S EP 86S PG 1 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 686TP UT WOS:000183337300090 ER PT J AU Ng, TH AF Ng, TH TI A concern of simultaneous tests for non-inferiority and superiority SO CONTROLLED CLINICAL TRIALS LA English DT Meeting Abstract CT Joint International Conference of the International-Society-for-Clinical-Biostatistics/Society-for-Clinical-Tr ials CY JUL 20-24, 2003 CL LONDON, ENGLAND SP Int Soc Clin Biostat, Soc Clin Trials C1 US FDA, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-2456 J9 CONTROL CLIN TRIALS JI Controlled Clin. Trials PD JUN PY 2003 VL 24 SU 3 MA P6 BP 96S EP 96S PG 1 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 686TP UT WOS:000183337300110 ER PT J AU Wysowski, DK Armstrong, G Governale, L AF Wysowski, DK Armstrong, G Governale, L TI Rapid increase in the use of oral antidiabetic drugs in the United States, 1990-2001 SO DIABETES CARE LA English DT Article ID OBESITY; ADULTS; TRENDS AB OBJECTIVE - To describe the use of oral antidiabetic drugs for management of type 2 diabetes in the U.S. from 1990 through 2001. RESEARCH DESIGN AND METHODS - Data on oral antidiabetic drugs were derived from two pharmaceutical marketing databases from IMS Health, the National Prescription Audit Plus and the National Disease and Therapeutic Index. RESULTS - In 1990, 23.4 million outpatient prescriptions of oral antidiabetic agents were dispensed. By 2001, this number had increased 3.9-fold, to 91.8 million prescriptions. Glipizide and glyburide, two sulfonylurea medications, accounted for similar to77% of prescriptions of oral antidiabetic drugs in 1990 and 35.5% of prescriptions in 2001. By 2001, the biguanide metformin (approved in 1995) had captured similar to33% of prescriptions, and the thiazolidinedione insulin sensitizers (rosiglitazone and pioglitazone marketed beginning in 1999) accounted for similar to17% of market share. Compared with patients treated in 1990, those in 2001 were proportionately younger and they more often used oral antidiabetic drugs and insulin in combination. Internists and general and family practitioners were the primary prescribers of this class of drugs. CONCLUSIONS - Consistent with the reported increase in the prevalence of type 2 diabetes, the number of dispensed outpatient prescriptions of oral antidiabetic drugs increased rapidly between 1990 and 2001. This period was marked by an increase in the treatment of younger people and the use of oral antidiabetic drugs in combination. With the approval in the last decade of several new types of oral antidiabetic medications with different mechanisms of action, options for management of type 2 diabetes have expanded. C1 US FDA, Off Drug Safety, Rockville, MD 20857 USA. RP Wysowski, DK (reprint author), US FDA, Off Drug Safety, HFD-430,Parklawn Bldg,Room 15B-08,5600 Fishers Ln, Rockville, MD 20857 USA. NR 15 TC 70 Z9 74 U1 1 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD JUN PY 2003 VL 26 IS 6 BP 1852 EP 1855 DI 10.2337/diacare.26.6.1852 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 724UR UT WOS:000185505500032 PM 12766122 ER PT J AU Gaborik, Z Jagadeesh, G Zhang, M Spat, A Catt, KJ Hunyady, L AF Gaborik, Z Jagadeesh, G Zhang, M Spat, A Catt, KJ Hunyady, L TI The role of a conserved region of the second intracellular loop in AT(1) angiotensin receptor activation and signaling SO ENDOCRINOLOGY LA English DT Article ID PROTEIN-COUPLED RECEPTORS; II TYPE-1 RECEPTOR; CONSTITUTIVELY ACTIVE MUTANTS; ADRENAL GLOMERULOSA CELLS; CARBOXYL-TERMINAL TAIL; M1 MUSCARINIC RECEPTOR; ALPHA(1B)-ADRENERGIC RECEPTOR; HORMONE RECEPTOR; CYTOPLASMIC LOOP; AMINO-ACIDS AB The pleiotropic actions of angiotensin II are mediated by the primarily G. protein-coupled type I angiotensin (AT(1)) receptor. In this study a mutational analysis of the function of the conserved DRYXXV/IXKPL domain in the second intracellular loop of the rat AT(1A) receptor was performed in COS7 cells. Alanine substitution studies showed that single replacement of the highly conserved Asp(125) and Arg(126), but not Tyr(127), moderately impaired angiotensin II-induced inositol phosphate signaling. However, concomitant substitution of both Asp(125) and Arg(126) caused marked reduction of both inositol phosphate signaling and receptor internalization. Alanine scanning of the adjacent residues showed that substitution of Ile(130), His(132), and Pro(133) reduced agonist-induced inositol phosphate signal generation, whereas mutations of Met(134) also impaired receptor internalization. Expression of the D125A mutant AT(1A) receptor in COS7 cells endowed the receptor with moderate constitutive activity, as indicated by its enhanced basal Elk1 promoter activity and inositol phosphate response to partial agonists. Angiotensin II- induced stimulation of the Elk1 promoter showed parallel impairment with inositol phosphate signal generation in receptors containing mutations in this region of the AT(1A) receptor. These data confirm that Ca2+ signal generation is required for the nuclear effects of angiotensin II-induced ERR activation. They are also consistent with the role of the conserved DRY sequence of the AT(1A) receptor in receptor activation, and of Asp(125) in constraining the receptor in its inactive conformation. Furthermore, in the cytoplasmic helical extension of the third helix, an apolar surface that includes Ile(130) and Met(134) appears to have a direct role in G protein coupling. C1 Semmelweis Univ, Fac Med, Dept Physiol, H-1088 Budapest, Hungary. Semmelweis Univ, Fac Med, Lab Cellular & Mol Physiol, H-1088 Budapest, Hungary. NICHHD, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA. US FDA, Div Cardiorenal Drug Prod, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Hunyady, L (reprint author), Semmelweis Univ, Fac Med, Dept Physiol, 8 POB 259, H-1444 Budapest, Hungary. EM hunyady@puskin.sote.hu NR 68 TC 81 Z9 82 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD JUN PY 2003 VL 144 IS 6 BP 2220 EP 2228 DI 10.1210/en.2002-0135 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 683KH UT WOS:000183146900009 PM 12746278 ER PT J AU Bannon, G Fu, TJ Kimber, I Hinton, DM AF Bannon, G Fu, TJ Kimber, I Hinton, DM TI Protein digestibility and relevance to allergenicity SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE allergenicity; protein stability; protein structure; proteolytic digestion; safety assessment; sequence homology; simulated gastric fluid ID MAJOR PEANUT ALLERGEN; FOOD ALLERGENS; SAFETY ASSESSMENT; ATOPIC-DERMATITIS; IN-VITRO; IDENTIFICATION; STABILITY; RESPONSES; TOMATOES; INVITRO AB In January 2001 a Joint Food and Agriculture Organization of the United Nations/World Health Organization Expert Consultation Committee on Allergenicity of Foods Derived from Biotechnology published a report outlining in detail an approach for assessing the allergenic potential of novel proteins. One component of this decision tree is a determination of whether the protein of interest is resistant to proteolytic digestion. Although these in vitro methodologies have been useful, the correlation between resistance to proteolysis and allergenic activity is not absolute. Two views and highlights of supporting research regarding the relationship of resistance to digestion and allergenicity are presented in this article. C1 Syngenta Cent Toxicol Lab, Macclesfield, Cheshire, England. US FDA, Ctr Food Safety & Appl Nutr, Laurel, MD USA. Prod Safety Ctr, St Louis, MO USA. US FDA, Natl Ctr Food Safety & Technol, Summit Argo, IL USA. RP Hinton, DM (reprint author), US FDA, 8301 Muirkirk Rd, Gaithersburg, MD 20878 USA. NR 34 TC 42 Z9 43 U1 0 U2 6 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 JUN PY 2003 VL 111 IS 8 BP 1122 EP 1124 PG 3 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 700QG UT WOS:000184122200013 PM 12826484 ER PT J AU Chen, JJ Chen, YJ Teuschler, LK Rice, G Hamernik, K Protzel, A Kodell, RL AF Chen, JJ Chen, YJ Teuschler, LK Rice, G Hamernik, K Protzel, A Kodell, RL TI Cumulative risk assessment for quantitative response data SO ENVIRONMETRICS LA English DT Article DE chemical mixture; classification tree; point of departure (POD); relative potency factor (RPF); similar action AB The Relative Potency Factor approach (RPF) is used to normalize and combine different toxic potencies among a group of chemicals selected for cumulative risk assessment. The RPF method assumes that the slopes of the dose-response functions are all equal; but this method depends on the choice of the index chemical, i.e. different index chemicals will give different predicted mean estimates. This article is part of an approach to explore and develop cumulative risk assessment strategies. As part of this approach this article proposes a procedure for cumulative risk assessment from exposure to multiple chemicals that have a common mechanism of toxicity. We propose two classification algorithms to cluster the chemicals into subclasses such that the chemicals in the same subclass have a common slope. The joint response is estimated by fitting the dose-response model of the mixture under dose addition. The proposed method will give the same predicted mean response regardless of the selection of the index chemical for the chemicals in the same subclass. The proposed method also allows one to estimate the joint response for chemicals having different slopes. An example data set of six hypothetical pesticide chemicals is used to illustrate the proposed procedure. Copyright (C) 2003 John Wiley Sons, Ltd. C1 US FDA, NCTR, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. US EPA, Natl Ctr Environm Assessment, Off Res & Dev, Cincinnati, OH 45268 USA. US EPA, Off Pesticide Programs, Div Hlth Effects, Washington, DC 20460 USA. RP Chen, JJ (reprint author), US FDA, NCTR, Div Biometry & Risk Assessment, HFT-20, Jefferson, AR 72079 USA. NR 13 TC 9 Z9 9 U1 0 U2 5 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 1180-4009 J9 ENVIRONMETRICS JI Environmetrics PD JUN PY 2003 VL 14 IS 4 BP 339 EP 353 DI 10.1002/env.587 PG 15 WC Environmental Sciences; Mathematics, Interdisciplinary Applications; Statistics & Probability SC Environmental Sciences & Ecology; Mathematics GA 686DT UT WOS:000183306600001 ER PT J AU Collins, TF Sprando, RL Black, TN Olejnik, N Wiesenfeld, PW Babu, US Bryant, M Flynn, TJ Ruggles, DI AF Collins, TF Sprando, RL Black, TN Olejnik, N Wiesenfeld, PW Babu, US Bryant, M Flynn, TJ Ruggles, DI TI Effects of flaxseed and defatted flaxseed meal on reproduction and development in rats SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article DE flaxseed; dietary supplement; reproduction; development; rat ID DIETARY PHYTOESTROGENS; PURIFIED LIGNAN; SECOISOLARICIRESINOL DIGLYCOSIDE; COLON CARCINOGENESIS; BREAST-CANCER; RENAL-DISEASE; FEMALE RATS; EXPOSURE; SUPPLEMENTATION; PRECURSOR AB Flaxseed, a rich source of reportedly beneficial n-3 fatty acid and phytoestrogens, has not been thoroughly tested for reproductive effects. High levels of flaxseed (FS, 20 or 40%) or defatted flaxseed meal (FLM, 13 or 26%) added to AIN-93 diet were evaluated in a two-phase study: dosed during gestation only or during gestation and maturation in a lifetime study. At cesarean section on gestation day 20, neither FS nor FLM affected fertility, body weight gain, litter size, or fetal development. FLM, but not FS, decreased gestation length. The offspring of dams allowed to litter were observed to postnatal day (PND) 21 or 90. Neither FS nor FLM affected PND 21 survival indices of F1 pups. FS (20 and 40%), but not FLM, increased the anogenital index (AGI) of F1 females at PND 21. The AGI of F1 males was not affected by either FS or FLM. FLM (13 and 26%), but not FS, delayed puberty in F1 males. Age and weight at the onset of puberty in females were not affected by ITS or FLM. FS and FLM caused dose-related increases in the number of F1 females with irregular estrous cycles. During PND 21-90, F1 females fed 20% FS, 13% FLM, or 26% FLM gained more weight than the controls. FS and FLM decreased thymus/body weight and thymus/brain weight ratios in weanling F1 males and females. FS and FLM decreased liver/body weight and liver/brain weight ratios in weanling F1 females, and 26% FLM decreased the same two ratios in F1 males. In conclusion, FS did not affect fetal development but did affect indices of postnatal development such as the estrous cycle. Published by Elsevier Science Ltd. C1 US FDA, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. RP Collins, TF (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 8301 Muirkirk Rd, Laurel, MD 20708 USA. OI Flynn, Thomas/0000-0002-7248-0643 NR 52 TC 34 Z9 35 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0278-6915 J9 FOOD CHEM TOXICOL JI Food Chem. Toxicol. PD JUN PY 2003 VL 41 IS 6 BP 819 EP 834 DI 10.1016/S0278-6915(03)00033-4 PG 16 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA 682YM UT WOS:000183120000009 PM 12738187 ER PT J AU Flynn, TJ Collins, TFX Sprando, RL Black, TN Ruggles, DI Wiesenfeld, PW Babu, US AF Flynn, TJ Collins, TFX Sprando, RL Black, TN Ruggles, DI Wiesenfeld, PW Babu, US TI Developmental effects of serum from flaxseed-fed rats on cultured rat embryos SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article DE flaxseed; embryotoxicity; in vitro ID SPRAGUE-DAWLEY RATS; SECOISOLARICIRESINOL DIGLYCOSIDE; REPRODUCTIVE INDEXES; IN-VITRO; EXPOSURE; LIGNAN; PHYTOESTROGENS; SPERMATOGENESIS; GENERATION; DEFICIENCY AB Gestation day 9.5 rat embryos were cultured for 45 h in serum obtained from pregnant rats that had been fed throughout gestation with either a control diet (based on the AIN-93 formulation), a diet supplemented with flaxseed (20% or 40%, w/w), or a diet supplemented with de-fatted flaxseed ("flaxseed meal", 13 or 26%, w/w). The embryos were fixed in neutral formalin at the end of culture. Overall growth and development was assessed, and the presence of abnormalities was noted. A significant inhibition of growth (as determined by crown-rump length) relative to control was observed in embryos cultured in serum from rats fed the 20% flaxseed diet. The incidence of spontaneous heart inversions was increased significantly in the embryos cultured in serum from the 20% flaxseed and 26% flaxseed meal fed rats. The incidence of flexion defects was increased significantly in embryos cultured in serum from 20% flaxseed-fed rats. The lack of an apparent dose response in any of the statistically significant effects suggests that the observed anomalies were chance occurrences unrelated to the treatment group from which serum was obtained. It is therefore concluded that diets high in flaxseed or flaxseed meal do not result in serum factors that are directly embryotoxic to organogenesis-staged rat embryos. This finding is consistent with the findings of a parallel in vivo rat teratology study where no significant embryotoxicity attributable to flaxseed exposure was observed. Published by Elsevier Science Ltd. C1 US FDA, Off Appl Res, MOD1 Labs, Laurel, MD 20708 USA. US FDA, Ctr Food Safety & Appl Nutr, MOD1 Labs, Laurel, MD 20708 USA. US FDA, Off Safety Assessment, MOD1 Labs, Laurel, MD 20708 USA. RP Flynn, TJ (reprint author), US FDA, Off Appl Res, MOD1 Labs, 8301 Muirkirk Rd, Laurel, MD 20708 USA. OI Flynn, Thomas/0000-0002-7248-0643 NR 35 TC 2 Z9 2 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0278-6915 J9 FOOD CHEM TOXICOL JI Food Chem. Toxicol. PD JUN PY 2003 VL 41 IS 6 BP 835 EP 840 DI 10.1016/S0278-6915(03)00034-6 PG 6 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA 682YM UT WOS:000183120000010 PM 12738188 ER PT J AU Wiesenfeld, PW Babu, US Collins, TFX Sprando, R O'Donnell, MW Flynn, TJ Black, T Olejnik, N AF Wiesenfeld, PW Babu, US Collins, TFX Sprando, R O'Donnell, MW Flynn, TJ Black, T Olejnik, N TI Flaxseed increased alpha-linolenic and eicosapentaenoic acid and decreased arachidonic acid in serum and tissues of rat dams and offspring SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article DE flaxseed; alpha-linolenic acid; fatty acids; pregnant rats ID N-3 FATTY-ACIDS; VITAMIN-E STATUS; DOCOSAHEXAENOIC-ACID; LIGNAN PRECURSOR; HYPERCHOLESTEROLEMIC ATHEROSCLEROSIS; SECOISOLARICIRESINOL DIGLYCOSIDE; DIETARY PHYTOESTROGENS; COLON CARCINOGENESIS; CONTROLLED CROSSOVER; LYMPHOCYTE FUNCTIONS AB The effects of dietary flaxseed (FS), and defatted flaxseed meal (FLM) on serum and tissue fatty acid profiles were investigated. Pregnant Sprague-Dawley rats were fed AIN-93 based diets balanced in calories, fat, nitrogen, and fiber. Diets contained 0, 20%, 40% FS or 13% or 26% FLM by weight. The control, FS and FLM diets differed in linoleic acid to alpha-linolenic acid (ALA) fatty acid ratio. These diets were fed continuously during gestation, suckling period and 8 weeks post-weaning (F-1). FS fatty acids were bioavailable and metabolized by pregnant and F-1 rats. ALA and eicosapentaenoic acid increased; linoleic and arachidonic acid decreased; and docosahexaeonic acid was unchanged in serum, 'gastric milk' and liver of FS and FLM-fed pregnant and F-1 rats. FS more than FLM, changed fatty acids profiles, but FLM and 40% FS significantly reduced serum cholesterol. Dietary 40% FS may have increased oxidative stress as evidenced by a reduction in liver vitamin E. Published by Elsevier Science Ltd. C1 US FDA, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. RP Wiesenfeld, PW (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 8301 Muirkirk Rd, Laurel, MD 20708 USA. OI Flynn, Thomas/0000-0002-7248-0643 NR 93 TC 17 Z9 20 U1 2 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0278-6915 J9 FOOD CHEM TOXICOL JI Food Chem. Toxicol. PD JUN PY 2003 VL 41 IS 6 BP 841 EP 855 DI 10.1016/S0278-6915(03)00035-8 PG 15 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA 682YM UT WOS:000183120000011 PM 12738189 ER PT J AU Jung, CT Wickett, RR Desai, PB Bronaugh, RL AF Jung, CT Wickett, RR Desai, PB Bronaugh, RL TI In vitro and in vivo percutaneous absorption of catechol SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article DE catechol; percutaneous absorption; skin; penetration; hair dye; rat; human ID HUMAN-SKIN; IN-VIVO; INVITRO; RAT; INVIVO; CARCINOGENICITY; METABOLISM; STOMACH; MICE AB The Cosmetic Ingredient Review Expert Panel found insufficient data to conclude that catechol could be used safely in permanent hair dye products. Information was lacking on the extent of oxidation and skin absorption of remaining catechol. In vitro percutaneous absorption studies were conducted in human and rat skin using a consumer permanent hair dye spiked with 0.6% catechol. A 30-min application demonstrated 0.4% of the applied dose was absorbed through human skin and 0.2% through rat skin. The minimal absorption observed was due to the short exposure time and to partial oxidation of catechol by the dye developer. The fate of catechol remaining in rat skin after exposure in vitro and in vivo was investigated with additional absorption studies using catechol in ethanol. At 72 h, 24-h application of 4% catechol resulted in skin absorption of 81% of the applied dose in vitro and 53% in vivo. Skin levels measured at 24 h remained unchanged after 72 h. Therefore the skin reservoir did not contribute to the estimated systemic absorption. A deconvolution technique employed to predict skin absorption using plasma levels from intravenous and dermal administration overestimated in vivo skin absorption due to volatility of catechol in an ethanolic vehicle. Published by Elsevier Science Ltd. C1 US FDA, Off Cosmet & Colors, Laurel, MD 20708 USA. Univ Cincinnati, Div Pharmaceut Sci, Cincinnati, OH 45267 USA. RP Jung, CT (reprint author), US FDA, Off Cosmet & Colors, Laurel, MD 20708 USA. NR 34 TC 13 Z9 14 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0278-6915 J9 FOOD CHEM TOXICOL JI Food Chem. Toxicol. PD JUN PY 2003 VL 41 IS 6 BP 885 EP 895 DI 10.1016/S0278-6915(03)00040-1 PG 11 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA 682YM UT WOS:000183120000016 PM 12738194 ER PT J AU Babu, US Wiesenfeld, PW Collins, TFX Sprando, R Flynn, TJ Black, T Olejnik, N Raybourne, RB AF Babu, US Wiesenfeld, PW Collins, TFX Sprando, R Flynn, TJ Black, T Olejnik, N Raybourne, RB TI Impact of high flaxseed diet on mitogen-induced proliferation, IL-2 production, cell subsets and fatty acid composition of spleen cells from pregnant and F1 generation Sprague-Dawley rats SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article DE flaxseed; alpha-linolenic acid; rats; spleen cell proliferation; IL-2; lymphocyte subsets ID ALPHA-LINOLENIC ACID; T-LYMPHOCYTE PROLIFERATION; SERUM-LIPID LEVELS; LONG-CHAIN N-3; IMMUNE CELLS; EICOSAPENTAENOIC ACID; EICOSANOID PRODUCTION; COLON CARCINOGENESIS; SPONTANEOUS-ABORTION; BACTERIAL CLEARANCE AB Flaxseed (FS) being rich in alpha-linolenic acid may alter the immune parameters. Therefore, we assessed the impact of FS and defatted flaxseed meal (FLM) on fatty acid composition, cell subsets, proliferation and IL-2 production by splenic lymphocytes. Pregnant female Sprague-Dawley rats were fed diets containing 0% FS and FLM, 20 or 40% FS, 13 or 26% FLM during gestation or gestation, lactation and 8 week post-weaning period. FS and FLM resulted in up to 8.3 fold and 4.6 fold increase in splenic ALA among pregnant rats, 4.5 fold and 1.2 fold increase in splenic ALA among F-1 generation rats. Splenic linoleic acid (LA) and arachidonic acid (AA) were 18 and 40% lower in 40% FS fed pregnant rats, and AA was 15% lower in all the other groups. Among F-1 rats, splenic LA and AA were 16 and 48% lower in 40% FS group, and AA was 18% lower in 20% FS and 26% FLM groups. Concanavalin A and phytohemagglutinin mediated proliferation of spleen cells were 60 and 52% lower in 40% FS fed pregnant and F-1 generation rats, respectively. No significant changes were observed in the cell subsets or IL-2 production by splenic cells from different groups. Published by Elsevier Science Ltd. C1 US FDA, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. RP Babu, US (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 8301 Muirkirk Rd, Laurel, MD 20708 USA. OI Flynn, Thomas/0000-0002-7248-0643 NR 99 TC 7 Z9 8 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0278-6915 J9 FOOD CHEM TOXICOL JI Food Chem. Toxicol. PD JUN PY 2003 VL 41 IS 6 BP 905 EP 915 DI 10.1016/S0278-6915(03)00043-7 PG 11 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA 682YM UT WOS:000183120000018 PM 12738196 ER PT J AU Holden, JP Selbie, WS Stanhope, SJ AF Holden, JP Selbie, WS Stanhope, SJ TI A proposed test to support the clinical movement analysis laboratory accreditation process SO GAIT & POSTURE LA English DT Article DE movement analysis; gait; laboratory accreditation; accuracy; kinematics; kinetics; force platform ID SPOT CHECK; SYSTEM; ACCURACY; RELIABILITY AB This paper describes a testing methodology and resultant set of four variables that can be used to quickly and easily document the correct installation, configuration, and combined working status of force platform (FP) and three-dimensional (3D) motion capture components of a clinical movement analysis (CMA) laboratory. Using a rigid, rod-shaped testing device, CMA laboratory data are collected simultaneously from the F and motion capture components (typically, video-based kinematic measurements) as the device is manually loaded while being pivoted broadly about a point on the FP. Using a computational method based on static equilibrium, it is possible to independently measure the rod's orientation and tip position during the moving trial, usingFP derived data exclusively, and to compare these estimates to rod orientation and tip position estimates derived exclusively from the motion capture component. The motion laboratory accreditation test (MLAT) variables include: the difference (angle) between the orientation of the long axis of the testing device as independently determined from kinematic measures (motion capture component) and the FP derived data; and the difference (x, y, z) between the center of pressure position (FP derived) and the position of the testing device tip (motion capture derived) that loads the FP. A numerical dynamics model was explored to evaluate the appropriateness of the static equilibrium-based FP data model and to determine guidelines for testing device movement frequency and FP loading. The MLAT technique provides a simple means of detecting the combined presence of errors from many sources, several of which are explored in this paper. The MLAT has been developed to help meet one criteria of the CMA laboratory, accreditation process, and to serve as a routine quality assessment tool. (C) 2002 Elsevier Science B.V. All rights reserved. C1 NIH, Phys Disabilities Branch, Bethesda, MD 20892 USA. US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. C Mot Inc, Rockville, MD 20855 USA. RP Stanhope, SJ (reprint author), NIH, Phys Disabilities Branch, Bldg 10,Room 6s235,MSC 1604, Bethesda, MD 20892 USA. EM steven_stanhope@nih.gov NR 20 TC 21 Z9 22 U1 1 U2 2 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0966-6362 J9 GAIT POSTURE JI Gait Posture PD JUN PY 2003 VL 17 IS 3 BP 205 EP 213 AR PII S0966-6362(02)00088-7 DI 10.1016/S0966-6362(02)00088-7 PG 9 WC Neurosciences; Orthopedics; Sport Sciences SC Neurosciences & Neurology; Orthopedics; Sport Sciences GA 688KE UT WOS:000183432700002 PM 12770634 ER PT J AU Ken, SLB Dennis, JE Zaharek, GL Eng, FJ AF Ken, SLB Dennis, JE Zaharek, GL Eng, FJ TI The impact of FDA's laser notice 50 on laser safety programs. SO HEALTH PHYSICS LA English DT Meeting Abstract C1 US FDA, Boise, ID 83701 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 0017-9078 EI 1538-5159 J9 HEALTH PHYS JI Health Phys. PD JUN PY 2003 VL 84 IS 6 SU 2 BP S226 EP S227 PG 2 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 683QE UT WOS:000183160000225 ER PT J AU Kent, SLB Dennis, JE AF Kent, SLB Dennis, JE TI FDA's regulatory program for lasers and electronic products. SO HEALTH PHYSICS LA English DT Meeting Abstract C1 US FDA, Boise, ID 83701 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 0017-9078 EI 1538-5159 J9 HEALTH PHYS JI Health Phys. PD JUN PY 2003 VL 84 IS 6 SU 2 BP S226 EP S226 PG 1 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 683QE UT WOS:000183160000224 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 pediatric radiology SO HEALTH PHYSICS LA English DT Meeting Abstract C1 Univ Florida, Gainesville, FL 32606 USA. US FDA, 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 0017-9078 EI 1538-5159 J9 HEALTH PHYS JI Health Phys. PD JUN PY 2003 VL 84 IS 6 SU 2 BP S258 EP S259 PG 2 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 683QE UT WOS:000183160000311 ER PT J AU Wear, KA AF Wear, KA TI Autocorrelation and cepstral methods for measurement of tibial cortical thickness SO IEEE TRANSACTIONS ON ULTRASONICS FERROELECTRICS AND FREQUENCY CONTROL LA English DT Article ID ULTRASOUND VELOCITY; QUANTITATIVE ULTRASOUND; HIP FRACTURE; BONE STATUS; SITES; WOMEN AB Cortical thickness of the tibia is related to stress fracture risk and overall skeletal status. Two methods are proposed for estimating tibial cortical thickness based on power spectra of ultrasonic echoes containing reflections from front and back surfaces of the cortex. The locations of the peaks in the autocorrelation function and the cepstrum are related to cortical thickness. Data were acquired on plastic plates in order to validate the methodology. These data indicate high correlations between estimated and true thickness with correlation coefficients r = 0.99, (95% confidence interval: 0.993-1.00) for the autocorrelation method and r = 0.99 (95% CI: 0.996-1.00) for the cepstral method. Data on six tibia samples in vitro indicate correlation coefficients of r = 0.92 (95% CI: 0.72-1.00) for the autocorrelation method and r = 0.85 (95% CI: 0.62-0.94) for the cepstral method. Estimates of precisions of the two methods were 0.3 +/- 0.1 mm (autocorrelation method) and 0.5 +/- 0.2 mm (cepstral method). One measurement in a human volunteer in vivo demonstrated clinical feasibility of the measurement and good agreement with cortical thickness assessed using peripheral quantitative computed tomography (QCT). This technology offers the promise of an inexpensive, fast, portable, simple, nonionizing technique for assessing skeletal status. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20852 USA. RP Wear, KA (reprint author), US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20852 USA. RI CHEN, Jiangang/A-1549-2011 NR 21 TC 28 Z9 28 U1 2 U2 4 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 0885-3010 J9 IEEE T ULTRASON FERR JI IEEE Trans. Ultrason. Ferroelectr. Freq. Control PD JUN PY 2003 VL 50 IS 6 BP 655 EP 660 DI 10.1109/TUFFC.2003.1209552 PG 6 WC Acoustics; Engineering, Electrical & Electronic SC Acoustics; Engineering GA 694GK UT WOS:000183765700010 PM 12839177 ER PT J AU Kothary, MH Lowman, H McCardell, BA Tall, BD AF Kothary, MH Lowman, H McCardell, BA Tall, BD TI Purification and characterization of enterotoxigenic El Tor-like hemolysin produced by Vibrio fluvialis SO INFECTION AND IMMUNITY LA English DT Article ID CHOLERAE NON-O1; FLUID ACCUMULATION; VULNIFICUS; MIMICUS; STRAINS; GENE; MICE AB The halophilic bacterium Vibrio fluvialis is an enteric pathogen that produces an extracellular hemolysin. This hemolysin was purified to homogeneity by using sequential hydrophobic-interaction chromatography with phenyl-Sepharose CL-4B and gel filtration with Sephacryl S-200. It has a molecular weight of 63,000 and an isoelectric point of 4.6, and its hemolytic activity is sensitive to heat, proteases, and preincubation with zinc ions. The hemolysin lyses erythrocytes of the eight different animal species that we tested, is cytotoxic against Chinese hamster ovary cells in tissue culture, and elicits fluid accumulation in suckling mice. Lysis of erythrocytes occurs by a temperature-dependent binding step followed by a temperature- and pH-dependent lytic step. Fourteen of the first 20 N-terminal amino acid residues (Val-Ser-Gly-Gly-Glu-Ala-Asn-Thr-Leu-Pro-His-Val-Ala-Phe-Tyr-Ile-Asn-Val-Asn-Arg) are identical to those of the El Tor hemolysin of Vibrio cholerae and the heat-labile hemolysin of Vibrio mimicus. This homology was further confirmed by PCR analysis using a 5' primer derived from the amino-terminal sequence of the hemolysin and a 3' primer derived from the El Tor hemolysin structural gene. The hemolysin also reacts with antibodies to the El Tor-like hemolysin of non-O1 V. cholerae. C1 US FDA, Div Virulence Assessment HFS 025, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. US FDA, Ctr Food Safety & Appl Nutr, Div Microbiol Studies, College Pk, MD 20740 USA. RP Kothary, MH (reprint author), US FDA, Div Virulence Assessment HFS 025, Ctr Food Safety & Appl Nutr, 8301 Muirkirk Rd, Laurel, MD 20708 USA. NR 31 TC 32 Z9 37 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 JUN PY 2003 VL 71 IS 6 BP 3213 EP 3220 DI 10.1128/IAI.71.6.3213-3220.2003 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 682WX UT WOS:000183116300029 PM 12761101 ER PT J AU Brody, BA Dickey, N Ellenberg, SS Heaney, RP Levine, RJ O'Brien, RL Purtilo, RB Weijer, C AF Brody, BA Dickey, N Ellenberg, SS Heaney, RP Levine, RJ O'Brien, RL Purtilo, RB Weijer, C TI Is the use of placebo controls ethically permissible in clinical trials of agents intended to reduce fractures in osteoporosis? SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE ethics; placebo controls; active controls; osteoporosis; clinical trials ID EXISTING VERTEBRAL FRACTURES; RANDOMIZED CONTROLLED TRIAL; ACTIVE-CONTROL TRIALS; BONE-MINERAL DENSITY; POSTMENOPAUSAL WOMEN; ELDERLY WOMEN; HIP FRACTURE; INTERVENTION TRIAL; RISK; ALENDRONATE AB Substantial progress has been made in developing treatments that reduce the risk of fractures in osteoporosis. However, available treatments are only partially effective, they are not widely used, and there is need to search for more effective means of fracture prevention. Currently known effective means of reducing fractures were found using randomized placebo-controlled trials. The use of placebo controls in clinical trials has been a subject of significant controversy in recent years. The Declaration of Helsinki revision of October 2000 caused great concern among clinical investigators about the future use of placebo controls if known effective therapeutic agents are available. A working group of ethicists, clinical trial design experts, and clinical investigators examined the current state of knowledge of osteoporosis treatment and trials. They concluded that if placebo controls put subjects at substantial risk of serious outcomes, they are not ethically permissible. Placebo controls in osteoporosis trials with fracture as the measured outcome are permissible only under narrowly defined conditions. Placebo controls may be used if competent, well-informed patients refuse approved therapies for sound reasons, there is a reasonable basis for substantial disagreement or lack of consensus among professionals about whether approved treatments are better than placebos, or subjects are refractory to known effective agents. Active control trials are permissible and desirable if they can be designed and conducted in ways that overcome the interpretive difficulties often associated with such trials. C1 Creighton Univ, Ctr Hlth Policy & Eth, Omaha, NE 68178 USA. Creighton Univ, Dept Med, Omaha, NE 68178 USA. Baylor Coll Med, Ctr Med Eth & Hlth Policy, Houston, TX 77030 USA. Rice Univ, Dept Philosophy, Houston, TX 77251 USA. Texas A&M Univ Syst, Hlth Sci Ctr, Off Vice Chancellor, College Stn, TX USA. US FDA, Ctr Biol Evaluat & Res, Div Biostat & Epidemiol, Rockville, MD 20857 USA. Yale Univ, Interdisciplinary Program Bioeth, New Haven, CT USA. Yale Univ, Ctr Interdisciplinary Res AIDS, New Haven, CT USA. Dalhousie Univ, Sch Med, Dept Bioeth, Halifax, NS, Canada. RP O'Brien, RL (reprint author), Creighton Univ, Ctr Hlth Policy & Eth, Omaha, NE 68178 USA. NR 45 TC 16 Z9 16 U1 0 U2 2 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD JUN PY 2003 VL 18 IS 6 BP 1105 EP 1109 DI 10.1359/jbmr.2003.18.6.1105 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 682JZ UT WOS:000183089600019 PM 12817764 ER PT J AU Ellenberg, SS AF Ellenberg, SS TI Scientific and ethical issues in the use of placebo and active controls in clinical trials SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article; Proceedings Paper CT Conference on Osteoporosis Trials - Ethics in Study Design CY JUN 14-15, 2002 CL BETHESDA, MARYLAND ID DEVELOPING-COUNTRIES; ORTHODOXY; MYTHS; RISK C1 US FDA, Ctr Biol Evaluat & Res, Off Biostat & Epidemiol, Rockville, MD 20852 USA. RP Ellenberg, SS (reprint author), US FDA, Ctr Biol Evaluat & Res, Off Biostat & Epidemiol, 1401 Rockville Pike,HFM-210, Rockville, MD 20852 USA. NR 25 TC 8 Z9 8 U1 1 U2 1 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD JUN PY 2003 VL 18 IS 6 BP 1121 EP 1124 DI 10.1359/jbmr.2003.18.6.1121 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 682JZ UT WOS:000183089600023 PM 12817767 ER PT J AU Colman, EG AF Colman, EG TI The food and drug administration's osteoporosis guidance document: Past, present, and future SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article; Proceedings Paper CT Conference on Osteoporosis Trials - Ethics in Study Design CY JUN 14-15, 2002 CL BETHESDA, MARYLAND ID FLUORIDE AB In December 1979, the Food and Drug Administration's (FDA) Division of Metabolic and Endocrine Drug Products issued its Guidelines for the Clinical Evaluation of Drugs Used in the Treatment of Osteoporosis. The Guidance Document recommended study designs, patient populations for study, and techniques for evaluating skeletal mass and fracture frequency that were considered central to showing the efficacy and safety of drugs used to treat and prevent postmenopausal osteoporosis (PMO). In this paper, I discuss the evolution of the Osteoporosis Guidance as it relates to the pharmaceutical industry's efforts to develop effective and safe anti-osteoporosis drugs. Current regulatory policy on osteoporosis drugs and thoughts on the future direction of the Osteoporosis Guidance are also provided. C1 US FDA, Ctr Drug Evaluat & Res, Div Metab & Endocrine Drug Prod, Dept Hlth & Human Serv, Rockville, MD 20857 USA. RP Colman, EG (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Metab & Endocrine Drug Prod, Dept Hlth & Human Serv, HFD-510,5600 Fishers Lane, Rockville, MD 20857 USA. NR 14 TC 7 Z9 8 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD JUN PY 2003 VL 18 IS 6 BP 1125 EP 1128 DI 10.1359/jbmr.2003.18.6.1125 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 682JZ UT WOS:000183089600024 PM 12817768 ER PT J AU Temple, RJ AF Temple, RJ TI Study designs in osteoporosis SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article; Proceedings Paper CT Conference on Osteoporosis Trials - Ethics in Study Design CY JUN 14-15, 2002 CL BETHESDA, MARYLAND ID TRIALS C1 Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Temple, RJ (reprint author), Ctr Drug Evaluat & Res, 5000 Fishers Lane,HFD-40, Rockville, MD 20857 USA. NR 4 TC 9 Z9 9 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD JUN PY 2003 VL 18 IS 6 BP 1129 EP 1132 DI 10.1359/jbmr.2003.18.6.1129 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 682JZ UT WOS:000183089600025 PM 12817769 ER EF