FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Tsai, CM Kao, G Zhu, PX AF Tsai, CM Kao, G Zhu, PX TI Influence of the length of the lipooligosaccharide alpha chain on its sialylation in Neisseria meningitidis SO INFECTION AND IMMUNITY LA English DT Article ID SERUM BACTERICIDAL ACTIVITY; LACTO-N-NEOTETRAOSE; SIALIC-ACID; LIPOPOLYSACCHARIDE; LECTIN; SPECIFICITY; EXPRESSION; GONOCOCCI; ANTIBODY; SEQUENCE AB The sialylation of lipooligosaccharide (LOS) in Neisseria meningitidis plays a role in the resistance of the organism to killing by normal human serum. The length of the a chain extending out from the heptose I [Hep (I)] moiety of LOS influenced sialylation of N. meningitidis LOS in vitro and in vivo. The alpha chain required a terminal Gal and a trisaccharide or longer oligosaccharide to serve as an acceptor for sialylation. The disaccharide lactose (Gal beta1-4Glc) in the alpha chain of immunotype L8 LOS could not function as an acceptor for the sialyltransferase, probably due to steric hindrance imposed by the neighboring Hep (II) with phosphorylethanolamine and another group attached. C1 US FDA, Ctr Biolog, Div Bacterial Parasit & Allergen Products, Bethesda, MD 20892 USA. RP Tsai, CM (reprint author), US FDA, Ctr Biolog, Div Bacterial Parasit & Allergen Products, HFM-428,1401 Rockville Pike, Rockville, MD 20852 USA. NR 31 TC 9 Z9 9 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JAN PY 2002 VL 70 IS 1 BP 407 EP 411 DI 10.1128/IAI.70.1.407-411.2002 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 504FX UT WOS:000172847600054 PM 11748209 ER PT S AU Rodriguez-Saona, LE Khambaty, FM Fry, FS Calvey, EM AF Rodriguez-Saona, LE Khambaty, FM Fry, FS Calvey, EM BE Jensen, JO Spellicy, RL TI Discrimination of bacterial strains by Fourier-transform near-infrared spectroscopy using an aluminum oxide membrane SO INSTRUMENTATION FOR AIR POLLUTION AND GLOBAL ATMOSPHERIC MONITORING SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Conference on Instrumentation for Air Pollution and Global Atmospheric Monitoring CY OCT 31-NOV 01, 2001 CL NEWTON, MA SP SPIE DE FT-NIR spectroscopy; multivariate analysis; bacterial classification ID IDENTIFICATION; SPECTRA; CLASSIFICATION; POLYPEPTIDES; RAMAN AB To address the need for a fast and sensitive method for the detection of bacterial contamination in solutions, the use of Fourier-transform near infrared (FT-NIR) spectroscopy and multivariate pattern recognition techniques was evaluated. The complex cellular composition of bacteria yields FT-NIR vibrational transitions (overtone and combination bands) that might be useful for identification and sub-typing. Bacteria including strains of Escherichia coli spp., Pseudomonas aeruginosa, Bacillus spp. and Listeria innocua were evaluated. The harvested cells were treated with ethanol (70% v/v) to reduce the safety concerns when evaluating pathogenic strains. The bacterial cells were concentrated on an aluminum oxide membrane to obtain a thin bacterial film. Spectra were collected by FT-NIR by using a diffuse reflection-integrating sphere. This simple membrane filtration procedure generated reproducible FT-NIR spectra that can be used for rapid discrimination among closely related strains. Principal Component Analysis (PCA) of transformed spectra in the 5000-4000 cm(-1) region exhibited clusters that discriminated between bacteria species at levels <1 mg, wet cells weight (similar to10(6)-10(7) CFU/mg). Variations in the growth conditions of the bacteria substantially affected the FT-NIR spectra and diminished the ability of PCA to differentiate among strains; this underscores the importance of developing robust sampling protocols. FT-NIR in conjunction with multivariate techniques can be used for the rapid and accurate evaluation of potential bacterial contamination in liquids with minimal sample manipulation. C1 Univ Maryland, Joint Inst Food Safety & Appl Nutr, College Pk, MD 20742 USA. RP Rodriguez-Saona, LE (reprint author), Univ Maryland, Joint Inst Food Safety & Appl Nutr, College Pk, MD 20742 USA. RI Rodriguez-Saona, Luis/A-8557-2013 NR 25 TC 3 Z9 3 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 0-8194-4302-6 J9 P SOC PHOTO-OPT INS PY 2002 VL 4574 BP 108 EP 118 DI 10.1117/12.455148 PG 11 WC Engineering, Environmental; Instruments & Instrumentation; Spectroscopy SC Engineering; Instruments & Instrumentation; Spectroscopy GA BU23E UT WOS:000175417900013 ER PT J AU Fang, GC Chang, CN Wu, YS Fu, PPC Chang, SC Yang, IL Yang, CJ AF Fang, GC Chang, CN Wu, YS Fu, PPC Chang, SC Yang, IL Yang, CJ TI Characteristic study of particulates and metallic elements at an urban sampling site in Taichung, central Taiwan SO INTERNATIONAL JOURNAL OF ENVIRONMENT AND POLLUTION LA English DT Article DE metallic elements; PM2.5; total suspended particulates ID DEPOSITION; POLLUTION; PARTICLES; AEROSOLS; REGION; MATTER AB Atmospheric total suspended particulate concentrations and metallic element concentrations were measured at three locations, characteristic of urban, suburban and rural sites. The sampling period was from July 2000 to August 2000. The results indicated that the urban sampling site had the highest total suspended particulate concentrations (average 108.6 mug m(-3)), followed by the suburban site (average 60.1 mug m(-3)) and the rural site (average 53.3 mug m(-3)). The average PM2.5 concentrations (24.1 mug m(-3)) were higher than the PM2.5-10 concentrations (12.8 mug m(-3)) at the urban site. The average distributed ratios for PM2.5/PM2.5-10 were about 1.29, 1.53, 0.12, 1.12 and 2.31 for Pb, Zn, Fe, Ni and Cr, respectively. The average total suspended particulate mass ratios for daytime and nighttime were about 1.72. As for the elements Cu, Pb, Zn, Fe, Ni and Cr, these ratios were about 0.63, 0.97, 0.54, 1.66, 0.53 and 1.12, respectively. The total suspended particulate daytime concentrations of Ph and Zn were positively correlated (R = 0.925) at the urban sampling site. The elements Ni and Cr were positively correlated both during the daytime (R = 0.648) and the nighttime (R = 0.511), revealing that they came from the same emission source during daytime and nighttime, at the urban sampling site. C1 Hungkuang Inst Technol, Air Tox & Environm Anal Lab, Taichung 433, Taiwan. Tunghai Univ, Dept Environm Sci, Taichung 407, Taiwan. Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. Hungkuang Inst Technol, Dept Comp Sci & Informat Engn, Taichung 433, Taiwan. RP Fang, GC (reprint author), Hungkuang Inst Technol, Air Tox & Environm Anal Lab, Taichung 433, Taiwan. NR 16 TC 0 Z9 0 U1 0 U2 4 PU INDERSCIENCE ENTERPRISES LTD PI GENEVA AEROPORT PA WORLD TRADE CENTER BLDG 110 AVE LOUSIS CASAI CP 306, CH-1215 GENEVA AEROPORT, SWITZERLAND SN 0957-4352 J9 INT J ENVIRON POLLUT JI Int. J. Environ. Pollut. PY 2002 VL 18 IS 1 BP 64 EP 75 DI 10.1504/IJEP.2002.000695 PG 12 WC Environmental Sciences SC Environmental Sciences & Ecology GA 601GM UT WOS:000178438200005 ER PT J AU Sistare, FD Thompson, KL Honchel, R DeGeorge, J AF Sistare, FD Thompson, KL Honchel, R DeGeorge, J TI Evaluation of the Tg.AC transgenic mouse assay for testing the human carcinogenic potential of pharmaceuticals - Practical pointers, mechanistic clues, and new questions SO INTERNATIONAL JOURNAL OF TOXICOLOGY LA English DT Article DE alternative bioassay; carcinogens; skin carcinogenesis; tumor promotion; Tg.AC transgenic mouse; v-Ha-ras gene ID V-HA-RAS; ZETA-GLOBIN GENE; GENETICALLY ALTERED MOUSE; SKIN CARCINOGENESIS; ORNITHINE-DECARBOXYLASE; IDENTIFYING CARCINOGENS; TRANSCRIPTION FACTORS; TUMOR PROMOTION; PHORBOL ESTERS; PROTEIN-KINASE AB Transgenic mouse strains with genetic alterations known to play a role in the multistage process of carcinogenesis are being used increasingly as models for evaluating the human carcinogenic potential of chemicals and pharmaceuticals. The Tg.AC transgenic mouse is one of the strains currently being used in such alternative short-term carcinogenicity testing protocols. This review is focused on recent data from studies designed to evaluate this model's ability to discriminate carcinogens from noncarcinogens. Details relating to protocol design that can significantly impact study outcome are described. Data relating to mechanisms of chemical tumor induction in the Tg.AC model are reviewed, and questions have been formulated to encourage research to further guide appropriate future applications of this model. C1 US FDA, Div Appl Pharmacol Res, Off Pharmaceut Sci, Ctr Drug Evaluat & Res, Laurel, MD 20708 USA. RP Sistare, FD (reprint author), US FDA, Div Appl Pharmacol Res, Off Pharmaceut Sci, Ctr Drug Evaluat & Res, 8301 Muirkirk Rd, Laurel, MD 20708 USA. EM sistare@cder.fda.gov NR 114 TC 8 Z9 8 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1091-5818 J9 INT J TOXICOL JI Int. J. Toxicol. PD JAN PY 2002 VL 21 IS 1 BP 65 EP 79 DI 10.1080/10915810252826028 PG 15 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 531HV UT WOS:000174410700008 PM 11936901 ER PT J AU Alston, M Valerio, C Dixon, A Morrow, K Slater, J AF Alston, M Valerio, C Dixon, A Morrow, K Slater, J TI Lyophilization does not affect the activity or secondary structure of cat allergen vaccines SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 US FDA, Bethesda, MD 20014 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 2002 VL 109 IS 1 SU S MA 387 BP S134 EP S134 DI 10.1016/S0091-6749(02)81523-8 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 519UX UT WOS:000173744800386 ER PT J AU Finlay, WJJ Goodyear, CS Slater, J AF Finlay, WJJ Goodyear, CS Slater, J TI Analysis of IgE heavy chain sequences from a small volume of peripheral blood from a mildly atopic individual SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. Univ Calif San Diego, La Jolla, CA 92093 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 2002 VL 109 IS 1 SU S MA 312 BP S112 EP S112 DI 10.1016/S0091-6749(02)81448-8 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 519UX UT WOS:000173744800311 ER PT J AU Hsieh, LS Moharram, R Akasawa, A Slater, J Martin, BM AF Hsieh, LS Moharram, R Akasawa, A Slater, J Martin, BM TI Banana allergen detection and identification using SELDI technology SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 NIMH, NIH, Bethesda, MD 20892 USA. US FDA, CBER, Rockville, MD 20857 USA. Natl Childrens Med Res Ctr, Tokyo 154, Japan. US FDA, Bethesda, MD 20014 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 2002 VL 109 IS 1 SU S MA 938 BP S305 EP S305 DI 10.1016/S0091-6749(02)82073-5 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 519UX UT WOS:000173744800935 ER PT J AU Lucas, AD Tomazic-Jezic, VJ AF Lucas, AD Tomazic-Jezic, VJ TI Binding propensity of NRL proteins to glove powder SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 US FDA, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 2002 VL 109 IS 1 SU S MA 784 BP S257 EP S257 DI 10.1016/S0091-6749(02)81919-4 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 519UX UT WOS:000173744800781 ER PT J AU Patterson, ML Cardinale, EJ O'Hehir, RE Sutherland, MF Slater, JY AF Patterson, ML Cardinale, EJ O'Hehir, RE Sutherland, MF Slater, JY TI Hev b 5 double mutant proteins SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 US FDA, Bethesda, MD 20014 USA. Monash Univ, Prahran, Vic 3168, Australia. RI O'Hehir, Robyn/H-3627-2011 OI O'Hehir, Robyn/0000-0002-3489-7595 NR 0 TC 0 Z9 0 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 2002 VL 109 IS 1 SU S MA 386 BP S133 EP S133 DI 10.1016/S0091-6749(02)81522-6 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 519UX UT WOS:000173744800385 ER PT J AU Rabin, RL Alston, M Farber, JM AF Rabin, RL Alston, M Farber, JM TI Dual roles for the chemokine receptor CXCR3 in adaptive immunity SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 US FDA, Bethesda, MD 20014 USA. NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 2002 VL 109 IS 1 SU S MA 1109 BP S356 EP S356 DI 10.1016/S0091-6749(02)82243-6 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 519UX UT WOS:000173744801105 ER PT J AU Soldatova, LN Marcovic-Housley, Z Luong, TN Mueller, UR Slater, J AF Soldatova, LN Marcovic-Housley, Z Luong, TN Mueller, UR Slater, J TI The role of glycosylation in the IgE binding of the major honeybee allergen, hyaluronidase SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 US FDA, Rockville, MD 20857 USA. Univ Basel, CH-4003 Basel, Switzerland. Zieglerspital Bern, Bern, Switzerland. NR 0 TC 1 Z9 2 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 JAN PY 2002 VL 109 IS 1 SU S MA 388 BP S134 EP S134 DI 10.1016/S0091-6749(02)81524-X PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 519UX UT WOS:000173744800387 ER PT J AU Valerio, C Solanki, MD Slater, J AF Valerio, C Solanki, MD Slater, J TI The effects of intratracheal lipopolysaccharide (LPS) on the cytokine responses of BALB/c mice to ovalbumin SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 US FDA, Bethesda, MD 20014 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 2002 VL 109 IS 1 SU S MA 82 BP S44 EP S44 DI 10.1016/S0091-6749(02)81219-2 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 519UX UT WOS:000173744800082 ER PT J AU Lue, LP Hadman, ST Vancura, A AF Lue, LP Hadman, ST Vancura, A TI Liquid chromatographic determination of amphotericin B in different pharmaceuticals SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID TISSUE DISTRIBUTION; HUMAN-SERUM; PLASMA; ASSAY; URINE AB Amphotericin B (AmB) is one of the most potent antifungal agents and the drug of choice in the treatment of serious fungal infections. A liquid chromatographic (LC) method was developed to determine AmB in pharmaceutical formulations for injection, tissue culture, cream, and lotion. muBondapak C-18 reversed-phase column and a simple mobile phase consisting of acetonitrile-water-acetic acid (40 + 54 + 6, v/v) was used. The flow rate was 1.8 mL/min and the effluent was monitored at 405 nm. The developed LC method uses piroxicam as an internal standard and has a limit of detection of 10 ng/mL, a limit of quantitation of 30 ng/mL, and the assay is linear from 0.01 to 100 mug/mL. AmB and piroxicam elute with retention times of 12.4 and 4.0 min, respectively, and the resolution between AmB and piroxicam was 10.6. In comparison with the official United States Pharmacopeia microbial assay for AmB, this LC method is more rapid, selective, sensitive, and offers positive identification. C1 US FDA, Dept Hlth & Human Serv, Off Regulatory Affairs, NE Reg Lab, Jamaica, NY 11433 USA. RP Lue, LP (reprint author), US FDA, Dept Hlth & Human Serv, Off Regulatory Affairs, NE Reg Lab, 158-15 Liberty Ave, Jamaica, NY 11433 USA. NR 19 TC 3 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 JAN-FEB PY 2002 VL 85 IS 1 BP 15 EP 19 PG 5 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 522JN UT WOS:000173893000003 PM 11878595 ER PT J AU Satchithanandam, S Fritsche, J Rader, JI AF Satchithanandam, S Fritsche, J Rader, JI TI Gas chromatographic analysis of infant formulas for total fatty acids, including trans fatty acids SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID LIPIDS AB Twelve powdered and 13 liquid infant formulas were analyzed by using an extension of AOAC Official Method 996.01 for fat analysis in cereal products. Samples were hydrolyzed with 8N HCl and extracted with ethyl and petroleum ethers. Fatty acid methyl esters were prepared by refluxing the mixed ether extracts with methanolic sodium hydroxide in the presence of 14% boron trifluoride in methanol. The extracts were analyzed by gas chromatography. In powdered formulas, saturated fatty acid (SFA) content (mean +/-SD; n = 12) was 41.05 +/- 3.94%, monounsaturated fatty acid (MUFA) content was 36.97 +/- 3.38%, polyunsaturated fatty acid (PUFA) content was 20.07 +/- 3.08%, and total trans fatty acid content was 1.30 +/- 1.27%. In liquid formulas, SFA content (mean +/-SD; n 13) was 42.29 +/- 2.98%, MUFA content was 36.05 +/- 2.47%, PUFA content was 20.65 +/- 2.40%, and total trans fatty acid content was 0.88 +/- 0.54%. Total fat content in powdered formulas ranged from 4.4 to 5.5 g/100 kcal and linoleic acid content ranged from 868 to 1166 mg/100 kcal. In liquid formulas, total fat content ranged from 4.1 to 5.1 g/100 kcal and linoleic acid content ranged from 820 to 1100 mg/100 kcal. There were no significant differences between powdered and liquid infant formulas in concentrations of total fat, SFA, MUFA, PUFA, or trans fatty acids. C1 US FDA, Off Nutr Prod Labeling & Dietary Supplements, Washington, DC 20204 USA. RP Satchithanandam, S (reprint author), US FDA, Off Nutr Prod Labeling & Dietary Supplements, HFS-840,200 C St SW, Washington, DC 20204 USA. NR 8 TC 6 Z9 8 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 JAN-FEB PY 2002 VL 85 IS 1 BP 86 EP 94 PG 9 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 522JN UT WOS:000173893000013 PM 11878624 ER PT J AU Parfitt, CH AF Parfitt, CH TI Multiclass multiresidue methods for organic compounds SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article C1 US FDA, Div Field Sci, Rockville, MD 20857 USA. RP Parfitt, CH (reprint author), US FDA, Div Field Sci, HFC-141,5600 Fishers Ln, Rockville, MD 20857 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 JAN-FEB PY 2002 VL 85 IS 1 BP 256 EP 258 PG 3 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 522JN UT WOS:000173893000038 PM 11878612 ER PT J AU Hammack, TS Andrews, WH AF Hammack, TS Andrews, WH TI Committee on microbiology and extraneous materials - Food microbiology - Non-dairy SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article C1 US FDA, Div Microbiol Studies, Washington, DC 20204 USA. RP Hammack, TS (reprint author), US FDA, Div Microbiol Studies, HFS-516,200 C St SW, Washington, DC 20204 USA. NR 7 TC 1 Z9 1 U1 0 U2 0 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD JAN-FEB PY 2002 VL 85 IS 1 BP 262 EP 269 PG 8 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 522JN UT WOS:000173893000040 PM 11878614 ER PT J AU Rivera, LE Mason, CJ Chechik, E Lee, JK Burns, AW Denning, R Hanks, AR Harbin, DN Marsh, D Ritland, CL AF Rivera, LE Mason, CJ Chechik, E Lee, JK Burns, AW Denning, R Hanks, AR Harbin, DN Marsh, D Ritland, CL TI Committee on Pesticides and Disinfectant Formulations SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article C1 Calif Dept Food & Agr, Sacramento, CA 95832 USA. Nevada Div Agr, Reno, NV 89502 USA. Maryland Dept Agr, State Chemist Sect, Annapolis, MD 21415 USA. US FDA, Washington, DC 20204 USA. US EPA, Off Pesticide Programs, Ft George G Meade, MD 20755 USA. N Carolina Dept Agr, Raleigh, NC 27611 USA. Purdue Univ, Off Indiana State Chemist, W Lafayette, IN 47907 USA. Bayer Corp, Ag Div, Kansas City, MO 64120 USA. Arizona Dept Agr, State Agr Lab, Phoenix, AZ 85009 USA. RP Rivera, LE (reprint author), Calif Dept Food & Agr, 3292 Meadowview Rd, Sacramento, CA 95832 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 JAN-FEB PY 2002 VL 85 IS 1 BP 274 EP 275 PG 2 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 522JN UT WOS:000173893000042 ER PT J AU Ang, CYW van Ginkel, LA Carson, MC Layloff, T Li, M Mazzo, DJ Ng, L Reeves, VB Kay, JF Radebaugh, GW Peterson, G Chen, J AF Ang, CYW van Ginkel, LA Carson, MC Layloff, T Li, M Mazzo, DJ Ng, L Reeves, VB Kay, JF Radebaugh, GW Peterson, G Chen, J TI Committee on Drugs and Related Topics SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article C1 US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Natl Inst Publ Hlth & Environm, NL-3720 BA Bilthoven, Netherlands. US FDA, Ctr Vet Med, Laurel, MD 20708 USA. Air Resources Board, Monitoring Lab Div, Sacramento, CA 95812 USA. Schering Plough Corp, Res Inst, Kenilworth, NJ 07033 USA. US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20850 USA. Vet Med Directorate, Surrey KT15 3LS, England. Bur Alcohol Tobacco & Firearms, Fremont, CA 94536 USA. US FDA, Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. RP Ang, CYW (reprint author), US FDA, Natl Ctr Toxicol Res, HFT-230,3900 NCTR Rd, Jefferson, AR 72079 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 JAN-FEB PY 2002 VL 85 IS 1 BP 276 EP 277 PG 2 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 522JN UT WOS:000173893000043 ER PT J AU Page, BD Hill, NR Thomas, LC Williams, SM Dugar, SM Hageman, LR Marion, AR Canas, BJ Reimann, L AF Page, BD Hill, NR Thomas, LC Williams, SM Dugar, SM Hageman, LR Marion, AR Canas, BJ Reimann, L TI Committee on additives, beverages, and process-related analytes SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article C1 Hlth Canada, Sir Frederick Banting Res Ctr, Ottawa, ON K1A 0L2, Canada. US Dept Treasury, Bur Alcohol Tobacco & Firearms, Walnut Creek, CA 94598 USA. Res It Inc, Henderson, NV 89014 USA. Off Texas State Chemist, College Stn, TX 77841 USA. Bur Alcohol Tobacco & Firearms, Natl Lab Ctr, Rockville, MD 20850 USA. Nestle USA Inc, Qual Assurance Lab, Dublin, OH 43017 USA. Campbell Soup Co, Camden, NJ 08103 USA. US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. Eurofins Sci, Memphis, TN 38104 USA. RP Page, BD (reprint author), Hlth Canada, Sir Frederick Banting Res Ctr, 2203D,Tunneys Pasture, Ottawa, ON K1A 0L2, Canada. 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 JAN-FEB PY 2002 VL 85 IS 1 BP 278 EP 280 PG 3 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 522JN UT WOS:000173893000044 ER PT J AU Cho, SS Bernetti, R Mossoba, MM Konings, EJM Li, BW Woollard, DC Roach, J Becoat, WC Phillips, JG AF Cho, SS Bernetti, R Mossoba, MM Konings, EJM Li, BW Woollard, DC Roach, J Becoat, WC Phillips, JG TI Committee on Food Nutrition SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article C1 Kellogg Co, Battle Creek, MI 49015 USA. Bernetti Associates, Hinsdale, IL 60521 USA. US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. Inspectorate Hlth Protect, NL-6243 DB Geulle, Netherlands. USDA, Food Composit Lab, Beltsville, MD 20705 USA. AgriQual NZ Ltd, Auckland, New Zealand. US FDA, Washington, DC 20204 USA. US FDA, Philadelphia Lab, Philadelphia, PA 19106 USA. USDA, Eastern Reg Res Ctr, Wyndmoor, PA 19038 USA. RP Cho, SS (reprint author), Kellogg Co, 205 Brentwood Dr, Battle Creek, MI 49015 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 JAN-FEB PY 2002 VL 85 IS 1 BP 285 EP 287 PG 3 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 522JN UT WOS:000173893000046 ER PT J AU Sullivan, DM Lynch, JM Henderson, J Cole, ME Ellis, PC Krueger, DA McCarthy, H Ngeh-Ngwainbi, J Kasturi, P Bennett, DA AF Sullivan, DM Lynch, JM Henderson, J Cole, ME Ellis, PC Krueger, DA McCarthy, H Ngeh-Ngwainbi, J Kasturi, P Bennett, DA TI Committee on Commodity Foods and Commodity Products SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article C1 Covance Labs, Madison, WI 53704 USA. Cornell Univ, Coll Agr & Life Sci, Dept Food Sci, Ithaca, NY 14853 USA. US FDA, Los Angeles, CA 90015 USA. US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. Rhode Isl Dept Hlth Labs, Riverside, RI 02915 USA. Krueger Food Labs Inc, Cambridge, MA 02138 USA. Rhode Isl Dept Hlth Labs, Providence, RI 02904 USA. WK Kellogg Inst, E Battle Creek, MI 49016 USA. Quaker Oats Co, Barrington, IL 60010 USA. Calif Dept Food & Agr, Sacramento, CA 95832 USA. RP Sullivan, DM (reprint author), Covance Labs, 3301 Kinsman Blvd, Madison, WI 53704 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 JAN-FEB PY 2002 VL 85 IS 1 BP 288 EP 291 PG 4 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 522JN UT WOS:000173893000047 ER PT J AU Krynitsky, AJ Beckett, P Weisburg, S Newell, R Bell, J Bontoyan, WR Capar, SG Cook, J Lee, SM Lehotay, SJ Olberding, EL AF Krynitsky, AJ Beckett, P Weisburg, S Newell, R Bell, J Bontoyan, WR Capar, SG Cook, J Lee, SM Lehotay, SJ Olberding, EL TI Committee on Residues and Related Topics SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article C1 US EPA, Ctr Environm Sci, Ft George G Meade, MD 20755 USA. Florida State Dept Agr, Chem Residue Lab, Tallahassee, FL 32399 USA. US FDA, Div Math, Washington, DC 20204 USA. Eurofins Sci, Memphis, TN 38103 USA. Maryland Dept Agr, State Chemist Off, Annapolis, MD 21401 USA. Calif Dept Food & Agr, Ctr Analyt Chem, Sacramento, CA 95832 USA. USDA, Eastern Reg Res Ctr, Wyndmoor, PA 19038 USA. Dow Agrosci LLC, Indianapolis, IN 46268 USA. RP Krynitsky, AJ (reprint author), US EPA, Ctr Environm Sci, 701 Mapes Rd, Ft George G Meade, MD 20755 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 JAN-FEB PY 2002 VL 85 IS 1 BP 292 EP 294 PG 3 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 522JN UT WOS:000173893000048 ER PT J AU Agin, JR Abeyta, C McClure, FD Abbott, DO Ferreira, JL Ledenbach, L Hitchins, AD Orth, DS Hill, W Curiale, MS In't Veld, PH AF Agin, JR Abeyta, C McClure, FD Abbott, DO Ferreira, JL Ledenbach, L Hitchins, AD Orth, DS Hill, W Curiale, MS In't Veld, PH TI Committee on Microbiology and Extraneous Materials SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article C1 Ohio Dept Agr, Reynoldsburg, OH 43068 USA. US FDA, Bothell, WA 98021 USA. US FDA, Washington, DC 20204 USA. US FDA, FSIS OPHS, Biosci Div, Athens, GA 30605 USA. US FDA, Atlanta, GA 30309 USA. Kraft Gen Foods Inc, Glenview, IL 60025 USA. Neutrogena Corp, Los Angeles, CA 90045 USA. USDA, FSIS, Washington, DC 20250 USA. Silliker Labs Grp Inc, Holland, IL 60473 USA. Inspectorate Publ Hlth Commodities, Den Bosch, Netherlands. RP Agin, JR (reprint author), Ohio Dept Agr, 8995 E Main St, Reynoldsburg, OH 43068 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 JAN-FEB PY 2002 VL 85 IS 1 BP 295 EP 299 PG 5 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 522JN UT WOS:000173893000049 ER PT J AU Coleman, MR Wetzler, L Walsh, MC Wiest, SC Hite, D Llames, CR Leadbetter, MG McCurdy, JD Merritt, DA Noel, RJ Roser, RL AF Coleman, MR Wetzler, L Walsh, MC Wiest, SC Hite, D Llames, CR Leadbetter, MG McCurdy, JD Merritt, DA Noel, RJ Roser, RL TI Committee on Feeds, Fertilizers, and Related Agricultural Topics SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article C1 Eli Lilly & Co, Elanco Anim Hlth, Anim Sci Chem Res, Greenfield, IN 46140 USA. Nebraska Dept Agr, Lincoln, NE 68502 USA. State Lab, Dublin 15, Ireland. Tennessee Dept Agr, Nashville, TN 37204 USA. Degussa Corp, Allendale, NJ 07401 USA. US FDA, Ctr Vet Med, Rockville, MD 20855 USA. US FDA, Ctr Vet Med, Rockville, MD 21770 USA. Pharmacia & Upjohn Inc, Kalamazoo, MI 49001 USA. Purdue Univ, Off Indiana State Chemist, W Lafayette, IN 47907 USA. Scotts Co, Marysville, OH 43041 USA. RP Coleman, MR (reprint author), Eli Lilly & Co, Elanco Anim Hlth, Anim Sci Chem Res, 2001 W Main St,DC GL 10, Greenfield, IN 46140 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 JAN-FEB PY 2002 VL 85 IS 1 BP 300 EP 304 PG 5 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 522JN UT WOS:000173893000050 ER PT J AU Vindiola, AG Chechik, E Walsh, MC Peterson, GF Williams, SM Abeyta, C Henderson, J Weisberg, CA AF Vindiola, AG Chechik, E Walsh, MC Peterson, GF Williams, SM Abeyta, C Henderson, J Weisberg, CA TI Safety Committee SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article C1 Texas A&M Univ, Off Texas State Chemist, College Stn, TX 77841 USA. Maryland Dept Agr, State Chemist Sect, Annapolis, MD 21415 USA. State Lab, Dublin 15, Ireland. Bur Alcohol Tobacco & Firearms, Fremont, CA 94536 USA. US FDA, Bothell, WA 98021 USA. US FDA, Los Angeles, CA 90015 USA. RP Vindiola, AG (reprint author), Texas A&M Univ, Off Texas State Chemist, PO Drawer 3160, College Stn, TX 77841 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 JAN-FEB PY 2002 VL 85 IS 1 BP 307 EP 307 PG 1 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 522JN UT WOS:000173893000052 ER PT J AU McClure, FD Cole, ME Phillips, JG Lee, JK Thomas, LC Newell, R Wiest, SC Chen, J Champaneri, AM Wehling, P Lindberg, K AF McClure, FD Cole, ME Phillips, JG Lee, JK Thomas, LC Newell, R Wiest, SC Chen, J Champaneri, AM Wehling, P Lindberg, K TI Statistics Committee SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article C1 US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. ARS, USDA, Eastern Reg Res Ctr, Wyndmoor, PA 19038 USA. Res It Inc, Henderson, NV 89014 USA. Kansas State Dept HFRR, Manhattan, KS 66506 USA. US FDA, Natl Ctr Toxicol Res, Little Rock, AR 72223 USA. USDA, Washington, DC 20090 USA. Gen Mills Inc, Minneapolis, MN 55427 USA. 3M Co, Microbiol Prod, St Paul, MN 55144 USA. RP McClure, FD (reprint author), US FDA, Ctr Food Safety & Appl Nutr, HFS-705,harvey W Wiley Bldg,5100 Paint Branch Pkw, College Pk, MD 20740 USA. NR 0 TC 0 Z9 0 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 JAN-FEB PY 2002 VL 85 IS 1 BP 308 EP 308 PG 1 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 522JN UT WOS:000173893000053 ER PT J AU Burkhardt, W Blackstone, GM Skilling, D Smith, AW AF Burkhardt, W Blackstone, GM Skilling, D Smith, AW TI Applied technique for increasing calicivirus detection in shellfish extracts SO JOURNAL OF APPLIED MICROBIOLOGY LA English DT Article ID POLYMERASE-CHAIN-REACTION; HEPATITIS-A VIRUS; REVERSE TRANSCRIPTION-PCR; ROUND-STRUCTURED VIRUSES; ENTERIC VIRUSES; NORWALK VIRUS; MOLLUSCAN SHELLFISH; AMPLIFICATION; SPECIMENS; OYSTERS AB Aims: Optimal detection of enteric RNA viruses in clinical, environmental, and food products using reverse transcription-PCR (RT-PCR) when inhibitory substances in extracted sample materials are present. Methods and Results: We adapted a device for detection of RNA viruses in plant tissues and insects to detect a calicivirus strain (San Miguel sea lion virus, serotype 17) in water and oyster tissue extracts. This single, compartmentalized tube-within-a-tube (TWT) device for RT-PCR-nested PCR was compared to a conventional protocol of RT-PCR-nested PCR. In the presence of 100 mg of shellfish tissue extract equivalent, this TWT device decreases the calicivirus assay detection limit 10-fold over that of conventional RT-PCR-nested PCR while maintaining an identical detection limit of viral nucleic acid suspended in water. Both the conventional and TWT methods estimated the total particle-to-infectious particle ratio for this strain of calicivirus at approximately 40 : 1. Conclusions: We believe that the TWT device with appropriate RT-PCR primers will decrease the detection limit for other calicivirus strains and RNA viruses in shellfish tissue extracts. Significance and Impact of the Study: We believe that the TWT approach is applicable to other situations where RT and/or PCR inhibitory materials are present or nucleic acid targets of bacteria or viruses are at low levels in extracts of food products or clinical specimens. C1 US FDA, Gulf Coast Seafood Lab, Dauphin Isl, AL 36528 USA. Oregon State Univ, Coll Vet Med, Lab Calicivirus Studies, Corvallis, OR 97331 USA. RP Burkhardt, W (reprint author), US FDA, Gulf Coast Seafood Lab, POB 158, Dauphin Isl, AL 36528 USA. EM Wburkhar@cfsan.fda.gov NR 23 TC 3 Z9 3 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1364-5072 EI 1365-2672 J9 J APPL MICROBIOL JI J. Appl. Microbiol. PY 2002 VL 93 IS 2 BP 235 EP 240 DI 10.1046/j.1365-2672.2002.01681.x PG 6 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 578YV UT WOS:000177149400006 PM 12147071 ER PT J AU Li, Y Brackett, RE Chen, J Beuchat, LR AF Li, Y Brackett, RE Chen, J Beuchat, LR TI Mild heat treatment of lettuce enhances growth of Listeria monocytogenes during subsequent storage at 5 degrees C or 15 degrees C SO JOURNAL OF APPLIED MICROBIOLOGY LA English DT Article ID PROCESSED FRESH ENDIVE; ICEBERG LETTUCE; PHENOLIC METABOLISM; MODIFIED ATMOSPHERE; CUT VEGETABLES; FATE; CHLORINE; TEMPERATURE; OUTBREAK; READY AB Aims: The objective of this study was to determine the influence of mild heat treatment, storage temperature and storage time on the survival and growth of Listeria monocytogenes inoculated onto cut iceberg lettuce leaves. Methods and Results: Before or after inoculation with L. monocytogenes, cut iceberg lettuce leaves were dipped in water (20 or 50degreesC), containing or not 20 mg l(-1) chlorine, for 90 s, then stored at 5degreesC for up to 18 days or 15degreesC for up to 7 days. The presence of 20 mg l(-1) chlorine in the treatment water did not significantly (alpha = 0.05) affect populations of the pathogen, regardless of other test parameters. The population of L. monocytogenes on lettuce treated at 50degreesC steadily increased throughout storage at 5degreesC for up to 18 days. At day 10 and thereafter, populations were 1.7-2.3 log(10) cfu g(-1) higher on lettuce treated at 50degreesC after inoculation compared with untreated lettuce or lettuce treated at 20degreesC, regardless of chlorine treatment. The population of L. monocytogenes increased rapidly on lettuce stored at 15degreesC. At 2 and 4 days, significantly higher populations were detected on lettuce that had been treated at 50degreesC, compared with respective samples that had been treated at 20degreesC, regardless of inoculation before or after treatment, or the presence of 20 mg l(-1) chlorine in the treatment water. Conclusions: The results clearly demonstrated that mild heat treatment of cut lettuce leaves enhances the growth of L. monocytogenes during subsequent storage at 5 or 15degreesC. Significance and Impact of the Study: Mild heat treatment of cut lettuce may result in a prolonged shelf life as a result of delaying the development of brown discoloration. However, heat treatment also facilitates the growth of L. monocytogenes during storage at refrigeration temperature, thereby increasing the potential risk of causing listeriosis. C1 Univ Georgia, Ctr Food Safety, Griffin, GA 30223 USA. Univ Georgia, Dept Food Sci & Technol, Griffin, GA 30223 USA. US FDA, Off Plant & Dairy Foods & Beverages, Washington, DC 20204 USA. RP Beuchat, LR (reprint author), Univ Georgia, Ctr Food Safety, 1109 Expt St, Griffin, GA 30223 USA. NR 33 TC 36 Z9 38 U1 1 U2 2 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 1364-5072 J9 J APPL MICROBIOL JI J. Appl. Microbiol. PY 2002 VL 92 IS 2 BP 269 EP 275 DI 10.1046/j.1365-2672.2002.01530.x PG 7 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 523UG UT WOS:000173973900011 PM 11849355 ER PT J AU Carlson, DB Perdew, GH AF Carlson, DB Perdew, GH TI A dynamic role for the Ah receptor in cell signaling? Insights from a diverse group of ah receptor interacting proteins SO JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY LA English DT Article DE Ah receptor; ARNT; signal transduction; bHLH-PAS proteins; protein-protein interactions; cross talk; estrogen receptor; NF kappa B; Rb; HSP90; protein kinase C; coregulators ID ARYL-HYDROCARBON RECEPTOR; NUCLEAR TRANSLOCATOR ARNT; FACTOR-KAPPA-B; DNA-BINDING ACTIVITY; BREAST-CANCER CELLS; KINASE-C; DIOXIN RECEPTOR; ESTROGEN-RECEPTOR; CROSS-TALK; RETINOBLASTOMA PROTEIN AB The aryl hydrocarbon (Ah) receptor (AhR) is a member of the basic helix-loop-helix PER-ARNTSIM (PAS) transcription factor family. Consistent with the notion that PAS proteins are biological sensors, AhR binding to Ah toxicants induces or represses transcription of a wide range of genes and results in a cascade of toxic responses. However, an endogenous role for AhR in development and homeostasis is supported by (1) the discovery of low affinity, endogenous ligands; (2) studies demonstrating a role for the receptor in development of liver and vascular systems, that were established using mice lacking AhR expression; and (3) the presence of functional dioxin-responsive elements in promoter regions of genes involved in cellular growth and differentiation. A large body of recent literature has implicated AhR in multiple signal transduction pathways. AhR is known to interact with signaling pathways that are mediated by estrogen receptor and other hormone receptors, hypoxia, nuclear factor kappaB, and retinoblastorna protein. In addition, AhR complexes may affect cellular signaling through interactions with various other regulatory and signaling proteins, including PAS heterodimerization partners (ARNT), chaperone and immunophilin-like proteins (e.g. HSP90, XAP2/ARA9/AIP, p23), protein kinases and phosphatases (e.g. tyrosine kinases, casein kinase 2, protein kinase C), and coactivators (e.g. SRC-1, RIP 140, CBP/p300). Here we summarize the types of molecular cross talk that have been identified between AhR and cell signaling pathways. (C) 2002 Wiley Periodicals, Inc. C1 Penn State Univ, Dept Vet Sci, Ctr Mol Toxicol & Carcinogenesis, University Pk, PA 16802 USA. RP Perdew, GH (reprint author), US FDA, CFSAN OFAS, HPS 265,5100 Paint Branch Pkwy, College Pk, MD 20740 USA. FU NIEHS NIH HHS [ES04869, ES05900] NR 82 TC 128 Z9 134 U1 0 U2 5 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1095-6670 J9 J BIOCHEM MOL TOXIC JI J. Biochem. Mol. Toxicol. PY 2002 VL 16 IS 6 BP 317 EP 325 DI 10.1002/jbt.10051 PG 9 WC Biochemistry & Molecular Biology; Toxicology SC Biochemistry & Molecular Biology; Toxicology GA 631NV UT WOS:000180174600007 PM 12481307 ER PT J AU Barker, PE Watson, MS Ticehurst, JR Colbert, JC O'Connell, CD AF Barker, PE Watson, MS Ticehurst, JR Colbert, JC O'Connell, CD TI NIST physical standards for DNA-based medical testing SO JOURNAL OF CLINICAL LABORATORY ANALYSIS LA English DT Article DE DNA; standard; diagnostics ID TECHNOLOGY NAT ASSAYS; PROFILING MEASUREMENTS; INTERNATIONAL STANDARD; POLYMORPHISM; DIAGNOSIS; SIZE AB As DNA and RNA become major targets for clinical laboratory analysis, benchmark reagents will play an increasingly important role in standardization. Reliable national and international nucleic acid standards promote automation and third-party reimbursement for clinical testing. Furthermore, nucleic acid standards provide materials for quality assurance and quality control (QA/QC), and proficiency testing. Standard methods and training initially evolved from consensus guidelines endorsed by professional societies and governmental agencies. The National Institute of Standards and Technology (NIST), a nonregulatory agency of the U.S. Department of Commerce, develops and certifies physical and chemical standards in support of national commerce, manufacturing, and science. In its role supporting U.S. science and industry, the NIST responds to specific standards needs, most recently for medically and biologically important analytes. Broad-based consensus developed through interdisciplinary NIST workshops initiated development of NIST-certified DNA standards. Such materials serve the diagnostic community and help manufacturers benchmark a variety of DNA diagnostic testing platforms. Here we summarize the NIST experience and programs for development of national standards for DNA-based medical diagnostic testing. (C) 2002 Wiley-Liss, Inc. C1 NIST, Biomarkers Validat lab, NCI, Natl Inst Stand & Technol, Gaithersburg, MD 20899 USA. Amer Coll Med Genet, Bethesda, MD USA. US FDA, Ctr Devices & Radiol Hlth, DCLD, ODE,Microbiol Branch, Rockville, MD 20857 USA. Johns Hopkins Med Inst, Dept Pathol, Div Microbiol, Baltimore, MD 21205 USA. Natl Inst Stand & Technol, Off Measurement Serv, NIST, SRM Program, Gaithersburg, MD 20899 USA. RP Barker, PE (reprint author), NIST, Biomarkers Validat lab, NCI, Natl Inst Stand & Technol, Room B248,Bldg 227,100 Bur Dr, Gaithersburg, MD 20899 USA. RI Ticehurst, John/I-7532-2012 FU NCI NIH HHS [Y1-CN-0103-1] NR 36 TC 2 Z9 3 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0887-8013 J9 J CLIN LAB ANAL JI J. Clin. Lab. Anal. PY 2002 VL 16 IS 1 BP 5 EP 10 DI 10.1002/jcla.2062 PG 6 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 514TF UT WOS:000173456600002 PM 11835524 ER PT J AU Lathers, CM AF Lathers, CM TI Endocrine disruptors: A new scientific role for clinical pharmacologists? Impact on human health, wildlife, and the environment SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Review ID HUMAN BREAST-CANCER; MALE REPRODUCTIVE-TRACT; MAMMARY-TUMOR GROWTH; UNITED-STATES; SPERM COUNTS; 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN TCDD; ANTITUMORIGENIC ACTIVITY; RECEPTOR SUPERFAMILY; TESTICULAR CANCER; PHYTO-ESTROGENS AB It is important for the clinical pharmacologist to understand the potential human health implications of exposure to environmental chemicals that may act as hormonally active agents. It is necessary to have an understanding of how pharmaceutical and personal cure products and other chemicals affect the ecosystem of planet Earth and to understand how they may negatively contribute to human disease. Clinical pharmacologists must understand the various definitions of endocrine disruptors and be able to "decipher" these terms for their patients. Understanding the need for the EPA endocrine disruptor screening program and possessing knowledge of the screening assays used to assess endocrine activity potential are two essential components relevant to the topic of endocrine disruptors. Clinical pharmacologists have an opportunity to play an important role in resolving the question of what role endocrine disruptors play in initiating human disease since some scientists argue that the present evidence is not compelling. Clinical pharmacologists can also play an important role in the evaluation of the risk assessment and use of risk management and risk communication tools required to address public health concerns related to actions of endocrine disruptors. It is important that clinical pharmacologists work with veterinary clinical pharmacologists, toxicologists, industrial chemists, regulators, the scientific community the general public, and environmental groups to understand the impact of endocrine disruptors on human health, wildlife, and the environment with un ultimate goal to minimize and/or alleviate the unwanted, detrimental effects of the endocrine disruptors. (C) 2002 the American College of Clinical Pharmacology. C1 US FDA, Ctr Vet Med, Off New Anim Drug Evaluat, Rockville, MD 20857 USA. RP Lathers, CM (reprint author), US FDA, Ctr Vet Med, Off New Anim Drug Evaluat, Rockville, MD 20857 USA. NR 107 TC 27 Z9 27 U1 1 U2 12 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD JAN PY 2002 VL 42 IS 1 BP 7 EP 23 DI 10.1177/0091270002042001001 PG 17 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 506VF UT WOS:000172991900001 PM 11808826 ER PT J AU Doerge, DR Churchwell, MI Beland, FA AF Doerge, DR Churchwell, MI Beland, FA TI Analysis of DNA adducts from chemical carcinogens and lipid peroxidation using liquid chromatography and electrospray mass spectrometry SO JOURNAL OF ENVIRONMENTAL SCIENCE AND HEALTH PART C-ENVIRONMENTAL CARCINOGENESIS & ECOTOXICOLOGY REVIEWS LA English DT Review DE DNA adducts; mass spectrometry; dosimetry ID RISK ASSESSMENT; QUANTITATIVE-ANALYSIS; OXIDATIVE DAMAGE; ETHYL CARBAMATE; HUMAN TISSUES; CANCER RISK; IN-VITRO; EXPOSURE; 1,N-6-ETHENODEOXYADENOSINE; 8-HYDROXYDEOXYGUANOSINE AB The identification and dosimetry of DNA adducts are cornerstones of research on cancer etiology in experimental animals and humans. DNA adducts can result from exposure to exogenous chemical carcinogens or through reactions with endogenous by-products of oxidative metabolism. An important research need is high throughput methodology for quantification of any and all adducts that are present at trace amounts in DNA derived from target tissues of animals and humans. This review describes some recent progress made through applications of liquid chromatography coupled with mass spectrometry to structural characterization of unknown DNA adducts and highly sensitive quantitative analysis of target adducts. C1 Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Doerge, DR (reprint author), Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 38 TC 8 Z9 8 U1 1 U2 8 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 1059-0501 J9 J ENVIRON SCI HEAL C JI J. Environ. Sci. Health Pt. C-Environ. Carcinog. Ecotoxicol. Rev. PY 2002 VL 20 IS 1 BP 1 EP 20 DI 10.1081/GNC-120003925 PG 20 WC Oncology; Environmental Sciences; Toxicology SC Oncology; Environmental Sciences & Ecology; Toxicology GA 562DV UT WOS:000176182900001 PM 12734050 ER PT J AU Wu, YS Fang, GC Fu, PPC Yang, CJ AF Wu, YS Fang, GC Fu, PPC Yang, CJ TI The measurements of ambient particulates (TSP, PM2.5, PM2.5-10), chemical component concentration variation, and mutagenicity study during 1998-2001 in central Taiwan SO JOURNAL OF ENVIRONMENTAL SCIENCE AND HEALTH PART C-ENVIRONMENTAL CARCINOGENESIS & ECOTOXICOLOGY REVIEWS LA English DT Review DE PM2.5; PM2.5; TSP; chemical component; Taiwan; mutagenic activity ID SIZE DISTRIBUTIONS; PM10 AEROSOLS; AIR-POLLUTION; URBAN AREAS; HONG-KONG; PARTICLES; TRANSPORT; SUBURBAN; SITES; VISIBILITY AB During June 1998 and February 2001, the experiments of this study were conducted at four sampling sites (THUPB, THUC, HKIT and CCRT) with different characters (suburban, rural and traffic). The chemical components (Cl-, NO3-, SO42-, Na+, NH4+, K+, Mg2+, Ca2+, Fe, Zn, Pb, Ni) in suspended particle were also analyzed simultaneously. The particulate mass concentrations are higher in the traffic site (CCRT) than the other sampling sites in this study. This is because that high traffic density flow characterized CCRT sampling site. Besides, the fine particle (PM2.5) concentration was the dominant species out of the total suspended particles in central Taiwan, Taichung. The same phenomenon is found in most of cities around the world. Moreover, chloride, nitrate sulfate and ammonium are higher in Taiwan than other sampling sites in the world. The results also indicated that the control of acidic and secondary aerosol pollutants have become an important issue in Taiwan. In addition, mutagenic assays on the organic extracts of airborne particulates at different sampling sites were also conducted in central Taiwan. The data obtained here also reflected that the mutagenicity of the suspended particulates are significantly higher in winter period than it occurred in summer period. C1 Hungkuang Inst Technol, Air Tox & Environm Anal Lab, Taichung 433, Taiwan. Hungkuang Inst Technol, Dept Comp Sci & Informat Engn, Taichung 433, Taiwan. Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Wu, YS (reprint author), Hungkuang Inst Technol, Air Tox & Environm Anal Lab, Sha Lu, Taichung 433, Taiwan. NR 29 TC 6 Z9 6 U1 1 U2 7 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 1059-0501 J9 J ENVIRON SCI HEAL C JI J. Environ. Sci. Health Pt. C-Environ. Carcinog. Ecotoxicol. Rev. PY 2002 VL 20 IS 1 BP 45 EP 59 DI 10.1081/GNC-120003928 PG 15 WC Oncology; Environmental Sciences; Toxicology SC Oncology; Environmental Sciences & Ecology; Toxicology GA 562DV UT WOS:000176182900004 PM 12734053 ER PT J AU Sahu, SC AF Sahu, SC TI Dual role of organosulfur compounds in foods: A review SO JOURNAL OF ENVIRONMENTAL SCIENCE AND HEALTH PART C-ENVIRONMENTAL CARCINOGENESIS & ECOTOXICOLOGY REVIEWS LA English DT Review DE organosulfur compounds; thiocompounds; toxicity; carcinogen; anticarcinogen; oxidant; antioxidant; oxygen radicals ID GARLIC ALLIUM-SATIVUM; ALLERGIC CONTACT-DERMATITIS; PRIMARY RAT HEPATOCYTES; DIALLYL SULFIDE; LIPID-PEROXIDATION; OXIDATIVE STRESS; AROMATIC DISULFIDES; FREE-RADICALS; GENUS ALLIUM; HEMOLYTIC-ACTIVITY AB Organosulfur compounds present in natural food are generally considered as beneficial for health because of their antioxidant and anticarcinogenic properties. This has led to their excessive and long-term consumption. However, there is also evidence that these compounds demonstrate toxicity and adverse health effects suggesting their potential dual biological roles. Thus, they can act as double-edged biological swords. C1 US FDA, Ctr Food Safety & Appl Nutr, Off Appl Res & Safety Assessment, Div In Vitro & Biochem Toxicol, Laurel, MD 20708 USA. RP Sahu, SC (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Appl Res & Safety Assessment, Div In Vitro & Biochem Toxicol, 8301 Muirkirk Rd, Laurel, MD 20708 USA. NR 100 TC 16 Z9 16 U1 0 U2 4 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 1059-0501 J9 J ENVIRON SCI HEAL C JI J. Environ. Sci. Health Pt. C-Environ. Carcinog. Ecotoxicol. Rev. PY 2002 VL 20 IS 1 BP 61 EP 76 DI 10.1081/GNC-120005388 PG 16 WC Oncology; Environmental Sciences; Toxicology SC Oncology; Environmental Sciences & Ecology; Toxicology GA 562DV UT WOS:000176182900005 PM 12734054 ER PT J AU Cook, DW O'Leary, P Hunsucker, JC Sloan, EM Bowers, JC Blodgett, RJ DePaola, A AF Cook, DW O'Leary, P Hunsucker, JC Sloan, EM Bowers, JC Blodgett, RJ DePaola, A TI Vibrio vulnificus and Vibrio parahaemolyticus in US retail shell oysters: A national survey from June 1998 to July 1999 SO JOURNAL OF FOOD PROTECTION LA English DT Article ID GULF-COAST OYSTERS; UNITED-STATES; INFECTIONS; GENE; TEMPERATURE; EMERGENCE; FLORIDA; GROWTH; PROBE AB From June 1998 to July 1999, 370 lots of oysters in the shell were sampled at 275 different establishments (71%, restaurants or oyster bars; 27%, retail seafood markets; and 2%, wholesale seafood markets) in coastal and inland markets throughout the United States, The oysters were harvested from the Gulf 49%), Pacific (14%), Mid-Atlantic (18%), and North Atlantic (11%) Coasts of die United States and from Canada (8%). Densities of Vibrio vulnificus and Vibrio parahaemoyticus were determined using a modification of the most probable number (MPN) techniques described in the Food and Drug Administration's Bacteriological Analytical Manual. DNA probes and enzyme immunoassay were used to identify suspect isolates and to determine the presence of the thermostable direct hemolysin gene associated with pathogenicity of V parahaemolyticus, Densities of both V vulnificus and V. parahaemolyticus in market oysters from all harvest regions followed a seasonal distribution, with highest densities in the summer. Highest densities of both organisms were observed in oysters harvested from the Gulf Coast, where densities often exceeded 10,000 MPN/g. The majority (78%) of lots harvested in the North Atlantic, Pacific, and Canadian Coasts had V. vulnificus densities below the detectable level of 0.2 MPN/g; none exceeded 100 MPN/g. V. parahaemolyticus densities were greater than those of V. vulnificus in lots from these same areas, with some lots exceeding 1,000 MPN/g for V parahaemolyticus. Some lots from the Mid-Atlantic states exceeded 10,000 MPN/g for both V. vulnificus and V. parahaemolyticus. Overall, there was a significant correlation between V. vulnificus and V. parahaemolyticus densities (r = 0.72, n = 202, P < 0.0001), but neither density correlated with salinity. Storage time significantly affected the V. vulnificus (10% decrease per day) and V. parahaemolyticus (7% decrease per day) densities in market oysters. The thermostable direct hemolysin gene associated with V. parahaemolyticus virulence was detected in 9 of 3,429 (03%) V. parahaemolyticus cultures and in 8 of 198 (4.0%) lots of oysters. These data can be used to estimate the exposure of raw oyster consumers to V. vulnificus and V. parahaemolyticus. C1 US FDA, Gulf Coast Seafood Lab, Dauphin Isl, AL 36528 USA. Univ Alabama, Sch Med, Birmingham, AL 35294 USA. US FDA, SE Reg Lab, Atlanta, GA 30309 USA. US FDA, Denver Dist Lab, Denver, CO 80225 USA. US FDA, Div Math & Stat, Washington, DC 20204 USA. RP DePaola, A (reprint author), US FDA, Gulf Coast Seafood Lab, Dauphin Isl, AL 36528 USA. NR 32 TC 95 Z9 99 U1 0 U2 6 PU INT ASSOC FOOD PROTECTION PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD JAN PY 2002 VL 65 IS 1 BP 79 EP 87 PG 9 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 511TP UT WOS:000173281900012 PM 11808810 ER PT J AU Erdmann, JJ Dickson, JS Grant, MA AF Erdmann, JJ Dickson, JS Grant, MA TI A new technique for Escherichia coli testing of beef and pork carcasses SO JOURNAL OF FOOD PROTECTION LA English DT Article ID ENUMERATION; PETRIFILM; COLIFORMS; EFFICACY; FOODS; COUNT AB A novel technique has been developed to monitor Escherichia coli contamination on carcasses using membrane filtration and m-ColiBlue24 (mCB). mCB is a membrane filtration medium that simultaneously detects total coliforms and E. coli (EC) in a period of 24 +/- 4 h. A study was conducted, using a sponge method to obtain samples from pork carcasses and the excision technique to remove samples from beef carcasses, that compared mCB to standard methods. On pork carcasses, (n = 77), the mean values for mCB and violet red bile agar were 7.4 CFU/15 cm(2) and 6.1 CFU/15 cm(2), respectively. The paired t test (P > 0.05) indicated no significant difference between the two methods (t = 0.5; P = 0.6). Samples from beef carcasses (n = 57) were used to compare mCB to both coliform count and EC Petrifilm. Of these samples, 27 were artificially inoculated with cattle manure. The mean total coliform count was 4.2 log CFU/cm(2) and 4.0 log CFU/cm(2) on mCB and coliform count Petrifilm, respectively. The mean EC count on mCB was 4.0 log CFU/cm(2) and 3.5 log CFU/cm(2) on EC Petrifilm. When comparing mCB to both coliform count (t = 2.4; P = 0,02) and EC (t = 3.5; P < 0,01) Petrifilm, paired t tests (P less than or equal to 0.05) indicated significant differences. C1 Iowa State Univ, Dept Microbiol, Ames, IA 50011 USA. Pillsbury Technol Ctr E, St Paul, MN 55114 USA. US FDA, Bothell, WA 98021 USA. RP Dickson, JS (reprint author), Iowa State Univ, Dept Microbiol, 207 Sci 1, Ames, IA 50011 USA. NR 30 TC 3 Z9 3 U1 0 U2 2 PU INT ASSOC FOOD PROTECTION PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD JAN PY 2002 VL 65 IS 1 BP 192 EP 195 PG 4 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 511TP UT WOS:000173281900029 PM 11808794 ER PT J AU Belay, N Rasooly, A AF Belay, N Rasooly, A TI Staphylococcus aureus growth and enterotoxin A production in an anaerobic environment SO JOURNAL OF FOOD PROTECTION LA English DT Article ID FOOD; PH; OXYGEN AB The effects of strict anaerobic conditions on the growth of Staphylococcus aureus and the production of staphylococcal enterotoxin A (SEA) were studied. The growth of S. aureus, a facultative anaerobic bacterium, is slower anaerobically than aerobically. When grown on brain heart infusion broth at 37degreesC, the anaerobic generation time at mid-log phase was 80 min, compared with 35 min for the aerobic control. In contrast to previous studies demonstrating that staphylococcal cell density was 9- to 17-fold greater in aerobic than in anaerobic cultures, data for a staphylococcal strain implicated in food poisoning showed that the cell density was only two to three times as great in aerobic cultures. Production of SEA was monitored by Western immunoblotting and shown to be growth dependent. With slower anaerobic growth, relatively less toxin was produced than under aerobic conditions, but in both cases SEA was detected after 120 min of incubation. The combined effects of temperature and aeration on S. aureus were also studied, Growth and toxin production of aerobic and anaerobic cultures at temperatures ranging from 14 to 37degreesC were analyzed. Growth was still observed at low temperatures in both environments. A linear model for S. aureus aerobic or anaerobic growth as a function of incubation temperature was developed from these studies. The model was tested from 17 to 35.5degreesC, and the results suggest that the model can accurately predict the S. aureus growth rate in this temperature range. The data suggest that anaerobic conditions are not an effective barrier against S. aureas growth. C1 US FDA, Div Microbiol Studies, Washington, DC 20204 USA. RP Rasooly, A (reprint author), US FDA, Div Microbiol Studies, 200 C St SW, Washington, DC 20204 USA. NR 16 TC 20 Z9 21 U1 2 U2 10 PU INT ASSOC FOOD PROTECTION PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD JAN PY 2002 VL 65 IS 1 BP 199 EP 204 PG 6 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 511TP UT WOS:000173281900031 PM 11808796 ER PT J AU Duffy, PH Lewis, SM Mayhugh, MA McCracken, A Thorn, BT Reeves, PG Blakely, SA Casciano, DA Feuers, RJ AF Duffy, PH Lewis, SM Mayhugh, MA McCracken, A Thorn, BT Reeves, PG Blakely, SA Casciano, DA Feuers, RJ TI Effect of the AIN-93M purified diet and dietary restriction on survival in Sprague-Dawley rats: Implications for chronic studies SO JOURNAL OF NUTRITION LA English DT Article DE AIN-93M; purified; dietary; restriction; survival; rats ID CHRONIC CALORIC RESTRICTION; FISCHER-344 RATS; B6C3F1 MICE; NUTRITIONAL INFLUENCES; MAMMARY-TUMORS; PATHOLOGY; MOUSE; VARIABLES; TOXICITY; RODENTS AB Survival, growth and dietary intake (DI) variables were monitored in a chronic 114-wk study in which male Sprague-Dawley rats [n = 120; National Center for Toxicological Research (NCTR) colony] consumed the AIN-93M purified diet ad libitum (AL), or an amount reduced by 31% of total AL intake inclusive of all macro- and micronutrients. The main objectives were to ascertain the survival characteristics of rats fed the AIN-93M diet and to determine whether dietary restriction (DR) increases longevity of rats fed this casein-based diet compared with the use of mixed-protein sources of the NIH-31 cereal-based diet in an earlier study. Body, liver, brain, the brain/body ratio, spleen, thymus and kidney weights, body length and body density were decreased (P < 0.05) by DR, whereas testis weight and skull length were not altered by DR. Significant age effects at 58 and 114 wk were found for body, brain, the brain/body ratio, liver and testis weights, and body density. Survival rates for the AL and 31% DR groups were 43.3 and 57.5%, respectively. Survival curves were not significantly different. The survival rate for AL rats fed the AIN-93M diet was not different from that of AL rats fed the NIH-31 diet (43.3 and 51.7%, respectively). However, the survival rate for 31% DR rats fed the AIN-93M diet was significantly lower than 25% DR rats fed the NIH-31 diet (57.5 and 87.5%, respectively) although both groups had similar body weights and energy intake at various ages. Nutritional components in the NIH-31 diet that are missing and/or reduced in the AIN-93M diet may interact with DR to increase 114-wk survival. Although the survivability, growth and anatomical results of this study suggest that the AIN-93M diet is suitable for chronic rodent studies, additional studies such as comprehensive histopathologic and physiologic investigations must be undertaken to complete the evaluation process. C1 US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. US FDA, Natl Ctr Toxicol Res, Bionet Corp, Jefferson, AR 72079 USA. US FDA, Natl Ctr Toxicol Res, ROW Sci Inc, Jefferson, AR 72079 USA. USDA ARS, Grand Forks Human Nutr Res Ctr, Grand Forks, ND 58202 USA. US FDA, Ctr Food Safety & Appl Nutr, US Publ Hlth Serv, Washington, DC 20204 USA. US FDA, Natl Ctr Toxicol Res, Off Director, Jefferson, AR 72079 USA. RP Duffy, PH (reprint author), US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. NR 34 TC 29 Z9 29 U1 0 U2 2 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD JAN PY 2002 VL 132 IS 1 BP 101 EP 107 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 508KX UT WOS:000173088600016 PM 11773515 ER PT J AU Whitby, JL Hitchins, VM AF Whitby, JL Hitchins, VM TI Endotoxin levels in steam and reservoirs of table-top steam sterilizers SO JOURNAL OF REFRACTIVE SURGERY LA English DT Article ID BIOFILMS AB PURPOSE: To document endotoxin levels in "Statim" cassette sterilizer reservoirs and in steam delivered to the cassette in the unwrapped instrument cycle. To document endotoxin levels in sterilizer reservoir water using different management protocols. METHODS: Endotoxin levels were determined using the Limulus Amebocyte Lysate test. Endotoxin preparations were from Escherichia coli and Ralstonia pickettii. All samples were collected in depyrogenated glassware and stored at -20degreesC until assayed. RESULTS: The majority of water samples contained <1.0 Endotoxin Unit (EU)/ml. The highest level found in sterilizers in clinical use was 5.3 EU/ml. Endotoxin was not detected in steam condensate within the limits of the assay. When the endotoxin level in the reservoir water was experimentally enhanced to 200 EU/ml, cassette steam condensate endotoxin levels were from 0.5% to 5% of the reservoir level. Daily and weekly emptying of the cassette reservoir consistently yielded low endotoxin levels as did monthly emptying, but with the latter there was a trend toward higher levels that favors weekly emptying as a precautionary measure. CONCLUSIONS: Endotoxin levels in the reservoirs of 23 sterilizers involving 240 samplings were never high enough to yield detectable endotoxin levels in steam in the sterilizer cassette. Regular weekly emptying of sterilizer reservoirs would eliminate the risk of endotoxin transfer during steam sterilization. C1 Univ Western Ontario, Dept Microbiol & Immunol, London, ON, Canada. US FDA, Ctr Devices & Radiol Hlth, Div Life Sci, Rockville, MD 20857 USA. RP Whitby, JL (reprint author), 1551 Ryersie Rd, London, ON N6G 2S2, Canada. NR 12 TC 11 Z9 13 U1 0 U2 1 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 JAN-FEB PY 2002 VL 18 IS 1 BP 51 EP 57 PG 7 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 514GF UT WOS:000173430100008 PM 11828908 ER PT J AU Schwartz, A Wang, L Early, E Gaigalas, A Zhang, YZ Marti, GE Vogt, RF AF Schwartz, A Wang, L Early, E Gaigalas, A Zhang, YZ Marti, GE Vogt, RF TI Quantitating fluorescence intensity from fluorophore: The definition of MESF assignment SO JOURNAL OF RESEARCH OF THE NATIONAL INSTITUTE OF STANDARDS AND TECHNOLOGY LA English DT Article DE flow cytometer; fluorescein; fluorescence; MESF; microbeads; quantitation; SRM 1932 AB The quantitation of fluorescence radiance may at first suggest the need to obtain the number of fluorophore that are responsible for the measured fluorescence radiance. This goal is beset by many difficulties since the fluorescence radiance depends on three parameters 1) the probability of absorbing a photon (molar extinction), 2) the number of fluorophores, and 3) the probability of radiative decay of the excited state (quantum yield). If we use the same fluorophore in the reference solution and the analyte then, to a good approximation, the molar extinction drops out from the comparison of fluorescence radiance and we are left with the comparison of fluorescence yield which is defined as the product of fluorophore concentration and the molecular quantum yield. The equality of fluorescence yields from two solutions leads to the notion of equivalent number of fluorophores in the two solutions that is the basis for assignment of MESF (Molecules of Equivalent Soluble Fluorophore) values. We discuss how MESF values are assigned to labeled microbeads and by extension to labeled antibodies, and how these assignments can lead to the estimate of the number of bound antibodies in flow cytometer measurements. C1 Ctr Quantitat Cytometry, San Juan, PR 00919 USA. Natl Inst Stand & Technol, Gaithersburg, MD 20899 USA. Mol Probes Inc, Eugene, OR 97402 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. CDC, Div Sci Lab, Atlanta, GA 30341 USA. RP Schwartz, A (reprint author), Ctr Quantitat Cytometry, POB 194344, San Juan, PR 00919 USA. EM lili.wang@nist.gov; edward.early@nist.gov; adolfas.gaigalas@nist.gov NR 11 TC 44 Z9 45 U1 1 U2 12 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPERINTENDENT DOCUMENTS,, WASHINGTON, DC 20402-9325 USA SN 1044-677X J9 J RES NATL INST STAN JI J. Res. Natl. Inst. Stand. Technol. PD JAN-FEB PY 2002 VL 107 IS 1 BP 83 EP 91 DI 10.6028/jres.107.009 PG 9 WC Instruments & Instrumentation; Physics, Applied SC Instruments & Instrumentation; Physics GA 538XX UT WOS:000174841400006 PM 27446720 ER PT J AU Allen, SS AF Allen, SS TI Regulatory and drug development issues related to female sexual dysfunction SO JOURNAL OF SEX & MARITAL THERAPY LA English DT Article; Proceedings Paper CT Annual Meeting of the International-Society-for-the-Study-of-Womens-Sexual-Health CY OCT 25-28, 2002 CL BOSTON, MASSACHUSETTS SP Int Soc Study Womens Sex Hlth AB Following the approval of sildenalfil for the treatment of erectile dysfuncttion, an increased awareness of and interest in female sexual dysfunction developed on the part of the academic and research communities as well as the pharmaceutical industry. This article will focus on regulatory, issues related to the development of drug products to treat female sexual dysfunction and will describe a recently published drug development guidance document for this indication. C1 US FDA, Div Reprod & Urol Drug Prod, Rockville, MD 20857 USA. RP Allen, SS (reprint author), US FDA, Div Reprod & Urol Drug Prod, HFD-580, Rockville, MD 20857 USA. NR 3 TC 1 Z9 1 U1 2 U2 2 PU BRUNNER-ROUTLEDGE PI PHILADELPHIA PA 325 CHESTNUT ST, 8TH FL, PHILADELPHIA, PA 19106 USA SN 0092-623X J9 J SEX MARITAL THER JI J. Sex Marital Ther. PY 2002 VL 28 SU 1 BP 11 EP 16 DI 10.1080/00926230252851159 PG 6 WC Psychology, Clinical; Family Studies SC Psychology; Family Studies GA 529VU UT WOS:000174322300003 PM 11898693 ER PT J AU Okayama, A Stuver, SO Tabor, E Tachibana, N Kohara, M Mueller, NE Tsubouchi, H AF Okayama, A Stuver, SO Tabor, E Tachibana, N Kohara, M Mueller, NE Tsubouchi, H TI Incident hepatitis C virus infection in a community-based population in Japan SO JOURNAL OF VIRAL HEPATITIS LA English DT Article DE cohort study; hepatitis C virus; incidence; seroepidemiologic methods ID ANTI-HCV ANTIBODY; BLOOD-DONORS; HETEROSEXUAL TRANSMISSION; HEPATOCELLULAR-CARCINOMA; SOUTHWESTERN JAPAN; CLINICAL OUTCOMES; MARRIED-COUPLES; RURAL AREA; PREVALENCE; SEROCONVERSION AB Hepatitis C virus (HCV) is an important cause of liver disease throughout the world. However, the natural history and pathogenesis of this infection is still not completely understood. The aim of this study was to characterize the evolution of incident, asymptomatic HCV infection in a community-based population in Japan. The Miyazaki Cohort Study is a prospective study of adult residents in two villages, one of which has a very high prevalence of HCV. Nine hundred and seventy-three people from this village were enrolled in the cohort between 1984 and 199 5, with antibodies to HCV (anti-HCV) found in 23%. During subsequent visits to annual health screens, new HCV seroconverters were identified among susceptible individuals, and their sequential samples were tested for anti-HCV, HCV-RNA, and HCV core antigen. Fourteen participants (six males, eight females) acquired anti-HCV during the first 11 years of study follow-up, at an incidence rate of 362 per 100 000 person-years. Detectable HCV-RNA and high anti-HCV titres (>1:2048) were observed for more than 5 years following seroconversion in 80% (8/10) of seroconverters with sufficient information, indicating the development of persistent infection in these subjects. Three (37.5%) of the eight sero converters with persistent infection had fairly consistent, albeit mild, alanine aminotransferase elevations (30-130 IU/L) during the study. Anti-HCV seroconversions occurred at a very high rate in this community-based population in Japan, in which this infection is endemic. Persistence also developed at a high frequency among the cases of newly acquired infection, although the associated liver enzyme abnormalities were mild. C1 Miyazaki Med Coll, Dept Internal Med 2, Miyazaki 88916, Japan. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. US FDA, Div Emerging & Transfus Transmitted Dis, Bethesda, MD 20014 USA. Tokyo Metropolitan Inst Med Sci, Tokyo 113, Japan. RP Okayama, A (reprint author), Miyazaki Med Coll, Dept Internal Med 2, 5200 Kihara, Miyazaki 88916, Japan. FU NCI NIH HHS [CA38450] NR 37 TC 34 Z9 35 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 1352-0504 J9 J VIRAL HEPATITIS JI J. Viral Hepatitis PD JAN PY 2002 VL 9 IS 1 BP 43 EP 51 DI 10.1046/j.1365-2893.2002.00331.x PG 9 WC Gastroenterology & Hepatology; Infectious Diseases; Virology SC Gastroenterology & Hepatology; Infectious Diseases; Virology GA 514CP UT WOS:000173420700006 PM 11851902 ER PT J AU Byrnes, KR Waynant, RW Ilev, IK Anders, JJ AF Byrnes, KR Waynant, RW Ilev, IK Anders, JJ TI Cellular invasion following spinal cord lesion and low power laser irradiation SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract C1 Uniformed Serv Univ Hlth Sci, Neurosci Program, Bethesda, MD 20814 USA. Uniformed Serv Univ Hlth Sci, Dept Anat Physiol & Genet, Bethesda, MD 20814 USA. US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. NR 0 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 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PY 2002 SU 14 MA 38 BP 11 EP 11 PG 1 WC Dermatology; Surgery SC Dermatology; Surgery GA 536XE UT WOS:000174726500037 ER PT J AU Anders, JJ Byrnes, KR Barna, L Chenault, VM Longo, L Miracco, C AF Anders, JJ Byrnes, KR Barna, L Chenault, VM Longo, L Miracco, C TI FGF expression increases with low power laser irradiation during healing of cutaneous wounds in normal and diabetic Psammomys obesus SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract C1 USUHS, Dept Anat Physiol & Genet, Bethesda, MD USA. USUHS, Program Neurosci, Bethesda, MD USA. US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. Univ Siena, Specializat Sch Gen Surg, I-53100 Siena, Italy. Univ Siena, Histopathol Inst, I-53100 Siena, Italy. 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 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PY 2002 SU 14 MA 41 BP 12 EP 12 PG 1 WC Dermatology; Surgery SC Dermatology; Surgery GA 536XE UT WOS:000174726500040 ER PT J AU Kaufman, GE Myers, ML Pass, CL Bej, AK Kaysner, CA AF Kaufman, GE Myers, ML Pass, CL Bej, AK Kaysner, CA TI Molecular analysis of Vibrio parahaemolyticus isolated from human patients and shellfish during US Pacific north-west outbreaks SO LETTERS IN APPLIED MICROBIOLOGY LA English DT Article ID DIRECT HEMOLYSIN TDH; UNITED-STATES; UREA HYDROLYSIS; GENES; TRH; OYSTERS AB Aims: The objective of this study was to investigate the occurrence and distribution of haemolysin genes, plasmid profile, serogroup analysis and cellular urease activity for Vibrio parahaemolyticus isolates from infected human patients and oysters from the Pacific northwestern United States between 1988 and 1997. Methods and Results: All of the clinical and environmental isolates tested in this study exhibited the presence of the thermolabile haemolysin gene, tl, confirming that all of the isolates were V. parahaemolyticus. Furthermore, the V parahaemolyticus isolates that contained either the thermostable direct haemolysin gene, tdh, or the thermostable direct haemolysin-related gene, trh, or both, were also positive for urease. Isolates from infected human patients belong to serogroups 01 and 04, whereas, the isolates from oysters belong to serogroups 01, 04 and O5. These results suggest that the presence of a V. parahaemolyticus serogroup 01 and 04 could indicate the presence of a virulent strain of this pathogen. In this study, the presence of the haemolysin genes, serogroup profiles and urease production in V. parahaemolyticus isolated from human patients correlated with the oysters collected during the outbreaks. However, no significant correlation of the plasmid profiles was detected, based on their distribution and molecular weights, between V. parahaemolyticus isolated from infected human patients and from oysters collected during this outbreak. Conclusions, Significance and Impact of the Study: It is apparent from this study that the identification of the haemolysin genes by multiplex PCR amplification, in conjunction with serogroup analysis and urease production, can be used to monitor shellfish for the presence of potentially pathogenic strains of V. parahaemolyticus. C1 Univ Alabama, Dept Biol, Birmingham, AL 35294 USA. US FDA, Seafood Prod Res Ctr, Bothell, WA USA. RP Bej, AK (reprint author), Univ Alabama, Dept Biol, 1300 Univ Blvd, Birmingham, AL 35294 USA. NR 21 TC 26 Z9 27 U1 1 U2 2 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0266-8254 J9 LETT APPL MICROBIOL JI Lett. Appl. Microbiol. PY 2002 VL 34 IS 3 BP 155 EP 161 DI 10.1046/j.1472-765x.2002.01076.x PG 7 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 532FX UT WOS:000174464600001 PM 11874534 ER PT S AU Leak, LV Petricoin, EF Jones, M Paweletz, CP Ardekani, AM Fusaro, VA Ross, S Liotta, LA AF Leak, LV Petricoin, EF Jones, M Paweletz, CP Ardekani, AM Fusaro, VA Ross, S Liotta, LA BE Rockson, SG TI Proteomic technologies to study diseases of the lymphatic vascular system SO LYMPHATIC CONTINUUM: LYMPHATIC BIOLOGY AND DISEASE SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on the Lymphatic Continuum CY MAY 03-04, 2002 CL NIH NATCHER CTR, BETHESDA, MARYLAND HO NIH NATCHER CTR DE proteomics; cancer; lymph; lymphatic endothelium; lymphedema; laser capture microdissection; protein microarrays; SELDI-TOF-mass spectroscopy ID LASER CAPTURE MICRODISSECTION; IMMOBILIZED PH GRADIENTS; MASS-SPECTROMETRY; 2-DIMENSIONAL ELECTROPHORESIS; HUMAN GENOME; VEGF-C; PROTEINS; CANCER; PROSTATE; CELLS AB Now that the human genome has been mapped, a new challenge has emerged: deciphering the various products of individual genes. Consequently, new proteomic technologies are being developed to monitor and identify protein function and interactions responsible for the total activities of the cell. The application of these new proteomic technologies to study cellular activities, will lead to a faster sample throughput and increased sensitivity for the detection of individual proteins, thus providing major opportunities for the discovery of new biomarkers for the early detection of protein alterations associated with the progression of the disease state. C1 NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. US FDA, Clin Proteom Program Therapeut Prot, CBER, Bethesda, MD 20892 USA. Howard Univ, Coll Med, Dept Anat, Washington, DC 20059 USA. NHLBI, Lab Anim Surg & Med, NIH, Bethesda, MD 20892 USA. RP Liotta, LA (reprint author), NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. NR 61 TC 6 Z9 8 U1 0 U2 2 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-414-5 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2002 VL 979 BP 211 EP 228 PG 18 WC Immunology; Multidisciplinary Sciences SC Immunology; Science & Technology - Other Topics GA BW05J UT WOS:000180751900021 PM 12543730 ER PT J AU Kumar, S Epstein, JE Richie, TL AF Kumar, S Epstein, JE Richie, TL TI Vaccines against asexual stage malaria parasites SO MALARIA IMMUNOLOGY, 2ND EDITION SE CHEMICAL IMMUNOLOGY LA English DT Review ID MEROZOITE SURFACE PROTEIN-1; PLASMODIUM-FALCIPARUM ANTIGEN; APICAL MEMBRANE ANTIGEN; CARBOXYL-TERMINAL FRAGMENT; SERINE-REPEAT ANTIGEN; INHIBITORY MONOCLONAL-ANTIBODIES; PROTECTIVE IMMUNE-RESPONSE; RECOMBINANT SERA PROTEIN; AMINO-ACID SEQUENCE; AOTUS MONKEYS C1 Naval Med Res Ctr, Malaria Program, Silver Spring, MD USA. RP Kumar, S (reprint author), US FDA, Lab Bacterial & Parasit Dis, Off Blood Review & Res, DETTD,CBER, HMF-313,1401 Rockville Pike, Rockville, MD 20852 USA. NR 139 TC 19 Z9 20 U1 1 U2 1 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 1015-0145 J9 CHEM IMMUNOL JI Chem.Immunol. PY 2002 VL 80 BP 262 EP 286 PG 25 WC Immunology SC Immunology GA BU66Z UT WOS:000176677300014 PM 12058644 ER PT S AU Beiden, SV Wagner, RF Doi, K Nishikawa, RM Freedman, M Ben Lo, SC Xu, XW AF Beiden, SV Wagner, RF Doi, K Nishikawa, RM Freedman, M Ben Lo, SC Xu, XW BE Chakraborty, DP Krupinski, EA TI On independent versus sequential reading in ROC studies of computer-assist modalities SO MEDICAL IMAGING 2002: IMAGE PERCEPTION, OBSERVER PERFORMANCE, AND TECHNOLOGY ASSESSMENT SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Medical Imaging 2002 Conference CY FEB 24-28, 2002 CL SAN DIEGO, CA SP SPIE, Amer Assoc Phys Med, Amer Physiol Soc, FDA Ctr Devices & Radiol Hlth, Soc Imaging Sci & Technol, Natl Elect Mfg Assoc, Diagnost Imaging & Therapy Syst Div, Radiol Soc N Amer, Soc Comp Applicat Radiol DE computer-aided diagnosis (CAD); multiple-reader multiple-case (MRMC) receiver operating characteristic (ROC) ID OF-VARIANCE MODELS; AIDED DIAGNOSIS; COMPONENTS; INDEX AB This paper provides results of a statistical analysis of two methods for arranging the temporal sequencing of the unaided vs computer-assisted reading in multiple-reader, multiple-case (MRMC) receiver operating characteristic (ROC) studies of computer-aided detection of solitary pulmonary nodules (SPNs) on chest radiographs. The modes are the "Independent" mode, in which the readings are separated by a time on the order of one month, and the "Sequential" mode, in which the CAD-assisted reading immediately follows the unassisted reading. The method of Beiden, Wagner, Campbell (BWC) was used to decompose the variance of the ROC area summary accuracy measure into the components that are correlated across unaided and aided reading conditions and the components that are uncorrelated across these reading conditions. The latter are the only components of variability that contribute to the uncertainty in a measurement of the difference in reader performance between reading conditions. These uncorrelated components were dramatically reduced in the Sequential reading mode compared to the Independent reading mode-while the total reader variability remained almost constant. The results were remarkably similar across two independent studies analyzed. This may have important practical consequences because the Sequential mode is the least demanding on reader logistics and time. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Beiden, SV (reprint author), US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. OI Nishikawa, Robert/0000-0001-7720-9951 NR 16 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 0-8194-4431-6 J9 P SOC PHOTO-OPT INS PY 2002 VL 4686 BP 198 EP 204 DI 10.1117/12.462678 PG 7 WC Engineering, Biomedical; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BU57U UT WOS:000176405400023 ER PT S AU Beiden, SV Maloof, MA Wagner, RF AF Beiden, SV Maloof, MA Wagner, RF BE Sonka, M Fitzpatrick, JM TI ROC components-of-variance analysis of competing classifiers SO MEDICAL IMAGING 2002: IMAGE PROCESSING, VOL 1-3 SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Medical Imaging 2002 Conference CY FEB 24-28, 2002 CL SAN DIEGO, CA SP SPIE, Amer Assoc Phys Med, Amer Physiol Soc, FDA Ctr Devices & Radiol Hlth, Soc Imaging Sci & Technol, Natl Elect Mfg Assoc, Diagnost Imaging & Therapy Syst Div, Radiol Soc N Amer, Soc Comp Applicat Radiol DE statistical pattern recognition; ROC analysis; training and testing; components-of-variance models; bootstrapping ID STATISTICAL PATTERN-RECOGNITION; SAMPLE-SIZE; PERFORMANCE; DESIGN; BOOTSTRAP; MODELS; CURVE; AREA AB In the last decade in the field of diagnostic imaging, the problem of variability of reader skill as well as patient case difficulty has given rise to a multivariate approach to receiver operating characteristic (ROC) analysis. The multivariate approach is the so-called multiple-reader, multiple-case (MRMC) ROC paradigm in which every reader reads every patient case and, where possible, in each of two modalities under comparison. The present paper demonstrates the isomorphism between patient cases, image readers, and imaging modalities in diagnostic imaging and, respectively, test sets, training sets, and competing discriminant algorithms in the field of statistical pattern recognition (SPR). Thus, the MRMC paradigm can be brought directly across from imaging to SPR. Recent MRMC ROC analytical methods are demonstrated in the context of SPR for the task of analyzing the natural components of variance in that problem involving test sets, training sets, and competing discriminants. Monte Carlo trials reported here indicate that the conventional wisdom that "the variance of measures of classifier accuracy comes mainly from the finite test set" is only true when assessing a single algorithm in a very limited context. In particular, it is generally not true when comparing competing discriminant algorithms; in that case the variance is dominated by the finite training set. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Beiden, SV (reprint author), US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. NR 26 TC 0 Z9 0 U1 0 U2 1 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-4429-4 J9 P SOC PHOTO-OPT INS PY 2002 VL 4684 BP 353 EP 362 DI 10.1117/12.467176 PG 10 WC Engineering, Biomedical; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Optics; Radiology, Nuclear Medicine & Medical Imaging GA BU94Y UT WOS:000177471900036 ER PT S AU Badano, A Leimbach, R AF Badano, A Leimbach, R BE Antonuk, LE Yaffe, MJ TI Depth-dependent phosphor blur in indirect x-ray imaging sensors SO MEDICAL IMAGING 2002: PHYSICS OF MEDICAL IMAGING SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Medical Imaging 2002 Conference CY FEB 24-28, 2002 CL SAN DIEGO, CA SP SPIE, Amer Assoc Phys Med, Amer Physiol Soc, FDA Ctr Devices & Radiol Hlth, Soc Imaging Sci & Technol, Natl Elect Mfg Assoc, Diagnost Imaging & Therapy Syst Div, Radiol Soc N Amer, Soc Comp Applicat Radiol ID RADIATION DETECTORS; SCREENS; SCINTILLATORS; LUMINESCENCE AB The influence of phosphor screens on the digital system image quality has been studied in a number of papers. However, there has been no detailed description of the effect of depth of x-ray interaction on the blur characteristics of the phosphor and on optical collection efficiency for both powder and structured screens. We present an analysis based on optical Monte Carlo simulations of the depth-dependent phosphor blur of two classes of single-layer phosphor screens: homogeneous and columnar. The spectral sensitivity of the optical sensor is modeled according to a typical a-Si:H photodiode absorption profile. We used Gd2O2S:Tb and CsI:Tl emission spectra respectively for the powder and columnar phosphor models. We present line-spread (LSF) and modulation transfer (MTF) functions associated with the spread of signal in the phosphor, and optical collection efficiencies. We find good agreement between the Monte Carlo estimates of the MTF and the analytical solutions available in the literature. Our optical collection efficiency results show depth dependence only for the screens with highly scattering and absorptive phosphor with reflective backing, and for the case of scattering phosphor with absorptive backing. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Badano, A (reprint author), US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. OI badano, aldo/0000-0003-3712-6670 NR 31 TC 12 Z9 12 U1 0 U2 2 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-4427-8 J9 P SOC PHOTO-OPT INS PY 2002 VL 4682 BP 94 EP 106 DI 10.1117/12.465546 PG 5 WC Engineering, Biomedical; Optics; Physics, Applied; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Optics; Physics; Radiology, Nuclear Medicine & Medical Imaging GA BU70C UT WOS:000176734000010 ER PT S AU Boswell, JS Badano, A Gagne, RM Gallas, BD Myers, KJ AF Boswell, JS Badano, A Gagne, RM Gallas, BD Myers, KJ BE Antonuk, LE Yaffe, MJ TI Assessment of lesion detectability by Monte Carlo modeling of digital radiography systems SO MEDICAL IMAGING 2002: PHYSICS OF MEDICAL IMAGING SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Medical Imaging 2002 Conference CY FEB 24-28, 2002 CL SAN DIEGO, CA SP SPIE, Amer Assoc Phys Med, Amer Physiol Soc, FDA Ctr Devices & Radiol Hlth, Soc Imaging Sci & Technol, Natl Elect Mfg Assoc, Diagnost Imaging & Therapy Syst Div, Radiol Soc N Amer, Soc Comp Applicat Radiol ID AMORPHOUS SELENIUM AB Previously we used a simple 2-D model to evaluate the imaging performance of a digital radiographic system while varying input parameters such as transducer blur and signal size. We extend this work using a realistic phosphor simulation to explore the effect of the incident x-ray spectrum and the depth dependence of the point spread function and optical collection efficiency. Initially we investigate one Swank screen type representative of a modem powder phosphor design. Images resulting from these simulations are used to get an estimate of the impact of these factors on lesion detectability. Results show that the simple 2-D model gives optimistic estimates of detectability. C1 Food & Drug Adm, Ctr Divices & Radiol Hlth, Rockville, MD 20857 USA. RP Boswell, JS (reprint author), Food & Drug Adm, Ctr Divices & Radiol Hlth, 12720 Twinbrook Pkwy, Rockville, MD 20857 USA. OI Gallas, Brandon/0000-0001-7332-1620; badano, aldo/0000-0003-3712-6670 NR 13 TC 4 Z9 4 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 0-8194-4427-8 J9 P SOC PHOTO-OPT INS PY 2002 VL 4682 BP 665 EP 674 DI 10.1117/12.465612 PG 4 WC Engineering, Biomedical; Optics; Physics, Applied; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Optics; Physics; Radiology, Nuclear Medicine & Medical Imaging GA BU70C UT WOS:000176734000069 ER PT S AU Badano, A Hipper, SJ Jennings, RJ AF Badano, A Hipper, SJ Jennings, RJ BE Mun, SK TI Luminance effects on display resolution and noise SO MEDICAL IMAGING 2002: VISUALIZATION, IMAGE-GUIDED PROCEDURES, AND DISPLAY SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Medical Imaging 2002 Conference CY FEB 24-28, 2002 CL SAN DIEGO, CA SP SPIE, Amer Assoc Phys Med, Amer Physiol Soc, FDA Ctr Devices & Radiol Hlth, Soc Imaging Sci & Technol, Natl Elect Mfg Assoc, Diagnost Imaging & Therapy Syst Div, Radiol Soc N Amer, Soc Comp Applicat Radiol DE medical display; active-matrix liquid crystal display; cathode-ray tube; resolution; modulation transfer function; noise; noise power spectrum AB The measurement of image quality in diagnostic monochrome display devices has been the focus of recent efforts. However, there has not been a complete understanding of the capabilities of such methods to appropriately characterize display resolution and noise. In addition to being influenced by the luminance level of the scene being displayed, both properties are affected by the intrinsic details of the pixel emissive structures. In this paper, we report on the resolution and noise properties of cathode-ray tubes (CRTs) and active-matrix liquid crystal displays (AMLCDs). We present results on the resolution and noise characteristics of 5-megapixel monochrome CRTs and a 3-megapixel monochrome AMLCD with dual-domain in-plane switching pixel design. The CCD camera was calibrated using a uniform light source constructed specifically for excellent spatial uniformity. The methods employed for resolution are based on either the measurement of line patterns or the broadband transfer method. Noise is analyzed in tern-is of 2-dimensional noise power and signal-to-noise ratios. We found that all 4 methods considered are affected by residual deterministic structure in the recorded images. Especially in AMLCDs, the MTFs computed by the line method and broadband response method do not agree, due to contributions of the non-stochastic component that remain in the analyzed images after subtraction of a representative background. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Badano, A (reprint author), US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. OI badano, aldo/0000-0003-3712-6670 NR 5 TC 11 Z9 11 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 0-8194-4426-X J9 P SOC PHOTO-OPT INS PY 2002 VL 4681 BP 305 EP 313 DI 10.1117/12.466932 PG 3 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging; Surgery SC Computer Science; Engineering; Radiology, Nuclear Medicine & Medical Imaging; Surgery GA BU70B UT WOS:000176733900033 ER PT J AU Reddy, VS Leelavathi, S Selvapandiyan, A Raman, R Giovanni, F Shukla, V Bhatnagar, RK AF Reddy, VS Leelavathi, S Selvapandiyan, A Raman, R Giovanni, F Shukla, V Bhatnagar, RK TI Analysis of chloroplast transformed tobacco plants with cry1Ia5 under rice psbA transcriptional elements reveal high level expression of Bt toxin without imposing yield penalty and stable inheritance of transplastome SO MOLECULAR BREEDING LA English DT Article DE Bacillus thuringiensis; Chloroplast transformation; Cry1Ia5; Homologus recombination; insect resistance; Maternal inheritance ID BACILLUS-THURINGIENSIS; TRANSGENIC PLANTS; INSECTICIDE RESISTANCE; HELIOTHIS-ARMIGERA; SELECTABLE MARKER; DELTA-ENDOTOXIN; PLASTID GENOME; FOREIGN GENES; PROTEIN GENES; SITE AB Stable inheritance and sustained-high level expression of foreign genes in the progeny are the most critical factors for successful application of genetic engineering in agriculture. In this study, we have transformed cry1Ia5 into tobacco chloroplasts and studied the expression, inheritance and resistance offered against Helicoverpa armigera over two generations. Under rice chloroplast transcription elements, the Cry1Ia5 protein accumulated up to 3% of total soluble protein in leaf tissue which is similar to 300 folds more when compared to the expression of the same protein in the nuclear transformed plants. Transgenic plants offered complete protection against larvae of H. armigera, irrespective of development stage. Analysis of T0, T1 and T2 generation plants revealed site-specific integration, maternal inheritance and uniform expression of transgenes without imposing any yield penalty. Our results suggest that the overexpression of insecticidal toxin coding genes in chloroplasts would be an effective strategy to delay the emergence of resistance among phytophagous pests. C1 Int Ctr Genet Engn & Biotechnol, New Delhi 67, India. US FDA, Lab Bacterial Parasit & Unconvent Agents, CBER, Bethesda, MD 20892 USA. Int Ctr Genet Engn & Biotechnol, I-34012 Trieste, Italy. RP Reddy, VS (reprint author), Int Ctr Genet Engn & Biotechnol, POB 10504, New Delhi 67, India. NR 45 TC 26 Z9 31 U1 0 U2 6 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1380-3743 J9 MOL BREEDING JI Mol. Breed. PY 2002 VL 9 IS 4 BP 259 EP 269 DI 10.1023/A:1020357729437 PG 11 WC Agronomy; Plant Sciences; Genetics & Heredity; Horticulture SC Agriculture; Plant Sciences; Genetics & Heredity GA 595FM UT WOS:000178097800005 ER PT J AU Ahram, M Best, CJM Flaig, MJ Gillespie, JW Leiva, IM Chuaqui, RF Zhou, G Shu, HJ Duray, PH Linehan, WM Raffeld, M Ornstein, DK Zhao, YM Petricoin, EF Emmert-Buck, MR AF Ahram, M Best, CJM Flaig, MJ Gillespie, JW Leiva, IM Chuaqui, RF Zhou, G Shu, HJ Duray, PH Linehan, WM Raffeld, M Ornstein, DK Zhao, YM Petricoin, EF Emmert-Buck, MR TI Proteomic analysis of human prostate cancer SO MOLECULAR CARCINOGENESIS LA English DT Article DE prostate cancer; proteomics; microarray; microdissection; heterogeneity ID GENE-EXPRESSION; MICROARRAYS; RESOURCES; CARCINOMA; TUMORS; MODEL AB Proteomics is a promising approach in the identification of proteins and biochemical pathways involved in tumorigenesis. In an effort to discover such proteins and pathways that are deregulated in prostate tumorigenesis, cellular proteomes of matched normal prostate epithelial cells and high-grade prostate cancer cells were analyzed by tissue microdissection, two-dimensional electrophoresis, and mass spectrometry. Forty protein alterations were detected in the tumors; however, the majority of these charges were not shared among the 12 neoplasms. In contrast, parallel cDNA microarray analysis identified a number of common gene expression changes. The marked heterogeneity of the observed protein alterations may have significance with regard to tumor biology and research strategies for molecular profiling analyses of human prostate cancer. Published 2002 Wiley-Liss, Inc.(dagger) C1 NCI, Pathogenet Unit, Pathol Lab, NIH, Bethesda, MD 20892 USA. NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. NCI, Sci Applicat Int Corp, NIH, Bethesda, MD 20892 USA. Univ Texas, SW Med Ctr, Dept Biochem, Dallas, TX 75235 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. Univ N Carolina, Dept Urol, Chapel Hill, NC USA. US FDA, Ctr Biol Evaluat & Res, Tissue Proteom Unit, Bethesda, MD USA. RP Emmert-Buck, MR (reprint author), NCI, Pathogenet Unit, Pathol Lab, NIH, Room 2A33,10 Ctr Dr,Bldg 10, Bethesda, MD 20892 USA. NR 23 TC 104 Z9 108 U1 0 U2 5 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD JAN PY 2002 VL 33 IS 1 BP 9 EP 15 DI 10.1002/mc.10019 PG 7 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA 511QK UT WOS:000173276900002 PM 11807953 ER PT J AU McVean, M Weinberg, WC Pelling, JC AF McVean, M Weinberg, WC Pelling, JC TI A p21(waf1)-independent pathway for inhibitory phosphorylation of cyclin-dependent kinase p34(cdc2) and concomitant G(2)/M arrest by the chemopreventive flavonoid apigenin SO MOLECULAR CARCINOGENESIS LA English DT Article DE apigenin; p21(waf1); skin cancer; chemoprevention; G(2)/M arrest ID WILD-TYPE P53; CELL-CYCLE; PROTEIN-KINASE; TYROSINE PHOSPHATASE; CDC25 PROTEIN; ACTIVATES P34CDC2; AGENT APIGENIN; FISSION YEAST; SKH-1 MICE; HUMAN WEE1 AB Apigenin, a nonmutagenic flavonoid, has been shown to inhibit ultraviolet light-induced skin tumorigenesis when topically applied to mouse skin. Our previous studies have shown that apigenin treatment of cultured mouse keratinocytes induces G(2)/M arrest accompanied by an increase in p53 protein stability and expression of p21(waf1). In this study, we determined whether the G(2)/M arrest induced by apigenin was dependent upon the presence of the cyclin dependent kinase inhibitor p21(waf1). We exposed WWT.8 (p21(waf1) wild-type) and WKO.16 (p21(waf1) null) mouse keratinocytes to various doses of apigenin for 24 h and observed G(2)/M arrest in both cell lines, thereby establishing that the apigenin-induced G(2)/M arrest was p21(waf1) independent. A 4-h treatment with apigenin induced increases in p53 protein level by sixfold and tenfold in the WWT.8 p21(waf1) wild-type cells and WKO.16 p21(waf1) null cells, respectively. After 24 h in WWT.8 cells, p21(waf1) protein also was induced in a dose-dependent manner, but it was not expressed in WKO.16 keratinocytes. We then measured the effect of apigenin treatment on the mammalian homologue of the yeast cdc2 gene (p34(cdc2)) cyclin-dependent kinase and cyclin B1 (cycB1), because these proteins complex to regulate G(2)/M progression. Apigenin treatment decreased the protein level of p34(cdc2), and p34(cdc2) kinase activity was inhibited in both p21(waf1+/+) and p21(waf1-/-) cell lines by approximately 40%. The inhibition of p34(cdc2) kinase activity by apigenin treatment correlated with increasing levels of p34(cdc2) phosphorylation at Tyr15, a site in the p34(cdc2) kinase that undergoes inhibitory phosphorylation by Wee1 kinase. Apigenin treatment also had no effect on the protein level or activity of the competing phosphatase, cdc25c, which dephosphorylates p34(cdc2) kinase at Tyr15. Apigenin had little effect on the accumulation of cycB1 protein. These results supported the conclusion that G(2)/M arrest induced by apigenin was accompanied by inhibition of the p34(cdc2) cyclin-dependent kinase protein level and activity in a p21(waf1) -independent manner. (C) 2002 Wiley-Liss, Inc. C1 Univ Kansas, Med Ctr, Dept Pathol & Lab Med, Kansas City, KS 66160 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. RP Pelling, JC (reprint author), Univ Kansas, Med Ctr, Dept Pathol & Lab Med, 3901 Rainbow Blvd, Kansas City, KS 66160 USA. RI Weinberg, Wendy/A-8920-2009 FU NCI NIH HHS [CA72987-05] NR 46 TC 38 Z9 43 U1 1 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD JAN PY 2002 VL 33 IS 1 BP 36 EP 43 DI 10.1002/mc.10016 PG 8 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA 511QK UT WOS:000173276900005 PM 11807956 ER PT J AU Umehara, H Inoue, H Huang, JY Kono, T Minami, Y Tanaka, Y Okazaki, T Mimori, T Bloom, ET Domae, N AF Umehara, H Inoue, H Huang, JY Kono, T Minami, Y Tanaka, Y Okazaki, T Mimori, T Bloom, ET Domae, N TI Role for adapter proteins in costimulatory signals of CD2 and IL-2 on NK cell activation SO MOLECULAR IMMUNOLOGY LA English DT Article DE NK cells; cellular activation; cytotoxicity; signal transduction; cell surface molecules ID NATURAL-KILLER-CELLS; TYROSINE KINASE P72(SYK); JURKAT T-CELLS; PHOSPHATIDYLINOSITOL 3-KINASE; LYMPHOCYTES-T; RECEPTOR; PHOSPHORYLATION; CBL; ANTIGEN; TRANSDUCTION AB Natural killer (NK) cells participate in both innate and adaptive immunity through the prompt secretion of cytokines and ability to lyse virally infected cells or tumor cells. Triggering of NK cells requires aggregation of surface receptors such as CD2 and CD16, and NK cell activity can be augmented in vitro by stimulation with IL-2. In this study, we examined the role of adapter proteins in the increased NK activation following CD2 crosslinking and IL-2 stimulation of NK3.3 cells. NK3.3 cells lysed NK-sensitive K562 cells in aCD2-dependent manner, and IL-2 markedly enhanced lytic activity in a 4h cytotoxic assay. IL-2 also enhanced spontaneous and CD2-mediated granule exocytosis from NK3.3 cells. CD2 crosslinking markedly induced tyrosine phosphorylation of Cbl associated with Grb2 or CrkL, Shc and LAT, compared with IL-2 stimulation. However, costimulation of IL-2 with CD2 crosslinking remarkably enhanced associations of Grb2-Shc and CrkL-Cbl, compared to IL-2 stimulation or CD2 crosslinking alone. In vitro binding studies using GST-fusion proteins revealed that interactions of Grb2-Shc and CrkL-Cbl were mediated through each SH2 domain in tyrosine phosphorylation-dependent manner. Furthermore, CD2 crosslinking, but not IL-2 stimulation, markedly induced tyrosine phosphorylation of LAT. Thus, tyrosine phosphorylation of different adapter proteins and consequent interactions between signaling molecules described here may explain the molecular mechanisms of the additive effects of IL-2 stimulation and CD2 crosslinking on NK cell activation. (C) 2002 Elsevier Science Ltd. All rights reserved. C1 Osaka Dent Univ, Dept Internal Med, Hirakata, Osaka 5731121, Japan. Kyoto Univ, Grad Sch Med, Dept Rheumatol & Clin Immunol, Kyoto 606, Japan. Osaka Dent Univ, Dept Physiol, Hirakata, Osaka 5731121, Japan. Nippon Boehringer Ingelheim, Kawanishi Pharma Inst, Dept Mol Cell Biol, Kawanishi 66001, Japan. Kobe Univ, Sch Med, Dept Biomed Regulat & Parasitol, Kobe, Hyogo 6500017, Japan. Univ Occupat & Environm Hlth, Sch Med, Dept Internal Med 1, Kitakyushu, Fukuoka 8078555, Japan. Kyoto Univ, Grad Sch Med, Dept Hematol & Oncol, Kyoto 606, Japan. US FDA, Ctr Biol Evaluat Res, Div Cellular & Gene Therapies HFM 518, Bethesda, MD 20892 USA. RP Umehara, H (reprint author), Osaka Dent Univ, Dept Internal Med, Hirakata, Osaka 5731121, Japan. NR 72 TC 8 Z9 10 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD JAN PY 2002 VL 38 IS 8 BP 587 EP 596 DI 10.1016/S0161-5890(01)00099-2 PG 10 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA 517PW UT WOS:000173619900003 PM 11792427 ER PT J AU Parshikov, IA Moody, JD Freeman, JP Lay, JO Williams, AJ Heinze, TM Sutherland, JB AF Parshikov, IA Moody, JD Freeman, JP Lay, JO Williams, AJ Heinze, TM Sutherland, JB TI Formation of conjugates from ciprofloxacin and norfloxacin in cultures of Trichoderma viride SO MYCOLOGIA LA English DT Article DE biotransformation; fluoroquinolones ID FUNGUS GLOEOPHYLLUM-STRIATUM; FLUOROQUINOLONE ENROFLOXACIN; MUCOR RAMANNIANUS; DEGRADATION; METABOLITES; TRANSFORMATION; IDENTIFICATION AB The formation of conjugates from two antibacterial fluoroquinolone drugs, ciprofloxacin and norfloxacin, was observed in cultures of Trichoderma vi-ride that had been grown in sucrose-peptone broth and extracted 16 d after dosing with the drugs. Both conjugates were purified by high-performance liquid chromatography and found to be optically active. They were identified by mass and proton nuclear magnetic resonance spectra as 4-hydroxy-3-oxo-4-vinylcyclopent-1-enyl ciprofloxacin and 4-hydroxy-3-oxo-4-vinylcyclopent-1-enyl norfloxacin. The transformation of veterinary fluoroquinolones in the presence of fungi may have ecological significance. C1 US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Sutherland, JB (reprint author), US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RI Lay, Jackson/G-1007-2011; OI Lay, Jackson/0000-0003-3789-2527; Parshikov, Igor/0000-0003-1466-1128 NR 13 TC 10 Z9 10 U1 0 U2 5 PU NEW YORK BOTANICAL GARDEN PI BRONX PA PUBLICATIONS DEPT, BRONX, NY 10458 USA SN 0027-5514 J9 MYCOLOGIA JI Mycologia PD JAN-FEB PY 2002 VL 94 IS 1 BP 1 EP 5 DI 10.2307/3761840 PG 5 WC Mycology SC Mycology GA 518ZC UT WOS:000173697600001 PM 21156472 ER PT J AU Li, SX Hartman, GL Jarvis, BB Tak, H AF Li, SX Hartman, GL Jarvis, BB Tak, H TI A Stachybotrys chartarum isolate from soybean SO MYCOPATHOLOGIA LA English DT Article DE DNA sequence; microscopy; mycotoxin; PCR; soybean pathogen; Stachybotrys chartarum ID TOXIN PRODUCTION; FUSARIUM; GLYCINES; INFANTS; GROWTH; ATRA AB As part of our effort to investigate fungi associated with soybean roots, Stachybotrys chartarum was isolated from soybean root lesions. Since this fungus has not been reported to cause a disease of soybean, the objectives were to identify and characterize this fungus using biological, chemical, and molecular approaches. Fungal morphology was examined using light and environmental scanning electron microscopy. Phialides bearing conidia arose from determinate, macronematous, dark olivaceous conidiophores. The phialides were obovate or ellipsoidal in whorls. Conidia were unicellular, round or ellipsoidal, 5-13 x 4-7 mum, initially hyaline with smooth walls then dark brown to black and rough-walled when mature. Radial growth of the fungus on cornmeal, oatmeal and potato dextrose agar was 38, 47, and 33 mm in diam., respectively, after 10 days at 25 degreesC. Pathogenicity was performed using sorghum grain colonized by S. chartarum placed below sown soybean seeds in a soil : sand (1 : 1) steam-pasteurized mix. Three weeks after inoculation, root lesions ranged from 7 to 25 mm long. The fungus was reisolated from soybean root lesions and was reidentified as S. chartarum. Biochemical analysis indicated that this soybean isolate produced satratoxins G and H along with roridin L-2, as well as the spircyclic lactones and lactams in rice culture. PCR using a S. chartarum-specific primer StacR3 and IT51 amplified a 198-bp DNA fragment from the total genomic DNA. The DNA sequence of the ITS region was 100% identical to the S. chartarum strain ATCC 9182, one nucleotide mismatch with S. chartarum strain UAMH 7900, and differed from all published sequences of 12 other species of Stachybotrys and 2 species of Memnoniella in GenBank with genetic divergence ranging from 5.26 to 9.98%. This molecular evidence further supports the identification of S. chartarum isolated from soybean root lesions. C1 Univ Illinois, Dept Crop Sci, Natl Soybean Res Ctr, Urbana, IL 61801 USA. Univ Illinois, USDA ARS, NSRC, Urbana, IL 61801 USA. Univ Maryland, Joint Inst Food Safety & Appl Nutr, Dept Chem & Biochem, College Pk, MD 20742 USA. RP Li, SX (reprint author), Univ Illinois, Dept Crop Sci, Natl Soybean Res Ctr, Urbana, IL 61801 USA. NR 30 TC 6 Z9 6 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0301-486X J9 MYCOPATHOLOGIA JI Mycopathologia PY 2002 VL 154 IS 1 BP 41 EP 49 DI 10.1023/A:1015297907991 PG 9 WC Mycology SC Mycology GA 543KJ UT WOS:000175100900007 PM 12041871 ER PT J AU Nielsen, KF Huttunen, K Hyvarinen, A Andersen, B Jarvis, BB Hirvonen, MR AF Nielsen, KF Huttunen, K Hyvarinen, A Andersen, B Jarvis, BB Hirvonen, MR TI Metabolite profiles of Stachybotrys isolates from water-damaged buildings and their induction of inflammatory mediators and cytotoxicity in macrophages SO MYCOPATHOLOGIA LA English DT Article DE atranones; satratoxins; mycotoxin; Stachybotrys; inflammation; TNF alpha; IL-6 ID TUMOR-NECROSIS-FACTOR; NITRIC-OXIDE; RAW264.7 MACROPHAGES; CHARTARUM; EXPOSURE; HEMORRHAGE; CYTOKINES; INFANTS; SPORES; FUNGI AB The metabolite profiles of 20 Stachybotrys spp. isolates from Finnish water-damaged buildings were compared with their biological activities. Effects of purified compounds on cytotoxicity and production of inflammatory mediators such as nitric oxide, IL-6 and TNFalpha in murine RAW264.7 macrophage cells were studied. The 11 isolates belonging to the satratoxin-producing chemotype were highly cytotoxic to the macrophages. The isolates inducing inflammatory mediators all belonged to the atranone-producing chemotype, but pure atranones B, and D did not elicit a response in the bioassay. Altogether, cytotoxicity of Stachybotrys sp. isolates appear to be related to satratoxin production whereas the specific component inducing inflammatory responses in atranone-producing isolates remains obscure. C1 Tech Univ Denmark, Biocentrum DTU, Mycol Grp, DK-2800 Lyngby, Denmark. Aalborg Univ, Danish Bldg Res Inst, Energy & Indoor Climate Div, DK-2970 Horsholm, Denmark. Natl Publ Hlth Inst, Dept Environm Hlth, FIN-70701 Kuopio, Finland. Univ Maryland, Dept Chem & Biochem, College Pk, MD 20742 USA. Univ Maryland, Joint Inst Food Safety & Appl Nutr, College Pk, MD 20742 USA. RP Nielsen, KF (reprint author), Tech Univ Denmark, Biocentrum DTU, Mycol Grp, Bldg 221, DK-2800 Lyngby, Denmark. EM kristian.f.nielsen@biocentrum.dtu.dk RI Nielsen, Kristian/C-7233-2011; Andersen, Birgitte/F-3922-2012; Huttunen, Kati/D-8755-2012 OI Nielsen, Kristian/0000-0002-5848-0911; Andersen, Birgitte/0000-0002-4544-9886; Huttunen, Kati/0000-0002-4888-9203 NR 20 TC 40 Z9 40 U1 0 U2 6 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0301-486X J9 MYCOPATHOLOGIA JI Mycopathologia PY 2002 VL 154 IS 4 BP 201 EP 205 DI 10.1023/A:1016383402963 PG 5 WC Mycology SC Mycology GA 573EM UT WOS:000176816400012 PM 12206322 ER PT S AU Musser, SM Eppley, RM Trucksess, MW AF Musser, SM Eppley, RM Trucksess, MW BE DeVries, JW Trucksess, MW Jackson, LS TI Electrospray mass spectrometry for fumonisin detection and method validation SO MYCOTOXINS AND FOOD SAFETY SE Advances in Experimental Medicine and Biology LA English DT Article; Proceedings Paper CT Symposium on Mycotoxins and Food Safety CY AUG 21-23, 2000 CL WASHINGTON, D.C. SP Amer Chem Soc, Div Agr & Food Chem ID PERFORMANCE LIQUID-CHROMATOGRAPHY; FUSARIUM-MONILIFORME; HYDROLYSIS PRODUCTS; ESOPHAGEAL CANCER; CORN PRODUCTS; B-1; PROLIFERATUM; MYCOTOXINS; FEED; HPLC AB Fumonisins are a structurally related group of mycotoxins, characterized by a 19-20 carbon aminopolyhydroxy-alkyl chain which is diesterified with propane-1,2,3-tricarboxylic acid (tricarballylic acid). These mycotoxins are commonly found in corn and corn-based food products and have been linked to a variety of animal toxicities. The widespread prevalence of fumonisins and the toxicity associated with ingestion has resulted in a number of analytical methods for determining the amount of fumonisins present in foods. Among the most common of these methods are liquid chromatographic (LC) separation with fluorescence detection, enzyme-linked immunosorbent assay (ELISA) and LC/mass spectrometry. LC and ELISA give quantitative results while LC/MS provide quantitative analysis as well as confirmation of identity of the fumonisins. C1 US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. RP Musser, SM (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. NR 37 TC 4 Z9 5 U1 0 U2 2 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0065-2598 BN 0-306-46780-1 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2002 VL 504 BP 95 EP 105 PG 11 WC Chemistry, Applied; Food Science & Technology; Medicine, Research & Experimental SC Chemistry; Food Science & Technology; Research & Experimental Medicine GA BU17X UT WOS:000175261000008 PM 11922102 ER PT S AU Roach, JAG Brause, AR Eisele, TA Rupp, HS AF Roach, JAG Brause, AR Eisele, TA Rupp, HS BE DeVries, JW Trucksess, MW Jackson, LS TI HPLC detection of patulin in apple juice with GC/MS confirmation of patulin identity SO MYCOTOXINS AND FOOD SAFETY SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT Symposium on Mycotoxins and Food Safety CY AUG 21-23, 2000 CL WASHINGTON, D.C. SP Amer Chem Soc, Div Agr & Food Chem ID GAS CHROMATOGRAPHY/MASS SPECTROMETRY; ISOTOPE DILUTION ASSAY; STANDARD AB The official patulin LC procedure was further examined (AOAC 995.10). Juice or juice concentrate was extracted with ethyl acetate and cleaned up with sodium carbonate. Patulin in the dried extract was determined by reversed-phase LC with UV detection (280 mm) in 1% THF aqueous solution after evaporation of the ethyl acetate. An end-capped C18 column was required to separate patulin from hydroxymethylfurfural. Patulin was detected in approximately half of the >1000 extracts examined. Only ca 10% of the extracts contained patulin at levels greater than 50 mug/L (50 ppb). Some presumptive findings were confirmed by capillary gas chromatography/mass spectrometry as the trimethyl silyl derivative using electron ionization or as underivatized patulin using negative ion chemical ionization. Trifluoropropylmethyl polysiloxane capillary columns provided superior gas chromatography of underivatized patulin compared to phenyl/methyl polysiloxane and methyl polysiloxane columns. C1 US FDA, CFSAN, Washington, DC 20204 USA. Columbia Inc, Analyt Chem Serv, Columbia, MD 21045 USA. Treetop Inc, Selah, WA 98942 USA. US FDA, Pacific Reg Lab NW, Bothell, WA 98021 USA. RP Roach, JAG (reprint author), US FDA, CFSAN, 200 C St SW, Washington, DC 20204 USA. NR 10 TC 14 Z9 14 U1 0 U2 4 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0065-2598 BN 0-306-46780-1 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2002 VL 504 BP 135 EP 140 PG 6 WC Chemistry, Applied; Food Science & Technology; Medicine, Research & Experimental SC Chemistry; Food Science & Technology; Research & Experimental Medicine GA BU17X UT WOS:000175261000011 PM 11924597 ER PT S AU Park, DL AF Park, DL BE DeVries, JW Trucksess, MW Jackson, LS TI Effect of processing on aflatoxin SO MYCOTOXINS AND FOOD SAFETY SE Advances in Experimental Medicine and Biology LA English DT Article; Proceedings Paper CT Symposium on Mycotoxins and Food Safety CY AUG 21-23, 2000 CL WASHINGTON, D.C. SP Amer Chem Soc, Div Agr & Food Chem ID CONTAMINATED CORN; FOOD; DESTRUCTION; FEED; STABILITY AB Naturally occurring toxicant contamination of foods with mycotoxins is unavoidable and unpredictable and poses a unique challenge to food safety. Aflatoxins are toxic mold metabolites produced by toxigenic strains of Aspergillus species. Primary commodities susceptible to aflatoxin contamination include corn, peanuts and cottonseed and animal-derived foods such as milk when the animal is fed aflatoxin-contaminated feed. Risks associated with aflatoxin-contaminated foods can be reduced through the use of specific processing and decontamination procedures. Factors, which influence the effectiveness of a specific processor procedure, include the chemical stability of the mycotoxin(s), nature of the process, type and interaction with the food/feed matrix and interaction with multiple mycotoxins if present. Practical decontamination procedures must: 1) inactivate, destroy, or remove the toxin, 2) not produce or leave toxic residues in the food/feed, 3) retain the nutritive value of the food/feed, 4) not alter the acceptability or the technological properties of the product, and, if possible, 5) destroy fungal spores. For aflatoxins, multiple processing and/or decontamination schemes have been successful in reducing aflatoxin concentrations to acceptable levels. Physical cleaning and separation procedures, where the mold-damaged kernel/seed/nut is removed from the intact commodity, can result in 40-80% reduction in aflatoxins levels. Processes such as dry and wet milling result in the distribution of aflatoxin residues into less utilized fractions of the commodity. The ammoniation of aflatoxin-contaminated commodities has altered the concentrations as well as toxic and carcinogenic effects of aflatoxin by greater than 99%. Nonbiological materials such as selected anticaking agents covalently bind aflatoxins from aqueous suspensions, diminish aflatoxin uptake by animals, prevent acute aflatoxicosis, and decrease aflatoxin residues in milk. Ultimately, the best processing or decontamination process is one that is approved by regulatory agencies, cost-effective, and reduces the mycotoxin concentration to acceptable levels. C1 US FDA, Ctr Food Safety & Appl Nutr, Div Nat Prod, Washington, DC 20204 USA. RP Park, DL (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Div Nat Prod, Washington, DC 20204 USA. NR 36 TC 56 Z9 62 U1 2 U2 10 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0065-2598 BN 0-306-46780-1 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2002 VL 504 BP 173 EP 179 PG 7 WC Chemistry, Applied; Food Science & Technology; Medicine, Research & Experimental SC Chemistry; Food Science & Technology; Research & Experimental Medicine GA BU17X UT WOS:000175261000014 PM 11922084 ER PT S AU Bullerman, LB Ryu, D Jackson, LS AF Bullerman, LB Ryu, D Jackson, LS BE DeVries, JW Trucksess, MW Jackson, LS TI Stability of fumonisins in food processing SO MYCOTOXINS AND FOOD SAFETY SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT Symposium on Mycotoxins and Food Safety CY AUG 21-23, 2000 CL WASHINGTON, D.C. SP Amer Chem Soc, Div Agr & Food Chem ID CORN-BASED FOODS; LINKED-IMMUNOSORBENT-ASSAY; HUMAN ESOPHAGEAL CANCER; FUSARIUM-MONILIFORME; CONTAMINATED CORN; EXTRUSION-COOKING; CULTURE MATERIAL; ANIMAL HEALTH; B-1; PRODUCTS AB Fumonisins are mycotoxins produced by Fusarium verticillioides (moniliforme) and Fusarium proliferatum that are found in corn and processed corn-based food products. Although generally heat stable, fumonisin concentrations appear to decline as processing temperatures increase. At processing temperatures of 125 degreesC or lower, losses of fumonisin are low (25-30%), whereas at temperatures of 175 degreesC and higher, losses are greater (90% or more). Processes such as baking and canning, where product temperatures rarely reach 175 degreesC, result in little or no loss of fumonisin. Processes such as frying and extrusion cooking, where temperatures can exceed 175 degreesC, result in greater losses. Heating fumonisin in the presence of glucose results in an apparent first order loss of the toxin. Adding glucose to corn muffins and extrusion mixes results in high losses of fumonisins during baking and extrusion processing. Little information exists on the effects of chemical and bioprocessing on fumonisins. Alkaline processing of corn, such as in the nixtamalization process, hydrolyzes fumonisins and results in a more toxic product. Additional research is needed to identify and to determine the toxicity of fumonisin decomposition products. C1 Univ Nebraska, Dept Food Sci & Technol, Lincoln, NE 68583 USA. US FDA, Natl Ctr Food Safety & Technol, Summit Argo, IL 60501 USA. RP Bullerman, LB (reprint author), Univ Nebraska, Dept Food Sci & Technol, Lincoln, NE 68583 USA. NR 80 TC 17 Z9 19 U1 1 U2 4 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0065-2598 BN 0-306-46780-1 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2002 VL 504 BP 195 EP 204 PG 10 WC Chemistry, Applied; Food Science & Technology; Medicine, Research & Experimental SC Chemistry; Food Science & Technology; Research & Experimental Medicine GA BU17X UT WOS:000175261000017 PM 11922088 ER PT S AU Ryu, D Jackson, LS Bullerman, LB AF Ryu, D Jackson, LS Bullerman, LB BE DeVries, JW Trucksess, MW Jackson, LS TI Effects of processing on zearalenone SO MYCOTOXINS AND FOOD SAFETY SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT Symposium on Mycotoxins and Food Safety CY AUG 21-23, 2000 CL WASHINGTON, D.C. SP Amer Chem Soc, Div Agr & Food Chem ID HUMAN BREAST-CANCER; LIQUID-CHROMATOGRAPHIC DETERMINATION; FUSARIUM MYCOTOXINS NIVALENOL; CONTAMINATED CORN; ALPHA-ZEARALENOL; FLUORESCENCE DETECTION; ESTROGENIC MYCOTOXIN; GAS-CHROMATOGRAPHY; MILLED FRACTIONS; ANABOLIC DRUGS AB Zearalenone (ZEN), a common contaminant of all major cereal grains worldwide, is produced by some plant pathogenic molds including Fusarium graminearum and F. culmorum. The biological activity of this mycotoxin is mainly attributed to its estrogenic activity that modulates/disrupts endocrine function in animals and possibly humans. Efforts have been made to reduce the level of ZEN by various chemical, physical, and biological processing methods. Some chemical treatments were shown to be effective in reducing zearalenone content in artificially or naturally contaminated foods. During physical processing, the fate of ZEN depended on its distribution in the food matrix and its chemical properties such as heat stability and solubility. For example, wet milling of contaminated corn resulted in starch that was essentially toxin-free. In contrast, animal feed fractions such as bran and germ, by-products of the wet milling process, tended to concentrate ZEN. Extrusion cooking, a complex process where food is subjected to heat, high pressures and shear stress, reduced ZEN levels in food as well as its estrogenic activity. Fermentation of foods with bacteria and yeast resulted in reduction in ZEN levels. However, fermentation can result in the conversion of ZEN to more potent derivatives such as a-zearalenol. Further efforts are needed to identify effective methods for removing/etoxifying ZEN in foods. C1 Univ Nebraska, Dept Food Sci & Technol, Lincoln, NE 68583 USA. US FDA, NCFST, Summit Argo, IL 60501 USA. RP Ryu, D (reprint author), Univ Nebraska, Dept Food Sci & Technol, Lincoln, NE 68583 USA. NR 91 TC 24 Z9 28 U1 2 U2 8 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0065-2598 BN 0-306-46780-1 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2002 VL 504 BP 205 EP 216 PG 12 WC Chemistry, Applied; Food Science & Technology; Medicine, Research & Experimental SC Chemistry; Food Science & Technology; Research & Experimental Medicine GA BU17X UT WOS:000175261000018 PM 11922089 ER PT S AU Henry, SH Bosch, FX Bowers, JC AF Henry, SH Bosch, FX Bowers, JC BE DeVries, JW Trucksess, MW Jackson, LS TI Aflatoxin, hepatitis and worldwide liver cancer risks SO MYCOTOXINS AND FOOD SAFETY SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT Symposium on Mycotoxins and Food Safety CY AUG 21-23, 2000 CL WASHINGTON, D.C. SP Amer Chem Soc, Div Agr & Food Chem ID REPUBLIC-OF-CHINA; HEPATOCELLULAR-CARCINOMA; DEVELOPING-COUNTRIES; B VACCINATION; OLTIPRAZ; QIDONG; EPIDEMIOLOGY; RESIDENTS AB Aflatoxins are among the most potent mutagenic and carcinogenic substances known. Differential potency of aflatoxin among species can be partially attributed to differences in metabolism; however, current information on competing aspects of metabolic activation and detoxification of aflatoxin in various species does not identify an adequate animal model for humans. Risk of liver cancer is influenced by a number of factors, most notably carriage of hepatitis B virus as determined by the presence in serum of the hepatitis B surface antigen (HBsAg-+- or HBsAg-). About 50 to 100% of liver cancer cases are estimated to be associated with persistent infection of hepatitis B (or C) virus. The potency of aflatoxin in HBsAg+ individuals is substantially higher (about a factor of 30) than the potency in HBsAg- individuals. Thus, reduction of the intake of aflatoxins in populations with a high prevalence of HBsAg+ individuals will have greater impact on reducing liver cancer rates than reductions in populations with a low prevalence of HbsAg+ individuals. The present analysis suggests that vaccination against hepatitis B (or protection against hepatits C), which reduces prevalence of carriers, would reduce the potency of the aflatoxins in vaccinated populations and reduce liver cancer risk. C1 US FDA, Washington, DC 20204 USA. Inst Oncol, Lhospitalet De Llobregat, Barcelona, Spain. RP Henry, SH (reprint author), US FDA, Washington, DC 20204 USA. RI BOSCH JOSE, FRANCESC XAVIER/J-6339-2012 OI BOSCH JOSE, FRANCESC XAVIER/0000-0002-7172-3412 NR 16 TC 48 Z9 55 U1 2 U2 10 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0065-2598 BN 0-306-46780-1 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2002 VL 504 BP 229 EP 233 PG 5 WC Chemistry, Applied; Food Science & Technology; Medicine, Research & Experimental SC Chemistry; Food Science & Technology; Research & Experimental Medicine GA BU17X UT WOS:000175261000020 PM 11922091 ER PT S AU Park, DL Troxell, TC AF Park, DL Troxell, TC BE DeVries, JW Trucksess, MW Jackson, LS TI US perspective on mycotoxin regulatory issues SO MYCOTOXINS AND FOOD SAFETY SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT Symposium on Mycotoxins and Food Safety CY AUG 21-23, 2000 CL WASHINGTON, D.C. SP Amer Chem Soc, Div Agr & Food Chem ID AFLATOXIN; FOOD; FEED AB Control programs set up by the Food and Drug Administration (FDA) for aflatoxin, an unavoidable natural contaminant produced by specific molds that invade a number of feedstuffs and basic foods, provide an example of forces that affect risk assessment and management strategies by a regulatory agency. More recently, on an international scale, efforts to establish international food standards for fumonisin, deoxynivalenol, ochratoxin A, zearalenone, and patulin, as well as for aflatoxin, demonstrate the complexity of developing regulations and/or standards designed to protect consumer health and ensure fair trade practices on a global scale. Current FDA regulations for aflatoxins address public health concerns for potential contamination in basic foods, residues in milk, and animal feeds for numerous commodities and applications. Regulatory limits, sampling and analytical procedures, decontamination and/or diversion to less risk uses for contaminated product are components of mycotoxin control programs. Current efforts by FDA to establish regulatory controls for deoxynivalenol, fumonisin, and patulin add further insight on the role that safety and risk assessment procedures play in the development of action levels and advisories for mycotoxins. C1 US FDA, Ctr Food Safety & Appl Nutr, Off Plant & Dairy Foods & Beverages, Washington, DC 20204 USA. RP Park, DL (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Plant & Dairy Foods & Beverages, Washington, DC 20204 USA. NR 19 TC 35 Z9 36 U1 0 U2 4 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0065-2598 BN 0-306-46780-1 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2002 VL 504 BP 277 EP 285 PG 9 WC Chemistry, Applied; Food Science & Technology; Medicine, Research & Experimental SC Chemistry; Food Science & Technology; Research & Experimental Medicine GA BU17X UT WOS:000175261000025 PM 11922095 ER PT B AU Ilev, IK Waynant, RW AF Ilev, IK Waynant, RW BE Peckerar, MC Postek, MT TI On-the-spot laser therapy using a smart, tissue-activated fiber probe SO NANOSTRUCTURE SCIENCE, METROLOGY AND TECHNOLOGY LA English DT Proceedings Paper CT Conference on Nanostructure Science, Metrology, and Technology CY SEP 05-07, 2001 CL GAITHERSBURG, MD SP SPIE, Natl Inst Stand & Technol, USN, Off Res DE on-the-spot laser delivery; optical fiber; tissue-activated fiber probe AB We present a new technique for laser radiation delivery into a precise (micron- and submicron-scale) tissue area using a smart, tissue-activated optical fiber probe. The operating principal of the laser delivery system is based on the use of a delivery fiber with a specially angle-shaped tip. When the fiber tip is out of the tissue area, the laser emission is backreflected at the angled tip due to total-internal-reflection. However, when the fiber tip is placed on absorbing tissue, it becomes "transparent" for laser emission because of the frustrated-total-internal-reflectance and the energy, then is coupled into the absorber. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Ilev, IK (reprint author), US FDA, Ctr Devices & Radiol Hlth, HFZ-134, Rockville, MD 20857 USA. NR 2 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 BN 0-8194-4347-6 PY 2002 BP 234 EP 238 DI 10.1117/12.437971 PG 5 WC Engineering, Aerospace; Engineering, Electrical & Electronic; Instruments & Instrumentation; Optics SC Engineering; Instruments & Instrumentation; Optics GA BV16M UT WOS:000178040400030 ER PT J AU Goldstein, DS Katzper, M Linares, O Kopin, IJ AF Goldstein, DS Katzper, M Linares, O Kopin, IJ TI Kinetic model for the fate of 6-[F-18]fluorodopamine in the human heart: a novel means to examine cardiac sympathetic neuronal function SO NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY LA English DT Article DE positron; fluorodopamine; sympathetic; norepinephrine; modeling ID INNERVATION; 6-FLUORODOPAMINE; NEUROTRANSMITTERS; METABOLISM; FAILURE AB After injection of 6-[F-18]fluorodopamine, thoracic positron emission tomographic scanning visualizes the sympathetic innervation of the heart. This report introduces a kinetic model that relates 6-[F-18]fluorodopamine positron emission tomographic scanning results to specific aspects of cardiac sympathoneural function. Inputs were the 6-[F-18]fluorodopamine concentration in arterial blood and the estimated contribution of circulating metabolites of 6-[F-18]fluorodopamine. All of the three compartments in the model were intraneuronal. Two compartments corresponded to vesicles in sympathetic nerves, consistent with the "multiple vesicular pool" hypothesis from preclinical studies. The model successfully fit the empirical time-activity curve for myocardial 6-[F-18]fluorodopamine-derived radioactivity and predicted correctly the effects of several neuropharmacological and physiological manipulations on the time-activity curve. Myocardial cell uptake of metabolites of 6-[F-18]fluorodopamine from the circulation could explain an immediate peak of 6-[F-18]fluorodopamine-derived radioactivity. The model seems useful in predicting effects of altered cardiac sympathetic function on time-activity curves for myocardial 6-[F-18]fluorodopamine-derived radioactivity in humans. C1 NINCDS, NIH, Bethesda, MD 20892 USA. NINCDS, Clin Neurocardiol Sect, Bethesda, MD 20892 USA. US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. Univ Michigan, Ann Arbor, MI 48109 USA. RP Goldstein, DS (reprint author), NINCDS, NIH, Bldg 10,Room 6N252,10 Ctr Dr MSC-1620, Bethesda, MD 20892 USA. NR 24 TC 14 Z9 14 U1 0 U2 1 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0028-1298 J9 N-S ARCH PHARMACOL JI Naunyn-Schmiedebergs Arch. Pharmacol. PD JAN PY 2002 VL 365 IS 1 BP 38 EP 49 DI 10.1007/s002100100426 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 510HP UT WOS:000173202900006 PM 11862332 ER PT J AU Ferguson, SA AF Ferguson, SA TI Effects on brain and behavior caused by developmental exposure to endocrine disrupters with estrogenic effects - Introduction SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Editorial Material DE endocrine disrupter; estrogen; development; brain; behavior ID SEXUAL-DIFFERENTIATION; RESEARCH NEEDS; RECEPTOR-BETA; CHEMICALS; WILDLIFE; FIELD; RATS C1 US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. RP Ferguson, SA (reprint author), HFT-132,3900 NCTR Rd, Jefferson, AR 72079 USA. NR 30 TC 5 Z9 5 U1 0 U2 0 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 2002 VL 24 IS 1 BP 1 EP 3 AR PII S0892-0362(01)00196-9 DI 10.1016/S0892-0362(01)00196-9 PG 3 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA 527UG UT WOS:000174205800001 PM 11836066 ER PT J AU Ferguson, SA Flynn, KM Delclos, KB Newbold, RR Gough, BJ AF Ferguson, SA Flynn, KM Delclos, KB Newbold, RR Gough, BJ TI Effects of lifelong dietary exposure to genistein or nonylphenol on amphetamine-stimulated striatal dopamine release in male and female rats SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Article DE estrogen; striatum; dopamine; microdialysis; genistein; nonylphenol; endocrine disrupter ID TYROSINE KINASE INHIBITOR; ESTROGEN-RECEPTOR-BETA; SPRAGUE-DAWLEY RATS; SMOOTH-MUSCLE CELLS; SEX-DIFFERENCES; TISSUE DISTRIBUTION; CALCIUM CURRENTS; IN-VITRO; MICRODIALYSIS; CYCLE AB Estrogen modulates baseline and amphetamine-stimulated dopamine (DA) release in the adult female rat striatum. The isoflavone found in soybeans, genistein, is a phytoestrogen and may have comparable effects on striatal DA levels. Similarly, the industrial intermediate and potential endocrine disrupter, para-nonylphenol, has estrogen-like effects. Here. Sprague-Dawley rats were continuously exposed to phytoestrogen-free diets containing 0, 100, or 500 ppm genistein (Experiment 1) or 0 or 200, or 750 ppm nonylphenol (Experiment 2) beginning at conception and continuing throughout. To eliminate estrous cycle influences on DA levels, females were ovariectomized at adulthood. As adults. striatal levels of DA and its metabolites [3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA)) were measured in unanesthetized male and female rats via cerebral microdialysis before and for 200 min after an intraperitoneal injection of 2 mg/kg D-amphetamine. Although baseline 5-hydroxyindoleacetic acid (5-HIAA) levels indicated an isolated effect in genistein-treated females, there were no meaningful differences among treatment groups in baseline levels of DA. DOPAC, or HVA. However, dietary exposure to 500 ppm genistein significantly potentiated amphetamine-stimulated DA release in males and a similar trend was apparent, but not statistically significant, in females. Dietary exposure to 200 or 750 ppm nonylphenol had no significant effects in males or females. These results suggest that dietary genistein exposure may act similarly to estradiol in augmenting amphetamine-stimulated DA release. (C) 2002 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, Toxicol Lab, Environm Toxicol Program, 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 53 TC 17 Z9 19 U1 0 U2 0 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 2002 VL 24 IS 1 BP 37 EP 45 AR PII S0892-0362(01)00193-3 DI 10.1016/S0892-0362(01)00193-3 PG 9 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA 527UG UT WOS:000174205800005 PM 11836070 ER PT J AU Scallet, AC Meredith, JM AF Scallet, AC Meredith, JM TI Quantitative three-dimensional reconstruction: Feasibility for studies of sexually dimorphic hypothalamic development in rats SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Article DE medial preoptic nucleus; hypothalamus; 3-D reconstruction; endocrine disrupters; estrogens ID PREOPTIC AREA; SUPRACHIASMATIC NUCLEUS; HUMAN-BRAIN; SEX-DIFFERENCES; HOMOSEXUAL MEN; DIFFERENTIATION; MECHANISMS AB The adult rat brain develops through an interplay of neuronal proliferation with programmed cell death. Sensory stimulation, as well as growth factors and steroids, may alter the balance between these competing processes. "Endocrine disrupters" (EDs) may do the same by mimicry or modulation of endogenous hormones. The sexually dimorphic nucleus (SDN) of the medial preoptic hypothalamus contains a high concentration of estrogen receptors (ERs). The SDN develops to a final adult volume, which may be used as an indication of the hormonal conditions during perinatal development. Although male rats have been repeatedly observed to have a greater adult SDN volume than female rats, variability between the actual measurements reported (both within and between laboratories) have been rather large. Exposure of female rats to testosterone (or excessive estradiol, beyond the binding capacity of alpha-fetoprotein) has been shown to masculinize them through a P450 aromatase that converts testosterone to estrogen in the SDN. Exposure of males to estradiol may feminize them at low doses through interference with the synthesis of their endogenous testosterone, which normally acts on SDN ERs following aromatization. We have employed computer-assisted reconstruction methods in order to render the SDN within the surrounding hypothalamus in 3-D for computation of its volume. Ongoing studies are investigating whether exposure through the diet to estrogenic endocrine disruptors such as genistein, nonylphenol, and ethinyl estradiol might produce effects similar to those of estradiol itself on the adult SDN. (C) 2002 Published by Elsevier Science Inc. C1 US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. RP Scallet, AC (reprint author), US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, HTF-132,3900 NCTR Dr, Jefferson, AR 72079 USA. NR 26 TC 5 Z9 5 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 2002 VL 24 IS 1 BP 81 EP 85 AR PII S0892-0362(01)00189-1 DI 10.1016/S0892-0362(01)00189-1 PG 5 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA 527UG UT WOS:000174205800009 PM 11836074 ER PT J AU Montgomery, BA Murphy, J Chen, JJ Desai, VG McGarrity, L Morris, SM Casciano, DA Aidoo, A AF Montgomery, BA Murphy, J Chen, JJ Desai, VG McGarrity, L Morris, SM Casciano, DA Aidoo, A TI Mutagenicity of food-derived carcinogens and the effect of antioxidant vitamins SO NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL LA English DT Article ID HETEROCYCLIC AROMATIC-AMINES; ALPHA-TOCOPHEROL; COOKED FOOD; 2-AMINO-1-METHYL-6-PHENYLIMIDAZO<4,5-B>PYRIDINE PHIP; RAT ESOPHAGEAL; BETA-CAROTENE; MAMMARY-GLAND; MUTATIONS; 2-AMINO-3-METHYLIMIDAZO<4,5-F>QUINOLINE; LYMPHOCYTES AB The food-derived heterocyclic amines (HCAs) 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) are mutagenic in the Ames test and produce tumors in laboratory animals, including monkeys, These HCAs have also been shown to induce gene mutations in vivo. To assess the antimutagenic effects of dietary antioxidant vitamins, beta-carotene, ascorbic acid (vitamin C), and a-tocopherol (vitamin E), on food-borne mutagens/carcinogens, we evaluated the mutagenic activity of the compounds alone or combined with antioxidant vitamins. We utilized the rat lymphocyte mutation assay at the hypoxanthine guanine phosphoribosyl transferase (Hprt) locus. Female Fischer 344 rats treated with different doses (0, 2.5, 5.0, 25.0, and 50.0 mg/kg) of the carcinogens were sacrificed 5 wk after mutagen treatment. Although IQ and MeIQ slightly increased mutation frequency (MF) at some doses, a significant (P < 0.0009) increase in MF was found in animals exposed to MeIQx at 25 mg/kg. PhIP was the most mutagenic of the HCAs, with increases (P < 0.0001) in MF detected at all dose levels compared with controls. Because PhIP was the most mutagenic, it was selected for studies using the dietary antioxidant vitamins, Addition of antioxidant vitamins, singly or in a mixture, caused a significant (P < 0.0001) decrease in PhIP-induced Hprt ME Vitamin E was the most effective at decreasing Hprt ME In addition, we determined whether carcinogen metabolism would be affected by ingestion of vitamins. The activities of endogenous detoxification enzymes, glutathione S-transferase and glutathione peroxidase (GPx), were thus examined. Intake of P-carotene and vitamin C without the carcinogen resulted in an increase (P < 0.05) in GPx activity. Also a modest increase in GPx activity was seen in animals that received the antioxidant mixture alone. Although the mechanisms of action of the antioxidants remain to be determined, the results indicate that dietary derived HCA treatment induced MF in rat lymphocytes and suggest that antioxidants in food or taken as supplements could, in part, counteract such mutagenic activities. C1 US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. Arkansas State Univ, State Univ, AR 72467 USA. RP Aidoo, A (reprint author), US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. NR 56 TC 6 Z9 6 U1 0 U2 5 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 USA SN 0163-5581 J9 NUTR CANCER JI Nutr. Cancer PY 2002 VL 43 IS 1 BP 103 EP 110 DI 10.1207/S15327914NC431_12 PG 8 WC Oncology; Nutrition & Dietetics SC Oncology; Nutrition & Dietetics GA 616QF UT WOS:000179313900012 PM 12467141 ER PT J AU Ramsey, SD Kessler, LG AF Ramsey, SD Kessler, LG TI Does economics matter when treating advanced non-small cell lung cancer? SO ONCOLOGIST LA English DT Editorial Material DE cost; non-small cell lung cancer; health insurer C1 Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA. Univ Washington, Dept Med, Seattle, WA USA. US FDA, Ctr Devices & Radiol Hlth, Off Surveillance & Biometr, Rockville, MD 20857 USA. RP Ramsey, SD (reprint author), Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1100 Fairview Ave N,MP-900, Seattle, WA 98109 USA. NR 7 TC 4 Z9 4 U1 0 U2 0 PU ALPHAMED PRESS PI MIAMISBURG PA ONE PRESTIGE PLACE, STE 290, MIAMISBURG, OH 45342-3758 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2002 VL 7 IS 3 BP 179 EP 180 DI 10.1634/theoncologist.7-3-179 PG 2 WC Oncology SC Oncology GA 563BR UT WOS:000176234200005 PM 12065788 ER PT J AU Cohen, MH Moses, ML Pazdur, R AF Cohen, MH Moses, ML Pazdur, R TI Gleevec (TM) for the treatment of chronic myelogenous leukemia: US food and drug administration regulatory mechanisms, accelerated approval, and orphan drug status SO ONCOLOGIST LA English DT Article DE Gleevec; imatinib mesylate; chronic myelogenous leukemia; food and drug administration; accelerated approval regulations; orphan drug regulations AB Gleevec(TM) (imatinib mesylate), a highly promising new drug for the treatment of chronic myelogenous leukemia in blast crisis, in accelerated phase, and in chronic phase after interferon failure or intolerance, received orphan drug status from the US. Food and Drug Administration (FDA) Office of Orphan Products Development on January 31, 2001, and accelerated approval from the FDA for the above three indications on May 10, 2001. The purpose of this report is to summarize FDA regulatory mechanisms, i.e., accelerated approval and orphan drug regulations, that have permitted patients to receive this drug as rapidly as possible. C1 US FDA, Div Oncol Drug Prod, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. US FDA, Off Orphan Prod Dev, Off Commissioner, Rockville, MD 20857 USA. RP Cohen, MH (reprint author), US FDA, Div Oncol Drug Prod, Ctr Drug Evaluat & Res, HFD-150,5600 Fishers Lane, Rockville, MD 20857 USA. NR 0 TC 20 Z9 21 U1 1 U2 1 PU ALPHAMED PRESS PI MIAMISBURG PA ONE PRESTIGE PLACE, STE 290, MIAMISBURG, OH 45342-3758 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2002 VL 7 IS 5 BP 390 EP 392 DI 10.1634/theoncologist.7-5-390 PG 3 WC Oncology SC Oncology GA 611XM UT WOS:000179043200001 PM 12401900 ER PT J AU Cohen, MH Dagher, R Griebel, DJ Ibrahim, A Martin, A Scher, NS Sokol, GH Williams, GA Pazdur, R AF Cohen, MH Dagher, R Griebel, DJ Ibrahim, A Martin, A Scher, NS Sokol, GH Williams, GA Pazdur, R TI US Food and Drug Administration drug approval summaries: Imatinib mesylate, mesna tablets, and zoledronic acid SO ONCOLOGIST LA English DT Article DE imatinib mesylate; gastrointestinal stromal tumors; mesna; ifosfamide; zoledronic acid; bone metastases; bisphosphonates ID GASTROINTESTINAL STROMAL TUMORS; TYROSINE KINASE INHIBITOR; C-KIT; MUTATIONS; PAMIDRONATE; PREVENTION; LEUKEMIA; BIOLOGY; BLOOD; BONE AB The purpose of this report is to summarize information on drugs recently approved by the U.S. Food and Drug Administration. Three drugs have recently been approved: Gleevec(TM) (imatinib mesylate) at a starting dose of 400 or 600 mg daily for the treatment of malignant unresectable and/or metastatic gastrointestinal stromal tumors; Mesnex(R) (mesna) tablets as a prophylactic agent to reduce the incidence of ifosfamide-induced hemorrhagic cystitis, and Zometa(R) (zoledronic acid) for the treatment of patients with multiple myeloma and for patients with 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 infused over 15 minutes every 3-4 weeks. These three drugs represent three different types of drug approval: Gleevec is an accelerated approval and supplemental new drug application (NDA); Mesnex tablets represent an oral formulation of a drug approved 14 years ago as an intravenous formulation, and Zometa represents a standard NDA for a noncytotoxic, supportive-care drug. Information provided includes rationale for drug development, study design, efficacy and safety results, and pertinent literature references. C1 US FDA, Div Oncol Drug Prod, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Cohen, MH (reprint author), US FDA, Div Oncol Drug Prod, Ctr Drug Evaluat & Res, HFD-150,5600 Fishers Lane, Rockville, MD 20857 USA. NR 25 TC 31 Z9 31 U1 0 U2 2 PU ALPHAMED PRESS PI MIAMISBURG PA ONE PRESTIGE PLACE, STE 290, MIAMISBURG, OH 45342-3758 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2002 VL 7 IS 5 BP 393 EP 400 DI 10.1634/theoncologist.7-5-393 PG 8 WC Oncology SC Oncology GA 611XM UT WOS:000179043200002 PM 12401901 ER PT J AU Bross, PF Cohen, MH Williams, GA Pazdur, R AF Bross, PF Cohen, MH Williams, GA Pazdur, R TI FDA drug approval summaries: Fulvestrant SO ONCOLOGIST LA English DT Article DE fulvestrant; breast cancer; metastatic; hormone therapy ID PHASE-III TRIALS; POSTMENOPAUSAL WOMEN; MEGESTROL-ACETATE; BREAST-CANCER; ANASTROZOLE AB Patients with hormone-sensitive breast cancer who have responded to tamoxifen may receive additional benefit from a second endocrine agent following progression or relapse after tamoxifen therapy. Fulvestrant (Faslodex(R), ICI 182780, AstraZeneca Pharmaceuticals; Wilmington, Delaware) is a selective antagonist of estrogen designed to have no estrogenic effects. Lack of aqueous solubility led to the development of a parenteral formulation for monthly intramuscular administration. Fulvestrant has been shown to inhibit the proliferative effects of estrogen on sensitive tissues in vitro and in vivo, and is without apparent measurable estrogenic activity. The data upon which marketing approval for fulvestrant was based are summarized below. Eight hundred fifty-one postmenopausal women with advanced breast cancer were enrolled in two phase III studies, 400 in a North American double-blind study and 451 in a European open-label study, comparing the efficacy and safety of fulvestrant with anastrozole. Four hundred twenty-eight patients were randomized to receive fulvestrant 250 mg monthly by intramuscular injection and 423 patients were to receive anastrozole 1 mg daily. Patients were considered hormone sensitive either by receptor status or previous response to endocrine therapy. Over 96% of patients had previously received tamoxifen, either in the adjuvant setting or as treatment for metastatic disease. The primary study end points were response rate and time to progression. Response rates for patients treated with fulvestrant were 17% and 20% in the North American and European trials, respectively, compared with 17% and 15% in the anastrozole treatment arms. There were no statistically significant differences in response rates, time to progression, or survival between treatment arms in either study. The most common adverse events attributed to the treatment (>10%) were injection-site reactions and hot flashes. Common events (1%-10%) included asthenia, headache, and gastrointestinal disturbances (nausea, vomiting, and diarrhea), as well as rash and urinary tract infections. A small increase in joint disorders was reported in the anastrozole-treated patients. On April 25, 2002, fulvestrant 250 mg by monthly intramuscular injection was approved by the U.S. Food and Drug Administration for the treatment of hormone receptor-positive metastatic breast cancer in postmenopausal women with disease progression following antiestrogen therapy. Approval was based on similarity of response rates and time to progression between fulvestrant and anastrozole. C1 US FDA, Div Oncol Drug Prod, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Bross, PF (reprint author), US FDA, Div Oncol Drug Prod, Ctr Drug Evaluat & Res, HFD-150,5600 Fishers Lane, Rockville, MD 20857 USA. NR 5 TC 18 Z9 19 U1 2 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 2002 VL 7 IS 6 BP 477 EP 480 DI 10.1634/theoncologist.7-6-477 PG 4 WC Oncology SC Oncology GA 628RK UT WOS:000180010200002 PM 12490735 ER PT S AU Pfefer, TJ Matchette, LS Bennett, CL Wilke, JN Durkin, AJ Ediger, MN AF Pfefer, TJ Matchette, LS Bennett, CL Wilke, JN Durkin, AJ Ediger, MN BE Alfano, RR TI Determination of optical properties in highly attenuating media with an endoscope-compatible reflectance approach SO OPTICAL BIOPSY IV SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Conference on Optical Biopsy IV CY JAN 21-23, 2002 CL SAN JOSE, CA SP SPIE DE optical properties; reflectance spectroscopy; Monte Carlo ID SOURCE-DETECTOR SEPARATIONS; HUMAN COLON TISSUE; DIFFUSE-REFLECTANCE; IN-VIVO; ABSORPTION-COEFFICIENTS; LIGHT TRANSPORT; TURBID MEDIA; MONTE-CARLO; SCATTERING; SPECTROSCOPY AB Accurate in vivo optical property data in the ultraviolet to visible range are scarce for many endoscope-accessible organs, yet such information is essential for understanding tight propagation and identifying dosimetry standards for biomedical optical spectroscopy. We have performed a preliminary study towards the development of a reflectance-based system for endoscopic measurement of tissue optical properties relevant to fluorescence spectroscopy. To address the constraint of instrument channel diameter and strong attenuation of light in the spectral region of interest, maximum fiber separation distance was limited to 2.5 nun. Measurements were performed on tissue phantoms for a range of optical properties relevant to gastrointestinal mucosal tissues in the ultraviolet to visible range: absorption coefficients from I to 25 cm(-1) and reduced scattering coefficients from 5 to 25 cm(-1). Neural network and partial least squares algorithms were trained on radial reflectance profiles generated by a Monte Carlo model as well as by experimental data. These routines were then used to estimate absorption and reduced scattering coefficients from reflectance data. Results are discussed in terms of the optimization of models for optical property determination. C1 US FDA, CDRH, Rockville, MD 20857 USA. RP Pfefer, TJ (reprint author), US FDA, CDRH, HFZ-134,12725 Twinbrook Pkwy,201, Rockville, MD 20857 USA. NR 20 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 0-8194-4352-2 J9 P SOC PHOTO-OPT INS PY 2002 VL 4613 BP 212 EP 221 DI 10.1117/12.465248 PG 10 WC Engineering, Biomedical; Optics; Physics, Applied; Spectroscopy SC Engineering; Optics; Physics; Spectroscopy GA BU69V UT WOS:000176733000028 ER PT J AU Gannot, I Ben-David, M Inberg, A Croitoru, N Waynant, RW AF Gannot, I Ben-David, M Inberg, A Croitoru, N Waynant, RW TI Beam shape analysis of waveguide delivered infrared lasers SO OPTICAL ENGINEERING LA English DT Article DE optical waveguides; lasers; ray tracing; optical waveguide theory; laser applications ID HOLLOW WAVE-GUIDES; MEDICAL APPLICATIONS; RAY MODEL; TRANSMISSION; RADIATION; SILVER; FIBERS AB A comprehensive theoretical model is developed to describe mid-IR laser radiation propagation in an optical cylindrical waveguide. The effects of various parameters of the beam as well as of the waveguide on the output beam shape are studied and analyzed. Parameters such as beam coupling misalignment, waveguide diameters, and inner wall roughness are studied. The same conditions are applied in the theoretical calculations as well as in the experiments. Good agreement between the theoretical and experimental results is found. (C) 2002 society of Photo-Optical Instrumentation Engineers. C1 Tel Aviv Univ, IL-69978 Tel Aviv, Israel. US FDA, Electroopt Branch, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Gannot, I (reprint author), Tel Aviv Univ, IL-69978 Tel Aviv, Israel. NR 22 TC 3 Z9 3 U1 0 U2 0 PU SPIE-INT SOCIETY OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 0091-3286 J9 OPT ENG JI Opt. Eng. PD JAN PY 2002 VL 41 IS 1 BP 244 EP 250 DI 10.1117/1.1420191 PG 7 WC Optics SC Optics GA 516XL UT WOS:000173582000033 ER PT S AU Waynant, RW Ilev, IK Mitra, K Gannot, I Jennings, RJ AF Waynant, RW Ilev, IK Mitra, K Gannot, I Jennings, RJ BE Gannot, I TI Transmission characteristics of an all-optical-waveguide biomedical system for x-ray delivery SO OPTICAL FIBERS AND SENSORS FOR MEDICAL APPLICATIONS II SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Optical Fibers and Sensors for Medical Applications II Conference CY JAN 22-23, 2002 CL SAN JOSE, CA SP SPIE DE x-rays; hollow waveguides; minimally invasive therapy ID UNCOATED HOLLOW TAPER; CAPILLARY OPTICS; LASER DELIVERY AB We have investigated the transmission characteristics of an alternative all-optical-waveguide system for x-ray delivery to a precise tissue area. The delivery system includes two basic optical elements: a funnnel-shaped uncoated hollow glass taper and a flexible hollow delivery waveguide. The hollow taper provides direct launching of the input x-ray radiation into a delivery waveguide. It is an uncoated glass taper whose operating principle is based on the grazing-incidence effect. We investigated both experimentally and theoretically how the transmission properties of the hollow taper depend on its geometrical parameters such as cone shape, length, input and output core diameters. The x-ray-source-to-taper coupling efficiency obtained was about 20-25%. That is relatively low in comparison with typical laser-to-taper coupling efficiencies due to the poorly collimated x-ray beam. Furthermore, we have studied the x-ray beam profile conversion by the grazing-incidence-based hollow taper. The x-ray radiation was launched into the delivery waveguide by a direct taper-to-waveguide coupling. In our experiment, we used both uncoated and metal-coated hollow waveguides with various geometrical parameters. The waveguide transmission characteristics, including the coupling efficiencies and beam profile conversion, were investigated for both straight and bent delivery waveguides. The results obtained as presented in this report give considerable confidence for successful application of the all-waveguide system as an alternative x-ray delivery technique for biomedical use. 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, Rockville, MD 20857 USA. RI Mitra, Kunal/C-6560-2016 OI Mitra, Kunal/0000-0002-7277-4908 NR 12 TC 2 Z9 2 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-4355-7 J9 P SOC PHOTO-OPT INS PY 2002 VL 4616 BP 121 EP 128 DI 10.1117/12.463803 PG 8 WC Engineering, Biomedical; Instruments & Instrumentation; Optics SC Engineering; Instruments & Instrumentation; Optics GA BU44B UT WOS:000175999200016 ER PT S AU Ilev, IK Waynant, RW Reiter, M AF Ilev, IK Waynant, RW Reiter, M BE Gannot, I TI Smart optical fiber probes for precise tissue treatment SO OPTICAL FIBERS AND SENSORS FOR MEDICAL APPLICATIONS II SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Optical Fibers and Sensors for Medical Applications II Conference CY JAN 22-23, 2002 CL SAN JOSE, CA SP SPIE DE optical fibers; laser delivery; total-internal reflectance; tissue treatment ID UNCOATED HOLLOW TAPER; LASER DELIVERY AB Optical features of a novel technique for fiber-optic-based laser delivery into a precise tissue area are investigated. As a key optical element, the technique includes a single delivery fiber with a specially angle shaped tip. Because of the frustrated-total-internal-reflectance caused by the refractive-index change of the surrounding medium, the angled fiber tip acts as a smart, tissue-activated probe. It provides a safe way for laser delivery that includes only two states of tissue illumination: (1) off-state (no tissue illumination), when the fiber tip is out of the tissue area and the laser emission is backreflected due to total-internal-reflection; and (2) on-state (maximum tissue illumination), when the fiber tip is on the absorbing tissue area and becomes "transparent" because of the frustrated-total-internal-reflectance and the laser energy is coupled into the absorber. Here, optical properties of tissue-activated fiber probes used for precise laser delivery are investigated both experimentally and theoretically by analyzing the backreflectance signal power. Optical fibers with various geometrical parameters are used and a spatial resolution of 2 mum is achieved when the fiber tip is moved toward the absorption tissue surface. The results confirm the system potential for on-the-spot laser delivery applicable to precise laser treatment, tissue diagnostics, and rnicro-scale surgical procedures. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Ilev, IK (reprint author), US FDA, Ctr Devices & Radiol Hlth, HFZ-134, Rockville, MD 20857 USA. NR 13 TC 2 Z9 2 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-4355-7 J9 P SOC PHOTO-OPT INS PY 2002 VL 4616 BP 220 EP 228 DI 10.1117/12.463817 PG 9 WC Engineering, Biomedical; Instruments & Instrumentation; Optics SC Engineering; Instruments & Instrumentation; Optics GA BU44B UT WOS:000175999200028 ER PT J AU Seo, PR Shah, VP Polli, JE AF Seo, PR Shah, VP Polli, JE TI Novel metrics to compare dissolution profiles SO PHARMACEUTICAL DEVELOPMENT AND TECHNOLOGY LA English DT Article DE dissolution; dissolution profile comparison; metoprolol tartrate; bioequivalence ID CURVE COMPARISON METRICS; BIOEQUIVALENCE AB Purpose: To evaluate four novel metrics that compare dissolution profiles and assess their performance characteristics by comparing dissolution profiles of FAST and SLOW immediate release metoprolol tartrate tablets. Methods: The four novel metrics (rho, rho(m), delta(a), and delta(s)), along with f(2), were applied to dissolution data from FAST and SLOW metoprolol tartrate tablets. For example, rho(m) is defined as: rho(m) = Sigma(t=1)(n) (R-t + T-t) [RATIO(t)-1]/Sigma(t=1)(n) (R-t + T-t) where R, is the percent dissolved of the reference product at time t, T-t the percent dissolved of the test product at time t, and RATIO(t) the larger of either R-t/T-t, or T-t/R-t, The mean metric values, upper (or lower) confidence limits, and skewness values were calculated, in order to characterize the performance of each metric. Results: The mean values of rho, rho(m), delta(a), delta(s), and f(2) were 1.80, 0.80, 0.47, 0.36, and 19.6, respectively. The novel metrics indicate that greater than a 50% relative difference exists between the FAST and SLOW profiles. The upper 95% confidence limits for rho, rho(m), delta(a), and delta(s) were 1.84, 0.83, 0.48, and 0.38, respectively, with f(2) having a lower limit of 19.1. Skewness values for ln-transformed rho, rho(m), delta(a), delta(s), and f(2) were 0.81, 0.71, 0.86, 0.47, and - 0.94, respectively, suggesting favorable metric distribution properties. Conclusions: The direct curve comparison metrics rho, rho(m), delta(a), and delta(s) appear to be viable methods to compare dissolution profiles, particularly rho(m). C1 Univ Maryland, Sch Pharm, Dept Pharmaceut Sci, Baltimore, MD 21201 USA. US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20855 USA. RP Polli, JE (reprint author), Univ Maryland, Sch Pharm, Dept Pharmaceut Sci, 20 N Pine St, Baltimore, MD 21201 USA. NR 11 TC 1 Z9 1 U1 0 U2 2 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 1083-7450 J9 PHARM DEV TECHNOL JI Pharm. Dev. Technol. PY 2002 VL 7 IS 2 BP 257 EP 265 DI 10.1081/PDT-120003493 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 560KK UT WOS:000176081100012 PM 12066580 ER PT J AU Haidar, SH Johnson, SB Fossler, MJ Hussain, AS AF Haidar, SH Johnson, SB Fossler, MJ Hussain, AS TI Modeling the pharmacokinetics and pharmacodynamics of a unique oral hypoglycemic agent using neural networks SO PHARMACEUTICAL RESEARCH LA English DT Article DE repaglinide; neural networks; pharmacokinetics-pharmacodynamics; models; type 2 diabetes ID IN-VITRO; PREDICTION AB Purpose. To develop a predictive population pharmacokinetic/pharmacodynamic (PK/PD) model for repaglinide (REP), an oral hypoglycemic agent, using artificial neural networks (ANNs). Methods. REP, glucose concentrations, and demographic data from a dose ranging Phase 2 trial were divided into a training set (70%) and a test set (30%). NeuroShell Predictor(TM) was used to create predictive PK and PK/PD models using population covariates; evaluate the relative significance of different covariates; and simulate the effect of covariates on the PK/PD of REP. Predictive performance was evaluated by calculating root mean square error and mean error for the training and test sets, These values were compared to naive averaging (NA) and randomly generated numbers (RN). Results. Covariates found to have an influence on PK of REP include dose, gender, race, age, and weight. Covariates affecting the glucose response included dose, gender, and weight. These differences are not expected to be clinically significant. Conclusions. We came to the following three conclusions: 1) ANNs are more precise than NA and RN for both PK and PD; 2) the bias was acceptable for ANNs as compared with NA and RN; and 3) neural networks offer a quick and simple method for predicting, for identifying significant covariates, and for generating hypotheses. C1 US FDA, Off Clin Pharmacol & Biopharmaceut, Rockville, MD 20857 USA. DuPont Pharmaceut, Drug Metab & Pharmacokinet, Newark, DE 19714 USA. US FDA, Off Testing & Res, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Haidar, SH (reprint author), 5600 Fishers Lane,HFD-870,Rm 13B17, Rockville, MD 20857 USA. NR 15 TC 16 Z9 18 U1 0 U2 1 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0724-8741 J9 PHARMACEUT RES JI Pharm. Res. PD JAN PY 2002 VL 19 IS 1 BP 87 EP 91 DI 10.1023/A:1013611617787 PG 5 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 516YL UT WOS:000173584300013 PM 11837705 ER PT J AU Gobburu, JVS Lawrence, J AF Gobburu, JVS Lawrence, J TI Application of resampling techniques to estimate exact significance levels for covariate selection during nonlinear mixed effects model building: Some inferences SO PHARMACEUTICAL RESEARCH LA English DT Article DE mixed effects modeling; covariate selection; hypothesis testing; resampling AB Purpose. One of the main objectives of the nonlinear mixed effects modeling is to provide rational individualized dosing strategies by explaining the interindividual variability using intrinsic and/or extrinsic factors (covariates). The aim of the current study was to evaluate, using computer simulations and real data, methods for estimating the exact significance level for including or excluding a covariate during model building. Methods. Original data were simulated using a simple one-compartment pharmacokinetic model with (full model) or without (null model) covariates (one or two). The covariate values in the original data were resampled (using either permutations or parametric bootstrap methods) to generate data under the null hypothesis that there is no covariate effect. The original and permuted data were fitted to null and full models, using first-order and first-order condition estimation (with or without interaction) methods in NONMEM, to compare the asymptotic and conditional p-value. Target log-likelihood ratio cutoffs for assessing covariate effects were derived. Results. The simulations showed that for sparse as well as dense data, the first-order condition estimation methods yielded the bust results while the first-order method performs somewhat better for sparse data. Depending on the modeling objective, the appropriate asymptotic p-value can be substituted for the conditional significance level. Target log-likelihood ratio cutoffs should be determined separately for each covariate when exact p-values are important. Conclusions. Resampling methods can be employed to estimate the exact significance level for including a covariate during nonlinear mixed effects model building. Some reasonable inferences can be drawn for potential application to design future population analyses. C1 US FDA, Div Pharmaceut Evaluat 1, Off Clin Pharmacol & Biopharmaceut, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. US FDA, Off Biostat, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Gobburu, JVS (reprint author), 1451 Rockville Pike,Room 5088,HFD-860, Rockville, MD 20852 USA. EM gobburuj@cder.fda.gov NR 11 TC 24 Z9 24 U1 0 U2 1 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0724-8741 J9 PHARM RES-DORDR JI Pharm. Res. PD JAN PY 2002 VL 19 IS 1 BP 92 EP 98 DI 10.1023/A:1013615701857 PG 7 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 516YL UT WOS:000173584300014 PM 11841044 ER PT J AU Walker, AM Wise, RP AF Walker, AM Wise, RP TI Precautions for proactive surveillance SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Article DE postmarketing drug surveillance; information retrieval systems; pattern recognition AB Four barriers confront the architects and users of surveillance systems. Bonferroni's Bind blunts our ability to act on real safety signals when the surveillance scheme is capable of producing realistic but wrong signals just by chance. The paradox of definitive data is that the results of a truly comprehensive scheme become untestable because there is no further relevant information to be had. Flexible priors augment the first two barriers by intensifying our instinctive cautions, and by giving almost any claim the appearance of empiric proof. The poverty of tabular summaries is that they presuppose the existance of relevant categories for tabulation, and that they fail to persuade. The resolution for proactive surveillance is sen/cen: high sensitivity to signals and vigorous censoring to filter out the noise. Copyright (C) 2002 John Wiley Sons, Ltd. C1 Ingenix Pharmaceut Serv, Div Epidemiol, Newton Lower Falls, MA 02462 USA. Harvard Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. RP Walker, AM (reprint author), Ingenix Pharmaceut Serv, Div Epidemiol, 1 Newton Execut Pk, Newton Lower Falls, MA 02462 USA. NR 2 TC 6 Z9 6 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD JAN-FEB PY 2002 VL 11 IS 1 BP 17 EP 20 DI 10.1002/pds.675 PG 4 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 535DA UT WOS:000174628900004 PM 11998546 ER PT J AU Dong, SM Yu, HT Hwang, HM Fu, PP AF Dong, SM Yu, HT Hwang, HM Fu, PP TI Effects of histidine on light-induced DNA single-strand cleavage by selected polycyclic aromatic hydrocarbons SO POLYCYCLIC AROMATIC COMPOUNDS LA English DT Article; Proceedings Paper CT 18th International Symposium on Polycyclic Aromatic Compounds CY SEP 09-13, 2001 CL UNIV CINCINNATI, CINCINNATI, OHIO SP Int Soc Polycycl Aromat Compounds HO UNIV CINCINNATI DE histidine; DNA cleavage; PAH; singlet oxygen; UVA light ID OXYGEN; DIPEPTIDES; SYSTEMS; DAMAGE AB The combination of UVA light and 1-aminopyrene, 1-hydroxypyrene, 1-hydroxybenzo[a]pyrene, 3-aminofluoranthene, 6-aminochrysene, or 5-, 6-, and 7-methylbenz[a]anthracenes causes DNA single-strand cleavage. 1-Hydroxypyrene, 1-hydroxybenzo[a]pyrene, and 5-methylbenz[a]anthracene have been shown to cause DNA cleavage, at least partially, by generating singlet oxygen. Therefore, the presence of histidine, a singlet oxygen quencher, should inhibit the DNA photocleavage. However, the presence of 50 mM histidine greatly enhances the DNA photocleavage caused by these compounds. This effect is due to the inhibition of the photodegradation of the PAH compounds. Therefore, care must be taken when interpreting the singlet oxygen quenching data by histidine. Histidine may coexist with PAHs that have entered the body. The presence of histidine can alter the photochemical reaction and, possibly, the phototoxicity mechanism of the PAHs. C1 Jackson State Univ, Dept Chem, Jackson, MS 39217 USA. Jackson State Univ, Dept Biol, Jackson, MS USA. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Dong, SM (reprint author), Jackson State Univ, Dept Chem, Jackson, MS 39217 USA. NR 22 TC 4 Z9 4 U1 0 U2 2 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1040-6638 J9 POLYCYCL AROMAT COMP JI Polycycl. Aromat. Compd. PY 2002 VL 22 IS 3-4 BP 451 EP 458 DI 10.1080/10406630290103663 PG 8 WC Chemistry, Organic SC Chemistry GA 592QX UT WOS:000177949300025 ER PT J AU Zeng, K Hwang, HM Fu, PP Yu, HT AF Zeng, K Hwang, HM Fu, PP Yu, HT TI Identification of 1-hydroxypyrene photoproducts and study of the effect of humic substances on its photolysis SO POLYCYCLIC AROMATIC COMPOUNDS LA English DT Article; Proceedings Paper CT 18th International Symposium on Polycyclic Aromatic Compounds CY SEP 09-13, 2001 CL UNIV CINCINNATI, CINCINNATI, OHIO SP Int Soc Polycycl Aromat Compounds HO UNIV CINCINNATI DE degradation; humic substance; 1-hydroxypyrene; light; photoproduct ID POLYCYCLIC AROMATIC-HYDROCARBONS; LEMNA-GIBBA; TOXICITY; PHENANTHRENE; METABOLITES; DEGRADATION; SEDIMENTS; EXPOSURE; CLEAVAGE; DUCKWEED AB Photolysis products of 1-hydrotypyrene (1-HP) were identified by liquid chromatography coupled with mass spectrometry (LC/MS/MS). It was found that the major photoproducts of 1-HP are 1,6 -, 1,8-, and one unidentified pyrene quinone and one pyrene quinone dimer based on their HPLC chromatogram and mass spectral data. The photolysis of 1-HP was conducted with pure water, natural river water, and pure water containing commercial humic substances. It was found that the photolysis rate of 1-HP can be inhibited by humic substances, depending on their type and concentration. C1 Jackson State Univ, Dept Biol, Jackson, MS 39217 USA. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Jackson State Univ, Dept Chem, Jackson, MS 39217 USA. RP Hwang, HM (reprint author), Jackson State Univ, Dept Biol, Jackson, MS 39217 USA. NR 27 TC 11 Z9 12 U1 0 U2 1 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1040-6638 J9 POLYCYCL AROMAT COMP JI Polycycl. Aromat. Compd. PY 2002 VL 22 IS 3-4 BP 459 EP 467 DI 10.1080/10406630290103672 PG 9 WC Chemistry, Organic SC Chemistry GA 592QX UT WOS:000177949300026 ER PT J AU Fu, PP Von Tungeln, LS Xia, QS Zhan, DJ Heflich, RH AF Fu, PP Von Tungeln, LS Xia, QS Zhan, DJ Heflich, RH TI Effect of nitro orientation on ras-protooncogene mutation in liver tumors from 7-nitrodibenz[a,h]anthracene-treated mice SO POLYCYCLIC AROMATIC COMPOUNDS LA English DT Article; Proceedings Paper CT 18th International Symposium on Polycyclic Aromatic Compounds CY SEP 09-13, 2001 CL UNIV CINCINNATI, CINCINNATI, OHIO SP Int Soc Polycycl Aromat Compounds HO UNIV CINCINNATI DE dibenz[a,h]anthracene; K-ras oncogene; liver tumors; neonatal mouse; 7-nitrodibenz[a,h]anthracene; nitro orientation ID POLYCYCLIC AROMATIC-HYDROCARBONS; NEONATAL B6C3F(1) MOUSE; H-RAS; TUMORIGENICITY; METABOLISM AB Dibenz[a,h]anthracene (DB[a,h]A) and 7-nitrodibenz[a,h]anthracene (7-NDB[a,h]A) induced liver tumors when administered to neonatal B6C3F(1) mice. For protooncogene analysis, RNA was isolated from each of the liver tumors from treated mice and reverse-transcribed into cDNA. Portions of the K- and H-ras protein coding sequences were then amplified and analyzed for DNA sequence alterations. DB[a,h]A-induced liver tumors had a 100% (23/23)frequency of ras-protooncogene mutation, with 83% (19/23) occurring at the first base of K-ras codon 13 and resulting in GGC --> CGC transversion; the remaining 17% (4/23) of the mutations were located at the second base of H-ras codon 61. In contrast, only four of nine (44%) of 7-NDB[a,h]A-induced liver tumors had ras-protooncogene mutations, with two each at K-ras codon 13 and H-ras codon 61. Combined with previous observations, the results indicate that the nitro substituent perpendicular to the aromatic moiety alters the chemical-induced protooncogene activation frequency and mutational pattern in liver tumors of B6C3F(1) mice. C1 Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Fu, PP (reprint author), Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 12 TC 1 Z9 1 U1 0 U2 1 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1040-6638 J9 POLYCYCL AROMAT COMP JI Polycycl. Aromat. Compd. PY 2002 VL 22 IS 3-4 BP 853 EP 859 DI 10.1080/10406630290104004 PG 7 WC Chemistry, Organic SC Chemistry GA 592QX UT WOS:000177949300059 ER PT J AU Yu, HT Dong, SM Fu, PP Hwang, HM AF Yu, HT Dong, SM Fu, PP Hwang, HM TI UVA light-induced DNA single-strand cleavage by hydroxybenzo[a]pyrenes SO POLYCYCLIC AROMATIC COMPOUNDS LA English DT Article; Proceedings Paper CT 18th International Symposium on Polycyclic Aromatic Compounds CY SEP 09-13, 2001 CL UNIV CINCINNATI, CINCINNATI, OHIO SP Int Soc Polycycl Aromat Compounds HO UNIV CINCINNATI DE benzo[a]pyrene; DNA cleavage; hydroxybenzo[a]pyrenes; light; metabolites; PAH ID POLYCYCLIC AROMATIC-HYDROCARBONS; CARCINOGENESIS; ENZYMES; ADDUCTS AB UVA light-induced DNA single-strand cleavage by 1-hydroxy, 3-hydroxy, 7-hydroxy, and 9-hydroxybenzo[a]pyrenes (OH-BaPs) and 6-acetoxybenzo[a]pyrene (6-OAc-BaP) was studied. Under experimental conditions, the concentrations of 1-OH, 3-OH, 7-OH, and 9-OH-BaPs and 6-OAc-BaP needed to cause 25% of the supercoiled form I plasmid DNA to become relaxed form II DNA were found to be 0.6, 2.5, 1.0, 1.3, and 1.1 muM, respectively. These concentrations are all smaller than that of BaP, which was 6 muM. These results indicate that on photoirradiation, OH-BaPs are more cytotoxic and/or genotoxic than their parent compound, BaP. Mechanistic studies reveal that singlet oxygen and superoxide free radicals are involved in causing DNA cleavage. C1 Jackson State Univ, Dept Chem, Jackson, MS 39217 USA. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Jackson State Univ, Dept Biol, Jackson, MS 39217 USA. RP Yu, HT (reprint author), Jackson State Univ, Dept Chem, Jackson, MS 39217 USA. NR 22 TC 3 Z9 3 U1 0 U2 1 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1040-6638 J9 POLYCYCL AROMAT COMP JI Polycycl. Aromat. Compd. PY 2002 VL 22 IS 3-4 BP 861 EP 870 DI 10.1080/104066320290104013 PG 10 WC Chemistry, Organic SC Chemistry GA 592QX UT WOS:000177949300060 ER PT J AU Jones, MB Krutzsch, H Shu, HJ Zhao, YM Liotta, LA Kohn, EC Petricoin, EF AF Jones, MB Krutzsch, H Shu, HJ Zhao, YM Liotta, LA Kohn, EC Petricoin, EF TI Proteomic analysis and identification of new biomarkers and therapeutic targets for invasive ovarian cancer SO PROTEOMICS LA English DT Article; Proceedings Paper CT Meeting of the British-Electrophoresis-Society CY APR 04-06, 2001 CL YORK, ENGLAND SP British Electrophoresis Soc DE ovarian; microdissection; cancer; biomarkers; laser capture ID LASER CAPTURE MICRODISSECTION; HUMAN PROSTATE-CANCER; MASS-SPECTROMETRY; GLYOXALASE-I; CARCINOMA; PROTEIN; DIAGNOSIS; RECEPTORS; TUMORS; CELLS AB Epithelial ovarian cancer kills almost 16 000 women each year in part due to late stage of presentation and lack of reliable biomarkers for disease detection. CA-125, the currently accepted serum marker, alone lacks the sensitivity for early stage diagnosis, as only 50% of early stage cases are detected with this marker. Although more early stage cases may be detected by lysophosphatidic acid, this marker is also elevated in other cancers. One major objective of the NCI-FDA Tissue Proteomics Initiative has been to combine the technique of laser capture microdissection (LCM) of epithelial tumor cells in human tissue specimens with two-dimensional gel electrophoresis (2-D PAGE) to identify proteins that may serve as invasive ovarian cancer-specific biomarkers for early detection and/or new therapeutic targets. We performed 2-D PAGE on lysates from five microdissected ovarian tumors (three invasive ovarian cancers and two non-invasive, low malignant potential (LMP) ovarian tumors). We then compared silver stained 2-D gels created from microdissected lysates with SYPRO-Ruby stained 2-D PAGE profiles of the patient-matched undissected bulk tumor lysates from all five patients. Twenty-three proteins were consistently differentially expressed between both the LMP and three invasive ovarian tumors in the limited study set. Thirteen were uniquely present in all three of the invasive ovarian cancer cases and absent or under-expressed in the two LMP cases. Ten were uniquely present in the LMP cases but absent or under-expressed in all invasive ovarian cancer cases. Credentialing and preliminary target validation of the mass spectrometry identified proteins cut from the Ruby-red stained gels was performed by LCM coupled Western blot and reverse-phase array technology in a study set of six cases (the aforementioned five cases used in the 2-D PAGE profiling component of the study plus one additional LMP case). The analysis revealed that the 52 kDa FK506 binding protein, Rho G-protein dissociation inhibitor (RhoGDI), and glyoxalase I are found to be uniquely over-expressed in invasive human ovarian cancer when compared to the LMP form of this cancer. The direct comparison of LCM generated proteomic profiles of invasive vs. LMP ovarian cancer may more directly generate important markers for early detection and/or therapeutic targets unique to the invasive phenotype. C1 NCI, US FDA,Clin Prote Program, Pathol Lab, Ctr Canc Res,NIH, Bethesda, MD USA. Univ Texas, SW Med Sch, Dept Biochem & Pharmacol, Dallas, TX 75230 USA. NCI, US FDA, Clin Prote Program, Div Therapeut Prod,Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Petricoin, EF (reprint author), Bldg 29A Room 2B02,8800 Rockville Pike, Bethesda, MD 20892 USA. NR 41 TC 222 Z9 251 U1 1 U2 11 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 JAN PY 2002 VL 2 IS 1 BP 76 EP 84 DI 10.1002/1615-9861(200201)2:1<76::AID-PROT76>3.3.CO;2-F PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 513BU UT WOS:000173358700010 PM 11788994 ER PT J AU Churchwell, MI Holder, CL Little, D Preece, S Smith, DJ Doerge, DR AF Churchwell, MI Holder, CL Little, D Preece, S Smith, DJ Doerge, DR TI Liquid chromatography/electrospray tandem mass spectrometric analysis of incurred ractopamine residues in livestock tissues SO RAPID COMMUNICATIONS IN MASS SPECTROMETRY LA English DT Article ID BETA-AGONIST; CLENBUTEROL AB Ractopamine HCl is a beta-adrenergic agonist (beta-agonist) recently approved by the U.S. Food and Drug Administration, but not other governmental agencies, for use in finishing swine. For these reasons, it was important to develop and validate mass spectrometric methods for the detection and confirmation of ractopamine residues in livestock marker tissues. Incurred tissues in cattle, sheep, turkeys, and ducks were generated during 7-day ractopamine feeding (20 ppm in diets) periods. Disposition of ractopamine residues in liver and pigmented retinal epithelium was determined in animals slaughtered with withdrawal periods of 0, 3, and 7 days. Ractopamine residues, purified using solid-phase extraction, were measured using liquid chromatography (LC) and electrospray with detection by tandem mass spectrometry (MS/MS) in the multiple reaction-monitoring (MRM) mode. Total ractopamine residues (parent ractopamine + hydrolyzed conjugates) in liver were detected in all species on withdrawal day 7 (<1 ppb) and were greatly diminished in all species by withdrawal day 7 (<1 ppb). Bovine and ovine retina had lower levels of ractopamine (0.5-3 ppb) than liver, and occular residues increased with withdrawal time, suggesting redistribution into this tissue. Lower limits of quantification were found to be approximately 0.1 ppb in liver and retina. Incurred ractopamine residues were confirmed by the precise and accurate agreement of MRM intensity ratios of diagnostic fragment ions (m/z 284, 164, and 121) from the protonated molecule between ractopamine residues in incurred samples and an authentic ractopamine standard. The limits of confirmation in liver and retina using recognized acceptance criteria were below 1 ppb. The high sensitivity and specificity for measurement and confirmation of ractopamine residues suggests this method will be applicable for regulatory residue surveillance programs. Copyright (C) 2002 John Wiley Sons, Ltd. C1 Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Micromass, Manchester, Lancs, England. USDA ARS, Biosci Res Lab, Fargo, ND 58105 USA. RP Doerge, DR (reprint author), Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. NR 9 TC 40 Z9 44 U1 1 U2 5 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0951-4198 J9 RAPID COMMUN MASS SP JI Rapid Commun. Mass Spectrom. PY 2002 VL 16 IS 13 BP 1261 EP 1265 DI 10.1002/rcm.717 PG 5 WC Chemistry, Analytical; Spectroscopy SC Chemistry; Spectroscopy GA 570HM UT WOS:000176652900002 PM 12112252 ER PT J AU Tabacova, SA Kimmel, CA AF Tabacova, SA Kimmel, CA TI Atenolol: pharmacokinetic/dynamic aspects of comparative developmental toxicity SO REPRODUCTIVE TOXICOLOGY LA English DT Review DE antihypertensive drug; beta-adrenoreceptor antagonists; atenolol; pharmacokinetics; pharmacodynamics; developmental toxicity; animal-human comparisons ID PREGNANCY-ASSOCIATED HYPERTENSION; BETA-ADRENOCEPTOR ANTAGONIST; UTERINE CIRCULATIONS; FETAL HEMODYNAMICS; CONTROLLED TRIAL; PROPRANOLOL; PINDOLOL; ACEBUTOLOL; METOPROLOL; INFUSION C1 US FDA, Natl Ctr Toxicol Res, Rockville, MD 20857 USA. US EPA, Natl Ctr Environm Assessment, Off Res & Dev, Washington, DC 20460 USA. RP Tabacova, SA (reprint author), US FDA, Natl Ctr Toxicol Res, Rockville, MD 20857 USA. NR 73 TC 20 Z9 21 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0890-6238 J9 REPROD TOXICOL JI Reprod. Toxicol. PD JAN-FEB PY 2002 VL 16 IS 1 BP 1 EP 7 AR PII S0890-6238(02)00193-9 DI 10.1016/S0890-6238(01)00193-9 PG 7 WC Reproductive Biology; Toxicology SC Reproductive Biology; Toxicology GA 539UC UT WOS:000174888700003 PM 11934527 ER PT J AU Doerge, DR Twaddle, NC Churchwell, MI Chang, HC Newbold, RR Delclos, KB AF Doerge, DR Twaddle, NC Churchwell, MI Chang, HC Newbold, RR Delclos, KB TI Mass spectrometric determination of p-nonylphenol metabolism and disposition following oral administration to Sprague-Dawley rats SO REPRODUCTIVE TOXICOLOGY LA English DT Article DE nonylphenol; mass spectrometry; toxicokinetics; alkylphenol ethoxylates ID TROUT ONCORHYNCHUS-MYKISS; TISSUE DISTRIBUTION; BISPHENOL-A; IN-VITRO; 4-NONYLPHENOL; OCTYLPHENOL; HEPATOCYTES; VIVO; DNA AB Isomers of 4-nonylphenol (NP), which are important industrial compounds and environmental breakdown products from widely used surfactants, have estrogenic activity in vitro and in vivo that has prompted interest in its potential for modulation of endocrine function in humans and wildlife. Mass spectrometry was used to quantify NP and metabolites in serum and endocrine-responsive tissues from dietary exposure in Sprague-Dawley rats. Tissue accumulation of NP aglycone was observed despite the predominance of glucuronidation in blood. Serum toxicokinetics of total NP, measured following gavage administration, showed rapid absorption and elimination (average half-times 0.8 and 3.5 h, respectively). NP was similarly administered by gavage to pregnant dams and total and aglycone NP were measured in clam serum and fetuses to show placental transfer into serum and brain. These data provide a basis for future correlations of biologic effects observed following dietary exposure in rats with those predicted from environmental exposures to humans. (C) 2002 Elsevier Science Inc. All rights reserved. C1 Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. NIEHS, Dev Endocrinol Sect, Reprod Toxicol Grp, Lab Toxicol,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 32 TC 35 Z9 38 U1 3 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0890-6238 J9 REPROD TOXICOL JI Reprod. Toxicol. PD JAN-FEB PY 2002 VL 16 IS 1 BP 45 EP 56 AR PII S0890-6238(01)00198-8 DI 10.1016/S0890-6238(01)00198-8 PG 12 WC Reproductive Biology; Toxicology SC Reproductive Biology; Toxicology GA 539UC UT WOS:000174888700007 PM 11934531 ER PT J AU Reeves, JB Reeves, VB AF Reeves, JB Reeves, VB TI Effects of apodization function, zero filling, background spectra, and absorbance transformation on mid-infrared calibrations for feed composition SO SPECTROSCOPY LETTERS LA English DT Article DE apodization function; zero filling; background spectra; absorbance transformation; mid-infrared calibrations; feed composition; multivariate analysis ID DIFFUSE-REFLECTANCE SPECTROSCOPY; PARTICLE-SIZE MORPHOLOGY; CARBOHYDRATE SYSTEMS; SAMPLE DILUTION AB Research has demonstrated that, diffuse. reflectance mid-infrared spectroscopy can, like near-infrared diffuse reflectance, be used to quantitatively determine the composition of ground samples of forages and soils without the need for KBr dilution. While it has been demonstrated that the accuracy of calibrations developed using mid-infrared spectra can be equal to or better than that achieved,using near-infrared spectra, the influence of factors such as apodization function has not been determined. Results based on the spectra of 173 treated forage samples obtained using a DigiLab FTS-60 spectrometer have demonstrated that many parameters associated with mid-infrared spectra have little or no effect on partial least squares calibrations. Additional zero filling of spectra had little effect other than to increase the derivative gaps found to produce optimal calibrations, but calibrations developed using Kubelka-Munk transformed data, as opposed to absorbance data, were not as accurate. Choice of apodization function also had little effect, although slightly better results were found using triangular or weak Norton-Beer. Likewise, the frequency of taking a background spectrum did not seem to have any great effect on calibrations, although results were slightly better with hourly or daily acquisitions as opposed to one for each sample as is done in the near-infrared. C1 USDA ARS, ANRI, AMBL, BARC E, Beltsville, MD 20705 USA. US FDA, CVM, Rockville, MD 20855 USA. RP Reeves, JB (reprint author), USDA ARS, ANRI, AMBL, BARC E, Bldg 306,Rm 101, Beltsville, MD 20705 USA. NR 23 TC 4 Z9 4 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0038-7010 J9 SPECTROSC LETT JI Spectr. Lett. PY 2002 VL 35 IS 5 BP 663 EP 680 DI 10.1081/SL-120014938 PG 18 WC Spectroscopy SC Spectroscopy GA 610VF UT WOS:000178981500004 ER PT J AU Greenberg, JP Yen, YF Scales, C Williams, C Bastings, EP Wittenberg, GF Pons, TP Good, DC AF Greenberg, JP Yen, YF Scales, C Williams, C Bastings, EP Wittenberg, GF Pons, TP Good, DC TI Serial functional magnetic resonance imaging of motor function after stroke SO STROKE LA English DT Meeting Abstract C1 Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA. Univ Western Ontario, London, ON, Canada. 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 0039-2499 J9 STROKE JI Stroke PD JAN PY 2002 VL 33 IS 1 MA P308 BP 417 EP 417 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 509KV UT WOS:000173147700486 ER PT J AU Zhang, J Herman, EH Knapton, A Chadwick, DP Whitehurst, VE Koerner, JE Papoian, T Ferrans, VJ Sistare, FD AF Zhang, J Herman, EH Knapton, A Chadwick, DP Whitehurst, VE Koerner, JE Papoian, T Ferrans, VJ Sistare, FD TI SK&F 95654-induced acute cardiovascular toxicity in Sprague-Dawley rats - Histopathologic, electron microscopic, and immunohistochemical studies SO TOXICOLOGIC PATHOLOGY LA English DT Article DE myocardial necrosis and inflammation; drug-induced vasculitis; vasodilatation; endothelial cell activation; endothelial and smooth muscle cell apoptosis; intercellular adhesion molecule-1 (ICAM-1); von Willebrand factor; mast cell degranulation ID ENDOTHELIAL-CELL ACTIVATION; SMOOTH-MUSCLE CELLS; PHOSPHODIESTERASE INHIBITORS; ADHESION MOLECULES; MAST-CELLS; APOPTOSIS; DEATH; CARDIOTOXICITY; INFLAMMATION; NOMENCLATURE AB The characteristics and pathogenesis of the cardiovascular toxicity induced by the type III selective phosphodiesterase inhibitor SK&F 95654 were examined in 2 studies. Sprague-Dawley rats received either a single sc injection of 50, 100, or 200 mg/kg SK&F 95654 and were euthanized at 24 hours after administration of the drug (Study 1), or were given a single subcutaneous (sc) injection of 100 mg/kg SK&F 95654 and euthanized at 1, 2, 4, 6, 8, 12, 24 hours, or 2 weeks after treatment (Study 2). Control rats received either DMSO or saline. Myocardial lesions and vascular lesions of the mesentery, spleen, and pancreas were seen 24 hours after dosing with either 50, 100, or 200 mg/kg SK&F 95654. The frequency and severity of these lesions (evaluated after the 100 mg/kg dose) increased with time over a period of 1 to 24 hours. By 2 weeks, the lesions subsided. Cardiac lesions consisted of myocyte necrosis with hypercontraction bands, inflammatory cell infiltration, interstitial hemorrhage, and interstitial edema. Vascular lesions of the mesentery were most prominent and consisted of vasodilatation and inflammation in the small-sized vessels, arterial medial necrosis and hemorrhage, and venous thrombosis. The vascular lesions included: leukocyte adhesion to endothelial cells, transendothelial migration of leukocytes, and inflammatory cell infiltration into vessel walls. Affected vessels included arteries, terminal arterioles, capillaries, postcapillary venules, and veins. Apoptosis of endothelial and smooth muscle cells was detected in the mesenteric vasculature by both TUNEL assay and electron microscopy. Evidence of endothelial cell activation in the mesenteric arteries and veins was also observed by electron microscopy. Immunohistochemical staining detected enhanced endothelial cell expression of intercellular adhesion molecule-1 (ICAM-1) and von Willebrand factor (vWF) in the mesenteric arteries and veins. Mast cells were noted to be more prevalent in affected mesenteric tissue from drug-treated animals. The present findings suggest that apoptosis of endothelial and smooth muscle cells, activation of endothelial cells, recruitment of mast cells, and increased expression of adhesion molecules are important factors to the overall pathogenesis of SK&F 95654-induced vasculitis. C1 US FDA, Ctr Drug Evaluat & Res, Div Appl Pharmacol Res HFD910, Laurel, MD 20708 USA. US FDA, Ctr Drug Evaluat & Res, Div Pulm Drug Prod HFD570, Rockville, MD 20857 USA. US FDA, Ctr Drug Evaluat & Res, Div Cardiorenal Drug Prod HFD110, Rockville, MD 20857 USA. US FDA, Ctr Drug Evaluat & Res, Div Anesthet Crit Care & Addict Drug Prod HFD170, Rockville, MD 20857 USA. NHLBI, Pathol Sect, NIH, Bethesda, MD 20892 USA. RP Herman, EH (reprint author), US FDA HFD910, Ctr Drug Evaluat & Res, Div Appl Pharmacol Res, 8301 Muirkirk Rd, Laurel, MD 20708 USA. NR 45 TC 37 Z9 37 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 JAN 1 PY 2002 VL 30 IS 1 BP 28 EP 40 DI 10.1080/01926230252824680 PG 13 WC Pathology; Toxicology SC Pathology; Toxicology GA 558ED UT WOS:000175952600006 PM 11890473 ER PT J AU Kuester, RK Waalkes, MP Goering, PL Fisher, BL McCuskey, RS Sipes, IG AF Kuester, RK Waalkes, MP Goering, PL Fisher, BL McCuskey, RS Sipes, IG TI Differential hepatotoxicity induced by cadmium in Fischer 344 and Sprague-Dawley rats SO TOXICOLOGICAL SCIENCES LA English DT Article DE cadmium; liver; Sprague-Dawley; Fischer344; heat shock protein 72; metallothionein; Kupffer cell; endothelial cell ID KUPFFER CELLS; LIVER; METALLOTHIONEIN; CHLORIDE; MACROPHAGES; TOXICITY; NEPHROTOXICITY; METABOLISM; MECHANISMS; TOLERANCE AB A number of reports document that Fischer 344 (F344) rats are more susceptible to chemically induced liver injury than Sprague-Dawley (SD) rats. Cadmium (CdCl2), a hepatotoxicant that does not require bioactivation, was used to better define the biological events that are responsible for the differences in liver injury between F344 and SD rats. CdCl2 (3 mg/kg) produced hepatotoxicity in both rat strains, but the hepatic injury was 18-fold greater in F344 rats as assessed by plasma alanine aminotransferase (ALT) activity. This difference in toxicity was not observed when isolated hepatocytes were incubated with CdCl2 in vitro, indicating that other cell types contribute to Cd-induced hepatotoxicity in vivo. Indeed, the sieve plates of hepatic endothelial cells (EC) in F344 rats were damaged to a greater degree than EC in SD rats. Additionally, Kupffer cell (KC) inhibition reduced hepatotoxicity in both strains, suggesting that this cell type is involved in the progression of CdCl2-induced hepatotoxicity. Moreover, enhanced synthesis of heat shock protein 72 occurred earlier in the SD rat. Maximal levels of hepatic metallothionein (MT), a protein associated with cadmium tolerance, were greater in SD rats. These protective factors may limit CdCl2-induced hepatocellular injury in SD compared with F344 rats by reducing KC activation and the subsequent inflammatory response that allows for the progression of hepatic injury. C1 Univ Arizona, Dept Pharmacol & Toxicol, Ctr Toxicol, Tucson, AZ 85721 USA. NIEHS, NCI, Res Triangle Pk, NC 27709 USA. US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Sipes, IG (reprint author), Univ Arizona, Dept Pharmacol & Toxicol, Ctr Toxicol, POB 210297, Tucson, AZ 85721 USA. FU NIEHS NIH HHS [ES-06694] NR 39 TC 50 Z9 55 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 JAN PY 2002 VL 65 IS 1 BP 151 EP 159 DI 10.1093/toxsci/65.1.151 PG 9 WC Toxicology SC Toxicology GA 508PJ UT WOS:000173097400017 PM 11752694 ER PT J AU Fang, GC Chu, CC Wu, YS Fu, PPC AF Fang, GC Chu, CC Wu, YS Fu, PPC TI Emission characters of particulate concentrations and dry deposition studies for incense burning at a Taiwanese temple SO TOXICOLOGY AND INDUSTRIAL HEALTH LA English DT Article DE dry deposition velocities; incense; metal element; particulate matter; size distribution; temple ID AEROSOLS; PM2.5; MATTER; PM10 AB Suspended particulate concentrations were measured at the Tzu Yun Yen temple in the Taichung region of Taiwan. The temple performs traditional incense burning. A universal sampler and a micro-orifice uniform deposited impactor (MOUDI) sampler with a dry deposition plate were used to measure the particulate concentrations. The results show that the average PM2.5/PM10 ratio was 74% during the incense burning period at this temple. In addition, the average suspended particulate (PM10) element concentration of anthropogenic element Zn(495 ng/m(3)) was higher than the other anthropogenic elements (Pb, Mn, Ni, and Cd). Furthermore, the average mass size distribution was bimodal with major peaks occurring at 0.32-0.56 mum and 5.6-10 mum during the incense burning period. The dry deposition velocities of Cd used fine particulates (PM2.5) and suspended particulate (PM10) mode were 1.86 and 0.99 cm/s in this study, respectively. C1 Hungkuang Univ, Air Tox & Environm Anal Lab, Taichung 433, Taiwan. Chien Yu Reg Teaching Hosp, Intens Care Unit, 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, Sha Lu, Taichung 433, Taiwan. NR 14 TC 8 Z9 8 U1 1 U2 7 PU ARNOLD, HODDER HEADLINE PLC PI LONDON PA 338 EUSTON ROAD, LONDON NW1 3BH, ENGLAND SN 0748-2337 J9 TOXICOL IND HEALTH JI Toxicol. Ind. Health PY 2002 VL 18 IS 4 BP 183 EP 190 DI 10.1191/0748233702th140oa PG 8 WC Public, Environmental & Occupational Health; Toxicology SC Public, Environmental & Occupational Health; Toxicology GA 721RA UT WOS:000185328300004 PM 12974541 ER PT J AU Saldanha, J Lelie, N Yu, MW Heath, A AF Saldanha, J Lelie, N Yu, MW Heath, A CA B19 Collaborative Study Grp TI Establishment of the first World Health Organization International Standard for human parvovirus B19 DNA nucleic acid amplification techniques SO VOX SANGUINIS LA English DT Article DE human parvovirus B19; International Standard; NAT assays; WHO collaborative study ID PLASMA POOLS; ASSAY; BLOOD AB Background and Objectives A collaborative study, involving 26 laboratories from 14 countries, was carried out in order to establish a World Health Organization (WHO) International Standard for human parvovirus B19 (B19) DNA nucleic acid amplification techniques (NAT). Materials and methods Four samples: AA, BB (which were lyophilized), CC and DD (which were liquid preparations) were analysed using several different NAT assays. The mean B19 DNA content of each sample was determined for each laboratory using an end-point dilution method. Results There was good agreement between the overall mean 'equivalents'/ml obtained by the different assays. The mean log(10) 'equivalents'/ml were 5.76 for sample AA, 5.73 for sample BB, 5.82 for sample CC and 7.70 for sample DD. The differences in titre among samples AA, BB and CC were not statistically significant, but the titre of DD was significantly higher. Conclusions Despite the range of NAT assays used in the study, it was possible to calculate the mean B19 DNA concentrations in the four preparations. Lyophilized preparation AA was established as the first International Standard for B19 DNA NAT assays and was assigned a concentration of 10(6) international units (IU)/ml. C1 Natl Inst Biol Standards & Controls, Div Virol, S Mimms EN6 30J, Herts, England. CLB, Amsterdam, Netherlands. FDA, CBER, Div Hematol, Bethesda, MD USA. Natl Inst Biol Standards & Controls, Infomat Div, S Mimms EN6 30J, Herts, England. RP Saldanha, J (reprint author), Natl Inst Biol Standards & Controls, Div Virol, Blanche Lane, S Mimms EN6 30J, Herts, England. OI Doyle, Sean/0000-0003-1679-3247 NR 20 TC 71 Z9 80 U1 0 U2 1 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0042-9007 J9 VOX SANG JI Vox Sang. PD JAN PY 2002 VL 82 IS 1 BP 24 EP 31 DI 10.1046/j.1423-0410.2002.00132.x PG 8 WC Hematology SC Hematology GA 513DL UT WOS:000173362600005 PM 11856464 ER PT J AU Wang, JH Guan, E Roderiquez, G Calvert, V Alvarez, R Norcross, MA AF Wang, JH Guan, E Roderiquez, G Calvert, V Alvarez, R Norcross, MA TI Role of tyrosine phosphorylation in ligand-independent sequestration of CXCR4 in human primary monocytes-macrophages SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; FOCAL ADHESION KINASE; HEMATOPOIETIC PROGENITOR CELLS; CHEMOKINE RECEPTOR CXCR4; HUMAN T-LYMPHOCYTES; SIGNAL-TRANSDUCTION; HIV-1 INFECTION; CCR5 EXPRESSION; BETA-ARRESTIN; BETA(2)-ADRENERGIC RECEPTOR AB The chemokine stromal cell-derived factor (SDF)-1 and its receptor, CXCR4, play important roles in human immunodeficiency virus type 1 (HIV-1) pathophysiology, leukocyte trafficking, inflammation, hematopoiesis, embryogenesis, angiogenesis, and cancer metastasis. The effects of cytokines on the regulation of CXCR4 function were investigated in human primary monocytes-macrophages. The expression of functional CXCR4 on the cell surface was demonstrated by the detection of ligand-in-induced Ca2+ mobilization, chemotaxis, and ligand-induced receptor endocytosis. Surface CXCR4 expression was down-regulated by cytokines interleukin-4 (IL-4), IL-13, and granulocyte-macrophage colony-stimulating factor (GM-CSF) and up-regulated by IL-10 and transforming growth factor-beta1. Down-regulation was mediated post-translationally, in the absence of protein degradation, through an endocytotic mechanism. In contrast to SDF-1alpha-induced CXCR4 endocytosis, cytokine-induced endocytosis of this receptor was independent of actin filament polymerization. GM-CSF increased the expression of G protein-coupled receptor kinase 3 (GRK3), beta-arrestin-1, Pyk2, and focal adhesion kinase (FAK). Cytokine treatment also increased the total and tyrosine-specific phosphorylation of CXCR4 as well as the phosphorylation of FAK on tyrosine 397. It also induced the formation of GRK3.CXCR4 or FAK.CXCR4 complexes. Infection of macrophages by primary R5X4 and X4 isolates of HIV-1 was inhibited by IL-4, IL-13, and GM-CSF, an effect that was associated with down-regulation of surface CXCR4 expression. These data indicate that ligand-dependent and ligand-independent endocytoses of CXCR4 are mediated by different mechanisms. Cytokine-induced endocytosis of chemokine receptors may be of therapeutic value in HIV-1 infection, inflammation, tumor metastasis, and defective hematopoiesis. C1 US FDA, Ctr Biol Evaluat & Res, Div Therapeut Prot, Lab Gene Regulat, Bethesda, MD 20892 USA. RP Norcross, MA (reprint author), US FDA, NIH,Ctr Biol Evaluat & Res, Div Therapeut Prot, Lab Gene Regulat, Bldg 29B,Rm 4E12,8800 Rockville Pike, Bethesda, MD 20892 USA. NR 67 TC 58 Z9 59 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 28 PY 2001 VL 276 IS 52 BP 49236 EP 49243 DI 10.1074/jbc.M108523200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 522XK UT WOS:000173922100081 PM 11668182 ER PT J AU Wilson, CA AF Wilson, CA TI Will some pig breeds or tissues be less likely to express infectious PERV? SO TRANSPLANTATION LA English DT Editorial Material ID ENDOGENOUS RETROVIRUS; HUMAN-CELLS; MICE C1 US FDA, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. RP Wilson, CA (reprint author), US FDA, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. NR 8 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD DEC 27 PY 2001 VL 72 IS 12 BP 1865 EP 1866 PG 2 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 508PU UT WOS:000173098300001 PM 11773881 ER PT J AU La Grenade, L Graham, D Nourjah, P AF La Grenade, L Graham, D Nourjah, P TI Underreporting of hemorrhagic stroke associated with phenylpropanolamine SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 US FDA, Rockville, MD 20857 USA. RP La Grenade, L (reprint author), US FDA, Rockville, MD 20857 USA. NR 3 TC 9 Z9 9 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD DEC 26 PY 2001 VL 286 IS 24 BP 3081 EP 3081 DI 10.1001/jama.286.24.3081 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 505QM UT WOS:000172927100023 PM 11754672 ER PT J AU Shvartsburg, AA Wilkes, JG Lay, JO Siu, KWM AF Shvartsburg, AA Wilkes, JG Lay, JO Siu, KWM TI Fragmentation and charge transfer in gas-phase complexes of divalent metal ions with acetonitrile SO CHEMICAL PHYSICS LETTERS LA English DT Article ID ELECTROSPRAY MASS-SPECTROMETRY; ALKALINE-EARTH; CHEMISTRY; MG; CA; BA; COORDINATION; IONIZATION; CLUSTERS; METHANOL AB The development of electrospray has enabled generation of gas-phase multiply charged metal ion complexes with various solvent molecules, These species exhibit rich fragmentation chemistry, involving competition among neutral ligand loss, ligand cleavage, and dissociative electron and proton transfer. Acetonitrile is a common aprotic solvent. Here we present a comprehensive MS/MS study on acetonitrile complexes of divalent metal cations. We measured the critical sizes below which dissociation channels other than the trivial neutral evaporation become operative and minimum sizes at which dications remain stable against charge reduction. For all sizes between the two, low-energy fragmentation patterns have been elucidated in detail. (C) 2001 Elsevier Science B.V. All rights reserved. C1 Natl Ctr Toxicol Res, Div Chem, Jefferson, AR 72079 USA. York Univ, Dept Chem, Toronto, ON M3J 1P3, Canada. York Univ, Ctr Res Mass Spectrometry, Toronto, ON M3J 1P3, Canada. RP Shvartsburg, AA (reprint author), Natl Ctr Toxicol Res, Div Chem, HFT-233,3900 NCTR Rd, Jefferson, AR 72079 USA. RI Lay, Jackson/G-1007-2011 OI Lay, Jackson/0000-0003-3789-2527 NR 28 TC 37 Z9 37 U1 0 U2 1 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 DEC 21 PY 2001 VL 350 IS 3-4 BP 216 EP 224 DI 10.1016/S0009-2614(01)01278-7 PG 9 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 507YG UT WOS:000173058400005 ER PT J AU Lighvani, AA Frucht, DM Jankovic, D Yamane, H Aliberti, J Hissong, BD Nguyen, BV Gadina, M Sher, A Paul, WE O'Shea, JJ AF Lighvani, AA Frucht, DM Jankovic, D Yamane, H Aliberti, J Hissong, BD Nguyen, BV Gadina, M Sher, A Paul, WE O'Shea, JJ TI T-bet is rapidly induced by interferon-gamma in lymphoid and myeloid cells SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE T helper 1; transcription factor; Stat ID TRANSCRIPTION FACTOR; DENDRITIC CELLS; TH2 CELLS; RESPONSES; INTERLEUKIN-12; STAT4; MICE; LYMPHOCYTES; GATA-3; IL-4 AB Differentiation of naive CD4(+) T cells into IFN-gamma -producing T helper 1 (T(H)1) cells is pivotal for protective immune responses against intracellular pathogens. T-bet, a recently discovered member of the T-box transcription factor family, has been reported to play a critical role in this process, promoting IFN-gamma production. Although terminal TH1 differentiation occurs over days, we now show that challenge of mice with a prototypical TH11-inclucing stimulus, Toxoplasma gondii soluble extract, rapidly induced IFN-gamma and T-bet; T-bet induction was substantially lower in IFN-rdeficient mice. Naive T cells expressed little T-bet, but this transcription factor was induced markedly by the combination of IFN-gamma and cognate antigen. Human myeloid antigen-presenting cells showed T-bet induction after IFN-gamma stimulation alone, and this induction was antagonized by IL-4 and granulocyte/macrophage colony-stimulating factor. Although T-bet was induced rapidly and directly by IFN-gamma it was not induced by IFN-alpha lipopolysaccharide, or IL-1, indicating that this action of IFN-gamma was specific. Moreover, T-bet induction was dependent on Stat1 but not Stat4. These data argue for a model in which IFN-gamma gene regulation involves an autocrine loop, whereby the cytokine regulates a transcription factor that promotes its own production. These findings substantially alter the current view of T-bet in IFN-gamma regulation and promotion of cell-mediated immune responses. C1 US FDA, Ctr Biol Evaluat & Res, Cell Biol Lab, Bethesda, MD 20892 USA. NIAMSD, Lymphocyte Cell Biol Sect, Arthrit & Rheumatism Branch, NIH, Bethesda, MD 20892 USA. NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Frucht, DM (reprint author), US FDA, Ctr Biol Evaluat & Res, Cell Biol Lab, Bldg 29B,Room 3NN22,HFM-558, Bethesda, MD 20892 USA. RI Aliberti, Julio/G-4565-2012; Aliberti, Julio/I-7354-2013 OI Aliberti, Julio/0000-0003-3420-8478 NR 22 TC 448 Z9 470 U1 1 U2 8 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 18 PY 2001 VL 98 IS 26 BP 15137 EP 15142 DI 10.1073/pnas.261570598 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 504GK UT WOS:000172848800072 PM 11752460 ER PT J AU Kawakami, K Kawakami, M Snoy, PJ Husain, SR Puri, RK AF Kawakami, K Kawakami, M Snoy, PJ Husain, SR Puri, RK TI In vivo overexpression of IL-13 receptor alpha 2 chain inhibits tumorigenicity of human breast and pancreatic tumors in immunodeficient mice SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE tumor antigen; neutrophil infiltration; tumorigenesis; IL-8; cytokine receptor ID CELL CARCINOMA-CELLS; AFFINITY INTERLEUKIN-4 RECEPTORS; PSEUDOMONAS EXOTOXIN; SIGNAL-TRANSDUCTION; CHIMERIC PROTEIN; CANCER-CELLS; (IL)-13 BINDING; SARCOMA-CELLS; EXPRESSION; CLONING AB Interleukin 13 receptor alpha2 (IL-13R alpha2) chain is highly expressed on some tumor cell lines and primary cell cultures. This receptor chain plays an important role in ligand binding and internalization. To determine the functional significance of overexpression of this chain, we stably transfected IL-13R alpha2 chain in human breast (MDA-MB-231) and pancreatic (PANC-1) cancer cell lines that naturally do not express this chain. There was no difference in growth between vector only transfected and IL-13R alpha2 chain transfected cells in vitro. However, surprisingly, in immunodeficient mice, tumorigenicity was profoundly inhibited in IL-13R alpha2 chain overexpressing tumors. Because breast tumors that grew later showed loss of IL-13R alpha2 gene expression, lack of tumorigenicity correlated positively with IL-13R alpha2 chain expression. Inflammatory cells including neutrophils and macrophages were identified in IL-13R alpha2 overexpressing regressing tumors and neutrophils were found to produce IL-13. IL-13 showed a modest antitumor activity to IL-13R alpha2 chain overexpressing tumors in vitro and in vivo. Furthermore, IL-13Ra2 chain overexpressing tumors constitutively produced IL-8 that has been shown to have antitumor effect. These results establish a novel function of a cytokine receptor chain and further suggest that the presence of this chain on tumor cells by itself may play a key role in tumorigenicity. C1 US FDA, Ctr Biol Evaluat & Res, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Vet Serv, Bethesda, MD 20892 USA. RP Puri, RK (reprint author), US FDA, Ctr Biol Evaluat & Res, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, MSC 4555,29 Lincoln Dr,Rm 2NN10,NIH Bldg 29B, Bethesda, MD 20892 USA. NR 50 TC 63 Z9 69 U1 0 U2 3 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD DEC 17 PY 2001 VL 194 IS 12 BP 1743 EP 1754 DI 10.1084/jem.194.12.1743 PG 12 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 505BJ UT WOS:000172890900006 PM 11748276 ER PT J AU Koller, E Schneider, B Bennett, K Dubitsky, G AF Koller, E Schneider, B Bennett, K Dubitsky, G TI Clozapine-associated diabetes SO AMERICAN JOURNAL OF MEDICINE LA English DT Article ID ADVERSE DRUG-REACTIONS; IMPAIRED GLUCOSE-TOLERANCE; OLANZAPINE TREATMENT; ANTIPSYCHOTIC-DRUGS; KETOACIDOSIS; SCHIZOPHRENIA; HYPERGLYCEMIA; MELLITUS; INSULIN; EVENTS AB PURPOSE: Clozapine is a potent antipsychotic agent that has been marketed since 1990. Several published reports of diabetes mellitus occurring with clozapine therapy have appeared during the past 5 years. Because the risk and characteristics of clozapine-associated diabetes mellitus remain unclear, we conducted a descriptive epidemiologic study of spontaneous adverse event reports of hyperglycemia occurring in clozapine-treated patients. MATERIAL AND METHODS: The Food and Drug Administration MedWatch surveillance program was queried (January 1990 through February 2001), and the results were pooled with published cases. Parameters assessed included documentation of diabetes, clinical severity, new-onset diabetes versus exacerbation of preexisting disease, demographic characteristics of patients, time to onset of hyperglycemia, and effect of drug discontinuation and rechallenge. RESULTS: We identified 384 reports. Of these, new-onset diabetes was diagnosed definitively in 242 patients, and 54 patients had exacerbation of preexisting disease. The mean (+/- SD) age was 40 +/- 12 years (range, 13 to 77). The male:female ratio was 2:0. Most cases appeared within 6 months of initiating clozapine therapy. One patient developed diabetes following a single 500-mg dose. There were 80 cases of metabolic acidosis or ketosis. Twenty-five patients died during hyperglycemic episodes. Forty-six patients had improved glycemic control after discontinuation or dose reduction of the drug. CONCLUSIONS: A causal relationship between clozapine and diabetes is suggested by the number of reports, the temporal relation to clozapine initiation, the relatively young age of the affected patients, and the prompt reversibility on withdrawal of the drug in some patients. The severity of reported cases ranged from mild glucose intolerance to diabetic ketoacidosis or hyperosmolar coma. Am J Med. 200 1; 111:716-723. (C) 2001 by Excerpta Medica, Inc. C1 US FDA, CDER, Div Endocrine & Metab Drug Prod, Rockville, MD 20857 USA. RP Koller, E (reprint author), US FDA, CDER, Div Endocrine & Metab Drug Prod, 5600 Fishers Lane,HFD 510,Parklawn Bldg, Rockville, MD 20857 USA. NR 59 TC 163 Z9 177 U1 1 U2 3 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD DEC 15 PY 2001 VL 111 IS 9 BP 716 EP 723 AR PII S0002-9343(01)01000-2 DI 10.1016/S0002-9343(01)01000-2 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 539CC UT WOS:000174851300007 PM 11747852 ER PT J AU Ball, LK Falk, LA Horne, AD Finn, TM AF Ball, LK Falk, LA Horne, AD Finn, TM TI Evaluating the immune response to combination vaccines SO CLINICAL INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT International Symposium on Combination Vaccines CY FEB 02-04, 2000 CL NIH, WASHINGTON, D.C. SP Natl Vaccine Program Off HO NIH ID B CONJUGATE VACCINE; ACELLULAR PERTUSSIS; INFANTS; IMMUNOGENICITY; DISEASE AB Assessment of the immune responses to combination vaccines in the United States has generally been based on randomized, controlled comparative trials, with such studies designed to rule out predefined differences. In designing clinical studies of the immune response to combination products, attention should be directed toward selecting the appropriate immunologic end points and control groups. Acceptable differences in immune responses between combination and control groups should be predefined, and an adequate statistical plan should be developed. In many cases, it may be necessary to evaluate simultaneous administration of other recommended vaccines, assess schedule changes for 1 or more components of a combination, and bridge immunologic data obtained from international studies to the population of the United States. We discuss the use of immunogenicity studies to support the licensure of combination vaccines when field efficacy studies are either not possible or not required and highlight some recent experiences with combination vaccines containing Haemophilus influenzae type b polysaccharide conjugates. C1 US FDA, Div Vaccines & Related Prod Applicat, Off Vaccines Res & Rev, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. US FDA, Div Biostat, Off Biostat & Epidemiol, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Ball, LK (reprint author), US FDA, Div Vaccines & Related Prod Applicat, Off Vaccines Res & Rev, Ctr Biol Evaluat & Res, 1401 Rockville Pike,HFM 475, Rockville, MD 20852 USA. NR 14 TC 10 Z9 10 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 DEC 15 PY 2001 VL 33 SU 4 BP S299 EP S305 DI 10.1086/322578 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 494QB UT WOS:000172293300007 PM 11709763 ER PT J AU Ellenberg, SS AF Ellenberg, SS TI Evaluating the safety of combination vaccines SO CLINICAL INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT International Symposium on Combination Vaccines CY FEB 02-04, 2000 CL NIH, WASHINGTON, D.C. SP Natl Vaccine Program Off HO NIH ID PERTUSSIS-VACCINE; CLINICAL-TRIALS AB The development of combination vaccines is important to facilitate protection of people from potentially life-threatening infectious diseases. As with all vaccines, the safety of these products is of critical importance. Although combination vaccines generally include components that have been studied and used previously, the possibility of new or more severe reactions arising from combining components cannot be dismissed. Controlled safety studies are needed for new combination vaccines to determine reliably whether risks are increased compared with administration of individual components. Such studies will generally be smaller than studies of vaccines with new immunogens, but the size of the study will depend on the types and rates of the reactions expected, given the vaccine's components, and on the level of increased risk that would be important to detect. 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,HFM-210, Rockville, MD 20852 USA. NR 16 TC 5 Z9 5 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 2001 VL 33 SU 4 BP S319 EP S322 DI 10.1086/322577 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 494QB UT WOS:000172293300010 PM 11709766 ER PT J AU Falk, LA Arciniega, J McVittie, L AF Falk, LA Arciniega, J McVittie, L TI Manufacturing issues with combining different antigens: A regulatory perspective SO CLINICAL INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT International Symposium on Combination Vaccines CY FEB 02-04, 2000 CL NIH, WASHINGTON, D.C. SP Natl Vaccine Program Off HO NIH ID POTENCY AB The regulation of biological products is conducted within the framework Title 21 of the US Code of Federal Regulations (CFR). These regulations describe product and clinical testing requirements for drugs and biological products, as well as the requirements for licensure of such products. The requirements outlined in the CFR also apply to combination vaccines. In addition, the Center for Biologics Evaluation and Research has issued a Guidance to Industry document that discusses the manufacturing, testing, and clinical evaluation of combination vaccines. However, as the complexity of mixing the different antigens increases, the challenges associated with product development (e.g., demonstration of comparability of the components and lot consistency) require early interactions with the US Food and Drug Administration. The many areas of difficulty in the arena of combination vaccine development underscore the need for continued reevaluation of current guidance documents in addressing the increasing complexity of vaccines. C1 US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Falk, LA (reprint author), US FDA, Ctr Biol Evaluat & Res, HFM-481,1401 Rockville Pike, Rockville, MD 20852 USA. NR 17 TC 4 Z9 4 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 2001 VL 33 SU 4 BP S351 EP S355 DI 10.1086/322579 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 494QB UT WOS:000172293300016 PM 11709772 ER PT J AU Goldenthal, KL Falk, LA Ball, L Geber, A AF Goldenthal, KL Falk, LA Ball, L Geber, A TI Prelicensure evaluation of combination vaccines SO CLINICAL INFECTIOUS DISEASES LA English DT Editorial Material ID CONJUGATE VACCINE; CLINICAL-TRIALS; IMMUNOGENICITY; SAFETY; ISSUES; POLYSACCHARIDE; INFANTS; POTENCY AB There is considerable public health interest in licensing safe and effective combination vaccines. Because combination vaccines may progress rapidly from phase 1 to a pivotal phase 2 immunogenicity trial, a rigorous approach to address product issues early in development is warranted. Clinical studies to evaluate the safety, immunogenicity, and (when necessary) clinical end point efficacy of combination vaccines should be randomized and well controlled in most cases. A large phase 3 safety study (i.e., a study that enrolls thousands of vaccinees) should be included in the development plan if a phase 3 (clinical end point) efficacy trial will not be conducted. Often, the new combination vaccine under development contains immunogens that have all been previously licensed, have demonstrated efficacy in earlier clinical trials, or both. For such products, comparative immunogenicity data may be sufficient to support efficacy. When applicable, clinical data to support simultaneous administration with other relevant vaccines should be obtained. Given the complexity of combination vaccine development, early consultation with United States Food and Drug Administration can be invaluable. C1 US FDA, Div Vaccines & Related Prod Applicat, Off Vaccines Res & Review, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. NIAID, Div Microbiol & Infect Dis, NIH, Bethesda, MD 20892 USA. RP Goldenthal, KL (reprint author), US FDA, Div Vaccines & Related Prod Applicat, Off Vaccines Res & Review, Ctr Biol Evaluat & Res, HFM-475,1401 Rockville Pike, Rockville, MD 20852 USA. NR 46 TC 9 Z9 9 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 2001 VL 33 SU 4 BP S267 EP S273 DI 10.1086/322561 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 494QB UT WOS:000172293300002 PM 11709758 ER PT J AU Horne, AD Lachenbruch, PA Getson, PR Hsu, HS AF Horne, AD Lachenbruch, PA Getson, PR Hsu, HS TI Analysis of studies to evaluate immune response to combination vaccines SO CLINICAL INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT International Symposium on Combination Vaccines CY FEB 02-04, 2000 CL NIH, WASHINGTON, D.C. SP Natl Vaccine Program Off HO NIH ID TRIALS AB The development and evaluation of new combination vaccines is an important public health endeavor. Trials to evaluate these vaccines are customarily designed and analyzed as noninferiority studies. We explain the concept of noninferiority and highlight important issues that can be challenging in the statistical evaluation of these vaccines. Topics covered include end points, hypotheses, and analyses for comparing geometric mean concentrations (or titers) of antibody and proportion of vaccine recipients responding; covariate adjustment; the problem of multiplicity and its impact on sample size; and choice of a meaningful difference to rule out. C1 US FDA, Vaccine & Blood Prod Evaluat Branch, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. US FDA, Div Biostat, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Horne, AD (reprint author), US FDA, Vaccine & Blood Prod Evaluat Branch, Ctr Biol Evaluat & Res, HFM-217,1401 Rockville Rd, Rockville, MD 20852 USA. NR 9 TC 15 Z9 16 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 2001 VL 33 SU 4 BP S306 EP S311 DI 10.1086/322566 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 494QB UT WOS:000172293300008 PM 11709764 ER PT J AU Taffs, RE AF Taffs, RE TI Potency tests of combination vaccines SO CLINICAL INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT International Symposium on Combination Vaccines CY FEB 02-04, 2000 CL NIH, WASHINGTON, D.C. SP Natl Vaccine Program Off HO NIH ID VALIDATION; ASSAYS AB Combination vaccines differ from single-component vaccines in composition and in how they are manufactured, which poses significant challenges to implementing effective quality-control tests, including measurement of potency. Because each combination vaccine is unique, existing guidelines often fail to provide sufficient information to overcome the inevitable problems encountered when developing and implementing potency tests. Success depends on careful consideration of scientific and regulatory issues. Significant problems may occur if potential interactions between different components in the vaccine are not taken into account during product and test development. Thorough analysis of critical assay parameters and attention to scientific and statistical justifications for the test increase the likelihood of its acceptance. Practical approaches based on experience include rational design of validation studies, complete evaluation and documentation of the potency tests under the conditions in which they are to be applied, and establishing the relationship between production lots of vaccine and lots used in clinical trials. C1 US FDA, Div Emerging & Transfus Transmitted Dis, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Taffs, RE (reprint author), US FDA, Div Emerging & Transfus Transmitted Dis, Ctr Biol Evaluat & Res, 1401 Rockville Pike,HFM-313, Rockville, MD 20852 USA. NR 20 TC 5 Z9 6 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD DEC 15 PY 2001 VL 33 SU 4 BP S362 EP S366 DI 10.1086/322574 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 494QB UT WOS:000172293300018 PM 11709774 ER PT J AU Yourtee, DM Smith, RE Russo, KA Burmaster, S Cannon, JM Eick, JD Kostoryz, EL AF Yourtee, DM Smith, RE Russo, KA Burmaster, S Cannon, JM Eick, JD Kostoryz, EL TI The stability of methacrylate biomaterials when enzyme challenged: Kinetic and systematic evaluations SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH LA English DT Article DE biomaterial hydrolysis; monomer leaching; esterases; dental resins; methacrylates; biocompatibility; biodurability ID POLYMERS; DEGRADATION; COMPONENTS; INVITRO; RESINS AB This study addressed whether methacrylate monomers and polymers used in dentistry might degrade from enzymolysis by acetylcholinesterase (ACHE), cholesterol esterase (CHE), porcine liver esterase (PRLE), and a pancreatic lipase (PNL). Short (hour) and long-term (day) exposures were performed. Product ratios were used to determine surface hydrolysis of the polymeric materials. Enzyme kinetics were studied for the monomers when challenged by ACHE, CHE, and PRLE. In the case of PRLE, the V-max for the dimethacrylate substrates varied slightly, but amounted to as much as 10% of that of p-nitrophenylacetate. The K-m for triethylene glycol dimethacrylate (TEGDMA) was 197 muM for ACHE and 1107 muM for CHE. The V-max was 2.7 nmol/min for ACHE and 3.5 nmol/min for CHE. TEGDMA was converted by CHE at 2% the rate of cholesteryl oleate. Long-term incubations of monomers with CHE and ACHE produced degrees of hydrolysis that evidenced structure dependency in the ability of the enzymes to effect hydrolysis. Particularly resistant were aromativ derivatives and those with branching in methacrylate linkages. Overall, the study confirms the ability of physiologically important esterases to catalyze the hydrolysis of biomaterial methacrylates. (C) 2001 John Wiley & Sons, Inc. C1 Univ Missouri, Sch Pharm, Div Pharmacol, Toxicore Lab, Kansas City, MO 64108 USA. Aventis Pharma, Kansas City, MO 64134 USA. US FDA, Kansas City Dist Off, Off Regulatory Affairs, Lenexa, KS 66061 USA. Univ Missouri, Sch Dent, Div Oral Biol, Kansas City, MO 64108 USA. RP Yourtee, DM (reprint author), Univ Missouri, Sch Pharm, Div Pharmacol, Toxicore Lab, Med Sch Bldg M5-C04,2411 Holmes St, Kansas City, MO 64108 USA. FU NIDCR NIH HHS [P01-DE09696] NR 19 TC 52 Z9 52 U1 2 U2 15 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0021-9304 J9 J BIOMED MATER RES JI J. Biomed. Mater. Res. PD DEC 15 PY 2001 VL 57 IS 4 BP 522 EP 531 DI 10.1002/1097-4636(20011215)57:4<522::AID-JBM1198>3.0.CO;2-9 PG 10 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 478YQ UT WOS:000171376800006 PM 11553882 ER PT J AU Binienda, ZK Ali, SF AF Binienda, ZK Ali, SF TI Neuroprotective role of L-carnitine in the 3-nitropropionic acid induced neurotoxicity SO TOXICOLOGY LETTERS LA English DT Article DE 3-nitropropionic acid (3-NPA); L-carnitine; succinate dehydrogenase; neuroprotection; brain; rat ID ACETYL-L-CARNITINE; SUCCINATE-DEHYDROGENASE; ENERGY-LEVELS; BRAIN; RAT; INHIBITION; QUANTITATION; DEGENERATION; TOXICITY; LESIONS AB L-carnitine (LC) plays an important regulatory role in the mitochondrial transport of long-chain free fatty acids (FFA). 3-Nitropropionic acid (3-NPA) is known to induce cellular energy deficit and oxidative stress related neurotoxicity via an irreversible inhibition of the mitochondrial enzyme succinate dehydrogenase (SDH). Protective effects Of L-carnitine on the neurotoxicity induced by 3-NPA have been shown in vitro. Here, the activities of SDH as well as the activity of the antioxidant enzymes, catalase (CAT), and superoxide dismutase (SOD) were measured in order to evaluate the protective action of LC against 3-NPA-induced neurotoxicity. Male, CD Sprague-Dawley rats, 3-month old, were injected with either 50 or 100 mg/kg of LC, i.p., 30-60 min prior to 3-NPA (30 mg/kg, s.c.) or with 3-NPA alone. Enzyme activities were assayed in caudate nucleus (CN), frontal cortex (FC), and hippocampus (HIP) post sacrifice. Increased activities of CAT and SOD were observed after treatment with 3-NPA alone. Pretreatment with low or high doses of LC was associated with attenuation of these increases equivalent to, or below, the control levels. In rats treated with 3-NPA alone, SDH activity was inhibited by 62% (CN), 50% (FC), and 65% (HIP) of controls. Pretreatment with LC prior to 3-NPA attenuated decreases of SDH activity in a dose-dependent manner. However, compared with control, the activity of SDH remained significantly lower in brain regions of treated rats despite the attenuation of inhibition by LC pretreatment (P<0.05). These data suggest protective effect of LC against 3-NPA-induced oxidative stress. It appears that the protective effect of LC against 3-NPA-induced oxidative stress is not mediated by the direct action of LC preventing the SDH inhibition but rather is achieved due to the actions of LC downstream of the SDH inhibition. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved. C1 US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Binienda, ZK (reprint author), US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 27 TC 45 Z9 45 U1 0 U2 2 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 15 PY 2001 VL 125 IS 1-3 BP 67 EP 73 DI 10.1016/S0378-4274(01)00415-5 PG 7 WC Toxicology SC Toxicology GA 498UX UT WOS:000172529800008 PM 11701224 ER PT J AU Bowyer, JF Hopkins, KJ Jakab, R Ferguson, SA AF Bowyer, JF Hopkins, KJ Jakab, R Ferguson, SA TI L-ephedrine-induced neuro degeneration in the parietal cortex and thalamus of the rat is dependent on hyperthermia and can be altered by the process of in vivo brain microdialysis SO TOXICOLOGY LETTERS LA English DT Article DE neurotoxicity; ephedrine; amphetamine; cortex; thalamus; microdialysis ID CENTRAL-NERVOUS-SYSTEM; STRIATAL DOPAMINE; METHAMPHETAMINE NEUROTOXICITY; D-AMPHETAMINE; NEUROTROPHIC FACTORS; GLUTAMATE; INJURY; USERS; ADDICTION; CAFFEINE AB Multiple doses of the dietary supplement L-ephedrine can cause severe hyperthermia, and modest dopamine depletions in the rat brain. Since D-amphetamine treatment can result in neurodegeneration, the potential of L-ephedrine to produce similar types of degeneration was investigated. Adult male rats, some implanted in the caudate/putamen (CPu) for microdialysis, were given four doses of 25 mg/kg L-ephedrine or 5 mg/kg D-amphetamine (2 h between doses) at an ambient temperature of 23 degreesC. L-ephedrine-induced degeneration in the forebrain was dependent on the degree of hyperthermia. Layer IV of the parietal cortex was the most Sensitive to L-ephedrine treatment with peak body temperatures of at most 40.0 degreesC necessary to produce degeneration. Extensive neurodegeneration in the parietal cortex after L-ephedrine treatment was as pronounced as that previously described for D-amphetamine treatment and also occurred in the intralaminar, ventromedial and ventrolateral thalamic nuclei in rats with severe hyperthermia (peak body temperatures>41.0 degreesC). The neurodegeneration induced by L-ephedrine may have resulted in part from excitotoxic mechanisms involving the indirect pathways of the basal ganglia and related areas. No differences were observed between microdialysis and non-implanted rats with respect to degree of tyrosine hydroxylase (TH) loss in the CPu after either D-amphetamine or L-ephedrine treatment. However, neuro degeneration resulting from D-amphetamine and L-ephedrine was reduced in the microdialysis animals in the hemisphere ipsilateral to the probe, which raises concerns when using the technique of in vivo microdialysis to evaluate neurodegeneration. The results of this study, in conjunction with human clinical evaluation of ephedrine neurotoxicity, indicate that regionally specific damage may occur in the cortex of some humans exposed to ephedrine in the absence of stroke or hemorrhage. (C) 2001 Published by Elsevier Science Ireland Ltd. C1 US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Bowyer, JF (reprint author), US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, HFT-132, Jefferson, AR 72079 USA. NR 52 TC 5 Z9 14 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0378-4274 J9 TOXICOL LETT JI Toxicol. Lett. PD DEC 15 PY 2001 VL 125 IS 1-3 BP 151 EP 166 DI 10.1016/S0378-4274(01)00440-4 PG 16 WC Toxicology SC Toxicology GA 498UX UT WOS:000172529800018 PM 11701234 ER PT J AU Moriya, O Matsui, M Osorio, M Miyazawa, H Rice, CM Feinstone, SM Leppla, SH Keith, JM Akatsuka, T AF Moriya, O Matsui, M Osorio, M Miyazawa, H Rice, CM Feinstone, SM Leppla, SH Keith, JM Akatsuka, T TI Induction of hepatitis C virus-specific cytotoxic T lymphocytes in mice by immunization with dendritic cells treated with an anthrax toxin fusion protein SO VACCINE LA English DT Article DE anthrax toxin; cytotoxic T lymphocytes; hepatitis C virus ID MAJOR HISTOCOMPATIBILITY COMPLEX; PROTECTIVE ANTIGEN; MEDIATED DELIVERY; DIPHTHERIA-TOXIN; LETHAL FACTOR; IN-VIVO; PEPTIDES; CORE; RECOGNITION; MOLECULES AB As a novel and safe vaccine strategy, the anthrax toxin-mediated antigen delivery system composed of lethal factor (LF) fusion protein and protective antigen (PA) has been studied to prime hepatitis C virus (HCV) core-specific cytotoxic T lymphocytes (CTLs) in vivo. The core epitope fused to LF (LF-core) tocrether with PA induces a negligible core-specific CTL response in mice, whereas core-specific CTL are effectively primed in mice by injecting dendritic cells (DCs) treated in vitro with LF-core and PA. These findings imply that LF fusion protein plus PA in combination with dendritic cells may be useful for a novel T cell vaccine against HCV infection. (C) 2001 Elsevier Science Ltd. All rights reserved. C1 Saitama Med Sch, Dept Microbiol, Moroyama, Saitama 3500495, Japan. Natl Inst Dent & Craniofacial Res, Oral Infect & Immun Branch, Bethesda, MD 20892 USA. Rockefeller Univ, Lab Virol & Infect Dis, New York, NY 10021 USA. US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Lab Hepatitis Viruses, Bethesda, MD 20892 USA. RP Akatsuka, T (reprint author), Saitama Med Sch, Dept Microbiol, Moroyama, Saitama 3500495, Japan. NR 39 TC 19 Z9 20 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 DEC 12 PY 2001 VL 20 IS 5-6 BP 789 EP 796 DI 10.1016/S0264-410X(01)00407-8 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 504TJ UT WOS:000172871700017 PM 11738742 ER PT J AU Schwetz, BA AF Schwetz, BA TI Oral sodium phosphate SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT News Item C1 US FDA, Rockville, MD 20857 USA. RP Schwetz, BA (reprint author), US FDA, Rockville, MD 20857 USA. NR 0 TC 9 Z9 10 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD DEC 5 PY 2001 VL 286 IS 21 BP 2660 EP 2660 DI 10.1001/jama.286.21.2660 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 498AU UT WOS:000172488300005 PM 11730423 ER PT J AU Schwetz, BA AF Schwetz, BA TI Remote data pacemaker SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT News Item C1 US FDA, Rockville, MD 20857 USA. RP Schwetz, BA (reprint author), US FDA, Rockville, MD 20857 USA. NR 0 TC 9 Z9 10 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD DEC 5 PY 2001 VL 286 IS 21 BP 2660 EP 2660 DI 10.1001/jama.286.21.2660 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 498AU UT WOS:000172488300006 PM 11730423 ER PT J AU Schwetz, BA AF Schwetz, BA TI New drug for HIV-1 infection SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT News Item C1 US FDA, Rockville, MD 20857 USA. RP Schwetz, BA (reprint author), US FDA, Rockville, MD 20857 USA. NR 0 TC 9 Z9 10 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD DEC 5 PY 2001 VL 286 IS 21 BP 2660 EP 2660 DI 10.1001/jama.286.21.2660 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 498AU UT WOS:000172488300004 PM 11730423 ER PT J AU Weagant, SD Bound, AJ AF Weagant, SD Bound, AJ TI Evaluation of techniques for enrichment and isolation of Escherichia coli O157 : H7 from artificially contaminated sprouts SO INTERNATIONAL JOURNAL OF FOOD MICROBIOLOGY LA English DT Article DE E. coli O157 : H7; enrichment methods; immunomagnetic separation ID RADISH SPROUTS; GROUND-BEEF; OUTBREAK; INFECTION; FOODS AB Because sprouted seed products are kept wet during and after production, have high levels of nutrients, and a neutral pH, they are subject to the outgrowth of pathogens such as Escherichia coli O157:H7. For these same reasons, these products also contain high levels of heterotrophic organisms and in particular coliform bacteria. Recent outbreaks have focused attention on the need to improve methodology for isolating this pathogen from sprouts. When 40 E. coli O157:H7 strains were grown in pure culture in enterohemorrhagic E. coli enrichment broth (EEB) as prescribed in the U.S. FDA-Bacteriological Analytical Manual (FDA-BAM) and in EEB modified by varying the cefixime concentration, outgrowth for all strains in EEB was inhibited at 0.05 mg/l but for only 2 of 40 strains when the cefixime level was adjusted to 0.0125 mg/l. These two enrichment formulae were compared to modified E. coli broth (mEC), modified Tryptic Soy Broth with 20 mg/l novobiocin. (mTSB + N), modified Buffered Peptone Water (mBPW), and mBPW with added 10 mg/l acriflavin, 10 mg/l cefsulodin, and 8 mg/l vancomycin (mBPW + ACV) for isolation of E. coli O157:H7 from sprouts. These comparisons were performed using low-level (0.12 to 0.42 cfu/g) artificially contaminated alfalfa and mixed salad sprouts. After enrichment, two isolation methods were compared for recovery; direct plating to Tellurite-Cefixime Sorbitol MacConkey agar (TCSMAC) and immunomagnetic separation (IMS) (Dynabeads anti-E. coli O157, Dynal, Oslo, Norway) followed by plating to TCSMAC. In addition, an immunoprecipitin detection kit, VIP (BioControl, Bellevue, WA), was evaluated for detection after enrichment. We found that five of the six enrichments were equivalent for detection or recovery while one enrichment (mTSB + N without agitation) was less productive. Incubation for 24 It was more effective in recovering E. coli O157:H7 from sprouts than 6 h for all enrichment broths. Plating after IMS was more productive than direct plating at these low levels of contamination, yielding recovery in 70 of 90 trials compared to 37 of 90 trials without IMS for six enrichments, The sensitivity of VIP for detection of E. coli O157:H7 varied depending on the enrichment broth. Because of the rapid rate of growth of E. coli O157:H7 in mBPW, the high productivity of mBPW + ACV after 24-h enrichment and its compatibility with both IMS and detection with immunoprecipitin tests, mBPW + ACV at 42 degreesC with agitation was found to be the most promising enrichment protocol for testing sprouts. Published by Elsevier Science B.V. C1 US FDA, Pacific Reg Lab NW, Bothell, WA 98021 USA. RP Weagant, SD (reprint author), US FDA, Pacific Reg Lab NW, 22201 23rd Dr SE, Bothell, WA 98021 USA. NR 19 TC 37 Z9 37 U1 1 U2 12 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 4 PY 2001 VL 71 IS 1 BP 87 EP 92 DI 10.1016/S0168-1605(01)00558-X PG 6 WC Food Science & Technology; Microbiology SC Food Science & Technology; Microbiology GA 499FD UT WOS:000172559600010 PM 11764896 ER PT J AU Ramanujam, M Hofmann, J Nakhasi, HL Atreya, CD AF Ramanujam, M Hofmann, J Nakhasi, HL Atreya, CD TI Effect of site-directed asparagine to isoleucine substitutions at the N-linked E1 glycosylation sites on rubella virus viability SO VIRUS RESEARCH LA English DT Article DE rubella virus; glycosylation; mutations; structural proteins; virus viability ID SUBGENOMIC MESSENGER-RNA; STRUCTURAL PROTEINS; COS CELLS; GLYCOPROTEIN; MUTATIONS; INFECTIVITY; CALNEXIN; GROWTH AB The role of three N-linked glycosylation sites in rubella virus (RV) E1 protein on virion release was analyzed by transfecting Vero 76 cells with infectious RV RNA (Robo302WT) containing isoleucine substitutions at N76, N177, and N209 (individually and in combinations). RV RNAs were detected and found to retain substitutions in the transfected cells, but RV capsid indicative of infection was undetectable, except for in Robo302WT and Robo302-N177I transfected cells. Only culture supernatants of Robo302WT and Robo302-N177I RNA transfected cells were positive for RV, suggestive of the virion release into the culture medium. Further, detection of intracellular RV E1 and newly released virion-associated E1 was possible only from cells previously incubated with Robo302-N177I and Robo302WT culture supernatants, suggesting that N177I substituted virus retained infectivity. These results suggest that while glycosylation at N177 is not critical, N76I and N209I mutations are lethal to RV viability. (C) 2001 Published by Elsevier Science B.V. C1 US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. Inst Virol, Leipzig, Germany. RP Atreya, CD (reprint author), Bldg 29A,Rm 2C-11,HFM-460,8800 Rockville Pike, Bethesda, MD 20892 USA. NR 27 TC 5 Z9 8 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-1702 J9 VIRUS RES JI Virus Res. PD DEC 4 PY 2001 VL 81 IS 1-2 BP 151 EP 156 DI 10.1016/S0168-1702(01)00374-4 PG 6 WC Virology SC Virology GA 495GH UT WOS:000172331500015 PM 11682134 ER PT J AU Verstraeten, T Baughman, AL Cadwell, B Zanardi, L Haber, P Chen, RT AF Verstraeten, T Baughman, AL Cadwell, B Zanardi, L Haber, P Chen, RT CA Vaccine Adverse Event Reporting Sy TI Enhancing Vaccine Safety Surveillance: A capture-recapture analysis of intussusception after rotavirus vaccination SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE intussusception; rotavirus; vaccines ID REPORTING-SYSTEM VAERS; UNITED-STATES; ADVERSE EVENTS; EPIDEMIOLOGY; IMMUNIZATION; COMPLETENESS; MORTALITY AB The Vaccine Adverse Event Reporting System (VAERS) is the passive reporting system for postmarketing surveillance of vaccine safety in the United States. The proportion of cases of an adverse event after vaccination that are reported to VAERS (i.e., VAERS reporting completeness) is mostly unknown. Therefore, the risk of such an event cannot be derived from VAERS only. To study whether its reporting sensitivity and risks could be estimated, VAERS was linked to data from a case-control and a retrospective cohort study in a capture-recapture analysis of intussusception after rotavirus vaccination (RV). Cases of intussusception after RV were selected from the common time frame (December 1998 through June 1999) and the common geographic area (19 states) of the three sources. Matching occurred on birth date, gender, state, date of vaccination, and date of diagnosis. Thirty-five matches were identified among a total of 84 cases. The estimated VAERS reporting completeness was 47%. The relative risks of intussusception in the periods 3-7 and 8-14 days after RV (relative risk = 22.7 and 4.4, respectively) were comparable with those reported in the two studies. Linkage of VAERS to complimentary data sources may permit more timely postmarketing assessment of vaccine safety. C1 Ctr Dis Control & Prevent, Epidem Intelligence Serv, Div Appl Publ Hlth Training, Epidemiol Program Off, Atlanta, GA USA. Ctr Dis Control & Prevent, Vaccine Safety & Dev Act, Div Epidemiol & Surveillance, Natl Immunizat Program, Atlanta, GA USA. Ctr Dis Control & Prevent, Div Data Management, Natl Immunizat Program, Atlanta, GA USA. Ctr Dis Control & Prevent, Child Vaccine Preventable Dis Branch, Div Epidemiol & Surveillance, Natl Immunizat Program, Atlanta, GA USA. US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. RP Verstraeten, T (reprint author), Bleuckeveldlaan 75, B-3080 Tervuren, Belgium. NR 29 TC 43 Z9 43 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD DEC 1 PY 2001 VL 154 IS 11 BP 1006 EP 1012 DI 10.1093/aje/154.11.1006 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 499NZ UT WOS:000172578400006 PM 11724716 ER PT J AU Hutchins, SS Dezayas, A Le Blond, K Heath, J Bellini, W Audet, S Beeler, J Wattigney, W Markowitz, L AF Hutchins, SS Dezayas, A Le Blond, K Heath, J Bellini, W Audet, S Beeler, J Wattigney, W Markowitz, L TI Evaluation of an early two-dose measles vaccination schedule SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE antibodies; immunity; infant; measles; measles vaccine; serologic tests; vaccines ID IMMUNE-RESPONSE; EARLY IMMUNIZATION; UNITED-STATES; AGE; CHILDREN; INFANTS; ANTIBODY; OUTBREAK; REIMMUNIZATION; POPULATION AB Vaccination at 6 months of age followed by routine revaccination is recommended when exposure of infants to measles is likely. Dade County, Florida, began this early two-dose schedule during a large epidemic in 1986-1987 (i.e., 22% of cases occurred in infants aged 6-11 months). This schedule was continued routinely in high-risk areas. The effect of an early two-dose schedule on measles prevention in the county was examined by comparing measles vaccination coverage and epidemiology before (1985-1987) and after (1988-1996) the schedule became routine. To assess serologic response, seroprevalence of measles antibody among children aged 4-6 years in 1995 was examined. To evaluate vaccine effectiveness, a case-control study was conducted among preschool-aged children. Among those aged 2 years, vaccination coverage with greater than or equal to1 dose increased from 75% to 94% in 1996. The number of annual cases declined, and endemic measles transmission reportedly ended after 1993. Seroprevalence of plaque reduction neutralization antibody (titer > 1:120) among those receiving vaccination according to an early two-dose schedule and a single dose at age greater than or equal to 12 months was 94% (95% confidence interval: 89, 98) and 98% (95% confidence interval: 95, 100). In these groups, vaccine effectiveness was comparably high. Early two-dose measles vaccination is associated with improved coverage and a comparably high level of humoral immunity and clinical protection as a single dose at age greater than or equal to 12 months. This strategy can be useful in areas at high risk for measles among infants. C1 Ctr Dis Control & Prevent, Natl Immunizat Program, Informat Ctr, Measles Eliminat Act, Atlanta, GA 30333 USA. Ctr Dis Control & Prevent, Epidem Intelligence Serv, Div Appl Publ Hlth Training, Epidemiol Program Off, Atlanta, GA 30333 USA. Dade Cty Dept Publ Hlth, Special Immunizat Program, Miami, FL USA. ABT Associates Inc, Cambridge, MA 02138 USA. Ctr Dis Control & Prevent, Measles Virus Sect, Natl Ctr Infect Dis, Atlanta, GA 30333 USA. US FDA, Lab Pediat & Resp Virus Dis, Bethesda, MD 20014 USA. Ctr Dis Control & Prevent, Natl Immunizat Program, Data Management Div, Atlanta, GA 30333 USA. RP Hutchins, SS (reprint author), Ctr Dis Control & Prevent, Natl Immunizat Program, Informat Ctr, Measles Eliminat Act, Mail Stop E-61, Atlanta, GA 30333 USA. NR 36 TC 23 Z9 24 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD DEC 1 PY 2001 VL 154 IS 11 BP 1064 EP 1071 DI 10.1093/aje/154.11.1064 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 499NZ UT WOS:000172578400014 PM 11724724 ER PT J AU Weaver, J Bonnel, RA Karwoski, CB Brinker, AD Beitz, J AF Weaver, J Bonnel, RA Karwoski, CB Brinker, AD Beitz, J TI GI events leading to death in association with celecoxib and rofecoxib SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Letter ID GASTROINTESTINAL TOXICITY; RHEUMATOID-ARTHRITIS C1 US FDA, Dept Hlth & Human Serv, Ctr Drug Evaluat & Res, Publ Hlth Serv,Off Postmarketing Drug Risk Assess, Rockville, MD 20857 USA. RP Bonnel, RA (reprint author), US FDA, Dept Hlth & Human Serv, Ctr Drug Evaluat & Res, Publ Hlth Serv,Off Postmarketing Drug Risk Assess, Rockville, MD 20857 USA. NR 4 TC 6 Z9 6 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD DEC PY 2001 VL 96 IS 12 BP 3449 EP 3450 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 502WV UT WOS:000172766500047 PM 11774975 ER PT J AU Carter, KC Mullen, AB Sundar, S Kenney, RT AF Carter, KC Mullen, AB Sundar, S Kenney, RT TI Efficacies of vesicular and free sodium stibogluconate formulations against clinical isolates of Leishmania donovani SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID ARSENITE-RESISTANT LEISHMANIA; VISCERAL LEISHMANIASIS; BALB/C MOUSE; AMASTIGOTES; MODEL; MICE; GENE AB In this study, the in vitro and in vivo efficacies of free sodium stibogluconate (SSG) and a nonionic surfactant vesicular formulation of SSG (SSG-NIV) against a laboratory strain of Leishmania donovani (MHONVET/67: LV82) and different clinical isolates of L. donovani were determined. Treatment with SSG-NIV was more effective against intramacrophage amastigotes than treatment with SSG. In vivo murine studies showed that there was interstrain variability in the infectivity of the different L. donovani strains, with two of the strains (20001 and 20003) giving low parasite burdens. In addition, interstrain variability in the antileishmanial efficacy of SSG in a single dose containing 300 mg of Sb(V)/kg of body weight was observed. This dose of free drug either caused a > 97% reduction in liver parasite burdens or had no significant effect on parasite burdens compared with the result with the respective control. In some instances, treatment with this free SSG dose also caused a significant reduction in spleen (strain 20006) or bone marrow (strains 20001 and 20009) parasite burdens. Treatment with SSG-NIV was more effective than that with SSG against all of the strains tested. In SSG-responsive strains, the reduction in liver parasite burdens by SSG-NIV treatment was similar to that caused by free SSG. In SSG-nonresponsive strains, SSG-NIV treatment caused at least a 95% reduction in liver parasite burdens. Overall, these results indicate that the use of a vesicular formulation of SSG is likely to increase its clinical efficacy against visceral leishmaniasis. C1 Univ Strathclyde, Dept Immunol, Glasgow G4 ONR, Lanark, Scotland. Univ Strathclyde, Dept Pharmaceut Sci, Glasgow G4 ONR, Lanark, Scotland. Banaras Hindu Univ, Inst Med Sci, Varanasi 221005, Uttar Pradesh, India. US FDA, Ctr Biol Evaluat & Res, Lab Parasit Biol & Biochem, Bethesda, MD USA. RP Carter, KC (reprint author), Univ Strathclyde, Dept Immunol, SIBS Bldg,31 Taylor St, Glasgow G4 ONR, Lanark, Scotland. NR 22 TC 18 Z9 18 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD DEC PY 2001 VL 45 IS 12 BP 3555 EP 3559 DI 10.1128/AAC.45.12.3555-3559.2001 PG 5 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 494UT UT WOS:000172304800042 PM 11709339 ER PT J AU Zhao, SH White, DG McDermott, PF Friedman, S English, L Ayers, S Meng, JH Maurer, JJ Holland, R Walker, RD AF Zhao, SH White, DG McDermott, PF Friedman, S English, L Ayers, S Meng, JH Maurer, JJ Holland, R Walker, RD TI Identification and expression of cephamycinase bla(CMY) genes in Escherichia coli and Salmonella isolates from food animals and ground meat SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID AMPC BETA-LACTAMASE; RESISTANCE; CEFOTAXIME; CEFTRIAXONE; SEQUENCE; PROTEIN; CMY-2 AB Twenty-one Salmonella and 54 Escherichia coli isolates, recovered from food animals and retail ground meats, that exhibited decreased susceptibilities to ceftiofur and ceftriaxone were shown to possess a bla(CMY) gene. The bla(CMY-4) gene was identified in an E. coli isolate recovered from retail chicken and was further shown to be responsible for resistance to cephalothin, ampicillin, and amoxicillin-clavulanic acid and elevated MICs of ceftriaxone, cefoxitin, and ceftiofur. C1 US FDA, CVM, Res Off, Div Anim & Food Microbiol, Laurel, MD 20708 USA. Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA. Univ Georgia, Dept Avian Med, Athens, GA 30602 USA. Iowa State Univ, Dept Vet Diagnost & Prod Anim Med, Ames, IA 50011 USA. RP Zhao, SH (reprint author), US FDA, CVM, Res Off, Div Anim & Food Microbiol, 8401 Muirkirk Rd, Laurel, MD 20708 USA. NR 23 TC 131 Z9 136 U1 1 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD DEC PY 2001 VL 45 IS 12 BP 3647 EP 3650 DI 10.1128/AAC.45.12.3647-3650.2001 PG 4 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 494UT UT WOS:000172304800064 PM 11709361 ER PT J AU Zhao, CW Ge, BL De Villena, J Studler, R Yeh, E Zhao, SH White, DG Wagner, D Meng, JH AF Zhao, CW Ge, BL De Villena, J Studler, R Yeh, E Zhao, SH White, DG Wagner, D Meng, JH TI Prevalence of Campylobacter spp., Escherichia coli, and Salmonella serovars in retail chicken, turkey, pork, and beef from the Greater Washington, DC, area SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID FOODBORNE PATHOGENS; POULTRY PRODUCTS; RAW MEAT; JEJUNI; CARCASSES; IDENTIFICATION; HUMANS; CONTAMINATION; O157-H7; SAMPLES AB A total of 825 samples of retail raw meats (chicken, turkey, pork and beef) were examined for the presence of Escherichia coli and Salmonella serovars, and 719 of these samples were also tested for Campylobacter spp. The samples were randomly obtained from 59 stores of four supermarket chains during 107 sampling visits in the Greater Washington, D.C., area from June 1999 to July 2000. The majority (70.7%) of chicken samples (n = 184) were contaminated with Campylobacter, and a large percentage of the stores visited (91%) had Campylobacter-contaminated chickens. Approximately 14% of the 172 turkey samples yielded Campylobacter, whereas fewer pork (1.7%) and beef (0.5%) samples were positive for this pathogen. A total of 722 Campylobacter isolates were obtained from 159 meat samples; 53.6% of these isolates were Campylobacter jejuni, 41.3% were Campylobacter coli, and 5.1% were other species. Of the 212 chicken samples, 82 (38.7%) yielded E. coli, while 19.0% of the beef samples, 16.3% of the pork samples, and 11.9% of the turkey samples were positive for E. coli. However, only 25 (3.0%) of the retail meat samples tested were positive for Salmonella. Significant differences in the bacterial contamination rates were observed for the four supermarket chains. This study revealed that retail raw meats are often contaminated with food-borne pathogens; however, there are marked differences in the prevalence of such pathogens in different meats. Raw retail meats are potential vehicles for transmitting food-borne diseases, and our findings stress the need for increased implementation of hazard analysis of critical control point (HACCP) and consumer food safety education efforts. C1 Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA. US FDA, Ctr Vet Med, 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 37 TC 302 Z9 315 U1 9 U2 46 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 2001 VL 67 IS 12 BP 5431 EP 5436 DI 10.1128/AEM.67.12.5431-5436.2001 PG 6 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 497JM UT WOS:000172451800011 PM 11722889 ER PT J AU Mohan, N Edwards, ET Cupps, TR Oliverio, PJ Sandberg, G Crayton, H Richert, JR Siegel, JN AF Mohan, N Edwards, ET Cupps, TR Oliverio, PJ Sandberg, G Crayton, H Richert, JR Siegel, JN TI Demyelination occurring during anti-tumor necrosis factor alpha therapy for inflammatory arthritides SO ARTHRITIS AND RHEUMATISM LA English DT Article ID MULTIPLE-SCLEROSIS; RHEUMATOID-ARTHRITIS; FACTOR RECEPTOR; INTERFERON BETA-1B; TRANSGENIC MICE; TNF; DISEASES; PATIENT; MODELS; INJURY AB Objective. To review the occurrence of neurologic events suggestive of demyelination during anti-tumor necrosis factor alpha (anti-TNF alpha) therapy for inflammatory arthritides. Methods. The Adverse Events Reporting System of the Food and Drug Administration (FDA) was queried following a report of a patient with refractory rheumatoid arthritis who developed confusion and difficulty with walking after receiving etanercept for 4 months. Results. Nineteen patients with similar neurologic events were identified from the FDA database, 17 following etanercept administration and 2 following infliximab administration for inflammatory arthritis. All neurologic events were temporally related to anti-TNF alpha therapy, with partial or complete resolution on discontinuation. One patient exhibited a positive rechallenge phenomenon. Conclusion. Further surveillance and studies are required to better define risk factors for and frequency of adverse events and their relationship to anti-TNF alpha therapies. Until more long-term safety data are available, consideration should be given to avoiding anti-TNF alpha therapy in patients with preexisting multiple sclerosis and to discontinuing anti-TNF alpha therapy immediately when new neurologic signs and symptoms occur, pending an appropriate evaluation. C1 Georgetown Univ, Med Ctr, Div Rheumatol Allergy & Immunol, Washington, DC 20007 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. Armed Forces Inst Pathol, Washington, DC 20306 USA. RP Mohan, N (reprint author), Georgetown Univ, Med Ctr, Div Rheumatol Allergy & Immunol, 3800 Reservoir Rd NW, Washington, DC 20007 USA. NR 30 TC 491 Z9 507 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 DEC PY 2001 VL 44 IS 12 BP 2862 EP 2869 DI 10.1002/1529-0131(200112)44:12<2862::AID-ART474>3.0.CO;2-W PG 8 WC Rheumatology SC Rheumatology GA 500PA UT WOS:000172634900019 PM 11762947 ER PT J AU D'Agnillo, F Alayash, AI AF D'Agnillo, F Alayash, AI TI Redox cycling of diaspirin cross-linked hemoglobin induces G2/M arrest and apoptosis in cultured endothelial cells SO BLOOD LA English DT Article ID ISCHEMIA-REPERFUSION INJURY; LOW-DENSITY-LIPOPROTEIN; ACUTE-RENAL-FAILURE; HYDROGEN-PEROXIDE; OXIDATIVE STRESS; LIPID-PEROXIDATION; GLUTATHIONE LEVELS; BLOOD SUBSTITUTES; ORGAN DYSFUNCTION; HEMORRHAGIC-SHOCK AB It is hypothesized that oxidative reactions of hemoglobin driven by reactive oxygen species in the vasculature lead to endothelial cell injury or death. Bovine aortic endothelial cells were incubated with diaspirin cross-linked hemoglobin (DBBF-Hb), developed as a hemoglobin-based oxygen carrier, and hydrogen peroxide (H2O2), generated by the glucose oxidase system. The low steady flux of H2O2 oxidizes the ferrous form of DBBF-Hb and drives the redox cycling of ferric and ferryl DBBF-Hb. Cells underwent rounding, swelling and detachment, and accumulated in the G2/M phase of the cell cycle. G2/M arrest preceded the onset of apoptosis as determined by increases in phosphatidylserine (PS) externalization and sub-G1 events. Redox cycling of unmodified hemoglobin also led to G2/M arrest and apoptosis. The rate and extent of DBBF-Hb oxidation correlated with the onset and extent of G2/M arrest and apoptosis and induced significant decreases in soluble reduced thiols. Earlier depletion of glutathione by pretreatment with buthionine sulfoximine rendered cells more susceptible to G2/M arrest and apoptosis. The caspase inhibitor, z-VAD-fmk, had no effect on the induction of G2/M arrest but completely inhibited the subsequent increases in PS externalization and sub-G1 events. Catalase inhibited DBBF-Hb oxidation, the loss of thiols, and the onset of G2/M arrest and apoptosis. These data support a causative role for the ferric-ferryl redox cycle in the development of endothelial cell injury. (Blood. 2001;98: 3315-3323) (C) 2001 by The American Society of Hematology. C1 US FDA, Lab Plasma Derivat, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Alayash, AI (reprint author), US FDA, Lab Plasma Derivat, Div Hematol, Ctr Biol Evaluat & Res, Bldg 29,Rm 112,8800 Rockville Pike, Bethesda, MD 20892 USA. NR 54 TC 60 Z9 61 U1 1 U2 11 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD DEC 1 PY 2001 VL 98 IS 12 BP 3315 EP 3323 DI 10.1182/blood.V98.12.3315 PG 9 WC Hematology SC Hematology GA 495BV UT WOS:000172321100022 PM 11719369 ER PT J AU Myers, MG Lipicky, RJ AF Myers, MG Lipicky, RJ TI Assessment of antihypertensive activity in the regulatory setting SO BLOOD PRESSURE MONITORING LA English DT Article DE antihypertensive therapy; blood pressure measurement; regulatory affairs ID TO-PEAK RATIO; BLOOD-PRESSURE AB Before a new antihypertensive drug receives regulatory approval, it must demonstrate a significant blood pressure-lowering effect over its entire dosing interval. The Food and Drug Administration recognizes several different methods for demonstrating antihypertensive activity, the gold standard continuing to be the office/ casual blood pressure at the end of the dosing interval (trough), There should be at least two studies demonstrating a significant anti hypertensive effect, at least one of which should include a placebo. Data obtained using ambulatory blood pressure monitoring are used for showing the time-course of the anti hypertensive effect, particular attention being given to possible marked differences between the drug's maximum (peak) effect and its activity during the trough. In Europe, the Committee for Proprietary Medicinal Products also considers the office/casual blood pressure at trough to be a primary measure of outcome, responder rates using office/casual readings also being noted. The Committee recomends that data be obtained using ambulatory blood pressure monitoring in order to demonstrate a drug's anti hypertensive activity. In addition, it specifically requests that a trough : peak ratio be calculated, whereas the Food and Drug Administration does not require this information. Blood (C) 2001 Lippincott Williams Wilkins. C1 Univ Toronto, Sunnybrook & Womens Coll, Hlth Sci Ctr, Div Cardiol, Toronto, ON M4N 3M5, Canada. Univ Toronto, Dept Med, Toronto, ON M4N 3M5, Canada. US FDA, Ctr Drug Evaluat & Res, Div Cardiorenal Drug Prod, Rockville, MD 20857 USA. RP Myers, MG (reprint author), Univ Toronto, Sunnybrook & Womens Coll, Hlth Sci Ctr, Div Cardiol, 2075 Bayview Ave,A202, Toronto, ON M4N 3M5, Canada. NR 10 TC 6 Z9 6 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1359-5237 J9 BLOOD PRESS MONIT JI Blood Press. Monit. PD DEC PY 2001 VL 6 IS 6 BP 309 EP 312 DI 10.1097/00126097-200112000-00008 PG 4 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 528DJ UT WOS:000174228900008 PM 12055407 ER PT J AU O'Brien, E van Montfrans, G Palatini, P Tochikubo, O Staessen, J Shirasaki, O Lipicky, R Myers, M AF O'Brien, E van Montfrans, G Palatini, P Tochikubo, O Staessen, J Shirasaki, O Lipicky, R Myers, M TI Task Force I: Methodological aspects of blood pressure measurement SO BLOOD PRESSURE MONITORING LA English DT Article DE International Protocol; device validation; algorithm integrity; Food and Drug Administration; placebo; ambulatory blood pressure measurement AB Objective To reach a consensus on important methodological aspects of blood pressure measurement Methods A Task Force on the methodological aspects of blood pressure measurement wrote this review after the Eighth International Consensus Conference on Ambulatory Blood Pressure Monitoring, in Sendai, Japan (28-31 October 2001). This consensus paper is based on the papers presented by Task Force I and on the discussion sessions, and is therefore representative of a broad spectrum of expert opinion. Points of consensus Consensus was reached on the following five issues: (1) there is an urgent need for a simplified protocol for the validation of blood pressure measuring devices; (2) there is a need for a means of updating the ''state of the market'' for validated devices so that users can have easy access to this information; (3) new devices must be validated independently, and existing devices that have not been validated must be reappraised; (4) manufacturers should confirm when new models use algorithms which have been validated previously; (5) the Food and Drug Administration now accepts that when ambulatory blood pressure measurement is used in clinical short-term trials in which side-effects are not being assessed, a placebo arm is not required. (C) 2001 Lippincott Williams Wilkins. C1 Beaumont Hosp, Blood Pressure Unit, Dublin 9, Ireland. Univ Amsterdam, Acad Med Ctr, Interne Ziekten, NL-1105 AZ Amsterdam, Netherlands. Univ Policlin Padua, Inst Clin Med 1, Padua, Italy. Yokohama City Univ, Sch Med, Dept Publ Hlth, Kanagawa Ku, Yokohama, Kanagawa, Japan. Katholieke Univ Leuven, B-3001 Louvain, Belgium. Omrom Inst Life Sci Co Ltd, Kyoto, Japan. US FDA, Rockville, MD 20857 USA. Sunnybrook Med Ctr, Div Cardiol, Hypertens Unit, Toronto, ON, Canada. RP O'Brien, E (reprint author), Beaumont Hosp, Blood Pressure Unit, Dublin 9, Ireland. RI Staessen, Jan/A-1065-2011 OI Staessen, Jan/0000-0002-3026-1637 NR 10 TC 6 Z9 6 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1359-5237 J9 BLOOD PRESS MONIT JI Blood Press. Monit. PD DEC PY 2001 VL 6 IS 6 BP 313 EP 315 DI 10.1097/00126097-200112000-00009 PG 3 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 528DJ UT WOS:000174228900009 PM 12055408 ER PT J AU Whittaker, P Chanderbhan, RF AF Whittaker, P Chanderbhan, RF TI Effect of increasing iron supplementation on blood lipids in rats SO BRITISH JOURNAL OF NUTRITION LA English DT Article DE iron; lipids; lipid peroxidation; cardiotoxicity; rats ID CORONARY HEART-DISEASE; HYDROXYL-RADICAL GENERATION; MYOCARDIAL-INFARCTION; IDIOPATHIC HEMOCHROMATOSIS; CAROTID ATHEROSCLEROSIS; RISK; PEROXIDATION; OVERLOAD; STORES; ISCHEMIA AB The effects of increasing levels of Fe on serum fatty acids, cholesterol, triacylglycerol, liver and heart were examined in male Sprague-Dawley rats fed either Fe-deficient or carbonyl Fe-supplemented diets with 35 (control), 350, 3500 and 20 000 mug Fe/g for 12 weeks. As intake of Fe increased, serum total cholesterol increased from 2.0 mmol/l in controls to 5.2 mmol/l at the highest level of Fe. Also, the total serum phospholipid fatty acids increased from 609 mg/dl in controls to 1292 mg/l at the highest level of Fe. Except for the highest dose of Fe, the ratio of saturated to unsaturated phospholipid fatty acids increased from 1.2 to 1.7. The serum total free fatty acid levels remained constant among all groups with a range from 162 to 228 mg/l, while a ratio of 0.6 to 0.8 for saturated to unsaturated fatty acids was maintained. A dose-related increase in liver non-haem Fe from 18 to 3500 mug/g correlated with increases in lipid peroxidation (r 0.87), measured by the lipid-conjugated diene assay. Oxidative changes in the liver may have resulted in alterations in sterol synthesis, leading to increased serum cholesterol levels with increases in serum phospholipids and changes in the ratios of their saturated to unsaturated fatty acids. Animals with heart damage showed myocardial degeneration and cardiomyopathy with haemosiderin in interstitial macrophages or myocardial fibres and, when these were coupled with the findings of increased non-haem Fe in the heart and lipid peroxidation in the liver, suggested that oxidative stress is involved in the pathogenesis of the lesions. C1 US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. RP Whittaker, P (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 200 C St SW,HFS-236, Washington, DC 20204 USA. NR 37 TC 10 Z9 10 U1 0 U2 1 PU C A B I PUBLISHING PI WALLINGFORD PA C/O PUBLISHING DIVISION, WALLINGFORD OX10 8DE, OXON, ENGLAND SN 0007-1145 J9 BRIT J NUTR JI Br. J. Nutr. PD DEC PY 2001 VL 86 IS 5 BP 587 EP 592 DI 10.1079/BJN2001439 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 500GU UT WOS:000172618900006 PM 11737956 ER PT J AU Hoffman, FA AF Hoffman, FA TI Regulation of dietary supplements in the United States: Understanding the Dietary Supplement Health and Education Act SO CLINICAL OBSTETRICS AND GYNECOLOGY LA English DT Article C1 US FDA, Rockville, MD 20857 USA. RP Hoffman, FA (reprint author), 23 Oak Lane, Mt Lakes, NJ 07046 USA. NR 10 TC 5 Z9 7 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-9201 J9 CLIN OBSTET GYNECOL JI Clin. Obstet. Gynecol. PD DEC PY 2001 VL 44 IS 4 BP 780 EP 788 DI 10.1097/00003081-200112000-00016 PG 9 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 489ZW UT WOS:000172024000013 PM 11600859 ER PT J AU Mossoba, MM McDonald, RE Yurawecz, MP Kramer, JKG AF Mossoba, MM McDonald, RE Yurawecz, MP Kramer, JKG TI Application of on-line capillary GC-FTIR spectroscopy to lipid analysis SO EUROPEAN JOURNAL OF LIPID SCIENCE AND TECHNOLOGY LA English DT Article ID CONJUGATED LINOLEIC-ACID; TRANSFORM INFRARED-SPECTROSCOPY; HYDROGENATED SOYBEAN OIL; GAS-CHROMATOGRAPHY; HEAT-TREATMENT; CLA ISOMERS; FATTY-ACIDS; IDENTIFICATION; METHYLATION; MONOMERS C1 US FDA, Ctr Food Safety & Appl Nutr, Off Sci Anal & Support, Washington, DC 20204 USA. US FDA, Ctr Food Safety & Appl Nutr, Off Plant & Dairy Foods & Beverages, Washington, DC 20204 USA. US FDA, Ctr Food Safety & Appl Nutr, Off Nutr Prod Labeling & Dietary Supplements, Washington, DC 20204 USA. Agr & Agri Food Canada, Food Res Program, Guelph, ON N1G 5C9, Canada. RP Mossoba, MM (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Sci Anal & Support, Mail Stop HFS 717,200 C St SW, Washington, DC 20204 USA. NR 22 TC 5 Z9 6 U1 0 U2 1 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1438-7697 J9 EUR J LIPID SCI TECH JI Eur. J. Lipid Sci. Technol. PD DEC PY 2001 VL 103 IS 12 BP 826 EP 830 DI 10.1002/1438-9312(200112)103:12<826::AID-EJLT826>3.0.CO;2-P PG 5 WC Food Science & Technology; Nutrition & Dietetics SC Food Science & Technology; Nutrition & Dietetics GA 508JG UT WOS:000173084500009 ER PT J AU Skelley, PE Kovarik, PW AF Skelley, PE Kovarik, PW TI Insect surveys in the southeast: Investigating a relictual entomofauna SO FLORIDA ENTOMOLOGIST LA English DT Article; Proceedings Paper CT Workshop on Cactoblastis Cactorum in North America CY SEP, 2000 CL TAMPA, FLORIDA DE Coleoptera; Histeridae; Geomyidae; pocket gopher; rarity; burrow fauna AB Rare insects can occur in specialized niches of familiar habitats. Fur example, the burrows of rodents, such as the pocket gopher, contain a relictual entumofauna or surprising diversity. The discovery and cataloging of this "cryptic" diversity is an ongoing process that will require patience, time, and resources. The role of the amateur naturalist and collector is far from extinct in modern systematics, particularly in surveys of these specialized environments. They can provide much of the manpower for local surveys and often have extensive regional knowledge. C1 Florida State Collect Arthropods, FDACS, DPI, Gainesville, FL 32614 USA. Museum Biol Divers, Columbus, OH 43212 USA. RP Skelley, PE (reprint author), Florida State Collect Arthropods, FDACS, DPI, POB 147100, Gainesville, FL 32614 USA. NR 3 TC 3 Z9 4 U1 0 U2 3 PU FLORIDA ENTOMOLOGICAL SOC PI LUTZ PA 16125 E LAKE BURRELL DR, LUTZ, FL 33548 USA SN 0015-4040 J9 FLA ENTOMOL JI Fla. Entomol. PD DEC PY 2001 VL 84 IS 4 BP 552 EP 555 DI 10.2307/3496387 PG 4 WC Entomology SC Entomology GA 507JZ UT WOS:000173025300015 ER PT J AU Burns, RE Harris, DL Moreno, DS Eger, JE AF Burns, RE Harris, DL Moreno, DS Eger, JE TI Efficacy of spinosad bait sprays to control Mediterranean and Caribbean fruit flies (Diptera : Tephritidae) in commercial citrus in Florida SO FLORIDA ENTOMOLOGIST LA English DT Article DE spinosad; bait spray; Mediterranean fruit fly; Caribbean fruit fly AB A serious infestation of Mediterranean fruit fly in Florida in 1997 and 1998 led tu the widespread aerial and foliar application of malathion-bait sprays. Public concerns over property damage, environmental impact and public health led to the immediate need and acceptability of alternative pesticide,,bait combinations. Preliminary work with spinosad, a derivative of a soil microorganism developed by Dow AgroSciences, in combination with a new bait (Sol-Bait) showed promise. To ensure that this product would be effective in Florida for fruit fly control, three field tests were conducted using aerial and/or foliar applications. Results indicated that sprays with spinosad-SolBait provided comparable and significant control levels for sterile Mediterranean and Caribbean fruit flies in comparison to standard malathion with NU-LURE(R) or SolBait treatments by aerial or foliar application. In one test, honey bees and hives were exposed to sprays in the treatment area and no significant treatment differences were observed in hive condition or brood. Insufficient data on effects of treatments on naturally occurring and introduced beneficial insects were collected for statistical analysis but it appears no harmful effects were observed. C1 FDACS, Div Plant Ind, Gainesville, FL 32614 USA. USDA, Agr Res Ctr, Kika de la Garza Subtrop Agr Res Ctr, Weslaco, TX 78596 USA. Dow AgroSci, Tampa, FL 33629 USA. RP Burns, RE (reprint author), FDACS, Div Plant Ind, POB 147100, Gainesville, FL 32614 USA. NR 17 TC 63 Z9 69 U1 2 U2 9 PU FLORIDA ENTOMOLOGICAL SOC PI LUTZ PA 16125 E LAKE BURRELL DR, LUTZ, FL 33548 USA SN 0015-4040 J9 FLA ENTOMOL JI Fla. Entomol. PD DEC PY 2001 VL 84 IS 4 BP 672 EP 678 DI 10.2307/3496400 PG 7 WC Entomology SC Entomology GA 507JZ UT WOS:000173025300028 ER PT J AU Horton, LR AF Horton, LR TI Risk analysis and the law: international law, the World Trade Organization, Codex Alimentarius and national legislation SO FOOD ADDITIVES AND CONTAMINANTS LA English DT Article; Proceedings Paper CT 1st Symposium on Risk Assessment and Communication for Food Safety CY JUN, 2000 CL YORK, ENGLAND SP Cent Sci Lab, Joint Inst Food Safety & Appl Nutr DE risk analysis; Codex Alimentarius; World Trade Organization (WTO); technical barrier to trade; precautionary principle AB This paper discusses the place of risk analysis in international trade from a US perspective, through looking at the activities of the World Trade Organization and the Codex Alimentarius Commission. After examining what the trade agreements say about risk analysis and how international bodies are advancing and using risk analysis, the paper goes on to assess how risk analysis is used at a national level. Finally, recommendations are made for strengthening international food safety initiatives. C1 US FDA, Off Commissioner, Rockville, MD 20857 USA. RP Horton, LR (reprint author), US FDA, Off Commissioner, 5600 Fishers Lane,Room 15A-55, Rockville, MD 20857 USA. NR 0 TC 8 Z9 8 U1 0 U2 1 PU TAYLOR & FRANCIS LTD PI LONDON PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND SN 0265-203X J9 FOOD ADDIT CONTAM JI Food Addit. Contam. PD DEC PY 2001 VL 18 IS 12 BP 1057 EP 1067 DI 10.1080/02652030110054470 PG 11 WC Chemistry, Applied; Food Science & Technology; Toxicology SC Chemistry; Food Science & Technology; Toxicology GA 493RY UT WOS:000172238300002 PM 11761116 ER PT J AU Hitchins, AD Whiting, RC AF Hitchins, AD Whiting, RC TI Food-borne Listeria monocytogenes risk assessment SO FOOD ADDITIVES AND CONTAMINANTS LA English DT Article; Proceedings Paper CT 1st Symposium on Risk Assessment and Communication for Food Safety CY JUN, 2000 CL YORK, ENGLAND SP Cent Sci Lab, Joint Inst Food Safety & Appl Nutr DE food borne listeriosis; food contamination; food intake; risk assessment ID MEAT-PRODUCTS; MODIFIED ATMOSPHERES; COMPARATIVE GROWTH; RETAIL FOODS; VACUUM; MICE; PREVALENCE; NUMBERS; CHEESE; MILK AB Listeria monocytogenes is ubiquitous in the environment and in food processing plants. Consequently, foods are frequently contaminated. However, the occurrence rate of listeriosis is only about five cases per million people per year. Listeriosis primarily strikes immunocompromised individuals, pregnant women and the elderly with a fatality rate of 20-25%. The FDA is in the process of finishing a risk assessment that is being conducted as an initial step in reviewing its approach to maximizing the public protection from foodborne L. monocytogenes. The risk assessment evaluated the presence and quantitative levels of L. monocytogenes in 21 groups of ready-to-eat foods. The potential growth of L. monocytogenes between retail point-of-sale, where contamination data originated, and consumption was modelled. The frequency and amount of consumption of these foods completed the data for the exposure assessment. For the hazard characterization or dose response part of the risk assessment, data from animal studies, virulence assays and epidemiological investigations were used to estimate the likelihood of illness for different human groups from consuming different numbers of L. monocytogenes. This risk assessment is a virtual review of current scientific knowledge. Quantitative modelling provides greater insight than a qualitative review and also indicates the uncertainty about our knowledge. The risk assessment does not attempt to der ne an acceptable or tolerable level of L. monocytogenes consumption or propose changes in regulations. These decisions are the responsibility of risk managers who consider additional factors such as food preferences, technical feasibility and societal values when evaluating regulatory policies. C1 US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. RP Hitchins, AD (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. NR 52 TC 21 Z9 21 U1 3 U2 22 PU TAYLOR & FRANCIS LTD PI LONDON PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND SN 0265-203X J9 FOOD ADDIT CONTAM JI Food Addit. Contam. PD DEC PY 2001 VL 18 IS 12 BP 1108 EP 1117 DI 10.1080/02652030110050104 PG 10 WC Chemistry, Applied; Food Science & Technology; Toxicology SC Chemistry; Food Science & Technology; Toxicology GA 493RY UT WOS:000172238300008 PM 11761122 ER PT J AU Joseph, SW Hayes, JR English, LL Carr, LE Wagner, DD AF Joseph, SW Hayes, JR English, LL Carr, LE Wagner, DD TI Implications of multiple antimicrobial-resistant enterococci associated with the poultry environment SO FOOD ADDITIVES AND CONTAMINANTS LA English DT Article; Proceedings Paper CT 1st Symposium on Risk Assessment and Communication for Food Safety CY JUN, 2000 CL YORK, ENGLAND SP Cent Sci Lab, Joint Inst Food Safety & Appl Nutr DE Enterococcus; antimicrobial; antibiotic; resistance; poultry ID INFECTIONS AB Poultry are increasingly being associated with carriage of multiresistant organisms that may cause disease in humans. Among these organisms are the enterococci, now regarded as a common cause of hospital-acquired infections. The use of antimicrobials for growth promotion in poultry production environments may facilitate the dissemination of resistance to Enterococcus spp. that have the potential to be clinically significant. To assess descriptively the degree of multiresistant enterococci in the poultry environment of the Delmarva (Delaware-Maryland-Virginia) East Coast region of the USA, litter samples from regional commercial poultry houses and transport container swabs from processing facilities were cultured for Enterococcus spp. Using a microtiter plate adaptation of a conventional biochemical screen, the predominant species identified were E. faecalis (61.2%), E. faecium (18.6%) and E. gallinarum (2.4%). Resistance to the cephalosporin, macrolide and tetracycline classes of antimicrobials was uniform with broader resistance to penicillin and derivatives present in a majority of E. faecium isolates. High-level streptomycin resistance was evident in close to 30% of all isolates with a majority of E. faecalis variants possessing resistance. High-level gentamicin resistance was detected at a low frequency (2.6%) only within the E. faecalis group with resistance to low-level gentamicin levels present in a majority of both the E. faecalis group and subsets of E. faecium. No unexpected vancomycin resistance was detected. Of particular interest was resistance to the streptogramin quinupristin-dalfopristin (Q-D or Synercid), which was present in 70.4% of E. faecium and E. faecium variants. C1 Univ Maryland, Dept Mol Genet & Cell Biol, College Pk, MD 20742 USA. Univ Maryland, Dept Biol Resources Engn, College Pk, MD 20742 USA. US FDA, Ctr Vet Med, Laurel, MD USA. RP Joseph, SW (reprint author), Univ Maryland, Dept Mol Genet & Cell Biol, College Pk, MD 20742 USA. NR 13 TC 18 Z9 19 U1 1 U2 1 PU TAYLOR & FRANCIS LTD PI LONDON PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND SN 0265-203X J9 FOOD ADDIT CONTAM JI Food Addit. Contam. PD DEC PY 2001 VL 18 IS 12 BP 1118 EP 1123 DI 10.1080/02652030110051275 PG 6 WC Chemistry, Applied; Food Science & Technology; Toxicology SC Chemistry; Food Science & Technology; Toxicology GA 493RY UT WOS:000172238300009 PM 11761123 ER PT J AU Brennan, MJ Delogu, G Chen, YP Bardarov, S Kriakov, J Alavi, M Jacobs, WR AF Brennan, MJ Delogu, G Chen, YP Bardarov, S Kriakov, J Alavi, M Jacobs, WR TI Evidence that mycobacterial PE_PGRS proteins are cell surface constituents that influence interactions with other cells SO INFECTION AND IMMUNITY LA English DT Article ID HEPARIN-BINDING HEMAGGLUTININ; BORDETELLA-PERTUSSIS; FILAMENTOUS HEMAGGLUTININ; TRANSPOSON MUTAGENESIS; GENOME SEQUENCE; TUBERCULOSIS; FIBRONECTIN; RECEPTORS; ADHESIN; IDENTIFICATION AB The elucidation of the genomic sequence of Mycobacterium tuberculosis revealed the presence of a novel multigene family designated PE/PE_PGRS that encodes numerous, highly related proteins of unknown function. In this study, we demonstrate that a transposon insertion in a PE_PGRS gene (1818(PE_PGRS)) found in Mycobacterium bovis BCG Pasteur, which is the BCG homologue of the M. tuberculosis H37Rv gene Rv1818c, introduces new phenotypic properties to this BCG strain. These properties include dispersed growth in liquid medium and reduced infection of macrophages. Complementation of the 1818(PE_PGRS)::Tn5367 mutant with the wild-type gene restores both aggregative growth (clumping) in liquid medium and reestablishes infectivity of macrophages to levels equivalent to those for the parent BCG strain. Western blot analysis using antisera raised against the 1818(PE_PGRS) protein shows that PE_PGRS proteins are found in cell lysates of BCG and M. tuberculosis H37Ra and in the cell wall fraction of M. tuberculosis H37Rv. Moreover, immunofluorescent labeling of mycobacteria indicates that certain PE_PGRS proteins, are localized at the cell surface of BCG and M. tuberculosis. Together these results suggest that certain PE_PGRS proteins may be found at the surface of mycobacteria and influence both cell surface interactions among mycobacteria as well as the interactions of mycobacteria with macrophages. C1 US FDA, Ctr Biol Evaluat & Res, Lab Mycobacterial Dis & Cellular Immunol, Bethesda, MD 20892 USA. Albert Einstein Coll Med, Howard Hughes Med Inst, Dept Microbiol & Immunol, Bronx, NY 10461 USA. RP Brennan, MJ (reprint author), US FDA, Ctr Biol Evaluat & Res, Lab Mycobacterial Dis & Cellular Immunol, Bldg 29,Room 502,29 Lincoln Dr,HFM 431, Bethesda, MD 20892 USA. RI Delogu, Giovanni/I-3701-2012 OI Delogu, Giovanni/0000-0003-0182-8267 NR 48 TC 166 Z9 173 U1 1 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD DEC PY 2001 VL 69 IS 12 BP 7326 EP 7333 DI 10.1128/IAI.69.12.7326-7333.2001 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 494QP UT WOS:000172297600017 PM 11705904 ER PT J AU McDermott, PF Barry, AL Jones, RN Stein, GE Thornsberry, C Wu, CC Walker, RD AF McDermott, PF Barry, AL Jones, RN Stein, GE Thornsberry, C Wu, CC Walker, RD TI Standardization of broth microdilution and disk diffusion susceptibility tests for Actinobacillus pleuropneumoniae and Haemophilus somnus: Quality control standards for ceftiofur, enrofloxacin, florfenicol, gentamicin, penicillin, tetracycline, tilmicosin, and trimethoprim-sulfamethoxazole SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID RESISTANCE AB Quality control (QC) standards for the in vitro antimicrobial susceptibility testing of two fastidious veterinary pathogens,Actinobacillus pleuropneumoniae and Haemophilus somnus, were developed in a multilaboratory study according to procedures established by the National Committee for Clinical Laboratory Standards for broth microdilution and disk diffusion testing. The medium recommended for the broth microdilution testing is cation-adjusted Mueller-Hinton broth supplemented with 2% lysed horse blood, 2% yeast extract, and 2% supplement C. This medium has been designated veterinary fastidious medium. The medium recommended for the disk diffusion testing is chocolate Mueller-Hinton agar. The recommended QC organisms are A. pleuropneumoniae ATCC 27090 and H. somnus ATCC 700025. The QC MICs of ceftiofur, enrofloxacin, florfenicol, gentamicin, penicillin, tetracycline, tilmicosin, and trimethoprim-sulfamethoxazole were determined for each isolate, as were the zone size ranges. Of the results from the participating laboratories, 94.0% of the zone diameter results and 97.0% of the MIC results fell within the suggested QC ranges for all compounds. These QC guidelines should allow greater accuracy in interpreting results when testing these antimicrobial agents against fastidious pathogens. C1 US FDA, Ctr Vet Med, Div Anim & Food Microbiol, Laurel, MD 20708 USA. Inst Clin Microbiol, Wilsonville, OR USA. JMI Labs, Jones Grp, N Liberty, IA USA. Michigan State Univ, Dept Med, E Lansing, MI 48824 USA. MRL Pharmaceut Serv, Brentwood, TN USA. Purdue Univ, Dept Vet Pathobiol, W Lafayette, IN 47907 USA. RP Walker, RD (reprint author), US FDA, Ctr Vet Med, Div Anim & Food Microbiol, HFV530, Laurel, MD 20708 USA. NR 13 TC 12 Z9 13 U1 1 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 DEC PY 2001 VL 39 IS 12 BP 4283 EP 4287 DI 10.1128/JCM.39.12.4283-4287.2001 PG 5 WC Microbiology SC Microbiology GA 500FT UT WOS:000172616100009 PM 11724833 ER PT J AU Blease, K Jakubzick, C Schuh, JM Joshi, BH Puri, RK Hogaboam, CM AF Blease, K Jakubzick, C Schuh, JM Joshi, BH Puri, RK Hogaboam, CM TI IL-13 fusion cytotoxin ameliorates chronic fungal-induced allergic airway disease in mice SO JOURNAL OF IMMUNOLOGY LA English DT Article ID GRASS-POLLEN IMMUNOTHERAPY; MESSENGER-RNA EXPRESSION; RECEPTOR CROSS-LINKING; CELL-DEFICIENT MICE; COMMON GAMMA-CHAIN; INTERLEUKIN-13 RECEPTOR; T-CELLS; INTERFERON-GAMMA; TH1/TH2 PARADIGM; MUCUS PRODUCTION AB IL-13 has emerged as a major contributor to allergic and asthmatic responses, and as such it represents an attractive target in these diseases. In this study, IL-13-responsive cells in the lung were targeted via the intranasal administration of IL-13-PE38QQR (IL-13-PE), comprised of human IL-13 and a derivative of Pseudomonas exotoxin, to Aspergillus fumigatus-sensitized mice challenged with A. fumigatus spores, or conidia. Mice received 50, 100, or 200 ng of IL-13-PE or diluent alone (i.e., control group) on alternate days from day 14 to day 28 after the conidia challenge. The control group of mice exhibited significant airway hyperreactivity, goblet cell hyperplasia, and peribronchial fibrosis at day 28 after conidia. Although the two lower doses of IL-13-PE had limited therapeutic effects in mice with fungal-induced allergic airway disease, the highest dose of IL-13-PE tested significantly reduced all features of airway disease compared with the control group. Whole lung mRNA expression of IL-4R alpha and IL-13R alpha1 was markedly reduced, whereas bronchoalveolar lavage and whole lung levels of IFN-gamma were significantly elevated in mice treated with 200 ng of IL-13-PE compared with the control group. This study demonstrates that a therapy designed to target IL-13-responsive cells in the lung ameliorates established fungal-induced allergic airway disease in mice. C1 Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI 48109 USA. US FDA, Ctr Biol Evaluat & Res, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, Bethesda, MD 20892 USA. RP Hogaboam, CM (reprint author), Univ Michigan, Sch Med, Dept Pathol, 1301 Catherine Rd, Ann Arbor, MI 48109 USA. RI hogaboam, cory /M-3578-2014 NR 73 TC 43 Z9 46 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 1 PY 2001 VL 167 IS 11 BP 6583 EP 6592 PG 10 WC Immunology SC Immunology GA 494WU UT WOS:000172309500067 PM 11714828 ER PT J AU Higgins, JA Fayer, R Trout, JM Xiao, LH Lal, AA Kerby, S Jenkins, MC AF Higgins, JA Fayer, R Trout, JM Xiao, LH Lal, AA Kerby, S Jenkins, MC TI Real-time PCR for the detection of Cryptosporidium parvum SO JOURNAL OF MICROBIOLOGICAL METHODS LA English DT Article DE Cryptosporidium parvum; PCR; TaqMan ID POLYMERASE-CHAIN-REACTION; SUBUNIT RIBOSOMAL-RNA; MESSENGER-RNA; NONINVASIVE DETECTION; PUTATIVE BIOMARKERS; FECAL SPECIMENS; WATER SAMPLES; GIARDIA CYSTS; COLON-CANCER; CELL-CULTURE AB Real time. TaqMan PCR assays were developed for the Cp11 and 18S rRNA genes of the protozoan parasite Cryptosporidium parvum. The TaqMan probes were specific for the genus Cryptosporidium, but could not hybridize exclusively with human-infectious C. parvum species and genotypes. In conjunction with development of the TaqMan assays, two commercial kits, the Mo Bio UltraClean (TM) Soil DNA kit, and the Qiagen QIAamp (TM) DNA Stool kit, were evaluated for DNA extraction from calf diarrhea and manure, and potassium dichromate and formalin preserved human feces. Real-time quantitation was achieved with the diarrhea samples., but nested PCR was necessary to detect C. parvum DNA in manure and human feces. Ileal tissues were obtained from calves at 3, 7, and 14 days post-infection, and DNA extracted and assayed, Nested PCR detected C. part,um DNA in the 7-day post-infection sample, but neither of the other time point samples were positive. These results indicate that real-time quantitation of C. parvum DNA, extracted using the commercial kits, is feasible on diarrheic feces, with large numbers of oocysts and small concentrations of PCR inhibitor(s). For samples with few oocysts and high concentrations of PCR inhibitor(s), such as manure, nested PCR is necessary for detection. Published by Elsevier Science B.V. C1 USDA ARS, Beltsville, MD 20705 USA. Ctr Dis Control, Atlanta, GA 30341 USA. US FDA, Bethesda, MD 20892 USA. RP Higgins, JA (reprint author), USDA ARS, Rm 202,Bldg 173,10300 Baltimore Blvd, Beltsville, MD 20705 USA. RI Xiao, Lihua/B-1704-2013 OI Xiao, Lihua/0000-0001-8532-2727 NR 33 TC 65 Z9 75 U1 0 U2 10 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 2001 VL 47 IS 3 BP 323 EP 337 DI 10.1016/S0167-7012(01)00339-6 PG 15 WC Biochemical Research Methods; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 498DF UT WOS:000172494000008 PM 11714523 ER PT J AU Brown, SL Pennello, G AF Brown, SL Pennello, G TI Silicone gel breast implants - Reply SO JOURNAL OF RHEUMATOLOGY LA English DT Letter C1 US FDA, Off Surveillance & Biometr, Rockville, MD 20857 USA. RP Brown, SL (reprint author), US FDA, Off Surveillance & Biometr, Rockville, MD 20857 USA. NR 5 TC 1 Z9 1 U1 0 U2 0 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO, ONTARIO M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD DEC PY 2001 VL 28 IS 12 BP 2761 EP 2762 PG 2 WC Rheumatology SC Rheumatology GA 498NP UT WOS:000172517800039 ER PT J AU Wear, KA AF Wear, KA TI Fundamental precision limitations for measurements of frequency dependence of backscatter: Applications in tissue-mimicking phantoms and trabecular bone SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID BAND ULTRASOUND ATTENUATION; BOVINE CANCELLOUS BONE; HUMAN CALCANEUS; QUANTITATIVE ULTRASOUND; MINERAL DENSITY; HIP FRACTURE; MECHANICAL-PROPERTIES; OS CALCIS; IN-VITRO; VELOCITY AB Various models for ultrasonic scattering from trabecular bone have been proposed. They may be evaluated to a certain extent by comparison with experimental measurements. In order to appreciate limitations of these comparisons, it is important to understand measurement precision. In this article, an approach proposed by Lizzi and co-workers is adapted to model precision of estimates of frequency-dependent backscatter for scattering targets (such as trabecular bone) that contain many scatterers per resolution cell. This approach predicts uncertainties in backscatter due to the random nature of the interference of echoes from individual scatterers as they are summed at the receiver. The model is validated in experiments on a soft-tissue-mimicking phantom and on 24 human calcaneus samples interrogated in vitro. It is found that while random interference effects only partially explain measured variations in the magnitude of backscatter, they are virtually entirely responsible for observed variations in the frequency dependence (exponent of a power law fit) of backscatter. (C) 2001 Acoustical Society of America. 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 56 TC 28 Z9 28 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 DEC PY 2001 VL 110 IS 6 BP 3275 EP 3282 DI 10.1121/1.1416907 PG 8 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA 502EW UT WOS:000172731600045 PM 11785828 ER PT J AU Evelyn, B Toigo, T Banks, D Pohl, D Gray, K Robins, B Ernat, J AF Evelyn, B Toigo, T Banks, D Pohl, D Gray, K Robins, B Ernat, J TI Participation of racial/ethnic groups in clinical trials and race-related labeling: A review of new molecular entities approved 1995-1999 SO JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION LA English DT Article DE clinical trials; ethnicity; product labeling AB Few recent data are available from formal evaluations of approved now drug applications to address perceptions that racial and ethnic groups are Under-rep resented in clinical trials of new drugs. This study reviews racial and ethnic group participation in clinical trials and race-related labeling for new molecular entities approved during a five-year period by the Food and Drug Administration's (FDA) Center for Drug Evaluation and Research (CDER). This was a retrospective review of FDA medical officers' reviews of clinical trial protocols and product labeling for 185 new molecular entities (NME's) approved by CDER between January 1, 1995, and December 31, 1999. Enrollment data were obtained from the reviews and tabulated according to race/ethnicity. The approved product labeling was searched for statements related to product testing in various racial/ethnic groups. All data were compiled and analyzed using Microsoft Access. This study quantifies the participation of racial/ethnic groups in clinical trials by year and therapeutic category. Additionally, the study categorizes labeling based on the types of effects described as related to race/ethnicity. Racial and ethnic groups appear to participate in clinical trials to varying degrees. African Americans participated in trials to the greatest extent; however, their participation steadily declined from 12% in 1995 to 6% in 1999. Among trials known to be conducted only in the U.S., African-American participation is comparable to their representation in the U.S. population. In all cases, participants designated as Hispanic appear to be far below their representation in the population. Some differences in participation for all racial and ethnic groups are seen when comparisons from year-to-year or among drug classes are made. Labeling for 45% (84/185) of the products contained some statement about race, although in only 8% (15/185) were differences related to race described. Fifty percent (50%) of the effects were pharmacokinetic, 39% were efficacy, and 11% were safety. One product label recommended a change in dosage based on racial differences. C1 US FDA, Off Special Hlth Issues, Off Commissioner, Rockville, MD 20857 USA. RP Evelyn, B (reprint author), US FDA, Off Special Hlth Issues, Off Commissioner, Rockville, MD 20857 USA. NR 4 TC 51 Z9 53 U1 0 U2 0 PU NATL MED ASSOC PI WASHINGON PA 1012 10TH ST, N W, WASHINGON, DC 20001 USA SN 0027-9684 J9 J NATL MED ASSOC JI J. Natl. Med. Assoc. PD DEC PY 2001 VL 93 IS 12 SU S BP 18S EP 24S PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 507RR UT WOS:000173041900005 PM 11798060 ER PT J AU Khan, AA Nawaz, MS Robertson, L Khan, SA Cerniglia, CE AF Khan, AA Nawaz, MS Robertson, L Khan, SA Cerniglia, CE TI Identification of predominant human and animal anaerobic intestinal bacterial species by terminal restriction fragment patterns (TRFPs): a rapid, PCR-based method SO MOLECULAR AND CELLULAR PROBES LA English DT Article DE PCR; terminal restriction fragment pattern; anaerobe; identification ID MICROFLORA; DIVERSITY; METABOLISM; SAMPLES; PROBES AB Identification of predominant human and animal intestinal tract anaerobes by conventional methods is cumbersome, time-consuming and less sensitive as compared to molecular methods. We have developed a molecular technique to identify most of the abundant intestinal microflora by polyermase chain reaction (PCR) amplification of a 16S rRNA gene fragment using a pair of universal PCR primers. The forward PCR primer was labelled with 6-carboxyfluorescein amino hexy (6-FAM) fluorescent dye to detect the terminal fragment of the PCR products after digestion with restriction enzymes. The PCR products were purified and digested with restriction enzymes and were analysed by capillary electrophoresis using an automated DNA sequencer. The data was analysed with GeneScan software 2.1. Eleven bacteria (Eubacterium biforme, E. limosum, Peptostreptococcus productus, Lactobacillus acidophilus, Bacteroides thetaiotaomicron, B. vulgatus, B. distasonis, Clostridium clostridiiforme, C. leptum, C. perfringens and Escherichia coli) that are predominant in human and animal intestinal tract were successfully identified by this rapid molecular technique. This protocol is rapid, accurate, sensitive and capable of identifying multiple organisms in a single sample. (C) 2001 Academic Press. C1 US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. RP Khan, AA (reprint author), US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. NR 24 TC 16 Z9 18 U1 0 U2 4 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 2001 VL 15 IS 6 BP 349 EP 355 DI 10.1006/mcpr.2001.0383 PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Cell Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Cell Biology GA 524RN UT WOS:000174026800004 PM 11851378 ER PT J AU Thompson, KL Rosenzweig, BA Honchel, R Cannon, RE Blanchard, KT Stoll, RE Sistare, FD AF Thompson, KL Rosenzweig, BA Honchel, R Cannon, RE Blanchard, KT Stoll, RE Sistare, FD TI Loss of critical palindromic transgene promoter sequence in chemically induced Tg.AC mouse skin papillomas expressing transgene-derived mRNA SO MOLECULAR CARCINOGENESIS LA English DT Article DE Ha-ras genes; hypomethylation; DNA instability; zeta-globin ID V-HA-RAS; DNA METHYLATION; MICE; CARCINOGENESIS; RECOMBINATION AB The Tg.AC transgenic mouse carries a v-Ha-ras transgene. Skin papillomas develop in Tg.AC mice upon repeated dermal application of tumor promoters and carcinogens. The transgene is inserted at a single site on chromosome 11 in a multiple-copy array. Although most of the greater than or equal to 40 copies are arranged in a direct-repeat orientation, two copies of the transgene are inserted in a palindromic, inverted-repeat orientation. Deletion of the palindromic transgene promoter sequence is associated strongly with and diagnostic of loss of phenotypic responsiveness to Tg.AC papillomagens, such as 12-O-tetradecanoylphorbol-13-acetate (TPA). Unexpectedly, a loss of palindromic transgene sequence, in the absence of an observable reduction in copy number of the direct-repeat-oriented transgene sequence, is seen in DNA from papillomas when compared to genomic DNA from tail clips or skin samples away from the application site. Transgene-derived transcripts were detectable in all Tg.AC papillomas sampled. The transgene locus was hypomethylated in papillomas but not in samples from tail clips from the same animal or from skin samples away from the application site in responder Tg.AC mice, as shown by loss of resistance to digestion by Hpall. A cell line derived from a Tg,AC squamous cell carcinoma showed complete loss of the palindromic transgene sequence, hypomethylation of the transgene locus, and strong expression of v-Ha-ras mRNA. These data indicate that the palindromic transgene sequence, which appears to be necessary for initial responsiveness to tumorigens, may be susceptible to deletion during rapid cellular proliferation and is not required for transgene expression in later phases of papilloma growth. Published 2001 Wiley-Liss, Inc. C1 Boehringer Ingelheim Pharmaceut Inc, Dept Toxicol & Safety Assessment, Ridgefield, CT 06877 USA. NIEHS, Lab Environm Carcinogenesis & Mutagenesis, Res Triangle Pk, NC 27709 USA. US FDA, Div Appl Pharmacol Res, Ctr Drug Evaluat & Res, Laurel, MD 20708 USA. RP Sistare, FD (reprint author), US FDA, Div Appl Pharmacol Res, Ctr Drug Evaluat & Res, 8301 Muirkirk Rd, Laurel, MD 20708 USA. NR 23 TC 8 Z9 8 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD DEC PY 2001 VL 32 IS 4 BP 176 EP 186 DI 10.1002/mc.10009 PG 11 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA 498QP UT WOS:000172522200002 PM 11746829 ER PT J AU Benimetskaya, L Miller, P Benimetsky, S Maciaszek, A Guga, P Beaucage, SL Wilk, A Grajkowski, A Halperin, AL Stein, CA AF Benimetskaya, L Miller, P Benimetsky, S Maciaszek, A Guga, P Beaucage, SL Wilk, A Grajkowski, A Halperin, AL Stein, CA TI Inhibition of potentially anti-apoptotic proteins by antisense protein kinase C-alpha (Isis 3521) and antisense bcl-2 (G3139) phosphorothioate oligodeoxynucleotides: Relationship to the decreased viability of T24 bladder and PC3 prostate cancer cells SO MOLECULAR PHARMACOLOGY LA English DT Article ID NF-KAPPA-B; FIBROBLAST GROWTH-FACTOR; STEREOCONTROLLED SYNTHESIS; GENE-EXPRESSION; FACTOR-BINDING; IN-VITRO; OLIGONUCLEOTIDES; INDUCTION; THERAPY; OVEREXPRESSION AB Isis 3521 and G3139 are 20- and 18-mer phosphorothioate oligonucleotides, respectively, targeted to the protein kinase C (PKC)-alpha and bcl-2 mRNAs. Treatment of T24 bladder and PC3 prostate carcinoma cells with full-length and 3'-truncation mutants of Isis 3521 causes down-regulation of PKC-a protein and mRNA. However, at the level of a 15-mer and shorter, downregulation of mRNA expression is no longer observed. Further, no diminution in cellular viability, as measured by 3-(4,5-dimethylthiazol-2-yl)2,5-diphenyl tetrazolium bromide assay, in response to increasing concentrations of paclitaxel, can be observed for these shorter oligomers. These observations not only indicate that PKC-alpha protein expression can be down-regulated by both RNase H-dependent and -independent mechanisms but also that down-regulation of PKC-alpha is insufficient by itself to "chemosensitize" cells. G3139, which down-regulates bcl-2 protein and mRNA expression, also down-regulates PKC-alpha protein and mRNA expression but not that of PKC-beta1, -epsilon, or -zeta. However, the down-regulation of PKC-alpha and bcl-2 are not linked. When the carrier Eufectin 5 is employed, only bcl-2 is down-regulated in both T24 and PC3 cells at 50 nM oligonucleotide concentration. At 100 nM, both bcl-2 and PKC-alpha expression are down-regulated, and only at this concentration can "chemosensitization" to paclitaxel and carboplatin be observed. In contrast, the down-regulation of bcl-2 seems to be linked with that of RelA (p65). However, this too is also not sufficient for chemosensitization, even though it leads to the loss of expression of genes under the putative control of nuclear factor-kappaB and to detachment of the cells from plastic surfaces. These results underscore the complexity of the intracellular requirements for the initiation of chemosensitization to anti-neoplastic agents. C1 Columbia Univ, Dept Pharmacol, New York, NY 10032 USA. Columbia Univ, Dept Med, New York, NY 10032 USA. Johns Hopkins Univ, Dept Biochem, Baltimore, MD USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Baltimore, MD USA. Polish Acad Sci, Ctr Mol & Macromol Studies, Dept Bioorgan Chem, Lodz, Poland. US FDA, Div Therapeut Prot, Bethesda, MD 20014 USA. RP Stein, CA (reprint author), Columbia Univ, Dept Pharmacol, 630 W 168th St, New York, NY 10032 USA. FU NIGMS NIH HHS [GM58791] NR 50 TC 50 Z9 50 U1 0 U2 1 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD DEC PY 2001 VL 60 IS 6 BP 1296 EP 1307 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 500LQ UT WOS:000172629400019 PM 11723237 ER PT J AU Brinker, A Beitz, J AF Brinker, A Beitz, J TI Spontaneous reports of pulmonary embolism in association with raloxifene SO OBSTETRICS AND GYNECOLOGY LA English DT Letter C1 US FDA, Ctr Drug Evaluat & Res, Off Postmkt Drug Risk Assessment, Poolesville, MD 20837 USA. RP Brinker, A (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Postmkt Drug Risk Assessment, Poolesville, MD 20837 USA. NR 5 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD DEC PY 2001 VL 98 IS 6 BP 1151 EP 1151 DI 10.1016/S0029-7844(01)01636-2 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 497UW UT WOS:000172474700037 PM 11755578 ER PT J AU Chen, ML Shah, V Patnaik, R Adams, W Hussain, A Conner, D Mehta, M Malinowski, H Lazor, J Huang, SM Hare, D Lesko, L Sporn, D Williams, R AF Chen, ML Shah, V Patnaik, R Adams, W Hussain, A Conner, D Mehta, M Malinowski, H Lazor, J Huang, SM Hare, D Lesko, L Sporn, D Williams, R TI Bioavailability and bioequivalence: An FDA regulatory overview SO PHARMACEUTICAL RESEARCH LA English DT Editorial Material DE bioavailability; bioequivalence; guidances; New Drug Applications; Abbreviated New Drug Applications; generic drugs ID SIMULATIONS; ABSORPTION; SINGLE; CMAX AB Bioavailability and/or bioequivalence studies play a key role in the drug development period for both new drug products and their generic equivalents. For both, these studies are also important in the postapproval period in the presence of certain manufacturing changes. Like many regulatory studies, the assessment of bioavailability and bioequivalence can generally be achieved by considering the following three questions. What is the primary question of the study? What are the tests that can be used to address the question? What deg ree of confidence is needed for the test outcome? This article reviews the regulatory science of bioavailability and bioequivalence and provides FDA's recommendations for drug sponsors who intend to establish bioavailability and/or demonstrate bioequivalence for their pharmaceutical products during the developmental process or after approval. C1 US FDA, Off Pharmaceut Sci, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Chen, ML (reprint author), US FDA, Off Pharmaceut Sci, Ctr Drug Evaluat & Res, HFD-350,5600 Fishers Lane, Rockville, MD 20857 USA. NR 26 TC 76 Z9 78 U1 3 U2 16 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0724-8741 J9 PHARMACEUT RES JI Pharm. Res. PD DEC PY 2001 VL 18 IS 12 BP 1645 EP 1650 DI 10.1023/A:1013319408893 PG 6 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 507BR UT WOS:000173007300001 PM 11785681 ER PT J AU Godar, DE AF Godar, DE TI UV doses of American children and adolescents SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID MELANOCYTIC SKIN-CANCER; CUTANEOUS MALIGNANT-MELANOMA; SUN EXPOSURE; ULTRAVIOLET EXPOSURE; SOLAR ULTRAVIOLET; UNITED-STATES; AUSTRALIA; RADIATION; CHILDHOOD; SUNLIGHT AB The ultraviolet (UV) doses of American young adults were never measured, but are needed for assessing UV-related health risks. These doses were calculated using a novel approach. The National Human Activity Pattern Survey recorded the daily minute-by-minute activities of about 2000 young adults (0-19 years) over the course of 2 years to assess their exposure to environmental pollutants. From that survey, only the outdoor daylight data of northern and southern girls and boys were extracted and stratified by season and age to find the time American children (0-5 and 6-12 years) and adolescents (13-19 years) spend outside. They spend about 10% of the day outdoors, but only get about 30% of the available terrestrial UV radiation (on a horizontal plane). American children have about the same percent personal ambients as adults (3.1%), 2.8% for girls and 3.4% for boys. Adolescents have the lowest personal ambients (2.6%), 2.1% for girls and 3.1% for boys. To get their UV doses, their percent ambients are multiplied by the total available terrestrial UV. Excluding vacation, the erythernally weighted UV doses for American children are 25 kJ/m(2)/year, 23 for girls and 28 for boys. Adolescents get the lowest UV exposure of any group, 21 kJ/m(2)/year, 18 for girls and 24 for boys. Young adult northern girls get 18 kJ/m(2)/year and boys get 21 kJ/m(2)/year, whereas southern girls get 24 kJ/m(2)/year and boys get 31 kJ/m(2)/year. The youngest children (0-5 years) get slightly higher summer doses. Thus, we can now assess the UV-related health risks for American children and adolescents. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20852 USA. RP Godar, DE (reprint author), US FDA, Ctr Devices & Radiol Hlth, HFZ-114,12709 Twinbrook Pkwy, Rockville, MD 20852 USA. NR 42 TC 48 Z9 48 U1 0 U2 2 PU AMER SOC PHOTOBIOLOGY PI AUGUSTA PA BIOTECH PARK, 1021 15TH ST, SUITE 9, AUGUSTA, GA 30901-3158 USA SN 0031-8655 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD DEC PY 2001 VL 74 IS 6 BP 787 EP 793 DI 10.1562/0031-8655(2001)074<0787:UDOACA>2.0.CO;2 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 504NY UT WOS:000172863800007 PM 11783934 ER PT J AU Sailstad, DM Hattan, D Hill, RN Stokes, WS AF Sailstad, DM Hattan, D Hill, RN Stokes, WS TI ICCVAM evaluation of the murine local lymph node assay - I. The ICCVAM review process SO REGULATORY TOXICOLOGY AND PHARMACOLOGY LA English DT Article DE ICCVAM; local lymph node assay; validation; alternative toxicological method ID CONTACT ALLERGENS; MAXIMIZATION TEST; SENSITIZATION; IDENTIFICATION; VALIDATION; TRIAL AB New test methods are being developed to improve the prediction of human and environmental risks and to benefit animal welfare by reducing, refining, and replacing animal use. Regulatory adoption of new test methods is often a complex and protracted process, requiring test method validation, regulatory acceptance, and implementation. Assessments of new test methods have not always been uniform within or among regulatory agencies. Thus, there have been increased pressures for a harmonized approach to test method evaluation and acceptance. In 1997, in response to these pressures and to U.S. Public Law 103-43, the National Institute of Environmental Health Sciences (NIEHS) established the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) to coordinate interagency consideration of new and revised test methods. This article describes the validation and acceptance criteria and process used for the first test method evaluated by ICCVAM, the murine local lymph node assay (LLNA). Based on ICCVAM's conclusions and recommendations, the LLNA has been accepted by U.S. regulatory agencies as a stand-alone assay for allergic contact dermatitis. Two related articles in this series of three present the results of the independent peer review evaluation of the LLNA and summarize the performance characteristics of the database substantiating the validity of the LLNA. C1 US EPA, Expt Toxicol Div, Off Res & Dev, Natl Hlth & Environm Effects Res Lab, Res Triangle Pk, NC 27711 USA. US FDA, Ctr Food Safety & Appl Nutr, Div Hlth Effects Evaluat, Bethesda, MD 20205 USA. US EPA, Off Pollut Prevent & Tox Subst, Washington, DC 20460 USA. NIEHS, NTP Interagcy Ctr Evaluat Alternat Toxicol Method, Res Triangle Pk, NC 27709 USA. RP Sailstad, DM (reprint author), US EPA, Expt Toxicol Div, Off Res & Dev, Natl Hlth & Environm Effects Res Lab, MD 92, Res Triangle Pk, NC 27711 USA. NR 23 TC 32 Z9 34 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 0273-2300 J9 REGUL TOXICOL PHARM JI Regul. Toxicol. Pharmacol. PD DEC PY 2001 VL 34 IS 3 BP 249 EP 257 DI 10.1006/rtph.2001.1496 PG 9 WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology SC Legal Medicine; Pharmacology & Pharmacy; Toxicology GA 511HY UT WOS:000173259600005 PM 11754529 ER PT J AU Dean, JH Twerdok, LE Tice, RR Sailstad, DM Hattan, DG Stokes, WS AF Dean, JH Twerdok, LE Tice, RR Sailstad, DM Hattan, DG Stokes, WS TI ICCVAM evaluation of the murine local lymph node assay - II. Conclusions and recommendations of an independent scientific peer review panel SO REGULATORY TOXICOLOGY AND PHARMACOLOGY LA English DT Article DE allergic contact dermatitis; local lymph node assay; guinea pig; mice ID SKIN SENSITIZATION TESTS; PIG MAXIMIZATION TEST; EAR SWELLING TEST; CONTACT ALLERGENS; GUINEA-PIG; METAL-SALTS; INTERLABORATORY EVALUATION; CELL-PROLIFERATION; DERMAL APPLICATION; SENSITIVITY AB The validation status of the murine local lymph node assay (LLNA), a method for assessing the allergic contact dermatitis potential of chemicals, was evaluated by an independent peer review panel (Panel) convened by the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM). The LLNA measures lymphocyte proliferation using incorporation of radioactive thymidine or iododeoxyuridine into cells of the draining lymph nodes of mice topically exposed to a test article. The Panel concluded that the assay performed as well as currently accepted guinea pig methods [guinea pig maximization test (GPMT)/Buehler assay (BA)] for the hazard identification of strong to moderate chemical sensitizing agents, but that it might not correctly identify all weak sensitizers or metals (potential false negative response) or all strong irritants (potential false positive response). The Panel concluded also that the LLNA involves less pain and distress than conventional guinea pig methods. The Panel unanimously recommended the LLNA as a stand-alone alternative for contact sensitization hazard assessment, provided that certain protocol modifications were made. These included collection of individual, rather than pooled, animal response data; the inclusion of a concurrent positive control; and consideration of dose-response information and statistical analyses. A standardized LLNA protocol is provided. (C) 2001 Elsevier Science. C1 Sanofi Synthelabo Inc, Sanofi Synthelabo Res, Malvern, PA 19355 USA. Amer Petr Inst, Washington, DC 20005 USA. NIEHS, Natl Toxicol Program, Interagcy Ctr Evaluat Alternat Toxicol Methods, Res Triangle Pk, NC 27709 USA. ILS Inc, Res Triangle Pk, NC 27709 USA. US EPA, Expt Toxicol Div, Res Triangle Pk, NC 27711 USA. US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20205 USA. RP Dean, JH (reprint author), Sanofi Synthelabo Inc, Sanofi Synthelabo Res, POB 3026, Malvern, PA 19355 USA. FU NIEHS NIH HHS [N01-ES-85424] NR 62 TC 92 Z9 95 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0273-2300 J9 REGUL TOXICOL PHARM JI Regul. Toxicol. Pharmacol. PD DEC PY 2001 VL 34 IS 3 BP 258 EP 273 DI 10.1006/rtph.2001.1497 PG 16 WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology SC Legal Medicine; Pharmacology & Pharmacy; Toxicology GA 511HY UT WOS:000173259600006 PM 11754530 ER PT J AU Renukaradhya, GJ Isloor, S Crowther, JR Robinson, M Rajasekhar, M AF Renukaradhya, GJ Isloor, S Crowther, JR Robinson, M Rajasekhar, M TI Development and field validation of an avidin-biotin enzyme-linked immunosorbent assay kit for bovine brucellosis SO REVUE SCIENTIFIQUE ET TECHNIQUE DE L OFFICE INTERNATIONAL DES EPIZOOTIES LA English DT Article DE avidin-biotin ELISA; bovine brucellosis; Brucella antibodies; enzyme-linked immunosorbent assay; India; surveillance ID INDIRECT ELISA; DIAGNOSIS; PREVALENCE; INDIA AB The avidin-biotin enzyme-linked immunosorbent assay (A-B ELISA), for use in surveillance for bovine brucellosis in India was developed and calibrated using the indirect brucellosis ELISA kit of the International Atomic Energy Agency (IAEA) as a reference. The reagents used in the A-B ELISA were as follows: the smooth lipopolysaccharide of Brucella abortus strain 99 (antigen); biotinylated anti-bovine immunoglobulin G (detection antibody); avidin-horseradish peroxidase (conjugate); and 0-phenylenediamine dihydrochloride (chromogen). The test results were interpreted using the IAEA software EDI version 2.1.1, which was modified for use in the A-B ELISA. The cut-off percentage positivity value was established using 500 brucellosis-positive and 500 brucellosis-negative serum samples, confirmed with reference to the sample data using the indirect ELISA kit. The overall specificity of A-B ELISA was 98.8% and overall sensitivity was 98.2%. Field validation of the A-B ELISA kit was undertaken in six laboratories in India. Screening of 7,040 cattle and 678 buffalo serum samples from 12 states revealed serological evidence of brucellosis in 8.7% of cattle and 10.2% of buffalo. This kit proved to be robust and performed with a similar sensitivity and specificity to the indirect ELISA. The kit can be supplied at a lower cost than current commercial ELISA kits. C1 PD ADMAS, Bangalore 560024, Karnataka, India. IAEA, Food & Agr Org, Joint Div, A-1400 Vienna, Austria. US FDA, Ctr Vet Med, Div Human Food Safety, Rockville, MD 20855 USA. RP Renukaradhya, GJ (reprint author), PD ADMAS, Bangalore 560024, Karnataka, India. RI pasuvalingam, visha/B-5717-2012; OI Gourapura, Renukaradhya/0000-0003-2861-180X NR 16 TC 15 Z9 15 U1 0 U2 0 PU OFFICE INT EPIZOOTIES PI PARIS PA 12 RUE DE PRONY, 75017 PARIS, FRANCE SN 0253-1933 J9 REV SCI TECH OIE JI Rev. Sci. Tech. Off. Int. Epizoot. PD DEC PY 2001 VL 20 IS 3 BP 749 EP 756 PG 8 WC Veterinary Sciences SC Veterinary Sciences GA 494EJ UT WOS:000172268500009 PM 11732417 ER PT J AU Vose, D Acar, J Anthony, F Franklin, A Gupta, R Nicholls, T Tamura, Y Thompson, S Threlfall, EJ van Vuuren, M White, DG Wegener, HC Costarrica, ML AF Vose, D Acar, J Anthony, F Franklin, A Gupta, R Nicholls, T Tamura, Y Thompson, S Threlfall, EJ van Vuuren, M White, DG Wegener, HC Costarrica, ML TI Antimicrobial resistance: risk analysis methodology for the potential impact on public health of antimicrobial resistant bacteria of animal origin SO REVUE SCIENTIFIQUE ET TECHNIQUE DE L OFFICE INTERNATIONAL DES EPIZOOTIES LA English DT Article DE antimicrobial resistance; containment of resistance; food; human medicine; international standards; public health; risk analysis; risk assessment; risk management; veterinary medicine AB The Ad hoc Group of experts on antimicrobial resistance, appointed by the Office International des Epizooties, has developed an objective, transparent and defensible risk analysis process, providing a valid basis for risk management decisions in respect to antimicrobial resistance. The components of risk analysis and of different possible approaches in risk assessment (qualitative, semiquantitative and quantitative) are defined. The Ad hoc Group recommended the following: an independent risk assessment based on scientific data; an iterative risk analysis process; a qualitative risk assessment systematically undertaken before considering a quantitative approach; the establishment of a risk assessment policy; and the availability of technical assistance for developing countries. C1 David Vose Consulting, F-24400 Les Leches, France. Univ Paris 06, Fdn Hop St Joseph, Serv Microbiol Med, F-75674 Paris 14, France. Fresh Acre Vet Surg, Bromyard HR7 4QR, Hereford, England. Natl Vet Inst SVA, Dept Antiobiot, SE-75189 Uppsala, Sweden. Govind Ballabh Pant Univ Agr & Technol, Dept Microbiol, Coll Vet Sci, Pantnagar 263145, Uttar Pradesh, India. Dept Agr Fisheries & Forestry, Anim Hlth Sci & Emergency Management Branch, Natl Off Anim Safety, Canberra, ACT 2601, Australia. Minist Agr Forestry & Fisheries, Natl Vet Assay Lab, Tokyo 1858511, Japan. Dept Hlth & Human Serv Liaison, Joint Inst Food Safety Res, Washington, DC 20250 USA. Cent Publ Hlth Lab, Publ Hlth Serv, Lab Enter Pathogens, London NW9 5HT, England. Univ Pretoria, Fac Vet Sci, Dept Vet Trop Dis, ZA-0110 Onderstepoort, South Africa. US FDA, Res Off, Ctr Vet Med, Laurel, MD 20708 USA. WHO, Div Emerging & Transmissible Dis, Anim & Food Related Publ Hlth Risks, CH-1211 Geneva, Switzerland. Food & Agr Org, Food Qual & Stand Serv, I-00100 Rome, Italy. Dept Agr Fisheries & Forestry, Natl Off Anim & Plant Hlth Safety, Anim Hlth Sci & Emergency Management Branch, Canberra, ACT 2601, Australia. Dept Agr Fisheries & Forestry, Natl Off Food Safety, Anim Hlth Sci & Emergency Management Branch, Canberra, ACT 2601, Australia. RP Vose, D (reprint author), David Vose Consulting, F-24400 Les Leches, France. RI pasuvalingam, visha/B-5717-2012; OI Wegener, Henrik Caspar/0000-0002-6888-2121 NR 23 TC 27 Z9 31 U1 1 U2 4 PU OFFICE INT EPIZOOTIES PI PARIS PA 12 RUE DE PRONY, 75017 PARIS, FRANCE SN 0253-1933 J9 REV SCI TECH OIE JI Rev. Sci. Tech. Off. Int. Epizoot. PD DEC PY 2001 VL 20 IS 3 BP 811 EP 827 PG 17 WC Veterinary Sciences SC Veterinary Sciences GA 494EJ UT WOS:000172268500016 PM 11732424 ER PT J AU Anthony, F Acar, J Franklin, A Gupta, R Nicholls, T Tamura, Y Thompson, S Threlfall, EJ Vose, D van Vuuren, M White, DG AF Anthony, F Acar, J Franklin, A Gupta, R Nicholls, T Tamura, Y Thompson, S Threlfall, EJ Vose, D van Vuuren, M White, DG TI Antimicrobial resistance: responsible and prudent use of antimicrobial agents in veterinary medicine SO REVUE SCIENTIFIQUE ET TECHNIQUE DE L OFFICE INTERNATIONAL DES EPIZOOTIES LA English DT Article DE antimicrobial resistance; competent authorities; containment of resistance; food; human medicine; international standards; marketing authorisation; Office International des Epizooties; public health; veterinary medicine AB A guideline on the responsible and prudent use of antimicrobials in animal husbandry has been developed by the Ad hoc Group of experts on antimicrobial resistance, created by the Office International des Epizooties. The objectives of responsible use are to maintain antibiotic efficacy, to avoid the dissemination of resistant bacteria or resistance determinants and to avoid the exposure of humans to resistance through food. The guideline attributes a central role to the competent authorities responsible for granting marketing authorisations for antimicrobial substances. Requirements before and after granting of marketing authorisations are defined. Important aspects include the control of the pharmaceutical product quality and the therapeutic efficacy, the assessment of the selection pressure, the protection of the environment, specific and nonspecific antimicrobial resistance surveillance. The guideline is also addressed to the veterinary pharmaceutical industry, veterinary practitioners, dispensing pharmacists and farmers. The respective roles and responsibilities of these groups are defined. C1 Fresh Acre Vet Surg, Bromyard HR7 4QR, Hereford, England. Univ Paris 06, Serv Microbiol Med, Fdn Hop St Joseph, F-75674 Paris 14, France. Natl Vet Inst SVA, Dept Antibiot, SE-75189 Uppsala, Sweden. Govind Ballabh Pant Univ Agr & Technol, Coll Vet Sci, Dept Microbiol, Pantnagar 263145, Uttar Pradesh, India. Dept Agr Forestry & Fisheries, Anim Hlth Sci & Emergency Management Branch, Natl Off Anim Safety, Canberra, ACT 2601, Australia. Dept Agr Forestry & Fisheries, Natl Off Anim & Plant Hlth Safety, Anim Hlth Sci & Emergency Management Branch, Canberra, ACT 2601, Australia. Minist Agr Forestry & Fisheries, Natl Vet Assay Lab, Tokyo 1858511, Japan. Dept Hlth & Human Serv Liaison, Joint Inst Food Safety Res, Washington, DC 20250 USA. Cent Publ Hlth Lab, Publ Hlth Lab Serv, Lab Enter Pathogens, London NW9 5HT, England. David Vose Consulting, F-24400 Les Leches, France. Univ Pretoria, Fac Vet Sci, Dept Vet Trop Dis, ZA-0110 Onderstepoort, South Africa. US FDA, Ctr Vet Med, Res Off, Laurel, MD 20708 USA. Dept Agr Fisheries & Forestry, Natl Off Food Safety, Anim Hlth Sci & Emergency Management Branch, Canberra, ACT 2601, Australia. RP Anthony, F (reprint author), Fresh Acre Vet Surg, Flaggoners Green, Bromyard HR7 4QR, Hereford, England. RI pasuvalingam, visha/B-5717-2012 NR 0 TC 14 Z9 16 U1 3 U2 12 PU OFFICE INT EPIZOOTIES PI PARIS PA 12 RUE DE PRONY, 75017 PARIS, FRANCE SN 0253-1933 J9 REV SCI TECH OIE JI Rev. Sci. Tech. Off. Int. Epizoot. PD DEC PY 2001 VL 20 IS 3 BP 829 EP 839 PG 11 WC Veterinary Sciences SC Veterinary Sciences GA 494EJ UT WOS:000172268500017 PM 11732425 ER PT J AU Nicholls, T Acar, J Anthony, F Franklin, A Gupta, R Tamura, Y Thompson, S Threlfall, EJ Vose, D van Vuuren, M White, DG Wegener, HC Costarrica, ML AF Nicholls, T Acar, J Anthony, F Franklin, A Gupta, R Tamura, Y Thompson, S Threlfall, EJ Vose, D van Vuuren, M White, DG Wegener, HC Costarrica, ML TI Antimicrobial resistance: monitoring the quantities of antimicrobials used in animal husbandry SO REVUE SCIENTIFIQUE ET TECHNIQUE DE L OFFICE INTERNATIONAL DES EPIZOOTIES LA English DT Article DE animal health; antimicrobial resistance; containment of resistance; human medicine; monitoring of antimicrobial use; Office International des Epizooties; public health; risk analysis; standards; veterinary medicine AB This guideline, developed by the Office International des Epizooties for the monitoring of the quantities of antimicrobials used in animal husbandry, provides the methodology required to assess the amounts of antimicrobials used, to supply data to be used for risk analysis and to improve guidance on the appropriate use of antimicrobials. Information may be gathered from a number of sources, such as the competent authorities, industry and users. The usefulness of different types of information is discussed and recommendations are given on how to collect detailed information, each year, on the antimicrobial quantities used per class and active substance. Information should also be collected on the route of administration (oral and parenteral) and the animal species. C1 Dept Agr Fisheries & Forestry, Natl Off Anim & Plant Hlth Safety, Anim Hlth Sci & Emergency Management Branch, Canberra, ACT 2601, Australia. Dept Agr Fisheries & Forestry, Natl Off Food Safety, Anim Hlth Sci & Emergency Management Branch, Canberra, ACT 2601, Australia. Univ Paris 06, Serv Microbiol Med, Fdn Hop St Joseph, F-75674 Paris, France. Fresh Acre Vet Surg, Bromyard HR7 4QR, Hereford, England. Natl Vet Inst SVA, Dept Antibiot, SE-75189 Uppsala, Sweden. Govind Ballabh Pant Univ Agr & Technol, Dept Microbiol, Coll Vet Sci, Pantnagar 263145, Uttar Pradesh, India. Minist Agr Forestry & Fisheries, Natl Vet Assay Lab, Tokyo 1858511, Japan. Dept Hlth & Human Serv Liaison, Joint Inst Food Safety Res, Washington, DC 20250 USA. Cent Publ Hlth Lab, Publ Hlth Lab Serv, Lab Enter Pathogens, London NW9 5HT, England. David Vose Consulting, F-24400 Les Leches, France. Univ Pretoria, Fac Vet Sci, Dept Vet Trop Dis, ZA-0110 Onderstepoort, South Africa. US FDA, Ctr Vet Med, Res Off, Laurel, MD 20708 USA. WHO, Div Emerging & Transmissible Dis Anim & Food Rela, CH-1211 Geneva, Switzerland. FAO, Food Qual & Stand Serv, I-00100 Rome, Italy. RP Nicholls, T (reprint author), Dept Agr Fisheries & Forestry, Natl Off Anim & Plant Hlth Safety, Anim Hlth Sci & Emergency Management Branch, POB 858, Canberra, ACT 2601, Australia. RI pasuvalingam, visha/B-5717-2012 NR 2 TC 32 Z9 34 U1 1 U2 8 PU OFFICE INT EPIZOOTIES PI PARIS PA 12 RUE DE PRONY, 75017 PARIS, FRANCE SN 0253-1933 J9 REV SCI TECH OIE JI Rev. Sci. Tech. Off. Int. Epizoot. PD DEC PY 2001 VL 20 IS 3 BP 841 EP 847 PG 7 WC Veterinary Sciences SC Veterinary Sciences GA 494EJ UT WOS:000172268500018 PM 11732426 ER PT J AU White, DG Acar, J Anthony, F Franklin, A Gupta, B Nicholls, T Tamura, Y Thompson, S Threlfall, EJ Vose, D van Vuuren, M Wegener, HC Costarrica, ML AF White, DG Acar, J Anthony, F Franklin, A Gupta, B Nicholls, T Tamura, Y Thompson, S Threlfall, EJ Vose, D van Vuuren, M Wegener, HC Costarrica, ML TI Antimicrobial resistance: standardisation and harmonisation of laboratory methodologies for the detection and quantification of antimicrobial resistance SO REVUE SCIENTIFIQUE ET TECHNIQUE DE L OFFICE INTERNATIONAL DES EPIZOOTIES LA English DT Article DE antimicrobial resistance; breakpoints; containment of resistance; harmonisation; international standards; laboratory methodology; Office International des Epizooties; public health; risk analysis; standardisation; threshold ID ANTIBIOTIC-RESISTANCE; IN-VITRO; SUSCEPTIBILITY; BACTERIA; SYSTEM; SURVEILLANCE; SALMONELLA AB The Ad hoc Group of experts on antimicrobial resistance of the Office International des Epizooties has developed a guideline on the standardisation and harmonisation of laboratory methodologies used for the detection and quantification of antimicrobial resistance. The existing methods (disk diffusion [including concentration gradient strips], agar dilution and broth dilution) are reviewed including a comparison of their advantages and disadvantages. The definitions of resistance characteristics of bacteria (susceptible, intermediate and resistant) are addressed and the criteria for the establishment of breakpoints are discussed. Due consideration has to be given to these aspects in the interpretation and comparison of resistance monitoring or surveillance data. The use of validated laboratory methods and the establishment of quality assurance (internal and external) for microbiological laboratory work and the reporting of quantitative test results is recommended. Equivalence of different methods and laboratory test results is also recommended to be established by external proficiency testing, which should be achieved by the means of a reference laboratory system. This approach allows the comparison of test results obtained using different methods generated by laboratories in different countries. C1 US FDA, Ctr Vet Med, Res Off, Laurel, MD 20708 USA. Univ Paris 06, Serv Microbiol Med, Fdn Hop St Joseph, F-75674 Paris 14, France. Fresh Acre Vet Surg, Bromyard HR7 4QR, Hereford, England. Natl Vet Inst SVA, Dept Antibiot, SE-75189 Uppsala, Sweden. Govind Ballabh Pant Univ Agr & Technol, Dept Microbiol, Coll Vet Sci, Pantnagar 263145, Uttar Pradesh, India. Dept Agr Fisheries & Forestry, Natl Off Anim & Plant Hlth Safety, Anim Hlth Sci & Emergency Management Branch, Canberra, ACT 2601, Australia. Dept Agr Fisheries & Forestry, Natl Off Food Safety, Anim Hlth Sci & Emergency Management Branch, Canberra, ACT 2601, Australia. Minist Agr Forestry & Fisheries, Natl Vet Assay Lab, Tokyo 1858511, Japan. Dept Hlth & Human Serv Liaison, Joint Inst Food Safety Res, Washington, DC 20250 USA. Cent Publ Hlth Lab, Publ Hlth Lab Serv, Lab Enter Pathogens, London NW9 5HT, England. David Vose Consulting, F-24400 Les Leches, France. Univ Pretoria, Fac Vet Sci, Dept Vet Trop Dis, ZA-0110 Onderstepoort, South Africa. WHO, Div Emerging & Transmissible Dis Anim & Food Rela, CH-1211 Geneva, Switzerland. FAO, Food Qual & Stand Serv, I-00100 Rome, Italy. RP White, DG (reprint author), US FDA, Ctr Vet Med, Res Off, HFV-530,8401 Muirkirk Rd, Laurel, MD 20708 USA. RI pasuvalingam, visha/B-5717-2012; OI Wegener, Henrik Caspar/0000-0002-6888-2121 NR 26 TC 35 Z9 36 U1 1 U2 5 PU OFFICE INT EPIZOOTIES PI PARIS PA 12 RUE DE PRONY, 75017 PARIS, FRANCE SN 0253-1933 J9 REV SCI TECH OIE JI Rev. Sci. Tech. Off. Int. Epizoot. PD DEC PY 2001 VL 20 IS 3 BP 849 EP 858 PG 10 WC Veterinary Sciences SC Veterinary Sciences GA 494EJ UT WOS:000172268500019 PM 11732427 ER PT J AU Franklin, A Acar, J Anthony, F Gupta, R Nicholls, T Tamura, Y Thompson, S Threlfall, EJ Vose, D van Vuuren, M White, DG Wegener, HC Costarrica, ML AF Franklin, A Acar, J Anthony, F Gupta, R Nicholls, T Tamura, Y Thompson, S Threlfall, EJ Vose, D van Vuuren, M White, DG Wegener, HC Costarrica, ML TI Antimicrobial resistance: harmonisation of national antimicrobial resistance monitoring and surveillance programmes in animals and in animal-derived food SO REVUE SCIENTIFIQUE ET TECHNIQUE DE L OFFICE INTERNATIONAL DES EPIZOOTIES LA English DT Article DE antimicrobial resistance; containment of resistance; harmonisation; human medicine; international standards; laboratory methodology; monitoring; Office International des Epizooties; public health; risk analysis; surveillance; veterinary medicine ID ANTIBIOTIC-RESISTANCE; SUSCEPTIBILITY AB A guideline on the harmonisation of national antimicrobial resistance monitoring and surveillance programmes in animals and animal-derived foods has been developed by the Ad hoc Group of experts on antimicrobial resistance of the Office International des Epizooties. The objective of the guideline is to allow the generation of comparable data from various national surveillance and monitoring systems in order to compare the situations in different regions or countries and to consolidate results at the national, regional and international level. Definitions of surveillance and monitoring are provided. National systems should be able to detect the emergence of resistance, and to determine the prevalence of resistant bacteria. The resulting data should be used in the assessment of risks to public health and should contribute to the establishment of a risk management policy. Specific factors identified for harmonisation include the animal species, food commodities, sampling plans, bacterial species, antimicrobials to be tested, laboratory methods, data reporting, database structure and the structure of reports. C1 Natl Vet Inst SVA, Dept Antibiot, SE-75189 Uppsala, Sweden. Univ Paris 06, Serv Microbiol Med, Fdn Hop St Joseph, F-75674 Paris 14, France. Fresh Acre Vet Surg, Bromyard HR7 4QR, Hereford, England. Govind Ballabh Pant Univ Agr & Technol, Dept Microbiol, Coll Vet Sci, Pantnagar 263145, Uttar Pradesh, India. Dept Agr Fisheries & Forestry, Natl Off Anim & Plant Hlth Safety, Anim Hlth Sci & Emergency Management Branch, Canberra, ACT 2601, Australia. Dept Agr Fisheries & Forestry, Natl Off Food Safety, Anim Hlth Sci & Emergency Management Branch, Canberra, ACT 2601, Australia. Minist Agr Forestry & Fisheries, Natl Vet Assay Lab, Tokyo 1858511, Japan. Dept Hlth & Human Serv Liaison, Joint Inst Food Safety Res, Washington, DC 20250 USA. Cent Publ Hlth Lab, Publ Hlth Lab Serv, Lab Enter Pathogens, London NW9 5HT, England. David Vose Consulting, F-24400 Les Leches, France. Univ Pretoria, Fac Vet Sci, Dept Vet Trop Dis, ZA-0110 Onderstepoort, South Africa. US FDA, Ctr Vet Med, Res Off, Laurel, MD 20708 USA. WHO, Div Emerging & Transmissible Dis Anim & Food Rela, CH-1211 Geneva, Switzerland. FAO, Food Qual & Stand Serv, I-00100 Rome, Italy. RP Franklin, A (reprint author), Natl Vet Inst SVA, Dept Antibiot, SE-75189 Uppsala, Sweden. RI pasuvalingam, visha/B-5717-2012; OI Wegener, Henrik Caspar/0000-0002-6888-2121 NR 22 TC 49 Z9 50 U1 0 U2 6 PU OFFICE INT EPIZOOTIES PI PARIS PA 12 RUE DE PRONY, 75017 PARIS, FRANCE SN 0253-1933 J9 REV SCI TECH OIE JI Rev. Sci. Tech. Off. Int. Epizoot. PD DEC PY 2001 VL 20 IS 3 BP 859 EP 870 PG 12 WC Veterinary Sciences SC Veterinary Sciences GA 494EJ UT WOS:000172268500020 PM 11732428 ER PT J AU Caron, A Mayer, JC Menu, P Alayash, A Marie, PY Vigneron, C AF Caron, A Mayer, JC Menu, P Alayash, A Marie, PY Vigneron, C TI Measurement of blood volume after haemodilution with haemoglobin-based oxygen carriers by a radiolabelled-albumin method SO TRANSFUSION MEDICINE LA English DT Article DE blood substitute; blood volume; haemodilution; haemoglobin-based oxygen carriers ID CROSS-LINKED HEMOGLOBIN; RANDOMIZED TRIAL; TRANSFUSION; SURGERY; RATS; HEMODILUTION; SUBSTITUTES; MECHANISMS; REDUCTION AB Recent studies have shown that the use of haemoglobin-based oxygen-carrying solutions (HBOCs) for perioperative haemodilution could significantly reduce the need for packed red blood cells in clinical practice. Though the effects of HBOCs on plasma volume have been characterized in experimental models of volume resuscitation from hypovolaemic shock, little is known about their action in normovolaemic haemodilution conditions. We therefore applied a radiolabelled serumalbumin method to determine blood volume after haemodilution with crosslinked or conjugated haemoglobin, in comparison with a reference solution of hydroxyethyl starch (HES). Three groups of New Zealand white rabbits were studied (n = 7 each group) subjected to moderate exchange transfusion with low molecular weight HES, bis(3,5-dibromosalicyl)fumarate crosslinked haemoglobin (alphaalpha-Hb), or dextran-conjugated haemoglobin (Hb-Dex-BTC). HES induced no changes in heart rate and blood pressure. The amplitude and duration of blood pressure increase and bradycardia were similar in both haemoglobin groups. A significant contraction of blood volume (12%) was observed 60 min after haemodilution with alphaalpha-Hb, compared to HES and Hb-Dex-BTC. At the same time point, a decrease in absolute haemoglobin (plasma haemoglobin x plasma volume) was also noted. This study suggests that in haemodilution conditions, the specific oncotic properties and circulating persistence of crosslinked and conjugated haemoglobin solutions affect the pattern of blood volume distribution differently. C1 Univ Nancy 1, Fac Pharm, Dept Haematol & Physiol, Lab Hematol & Physiol, F-54001 Nancy, France. Nancy Brabois Univ Hosp, Dept Nucl Med, F-54511 Vandoeuvre Les Nancy, France. US FDA, Lab Plasma Derivat, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. Nancy Brabois Univ Hosp, Dept Transfus Biol, F-54511 Vandoeuvre Les Nancy, France. RP Caron, A (reprint author), Univ Nancy 1, Fac Pharm, Dept Haematol & Physiol, Lab Hematol & Physiol, 5 Rue Albert Lebrun, F-54001 Nancy, France. NR 34 TC 6 Z9 6 U1 0 U2 1 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0958-7578 J9 TRANSFUSION MED JI Transfus. Med. PD DEC PY 2001 VL 11 IS 6 BP 433 EP 442 DI 10.1046/j.1365-3148.2001.00337.x PG 10 WC Hematology SC Hematology GA 515BD UT WOS:000173474800004 PM 11851941 ER PT J AU Ferguson, SA Cada, AM Gray, EP Paule, MG AF Ferguson, SA Cada, AM Gray, EP Paule, MG TI No alterations in the performance of two interval timing operant tasks after alpha-difluoromethylornithine (DFMO)-induced cerebellar stunting SO BEHAVIOURAL BRAIN RESEARCH LA English DT Article DE time estimation; difluoromethylornithine; temporal processing; differential reinforcement of low rate; cerebellum ID POSITRON-EMISSION TOMOGRAPHY; CONDITIONED EYELID RESPONSES; ORNITHINE DECARBOXYLASE; TIME PERCEPTION; RATS; LESIONS; CORTEX; DOPAMINE; BRAIN; HUMANS AB The cerebellum is critically involved in temporal processes in the millisecond range and may be involved in longer time estimations (i.e. in the seconds range). Estimates in the millisecond range are impaired after developmentally induced cerebellar alterations, however, little is known about the effects of similar alterations on longer timing performance. Appropriately timed DFMO treatment reliably causes cerebellar stunting in rats, however, its effects on temporal estimation performance are unknown. Here, male and female Sprague-Dawley rats were treated with subcutaneous injections of 500 mg/kg DFMO on postnatal days 5-12, causing a 10% cerebellar weight reduction at adulthood. As adults, subjects were tested under one of two paradigms - a differential reinforcement of low response rate (DRL) task requiring that subjects withhold a lever press response for 10-14 s or a temporal response differentiation (TRD) task requiring that subjects maintain a lever press response for 10-14 s. Training and steady-state performance of the DRL and TRD tasks were not significantly altered by DFMO treatment. Performance after acute challenges with two dopaminergic agonists (2.00-7.50 mg/kg methylphenidate and 0.10-1.00 mg/kg d-amphetamine) was measured after which all subjects underwent behavioral extinction. Generally, performance after methylphenidate and d-amphetamine was similar in control and DFMO-treated rats and DFMO treatment had no differential effects on performance during extinction. These results support findings from an earlier study [Ferguson SA, Paule MG, Holson RR. Neonatal dexamethasoneon day 7 in rats causes behavioral alterations reflective of hippocampal, but not cerebellar, deficits. Neurotoxicol Teratol, 2001; 23:57-69] indicating that developmental cerebellar stunting has few effects on time estimation within the range of seconds, (C) 2001 Elsevier Science B.V. All rights reserved. C1 US FDA, Natl Ctr Toxicol Res, Neurobehav Teratol Lab, Div Neurotoxicol, Jefferson, AR 72079 USA. RP Ferguson, SA (reprint author), US FDA, Natl Ctr Toxicol Res, Neurobehav Teratol Lab, Div Neurotoxicol, HFT-132,3900 NCTR Rd, Jefferson, AR 72079 USA. NR 48 TC 8 Z9 8 U1 2 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-4328 J9 BEHAV BRAIN RES JI Behav. Brain Res. PD NOV 29 PY 2001 VL 126 IS 1-2 BP 135 EP 146 DI 10.1016/S0166-4328(01)00259-5 PG 12 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 496YD UT WOS:000172425200014 PM 11704259 ER PT J AU Koller, E Malozowski, S Doraiswamy, PM AF Koller, E Malozowski, S Doraiswamy, PM TI Atypical antipsychotic drugs and hyperglycemia in adolescents SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 US FDA, Ctr Drug Evaluat & Review, Rockville, MD 20857 USA. Duke Univ, Med Ctr, Dept Psychiat, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. RP Koller, E (reprint author), US FDA, Ctr Drug Evaluat & Review, Rockville, MD 20857 USA. NR 8 TC 28 Z9 28 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 28 PY 2001 VL 286 IS 20 BP 2547 EP 2548 DI 10.1001/jama.286.20.2547 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 496FH UT WOS:000172385200027 PM 11722267 ER PT J AU Kirschbaum, NE Wood, L Lachenbruch, PA Weinstein, M Hubbard, A Barrowcliffe, T Daas, A Spieser, JM AF Kirschbaum, NE Wood, L Lachenbruch, PA Weinstein, M Hubbard, A Barrowcliffe, T Daas, A Spieser, JM TI Preparation of the Mega 2 standard for coagulation Factor VIII concentrates. SO BLOOD LA English DT Meeting Abstract C1 US FDA, Ctr Biol Evaluat & Res, CBER, Rockville, MD 20857 USA. European Pharmacopoeia, European Directorate Qual Med, EP, Strasbourg, France. Natl Inst Biol Stand & Controls, NIBSC, Potters Bar EN6 3QG, Herts, England. RI Hubbard, Anthony/E-2605-2013 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 2001 VL 98 IS 11 MA 158 BP 40A EP 40A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134100159 ER PT J AU D'Agnillo, F Alayash, AI AF D'Agnillo, F Alayash, AI TI Synergistic toxicity of acellular hemoglobin and lipopolysaccharide in cultured endothelial cells under oxidative conditions. SO BLOOD LA English DT Meeting Abstract C1 US FDA, Ctr Biol Evaluat & Res, Div Hematol, Bethesda, MD 20892 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 2001 VL 98 IS 11 MA 3824 BP 53B EP 53B PN 2 PG 1 WC Hematology SC Hematology GA 491WZ UT WOS:000172134200237 ER PT J AU Risitano, AM Holada, K Chen, GB Simak, J Vostal, JG Young, NS Maciejewski, JP AF Risitano, AM Holada, K Chen, GB Simak, J Vostal, JG Young, NS Maciejewski, JP TI CD34+cells from paroxysmal nocturnal hemoglobinuria patients are deficient in surface expression of cellular prion protein (PrPc). SO BLOOD LA English DT Meeting Abstract C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Lab Cellular Hematol, Bethesda, MD USA. 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 2001 VL 98 IS 11 MA 4131 BP 119B EP 120B PN 2 PG 2 WC Hematology SC Hematology GA 491WZ UT WOS:000172134200544 ER PT J AU Holada, K Simak, J Risitano, AM Maciejewski, J Young, NS Vostal, JG AF Holada, K Simak, J Risitano, AM Maciejewski, J Young, NS Vostal, JG TI Activated platelets of patients with paroxysmal noctural hemoglobinuria express cellular prion protein (PrPc). SO BLOOD LA English DT Meeting Abstract C1 US FDA, Ctr Biol Evaluat & Res, Lab Cellular Hematol, Bethesda, MD USA. NIH, NHLBI, Hematol Branch, Bethesda, MD USA. 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 2001 VL 98 IS 11 MA 923 BP 221A EP 221A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134100927 ER PT J AU Wolins, NE Mondoro, TH Lozier, JN Eggerman, T Jones, E Morgan, RA Aguilar-Cordova, E Vostal, JG AF Wolins, NE Mondoro, TH Lozier, JN Eggerman, T Jones, E Morgan, RA Aguilar-Cordova, E Vostal, JG TI Intravenous administration of replication-incompetent adenovirus to rhesus monkeys induces thrombocytopenia by increasing in vivo platelet clearance. SO BLOOD LA English DT Meeting Abstract C1 US FDA, CBER, Bethesda, MD USA. NIH, NHGRI, Bethesda, MD USA. NIH, NCI, Bethesda, MD USA. Harvard Univ, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 2916 BP 698A EP 698A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134102929 ER PT J AU Simak, J Holada, K Vostal, JG AF Simak, J Holada, K Vostal, JG TI Cellular prion protein (PrPc) is present on endothelial microparticles in plasma of healthy blood donors. SO BLOOD LA English DT Meeting Abstract C1 US FDA, Lab Cellulat Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. 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 2001 VL 98 IS 11 MA 2962 BP 709A EP 709A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134102975 ER PT J AU Thiriet, N Zwiller, J Ali, SF AF Thiriet, N Zwiller, J Ali, SF TI Induction of the immediate early genes egr-1 and c-fos by methamphetamine in mouse brain SO BRAIN RESEARCH LA English DT Article DE methamphetamine; immediate early gene (IEG); egr-1, c-fos dopaminergic neurotoxicity ID DISMUTASE TRANSGENIC MICE; NITRIC-OXIDE SYNTHASE; MESSENGER-RNA EXPRESSION; S-TRANSFERASE GENE; RAT-BRAIN; DOPAMINERGIC NEUROTOXICITY; SUPEROXIDE RADICALS; OXIDATIVE STRESS; NERVOUS-SYSTEM; COCAINE AB Methamphetamine (METH) is one of the most commonly abused psychostimulant, and is known to induce dopaminergic neurotoxicity by generating oxidative stress and free radicals. In the present study we investigated the effects of METH on egr-1 and c-fos immediate early gene induction in different regions of mouse brain, at different doses and different time courses. We also measured the tissue levels of monoamines in order to correlate their changes with gene expression. A single injection of METH (40 mg/kg) significantly increased egr-1 and c-fos mRNA expression within 30 min in frontal cortex, nucleus accumbens, caudate putamen, septum and CAI region of hippocampus. Time course studies showed that in most cases, both genes were expressed within 30 min and decreased after 60 min. METH produced a significant decrease in striatal dopamine level, reaching a very low level after 24 h. Striatal serotonin level significantly increased and returned to control levels after 2 h. These data show that METH induced egr-1 and c-fos mRNA expression in selective brain areas, which correlated with an alteration in monoamines. (C) 2001 Published by Elsevier Science B.V. C1 Natl Ctr Toxicol Res, Div Neurotoxicol, Neurochem Lab, Food & Drug Adm, Jefferson, AR 72079 USA. INSERM, Ctr Neurochim, U338, F-67084 Strasbourg, France. RP Ali, SF (reprint author), Natl Ctr Toxicol Res, Div Neurotoxicol, Neurochem Lab, Food & Drug Adm, 3900 NCTR Rd, Jefferson, AR 72079 USA. NR 46 TC 27 Z9 27 U1 1 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 NOV 16 PY 2001 VL 919 IS 1 BP 31 EP 40 DI 10.1016/S0006-8993(01)02991-2 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 494TQ UT WOS:000172302300004 PM 11689160 ER PT J AU Bowyer, JF Holson, RR Miller, DB O'Callaghan, JP AF Bowyer, JF Holson, RR Miller, DB O'Callaghan, JP TI Phenobarbital and dizocilpine can block methamphetamine-induced neurotoxicity in mice by mechanisms that are independent of thermoregulation SO BRAIN RESEARCH LA English DT Article DE methamphetamine; hypothermia; striatum; dopamine; neurotoxicity ID TYROSINE-HYDROXYLASE ACTIVITY; SUBSTITUTED AMPHETAMINES; DOPAMINE RELEASE; C57BL/6J MOUSE; PROTEIN; HYPERTHERMIA; ENVIRONMENT; TEMPERATURE; GLUTAMATE; STRIATUM AB Body temperature profiles observed during methamphetamine (METH) exposure are known to affect dopamine and tyrosine hydroxylase (TH) levels in the striatum of mice; hyperthermia potentiates depletion while hypothermia is protective against depletions. In the current study, the doses of METH were sufficiently great that significant dopamine and TH depletions occurred even though hypothermia occurred. Four doses, administered at 2 h intervals, of 15 mg/kg (4x15 mg/kg) D-METH significantly decreased TH and dopamine levels to 50% of control in mice becoming hypothermic during dosing in a 13 degreesC environment. Phenobarbital or dizocilpine during METH exposure blocked the depletions while diazepam did not. Phenobarbital and dizocilpine did not block depletions by altering the hypothermic profiles from that observed during METH only exposure. Here we show that phenobarbital and dizocilpine can block measures of METH neurotoxicity by non-thermoregulatory mechanisms. (C) 2001 Elsevier Science BY All rights reserved. C1 Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. New Mexico Inst Min & Technol, Dept Psychol, Socorro, NM 87801 USA. NIOSH, Ctr Dis Control & Prevent, Morgantown, WV 26505 USA. RP Bowyer, JF (reprint author), Natl Ctr Toxicol Res, Div Neurotoxicol, HFT-132, Jefferson, AR 72079 USA. RI Miller, Diane/O-2927-2013; O'Callaghan, James/O-2958-2013 NR 23 TC 15 Z9 15 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD NOV 16 PY 2001 VL 919 IS 1 BP 179 EP 183 DI 10.1016/S0006-8993(01)03051-7 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 494TQ UT WOS:000172302300022 PM 11689178 ER PT J AU Selvapandiyan, A Duncan, R Debrabant, A Bertholet, S Sreenivas, G Negi, NS Salotra, P Nakhasi, HL AF Selvapandiyan, A Duncan, R Debrabant, A Bertholet, S Sreenivas, G Negi, NS Salotra, P Nakhasi, HL TI Expression of a mutant form of Leishmania donovani centrin reduces the growth of the parasite SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID POLYMERASE CHAIN-REACTIONS; SPINDLE POLE BODY; MOLECULAR-CLONING; SACCHAROMYCES-CEREVISIAE; CDC31 GENE; PROTEIN; BINDING; IDENTIFICATION; CELLS; YEAST AB Leishmania donovani, a protozoan parasite, causes visceral disease in humans. To identify genes that control growth, we have isolated for the first time in the order Kinetoplastida a gene encoding for centrin from L. donovani. Centrin is a calcium-binding cytoskeletal protein essential for centrosome duplication or segregation. Protein sequence similarity and immunoreactivity confirmed that Leishmania centrin is a homolog of human centrin 2. Immunofluorescence analysis localized the protein in the basal body. Calcium binding analysis revealed that its C-terminal Ca2+ binding domain binds 16-fold more calcium than the N-terminal domain. Electrophoretic mobility shift of centrin treated with EGTA and abrogation of the shift in its mutants lacking a Ca2+ binding site suggest that Ca2+ binding to these regions may have a role in the protein conformation. The levels of centrin mRNA and protein were high during the exponential growth of the parasite in culture and declined to a low level in the stationary phase. Expression of N-terminal-deleted centrin in the parasite significantly reduces its growth rate, and it was found that significantly more cells are arrested in the G(2)/M stage than in control cells. These studies indicate that centrin may have a functional role in Leishmania growth. C1 US FDA, Lab Bacterial Parasit & Unconvent Agents, Div Emerging & Transfus Transmitted Dis, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. US FDA, Lab Parasit Biol & Biochem, Div Bacterial Parasit & Allergen Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. Safdarjang Hosp, New Delhi 110029, India. Indian Council Med Res, Inst Pathol, New Delhi 110029, India. RP Nakhasi, HL (reprint author), US FDA, Lab Bacterial Parasit & Unconvent Agents, Div Emerging & Transfus Transmitted Dis, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RI Duncan, Robert/I-8168-2015 OI Duncan, Robert/0000-0001-8409-2501 FU NIAID NIH HHS [Y3-AI-9319-01] NR 46 TC 43 Z9 46 U1 1 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 16 PY 2001 VL 276 IS 46 BP 43253 EP 43261 DI 10.1074/jbc.M106806200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 492LF UT WOS:000172169300081 PM 11544261 ER PT J AU Joshi, BH Leland, P Asher, A Prayson, RA Varricchio, F Puri, RK AF Joshi, BH Leland, P Asher, A Prayson, RA Varricchio, F Puri, RK TI In situ expression of interleukin-4 (IL-4) receptors in human brain tumors and cytotoxicity of a recombinant IL-4 cytotoxin in primary glioblastoma cell cultures SO CANCER RESEARCH LA English DT Article ID CIRCULARLY PERMUTED INTERLEUKIN-4; PSEUDOMONAS EXOTOXIN; CHIMERIC PROTEIN; CARCINOMA-CELLS; SARCOMA-CELLS; CANCER-CELLS; IN-VIVO; THERAPY; TOXIN; CHAIN AB We have reported that human malignant glioma cell lines express high levels of plasma membrane interleukin-4 receptors (IL-4R). We have also reported that biopsy/surgical samples or primary explant cell cultures from brain tumors express mRNA and protein for the IL-4R alpha chain, a primary IL4-binding protein. However, whether IL-4R are expressed in brain tumors ill situ has not been resolved. In addition, expression of IL-4R on the cell surface of various normal brain tissues is not known. We examined the expression of IL-4R by using a monoclonal antibody to the IL-4R alpha chain (also known as IL-4R beta) in surgical/biopsy samples of brain tumor tissues ti immunohistochemistry. Our data indicate that 15 of 18 glioblastoma multiforme (GBMs) tumors obtained from two different institutions and 12 other brain tumor samples are moderately to intensely positive for IL-4R alpha. In contrast, although IL-4R alpha mRNA was expressed, no IL-4R protein was detectable in two adult and one pediatric brain tissue specimens. In addition, a commercially available human neural tissue grid containing fixed tissues from various areas of brain showed no positive staining for the IL-4R alpha chain. IL-4R alpha expression was also demonstrated on astrocytoma grades I, II, and III. Because IL-4 cytotoxin comprised of a circularly permutated IL-4 and a mutated form of Pseudomonas exotoxin [IL4(38-37)-PE38KDEL] is cytotoxic to IL-4R-expressing cells, we tested whether primary GBM explant cell cultures are sensitive to IL-4 cytotoxin. Our data indicate that 13 of 15 GBM cell cultures were 25-74 times more sensitive to IL-4 cytotoxin compared with normal human astrocytes or the NT2 neuronal cell line. These observations indicate that human brain tumors ill situ overexpress IL-4R compared with normal brain tissues, thus confirming our previous conclusions that IL-4R in brain tumors may serve as an attractive target for anticancer therapy. C1 US FDA, Ctr Biol Evaluat & Res, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Biostat & Epidemiol, Bethesda, MD 20892 USA. Carolina Neurosurg & Spine, Charlotte, NC 28207 USA. Cleveland Clin Fdn, Dept Pathol, Cleveland, OH 44195 USA. RP Puri, RK (reprint author), US FDA, Ctr Biol Evaluat & Res, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, NIH Bldg 29B,Room 2NN10,29 Lincoln Dr,MSC 4555, Bethesda, MD 20892 USA. NR 20 TC 49 Z9 53 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 15 PY 2001 VL 61 IS 22 BP 8058 EP 8061 PG 4 WC Oncology SC Oncology GA 495AF UT WOS:000172317500002 PM 11719427 ER PT J AU White, RM AF White, RM TI Fluorouracil (5FU) pharmacokinetics in 5FU prodrug formulations with a dihydropyrimidine dehydrogenase inhibitor - In reply SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Letter ID S-1 C1 US FDA, Rockville, MD 20857 USA. RP White, RM (reprint author), US FDA, Rockville, MD 20857 USA. NR 11 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD NOV 15 PY 2001 VL 19 IS 22 BP 4268 EP 4269 PG 2 WC Oncology SC Oncology GA 493DJ UT WOS:000172206500012 ER PT J AU Arduino, JM Stuver, SO Spiegelman, D Okayama, A Tabor, E Yu, MYW Kohara, M Tsubouchi, H Mueller, NE AF Arduino, JM Stuver, SO Spiegelman, D Okayama, A Tabor, E Yu, MYW Kohara, M Tsubouchi, H Mueller, NE TI Assessment of markers of hepatitis C virus infection in a Japanese adult population SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 10th International Symposium on Viral Hepatitis and Liver Disease CY APR 09-13, 2000 CL ATLANTA, GEORGIA ID HTLV-I CARRIERS; ENZYME-IMMUNOASSAY; TRANSMISSION; AREA; SUPPRESSION; VIREMIA AB Latent-class analysis was used to evaluate the usefulness of markers of hepatitis C virus (HCV) infection in characterizing the true, underlying infection in a community-based Japanese population. Antibodies to HCV were detected in 24%, HCV RNA in 22%, and HCV core protein in 19% of stored serum samples from 372 adults. A 2-class model suggested that positive results for any 2 virus markers defined the current HCV infection class, with an estimated prevalence of 22% (95% confidence interval, 18%-26%). The sensitivity for detection of current HCV infection was highest for anti-HCV (97%) and was more moderate for HCV RNA (91%) and HCV core protein (85%). The specificity for each marker was greater than or equal to 96%. In general, the association between demographic factors and current HCV infection status was strengthened by use of latent-class analysis that combined data for markers of HCV infection, when compared with results of logistic regression analysis for each marker separately. C1 Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Miyazaki Med Coll, Miyazaki 88916, Japan. Tokyo Metropolitan Inst Med Sci, Tokyo 113, Japan. US FDA, Bethesda, MD 20014 USA. RP Stuver, SO (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, 677 Huntington Ave, Boston, MA 02115 USA. FU NCI NIH HHS [CA38450] NR 23 TC 1 Z9 1 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD NOV 15 PY 2001 VL 184 IS 10 BP 1229 EP 1235 DI 10.1086/324006 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 487NZ UT WOS:000171883300001 PM 11679910 ER PT J AU Liotta, LA Kohn, EC Petricoin, EF AF Liotta, LA Kohn, EC Petricoin, EF TI Clinical proteomics - Personalized molecular medicine SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID IMMOBILIZED PH GRADIENTS; 2-DIMENSIONAL ELECTROPHORESIS; QUANTITATIVE-ANALYSIS; PROTEIN; CANCER; COMPLEXES C1 NCI, CCR, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. RP Liotta, LA (reprint author), 10 Ctr Dr,MSC 1500, Bethesda, MD 20892 USA. NR 25 TC 162 Z9 173 U1 1 U2 26 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 14 PY 2001 VL 286 IS 18 BP 2211 EP 2214 DI 10.1001/jama.286.18.2211 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 491VA UT WOS:000172129700001 PM 11710876 ER PT J AU Schwetz, BA AF Schwetz, BA TI New combination therapy for advanced breast cancer SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT News Item C1 US FDA, Off Commissioner Food & Drugs, Rockville, MD 20857 USA. RP Schwetz, BA (reprint author), US FDA, Off Commissioner Food & Drugs, HF-1,Room 14-71,5600 Fishers Ln, Rockville, MD 20857 USA. NR 0 TC 1 Z9 2 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 7 PY 2001 VL 286 IS 17 BP 2085 EP 2085 DI 10.1001/jama.286.17.2085 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 490CD UT WOS:000172032100006 PM 11694130 ER PT J AU Schwetz, BA AF Schwetz, BA TI Grant applications for clinical trials SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT News Item C1 US FDA, Off Commissioner Food & Drugs, Rockville, MD 20857 USA. RP Schwetz, BA (reprint author), US FDA, Off Commissioner Food & Drugs, HF-1,Room 14-71,5600 Fishers Ln, Rockville, MD 20857 USA. NR 0 TC 1 Z9 2 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 7 PY 2001 VL 286 IS 17 BP 2085 EP 2085 DI 10.1001/jama.286.17.2085 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 490CD UT WOS:000172032100009 PM 11694130 ER PT J AU Schwetz, BA AF Schwetz, BA TI Pacemaker for congestive heart failure SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT News Item C1 US FDA, Off Commissioner Food & Drugs, Rockville, MD 20857 USA. RP Schwetz, BA (reprint author), US FDA, Off Commissioner Food & Drugs, HF-1,Room 14-71,5600 Fishers Ln, Rockville, MD 20857 USA. NR 0 TC 1 Z9 2 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 7 PY 2001 VL 286 IS 17 BP 2085 EP 2085 DI 10.1001/jama.286.17.2085 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 490CD UT WOS:000172032100008 PM 11694130 ER PT J AU Schwetz, RA AF Schwetz, RA TI Safety assessment of DEHP SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT News Item C1 US FDA, Off Commissioner Food & Drugs, Rockville, MD 20857 USA. RP Schwetz, RA (reprint author), US FDA, Off Commissioner Food & Drugs, HF-1,Room 14-71,5600 Fishers Ln, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 7 PY 2001 VL 286 IS 17 BP 2085 EP 2085 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 490CD UT WOS:000172032100007 ER PT J AU Khan, AS Muller, J Sears, JF AF Khan, AS Muller, J Sears, JF TI Early detection of endogenous retroviruses in chemically induced mouse cells SO VIRUS RESEARCH LA English DT Article DE murine leukemia virus; endogenous retrovirus induction; 5-iododeoxyuridine; 5-azacytidine; product-enhanced reverse transcriptase assay ID REVERSE-TRANSCRIPTASE ASSAY; MURINE LEUKEMIA-VIRUS; 5-BROMODEOXYURIDINE; 5-IODODEOXYURIDINE; ACTIVATION; LINE AB Endogenous retroviral sequences are present as an integral part of eukaryotic genomes. Although the majority of these sequences are defective, a few can produce infectious virus, either spontaneously upon long-term culture or by treatment with various chemical or other agents. Early, extensive studies of retrovirus induction were done in mouse cells; however, similar studies have not been done using state-of-the-art vir-us detection assays and with cells of other mammalian species. To investigate induction and detection of occult retroviruses in cells of different species, especially primate cells that are used in production of biologics, we have initially determined the optimum conditions for retrovirus induction in chemically treated K-BALB mouse cells using highly sensitive product-enhanced reverse transcriptase (PERT) assays as well as transmission electron microscopy (TEM). Retrovirus induction was detected at day I post-drug treatment under all test conditions but was optimum using 30 mug ml(-1) of 5-iododeoxyuridine (IdU) for 24 h. Additionally, the combination of IdU and 5-azacytidine specifically enhanced activation of type C particles. RT activity was detected by PERT assays in one microliter equivalent of test sample and retroviral particle production was seen by TEM analysis. The induction of infectious murine leukemia retroviruses was confirmed by infectivity assays and correlated with PERT activity. These results indicate that strategies for detection of occult viral agents should include optimization of induction conditions using multiple viral detection assays to evaluate virus activation. (C) 2001 Elsevier Science B.V. All rights reserved. C1 US FDA, Ctr Biol Evaluat & Review, Div Viral Prod, Lab Retrovirus Res, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Lab Vector Borne Viral Dis, Bethesda, MD 20892 USA. RP Khan, AS (reprint author), 1401 Rockville Pike,HFM-454, Rockville, MD 20852 USA. NR 21 TC 22 Z9 22 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-1702 J9 VIRUS RES JI Virus Res. PD NOV 5 PY 2001 VL 79 IS 1-2 BP 39 EP 45 DI 10.1016/S0168-1702(01)00280-5 PG 7 WC Virology SC Virology GA 477GL UT WOS:000171274900004 PM 11551644 ER PT J AU Xiao, XL Tang, YS Mackins, JY Sun, XL Jayaram, HN Hansen, DK Antony, AC AF Xiao, XL Tang, YS Mackins, JY Sun, XL Jayaram, HN Hansen, DK Antony, AC TI Isolation and characterization of a folate receptor mRNA-binding trans-factor from human placenta - Evidence favoring identity with heterogeneous nuclear ribonucleoprotein E1 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NEURAL-TUBE DEFECTS; KH-DOMAIN PROTEINS; MESSENGER-RNA; MOLECULAR-CLONING; GENE-EXPRESSION; IDENTIFICATION; REGION; INVITRO; COMPLEX; TRANSLATION AB The interaction of an 18-base cis-element in the 5'-untranslated region of human folate receptor (FR)-alpha mRNA with a cytosolic trans-factor protein is critical for the translation of FR (Sun, X.-L., and Antony, A. C. (1996) J. Biol. Chem. 271, 25539-25547). This trans-factor was isolated to apparent homogeneity as a 43- and 38-kDa doublet from human placenta using poly(U)-Sepharose, followed by preparative sodium dodecyl sulfate-polyacrylamide gel electrophoresis and electro-elution as major purification steps. Amino acid microsequencing of two cyanogen bromide-generated peptide fragments of the 43-kDa trans-factor revealed complete identity with 43-kDa heterogeneous nuclear ribonucleoprotein E1 (hnRNP E1). Purified specific rabbit anti-hnRNP E1 peptide antibodies (generated against a synthetic oligopeptide that was not represented in microsequenced peptides of the trans-factor) also recognized the purified trans-factor on Western blots. Conversely, the 18-base FR RNA cis-element also bound hnRNP E1 protein on Northwestern blots. Moreover, a 19-base RNA cis-element in the 3'-untranslated region of 15-lipoxygenase mRNA that is known to bind hnRNP E1 also interacted with placental 43-kDa trans-factor. In addition, several murine tissues containing a hnRNP E1-related protein (also known as alpha CP-1) readily interacted with the 18-base FR RNA cis-element. Finally, anti-hnRNP El antibodies specifically inhibited translation of FR in vitro in a dose-dependent manner, and the antibody effect could be reversed in a dose-dependent manner by either purified trans-factor or hnRNP E1. Collectively, the data favor identity of the FR mRNA-binding trans-factor and hnRNP E1, confirm its critical role in the translation of FR, and highlight yet another role of multifunctional hnRNP E1 in eukaryotic mRNA regulation. C1 Indiana Univ, Sch Med, Indiana Canc Res Inst, Dept Med,Div Hematol Oncol, Indianapolis, IN 46202 USA. Indiana Univ, Sch Med, Dept Biochem & Mol Biol, Indianapolis, IN 46202 USA. Richard L Roudebush Vet Affairs Med Ctr, Indianapolis, IN 46202 USA. US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. RP Antony, AC (reprint author), Indiana Univ, Sch Med, Indiana Canc Res Inst, Dept Med,Div Hematol Oncol, R4-266,1044 W Walnut St, Indianapolis, IN 46202 USA. FU NCI NIH HHS [R01CA58919]; NICHD NIH HHS [R01 HD39295] NR 40 TC 29 Z9 34 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 2 PY 2001 VL 276 IS 44 BP 41510 EP 41517 DI 10.1074/jbc.M106824200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 488FM UT WOS:000171925600149 PM 11527973 ER PT J AU Stan, AC Casares, S Brumeanu, TD Klinman, DM Bona, CA AF Stan, AC Casares, S Brumeanu, TD Klinman, DM Bona, CA TI CpG motifs of DNA vaccines induce the expression of chemokines and MHC class II molecules on myocytes SO ACTA NEUROPATHOLOGICA LA English DT Meeting Abstract C1 Hannover Med Sch, Inst Neuropathol, D-3000 Hannover, Germany. CUNY Mt Sinai Sch Med, Dept Microbiol, New York, NY 10029 USA. US FDA, Ctr Biol Evaluat & Res, Lab Retrovirol & Immunol, Div Viral Prod, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0001-6322 J9 ACTA NEUROPATHOL JI Acta Neuropathol. PD NOV PY 2001 VL 102 IS 5 BP 543 EP 543 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 483XY UT WOS:000171662200128 ER PT J AU Gavigan, CS Machado, SG Dalton, JP Bell, A AF Gavigan, CS Machado, SG Dalton, JP Bell, A TI Analysis of antimalarial synergy between bestatin and endoprotease inhibitors using statistical response-surface modelling SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID PARASITE PLASMODIUM-FALCIPARUM; HEMOGLOBIN DEGRADATION; PROTEASE INHIBITORS; CHABAUDI CHABAUDI; DRUG-RESISTANCE; MALARIA; CYSTEINE; COMBINATION; AGENTS; IDENTIFICATION AB The pathway of hemoglobin degradation by erythrocytic stages of the human malarial parasite Plasmodium falciparum involves initial cleavages of globin chains, catalyzed by several endoproteases, followed by liberation of amino acids from the resulting peptides, probably by aminopeptidases. This pathway is considered a promising chemotherapeutic target, especially in view of the antimalarial synergy observed between inhibitors of aspartyl and cysteine endoproteases. We have applied response-surface modelling to assess antimalarial interactions between endoprotease and aminopeptidase inhibitors using cultured P.falciparum parasites. The synergies observed were consistent with a combined role of endoproteases and aminopeptidases in hemoglobin catabolism in this organism. As synergies between antimicrobial agents are often inferred without proper statistical analysis, the model used may be widely applied in studies of antimicrobial drug interactions. C1 Univ Dublin Trinity Coll, Moyne Inst, Dept Microbiol, Dublin 2, Ireland. Dublin City Univ, Sch Biotechnol, Dublin 9, Ireland. US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Bell, A (reprint author), Univ Dublin Trinity Coll, Moyne Inst, Dept Microbiol, Dublin 2, Ireland. RI Dalton, John/K-4457-2014; OI Bell, Angus/0000-0002-0578-8656 NR 34 TC 17 Z9 17 U1 0 U2 3 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 NOV PY 2001 VL 45 IS 11 BP 3175 EP 3181 DI 10.1128/AAC.45.11.3175-3181.2001 PG 7 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 483ZC UT WOS:000171664900030 PM 11600374 ER PT J AU Rafii, F Hehman, G Lunsford, P AF Rafii, F Hehman, G Lunsford, P TI Purification and characterization of an enzyme from Mycobacterium sp Pyr-1, with nitroreductase activity and an N-terminal sequence similar to lipoamide dehydrogenase SO ARCHIVES OF MICROBIOLOGY LA English DT Article DE Mycobacterium; nitroreductase; ADEPT; lipoamide dehydrogenase; nitro compounds ID SALMONELLA-TYPHIMURIUM; ENTEROBACTER-CLOACAE; NUCLEOTIDE-SEQUENCE; TRYPANOSOMA-CRUZI; 1-NITROPYRENE; GENE; METABOLISM AB Mycobacterium sp. Pyr-1 produces an enzyme with nitroreductase activity that reduces 1-nitropyrene and 4-nitrobenzoic acid to the corresponding aromatic amines. This enzyme was constitutive and required NADH; and its activity was enhanced by FAD. It was inhibited by antimycin A, dicumarol, and o-iodosobenzoic acid; and it was inactivated by ammonium sulfate precipitation. After purification to homogeneity, the protein produced a single band on native and SDS-polyacrylamide gels and had a single amino-terminal sequence. The N-terminal amino acid sequence was identical to the corresponding sequences of the lipoamide dehydrogenases of M. leprae, M. tuberculosis and Corynebacterium glutamicum. The amino-terminal sequence was also similar to lipoamide dehydrogenases from M. smegmatis and several other bacteria. The amino acid sequence of an internal peptide (12 of 13 amino acids) was nearly identical to the corresponding sequences of lipoamide dehydrogenases from M. leprae and M. tuberculosis and was similar to those of C. glutamicum, Streptomyces coelicolor and S. seoulensis. The data show that a unique lipoamide dehydrogenase in Mycobacterium sp. Pyr-1, which differs from classic (Type I) bacterial nitroreductases, reduces aromatic nitro compounds to aromatic amines. C1 US FDA, Natl Ctr Toxicol Res, Dept Microbiol, Jefferson, AR 72079 USA. RP Rafii, F (reprint author), US FDA, Natl Ctr Toxicol Res, Dept Microbiol, Jefferson, AR 72079 USA. NR 23 TC 6 Z9 6 U1 0 U2 2 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 NOV PY 2001 VL 176 IS 5 BP 381 EP 385 PG 5 WC Microbiology SC Microbiology GA 495NY UT WOS:000172348300010 PM 11702081 ER PT J AU Derrick, SC Ihler, GM AF Derrick, SC Ihler, GM TI Deformin, a substance found in Bartonella bacilliformis culture supernatants, is a small, hydrophobic molecule with an affinity for albumin SO BLOOD CELLS MOLECULES AND DISEASES LA English DT Article DE Bartonella bacilliformis; deformin; albumin; erythrocyte; membrane; purification ID ERYTHROCYTE-MEMBRANES; DEFORMATION AB Culture supernatants of Bartonella bacilliformis were previously shown to contain a factor, called deforming factor or deformin, which causes deformation and invagination of red cell membranes and formation of intracellular vacuoles. This factor is here shown to be a small water-soluble molecule, approximately 1400 Da as estimated by gel-filtration chromatography. Deforming factor binds tightly to albumin, especially albumin dimers and multimers, present in the growth medium. It can be released from albumin with 50% ethanol and has been partially purified by filtration and HPLC. (C) 2001 Elsevier Science. C1 Texas A&M Univ, Syst Hlth Sci Ctr, Coll Med, Dept Med Biochem & Genet, College Stn, TX 77843 USA. US FDA, Ctr Biol Evaluat & Res, Lab Mycobacteria, Bethesda, MD 20892 USA. RP Ihler, GM (reprint author), Texas A&M Univ, Syst Hlth Sci Ctr, Coll Med, Dept Med Biochem & Genet, College Stn, TX 77843 USA. NR 6 TC 9 Z9 10 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1079-9796 J9 BLOOD CELL MOL DIS JI Blood Cells Mol. Dis. PD NOV-DEC PY 2001 VL 27 IS 6 BP 1013 EP 1019 DI 10.1006/bcmd.2001.0475 PG 7 WC Hematology SC Hematology GA 523VD UT WOS:000173977200007 PM 11831868 ER PT J AU Klecker, RW Collins, JM AF Klecker, RW Collins, JM TI Thymidine phosphorylase as a target for imaging and therapy with thymine analogs SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE thymine analogs; thymidine phosphorylase; angiogenesis; PET imaging ID CELL GROWTH-FACTOR; HUMAN CANCER XENOGRAFTS; COLORECTAL-CANCER; DNA INCORPORATION; IN-VIVO; CAPECITABINE; EXPRESSION; PHARMACOKINETICS; EFFICACY; 5-FLUOROURACIL AB Purpose: Thymidine phosphorylase (TPase; platelet-derived endothelial cell growth factor) is an attractive target for imaging and therapy because of the strong relationship between its expression in tumor biopsies and clinical outcome in many tumor types. Although the mechanism has yet to be explained, expression of TPase is highly associated with angiogenesis. Methods: Tumor cells were phenotyped for TPase activity, and incubated with thymine or its analogs (5-X-Ura). After intracellular conversion to thymidine analogs via the reverse reaction for TPase, these molecules were phosphorylated and incorporated into DNA. Results: Preferential localization was found in cells with high TPase, e.g. U937. Incorporation was enhanced in cells with high TPase by coincubation with modulators such as deoxyuridine. Conclusions: 5-X-Ura molecules can be readily labeled with positron emitters, and this finding provides support for further evaluation in vivo of their potential as probes for noninvasive external imaging of TPase, both at the time of diagnosis and during maneuvers intended to manipulate TPase. If the 5-X-Ura molecules were labeled with a therapeutic isotope, e.g. I-125 or At-211, selective cytotoxicity would be expected in cells with high TPase expression. However, direct evaluation of the safety in vivo of the therapeutic approach is required. The 5-X-Ura compounds constitute a novel approach to both imaging and therapy directed towards TPase. Further, there are distinct advantages to using the imaging mode to identify tumors likely to benefit from therapy with the same set of molecules. C1 US FDA, Ctr Drug Evaluat & Res, Lab Clin Pharmacol, Rockville, MD 20850 USA. RP Klecker, RW (reprint author), US FDA, Ctr Drug Evaluat & Res, Lab Clin Pharmacol, 4 Res Court,Room 314, Rockville, MD 20850 USA. NR 22 TC 6 Z9 7 U1 0 U2 0 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 NOV PY 2001 VL 48 IS 5 BP 407 EP 412 PG 6 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 498BF UT WOS:000172489400010 PM 11761459 ER PT J AU Kawakami, K Husain, SR Bright, RK Puri, RK AF Kawakami, K Husain, SR Bright, RK Puri, RK TI Gene transfer of interleukin 13 receptor alpha 2 chain dramatically enhances the antitumor effect of IL-13 receptor-targeted cytotoxin in human prostate cancer xenografts SO CANCER GENE THERAPY LA English DT Article DE interleukin-13 receptor; cytotoxin therapy; gene therapy; prostate cancer; sensitization; Pseudomonas exotoxin ID GROWTH-FACTOR RECEPTORS; CELL CARCINOMA-CELLS; PSEUDOMONAS EXOTOXIN; CHIMERIC PROTEIN; SIGNAL-TRANSDUCTION; (IL)-13 BINDING; SARCOMA-CELLS; CLONING; COMPONENT; IMMUNOTOXINS AB IL-13R alpha2 chain, the primary interleukin-13 (IL-13) binding protein, plays an important role in IL-13 binding and internalization. Based on these findings, in our previous study we transiently transfected four cancer cell lines that do not express IL-13R alpha2 chain and demonstrated that these cells acquired increased sensitivity to IL-13 receptor-targeted recombinant cytotoxin, IL13-PE38QQR, which is composed of IL-13 and a mutated form of a Pseudomonas exotoxin. Although some prostate cancer cell lines express functional IL-13R, they are not highly sensitive to IL-13 cytotoxin. Here we investigated whether human prostate cancer and normal prostate epithelial cell lines express IL-13R alpha2 chain and whether they can be sensitized to the cytotoxic effect of IL-13 cytotoxin after transient or stable gene transfer of IL-13R alpha2 chain. Gene transfer of IL-13R alpha2 chain improved binding activity of IL-13 and sensitivity to IL-13 cytotoxin in vitro. In vivo experiments demonstrated that gene transfer of IL-13R alpha2 chain dramatically enhanced the antitumor activity of IL-13 cytotoxin in human prostate cancer xenograft models. These results suggest that IL-13R-targeted cytotoxin therapy of prostate cancer may be dramatically enhanced by gene transfer of IL-13R alpha2 chain and this strategy, the combination of gene therapy and cytotoxin therapy, may be utilized in the treatment of localized prostate cancer. C1 US FDA, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. Chiles Res Inst, Franz Canc Res Ctr, Portland, OR 97213 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 36 TC 29 Z9 30 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0929-1903 J9 CANCER GENE THER JI Cancer Gene Ther. PD NOV PY 2001 VL 8 IS 11 BP 861 EP 868 DI 10.1038/sj.cgt.7700373 PG 8 WC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Research & Experimental Medicine GA 494GA UT WOS:000172272300004 PM 11773976 ER PT J AU Rodriguez-Saona, LE Fry, FS McLaughlin, MA Calvey, EM AF Rodriguez-Saona, LE Fry, FS McLaughlin, MA Calvey, EM TI Rapid analysis of sugars in fruit juices by FT-NIR spectroscopy SO CARBOHYDRATE RESEARCH LA English DT Article DE sugars; fruit juices; FT-NIR spectroscopy; multivariate analysis ID NEAR-INFRARED SPECTROSCOPY; TOTAL DIETARY FIBER; QUANTITATIVE-ANALYSIS; INDIVIDUAL SUGARS; DRY-EXTRACT; REFLECTANCE; SPECTRA; CHROMATOGRAPHY; MIXTURES; RAMAN AB A simple analytical procedure using FT-NIR and multivariate techniques for the rapid determination of individual sugars in fruit juices was evaluated. Different NIR detection devices and sample preparation methods were tested by using model solutions to determine their analytical performance. Aqueous solutions of sugar mixtures (glucose, fructose, and sucrose; 0-8% w/v) were used to develop a calibration model. Direct measurements were made by transflection using a reflectance accessory, by transmittance using a 0.5-mm cell, and by reflectance using a fiberglass paper filter. FT-NIR spectral data were transformed to the second derivative. Partial least-squares regression (PLSR) was used to create calibration models that were cross-validated (leave-one-out approach). The prediction ability of the models was evaluated on fruit juices and compared with HPLC and standard enzymatic techniques. The PLSR loading spectra showed characteristic absorption bands for the different sugars. Models generated from transmittance spectra gave the best performance with standard error of prediction (SEP) < 0.10% and R-2 of 99.9% that accurately and precisely predicted the sugar levels in juices, whereas lower precision was obtained with models generated from reflectance spectra. FT-NIR spectroscopy allowed for the rapid ( similar to 3 min analysis time), accurate and non-destructive analysis of sugars in juices and could be applied in quality control of beverages or to monitor for adulteration or contamination. (C) 2001 Elsevier Science Ltd. All rights reserved. C1 US FDA, Washington, DC 20204 USA. JIFSAN, Washington, DC 20204 USA. RP Calvey, EM (reprint author), US FDA, 200 C St SW, Washington, DC 20204 USA. RI Rodriguez-Saona, Luis/A-8557-2013 NR 29 TC 78 Z9 85 U1 3 U2 64 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0008-6215 J9 CARBOHYD RES JI Carbohydr. Res. PD NOV 1 PY 2001 VL 336 IS 1 BP 63 EP 74 DI 10.1016/S0008-6215(01)00244-0 PG 12 WC Biochemistry & Molecular Biology; Chemistry, Applied; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 488KT UT WOS:000171934900005 PM 11675027 ER PT J AU Kim, PN Jonasch, E Mosterman, BC Mier, JW Janssen, RAJ AF Kim, PN Jonasch, E Mosterman, BC Mier, JW Janssen, RAJ TI Radicicol suppresses transformation and restores tropomyosin-2 expression in both ras- and MEK-transformed cells without inhibiting the Raf/MEK/ERK signaling cascade SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID NIH 3T3 CELLS; ACTIVATION; KINASE; PATHWAYS; FAMILY; PHOSPHORYLATION; GROWTH; AP-1; RHOA; CDNA AB The antibiotic radicicol suppresses transformation in a variety of transformed cells. The antineoplastic effects of the drug have been attributed to the degradation of Raf and the inactivation of the Ras/Raf/ mitogen-activated protein kinase kinase (MEK)/ extracellular signal-regulated kinase (ERK) signaling cascade. Here we demonstrate that radicicol induces cell spreading, suppresses anchorage-independent cell growth, and increases the expression of the high-molecular weight tropomyosin isoform TM-2 in cells stably expressing a constitutively active form of MEK-1 as well as in ras-transformed cells. Furthermore, the reverting effects of the drug are achieved at concentrations below those required to deplete Raf from the cell or to inhibit the phosphorylation of ERK or its substrates Elk and pp90(RSK). In contrast, low concentrations of radicicol significantly inhibited activator protein (AP-1) and serum response factor (SRF)-mediated transcription. The lack of correlation between the effects of radicicol on cell phenotype and on the signaling activities of the Raf/MEK/ERK pathway indicate that Raf depletion or disruption of proximal signaling events in the mitogen:activated protein kinase pathway are not the predominant mechanisms by which the drug suppresses the transformed phenotype. Our observation that low concentrations of radicicol block transcriptional activities mediated by AP-1 and SRF suggests that interference with signaling upstream of these transcription factors may contribute to the reverting effects of the drug. C1 US FDA, Ctr Biol Evaluat & Res, OTRR, DMA,Lab Immunobiol, Bethesda, MD 20892 USA. Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. RP Janssen, RAJ (reprint author), US FDA, Ctr Biol Evaluat & Res, OTRR, DMA,Lab Immunobiol, Bldg 29B,Room 3NN22,29 Lincoln Dr,HFM 564, Bethesda, MD 20892 USA. FU NCI NIH HHS [CA74401] NR 44 TC 4 Z9 4 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1044-9523 J9 CELL GROWTH DIFFER JI Cell Growth Differ. PD NOV PY 2001 VL 12 IS 11 BP 543 EP 550 PG 8 WC Cell Biology SC Cell Biology GA 496JD UT WOS:000172391700003 PM 11714635 ER PT J AU Wulfkuhle, JD McLean, K Sgroi, D Sahin, A Petricoin, E Steeg, P AF Wulfkuhle, JD McLean, K Sgroi, D Sahin, A Petricoin, E Steeg, P TI Proteomic analysis of breast cancer progression. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 NIH, NCI, Bethesda, MD 20892 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 2001 VL 7 IS 11 SU S MA 153 BP 3684S EP 3684S PG 1 WC Oncology SC Oncology GA 491RE UT WOS:000172121800152 ER PT J AU Bichsel, VE Calvert, VS Charboneau, L Trock, BJ Sgroi, DC Liotta, LA Petricoin, EF AF Bichsel, VE Calvert, VS Charboneau, L Trock, BJ Sgroi, DC Liotta, LA Petricoin, EF TI Profiling of signal transduction pathways in laser capture micro-dissected breast cancer epithelium. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 NIH, Natl Canc Inst, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. Johns Hopkins Med Inst, Baltimore, MD 21205 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 2001 VL 7 IS 11 SU S MA 202 BP 3693S EP 3693S PG 1 WC Oncology SC Oncology GA 491RE UT WOS:000172121800199 ER PT J AU Eiseman, JL Hamburger, DR Egorin, MJ Collins, JM Klecker, RW AF Eiseman, JL Hamburger, DR Egorin, MJ Collins, JM Klecker, RW TI Deoxyuridine distribution in human colorectal tumor xenografts: impact of fluorouracil, rationale for a PET probe of thymidylate synthase, and treatment strategies. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. US FDA, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 2001 VL 7 IS 11 SU S MA 237 BP 3700S EP 3700S PG 1 WC Oncology SC Oncology GA 491RE UT WOS:000172121800234 ER PT J AU Malozowski, S Purucker, M AF Malozowski, S Purucker, M TI Growth as a biological marker of inhaled corticosteroid activity SO CURRENT THERAPEUTIC RESEARCH-CLINICAL AND EXPERIMENTAL LA English DT Article; Proceedings Paper CT Workshop on Adverse Drug Events in Pediatrics CY APR 09-10, 2001 CL ROCKVILLE, MARYLAND DE growth; biological marker; inhaled corticosteroids; adverse drug events; pediatrics ID FLUTICASONE PROPIONATE; ADRENAL SUPPRESSION; HEIGHT VELOCITY; CHILDREN; ASTHMA; BECLOMETHASONE; BUDESONIDE; STANDARDS; STEROIDS AB Background: Inhaled corticosteroids (ICSs) are among the standard therapies used to control symptoms of asthma. Current evidence shows that these agents are available systemically and have the capability of negatively affecting growth when administered to children at labeled doses. However, the impact of growth cannot be predicted by most conventional measures of hypothalamicpituitary-adrenal axis function. Target organs such as bone are likely involved in this effect. Objective: The purpose of this paper was to review the evidence for systemic adverse effects of ICSs in children, particularly with regard to growth. Results: Results of well-designed 1-year studies comparing ICSs with non-ICS standard care have demonstrated that ICSs administered at recommended doses are capable of causing a mean decrease in growth velocity of similar to1 cm/year (range, 0.5 to 1.8 cm/year) in prepubertal asthmatic children. Conclusions: Children treated with these products should be monitored regularly with stadiometric measurements of growth velocity and titrated individually to the lowest dose that effectively controls their symptoms. It is important for practitioners to recognize the potential systemic impact of these highly effective products in pediatric patients. C1 US FDA, Ctr Drug Evaluat & Res, Div Pulm & Allergy Drug Prod, Rockville, MD 20857 USA. RP Purucker, M (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Pulm & Allergy Drug Prod, 5600 Fishers Lane, Rockville, MD 20857 USA. NR 28 TC 3 Z9 3 U1 0 U2 1 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0011-393X J9 CURR THER RES CLIN E JI Curr. Ther. Res.-Clin. Exp. PD NOV PY 2001 VL 62 IS 11 BP 796 EP 802 DI 10.1016/S0011-393X(01)80086-2 PG 7 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 501VN UT WOS:000172706900006 ER PT J AU Ardekani, AM Herman, EH Sistare, FD Liotta, LA Petricoin, EF AF Ardekani, AM Herman, EH Sistare, FD Liotta, LA Petricoin, EF TI Molecular profiling of cancer and drug-induced toxicity using new proteomic technologies SO CURRENT THERAPEUTIC RESEARCH-CLINICAL AND EXPERIMENTAL LA English DT Article; Proceedings Paper CT Workshop on Adverse Drug Events in Pediatrics CY APR 09-10, 2001 CL ROCKVILLE, MD DE proteomics; toxicity; cancer; SELDI-TOF; microdissection ID LASER CAPTURE MICRODISSECTION; GENE-EXPRESSION PATTERNS; POLYACRYLAMIDE-GEL ELECTROPHORESIS; TRANSITIONAL-CELL CARCINOMAS; PROSTATE-SPECIFIC ANTIGEN; ACID-BINDING PROTEIN; LOW-FEMTOMOLE LEVEL; MASS-SPECTROMETRY; MESSENGER-RNA; EPITHELIAL-CELLS AB Background: Completion of the mapping of the human genome has brought the field of research in biological sciences into a new dawn of discovery. Within this postgenomics era in science, proteomic technologies are positioned to play a major role in discovery of new biomarkers for early detection of diseases and drug-induced toxicity, new molecular targets for therapy, and new end points for therapeutic efficacy and toxicity. Objective: Development of patient-specific targeted therapeutics with reduced toxicity and increased efficacy using cells or sera from patients with disease. Methods: New proteomic technologies such as laser capture microscopy are providing rapid, easy access to the purified, diseased human cells from tissue specimens that previously has not been possible. Due to limited availability of patient material, highly sensitive mass spectrometric techniques such as surface-enhanced laser desorption ionization time-of-flight (SELDI-TOF) are used to complement 2-dimensional gel electrophoresis for multiparametric protein characterization. Results: The use of high-throughput SELDI-TOF protein pattern generation techniques should prove valuable for new molecular classification of human tumors, disease stages, and drug-induced toxicity. The use of newly developed high-density protein arrays, antibody arrays, and small molecular arrays in conjunction with laser capture microscopy could have a substantial impact on proteomic profiling of human tumors and human tissues affected in response to drug treatments. SELDI-TOF and laser capture microscopy technologies in conjunction with new bioinformatic software will be powerful tools in the near future for identifying protein fingerprints in cells or sera of patients to predict the outcomes of therapies for any diagnosed disease. Conclusions: The application of all new proteomic technologies should enhance our efforts in designing rational drug therapy strategies that are based on an individual patient's molecular profiling of cellular proteins in the disease state and can identify proteomic fingerprints associated with drug-induced toxicity directly in sera samples. This should provide us with the detailed knowledge necessary to develop novel therapeutics for the treatment of diseases and/or detection of diseases and toxicity at an early stage. C1 NCI, Div Therapeut Prod, US FDA, Clin Proteom Program,Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. NCI, Pathol Lab, Canc Res Ctr, Bethesda, MD 20892 USA. US FDA, Div Appl Pharmacol Res, Ctr Drug Evaluat & Res, Laurel, MD USA. RP Petricoin, EF (reprint author), NCI, Div Therapeut Prod, US FDA, Clin Proteom Program,Ctr Biol Evaluat & Res, 8800 Rockville Pike,Bldg 29A,Room 2B02, Bethesda, MD 20892 USA. EM petricoin@cber.fda.gov NR 73 TC 7 Z9 7 U1 1 U2 2 PU ELSEVIER PI BRIDGEWATER PA 685 ROUTE 202-206, BRIDGEWATER, NJ 08807 USA SN 0011-393X J9 CURR THER RES CLIN E JI Curr. Ther. Res.-Clin. Exp. PD NOV PY 2001 VL 62 IS 11 BP 803 EP 819 DI 10.1016/S0011-393X(01)80087-4 PG 17 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 501VN UT WOS:000172706900007 ER PT J AU Paule, MG AF Paule, MG TI Using identical behavioral tasks in children, monkeys, and rats to study the effects of drugs SO CURRENT THERAPEUTIC RESEARCH-CLINICAL AND EXPERIMENTAL LA English DT Article; Proceedings Paper CT Workshop on Adverse Drug Events in Pediatrics CY APR 09-10, 2001 CL ROCKVILLE, MARYLAND DE clinical trials; comparative psychology; automated cognitive assessment; children; animal intelligence; postmarket surveillance ID OPERANT TEST BATTERY; CHRONIC COCAINE EXPOSURE; RHESUS-MONKEY; INFANT OUTCOMES; PERFORMANCE; PREGNANCY; CHLORPROMAZINE; ACQUISITION; ATROPINE AB Background: The need to use animal models to predict the effects of drugs on the nervous system has led to the development of automated systems for the assessment of specific behaviors-identical in both humans and laboratory animals-that represent aspects of specific cognitive processes. At the National Center for Toxicological Research (NCTR), a battery of operant behavioral tasks (the NCTR Operant Test Battery, or OTB) has been developed to model specific behaviors associated with motivation, color and position discrimination, time estimation, short-term memory and attention, and learning. Objectives: The goals of this paper were to describe interspecies similarities in specific behaviors designed to model a variety of cognitive functions and to argue for the use of such behaviors in risk assessments (preclinical studies), monitoring treatment efficacy, and postmarket surveillance. Methods: The literature search was primarily limited to automated systems that are useful in rodents, monkeys, and children. Results: Maintenance of task continuity across species allows for the determination of interspecies similarities in brain function and aids in the extrapolation of data from animals to humans. Comparative data indicate, for example, that the OTB performance of well-trained monkeys is generally indistinguishable from that of children. The demonstration that human OTB performance correlates significantly with intelligence (IQ scores) highlights the relevance of these measures. Results of comparative drug studies indicate that monkeys are good predictors of drug effects in humans. Recent studies have shown that rodent performance in some of these complex tasks is also similar to that of monkeys and children, and that for some drugs, responses are similar to those for monkeys and, presumably, humans. Conclusions: Tools such as the NCTR OTB may provide the opportunity for extensive interspecies comparisons of cognitive processes and provide the means for studying the effects of psychoactive agents by use of relevant end points in a variety of animal models. Such approaches may provide laboratory animal data that could predict adverse drug events in humans, as defined by disturbances in aspects of complex brain function. Likewise, use of similar instruments in the clinic, even in the pediatric setting, could provide longitudinal data-in the same patients-on treatment efficacy and toxicity during clinical trials and postmarket surveillance. C1 US FDA, Natl Ctr Toxicol Res, Behav Toxicol Lab, Div Neurotoxicol, Jefferson, AR 72079 USA. RP Paule, MG (reprint author), US FDA, Natl Ctr Toxicol Res, Behav Toxicol Lab, Div Neurotoxicol, HFT-132,3900 NCTR Rd, Jefferson, AR 72079 USA. NR 25 TC 6 Z9 7 U1 3 U2 3 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0011-393X J9 CURR THER RES CLIN E JI Curr. Ther. Res.-Clin. Exp. PD NOV PY 2001 VL 62 IS 11 BP 820 EP 833 DI 10.1016/S0011-393X(01)80088-6 PG 14 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 501VN UT WOS:000172706900008 ER PT J AU Li, CL Guo, HM Xu, XL Weinberg, W Deng, CX AF Li, CL Guo, HM Xu, XL Weinberg, W Deng, CX TI Fibroblast growth factor receptor 2 (Fgfr2) plays an important role in eyelid and skin formation and patterning SO DEVELOPMENTAL DYNAMICS LA English DT Article DE mouse; Fgfr2; cell proliferation; morphogenetic transition; organogenesis ID TARGETED DISRUPTION; LIMB DEVELOPMENT; HAIR FOLLICLE; INNER-EAR; MICE; MOUSE; MORPHOGENESIS; PROLIFERATION; EXPRESSION; MUTATION AB Initiating as protruding ridges above and below the optic vesicle, the eyelids of mice grow across the eye and temporarily fuse in fetal life. Mutations of a number of genes disrupt this developmental process and result in a birth defect, "open-eyelids at birth." Here we show that a critical event for eyelid induction occurs at embryonic day 11.5 (E11.5) when the single cell-layered ectoderm in the presumptive eyelid territory increases proliferation and undergoes morphologic transition to form cube-shaped epithelial cells. Using embryos lacking the Fgfr2 Ig domain III (Fgfr2(Delta III/Delta III)) generated by tetraploid rescue and chimeric embryo formation approaches, we demonstrate that this event is controlled by Fgfr2 signals as the Fgfr2(Delta III/Delta III) mutation blocks these changes and results in embryos without eyelids. Fgfr2 and its ligands are differentially expressed in the ectoderm and underlying mesenchyme and function in a reciprocal interacting loop that specifies eyelid development. We also demonstrate that similar defects account for failure of skin formation at early stages. Interestingly, Fgfr2-independent skin formation occurs at E14.5 mutant embryos, resulting in much thinner, yet well-differentiated epidermis. Notably, mutant skin remains thin with decreased hair density after transplantation to wild-type recipients. These data demonstrate an essential role of Fgfr2 in eyelid and skin formation and patterning. Published 2001 Wiley-Liss, Inc. C1 NIDDKD, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, DMA, Bethesda, MD USA. RP Deng, CX (reprint author), NIDDKD, Genet Dev & Dis Branch, NIH, 10-9N105,10 Ctr Dr, Bethesda, MD 20892 USA. RI deng, chuxia/N-6713-2016 NR 56 TC 44 Z9 47 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 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD NOV PY 2001 VL 222 IS 3 BP 471 EP 483 DI 10.1002/dvdy.1205 PG 13 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 489XT UT WOS:000172018600014 PM 11747081 ER PT J AU Flurer, CL AF Flurer, CL TI Analysis of antibiotics by capillary electrophoresis SO ELECTROPHORESIS LA English DT Review DE capillary electrophoresis; antibiotics; review ID MICELLAR ELECTROKINETIC CHROMATOGRAPHY; LASER-INDUCED FLUORESCENCE; SOLID-PHASE EXTRACTION; ZONE-ELECTROPHORESIS; AMPEROMETRIC DETECTION; PLASMA SAMPLES; VOLTAMMETRIC DETECTION; MACROLIDE ANTIBIOTICS; SEPARATION; QUINOLONES AB This article reviews recent developments in the characterization of antibiotics. Many capillary electrophoretic techniques have been utilized in their analyses, addressing various aspects of quantifying, profiling and monitoring. Sensitive electrochemical and laser-induced fluorescence detection systems have been utilized, demonstrating trace level determinations in clinical settings and in environmental samples. 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 45237 USA. RP Flurer, CL (reprint author), US FDA, Forens Chem Ctr, 6751 Steger Dr, Cincinnati, OH 45237 USA. NR 51 TC 26 Z9 27 U1 3 U2 14 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 NOV PY 2001 VL 22 IS 19 BP 4249 EP 4261 DI 10.1002/1522-2683(200111)22:19<4249::AID-ELPS4249>3.0.CO;2-8 PG 13 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 502TD UT WOS:000172758100015 PM 11824641 ER PT J AU Rosenthal, SR Merchlinsky, M Kleppinger, C Goldenthal, KL AF Rosenthal, SR Merchlinsky, M Kleppinger, C Goldenthal, KL TI Developing new smallpox vaccines SO EMERGING INFECTIOUS DISEASES LA English DT Article ID VIRUS; TERRORISM; STRAIN AB New stockpiles of smallpox vaccine are required as a contingency for protecting civilian and military personnel against deliberate dissemination of smallpox virus by terrorists or unfriendly governments. The smallpox vaccine in the current stockpile consists of a live animal poxvirus (Vaccinia virus [VACV]) that was grown on the skin of calves. Because of potential issues with controlling this earlier manufacturing process, which included scraping VACV lesions from calfskin, new vaccines are being developed and manufactured by using viral propagation on well-characterized cell substrates. We describe, from a regulatory perspective, the various strains of VACV, the adverse events associated with calf lymph-propagated smallpox vaccine, the issues regarding selection and use of cell substrates for vaccine production, and the issues involved in demonstrating evidence of safety and efficacy. C1 US FDA, CBER, Rockville, MD 20852 USA. RP Rosenthal, SR (reprint author), US FDA, CBER, HFM-475,1401 Rockville Pike, Rockville, MD 20852 USA. NR 58 TC 89 Z9 93 U1 0 U2 2 PU CENTER DISEASE CONTROL PI ATLANTA PA ATLANTA, GA 30333 USA SN 1080-6040 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD NOV-DEC PY 2001 VL 7 IS 6 BP 920 EP 926 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 495JR UT WOS:000172337900002 PM 11747717 ER PT J AU Martin, M Weld, LH Tsai, TF Mootrey, GT Chen, RT Niu, M Cetron, MS AF Martin, M Weld, LH Tsai, TF Mootrey, GT Chen, RT Niu, M Cetron, MS CA GeoSentinel Yellow Fever Working G TI Advanced age a risk factor for illness temporally associated with yellow fever vaccination SO EMERGING INFECTIOUS DISEASES LA English DT Article ID UNITED-STATES; VIRUS; POLIOMYELITIS; ENCEPHALITIS; DISEASE; DECADE AB In 1998, the Centers for Disease Control and Prevention was notified of severe illnesses and one death, temporally associated with yellow fever (YF) vaccination, in two elderly U.S. residents. Because the cases were unusual and adverse events following YF vaccination had not been studied, we estimated age-related reporting rates for systemic illness following YF vaccination. We found that the rate of reported adverse events among elderly vaccinees was higher than among vaccinees 25 to 44 years of age. We also found two additional deaths among elderly YF vaccinees. These data signal a potential problem but are not sufficient to reliably estimate incidence rates or to understand potential underlying mechanisms; therefore, enhanced surveillance is needed. YF remains an important cause of severe illness and death, and travel to disease-endemic regions is increasing. For elderly travelers, the risk for severe illness and death due to YF infection should be balanced against the risk for systemic illness due to YF vaccine. C1 Ctr Dis Control, Natl Ctr Infect Dis, Div Global Migrat & Quarantine, Atlanta, GA 30333 USA. Ctr Prevent, Atlanta, GA 30333 USA. Emory Univ, Sch Med, Atlanta, GA USA. US FDA, Ctr Biol Evaluat, Rockville, MD USA. RP Cetron, MS (reprint author), Ctr Dis Control, Natl Ctr Infect Dis, Div Global Migrat & Quarantine, Mailstop E03,1600 Clifton Rd, Atlanta, GA 30333 USA. NR 43 TC 78 Z9 80 U1 0 U2 1 PU CENTER DISEASE CONTROL PI ATLANTA PA ATLANTA, GA 30333 USA SN 1080-6040 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD NOV-DEC PY 2001 VL 7 IS 6 BP 945 EP 951 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 495JR UT WOS:000172337900005 PM 11747720 ER PT J AU Cummings, K Barrett, E Mohle-Boetani, JC Brooks, JT Farrar, J Hunt, T Fiore, A Komatsu, K Werner, SB Slutsker, L AF Cummings, K Barrett, E Mohle-Boetani, JC Brooks, JT Farrar, J Hunt, T Fiore, A Komatsu, K Werner, SB Slutsker, L TI A multistate outbreak of Salmonella enterica serotype baildon associated with domestic raw tomatoes SO EMERGING INFECTIOUS DISEASES LA English DT Article ID MONTEVIDEO; GROWTH AB Salmonella enterica serotype Baildon, a rare serotype, was recovered from 86 persons in eight states; 87% of illnesses began during a 3-week period ending January 9, 1999. Raw restaurant-prepared tomatoes were implicated in multiple case-control studies. Contamination likely occurred on the farm or during packing; more effective disinfection and prevention strategies are needed. C1 Calif Dept Hlth Serv, Berkeley, CA 94704 USA. Virginia Dept Hlth, Richmond, VA USA. Ctr Dis Control & Prevent, Atlanta, GA USA. Calif Dept Hlth Serv, Sacramento, CA USA. US FDA, Pittsburgh, PA USA. Arizona Dept Hlth Serv, Phoenix, AZ 85007 USA. RP Cummings, K (reprint author), Div Communicable Dis Control, Dis Invest Sect, 2151 Berkeley Way,Room 708, Berkeley, CA 94704 USA. NR 15 TC 99 Z9 100 U1 0 U2 6 PU CENTER DISEASE CONTROL PI ATLANTA PA ATLANTA, GA 30333 USA SN 1080-6040 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD NOV-DEC PY 2001 VL 7 IS 6 BP 1046 EP 1048 PG 3 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 495JR UT WOS:000172337900025 PM 11747740 ER PT J AU Do Luu, HM Hutter, JC AF Do Luu, HM Hutter, JC TI Bioavailability of octamethylcyclotetrasiloxane (D-4) after exposure to silicones by inhalation and implantation SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE bioavailability; breast implant; D-4; implantation; inhalation; octamethylcyclotetrasiloxane; PBPK; physiologically based pharmacokinetic model; risk assessment; silicone ID MOLECULAR-WEIGHT SILICONES; BREAST IMPLANTS; COEFFICIENTS; DIFFUSION; MIGRATION; HUMANS; SINGLE; VAPOR; WOMEN; LIVER AB We developed a physiologically based pharmacokinetic (PBPK) model to predict the target organ doses of octamethylcyclotetrasitoxane (D-4) after intravenous (IV), inhalation, or implantation exposures. The model used C-14-D-4 IV disposition data in rats to estimate tissue distribution coefficients, metabolism, and excretion parameters. We validated the model by comparing the predicted blood and tissues concentrations of D-4 after inhalation to experimental results in both rats and humans. We then used the model to simulate D-4 kinetics after single and/or repeated D-4 exposures in rats and humans. The model predicted bioaccumulation of D-4 in fatty tissues (e.g., breast), especially in women. Because of its high lipid solubility (Log P-oct/water = 5. 1), D-4 persisted in fat with a half life of 11.1 days after inhalation and 18.2 days after breast implant exposure. Metabolism and excretion remained constant with repeated exposures, larger doses, and/or different routes of exposure. The accumulation of D4 in fatty tissues should play an important role in the risk assessment of D4 especially in women exposed daily to multiple personal care products and silicone breast implants. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20852 USA. RP Do Luu, HM (reprint author), US FDA, Ctr Devices & Radiol Hlth, 12725 Twinbrook Pkwy,HFZ-150, Rockville, MD 20852 USA. NR 33 TC 0 Z9 1 U1 0 U2 5 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 EI 1552-9924 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD NOV PY 2001 VL 109 IS 11 BP 1095 EP 1101 PG 7 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 501EB UT WOS:000172668900018 ER PT J AU Thiriet, N Jouvert, P Gobaille, S Solov'eva, O Gough, B Aunis, D Ali, S Zwiller, J AF Thiriet, N Jouvert, P Gobaille, S Solov'eva, O Gough, B Aunis, D Ali, S Zwiller, J TI C-type natriuretic peptide (CNP) regulates cocaine-induced dopamine increase and immediate early gene expression in rat brain SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE c-fos; egr-1; extracellular dopamine; guanylyl cyclase; junB ID DEPENDENT PROTEIN-KINASE; 2 SIZE FORMS; DIFFERENTIAL PHOSPHORYLATION; GUANYLYL CYCLASE; MESSENGER-RNAS; NITRIC-OXIDE; STRIATUM; RECEPTOR; INVOLVEMENT; LOCALIZATION AB The neuropeptide C-type natriuretic peptide (CNP) is the primary biologically active natriuretic peptide in brain. Using in situ hybridization, the present report demonstrates that CNP regulates egr-1, c-fos and junB immediate early gene expression in rat brain. In the frontal cortex, CNP induced immediate early gene expression whereas it inhibited dose-dependently the cocaine-induced early gene expression in the dopaminergic projection fields nucleus accumbens and caudate-putamen. CNP may produce its effect directly on dopaminergic neurons because we found that its receptor, guanylyl cyclase GC-B, was expressed in the mesencephalon where dopaminergic neurons originate, as well as in their projection fields. The inhibition by CNP of the early gene expression elicited by cocaine in the caudate-putamen is correlated with a CNP-evoked decrease in cocaine-induced rise in extracellular dopamine, measured by in vivo microdialysis experiments. The significance of the inhibition of cocaine-induced dopamine release and early gene induction by the endogenous peptide CNP is demonstrated by data indicating that CNP reduced the cocaine-induced spontaneous locomotor activation. By inhibiting dopaminergic neuronal activity, CNP represents a potential negative regulator of related behavioural effects of cocaine. C1 Ctr Neurochim, INSERM, U338, F-67084 Strasbourg, France. IFR 037, F-67084 Strasbourg, France. Russian Acad Sci, Inst Bioorgan Chem, Moscow 117871, Russia. US FDA, Neurochem Lab, Div Neurotoxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Zwiller, J (reprint author), Ctr Neurochim, INSERM, U338, 5 Rue Blaise Pascal, F-67084 Strasbourg, France. NR 39 TC 16 Z9 16 U1 1 U2 3 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD NOV PY 2001 VL 14 IS 10 BP 1702 EP 1708 DI 10.1046/j.0953-816x.2001.01791.x PG 7 WC Neurosciences SC Neurosciences & Neurology GA 501NW UT WOS:000172692400012 PM 11860464 ER PT J AU Laughren, TP AF Laughren, TP TI The scientific and ethical basis for placebo-controlled trials in depression and schizophrenia: an FDA perspective SO EUROPEAN PSYCHIATRY LA English DT Article DE depression; ethics; placebo; psychopharmacology; schizophrenia ID ACTIVE-CONTROL TRIALS; SUICIDE; ISSUES AB There is a tension between the need for scientifically valid trials of new psychotropic drugs and concern about conducting placebo-controlled trials, the trials psychopharmacologists consider the gold standard trial, when this requires that some patients be denied existing effective therapy. This paper will review the scientific principles supporting the need for placebo-controlled trials in depression and schizophrenia, and will provide preliminary data on failure rates of placebo-controlled trials for these disorders, as illustrations of the application of these principles. Next, the ethical issues pertinent to the conduct of placebo-controlled trials for these two serious psychiatric disorders will be reviewed. Preliminary data on suicides in placebo-controlled depression and schizophrenia trials will be presented to argue for the ethical acceptability of the conduct of placebo-controlled trials in these two conditions. (C) 2001 Editions scientifiques et medicales Elsevier SA. C1 US FDA, Psychiat Drug Prod Grp, Div Neuropharmacol Drug Prod HFD 120, Rockville, MD 20857 USA. RP Laughren, TP (reprint author), US FDA, Psychiat Drug Prod Grp, Div Neuropharmacol Drug Prod HFD 120, 5600 Fishers Lane, Rockville, MD 20857 USA. NR 11 TC 55 Z9 58 U1 0 U2 2 PU EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS CEDEX 15 PA 23 RUE LINOIS, 75724 PARIS CEDEX 15, FRANCE SN 0924-9338 J9 EUR PSYCHIAT JI Eur. Psychiat. PD NOV PY 2001 VL 16 IS 7 BP 418 EP 423 DI 10.1016/S0924-9338(01)00600-9 PG 6 WC Psychiatry SC Psychiatry GA 501LX UT WOS:000172687100007 PM 11728855 ER PT J AU Virador, VM Muller, J Wu, XF Abdel-Malek, ZA Yu, ZX Ferrans, VJ Kobayashi, N Wakamatsu, K Ito, S Hammer, JA Hearing, VJ AF Virador, VM Muller, J Wu, XF Abdel-Malek, ZA Yu, ZX Ferrans, VJ Kobayashi, N Wakamatsu, K Ito, S Hammer, JA Hearing, VJ TI Influence of alpha-melanocyte-stimulating hormone and of ultraviolet radiation on the transfer of melanosomes to keratinocytes SO FASEB JOURNAL LA English DT Article DE skin color; tanning; melanosome transfer ID MOUSE MELANOCYTES; EPIDERMAL-KERATINOCYTES; IN-VITRO; PROTEIN; CELLS; EXOCYTOSIS; SYNTAXIN-4; TRANSPORT; SECRETION; SNAP-23 AB The epidermal melanin unit in human skin is composed of melanocytes and keratinocytes. Melanocytes, located in the basal layer of the epidermis, manufacture melanin-loaded organelles called melanosomes. Through their dendritic processes, melanocytes distribute melanosomes to neighboring keratinocytes, where their presence confers to the skin its characteristic color and photoprotective properties. In this study, we used murine melanocytes and keratinocytes alone and in coculture to characterize the processes involved in melanosome transfer. Ultraviolet (UV) radiation induced an accumulation of melanosomes in melanocytes, whereas treatment with alpha -melanocyte-stimulating hormone (MSH) induced exocytosis of melanosomes accompanied by ruffling of the melanocyte membrane. We found that keratinocytes phagocytose melanosomes and latex beads equally well and that this phagocytic process was increased by exposure of keratinocytes to UV radiation or to MSH. Coculture of melanocytes and keratinocytes resulted in an increase in MSH released to the medium. Gene array analysis of MSH-treated melanocytes showed up-regulation of many genes associated with exocytosis. In our studies, we never observed cytophagocytosis of melanosome-filled processes. This result, together with the other findings, suggests that a combination of signals that increase melanosome production and release by melanocytes and that stimulate phagocytosis by keratinocytes are the most relevant mechanisms involved in skin tanning. C1 NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Bethesda, MD 20892 USA. NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. Univ Cincinnati, Dept Dermatol, Cincinnati, OH 45267 USA. NHLBI, Pathol Sect, Bethesda, MD 20892 USA. Nara Med Univ, Dept Dermatol, Kashihara, Nara 634, Japan. Fujita Hlth Univ, Sch Hlth Sci, Dept Chem, Toyoake, Aichi 4701192, Japan. RP Hearing, VJ (reprint author), NCI, Cell Biol Lab, NIH, Bldg 37,Room 1B25, Bethesda, MD 20892 USA. EM hearingv@nih.gov NR 53 TC 6 Z9 6 U1 1 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 NOV PY 2001 VL 15 IS 13 BP 105 EP + DI 10.1096/fj.01-0518fje PG 27 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 496WR UT WOS:000172420500031 ER PT J AU Gaines, DW McClure, D Braunberg, RC Luu, A Jackson, N Barton, C Friedman, L AF Gaines, DW McClure, D Braunberg, RC Luu, A Jackson, N Barton, C Friedman, L TI Ornithine decarboxylase and thymidine kinase activities and polyamine levels from selected organs of adult miniature swine receiving three concentrations of dietary menhaden oil SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article DE ODC; TK; polyamines; menhaden oils; cholesterol ID FATTY-ACID COMPOSITION; BREAST-CANCER; CELL-PROLIFERATION; PROSTATE-CANCER; COLON-CANCER; COLORECTAL-CANCER; PANCREATIC-CANCER; RISK-FACTORS; MEN; TUMOR AB Mature, female swine were randomly assigned to one of seven dietary groups. Swine in groups 1-3 were fed a cholesterol-rich diet for 55 days while the remaining groups remained on a basal swine diet. At the end of the cholesterol(Chol)-preloading period the swine in groups 1-7 were placed on menhaden oil (MO) and/or corn oil (CO) as follows: groups 1 and 4, 15% CO (control); groups 2 and 5, 0.75% MO + 14.25% CO; groups 3 and 7, 15% MO; and group 6, 7.5% MO + 7.5% CO. Animals were killed at the end of the approximately 6-month feeding period and portions of liver, pancreas and colon mucosa were analyzed for both ornithine decarboxylase (ODC) and thymidine kinase (TK) activity while polyamine levels were measured in the liver and pancreas. Statistical analyses were carried out by one-way and two-way ANOVA and by trend analysis. In the pancreas, the highest MO group (group 7) had significantly higher ODC levels when compared with the CO control (group 4) and the next to highest MO group (group 6) (one-way ANOVA)-all non-cholesterol preloaded groups. Using a two-way ANOVA (Chol-by-MO), liver ODC was significantly lower in the CO control when compared with the lowest and highest MO groups (groups 5 and 7, respectively), again in the non-cholesterol-preloaded animals. In the colon, the swine in the Chol-low MO group (group 2) had significantly lower TK activity than the Chol/CO control group (group 1) and Chol/Hi MO group (group 3) (one-way ANOVA) and also had significantly lower activity than all groups except the CO control (group 4) (two-way ANOVA). Liver acetylputrescine in the lowest and highest MO groups (groups 5 and 7, respectively) was significantly higher than in the CO group (group 4). Liver spermidine in the Chol-Hi MO group (group 3) was significantly higher than the Chol-Lo PAO group (group 2), while the highest MO group (group 7) had a statistically higher level than the other non-cholesterol groups (groups 4-6) (one-way ANOVA). Liver spermine was significantly higher in the Chol-Hi MO group (group 3) when compared to the CO control (group 1) and the Chol-Lo MO group (group 2) (one-way ANOVA). Pancreatic putrescine in the CO control (group 4) was significantly higher than all other groups (two-way ANOVA) while spermine from the 2 Chol-MO groups (groups 2 and 3) was higher than the Chol-CO control (group 1) (one-way ANOVA). Using trend analysis, liver TK, putrescine and spermidine increased in the non-cholesterol preloaded groups with increasing dietary MO, similar to the increase seen in ODC. Thus, of the three organs studied, only liver responded to menhaden oil with changes in both ODC itself or some of its metabolic engendered products and thymidine kinase; at least for one of the parameters, ODC, change associated with dietary MO was dependent on whether the swine were preloaded with cholesterol. Published by Elsevier Science Ltd. C1 US FDA, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. RP Gaines, DW (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 8301 Muirkirk Rd, Laurel, MD 20708 USA. NR 55 TC 0 Z9 0 U1 0 U2 3 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 NOV PY 2001 VL 39 IS 11 BP 1109 EP 1117 DI 10.1016/S0278-6915(01)00066-7 PG 9 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA 475RL UT WOS:000171178000008 PM 11527570 ER PT J AU Baladron, V Ruiz-Hidalgo, MJ Gubina, E Bonvini, E Laborda, J AF Baladron, V Ruiz-Hidalgo, MJ Gubina, E Bonvini, E Laborda, J TI Specific regions of the extracellular domain of dlk, an EGF-like homeotic protein involved in differentiation, participate in intramolecular interactions SO FRONTIERS IN BIOSCIENCE LA English DT Article DE dlk; adipogenesis; EGF-like domain; Yeast Two Hybrid System; intra molecular interactions; dimerization ID EPIDERMAL GROWTH-FACTOR; IN-SITU HYBRIDIZATION; ADIPOCYTE DIFFERENTIATION; TRANSCRIPTIONAL CONTROL; CELL-DIFFERENTIATION; REPEAT MOTIFS; PREF-1; EXPRESSION; GENE; RECEPTOR AB The level of expression of dlk, an EGF-like protein possessing six EGF-like repeats in its extracellular region, is critical for 3T3-L1 fibroblasts to differentiate into adipocytes in response to IGF1. The mechanism of action of dlk is not well understood, but its localization on the cell membrane suggests that dlk may function as a receptor, as a ligand or as a regulatory protein modulating the binding, the signaling, or the expression of other molecules involved in cell differentiation and growth. In this work, we demonstrate, by using the Yeast Two-Hybrid system, that dlk interacts with itself through specific regions of its extracellular domain. The strongest interactions were observed between specific EGF-like repeats and between a non EFG-like region where unknown proteases act to generate soluble forms of dlk. These observations suggest that the interaction between two membrane dlk molecules belonging to the same or to different cells, or the interaction between soluble and membrane dlk variants, may be important to regulate dlk function. C1 US FDA, Immunobiol Lab, Div Monoclonal Antibodies, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Laborda, J (reprint author), Univ Castilla La Mancha, Fac Med, Campus Albacete,Edificio Benjamin Palencia S-N, Albacete 02071, Spain. RI Laborda, Jorge/L-5726-2014; Ruiz-Hidalgo, Maria/L-1956-2014; Baladron, Victoriano/L-1758-2014 OI Laborda, Jorge/0000-0002-9210-838X; Baladron, Victoriano/0000-0003-4574-8760 NR 37 TC 13 Z9 13 U1 0 U2 3 PU FRONTIERS IN BIOSCIENCE INC PI MANHASSET PA C/O NORTH SHORE UNIV HOSPITAL, BIOMEDICAL RESEARCH CENTER, 350 COMMUNITY DR, MANHASSET, NY 11030 USA SN 1093-9946 J9 FRONT BIOSCI JI Front. Biosci. PD NOV PY 2001 VL 6 BP A25 EP A32 DI 10.2741/baladron PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 488FE UT WOS:000171924900001 PM 11689349 ER PT J AU Wedemeyer, H Gagneten, S Davis, A Bartenschlager, R Feinstone, S Rehermann, B AF Wedemeyer, H Gagneten, S Davis, A Bartenschlager, R Feinstone, S Rehermann, B TI Oral immunization with HCV-NS3-transformed Salmonella: Induction of HCV-specific CTL in a transgenic mouse model SO GASTROENTEROLOGY LA English DT Article ID HEPATITIS-C VIRUS; CELLULAR IMMUNE-RESPONSES; CYTOTOXIC T-LYMPHOCYTES; NONSTRUCTURAL PROTEINS; DENDRITIC CELLS; DNA VACCINATION; INFECTION; TYPHIMURIUM; VACCINES; IDENTIFICATION AB Background & Aims: The ability to induce cytotoxic T cells is considered an important feature of a candidate hepatitis C virus (HCV) vaccine. We used an oral immunization strategy with attenuated HCV-NS3-transformed Salmonella typhimurium to deliver DNA directly to the gut-associated lymphoid tissue. Methods: HLA-A2.1 transgenic mice were immunized once with transformed attenuated Salmonella. HCV-specific CD8(+) T cells were analyzed in vitro as well as in vivo by challenge of mice with recombinant HCV-NS3 vaccinia virus. Results. Salmonella (10(8) colony-forming units; 20 mug plasmid DNA) induced cytotoxic and IFN-gamma -producing CD8+ T cells specific for the immunodominant epitope NS3-1073 in 26 of 30 mice (86%) that persisted for at least 10 months. A second epitope (NS3-1169) was also recognized by cytotoxic and IFN-gamma -producing T cells, whereas a third. one (NS3-1406) stimulated IFN-gamma production without cytotoxicity. The minimal amount of: plasmid DNA required to induce CTLs was 2 ng. Upon challenge with recombinant HCV-NS3- expressing vaccinia virus, vaccinia titers were significantly lower in mice immunized with Salmonella-NS3 than in mice immunized with control Salmonella, demonstrating the in vivo function of CTLs. Conclusions:, Oral immunization with attenuated Salmonella typhimurium as a carrier for HCV DNA induces long-lasting T-cell responses. C1 NIDDK, Liver Dis Sect, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Bethesda, MD 20014 USA. Univ Mainz, Inst Virol, D-6500 Mainz, Germany. RP Rehermann, B (reprint author), NIDDK, Liver Dis Sect, NIH, Bldg 10,Room 9B16,10 Ctr Dr MSC 1800, Bethesda, MD 20892 USA. RI Bartenschlager, Ralf/L-2582-2015 NR 45 TC 52 Z9 56 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD NOV PY 2001 VL 121 IS 5 BP 1158 EP 1166 DI 10.1053/gast.2001.29311 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 487RY UT WOS:000171890100020 PM 11677208 ER PT J AU Claycamp, HG Sussman, NB Okladnikova, ND Azizova, TV Pesternikova, VS Sumina, MV Teplyakov, II AF Claycamp, HG Sussman, NB Okladnikova, ND Azizova, TV Pesternikova, VS Sumina, MV Teplyakov, II TI Classification of chronic radiation sickness cases using neural networks and classification trees SO HEALTH PHYSICS LA English DT Article DE health effects; radiation effects; exposure, occupational; modeling, dose assessment ID LEUKOCYTE COUNT; DIAGNOSIS; WORKERS AB Chronic radiation sickness is a deterministic radiation health effect observed among the Mayak Production Association workers in Russia. In this study, unsupervised neural networks were used to cluster hematological measurements in a subset (n = 88) of the Mayak Production Association population while excluding from the analysis the radiation dose and the historical clinical diagnosis. Clusters of observations that had lower average leukocyte and thrombocyte counts were labeled "affected" and those having higher average blood cell counts were labeled "unaffected." The class (cluster) membership for each individual was used subsequently as a dependent variable in a classification tree model in order to identify significant features of the underlying classification model. After re-classification of cases using this method, the results showed a better data separation between the blood cell counts for affected vs. unaffected groups compared to those based on historical classification, and a greater difference between group means for differential blood counts was observed than for the historical diagnosis. The reclassification of diagnostic groups changed the group mean radiation doses. The geometric means (and 95% CL) of cumulative radiation dose equivalent from external exposures, based on the historical diagnosis, are 0.31 (0.0035, 3.4) vs. 1.7 (0.0007, 18) Sv. After clustering and classification tree analyses, the group geometric means were 0.78 (0.0014, 8.6) vs. 1.5 (0.0007, 17) and 0.82 (0.0013, 9.0) vs. 1.4 (0.0008, 16) Sv, using (respectively) whole blood cell counts or differential counts as the independent variables. The approach presented here is useful as a diagnostic aid for both retrospective analyses and in the event of future radiation accidents. C1 Univ Pittsburgh, Dept Environm & Occupat Hlth, Pittsburgh, PA 15238 USA. Biophys Inst, Branch 1, Chelyabinsk 456780, Russia. MAYAK Prod Assoc, Ozyorsk, Chelyabinsk Reg, Russia. RP Claycamp, HG (reprint author), US FDA, Ctr Vet Med, 7500 Standish Pl,HFV-100, Rockville, MD 20855 USA. EM HClaycam@cvm.fda.gov NR 33 TC 2 Z9 4 U1 0 U2 1 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 NOV PY 2001 VL 81 IS 5 BP 522 EP 529 DI 10.1097/00004032-200111000-00006 PG 8 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 484GZ UT WOS:000171683000006 PM 11669205 ER PT J AU Gannot, I Waynant, RW AF Gannot, I Waynant, RW TI Introduction to the issue on lasers in medicine and biology SO IEEE JOURNAL OF SELECTED TOPICS IN QUANTUM ELECTRONICS LA English DT Editorial Material C1 Tel Aviv Univ, Fac Engn, Dept Biomed Engn, IL-69978 Tel Aviv, Israel. US FDA, Ctr Devices & Radiol Hlth, Electroopt Branch, Rockville, MD 20857 USA. RP Gannot, I (reprint author), Tel Aviv Univ, Fac Engn, Dept Biomed Engn, IL-69978 Tel Aviv, Israel. NR 0 TC 1 Z9 1 U1 0 U2 1 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 USA SN 1077-260X J9 IEEE J SEL TOP QUANT JI IEEE J. Sel. Top. Quantum Electron. PD NOV-DEC PY 2001 VL 7 IS 6 BP 873 EP 873 AR PII S1077-260X(01)11359-6 DI 10.1109/JSTQE.2001.983286 PG 1 WC Engineering, Electrical & Electronic; Optics; Physics, Applied SC Engineering; Optics; Physics GA 523BM UT WOS:000173931500001 ER PT J AU Pfefer, TJ Schomacker, KT Ediger, MN Nishioka, NS AF Pfefer, TJ Schomacker, KT Ediger, MN Nishioka, NS TI Light propagation in tissue during fluorescence spectroscopy with single-fiber probes SO IEEE JOURNAL OF SELECTED TOPICS IN QUANTUM ELECTRONICS LA English DT Article DE computational modeling; fiberoptic; fluorescence spectroscopy; Monte Carlo ID LASER-INDUCED FLUORESCENCE; HUMAN COLON TISSUE; IN-VIVO; TURBID MEDIA; SPECTRAL-CHARACTERIZATION; PHOTODYNAMIC THERAPY; BARRETTS-ESOPHAGUS; OPTICAL-PROPERTIES; AUTOFLUORESCENCE; MODEL AB Fluorescence spectroscopy systems designed for clinical use commonly employ fiberoptic probes to deliver excitation light to a tissue site and collect remitted fluorescence. Although a wide variety of probes have been implemented, there is little known about the influence of probe design on light propagation and the origin of detected signals. In this study, we examined the effect of optical fiber diameter, probe-tissue spacing and numerical aperture on light propagation during fluorescence spectroscopy with a single-fiber probe. A Monte Carlo model was used to simulate light transport in tissue. Two distinct sets of excitation-emission wavelength pairs were studied (337/450 nm and 400/630 nm). Simulation results indicated that increasing fiber diameter or fiber-tissue spacing increased the mean excitation-emission photon pair pathlength and produced a transition from high selectivity for superficial fluorophores to a more homogeneous probing with depth. Increasing numerical aperture caused an increase in signal intensity, but axial emission profiles and pathlengths were not significantly affected for numerical aperture values less than 0.8. Tissue optics mechanisms and implications for probe design are discussed. This study indicates that single-fiber probe parameters can strongly affect fluorescence detection and should be considered in the design of optical diagnostic devices. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed, Boston, MA 02114 USA. RP Pfefer, TJ (reprint author), US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RI Pfefer, Josh/I-9055-2012 NR 40 TC 39 Z9 39 U1 0 U2 4 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 USA SN 1077-260X J9 IEEE J SEL TOP QUANT JI IEEE J. Sel. Top. Quantum Electron. PD NOV-DEC PY 2001 VL 7 IS 6 BP 1004 EP 1012 AR PII S1077-260X(01)11251-7 DI 10.1109/2944.983306 PG 9 WC Engineering, Electrical & Electronic; Optics; Physics, Applied SC Engineering; Optics; Physics GA 523BM UT WOS:000173931500021 ER PT J AU Long, MC Kisielewski, RW Richardson, DC Schroeder, LW AF Long, MC Kisielewski, RW Richardson, DC Schroeder, LW TI An experimental technique for determining biaxial fatigue lifetimes in biomedical elastomers SO INTERNATIONAL JOURNAL OF FATIGUE LA English DT Article DE multiaxial fatigue; rubber; polymers; crack detection; fatigue test methods ID LATEX AB A novel test apparatus was developed to determine fatigue lifetimes of elastomeric materials. Thin elastomeric sheets (membranes) are biaxially fatigued while contained within a temperature controlled liquid environment. Membranes are displaced in a smooth sinusoidal motion by pumping the surrounding fluid through the equipment's inner cells. An electrical signal (AC) passes through the membrane during fatigue and is used to monitor changes in the elastomer's physical characteristics. In addition, the test cell is designed to allow optical observation of the membrane throughout the fatiguing process. Thus the design results in a test rig apparatus that permits failure determination by both material property changes and obvious fracture. Cyclic fatigue frequencies range from 0.2 to 1.2 Hz. (C) 2001 Elsevier Science Ltd. All rights reserved. C1 US FDA, Div Mech & Mat Sci, Off Sci & Technol, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. RP Long, MC (reprint author), US FDA, Div Mech & Mat Sci, Off Sci & Technol, Ctr Devices & Radiol Hlth, 9200 Corp Blvd,HFZ-150, Rockville, MD 20850 USA. NR 8 TC 3 Z9 3 U1 0 U2 5 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0142-1123 J9 INT J FATIGUE JI Int. J. Fatigue PD NOV PY 2001 VL 23 IS 10 BP 911 EP 916 DI 10.1016/S0142-1123(01)00046-9 PG 6 WC Engineering, Mechanical; Materials Science, Multidisciplinary SC Engineering; Materials Science GA 484JW UT WOS:000171687300009 ER PT J AU Essayan, DM AF Essayan, DM TI Cyclic nucleotide phosphodiesterases SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Review DE cyclic AMP; cyclic GMP; cyclic nucleotide phosphodiesterase; immunosuppression; inflammation ID CAMP-SPECIFIC PHOSPHODIESTERASE; DEPENDENT PROTEIN-KINASE; BLOOD MONONUCLEAR-CELLS; NECROSIS-FACTOR-ALPHA; AMP-SPECIFIC PHOSPHODIESTERASES; HUMAN MAST-CELLS; PDE INHIBITORS; ENDOTHELIAL-CELLS; TNF-ALPHA; IN-VITRO AB Cyclic nucleotide second messengers (cAMP and cGMP) play a central role in signal transduction and regulation of physiologic responses. Their intracellular levels are controlled by the complex superfamily of cyclic nucleotide phosphodiesterase (PDE) enzymes. Continuing advances in our understanding of the molecular pharmacology of these enzymes has led to the development of selective inhibitors as therapeutic agents for disease states ranging from cancer and heart failure to depression and sexual dysfunction. Several PDE types have been identified as therapeutic targets for immune/inflammatory diseases. This article briefly reviews the available in vitro, preclinical, and clinical data supporting the potential for selective PDE inhibitors as immunomodulatory agents. C1 US FDA, DCTDA, OTRR, CBER, Rockville, MD 20852 USA. US FDA, Div Cellular & Gene Therapies, OTRR, CBER, Rockville, MD 20852 USA. RP Essayan, DM (reprint author), US FDA, DCTDA, OTRR, CBER, 1401 Rockville Pike,HFM-579, Rockville, MD 20852 USA. NR 142 TC 241 Z9 250 U1 1 U2 7 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 NOV PY 2001 VL 108 IS 5 BP 671 EP 680 PG 10 WC Allergy; Immunology SC Allergy; Immunology GA 498RG UT WOS:000172523800002 PM 11692087 ER PT J AU Trucksess, MW AF Trucksess, MW TI Determination of Cry9C protein in corn-based foods by enzyme-linked immunosorbent assay: Interlaboratory study SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article AB The performance of a commercially available enzyme-linked immunosorbent assay kit (EnviroLogix) was assessed for the determination of Cry9C protein, which is produced by the genetically modified corn StarLink, in 8 types of corn-based foods (starch, refined oil, soft tortillas, tortilla chips, corn flakes, corn puffs, corn muffins, and corn bread) in an interlaboratory study involving 7 laboratories in the United States. The assay kit is a double antibody sandwich and is based on the specific interaction between antibody and antigen. The Cry9C protein analyte is sandwiched between 2 antibodies, one to capture the analyte and the other is conjugated to the enzyme, horseradish peroxidase. The enzyme uses tetramethylbenzidine/peroxide for color development. A strong acid stopping reagent is then used to change the color from blue to a stable yellow. The intensity of the color is proportional to the concentration of the Cry9C protein. In this study blind duplicates of control samples (blank material prepared from non-StarLink corn), spiked samples (blank material with the addition of Cry9C protein), and samples containing incurred analyte (products prepared with StarLink corn) were analyzed. Cry9C protein from 2 different sources was used to spike the food products. Cry9C protein produced and purified from a bacterial host was used to prepare spiked test samples at 2.72 and 6.8 ng/g. Cry9C protein from StarLink corn flour was used to prepare spiked samples at 1.97 ng/g. Average recoveries for samples spiked with corn flour Cry9C protein at 1.97 ng/g ranged from 73 to 122 %, within-laboratory relative standard deviations (RSDr) ranged from 6 to 22%, and between-laboratories relative standard deviations (RSDR) ranged from 16 to 56%. Average recoveries for samples spiked with bacterial Cry9C protein at 2.72 and 6.8 ng/g ranged from 27 to 96% and from 32 to 113%, respectively; RSDr values ranged from 10 to 35% and from 7 to 38%, respectively; and the RSDR ranged from 28 to 84% and 15 to 75%, respec- tively. The incurred test samples were found to contain Cry9C protein at levels ranging from 0.8 to 3187 ng/g depending on the product, RSDr values ranged from 5 to 16% and RSDR values ranged from 11 to 71 %. Results of the statistical analysis indicate that this method is applicable to the determination of Cry9C protein in the 8 types of collaboratively studied corn-based products containing Cry9C protein (from StarLink) at levels of greater than or equal to2 ng/g. C1 US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. RP Trucksess, MW (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. NR 4 TC 11 Z9 11 U1 1 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 NOV-DEC PY 2001 VL 84 IS 6 BP 1891 EP 1901 PG 11 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 498BL UT WOS:000172489900031 ER PT J AU Callahan, JD Wu, SJL Dion-Schultz, A Mangold, BE Peruski, LF Watts, DM Porter, KR Murphy, GR Suharyono, W King, CC Hayes, CG Temenak, JJ AF Callahan, JD Wu, SJL Dion-Schultz, A Mangold, BE Peruski, LF Watts, DM Porter, KR Murphy, GR Suharyono, W King, CC Hayes, CG Temenak, JJ TI Development and evaluation of serotype- and group-specific fluorogenic reverse transcriptase PCR (TaqMan) assays for dengue virus SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID HEPATITIS-C VIRUS; RNA CONTROLS; ARMORED RNA; DIAGNOSIS; INFECTION; SEQUENCE; SYSTEM; DNA AB Five fluorogenic probe hydrolysis (TaqMan) reverse transcriptase PCR (RT-PCR) assays were developed for serotypes 1 to 4 and group-specific detection of dengue virus. Serotype- and group-specific oligonucleotide primers and fluorogenic probes were designed against conserved regions of the dengue virus genome. The RT-PCR assay is a rapid single-tube method consisting of a 30-min RT step linked to a 45-cycle PCR at 95 and 60 degreesC that generates a fluorogenic signal in positive samples. Assays were initially evaluated against cell culture-derived dengue stock viruses and then with 67 dengue viremic human sera received from Peru, Indonesia, and Taiwan. The TaqMan assays were compared to virus isolation using C6/36 cells followed by an immunofluorescence assay using serotype-specific monoclonal antibodies. Viral titers in sera were determined by plaque assay in Vero cells. The serotype-specific TaqMan RT-PCR assay detected 62 of 67 confirmed dengue virus-positive samples, for a sensitivity of 92.5%, while the group-specific assay detected 66 of 67 confirmed dengue virus-positive samples, for a sensitivity of 98.5%. The TaqMan RT-PCR assays have a specificity of 100% based on the serotype concordance of all assays compared to cell culture isolation and negative results obtained when 21 normal human sera and plasma samples were tested. Our results demonstrate that the dengue virus TaqMan RT-PCR assays may be utilized as rapid, sensitive, and specific screening and serotyping tools for epidemiological studies of dengue virus infections. C1 USN, Med Res Ctr, Viral & Rickettsial Dis Dept, Silver Spring, MD 20910 USA. USN, Med Res Ctr, Biol Def Res Directorate, Silver Spring, MD 20910 USA. Walter Reed Army Inst Res, Viral Dis Dept, Silver Spring, MD 20910 USA. Univ Maryland, Dept Pathol, Baltimore, MD 21201 USA. USN, Med Res Ctr Detachment, Amer Embassy, APO, AA 34031 USA. USN, Med Res Unit 2, APO, AP 96520 USA. Minist Hlth, Natl Inst Hlth Res & Dev, Jakarta, Indonesia. Natl Taiwan Univ, Inst Epidemiol, Taipei 10764, Taiwan. RP Temenak, JJ (reprint author), US FDA, Ctr Biol Evaluat & Res, Off Vaccines Res & Review, Div Vaccines & Related Prod Applicat, 1401 Rockville Pike,HFM 481, Rockville, MD 20852 USA. OI King, Chwan-Chuen/0000-0002-6078-2601 NR 22 TC 109 Z9 121 U1 0 U2 10 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD NOV PY 2001 VL 39 IS 11 BP 4119 EP 4124 DI 10.1128/JCM.39.11.4119-4124.2001 PG 6 WC Microbiology SC Microbiology GA 488KK UT WOS:000171934200048 PM 11682539 ER PT J AU Skinner, GE Gendel, SM Solomon, HM AF Skinner, GE Gendel, SM Solomon, HM TI "Differentiation between types and strains of Clostridium botulinum by riboprinting," a comment on: J. Food Prot. 63(10): 1347-1352 (2000) - Response SO JOURNAL OF FOOD PROTECTION LA English DT Letter C1 US FDA, Food Proc Hazard Anal Branch, Div Food Proc & Packaging, Summit Argo, IL 60501 USA. Natl Ctr Food Safety & Technol, Summit Argo, IL 60501 USA. RP Skinner, GE (reprint author), US FDA, Food Proc Hazard Anal Branch, Div Food Proc & Packaging, 6502 S Archer Rd, Summit Argo, IL 60501 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU INT ASSOC FOOD PROTECTION PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD NOV PY 2001 VL 64 IS 11 BP 1654 EP 1654 PG 1 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 493XB UT WOS:000172247800002 ER PT J AU Ciolino, LA Mesmer, MZ Satzger, RD Machal, AC McCauley, HA Mohrhaus, AS AF Ciolino, LA Mesmer, MZ Satzger, RD Machal, AC McCauley, HA Mohrhaus, AS TI The chemical interconversion of GHB and GBL: Forensic issues and implications SO JOURNAL OF FORENSIC SCIENCES LA English DT Article; Proceedings Paper CT 52nd Annual Meeting of the American-Academy-of-Forensic-Sciences CY FEB, 2000 CL RENO, NEVADA SP Amer Acad Forens Sci DE forensic science; GHB; GBL; gamma-hydroxybutyric acid; gamma-butyrolactone; gamma-hydroxybutyrate; inter-conversion; stability; high performance liquid chromatography ID GAMMA-HYDROXYBUTYRATE GHB; FACILITATED SEXUAL ASSAULTS; MASS-SPECTROMETRY; DRUGS; RECOMMENDATIONS; CHROMATOGRAPHY; TRENDS; URINE AB In this work, the interconversion of GHB and GBL in a variety of aqueous media was studied, The effects of solution pH and time were determined by spiking GHB or GBL into pure water and buffered aqueous solutions, and determining the GHB and GBL contents at various time intervals. The degree of GBL hydrolysis to GHB was determined for several commercial aqueous-based GBL products, and further studied as a function of time. The effects of temperature and time were also determined for five commercial beverages spiked with GHB or GBL. GHB and GBL contents were determined using high performance liquid chromatography (HPLC). GHB and/or GBL confirmations were made using gas chromatography-mass spectrometry (GC-MS) and/or infrared Spectroscopy (IR). Solution pH, time, and storage temperature were determined to be important factors affecting the rate and extent of GBL hydrolysis to GHB. Under strongly alkaline conditions (pH 12.0), GBL was completely converted to GHB within minutes. In pure water, GBL reacted to form an equilibrium mixture comprising ca. 2:1 GBL:GHB over a period of months. This same equilibrium mixture was established from either GHB or GBL in strongly acidic solution (pH 2.0) within days. A substantial portion of GBL (ca. 1/3) was hydrolyzed to GHB in aqueous-based GBL products, and in spiked commercial beverages, after ambient storage for a period ranging from several weeks to several months. Heat increased and refrigeration decreased the rate of GBL hydrolysis relative to ambient conditions. These studies show that hydrolysis of GBL to GHB does occur in aqueous-based solutions, with samples and time frames that are relevant to forensic testing. Implications for forensic testing and recommendations are discussed. C1 US FDA, Forens Chem Ctr, Cincinnati, OH 45237 USA. RP Ciolino, LA (reprint author), US FDA, Forens Chem Ctr, 6751 Steger Dr, Cincinnati, OH 45237 USA. NR 30 TC 58 Z9 59 U1 0 U2 17 PU AMER SOC TESTING MATERIALS PI W CONSHOHOCKEN PA 100 BARR HARBOR DR, W CONSHOHOCKEN, PA 19428-2959 USA SN 0022-1198 J9 J FORENSIC SCI JI J. Forensic Sci. PD NOV PY 2001 VL 46 IS 6 BP 1315 EP 1323 PG 9 WC Medicine, Legal SC Legal Medicine GA 487RA UT WOS:000171888000007 PM 11714141 ER PT J AU Meager, A Das, RG Zoon, K Mire-Sluis, A AF Meager, A Das, RG Zoon, K Mire-Sluis, A TI Establishment of new and replacement World Health Organization International Biological Standards for human interferon alpha and omega SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE interferon alpha; collaborative study; standardisation; assays; potency AB The complexity of the human interferon-alpha (IFN-alpha) family, with its multiple molecular forms and various biological activities, raises a number of scientific issues with regard to the biological standardisation of natural and recombinant IFN-U products. To address such issues and to achieve an appropriate biological standardisation of human interferon-alpha (IFN-alpha) preparations, the National Institute for Biological Standards and Control (NIBSC) of the United Kingdom (UK), in association with the Centre for Biologics Evaluation and Research (CBER) of the United States of America (USA), organised an international collaborative study, which was subsequently divided into two parts, Ninety-three participating laboratories from 29 countries worldwide participated in the first part of the study. They performed titrations on up to 15 different IFN-alpha preparations and one IFN-omega (omega) preparation in a variety of assays, including those based upon antiviral, antiproliferative, and other biological activities of IFN, and contributed raw data from these assays to NIBSC for analysis and calculation of relative activities. Analysis of data from this part of the study showed a greater than expected assay-dependent disparity between the relative activities of different IFN-alpha preparations. This disparity was found when only antiviral assays were considered and even when there were only small molecular dissimilarities between two otherwise closely related IFN-alpha preparations. The lack of assay independence and relative activity equivalence has indicated that a single biological potency standard for all IFN-alpha subtypes and mixtures would be inappropriate. Hence, individual, homologous standards, each with a separate unitage, were required for biological standardisation and potency determinations of individual IFN-alpha subtypes. At this stage, potency assignments to the IFN-alpha and -omega preparations included in the study were made as far as possible on the basis of comparison of antiviral activity with that of the Ist International Reference Preparation (IRP) for IFN, human leukocyte. 69/19. However, it was recognised that other standards had been used in assays to estimate potencies of widely available. current, therapeutic IFN-alpha products. Thus, to ensure the continuity of unitages already in use for IFN-alpha products, the second part of the study, which involved 12 members of the International Federation of Pharmaceutical Manufacturers Association (IFPMA), was carried out using for calibration of antiviral assays those IFN-alpha preparations that most closely matched manufacturers' products or that had been previously used for assay calibration by a manufacturer for a particular product. On the basis of data analysis from the second part of the study, potency assignments to the IFN-alpha preparations, as made in the first part of the study. were either left unchanged or changed to potency assignments that ensured as far as possible continuity with existing unitages. From among the IFN preparations evaluated. the following were recommended as the most suitable to continue or replace existing WHO international standards (IS) and have subsequently been formally established as WHO IS at the 51st meeting (October 1999) of the WHO ECBS: 83/514. 1st WHO IS for human IFN-alpha1 8000 international units (IU): 95/650. 2nd WHO IS for human IFN-alpha 2a, 63,000 IU, 95/566. 2nd WHO IS for human IFN-alpha 2b, 70,000 IU; 95/580, 1st WHO IS for human IFN-alpha 2c, 40,000 IU; 95/572, 1st WHO IS for human IFN-alpha 1/8, 27,000 IU: 94/786, 1st WHO IS for human IFN-alpha Con1, 100,000 IU; 94/784, 2nd WHO IS for human IFN-alpha (leukocyte), 11,000 IU; 95/574, 1st WHO IS for human IFN-alpha (leukocyte n3), 60,000 IU; 95/568, 2nd WHO IS for human IFN-alpha (lymphoblastoid n1), 38,000 IU; 94/754. 1st WHO IS for human IFN-omega, 20,000 IU. These WHO IS are available upon request to NIBSC. (C) 2001 Elsevier Science B.V. All rights reserved. C1 Natl Inst Biol Stand & Controls, Div Immunobiol, Potters Bar EN6 3QG, Herts, England. Natl Inst Biol Stand & Controls, Dept Informat, Potters Bar EN6 3QG, Herts, England. US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Meager, A (reprint author), Natl Inst Biol Stand & Controls, Div Immunobiol, Blanche Lane S Mimms, Potters Bar EN6 3QG, Herts, England. NR 7 TC 26 Z9 27 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-1759 J9 J IMMUNOL METHODS JI J. Immunol. Methods PD NOV 1 PY 2001 VL 257 IS 1-2 BP 17 EP 33 DI 10.1016/S0022-1759(01)00460-4 PG 17 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA 489JT UT WOS:000171988800002 PM 11687235 ER PT J AU Okuda, K Xin, KQ Haruki, A Kawamoto, S Kojima, Y Hirahara, F Okada, H Klinman, D Hamajima, K AF Okuda, K Xin, KQ Haruki, A Kawamoto, S Kojima, Y Hirahara, F Okada, H Klinman, D Hamajima, K TI Transplacental genetic immunization after intravenous delivery of plasmid DNA to pregnant mice SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MEDIATED IMMUNE-RESPONSES; T-CELLS; NEONATAL TOLERANCE; INDUCTION; INJECTION; INFLUENZA; VACCINE; HIV-1; LYMPHOCYTES; LIPOSOMES AB A number of factors influence the development of tolerance, including the nature, concentration, and mode of Ag presentation to the immune system, as well as the age of the host. The studies were conducted to determine whether immunizing pregnant mice with liposome-encapsulated DNA vaccines had an effect on the immune status of their offspring. Two different plasmids (encoding Ags from HIV-1 and influenza virus) were administered Lv. to pregnant mice. We examined the uptake of plasmid DNA by the fetuses until the 21st postcoital day, but little such transfer occurred in early pregnancy. At 9.5 days postconception with cationic liposomes, injected plasmid was present in the tissues of the fetus, consistent with transplacental transfer. When the offspring of vaccinated dams were immunized with DNA vaccine, they mounted stronger Ag-specific immune responses than controls, and were protected against challenge by homologous influenza virus after vaccination. Moreover, such immune responses were strong in the offspring of mothers injected with DNA plasmid 9.5 days after coitus. These results suggest that DNA-vaccinated mothers confer the Ag-specific immunity to their progeny. C1 Yokohama City Univ, Sch Med, Dept Bacteriol, Kanazawa Ku, Yokohama, Kanagawa 2360004, Japan. Yokohama City Univ, Sch Med, Dept Gynecol, Yokohama, Kanagawa 2360004, Japan. Nagoya City Univ, Dept Mol Biol, Sch Med, Nagoya, Aichi 467, Japan. Ctr Biol Evaluat & Res Food & Drug Adm, Bethesda, MD 20892 USA. RP Okuda, K (reprint author), Yokohama City Univ, Sch Med, Dept Bacteriol, Kanazawa Ku, 3-9 Fukuura, Yokohama, Kanagawa 2360004, Japan. NR 35 TC 12 Z9 14 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 2001 VL 167 IS 9 BP 5478 EP 5484 PG 7 WC Immunology SC Immunology GA 487DN UT WOS:000171858500089 PM 11673568 ER PT J AU Scott, WL Collier, P AF Scott, WL Collier, P TI The vessel dilator for central venous catheter placement: Forerunner for success or vascular misadventure? SO JOURNAL OF INTENSIVE CARE MEDICINE LA English DT Review ID POSSIBLE MECHANISMS; VEIN; CANNULATION; INSERTION; COMPLICATIONS; SUGGESTIONS; PREVENTION; ARTERY; INJURY AB During placement of a central venous catheter (CVC), the vessel dilator and/or combination dilator/sheath-introducer are recognized as potential causative agents in numerous traumatic complications that may he erroneously ascribed to the catheter, placement needle, or guidewire. A review of the literature and device-user survey are offered in support of the need for additional training in safe dilator use, as well as the need to address device labeling and device design. C1 US FDA, Off Hlth Program, Div Device User Programs & Syst Anal, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. US FDA, Off Ind Program, Div Device User Programs & Syst Anal, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. Sewickley Valley Hosp, Dept Surg, Sewickley, PA USA. Sewickley Valley Hosp, Noninvas Vasc Lab, Sewickley, PA USA. RP Scott, WL (reprint author), US FDA, Off Hlth Program HFZ230, Div Device User Programs & Syst Anal, 1350 Piccard Dr, Rockville, MD 20850 USA. NR 31 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0885-0666 J9 J INTENSIVE CARE MED JI J. Intensive Care Med. PD NOV-DEC PY 2001 VL 16 IS 6 BP 263 EP 269 DI 10.1046/j.1525-1489.2001.00263.x PG 7 WC Critical Care Medicine SC General & Internal Medicine GA 495LM UT WOS:000172342700002 ER PT J AU Caudill, MA Wang, JC Melnyk, S Pogribny, IP Jernigan, S Collins, MD Santos-Guzman, J Swendseid, ME Cogger, EA James, SJ AF Caudill, MA Wang, JC Melnyk, S Pogribny, IP Jernigan, S Collins, MD Santos-Guzman, J Swendseid, ME Cogger, EA James, SJ TI Intracellular S-adenosylhomocysteine concentrations predict global DNA hypomethylation in tissues of methyl-deficient cystathionine beta-synthase heterozygous mice SO JOURNAL OF NUTRITION LA English DT Article DE cystathionine beta-synthase; S-adenosylhomocysteine; methylation; homocysteine; mice ID METHYLENETETRAHYDROFOLATE-REDUCTASE GENE; MODERATE FOLATE-DEPLETION; PLASMA HOMOCYSTEINE; RAT-LIVER; METHIONINE ADENOSYLTRANSFERASE; METABOLISM; ADENOSYLMETHIONINE; CARCINOGENESIS; MAMMALS; DISEASE AB Because S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) are the substrate and product of essential methyltransferase reactions; the ratio of SAM:SAH is frequently used as an indicator of cellular methylation potential. However, it is not clear from the ratio whether substrate insufficiency, product inhibition or both are required to negatively affect cellular methylation capacity. A combined genetic and dietary approach was used to modulate intracellular concentrations of SAM and SAH. Wild-type (WT) or heterozygous cystathionine P-synthase (CBS +/-) mice consumed a control or methyl-deficient diet for 24 wk. The independent and combined effect of genotype and diet on SAM, SAH and the SAM:SAH ratio were assessed in liver, kidney, brain and testes and were correlated with relative changes in tissue-specific global DNA methylation. The combined results from the different tissues indicated that a decrease in SAM alone was not sufficient to affect DNA methylation in this model, whereas an increase in SAH, either alone or associated with a decrease in SAM, was most consistently associated with DNA hypomethylation. A decrease in SAM:SAH ratio was predictive of reduced methylation capacity only when associated with an increase in SAH; a decrease in the SAM:SAH ratio due to SAM depletion alone was not sufficient to affect DNA methylation in this model. Plasma homocysteine levels were positively correlated with intracellular SAH levels in all tissues except kidney. These results support the possibility that plasma SAH concentrations may provide a sensitive biomarker for cellular methylation status. C1 Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. Calif State Polytech Univ Pomona, Food Nutr & Consumer Sci Dept, Pomona, CA 91768 USA. Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. RP James, SJ (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. EM jjames@nctr.fda.gov FU NCI NIH HHS [P01CA42710] NR 49 TC 151 Z9 157 U1 0 U2 9 PU AMER SOC NUTRITIONAL SCIENCE PI BETHESDA PA 9650 ROCKVILLE PIKE, RM L-2407A, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD NOV PY 2001 VL 131 IS 11 BP 2811 EP 2818 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 493VN UT WOS:000172244300001 PM 11694601 ER PT J AU Ju, YH Allred, CD Allred, KF Karko, KL Doerge, DR Helferich, WG AF Ju, YH Allred, CD Allred, KF Karko, KL Doerge, DR Helferich, WG TI Physiological concentrations of dietary genistein dose-dependently stimulate growth of estrogen-dependent human breast cancer (MCF-7) tumors implanted in athymic nude mice SO JOURNAL OF NUTRITION LA English DT Article DE genistein; MCF-7; athymic nude mouse; pS2; BrdU ID SUPPRESSES MAMMARY-CANCER; SOY-PROTEIN; TISSUE DISTRIBUTION; DNA-SYNTHESIS; CELLS; RATS; ISOFLAVONES; WOMEN; SUPPLEMENTATION; PREMENOPAUSAL AB Previously our laboratory has shown that the soy isoflavone, genistein, stimulates growth of human breast cancer (MCF-7) cells in vivo and in vitro. In this study, the dose-response analysis of genistein at the physiologically achievable concentration range between 125 and 1,000 mug/g in the diet was conducted in ovariectomized athymic nude mice implanted with MCF-7 cells. We hypothesized that genistein at this concentration range can stimulate dose-dependently the breast tumor growth, cell proliferation and an estrogen-responsive pS2 gene induction. Tumor size and body weight were monitored weekly. At completion of the study, we analyzed cellular proliferation of tumors using incorporation of BrdU, pS2 expression of tumors using a Northern blot analysis and total genistein level in plasma using liquid chromatography-isotope dilution mass spectrometry (LC-ES/MS). Dietary genistein (greater than or equal to 250 kg/g) increased tumor size in a dose-dependent manner [8.4x the negative control (NC) group in the 250 mug/g group, 12.0x in the 500 mug/g group, 20.2x in the 1,000 mug/g group and 23.2x in the positive control (PC) group]. The percentage of proliferating cells was significantly increased by genistein at and above 250 mug/g (5.3x the NC group in the 250 mug/g, 5.6x in the 500 mug/g, 5.0x in the 1,000 mug/g and 4.8x in the PC group). Expression of pS2 mRNA was also significantly increased with increasing dietary genistein levels (11.25x the NC group in the 500 mug/g group and 15.84x in the 1,000 mug/g group). Total plasma genistein concentrations were between 0.39 and 3.36 mu mol/L in mice fed between 125 and 1,000 mug/g genistein. In conclusion, dietary treatment with genistein at physiological concentrations produces blood levels of genistein sufficient to stimulate estrogenic effects, such as breast tumor growth, cellular proliferation and pS2 expression in athymic mice in a dose-responsive manner similar to that seen in vitro. C1 Univ Illinois, Dept Food Sci & Human Nutr, Urbana, IL 61801 USA. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Helferich, WG (reprint author), Univ Illinois, Dept Food Sci & Human Nutr, Urbana, IL 61801 USA. FU NCI NIH HHS [CA77355] NR 51 TC 178 Z9 191 U1 0 U2 6 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 2001 VL 131 IS 11 BP 2957 EP 2962 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 493VN UT WOS:000172244300025 PM 11694625 ER PT J AU Franolic, JD Lehr, GJ Barry, TL Petzinger, G AF Franolic, JD Lehr, GJ Barry, TL Petzinger, G TI Isolation of a 2 : 1 hydrochlorothiazide-formaldehyde adduct impurity in hydrochlorothiazide drug substance by preparative chromatography and characterization by electrospray ionization LC-MS SO JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS LA English DT Article DE hydrochlorothiazide; impurities; adduct; liquid chromatography; thin-layer chromatography; electrospray ionization mass spectrometry ID PERFORMANCE LIQUID-CHROMATOGRAPHY; MASS-SPECTROMETRY; IDENTIFICATION; SPECTROSCOPY; PROFILES AB Hydrochlorothiazide drug substance (19 lots) from five different manufacturers and four different countries of origin (USA, Italy. Hungary. and Croatia) were analyzed for the presence of impurities using a gradient elution chromatographic system, with acetonitrile-water as the mobile phase. Two known impurities of hydrochlorothiazide, 4-amino-6-chloro-1,3-benzenedisulfonamide and chlorothiazide, were separated. as well as a late-eluting, unknown, recurring impurity. The unknown impurity was isolated by preparative liquid chromatography followed by preparative thin-layer chromatography, It was characterized by electrospray ionization LC-MS as a 2:1 hydrochlorothiazide-formaldehyde adduct of the parent drug substance. The adduct is believed to form through the double condensation reaction of hydrochlorothiazide with excess formaldehyde during the parent compound's synthesis. The concentration of this impurity ranged from 0.02 to 1.1%, (area%), and was above the 0.1% USP Other Impurities threshold in 16 of the 19 lots examined. (C) 2001 Published by Elsevier Science B.V. All rights reserved. C1 US FDA, Dept Hlth & Human Serv, NE Reg Lab, Jamaica, NY 11433 USA. RP Lehr, GJ (reprint author), US FDA, Dept Hlth & Human Serv, NE Reg Lab, 158-15 Liberty Ave, Jamaica, NY 11433 USA. NR 23 TC 18 Z9 19 U1 0 U2 4 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 PY 2001 VL 26 IS 4 BP 651 EP 663 DI 10.1016/S0731-7085(01)00437-X PG 13 WC Chemistry, Analytical; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 485CG UT WOS:000171735500017 PM 11516917 ER PT J AU Rege, BD Yu, LX Husain, AS Polli, JE AF Rege, BD Yu, LX Husain, AS Polli, JE TI Effect of common excipients on Caco-2 transport of low-permeability drugs SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article DE excipients; Caco-2; permeability; bioavailability; efflux ID INTESTINAL-ABSORPTION; IN-VITRO; CELLS; MONOLAYERS; ENHANCERS; RAT; CLASSIFICATION; SURFACTANTS; INHIBITION; MEMBRANE AB The Biopharmaceutics Classification System (BCS) allows waivers of in vivo bioequivalence for rapidly dissolving immediate-release (IR) formulations of drugs with high solubility and high permeability. One potential issue in possibly extending BCS biowaivers to low-permeability drugs is the potential for excipients to modulate the intestinal permeability of the drug. The objective of this work was to evaluate the effect of nine individual excipients on the Caco-2 permeability of seven low-permeable compounds that differ in their physiochemical properties. Generally, most excipients had no influence on drug permeability. With the exception of sodium lauryl sulfate, no excipient affected Caco-2 monolayer integrity. Sodium lauryl sulfate moderately increased the permeability of almost all the drugs. Tween 80 significantly increased the apical-to-basolateral direction permeability of furosemide, cimetidine, and hydrochlorothiazide, presumably by inhibiting their active efflux, without affecting mannitol permeability. Additionally, docusate sodium moderately increased cimetidine permeability. Other excipients did not have significant effect on the permeability of these three drugs. Further work is needed to interpret the in vivo consequences of these observations from cell culture. (C) 2001 Wiley-Liss, Inc. and the American Pharmaceutical Association. C1 Univ Maryland, Sch Pharm, Dept Pharmaceut Sci, Baltimore, MD 21201 USA. US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Polli, JE (reprint author), Univ Maryland, Sch Pharm, Dept Pharmaceut Sci, Baltimore, MD 21201 USA. NR 19 TC 103 Z9 109 U1 3 U2 16 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0022-3549 J9 J PHARM SCI JI J. Pharm. Sci. PD NOV PY 2001 VL 90 IS 11 BP 1776 EP 1786 DI 10.1002/jps.1127 PG 11 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 491JP UT WOS:000172105500009 PM 11745735 ER PT J AU Chaput, MP Margolin, AB AF Chaput, MP Margolin, AB TI Evaluation of powdered latex medical gloves using ASTM D 6124-00 SO JOURNAL OF TESTING AND EVALUATION LA English DT Article DE powdered medical gloves; latex allergy; health care workers; maximum powder limits; ASTM D 6124 ID SURGICAL GLOVES; PREVALENCE AB Natural rubber latex proteins are recognized as a cause of Type I (Immediate Type Hypersensitivity) reaction in some individuals who have been exposed to latex devices. Residual former-release, stripping, and/or donning powders have been found to carry these allergenic proteins into the air during handling and use. Exposure to airborne glove powder contaminated with latex allergens is known to provoke respiratory allergic symptoms in latex-sensitized individuals and may make it difficult for these individuals to continue working in jobs involving such exposure. The Food and Drug Administration has proposed a maximum level of 120 mg of donning powder/particulates per glove on powdered gloves. A survey was conducted to determine current powder levels on commercially available powdered latex patient examination gloves and surgeons' gloves. Ninety-seven samples of powdered latex medical gloves representing 32 different brands produced by foreign and domestic manufacturers for the U.S. market were evaluated for residual powders per glove by ASTM D 6124-00, Standard Test Method for Residual Powder on Medical Gloves. Powder levels ranged from 37 to 260 mg per glove for patient examination gloves and 30 to 513 mg per glove for surgeons' gloves. Of the gloves tested, 55.7% met the new maximum powder guidelines. C1 US FDA, Winchester Engn & Analyt Ctr, Winchester, MA 01890 USA. Univ New Hampshire, Dept Microbiol, Durham, NH 03824 USA. RP Chaput, MP (reprint author), US FDA, Winchester Engn & Analyt Ctr, Winchester, MA 01890 USA. NR 10 TC 0 Z9 0 U1 0 U2 0 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 2001 VL 29 IS 6 BP 579 EP 581 PG 3 WC Materials Science, Characterization & Testing SC Materials Science GA 497LL UT WOS:000172456900009 ER PT J AU Brinker, AD Bonnel, RA Feight, AG AF Brinker, AD Bonnel, RA Feight, AG TI Celecoxib and rofecoxib SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Letter ID GASTROINTESTINAL TOXICITY; RHEUMATOID-ARTHRITIS C1 US FDA, Ctr Drug Evaluat & Res, Off Postmkt Drug Risk Assessment, Rockville, MD 20857 USA. RP Brinker, AD (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Postmkt Drug Risk Assessment, Rockville, MD 20857 USA. NR 4 TC 2 Z9 2 U1 0 U2 1 PU AMER DENTAL ASSN PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 USA SN 0002-8177 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD NOV PY 2001 VL 132 IS 11 BP 1502 EP + PG 2 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 493KE UT WOS:000172221100004 PM 11806062 ER PT J AU Fuller, J Parmentier, C AF Fuller, J Parmentier, C TI Dental device-associated problems - An analysis of FDA postmarket surveillance data SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article AB Background. The authors provide an analysis of dental device adverse event reports collected through the U.S. Food and Drug Administration's, or FDA's, mandatory and voluntary reporting programs between Aug. 1, 1996, and June 30, 1999. Methods. This study includes an analysis of the total number of dental device adverse events reported during the study period and uses descriptive statistics to depict reporters' occupations, types of adverse events (deaths, injuries, malfunctions), device categories, device problems and patient problems. Results. A total of 272,241 device were received during the 35-month study period, 28,555 (10.5 percent) of which involved dental devices. Within these reports, two deaths (0.007 percent), 18,406 injuries (64.4 percent) and 9,942 device ik malfunctions (34.8 percent) were reported. The most commonly reported dental devices were endosseous implants, which represented more than 90 percent of all dental percent) device reports. Most reports (84.1 percent provided the reporter's occupation, and the most frequently cited occupation was dentist (76.3 percent), followed by dental assistant (4.2 percent). Conclusions. Dentists and dental staff members are a vital link in the FDA's adverse event reporting system and are encouraged to report device problems to the FDA MedWatch program. C1 US FDA, Div Postmarket Surveillance, Off Surveillance & Biometr, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. RP Fuller, J (reprint author), US FDA, Div Postmarket Surveillance, Off Surveillance & Biometr, Ctr Devices & Radiol Hlth, 1350 Piccard Dr,Room 300,HFZ-520, Rockville, MD 20850 USA. NR 3 TC 5 Z9 5 U1 0 U2 1 PU AMER DENTAL ASSN PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 USA SN 0002-8177 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD NOV PY 2001 VL 132 IS 11 BP 1540 EP 1548 PG 9 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 493KE UT WOS:000172221100021 PM 11806067 ER PT J AU Neznanov, N Kondratova, A Chumakov, KM Angres, B Zhumabayeva, B Agol, VI Gudkov, AV AF Neznanov, N Kondratova, A Chumakov, KM Angres, B Zhumabayeva, B Agol, VI Gudkov, AV TI Poliovirus protein 3A inhibits tumor necrosis factor (TNF)-induced apoptosis by eliminating the TNF receptor from cell surface SO JOURNAL OF VIROLOGY LA English DT Article ID NF-KAPPA-B; FACTOR RECEPTOR-1-INDUCED APOPTOSIS; VIRUS CORE PROTEIN; INFECTED CELLS; E3-10.4K/14.5K COMPLEX; ANTIGEN PRESENTATION; DEATH; 2BC; CYTOKINES; DOMAIN AB Viral infections often trigger host defensive reactions by activating intrinsic (intracellular) and extrinsic (receptor-mediated) apoptotic pathways. Poliovirus is known to encode an antiapoptotic function(s) suppressing the intrinsic pathway. Here, the effect of poliovirus nonstructural proteins on cell sensitivity to tumor necrosis factor (TN-F)-induced (i.e., receptor-mediated) apoptosis was studied. This sensitivity is dramatically enhanced by the viral proteinase 2A, due, most likely, to inhibition of cellular translation. On the other hand, cells expressing poliovirus noncapsid proteins 3A and 2B exhibit strong TNF resistance. Expression of 3A neutralizes the proapoptotic activity of 2A and results in a specific suppression of TNF signaling, including the lack of activation of NF-kappaB, due to elimination of the TNF receptor from the cell surface. In agreement with this, poliovirus infection results in a dramatic decrease in TNF receptor abundance on the surfaces of infected cells as early as 4 h postinfection. Poliovirus proteins that confer resistance to TNF interfere with endoplasmic reticulum-Golgi protein trafficking, and their effect on TNF signaling can be imitated by brefeldin A, suggesting that the mechanism of poliovirus-mediated resistance to TNF is a result of aberrant TNF receptor trafficking. C1 Univ Illinois, Dept Mol Genet, Chicago, IL 60607 USA. Quark Biotech Inc, Pleasanton, CA 94566 USA. Russian Acad Sci, VA Engelhardt Mol Biol Inst, Moscow 117984, Russia. Russian Acad Med Sci, MP Chumakov Inst Poliomyelitis & Viral Encephalit, Moscow 142782, Russia. Moscow MV Lomonosov State Univ, Moscow 119899, Russia. US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. Clontech Labs, Palo Alto, CA 94303 USA. RP Neznanov, N (reprint author), Cleveland Clin Fdn, Lerner Res Inst, Dept Mol Biol, 9500 Euclid Ave, Cleveland, OH 44195 USA. RI Agol, Vadim/E-1941-2013 NR 66 TC 92 Z9 99 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 NOV PY 2001 VL 75 IS 21 BP 10409 EP 10420 DI 10.1128/JVI.75.21.10409-10420.2001 PG 12 WC Virology SC Virology GA 480DZ UT WOS:000171447900040 PM 11581409 ER PT J AU Kim, KD Lawrence, SM Park, J Pitts, L Vann, WF Betenbaugh, MJ Palter, KB AF Kim, KD Lawrence, SM Park, J Pitts, L Vann, WF Betenbaugh, MJ Palter, KB TI Expression of a functional Drosophila melanogaster N-acetylneuraminic acid (Neu5Ac) phosphate synthase gene provides evidence that insects have endogenous sialic acid biosynthetic ability SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Temple Univ, Dept Biol, Philadelphia, PA 19122 USA. Johns Hopkins Univ, Dept Chem Engn, Baltimore, MD 21218 USA. US FDA, Lab Bacterial Toxins, Rockville, MD 20857 USA. US FDA, Lab Bacterial Polysaccharides, Rockville, MD 20857 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2001 VL 12 SU S MA 2786 BP 506A EP 506A PG 1 WC Cell Biology SC Cell Biology GA 496AL UT WOS:000172372502779 ER PT J AU Duncan, R Alvarez, R Jaffe, CL Wiese, M Klutch, M Shakarian, A Dwyer, D Nakhasi, HL AF Duncan, R Alvarez, R Jaffe, CL Wiese, M Klutch, M Shakarian, A Dwyer, D Nakhasi, HL TI Early response gene expression during differentiation of cultured Leishmania donovani SO PARASITOLOGY RESEARCH LA English DT Article ID DEVELOPMENTALLY-REGULATED GENE; HEAT-SHOCK PROTEINS; MAP KINASE KINASE; GLUCOSE-TRANSPORTER; CLONING; AMASTIGOTES; IDENTIFICATION; PROMASTIGOTES; CHAGASI; LIPOPHOSPHOGLYCAN AB The promastigote form of the unicellular parasite, Leishmania donovani, must differentiate into the amastigote form to establish an infection in a mammalian host. Identification of genes whose expression changes during differentiation could help reveal mechanisms of Leishmania gene regulation and identify targets for controlling the diseases caused by this human pathogen. Two genomic clones were isolated, P9 that is more highly expressed in promastigotes than in axenic amastigotes and A14 that is preferentially expressed in axenic amastigotes. Analysis of the DNA sequences revealed open reading frames that would encode 55.5 kDa and 100 kDa proteins, respectively, with no homology to known proteins. The mRNA level for these genes during 24 h time courses of parasite differentiation in culture was compared to two genes known to be differentially expressed, c-lpk2 and mkk. Changes in RNA level occurred within 2 h for each gene and continued in advance of morphological changes. The expression levels of these four genes in axenic amastigotes correlated with results from animal-derived parasites. C1 US FDA, Ctr Biol Evaluat & Res, Lab Bacterial Parasit & Unconvent Agents, Bethesda, MD 20892 USA. US FDA, Lab DNA Viruses, Ctr Biol Evaluat & Res, Bethesda, MD USA. Hebrew Univ Jerusalem, Hadassah Med Sch, Dept Parasitol, IL-91010 Jerusalem, Israel. Max Planck Inst Biol, D-7400 Tubingen, Germany. NIAID, Parasit Dis Lab, Bethesda, MD 20892 USA. RP Duncan, R (reprint author), US FDA, Ctr Biol Evaluat & Res, Lab Bacterial Parasit & Unconvent Agents, Bldg 29,Rm 425,HFM 310,8800 Rockville Pk, Bethesda, MD 20892 USA. RI Duncan, Robert/I-8168-2015 OI Duncan, Robert/0000-0001-8409-2501 NR 43 TC 19 Z9 19 U1 0 U2 2 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0932-0113 J9 PARASITOL RES JI Parasitol. Res. PD NOV PY 2001 VL 87 IS 11 BP 897 EP 906 PG 10 WC Parasitology SC Parasitology GA 495VU UT WOS:000172361700002 PM 11728012 ER PT J AU Coles, BF Morel, F Rauch, C Huber, WW Yang, M Teitel, CH Green, B Lang, NP Kadlubar, FF AF Coles, BF Morel, F Rauch, C Huber, WW Yang, M Teitel, CH Green, B Lang, NP Kadlubar, FF TI Effect of polymorphism in the human glutathione S-transferase A1 promoter on hepatic GSTA1 and GSTA2 expression SO PHARMACOGENETICS LA English DT Article DE expression; glutathione S-transferase A1; human; liver; polymorphism ID ALPHA; CANCER; GENES; CARCINOGENESIS; EPIDEMIOLOGY; CONJUGATION; MODULATION; SEQUENCES; GENOTYPES; BINDING AB The patterns of expression of glutathione S-transferases A1 and A2 in human liver (hGSTA1 and hGSTA2, respectively) are highly variable, notably in the ratio of hGSTA1/hGSTA2. We investigated if this variation had a genetic basis by sequencing the proximal promoters (-721 to -1 nucleotides) of hGSTA1 and hGSTA2, using 55 samples of human liver that exemplified the variability of hGSTA1 and hGSTA2 expression. Variants were found in the hGSTA1 gene: -631T or G, -567T, -69C, -52G, designated as hGSTA1*A; and -631 G, -567G, -69T, -52A, designated as hGSTA1*B. Genotyping for the substitution -69C > T by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP), showed that the polymorphism was widespread in Caucasians, African Americans and Hispanics, and that it appeared to conform to allelic variation. Constructs consisting of the proximal promoters of hGSTA1*A, hGSTA1*B or hGSTA2, with luciferase as a reporter gene, showed differential expression when transfected into HepG2 cells: hGSTA1*A hGSTA2 > hGSTA1*B. Similarly, mean levels of hGSTA1 protein expression in liver cytosols decreased significantly according to genotype: hGSTA1*A > hGSTA1-heterozygous > hGSTA1*B. Conversely, mean hGSTA2 expression increased according to the same order of hGSTA1 genotype. Consequently, the ratio of GSTA1/GSTA2 was highly hGSTA1 allele-specific. Because the polymorphism in hGSTA1 correlates with hGSTA1 and hGSTA2 expression in liver, and hGSTA1-1 and hGSTA2-2 exhibit differential catalysis of the detoxification of carcinogen metabolites and chemotherapeutics, the polymorphism is expected to be of significance for individual risk of cancer or individual response to chemotherapeutic agents. Pharmacogenetics 11:663-669 (C) 2001 Lippincott Williams & Wilkins. C1 Natl Ctr Toxicol Res, Div Mol Epidemiol, Jefferson, AR 72079 USA. Fac Pharm, INSERM, U456, Rennes, France. Inst Krebsforsch, Abt Onkol Toxikol, Vienna, Austria. Univ Arkansas Med Sci, Dept Surg, Div Surg Oncol, Little Rock, AR 72205 USA. Cent Arkansas Vet Healthcare Syst, Surg Serv, Little Rock, AR USA. RP Coles, BF (reprint author), Natl Ctr Toxicol Res, Div Mol Epidemiol, HFT 100,3900 NCTR Rd, Jefferson, AR 72079 USA. FU NCI NIH HHS [R01-CA58697] NR 31 TC 159 Z9 163 U1 3 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0960-314X J9 PHARMACOGENETICS JI Pharmacogenetics PD NOV PY 2001 VL 11 IS 8 BP 663 EP 669 DI 10.1097/00008571-200111000-00004 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy GA 493TY UT WOS:000172240600004 PM 11692074 ER PT J AU Delclos, KB Bucci, TJ Lomax, LG Latendresse, JR Warbritton, A Weis, CC Newbold, RR AF Delclos, KB Bucci, TJ Lomax, LG Latendresse, JR Warbritton, A Weis, CC Newbold, RR TI Effects of dietary genistein exposure during development on male and female CD (Sprague-Dawley) rats SO REPRODUCTIVE TOXICOLOGY LA English DT Article DE genistein; isoflavones; soy; endocrine disruptors; reproductive toxicity ID REPRODUCTIVE ORGAN DEVELOPMENT; PREMENOPAUSAL JAPANESE WOMEN; SUPPRESSES MAMMARY-CANCER; ESTROGEN-RECEPTORS ALPHA; IN-VIVO; SOY ISOFLAVONES; BISPHENOL-A; POSTMENOPAUSAL WOMEN; NEONATAL EXPOSURE; PHYTO-ESTROGENS AB Genistein is a naturally occurring isoflavone that interacts with estrogen receptors and multiple other molecular targets. Human exposure to genistein is predominantly through consumption of soy products, including soy-based infant formula and dietary supplements. A dose range-finding study was conducted as a prelude to a multigeneration bioassay to assess potential toxicities associated with genistein consumption. Genistein was administered in a soy- and alfalfa-free diet at 0, 5, 25, 100, 250, 625, or t250 ppm to pregnant dams starting on Gestation day 7 and continuing throughout pregnancy. Dietary exposure of the dams continued through lactation, and pups were maintained on the same dosed feed as their mother after weaning until sacrifice at Postnatal day 50. Body weight and feed consumption of the treated dams prior to parturition showed a decreasing trend with a significant reduction at the highest dose. Litter birth weight was depressed in the t250 ppm dose group, and pups of both sexes in that dose group had significantly decreased body weights relative to controls at the time of sacrifice. The most pronounced organ weight effects in the pups were decreased ventral prostate weight in males at the 1250 ppm dose and a trend toward higher pituitary gland to body weight ratios in both sexes. Histopathologic examination of female pups revealed ductal/alveolar hyperplasia of the mammary glands at 250 to 1250 ppm. Ductal/alveolar hyperplasia and hypertrophy also occurred in males, with significant effects seen at 25 ppm and above. Abnormal cellular maturation in the vagina was observed at 625 and 1250 ppm, and abnormal ovarian antral follicles were observed at 1250 ppm. In males, aberrant or delayed spermatogenesis in the seminiferous tubules relative to controls wag observed at 1250 ppm, There was a deficit of sperm in the epididymis at 625 and 1250 ppm relative to controls, although testicular spermatid head counts and epididymal spermatozoa counts did not show significant differences from controls at these doses. Both sexes showed an increase in the incidence and/or severity of renal tubal mineralization at doses of 250 ppm and above. Dietary genistein thus produced effects in multiple estrogen-sensitive tissues in males and females that are generally consistent with its estrogenic activity. These effects occurred within exposure ranges achievable in humans. (C) 2001 Elsevier Science Inc. All rights reserved. C1 Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. Pathol Associates Int, Jefferson, AR 72079 USA. NIEHS, Environm Toxicol Program, Toxicol Lab, Dev Endocrinol Sect, Res Triangle Pk, NC 27709 USA. RP Delclos, KB (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. EM bdelclos@nctr.fda.gov RI Latendresse, John/A-9215-2009 FU PHS HHS [224-93-0001] NR 91 TC 127 Z9 139 U1 1 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0890-6238 J9 REPROD TOXICOL JI Reprod. Toxicol. PD NOV-DEC PY 2001 VL 15 IS 6 BP 647 EP 663 DI 10.1016/S0890-6238(01)00177-0 PG 17 WC Reproductive Biology; Toxicology SC Reproductive Biology; Toxicology GA 501GF UT WOS:000172676400006 PM 11738518 ER PT J AU Miller, FW Rider, LG Chung, YL Cooper, R Danko, K Farewell, V Lundberg, I Morrison, C Oakley, L Oakley, I Pilkington, C Vencovsky, J Vincent, K Scott, DL Isenberg, DA AF Miller, FW Rider, LG Chung, YL Cooper, R Danko, K Farewell, V Lundberg, I Morrison, C Oakley, L Oakley, I Pilkington, C Vencovsky, J Vincent, K Scott, DL Isenberg, DA CA Int Myositis Outcome Assessment Co TI Proposed preliminary core set measures for disease outcome assessment in adult and juvenile idiopathic inflammatory myopathies SO RHEUMATOLOGY LA English DT Article DE idiopathic inflammatory myopathies; outcome measures ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; INTRAVENOUS GAMMA-GLOBULIN; HEALTH ASSESSMENT QUESTIONNAIRE; RHEUMATOLOGY DAMAGE INDEX; INCLUSION-BODY MYOSITIS; MUSCLE TESTING MMT; POLYMYOSITIS-DERMATOMYOSITIS; REFRACTORY POLYMYOSITIS; CONTROLLED TRIAL; THERAPY AB In order to develop a preliminary core set of disease outcome measures for use in clinical trials of idiopathic inflammatory myopathies (IIM), we evaluated those measures used in previous trials, assessed the validation of published instruments and discussed these at an international consensus conference. The initial proposals were further refined by a multidisciplinary group of adult and paediatric specialists experienced in IIM using the Delphi method. The proposed preliminary core set of disease activity measures consists of five domains: physician and patient parent global assessments of disease activity; muscle strength: physical function, serum activity of muscle enzymes; and an assessment tool to capture extra-skeletal muscle disease activity. The group recommended further development of a core set of disease damage measures for assessment of persistent changes in anatomy, pathology and function of at least 6 months' duration. The group recommended that patient-reported outcomes should include generic health-related quality of life assessments using the Medical Outcomes Study 36-item Short Form (SF-36) health survey in adult IIM patients and a validated quality of life instrument for paediatric patients. We propose the core set of outcome measures as a minimum group of assessments to include in all IIM therapeutic studies. The use of this core set should assist in standardizing outcome measurement and in optimizing therapeutic trials in myositis. C1 US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. Hammersmith Hosp, MRI Unit, London W12 0HS, England. Hope Hosp, Ctr Rheumat Dis, Salford M6 8HD, Lancs, England. Univ Debrecen, Dept Internal Med, Debrecen, Hungary. UCL, London WC1E 6BT, England. Karolinska Inst, Dept Med, Rheumatol Unit, S-17176 Stockholm, Sweden. Kings Coll Hosp Dulwich, Dept Rheumatol, London SE22 8PT, England. Dermatomyositis & Polymyositis Support Grp, Southampton SO19 9HR, Hants, England. Middlesex Hosp, Ctr Rheumatol, London W1P 9PL, England. Inst Rheumatol, Prague 12850 2, Czech Republic. Weston Educ Ctr, Dept Acad Rheumatol GKT, London SE5 9PJ, England. Kings Coll Hosp Dulwich, London W1P 9PG, England. UCL Hosp, Ctr Rheumatol, London W1P 9PC, England. RP Miller, FW (reprint author), NIEHS, Environm Autoimmun Grp, Off Clin Res, NIH, 9 Mem Dr,Room 1W101,MSC 0958, Bethesda, MD 20892 USA. RI Song, Yeong Wook/J-2765-2012; OI Farewell, Vernon/0000-0001-6704-5295; Isenberg, David/0000-0001-9514-2455; Rider, Lisa/0000-0002-6912-2458; Miller, Frederick/0000-0003-2831-9593 NR 57 TC 135 Z9 138 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1462-0324 EI 1462-0332 J9 RHEUMATOLOGY JI RHEUMATOLOGY PD NOV PY 2001 VL 40 IS 11 BP 1262 EP 1273 DI 10.1093/rheumatology/40.11.1262 PG 12 WC Rheumatology SC Rheumatology GA 496CQ UT WOS:000172378500009 PM 11709610 ER PT J AU Artlett, CM Miller, FW Rider, LG AF Artlett, CM Miller, FW Rider, LG CA Childhood Myositis Heterogeneity C TI Persistent maternally derived peripheral microchimerism is associated with the juvenile idiopathic inflammatory myopathies SO RHEUMATOLOGY LA English DT Article DE microchimerism; maternal-fetal exchange; dermatomyositis; polymyositis; graft versus host reaction; inflammatory myopathy ID SYSTEMIC-SCLEROSIS; CELLS; DERMATOMYOSITIS; ORIGIN; IDENTIFICATION; POLYMYOSITIS; ANTIGENS; DISEASE; LIFE AB Objective. Fetal cells have been demonstrated in the active lesions of adult women with systemic sclerosis. Because the juvenile idiopathic inflammatory myopathies (JIIM) share clinical and histopathological features with systemic sclerosis and graft-vs-host disease, we explored the possibility that maternal cells persist and play a role in the pathogenesis of JIIM. Methods. DNA samples extracted from peripheral blood of 28 JIIM patients (14 females. 14 males) and 23 healthy controls were assessed for microchimerism by the HLA Cw polymerase chain reaction method. HLA Cw alleles from eight mothers and three healthy siblings of JIIM patients were also examined. Results. A microchimeric allele was identified in 19 of 26 JIIM patients whose data were able to be interpreted, compared with two of 21 healthy controls (P<0.001). Subjects with microchimerism ranged in age from 4 to 28 yr. In eight cases in which maternal peripheral blood was available. the additional Cw allele present in the patients was confirmed to be identical to a maternal allele. Three healthy siblings of JIIM patients did not have evidence of a microchimeric Cw allele. Conclusion. Maternal cells can persist in the peripheral blood of their children up to three decades after birth, and are found in a higher proportion in JIIM patients compared with controls. These findings, with other data, suggest that maternal cells may be involved in the immunopathogenesis of JIIM. C1 Thomas Jefferson Univ, Div Rheumatol, Philadelphia, PA 19107 USA. US FDA, Ctr Biol Evaluat & Res, Div Monoclonal Antibodies, Bethesda, MD USA. NIAMSD, Arthrit & Rheumatism Branch, NIH, Bethesda, MD 20892 USA. RP Artlett, CM (reprint author), Thomas Jefferson Univ, Div Rheumatol, 233 S 10th St, Philadelphia, PA 19107 USA. OI Rider, Lisa/0000-0002-6912-2458; Miller, Frederick/0000-0003-2831-9593 NR 22 TC 28 Z9 28 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1462-0324 J9 RHEUMATOLOGY JI RHEUMATOLOGY PD NOV PY 2001 VL 40 IS 11 BP 1279 EP 1284 DI 10.1093/rheumatology/40.11.1279 PG 6 WC Rheumatology SC Rheumatology GA 496CQ UT WOS:000172378500011 PM 11709612 ER PT J AU Sen, K Asher, DM AF Sen, K Asher, DM TI Multiplex PCR for detection of Enterobacteriaceae in blood SO TRANSFUSION LA English DT Article ID RIBOSOMAL-RNA GENE; YERSINIA-ENTEROCOLITICA; RAPID IDENTIFICATION; RED-CELLS; BACTERIAL-CONTAMINATION; TRANSFUSION; SEPSIS; CULTURES; PROBES; OLIGONUCLEOTIDES AB BACKGROUND: Rapid and sensitive methods are needed to detect the small numbers of bacteria that may sometimes contaminate units of blood during collection. A multiplex 5'-nuclease TaqMan PCR assay (PE Applied Biosystems) was used to detect several bacterial species that may contaminate blood. STUDY DESIGN AND METHODS: Oligonucleotide primers were made for regions of the 16S rRNA gene conserved in four different bacterial species: Yersinia enterocolitica and Serratia, Klebsiella, and Enterobacter species. Two probes were designed: SL-1 detected Serratia, Klebsiella, and Enterobacter species, and YE-3 detected Y. enterocolitica. RESULTS: When TaqMan PCR was performed with chromosomal DNA isolated from pure cultures of Serratia liquefaciens, Klebsiella oxytoca, Klebsiella pneumoniae, Enterobacter cloacae, and Enterobacter agglomerans, the limit of detection with probe SL-1 was 1 to 2 CFUs. For S. marcescens, the sensitivity was 8 CFUs. The limit of detection for Y enterocolitica with probe YE-3 was 2 CFUs. When total chromosomal DNA was extracted from whole-blood samples spiked with different numbers of Y enterocolitica, S. liquefaciens, E cloacae, or K pneumoniae bacteria, the TaqMan PCR detected 12 to 16 organisms in 1 mL of blood. CONCLUSION: The 5'-nuclease TaqMan PCR assay takes only 3 hours to perform and has the potential to detect very small numbers of bacteria. C1 US FDA, Div Emergin & Transfus Transmitted Dis, Rockville, MD 20857 USA. RP Sen, K (reprint author), US FDA, Div Emergin & Transfus Transmitted Dis, Rockville, MD 20857 USA. NR 32 TC 23 Z9 23 U1 2 U2 8 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 2001 VL 41 IS 11 BP 1356 EP 1364 DI 10.1046/j.1537-2995.2001.41111356.x PG 9 WC Hematology SC Hematology GA 497AE UT WOS:000172429900008 PM 11724978 ER PT J AU Umehara, H Bloom, ET Okazaki, T Domae, N Imai, T AF Umehara, H Bloom, ET Okazaki, T Domae, N Imai, T TI Fractalkine and vascular injury SO TRENDS IN IMMUNOLOGY LA English DT Article ID ENDOTHELIAL-CELLS; CHEMOKINE RECEPTORS; NK CELLS; ADHESION; CX(3)CR1; EXPRESSION; MECHANISMS; GENE; INVOLVEMENT; INHIBITION AB The vascular endothelium plays a central role in the recruitment and migration of circulating effector cells into sites of inflammation and immune responses. The unique CX3C-chemokine,fractalkine, is expressed on activated endothelial cells, and its receptor, CX(3)CR1, is expressed on natural killer cells, monocytes and some CD8(+) T cells, all of which possess cytolytic function. Accumulating evidence that fractalkine is expressed on endothelial cells during glomerulonephritis and cardiac allograft rejection, as well as on cardiac endothelial cells activated by pro-inflammatory cytokines, might provide insight into the pathogenesis of vascular injury. Here, we propose a model in which fractalkine mediates vascular injury through the accumulation and activation of killer cells. C1 Kyoto Univ, Grad Sch Med, Dept Rheumatol & Clin Immunol, Sakyo Ku, Kyoto 6068507, Japan. US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies HFM518, Bethesda, MD 20892 USA. Kyoto Univ, Grad Sch Med, Dept Hematol & Oncol, Sakyo Ku, Kyoto 6068507, Japan. Osaka Dent Univ, Dept Internal Med, Hirakata, Osaka 5731121, Japan. Kan Res Inst, Shimogyo Ku, Kyoto 6008815, Japan. RP Umehara, H (reprint author), Kyoto Univ, Grad Sch Med, Dept Rheumatol & Clin Immunol, Sakyo Ku, 54 Kawahara Cho, Kyoto 6068507, Japan. NR 50 TC 84 Z9 101 U1 0 U2 2 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 NOV PY 2001 VL 22 IS 11 BP 602 EP 607 DI 10.1016/S1471-4906(01)02051-8 PG 6 WC Immunology SC Immunology GA 491TF UT WOS:000172124500005 PM 11698220 ER PT J AU Sutherland, JB Freeman, JP Heinze, TM Moody, JD Parshikov, IA Williams, AJ Zhang, D AF Sutherland, JB Freeman, JP Heinze, TM Moody, JD Parshikov, IA Williams, AJ Zhang, D TI Oxidation of phenothiazine and phenoxazine by Cunninghamella elegans SO XENOBIOTICA LA English DT Article ID MICROSOMAL METABOLISM; HOMOLOGOUS SERIES; P-GLYCOPROTEIN; IDENTIFICATION; BIOTRANSFORMATION; DIBENZOTHIOPHENE; XENOBIOTICS; EXPRESSION; ETHERS; LIVER AB 1. To determine the ability of fungi to metabolize sulphur- and oxygen-containing azaarenes, Cunninghamella elegans ATCC 9245 was grown in 125-ml flasks containing fluid Sabouraud medium. The cultures and controls were incubated at 28 degreesC with shaking and dosed with 16.7 mM phenothiazine or phenoxazine. After incubation for 72 h, the mycelia and filtrates were extracted with ethyl acetate and the combined residues analysed by high-performance liquid chromatography. Residual phenothiazine and phenoxazine were 21 and 22%, respectively, of the total UV absorbance at 254 nm. 2. The metabolites were identified by mass spectrometry and proton nuclear magnetic resonance spectroscopy. The fungus oxidized phenothiazine to phenothiazine sulphoxide, 3-hydroxyphenothiazine sulphoxide, phenothiazin-3-one, and 3-hydroxyphenothiazine and oxidized phenoxazine to phenoxazin-3-one. 3. Three of the four compounds produced by C. elegans from phenothiazine were identical to those produced by mammals, supporting the use of the fungus as a microbial model for drug metabolism. C1 US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Sutherland, JB (reprint author), US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. OI Parshikov, Igor/0000-0003-1466-1128 NR 36 TC 9 Z9 9 U1 0 U2 6 PU TAYLOR & FRANCIS LTD PI LONDON PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND SN 0049-8254 J9 XENOBIOTICA JI Xenobiotica PD NOV PY 2001 VL 31 IS 11 BP 799 EP 809 PG 11 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 493AU UT WOS:000172200500004 PM 11765142 ER PT J AU Honkanen, VEA Siegel, AF Szalai, JP Berger, V Feldman, BM Siegel, JN AF Honkanen, VEA Siegel, AF Szalai, JP Berger, V Feldman, BM Siegel, JN TI A three-stage clinical trial design for rare disorders SO STATISTICS IN MEDICINE LA English DT Article ID RHEUMATOID-ARTHRITIS; CHILDREN; WITHDRAWAL; CANCER; ENTRY AB Many clinical trials of uncommon diseases are underpowered because of the difficulty of recruiting adequate numbers of subjects. We propose a clinical trial design with improved statistical power compared to the traditional randomized trial for use in clinical trials of rare diseases. The three-stage clinical trial design consists of an initial randomized placebo-controlled stage, a randomized withdrawal stage for subjects who responded, and a third randomized stage for placebo non-responders who subsequently respond to treatment. Test level and power were assessed by computer-intensive exact calculations. The three-stage clinical trial design was found to be consistently superior to the traditional randomized trial design in all cases examined, with sample sizes typically reduced by 20 per cent to 30 per cent while maintaining comparable power. When a treatment clearly superior to placebo was considered, our design reached a power of 75 per cent with a sample of 21 patients compared with the 52 needed to attain this power when only a randomized controlled trial was used. In situations where patient numbers are limited, a three-stage clinical trial design may be a more powerful design than the traditional randomized trial for detecting clinical benefits. Copyright (C) 2001 John Wiley & Sons, Ltd. C1 Hosp Sick Children, Div Rheumatol, Toronto, ON M5G 1X8, Canada. Univ Toronto, Toronto, ON, Canada. Univ Helsinki, Childrens Hosp, Helsinki, Finland. Univ Washington, Dept Management Sci, Seattle, WA 98195 USA. Univ Washington, Dept Finance, Seattle, WA 98195 USA. Univ Washington, Dept Stat, Seattle, WA 98195 USA. Univ Washington, Dept Mol Biotechnol, Seattle, WA 98195 USA. Inst Syst Biol, Seattle, WA USA. Sunnybrook Hlth Sci Ctr, Dept Res Design & Biostat, Toronto, ON M4N 3M5, Canada. US FDA, Ctr Biol Evaluat & Res, Off Estab Licensing & Prod Surveillance, Div Biostat & Epidemiol, Rockville, MD 20857 USA. Univ Toronto, Dept Paediat & Community Med, Toronto, ON, Canada. US FDA, Ctr Biol Evaluat & Res, Off Therapeut Res & Review, Div Clin Trial Design & Anal, Rockville, MD 20857 USA. RP Feldman, BM (reprint author), Hosp Sick Children, Div Rheumatol, 555 Univ Ave, Toronto, ON M5G 1X8, Canada. RI Feldman, Brian/A-8586-2011 NR 18 TC 16 Z9 16 U1 0 U2 1 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 OCT 30 PY 2001 VL 20 IS 20 BP 3009 EP 3021 DI 10.1002/sim.980.abs PG 13 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 482EY UT WOS:000171563800002 PM 11590629 ER PT J AU Chen, ZG Lovanna, JL Moucadel, V Eggerman, TL Patterson, AP AF Chen, ZG Lovanna, JL Moucadel, V Eggerman, TL Patterson, AP TI Cdx1, an important factor in small intestinal development, upregulates apoB mRNA editing SO CIRCULATION LA English DT Meeting Abstract C1 NIH, NHLBI, Bethesda, MD USA. INSERM 315, Lab Res Physiol & Pathol Digest, Marseille, France. Ctr Biol Evaluat & Res, Bethesda, MD USA. NR 0 TC 1 Z9 1 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 23 PY 2001 VL 104 IS 17 SU S MA 67 BP 15 EP 15 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 487UW UT WOS:000171895000067 ER PT J AU Remaley, AT Thomas, F Stonik, J Demosky, SJ Neufeld, EB Bocharov, AV Vishnyakova, TG Patterson, AP Eggerman, T Santamarina-Fojo, S Brewer, HB AF Remaley, AT Thomas, F Stonik, J Demosky, SJ Neufeld, EB Bocharov, AV Vishnyakova, TG Patterson, AP Eggerman, T Santamarina-Fojo, S Brewer, HB TI ABCA1 transporter dependent and independent lipid efflux to synthetic peptide acceptors SO CIRCULATION LA English DT Meeting Abstract C1 NIH, NHLBI, Bethesda, MD USA. NIH, Mol Dis Branch, Bethesda, MD USA. US FDA, 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 23 PY 2001 VL 104 IS 17 SU S MA 709 BP 147 EP 147 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 487UW UT WOS:000171895000705 ER PT J AU Baranova, I Vishnyakova, T Bocharov, A Chen, ZG Remaley, AT Stonik, J Eggerman, TL Patterson, AP AF Baranova, I Vishnyakova, T Bocharov, A Chen, ZG Remaley, AT Stonik, J Eggerman, TL Patterson, AP TI Lipopolysaccharide (LPS) down regulates both scavenger receptor B1 (SRB1) and ATP binding cassette A1 (ABCA1) in raw cells SO CIRCULATION LA English DT Meeting Abstract C1 NIH, NHLBI, Bethesda, MD USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 23 PY 2001 VL 104 IS 17 SU S MA 711 BP 148 EP 148 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 487UW UT WOS:000171895000707 ER PT J AU Djuric, Z Chen, G Doerge, DR Heilbrun, LK Kucuk, O AF Djuric, Z Chen, G Doerge, DR Heilbrun, LK Kucuk, O TI Effect of soy isoflavone supplementation on markers of oxidative stress in men and women SO CANCER LETTERS LA English DT Article DE soy; oxidative damage; isoflavone; DNA damage ID LOW-DENSITY-LIPOPROTEIN; DNA-DAMAGE; MASS-SPECTROMETRY; BLOOD; GENISTEIN; PHYTOESTROGENS; RESISTANCE; DAIDZEIN; CANCER; HUMANS AB Dietary intake of soy has been linked with decreased cancer risk, and the active compounds in soy that have been identified include the isoflavones genistein and daidzein. Since these compounds have antioxidant properties, we examined levels of oxidative damage in blood of six women and six men before and during soy supplementation using Novasoy tablets. Blood samples were obtained at weekly intervals for 3 weeks from the women taking 50-mg isoflavones once daily and the men taking 50-mg isoflavones twice daily. Plasma levels of genistein and daidzein increased after supplementation with maximal levels occurring at 2 weeks for the women while levels in men kept increasing over the 3 weeks of study. There was wide variation between individuals in the levels of isoflavones achieved. Mean levels of 5-hydroxymethyl-2'-deoxyuridine (5-OHmdU) in DNA from nucleated blood cells decreased after I week of supplementation in the women, with a decrease of 47% in mean 5-OHmdU levels after 3 weeks. In men, mean 5-OHmdU levels did not decrease until after 3 weeks of supplementation, at which there was 61% decrease. Mean plasma levels of 8-isoprostanes were not changed appreciably in either men or women. These pilot results suggest that soy isoflavone supplementation decreases levels of oxidative DNA damage in humans, and this may be a mechanism behind the cancer-preventive effects of soy isoflavones. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved. C1 Barbara Ann Karmanos Canc Inst, Detroit, MI 48201 USA. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Djuric, Z (reprint author), Barbara Ann Karmanos Canc Inst, 110 E Warren, Detroit, MI 48201 USA. RI Djuric, Zora/H-5147-2013 OI Djuric, Zora/0000-0002-8886-8853 FU NCI NIH HHS [CA 22453] NR 24 TC 96 Z9 109 U1 0 U2 6 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 OCT 22 PY 2001 VL 172 IS 1 BP 1 EP 6 DI 10.1016/S0304-3835(01)00627-9 PG 6 WC Oncology SC Oncology GA 476PX UT WOS:000171238900001 PM 11595123 ER PT J AU Juneja, VK Eblen, BS Marks, HM AF Juneja, VK Eblen, BS Marks, HM TI Modeling non-linear survival curves to calculate thermal inactivation of Salmonella in poultry of different fat levels SO INTERNATIONAL JOURNAL OF FOOD MICROBIOLOGY LA English DT Article DE D-value; lag times; poultry; concave survival curves; spline regression; non-linear regression ID UNITED-STATES; CHICKEN; MEAT AB Survival curves of a cocktail of eight serotypes of Salmonella in ground poultry of different fat levels (1-12%), when heated rapidly to specified temperatures (58-65 degreesC), were examined. Because many of the survival curves were concave, values for two parameters: the asymptotic D-value and the "lag" times were estimated and used to develop secondary models for estimating the time needed to obtain a 7 log(10) relative reduction as a function of fat level and temperature. To compute the necessary time, at a given temperature and fat level, the estimated lag time should be added to the product of 7 and the estimated asymptotic D-value. A model was also developed for estimating the standard error of the estimated times, so that upper confidence bounds for the necessary times can be computed. It was found that lag times increase with higher fat levels. The effect of fat on D-values depended on the species; it is estimated that, for a given increase of fat level, the increase of the D-value would be greater for ground chicken than that for ground turkey. In addition, there was a statistically significant species effect on D-values, with higher D-values for ground turkey than for ground chicken at the higher temperatures studied. The thermal death curves displayed a non-linear tendency, however, for estimation purposes, a linear curve was assumed. There was not a statistically significant interaction effect of fat levels and temperatures on D-values, thus, for modeling, it was assumed that z-values were not dependent on the fat levels. The z-values for ground chicken and turkey were estimated to be 5.5 degreesC and 6.1 degreesC, respectively, and are statistically significantly different. These findings should have substantial practical importance to food processors of cooked poultry, allowing them to vary their thermal treatment of ready-to-eat poultry products in a safe manner. Published by Elsevier Science B.V. C1 ARS, Food Safety Res Unit, Eastern Reg Res Ctr, USDA, Wyndmoor, PA 19038 USA. US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20250 USA. Food Safety Inspect Serv, USDA, Washington, DC 20250 USA. RP Juneja, VK (reprint author), ARS, Food Safety Res Unit, Eastern Reg Res Ctr, USDA, 600 E Mermaid Lane, Wyndmoor, PA 19038 USA. NR 23 TC 61 Z9 65 U1 3 U2 19 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 22 PY 2001 VL 70 IS 1-2 BP 37 EP 51 DI 10.1016/S0168-1605(01)00518-9 PG 15 WC Food Science & Technology; Microbiology SC Food Science & Technology; Microbiology GA 495YQ UT WOS:000172368300005 PM 11759761 ER PT J AU Prival, MJ AF Prival, MJ TI Anomalous mutagenicity profile of cyclohexanone oxime in bacteria: cell survival in background lawns SO MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS LA English DT Article DE cyclohexanone oxime; Salmonella; Ames test; toxicity measurement; pKM101 ID ESCHERICHIA-COLI; SALMONELLA-TYPHIMURIUM; HOMOLOGOUS RECOMBINATION; GENETIC-ANALYSIS; SOS MUTAGENESIS; DNA-POLYMERASE; COMPLEX; RESISTANCE; UMUD'C-2; PLASMIDS AB The basis for the observed mutagenicity of cyclohexanone oxime in the presence of hamster liver S9 in Salmonella typhimurium strain TA1535, but not in TA100, was explored. While the chemical had no effect on the appearance of the background lawn in either strain, it did cause a reduction in mutant colony counts in strain TA100, raising the possibility of selective toxicity to this strain. Viability of the two strains was determined directly by titering the cells in background lawns over a 3 day period. In order to do this, cells embedded in top agar overlays were released by extruding agar plugs through small holes in the bottoms of centrifuge tubes, followed by vigorous vortexing. Viable cell counts in background lawns of strain TA100, but not strain TA1535, were greatly reduced in the presence of cyclohexanone oxime. Most of the loss of viable TA100 cells occurred on days 2 and 3 following plating, after the cells had exhausted the histidine in the medium and stopped growing. Therefore, the observed loss of background lawn viable cells is unlikely to be the cause of the non-mutagenicity of cyclohexanone in strain TA100. Analysis of reversion spectra showed that cyclohexanone oxime-induced C --> T transitions in the second position of the CCC triplet at the his mutation site in strain TA1535, but had no significant effect on any transition or transversion in strain TA100. Published by Elsevier Science B.V. C1 US FDA, Genet Toxicol Branch, Washington, DC 20204 USA. RP Prival, MJ (reprint author), US FDA, Genet Toxicol Branch, HFS-236,200 C St SW, Washington, DC 20204 USA. NR 31 TC 1 Z9 1 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 OCT 18 PY 2001 VL 497 IS 1-2 BP 1 EP 9 DI 10.1016/S1383-5718(01)00196-6 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 472AF UT WOS:000170960300001 PM 11525902 ER PT J AU White, DG Zhao, S Sudler, R Ayers, S Friedman, S Chen, S McDermott, PF McDermott, S Wagner, DD Meng, JH AF White, DG Zhao, S Sudler, R Ayers, S Friedman, S Chen, S McDermott, PF McDermott, S Wagner, DD Meng, JH TI The isolation of antibiotic-resistant Salmonella from retail ground meats. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID TYPHIMURIUM DT104 INFECTIONS; FIELD GEL-ELECTROPHORESIS; PHAGE TYPE DT104; RAW-MILK CHEESE; MULTIDRUG-RESISTANT; UNITED-STATES; ANTIMICROBIAL RESISTANCE; INTEGRONS; GENES; CONSEQUENCES AB Background: Salmonella is a leading cause of food-borne illness. The emergence of antimicrobial-resistant salmonella is associated with the use of antibiotics in animals raised for food; resistant bacteria can be transmitted to humans through foods, particularly those of animal origin. We identified and characterized strains of salmonella isolated from ground meats purchased in the Washington, D.C., area. Methods: Salmonella was isolated from samples of ground chicken, beef, turkey, and pork purchased at three supermarkets. The isolates were characterized by serotyping, antimicrobial-susceptibility testing, phage typing, and pulsed-field gel electrophoresis. The polymerase chain reaction and DNA sequencing were used to identify resistance integrons and extended spectrum beta -lactamase genes. Results: Of 200 meat samples, 41 (20 percent) contained salmonella, with a total of 13 serotypes. Eighty-four percent of the isolates were resistant to at least one antibiotic, and 53 percent were resistant to at least three antibiotics. Sixteen percent of the isolates were resistant to ceftriaxone, the drug of choice for treating salmonellosis in children. Bacteriophage typing identified four isolates of Salmonella enterica serotype typhimurium definitive type 104 (DT104), one of DT104b, and two of DT208. Five isolates of S. enterica serotype agona had resistance to 9 antibiotics, and the two isolates of serotype typhimurium DT208 were resistant to 12 antibiotics. Electrophoretic patterns of DNA that were indistinguishable from one another were repeatedly found in isolates from different meat samples and different stores. Eighteen isolates, representing four serotypes, had integrons with genes conferring resistance to aminoglycosides, sulfonamides, trimethoprim, and beta -lactams. Conclusions: Resistant strains of salmonella are common in retail ground meats. These findings provide support for the adoption of guidelines for the prudent use of antibiotics in food animals and for a reduction in the number of pathogens present on farms and in slaughterhouses. National surveillance for antimicrobial-resistant salmonella should be extended to include retail meats. (N Engl J Med 2001;345:1147-54.) Copyright (C) 2001 Massachusetts Medical Society. C1 Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA. US FDA, Ctr Vet Med, Div Anim & Food Microbiol Off Res, Laurel, MD USA. RP Meng, JH (reprint author), Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA. NR 38 TC 266 Z9 281 U1 4 U2 47 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 18 PY 2001 VL 345 IS 16 BP 1147 EP 1154 DI 10.1056/NEJMoa010315 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 482YX UT WOS:000171605800001 PM 11642230 ER PT J AU Sen, S Mabuni, C Walsh, D AF Sen, S Mabuni, C Walsh, D TI Development of a methodology for characterizing commercial chlorinated latex gloves SO JOURNAL OF APPLIED POLYMER SCIENCE LA English DT Article DE natural rubber latex; glove; chlorination; methodology; infrared spectrometry; ion chromatography AB Chlorination of gloves has gained popularity as a more permanent method of reducing the inherent tackiness of natural rubber latex compared to using powder as a dusting lubricant. Transmission of proteins in natural rubber latex into the air as a result of using powder on natural rubber latex gloves may cause serious complications to allergic individuals. A methodology for characterizing commercial chlorinated natural rubber latex gloves using a combination of attenuated total reflectance (ATR)Fourier transform infrared (FTIR) spectroscopy and ion chromatography (IC) is described. ATR-FTIR studies established that 930-915 and 670-650 cm(-1) are definitive wavenumber ranges for the identification of chlorine in commercial chlorinated latex gloves. Confirmation of the ATR-FTIR results and semiquantification of the chlorine content in the latex gloves was carried out by the IC technique. This methodology can be used by glove manufacturers to determine the amount of chlorine in batches of commercial gloves, and thereby prevent possible threats to public health arising from the deterioration of surgical and examination chlorinated latex gloves under severe storage conditions before the end of their expected shelf life. (C) 2001 John Wiley & Sons, Inc. C1 US FDA, Pacific Reg Lab SW, Los Angeles, CA 90015 USA. Calif Dept Hlth Serv, Food & Drug Lab Branch, Los Angeles, CA 90015 USA. US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20852 USA. RP Sen, S (reprint author), US FDA, Pacific Reg Lab SW, Los Angeles, CA 90015 USA. NR 13 TC 4 Z9 4 U1 0 U2 3 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0021-8995 J9 J APPL POLYM SCI JI J. Appl. Polym. Sci. PD OCT 17 PY 2001 VL 82 IS 3 BP 672 EP 682 DI 10.1002/app.1895 PG 11 WC Polymer Science SC Polymer Science GA 463ZZ UT WOS:000170508700017 ER PT J AU Dean-Ross, D Moody, JD Freeman, JP Doerge, DR Cerniglia, CE AF Dean-Ross, D Moody, JD Freeman, JP Doerge, DR Cerniglia, CE TI Metabolism of anthracene by a Rhodococcus species SO FEMS MICROBIOLOGY LETTERS LA English DT Article ID POLYCYCLIC AROMATIC-HYDROCARBONS; MYCOBACTERIUM SP; DEGRADATION; PYRENE; OXIDATION; BIODEGRADATION; BIOREMEDIATION; PHENANTHRENE; SEDIMENT; BAY AB A Rhodococcus sp. isolated from contaminated river sediment was investigated to determine if the isolate could degrade high molecular mass polycyclic aromatic hydrocarbons. The Rhodococcus sp. was able to utilize anthracene (53%), phenanthrene (31%), pyrene (13%), and fluoranthene (5%) as sole source of carbon and energy, but not naphthalene or chrysene. In a study of the degradation of anthracene by a Rhodococcus sp., the identification of ring-fission products indicated at least two ring-cleavage pathways. One results in the production of 6,7-benzocoumarin, previously shown to be produced chemically from the product of meta cleavage of 1,2-dihydroxyanthracene, a pathway which has been well established in Gram-negative bacteria. The second is an ortho cleavage of 1,2-dihydroxyanthracene that produces 3-(2-carboxyvinyl)naphthalene-2-carboxylic acid, a dicarboxylic acid rin.-fission product. This represents a novel metabolic pathway only identified in Gram-positive bacteria. (C) 2001 Federation of European Microbiological Societies. Published by Elsevier Science BY. All rights reserved. C1 Indiana Univ Purdue Univ, Dept Biol, Ft Wayne, IN 46805 USA. US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. US FDA, Natl Ctr Toxicol Res, Div Chem, Jefferson, AR 72079 USA. US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Dean-Ross, D (reprint author), Indiana Univ Purdue Univ, Dept Biol, Ft Wayne, IN 46805 USA. NR 29 TC 80 Z9 93 U1 1 U2 11 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 OCT 16 PY 2001 VL 204 IS 1 BP 205 EP 211 DI 10.1016/S0378-1097(01)00404-9 PG 7 WC Microbiology SC Microbiology GA 489QV UT WOS:000172003700034 PM 11682202 ER PT J AU Desai, VG Casciano, D Feuers, RJ Aidoo, A AF Desai, VG Casciano, D Feuers, RJ Aidoo, A TI Activity profile of glutathione-dependent enzymes and respiratory chain complexes in rats supplemented with antioxidants and treated with carcinogens SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE dietary antioxidant vitamins; selenium; DMBA; BLM; Se-dependent glutathione peroxidase; Se-independent glutathione peroxidase; glutathione S-transferases ID DIETARY SELENIUM; MAMMARY CARCINOGENESIS; VITAMIN-E; LIVER; PEROXIDASE; BLEOMYCIN; INHIBITION; OXIDANTS; CAROTENE; FEMALE AB Appropriate dietary interventions may reduce the potentially damaging effects of free radicals generated during metabolism and various physiological conditions. We have investigated the effects of dietary vitamins C, E, beta -carotene, or selenium (Se) on the activity of endogenous antioxidant enzymes and respiratory chain complexes in rats exposed to 7,12-dimethylbenz[alpha ]anthracene (DMBA), a mammary carcinogen and bleomycin (BLM), an antineoplastic drug. These agents are known to generate DNA-reactive species during their metabolism, which may enhance oxidative stress in cells. Female Fischer 344 rats aged 4 months were given antioxidant supplements singly or as a mixture 2 weeks prior to mutagen treatments; antioxidant supplementation continued for an additional 4 weeks. In rats treated with mutagens, the antioxidant intake lowered the activity of So-dependent glutathione peroxidase (Se-GPx) in liver cytosolic and mitochondrial fractions, compared to activity in rats treated with mutagens alone. However, the vitamins, but not Se supplement, persistently increased Se-GPx activity in untreated control animals. Treatment of animals with mutagen raised K-m value of Se-GPx and this correlated with an increase in V-max. However, Se intake, either singly or mixture, significantly reduced K-m value in mutagen-treated and untreated rats in both fractions. Se intake increased glutathione S-transferases (GST) activity (P < 0.05) in both liver fractions of mutagen-treated and untreated animals. Similar response was seen in Se-independent GPx. Since GST-alpha possesses Se-independent GPx activity, the enhanced effect observed in GST activity may be due, in part, to increase activity in Se-independent GPx. Also, selenium or the antioxidant vitamin supplementation increased the activity of all four respiratory chain complexes in untreated rats. Although BLM treatment significantly increased the activity of electron transport complexes III and IV, selenium or the vitamin supplements modulated the responses. These results indicate that the intake of dietary vitamins or Se enhances antioxidant capacity in chemically exposed animals compared to animals receiving antioxidants alone. Furthermore, in addition to being an enhancer of the catalytic function of glutathione peroxidase, selenium may directly play a role as an antioxidant. (C) 2001 Academic Press. C1 US FDA, Dept Hlth & Human Serv, Jefferson Labs, Natl Ctr Toxicol Res,Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. RP Desai, VG (reprint author), US FDA, Dept Hlth & Human Serv, Jefferson Labs, Natl Ctr Toxicol Res,Div Genet & Reprod Toxicol, HFT-120, Jefferson, AR 72079 USA. NR 44 TC 21 Z9 21 U1 0 U2 0 PU ACADEMIC PRESS INC 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 OCT 15 PY 2001 VL 394 IS 2 BP 255 EP 264 DI 10.1006/abbi.2001.2548 PG 10 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 486ME UT WOS:000171820900016 PM 11594740 ER PT J AU Lavigne, JA Goodman, JE Fonong, T Odwin, S He, P Roberts, DW Yager, JD AF Lavigne, JA Goodman, JE Fonong, T Odwin, S He, P Roberts, DW Yager, JD TI The effects of catechol-O-methyltransferase inhibition on estrogen metabolite and oxidative DNA damage levels in estradiol-treated MCF-7 cells SO CANCER RESEARCH LA English DT Article ID BREAST-CANCER CELLS; UDP-GLUCURONOSYLTRANSFERASES; INDUCED CARCINOGENESIS; EPITHELIAL-CELLS; MAMMARY-TUMORS; FREE-RADICALS; EXPRESSION; 17-BETA-ESTRADIOL; RISK; COMT AB Many of the major identified risk factors for breast cancer are associated with exposure to endogenous estrogen. In addition to the effects of estrogen as a growth factor, experimental and epidemiological evidence suggest that catechol metabolites of estrogen also contribute to estrogen carcinogenesis by both direct and indirect genotoxic mechanisms. O-Methylation catalyzed by catechol-O-methyltransferase (COMT) is a Phase II metabolic inactivation pathway for catechol estrogens. We and others have found that a polymorphism in the COMT gene, which codes for a low activity variant of the COMT enzyme, is associated with an increased risk of developing breast cancer; therefore, the goal of the current study was to investigate the role of decreased COMT activity on estrogen catechol levels and on oxidative DNA damage, as measured by 8-hydroxy-2'-deoxyguanosine (8-oxo-dG) levels. MCF-7 cells were pretreated with dioxin as a means to increase estrogen metabolism to catechol estrogens, then treated with estradiol (E-2) +/- Ro 41-0960, a COMT-specific inhibitor. After extraction from culture medium, estrogen metabolites were separated using an high-performance liquid chromatography-electrochemical detection method. As expected, dioxin dramatically increased E-2 oxidative metabolism, primarily to its 2-OH and 2-methoxy metabolites. The COMT inhibitor blocked 2-methoxy E-2 formation. This was associated with increased 2-hydroxy E-2 (2-OH E-2) and 8-oxo-dG levels. In the presence of COMT inhibition, increased oxidative DNA damage was detected in MCF-7 cells exposed to as low as 0.1 muM E-2, whereas in the absence of COMT inhibition, no increase in 8-oxo-dG was detected at E-2 concentrations less than or equal to 10 muM. This study is the first to show that O-methylation of 2-OH E-2 by COMT is protective against oxidative DNA damage caused by 2-OH E-2, a major oxidative metabolite of E-2. C1 Johns Hopkins Univ, Bloombert Sch Publ Hlth, Dept Environm Hlth Sci, Div Toxicol Sci, Baltimore, MD 21205 USA. Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Yager, JD (reprint author), Johns Hopkins Univ, Bloombert Sch Publ Hlth, Dept Environm Hlth Sci, Div Toxicol Sci, Room 7032,615 N Wolfe St, Baltimore, MD 21205 USA. FU NCI NIH HHS [CA77550]; NIEHS NIH HHS [P30 ES03819, T32 ES07141, T32ES07141] NR 59 TC 76 Z9 78 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD OCT 15 PY 2001 VL 61 IS 20 BP 7488 EP 7494 PG 7 WC Oncology SC Oncology GA 484UF UT WOS:000171707400022 PM 11606384 ER PT J AU Liappis, AP Kan, VL Rochester, CG Simon, GL AF Liappis, AP Kan, VL Rochester, CG Simon, GL TI The effect of statins on mortality in patients with bacteremia SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID CARDIOVASCULAR EVENTS; PROTEIN PRENYLATION; MEVALONATE PATHWAY; PRAVASTATIN; INTERVENTION; INFLAMMATION; CHEMOTAXIS AB The statins, inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, act to regulate the biosynthesis of cholesterol. Statins also deplete nonsterol cholesterol precursors, the isoprenoids, which are necessary for prenylation of critical membrane proteins that regulate cellular communication, including the inflammatory response. In a retrospective review of 388 bacteremic infections due to aerobic gram-negative bacilli and Staphylococcus aureus, there was a significant reduction in both overall (6% vs. 28%; P = .002) and attributable (3% vs. 20%; P = .010) mortality among patients taking statins compared with patients not taking statins. This reduction in mortality persisted in a multivariate analysis (odds ratio, 7.6; 95% confidence interval, 1.01-57.5). Among the statin group, diabetes, hypertension, and coronary artery disease were more prevalent (P < .001), and there were more skin and soft tissue infections identified as sources of bacteremia (P = .008). These data suggest a potential clinical role of statins in bacteremic infection; however, the mechanism by which mortality is reduced remains undefined. C1 George Washington Univ, Med Ctr, Div Infect Dis, Washington, DC 20037 USA. Vet Affairs Med Ctr, Dept Med, Div Infect Dis, Washington, DC 20422 USA. US FDA, Ctr Drug Evaluat & Res, Div Biometr 3, Rockville, MD 20857 USA. RP Simon, GL (reprint author), George Washington Univ, Med Ctr, Div Infect Dis, 2150 Penn Ave NW,Suite 5-411, Washington, DC 20037 USA. NR 15 TC 204 Z9 215 U1 1 U2 5 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD OCT 15 PY 2001 VL 33 IS 8 BP 1352 EP 1357 DI 10.1086/323334 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 476NZ UT WOS:000171235600012 PM 11565076 ER PT J AU Lin, FYC Philips, JB Azimi, PH Weisman, LE Clark, P Rhoads, GG Regan, J Concepcion, NF Frasch, CE Troendle, J Brenner, RA Gray, BM Bhushan, R Fitzgerald, G Moyer, P Clemens, JD AF Lin, FYC Philips, JB Azimi, PH Weisman, LE Clark, P Rhoads, GG Regan, J Concepcion, NF Frasch, CE Troendle, J Brenner, RA Gray, BM Bhushan, R Fitzgerald, G Moyer, P Clemens, JD TI Level of maternal antibody required to protect neonates against early-onset disease caused by group B streptococcus type Ia: A multicenter, seroepidemiology study SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID CONJUGATE VACCINES; III POLYSACCHARIDE; MOUSE PROTECTION; IGG ANTIBODY; INFECTION; SUSCEPTIBILITY; IMMUNIZATION; SERUM; IMMUNOGENICITY; PREVENTION AB Because of the difficulty of conducting efficacy trials of vaccines against group B streptococcus (GBS), the licensure of these vaccines may have to rely on studies that measure vaccine-induced antibody levels that correlate with protection. This study estimates the level of maternal antibody required to protect neonates against early-onset disease (EOD) caused by GBS type Ia. Levels of maternal serum IgG GBS Ia antibodies, measured by ELISAs in 45 case patients (neonates with EOD caused by GBS Ia) and in 319 control subjects (neonates colonized by GBS Ia but without EOD) born at greater than or equal to 34 weeks gestation were compared. The probability of developing EOD declined with increasing maternal levels of IgG GBS Ia antibody (P = .03). Neonates whose mothers had levels of IgG GBS Ia antibody greater than or equal to5 mug/mL had an 88% lower risk (95% confidence interval, 7%-98%) of developing type-specific EOD, compared with those whose mothers had levels <0.5 g/mL. A vaccine that induces IgG GBS Ia antibody levels greater than or equal to5 mug/mL in mothers can be predicted to confer a high degree of type-specific immunity to EOD to their infants. C1 NICHHD, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. Univ Alabama, Dept Pediat, Birmingham, AL USA. Westat Corp, Rockville, MD USA. Childrens Hosp Med Ctr No Calif, Oakland, CA USA. Baylor Coll Med, Houston, TX 77030 USA. Univ Florida, Dept Obstet & Gynecol, Gainesville, FL 32611 USA. Univ Med & Dent New Jersey, Dept Environm & Community Med, Piscataway, NJ 08854 USA. Columbia Univ Hlth Sci, New York, NY USA. RP Lin, FYC (reprint author), 6100 Execut Blvd,Rm 7b03,MSC 7510, Bethesda, MD 20892 USA. FU NICHD NIH HHS [HD-43217, HD-43220, HD-43219, HD-43215, HD-53233, HD-43214, HD-43218] NR 42 TC 51 Z9 52 U1 0 U2 2 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 2001 VL 184 IS 8 BP 1022 EP 1028 DI 10.1086/323350 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 476NG UT WOS:000171233200010 PM 11574917 ER PT J AU Keane, J Gershon, S Wise, RP Mirabile-Levens, E Kasznica, J Schwieterman, WD Siegel, JN Braun, MM AF Keane, J Gershon, S Wise, RP Mirabile-Levens, E Kasznica, J Schwieterman, WD Siegel, JN Braun, MM TI Tuberculosis associated with infliximab, a tumor necrosis factor (alpha)-neutralizing agent SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID MYCOBACTERIUM-TUBERCULOSIS; FACTOR-ALPHA; RHEUMATOID-ARTHRITIS; CELL-DEATH; APOPTOSIS; INFECTION; MACROPHAGES; GAMMA; MICE; TNF AB Background: Infliximab is a humanized antibody against tumor necrosis factor (alpha) (TNF-(alpha)) that is used in the treatment of Crohn's disease and rheumatoid arthritis. Approximately 147,000 patients throughout the world have received infliximab. Excess TNF-(alpha) in association with tuberculosis may cause weight loss and night sweats, yet in animal models it has a protective role in the host response to tuberculosis. There is no direct evidence of a protective role of TNF-(alpha) in patients with tuberculosis. Methods: We analyzed all reports of tuberculosis after infliximab therapy that had been received as of May 29, 2001, through the MedWatch spontaneous reporting system of the Food and Drug Administration. Results: There were 70 reported cases of tuberculosis after treatment with infliximab for a median of 12 weeks. In 48 patients, tuberculosis developed after three or fewer infusions. Forty of the patients had extrapulmonary disease (17 had disseminated disease, 11 lymph-node disease, 4 peritoneal disease, 2 pleural disease, and 1 each meningeal, enteric, paravertebral, bone, genital, and bladder disease). The diagnosis was confirmed by a biopsy in 33 patients. Of the 70 reports, 64 were from countries with a low incidence of tuberculosis. The reported frequency of tuberculosis in association with infliximab therapy was much higher than the reported frequency of other opportunistic infections associated with this drug. In addition, the rate of reported cases of tuberculosis among patients treated with infliximab was higher than the available background rates. Conclusions: Active tuberculosis may develop soon after the initiation of treatment with infliximab. Before prescribing the drug, physicians should screen patients for latent tuberculosis infection or disease. (N Engl J Med 2001;345:1098-104.) Copyright (C) 2001 Massachusetts Medical Society. C1 Boston Univ, Sch Med, Ctr Pulm, Dept Med, Boston, MA 02118 USA. US FDA, Ctr Biol Evaluat & Res, Off Biostat & Epidemiol, Div Epidemiol, Rockville, MD 20857 USA. US FDA, Off Therapeut Res & Review, Rockville, MD 20857 USA. RP Keane, J (reprint author), Boston Univ, Sch Med, Ctr Pulm, Dept Med, 80 E Concord St,R-304, Boston, MA 02118 USA. OI Keane, Joseph/0000-0001-5313-385X FU NHLBI NIH HHS [HL-03964] NR 40 TC 2124 Z9 2187 U1 16 U2 80 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 11 PY 2001 VL 345 IS 15 BP 1098 EP 1104 DI 10.1056/NEJMoa011110 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 480QH UT WOS:000171473100004 PM 11596589 ER PT J AU Amexis, G Oeth, P Abel, K Ivshina, A Pelloquin, F Cantor, CR Brau, A Chumakov, K AF Amexis, G Oeth, P Abel, K Ivshina, A Pelloquin, F Cantor, CR Brau, A Chumakov, K TI Quantitative mutant analysis of viral quasispecies by chip-based matrix-assisted laser desorption/ionization time-of-flight mass spectrometry SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID MUMPS VACCINE STRAIN; NUCLEOTIDE-SEQUENCE; POLIOVIRUS VACCINE; MALDI; IDENTIFICATION; MENINGITIS; EXTENSION; ARRAYS; VIRUS AB RNA viruses exist as quasispecies, heterogeneous and dynamic mixtures of mutants having one or more consensus sequences. An adequate description of the genomic structure of such viral populations must include the consensus sequence(s) plus a quantitative assessment of sequence heterogeneities. For example, in quality control of live attenuated viral vaccines, the presence of even small quantities of mutants or revertants may indicate incomplete or unstable attenuation that may influence vaccine safety. Previously, we demonstrated the monitoring of oral poliovirus vaccine with the use of mutant analysis by PCR and restriction enzyme cleavage (MAPREC). In this report, we investigate genetic variation in live attenuated mumps virus vaccine by using both MAPREC and a platform (DNA MassArray) based on matrix-assisted laser desportion/ionization time-of-flight (MALDI-TOF) mass spectrometry. Mumps vaccines prepared from the Jeryl Lynn strain typically contain at least two distinct viral substrains, JL1 and JL2, which have been characterized by full length sequencing. We report the development of assays for characterizing sequence variants in these substrains and demonstrate their use in quantitative analysis of substrains and sequence variations in mixed virus cultures and mumps vaccines. The results obtained from both the MAPREC and MALDI-TOF methods showed excellent correlation. This suggests the potential utility of MALDI-TOF for routine quality control of live viral vaccines and for assessment of genetic stability and quantitative monitoring of genetic changes in other RNA viruses of clinical interest. C1 US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. SEQUENOM Inc, Genom Dept, San Diego, CA 92121 USA. Aventis Pasteur, F-69280 Marcy Letoile, France. RP Chumakov, K (reprint author), US FDA, Ctr Biol Evaluat & Res, 1401 Rockville Pike,HFM 470, Rockville, MD 20852 USA. NR 30 TC 35 Z9 35 U1 0 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 9 PY 2001 VL 98 IS 21 BP 12097 EP 12102 DI 10.1073/pnas.211423298 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 482DE UT WOS:000171558900051 PM 11593021 ER PT J AU Takeshita, S Takeshita, F Haddad, DE Janabi, N Klinman, DM AF Takeshita, S Takeshita, F Haddad, DE Janabi, N Klinman, DM TI Activation of microglia and astrocytes by CpG oligodeoxynucleotides SO NEUROREPORT LA English DT Article DE astrocyte; CpG oligodeoxynucleotides; cytokines; microglia ID TUMOR NECROSIS FACTOR; MOTIFS; CELLS; DNA; INTERLEUKIN-6; CYTOKINES; INDUCTION AB Bacterial DNA and synthetic oligodeoxynucleotides (ODN) containing unmethylated CpG motifs stimulate cells of the immune system to secrete a variety of cytokines and chemokines. This function can be carried out by microglia and astrocytes in the CNS. To evaluate the effect of CpG ODIN on microglia and astrocytes, purified cells were isolated and cultured in vitro. CpG ODN rapidly up-regulated their production of IL-1 beta, IL-6, IL-12, TNF alpha, MIP-I alpha and/or MIP-1 beta. In vivo, systemically administered CpG ODIN up-regulated the expression of mRNA encoding cytokines and chemokines in normal mouse brain. These findings suggest that CpG ODN can directly activate immune cells of the CNS. NeuroReport 12:3029-3032 (C) 2001 Lippincott Williams & Wilkins. C1 US FDA, Sect Retroviral Immunol, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. USN, Malaria Program, Med Res Inst, Bethesda, MD 20084 USA. NINCDS, Lab Mol Med & Neurosci, NIH, Bethesda, MD 20892 USA. RP Klinman, DM (reprint author), US FDA, Sect Retroviral Immunol, Ctr Biol Evaluat & Res, Bldg 29A,Rm 3 D 10, Bethesda, MD 20892 USA. NR 20 TC 55 Z9 58 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD OCT 8 PY 2001 VL 12 IS 14 BP 3029 EP 3032 DI 10.1097/00001756-200110080-00010 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 476ND UT WOS:000171232800009 PM 11568631 ER PT J AU Schwetz, BA AF Schwetz, BA TI Hypercalcemia of malignancy SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT News Item C1 US FDA, Off Commissioner Food & Drugs, Rockville, MD 20857 USA. RP Schwetz, BA (reprint author), US FDA, Off Commissioner Food & Drugs, HF-1,Room 14-71,5600 Fishers Ln, Rockville, MD 20857 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD OCT 3 PY 2001 VL 286 IS 13 BP 1569 EP 1569 DI 10.1001/jama.286.13.1569-b PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 478HH UT WOS:000171340600005 PM 11585463 ER PT J AU Schwetz, BA AF Schwetz, BA TI Congestive heart failure treatment SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT News Item C1 US FDA, Off Commissioner Food & Drug, Rockville, MD 20857 USA. RP Schwetz, BA (reprint author), US FDA, Off Commissioner Food & Drug, HF-1,Room 14-71,5600 Fishers Ln, Rockville, MD 20857 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD OCT 3 PY 2001 VL 286 IS 13 BP 1569 EP 1569 DI 10.1001/jama.286.13.1569-b PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 478HH UT WOS:000171340600006 PM 11585463 ER PT J AU Schwetz, BA AF Schwetz, BA TI Reprocessing of single-use devices SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT News Item C1 US FDA, Off Commissioner Food & Drugs, Rockville, MD 20857 USA. RP Schwetz, BA (reprint author), US FDA, Off Commissioner Food & Drugs, HF-1,Room 14-71,5600 Fishers Ln, Rockville, MD 20857 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD OCT 3 PY 2001 VL 286 IS 13 BP 1569 EP 1569 DI 10.1001/jama.286.13.1569-b PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 478HH UT WOS:000171340600007 PM 11585463 ER PT J AU Joseph, L Sweeney, C Coles, B Fares, M Hutchins, L Ambrosone, C AF Joseph, L Sweeney, C Coles, B Fares, M Hutchins, L Ambrosone, C TI Glutathione S-transferase pi and alpha enzyme expression and patient survival in primary breast carcinoma. SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Meeting Abstract C1 Univ Arkansas Med Sci, Dept Pathol, Little Rock, AR 72205 USA. Univ Arkansas Med Sci, Dept Surg, Little Rock, AR USA. Natl Ctr Toxicol Res, Div Mol Epidemiol, Jefferson, AR USA. Univ Arkansas Med Sci, Div Hematol & Oncol, Little Rock, AR 72205 USA. Mt Sinai Sch Med, Derald H Ruttenberg Canc Ctr, Canc Epidemiol Program, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLIN PATHOLOGISTS PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD OCT PY 2001 VL 116 IS 4 MA 35 BP 598 EP 598 PG 1 WC Pathology SC Pathology GA 478HW UT WOS:000171341800051 ER PT J AU Phillips, J Beam, S Brinker, A Holquist, C Honig, P Lee, LY Pamer, C AF Phillips, J Beam, S Brinker, A Holquist, C Honig, P Lee, LY Pamer, C TI Retrospective analysis of mortalities associated with medication errors SO AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY LA English DT Article DE communication; data collection; death; dosage; drug administration routes; errors; medication; Food and Drug Administration (US); reports; toxicity ID ADVERSE DRUG-REACTIONS; INTENSIVE-CARE UNIT; HOSPITALIZED-PATIENTS; EVENTS; COST AB The types, causes, contributing factors, and patient demographics of fatal medication errors were reviewed. Case reports of medication errors from hospitals, ambulatory care settings, and patients' homes that were entered in FDA's Adverse Event Reporting System during 1993-98 were the source of information on fatal medication errors. Each report was classified using predefined criteria and a taxonomy developed by the National Coordinating Council for Medication Error Reporting and Prevention. The types, causes, contributing factors, and patient demographics were identified, and the causality of each case was assessed to prevent future fatalities. The data indicated 5366 medication error reports. Fifty-nine reports were excluded and classified as duplicate reports or intentional overdoses. Of the remaining medication error reports, 68.2% resulted in serious patient outcomes and 9.8% were fatal. Of the 469 fatal medication error reports, 48.6% occurred in patients over 60 years. The most common types of errors resulting in patient death involved administering an improper dose (40.9%), administering the wrong drug (16%), and using the wrong route of administration (9.5%). The most common causes of errors were performance and knowledge deficits (44%) and communication errors (15.8%). Fatal medication errors accounted for approximately 10% of medication errors reported to FDA and were most frequently the result of improper dosing of the intended drug and administration of an incorrect drug. A review of case reports of medication errors from 1993 to 1998 yielded information on the most frequent causes of and contributing factors involved in fatal medication errors. C1 US FDA, Off Post Mkt Drug Risk Assessment, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. Natl Coordinating Council Safe Medicat Practices, Rockville, MD USA. RP Phillips, J (reprint author), US FDA, Off Post Mkt Drug Risk Assessment, Ctr Drug Evaluat & Res, HFD-400 Room 15B03,5600 Fishers Lane, Rockville, MD 20857 USA. NR 19 TC 122 Z9 130 U1 2 U2 5 PU AMER SOC HEALTH-SYSTEM PHARMACISTS PI BETHESDA PA 7272 WISCONSIN AVE, BETHESDA, MD 20814 USA SN 1079-2082 J9 AM J HEALTH-SYST PH JI Am. J. Health-Syst. Pharm. PD OCT 1 PY 2001 VL 58 IS 19 BP 1835 EP 1841 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 479PF UT WOS:000171412200020 PM 11596700 ER PT J AU Al-Gazali, LI Padmanabhan, R Melnyk, S Yi, P Pogribny, IP Pogribna, M Bakir, M Hamid, ZA Abdulrazzaq, Y Dawodu, A James, SJ AF Al-Gazali, LI Padmanabhan, R Melnyk, S Yi, P Pogribny, IP Pogribna, M Bakir, M Hamid, ZA Abdulrazzaq, Y Dawodu, A James, SJ TI Abnormal folate metabolism and genetic polymorphism of the folate pathway in a child with Down syndrome and neural tube defect SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE Down syndrome; neural tube defect; defective folate metabolism ID COULOMETRIC ELECTROCHEMICAL DETECTION; MATERNAL RISK-FACTORS; METHYLENETETRAHYDROFOLATE REDUCTASE; DOWN-SYNDROME; DNA METHYLATION; SPINA-BIFIDA; HOMOCYSTEINE; INDIVIDUALS; CHROMOSOME; POPULATION AB The association of neural tube defects (NTDs) with Down syndrome (trisomy 21) and altered folate metabolism in both mother and affected offspring provide a unique opportunity for insight into the etiologic role of folate deficiency in these congenital anomalies. We describe here the case of a male child with trisomy 21, cervical meningomyelocele, agenesis of corpus callosum, hydrocephaly, cerebellar herniation into the foramen magnum, and shallow posterior cranial fossa. Molecular analysis of the methylenetetrahydrofolate (MTHFR) gene revealed homozygosity for the mutant 677C-->T polymorphism in both the mother and child. The plasma homocysteine of the mother was highly elevated at 25.0 mu mol/L and was associated with a low methionine level of 22.1 mu mol/L. Her S-adenosylhomocysteine (SAH) level was three times that of reference normal women, resulting in a markedly reduced ratio of S-adenosylmethionine (SAM) to SAH and significant DNA hypomethylation in lymphocytes. The child had low plasma levels of both homocysteine and methionine and a reduced SAM/SAH ratio that was also associated with lymphocyte DNA hypomethylation. In addition, the child had a five-fold increase in cystathionine level relative to normal children, consistent with over-expression of the cystathionine beta synthase gene present on chromosome 21. We suggest that altered folate status plus homozygous mutation in the MTHFR gene in the mother could promote chromosomal instability and meiotic non-disjunction resulting in trisomy 21. Altered folate status and homozygous TT mutation in the MTHFR gene in both mother and child would be expected to increase the risk of neural tube defects. The presence of both trisomy 21 and postclosure NTD in the same child supports the need for an extended periconceptional period of maternal folate supplementation to achieve greater preventive effects for both NTD and trisomy 21. (C) 2001 Wiley-Liss, Inc. C1 UAE Univ, Fac Med & Hlth Sci, Dept Pediat, Al Ain, U Arab Emirates. UAE Univ, Fac Med & Hlth Sci, Dept Anat, Al Ain, U Arab Emirates. Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. Al Ain Hosp, Dept Paediat, Al Ain, U Arab Emirates. RP Al-Gazali, LI (reprint author), UAE Univ, Fac Med & Hlth Sci, Dept Pediat, POB 17666, Al Ain, U Arab Emirates. RI dawodu, adekunle/M-9985-2014 OI dawodu, adekunle/0000-0002-2050-800X NR 35 TC 59 Z9 61 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 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD OCT 1 PY 2001 VL 103 IS 2 BP 128 EP 132 DI 10.1002/ajmg.1509 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 473LK UT WOS:000171045300005 PM 11568918 ER PT J AU Kang, H Magee, C Mahan, C Lee, K Murphy, F Jackson, L Matanoski, G AF Kang, H Magee, C Mahan, C Lee, K Murphy, F Jackson, L Matanoski, G TI Pregnancy outcomes among US Gulf War veterans: A population-based survey of 30,000 veterans SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE Gulf War; birth defects; spontaneous abortions ID SPONTANEOUS-ABORTION; BIRTH-DEFECTS; CHILDREN; RISK AB PURPOSE: We evaluated an association between veterans' Gulf War service and reported adverse pregnancy Outcomes. METHODS: We conducted a health survey in which selected reproductive outcomes of a population-based sample of 15,000 Gulf War veterans representing four military branches and three unit components (active, reserve, and National Guard) were compared to those of 15,000 non-Gulf veteran controls. RESULTS: Male Gulf veterans, compared with their non-Gulf veteran controls, reported a significantly higher rate of miscarriage (odds ratio [OR] = 1.62; 95% confidence interval [CI] = 1.32-1.99). Female Gulf veterans also reported more miscarriages than their respective controls, although their excess was not statistically significant (OR= 1.35; CI = 0.97-1.89). Both men and women deployed to the Gulf theater reported significant excesses of birth defects among their liveborn infants. These excess rates also extended to the subset of "moderate to severe" birth defects [males: OR= 1.78 (CI = 1.19-2.66); females: OR = 2.80 (CI = 1.26-6.25)]. No statistically significant differences by deployment status were found among men or women for stillbirths, pre-term deliveries or infant mortality. CONCLUSION: The risk of veterans reporting birth defects among their children was significantly associated with veteran's military service in the Gulf War. This observation needs to lie confirmed by a review of medical records to rule out possible reporting bias. (C) 2001 Elsevier Science Inc. All rights reserved. C1 Dept Vet Affairs, Environm Epidemiol Serv, Washington, DC 20036 USA. Dept Hlth & Human Serv, Food & Drug Adm, Washington, DC USA. Dept Vet Affairs, Off Under Secretary Hlth, Washington, DC USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Baltimore, MD USA. RP Kang, H (reprint author), Dept Vet Affairs, Environm Epidemiol Serv, 1120 20th St NW,Suite 950, Washington, DC 20036 USA. NR 22 TC 44 Z9 44 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 1047-2797 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD OCT PY 2001 VL 11 IS 7 BP 504 EP 511 DI 10.1016/S1047-2797(01)00245-9 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 475LH UT WOS:000171165100009 PM 11557183 ER PT J AU Simjee, S McDermott, PF Wagner, DD White, DG AF Simjee, S McDermott, PF Wagner, DD White, DG TI Variation within the vat(E) allele of Enterococcus faecium isolates from retail poultry samples SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID SATA GENE; RESISTANCE; ANIMALS AB In a survey of retail meat samples, twelve quinupristin-dalfopristin-resistant (MICs, greater than or equal to4 mg/liter) Entero-coccus faecium isolates that carried a vat(E) gene were recovered. DNA sequence comparison revealed five new variations in the vat(E) allele among 12 isolates, which were designated vat(E-4) through vat(E-8); two isolates had vat(E-1). There was no correlation between the number of base changes and the quinupristin-dalfopristin MIC. C1 US FDA, Res Off, Ctr Vet Med, Div Anim & Food Microbiol, Laurel, MD 20708 USA. RP Simjee, S (reprint author), US FDA, Res Off, Ctr Vet Med, Div Anim & Food Microbiol, Laurel, MD 20708 USA. NR 7 TC 10 Z9 11 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 OCT PY 2001 VL 45 IS 10 BP 2931 EP 2932 DI 10.1128/AAC.45.10.2931-2932.2001 PG 2 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 475GQ UT WOS:000171154500042 PM 11557494 ER PT J AU Guo, X Chen, JR Brackett, RE Beuchat, LR AF Guo, X Chen, JR Brackett, RE Beuchat, LR TI Survival of Salmonellae on and in tomato plants from the time of inoculation at flowering and early stages of fruit development through fruit ripening SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID ESCHERICHIA-COLI; PRODUCE; GROWTH; MONTEVIDEO; OUTBREAK; SPROUTS AB The fate of salmonellae applied to tomato plants was investigated. Five Salmonella serotypes were used to inoculate tomato plants before and after fruits set, either by injecting stems with inoculum or brushing flowers with it. Ripe tomato fruits were subjected to microbiological analysis. Peptone wash water, homogenates of stem scar tissues, and homogenates of fruit pulp were serially diluted and plated on bismuth sulfite agar before and after enrichment. Presumptive Salmonella colonies were confirmed by serological tests, PCR assay using HILA2 primers, and enterobacterial repetitive intergenic consensus PCR. Of 30 tomatoes harvested from inoculated plants, 11 (37%) were positive for Salmonella. Of the Salmonella-positive tomatoes, 43 and 40%, respectively, were from plants receiving stem inoculation before and after flower set. Two of eight tomatoes produced from inoculated flowers contained Salmonella. Higher percentages of surface (82%) and stem scar tissue (73%) samples, compared to pulp of Salmonella-positive tomatoes (55%), harbored the pathogen. Of the five serotypes in the inoculum, Montevideo was the most persistent, being isolated from tomatoes 49 days after inoculation, and Poona was the most dominant, being present in 5 of 11 Salmonella-positive tomatoes. Results suggest that Salmonella cells survive in or on tomato fruits from the time of inoculation at flowering through fruit ripening. Tomato stems and flowers are possible sites at which Salmonella may attach and remain viable during fruit development, thus serving as routes or reservoirs for contaminating ripened fruit. C1 Univ Georgia, Ctr Food Safety, Griffin, GA 30223 USA. Univ Georgia, Dept Food Sci & Technol, Griffin, GA 30223 USA. US FDA, Off Plant Dairy Foods & Beverages, Washington, DC 20204 USA. RP Beuchat, LR (reprint author), Univ Georgia, Ctr Food Safety, 1109 Expt St, Griffin, GA 30223 USA. NR 32 TC 140 Z9 147 U1 0 U2 15 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 2001 VL 67 IS 10 BP 4760 EP 4764 DI 10.1128/AEM.67.10.4760-4764.2001 PG 5 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 476PJ UT WOS:000171237700048 PM 11571182 ER PT J AU Hofacre, CL White, DG Maurer, JJ Morales, C Lobsinger, C Hudson, C AF Hofacre, CL White, DG Maurer, JJ Morales, C Lobsinger, C Hudson, C TI Characterization of antibiotic-resistant bacteria in rendered animal products SO AVIAN DISEASES LA English DT Article DE antibiotic resistance; rendered products; feed; Salmonella; Enterobacteriaceae; integrons ID ESCHERICHIA-COLI; SALMONELLA; POULTRY; GENE; ENTEROBACTERIACEAE; INTEGRON; FLORFENICOL; CHICKENS; PLANTS; FEED AB Antibiotics are used in food animal production to treat diseases and also to improve performance. Antibiotics are riot used on all farms, and antibiotic resistance is occasionally found on farms that do not use antibiotics. Rendered animal protein products a-re often included in poultry feeds and could potentially serve as a source of antibiotic-resistant bacteria. One hundred sixty-five rendered animal protein products from cattle, poultry, and fish were aseptically collected from poultry feed mills. Fifty-five percent of the poultry meal samples had detectable levels of gram-negative bacteria ranging from 40 to 10,440 colony-forming units/g of sample. Poultry meal and meat and bone meal had the greatest number of samples With bacteria resistant to five or more antibiotics. A high percentage of feed samples (85%) contained bacteria resistant to amoxicillin, ampicillin, clavulanic acid, or cephalothin, whereas few samples contained bacteria resistant to ciprofloxacin, kanamycin, or trimethoprim/sulfamethoxazole. Acinetobacter calcoaceticus, Citrobacter freundii, and Enterobacter cloacae were the most commonly isolated antibiotic-resistant bacteria. Isolation for Salmonella was also performed, with 14% of tire meat and bone meal samples containing Salmonella sp. Only one of the meat and bone meal isolates, Salmonella livingstone, was resistant to five or more antibiotics. Many of the antibiotic-resistant bacteria contained integrons, genetic elements that mediate multiple drug resistance. C1 Univ Georgia, Coll Vet Med, Dept Avian Med, Athens, GA 30602 USA. US FDA, Dept Hlth & Human Serv, Ctr Vet Med B, Res Off, Laurel, MD 20708 USA. RP Hofacre, CL (reprint author), Univ Georgia, Coll Vet Med, Dept Avian Med, Athens, GA 30602 USA. NR 30 TC 21 Z9 22 U1 0 U2 11 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 2001 VL 45 IS 4 BP 953 EP 961 DI 10.2307/1592874 PG 9 WC Veterinary Sciences SC Veterinary Sciences GA 506XZ UT WOS:000172998200018 PM 11785899 ER PT J AU Ye, XM Carp, RI Schmued, LC Scallet, AC AF Ye, XM Carp, RI Schmued, LC Scallet, AC TI Fluoro-Jade and silver methods: application to the neuropathology of scrapie, a transmissible spongiform encephalopathy SO BRAIN RESEARCH PROTOCOLS LA English DT Article DE hamsters; rats; prions; astrocytes; ibogaine; kainic acid; neurodegeneration ID NEURONAL DEGENERATION; MURINE SCRAPIE; INFECTED MICE; NEURODEGENERATION; RAT; CEREBELLUM; APOPTOSIS; IBOGAINE; LOCALIZATION; CELLS AB Traditional methods for evaluating neurodegeneration include variations of Nauta's selective silver-staining techniques. The Fluoro-Jade (FJ) method applies a novel florescent, anionic stain for localizing degenerating neurons. FJ has produced comparable results to the silver methods, when both have been applied to detect neurodegeneration in animals treated acutely with a variety of neurotoxins, including kainic acid (KA). ibogaine (IBO), 3-nitropropionic acid (3-NPA), domoic acid and others. The potential value of methods selective for neurodegeneration in elucidating the pathophysiology of transmissible spongiform encephalopathies (TSEs), such as the prion disease 'scrapie', has not yet been investigated. Using frozen or paraffin sections stained with FJ or silver, we evaluated the brains of hamsters inoculated with either the 263K or the 139H strains of scrapie, originally passaged from sheep into mice and then into hamsters. As a positive control, e also examined sections from IBO-treated rats, which experience degeneration restricted to small clusters of Purkinje neurons located in the paravermal region of the cerebellum. As expected. both FJ and silver methods delineated this identical pattern of neurodegeneration. characteristic of IBO exposure, Surprisingly, only a small number of FJ or silver-labeled cortical neurons were observed in scrapie-infected hamsters evaluated near the end of their incubation period but before obvious spongiform pathology. Instead. there was intense fluorescent staining of astrocytes in scrapie-infected hamsters, especially in the Cortex, Corpus callosum. and hypothalamus. Detailed protocols describing the application of the degeneration-selective methods we utilized are presented and compared. (C) 2001 Elsevier Science B.V. All rights reserved. C1 New York State Inst Basic Res Dev Disabil, Staten Isl, NY 10314 USA. Natl Ctr Toxicol Res, FDA, Div Neurotoxicol, Jefferson, AR USA. RP Ye, XM (reprint author), New York State Inst Basic Res Dev Disabil, 1050 Forest Hill Rd, Staten Isl, NY 10314 USA. FU NIA NIH HHS [AG09017] NR 26 TC 39 Z9 42 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1385-299X J9 BRAIN RES PROTOC JI Brain Res. Protoc. PD OCT PY 2001 VL 8 IS 2 BP 104 EP 112 DI 10.1016/S1385-299X(01)00086-1 PG 9 WC Biochemical Research Methods; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 496YG UT WOS:000172425500003 PM 11673092 ER PT J AU Herman, EH Zhang, J Rifai, N Lipshultz, SE Hasinoff, BB Chadwick, DP Knapton, A Chai, J Ferrans, VJ AF Herman, EH Zhang, J Rifai, N Lipshultz, SE Hasinoff, BB Chadwick, DP Knapton, A Chai, J Ferrans, VJ TI The use of serum levels of cardiac troponin T to compare the protective activity of dexrazoxane against doxorubicin and mitoxantrone-induced cardiotoxicity SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE doxorubicin; mitoxantrone; dexrazoxane; cardiotoxicity; cardiac troponin T ID SPONTANEOUSLY HYPERTENSIVE RATS; ACUTE MYOCARDIAL-INFARCTION; CARDIOPROTECTIVE AGENT; BEAGLE DOGS; DIAGNOSTIC EFFICIENCY; ANTICANCER COMPOUND; SAFETY ASSESSMENT; BREAST-CANCER; ICRF-187; TOXICITY AB Purpose: To compare the protective effect of dexrazoxane (DRZ) against cardiotoxicity induced by doxorubicin (DXR) and mitoxantrone (MTX). Methods: Adult male spontaneously hypertensive rats (SHR) were treated with 1 mg/kg DXR (i.v.) or 0.5 mg/kg MTX (i.v.), either alone or 30 min after 25 mg/kg DRZ (i.p.) weekly for up to 12 weeks. Animals treated with DXR alone either died (n = 2) or were killed (n = 3) at a cumulative dose of 10 mg/kg. The severity of cardiac lesions (cytoplasmic vacuolization and myofibrillar loss) were graded semiquantitatively by light microscopy on a scale of 0 to 3. Results: Cardiac lesions were observed in all SHR given DXR or MTX alone, and were attenuated in those given DRZ prior to either DXR (mean lesion scores 2.7 vs 1.5; P < 0.05) or MTX (mean lesion scores 2.0 vs 1.25; P <0.05). Cardioprotection was also demonstrated by monitoring serum levels of cardiac troponin T (cTnT), which were elevated in all animals receiving DXR or MTX alone. These elevations were attenuated in SHR given the combination of DXR and DRZ (mean values 0.79 ng/ml vs 0.24 ng/ml; P < 0.05) and MTX and DRZ (mean values 0.19 ng/ml vs 0.04 ng/ml; P < 0.05). Biochemical studies have shown that both DXR and MTX form potentially cardiotoxic complexes with iron. ADR-925 (the hydrolysis product of DRZ) and other chelators (EDTA., diethylenetriaminepentaacetic acid and desferrioxamine) removed Fe(III) from its complex with MTX or DXR. Conclusions: The present study showed that DRZ significantly attenuates the cardiotoxicity induced by DXR and MTX, and that this protective activity can be assessed by morphological evaluation of cardiac tissues and by monitoring the concentrations of cTnT in serum. C1 US FDA, Ctr Drug Evaluat & Res, Div Appl Pharmacol Res HFD910, Laurel, MD 20708 USA. Harvard Univ, Childrens Hosp, Sch Med, Dept Lab Med, Boston, MA 02115 USA. Univ Rochester, Med Ctr, Sch Med & Dent, Div Pediat Cardiol, Rochester, NY 14642 USA. Univ Manitoba, Fac Pharm, Winnipeg, MB R3T 2N2, Canada. NHLBI, Pathol Sect, NIH, Bethesda, MD 20892 USA. RP Herman, EH (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Appl Pharmacol Res HFD910, 8301 Muirkirk Rd, Laurel, MD 20708 USA. NR 42 TC 74 Z9 76 U1 0 U2 1 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 OCT PY 2001 VL 48 IS 4 BP 297 EP 304 DI 10.1007/s002800100348 PG 8 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 486EQ UT WOS:000171805800007 PM 11710630 ER PT J AU Ambrosone, CB Sweeney, C Coles, BF Thompson, PA McClure, GY Korourian, S Fares, MY Stone, A Kadlubar, FF Hutchins, LF AF Ambrosone, CB Sweeney, C Coles, BF Thompson, PA McClure, GY Korourian, S Fares, MY Stone, A Kadlubar, FF Hutchins, LF TI Polymorphisms in glutathione S-transferases (GSTM1 and GSTT1) and survival after treatment for breast cancer SO CANCER RESEARCH LA English DT Article ID GENETIC POLYMORPHISMS; OVARIAN-CANCER; TUMOR-MARKER; CYCLOPHOSPHAMIDE; ANTIOXIDANT; ASSOCIATION; ADRIAMYCIN; ENZYMES; M1; P1 AB The response to treatment for breast cancer is likely predicted by a number of disease and tumor tissue characteristics, many of which are under active investigation. One area that has received little attention is that of endogenous capabilities to respond to reactive oxygen species and subsequent byproducts resulting from radiation therapy and a number of chemotherapeutic agents, preventing cytotoxicity toward tumor cells. The glutathione S-transferases are key conjugating enzymes in this response, and GSTM1 and GSTT1 have deletion polymorphisms that result in no enzyme activity. In this retrospective study, we evaluated the role of GSTM1- and GSTT1-null genotypes on disease-free and overall survival among 251 women who received treatment for incident, primary breast cancer. Women were identified through Tumor Registry records and normal archived tissue retrieved for genotyping. Adjusting for age, race, and stage at diagnosis, women with null genotypes for GSTM1 and GSTT1 had reduced hazard of death [adjusted hazard ratio (HR), 0.59; 95% confidence interval (CI), 0.36-0.97; and HR, 0.51; CI, 0.29-0.90, respectively] in relation to those with alleles present. Furthermore, women who were null for both GSTM1 and GSTT1 had one-third the hazard of death of those with alleles for both genes present (adjusted HR, 0.28; 95% CI, 0.11-0.70). Similar relationships were noted for risk of recurrence. These data indicate that interindividual differences in activity of enzymes that prevent therapy-generated reactive oxidant damage may have an important impact on disease recurrence and overall survival. C1 Mt Sinai Sch Med, Derald H Ruttenberg Canc Ctr, New York, NY 10029 USA. Univ Minnesota, Div Epidemiol, Minneapolis, MN 55454 USA. Natl Ctr Toxicol Res, Div Mol Epidemiol, Jefferson, AR 72079 USA. Univ Arkansas Med Sci, Arkansas Canc Res Ctr, Little Rock, AR 72205 USA. Univ Texas, MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA. RP Ambrosone, CB (reprint author), Mt Sinai Sch Med, Derald H Ruttenberg Canc Ctr, Box 1130,1 Gustave L Levy Pl, New York, NY 10029 USA. OI Sweeney, Carol/0000-0003-1113-7160 NR 41 TC 134 Z9 139 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD OCT 1 PY 2001 VL 61 IS 19 BP 7130 EP 7135 PG 6 WC Oncology SC Oncology GA 479PB UT WOS:000171411800028 PM 11585745 ER PT J AU Moxey-Mims, MM Serge, MJ Melvin, MN AF Moxey-Mims, MM Serge, MJ Melvin, MN TI Informed consent in clinical trials of in vitro diagnostic devices: Perspectives from the FDA and manufacturers - A perspective from the Food and Drug Administration SO CLINICAL CHEMISTRY LA English DT Article C1 US FDA, Div Clin Lab Devices, Off Device Evaluat, Rockville, MD 20850 USA. US FDA, Div Biores Monitoring, Off Compliance, Rockville, MD 20850 USA. US FDA, Program Operat Staff, Off Device Evaluat, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. RP Moxey-Mims, MM (reprint author), 2098 Gaither Rd,HFZ-440, Rockville, MD 20850 USA. NR 7 TC 0 Z9 0 U1 0 U2 1 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 OCT PY 2001 VL 47 IS 10 BP 1753 EP 1755 PG 3 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 474GU UT WOS:000171098600001 PM 11568082 ER PT J AU Olsen, SJ Ying, M Davis, M Deasy, M Holland, B Iampietri, L Baysinger, CM Sassano, F Polk, LD Gormley, B Hung, MJ Pilot, K Orsini, M Rankin, S Genese, C Smucker, J Moll, M Sobel, J AF Olsen, SJ Ying, M Davis, M Deasy, M Holland, B Iampietri, L Baysinger, CM Sassano, F Polk, LD Gormley, B Hung, MJ Pilot, K Orsini, M Rankin, S Genese, C Smucker, J Moll, M Sobel, J TI Multistate outbreak of multidrug-resistant Salmonella Typhimurium infections due to post-pasteurization contaminated milk SO CLINICAL INFECTIOUS DISEASES LA English DT Meeting Abstract C1 CDC, Atlanta, GA 30333 USA. Penn Dept Hlth, Harrisburg, PA 17108 USA. Montgomery Cty Hlth Dept, Norristown, PA USA. Bucks Cty Dept Hlth, Doylestown, PA USA. Gloucester Cty Hlth Dept, Turnersville, NJ USA. New Jersey State Dept Hlth, Trenton, NJ 08625 USA. Univ Penn, Kennett Sq, PA USA. US FDA, Washington, DC 20204 USA. NR 0 TC 0 Z9 0 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 OCT 1 PY 2001 VL 33 IS 7 MA 26 BP 1093 EP 1093 PG 1 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 476KU UT WOS:000171226900052 ER PT J AU Ball, LK Ball, R Kleppinger, C Kohl, K Pratt, RD AF Ball, LK Ball, R Kleppinger, C Kohl, K Pratt, RD TI Reports to the vaccine adverse event reporting system (VAERS) of abscesses after vaccination: Clinical and microbiological features of serious reports SO CLINICAL INFECTIOUS DISEASES LA English DT Meeting Abstract C1 US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. CDC, Natl Immunizat Program, Atlanta, GA 30333 USA. NR 0 TC 0 Z9 0 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 OCT 1 PY 2001 VL 33 IS 7 MA 390 BP 1155 EP 1155 PG 1 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 476KU UT WOS:000171226900416 ER PT J AU McKnew, DL Lynn, F Zenilman, JM Yuenger, J Bash, MC AF McKnew, DL Lynn, F Zenilman, JM Yuenger, J Bash, MC TI Examination of clinical Neisseria gonorrhoeae isolates over a ten year period using a porin genotyping method SO CLINICAL INFECTIOUS DISEASES LA English DT Meeting Abstract C1 US FDA, Ctr Biol Evaluat & Res, Rockville, MD USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. NR 0 TC 0 Z9 0 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 OCT 1 PY 2001 VL 33 IS 7 MA 917 BP 1245 EP 1245 PG 1 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 476KU UT WOS:000171226900943 ER PT J AU Rex, JH Pfaller, MA Walsh, TJ Chaturvedi, V Espinel-Ingroff, A Ghannoum, MA Gosey, LL Odds, FC Rinaldi, MG Sheehan, DJ Warnock, DW AF Rex, JH Pfaller, MA Walsh, TJ Chaturvedi, V Espinel-Ingroff, A Ghannoum, MA Gosey, LL Odds, FC Rinaldi, MG Sheehan, DJ Warnock, DW TI Antifungal susceptibility testing: Practical aspects and current challenges SO CLINICAL MICROBIOLOGY REVIEWS LA English DT Review ID IN-VITRO SUSCEPTIBILITY; AMPHOTERICIN-B SUSCEPTIBILITY; BROTH MICRODILUTION METHODS; FLUCONAZOLE-RESISTANT CANDIDA; LABORATORY STANDARDS METHOD; MEDIATED GROWTH-INHIBITION; VIRUS-INFECTED PATIENTS; TIME-KILL METHODS; CRYPTOCOCCUS-NEOFORMANS; ASPERGILLUS-FUMIGATUS C1 Univ Texas, Sch Med, Ctr Study Emerging & Reemerging Pathogens, Dept Internal Med,Div Infect Dis, Houston, TX 77030 USA. Univ Iowa, Coll Med, Iowa City, IA 52242 USA. NCI, Pediat Branch, Infect Dis Sect, Bethesda, MD 20892 USA. New York State Dept Hlth, Albany, NY 12201 USA. Virginia Commonwealth Univ, Med Coll Virginia, Richmond, VA 23298 USA. Case Western Reserve Univ, Dept Dermatol, Cleveland, OH 44106 USA. US FDA, Rockville, MD 20857 USA. Inst Med Sci, Aberdeen, Scotland. Vet Adm Med Ctr, San Antonio, TX 78284 USA. Pfizer Inc, Pfizer Pharmaceut Grp, New York, NY 10017 USA. Ctr Dis Control & Prevent, Mycot Dis Branch, Atlanta, GA USA. RP Rex, JH (reprint author), 6431 Fannin,1728 JFB, Houston, TX 77030 USA. NR 218 TC 260 Z9 284 U1 1 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0893-8512 J9 CLIN MICROBIOL REV JI Clin. Microbiol. Rev. PD OCT PY 2001 VL 14 IS 4 BP 643 EP 658 DI 10.1128/CMR.14.4.643-658.2001 PG 16 WC Microbiology SC Microbiology GA 482KP UT WOS:000171575600001 PM 11585779 ER PT J AU Wang, ZQ Gorski, C Hamman, MA Huang, SM Lesko, LJ Hall, SD AF Wang, ZQ Gorski, C Hamman, MA Huang, SM Lesko, LJ Hall, SD TI The effects of St John's wort (Hypericum perforatum) on human cytochrome P450 activity SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID P-GLYCOPROTEIN; CONSTITUENTS; VOLUNTEERS; METABOLISM; MIDAZOLAM; CYP3A; 2D6 AB Background St John's wort (Hypericum perforatum) is a popular over-the-counter dietary supplement and herbal remedy that has been implicated in drug interactions with substrates of several cytochrome P450 (CYP) isozymes. The effect of St John's wort on CYP activity in vivo was examined with a probe drug cocktail. Methods: Twelve healthy subjects (5 female, 7 male) completed this 3-period, open-label, fixed schedule study. Tolbutamide (CYP2C9), caffeine (CYP1A2), dextromethorphan (CYP2D6), oral midazolam (intestinal wall and hepatic CYP3A), and intravenous midazolam (hepatic CYP3A) were administered before, with short-term St John's wort dosing (900 mg), and after 2 weeks of intake (300 ing 3 times a day) to determine CYP activities. Results. Short-term administration of St John's wort had no effect on CYP activities. Long-term St John's wort administration caused a significant (P < .05) increase in oral clearance of midazolam from 121.8 +/- 70.7 to 254.5 +/- 127.8 and a corresponding significant decline in oral bioavailability from 0.28 +/- 0.15 to 0.17 +/- 0.06. In contrast to the > 50% decrease in the area under the plasma concentration-time curve (AUC) when midazolam was administered orally, long-term St John's wort administration caused a 20% decrease in AUC when midazolam was given intravenously. There was no change in CYP1A2, CYP2C9, or CYP2D6 activities as a result of St John's wort administration. Conclusion: Long-term St John's wort administration resulted in a significant and selective induction of CYP3A activity in the intestinal wall. St John's wort did not alter the CYP2C9, CYP1A2, or CYP2D6 activities. Reduced therapeutic efficacy of drugs metabolized by CYP3A should be anticipated during longterm administration of St John's wort. C1 Indiana Univ, Sch Med, Dept Med, Div Clin Pharmacol, Indianapolis, IN USA. US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Hall, SD (reprint author), Wishard Mem Hosp, OPW, Room 320,1001 W 10th St, Indianapolis, IN 46202 USA. FU NCRR NIH HHS [MO1-RR00750]; NIGMS NIH HHS [T32 GM08425] NR 30 TC 218 Z9 228 U1 1 U2 19 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 OCT PY 2001 VL 70 IS 4 BP 317 EP 326 DI 10.1016/S0009-9236(01)17221-8 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 489KA UT WOS:000171989500003 PM 11673747 ER PT J AU Morrow, KS Slater, JE AF Morrow, KS Slater, JE TI Regulatory aspects of allergen vaccines in the US SO CLINICAL REVIEWS IN ALLERGY & IMMUNOLOGY LA English DT Review ID POTENCY; EXTRACTS; STANDARDIZATION; STABILITY C1 US FDA, Lab Immunobiochem, Div Bacterial Parasit & Allergen Prod, Off Vaccines Regulat & Res,Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. RP Slater, JE (reprint author), US FDA, Lab Immunobiochem, Div Bacterial Parasit & Allergen Prod, Off Vaccines Regulat & Res,Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. NR 23 TC 17 Z9 17 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1080-0549 J9 CLIN REV ALLERG IMMU JI Clin. Rev. Allergy Immunol. PD OCT PY 2001 VL 21 IS 2-3 BP 141 EP 152 DI 10.1385/CRIAI:21:2-3:141 PG 12 WC Allergy; Immunology SC Allergy; Immunology GA 485LC UT WOS:000171755000004 PM 11725602 ER PT J AU De Gruttola, VG Clax, P DeMets, DL Downing, GJ Ellenberg, SS Friedman, L Gail, MH Prentice, R Wittes, J Zeger, SL AF De Gruttola, VG Clax, P DeMets, DL Downing, GJ Ellenberg, SS Friedman, L Gail, MH Prentice, R Wittes, J Zeger, SL TI Considerations in the evaluation of surrogate endpoints in clinical trials: Summary of a National Institutes of Health Workshop SO CONTROLLED CLINICAL TRIALS LA English DT Article DE surrogate endpoints; biomarkers; meta-analysis ID END-POINTS; TRANSMISSION; ZIDOVUDINE; DYNAMICS; MARKERS; AIDS AB We report on recommendations from a National Institutes of Health Workshop on methods for evaluating the use of surrogate endpoints in clinical trials, which was attended by experts in biostatistics and clinical trials from a broad array of disease areas. Recent advances in biosciences and technology have increased the ability to understand, measure, and model biological mechanisms; appropriate application of these advances in clinical research settings requires collaboration of quantitative and laboratory scientists. Biomarkers, new examples of which arise rapidly from new technologies, are used frequently in such areas as early detection of disease and identification of patients most likely to benefit from new therapies. There is also scientific interest in exploring whether, and under what conditions, biomarkers may substitute for clinical endpoints of phase III trials, although workshop participants agreed that these considerations apply primarily to situations where trials using clinical endpoints are not feasible. Evaluating candidate biomarkers in the exploratory phases of drug development and investigating surrogate endpoints in confirmatory trials require the establishment of a statistical and inferential. framework. As a first step, participants reviewed methods for investigating the degree to which biomarkers can explain or predict the effect of treatments on clinical endpoints measured in clinical trials. They also suggested new approaches appropriate in settings where biomarkers reflect only indirectly the important processes on the causal path to clinical disease and where biomarker measurement errors are of concern. Participants emphasized the need for further research on development of such models, whether they are empirical in nature or attempt to describe mechanisms in mathematical terms. Of special interest were meta-analytic models for combining information from multiple studies involving interventions for the same condition. Recommendations also included considerations for design and conduct of trials and for assemblage of databases needed for such research. Finally, there was a strong recommendation for increased training of quantitative scientists in biologic research as well as in statistical methods and modeling to ensure that there will be an adequate workforce to meet future research needs. Control Clin Trials 2001; 22:485-502 (C) Elsevier Science Inc. 2001. C1 Harvard Univ, Sch Publ Hlth, Adult Stat & Data Anal Ctr, Boston, MA 02115 USA. NIAID, Bethesda, MD 20892 USA. NIH, Off Director, Bethesda, MD USA. US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. NHLBI, Bethesda, MD 20892 USA. NCI, Bethesda, MD 20892 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Stat Collaborat, Washington, DC USA. Johns Hopkins Univ, Sch Publ Hlth, Baltimore, MD USA. Univ Wisconsin, Madison, WI USA. RP De Gruttola, VG (reprint author), Harvard Univ, Sch Publ Hlth, Adult Stat & Data Anal Ctr, Bldg 2-439,655 Huntington Ave, Boston, MA 02115 USA. NR 17 TC 211 Z9 222 U1 1 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0197-2456 J9 CONTROL CLIN TRIALS JI Controlled Clin. Trials PD OCT PY 2001 VL 22 IS 5 BP 485 EP 502 DI 10.1016/S0197-2456(01)00153-2 PG 18 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 474JH UT WOS:000171103000001 PM 11578783 ER PT J AU Dixon, DO AF Dixon, DO TI Untitled SO CONTROLLED CLINICAL TRIALS LA English DT Letter C1 NIAID, Biostat Res Branch, Bethesda, MD 20892 USA. US FDA, Ctr Devices & Radiol Hlth, Div Biostat, Rockville, MD 20857 USA. RP Dixon, DO (reprint author), NIAID, Biostat Res Branch, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 7 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0197-2456 J9 CONTROL CLIN TRIALS JI Controlled Clin. Trials PD OCT PY 2001 VL 22 IS 5 BP 548 EP 550 DI 10.1016/S0197-2456(01)00151-9 PG 3 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 474JH UT WOS:000171103000006 PM 11589208 ER PT J AU Rodriguez, W Roberts, R Murphy, D AF Rodriguez, W Roberts, R Murphy, D TI Adverse drug events in children: The US food and drug administration perspective SO CURRENT THERAPEUTIC RESEARCH-CLINICAL AND EXPERIMENTAL LA English DT Article; Proceedings Paper CT Workshop on Adverse Drug Events in Pediatrics CY APR 09-10, 2001 CL ROCKVILLE, MARYLAND DE adverse events; off-label use; pediatric drugs; exclusivity initiative ID SPONTANEOUS REPORTING SYSTEM; LARGE FREQUENCY TABLES; TOXICITY AB Background: Adverse events are unwelcome occurrences associated with drug use. Some of these events are predictable or preventable, whereas others are idiosyncratic. The "off-label" use of drugs in pediatric patients further complicates the assessment of adverse events because pediatric dosing based on recommended adult doses may not be appropriate. Adverse events often occur in pediatric patients in an environment of incomplete information about the drug's pharmacokinetics in the pediatric population, and the inherent metabolic differences between adults and children may not be detected with extrapolating maneuvers. Adverse event information may be acquired during the drug development process, including the preclinical, preapproval, and postapproval processes. However, the lack of clinical trials in pediatric patients indicates that such information is not available. Objective: This paper reviews the pharmacologic basis for the different types of adverse events in children and adults and provides examples of the differences between these 2 groups. Methods: Data from spontaneous reports of adverse events that support a trend may assist with initiating and identifying an early signal for an adverse event and an assessment of its occurrence. We summarized our experience with the exclusivity initiative aimed at improving the acquisition of knowledge about use of drugs in children. We also summarized the data available from some spontaneous adverse event reports as well as examined pertinent literature to provide state-of-knowledge information on the specific adverse events. Results: Of the first 16 products that were subsequently studied in children, 6 (37.5%) had significant changes in labeling that had an impact on safety or efficacy. Specifically, we were able to identify situations in which proposed dosing could have led to overdosing or underdosing. We also identified situations in which adverse events, previously undescribed, could be expected. Conclusions: This information provides a better understanding of potential reasons for adverse events and defines unique pediatric adverse events. The exclusivity initiative supports the need for formal studies in the pediatric population if the therapy is to be used in children. C1 US FDA, DHHS, CDER, ORM,ODE 4, Rockville, MD 20850 USA. RP Rodriguez, W (reprint author), US FDA, DHHS, CDER, ORM,ODE 4, 9201 Corp Blvd,HFD-104, Rockville, MD 20850 USA. NR 42 TC 13 Z9 14 U1 0 U2 1 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0011-393X J9 CURR THER RES CLIN E JI Curr. Ther. Res.-Clin. Exp. PD OCT PY 2001 VL 62 IS 10 BP 711 EP 723 DI 10.1016/S0011-393X(01)80078-3 PG 13 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 493FT UT WOS:000172211900005 ER PT J AU Koti, KM AF Koti, KM TI Failure-time mixture models: Yet another way to establish efficacy SO DRUG INFORMATION JOURNAL LA English DT Article DE clinical trial; accelerated failure-time; surviving fraction; Wald test ID LONG-TERM SURVIVORS AB We propose to use mixture survival models to establish the efficacy of the trial treatment. In particular we consider the lognormal distribution to model the right-censored event time and a logistic regression for the incidence part of the model. The model attempts to estimate simultaneously the effects of treatments on the acceleration/deceleration of the timing of a given event and the surviving fraction-the proportion of the population for which the event may never occur We use the SAS/IML subroutine NLPTR to obtain the maximum likelihood estimates of the model parameters. The estimates of the standard errors of the parameter estimates are computed from, the inverse of the observed information matrix. We use the Cox-Snell residual plot based on the unconditional survivor junction for evaluating goodness-of-fit of the model. The principal research hypothesis will be that under the trial treatment, the time-to-event will be more decelerated/accelerated compared to the control, given that the event occurs. W suggest that this methodology could be considered as a means to establish efficacy. We emphasize that there can be a substantial advantage to using mixture models even when the log-rank test is valid and significant. Data on overall survival time from a typical colorectal cancer clinical trial are used to illustrate the procedure. C1 US FDA, Rockville, MD 20857 USA. RP Koti, KM (reprint author), US FDA, HFD-710,Room 15B45,5600 Fishers Lane, Rockville, MD 20857 USA. EM KotiK@cder.fda.gov NR 24 TC 4 Z9 4 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0092-8615 J9 DRUG INF J JI Drug Inf. J. PD OCT-DEC PY 2001 VL 35 IS 4 BP 1253 EP 1260 PG 8 WC Health Care Sciences & Services; Pharmacology & Pharmacy SC Health Care Sciences & Services; Pharmacology & Pharmacy GA 496GW UT WOS:000172388700023 ER PT J AU Ng, TH AF Ng, TH TI Choice of delta in equivalence testing SO DRUG INFORMATION JOURNAL LA English DT Article; Proceedings Paper CT DIA Workshop on Statistical Methodology in Clinical R and D CY APR 02, 2001 CL VIENNA, AUSTRIA DE active control; equivalence margin; equivalence testing; discounting; preservation ID ACTIVE-CONTROL; CLINICAL-TRIALS; ISSUES; DESIGN AB A valid interpretation of an active control equivalence study without a concurrent placebo control depends on the assumptions that 1. The active control is effective in the current trial (ie, assay sensitivity), and 2. The effect size is the same across the studies (ie, constancy assumption). The equivalence margin delta should be a small fraction (eg, 0.2) of the therapeutic effect of the active control as compared to placebo. However a larger delta can be justified if the objective is to establish the efficacy of the experimental treatment as compared to placebo through its comparison to the standard therapy without claiming equivalence. The proposed delta may be interpreted as preserving a percentage of the active control effect as compared to placebo. The assumption that the active control effect is constant across studies may be discounted by using a smaller delta. Preservation and discounting are two distinct concepts, although they are indistinguishable mathematically. Placebo controls are not necessarily unethical when known effective therapy exists for a condition. When a placebo control is ethical, it is a clear choice if the study objective is to establish the efficacy of the test treatment. A three-arm trial (test treatment, active control, and placebo) would be an ideal design: if the study objective is to establish the efficacy of the test treatment relative to an active control. When a placebo control is unethical and there can be no concurrent placebo, an evaluation of the efficacy of the test treatment depends on the discount factor to be used. The discount factor is often difficult to justify. In such a situation, an evaluation of the efficacy of the test treatment may be supplemented by other designs such as an "add on" design or an early escape design. In fact, a hybrid of the active control design with the "add on" design (test treatment, active control, and combination) is an ideal design when the test treatment and the active control possess different pharmacologic mechanisms. On the other hand, the discounting factor plays a less important role in an evaluation of the relative efficacy of the test treatment. C1 US FDA, Ctr Biol Evaluat & Res, Rockville, MD USA. RP Ng, TH (reprint author), 1401 Rockville Pike 273S,HFM-217, Rockville, MD 20852 USA. NR 24 TC 19 Z9 20 U1 0 U2 0 PU DRUG INFORMATION ASSOCIATION PI FORT WASHINGTON PA 501 OFFICE CENTER DR, STE 450, FORT WASHINGTON, PA 19034-3212 USA SN 0092-8615 J9 DRUG INF J JI Drug Inf. J. PD OCT-DEC PY 2001 VL 35 IS 4 BP 1517 EP 1527 PG 11 WC Health Care Sciences & Services; Pharmacology & Pharmacy SC Health Care Sciences & Services; Pharmacology & Pharmacy GA 496GW UT WOS:000172388700047 ER PT J AU Raybourne, RB Roth, G Deuster, PA Sternberg, EM Singh, A AF Raybourne, RB Roth, G Deuster, PA Sternberg, EM Singh, A TI Uptake and killing of Listeria monocytogenes by normal human peripheral blood granulocytes and monocytes as measured by flow cytometry and cell sorting SO FEMS IMMUNOLOGY AND MEDICAL MICROBIOLOGY LA English DT Article DE flow cytometry; human; neutrophil; monocyte; peripheral blood; Listeria monocytogenes ID MONOCLONAL-ANTIBODY; MURINE LISTERIOSIS; PHOSPHOLIPASE-C; HOST-DEFENSE; NEUTROPHILS; INFECTION; MICE; HEMOLYSIN; GROWTH; ROLES AB Cellular components of innate immunity (NK cells, monocytes and granulocytes) play an important role in early resistance to Listeria monocytogenes in the mouse model. Minimally invasive methods of measuring the bacteriocidal capacity of these cells may be useful as a biomarker of susceptibility in humans. A technique was developed whereby the uptake and survival of L. monocytogenes could be measured in human granulocytes and monocytes using small volumes of peripheral blood. This method used flow cytometry to detect the presence of PKH-2-labeled bacteria within these cells. Survival of bacteria was determined by sorting of infected cells based on a combination of fluorescence and light scattering properties. Considerable variation in bacterial recovery was seen between normal volunteers. There was consistently greater survival of a fully virulent strain of L. monocytogenes within monocytes and granulocytes compared with an isogenic strain lacking the hemolysin, listeriolysin O, when measured at baseline. There was no evidence of longer-term bacterial survival or growth at 2 or 24 h. This technique may be useful for assessment of both host resistance and pathogen virulence. (C) 2001 Federation of European Microbiological Societies. Published by Elsevier Science BN. All rights reserved. C1 US FDA, Immunobiol Branch, Laurel, MD 20708 USA. Uniformed Serv Univ Hlth Sci, Dept Mil & Emergency Med, Bethesda, MD 20814 USA. NIMH, Clin Neuroendocrinol Branch, Bethesda, MD 20892 USA. RP Raybourne, RB (reprint author), US FDA, Immunobiol Branch, MOD 1,8301 Muirkirk Rd, Laurel, MD 20708 USA. RI Deuster, Patricia/G-3838-2015 OI Deuster, Patricia/0000-0002-7895-0888 NR 24 TC 4 Z9 4 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0928-8244 J9 FEMS IMMUNOL MED MIC JI FEMS Immunol. Med. Microbiol. PD OCT PY 2001 VL 31 IS 3 BP 219 EP 225 DI 10.1016/S0928-8244(01)00264-4 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 496MG UT WOS:000172398900009 PM 11720818 ER PT J AU Louch, HA Buczko, ES Venable, RM Pastor, RW Vann, WF AF Louch, HA Buczko, ES Venable, RM Pastor, RW Vann, WF TI Mapping the ganglioside-binding domain of tetanus toxin SO GLYCOBIOLOGY LA English DT Meeting Abstract C1 US FDA, Ctr Biol Evaluat & Res, 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 OCT PY 2001 VL 11 IS 10 MA 106 BP 899 EP 899 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 480JG UT WOS:000171457800113 ER PT J AU Nascimbeni, M Major, M Mihalik, K Rice, CM Feinstone, SM Rehermann, B AF Nascimbeni, M Major, M Mihalik, K Rice, CM Feinstone, SM Rehermann, B TI Intrahepatic innate and adaptive immune responses in HCV infected chimpanzees. SO HEPATOLOGY LA English DT Meeting Abstract C1 NIDDK, Liver Dis Sect, NIH, Bethesda, MD USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. Rockefeller Univ, New York, NY 10021 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 2001 VL 34 IS 4 SU S MA 669 BP 339A EP 339A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 476KE UT WOS:000171224700662 ER PT J AU Shankar, K Vaidya, VS Wang, T Manautou, JE Bucci, TJ Mehendale, HM AF Shankar, K Vaidya, VS Wang, T Manautou, JE Bucci, TJ Mehendale, HM TI Decreased bioactivation and/or detoxification does not explain resiliency of diabetic mice to acetaminophen hepatotoxicity and lethality. SO HEPATOLOGY LA English DT Meeting Abstract C1 Univ Louisiana, Dept Toxicol, Monroe, LA USA. Univ Connecticut, Dept Pharmaceut Sci, Storrs, CT USA. Natl Ctr Toxicol Res, Pathol Associates Int, Jefferson, AR USA. NR 0 TC 1 Z9 1 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 2001 VL 34 IS 4 SU S MA 1129 BP 454A EP 454A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 476KE UT WOS:000171224701120 ER PT J AU Villanueva, JA James, SJ Shigenaga, MK Garrow, TA Chandler, CJ Devlin, AM Halsted, CH AF Villanueva, JA James, SJ Shigenaga, MK Garrow, TA Chandler, CJ Devlin, AM Halsted, CH TI Hepatic methionine metabolism mediates and folate deficiency promotes alcoholic liver disease in micropigs. SO HEPATOLOGY LA English DT Meeting Abstract C1 Univ Calif Davis, Davis, CA 95616 USA. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Childrens Hosp, Oakland Res Inst, Oakland, CA 94609 USA. Univ Illinois, Urbana, IL 61801 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 2001 VL 34 IS 4 SU S MA 1172 BP 465A EP 465A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 476KE UT WOS:000171224701165 ER PT J AU Yamaguchi, R Momosaki, S Hsia, CC Guang, G Kojiro, M Scudamore, C Tabor, E AF Yamaguchi, R Momosaki, S Hsia, CC Guang, G Kojiro, M Scudamore, C Tabor, E TI Sequence analysis of the hepatitis C virus core gene: Truncated core proteins encoded in hepatocellular carcinomas. SO HEPATOLOGY LA English DT Meeting Abstract C1 US FDA, CBER, OBRR, DETTD, Rockville, MD 20857 USA. Kurume Univ, Dept Pathol, Kurume, Fukuoka 830, Japan. Univ British Columbia, Dept Surg, Vancouver, BC V6T 1W5, Canada. 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 2001 VL 34 IS 4 SU S MA 1530 BP 554A EP 554A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 476KE UT WOS:000171224701521 ER PT J AU Biswas, R Hsia, CC Busch, M Laycock, M Hirschkorn, D Wright, D Epstein, J Tabor, E AF Biswas, R Hsia, CC Busch, M Laycock, M Hirschkorn, D Wright, D Epstein, J Tabor, E TI Early detection of hepatitis B virus infection: Comparative sensitivity of HBV DNA detection by PCR and HBsAg detection by a new generation of assays. SO HEPATOLOGY LA English DT Meeting Abstract C1 US FDA, Bethesda, MD 20014 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. WESTAT Corp, San Luis Obispo, CA USA. US FDA, Rockville, MD 20857 USA. NR 0 TC 5 Z9 5 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 2001 VL 34 IS 4 SU S MA 1754 BP 610A EP 610A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 476KE UT WOS:000171224701745 ER PT J AU Ye, X Meeker, HC Scallet, AC Carp, RI AF Ye, X Meeker, HC Scallet, AC Carp, RI TI Comparison of NADPH diaphorase activity in the brains of hamsters infected with scrapie strains 139H or 263K or with normal hamster brain homogenate SO HISTOLOGY AND HISTOPATHOLOGY LA English DT Article DE NADPH; scrapie; hamster; astrocytosis; vacuolation ID NITRIC-OXIDE SYNTHASE; ACTIVATED ASTROCYTES; HUNTINGTONS-DISEASE; REACTIVE ASTROCYTES; NEUROPEPTIDE-Y; EXPRESSION; NEURONS; CELLS; MICE; RAT AB Previous studies showed that the histopathological changes found in the brains of scrapie-infected animals included amyloid plaque formation, vacuolation, gliosis and neuronal and neurite degeneration. There were differences in the histopathological findings as a function of the scrapie strain-host combination. NADPH-diaphorase (NADPH-d) has been shown to be a selective histochemical marker for neurons containing nitric oxide (NO) synthase. Neuronal cell damage caused by NOS in brain has been reported to be associated with many neurodegenerative diseases. In this study, we used NADPH-d histostaining to investigate changes in the NOS system in brains of 139H- and 263K-infected hamsters and compared the results to normal hamster brain (NHB) injected animals. We observed that some of the NADPH-d histostaining neurons in the cortex of scrapie -infected hamsters appeared to be atrophic: the neurons were smaller and had fewer neurites. The NADPH-d histostaining intensity of neurons or astrocytes in septum, thalamus, hypothalamus and amygdala of 139H- and 263K-infected hamsters was greater than in control hamsters. Astrocytes in the thalamus, hypothalamus and lower part of the cortex (layers 4 to 6) in 263K-infected hamsters were more intensely stained for NADPH-d than in either 139H-infected hamsters or controls. Our results suggest that changes in NADPH-d system might play a role in the diversity of scrapie induced neurodegenerative changes. C1 New York State Inst Basic Res Dev Disabil, Staten Isl, NY 10314 USA. US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. RP Ye, X (reprint author), New York State Inst Basic Res Dev Disabil, 1050 Forest Hill Rd, Staten Isl, NY 10314 USA. NR 57 TC 2 Z9 2 U1 0 U2 0 PU F HERNANDEZ PI MURCIA PA PLAZA FUENSANTA 2-7 C, 30008 MURCIA, SPAIN SN 0213-3911 J9 HISTOL HISTOPATHOL JI Histol. Histopath. PD OCT PY 2001 VL 16 IS 4 BP 997 EP 1004 PG 8 WC Cell Biology; Pathology SC Cell Biology; Pathology GA 482BA UT WOS:000171553900002 PM 11642749 ER PT J AU Hanes, DE Robl, MG Schneider, CM Burr, DH AF Hanes, DE Robl, MG Schneider, CM Burr, DH TI New Zealand white rabbit as a nonsurgical experimental model for Salmonella enterica gastroenteritis SO INFECTION AND IMMUNITY LA English DT Article ID TYPHIMURIUM; CALVES; CHOLERAESUIS; VIRULENCE; SEGMENTS; PORCINE; DUBLIN; PIGS AB Rabbits orally challenged with Salmonella enterica developed a dose-dependent diarrheal disease comparable to human salmonellosis. Viable Salmonella organisms recovered from the intestine and deep tissues indicate local and systemic infections. Therefore, results show that the rabbit can be used as a model for diarrheal disease and sequelae associated vith salmonellosis. C1 US FDA, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. Temple Univ, Philadelphia, PA 19122 USA. RP Hanes, DE (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 8301 Muirkirk Rd, Laurel, MD 20708 USA. NR 21 TC 6 Z9 6 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD OCT PY 2001 VL 69 IS 10 BP 6523 EP 6526 DI 10.1128/IAI.69.10.6523-6526.2001 PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 474RR UT WOS:000171121100069 PM 11553599 ER PT J AU Lehotay, SJ Lightfield, AR Harman-Fetcho, JA Donoghue, DJ AF Lehotay, SJ Lightfield, AR Harman-Fetcho, JA Donoghue, DJ TI Analysis of pesticide residues in eggs by direct sample introduction/gas chromatography/tandem mass spectrometry SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE pesticide residue analysis; direct sample introduction; gas chromatography; tandem mass spectrometry; eggs ID SUPERCRITICAL-FLUID EXTRACTION; GAS-CHROMATOGRAPHY; VEGETABLES; FRUITS; FOODS AB Direct sample introduction (DSI) or "dirty sample injection" is a rapid, rugged, and inexpensive approach to large volume injection in gas chromatography (GC) for semivolatile analytes such as pesticides. DSI of complex samples such as eggs requires a very selective, detection technique, such as tandem mass spectrometry (MS-MS), to determine the analytes among the many semivolatile matrix components that also appear. In DSI, the nonvolatile matrix components that normally would contaminate the GC system in traditional injection methods remain in a disposable microvial, which is removed after every injection. For example, 3 mug of nonvolatile residue typically remained in the microvial after an injection of egg extract using the DSI method. This analytical procedure involves the following: W weighing 10 g of egg in a centrifuge tube and adding 2 g of NaCl and 19.3 mL of acetonitrile (MeCN); (ii) blending for 1 min using a probe blender; (iii) centrifuging for 10 min; and (iv) analyzing 10 muL (5 mg of egg equivalent) of the extract using DSI/GC/MS-MS. No sample cleanup or solvent evaporation steps were required to achieve quantitative and confirmatory results with < 10 ng/g detection limits for 25 of 43 tested pesticides from several chemical classes. The remaining pesticides gave higher detection limits due to poor fragmentation characteristics in electron impact ionization and/or degradation. Analysis of eggs incurred with chlorpyrifos-methyl showed a similar trend in the results as a more traditional approach. C1 USDA ARS, Eastern Reg Res Ctr, Wyndmoor, PA 19038 USA. USDA ARS, Beltsville Agr Res Ctr, Beltsville, MD 20705 USA. US FDA, Ctr Vet Med, Div Anim Res, Laurel, MD 20708 USA. RP Lehotay, SJ (reprint author), USDA ARS, Eastern Reg Res Ctr, 600 E Mermaid Lane, Wyndmoor, PA 19038 USA. EM slehotay@arserrc.gov NR 21 TC 74 Z9 75 U1 3 U2 18 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0021-8561 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD OCT PY 2001 VL 49 IS 10 BP 4589 EP 4596 DI 10.1021/jf0104836 PG 8 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 483CA UT WOS:000171615100012 PM 11599993 ER PT J AU Heller, DN Lewis, KM Cui, W AF Heller, DN Lewis, KM Cui, W TI Method for determination of pentobarbital in dry dog food by gas chromatography/mass spectrometry SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE pentobarbital; quantitation; gas chromatography/mass spectrometry; feed; euthanasia ID MASS-SPECTROMETRY; INTERNAL STANDARD AB A procedure has been developed and validated for measuring the concentration of pentobarbital residues in dry, extruded animal feed in the range of 3-200 ng/g (ppb) with an estimated limit of quantitation of 2 ppb. The method was developed for surveillance purposes: to measure the concentration of euthanizing agent which might be present in feeds incorporating rendered products which themselves might include some fraction of euthanized animals. A previously published qualitative procedure was modified by adding isotopically labelled pentobarbital as an internal standard. Dry feed was ground and extracted with methanol. The extract was loaded on a mixed-mode (C-18, anion exchange) solid-phase extraction cartridge designed for barbiturate residues. Pentobarbital was eluted and derivatized for gas chromatography/mass spectrometry in positive ion chemical ionization mode. Quantitation was based on the ratio of dimethyl-pentobarbital MH+ (m/z 255) vs dimethyl-pentobarbital-d(5) (m/z 260) in standards and extracts. Accuracy ranged from 112% at 3 ppb to 96% at 200 ppb, with relative standard deviations ranging from 4% at 3 ppb to 2% at 200 ppb. C1 US FDA, Ctr Vet Med, Laurel, MD 20708 USA. RP Heller, DN (reprint author), US FDA, Ctr Vet Med, Laurel, MD 20708 USA. NR 6 TC 7 Z9 8 U1 1 U2 7 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0021-8561 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD OCT PY 2001 VL 49 IS 10 BP 4597 EP 4602 DI 10.1021/jf0106188 PG 6 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 483CA UT WOS:000171615100013 PM 11599994 ER PT J AU Myers, MR Das, B AF Myers, MR Das, B TI Virus transmission through compromised synthetic barriers: Part I - Effect of unsteady driving pressures SO JOURNAL OF BIOMECHANICAL ENGINEERING-TRANSACTIONS OF THE ASME LA English DT Article ID TRANSPORT; PORES AB Although synthetic membranes such as gloves, condoms, and instrument sheaths are used in environments with highly time-varying stresses, their effectiveness (is barriers to virus transmission is almost always tested under static conditions. lit this paper it is shown how a previously developed mathematical model can be used to transform information from static barrier tests into predictions for more realistic use conditions. Using a rate constant measured for herpes adsorption to latex in saline, and an oscillatory trans-membrane pressure representative of coitus, the amount of virus transmitted through a hole (2 mum diameter) in a condom is computed. Just beyond the exit orifice of the pore, transport is dominated by the rapidly dissipating viscous jet of virus suspension, which results in (in accumulation of viruses roughly 20 pore radii from the barrier surface (hiring each cycle. Due to virus adsorption to the barrier surfaces. the simulations reveal a gradual decrease in virus flow with increasing number of cycles, and thus a slow divergence front predictions based upon steady-state conditions. Still, over the 500 cycles simulated, steady-state predictions approximate the net number of viruses transmitted to within 25 percent error C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20852 USA. RP Myers, MR (reprint author), US FDA, Ctr Devices & Radiol Hlth, HFZ-132,12725 Twinbrook Pkwy, Rockville, MD 20852 USA. RI Das, Bigyani/P-4064-2014 NR 12 TC 0 Z9 0 U1 0 U2 1 PU ASME-AMER SOC MECHANICAL ENG PI NEW YORK PA THREE PARK AVE, NEW YORK, NY 10016-5990 USA SN 0148-0731 J9 J BIOMECH ENG-T ASME JI J. Biomech. Eng.-Trans. ASME PD OCT PY 2001 VL 123 IS 5 BP 506 EP 512 DI 10.1115/1.1394198 PG 7 WC Biophysics; Engineering, Biomedical SC Biophysics; Engineering GA 478QH UT WOS:000171356500017 PM 11601737 ER PT J AU Das, B Myers, MR AF Das, B Myers, MR TI Virus transmission through compromised synthetic barriers: Part II - Influence of pore geometry SO JOURNAL OF BIOMECHANICAL ENGINEERING-TRANSACTIONS OF THE ASME LA English DT Article ID LABORATORY TESTS; VIRAL BARRIERS; LATEX; PERMEABILITY; CONDOMS AB When stressed during normal use, synthetic barriers such as gloves and condoms can develop tears that are undetectable by the user. It is of considerable public-health importance to estimate the quantity of virus transmitted through the tear in the event of viral contamination of the fluid medium. A mathematical model that accounts for virus adsorption to the barrier material was used to compute the quantity of virus transmitted through defects of various geometries. Slits were modeled as cylinders of elliptic cross section, and upper and lower bounds for the transmission rate of HIV and Hepatitis B virus (HBV) were calculated for barrier-use scenarios such as coitus and gripping of surgical instruments. For a 1-mum high slit, HIV transmission was found to be negligible for all likely use scenarios. HIV transmission became potentially significant for a 5-mum slit. Due to its high titer HBV transmitted at potentially important levels even through the 1-mum slit. The dependence of the transmission rate upon pore aspect ratio was determined and found to be very strong for high-adsorption situations and near-circular pores. Numerical predictions of virus transport through a laser-drilled hole in a condom matched experimental measurements well, even when the tapered nature of the geometry is ignored. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20852 USA. RP Das, B (reprint author), US FDA, Ctr Devices & Radiol Hlth, HFZ-132,12725 Twinbrook Pkwy, Rockville, MD 20852 USA. RI Das, Bigyani/P-4064-2014 NR 23 TC 1 Z9 1 U1 0 U2 2 PU ASME-AMER SOC MECHANICAL ENG PI NEW YORK PA THREE PARK AVE, NEW YORK, NY 10016-5990 USA SN 0148-0731 J9 J BIOMECH ENG-T ASME JI J. Biomech. Eng.-Trans. ASME PD OCT PY 2001 VL 123 IS 5 BP 513 EP 518 DI 10.1115/1.1394199 PG 6 WC Biophysics; Engineering, Biomedical SC Biophysics; Engineering GA 478QH UT WOS:000171356500018 PM 11601738 ER PT J AU Proctor, ME Hamacher, M Tortorello, ML Archer, JR Davis, JP AF Proctor, ME Hamacher, M Tortorello, ML Archer, JR Davis, JP TI Multistate outbreak of Salmonella serovar Muenchen infections associated with alfalfa sprouts grown from seeds pretreated with calcium hypochlorite SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID CHEMICAL TREATMENTS AB During September 1999, a multistate outbreak of Salmonella serovar Muenchen infection associated with eating raw alfalfa sprouts was identified in Wisconsin. Despite use of a calcium hypochlorite sanitizing procedure to pretreat seeds before sprouting, at least 157 outbreak-related illnesses were identified in seven states having sprouters who received alfalfa seed from a specific lot. The continued occurrence of sprout-related outbreaks despite presprouting disinfection supports the concern that no available treatment will eliminate pathogens from seeds before sprouting and reinforces the need for additional safeguards to protect the public. A lack of consumer knowledge regarding exposure to sprouts documented in this investigation suggests that more-targeted outreach to high-risk individuals may be needed to reduce their risk. C1 Wisconsin Dept Hlth & Family Serv, Div Publ Hlth, Bur Communicable Dis, Madison, WI 53701 USA. Univ Wisconsin, Wisconsin State Lab Hyg, Madison, WI 53706 USA. US FDA, Natl Ctr Food Safety & Technol, Summit Argo, IL 60501 USA. RP Proctor, ME (reprint author), Wisconsin Div Publ Hlth, Dept Hlth & Family Serv, POB 2659, Madison, WI 53701 USA. FU PHS HHS [U50/CCU514391-03] NR 21 TC 67 Z9 68 U1 1 U2 7 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 OCT PY 2001 VL 39 IS 10 BP 3461 EP 3465 DI 10.1128/JCM.39.10.3461-3465.2001 PG 5 WC Microbiology SC Microbiology GA 479AW UT WOS:000171382600006 PM 11574556 ER PT J AU Gobburu, JVS Tammara, V Lesko, L Jhee, SS Sramek, JJ Cutler, NR Yuan, RH AF Gobburu, JVS Tammara, V Lesko, L Jhee, SS Sramek, JJ Cutler, NR Yuan, RH TI Pharmacokinetic-pharmacodynamic modeling of rivastigmine, a cholinesterase inhibitor, in patients with Alzheimer's disease SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article ID ACETYLCHOLINESTERASE INHIBITION; DISPOSITION; ENA-713; CSF AB Rivastigmine is a cholinersterase inhibitor approved recently for the treatment of Alzheimer's disease (AD). The objective of this study is to characterize the pharmacokinetics-pharmacodynamics of rivastigmine in patients with AD. Eighteen AD patients received doses ranging from 1 to 6 mg bid for about 11 weeks. Rivastigmine and its active (major) metabolite (ZNS 114-666, also called NAP 226-90), plasma, and cerebrospinal fluid (CSF) concentrations were determined together with the ACNE activity and computerized neuropsychological test battery (CNTB) scores. Nonlinear mixed-effects modeling of pharmacokinetic and pharmacodynamic data was conducted using NONMEM. Rivastigmine and its metabolite exhibited dose-disproportional pharmacokinetics. The apparent clearance and volume of distribution (plasma) of rivastigmine were estimated to be 120 L/h and 236 L, respectively. The relative bioavailability at the 6 mg dose was about 140%. The metabolite had a clearance of about 100 L/h and a volume of distribution of 256 L. The kinetics of the parent and metabolite in CSF showed an equilibration half-life of about 0.2 and 0.5 hours, respectively. The metabolite levels in CSF correlated very well with the acetylcholinesterase inhibition, with a ZNS 114-666 concentration of about 5.4 mug/L required for half-maximal inhibition of acetylcholinesterase activity. No statistically significant correlation of the CNTB scores with enzyme inhibition, parent or metabolite concentration (plasma/CSF), or rivastigmine dose could be established. The PK-PD model presented in this study can provide valuable information to optimize the drug development of rivastigmine and other related compounds and also in rationalizing dosing recommendations. (C) 2001 the American College of Clinical Pharmacology. C1 US FDA, Off Clin Pharmacol & Biopharmaceut, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Gobburu, JVS (reprint author), 1451 Rockville Pike,Room 5088,HFD-860, Rockville, MD 20852 USA. NR 17 TC 16 Z9 16 U1 0 U2 6 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 OCT PY 2001 VL 41 IS 10 BP 1082 EP 1090 DI 10.1177/00912700122012689 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 474LL UT WOS:000171108500006 PM 11583476 ER PT J AU Aweeka, F Trapnell, C Chernoff, M Jayewardene, A Spritzler, J Bellibas, SE Lizak, P Jacobson, J AF Aweeka, F Trapnell, C Chernoff, M Jayewardene, A Spritzler, J Bellibas, SE Lizak, P Jacobson, J TI Pharmacokinetics and pharmacodynamics of thalidomide in HIV patients treated for oral aphthous ulcers: ACTG protocol 251 SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article ID HEALTHY MALE-VOLUNTEERS; CYTOCHROME-P-450; METABOLISM; EXCRETION; PLASMA AB Thalidomide has increasing clinical benefits, including the healing of aphthous ulcers in patients with HIV. Unfortunately, pharmacological information addressing the pharmacokinetics (PK) of this compound in HIV patients is limited. Concern exists as to whether thalidomide may alter its own metabolism owing to in vitro data previously reported. Furthermore, no information is available defining the relationship between drug exposure and clinical response. This study evaluated the PK and pharmacodynamics (PD) of thalidomide in patients enrolled in AIDS Clinical Trials Group Protocol 251. Study patients had HIV infection and oral aphthous ulcers of at least 2 weeks' duration. Pharmacologic studies were completed in those subjects randomized to receive active thalidomide at a dose of 200 mg daily for the 4week study period. PK studies involving serial sampling were carried out in 7 subjects following multiple dosing during study weeks 1 and 4. In addition, trough measurements were done in 20 subjects during each of the 4 study weeks to explore the relationship between time-averaged trough values and extent of clinical response. All samples were analyzed using a validated HPLC method, and parameters were determined using noncompartmental PK analysis. Thalidomide oral clearance averaged 0.14 +/- 0.08 and 0.12 +/- 0.05 l/h/kg on weeks 1 and 4 (p = 0.72), while the terminal elimination half-life averaged 5.7 +/- 1.5 and 7.3 +/- 1.7 hours (p = 0.12). The median time-averaged trough value for subjects deemed complete responders was 0.60, while the median value for noncomplete responders was 0.54. Adjusting for baseline CD4 count and initial index ulcer area, no significant effects were observed of increased thalidomide levels on response. In summary, this study provides steady-state PK data in HIV patients managed with thalidomide and suggests negligible effect of chronic dosing on drug clearance (comparing results from weeks 1 and 4). Furthermore, variable trough measurements between patients do not directly influence the effectiveness of thalidomide for oral aphthous ulcers. (C) 2001 the American College of Clinical Pharmacology. C1 Univ Calif San Francisco, Dept Clin Pharm, San Francisco, CA 94143 USA. US FDA, Ctr Biol Evaluat & Review, Rockville, MD 20857 USA. Harvard Univ, Sch Publ Hlth, SDAC, Boston, MA 02115 USA. CUNY Mt Sinai Sch Med, New York, NY 10029 USA. RP Aweeka, F (reprint author), Univ Calif San Francisco, Dept Clin Pharm, C-152, San Francisco, CA 94143 USA. OI Bellibas, S. Eralp/0000-0002-3955-5156 FU NCRR NIH HHS [5-M01-RR-00083-360]; PHS HHS [A127633] NR 18 TC 21 Z9 23 U1 2 U2 4 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD OCT PY 2001 VL 41 IS 10 BP 1091 EP 1097 DI 10.1177/00912700122012698 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 474LL UT WOS:000171108500007 PM 11583477 ER PT J AU Wood, G Lee, Y Egan, K Bolger, M AF Wood, G Lee, Y Egan, K Bolger, M TI US Food and Drug Administration's monitoring and surveillance programs for mycotoxins, pesticides and contaminants in food SO JOURNAL OF ENVIRONMENTAL MONITORING LA English DT Editorial Material ID FEEDS C1 US FDA, Ctr Food Safety & Appl Nutr, Div Risk Assessment, Washington, DC 20204 USA. RP Wood, G (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Div Risk Assessment, 200 CSW, Washington, DC 20204 USA. NR 22 TC 3 Z9 3 U1 0 U2 3 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD,, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1464-0325 J9 J ENVIRON MONITOR JI J. Environ. Monit. PD OCT PY 2001 VL 3 IS 5 BP 79N EP 83N PG 5 WC Chemistry, Analytical; Environmental Sciences SC Chemistry; Environmental Sciences & Ecology GA 485ZZ UT WOS:000171794600002 PM 11695128 ER PT J AU Gendel, SM Ulaszek, J Nishibuchi, M DePaola, A AF Gendel, SM Ulaszek, J Nishibuchi, M DePaola, A TI Automated ribotyping differentiates Vibrio parahaemolyticus O3 : K6 strains associated with a Texas outbreak from other clinical strains SO JOURNAL OF FOOD PROTECTION LA English DT Article ID LISTERIA-MONOCYTOGENES; PANDEMIC SPREAD; EMERGENCE; DIVERSITY; CLONE AB Automated ribotyping with a Qualicon Riboprinter was used to determine whether clinical isolates of Vibrio parahaemolyticus O3:K6 recovered during two U.S. outbreaks of oyster-associated gastroenteritis in 1998 were related to each other and to a previously identified highly virulent Asian clone of this serotype. The patterns produced using the restriction enzymes Eco RI and Pst I suggest that the outbreak in the Northeastern United States was caused by a single strain closely related to the Asian clone. In contrast, it appears that multiple strains were involved in the Texas outbreak and that the predominant type was genetically distinct from the Northeastern and Asian clone. C1 US FDA, Summit Argo, IL 60501 USA. IIT, Natl Ctr Food Safety & Technol, Summit Argo, IL 60501 USA. Kyoto Univ, Ctr SE Asian Studies, Sakyo Ku, Kyoto 6068501, Japan. US FDA, Dauphin Isl, AL 36528 USA. RP Gendel, SM (reprint author), US FDA, 6502 S Archer Rd, Summit Argo, IL 60501 USA. FU FDA HHS [FD-000431] NR 14 TC 17 Z9 18 U1 0 U2 4 PU INT ASSOC FOOD PROTECTION PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD OCT PY 2001 VL 64 IS 10 BP 1617 EP 1620 PG 4 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 484CP UT WOS:000171672900027 PM 11601716 ER PT J AU Takeshita, F Leifer, CA Gursel, I Ishii, KJ Takeshita, S Gursel, M Klinman, DM AF Takeshita, F Leifer, CA Gursel, I Ishii, KJ Takeshita, S Gursel, M Klinman, DM TI Cutting edge: Role of toll-like receptor 9 in CpG DNA-induced activation of human cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID BACTERIAL-DNA; B-CELLS; MOTIFS; OLIGODEOXYNUCLEOTIDES AB Unmethylated CpG motifs present in bacterial DNA stimulate a rapid and robust innate immune response. Human cell lines and PBMC that recognize CpG DNA express membrane-bound human Toll-like receptor 9 (hTLR9). Cells that are not responsive to CpG DNA become responsive when transfected with hTLR9. Expression of hTLR9 dramatically increases uptake of CpG (but not control) DNA into endocytic vesicles. Upon cell stimulation, hTLR9 and CpG DNA are found in the same endocytic vesicles. Cells expressing hTLR9 are stimulated by CpG motifs that are active in primates but not rodents, suggesting that evolutionary divergence between TLR9 molecules underlies species-specific differences in the recognition of bacterial DNA. These findings indicate that hTLR9 plays a critical role in the CpG DNA-mediated activation of human cells. 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,Room 3 D 10, 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 20 TC 390 Z9 414 U1 3 U2 17 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD OCT 1 PY 2001 VL 167 IS 7 BP 3555 EP 3558 PG 4 WC Immunology SC Immunology GA 496JH UT WOS:000172392100003 PM 11564765 ER PT J AU Gans, H Yasukawa, L Rinki, M DeHovitz, R Forghani, B Beeler, J Audet, S Maldonado, Y Arvin, AM AF Gans, H Yasukawa, L Rinki, M DeHovitz, R Forghani, B Beeler, J Audet, S Maldonado, Y Arvin, AM TI Immune responses to measles and mumps vaccination of infants at 6, 9, and 12 months SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 38th Annual Meeting of the Infectious-Diseases-Society-of-America CY SEP 07-10, 2000 CL NEW ORLEANS, LOUISIANA SP Infect Dis Soc Amer ID DENDRITIC CELLS; NEUTRALIZATION TEST; INTERFERON-GAMMA; MMR VACCINATION; UNITED-STATES; VIRUS; ANTIBODY; IMMUNIZATION; CHILDREN; ACTIVATION AB Immunizing infants against measles at the youngest age possible has the potential to reduce morbidity and mortality. The ability of infants at 6, 9, or 12 months to respond to measles and mumps vaccines was evaluated by measuring T cell proliferation, interferon-gamma production, and neutralizing antibody titers before and after vaccination. Infants in all age groups had equivalent cellular immune responses to measles or mumps viruses, with or without passive antibodies when immunized. In contrast, 6-month-old infants without passive antibodies had low geometric mean titers of antibody to measles or mumps viruses and low seroconversion rates. Geometric mean titers of antibody to measles virus increased if infants were revaccinated at 12 months. Six-month-old infants had limited humoral responses to paramyxovirus vaccines, whereas cellular immunity was equivalent to that of older infants. T cell responses can be established by immunization with these live attenuated virus vaccines during the first year, despite the presence of passive antibodies. C1 Stanford Univ, Sch Med, Dept Pediat, Stanford, CA 94305 USA. Palo Alto Med Fdn, Dept Pediat, Palo Alto, CA USA. Calif Dept Hlth Serv, Viral & Rickettsial Dis Lab, Richmond, CA USA. US FDA, Div Viral Prod, Bethesda, MD 20014 USA. RP Gans, H (reprint author), Stanford Univ, Sch Med, Dept Pediat, 300 Pasteur Dr,Rm G312, Stanford, CA 94305 USA. FU NIAID NIH HHS [AI-37127]; NICHD NIH HHS [HD-01310, HD-33698] NR 46 TC 118 Z9 122 U1 0 U2 4 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 2001 VL 184 IS 7 BP 817 EP 826 DI 10.1086/323346 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 476LK UT WOS:000171228400002 PM 11528592 ER PT J AU Monday, SR Whittam, TS Feng, PCH AF Monday, SR Whittam, TS Feng, PCH TI Genetic and evolutionary analysis of mutations in the gusA gene that cause the absence of beta-glucuronidase activity in Escherichia coli O157 : H7 SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 101st General Meeting of the American-Society-for-Microbiology CY MAY, 2001 CL ORLANDO, FLORIDA SP Ameri Soc Microbiol ID SEROTYPE O157-H7; UIDA EXPRESSION; MULTIPLEX PCR; ASSAYS AB Escherichia coli serotype O157:H7 do not exhibit beta -glucuronidase (GUD) activity but carry the gusA gene (uidA) that encodes for GUD. In trans-complementation, the gusA gene cloned from the GUD-positive variant strain 493-89 effectively restored GUD activity in O157:H7 strain 35150. Comparison of gusA sequences from the GUD-negative 35150 strain to that of 493-89 revealed several base mutations, including a guanosine (G) dinucleotide insertion that caused a frameshift in the 35150 gusA gene and introduced a predicted premature termination codon. This explains the absence of GUD activity in O157:H7. A 35150 gusA construct from which the G-G insertion was deleted restored activity in GUD-negative O157:H7 transformants. The G-G insertion was present in all GUD-negative O157:H7 strains but was absent in their GUD-positive variants. The G-G insertion that produced the characteristic GUD-negative phenotype to O157:H7 strains appeared later than the other gusA mutations in the evolutionary emergence of O157:H7. C1 US FDA, Div Microbiol Studies, Washington, DC 20204 USA. Natl Food Safety & Toxicol Ctr, E Lansing, MI USA. RP Feng, PCH (reprint author), US FDA, Div Microbiol Studies, HFS-516,200 C St SW, Washington, DC 20204 USA. NR 15 TC 39 Z9 40 U1 1 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD OCT 1 PY 2001 VL 184 IS 7 BP 918 EP 921 DI 10.1086/323154 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 476LK UT WOS:000171228400016 PM 11510000 ER PT J AU Ho, HS AF Ho, HS TI Safety of metallic implants in magnetic resonance imaging SO JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article DE MRI; safety; heating; leads; implants; SAR AB Magnetic resonance (MR) imaging has become a commonly accepted medical procedure. Manufacturers of medical implant devices are submitting claims that their devices are safe and effective in a MR environment. This paper concentrates on the issue of heating of patients due to the interaction of metallic implants with the strong radiofrequency magnetic field produced by the MR scanner. The commercially available program XFDTD was used to calculate the specific absorption rate (SAR) distribution in a realistic model of the human body. The body contained a metallic implant and was exposed to RF magnetic fields at 64 MHz from a model of a MR birdcage body coil. The results of the calculation showed that the magnitude of the increased heating of tissues due to the presence of the metallic implant depended on the dimensions, orientation, shape, and location of the metallic implant in the patient. This increased heating of surrounding tissues primarily concentrates in a small volume near the tip of the metallic wire. When the whole-body SAR was normalized to 1 W/kg, a calculated value of 41 W/kg was obtained at this location if the absorption was averaged over 1 g of tissue. However, a maximum value of 310 W/kg was calculated when the absorption was averaged over 1/8 g of tissue. Published 2001 Viriley-Liss, Inc. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. RP Ho, HS (reprint author), US FDA, Ctr Devices & Radiol Hlth, 9200 Corp Blvd,HFZ-133, Rockville, MD 20850 USA. NR 11 TC 38 Z9 39 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1053-1807 J9 J MAGN RESON IMAGING JI J. Magn. Reson. Imaging PD OCT PY 2001 VL 14 IS 4 BP 472 EP 477 DI 10.1002/jmri.1209 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 537KU UT WOS:000174758400018 PM 11599073 ER PT J AU Wysowski, DK Pitts, M Beitz, J AF Wysowski, DK Pitts, M Beitz, J TI An analysis of reports of depression and suicide in patients treated with isotretinoin SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID RETINOID-BINDING PROTEINS; ACNE-VULGARIS; THERAPY; ACID; ADOLESCENTS; DISORDER; SYSTEM AB Background. The Food and Drug Administration (FDA) has received reports of depression and suicide in patients treated with isotretinoin. Objective: Our purpose was to provide the number and describe the cases of depression and suicide reported to the FDA in US patients treated with isotretinoin and to consider the nature of a possible association between isotretinoin and depression, Methods: An analysis was made of reports of depression, suicidal ideation, suicide attempt, and suicide in US isotretinoin users voluntarily submitted to the manufacturer and the FDA from 1982 to May 2000 and entered in the FDAs Adverse Event Reporting System database. Results. From marketing of isotretinoin in 1982 to May 2000, the FDA received reports of 37 US patients treated with isotretinoin who committed suicide; 110 who were hospitalized for depression, suicidal ideation, or suicide attempt; and 284 with nonhospitalized depression, for a total of 431 patients. Factors suggesting a possible association between isotretinoin and depression include a temporal association between use of the drug and depression, positive dechallenges (often with psychiatric treatment), positive rechallenges, and possible biologic plausibility. Compared with all drugs in the FDAs Adverse Event Reporting System database to June 2000, isotretinoin ranked within the top 10 for number of reports of depression and suicide attempt. Conclusion: The FDA has received reports of depression, suicidal ideation, suicide attempt, and suicide in patients treated with isotretinoin. Additional studies are needed to determine whether isotretinoin causes depression and to identify susceptible persons. In the meantime, physicians are advised to inform patients prescribed isotretinoin (and parents, if appropriate) of the possibility of development or worsening of depression. They should advise patients (and parents) to immediately report mood swings and symptoms suggestive of depression such as sadness, crying, loss of appetite, unusual fatigue, withdrawal, and inability to concentrate so that patients can be promptly evaluated for appropriate treatment, including consideration of drug discontinuation and referral for psychiatric care. C1 US FDA, Ctr Drug Evaluat & Res, Div Drug Risk Evaluat 1, Off Post Mkt Drug Risk Assessment, Rockville, MD 20857 USA. RP Wysowski, DK (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Drug Risk Evaluat 1, Off Post Mkt Drug Risk Assessment, HFD-430,Parklawn Bldg,Room 15B-08, Rockville, MD 20857 USA. NR 32 TC 102 Z9 103 U1 0 U2 3 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD OCT PY 2001 VL 45 IS 4 BP 515 EP 519 DI 10.1067/mjd.2001.117730 PG 5 WC Dermatology SC Dermatology GA 476AR UT WOS:000171204300004 PM 11568740 ER PT J AU Teruya-Feldstein, J Kingma, DW Weiss, A Sorbara, L Burd, PR Raffeld, M Mueller, BU Tosato, G Jaffe, ES AF Teruya-Feldstein, J Kingma, DW Weiss, A Sorbara, L Burd, PR Raffeld, M Mueller, BU Tosato, G Jaffe, ES TI Chemokine gene expression and clonal analysis of B cells in tissues involved by lymphoid interstitial pneumonitis from HIV-infected pediatric patients SO MODERN PATHOLOGY LA English DT Article DE chemokine; HIV; LIP; lymphoma; pediatric ID IMMUNODEFICIENCY-VIRUS-INFECTION; MULTILOCULAR THYMIC CYSTS; T-CELLS; INDUCIBLE PROTEIN-10; MALIGNANT-LYMPHOMA; CHILDREN; DISEASE; MALT; CYTOKINE; GAMMA AB Lymphoid interstitial pneumonitis (LIP), a frequent pulmonary complicationini HIV-infected pediatric patients, is characterized histologically by marked infiltration of lymphoid cells. We sought to evaluate the nature and pathogenesis of the lymphoid infiltrates and to examine the relationship of UP to pulmonary MALT lymphoma that has been described in pediatric HIV positive patients. To examine the potential contribution of chemokines and cytokines to the inflammatory cell recruitment in tissues involved by lymphoid interstitial pneumonitis from HIV-infected pediatric patients, RNA was extracted from paraffin-embedded tissues from five lung biopsies in four pediatric HIV-positive patients and from five control, normal lung biopsies in five HIV-negative patients and was analyzed by semiquantitative RT-PCR for the expression of cytokines (TNF-alpha, GM-CSF, IFN-gamma, IL-4, IL-6, IL-10, and IL-18) and chemokines (IL-10, Mig, regulated upon activation, normal T expressed and secreted [RANTES], and MIP1-alpha and beta) after normalization for G3PDH. Expression of IL-18 was increased, as well as expression of IFN-gamma -inducible chemokines IP-10 and Mig in LIP tissues compared with controls. RANTES and MIP1-alpha and -beta were also increased in pediatric UP lesions compared with controls. In contrast, expression of TNF-alpha, GM-CSF, IL-10, and IL-6 was variable in UP tissues and controls. In addition, clonality of the B-cell population was evaluated by VDJ-PCR. A polyclonal B-cell population was shown hi all five biopsies from five patients with LIP; and in one patient with concurrent LIP and MALT lymphoma, a band of increased intensity was observed in the LIP biopsy that was identical in size to the monoclonal band In the concurrent MALT lymphoma biopsy. These results provide evidence of high-level expression of certain chemokines in lymphoid interstitial pneumonitis tissues and suggest that chemokines and cytokines may play an important role in the recruitment of inflammatory cell infiltrates into these tissues. In addition, UP may represent an early stage of MALT lymphoma or an immunologic response to a chronic antigenic stimulus that may provide a milieu or microenvironment for the evolution of a monoclonal B-cell population. C1 NCI, Pathol Lab, Hematopathol Sect, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. Texas Childrens Canc Ctr, Houston, TX USA. RP Jaffe, ES (reprint author), NCI, Pathol Lab, Hematopathol Sect, NIH, Bldg 10,Room 2N202,10 Ctr Dr MSC 1500, Bethesda, MD 20892 USA. NR 30 TC 11 Z9 11 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD OCT PY 2001 VL 14 IS 10 BP 929 EP 936 DI 10.1038/modpathol.3880414 PG 8 WC Pathology SC Pathology GA 481UU UT WOS:000171539500001 PM 11598160 ER PT J AU Veri, MC DeBell, KE Seminario, MC DiBaldassarre, A Reischl, I Rawat, R Graham, L Noviello, C Rellahan, BL Miscia, S Wange, RL Bonvini, E AF Veri, MC DeBell, KE Seminario, MC DiBaldassarre, A Reischl, I Rawat, R Graham, L Noviello, C Rellahan, BL Miscia, S Wange, RL Bonvini, E TI Membrane raft-dependent regulation of phospholipase C gamma-1 activation in T lymphocytes SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID CELL ANTIGEN RECEPTOR; PROTEIN-TYROSINE KINASE; TEC FAMILY KINASES; SIGNAL-TRANSDUCTION; PLASMA-MEMBRANE; GENETIC-EVIDENCE; PHOSPHORYLATION; ZAP-70; LAT; LOCALIZATION AB Numerous signaling molecules associate with lipid rafts, either constitutively or after engagement of surface receptors. One such molecule, phospholipase C gamma -1 (PLC gamma1), translocates from the cytosol to lipid rafts during T-cell receptor (TCR) signaling. To investigate the role played by lipid rafts in the activation of this molecule in T cells, an influenza virus hemagglutinin A (HA)-tagged PLC gamma1 was ectopically expressed in Jurkat T cells and targeted to these microdomains by the addition of a dual-acylation signal. Raft-targeted PLC gamma1 was constitutively tyrosine phosphorylated and induced constitutive NF-AT-dependent transcription and interleukin-2 secretion in Jurkat cells. Tyrosine phosphorylation of raft-targeted PLC gamma1 did not require Zap-70 or the interaction with the adapters Lat and Slp-76, molecules that are necessary for TCR signaling. In contrast, the Src family kinase Lek was required. Coexpression in HEK 293T cells of PLC gamma1-HA with Lek or the Tec family kinase Rlk resulted in preferential phosphorylation of raft-targeted PLC gamma1 over wild-type PLC gamma1. These data show that localization of PLC gamma1 in lipid rafts is sufficient for its activation and demonstrate a role for lipid rafts as microdomains that dynamically segregate and integrate PLC gamma1 with other signaling components. C1 Ctr Biol Evaluat & Res, Immunobiol Lab, Div Monoclonal Antibodies, LIB,OTRR, Bethesda, MD 20892 USA. NIAMSD, Arthrit & Rheumatism Branch, NIH, Bethesda, MD 20892 USA. NIA, Gerontol Res Ctr, Biol Chem Lab, NIH, Baltimore, MD 21224 USA. Univ G DAnnunzio, Ist Morfol Umana Normale, I-66100 Chieti, Italy. RP Bonvini, E (reprint author), Ctr Biol Evaluat & Res, Immunobiol Lab, Div Monoclonal Antibodies, LIB,OTRR, HFM-564,Bldg 29B,Rm 3NN10,29 Lincoln Dr,MSC-4555, Bethesda, MD 20892 USA. NR 49 TC 51 Z9 54 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD OCT PY 2001 VL 21 IS 20 BP 6939 EP 6950 DI 10.1128/MCB.21.20.6939-6950.2001 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 474NC UT WOS:000171112500021 PM 11564877 ER PT J AU Coles, B Nowell, SA MacLeod, SL Sweeney, C Lang, NP Kadlubar, FF AF Coles, B Nowell, SA MacLeod, SL Sweeney, C Lang, NP Kadlubar, FF TI The role of human glutathione S-transferases (hGSTs) in the detoxification of the food-derived carcinogen metabolite N-acetoxy-PhIP, and the effect of a polymorphism in hGSTA1 on colorectal cancer risk SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article DE human glutathione S-transferases; hGSTA1 genetic polymorphism; colorectal cancer; PhIP; detoxification ID MUTAGEN 2-AMINO-1-METHYL-6-PHENYLIMIDAZO<4,5-B>PYRIDINE PHIP; HETEROCYCLIC AMINE CARCINOGENS; ALPHA-CLASS; TISSUE DISTRIBUTION; LIVER-MICROSOMES; COLON-CANCER; DNA-ADDUCTS; IN-VITRO; RAT; IDENTIFICATION AB Food-derived heterocyclic amines (HCAs), particularly 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), are implicated in the etiology of human colorectal cancer (CRC) via a process of N-oxidation followed by O-acetylation or O-sulfation to form electrophilic metabolites that react with DNA. Glutathione S-transferases (GSTs) detoxify activated carcinogen metabolites by catalysis of their reaction with GSH. However, among HCAs, only N-acetoxy-PhIP has been shown to be a substrate for the GSTs. By using a competitive DNA-binding assay, we confirm that hGSTA1-1 is an efficient catalyst of the detoxification of N-acetoxy-PhIP. Further, we show that hGSTs A2-2, P1-1, M1-1, T1-1 and T2-2 appear to have low activity towards N-acetoxy-PhIP, and that hGSTs A4-4, M2-2, M4-4 and Z1-1 appear to have no activity towards N-acetoxy-PhIP. A genetic polymorphism in the 5 ' -regulatory sequence of hGSTA1 has been shown to correlate with the relative and absolute levels of expression of GSTA1/GSTA2 in human liver. Examination of hGSTA1 allele frequency in 100 Caucasian CRC patients and 226 Caucasian controls demonstrated a significant over-representation of the homozygous hGSTA1*B genotype among cases compared to controls (24.0 and 13.7%, respectively, P = 0.04). This corresponds to an odds ratio for risk of CRC of 2.0 (95% Cl 1.0-3.7) when comparing homozygous hGSTA1*B individuals with all other genotypes. Thus. individuals who are homozygous hGSTA1*B, and who would be predicted to have the lowest levels of hGSTA1 expression in their livers, appear to be at risk of developing CRC, possibly as a result of inefficient hepatic detoxification of N-acetoxy-PhIP. (C) 2001 Elsevier Science B.V. All rights reserved. C1 Natl Ctr Toxicol Res, Div Mol Epidemiol, Jefferson, AR 72079 USA. Univ Arkansas Med Sci, Div Surg Oncol, Dept Surg, Little Rock, AR 72205 USA. Cent Arkansas Vet Healthcare Syst, Surg Serv, Little Rock, AR 72205 USA. RP Coles, B (reprint author), Natl Ctr Toxicol Res, Div Mol Epidemiol, HFT 100,3900 NCTR Rd, Jefferson, AR 72079 USA. RI yang, min/G-3030-2011; OI Sweeney, Carol/0000-0003-1113-7160 FU NCI NIH HHS [1RO1CA58697, 1RO1CA55751]; NIA NIH HHS [R01AG15722] NR 51 TC 71 Z9 75 U1 1 U2 2 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 OCT 1 PY 2001 VL 482 IS 1-2 SI SI BP 3 EP 10 DI 10.1016/S0027-5107(01)00187-7 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 474BE UT WOS:000171083800002 PM 11535243 ER PT J AU Schoket, B Papp, G Levay, K Mrackova, G Kadlubar, FF Vincze, I AF Schoket, B Papp, G Levay, K Mrackova, G Kadlubar, FF Vincze, I TI Impact of metabolic genotypes on levels of biomarkers of genotoxic exposure SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article DE genetic polymorphism; metabolic genotype; molecular epidemiology; polycyclic aromatic hydrocarbons; biomarker; genotoxic exposure; DNA adduct; 1-hydroxypyrene ID DNA ADDUCT LEVELS; COKE-OVEN WORKERS; S-TRANSFERASE M1; WHITE BLOOD-CELLS; AMBIENT AIR-POLLUTION; HPRT MUTANT FREQUENCY; CYTOCHROME-P450 1A1; NAT2 GENOTYPES; LUNG-CANCER; GLUTATHIONE TRANSFERASES AB Phase I and Phase II xenobiotic-metabolising enzyme families are involved in the metabolic activation and detoxification of various classes of environmental carcinogens. Particular genetic polymorphisms of these enzymes have been shown to influence individual cancer risk. A brief overview is presented about recent research of the relationship between metabolic genotypes and internal dose, biologically effective dose and cytogenetic effects of complex and specific genotoxic exposures of human study populations, and we report our new results from two molecular epidemiological studies. We investigated the effects of multiple interactions among CYP1A1 Ile462Val CYP1A1 MspI, CYP1B1 Leu432Val, CYP2C9 Arg144Cys, CYP2C9 Ile359Leu, NQO1 Pro189Ser, GSTM1 gene deletion and GSTP1 Ile105Val genotypes on the levels of carcinogen-DNA adducts determined by P-32-postlabelling and PAH-DNA immunoassay in peripheral blood lymphocytes from workers occupationally exposed to polycyclic aromatic hydrocarbons in aluminium plants, and in bronchial tissue from smoking lung patients. A statistically significant positive linear correlation was observed between white blood cell aromatic DNA adduct and urinary 1-hydroxypyrene (1-OHPY) levels from potroom workers with GSTM1 null genotype (P = 0.011). Our results suggest interactions between GSTM1 and GSTP1 alleles in modulation of urinary 1-OHPY levels and white blood cell DNA adduct levels in the PAH-exposed workers. Interactions between GSTM1 and GSTP1 alleles, in association with particular genotype combinations of CYPs, were also recognised in bronchial aromatic DNA adduct levels of smoking lung patients, The impact of single metabolic genotypes and their combinations on biomarkers of exposure was usually weak, if any, in both our studies and reports of the literature. The effect of special metabolic gene interactions may be better recognised if the compared groups of individuals are stratified for multiple potential modulators of the observable biomarker end-point, and/or if chemical structure-specific biomarker methods are applied. (C) 2001 Elsevier Science B.V. All rights reserved. C1 Jozef Fodor Natl Ctr Publ Hlth, Natl Inst Environm Hlth, Dept Biochem, H-1097 Budapest, Hungary. Natl Ctr Toxicol Res, Div Mol Epidemiol, Jefferson, AR 72079 USA. RP Schoket, B (reprint author), Jozef Fodor Natl Ctr Publ Hlth, Natl Inst Environm Hlth, Dept Biochem, H-1097 Budapest, Hungary. NR 62 TC 63 Z9 69 U1 0 U2 4 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 OCT 1 PY 2001 VL 482 IS 1-2 SI SI BP 57 EP 69 DI 10.1016/S0027-5107(01)00210-X PG 13 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 474BE UT WOS:000171083800008 PM 11535249 ER PT J AU Kadlubar, FF AF Kadlubar, FF TI Concluding remarks: symposium on Genetic Susceptibility to Environmental Toxicants SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article DE genetic polymorphisms; risk assessment; carcinogen exposure; ethics AB The symposium on "Genetic Susceptibility to Environmental Toxicants" provided a state-of-the-art forum on the role of genetic susceptibility involving exposures to occupational, dietary, and other environmental toxicants. While much of the work focused on single gene-environmental interactions, there was a clear understanding that multiple gene polymorphisms in a metabolic pathway would prove to be essential knowledge in better assessing health risks. A clear need to couple these advances with better measures of exposure was also appreciated, along with improved methods to conduct individual risk assessment procedures. The ethics of these new paradigms was also discussed. (C) 2001 Elsevier Science B.V. All rights reserved. C1 Natl Ctr Toxicol Res, Div Mol Epidemiol, Jefferson, AR 72079 USA. RP Kadlubar, FF (reprint author), Natl Ctr Toxicol Res, Div Mol Epidemiol, Jefferson, AR 72079 USA. NR 13 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0027-5107 J9 MUTAT RES-FUND MOL M JI Mutat. Res.-Fundam. Mol. Mech. Mutagen. PD OCT 1 PY 2001 VL 482 IS 1-2 SI SI BP 111 EP 113 DI 10.1016/S0027-5107(01)00216-0 PG 3 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 474BE UT WOS:000171083800014 PM 11535255 ER PT J AU McKinzie, PB Delongchamp, RR Heflich, RH Parsons, BL AF McKinzie, PB Delongchamp, RR Heflich, RH Parsons, BL TI Prospects for applying genotypic selection of somatic oncomutation to chemical risk assessment SO MUTATION RESEARCH-REVIEWS IN MUTATION RESEARCH LA English DT Review DE point mutation; risk assessment; genotypic selection; ras; p53 ID K-RAS MUTATIONS; ETHYL-N-NITROSOUREA; COLORECTAL-CANCER PATIENTS; TUMOR-SUPPRESSOR GENE; BETA-CATENIN GENE; POLYMERASE-CHAIN-REACTION; LAMBDA/LACI TRANSGENIC RATS; HAMSTER OVARY CELLS; EXPOSED IN-VIVO; CONFORMATION POLYMORPHISM ANALYSIS AB Genotypic selection methods detect rare sequence changes in populations of DNA molecules. These methods have been used to investigate the chemical induction of mutation and for the detection and diagnosis of cancer. The possible use of genotypic selection for improving current risk assessment practices is based on the premise that the frequency of somatic mutation is of critical importance in understanding and modeling carcinogenesis. If genotypic selection can measure the induction of specific mutations that disrupt normal cell/tissue homeostasis, then it could provide key mechanistic information for cancer risk assessment. For example, genotypic selection data might support a particular low-dose extrapolation method or characterize the relationship between rodent and human cancer risk. Strategies for evaluating the use of genotypic selection in cancer risk assessment include the concept of developing a battery of targets that detect a range of agent-specific effects. Ideal targets to examine by genotypic selection are the oncogene and tumor suppressor gene mutations frequently detected in human tumors because these are thought to represent tumor-initiating events. The most commonly occurring basepair (bp) substitutions within the ras and p53 genes are identified. Also, the battery of genotypic selection methods is defined in terms of the most important mutational specificities to include. In theory, the major basepair substitution mutations induced by 29 of 31 chemical carcinogens could be detected by analyzing three different mutations: G:C --> T:A, G:C --> A:T, and A:T --> T:A. Genotypic selection will have the greatest impact on risk assessment if measurement of spontaneous mutation is possible. Data from phenotypic selection assays suggest this corresponds to detection of mutant fractions of similar to 10(-7), and this would necessitate examining DNA samples containing > 10(7) target molecules. Despite its apparent potential, considerable development and validation is needed before genotypic selection data can be applied to cancer risk assessment. (C) 2001 Elsevier Science B.V. All rights reserved. C1 Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, 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 247 TC 25 Z9 25 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1383-5742 J9 MUTAT RES-REV MUTAT JI Mutat. Res.-Rev. Mutat. Res. PD OCT PY 2001 VL 489 IS 1 BP 47 EP 78 DI 10.1016/S1383-5742(01)00063-1 PG 32 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 480RT UT WOS:000171476600003 PM 11673089 ER PT J AU Michael, SL Mayeux, PR Bucci, TJ Warbritton, AR Irwin, LK Pumford, NR Hinson, JA AF Michael, SL Mayeux, PR Bucci, TJ Warbritton, AR Irwin, LK Pumford, NR Hinson, JA TI Acetaminophen-induced hepatotoxicity in mice lacking inducible nitric oxide synthase activity SO NITRIC OXIDE-BIOLOGY AND CHEMISTRY LA English DT Article DE acetaminophen; peroxynitrite; nitrotyrosine; acetaminophen-cysteine; lipid peroxidation; liver necrosis; inducible nitric oxide synthase; hepatotoxicity. ID NITROTYROSINE-PROTEIN ADDUCTS; PARA-BENZOQUINONE IMINE; LIPID-PEROXIDATION; COVALENT BINDING; IMMUNOHISTOCHEMICAL LOCALIZATION; CARBON-TETRACHLORIDE; TREATED MICE; PEROXYNITRITE; TOXICITY; HEPATOCYTES AB We recently reported that nitrotyrosine and acetaminophen (APAP)-cysteine protein adducts colocalize in the hepatic centrilobular cells following a toxic dose of A-PAP to mice. Whereas APAP-adducts are formed by reaction of the metabolite N-acetyl-p-benzoquinone imine with cysteine, nitrotyrosine residues are formed by reaction of tyrosine with peroxynitrite. Peroxynitrite is formed from nitric oxide (NO) and superoxide. This manuscript examines APAP (300 mg/kg) hepatotoxicity in mice lacking inducible nitric oxide synthase activity (NOS2 null or knockout mice; C57BL/6-Nos2(tm1Lau)) and in the wildtype mice. In a time course the ALT levels in the exposed NOS2 null mice were approximately 50% of the wildtype mice; however, histological examination of liver sections indicated similar levels of centrilobular hepatic necrosis in both wild-type and NOS2 null mice. Serum nitrate plus nitrite levels (NO synthesis) were identical in saline-treated NOS2 null and wild-type mice (53 +/- 2 muM). APAP increased NO synthesis in wild-type mice only. The increases paralleled the increases in ALT levels with peak levels of serum nitrate plus nitrite at 6 h (168 +/- 27 muM). In wild-type mice hepatic tyrosine nitration was greatly increased relative to saline treated controls. Tyrosine nitration increased in NOS2 null mice also, but the increase was much less. APAP increased hepatic malonaldehyde levels (lipid peroxidation) in NOS2 null mice only. The results suggest the presence of multiple pathways to APAP-mediated hepatic necrosis, one via nitrotyrosine, as in the wild-type mice, and another that is not dependent upon inducible nitric oxide synthase activity, but which may involve increased superoxide. (C) 2001 Academic Press. C1 Univ Arkansas Med Sci, Coll Med, Dept Pharmacol & Toxicol, Little Rock, AR 72205 USA. Pathol Associates Ins, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Hinson, JA (reprint author), Univ Arkansas Med Sci, Coll Med, Dept Pharmacol & Toxicol, Little Rock, AR 72205 USA. FU NIGMS NIH HHS [GM58884] NR 37 TC 60 Z9 62 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1089-8603 J9 NITRIC OXIDE-BIOL CH JI Nitric Oxide-Biol. Chem. PD OCT PY 2001 VL 5 IS 5 BP 432 EP 441 DI 10.1006/niox.2001.0385 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 482HX UT WOS:000171571700002 PM 11587558 ER PT J AU Ellenberg, SS AF Ellenberg, SS TI Surrogate endpoints: the debate goes on SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Editorial Material ID ANTIHYPERTENSIVE DRUG-TREATMENT; CLINICAL-TRIALS; CALCIUM-ANTAGONISTS; HEART-FAILURE; END-POINTS; METAANALYSIS; MORTALITY; OUTCOMES; DISEASE; MARKERS 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, Rockville, MD 20852 USA. NR 24 TC 8 Z9 8 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD OCT-NOV PY 2001 VL 10 IS 6 BP 493 EP 496 DI 10.1002/pds.655 PG 4 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 514EX UT WOS:000173426600003 PM 11828830 ER PT J AU Wulfkuhle, JD McLean, KC Paweletz, CP Sgroi, DC Trock, BJ Steeg, PS Petricoin, EF AF Wulfkuhle, JD McLean, KC Paweletz, CP Sgroi, DC Trock, BJ Steeg, PS Petricoin, EF TI New approaches to proteomic analysis of breast cancer SO PROTEOMICS LA English DT Review DE breast cancer; surface-enhanced laser desorption/ionization two-dimensional polyacrylamide gel electrophoresis; laser capture microdissection pharmacoproteomics; review ID 2-DIMENSIONAL GEL-ELECTROPHORESIS; LASER CAPTURE MICRODISSECTION; MAMMARY EPITHELIAL-CELLS; PROTEIN EXPRESSION; POLYPEPTIDE EXPRESSION; DUCTAL CARCINOMA; RISK; HYPERPLASIA; PROGRESSION; DISEASE AB Proteomic based approaches are beginning to be utilized to study the natural history and treatment of breast cancer. A variety of proteomics approaches are under study, and are summarized herein. Two-dimensional gel electrophoresis (2D-PAGE) is still the foundation of most proteomics studies. We present an analysis of 2D-PAGE studies reported to date in breast cancer, including those examining normal/tumor differences and selected populations of breast cells. Newer technologies such as laser capture microdissection and highly sensitive mass spectrometry methods are currently being used together to identify greater numbers of lower abundance proteins that are differentially expressed between defined cell populations. Novel technologies still in developmental phases will enable identification of validated targets in small biopsy specimens, including high density protein arrays, antibody arrays and lysate arrays. Surface-enhanced laser desorption/ionization time-of-flight (SELDI-TOF) analysis enables the high throughput characterization of lysates from very few tumor cells and may be best suited for clinical biomarker studies. We present SELDI-TOF data herein to show the accuracy of the method in a small cohort of breast tumors, as well as its potential discriminatory capability. Such technologies are expected to supplement our armamentarium of mRNA-based assays, and provide critical information on protein levels and post-translational modifications. C1 US FDA, NCI,CBER, Div Therapeut Prod, Clin Proteom Program, Bethesda, MD 20892 USA. NCI, Canc Res Ctr, Pathol Lab, Womens Canc Sect, Bethesda, MD 20892 USA. NCI, Ctr Canc Res, Pathol Lab, Bethesda, MD 20892 USA. Georgetown Univ, Dept Chem, Washington, DC 20057 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Mol Pathol Unit, Boston, MA 02114 USA. Georgetown Univ, Med Ctr, Vincent T Lombardi Canc Res Ctr, Washington, DC 20007 USA. RP Petricoin, EF (reprint author), US FDA, NCI,CBER, Div Therapeut Prod, Clin Proteom Program, Bldg 29A,Room 2B02,8800 Rockville Pike, Bethesda, MD 20892 USA. NR 62 TC 151 Z9 154 U1 1 U2 13 PU WILEY-V C H VERLAG GMBH PI BERLIN PA PO BOX 10 11 61, D-69451 BERLIN, GERMANY SN 1615-9853 J9 PROTEOMICS JI Proteomics PD OCT PY 2001 VL 1 IS 10 BP 1205 EP 1215 DI 10.1002/1615-9861(200110)1:10<1205::AID-PROT1205>3.3.CO;2-O PG 11 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 486WF UT WOS:000171839400004 PM 11721633 ER PT J AU Knezevic, V Leethanakul, C Bichsel, VE Worth, JM Prabhu, VV Gutkind, JS Liotta, LA Munson, PJ Petricoin, EF Krizman, DB AF Knezevic, V Leethanakul, C Bichsel, VE Worth, JM Prabhu, VV Gutkind, JS Liotta, LA Munson, PJ Petricoin, EF Krizman, DB TI Proteomic profiling of the cancer microenvironment by antibody arrays SO PROTEOMICS LA English DT Article DE oral cavity cancer; antibody array; microenvironment ID LASER-CAPTURE MICRODISSECTION; ORGAN-SPECIFIC FIBROBLASTS; SQUAMOUS-CELL CARCINOMA; GENE-EXPRESSION; CDNA MICROARRAY; IN-VIVO; PROGRESSION; IMMUNOASSAY; FABRICATION; STATISTICS AB Critical changes in protein expression that enable tumors to initiate and progress originate in the local tissue microenvironment, and there are increasing indications that these microenviron mental alterations in protein expression play critical roles in shaping and directing this process. As a model to better understand how patterns of protein expression shape the tissue microenvironment, we analyzed protein expression in tissue derived from squamous cell carcinoma of the oral cavity through an antibody microarray approach for high-throughput proteomic analysis. Utilizing laser capture microdissection to procure total protein from specific microscopic cellular populations, we demonstrate that quantitative, and potentially qualitative, differences in expression patterns of multiple proteins within epithelial cells reproducibly correlate with oral cavity tumor progression. Furthermore, differential expression of multiple proteins was also found in stromal cells surrounding and adjacent to regions of diseased epithelium that directly correlated with tumor progression of the epithelium. Most of the proteins identified in both cell types are involved in signal transduction pathways, thus we hypothesize that extensive molecular communication involving complex cellular signaling between epithelium and stroma play a key role in driving oral cavity cancer progression. C1 NCI, Adv Technol Ctr 134F, Pathol Lab, NIH, Gaithersburg, MD 20877 USA. NCI, Canc Genome Anat Project, NIH, Bethesda, MD USA. SAIC, Frederick, MD USA. Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA. US FDA, CBER, Div Therapeut Prod, Tissue Proteom Unit, Bethesda, MD 20014 USA. RP Krizman, DB (reprint author), NCI, Adv Technol Ctr 134F, Pathol Lab, NIH, 8717 Grovement Circle, Gaithersburg, MD 20877 USA. RI Gutkind, J. Silvio/A-1053-2009 FU NCI NIH HHS [N01-CO-56000] NR 37 TC 220 Z9 228 U1 1 U2 8 PU WILEY-V C H VERLAG GMBH PI BERLIN PA PO BOX 10 11 61, D-69451 BERLIN, GERMANY SN 1615-9853 J9 PROTEOMICS JI Proteomics PD OCT PY 2001 VL 1 IS 10 BP 1271 EP 1278 DI 10.1002/1615-9861(200110)1:10<1271::AID-PROT1271>3.3.CO;2-Y PG 8 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 486WF UT WOS:000171839400009 PM 11721638 ER PT J AU Papaconstantinou, AD Fisher, BR Umbreit, TH Goering, PL Lappas, NT Brown, KM AF Papaconstantinou, AD Fisher, BR Umbreit, TH Goering, PL Lappas, NT Brown, KM TI Effects of beta-estradiol and bisphenol a on heat shock protein levels and localization in the mouse uterus are antagonized by the antiestrogen ICI 182,780 SO TOXICOLOGICAL SCIENCES LA English DT Article DE bisphenol A (BPA); ICI 182; 780 (ICI); beta-estradiol (E-2); estrogen receptor (ER); uterus; heat shock proteins; hsp90 alpha localization; B6C3F1 mouse ID ESTROGEN-RECEPTOR-ALPHA; MESSENGER-RIBONUCLEIC-ACID; UTEROTROPHIC ACTIVITY; OVARIECTOMIZED RATS; HUMAN ENDOMETRIUM; GENE-EXPRESSION; 90 KDA; C-FOS; GROWTH; HSP90 AB Bisphenol A (BPA) exhibits many estrogen-like effects in the rodent uterus, but not all of these can be attenuated by antiestrogens. This suggests the involvement of alternate pathways of BPA action that do not involve the estrogen receptor (ER). An examination of the in vivo effects of BPA on uterine gene expression and protein levels should contribute to an understanding of its mechanism of action. In this study we examined the dose-related effects of BPA on levels of a suite of heat shock proteins (hsps) and on the localization of hsp90 alpha, a chaperone of the ER, in uteri of ovariectomized B6C3F1 mice and compared these effects with those of beta -estradiol (E-2). The antiestrogen ICI 182,780 (ICI) was co-administered with BPA or E-2 in order to examine the potential role of the ER. BPA, although less potent than E-2, increased hsp90 alpha and grp94 to similar levels, but was much less effective than E-2 in increasing levels of hsp72. Treatment with 100 mg BPA/kg/day or 2 mug E-2/kg/day increased hsp90 alpha to 300% of control levels and altered its tissue expression pattern. In uteri of corn oil (control)-treated mice, hsp90 alpha predominantly localized in the cytoplasm and nuclei of epithelial cells. Upon treatment with BPA or E-2 there was increased intensity of staining in the stroma and myometrium, and in the epithelium hsp90 alpha was localized almost exclusively in the cytoplasm. The effects of BPA or E-2 on hsp levels and hsp90 alpha localization were attenuated by ICI. These results suggest an involvement of the ER in BPA- and E-2-induced increases in uterine levels of hsp90 alpha, grp94, and hsp72, and localization of hsp90 alpha. C1 George Washington Univ, Dept Biol Sci, Washington, DC 20052 USA. US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. George Washington Univ, Dept Forens Sci, Washington, DC 20052 USA. RP Brown, KM (reprint author), George Washington Univ, Dept Biol Sci, 332 Lisner Hall,2023 G St NW, Washington, DC 20052 USA. NR 57 TC 33 Z9 36 U1 0 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD OCT PY 2001 VL 63 IS 2 BP 173 EP 180 DI 10.1093/toxsci/63.2.173 PG 8 WC Toxicology SC Toxicology GA 477XW UT WOS:000171310400005 PM 11568360 ER PT J AU Yazal, JE Rao, SN Mehl, A Slikker, W AF Yazal, JE Rao, SN Mehl, A Slikker, W TI Prediction of organophosphorus acetylcholinesterase inhibition using three-dimensional quantitative structure-activity relationship (3D-QSAR) methods SO TOXICOLOGICAL SCIENCES LA English DT Article DE 3-D pharmacophore; hypothesis; conformation; hydrophobic; hydrogen bond acceptor; insecticides ID INDUCED DELAYED NEUROTOXICITY; IN-VITRO; BRAIN ACETYLCHOLINESTERASE; 3-DIMENSIONAL STRUCTURE; ALZHEIMERS-DISEASE; SITE GORGE; CHLORPYRIFOS; DOCKING; EXPOSURE; BINDING AB Neurotoxic organophosphorous compounds are known to modulate their biological effects through the inhibition of a number of esterases including acetylcholinesterase (AChE), the enzyme responsible for the degradation of the neurotransmitter acetylcholine. In this light, molecular modeling studies were performed on a collection of organophosphorous acetylcholinesterase inhibitors by the combined use of conformational analysis and 3D-QSAR methods to rationalize their inhibitory potencies against the enzyme. The Catalyst program was used to identify the structural features in the group of 8 inhibitors whose IC50 values ranged from 0.34 nM to 1.2 muM. The 3-D pharmacophore models are characterized by at least one hydrogen bond acceptor site and 2-3 hydrophobic sites and demonstrate very good correlation between the predicted and experimental IC50 values. Our models can be useful in screening databases of organophosphorous compounds for their neurotoxicity potential via the inhibition of acetylcholinesterase. Also, the pharmacophores offer an additional means of designing AChE inhibitors as potential therapeutic agents for central nervous system diseases. C1 US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. Mol Simulat Inc, San Diego, CA 92121 USA. RP Slikker, W (reprint author), US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. NR 54 TC 18 Z9 24 U1 6 U2 14 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 2001 VL 63 IS 2 BP 223 EP 232 DI 10.1093/toxsci/63.2.223 PG 10 WC Toxicology SC Toxicology GA 477XW UT WOS:000171310400011 ER PT J AU Sahu, SC Flynn, TJ Bradlaw, JA Roth, WL Barton, CN Yates, JG AF Sahu, SC Flynn, TJ Bradlaw, JA Roth, WL Barton, CN Yates, JG TI Pro-oxidant effects of the flavonoid myricetin on rat hepatocytes in culture SO TOXICOLOGY METHODS LA English DT Article DE flavonoids; hepatocytes; myricetin; oxidative stress ID NUCLEAR-DNA DAMAGE; LIPID-PEROXIDATION; STRAND BREAKS; LIVER NUCLEI; QUERCETIN; OXYGEN; CELLS; MUTAGENICITY; MECHANISMS; RADICALS AB Myricetin was selected as a model polyphenolic flavonoid for study of its prooxidant activity in rat hepatocytes in culture. Its activity was compared with that of a known oxidant, potassium dichromate. Cytotoxicity, membrane lipid peroxidation, and DNA strand breaks were used as endpoints of oxidative cell injury. Myricetin, like potassium dichromate, induced a concentration-dependent increase in cytotoxicity and membrane lipid peroxidation concurrent with a decrease in double-stranded DNA content in cultured rat hepatocytes. However, myricetin was a less potent oxidant than dichromate. Myricetin appears to be less effective in inducing oxidative DIVA damage in rat hepatocytes in culture when compared with our previously published studies on isolated rat liver nuclei. C1 US FDA, Div Toxicol Res, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. RP Sahu, SC (reprint author), US FDA, Div Toxicol Res, Ctr Food Safety & Appl Nutr, 8301 Muirkirk Rd, Laurel, MD 20708 USA. OI Flynn, Thomas/0000-0002-7248-0643 NR 27 TC 4 Z9 4 U1 1 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1051-7235 J9 TOXICOL METHOD JI Toxicol. Method. PD OCT-DEC PY 2001 VL 11 IS 4 BP 277 EP 283 DI 10.1080/105172301320254707 PG 7 WC Toxicology SC Toxicology GA 498WP UT WOS:000172536800003 ER PT J AU Vostal, JG Holada, K Simak, J AF Vostal, JG Holada, K Simak, J TI Expression of cellular prion protein on blood cells: Potential functions in cell physiology and pathophysiology of transmissible spongiform encephalopathy diseases SO TRANSFUSION MEDICINE REVIEWS LA English DT Review ID CREUTZFELDT-JAKOB-DISEASE; LYMPHOCYTE-ACTIVATION; PHOSPHOLIPASE-C; VARIANT CJD; SCRAPIE; MICE; PRP; SPLEEN; AGENT; PATHOGENESIS AB The cellular prion protein (PrPc) holds a central role in the pathophysiology of transmissible spongiform encephalopathies (TSE). The hallmark of these progressive neurodegenerative diseases is the accumulation of the protease-resistant, pathologic conformation of prion protein (PrPres) in the CNS. The conformational change is thought to be propagated by a template-like effect in which a normal prion protein (PrPc) interacts with its PrPres isoform and assumes the pathologic conformation. In its natural conformation, the prion protein is expressed on many different cell types, but its physiological function has yet to be clearly defined. PrPc expressed on blood cells or present in plasma may contribute to the transport of TSE infectivity found in blood of infected animal models. We examine the expression of PrPc on human and animal blood cells and its potential functional roles and discuss studies of transfusion-mediated transmission of TSE infectivity in animals. Copyright (C) 2001 by W.B. Saunders Company. C1 US FDA, Ctr Biol Evaluat & Res, Div Hematol, Lab Cellular Hematol, Bethesda, MD 20892 USA. RP Vostal, JG (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Hematol, Lab Cellular Hematol, Bldg 29,Room 323,HFM 335,8800 Rockville Pike, Bethesda, MD 20892 USA. RI Simak, Jan/C-1153-2011 NR 87 TC 16 Z9 16 U1 0 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0887-7963 J9 TRANSFUS MED REV JI Transf. Med. Rev. PD OCT PY 2001 VL 15 IS 4 BP 268 EP 281 DI 10.1053/tmrv.2001.26957 PG 14 WC Hematology SC Hematology GA 482CC UT WOS:000171556400002 PM 11668434 ER PT J AU Lillehoj, HS Min, WG Choi, KD Babu, US Bumside, J Miyamoto, T Rosenthal, BM Lillehoj, EP AF Lillehoj, HS Min, WG Choi, KD Babu, US Bumside, J Miyamoto, T Rosenthal, BM Lillehoj, EP TI Molecular, cellular, and functional characterization of chicken cytokines homologous to mammalian IL-15 and IL-2 SO VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY LA English DT Article DE chickens; cytokine; interleukin-15; interleukin-2; T-cell growth factor ID DELTA T-CELLS; ACTIVATED KILLER-CELLS; MESSENGER-RNA; INTERLEUKIN (IL)-15; GROWTH-FACTOR; BETA-CHAIN; RECEPTOR; EXPRESSION; INDUCTION; LYMPHOKINE AB DNA sequence analysis of a chicken interleukin (IL)-15 cDNA identified a 187 amino acid open reading frame encoding a protein with a predicted molecular weight of 21,964 Da, two potential N-linked glycosylation sites, four highly conserved Cys residues, two out-of-frame AUG initiation codons in the 5' untranslated region, and an unusually long (66 amino acid) signal peptide such that the expected size of the mature protein is 14,462 Da. Chicken IL-15 and IL-2 were compared with regard to their molecular,, cellular, and functional characteristics. The predicted amino acid sequences of both chicken cytokines showed greater homologies with mammalian IL-15s compared with mammalian IL-2s. Nor-them hybridization and RT-PCR demonstrated chicken IL-15 gene transcripts in a wide variety of tissues and cell types while the chicken IL-2 gene was expressed only in concanavalin A (con A)-activated spleen cells. Both recombinant cytokines stimulated the growth of spleen T-cells and enhanced the activity of natural killer (NK) cells in vitro. Subcutaneous injection with an expression plasmid encoding IL-15 increased the percentage of CD3(+) spleen T-lymphocytes whereas injection of an IL-2 cDNA augmented CD3+, CD4(+), CD8(+), T-cell receptor (TCR)1(+), and TCR2(+) T-cells. Collectively, these results indicate that chicken IL-15 and IL-2 are T-cell growth factors potentially capable of enhancing cell-mediated immunity in vivo. Published by Elsevier Science B.V. C1 USDA, Anim & Nat Resource Inst, Parasite Biol Epidemiol & Systemat Lab, Beltsville, MD 20705 USA. US FDA, Div Sci & Appl Technol, Off Special Nutr, Laurel, MD 20708 USA. Univ Delaware, Dept Anim Sci & Agr Biotechnol, Newark, DE 19717 USA. Univ Maryland, Sch Pharm, Dept Pharmaceut Sci, Baltimore, MD 21201 USA. RP Lillehoj, HS (reprint author), USDA, Anim & Nat Resource Inst, Parasite Biol Epidemiol & Systemat Lab, Beltsville, MD 20705 USA. OI Rosenthal, Benjamin/0000-0002-0224-3773; Min, Wongi/0000-0003-2437-7366 NR 39 TC 62 Z9 69 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-2427 J9 VET IMMUNOL IMMUNOP JI Vet. Immunol. Immunopathol. PD OCT PY 2001 VL 82 IS 3-4 BP 229 EP 244 DI 10.1016/S0165-2427(01)00360-9 PG 16 WC Immunology; Veterinary Sciences SC Immunology; Veterinary Sciences GA 488AR UT WOS:000171912300008 PM 11587737 ER PT J AU Xu, Z Seidler, FJ Ali, SF Slikker, W Slotkin, TA AF Xu, Z Seidler, FJ Ali, SF Slikker, W Slotkin, TA TI Fetal and adolescent nicotine administration: effects on CNS serotonergic systems SO BRAIN RESEARCH LA English DT Article DE adolescence; nicotine; paroxetine binding; serotonin; serotonin transporter; tobacco ID RAT-BRAIN REGIONS; MESSENGER-RNA EXPRESSION; H-3 PAROXETINE BINDING; CATECHOLAMINE SYSTEMS; CIGARETTE-SMOKING; PRENATAL EXPOSURE; AGING BRAIN; TRANSPORTER; NEURONS; RECEPTORS AB Nicotine is a neuroteratogen that targets synaptic function during critical developmental stages and recent studies indicate that CNS vulnerability extends into adolescence, the time that smoking typically commences. We administered nicotine to pregnant or adolescent rats via continuous minipump infusions, using dose rates that replicate the plasma nicotine levels found in smokers. Fetal nicotine exposure (gestational days 4-21) decreased the cerebrocortical binding of paroxetine (PXT), a marker for the serotonin (5HT) transporter, likely indicative of a decrease in nerve terminals in that region; the effect lasted into adulthood. There was a corresponding increase in PXT binding in the midbrain/brainstem, the region containing the 5HT cell bodies that project to the cerebral cortex, a pattern typical of reactive sprouting in response to nerve terminal damage. After adolescent nicotine treatment (postnatal days 30-47), PXT binding was reduced in the hippocampus and striatum instead of the cerebral cortex, again accompanied by increased binding in the midbrain and brainstem; the patterns of effects within each region were gender-selective, although both males and females displayed abnormalities. Superimposed on this overall effect, there were transient increases in PXT binding, likely due to acute stimulant effects of nicotine. We also assessed 5HT presynaptic activity (5HIAA/5HT ratio). Withdrawal from adolescent nicotine treatment led to suppression of activity in the cerebral cortex and activation in the midbrain. These results indicate that both fetal and adolescent nicotine exposure elicit apparent damage to 5HT projections with reactive increases in regions containing 5HT cell bodies. Long-term changes in 5HT innervation and/or synaptic activity may play a role in the subsequent development of depression in the offspring of women who smoke during pregnancy or in adolescent smokers. (C) 2001 Elsevier Science BY All rights reserved. C1 Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Durham, NC 27710 USA. Univ Arkansas Med Sci, Dept Pharmacol & Toxicol, Little Rock, AR USA. US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. RP Slotkin, TA (reprint author), Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Durham, NC 27710 USA. FU NIDA NIH HHS [DA14247] NR 54 TC 133 Z9 135 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 SEP 28 PY 2001 VL 914 IS 1-2 BP 166 EP 178 DI 10.1016/S0006-8993(01)02797-4 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 479JD UT WOS:000171400500018 PM 11578609 ER PT J AU Kakhniashvili, DG Chaudhary, T Zimmer, WE Bencsath, FA Jardine, I Goodman, SR AF Kakhniashvili, DG Chaudhary, T Zimmer, WE Bencsath, FA Jardine, I Goodman, SR TI Erythrocyte spectrin is an E2 ubiquitin conjugating enzyme SO BIOCHEMISTRY LA English DT Article ID IRREVERSIBLY SICKLED CELLS; SITE-SPECIFIC PHOSPHORYLATION; AMINO-ACID-SEQUENCES; HEINZ BODY FORMATION; KAPPA-B-ALPHA; BETA-SPECTRIN; PROTEIN LIGASE; MEMBRANE SKELETON; ACTIN-BINDING; IN-VIVO AB The involvement of red blood cell spectrin in the ubiquitination process was studied. Spectrin was found to form two ubiquitin-associated derivatives, a DTT-sensitive ubiquitin adduct and a DTT-insensitive conjugate, characteristic intermediate and final products of the ubiquitination reaction cascade. In addition to spectrin and ubiquitin, ubiquitin-activating enzyme (El) and ATP were necessary and sufficient to form both the spectrin-ubiquitin adduct and conjugate. No exogenous ubiquitin-conjugating (E2) or ligase (E3) activities were required, suggesting that erythrocyte spectrin is an E2 ubiquitin-conjugating enzyme able to target itself. Both ubiquitin adduct and conjugate were linked to the alpha subunit of spectrin, suggesting that the ubiquitin-conjugating (UBC) domain and its target regions reside on the same subunit. C1 Univ S Alabama, Coll Med, Dept Neurosci & Cell Biol, Mobile, AL 36688 USA. Univ S Alabama, Coll Med, Dept Biochem & Mol Biol, Mobile, AL 36688 USA. Univ S Alabama, Coll Med, Ctr Comprehens Sickle Cell, Mobile, AL 36688 USA. Thermoquest, San Jose, CA 95134 USA. US FDA, Gulf Coast Seafood Lab, Dauphin Isl, AL 36528 USA. RP Goodman, SR (reprint author), Univ S Alabama, Coll Med, Dept Neurosci & Cell Biol, Mobile, AL 36688 USA. FU NHLBI NIH HHS [3P60HL38635] NR 96 TC 18 Z9 18 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD SEP 25 PY 2001 VL 40 IS 38 BP 11630 EP 11642 DI 10.1021/bi010176t PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 476BA UT WOS:000171205300039 PM 11560514 ER PT J AU Zhu, PX Klutch, MJ Tsai, CM AF Zhu, PX Klutch, MJ Tsai, CM TI Genetic analysis of conservation and variation of lipooligosaccharide expression in two L8-immunotype strains of Neisseria meningitidis SO FEMS MICROBIOLOGY LETTERS LA English DT Article DE Neisseria; lipooligosaccharide; glycosyltransferase; lgt ID BETA-CHAIN; LIPOPOLYSACCHARIDE; BIOSYNTHESIS; GONORRHOEAE; LOCUS; SEQUENCE AB Neisseria meningitidis strains A I and M978 both express the lipooligosaccharide (LOS) L8 immunotype [Gu et al., J. Clin. Microbiol. 30 (1992) 2047-2053]. Under different growth conditions. strain Al did not change its LOS profile whereas strain M978 produced variable LOS profiles on SDS-PAGE. To understand the genetic basis of LOS conservation and variation. their Igt locus encoding glycosyltransferases responsible for the biosynthesis of the cc-chain of LOS was analyzed. Strain Al possessed only two genes. lgtA and lgtH., at the Igt locus. The lgtA gene was inactivated due to a frameshift mutation, thus strain Al expressed only L8 LOS. In contrast, strain M978 contained five genes lgtZ. lgtC, lgtA. lgtB and lgtE at this locus, thus it had a potential to express L1, L3.7 in addition to the L8 LOS. The data showed that strain Al is a better reference strain for the L8 immunotype because of the stability of L8 LOS expression resulting from its unique Igt locus, In addition. these two strains had two new genetic organizations, lgtAH and lgtZCABE, compared to the reported gene organization at the Igt locus in N. meningitidis. (C) 2001 Federation or European Microbiological Societies. Published by Elsevier Science B.V. All rights reserved. C1 US FDA, Ctr Biol Evaluat & Res, Div Bacterial Parasit & Allergen Prod, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Bethesda, MD 20892 USA. RP Tsai, CM (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Bacterial Parasit & Allergen Prod, 8800 Rockville Pike, Bethesda, MD 20892 USA. NR 17 TC 9 Z9 9 U1 0 U2 0 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 SEP 25 PY 2001 VL 203 IS 2 BP 173 EP 177 DI 10.1111/j.1574-6968.2001.tb10837.x PG 5 WC Microbiology SC Microbiology GA 479UT UT WOS:000171422500007 PM 11583844 ER PT J AU Cha, CJ Coles, BF Cerniglia, CE AF Cha, CJ Coles, BF Cerniglia, CE TI Purification and characterization of a glutathione S-transferase from the fungus Cunninghamella elegans SO FEMS MICROBIOLOGY LETTERS LA English DT Article DE glutathione S-transferase; enzyme purification; Cunninghamella elegans ID METABOLISM; THETA; XENOBIOTICS; ISOENZYMES; EVOLUTION; CLONING; ENZYMES; CDNA; GST; RAT AB Cunninghamella elegans grown on Sabouraud dextrose broth had glutathione S-transferase (GST) activity. The enzyme was purified 172-fold from the cytosolic fraction (120000 X g) of the extract from a culture of C elegans, using Q-Sepharose ion exchange chromatography and glutathione affinity chromatography. The GST showed activity against 1-chloro-2.4-dinitrobenzene, 1,2-dichloro-4-nitrobenzene. 4-nitrobenzyl chloride. and ethacrynic acid. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis gel filtration chromatography revealed that the native enzyme was homodimeric with a Subunit of M-r 27000. Comparison by Western blot analysis implied that this fungal GST had no relationship with mammalian alpha-, mu-, and pi -class GSTs. although it showed a small degree of crossreactivity with a theta -class GST. The N-terminal amino acid sequence of the purified enzyme showed no significant homology with other known GSTs. (C) 2001 Federation of European Microbiological Societies. Published by Elsevier Science B.V. Alt rights reserved. C1 US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. US FDA, Natl Ctr Toxicol Res, Div Mol Epidemiol, Jefferson, AR 72079 USA. RP Cerniglia, CE (reprint author), US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. NR 28 TC 8 Z9 9 U1 2 U2 6 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 SEP 25 PY 2001 VL 203 IS 2 BP 257 EP 261 DI 10.1016/S0378-1097(01)00360-3 PG 5 WC Microbiology SC Microbiology GA 479UT UT WOS:000171422500020 PM 11583857 ER PT J AU Wu, CJ O'Rourke, DM Feng, GS Johnson, GR Wang, Q Greene, MI AF Wu, CJ O'Rourke, DM Feng, GS Johnson, GR Wang, Q Greene, MI TI The tyrosine phosphatase SHP-2 is required for mediating phosphatidylinositol 3-kinase/Akt activation by growth factors SO ONCOGENE LA English DT Article DE SHP-2; phosphatidylinositol 3-kinase (PI3K); Akt; growth factors; signaling ID HUMAN GLIOBLASTOMA CELLS; FACTOR RECEPTOR; PHOSPHOINOSITIDE-3-OH KINASE; PHOSPHOTYROSINE PHOSPHATASE; HEMATOPOIETIC-CELLS; SIGNAL-TRANSDUCTION; FOCAL ADHESION; SH2 DOMAINS; ERBB FAMILY; PROTEIN AB SHP-2 is a ubiquitously expressed non-transmembrane tyrosine phosphatase with two SH2 domains. Multiple reverse-genetic studies have indicated that SHP-2 is a required component for organ and animal development. SHP-2 wild-type and homozygous mutant mouse fibroblast cells in which the N-terminal SH2 domain was target-deleted were used to examine the function of SHP-2 in regulating Phosphatidylinositol 3-Kinase (PI3K) activation by growth factors. In addition, SHP-2 and various mutants were introduced into human glioblastoma cells as well as SHP-2(-/-) mouse fibroblasts. We found that EGF stimulation and EGFR oncoprotein (Delta EGFR) expression independently induced the co-immunoprecipitation of the p85 subunit of PI3K with SHP-2. Targeted deletion of the N-terminal SH2 domain of SHP-2 severely impaired PDGF- and IGF-induced Akt phosphorylation. Ectopic expression of SHP-2 in U87MG gliobastoma cells elevated EGF-induced Akt phosphorylation, and the effect was abolished by mutation of its N-terminal SH2 domain. Likewise, the reconstitution of SHP-2 expression in the SHP-2(-/-) cells enhanced Akt phosphorylation induced by EGF while rescuing that induced by PDGF and IGF. Further lipid kinase activity assays confirmed that SHP-2 modulation of Akt phosphorylation correlated with its regulation of PI3K activation. Based on these results, we conclude that SHP-2 is required for mediating PI3K/Akt activation, and the N-terminal SH2 domain is critically important for a 'positive' role of SHP-2 in regulating PI3K pathway activation. C1 Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Neurosurg, Philadelphia, PA 19104 USA. Burnham Inst, La Jolla, CA 92037 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Greene, MI (reprint author), Univ Penn, Sch Med, Dept Pathol & Lab Med, 252 John Morgan Bldg,36th & Hamilton Walk, Philadelphia, PA 19104 USA. EM greene@reo.med.upenn.edu RI Wang, Qiang/N-7310-2015 OI Wang, Qiang/0000-0001-9409-0251 NR 39 TC 90 Z9 91 U1 0 U2 5 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 20 PY 2001 VL 20 IS 42 BP 6018 EP 6025 DI 10.1038/sj.onc.1204699 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 473QF UT WOS:000171056300009 PM 11593409 ER PT J AU Alper, O Bergmann-Leitner, ES Bennett, TA Hacker, NF Stromberg, K Stetler-Stevenson, WG AF Alper, O Bergmann-Leitner, ES Bennett, TA Hacker, NF Stromberg, K Stetler-Stevenson, WG TI Epidermal growth factor receptor signaling and the invasive phenotype of ovarian carcinoma cells SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID EXTRACELLULAR-MATRIX PROTEINS; PHOSPHOINOSITIDE 3-OH KINASE; BASEMENT-MEMBRANE; TUMOR-CELLS; ALPHA-6-BETA-4 INTEGRIN; TYROSINE KINASE; EGF RECEPTOR; FACTOR-ALPHA; CANCER; EXPRESSION AB Background: Most (70%-100%) ovarian carcinomas express high levels of the epidermal growth factor receptor (EGFR). To examine the relationship between EGFR and the invasive phenotype, we assessed integrin expression, adhesion, matrix metalloproteinase (MMP) activity, and migration in ovarian cancer cells in which EGFR expression was modified. Methods: NIH:OVCAR-8 human ovarian carcinoma cells were transfected with an expression vector containing the human EGFR complementary DNA in an antisense orientation (EGFR-antisense cells) or the vector alone (vector control cells). We compared vector control and EGFR-antisense cells for cell morphology and adhesion by light microscopy, expression of alpha (6)- and alpha (3)-integrin subunits by flow cytometry, MMP and tissue inhibitor of MMP (TIMP) activity by zymography, and migration by a wound migration assay. In some experiments, EGFR kinase activity in parental cells was inhibited by treatment with PD153035. All statistical tests were two-sided. Results: EGFR-antisense cells were morphologically distinct from vector control cells and had a selective decrease in adhesion to laminin-1 that was not observed with vector control cells (P =.008) or on other extracellular matrix substrates. Compared with vector control cells, cell surface alpha (6)-integrin expression decreased by approximately 80% (difference = 78.7%; 95% confidence interval [CI] = 77.8% to 79.6), MMP-9 activity decreased by approximately 50%, and TIMP activity increased by, approximately 50% in EGFR-antisense cells. Vector control cells were highly motile (5.51 arbitrary distance unit; 95% CI = 4.98 to 6.04), whereas the EGFR-antisense cells were not (0.99 arbitrary distance units; 95% CI = 0.38 to 1.60). The morphology and integrin profile of NIH:OVCAR-8 parental cells treated with PD153035 were similar to those of the EGFR-antisense cells. Conclusions: Reduced EGFR expression in ovarian carcinoma cells decreased their adhesion to laminin-1, expression of the alpha (6)-integrin subunit (a well-characterized laminin-1 receptor), and MMP-9 activity. These data support the hypothesis that EGFR overexpression in ovarian cancer cells results in multiple phenotypic changes that enhance the invasive phenotype. C1 Georgetown Univ, Dept Oncol, Washington, DC USA. NCI, Tumor Immunol & Biol Lab, Bethesda, MD 20892 USA. NCI, Extracellular Matrix Pathol Sect, Pathol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. Royal Hosp Women, Gynaecol Canc Ctr, Randwick, NSW, Australia. US FDA, Div Therapeut Prot, Ctr Biol Evaluat & Res, NIH, Bethesda, MD 20014 USA. RP Stetler-Stevenson, WG (reprint author), NIH, Bldg 10,Rm 2A33,MSC 1500, Bethesda, MD 20892 USA. RI Bergmann-Leitner, Elke/B-3548-2011; Stetler-Stevenson, William/H-6956-2012 OI Bergmann-Leitner, Elke/0000-0002-8571-8956; Stetler-Stevenson, William/0000-0002-5500-5808 NR 49 TC 101 Z9 111 U1 0 U2 3 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD SEP 19 PY 2001 VL 93 IS 18 BP 1375 EP 1384 DI 10.1093/jnci/93.18.1375 PG 10 WC Oncology SC Oncology GA 473GZ UT WOS:000171033300008 PM 11562388 ER PT J AU Chikhale, EG Balbo, A Galdzicki, Z Rapoport, SI Shetty, HU AF Chikhale, EG Balbo, A Galdzicki, Z Rapoport, SI Shetty, HU TI Measurement of myo-inositol turnover in phosphatidylinositol: Description of a model and mass spectrometric method for cultured cortical neurons SO BIOCHEMISTRY LA English DT Article ID RAT-BRAIN; 1-2-CYCLIC PHOSPHATE; CEREBROSPINAL-FLUID; ALZHEIMERS-DISEASE; DOWNS-SYNDROME; MYOINOSITOL; LITHIUM; CHROMATOGRAPHY; PHOSPHOLIPIDS; METABOLISM AB Rates of myo-inositol (Ins) incorporation and turnover in phosphatidylinositol (PtdIns) were determined in cultured mouse cortical neurons. Cells were incubated with deuterium-labeled myo-inositol (Ins*) in culture medium free of unlabeled Ins. The time-dependent changes in the specific activity of cytosolic Ins* and membrane PtdIns* were measured by mass spectrometry. PtdIns turnover was modeled incorporating values for Ins* flux, cytosolic dilution, PtdIns concentration, and rate of incorporation into PtdIns. Recycled Ins diluted the labeled precursor pool, and a time course was obtained for this cytosolic process. The specific activity of the precursor pool at the plateau of the time-course curve was 0.43 +/- 0.04 (mean SD). The incorporation of the tracer into PtdIns was linear between 4 and 10 h incubation of the neurons. After factoring in the extent of dilution of the tracer in the precursor pool, the rate of Ins incorporation into PtdIns was found to be 315 +/- 51 nmol (g of protein)(-1) h(-1). The half-life of Ins in PtdIns was calculated for each point on the linear incorporation curve and then corrected for the tracer reincorporation. The half-life of Ins in PtdIns was 6.7 +/- 0.2 h, which translates into a basal turnover rate of 10.3%/h in this in vitro system. The mathematical model and the stable isotope method described here should allow assessment of the dynamics of PtdIns signaling altered in certain diseases or by agents. C1 NIA, Sect Brain Physiol & Metab, NIH, Bethesda, MD 20892 USA. US FDA, Off New Drug Chem, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Shetty, HU (reprint author), NIA, Sect Brain Physiol & Metab, NIH, Bldg 10,Room 6N 202,10 Ctr Dr Msc 1582, Bethesda, MD 20892 USA. NR 43 TC 7 Z9 7 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 SEP 18 PY 2001 VL 40 IS 37 BP 11114 EP 11120 DI 10.1021/bi010817k PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 473GP UT WOS:000171032400024 PM 11551209 ER PT J AU Gursel, I Gursel, M Ishii, KJ Klinman, DM AF Gursel, I Gursel, M Ishii, KJ Klinman, DM TI Sterically stabilized cationic liposomes improve the uptake and immunostimulatory activity of CpG oligonucleotides SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NATURAL-KILLER ACTIVITY; PH-SENSITIVE LIPOSOMES; IN-VIVO; BACTERIAL-DNA; PLASMID DNA; OLIGODEOXYNUCLEOTIDES; MOTIFS; INFLAMMATION; ACTIVATION; SEQUENCES AB Immunostimulatory CpG oligonucleotides (ODN) show promise as immune adjuvants, anti-allergens, and immunoprotective agents. Increasing the bioavailability and duration of action of CpG ODN should improve their therapeutic utility. Encapsulating ODN in sterically stabilized cationic liposomes provides protection from serum nucleases while facilitating uptake by B cells, dendritic cells, and macrophages. In a pathogen challenge model, sterically stabilized cationic liposomes encapsulation doubled the duration of CpG ODN-induced immune protection. In an immunization model, coencapsulation of CpG ODN with protein Ag (OVA) magnified the resultant Ag-specific IFN-gamma and IgG responses by 15- to 40-fold compared with Ag plus CpG ODN alone. These findings support the use of sterically stabilized cationic liposomes to significantly enhance the therapeutic efficacy of CpG ODN. 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,Room 3 D 10, 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 41 TC 128 Z9 136 U1 0 U2 8 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 2001 VL 167 IS 6 BP 3324 EP 3328 PG 5 WC Immunology SC Immunology GA 496JG UT WOS:000172392000038 PM 11544321 ER PT J AU Wang, JH Guan, E Roderiquez, G Norcross, MA AF Wang, JH Guan, E Roderiquez, G Norcross, MA TI Synergistic induction of apoptosis in primary CD4(+) T cells by macrophage-tropic HIV-1 and TGF-beta 1 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; GROWTH-FACTOR-BETA; CASPASE-ACTIVATED DNASE; FAS LIGAND EXPRESSION; TGF-BETA; UP-REGULATION; CCR5 EXPRESSION; CYTOCHROME-C; HOST FACTORS; B-CELLS AB Depletion of CD4(+) T lymphocytes is a central immunological characteristic of HIV-1 infection. Although the mechanism of such CD4(+) cell loss following macrophage-tropic (R5) HIV-1 infection remains unclear, interactions between viral and host cell factors are thought to play an important role in the pathogenesis of HIV-1 disease. Based on the observation that TGF-beta1 enhanced expression of HIV chemokine coreceptors, the role of this host factor in virus effects was investigated using PBLs cultured in a nonmitogen-added system in the absence or presence of TGF-beta1. Most CD4 cells in such cultures had the phenotype CD25(-)CD69(-)DR(-)Ki67(-) and were CD45RO(bright)CD45(dim). Cultured cells had increased expression of CCR5 and CXCR4 and supported both HIV-1 entry and completion of viral reverse transcription. Virus production by cells cultured in the presence of IL-2 was inhibited by TGF-beta1, and this inhibition was accompanied by a loss of T cells from the culture and an increase in CD4(+) T cell apoptosis. Whereas R5X4 and X4 HIV-1 infection was sufficient to induce T cell apoptosis, R5 HIV-1 failed to induce apoptosis of PBLs in the absence of TGF-beta1 despite the fact that R5 HIV-1 depletes CD4(+) T cells in vivo. Increased apoptosis with HIV and TGF-beta1 was associated with reduced levels of Bcl-2 and increased expression of apoptosis-inducing factor, caspase-3, and cleavage of BID, c-IAP-1, and X-linked inhibitor of apoptosis. These results show that TGF-beta1 promotes depletion of CD4(+) T cells after R5 HIV-1 infection by inducing apoptosis and suggest that TGF-beta1 might contribute to the pathogenesis of HIV-1 infection in vivo. C1 NIH, Div Therapeut Prot, Ctr Biol Evaluat & Res, US FDA,Lab Gene Regulat, Bethesda, MD 20892 USA. RP Wang, JH (reprint author), NIH, Div Therapeut Prot, Ctr Biol Evaluat & Res, US FDA,Lab Gene Regulat, Bldg 29B,Room 4E12,8000 Rockville Pike, Bethesda, MD 20892 USA. NR 71 TC 18 Z9 19 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 2001 VL 167 IS 6 BP 3360 EP 3366 PG 7 WC Immunology SC Immunology GA 496JG UT WOS:000172392000043 PM 11544326 ER PT J AU Lachenbruch, P Marzella, L Schwieterman, W Weiss, K Siegel, J AF Lachenbruch, P Marzella, L Schwieterman, W Weiss, K Siegel, J TI Poisson distribution to assess actinic keratoses in xeroderma pigmentosum SO LANCET LA English DT Letter C1 US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20851 USA. RP Weiss, K (reprint author), US FDA, Ctr Biol Evaluat & Res, 1401 Rockville Pike, Rockville, MD 20851 USA. NR 2 TC 2 Z9 3 U1 0 U2 0 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD SEP 15 PY 2001 VL 358 IS 9285 BP 925 EP 925 DI 10.1016/S0140-6736(01)06054-8 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 474CP UT WOS:000171087000042 PM 11575371 ER PT J AU Ellenberg, SS AF Ellenberg, SS TI Independent data monitoring committees: rationale, operations and controversies SO STATISTICS IN MEDICINE LA English DT Article; Proceedings Paper CT 3rd International Conference on Medical Statistics CY JUL 28-30, 1999 CL DE MONTFORT UNIV, LEICESTER, ENGLAND HO DE MONTFORT UNIV ID CLINICAL-TRIALS; SEQUENTIAL-METHODS; BOUNDARIES; ISSUES AB Data monitoring committees (DMCs) have become an increasingly common component of randomized clinical trials in recent years. As experience has accumulated, and more individuals and organizations have become involved in such activities, a variety of approaches to the operation of such committees has inevitably arisen. Because these committees play such a critical role in the process of new drug development, it is important to consider the implications of the different approaches that are being used. It is also timely to consider the present and possible future regulatory status of data monitoring committees. Published in 2001 by John Wiley & Sons, Ltd. 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,HFM-210, Rockville, MD 20852 USA. NR 38 TC 10 Z9 10 U1 0 U2 1 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 SEP 15 PY 2001 VL 20 IS 17-18 BP 2573 EP 2583 DI 10.1002/sim.730 PG 11 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 469HQ UT WOS:000170808800005 PM 11523070 ER PT J AU Niu, MT Erwin, DE Braun, MM AF Niu, MT Erwin, DE Braun, MM TI Data mining in the US Vaccine Adverse Event Reporting System (VAERS): early detection of intussusception and other events after rotavirus vaccination SO VACCINE LA English DT Article DE data mining; VAERS; intussusception ID LARGE FREQUENCY TABLES AB The Vaccine Adverse Event Reporting System (VAERS) is the US passive surveillance system monitoring vaccine safety. A major limitation of VAERS is the lack of denominator data (number of doses of administered vaccine), an element necessary for calculating reporting rates. Empirical Bayesian data mining, a data analysis method, utilizes the number of events reported for each vaccine and statistically screens the database for higher than expected vaccine-event combinations signaling a potential vaccine-associated event. This is the first study of data mining in VAERS designed to test the utility of this method to detect retrospectively a known side effect of vaccination-intussusception following rotavirus (RV) vaccine. From October 1998 to December 1999, 112 cases of intussusception were reported. The data mining method was able to detect a signal for RV-intussusception in February 1999 when only four cases were reported. These results demonstrate the utility of data mining to detect significant vaccine-associated events at early date. Data mining appears to be an efficient and effective computer-based program that may enhance early detection of adverse events in passive surveillance systems. Published by Elsevier Science Ltd. C1 US FDA, Ctr Biol Evaluat & Res, Off Biostat & Epidemiol, Div Epidemiol,Vaccine Safety Branch, Rockville, MD 20852 USA. US FDA, Ctr Biol Evaluat & Res, Off Biostat & Epidemiol, Div Epidemiol, Rockville, MD 20852 USA. Informat Management Serv Inc, Rockville, MD USA. RP Niu, MT (reprint author), US FDA, Ctr Biol Evaluat & Res, Off Biostat & Epidemiol, Div Epidemiol,Vaccine Safety Branch, 1401 Rockville Pike,HFM-210, Rockville, MD 20852 USA. NR 13 TC 50 Z9 50 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 14 PY 2001 VL 19 IS 32 BP 4627 EP 4634 DI 10.1016/S0264-410X(01)00237-7 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 473HR UT WOS:000171035500007 PM 11535310 ER PT J AU Schwetz, BA AF Schwetz, BA TI Treatment for hepatitis C SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT News Item C1 US FDA, Off Commissioner Food & Drugs, Rockville, MD 20857 USA. RP Schwetz, BA (reprint author), US FDA, Off Commissioner Food & Drugs, HF-1,Room 14-71,5600 Fishers Ln, Rockville, MD 20857 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD SEP 12 PY 2001 VL 286 IS 10 BP 1166 EP 1166 DI 10.1001/jama.286.10.1166 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 471CR UT WOS:000170910400006 PM 11559244 ER PT J AU Schwetz, BA AF Schwetz, BA TI Novel imaging device SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT News Item C1 US FDA, Off Commissioner Food & Drugs, Rockville, MD 20857 USA. RP Schwetz, BA (reprint author), US FDA, Off Commissioner Food & Drugs, HF-1,Room 14-71,5600 Fishers Ln, Rockville, MD 20857 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD SEP 12 PY 2001 VL 286 IS 10 BP 1166 EP 1166 DI 10.1001/jama.286.10.1166 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 471CR UT WOS:000170910400005 PM 11559244 ER PT J AU Schwetz, BA AF Schwetz, BA TI New FDA Web sites SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT News Item C1 US FDA, Off Commissioner Food & Drugs, Rockville, MD 20857 USA. RP Schwetz, BA (reprint author), US FDA, Off Commissioner Food & Drugs, HF-1,Room 14-71,5600 Fishers Ln, Rockville, MD 20857 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD SEP 12 PY 2001 VL 286 IS 10 BP 1166 EP 1166 DI 10.1001/jama.286.10.1166 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 471CR UT WOS:000170910400007 PM 11559244 ER PT J AU Kushimoto, T Basrur, V Valencia, J Matsunaga, J Vieira, WD Ferrans, VJ Muller, J Appella, E Hearing, VJ AF Kushimoto, T Basrur, V Valencia, J Matsunaga, J Vieira, WD Ferrans, VJ Muller, J Appella, E Hearing, VJ TI A model for melanosome biogenesis based on the purification and analysis of early melanosomes SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE pigment; melanin; tyrosinase; melanoma ID II OCULOCUTANEOUS ALBINISM; TYROSINASE GENE FAMILY; MAMMALIAN TYROSINASE; MEMBRANE-PROTEINS; LOCUS PROTEIN; PIGMENTATION; IDENTIFICATION; TRANSPORT; SIGNALS; PMEL-17 AB Melanosome biogenesis and function were studied after purification of early stage melanosomes and characterization of specific proteins sorted to that organelle. Melanosomes were isolated from highly pigmented human MNT1 melanoma cells after disruption and initial separation by sucrose density gradient centrifugation. Low-density sucrose fractions were found by electron microscopy to be enriched in stage I and stage II melanosomes, and these fractions were further separated and purified by free flow electrophoresis. Tyrosinase and dopachrome tautomerase (DCT) activities were found exclusively in stage II melanosomes, even though DCT (and to some extent tyrosinase) proteins were sorted to stage I melanosomes. Western immunoblotting revealed that these catalytic proteins, as well as TYRP1, MART1, and GP100, were cleaved and inactivated in stage I melanosomes. Proteolytic cleavage was critical for the refolding of GP100 within the melanosomal milieu, and subsequent reorganization of amorphous stage I melanosomes into fibrillar, ovoid, and highly organized stage II melanosomes appears to stabilize the catalytic functions of melanosomal enzymes and allows melanin biosynthesis to begin. These results provide a better understanding of the structural features seen during melanosome biogenesis, and they yield further clues as to the physiological regulation of pigmentation. C1 NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. NHLBI, Pathol Sect, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Hearing, VJ (reprint author), NCI, Cell Biol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 41 TC 144 Z9 148 U1 1 U2 9 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 11 PY 2001 VL 98 IS 19 BP 10698 EP 10703 DI 10.1073/pnas.191184798 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 472CZ UT WOS:000170966800038 PM 11526213 ER PT J AU Bogusz, S Venable, RM Pastor, RW AF Bogusz, S Venable, RM Pastor, RW TI Molecular dynamics simulations of octyl glucoside micelles: Dynamic properties SO JOURNAL OF PHYSICAL CHEMISTRY B LA English DT Article ID DODECYL-SULFATE MICELLE; BETA-D-GLUCOSIDE; AQUEOUS-SOLUTION; CHEMICAL PROPERTIES; MEMBRANE PEPTIDES; NMR RELAXATION; OCTYLGLUCOSIDE; PROTEINS; MACROMOLECULES; PURIFICATION AB Dynamic properties of octyl glucoside (OG) micelles were explored using molecular dynamics simulations. Systems studied included individual beta -OG micelles containing 10, 20, 27, 34, 50, and 75 lipids; two 20 lipid P-OG micelles; a disperse solution of 27 beta -OG, and four molecules of glucose. Calculated C-13 NMR T-1 relaxation times for the tail carbons of micelle aggregation numbers between 34 and 75 agreed well with experiment; these results are consistent with estimates of the micelle size based on translational diffusion. However, TI's for the head-roup carbons, which couple strongly with the solvent, were too large. This was primarily due to the low viscosity of the TIP3P water model, and subsequent scaling of the relaxation times led to agreement with experiment for the carbons in the glucose ring, but not the exocyclic carbon; the likely reason for the latter discrepancy is a torsional potential barrier that is slightly too high. A detailed analysis of the micelle dynamics revealed shape changes on the time scale of tens to hundreds of picoseconds, while rotation and lipid diffusion within the micelle occur over nanoseconds. The primary components of NMR Ti relaxation are lipid wobble and chain isomerization, as well as slower concerted motions on the time scale of the shape changes. Lipid lateral diffusion and overall micelle. tumbling do not contribute significantly to NMR relaxation. Micelle self-assembly on the nanosecond time scale was also demonstrated. The two 20 lipid micelles merged and the 27 dispersed lipids aggregated, highlighting a new range of behavior accessible to molecular dynamics simulation. C1 US FDA, Biophys Lab, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Pastor, RW (reprint author), US FDA, Biophys Lab, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. NR 54 TC 72 Z9 72 U1 2 U2 9 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1520-6106 J9 J PHYS CHEM B JI J. Phys. Chem. B PD SEP 6 PY 2001 VL 105 IS 35 BP 8312 EP 8321 DI 10.1021/jp004475o PG 10 WC Chemistry, Physical SC Chemistry GA 470MQ UT WOS:000170876100008 ER PT J AU Rosebraugh, CJ Honig, PK Yasuda, SU Pezzullo, JC Flockhart, DA Woosley, RL AF Rosebraugh, CJ Honig, PK Yasuda, SU Pezzullo, JC Flockhart, DA Woosley, RL TI Formal education about medication errors in internal medicine clerkships SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 US FDA, Rockville, MD 20857 USA. Georgetown Univ, Dept Pharmacol, Washington, DC USA. Georgetown Univ, Dept Internal Med, Washington, DC USA. RP Rosebraugh, CJ (reprint author), US FDA, Rockville, MD 20857 USA. FU AHRQ HHS [U18HS10385]; NIGMS NIH HHS [T32 GM008386] NR 5 TC 17 Z9 17 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD SEP 5 PY 2001 VL 286 IS 9 BP 1019 EP 1020 DI 10.1001/jama.286.9.1019 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 469EW UT WOS:000170802500002 PM 11559279 ER PT J AU Laughren, T AF Laughren, T TI A regulatory perspective on psychiatric syndromes in Alzheimer disease SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Editorial Material C1 US FDA, Rockville, MD 20857 USA. RP Laughren, T (reprint author), US FDA, Rockville, MD 20857 USA. NR 3 TC 33 Z9 33 U1 0 U2 1 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 1064-7481 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD FAL PY 2001 VL 9 IS 4 BP 340 EP 345 DI 10.1176/appi.ajgp.9.4.340 PG 6 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 484PF UT WOS:000171698200003 PM 11739061 ER PT J AU Sundar, S Pai, K Kumar, R Pathak-Tripathi, K Gam, AA Ray, M Kenney, RT AF Sundar, S Pai, K Kumar, R Pathak-Tripathi, K Gam, AA Ray, M Kenney, RT TI Resistance to treatment in Kala-azar: Speciation of isolates from northeast India SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID VISCERAL LEISHMANIASIS; PENTAVALENT ANTIMONY; INTERFERON-GAMMA; SODIUM STIBOGLUCONATE; DONOVANI; AMASTIGOTES; BIHAR; MILTEFOSINE; ANTIBODIES; EFFICACY AB Kala-azar in India is becoming increasingly difficult to treat, which may be due to the presence of species other than Leishmania donovani; Leishmania tropica was reported to cause the same clinical syndrome in the area. Over the past 3 years, we have collected samples from 241 patients with visceral leishmaniasis from across the region. Of the 189 isolates that grew on diphasic medium, 159 were successfully transferred to liquid medium for typing. Clinically, 80% of these were resistant to antimony. Lipophosphoglycan-specific monoclonal antibodies were used to distinguish the 2 species by agglutination of promastigotes; all 159 were shown to be L. donovani. Eighty-three isolates were confirmed to be L. donovani by isoenzyme analysis, by amplification of kinetoplast DNA, or both, in comparison with multiple reference strains; none were L. tropica. Thus, the rising incidence of clinical resistance to treatment is unlikely to be due to a different species causing kala-azar in north Bihar. C1 Banaras Hindu Univ, Inst Med Sci, Dept Med, Kala Azar Med Res Ctr, Varanasi 221005, Uttar Pradesh, India. US FDA, Ctr Biol Evaluat & Res, Lab Parasit Biol & Biochem, Bethesda, MD USA. RP Kenney, RT (reprint author), IOMAI Corp, Firstfield Rd 250, Gaithersburg, MD 20878 USA. NR 26 TC 35 Z9 35 U1 0 U2 1 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD SEP PY 2001 VL 65 IS 3 BP 193 EP 196 PG 4 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 471MP UT WOS:000170933400007 PM 11561703 ER PT J AU Lee, CH Frasch, CE AF Lee, CH Frasch, CE TI Quantification of bacterial polysaccharides by the purpald assay: Measurement of periodate-generated formaldehyde from glycol in the repeating unit SO ANALYTICAL BIOCHEMISTRY LA English DT Article ID GROUP-B STREPTOCOCCUS; RESOLUTION NMR-SPECTROSCOPY; CAPSULAR POLYSACCHARIDE; STRUCTURAL DETERMINATION; IMMUNOCHEMICAL CHARACTERIZATION; ANTIGEN; ASSIGNMENT AB We have adapted the purpald assay for measurement of bacterial polysaccharides (PS) containing substituted and/or unsubstituted glycol (SG or UG) in residues such as glycerol, ribitol, arabinitol, furanosyl galactose, and sialic acid. For the purpald assay of UG-containing PS, 50 muL of PS samples was consecutively reacted with 50 muL of 16 mM NaIO4 for 20 min, 50 muL of 136 mM purpald reagent in 2 N NaOH for 20 min, and 50 muL of 64 mM NaIO4. for 20 min in a 96-well tissue culture plate followed by a measurement of absorbance at 550 nm with a plate reader. For SG-containing PS, conversion of SG to UG with 25 muL of 0.3 N NaOH, 1 h at room temperature for de-O-acetylation followed by 25 muL of 0.6 M H2SO4, 1 h at 80 degreesC for acid hydrolysis of PS precedes the periodate treatment in the purpald assay. The concentration of the samples can be calculated from the sample absorbance and the reference standard curve constructed from the reference concentrations of the same PS (well-characterized) and their corresponding absorbance values assayed in the same plate. The purpald assay provides a tool in addition to the existing ones for the measurement of glycol-containing PS. Among the usefulness of this method are the determinations of the glycerol content in the phospho-glycerol-containing PS and the SG and UG contents and structural integrity in PS and conjugate vaccines. (C) 2001 Academic Press. C1 US FDA, CBER, OVRR,Lab Bacterial Polysaccharides, Div Bacterial Parasit & Allergen Prod, Bethesda, MD 20892 USA. RP Lee, CH (reprint author), US FDA, CBER, OVRR,Lab Bacterial Polysaccharides, Div Bacterial Parasit & Allergen Prod, 8800 Rockville Pike, Bethesda, MD 20892 USA. NR 28 TC 14 Z9 14 U1 2 U2 7 PU ACADEMIC PRESS INC 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 SEP 1 PY 2001 VL 296 IS 1 BP 73 EP 82 DI 10.1006/abio.2001.5230 PG 10 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 470LC UT WOS:000170872600009 PM 11520034 ER PT J AU Sietmann, R Hammer, E Specht, M Cerniglia, CE Schauer, F AF Sietmann, R Hammer, E Specht, M Cerniglia, CE Schauer, F TI Novel ring cleavage products in the biotransformation of biphenyl by the yeast Trichosporon mucoides SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID AROMATIC-HYDROCARBONS; PHANEROCHAETE-CHRYSOSPORIUM; ASPERGILLUS-TOXICARIUS; TRAMETES-VERSICOLOR; METABOLISM; HYDROXYLATION; TRANSFORMATION; CUTANEUM; FUNGI AB The yeast Trichosporon mucoides, grown on either glucose or phenol, was able to transform biphenyl into a variety of mono-, di-, and trihydroxylated derivatives hydroxylated on one or both aromatic rings. While some of these products accumulated in the supernatant as dead end products, the ortho-substituted dihydroxylated biphenyls were substrates for further oxidation and ring fission. These ring fission products were identified by high-performance liquid chromatography, gas chromatography-mass spectrometry, and nuclear magnetic resonance analyses as phenyl derivatives of hydroxymuconic acids and the corresponding pyrones. Seven novel products out of eight resulted from the oxidation and ring fission of 3,4-dihydroxybiphenyl. Using this compound as a substrate, 2-hydroxy-4-phenylmuconic acid, (5-oxo-3-phenyl-2,5-dihydrofuran-2-yl)acetic acid, and 3-phenyl-2-pyrone-6-carboxylic acid were identified. Ring cleavage of 3,4,4 ' -trihydroxybiphenyl resulted in the formation of (5-oxo-3-(4 ' -hydroxyphenyl)-2,5-dihydrofuran-2-yl) acetic acid, 4-(4'-hydroxyphenyl)-2-pyrone-6-carboxylic acid, and 3-(4 ' -hydroxyphenyl)-2-pyrone-6-carboxylic acid. 2,3,4-Trihydroxybiphenyl was oxidized to 2-hydroxy-5-phenylmuconic acid, and 4-phenyl-2-pyrone-6-carboxylic acid was the transformation product of 3,4,5-trihydroxybiphenyl. All these ring fission products were considerably less toxic than the hydroxylated derivatives. C1 Univ Greifswald, Inst Mikrobiol & Mol Biol, D-17487 Greifswald, Germany. Univ Hamburg, Inst Organ Chem, D-20146 Hamburg, Germany. US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Sietmann, R (reprint author), Univ Greifswald, Inst Mikrobiol & Mol Biol, FL Jahn Str 15, D-17487 Greifswald, Germany. NR 37 TC 10 Z9 11 U1 1 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0099-2240 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD SEP PY 2001 VL 67 IS 9 BP 4158 EP 4165 DI 10.1128/AEM.67.9.4158-4165.2001 PG 8 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 468FH UT WOS:000170747100054 PM 11526019 ER PT J AU Cha, CJ Doerge, DR Cerniglia, CE AF Cha, CJ Doerge, DR Cerniglia, CE TI Biotransformation of malachite green by the fungus Cunninghamella elegans SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID TRIPHENYLMETHANE DYES; GENTIAN-VIOLET; PHANEROCHAETE-CHRYSOSPORIUM; LIQUID-CHROMATOGRAPHY; LEUCOMALACHITE GREEN; CRYSTAL VIOLET; METABOLISM; DECOLORIZATION; AZO; BIODEGRADATION AB The filamentous fungus Cunninghamella elegans ATCC 36112 metabolized the triphenylmethane dye malachite green with a first-order rate constant of 0.029 mu mol h(-1) (mg of cells)(-1). Malachite green was enzymatically reduced to leucomalachite green and also converted to N-demethylated and N-oxidized metabolites, including primary and secondary arylamines. Inhibition studies suggested that the cytochrome P450 system mediated both the reduction and the N-demethylation reactions. 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. RP Cerniglia, CE (reprint author), US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. NR 28 TC 122 Z9 134 U1 3 U2 18 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 SEP PY 2001 VL 67 IS 9 BP 4358 EP 4360 DI 10.1128/AEM.67.9.4358-4360.2001 PG 3 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 468FH UT WOS:000170747100082 PM 11526047 ER PT J AU Hutter, JC Long, MC Luu, HMD Schroeder, LW AF Hutter, JC Long, MC Luu, HMD Schroeder, LW TI Prediction of the shelf life of cellulose acetate hemodialyzers by Monte Carlo simulation SO ASAIO JOURNAL LA English DT Article ID THERMAL-DEGRADATION; DIALYZERS AB A previous investigation by our laboratory linked cellulose acetate degradation with adverse health effects in hemodialysis patients.(1) To establish the accumulation of degradation products with time, a Monte Carlo model of degradation kinetics was developed. The model tracks changes in a population of molecules representative of the dialyzer membrane during the degradation process. The degradation calculation is a two step process: First, the model uses a random number to select an individual polymer molecule out of the population, and then a second random number is used to identify a site on the selected molecule for the degradation reaction to occur. After the reaction calculation, the resulting degraded molecules are redistributed into the population. The course of the reaction is determined by recalculating the molecular weight averages in the changing population as the calculations proceed. The model was validated using gel permeation chromatography molecular weight results and total acetyl content measurements on dialyzers stored up to 13.3 years after manufacture. It was found that the degradation reactions can be accurately modeled as random events and that the chain scissions and deacetylation events occur at constant rates. The shelf life of these devices was estimated using the model predictions and animal test results. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20852 USA. RP Hutter, JC (reprint author), US FDA, Ctr Devices & Radiol Hlth, 12725 Twinbrook Pky,HFZ-150, Rockville, MD 20852 USA. NR 24 TC 2 Z9 2 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1058-2916 J9 ASAIO J JI Asaio J. PD SEP-OCT PY 2001 VL 47 IS 5 BP 522 EP 527 DI 10.1097/00002480-200109000-00025 PG 6 WC Engineering, Biomedical; Transplantation SC Engineering; Transplantation GA 472QV UT WOS:000170997200025 PM 11575830 ER PT J AU O'Reilly, S Hartman, NR Bowling, KM Rowinsky, EK Donehower, RC Collins, J Strong, JM AF O'Reilly, S Hartman, NR Bowling, KM Rowinsky, EK Donehower, RC Collins, J Strong, JM TI Bioavailablility of penclomedine and systemic exposure to 4-O-demethylpenclomedine in patients receiving oral and intravenous penclomedine SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article; Proceedings Paper CT 89th Annual Meeting of the American-Association-for-Cancer-Research CY MAR 27-APR 01, 1998 CL NEW ORLEANS, LOUISIANA SP Amer Assoc Canc Res DE penclomedine; 4-0-demethyl penclomedine; pharmacokinetics; clinical trial; antitumor ID PRECLINICAL ANTITUMOR-ACTIVITY; PHASE-I; METABOLISM; MURINE; PHARMACOKINETICS; BIOAVAILABILITY; NSC-338720; TUMORS AB Purpose: Oral administration of penclomedine was investigated based on preclinical studies indicating that an oral schedule of penclomedine treatment may prevent the neurotoxicity observed in phase I studies of an intravenous (i.v.) formulation, possibly by reducing maximum plasma concentrations (C-max) of the neurotoxic parent species. Methods: Penclomedine was administered i.v. (200 mg/m(2)) and orally (250 mg/m(2)) in alternate sequences to patients with solid tumor malignancies. Plasma concentrations of parent drug and the principal metabolite, 4-O-demethylpenclomedine, were determined by a reversed-phase HPLC assay. Results: Penclomedine was detectable in the plasma of all patients within 1 h of oral penclomedine treatment and C-max was reached within 1 to 4 h. Consistent with the hypothesis that an oral schedule of administration may circumvent neurotoxicity, a paired data analysis demonstrated a significant reduction in C-max values following oral administration (P=0.017). However the magnitude of this reduction was highly variable. Similarly an extensive range in the relative exposure to both parent drug and metabolite were observed. The bioavailability of penclomedine ranged from 28% to 98% (median 73%). Conclusions: Oral penclomedine does produce systemic exposure, but substantial interpatient variability in absorption and systemic exposure is present which may limit the clinical role of the oral route of administration. C1 US FDA, Ctr Drug Evaluat & Res, Laurel, MD 20708 USA. Johns Hopkins Oncol Ctr, Baltimore, MD 21287 USA. RP Strong, JM (reprint author), US FDA, Ctr Drug Evaluat & Res, 8301 Muirkirk Rd, Laurel, MD 20708 USA. FU NCI NIH HHS [N01 CM 07302] NR 17 TC 2 Z9 2 U1 0 U2 0 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 SEP PY 2001 VL 48 IS 3 BP 223 EP 228 DI 10.1007/s002800100346 PG 6 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 476XZ UT WOS:000171255200007 PM 11592344 ER PT J AU Pilaro, AM AF Pilaro, AM TI USFDA regulatory expectations for preclinical demonstration of safety of genetic anticancer agents SO CANCER GENE THERAPY LA English DT Meeting Abstract C1 US FDA, Ctr Biol Evaluat & Res, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0929-1903 J9 CANCER GENE THER JI Cancer Gene Ther. PD SEP PY 2001 VL 8 IS 9 MA 10 BP 686 EP 687 PG 2 WC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Research & Experimental Medicine GA 475QM UT WOS:000171175600018 ER PT J AU Moxey-Mims, MM AF Moxey-Mims, MM TI Comment on "High-sensitivity C-reactive protein: Product claims and the food and drug administration" SO CLINICAL CHEMISTRY LA English DT Letter C1 US FDA, CDRH, ODE, DCLD,Clin Chem Branch, Rockville, MD 20850 USA. RP Moxey-Mims, MM (reprint author), US FDA, CDRH, ODE, DCLD,Clin Chem Branch, 2098 Gaither Rd,HFZ-440, Rockville, MD 20850 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 SEP PY 2001 VL 47 IS 9 BP 1743 EP 1743 PG 1 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 466GJ UT WOS:000170636600038 ER PT J AU Averbuch, M Katzper, M AF Averbuch, M Katzper, M TI Gender and the placebo analgesic effect in acute pain SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID SEX-DIFFERENCES; GENERAL-POPULATION; THRESHOLD; STIMULI; WOMEN AB Objective: Our objective was to examine the placebo arms from a series of clinical trials in which the post-third molar extraction dental pain model was used to elucidate the time course of the placebo effect and the proportion of the population that are responders, as well as to evaluate whether the placebo analgesic response of female subjects may differ from that of male subjects. Methods: We performed a meta-analysis of 596 subjects included in the placebo treatment arm of 16 double-blind, post-third molar extraction dental pain (moderate to severe) studies submitted to the Food and Drug Administration electronically. The inclusion and exclusion criteria were practically identical in all studies. Pain relief and pain intensity measurements used the same metrics in all studies. The measurements were recorded just before drug administration and at least at postdose hours 0.5, 1, 1.5, 2, 3, 4, 5, and 6. Results: There were325 female subjects and 271 male subjects. They were all otherwise healthy; with a mean age of 21.6 years for female subjects and 22.3 years for male subjects. The postoperative baseline pain was greater in female subjects than in male subjects, and this difference was statistically significant. Both pain intensity and pain relief scores demonstrate the well-established placebo effect in 10% of the pooled subjects, as well as in all the individual studies: Over time, however, the mean pain intensity and pain relief scores for the female and male treatment groups were not noticeably different at any time point after medication. Further analysis of the data showed no gender difference in duration of action of the placebo. Conclusions: The results demonstrated no gender difference in response to placebo. These results were obtained from the post-third molar extraction situation, in which the least possible confounding factors were present. To fully establish the generality of this phenomenon, studies should be carried out in other pain models. C1 US FDA, Ctr Drug Evaluat & Res, Div Analges Antiinflammatory & Ophthalm Drug Prod, Rockville, MD 20857 USA. RP Katzper, M (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Analges Antiinflammatory & Ophthalm Drug Prod, HFD-500,5600 Fishers Lane, Rockville, MD 20857 USA. NR 27 TC 34 Z9 36 U1 1 U2 3 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD SEP PY 2001 VL 70 IS 3 BP 287 EP 291 DI 10.1067/mcp.2001.118366 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 475XW UT WOS:000171196100012 PM 11557917 ER PT J AU Trontell, AE AF Trontell, AE TI How the US Food and Drug Administration defines and detects adverse drug events SO CURRENT THERAPEUTIC RESEARCH-CLINICAL AND EXPERIMENTAL LA English DT Article; Proceedings Paper CT Workshop on Adverse Drug Events in Pediatrics CY APR 09-10, 2001 CL ROCKVILLE, MARYLAND DE US Food and Drug Administration; adverse drug events; pediatrics ID SPONTANEOUS REPORTING SYSTEM; LARGE FREQUENCY TABLES AB Background: Examination of pediatric adverse drug events (ADEs) requires an understanding of the US Food and Drug Administration's (FDA's) regulatory definitions of ADEs and methods for their assessment. Objective: The aim of this paper was to characterize the tools used by the FDA to define ADEs. Methods: FDA regulations and ADE reporting databases and resources were examined, including the Adverse Event Reporting System (AERS), drug-use profiles, population databases, and active surveillance systems. Results: The US Code of Federal Regulations defines ADEs and degrees of seriousness of ADEs for regulatory reporting purposes. Drug manufacturers must report certain ADEs to the FDA, whereas health care professionals and consumers may report such events voluntarily using the MedWatch program. All reported ADEs constitute the FDA's AERS, which is used along with other postmarketing surveillance components to determine drug safety signals. AERS detects rare ADEs well and inexpensively, but underreporting and the variable quality of reports can limit its usefulness. AERS is best used in conjunction with other data resources, such as active surveillance systems, information on the volume and patterns of medication use, disease-specific background incidence rates, and population databases that can link outcomes with drug exposures. Conclusions: The FDA uses a network of data resources to supplement detection of ADEs via AERS. These data resources can be used to amplify, validate, and quantify ADE signals and then compare them to their expected background occurrence in the population. Use of additional databases and perspectives will improve the ability to detect ADEs in all settings, including the pediatric population, and to monitor risk management efforts to curtail the occurrence of known ADEs. C1 US FDA, Off Postmkt Drug Risk Assessment, Div Drug Risk Evaluat 1, Rockville, MD 20857 USA. RP Trontell, AE (reprint author), US FDA, Off Postmkt Drug Risk Assessment, Div Drug Risk Evaluat 1, HFD-430,Parklawn Room 15B-08,5600 Fishers Lane, Rockville, MD 20857 USA. NR 11 TC 14 Z9 14 U1 0 U2 2 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0011-393X J9 CURR THER RES CLIN E JI Curr. Ther. Res.-Clin. Exp. PD SEP PY 2001 VL 62 IS 9 BP 641 EP 649 DI 10.1016/S0011-393X(01)80070-9 PG 9 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 486DZ UT WOS:000171804300004 ER PT J AU O'Neill, RT Szarfman, A AF O'Neill, RT Szarfman, A TI Some US Food and Drug Administration perspectives on data mining for pediatric safety assessment SO CURRENT THERAPEUTIC RESEARCH-CLINICAL AND EXPERIMENTAL LA English DT Article; Proceedings Paper CT Workshop on Adverse Drug Events in Pediatrics CY APR 09-10, 2001 CL ROCKVILLE, MARYLAND DE data mining; adverse drug events; pediatrics; US Food and Drug Administration ID SPONTANEOUS REPORTING SYSTEM; LARGE FREQUENCY TABLES AB Background: The US Food and Drug Administration's (FDA's) large spontaneous reporting database contains > 110,000 voluntary reports of adverse drug events (ADEs) observed during postmarketing pediatric practice and submitted to the FDA by manufacturers, health care providers, or consumers. These reports may provide evidence about known or unknown harm associated with single or combination drug treatments in pediatric patients. We recently implemented new Bayesian data mining tools to evaluate >2 million reports stored in this database to help systematically identify safety signals that appear with unexpectedly high frequency. Objective: The purpose of this paper was to describe the current status of the application of Bayesian data mining tools to screen pediatric reports of ADEs submitted spontaneously to the FDA. Methods: We applied DuMouchel's empirical Bayesian data mining algorithms to the FDA's spontaneous reporting database. These methods circumvent the lack of exposure denominators in passive surveillance data. The first method implemented, the Gamma-Poisson Shrinkage model (GPS) computer program, detects higher-than-expected associations between drugs and adverse events. The method currently being used, the updated GPS program implemented in a software program called MGPS, adjusts for the multiplicity of drugs and events per record in the data reported after October 1997 and generalizes to multiple combinations of drugs and events (eg, triples, quadruples) that occur together in reports with unexpectedly high frequency. MGPS also identifies how much these unusually frequent itemsets can be explained by pairwise associations. For this article, we used the MGPS program to analyze pairwise, higher-than-expected associations between drugs and adverse events in pediatric reports. Results: We illustrate the potential of the data mining techniques to improve the early detection and analysis of new adverse events involving unusually frequent drug-event pairs in pediatric reports and to verify the significance of known ADEs. Conclusions: New data mining techniques help skilled safety evaluators and epidemiologists at the FDA analyze reports of pediatric ADEs submitted to the FDA spontaneously. These tools are not intended to replace current pharma-covigilance techniques but to enhance them. In the near future, these techniques should facilitate our study of potential drug interactions, a serious problem for pediatric patients requiring complicated medication regimens. C1 US FDA, Off Biostat, Ctr Drug Evaluat & Res, Rockville, MD 20850 USA. RP O'Neill, RT (reprint author), US FDA, Off Biostat, Ctr Drug Evaluat & Res, 9201 Corp Blvd,HFD-104, Rockville, MD 20850 USA. NR 15 TC 26 Z9 26 U1 1 U2 5 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0011-393X J9 CURR THER RES CLIN E JI Curr. Ther. Res.-Clin. Exp. PD SEP PY 2001 VL 62 IS 9 BP 650 EP 663 DI 10.1016/S0011-393X(01)80071-0 PG 14 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 486DZ UT WOS:000171804300005 ER PT J AU Cherstniakova, SA Bi, DQ Fuller, DR Mojsiak, JZ Collins, JM Cantilena, LR AF Cherstniakova, SA Bi, DQ Fuller, DR Mojsiak, JZ Collins, JM Cantilena, LR TI Metabolism of vanoxerine, 1-[2-[bis(4-fluorophenyl)methoxy]ethyl]-4-(3-phenylpropyl) piperazine, by human cytochrome P450 enzymes SO DRUG METABOLISM AND DISPOSITION LA English DT Article ID COCAINE-MEDIATED HEPATOTOXICITY; DOPAMINE REUPTAKE INHIBITOR; GBR-12909; GBR12909; RAT; BEHAVIOR; HISTORY AB Vanoxerine (1-[2-[bis(4-fluorophenyl)methoxy]ethyl]-4-(3-phenylpropyl)piperazine; GBR12909) is a promising agent for the treatment of cocaine dependence. Knowledge of the major pathway for GBR12909 metabolism is important for prediction of the likelihood of drug-drug interactions, which may affect the therapeutic clinical outcome, when this agent is used in cocaine-dependent individuals receiving multiple drug therapy. We studied biotransformation of GBR12909 in human liver microsomes (n = 4), human hepatocytes, and microsomes containing cDNA-expressed human P450 isoforms with GBR12909 concentrations within the range of steady-state plasma concentrations detected in healthy volunteers. A high-pressure liquid chromatography assay was used to measure parent GBR12909 and its primary metabolite. GBR12909 was metabolized by human liver microsomes, hepatocytes, and cDNA-expressed human P450s to a single metabolite. Ketoconazole, a selective inhibitor of CYP3A, reduced GBR12909 biotransformation in human liver microsomes and primary hepatocytes; by 92 +/- 2 and 92.4 +/- 0.4%, respectively. Quercetin (an inhibitor of CYP2C8/3A4) was a less effective inhibitor producing 62 +/- 22% inhibition in human liver microsomes and 54 +/- 35% in hepatocytes. Other P450 selective inhibitors did not decrease GBR12909 biotransformation more than 29% in either human liver microsomes or hepatocytes with the exception of chlorzoxazone (CYP2E1), which inhibited GBR12909 biotransformation by 71.4 +/- 18.5% in primary human hepatocytes. Ciprofloxacin (CYP1A2), sulfaphenazole (CYP2C9), quinidine (CYP2D6), chlorzoxazone (CYP2E1), and mephenytoin (CYP2C19) did not demonstrate statistically significant inhibition (p > 0.05) of GBR12909 biotransformation in liver microsomes. cDNA-expressed P450 3A4 metabolized GBR12909 to a greater extent than 2C8 and 2E1. These data suggest the possibility that multiple P450 isoforms may be involved in human GBR12909 metabolism but that CYP3A appears to be the major enzyme responsible for human GBR12909 biotransformation. C1 Uniformed Serv Univ Hlth Sci, Div Clin Pharmacol & Med Toxicol, Bethesda, MD 20814 USA. NIDA, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Drug Evaluat, Lab Clin Pharmacol, Rockville, MD 20857 USA. RP Cantilena, LR (reprint author), Uniformed Serv Univ Hlth Sci, Div Clin Pharmacol & Med Toxicol, 4301 Jones Bridge Rd,Room B2020, Bethesda, MD 20814 USA. FU NIDA NIH HHS [Y1 DA-9094-02] NR 29 TC 5 Z9 6 U1 1 U2 1 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0090-9556 J9 DRUG METAB DISPOS JI Drug Metab. Dispos. PD SEP PY 2001 VL 29 IS 9 BP 1216 EP 1220 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 465MV UT WOS:000170593500009 PM 11502731 ER PT J AU Roe, B Teisl, MF Levy, A Russell, M AF Roe, B Teisl, MF Levy, A Russell, M TI US consumers' willingness to pay for green electricity SO ENERGY POLICY LA English DT Article DE electricity deregulation; Green marketing; willingness to pay ID CONJOINT-ANALYSIS AB We analyze US consumers' demand for environmental attributes of deregulated residential electricity services using results from a survey designed to elicit consumers' willingness to pay for such attributes and using results from a hedonic analysis of actual price premiums charged for green electricity in several deregulated markets. Survey results suggest that many population segments are willing to pay for decreased air emissions even if there is no alteration in fuel source. Furthermore, several groups are willing to pay significantly more when emissions reductions stem from increased reliance upon renewable fuels. The hedonic analysis suggests that several product features not considered in the survey help explain real price premiums. including fuel mix from newly created renewable generation capacity, Green-e certification, brand name and state of offer. While survey and hedonic results are not easily compared due to limitations of the survey, both point to similar values for key environmental attributes, though the survey results are likely to overstate actual willingness to pay. In sum, the results suggest that consumer driven purchases can, in part, support the future of renewable generation capacity in the United States, though reliance upon other policy alternatives may be needed if energy prices spike. (C) 2001 Elsevier Science Ltd. All rights reserved. C1 Ohio State Univ, Dept Agr Environm & Dev Econ, Columbus, OH 43210 USA. Univ Maine, Dept Resource Econ & Policy, Orono, ME 04469 USA. US FDA, Consumer Studies Branch, Bethesda, MD 20205 USA. RP Roe, B (reprint author), Ohio State Univ, Dept Agr Environm & Dev Econ, Room 225,Agr Adm Bldg,2120 Fyffe Rd, Columbus, OH 43210 USA. RI Roe, Brian/A-7386-2009; OI Roe, Brian/0000-0003-4228-2889; teisl, mario/0000-0002-2021-9208 NR 8 TC 185 Z9 186 U1 6 U2 54 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0301-4215 J9 ENERG POLICY JI Energy Policy PD SEP PY 2001 VL 29 IS 11 BP 917 EP 925 DI 10.1016/S0301-4215(01)00006-4 PG 9 WC Energy & Fuels; Environmental Sciences; Environmental Studies SC Energy & Fuels; Environmental Sciences & Ecology GA 460WB UT WOS:000170330500008 ER PT J AU Syin, C Parzy, D Traincard, F Boccacio, I Joshi, MB Lin, DT Yang, XM Assemat, K Doerig, C Langsley, G AF Syin, C Parzy, D Traincard, F Boccacio, I Joshi, MB Lin, DT Yang, XM Assemat, K Doerig, C Langsley, G TI The H89 cAMP-dependent protein kinase inhibitor blocks Plasmodium falciparum development in infected erythrocytes SO EUROPEAN JOURNAL OF BIOCHEMISTRY LA English DT Article DE parasite; PKA; inhibition; H89 ID CYCLIC ADENOSINE-MONOPHOSPHATE; CATALYTIC SUBUNIT; CONTINUOUS CULTURE; ADENYLATE-CYCLASE; GAMETOCYTOGENESIS; EXPRESSION; DOMAINS; GENE; PKA AB In Plasmodium falciparum, the causative agent of human malaria, the catalytic subunit gene of cAMP-dependent protein kinase (Pfpka-c) exists as a single copy. Interestingly, its expression appears developmentally regulated, being at higher levels in the pathogenic asexual stages than in the sexual forms of parasite that are responsible for transmission to the mosquito vector. Within asexual parasites, PfPKA activity can be readily detected in schizonts. Similar to endogenous PKA activity of noninfected red blood cells, the parasite enzyme can be stimulated by cAMP and inhibited by protein kinase inhibitor. Importantly, ex vivo treatment of infected erythrocytes with the classical PKA-C inhibitor H89 leads to a block in parasite growth. This suggests that the PKA activities of infected red blood cells are essential for parasite multiplication. Finally, structural considerations suggest that drugs targeting the parasite, rather than the erythrocyte enzyme, might be developed that could help in the fight against malaria. C1 Inst Pasteur, Dept Immunol, Lab Signalizat Immunoparasitaire, CNRS,URA 1960, F-75724 Paris 15, France. Serv Sante Armees, Inst Trop Med, Marseille, France. US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. Inst Pasteur, Dept Biol Mol, CNRS, FRE 2364,Unite Regulat Enzymat Act Cellulaires, Paris, France. Inst Pasteur, Dept Immunol, Unite Biochim Struct, F-75724 Paris, France. INSERM, U511, Paris, France. INSERM, U399, F-13258 Marseille, France. RP Langsley, G (reprint author), Inst Pasteur, Dept Immunol, Lab Signalizat Immunoparasitaire, CNRS,URA 1960, F-75724 Paris 15, France. OI Doerig, Christian/0000-0002-3188-094X NR 26 TC 68 Z9 70 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0014-2956 J9 EUR J BIOCHEM JI Eur. J. Biochem. PD SEP PY 2001 VL 268 IS 18 BP 4842 EP 4849 DI 10.1046/j.1432-1327.2001.02403.x PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 477MA UT WOS:000171286300003 PM 11559352 ER PT J AU Kramer, JKG Zhou, JQ AF Kramer, JKG Zhou, JQ TI Conjugated linoleic acid and octadecenoic acids: Extraction and isolation of lipids SO EUROPEAN JOURNAL OF LIPID SCIENCE AND TECHNOLOGY LA English DT Article ID PERFORMANCE LIQUID-CHROMATOGRAPHY; SIMULTANEOUS CLASS SEPARATION; TRANS-FATTY-ACIDS; QUANTITATIVE EXTRACTION; GAS-CHROMATOGRAPHY; DAIRY-PRODUCTS; MILK LIPIDS; RAT-LIVER; ISOMERS; IDENTIFICATION C1 US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. RP Kramer, JKG (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 200 C St SW, Washington, DC 20204 USA. NR 45 TC 72 Z9 77 U1 1 U2 6 PU WILEY-V C H VERLAG GMBH PI BERLIN PA PO BOX 10 11 61, D-69451 BERLIN, GERMANY SN 1438-7697 J9 EUR J LIPID SCI TECH JI Eur. J. Lipid Sci. Technol. PD SEP PY 2001 VL 103 IS 9 BP 594 EP 600 PG 7 WC Food Science & Technology; Nutrition & Dietetics SC Food Science & Technology; Nutrition & Dietetics GA 480NF UT WOS:000171467200007 ER PT J AU Mossoba, MM AF Mossoba, MM TI Analytical techniques for conjugated linoleic acid (CLA) analysis SO EUROPEAN JOURNAL OF LIPID SCIENCE AND TECHNOLOGY LA English DT Editorial Material C1 US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. RP Mossoba, MM (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 200 C St SW, Washington, DC 20204 USA. NR 0 TC 3 Z9 3 U1 1 U2 3 PU WILEY-V C H VERLAG GMBH PI BERLIN PA PO BOX 10 11 61, D-69451 BERLIN, GERMANY SN 1438-7697 J9 EUR J LIPID SCI TECH JI Eur. J. Lipid Sci. Technol. PD SEP PY 2001 VL 103 IS 9 BP 594 EP 594 DI 10.1002/1438-9312(200109)103:9<594::AID-EJLT5941>3.0.CO;2-U PG 1 WC Food Science & Technology; Nutrition & Dietetics SC Food Science & Technology; Nutrition & Dietetics GA 480NF UT WOS:000171467200006 ER PT J AU Yurawecz, MP Morehouse, KM AF Yurawecz, MP Morehouse, KM TI Silver-ion HPLC of conjugated linoleic acid isomers SO EUROPEAN JOURNAL OF LIPID SCIENCE AND TECHNOLOGY LA English DT Article ID PERFORMANCE LIQUID-CHROMATOGRAPHY; FATTY-ACIDS; GAS-CHROMATOGRAPHY; SEPARATION; IDENTIFICATION; DERIVATIVES; TISSUE; CHEESE; BEEF; MILK C1 US FDA, Ctr Food Safety & Appl Nutr, Off Food Labelling HFS840, Washington, DC 20204 USA. RP Yurawecz, MP (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Food Labelling HFS840, 200 C St SW, Washington, DC 20204 USA. NR 17 TC 15 Z9 15 U1 0 U2 2 PU WILEY-V C H VERLAG GMBH PI BERLIN PA PO BOX 10 11 61, D-69451 BERLIN, GERMANY SN 1438-7697 J9 EUR J LIPID SCI TECH JI Eur. J. Lipid Sci. Technol. PD SEP PY 2001 VL 103 IS 9 BP 609 EP 613 DI 10.1002/1438-9312(200109)103:9<609::AID-EJLT6090>3.3.CO;2-# PG 5 WC Food Science & Technology; Nutrition & Dietetics SC Food Science & Technology; Nutrition & Dietetics GA 480NF UT WOS:000171467200009 ER PT J AU Roach, JAG AF Roach, JAG TI Analysis of CLA derivatives by GC/MS SO EUROPEAN JOURNAL OF LIPID SCIENCE AND TECHNOLOGY LA English DT Article ID LINOLEIC-ACID ISOMERS; GAS-CHROMATOGRAPHY; FATTY-ACIDS; IDENTIFICATION; CHEESE C1 US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. RP Roach, JAG (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 200 C St SW, Washington, DC 20204 USA. NR 11 TC 2 Z9 2 U1 0 U2 1 PU WILEY-V C H VERLAG GMBH PI BERLIN PA PO BOX 10 11 61, D-69451 BERLIN, GERMANY SN 1438-7697 J9 EUR J LIPID SCI TECH JI Eur. J. Lipid Sci. Technol. PD SEP PY 2001 VL 103 IS 9 BP 621 EP 624 PG 4 WC Food Science & Technology; Nutrition & Dietetics SC Food Science & Technology; Nutrition & Dietetics GA 480NF UT WOS:000171467200012 ER PT J AU Mossoba, MM AF Mossoba, MM TI Application of gas chromatography-infrared spectroscopy to the confirmation of the double bond configuration of conjugated linoleic acid isomers SO EUROPEAN JOURNAL OF LIPID SCIENCE AND TECHNOLOGY LA English DT Article ID PERFORMANCE LIQUID-CHROMATOGRAPHY; ADIPOSE-TISSUE; CLA ISOMERS; SOYBEAN OIL; FATTY-ACIDS; IDENTIFICATION; MONOMERS; CHEESE C1 US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. RP Mossoba, MM (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 200 C St SW, Washington, DC 20204 USA. NR 23 TC 3 Z9 3 U1 0 U2 2 PU WILEY-V C H VERLAG GMBH PI BERLIN PA PO BOX 10 11 61, D-69451 BERLIN, GERMANY SN 1438-7697 J9 EUR J LIPID SCI TECH JI Eur. J. Lipid Sci. Technol. PD SEP PY 2001 VL 103 IS 9 BP 624 EP 627 DI 10.1002/1438-9312(200109)103:9<624::AID-EJLT6240>3.3.CO;2-B PG 4 WC Food Science & Technology; Nutrition & Dietetics SC Food Science & Technology; Nutrition & Dietetics GA 480NF UT WOS:000171467200013 ER PT J AU Kaferstein, FK AF Kaferstein, FK TI Mycobacterium avium subsp paratuberculosis - a human pathogen? The arguments pro and contra SO FOOD CONTROL LA English DT Editorial Material C1 US FDA, Washington, DC 20204 USA. Food Safety & Inspect Serv, Washington, DC USA. RP Kaferstein, FK (reprint author), US FDA, Washington, DC 20204 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0956-7135 J9 FOOD CONTROL JI Food Control PD SEP PY 2001 VL 12 IS 6 BP 329 EP 329 DI 10.1016/S0956-7135(01)00037-8 PG 1 WC Food Science & Technology SC Food Science & Technology GA 462VR UT WOS:000170440900001 ER PT J AU Motarjemi, Y vanSchothorst, M Kaferstein, F AF Motarjemi, Y vanSchothorst, M Kaferstein, F TI Future challenges in global harmonization of food safety legislation SO FOOD CONTROL LA English DT Article; Proceedings Paper CT International Congress of Foodmicrobiology (Food Micro 99) CY SEP, 1999 CL NETHERLANDS C1 US FDA, Washington, DC 20204 USA. Food Safety & Inspect Serv, Washington, DC USA. WHO, Food Safety Unit, CH-1211 Geneva, Switzerland. Nestle, Vevey, Switzerland. RP Kaferstein, F (reprint author), US FDA, Washington, DC 20204 USA. NR 7 TC 10 Z9 10 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0956-7135 J9 FOOD CONTROL JI Food Control PD SEP PY 2001 VL 12 IS 6 BP 339 EP 346 DI 10.1016/S0956-7135(01)00036-6 PG 8 WC Food Science & Technology SC Food Science & Technology GA 462VR UT WOS:000170440900004 ER PT J AU Molins, RA Motarjemi, Y Kaferstein, FK AF Molins, RA Motarjemi, Y Kaferstein, FK TI Irradiation: a critical control point in ensuring the microbiological safety of raw foods SO FOOD CONTROL LA English DT Article; Proceedings Paper CT International Congress of Foodmicrobiology (Food Micro 99) CY SEP, 1999 CL NETHERLANDS DE irradiation; HACCP; decontamination; food safety; food contamination ID ESCHERICHIA-COLI; LISTERIA-MONOCYTOGENES; YERSINIA-ENTEROCOLITICA; FOODBORNE PATHOGENS; MEAT; BEEF; CONTAMINATION; INFECTION; RADIATION; SURVIVAL AB The widespread and increasing incidence of foodborne diseases and the resultant social and economic impact on the human population have brought food safety to the forefront of public health concerns. This has prompted public health authorities worldwide to reassess their methods of food safety assurance, and to resort to a more cost-effective, preventive method that is known as hazard analysis and critical control point (HACCP). Ensuring food safety depends on effective control measures, i.e., methods to prevent food contamination and, when necessary, decontamination. Present production methods cannot totally prevent food contamination, and the complexity of food handling and processing provides ample opportunity for contamination as well as survival and growth of pathogenic organisms. It is also unlikely that the methods of production can ensure foods totally free from in the near future, for many pathogens are part of the normal flora of the environment. The application of an HACCP-based approach as a method for the management of hazards of the food chain demonstrates the need for applying a cold decontamination treatment as a control measure in the production of foods which are to be marketed raw or minimally processed. Irradiation (increasingly referred to as "cold pasteurization") is such a control measure in the production of several types of raw or minimally processed foods such as poultry, meat and meat products, fish, seafood, and fruits and vegetables. In the production of these foodstuffs, irradiation may thus be a critical control point (CCP), It has the potential to eliminate vegetative forms of bacterial pathogens as well as parasites. Moreover, irradiation fulfils other criteria for a CCP, i.e., critical limits (minimum and maximum doses) can be established and monitored, and process control is well known. Corrective actions can also be taken when necessary. Irradiation is a safe technology and has been recognized as such by the FAO/WHO Codex Alimentarius Commission. It certainly merits the attention of industry and public health authorities. Today, 40 countries permit the irradiation of one or more foodstuffs: 12 countries have approved its use for pathogen control in poultry, 8 other for use in meats, and 13 in fish and seafood. (C) 2001 Elsevier Science Ltd. All rights reserved. C1 US FDA, Washington, DC 20204 USA. Food Safety & Inspect Serv, Washington, DC 20204 USA. Natl Acad, Inst Med, Food & Nutr Board, Washington, DC USA. WHO, Programme Food Safety & Food Aid, Food Safety Unit, CH-1211 Geneva, Switzerland. RP Kaferstein, FK (reprint author), US FDA, Washington, DC 20204 USA. NR 95 TC 62 Z9 64 U1 4 U2 23 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0956-7135 J9 FOOD CONTROL JI Food Control PD SEP PY 2001 VL 12 IS 6 BP 347 EP 356 DI 10.1016/S0956-7135(01)00035-4 PG 10 WC Food Science & Technology SC Food Science & Technology GA 462VR UT WOS:000170440900005 ER PT J AU Mermelstein, NH AF Mermelstein, NH TI Top executives analyze food R&D in 2001 and beyond SO FOOD TECHNOLOGY LA English DT Article C1 Givaudan Flavors Corp, Sci & Technol, Cincinnati, OH USA. Procter & Gamble Far E Inc, Food & Beverage R&D, Kobe, Hyogo, Japan. McCormick & Co, Res & Dev, Hunt Valley, MD USA. Univ Maryland, Joint Inst Food Safety & Appl Nutr, College Pk, MD USA. Campbell Soup Co, Global R&D & Qual Assurance, Camden, NJ USA. USDA, Cooperat State Res Educ & Extens Serv, Washington, DC USA. David Michael & Co, Davis, CA USA. Purdue Univ, Dept Foods & Nutr, W Lafayette, IN 47907 USA. Gen Foods Corp, Greenwich, CT USA. RP Mermelstein, NH (reprint author), Gen Foods Corp, Greenwich, CT USA. NR 0 TC 3 Z9 5 U1 0 U2 0 PU INST FOOD TECHNOLOGISTS PI CHICAGO PA SUITE 300 221 N LASALLE ST, CHICAGO, IL 60601-1291 USA SN 0015-6639 J9 FOOD TECHNOL-CHICAGO JI Food Technol. PD SEP PY 2001 VL 55 IS 9 BP 36 EP + PG 14 WC Food Science & Technology SC Food Science & Technology GA 472WC UT WOS:000171007100012 ER PT J AU Ding, LN Shevach, EM AF Ding, LN Shevach, EM TI Inhibition of the function of the Fc gamma RIIB by a monoclonal antibody to thymic shared antigen-1, a Ly-6 family antigen SO IMMUNOLOGY LA English DT Article ID T-CELL ACTIVATION; IL-2 PRODUCTION; NEGATIVE REGULATION; CD40 LIGAND; B-CELLS; RECEPTOR; IDENTIFICATION; LYMPHOCYTES; EXPRESSION; INDUCTION AB Thymic shared antigen-1 (TSA-1) is a member of the Ly-6 family of glycosyl-phosphatidylinositol (GPI)-linked proteins. While it has been proposed that TSA-1 may play a role in thymic development, a physiological ligand for this antigen has not been identified. Here we report that a monoclonal antibody (mAb) to TSA-1, generated by ininaunizing a hamster with CD40 ligand (CD40L) -activated B cells, interferes with the function of Fc gamma RIIB on splenic B cells and the B-cell lymphoma cell line, M12, by binding to TSA on the same cells. The interaction of anti-TSA with Fc gamma RIIB resulted in an inhibition of the ability of the Fc gamma RIIB to cross-link and/or aggregate soluble anti-CD3 or soluble anti-C beta T-cell receptor (TCR), leading to an inhibition of induction of expression of CD25 and CD69, interleukin (IL)-2 production and proliferation of naive T cells. Cross-blocking studies with mAbs strongly suggested that a physical association exists between TSA-1 and the Fc gamma RIIB on the surface of activated B cells and favour the view that a functional intermolecular association exists between these two distinct membrane antigens. C1 US FDA, Mol Virol Lab, Div Emerging & Transfus Transmitted Dis, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Ding, LN (reprint author), US FDA, Mol Virol Lab, Div Emerging & Transfus Transmitted Dis, Ctr Biol Evaluat & Res,HFM 315, 1401 Rockville Pike, Rockville, MD 20852 USA. NR 45 TC 5 Z9 5 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0019-2805 J9 IMMUNOLOGY JI Immunology PD SEP PY 2001 VL 104 IS 1 BP 28 EP 36 DI 10.1046/j.1365-2567.2001.01275.x PG 9 WC Immunology SC Immunology GA 481CA UT WOS:000171501300005 PM 11576217 ER PT J AU Lucas, AD AF Lucas, AD TI Strategies for the in vitro testing of in situ polymers SO IN VITRO & MOLECULAR TOXICOLOGY-A JOURNAL OF BASIC AND APPLIED RESEARCH LA English DT Article ID BONE CEMENTS; CELL-DEATH; IN-VITRO; FLOW-CYTOMETRY; CYTOTOXICITY; LEUKOCYTES; APOPTOSIS; IMMEDIATE; NECROSIS; RESINS AB In situ polymers are used by mixing two or more compounds that are then placed directly in tissues to form a unique product. This type of reaction can generate heat, reactive oxygen species, free radicals, and other by-products of unknown toxicities, but the polymer itself is biocompatible. Many regulatory agencies require in vitro testing, however, standard guidelines (ASTM, ISO, AAMI) test polymers in a final form prior to use as a medical device. To better estimate the cytotoxicity of these in situ polymers, various means of Introducing the reacting material to cells in culture were explored. Coating the material on a sterile glass cover slip then adding the cover slip to the in vitro test system immediately provided reasonable cytotoxicity data that reflected actual use conditions. For in situ polymeric devices that are more viscous, such as dental materials and bone cements, a mold was used that was placed directly into cell culture. This approach in testing in situ polymers generated in vitro toxicity data that reflects the actual use of the material. C1 US FDA, CDRH, OST, HFZ 112, Rockville, MD 20852 USA. RP Lucas, AD (reprint author), US FDA, CDRH, OST, HFZ 112, 12709 Twinbrook Pkwy, Rockville, MD 20852 USA. NR 22 TC 1 Z9 1 U1 0 U2 2 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1097-9336 J9 IN VITRO MOL TOXICOL JI In Vitro Mol. Toxicol.-J. Basic Appl. Res. PD FAL PY 2001 VL 14 IS 3 BP 169 EP 175 PG 7 WC Toxicology SC Toxicology GA 513GQ UT WOS:000173369900004 ER PT J AU Chew, GL Douwes, J Doekes, G Higgins, KM van Strien, R Spithoven, J Brunekreef, B AF Chew, GL Douwes, J Doekes, G Higgins, KM van Strien, R Spithoven, J Brunekreef, B TI Fungal extracellular polysaccharides, beta (1 -> 3)-glucans and culturable fungi in repeated sampling of house dust SO INDOOR AIR-INTERNATIONAL JOURNAL OF INDOOR AIR QUALITY AND CLIMATE LA English DT Article DE fungi; EPS; glucan; house dust; mold ID HOME DAMPNESS; RESIDENTIAL CHARACTERISTICS; RESPIRATORY SYMPTOMS; EXPOSURE; HEALTH; CHILDREN; (1->3)-BETA-D-GLUCAN; ENVIRONMENTS; VARIABILITY; PREVALENCE AB Fungal exposure inside homes has been associated with adverse respiratory symptoms in children and adults. While fungal assessment has traditionally relied upon questionnaires, fungal growth on culture plates and spore counts, new immunoassays for extracellular polysaccharides (EPS) and beta (1-->3)-glucans have enabled quantitation of fungal agents in house dust in a more timely and cost-effective manner, possibly providing a better measure of fungal exposure. We investigated associations among measurements of EPS, beta (1-->3)-glucans and culturable fungi obtained from 23 Dutch homes. From each home, dust samples were vacuumed from the living room floor twice during the Fall, Winter and Spring seasons for a total of six collections (every 6 weeks from October 1997 to May 1998). Samples were sieved and fine dust was analyzed for EPS from Aspergillus and Penicillium spp. combined, beta (1-->3)-glucans and culturable fungi. EPS was positively associated with glucan; an increase from the 25th to the 75th percentile of glucan concentration was associated with a 1.6-fold increase in EPS concentration (95% CI=1.3 to 2.0; p<0.01). The most significant variables associated with EPS and glucan concentrations were the surface type that was vacuumed an the concentration of total culturable fungi (in colony forming units (CFU)/g dust), with an increase in CFU/g from the 25th to the 75th percentile associated with a 1.3 (1.1-1.6)-fold increase in glucan and a 1.7 (1.3-2.2)-fold increase in EPS concentrations. In addition, the within-home variation of EPS levels were smaller than those between homes (25,646 U/g vs. 50,635 U/g), whereas the variation of glucan levels was similar within and between homes (1,300 vs. 1,205 g/g). These positive associations suggest that house dust concentrations of beta (1-->3)-glucan, and particularly those of EPS, are good markers for the overall levels of fungal concentrations in floor dust which is a surrogate for estimating airborne fungal exposure. C1 Columbia Univ, Div Environm Hlth Sci, JL Mailman Sch Publ Hlth, New York, NY 10032 USA. Univ Wageningen & Res Ctr, Dept Environm Sci, Environm & Occupat Hlth Grp, Wageningen, Netherlands. US FDA, Rockville, MD 20857 USA. RP Chew, GL (reprint author), Columbia Univ, Div Environm Hlth Sci, JL Mailman Sch Publ Hlth, New York, NY 10032 USA. NR 27 TC 61 Z9 62 U1 0 U2 4 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0905-6947 J9 INDOOR AIR JI Indoor Air-Int. J. Indoor Air Qual. Clim. PD SEP PY 2001 VL 11 IS 3 BP 171 EP 178 DI 10.1034/j.1600-0668.2001.011003171.x PG 8 WC Construction & Building Technology; Engineering, Environmental; Public, Environmental & Occupational Health SC Construction & Building Technology; Engineering; Public, Environmental & Occupational Health GA 463MZ UT WOS:000170481100007 PM 11521501 ER PT J AU Scharf, O Agranovich, I Lee, K Eller, NL Levy, L Inman, J Scott, DE Golding, B AF Scharf, O Agranovich, I Lee, K Eller, NL Levy, L Inman, J Scott, DE Golding, B TI Ontogeny of Th1 memory responses against a Brucella abortus conjugate SO INFECTION AND IMMUNITY LA English DT Article ID CYTOKINE GENE-EXPRESSION; STIMULATORY FACTOR-I; CD4+ T-CELLS; IFN-GAMMA; INTERFERON-GAMMA; IMMUNE-RESPONSES; IGE RESPONSES; TYPE-1; SELECTION; ANTIBODY AB Protective immune responses to intracellular pathogens such as Brucella abortus are characteristically Th1-like. Recently we demonstrated that heat-killed B. abortus (HKBa), a strong Th1 stimulus, conjugated to ovalbumin (HKBA-OVA), but not B. abortus alone, can alter the antigen-specific cytokine profile from Th2- to Th1-like. In this report we study the ability of a single injection of B. abortus to switch a Th2 to a Th1 response in immature mice. One-day- and 1-week-old mice were given a single injection of B. abortus in the absence or presence of OVA, and at maturity mice were challenged with an allergenic preparation, OVA with alum (OVA-A). B. abortus given without OVA did not diminish the subsequent Th2 response in either age group. In contrast, mice receiving a single injection of B. abortus-OVA at the age of 1 week, but not those injected at the age of 1 day, had reversal of the ratio of OVA-specific Th1 to Th2 cells and decreased immunoglobulin E levels after allergen challenge as adults. Within 6 h both 1-day- and 1-week-old mice expressed interleukin-12 p40 mRNA following either B. abortus or B. abortus-OVA administration. However, only the 1-week-old mice exhibited increased expression of gamma interferon (IFN-gamma) mRNA. The absence of the early IFN-gamma response in 1-day-old mice may explain their inability to generate a Th1 memory response. These results suggest that at early stages of immune development, responses to intracellular bacteria may be Th2- rather than Th1-like. Furthermore, they suggest that the first encounter with antigen evokes either a Th1- or a Th2-like response which becomes imprinted, so that subsequent memory responses conform to the original Th bias. This has implications for protection against infectious agents and development of allergic responses. C1 US FDA, Lab Plasma Derivat, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. NIAID, NIH, Bethesda, MD 20892 USA. RP Golding, B (reprint author), US FDA, Lab Plasma Derivat, Div Hematol, Ctr Biol Evaluat & Res, Bldg 29,Rm 232,8800 Rockville Pike, Bethesda, MD 20892 USA. EM golding@cber.fda.gov NR 25 TC 5 Z9 5 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 SEP PY 2001 VL 69 IS 9 BP 5417 EP 5422 DI 10.1128/IAI.69.9.5417-5422.2001 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 464PB UT WOS:000170540000025 PM 11500412 ER PT J AU Delogu, G Brennan, MJ AF Delogu, G Brennan, MJ TI Comparative immune response to PE and PE_PGRS antigens of Mycobacterium tuberculosis SO INFECTION AND IMMUNITY LA English DT Article ID DELAYED-TYPE HYPERSENSITIVITY; FIBRONECTIN-BINDING PROTEINS; VIRUS NUCLEAR ANTIGEN-1; T-CELL RESPONSES; PROTECTIVE EFFICACY; GENOME SEQUENCE; BCG VACCINES; VACCINATION; FAMILY; IMMUNOGENICITY AB Sequencing of the entire genome of Mycobacterium tuberculosis identified a novel multigene family composed of two closely related subfamilies designated PE and PE PGRS. The major difference between these two families is the presence of a domain containing numerous Gly-Ala repeats extending to the C terminus of the PE PGRS genes. We have used a representative PE PGRS gene from M. tuberculosis, Rv1818c (1818(PE_PGRS)), and its amino-terminal PE region (1818(PE)), to investigate the immunological response to these proteins during experimental tuberculosis and following immunization with DNA constructs. During infection of mice with M. tuberculosis, a significant humoral immune response was observed against recombinant 1818(PE_PGRS) but not toward the 1818PE protein. Similarly, immunization with a 1818(PE_PGRS) DNA construct induced antibodies directed against 1818(PE_PGRS) but not against 1818PE proteins, and no humoral response was induced by 1818(PE) DNA. These results suggest that certain PE_PGRS genes are expressed during infection of the host with M. tuberculosis and that an antibody response is directed solely against the Gly-Ala-rich PGRS domain. Conversely, splenocytes from 1818(PE)-vaccinated mice but not mice immunized with 1818(PE_PGRS) secreted gamma interferon following in vitro restimulation and demonstrated protection in the mouse tuberculosis challenge model. These results suggest that the PE vaccine can elicit an effective cellular immune response and that immune recognition of the PE antigen is influenced by the Gly-Ala-rich PGRS domain. C1 US FDA, Lab Mycobacterial Dis & Cell Immunol, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP US FDA, Lab Mycobacterial Dis & Cell Immunol, Ctr Biol Evaluat & Res, Bldg 29,Rm 502,29 Lincoln Dr,HFM-431, Bethesda, MD 20892 USA. EM Brennan@cber.fda.gov RI Delogu, Giovanni/I-3701-2012 OI Delogu, Giovanni/0000-0003-0182-8267 NR 29 TC 124 Z9 136 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 EI 1098-5522 J9 INFECT IMMUN JI Infect. Immun. PD SEP PY 2001 VL 69 IS 9 BP 5606 EP 5611 DI 10.1128/IAI.69.9.5606-5611.2001 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 464PB UT WOS:000170540000048 PM 11500435 ER PT J AU Chetty, CS Reddy, GR Suresh, A Desaiah, D Ali, SF Slikker, WJ AF Chetty, CS Reddy, GR Suresh, A Desaiah, D Ali, SF Slikker, WJ TI Effects of manganese on inositol polyphosphate receptors and nitric oxide synthase activity in rat brain SO INTERNATIONAL JOURNAL OF TOXICOLOGY LA English DT Article DE cerebellum; cerebral cortex; inositol polyphosphate receptors; manganese; nitric oxide synthase ID NEUROTOXICITY; PHENCYCLIDINE; DYSFUNCTION; CALCIUM; BINDING; CELLS AB The neurotoxic effects of excessive exposure to manganese (Mn) include degeneration of dopaminergic neurons, impairment of energy metabolism, and perturbations in phosphoinositide (PI) hydrolysis leading to altered calcium (Ca2+) homeostasis. This study is designed to assess the in vitro and in vivo effects of Mn on Ca2+/calmodulin-dependent neuronal nitric oxide synthase (nNOS) activity and on the regulation of inositol 1,4,5-trisphosphate (InsP(3)) and inositol 1,3,4,5-tetrakisphosphate (InsP(4)) receptors involved in intracellular and extracellular mobilization of Ca2+. In vivo Mn exposure significantly increased H-3-InsP(3) and H-3-InsP(4) binding in the cerebellum and the cerebral cortex in a dose-dependent manner. However, in vitro Mn decreased H-3-InsP(3) binding and increased H-3-InsP(4) binding. In vitro and in vivo exposure of Mn inhibited nNOS activity in the cerebellum and the cerebral cortex. Immunohistochemical studies also showed a notable decrease in nNOS immunoreactivity in the granule cell layer of the cerebellum, whereas no significant changes were observed in the cerebral cortex. These data suggest that Mn neurotoxicity may be due to altered calcium homeostasis by its modulation of inositol polyphosphate receptors. Further, the inhibition of nNOS by Mn is of considerable importance because NO regulates a number of neurotransmitter functions. C1 Savannah State Univ, Dept Biol, Savannah, GA 31404 USA. Univ Mississippi, Med Ctr, Dept Neurol, Jackson, MS 39216 USA. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Chetty, CS (reprint author), Savannah State Univ, Dept Biol, POB 20600, Savannah, GA 31404 USA. FU NIGMS NIH HHS [GM 60853] NR 24 TC 6 Z9 7 U1 1 U2 4 PU TAYLOR & FRANCIS LTD PI LONDON PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND SN 1091-5818 J9 INT J TOXICOL JI Int. J. Toxicol. PD SEP PY 2001 VL 20 IS 5 BP 275 EP 280 PG 6 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 495JE UT WOS:000172336400004 PM 11766125 ER PT J AU Meyer, RJ AF Meyer, RJ TI Comment on call for worldwide withdrawal of BAC from nebulizer solutions SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Letter C1 US FDA, Div Pulm & Allergy Drug Prod, Rockville, MD 20857 USA. RP Meyer, RJ (reprint author), US FDA, Div Pulm & Allergy Drug Prod, 5600 Fishers Lane, Rockville, MD 20857 USA. NR 1 TC 1 Z9 1 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD SEP PY 2001 VL 108 IS 3 BP 469 EP 469 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 476FK UT WOS:000171215400026 PM 11544474 ER PT J AU Ferreira, JL Eliasberg, SJ Harrison, MA Edmonds, P AF Ferreira, JL Eliasberg, SJ Harrison, MA Edmonds, P TI Detection of preformed type A botulinal toxin in hash brown potatoes by using the mouse bioasssay and a modified ELISA test SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID NEUROTOXIN; OUTBREAK AB A foodborne illness caused by type A toxin-producing Clostridium botulinum was investigated by using the standard mouse bioassay and a rapid invitro test for toxin detection. The patient, who consumed improperly stored hash brown potatoes that contained the preformed toxin, was diagnosed with type A botulism. C. botulinum type A toxin was detected in the hash brown potatoes as well as in the tryptone-peptone-glucose-yeast extract (TPGY) medium subcultures of this food using the mouse bioassay and an amplified ELISA technique. The mouse bioassay revealed preformed toxin at 10 000 minimum lethal dose (MLD)/g uncooked product and the amplified ELISA an equivalent 50 000 MLD/g. The cultural toxin from the uncooked product killed mice at the 10(6) dilution and a modification of the ELISA procedure was positive at the 10(3) dilution. Cooked food obtained from the consumer's waste can contained 100 MLD/g and the ELISA was also positive at the same dilution of the product. The culture of the cooked product obtained from the waste can was lethal for mice at the 10(7) dilution and positive using the modified ELISA at the 10(4) dilution. The unmodified amplified ELISA method indicated a toxin level of approximately 1 ng/mL (equivalent to 5 x 10(5) MLD/mL) in diluted culture fluid from the uncooked food and the culture of cooked food obtained from the waste can. The hash brown potatoes were negative for types B, E, and F preformed and cultural botulinal toxins using both assays. C1 US FDA, Atlanta, GA 30309 USA. Univ Georgia, Dept Food Sci & Technol, Athens, GA 30602 USA. Georgia Inst Technol, Sch Biol, Atlanta, GA 30332 USA. RP Ferreira, JL (reprint author), US FDA, 60 8th St, Atlanta, GA 30309 USA. NR 10 TC 24 Z9 26 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 SEP-OCT PY 2001 VL 84 IS 5 BP 1460 EP 1464 PG 5 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 479UB UT WOS:000171421000020 PM 11601465 ER PT J AU Mann, DL Chase, GW Eitenmiller, RR AF Mann, DL Chase, GW Eitenmiller, RR TI Liquid chromatographic analysis of vitamin B-6 in soy-based infant formula SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID PYRIDOXINE; FOODS AB A liquid chromatographic (LC) method is described for determination of total vitamin B-6 in soy-based infant formula. Total vitamin B-6 is quantitated by using ion-pair LC after precolumn transformation of phosphorylated and free vitamers into pyridoxol. The limit of detection is 0.3 ng and the limit of quantitation is 1.0 ng on-column (injection volume = 100 muL). Linear response ranged from 39 to 616 ng/mL (r(2) = 0.99986). Analysis of a soy-based infant formula control fortified at 6 different concentration levels gave recoveries that averaged 104%. Assay of SRM 1846 gave results within the certified range (8.6 +/-0.086 mg/kg versus the certified value of 8.4 +/-1.0 mg/kg). The method provides a rapid and specific assay for the analysis of total vitamin B-6 in fortified soy-based infant formula. C1 US FDA, SE Reg Lab, Atlanta, GA 30309 USA. US FDA, Pacific Reg Lab NW, Bothell, WA 98021 USA. Univ Georgia, Dept Food Sci & Technol, Athens, GA 30602 USA. RP Mann, DL (reprint author), US FDA, SE Reg Lab, 60 80th St NE, Atlanta, GA 30309 USA. NR 14 TC 3 Z9 3 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 SEP-OCT PY 2001 VL 84 IS 5 BP 1593 EP 1599 PG 7 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 479UB UT WOS:000171421000036 PM 11601481 ER PT J AU Park, YK Barton, CN Calvo, MS AF Park, YK Barton, CN Calvo, MS TI Dietary contributions to serum 25(OH) vitamin D levels [25(OH) D] differ in black and white adults in the United States: Results from NHANES III. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. NR 0 TC 0 Z9 0 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 SEP PY 2001 VL 16 SU 1 BP S212 EP S212 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 467MU UT WOS:000170709000307 ER PT J AU Beger, RD Wilkes, JG AF Beger, RD Wilkes, JG TI Models of polychlorinated dibenzodioxins, dibenzofurans, and biphenyls binding affinity to the aryl hydrocarbon receptor developed using C-13 NMR data SO JOURNAL OF CHEMICAL INFORMATION AND COMPUTER SCIENCES LA English DT Article ID CHEMICAL-SHIFTS; AH RECEPTOR; P-DIOXINS; QSAR; MECHANISM; PREDICTION; TOXICOLOGY; INVITRO; INVIVO AB Quantitative spectroscopic data-activity relationship (QSDAR) models for polychlorinated dibenzofurans (PCDFs), dibenzodioxins (PCDDs), and biphenyls (PCBs) binding to the aryl hydrocarbon receptor (AhR) have been developed based on simulated C-13 nuclear magnetic resonance (NMR) data. All the models were based on multiple linear regression of comparative spectral analysis (CoSA) between compounds. A 1.0 ppm resolution CoSA model for 26 PCDF compounds based on chemical shifts in five bins had an explained variance (r(2)) of 0.93 and a leave-one-out (LOO) cross-validated variance (q(2)) of 0.90. A 2.0 ppm resolution CoSA model for 14 PCDD compounds based on chemical shifts in five bins had an r(2) of 0.91 and a q(2) of 0.81. The 1.0 ppm resolution CoSA model for 12 PCB compounds based on chemical shifts in five bins had an r(2) of 0.87 and a q(2) of 0.45. The models with more compounds had a better q(2) because there are more multiple chemical shift populated bins available on which to base the linear regression. A 1.0 ppm, resolution CoSA model for all 52 compounds that was based on chemical shifts in 12 bins had an r(2) of 0.85 and q(2) of 0.71. A canonical variance analysis of the 1.0 ppm CoSA model for all 52 compounds when they were separated into 27 strong binding and 25 weak binding compounds was 98% correct. Conventional quantitative structure-activity relationship (QSAR) modeling suffer from errors introduced by the assumptions and approximations involved in calculated electrostatic potentials and the molecular alignment process. QSDAR modeling is not limited by such errors since electrostatic potential calculations and molecular alignment are not done. The QSDAR models provide a rapid, simple and valid way to model the PCDF, PCDD, and PCB binding activity in relation to the aryl hydrocarbon receptor (AhR). C1 US FDA, Natl Ctr Toxicol Res, Div Chem, Jefferson, AR 72079 USA. RP Beger, RD (reprint author), US FDA, Natl Ctr Toxicol Res, Div Chem, Jefferson, AR 72079 USA. NR 38 TC 35 Z9 37 U1 0 U2 14 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0095-2338 J9 J CHEM INF COMP SCI JI J. Chem. Inf. Comput. Sci. PD SEP-OCT PY 2001 VL 41 IS 5 BP 1322 EP 1329 DI 10.1021/ci000312l PG 8 WC Chemistry, Multidisciplinary; Computer Science, Information Systems; Computer Science, Interdisciplinary Applications SC Chemistry; Computer Science GA 476YZ UT WOS:000171257500024 PM 11604033 ER PT J AU Beger, RD Buzatu, DA Wilkes, JG Lay, JO AF Beger, RD Buzatu, DA Wilkes, JG Lay, JO TI C-13 NMR quantitative spectrometric data-activity relationship (QSDAR) models of steroids binding the aromatase enzyme SO JOURNAL OF CHEMICAL INFORMATION AND COMPUTER SCIENCES LA English DT Article ID AUTOMATED STRUCTURE EVALUATION; BREAST-CANCER; INHIBITORS; QSAR; PREDICTION AB Five quantitative spectroscopic data-activity relationships (QSDAR) models for 50 steroidal inhibitors binding to aromatase enzyme have been developed based on simulated C-13 nuclear magnetic resonance (NMR) data. Three of the models were based on comparative spectral analysis (CoSA), and the two other models were based on comparative structurally assigned spectral analysis (CoSASA). A CoSA QSDAR model based on five principal components had an explained variance (r(2)) of 0.78 and a leave-one-out (LOO) cross-validated variance (q(2)) of 0.71. A CoSASA model that used the assigned C-13 NMR chemical shifts from a steroidal backbone at five selected positions gave an r(2) of 0.75 and a q2 of 0.66. The C-13 NMR chemical shifts from atoms in the steroid template position 9, 6, 3, and 7 each had correlations greater than 0.6 with the relative binding activity to the aromatase enzyme. All five QSDAR models had explained and cross-validated variances that were better than the explained and cross-validated variances from a five structural parameter quantitative structure-activity relationship (QSAR) model of the same compounds. QSAR modeling suffers from errors introduced by the assumptions and approximations used in partial charges, dielectric constants, and the molecular alignment process of one structural conformation. One postulated reason that the variances of QSDAR models are better than the QSAR models is that C-13 NMR spectral data, based on quantum mechanical principles, are more reflective of binding than the QSAR model's calculated electrostatic potentials and molecular alignment process. The QSDAR models provide a rapid, simple way to model the steroid inhibitor activity in relation to the aromatase enzyme. C1 US FDA, Natl Ctr Toxicol Res, Div Chem, Jefferson, AR 72079 USA. RP Beger, RD (reprint author), US FDA, Natl Ctr Toxicol Res, Div Chem, Jefferson, AR 72079 USA. RI Lay, Jackson/G-1007-2011 OI Lay, Jackson/0000-0003-3789-2527 NR 34 TC 25 Z9 25 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0095-2338 J9 J CHEM INF COMP SCI JI J. Chem. Inf. Comput. Sci. PD SEP-OCT PY 2001 VL 41 IS 5 BP 1360 EP 1366 DI 10.1021/ci010285e PG 7 WC Chemistry, Multidisciplinary; Computer Science, Information Systems; Computer Science, Interdisciplinary Applications SC Chemistry; Computer Science GA 476YZ UT WOS:000171257500029 PM 11604038 ER PT J AU Yamano, S Scott, DE Huang, LY Mikolajczyk, M Pillemer, SR Chiorini, JA Golding, B Baum, BJ AF Yamano, S Scott, DE Huang, LY Mikolajczyk, M Pillemer, SR Chiorini, JA Golding, B Baum, BJ TI Protection from experimental endotoxemia by a recombinant adeno-associated virus encoding interleukin 10 SO JOURNAL OF GENE MEDICINE LA English DT Article DE adeno-associated virus; cytokines; gene transfer; immunotherapy; immunoregulation ID TUMOR-NECROSIS-FACTOR; TERM GENE-TRANSFER; ADENOASSOCIATED VIRUS; SEPTIC SHOCK; IMMUNE-RESPONSES; IFN-GAMMA; VECTORS; MICE; MUSCLE; EXPRESSION AB Background Interleukin 10 (IL-10) is a homodimeric cytokine that shows considerable clinical promise. Adeno-associated virus (AAV) vectors appear increasingly useful for in vivo gene-transfer applications. Methods A recombinant AAV type 2 vector encoding human IL-10 (rAAVhIL10) was constructed by using an adenoviral-free, three-plasmid co-transfection. Cytokine production was measured by using an enzyme-linked immunosorbent assay. Endotoxic shock was induced by lipopolysaccharide (LPS) injection. Results As media from rAAVhIL10-infected COS cells caused a dose-dependent blockade of IL-12 secretion from spleen cells of IL-10 knockout (KO) mice challenged with Brucella abortus, it was clear that vector-derived hIL-10 was biologically active in vitro. Intravenous or intramuscular administration of relatively modest levels of rAAVhIL10 (10(10) genomes) to IL-10 KO mice resulted in hIL-10 secretion into the bloodstream, which at 8, weeks, gave median serum levels of 0.9 and 0.45 pg/ml, respectively. Acute endotoxic shock led to a 33% mortality rate, and severe morbidity, in control IL-10 KO mice, whereas no mortality and little morbidity were seen in IL-10 KO mice given rAAVhIL10 7 weeks earlier. Conclusions The findings demonstrate that a modest dose of rAAVhIL10 administered in vivo provides long-term protection against LPS-induced endotoxic shock in a murine model. Thus, this vector may be useful for clinical applications requiring sustained IL-10 expression, for example in the treatment of several autoimmune diseases. Copyright (C) 2001 John Wiley & Sons, Ltd. C1 NIDCR, GTTB, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Hematol, Bethesda, MD 20892 USA. RP Yamano, S (reprint author), NIDCR, GTTB, NIH, 10 Ctr Dr,MSC 1190,Bldg 10,Room 1A01, Bethesda, MD 20892 USA. OI Yamano, Seiichi/0000-0003-2056-4359 NR 55 TC 11 Z9 11 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 1099-498X J9 J GENE MED JI J. Gene. Med. PD SEP-OCT PY 2001 VL 3 IS 5 BP 450 EP 457 DI 10.1002/jgm.213 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 479LZ UT WOS:000171407000005 PM 11601758 ER PT J AU Ishii, KJ Suzuki, K Coban, C Takeshita, F Itoh, Y Matoba, H Kohn, LD Klinman, DM AF Ishii, KJ Suzuki, K Coban, C Takeshita, F Itoh, Y Matoba, H Kohn, LD Klinman, DM TI Genomic DNA released by dying cells induces the maturation of APCs SO JOURNAL OF IMMUNOLOGY LA English DT Article ID COLONY-STIMULATING FACTOR; DENDRITIC CELLS; BACTERIAL-DNA; CPG MOTIFS; IMMUNE-RECOGNITION; INNATE IMMUNITY; APOPTOTIC CELLS; ACTIVATION; TOLERANCE; NUCLEUS AB Mature APCs play a key role in the induction of Ag-specific immunity. This work examines whether genomic DNA released by dying cells provides a stimulus for APC maturation. Double-stranded but not single-stranded genomic DNA triggered APC to up-regulate expression of MHC class I/II and various costimulatory molecules. Functionally, dsDNA enhanced APC function in vitro and improved primary cellular and humoral immune responses in vivo. These effects were dependent on the length and concentration of the dsDNA but were independent of nucleotide sequence. The maturation of APC induced by dsDNA may promote host survival by improving immune surveillance at sites of tissue injury/infection. C1 Food & Drug Adm, Ctr Biol Evaluat & Res, Sect Retroviral Immunol, Bethesda, MD 20892 USA. NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. NIDDK, Metab Dis Branch, Bethesda, MD 20892 USA. RP Klinman, DM (reprint author), Food & Drug Adm, Ctr Biol Evaluat & Res, Sect Retroviral Immunol, Bldg 29A Rm 3 D 10, Bethesda, MD 20892 USA. EM Klinman@CBER.FDA.GOV RI Coban, Cevayir/B-2129-2012; Ishii, Ken/B-1685-2012 OI Ishii, Ken/0000-0002-6728-3872 NR 36 TC 153 Z9 163 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 1 PY 2001 VL 167 IS 5 BP 2602 EP 2607 PG 6 WC Immunology SC Immunology GA 496JE UT WOS:000172391800023 PM 11509601 ER PT J AU Weisz, A Andrzejewski, D Fales, HM Mandelbaum, A AF Weisz, A Andrzejewski, D Fales, HM Mandelbaum, A TI Structural assignment of isomeric 2-(2-quinolinyl)-1H-indene-1,3(2H)-dione mono- and disulfonic acids by liquid chromatography electrospray and atmospheric pressure chemical ionization tandem mass spectrometry SO JOURNAL OF MASS SPECTROMETRY LA English DT Article DE sulfonic acids; positional isomers; tandem mass spectrometry; regiospecific fragmentations; electrospray ionization; atmospheric pressure chemical ionization AB td2 C1 US FDA, Off Cosmet & Colors, Washington, DC 20204 USA. US FDA, Off Sci Anal & Support, Washington, DC 20204 USA. NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. Technion Israel Inst Technol, Dept Chem, IL-32000 Haifa, Israel. RP Weisz, A (reprint author), US FDA, Off Cosmet & Colors, Washington, DC 20204 USA. NR 13 TC 4 Z9 4 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 1076-5174 J9 J MASS SPECTROM JI J. Mass Spectrom. PD SEP PY 2001 VL 36 IS 9 BP 1024 EP 1030 DI 10.1002/jms.205 PG 7 WC Biophysics; Chemistry, Organic; Spectroscopy SC Biophysics; Chemistry; Spectroscopy GA 476MP UT WOS:000171231100004 PM 11599080 ER PT J AU Imam, SZ Itzhak, Y Cadet, JL Slikker, W Ali, SF AF Imam, SZ Itzhak, Y Cadet, JL Slikker, W Ali, SF TI Role of peroxynitrite and apoptosis related proteins, p53 and bcl-2, in methamphetamine-induced neurotoxicity SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Neurochem Lab, Jefferson, AR 72079 USA. Univ Miami, Sch Med, Dept Psychiat & Behav Sci, Miami, FL 33101 USA. NIDA, IRP, Mol Neuropsychiat Sect, Baltimore, MD 21224 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD SEP PY 2001 VL 78 SU 1 BP 129 EP 129 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 469AF UT WOS:000170789800451 ER PT J AU Ali, SF Newport, GD Slikker, W Imam, SZ AF Ali, SF Newport, GD Slikker, W Imam, SZ TI Methamphetamine produces age-dependent neurotoxicity in rats: role of peroxynitrite in dopaminergic neurotoxicity and hyperthermia SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 US FDA, Natl Ctr Toxicol Res, Neurochem Lab, Div Neurotoxicol, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD SEP PY 2001 VL 78 SU 1 BP 154 EP 154 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 469AF UT WOS:000170789800549 ER PT J AU Thiriet, P Jouvert, N Gobaille, S Gough, B Ali, SF Zwiller, J AF Thiriet, P Jouvert, N Gobaille, S Gough, B Ali, SF Zwiller, J TI CNP peptide modulates the cocaine-induced egr-1 gene expression through the activation of cGMP-dependent protein kinase (PKG) in rat striatum SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 INSERM, U338, Strasbourg, France. IFR 037, Strasbourg, France. FDA, NCTR, Jefferson, AR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD SEP PY 2001 VL 78 SU 1 BP 171 EP 171 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 469AF UT WOS:000170789800614 ER PT J AU Imam, SZ Ali, SF AF Imam, SZ Ali, SF TI Aging increases the susceptiblity to methamphetamine-induced dopaminergic neurotoxicity in rats: correlation with peroxynitrite production and hyperthermia SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE aging; dopamine; methamphetamine; oxidative stress; peroxynitrite ID NITRIC-OXIDE SYNTHASE; STRIATAL DOPAMINE; SERCA2A ISOFORM; SKELETAL-MUSCLE; BRAIN; MICE; AGE; AMPHETAMINE; ANTIOXIDANT; NITRATION AB Methamphetamine (METH) produces dopaminergic neurotoxicity by the production of reactive oxygen (ROS) and nitrogen (RNS) species. The role of free radicals has also been implicated in the process of aging. The present study was designed to evaluate whether METH-induced dopaminergic neurotoxicity and hyperthermia is a result of peroxynitrite production and if these effects correlate with age. One-, six-and 12-month-old male rats (n = 8) were administered a single dose of METH (0, 5, 10, 20, and 40 mg/kg, intraperitoneally). The formation of 3-nitrotyrosine (3-NT) as a marker of peroxynitrite production as well as dopamine and its metabolites DOPAC and HVA were measured in the striatum 4-h after METH-administration. Rectal temperature was monitored every 30 min after METH administration until 4 h. At 40 mg/kg METH, a 100% mortality in 12-month-old animals was observed, whereas no deaths occurred in 1- or 6-month-old rats. An age-dependent increase in hyperthermia was observed after METH-administration. A similar pattern of dose-dependent increase in the formation of 3-NT and in the depletion of dopamine and its metabolites with age was observed in the striatum. Furthermore, no effect was observed at 5 mg/kg METH in 1-month-old animals, whereas the effect was significant in 6- and 12-month-old animals. These data suggest that aging increases the susceptibility of the animals toward METH-induced peroxynitrite generation and striatal dopaminergic neurotoxicity. C1 US FDA, Natl Ctr Toxicol Res, Neurochem Lab, Div Neurotoxicol, Jefferson, AR 72079 USA. RP Ali, SF (reprint author), US FDA, Natl Ctr Toxicol Res, Neurochem Lab, Div Neurotoxicol, HFT-132,3900 NCTR Rd, Jefferson, AR 72079 USA. NR 32 TC 49 Z9 51 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD SEP PY 2001 VL 78 IS 5 BP 952 EP 959 DI 10.1046/j.1471-4159.2001.00477.x PG 8 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 467MG UT WOS:000170707900003 PM 11553669 ER PT J AU Auger, AP Meredith, JM Snyder, GL Blaustein, JD AF Auger, AP Meredith, JM Snyder, GL Blaustein, JD TI Oestradiol increases phosphorylation of a dopamine- and cyclic AMP-regulated phosphoprotein (DARPP-32) in female rat brain SO JOURNAL OF NEUROENDOCRINOLOGY LA English DT Article DE oestrogen; steroids; dopamine; hypothalamus; brain ID ADENOSINE 3'-5'-MONOPHOSPHATE-REGULATED PHOSPHOPROTEIN; STEROID-HORMONE RECEPTORS; NITRIC-OXIDE SYNTHASE; SEXUAL-BEHAVIOR; PROGESTERONE-RECEPTOR; ESTROUS-CYCLE; AUTORADIOGRAPHIC LOCALIZATION; PROTEIN-PHOSPHORYLATION; FOS-IMMUNOREACTIVITY; HYPOTHALAMIC SLICES AB Recent studies suggest that oestrogen and progestin receptors may be activated by the neurotransmitter dopamine, as well as by their respective ligands. Because intracerebroventricular infusion of D-1, but not D-2, dopaminergic receptor agonists increases oestrous behaviour in oestradiol-primed rats, we wanted to determine if treatment with oestradiol alters the activity of D-1 receptor-associated processes in steroid receptor-containing areas in female rat brain. One D-1 receptor-associated phosphoprotein that may be influenced by oestradiol is a dopamine- and cyclic AMP-regulated phosphoprotein, M-r=32 000 (DARPP-32). Because DARPP-32 is phosphorylated in response to dopamine acting via a cAMP-dependent protein kinase, it provides a useful marker to examine where in the brain a particular stimulus might be altering the activity of D-1 receptor-containing neurones. To determine if oestradiol alters the phosphorylation of DARPP-32, we stained immunocytochemically brain sections of female rats treated with behaviourally relevant doses of oestradiol or oil vehicle with an antibody that detects only the threonine 34-phosphorylated form of DARPP-32. Behaviourally effective doses of oestradiol increase the phosphorylation of DARPP-32 within the medial preoptic nucleus, bed nucleus of the stria terminalis, paraventricular nucleus of the hypothalamus and the ventromedial nucleus of the hypothalamus, 48 h after treatment. These data suggest that oestradiol increases the activity of D-1 dopamine receptor-associated processes in oestrogen receptor-containing areas of female rat forebrain. C1 Univ Massachusetts, Neurosci & Behav Program, Ctr Neuroendocrine Studies, Amherst, MA 01003 USA. US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Rockefeller Univ, Mol & Cellular Neurosci Lab, New York, NY 10021 USA. RP Auger, AP (reprint author), Univ Maryland, Sch Med, Dept Physiol, 655 W Baltimore St, Baltimore, MD 21201 USA. FU CSAP SAMHSA HHS [USPHS 40899]; NIMH NIH HHS [MH11392, MH 01312, MH10650]; NINDS NIH HHS [NS 19327] NR 61 TC 20 Z9 20 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0953-8194 J9 J NEUROENDOCRINOL JI J. Neuroendocrinol. PD SEP PY 2001 VL 13 IS 9 BP 761 EP 768 DI 10.1046/j.1365-2826.2001.00700.x PG 8 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 477LP UT WOS:000171285300004 PM 11578525 ER PT J AU Bhathena, SJ Berlin, E McClure, D Peters, RC AF Bhathena, SJ Berlin, E McClure, D Peters, RC TI Effects of dietary fats on red blood cell membrane insulin receptor in normo- and hypercholesterolemic miniature swine SO JOURNAL OF NUTRITIONAL BIOCHEMISTRY LA English DT Article DE plasma insulin; insulin binding; cholesterol; n-3 fatty acids; n-6 fatty acids; miniature swine ID DEPENDENT DIABETES-MELLITUS; ACID ETHYL-ESTER; FISH-OIL; LIPID-COMPOSITION; PREMENOPAUSAL WOMEN; GLUCOSE-METABOLISM; VITAMIN-E; BINDING; FLUIDITY; RATS AB It has been demonstrated that the type of dietary fat affects insulin receptors in various tissues in normal humans and animals by altering membrane fluidity. This study compares the effects of n-3 fatty acids from fish oil and n-6 fatty acids from corn oil on red blood cell membrane insulin receptors in normal and hypercholesterolemic minipigs. A group of minipigs were made hypercholesterolemic by feeding cholesterol and lard for 2 months; the other group served as controls and was fed stock diet. Both groups were then fed experimental diets containing either com. oil or menhaden oil or a mixture of the two for 23 additional weeks. Blood was collected at 0, 2, 12 and 23 weeks after the start of the experimental diets and membranes were prepared from the red blood cells. Insulin binding to red blood cell membranes was measured by radioreceptor assay. Plasma insulin was measured by radioimmunoassay. Insulin binding to red blood cell membrane was compared with the fluidity of the membrane measured and reported earlier. There was no significant effect of cholesterol feeding on plasma insulin concentrations. After 23 weeks on experimental diet plasma insulin was significantly higher in minipigs fed menhaden oil compared to those fed com. oil. No such effect was observed in hypercholesterolemic minipigs. No significant effect of either hypercholesterolemia or fish oil was observed on red blood cell insulin binding. A significant negative relationship was observed between insulin binding and anisotropy at 4 degreesC for all probes but at 37 degreesC significant negative relationship was observed only with polar probes. The data suggest that n-3 fatty acids from fish oil significantly increases plasma insulin in minipigs compared to n-6 fatty acids from com oil. However, the unsaturation has no significant effect on insulin receptors on erythrocytes. Similarly, prior hypercholesterolemic state also has no effect on plasma insulin levels or the insulin binding to red blood cell membranes. (C) 2001 Elsevier Science Inc. All rights reserved. C1 USDA ARS, Phytonutr Lab, Beltsville, MD 20705 USA. USDA ARS, Metab & Nutr Interact Lab, Beltsville Human Nutr Res Ctr, Beltsville, MD USA. US FDA, Ctr Food Safety & Appl Nutr, Div Toxicol Studies, Beltsville Res Facil,US Dept HHS, Laurel, MD USA. RP Bhathena, SJ (reprint author), USDA ARS, Phytonutr Lab, Beltsville, MD 20705 USA. NR 56 TC 2 Z9 2 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0955-2863 J9 J NUTR BIOCHEM JI J. Nutr. Biochem. PD SEP PY 2001 VL 12 IS 9 BP 529 EP 535 DI 10.1016/S0955-2863(01)00171-1 PG 7 WC Biochemistry & Molecular Biology; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Nutrition & Dietetics GA 473MC UT WOS:000171047100005 ER PT J AU Freedberg, DI Kopelevich, M Anet, FAL AF Freedberg, DI Kopelevich, M Anet, FAL TI Deuterium conformational equilibrium isotope effects in 1,3,5-cycloheptatriene-7-d SO JOURNAL OF PHYSICAL ORGANIC CHEMISTRY LA English DT Article DE deuterium; conformational isotope effect; cycloheptatriene; homoaromaticity; ab initio; NMR ID MAGNETIC-RESONANCE SPECTRA; NUCLEAR; PERTURBATION; CATION; REARRANGEMENTS; NORCARADIENE; MOLECULES; SHIFTS; ION AB We report a reinvestigation of the conformational equilibrium of 1,3,5-cycloheptatriene-7-d (CHT-7-d) by solution H-1 NMR at 500 MHz over a wide range of temperatures, and ab initio calculations up to the MP4 level. Lineshape analysis provided a barrier to ring inversion of approximately 6 kcal mol(-1). Equilibrium constants were measured in CBrF3 and CClF2H by: integration when the ring-inversion rate is low; lineshape analysis when the ring-inversion rate is on the order of the chemical shift difference; and temperature-dependent chemical shift differences between CHT and CHT-7-d when the ring-inversion rate is fast. The three independent measurements confirm an equilibrium biased toward an equatorial deuterium, with DeltaG degrees = 52 +/- 8 cal mol(-1) (at - 173 degreesC), DeltaH degrees = 55 +/- 8 cal mol(-1) and DeltaS degrees = 0.03 +/- 0.05 cal mol(-1) K-1 in CBrF3. Supporting ab initio calculations yield: DeltaH degrees = 34 cal mol(-1), DeltaS degrees = 0.014 cal mol(-1) K-1 (MP2/6-31G*); DeltaH degrees = 57 cal mol(-1) and DeltaS degrees = 0.03 cal mol(-1) K-1 (RHF/6-31G*); and a barrier to ring inversion in CHT of 4.26 kcal mol(-1) (RHF/6-31G*), 9.76 kcal mol(-1) (MP2/6-31G*), and 7.34 kcal mol(-1) (MP4/6-31G* single point). The differences in calculated barrier heights due to exclusion or inclusion of Moller-Plesset energies indicate that the ground state is stabilized relative to the transition state at the MP2 and MP4 levels. This implies that homoconjugation is important in CHT, a neutral molecule. Our experimental values differ from those originally deduced by Jensen and Smith (J. Am. Chem. Soc. 1964; 86: 956): DeltaG degrees = 72 cal mol(-1), DeltaH degrees = 142 +/- 30 cal mol(-1) and DeltaS degrees = 0.7 +/- 0.3 cal mol(-1) K-1. Copyright (C) 2001 John Wiley & Sons, Ltd. C1 US FDA, CBER, Biophys Lab, Rockville, MD 20852 USA. Univ Calif Los Angeles, Dept Chem & Biochem, Los Angeles, CA 90024 USA. RP Freedberg, DI (reprint author), US FDA, CBER, Biophys Lab, 1404 Rockville Pike,HFM-419, Rockville, MD 20852 USA. NR 49 TC 6 Z9 6 U1 0 U2 2 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0894-3230 J9 J PHYS ORG CHEM JI J. Phys. Org. Chem. PD SEP PY 2001 VL 14 IS 9 BP 625 EP 635 DI 10.1002/poc.410.abs PG 11 WC Chemistry, Organic; Chemistry, Physical SC Chemistry GA 466RP UT WOS:000170659300006 ER PT J AU Tavris, D Gross, T Gallauresi, B Kessler, L AF Tavris, D Gross, T Gallauresi, B Kessler, L TI Editorial comment - Arteriotomy closure devices - The FDA perspective SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Editorial Material ID ARTERIAL PUNCTURE SITE; MANUAL COMPRESSION; RANDOMIZED TRIAL; HEMOSTASIS DEVICE; ANGIOPLASTY; CATHETERIZATION; MANAGEMENT C1 US FDA, Div Postmarket Surveillance, Off Surveillance & Biometr, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. RP Tavris, D (reprint author), US FDA, Div Postmarket Surveillance, Off Surveillance & Biometr, Ctr Devices & Radiol Hlth, 1350 Piccard Dr,HFZ-451, Rockville, MD 20850 USA. NR 15 TC 14 Z9 14 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD SEP PY 2001 VL 38 IS 3 BP 642 EP 644 DI 10.1016/S0735-1097(01)01453-X PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 469PG UT WOS:000170823600007 PM 11527610 ER PT J AU Wang, KN Pesnicak, L Guancial, E Krause, PR Straus, SE AF Wang, KN Pesnicak, L Guancial, E Krause, PR Straus, SE TI The 2.2-kilobase latency-associated transcript of herpes simplex virus type 2 does not modulate viral replication, reactivation, or establishment of latency in transgenic mice SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN TRIGEMINAL GANGLIA; GENE MESSENGER-RNA; GENITAL HERPES; INFECTED MICE; STABLE INTRON; IN-VIVO; EXPRESSION; PROMOTER; NEURONS; REGION AB To better understand the mechanisms responsible for the observed effects of deletions in the promoter region of the latency-associated transcript (LAT) gene in impairing herpes simplex virus (HSV) reactivation, we generated mice transgenic for a 5.5-kb HSV type 2 (HSV-2) genomic fragment spanning the major LAT, along with the LAT promoter and flanking regions, in the C57BL/6 background. The mice expressed abundant 2.2-kb major LATs in trigeminal ganglia (TG) and other tissues. The effects of the transgene on HSV-2 infection, latency, and reactivation were assessed. When infected with wild-type (WT) HSV-2 or its LAT promoter deletion (LAT(-)) mutant, primary lung fibroblast lines established from normal C57BL/6 and transgenic mice supported virus growth equally well. The replication of these viruses in the mouse eye and their spread to TG and brains were similar. The quantities of latent viral DNA in TG of transgenic and normal mice, as determined by real-time PCR, were comparable. UV light-induced reactivation of the LAT- mutant from transgenic mice (0 to 7%) was no more frequent than that from normal mice (0 to 14%), while WT virus was reactivated from 13 to 54% of normal mice and 22 to 54% of transgenic mice. The cumulative data indicate that, when expressed transgenically, the HSV-2 major LAT cannot influence HSV-2 infection or latency and cannot complement the defect in reactivation of the LAT- mutant. These results imply that the phenotype of reduced reactivation associated with the LAT- mutant is related to a function encoded in the LAT promoter but not to the major LAT itself. C1 NCI, NIAID, NIH, Lab Clin Invest,Med Virol Sect, Bethesda, MD 20892 USA. Ctr Biol Evaluat & Res Food & Drug Adm, Div Viral Prod, Bethesda, MD 20892 USA. RP Wang, KN (reprint author), NCI, NIAID, NIH, Lab Clin Invest,Med Virol Sect, 10 Ctr Dr,Rm 11N228, Bethesda, MD 20892 USA. NR 29 TC 18 Z9 19 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 SEP PY 2001 VL 75 IS 17 BP 8166 EP 8172 DI 10.1128/JVI.75.17.8166-8172.2001 PG 7 WC Virology SC Virology GA 461AZ UT WOS:000170343900041 PM 11483762 ER PT J AU De Rosny, E Vassell, R Wingfield, PT Wild, CT Weiss, CD AF De Rosny, E Vassell, R Wingfield, PT Wild, CT Weiss, CD TI Peptides corresponding to the heptad repeat motifs in the transmembrane protein (gp41) of human immunodeficiency virus type 1 elicit antibodies to receptor-activated conformations of the envelope glycoprotein SO JOURNAL OF VIROLOGY LA English DT Article ID HIV-1 GP41; SYNTHETIC PEPTIDE; ATOMIC-STRUCTURE; DOMAIN; INHIBITION; FUSION; RESIDUES AB Two heptad repeat regions in the ectodomain of the human immunodeficiency virus type 1 (HIV-1) transmembrane subunit (gp41) self-assemble into a six-helix bundle structure that is critical for virus entry. Immunizations with peptides corresponding to these regions generated antibodies specific to the receptor-activated conformations of gp41. C1 US FDA, Ctr Biol Evaluat & Res, Off Vaccines, Bethesda, MD 20892 USA. NIAMSD, Prot Express Lab, NIH, Bethesda, MD 20892 USA. Panacos Pharmaceut, Gaithersburg, MD USA. RP Weiss, CD (reprint author), US FDA, Ctr Biol Evaluat & Res, Off Vaccines, HFM-466,NIH Bldg 29,Room 532,29 Lincoln Dr, Bethesda, MD 20892 USA. RI Weiss, Carol/F-6438-2011 OI Weiss, Carol/0000-0002-9965-1289 NR 18 TC 48 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 SEP PY 2001 VL 75 IS 18 BP 8859 EP 8863 DI 10.1128/JVI.75.18.8859-8863.2001 PG 5 WC Virology SC Virology GA 464BL UT WOS:000170512800053 PM 11507232 ER PT J AU Poirier, LA Brown, AT Fink, LM Wise, CK Randolph, CJ Delongchamp, RR Fonseca, VA AF Poirier, LA Brown, AT Fink, LM Wise, CK Randolph, CJ Delongchamp, RR Fonseca, VA TI Blood S-adenosylmethionine concentrations and lymphocyte methylenetetrahydrofolate reductase activity in diabetes mellitus and diabetic nephropathy SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article ID HOMOCYSTEINE METABOLISM; DNA METHYLATION; PLASMA HOMOCYSTEINE; CEREBROSPINAL-FLUID; FOLATE-DEFICIENCY; FOLLOW-UP; DISEASE; RATS; HYPERHOMOCYSTEINEMIA; METHIONINE AB The erythrocyte concentrations of the body's chief physiologic methyl donor S-adenosylmethionine (SAM) and of its metabolite and inhibitor S-adenosylhomocysteine (SAH), the plasma concentrations of total homocysteine (tHcy), and the activity of N-5,N-10 methylenetetrahydrofolate reductase (MTHFR) in lymphocytes were determined in healthy subjects and patients with diabetes mellitus without complications and at various stages of diabetic nephropathy, categorized according to the degree of progression of the disease. These groups were as follows: 1, control; 2, diabetics with no complications; 3, patients with albuminuria; 4, patients with an elevated plasma creatinine; and 5, patients on dialysis. No parameter studied exhibited significant differences between the type 1 and the type 2 diabetics. In control subjects, the blood concentrations of SAM were proportional to the activity of MTHFR; in diabetics, it was not. Consistent with previous observations, progression of nephropathy was accompanied by increased concentrations of tHcy. Increased erythrocyte concentrations of SAH, decreased erythrocyte concentrations of SAM, SAM/SAH ratios, and lymphocyte MTHFR activity also accompanied disease progression. The blood concentrations of SAH paralleled those of tHcy, while the concentrations of SAM showed a bimodal relationship with those of tHcy. These results provide further evidence that alterations in the blood concentrations of SAM and related compounds are abnormal in patients with diabetes, particularly in those with nephropathy. The deficiency of SAM may lead to methyl deficiencies, which may contribute to the high morbidity and mortality in patients with diabetic nephropathy. We have also demonstrated a decrease in lymphocyte MTHFR activity in patients with advanced nephropathy, suggesting that hyperhomocysteinemia in these patients may be due to a generalized metabolic abnormality. Further studies are needed to determine the pathogenesis of these abnormalities and whether they are present in renal failure due to causes other than diabetes or whether they are specific to diabetic nephropathy. Copyright (C) 2001 by W.B. Saunders Company. C1 Tulane Univ, Hlth Sci Ctr, Sch Med, Dept Med,Sect Endocrinol, New Orleans, LA 70112 USA. US FDA, Div Mol Epidemiol, Natl Ctr Toxicol Res, Jefferson, AR USA. John L McClellan Vet Adm Hosp, Div Endocrinol & Metab, Little Rock, AR USA. RP Fonseca, VA (reprint author), Tulane Univ, Hlth Sci Ctr, Sch Med, Dept Med,Sect Endocrinol, 1430 Tulane Ave,SL-53, New Orleans, LA 70112 USA. NR 49 TC 62 Z9 65 U1 2 U2 5 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD SEP PY 2001 VL 50 IS 9 BP 1014 EP 1018 DI 10.1053/meta.2001.15655 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 472DG UT WOS:000170967600006 PM 11555831 ER PT J AU Khaidakov, M Bishop, ME Manjanatha, MG Lyn-Cook, LE Desai, VG Chen, JJ Aidoo, A AF Khaidakov, M Bishop, ME Manjanatha, MG Lyn-Cook, LE Desai, VG Chen, JJ Aidoo, A TI Influence of dietary antioxidants on the mutagenicity of 7,12-dimethylbenz[a]anthracene and bleomycin in female rats SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article DE bleomycin; 7,12-dimethylbenz[a]anthracene; mutagenicity; Hprt; locus; dietary antioxidants ID DNA ADDUCT FORMATION; POLYCYCLIC AROMATIC-HYDROCARBONS; SISTER-CHROMATID EXCHANGES; HPRT MUTANT FREQUENCY; BETA-CAROTENE; VITAMIN-C; IN-VIVO; MOLECULAR ANALYSIS; OXIDATIVE DAMAGE; ASCORBIC-ACID AB Studies on agents that modulate carcinogen-induced genotoxic effects in experimental animals provide end points that can be used for assessing the antimutagenic or anticarcinogenic properties of putative chemopreventive compounds and for predicting their protective efficacy in humans. In this study, we investigated the ability of the dietary antioxidant Vitamins C, E, beta -carotene and the mineral selenium to inhibit the mutant frequency (MF) induced by treatment of rats with 7,12-dimethylbenz[a]anthracene (DMBA), a mammary carcinogen and bleomycin (BLM), an anti-tumor agent that can damage DNA by free radical mechanisms. Both chemicals have been previously shown to be mutagenic in the rat lymphocyte Hprt assay. Adult female Fischer 344 rats were given the antioxidants singly or in a combination 2 weeks prior to mutagen treatment. Antioxidant intake continued for an additional 4 weeks post-mutagen treatment. At sacrifice, spleens were aseptically removed for the isolation of lymphocytes to conduct the mutagenesis assay at the Hprt locus. The DMBA and BLM treatment induced a marked increase in MF, 52.8 x 10(-6) and 19.2 x 10(-6), respectively, over the controls. The MFs seen in the individual antioxidants alone (single or mixture) were relatively similar to the controls, with the exception of Vitamins C and E, that had 1.7- and 1.5-fold increase, respectively. The degree of inhibitory response was dependent on the type of mutagen and the particular antioxidant. BLM]antioxidant combination had inhibitions ranging from 44 to 80%, while DMBA/antioxidant system ranged from 60 to 93%, with Vitamins C and E achieving the highest inhibition in both systems. The mixture displayed low inhibitory responses, 44.6% for BLM/mix and 47% DMBA/mix. On the whole, the results indicate that the dietary constituents tested are antimutagenic; however, because of the gradations seen with the responses, the protective efficacy of these antioxidants may depend on the type of mutagen/carcinogen they encounter. Pending molecular analysis of mitochondrial DNA mutations will also indicate whether there is a shift in the mutational spectra produced by the carcinogens in the presence of antioxidants. (C) 2001 Elsevier Science B.V. All rights reserved. C1 US FDA, Div Genet & Reprod Toxicol, Natl Ctr Toxicol Res, Jefferson Labs, Jefferson, AR 72079 USA. US FDA, Div Biometry & Risk Assessment, Natl Ctr Toxicol Res, Jefferson Labs, Jefferson, AR 72079 USA. RP Aidoo, A (reprint author), US FDA, Div Genet & Reprod Toxicol, Natl Ctr Toxicol Res, Jefferson Labs, Jefferson, AR 72079 USA. NR 51 TC 14 Z9 14 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0027-5107 J9 MUTAT RES-FUND MOL M JI Mutat. Res.-Fundam. Mol. Mech. Mutagen. PD SEP 1 PY 2001 VL 480 SI SI BP 163 EP 170 DI 10.1016/S0027-5107(01)00180-4 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 467AK UT WOS:000170678200017 PM 11506810 ER PT J AU Hanna, GM Lau-Cam, CA AF Hanna, GM Lau-Cam, CA TI A stability-indicating proton nuclear magnetic resonance spectroscopic method for the analysis of propantheline bromide in pharmaceutical samples SO PHARMAZIE LA English DT Article ID PERFORMANCE LIQUID-CHROMATOGRAPHY; ELECTRODES; TABLETS; DRUGS; PHASE; HPLC AB A rapid, specific and accurate proton nuclear magnetic resonance (H-1 NMR) spectroscopic method was developed for the simultaneous quantitative analysis of propantheline bromide and its degradation product, xanthanoic acid, in bulk materials and tablets. 1,3,5-Trinitrobenzene served as an internal standard and deuterochloroform was used as the solvent for the analytical samples. The quantities of propantheline bromide and xanthanoic acid were calculated on the basis of the integrals for signals of the methine proton of propantheline at 5.09 ppm, the methine proton of xanthanoic acid at 4.99 ppm, and the aromatic protons of the internal standard at 9.39 ppm. The accuracy of the method was established through the analysis of synthetic mixtures containing the parent compound, its degradation product and the internal standard. An excellent agreement was verified between the assay results and the quantities of the various compounds in the mixtures. The mean SID recovery values for propantheline bromide and xanthanoic acid from a set of 10 synthetic mixtures were 99.6 +/- 0.8% and 98.9 +/- 1.8%, respectively. The assay of 10 lots of commercial propantheline bromide tablets by H-1 NMR spectroscopy indicated drug and degradate contents in the ranges 97.1-99.8% and 0.1-0.9%, respectively. In addition, the proposed analytical method was found suitable for detecting the formation of xanthanoic acid from propantheline bromide in aqueous media in concentrations below 0.1% of that of the parent compound. C1 US FDA, Dept Hlth & Human Serv, New York Reg Lab, Jamaica, NY 11433 USA. St Johns Univ, Coll Pharm & Allied Hlth Profess, Jamaica, NY 11439 USA. RP Hanna, GM (reprint author), US FDA, Dept Hlth & Human Serv, New York Reg Lab, 158-15 Liberty Ave, Jamaica, NY 11433 USA. NR 31 TC 3 Z9 3 U1 0 U2 0 PU GOVI-VERLAG GMBH PI ESCHBORN PA PHARMAZEUTISCHER VERLAG GINNHEIMER STRASSE 26, D-65760 ESCHBORN, GERMANY SN 0031-7144 J9 PHARMAZIE JI Pharmazie PD SEP PY 2001 VL 56 IS 9 BP 700 EP 703 PG 4 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 477AH UT WOS:000171260600006 PM 11593989 ER PT J AU Tabacova, SA Kimmel, CA AF Tabacova, SA Kimmel, CA TI Enalapril: pharmacokinetic/dynamic inferences for comparative developmental toxicity - A review SO REPRODUCTIVE TOXICOLOGY LA English DT Review DE ACE inhibitors; enalapril; pharmacokinetics; pharmacodynamics; developmental toxicity; animal-human comparisons ID ANGIOTENSIN-CONVERTING ENZYME; PREGNANCY-INDUCED HYPERTENSION; NEONATAL RENAL-FAILURE; II RECEPTOR SUBTYPES; BLOOD-FLOW; RHESUS MACAQUES; ACE-INHIBITION; MESSENGER-RNAS; PLASMA-RENIN; RAT FETUS AB Enalapril is an antihypertensive drug of the class of angiotensin-converting enzyme inhibitors (ACEI) used in pregnancy for treatment of pre-existing or pregnancy-induced hypertension. The use of ACE inhibitors (drugs that act directly on the renin-angiotensin system) during the second and third trimester of pregnancy in humans is associated with specific fetal and neonatal injury, The syndrome, termed "ACEI fetopathy" in humans, does not appear to have a similar counterpart in experimental animals. The present paper reviews pharmacokinetic and pharmacodynamic aspects of enalapril that are physiologically important during pregnancy and intrauterine development in humans and in experimental animal species with the aim of better understanding the comparability of the manifestations of enalapril developmental toxicity in animals and humans. The human fetus is at a disadvantage with regard to in utero enalapril exposure in comparison to some of the animal species for which gestational pharmacokinetic data are available. Important reasons for the higher vulnerability of the human fetus are its accessibility by enalapril and the earlier (relative to animal species) intrauterine development of organ systems that are specific targets of ACEI pharmacologic effect (the kidney and the renin-angiotensin system). In humans, these systems develop prior to calcarial ossification at the end of first trimester of pregnancy. The specific pharmacodynamic action of enalapril on these systems during fetal life is the chief determinant of the etiology and pathogenesis of ACEI fetopathy in humans. In contrast, in most of the studied animal species, these target systems are not developed until close to term when the fetus is relatively more mature (and therefore less vulnerable), so that the window of vulnerability is narrower in comparison to the human. Among animal species, the best concordance in fetal pharmacodynamics to the human is seen in the rhesus monkey, but further studies are necessary to determine if similar developmental pathology is induced in this animal model upon repeated administration of the drug during the relevant period of intrauterine development. Animal-human concordance of developmental toxicity is least likely in the rat because of greater disparities in enalapril availability to the fetus and the relative development of the kidney and skeletal ossification compared to that in humans. (C) 2001 Elsevier Science Inc. All rights reserved. C1 US FDA, Natl Ctr Toxicol Res, Rockville, MD 20857 USA. US EPA, Natl Ctr Environm Assessment, Off Res & Dev, Washington, DC 20460 USA. RP Tabacova, SA (reprint author), US FDA, Natl Ctr Toxicol Res, 5600 Fishers Lane,Room 16-53,HFT-10, Rockville, MD 20857 USA. NR 95 TC 32 Z9 32 U1 1 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0890-6238 J9 REPROD TOXICOL JI Reprod. Toxicol. PD SEP-OCT PY 2001 VL 15 IS 5 BP 467 EP 478 DI 10.1016/S0890-6238(01)00161-7 PG 12 WC Reproductive Biology; Toxicology SC Reproductive Biology; Toxicology GA 473PY UT WOS:000171055600001 PM 11780954 ER PT J AU McClain, RM Keller, D Casciano, D Fu, P MacDonald, J Popp, J Sagartz, J AF McClain, RM Keller, D Casciano, D Fu, P MacDonald, J Popp, J Sagartz, J TI Neonatal mouse model: Review of methods and results SO TOXICOLOGIC PATHOLOGY LA English DT Article DE neonatal mouse; bioassay; short-term; 52-weeks; alternatives; carcinogenicity; testing ID TUMORIGENICITY; BIOASSAY AB The neonatal mouse model, in various forms, has been used experimentally since 1959 and a large number of chemicals have been tested. The neonatal model is known to be very sensitive for the detection of carcinogens that operate via a genotoxic mode of action. In contrast, it is known not to respond to chemicals that act via epigenetic mechanisms. commonly observed lit the two-year carcinogenicity studies. As such, the model has a high sensitivity and specificity in its response. Dose selection for the neonatal model is based on the maximum tolerated or feasible dose. Traditionally, compounds have been tested via the IP route of administration in this model. In some cases, this has limited the amount of material that can be administered because of the low dosing volumes (10 to 20 muL) that can be administered IP. For the ILSI project, the neonatal model was adapted for oral administration, which has the advantages of being the sane route for which most pharmaceuticals are administered. In addition. a 10-fold increase in the volume of administration (100 to 200 muL) and the ability to dose drugs in suspension. pen-nits much higher doses to be used as compared to the IP route of administration. The spontaneous tumors in the neonatal model occurred mainly in the liver of male mice and lung of male and female mice with a few tumors observed in the Harderian gland. The positive control, DEN produced a robust. uniform. and reproducible tumor response with the target organs essentially limited to liver and lung. A total of 13 compounds out of tire 21 ILSI ACT compounds were evaluated in the neonatal model involving 18 studies with duplicate studies for some compounds. The genotoxic carcinogens including those used as positive controls were clearly positive (cyclophosphamide, diethylnitrosamine, 6-nitrochrysene). The non-genotoxic rodent carcinogens were clearly negative (chlorpromazine. sulfisoxazole. sulfamethoxazole, clofibrate, DEHP. haloperidol, metaproteranol, and phenobarbital). The non-genotoxic human carcinogen (cyclosporin) was clearly negative. The two other human carcinogens phenacetin and DES were negative and interestingly estradiol was negative in one of the two oral studies, but was clearly positive in the other. Considering the mode of action for three of the human carcinogens (DES, cyclosporin and phenacetin). which were negative in this model, the mode of action in humans is likely to be epigenetic. Overall, for the 3 clearly genotoxic chemicals. all were positive. For the 9 clearly non-genotoxic chemicals, all 9 were negative. The two human carcinogens for which genotoxicity may or may not play a role (DES and phenacetin) were negative and estradiol was positive in I of the two oral studies. Overall. the extensive database for compounds tested in the neonatal mouse model would support its use as an alternative model for the assessment of the carcinogenic potential of a chemical. The model responds to chemicals that act via a genotoxic mode of action that represent a greater concern for human cancer risk. C1 Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. US FDA, Rockville, MD 20857 USA. Sanofi Synthelabo Res, New York, NY 10016 USA. Schering Plough Res Inst, Kenilworth, NJ 07033 USA. DuPont Pharmaceut Co, Wilmington, DE 19805 USA. RP McClain, RM (reprint author), 10 Powder Horn Terrace, Randolph, NJ 07869 USA. OI Keller, Douglas/0000-0002-6186-2881 NR 9 TC 30 Z9 30 U1 2 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 SEP 1 PY 2001 VL 29 SU 1 BP 128 EP 137 DI 10.1080/019262301753178537 PG 10 WC Pathology; Toxicology SC Pathology; Toxicology GA 558DR UT WOS:000175951500013 PM 11695548 ER PT J AU Walker, LM York, JL Imam, SZ Ali, SF Muldrew, KL Mayeux, PR AF Walker, LM York, JL Imam, SZ Ali, SF Muldrew, KL Mayeux, PR TI Oxidative stress and reactive nitrogen species generation during renal ischemia SO TOXICOLOGICAL SCIENCES LA English DT Article DE 3-nitrotyrosine; peroxynitrite; superoxide; 4-hydroxynonenal; renal ischemia; acute renal failure; glutathione ID OXIDE SYNTHASE ACTIVITY; NITRIC-OXIDE; LIPID-PEROXIDATION; REPERFUSION INJURY; GLUTATHIONE-PEROXIDASE; RAT-KIDNEY; 4-HYDROXY-2-NONENAL-MODIFIED PROTEINS; PEROXYNITRITE; INACTIVATION; LIPOPOLYSACCHARIDE AB Previous evidence suggests that both oxygen radicals and nitric oxide (NO) are important mediators of injury during renal ischemia-reperfusion (I-R) injury. However, the generation of reactive nitrogen species (RNS) has not been evaluated in this model at early time points. The purpose of these studies was to examine the development of oxidant stress and the formation of RNS during I-R injury. Male Sprague-Dawley rats were anesthetized and subjected to 40 min of bilateral renal ischemia followed by 0, 3, or 6 h of reperfusion. Control animals received a sham operation. Plasma urea nitrogen and creatinine levels were monitored as markers of renal injury. Glutathione (GSH) oxidation and 4-hydroxynonenal (4-HNE)-protein adducts were used as markers of oxidant stress. 3-Nitrotyrosine (3-NT) was used as a biomarker of RNS formation. Significant increases in plasma creatinine concentrations and urea nitrogen levels were found following both 3 and 6 h of reperfusion. Increases in GSH oxidation, 4-HNE-protein adduct levels, and 3-NT levels were observed following 40 min of ischemia with no reperfusion. Since these results suggested RNS generation during the 40 min of ischemia, a time course of RNS generation following 0, 5, 10, 20, and 40 min of ischemia was evaluated. Significant increases in 3-NT generation was detected as early as 10 min of ischemia and rose to values nearly 10-fold higher than Control at 40 min of ischemia. No additional increase was observed following reperfusion. The data clearly demonstrate that oxidative stress and RNS generation occur in the kidney during ischemia. C1 Univ Arkansas Med Sci, Dept Pharmacol & Toxicol, Little Rock, AR 72205 USA. Univ Arkansas Med Sci, Dept Biochem & Mol Biol, Little Rock, AR 72205 USA. US FDA, Div Neurotoxicol, Neurochem Lab, Jefferson, AR 72079 USA. RP Mayeux, PR (reprint author), Univ Arkansas Med Sci, Dept Pharmacol & Toxicol, Mail Slot 611,4301 W Markham St, Little Rock, AR 72205 USA. EM mayeuxphilipr@uams.edu FU NIDDK NIH HHS [DK44716] NR 43 TC 61 Z9 62 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 SEP PY 2001 VL 63 IS 1 BP 143 EP 148 DI 10.1093/toxsci/63.1.143 PG 6 WC Toxicology SC Toxicology GA 467LC UT WOS:000170702400019 PM 11509754 ER PT J AU Biswas, R Busch, M Hsia, C Laycock, M Hirschkorn, D Tabor, E AF Biswas, R Busch, M Hsia, C Laycock, M Hirschkorn, D Tabor, E TI Comparative sensitivity of HBVNAT and HBsAg donor testing SO TRANSFUSION LA English DT Meeting Abstract C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. US FDA, Rockville, MD 20857 USA. US FDA, Bethesda, MD 20014 USA. NR 0 TC 8 Z9 8 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 2001 VL 41 IS 9 SU S BP 8S EP 8S PG 1 WC Hematology SC Hematology GA 472TV UT WOS:000171001800030 ER PT J AU Holness, LG Callaghan, EG Knippen, MA Simmons, LE Williams, AE AF Holness, LG Callaghan, EG Knippen, MA Simmons, LE Williams, AE TI Transfusion related acute lung injury: An update SO TRANSFUSION LA English DT Meeting Abstract C1 US FDA, Rockville, MD 20857 USA. NR 0 TC 1 Z9 1 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 2001 VL 41 IS 9 SU S BP 18S EP 19S PG 2 WC Hematology SC Hematology GA 472TV UT WOS:000171001800070 ER PT J AU Glynn, SA Schreiber, GB Bethel, J Higgins, MJ Garratty, G Chang, D Williams, AE AF Glynn, SA Schreiber, GB Bethel, J Higgins, MJ Garratty, G Chang, D Williams, AE CA NHLBI Retrovirus Epidemiology Dono TI Appeal of incentive programs at different donation sites SO TRANSFUSION LA English DT Meeting Abstract C1 WESTAT Corp, Rockville, MD 20850 USA. St Johns Hosp, Detroit, MI USA. Amer Red Cross Blood Serv, Los Angeles, CA USA. US FDA, Rockville, MD 20857 USA. 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 2001 VL 41 IS 9 SU S BP 21S EP 21S PG 1 WC Hematology SC Hematology GA 472TV UT WOS:000171001800079 ER PT J AU Schreiber, GB Sanchez, AM Garratty, G Nass, CC Tu, Y Busch, MP Williams, AE AF Schreiber, GB Sanchez, AM Garratty, G Nass, CC Tu, Y Busch, MP Williams, AE CA NHLBI Retrovirus Epidemiology Dono TI Mammalian brain consumption by US blood donors: Brains today, deferred tomorrow? SO TRANSFUSION LA English DT Meeting Abstract C1 Amer Red Cross Blood Serv, Los Angeles, CA USA. WESTAT Corp, Rockville, MD 20850 USA. Amer Red Cross Blood Serv, Baltimore, MD USA. Blood Ctr Pacific, San Francisco, CA USA. US FDA, Rockville, MD 20857 USA. NR 0 TC 1 Z9 1 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 2001 VL 41 IS 9 SU S BP 35S EP 35S PG 1 WC Hematology SC Hematology GA 472TV UT WOS:000171001800130 ER PT J AU Huang, XY Liu, T Muller, J Levandowski, RA Ye, ZP AF Huang, XY Liu, T Muller, J Levandowski, RA Ye, ZP TI Effect of influenza virus matrix protein and viral RNA on ribonucleoprotein formation and nuclear export SO VIROLOGY LA English DT Article DE influenza virus; M1 protein; interaction of M1 and RNP; quaternary structure of RNP; nuclear export ID M1 PROTEIN; A VIRUS; NUCLEOPROTEIN; POLYMERASE; CELLS; REPLICATION; TRANSPORT; PARTICLES; RIBOZYME; ELEMENTS AB The formation of influenza virus ribonucleoprotein (RNP) is a necessary step in viral assembly and maturation in infected cells, but the mechanism remains incompletely understood. Influenza virus proteins such as matrix (M1) and cellular proteins have been implicated in assembly and transport of RNP. To study the assembly of RNP and the translocation of RNP complexes in cells, RNPs were reconstituted from nucleoprotein (NP), M1, and viral RNA (vRNA) synthesized in vitro. The syntheses were accomplished using specific plasmids in a system coupling transcription and translation under the control of the T7 promoter. The density of the resulting RNP complexes was analyzed by glycerol gradient centrifugation and the morphology was examined by transmission electron microscopy. Protomers of NP self-assembled into circular oligomers regardless of the presence of vRNA or M1. However, helical structures similar in conformation and density to RNPs purified directly from influenza virus were formed only when M1 and vRNA were also present. In the absence of vRNA, no helical structures were formed from NP and M1. The plasmids also contained the CMV promoter, which permitted expression of M1, NP, and vRNA in Madin-Darby canine kidney (MDCK). M1 and NP were both present in the cytoplasm of MDCK also expressing vRNA, but NP was retained in the nucleus of cells expressing M1 without vRNA. Our data demonstrate for the first time that vRNA and M1 together promote the self-assembly of influenza virus NP into the quaternary helical structure typical of the viral RNP. The results also indicate that the interaction of NP with vRNA and M1 in a system devoid of other viral proteins can lead to translocation of RNP from nucleus to cytoplasm. C1 US FDA, Lab Pediat & Resp Viral Dis, Div Viral Prod,Off Vaccines Res & Review, Ctr Biol & Evaluat & Res, Bethesda, MD 20892 USA. US FDA, Lab Vector Borne Viral Dis, Div Viral Prod,Off Vaccines Res & Review, Ctr Biol & Evaluat & Res, Bethesda, MD 20892 USA. RP Ye, ZP (reprint author), Bldg 29A,Rm 2B17,8800 Rockville Pike, Bethesda, MD 20982 USA. NR 46 TC 37 Z9 42 U1 0 U2 9 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD SEP 1 PY 2001 VL 287 IS 2 BP 405 EP 416 DI 10.1006/viro.2001.1067 PG 12 WC Virology SC Virology GA 471GY UT WOS:000170921500016 PM 11531417 ER PT J AU Colman, E AF Colman, E TI A brief note on Man SO LANCET LA English DT Letter C1 US FDA, Rockville, MD 20897 USA. RP Colman, E (reprint author), US FDA, Rockville, MD 20897 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD AUG 25 PY 2001 VL 358 IS 9282 BP 674 EP 674 DI 10.1016/S0140-6736(05)71682-2 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 465XP UT WOS:000170615500057 PM 11545093 ER PT J AU Yanes, EG Gratz, SR Baldwin, MJ Robison, SE Stalcup, AM AF Yanes, EG Gratz, SR Baldwin, MJ Robison, SE Stalcup, AM TI Capillary electrophoretic application of 1-alkyl-3-methylimidazolium-based ionic liquids SO ANALYTICAL CHEMISTRY LA English DT Article ID ZONE-ELECTROPHORESIS; CHROMATOGRAPHY; SEPARATION; TEA; WINES; DERIVATIVES; CATECHINS; EXTRACTS; PLASMA; ARRAY AB Ionic substances with melting points at or close to room temperature are referred to as ionic liquids. Interest in ionic liquids for their potential in different chemical processes is increasing, because they are environmentally benign and are good solvents for a wide range of both organic and inorganic materials. In this study, a capillary electrophoretic method for resolving phenolic compounds found in grape seed extracts is reported. The method, Mi which 1-alkyl-3-methylimidazolium-based ionic liquids are used as the running electrolytes, is simple and reproducible. The separation mechanism seems to involve association between the imidazolium cations and the polyphenols. The role of the alkyl substituents on the imidazolium cations was investigated and will be discussed. C1 Univ Cincinnati, Dept Chem, Cincinnati, OH 45221 USA. US FDA, Forens Chem Ctr, Cincinnati, OH 45237 USA. RP Stalcup, AM (reprint author), Univ Cincinnati, Dept Chem, POB 210172, Cincinnati, OH 45221 USA. RI Stalcup, A. M./E-9386-2013 OI Stalcup, A. M./0000-0003-1537-0437 NR 41 TC 260 Z9 281 U1 3 U2 25 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 AUG 15 PY 2001 VL 73 IS 16 BP 3838 EP 3844 DI 10.1021/ac010263r PG 7 WC Chemistry, Analytical SC Chemistry GA 463NT UT WOS:000170482800007 PM 11534705 ER PT J AU Gratz, SR Schneiderman, E Mertens, TR Stalcup, AM AF Gratz, SR Schneiderman, E Mertens, TR Stalcup, AM TI Use of dyes to investigate migration of the chiral selector in CFFE and the impact on the chiral separations SO ANALYTICAL CHEMISTRY LA English DT Article ID FREE-FLOW ELECTROPHORESIS; CLASSICAL GEL-ELECTROPHORESIS; SULFATED BETA-CYCLODEXTRIN; CAPILLARY-ELECTROPHORESIS; ZONE ELECTROPHORESIS; ENANTIOMERS; PURIFICATION; TERBUTALINE; SIMULATION AB Continuous free flow electrophoresis was investigated as a tool for the preparative chiral separation of piperoxan enantiomers using sulfated beta -cyclodextrin (s beta -CD) as the chiral additive. Bulk migration of s beta -CD was confirmed using LC-MS analysis of the individual fractions collected and visualized with the addition of crystal violet to the separation buffer. In the absence of s beta -CD, the crystal violet-containing buffer was reddish/purple and the crystal violet was deflected cathodically in the chamber. In the presence of s beta -CD, the crystal violet-containing buffer was blue and was deflected anodically. However, formation of accumulation and depletion zones was apparent in both cases. The addition of s beta -CD to the cathodic wash solution allowed for almost complete resolution of the piperoxan enantiomers with a processing rate of 0.45 mg/h. C1 Univ Cincinnati, Dept Chem, Cincinnati, OH 45221 USA. Procter & Gamble Co, Ivorydale Tech Ctr, Cincinnati, OH 45217 USA. US FDA, Forens Chem Ctr, Cincinnati, OH 45237 USA. RP Stalcup, AM (reprint author), Univ Cincinnati, Dept Chem, POB 210172, Cincinnati, OH 45221 USA. RI Stalcup, A. M./E-9386-2013 OI Stalcup, A. M./0000-0003-1537-0437 FU NIGMS NIH HHS [GM59675-01] NR 35 TC 11 Z9 11 U1 0 U2 5 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 AUG 15 PY 2001 VL 73 IS 16 BP 3999 EP 4005 DI 10.1021/ac010220a PG 7 WC Chemistry, Analytical SC Chemistry GA 463NT UT WOS:000170482800030 PM 11534728 ER PT J AU Kawakami, K Kawakami, M Joshi, BH Puri, RK AF Kawakami, K Kawakami, M Joshi, BH Puri, RK TI Interleukin-13 receptor-targeted cancer therapy in an immunodeficient animal model of human head and neck cancer SO CANCER RESEARCH LA English DT Article ID CELL CARCINOMA-CELLS; PSEUDOMONAS EXOTOXIN; CHIMERIC PROTEIN; ALPHA CHAIN; SIGNAL-TRANSDUCTION; (IL)-13 BINDING; SARCOMA-CELLS; CLONING; IL-13; COMPONENT AB Although interleukin-13 receptors (IL-13R) are overexpressed on several head and neck cancer cell lines, a majority of cell lines express only low levels of IL-13R. We have found that the primary interletikin-13-binding protein IL-13R alpha2 chain plays an important role in ligand binding and internalization. We showed that the gene transfer of IL-13R alpha2 chain into various solid tumor cell lines that express few IL-13Rs can dramatically sensitize cells to the cytotoxic effect of a recombinant chimeric protein composed of interleukin-13 and a mutated form of Pseudomonas exotoxin A, IL13-PE38QQR. Based on the expression of IL-13R,,Ne have classified five head and neck cancer cell lines into two groups: (a) IL-13R alpha2 chain-positive cell lines (SCC-25 and KCCT873); and (b) IL-13R alpha2 chain-negative cell lines (A253, YCUT891, and KCCT871). By plasm id-mediated stable gene transfer, we demonstrate that rot only IL-13R alpha2 chain-positive head and neck cancer cell lines but also IL13R alpha2 chain-negative cell lines can dramatically increase sensitivity to IL-13 toxin by 520-1000-fold compared with mock-transfected control cells after genetic alteration to express high levels of the IL-13R alpha2 chain. In animal studies, i.p. or intratumoral administration of IL13-PE38QQR given daily or on alternate days for 3-5 days showed dramatic tumor response with complete remission in intratumorally injected tumors in both IL-13R alpha2 chain-positive and -negative but transfected with IL13R alpha2 chain head and neck tumor implanted s.c. in nude mice. These results demonstrate that by using a combination approach of gene transfer and systemic or locoregional cytotoxin therapy, the IL-13R represents a new potent target for head and neck cancer therapy. C1 US FDA, Ctr Biol Evaluat & Res, Div Cellulare & Gene Therapies, Lab Mol Tumor Biol, Bethesda, MD 20892 USA. RP Puri, RK (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Cellulare & Gene Therapies, Lab Mol Tumor Biol, NIH Bldg 29B,Room 2NN10,29 Lincoln Dr,MSC 4555, Bethesda, MD 20892 USA. NR 31 TC 59 Z9 61 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 AUG 15 PY 2001 VL 61 IS 16 BP 6194 EP 6200 PG 7 WC Oncology SC Oncology GA 464EW UT WOS:000170521100040 PM 11507072 ER PT J AU Graham, DJ Drinkard, CR Shatin, D Tsong, Y Burgess, MJ AF Graham, DJ Drinkard, CR Shatin, D Tsong, Y Burgess, MJ TI Liver enzyme monitoring in patients treated with troglitazone SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID HEPATIC-FAILURE AB Context Soon after initial marketing in March 1997, troglitazone, the first thiazolidinedione antidiabetic agent, was found to cause life-threatening acute liver failure. The drug was removed from the market in March 2000. Objective To evaluate the effect of US Food and Drug Administration (FDA) risk management efforts, including repeated labeling changes and "Dear Healthcare Professional" letters, on periodic liver enzyme monitoring of patients taking troglitazone. Design, Setting, and Participants Claims data from a large, multistate managed care organization were used to establish 4 cohorts of patients (N = 7603) with at least 90 days of health plan enrollment before first troglitazone prescription during 4 consecutive periods spanning April 1997 to September 1999 and representing 4 progressively stringent liver monitoring recommendations. Main Outcome Measures Percentage of eligible troglitazone users in each cohort with baseline, monthly (for up to 6 months of continuous use), and complete (baseline and monthly) enzyme monitoring, based on computerized records of laboratory claims. Results Baseline testing increased from 15% before any FDA monitoring recommendations (cohort 1) to 44.6% following 4 separate FDA interventions (cohort 4; P<.001). In cohort 4, 33.4% of users had follow-up testing after 1 month of therapy, falling to 13% after 5 months of continuous use. in all cohorts, less than 5% received all recommended liver enzyme tests by the third month of continuous use. Conclusions The FDA risk management efforts did not achieve meaningful or sustained improvement in liver enzyme testing. Evaluation of the impact of regulatory actions is needed before such actions can be regarded as effective or sufficient. C1 US FDA, Off Postmarketing Drug Risk Assessment, Rockville, MD 20857 USA. US FDA, Off Biostat, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. United Hlth Grp, Ctr Hlth Care Policy & Evaluat, Minneapolis, MN USA. RP Graham, DJ (reprint author), US FDA, Off Postmarketing Drug Risk Assessment, 5600 Fishers Ln,HFD-400,Room 15B-32, Rockville, MD 20857 USA. FU FDA HHS [FD-U-000149, FD-U-0001643-01/02] NR 16 TC 87 Z9 89 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 AUG 15 PY 2001 VL 286 IS 7 BP 831 EP 833 DI 10.1001/jama.286.7.831 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 462PU UT WOS:000170429600031 PM 11497537 ER PT J AU Badano, A Kanicki, J AF Badano, A Kanicki, J TI Monte Carlo analysis of the spectral photon emission and extraction efficiency of organic light-emitting devices SO JOURNAL OF APPLIED PHYSICS LA English DT Article ID EXTERNAL-QUANTUM-EFFICIENCY; DIODES; PHOTOLUMINESCENCE; SCATTERING AB We report on a Monte Carlo method for modeling light transport phenomena in multilayer organic polymer light-emitting devices on plastic flexible substrates. The method allows modeling of Cartesian geometrical structures describing the fate of photons through multiple scattering events determined by the wavelength-dependent material optical properties. We apply the method to analyze the wavelength distribution of emitted light spectra. We find that for all organic polymers considered, the light emission is slightly shifted toward the longer wavelengths, and that this shift is maximum for light emissions with peaks around 530 nm. The photon extraction efficiency is higher (0.430) for organic polymers emitting in the longer wavelengths, while the photon absorbed fraction is higher (0.676) for spectra with a maximum in the short wavelengths. (C) 2001 American Institute of Physics. C1 Univ Michigan, Dept Elect Engn & Comp Sci, Solid State Elect Lab, 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 14 TC 28 Z9 30 U1 0 U2 4 PU AMER INST PHYSICS PI MELVILLE PA 2 HUNTINGTON QUADRANGLE, STE 1NO1, MELVILLE, NY 11747-4501 USA SN 0021-8979 J9 J APPL PHYS JI J. Appl. Phys. PD AUG 15 PY 2001 VL 90 IS 4 BP 1827 EP 1830 DI 10.1063/1.1385571 PG 4 WC Physics, Applied SC Physics GA 458YN UT WOS:000170223200025 ER PT J AU Mancuso, JY Ahn, H Chen, JJ AF Mancuso, JY Ahn, H Chen, JJ TI Order-restricted dose-related trend tests SO STATISTICS IN MEDICINE LA English DT Article ID CARCINOGENICITY; MORTALITY; ANIMALS AB Methods of isotonic regression are proposed to increase the power of common trend tests in situations where a monotonicity constraint is imposed upon the dose-response function. Isotonic versions of Cochran-Armitage type trend tests for binary response data are developed, and the bootstrap method is used in finding the empirical distributions of the test statistics and their critical values. The isotonic likelihood ratio test with a survival adjustment is also proposed. This survival adjustment can be applied to the likelihood ratio test for either the order-restricted or unrestricted parameter cases. To achieve the isotonic modifications, an amalgamation algorithm is applied when the observed dose-response is non-monotonic. A Monte Carlo simulation study comparing these trend tests shows the advantages of the isotonic modifications and survival adjustment. By applying the proposed methods to data from a toxicology and carcinogenesis study conducted as part of the National Toxicology Program, the effect of Cl Pigment Red 23 is investigated. Copyright (C) 2001 John Wiley & Sons, Ltd. C1 SUNY Stony Brook, Dept Appl Math & Stat, Stony Brook, NY 11794 USA. US FDA, Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. RP Ahn, H (reprint author), SUNY Stony Brook, Dept Appl Math & Stat, Stony Brook, NY 11794 USA. FU NCI NIH HHS [R29 CA77289-03] NR 11 TC 10 Z9 10 U1 2 U2 4 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 AUG 15 PY 2001 VL 20 IS 15 BP 2305 EP 2318 DI 10.1002/sim.849 PG 14 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 458TC UT WOS:000170209800005 PM 11468765 ER PT J AU Sams, RL Couch, LH Miller, BJ Okerberg, CV Warbritton, A Wamer, WG Beer, JZ Howard, PC AF Sams, RL Couch, LH Miller, BJ Okerberg, CV Warbritton, A Wamer, WG Beer, JZ Howard, PC TI Basal cell proliferation in female SKH-1 mice treated with alpha- and beta-hydroxy acids SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE glycolic acid; proliferation; BrdU; SKH-1 hairless mice; epidermis ID GLYCOLIC ACID; LACTIC-ACID; EPIDERMAL PROLIFERATION; BARRIER FUNCTION; PHOTOAGED SKIN; CLINICAL-TRIAL; EXPRESSION AB alpha- and beta -Hydroxy acids are compounds that have been used extensively in cosmetic and dermatological formulations. Clinical and qualitative effects of alpha- and beta -hydroxy acids have been well characterized, but little is known about their mechanism of action or acute and chronic biochemical effects. In the present study, we examined the acute proliferative effects of glycolic and salicylic acids on cell proliferation in the epidermis of SKH-1 female mice, using BrdU incorporation as a marker of epidermal proliferation. In preliminary experiments, we observed an increase in the rate of proliferation after 3 days of treatment with 10% glycolic acid-containing cream and this was sustained throughout a 6.5-week (treatment 5 days/week) time course compared with untreated control animals. After each treatment with cream containing glycolic acid there was a wave of proliferation that was maximal 12 to 16 h (significant at p<0.05) after treatment, followed by a subsequent increase in epidermal thickness at 18 to 20 h (significant at p<0.05). The effects of the concentration and pH level of glycolic acid- and salicylic acid-containing creams on the rate of proliferation and increases in skin thickness in SKH-1 epidermis were also investigated. We observed a dose-dependent increase in epidermal proliferation of animals treated with either glycolic or salicylic acid. A similar time-dependent response was observed in the epidermal thickness in animals treated with salicylic acid, but not with glycolic acid. Differences in pH (3.5 or 4.0) had no significant effect on either epidermal proliferation or skin thickness. The data that we present here should be useful in characterizing not only the beneficial but also the adverse effects that occur following acute or chronic usage of a-hydroxy acids. (C) 2001 Academic Press. C1 US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. Pathol Associates Int, Jefferson, AR 72079 USA. US FDA, Ctr Food Safety & Appl Nutr, Off Cosmet & Colors, Washington, DC 20201 USA. US FDA, Ctr Devices & Radiol Hlth, Off Sci & Technol, Rockville, MD 20857 USA. RP Sams, RL (reprint author), US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, HFT-110,3900 NCTR Rd, Jefferson, AR 72079 USA. NR 30 TC 10 Z9 10 U1 0 U2 0 PU ACADEMIC PRESS INC 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 AUG 15 PY 2001 VL 175 IS 1 BP 76 EP 82 DI 10.1006/taap.2001.9232 PG 7 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 466EJ UT WOS:000170631300009 PM 11509029 ER PT J AU Amexis, G Fineschi, N Chumakov, K AF Amexis, G Fineschi, N Chumakov, K TI Correlation of genetic variability with safety of mumps vaccine Urabe AM9 strain SO VIROLOGY LA English DT Article DE nucleotide polymorphism; reversion; neurovirulence; vaccine production; quality control ID ORAL POLIOVIRUS VACCINE; HEMAGGLUTININ-NEURAMINIDASE GENE; ASEPTIC-MENINGITIS; NUCLEOTIDE-SEQUENCE; RUBELLA VACCINE; NEUROVIRULENCE TEST; SABIN-2 STRAIN; VIRUS STRAINS; MEASLES; STABILITY AB The Urabe AM9 strain of mumps vaccine live is known for its genetic instability and some vaccines derived from this strain were withdrawn from the market due to an excessive number of vaccine-associated parotitis and meningitis cases. To identify the molecular basis of this instability, we determined complete nucleotide sequences of several stocks of the Urabe strain used for vaccine production by different manufacturers and of two clinical Isolates from cases of vaccine-associated meningitis. In contrast to previously published studies relating the Lys(335) --> Glu mutation in the viral HN gene with neurovirulence of mumps virus, we could not confirm any association of this mutation with the safety of mumps vaccine. Each of the three vaccine stocks studied had its own characteristic profile of mutations that was identified by cDNA sequencing and quantitated by mutant analysis by PCR and restriction enzyme cleavage. Determination of the mutational profile of mumps vaccine lots could allow vaccine manufacturers to characterize seed viruses and monitor the consistency of vaccine production to prevent emergence of virulent revertants. C1 US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. Chiron SpA, Siena, Italy. RP Chumakov, K (reprint author), US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. NR 43 TC 26 Z9 26 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD AUG 15 PY 2001 VL 287 IS 1 BP 234 EP 241 DI 10.1006/viro.2001.1009 PG 8 WC Virology SC Virology GA 465TT UT WOS:000170606600024 PM 11504558 ER PT J AU Wilk, A Chmielewski, MK Grajkowski, A Phillips, LR Beaucage, SL AF Wilk, A Chmielewski, MK Grajkowski, A Phillips, LR Beaucage, SL TI The 4-oxopentyl group as a labile phosphate/thiophosphate protecting group for synthetic oligodeoxyribonucleotides SO TETRAHEDRON LETTERS LA English DT Article ID SULFUR-TRANSFER REAGENT; 3H-1,2-BENZODITHIOL-3-ONE 1,1-DIOXIDE; MONOMERS AB An efficient and economical method for the solid-phase synthesis of oligodeoxyribonucleotides and their phosphorothioate analogues is described. The method entails the use of the 4-oxopentyl group for phosphate thiophosphate protection. Post-synthesis removal of the protecting group is easily and rapidly achieved under mild conditions at ambient temperature using either pressurized gaseous amines or concentrated ammonium hydroxide. (C) 2001 Elsevier Science Ltd. All rights reserved. C1 US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. NCI, Frederick, MD 21701 USA. RP Beaucage, SL (reprint author), US FDA, Ctr Biol Evaluat & Res, 8800 Rockville Pike, Bethesda, MD 20892 USA. NR 12 TC 22 Z9 22 U1 1 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0040-4039 J9 TETRAHEDRON LETT JI Tetrahedron Lett. PD AUG 13 PY 2001 VL 42 IS 33 BP 5635 EP 5639 DI 10.1016/S0040-4039(01)01094-2 PG 5 WC Chemistry, Organic SC Chemistry GA 460LU UT WOS:000170309700012 ER PT J AU Volety, AK McCarthy, SA Tall, BD Curtis, SK Fisher, WS Genthner, FJ AF Volety, AK McCarthy, SA Tall, BD Curtis, SK Fisher, WS Genthner, FJ TI Responses of oyster Crassostrea virginica hemocytes to environmental and clinical isolates of Vibrio parahaemolyticus SO AQUATIC MICROBIAL ECOLOGY LA English DT Article DE oyster; Vibrio parahaemolyticus; hemocytes; capsule ID THERMOSTABLE DIRECT HEMOLYSIN; THERMOLABILE HEMOLYSIN; ESCHERICHIA-COLI; COAST OYSTERS; VULNIFICUS; DEPURATION; VIRULENCE; PURIFICATION; ASSOCIATION; BACTERIA AB Ingestion of bacteria by oysters Crassostrea virginica and bactericidal activity of oyster hemocytes were studied using 4 environmental isolates (shellfish) and 3 clinical isolates (fecal) of Vibrio parahaemolyticus, Clinical isolates (2030, 2062, 2107) were obtained from the feces of patients with gastroenteritis who became ill during the 1998 food poisoning outbreak traced to consumption of raw oysters from Galveston Bay, Texas. This outbreak was the first reported occurrence in the United States of the virulent serotype O3:K6, Environmental isolates were from oysters (1094, 1100), crab (1163) and sardines (ATCC 17802). All isolates possessed the thermolabile direct hemolysin (tlh) gene, whereas only the clinical isolates possessed the thermostable direct hemolysin (tdh) gene, a virulence determinant. On average, environmental isolates were more susceptible than clinical isolates to killing by oyster hemocytes, as determined by an in vitro dye reduction assay. Isolate 2062 was the most susceptible of the clinical isolates; it lacked identifiable capsular material present in the other clinical isolates and displayed the most diffuse colony morphology on nutrient agar plates. When oysters were exposed in vivo to mixtures of a clinical (2030) and an environmental (1163) isolate, more clinical than environmental isolates were found in the tissues and hemolymph. C1 US EPA, Natl Hlth & Environm Effects Res Lab, Gulf Ecol Div, Gulf Breeze, FL 32561 USA. Florida Gulf Coast Univ, Ft Myers, FL 33965 USA. US FDA, Ctr Food Safety & Appl Nutr, Dauphin Isl, AL 36528 USA. US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. RP Genthner, FJ (reprint author), US EPA, Natl Hlth & Environm Effects Res Lab, Gulf Ecol Div, Gulf Breeze, FL 32561 USA. EM genthner.fred@epa.gov OI Tall, Ben/0000-0003-0399-3629 NR 55 TC 5 Z9 5 U1 2 U2 4 PU INTER-RESEARCH PI OLDENDORF LUHE PA NORDBUNTE 23, D-21385 OLDENDORF LUHE, GERMANY SN 0948-3055 EI 1616-1564 J9 AQUAT MICROB ECOL JI Aquat. Microb. Ecol. PD AUG 10 PY 2001 VL 25 IS 1 BP 11 EP 20 DI 10.3354/ame025011 PG 10 WC Ecology; Marine & Freshwater Biology; Microbiology SC Environmental Sciences & Ecology; Marine & Freshwater Biology; Microbiology GA 469LG UT WOS:000170816500002 ER PT J AU Ye, XM Rountree, R Scallet, A Meeker, HC Carp, RI AF Ye, XM Rountree, R Scallet, A Meeker, HC Carp, RI TI Evaluation of neurodegeneration in scrapie-infected animals by selective methods that detect cellular degeneration SO BRAIN RESEARCH LA English DT Article DE silver stain; scrapie; degeneration; neuropathology; neurotoxin ID NEURONAL DEGENERATION; MURINE SCRAPIE; APOPTOSIS; BRAINS; MICE; LOCALIZATION; IBOGAINE; MOUSE; RAT AB Scrapie is a fatal neurodegenerative disease of sheep and goats. The precise details of neuronal and neurite degeneration in scrapie-infected animals remain unknown. Using specific silver staining methods, we compared the neurodegeneration caused by treatment of rats with kainic acid (KA) or ibogaine (IBO) to the neuropathology observed in mice infected with the C602 strain of scrapie. As reported previously, KA resulted in extensive silver labeling of neurons, especially in the cortex, putamen and hippocampus. IBO silver labeling was observed only in small clusters of Purkinje neurons in the paravermal region of the cerebellum. However, in scrapie-infected mice, a few silver stained neurons (differing from the dark degenerating neurons observed following neurotoxic exposure) were found in layer II of cortex, cingulate cortex, zona incerta, thalamus and hypothalamus. Some silver grains were observed in glial-like cells, especially those in the paraventricular region. Degenerating axons were positive for silver staining and were found in the cortex, cingulate cortex, corpus callosum, habenulae, septum, fornix, thalamus, caudate putamen and a few in fasciculus retroflexus and substantia nigra. Our results suggest that the limbic system is one of the important loci for the neurodegenerative effect of at least some scrapie strains. (C) 2001 Elsevier Science B.V. All rights reserved. C1 New York State Inst Basic Res Dev Disabil, Staten Isl, NY 10314 USA. US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. RP Ye, XM (reprint author), New York State Inst Basic Res Dev Disabil, 1050 Forest Hill Rd, Staten Isl, NY 10314 USA. NR 20 TC 2 Z9 2 U1 0 U2 0 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 10 PY 2001 VL 910 IS 1-2 BP 175 EP 178 DI 10.1016/S0006-8993(01)02616-6 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 467CQ UT WOS:000170683300020 PM 11489267 ER PT J AU Galson, S Kweder, S Houn, F Raczkowski, V Honig, PK AF Galson, S Kweder, S Houn, F Raczkowski, V Honig, PK TI The FDA and The Lancet: an exchange SO LANCET LA English DT Letter C1 US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Galson, S (reprint author), US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. NR 1 TC 3 Z9 3 U1 0 U2 1 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD AUG 4 PY 2001 VL 358 IS 9279 BP 415 EP 415 DI 10.1016/S0140-6736(01)05560-X PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 459DE UT WOS:000170235100038 PM 11503619 ER PT J AU Hirschfeld, S Kieffer, L McGuinn, WD Rothmann, M Timmer, WC AF Hirschfeld, S Kieffer, L McGuinn, WD Rothmann, M Timmer, WC TI The FDA and The Lancet: an exchange SO LANCET LA English DT Letter C1 US FDA, Ctr Drug Evaluat & Res, Div Oncol Drug Prod, Rockville, MD 20852 USA. RP Hirschfeld, S (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Oncol Drug Prod, 1451 Rockville Pike,HFD-150, Rockville, MD 20852 USA. RI Hirschfeld, Steven/E-2987-2016 OI Hirschfeld, Steven/0000-0003-0627-7249 NR 1 TC 1 Z9 1 U1 0 U2 0 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD AUG 4 PY 2001 VL 358 IS 9279 BP 415 EP 416 DI 10.1016/S0140-6736(01)05561-1 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 459DE UT WOS:000170235100039 PM 11503618 ER PT J AU Malozowski, S AF Malozowski, S TI The FDA and The Lancet: an exchange SO LANCET LA English DT Letter C1 US FDA, Ctr Drug Evaluat & Res, Div Metab & Endocrine Drug Prod, US Dept HHS, Rockville, MD 20857 USA. RP Malozowski, S (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Metab & Endocrine Drug Prod, US Dept HHS, HFD-510, Rockville, MD 20857 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD AUG 4 PY 2001 VL 358 IS 9279 BP 416 EP 417 DI 10.1016/S0140-6736(01)05562-3 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 459DE UT WOS:000170235100040 PM 11503620 ER PT J AU Adams, MA AF Adams, MA TI FDA perspective on the food contact notification program. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA, Ctr Food Safety & Appl Nutr, Chem & Exposure Assessment Team, Washington, DC 20204 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG PY 2001 VL 222 MA 14-CHAL BP U305 EP U305 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 467ET UT WOS:000170690001565 ER PT J AU Bailey, J AF Bailey, J TI Role of research in ensuring a safe and healthy food supply. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA, Ctr Food Safety & Appl Nutr, Off Appl Res & Safety Assessment, Washington, DC 20204 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG PY 2001 VL 222 MA 5-CSCI BP U434 EP U434 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 467EU UT WOS:000170690102402 ER PT J AU da Costa, GG Marques, MM Freeman, JP Beland, FA AF da Costa, GG Marques, MM Freeman, JP Beland, FA TI alpha-hydroxy-N,N-didesmethyltamoxifen, a proximate metabolite in the metabolic activation of tamoxifen to a carcinogen? SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Univ Tecn Lisboa, Ctr Quim Estrutural, Inst Super Tecn, P-1049 Lisbon, Portugal. Natl Ctr Toxicol Res, Div Chem, Jefferson, AR USA. Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. EM ic025@alfa.ist.utl.pt; 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 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 AUG PY 2001 VL 222 MA 73-TOXI BP U299 EP U299 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 467ET UT WOS:000170690001532 ER PT J AU Doerge, DR Delclos, KB Newbold, RR AF Doerge, DR Delclos, KB Newbold, RR TI Genistein distribution in target tissues from dietary exposure in adult rats and evidence for modulation of endocrine function. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. NIEHS, Toxicol Lab, Dev Endocrinol Sect, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG PY 2001 VL 222 MA 118-AGFD BP U44 EP U44 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 467ET UT WOS:000170690000118 ER PT J AU Du, X Shrake, A AF Du, X Shrake, A TI Development of a procedure to create an FDA alpha-1-proteinase inhibitor (human) [A1-PI] reference standard. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA, Ctr Biol Evaluat & Res, Div Hematol, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG PY 2001 VL 222 MA 45-ANYL BP U85 EP U86 PN 1 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 467ET UT WOS:000170690000347 ER PT J AU Frasch, CE Lee, CH AF Frasch, CE Lee, CH TI Use of physical and chemical methods to assess the stability of bacterial polysaccharide and polysaccharide-protein conjugate vaccines. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA, Ctr Biolog Evaluat & Res, Div Bacterial Prod, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG PY 2001 VL 222 MA 51-CARB BP U169 EP U169 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 467ET UT WOS:000170690000819 ER PT J AU Hutter, JC Long, MC Schroeder, LW AF Hutter, JC Long, MC Schroeder, LW TI Modeling the degradation of common hemodialysis membrane materials. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG PY 2001 VL 222 MA 169-PMSE BP U366 EP U366 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 467EU UT WOS:000170690102040 ER PT J AU McNeal, TP Diachenko, GW AF McNeal, TP Diachenko, GW TI Determination of volatile and semi-volatile industrial chemicals in foods and food packaging. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA, Ctr Food Safety & Appl Nutr, Div Prod Manufacture & Use, Washington, DC 20204 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG PY 2001 VL 222 MA 106-ENVR BP U436 EP U436 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 467ET UT WOS:000170690002227 ER PT J AU Paul, DW Snellings, SL AF Paul, DW Snellings, SL TI Development of an acoustic wave biosensor for human low-density lipoprotein particles. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Univ Arkansas, Dept Chem & Biochem, Fayetteville, AR 72701 USA. US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG PY 2001 VL 222 MA 46-ANYL BP U86 EP U86 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 467ET UT WOS:000170690000348 ER PT J AU Petigara, BR Weisz, A AF Petigara, BR Weisz, A TI Quantitative analysis of components of the color additive D&C Orange No. 5 using thin-layer chromatography and video densitometry. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG PY 2001 VL 222 MA 122-ANYL BP U98 EP U98 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 467ET UT WOS:000170690000424 ER PT J AU Rybak, ME Calvey, EM Harnly, JM AF Rybak, ME Calvey, EM Harnly, JM TI Isolation and determination of organosulfur compounds in allium vegetables using supercritical fluid extraction. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 USDA, Beltsville Human Nutr Res Ctr, Food Composit Lab, Beltsville, MD 20705 USA. US FDA, Ctr Food Safety & Appl Nutr, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG PY 2001 VL 222 MA 70-AGFD BP U35 EP U36 PN 1 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 467ET UT WOS:000170690000070 ER PT J AU Schenck, FJ Vega, V Lehotay, SJ AF Schenck, FJ Vega, V Lehotay, SJ TI Optimizing solid phase extraction (SPE) cleanup for the GC analysis of pesticides in foods at low part per billion levels. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA, SE Reg Lab, Atlanta, GA 30309 USA. USDA ARS, Eastern Reg Res Ctr, Washington, DC 20250 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG PY 2001 VL 222 MA 35-AGRO BP U58 EP U58 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 467ET UT WOS:000170690000193 ER PT J AU Taub, IA Morehouse, KM Buchala, R Sevilla, MD AF Taub, IA Morehouse, KM Buchala, R Sevilla, MD TI Food irradiation: From basic chemistry to practical applications. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 USA, Natick Soldier Ctr, Natick, MA 01760 USA. US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. Oakland Univ, Dept Chem, Rochester, MN USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG PY 2001 VL 222 MA 401-CHED BP U252 EP U252 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 467ET UT WOS:000170690001288 ER PT J AU Weisz, A Murphy, CM Mazzola, EP Ito, Y AF Weisz, A Murphy, CM Mazzola, EP Ito, Y TI Preparation of starting materials for components of the color additive D&C Yellow No. 10 (Quinoline Yellow). SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG PY 2001 VL 222 MA 83-AGFD BP U37 EP U38 PN 1 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 467ET UT WOS:000170690000083 ER PT J AU Yan, J Yang, YC Williams, L Xia, QS Doerge, DR Chou, MW Fu, PP AF Yan, J Yang, YC Williams, L Xia, QS Doerge, DR Chou, MW Fu, PP TI Development of an alternative strategy for detection of carcinogen-modified DNA adducts in vitro and in vivo by P-32-postlabeling/HPLC. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 1 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 AUG PY 2001 VL 222 MA 47-ANYL BP U86 EP U86 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 467ET UT WOS:000170690000349 ER PT J AU Yu, HT Dong, SM Fu, PP Shirsat, RN Hwang, HM Leszczynski, J AF Yu, HT Dong, SM Fu, PP Shirsat, RN Hwang, HM Leszczynski, J TI UVA light-induced DNA cleavage by isomeric methylbenz[a]anthracenes. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Jackson State Univ, Jackson, MS 39217 USA. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 1 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 AUG PY 2001 VL 222 MA 66-TOXI BP U298 EP U298 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 467ET UT WOS:000170690001525 ER PT J AU Lathers, CM Mukai, C Smith, CM Schraeder, PL AF Lathers, CM Mukai, C Smith, CM Schraeder, PL TI A new goldfish model to evaluate pharmacokinetic and pharmacodynamic effects of drugs used for motion sickness in different gravity loads SO ACTA ASTRONAUTICA LA English DT Article; Proceedings Paper CT 13th IAA Humans in Space Symposium CY MAY 21-25, 2000 CL SANTORINI, GREECE SP Greek Aerosp Med Assoc ID VESTIBULAR COMPENSATION; VALVULA-CEREBELLI; SPACE-FLIGHT; WEIGHTLESSNESS; BEHAVIOR; RECOVERY; CARP AB This paper proposes a new goldfish model to predict pharmacodynamic/pharmacokinetic effects of drugs used to treat motion sickness administered in differing gravity loads. The assumption of these experiments is that the vestibular system is dominant in producing motion sickness and that the visual system is secondary or of small import in the production of motion sickness. Studies will evaluate the parameter of gravity and the contribution of vision to the role of the neurovestibular system in the initiation of motion sickness with and without pharmacologic agents. Promethazine will be studied first. A comparison of data obtained in different groups of goldfish will be done (normal vs. acutely and chronically bilaterally blinded vs. sham operated). Some fish will be bilaterally blinded 10 months prior to initiation of the experiment (designated the chronically bilaterally blinded group of goldfish) to evaluate the neuroplasticity of the nervous system and the associated return of neurovestibular function. Data will be obtained under differing gravity loads with and without a pharmacological agent for motion sickness. Experiments will differentiate pharmacological effects on vision vs. neurovestibular input to motion sickness. Comparison of data obtained in the normal fish and in acutely and chronically bilaterally blinded fish with those obtained in fish with intact and denervated otoliths will differentiate if the visual or neurovestibular system is dominant in response to altered gravity and/or drugs. Experiments will contribute to validation of the goldfish as a model for humans since plasticity of the central nervous system allows astronauts to adapt to the altered visual stimulus conditions of 0-g. Space motion sickness may occur until such an adaptation is achieved. (C) 2001 Elsevier Science Ltd. All rights reserved. C1 US FDA, Ctr Vet Med, Off New Anim Druv Evaluat, Rockville, MD 20857 USA. RP Lathers, CM (reprint author), US FDA, Ctr Vet Med, Off New Anim Druv Evaluat, Rockville, MD 20857 USA. NR 44 TC 5 Z9 7 U1 0 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0094-5765 J9 ACTA ASTRONAUT JI Acta Astronaut. PD AUG-NOV PY 2001 VL 49 IS 3-10 BP 419 EP 440 DI 10.1016/S0094-5765(01)00117-5 PG 22 WC Engineering, Aerospace SC Engineering GA 468HK UT WOS:000170751900031 PM 11669128 ER PT J AU Duffy, PH Seng, JE Lewis, SM Mayhugh, MA Aidoo, A Hattan, DG Casciano, DA Feuers, RJ AF Duffy, PH Seng, JE Lewis, SM Mayhugh, MA Aidoo, A Hattan, DG Casciano, DA Feuers, RJ TI The effects of different levels of dietary restriction on aging and survival in the Sprague-Dawley rat: Implications for chronic studies SO AGING-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE aging; chronic; dietary restriction; survival; rat ID CHRONIC CALORIC RESTRICTION; FISCHER-344 RATS; MAMMARY-TUMORS; PATHOLOGY; TOXICITY; VARIABILITY; VARIABLES; MICE AB A study was undertaken to determine the effects of incremental levels of dietary restriction (DR) in rats. Survival, growth, reproductive, and dietary intake (DI) variables were monitored in a chronic study in which male Sprague Dawley (SD) rats (NCTR colony) were fed their ration ad libitum (AL), or DR. The main objectives were to determine if low levels of DR could be used to increase the survival rate of SD rats in the chronic bioassay, and to identify the survival characteristics of a long-lived SD rat strain (NCTR colony). The average life span of AL rats was 115 months. At 104 weeks on study (110 weeks of age), the survival rate for the AL and 10%, 25%, and 40% DR groups was 63.4, 87.5, 87.5, and 97.5%, respectively. The largest increase in survival (24.1%) occurred between AL and 10% DR, indicating that very low levels of DR have a significant effect on survival. Whole-body, liver, prostate, and epididymis weights and body length were decreased by DR, whereas brain weight, testicular weight, and skull length were not altered by DR. Rats from the NCTR colony were found to be ideal for chronic studies because they are much longer-lived than other SD stocks. Although the 104-week survival rate for these SD, non-obese AL rats exceeds the FDA's "Redbook" survival guideline (> 50%) for chronic bioassays, the use of DR is advocated because it reduces individual variability in body weight. (C) 2001, Editrice Kurtis. C1 US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. RP Duffy, PH (reprint author), US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. NR 29 TC 42 Z9 42 U1 0 U2 1 PU EDITRICE KURTIS S R L PI MILAN PA VIA LUIGI ZOJA 30, 20153 MILAN, ITALY SN 0394-9532 J9 AGING-CLIN EXP RES JI Aging-Clin. Exp. Res. PD AUG PY 2001 VL 13 IS 4 BP 263 EP 272 PG 10 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 478JM UT WOS:000171343300002 PM 11695495 ER PT J AU Hassold, TJ Burrage, LC Chan, ER Judis, LM Schwartz, S James, SJ Jacobs, PA Thomas, NS AF Hassold, TJ Burrage, LC Chan, ER Judis, LM Schwartz, S James, SJ Jacobs, PA Thomas, NS TI Maternal folate polymorphisms and the etiology of human nondisjunction SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID METHYLENETETRAHYDROFOLATE REDUCTASE GENE; ABERRANT RECOMBINATION; DOWN-SYNDROME; RISK-FACTORS; ORIGIN; TRISOMY-18; METABOLISM; MUTATION AB Attempts to identify genetic contributors to human meiotic nondisjunction have met with little, if any, success. Thus, recent reports linking Down syndrome to maternal polymorphisms at either of two folate metabolism enzymes, methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR), have generated considerable interest. In the present report, we asked whether variation at MTHFR (677C-->T) or MTRR (66A-->G) might be associated with human trisomies other than trisomy 21. We analyzed maternal polymorphisms at MTHFR and MTRR in 93 cases of sex-chromosome trisomy, 44 cases of trisomy 18, and 158 cases of autosomal trisomies 2, 7, 10, 13, 14, 15, 16, 18, or 22, and compared the distributions of genotypes to those of control populations. We observed a significant increase in the MTHFR polymorphism in mothers of trisomy 18 conceptuses but were unable to identify any other significant associations. Overall, our observations suggest that, at least for the sex chromosomes and for a combined set of autosomal trisomies, polymorphisms in the folate pathway are not a significant contributor to human meiotic nondisjunction. C1 Case Western Reserve Univ, Dept Genet, Cleveland, OH 44106 USA. Case Western Reserve Univ, Ctr Human Genet, Cleveland, OH 44106 USA. Univ Hosp Cleveland, Cleveland, OH 44106 USA. US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, Jefferson, AR USA. Salisbury Dist Hosp, Wessex Reg Genet Lab, Salisbury, Wilts, England. RP Hassold, TJ (reprint author), Case Western Reserve Univ, Dept Genet, 10900 Euclid Ave, Cleveland, OH 44106 USA. FU NICHD NIH HHS [R37 HD021341, HD21341, R01 HD021341] NR 19 TC 38 Z9 42 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD AUG PY 2001 VL 69 IS 2 BP 434 EP 439 DI 10.1086/321971 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 456XN UT WOS:000170108200018 PM 11443546 ER PT J AU Sorof, JM Urbina, EM Cunningham, RJ Hogg, RJ Moxey-Mims, M Eissa, MA Rolf, C AF Sorof, JM Urbina, EM Cunningham, RJ Hogg, RJ Moxey-Mims, M Eissa, MA Rolf, C CA Ziac Pediat Hypertension Study Grp TI Screening for eligibility in the study of antihypertensive medication in children: Experience from the Ziac Pediatric Hypertension Study SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Article DE hypertension; child; clinical trials ID BLOOD-PRESSURE; ADOLESCENTS; CHILDHOOD; TRIALS AB Background: The FDA Modernization Act has resulted in an increase in pediatric trials of antihypertensive medications. As experience is limited in children to guide the planning of these studies, we reviewed data from the Ziac Pediatric Hypertension Study to determine patterns of early study termination to help future studies. Methods: For inclusion., subjects aged 6 to 17 years were required to have an average systolic blood pressure (SBP) or diastolic blood pressure (DBP) above the 95th percentile at the last of three visits during 2 weeks of single-blind placebo screening. Early study termination was defined as early termination for any reason. Screening termination was defined as normalization of blood pressure (BP) during the placebo screening phase. Results: Early study termination rate was 27% (38 of 140 subjects). The most common reason was screening termination due to normalization of BP, accounting for 63% of all early study terminations. Among screening termination subjects who completed three screening visits, SBP was higher (P < .001) at visit 1 (129 +/- 8 mm Hg) than at visit 2 (123 +/- 7 mm Hg) or visit 3 (121 +/- 8 mm Hg), but did not differ between visits 2 and 3. Screening termination occurred in 15% with isolated SBP hypertension, and 21%. with isolated DBP hypertension. At randomization. 83% had SBP hypertension and 53% had DBP hypertension. Conclusions. These data suggest that SBP hypertension should be part of inclusion criteria to increase enrollment and reduce the rate of screening termination, and that 1-week placebo screening is necessary and sufficient to minimize inclusion of transiently hypertensive subjects. (C) 2001 American Journal of Hypertension, Ltd. C1 Univ Texas, Sch Med, Div Pediat Nephrol & Hypertens, Houston, TX 77030 USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Columbia Hosp, Dallas, TX USA. US FDA, Rockville, MD 20857 USA. Procter & Gamble Pharmaceut, Cincinnati, OH USA. Tulane Univ, New Orleans, LA USA. RP Sorof, JM (reprint author), Univ Texas, Sch Med, Div Pediat Nephrol & Hypertens, 6431 Fannin St Rm 3-124, Houston, TX 77030 USA. RI Cunningham, Robert/G-2297-2011 NR 15 TC 22 Z9 23 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0895-7061 J9 AM J HYPERTENS JI Am. J. Hypertens. PD AUG PY 2001 VL 14 IS 8 BP 783 EP 787 DI 10.1016/S0895-7061(01)01295-X PN 1 PG 5 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 458JK UT WOS:000170191100008 PM 11497194 ER PT J AU Khan, AA Wang, RF Cao, WW Doerge, DR Wennerstrom, D Cerniglia, CE AF Khan, AA Wang, RF Cao, WW Doerge, DR Wennerstrom, D Cerniglia, CE TI Molecular cloning, nucleotide sequence, and expression of genes encoding a polcyclic aromatic ring dioxygenase from Mycobacterium sp strain PYR-1 SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID PSEUDOMONAS-PUTIDA; HYDROCARBON DEGRADATION; NAPHTHALENE DIOXYGENASE; DEGRADING BACTERIUM; ESCHERICHIA-COLI; IDENTIFICATION; PYRENE; BIODEGRADATION; PHENANTHRENE; FLUORANTHENE AB Mycobacterium sp. strain PYR-1 degrades high-molecular-weight polycyclic hydrocarbons (PAHs) primarily through the introduction of both atoms of molecular oxygen by a dioxygenase. To clone the dioxygenase genes involved in PAH degradation, two-dimensional (2D) gel electrophoresis of PAH-induced proteins from cultures of Mycobacterium sp. strain PYR-1 was used to detect proteins that increased after phenanthrene, dibenzothiophene, and pyrene exposure. Comparison of proteins from induced and uninduced cultures on 2D gels indicated that at least six major proteins were expressed (105, 81, 52, 50, 43, and 13 kDa). The N-terminal sequence of the 50-kDa protein was similar to those of other dioxygenases. A digoxigenin-labeled oligonucleotide probe designed from this protein sequence was used to screen dioxygenase-positive clones from a genomic library of Mycobacterium sp. strain PYR-1. Three clones, each containing a 5,288-bp DNA insert with three genes of the dioxygenase system, were obtained. The genes in the DNA insert, from the 5' to the 3' direction, were a dehydrogenase, the dioxygenase small (beta)-subunit, and the dioxygenase large (a)-subunit genes, arranged in a sequence different from those of genes encoding other bacterial dioxygenase systems. Phylogenetic analysis showed that the large a subunit did not cluster with most of the known a-subunit sequences but rather with three newly described alpha subunits of dioxygenases from Rhodococcus spp. and Nocardioides spp. The genes from Mycobacterium sp. strain PYR-1 were subcloned and overexpressed in Escherichia coli with the pBAD/ThioFusion system. The functionality of the genes for PAH degradation was confirmed in a phagemid clone containing all three genes, as well as in plasmid subelones containing the two genes encoding the dioxygenase subunits. C1 US FDA, Natl Ctr Toxicol Res, Food & Drug Adm, Div Microbiol, Jefferson, AR 72079 USA. US FDA, Natl Ctr Toxicol Res, Food & Drug Adm, Div Biochem Toxicol, Jefferson, AR 72079 USA. Univ Arkansas Med Sci, Dept Microbiol & Immunol, Little Rock, AR 72205 USA. RP Cerniglia, CE (reprint author), US FDA, Natl Ctr Toxicol Res, Food & Drug Adm, Div Microbiol, Jefferson, AR 72079 USA. NR 33 TC 124 Z9 137 U1 3 U2 18 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 2001 VL 67 IS 8 BP 3577 EP 3585 DI 10.1128/AEM.67.8.3577-3585.2001 PG 9 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 460FP UT WOS:000170297800034 PM 11472934 ER PT J AU Kothary, MH Delston, RB Curtis, SK McCardell, BA Tall, BD AF Kothary, MH Delston, RB Curtis, SK McCardell, BA Tall, BD TI Purification and characterization of a vulnificolysin-like cytolysin produced by Vibrio tubiashii SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID EL-TOR HEMOLYSIN; CHOLERAE; TOXIN AB An extracellular cytolysin from Vibrio tubiashii was purified by sequential hydrophobic interaction chromatography with phenyl-Sepharose CL-4B and gel filtration with Sephacryl S-200. This protein is sensitive to heat and proteases, is inhibited by cholesterol, and has a molecular weight of 59,000 and an isoelectric point of 5.3. In addition to lysing various erythrocytes, it is cytolytic and/or cytotoxic to Chinese hamster ovary cells, Caco-2 cells, and Atlantic menhaden liver cells in tissue culture. Lysis of erythrocytes occurs by a multihit process that is dependent on temperature and pH. Twelve of the first 17 N-terminal amino acid residues (Asp-Asp-Tyr-Val-Pro-Val-Val-Glu-Lys-Val-Tyr-Tyr-Ile-Thr-Ser-Ser-Lys) are identical to those of the Vibrio vulnificus cytolysin. C1 US FDA, Ctr Food Safety & Appl Nutr, Div Virulence Assessment HFS 327, Washington, DC 20204 USA. US FDA, Ctr Food Safety & Appl Nutr, Div Microbiol Studies, Washington, DC 20204 USA. RP Kothary, MH (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Div Virulence Assessment HFS 327, 200 C St SW, Washington, DC 20204 USA. OI Tall, Ben/0000-0003-0399-3629 NR 28 TC 21 Z9 22 U1 1 U2 1 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 2001 VL 67 IS 8 BP 3707 EP 3711 DI 10.1128/AEM.67.8.3707-3711.2001 PG 5 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 460FP UT WOS:000170297800051 PM 11472951 ER PT J AU Cha, CJ AF Cha, CJ TI Biological production of optically active muconolactones by Rhodococcus rhodochrous SO APPLIED MICROBIOLOGY AND BIOTECHNOLOGY LA English DT Article ID MODIFIED 3-OXOADIPATE PATHWAY; 4-METHYLMUCONOLACTONE; PSEUDOMONAS; METABOLISM; 3-METHYLMUCONOLACTONE; 4-METHYLCATECHOL; ACID AB Optically active (-)-3-methylmuconolactone was biologically produced using a mutant strain of Rhodococcus rhodochrous N75 that is capable of metabolizing 4-methylcatechol via a modified ortho-cleavage pathway. The mutant strain (CJ30) was prepared by mutagenesis using N-methyl-N ' -nitro-N-nitrosoguanidine and found to be blocked in the degradation of 3-methyl-muconolactone. Cells of the mutant CJ30, which had been previously grown on yeast extract and induced with p-toluate, transformed p-toluate (11.5 mM) to optically active (-)-3-methylmuconolactone with a yield of 53%. The structure of 3-methylmuconolactone was confirmed by NMR spectroscopy and mass spectrometry. Cell-free extracts of R. rhodochrous N75 also transformed a range of 4-alkylcatechols, such as 4-ethylcatechol, 4-iso-propylcatechol, and 4-tert-butylcatechol, to the corresponding 4-alkyl-substituted muconolactones. C1 Univ Cambridge, Inst Biotechnol, Cambridge CB2 1QT, England. RP Cha, CJ (reprint author), US FDA, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. NR 13 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0175-7598 J9 APPL MICROBIOL BIOT JI Appl. Microbiol. Biotechnol. PD AUG PY 2001 VL 56 IS 3-4 BP 453 EP 457 PG 5 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 465UP UT WOS:000170608600024 PM 11549019 ER PT J AU Parshikov, IA Heinze, TM Moody, JD Freeman, JP Williams, AJ Sutherland, JB AF Parshikov, IA Heinze, TM Moody, JD Freeman, JP Williams, AJ Sutherland, JB TI The fungus Pestalotiopsis guepini as a model for biotransformation of ciprofloxacin and norfloxacin SO APPLIED MICROBIOLOGY AND BIOTECHNOLOGY LA English DT Article ID FLUOROQUINOLONE ENROFLOXACIN; GLOEOPHYLLUM-STRIATUM; MICROBIAL MODELS; DEGRADATION; METABOLITES; TRANSFORMATION; IDENTIFICATION AB The metabolism of the fluoroquinolone drugs ciprofloxacin and norfloxacin by Pestalotiopsis guepini strain P-8 was investigated. Cultures were grown at 28 degreesC in sucrose/peptone broth for 18 days after dosing with ciprofloxacin (300 muM) or norfloxacin (313 muM). Four major metabolites were produced from each drug; and these were purified by high-performance liquid chromatography and identified by mass spectrometry and proton nuclear magnetic resonance spectroscopy. Ciprofloxacin metabolites included N-acetylciprofloxacin (52.0%), desethylene-N-acetylciprofloxacin (9.2%), N-formylciprofloxacin (4.2%), and 7-amino-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid (2.3%). Norfloxacin metabolites included N-acetylnorfloxacin (55.4%), desethylene-N-acetylnorfloxacin (8.8%), N-formylnorfloxacin (3.6%), and 7-amino-1-ethyl-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid (2.1%). N-Formylciprofloxacin and the four transformation products from norfloxacin are all known to be mammalian metabolites. 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 Sutherland, JB (reprint author), US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. OI Parshikov, Igor/0000-0003-1466-1128 NR 19 TC 40 Z9 40 U1 4 U2 15 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0175-7598 J9 APPL MICROBIOL BIOT JI Appl. Microbiol. Biotechnol. PD AUG PY 2001 VL 56 IS 3-4 BP 474 EP 477 PG 4 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 465UP UT WOS:000170608600027 PM 11549022 ER PT J AU Wysowski, DK Beitz, J AF Wysowski, DK Beitz, J TI Methodological limitations of the study "isotretinoin use and risk of depression, psychotic symptoms, suicide, and attempted suicide" SO ARCHIVES OF DERMATOLOGY LA English DT Letter C1 US FDA, Off Postmkt Drug Risk Assessment, DDREI, Rockville, MD 20857 USA. RP Wysowski, DK (reprint author), US FDA, Off Postmkt Drug Risk Assessment, DDREI, HFD-430,Parklawn Bldg,Room 15B-08, Rockville, MD 20857 USA. NR 6 TC 12 Z9 12 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD AUG PY 2001 VL 137 IS 8 BP 1102 EP 1102 PG 1 WC Dermatology SC Dermatology GA 461MD UT WOS:000170367300028 PM 11493109 ER PT J AU Chen, ZG Eggerman, TL Patterson, AP AF Chen, ZG Eggerman, TL Patterson, AP TI Phosphorylation is a regulatory mechanism in apolipoprotein B mRNA editing SO BIOCHEMICAL JOURNAL LA English DT Article DE APOBEC-1; kinase; mutation; quantification ID PROTEIN-KINASE-C; MESSENGER-RNA; CATALYTIC SUBUNIT; MOLECULAR-CLONING; RAT-LIVER; SUBCELLULAR-LOCALIZATION; ETHANOL ALTERS; ENZYME-COMPLEX; GROWTH-HORMONE; APOBEC-1 AB The editing of apolipoprotein B (apoB) mRNA is under tissue-specific, developmental and metabolic regulation. We found that multiple protein kinase inhibitors or activators increased apoB mRNA editing up to 2.5-fold in Caco-2 cells and 3-8-fold in McA7777 and FAO rat cells respectively. The phosphorylation-agent-induced modulation is independent of the apolipoprotein B editing catalytic subunit 1 (APOBEC-1) and of apoB mRNA expression levels, indicating the involvement of a protein modification, such as phosphorylation, regulating the cellular editing of apoB mRNA. Transient expression of protein kinase C-theta more than doubled apoB mRNA editing in FAO cells. Chronic exposure to ethanol, a treatment known to increase the expression of protein kinases and to change protein phosphorylation status, increased apoB mRNA editing in FAO cells up to 2.5-fold without increasing the mRNA abundance of APOBEC-1. The elimination of potential phosphorylation sites 47 and 72 of human APOBEC-1 decreased its activity to approx. one-eighth of control levels by a Ser(47) --> Ala mutation, but more than doubled the activity by a Ser(72) --> Ala mutation. The activity modulation was reversed by a Ser Asp mutation at sites 47 and 72, which introduced a phosphorylation-like carbonic acid group. Both human APOBEC-1 dephosphorylated by alkaline phosphase and the Ser(47),(72)-to-alanine double mutant protein demonstrated a shifted isoelectric focusing pattern compared with the wild type, indicating phosphorylation at these sites. Taken together, these results suggest that phosphorylation might be an important mechanism in the regulation of apoB mRNA editing. C1 NHLBI, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Bethesda, MD 20892 USA. RP Patterson, AP (reprint author), NHLBI, NIH, 6000 Execut Blvd,Suite 302, Bethesda, MD 20892 USA. NR 64 TC 12 Z9 13 U1 0 U2 0 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON W1N 3AJ, ENGLAND SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD AUG 1 PY 2001 VL 357 BP 661 EP 672 DI 10.1042/0264-6021:3570661 PN 3 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 462DQ UT WOS:000170405800006 PM 11463337 ER PT J AU da Costa, GG McDaniel-Hamilton, LP Heflich, RH Marques, MM Beland, FA AF da Costa, GG McDaniel-Hamilton, LP Heflich, RH Marques, MM Beland, FA TI DNA adduct formation and mutant induction in Sprague-Dawley rats treated with tamoxifen and its derivatives SO CARCINOGENESIS LA English DT Article ID BREAST-CANCER PATIENTS; ETHYL-N-NITROSOUREA; ALPHA-HYDROXYTAMOXIFEN; METABOLIC-ACTIVATION; IN-VIVO; HYDROXYSTEROID SULFOTRANSFERASE; ENDOMETRIAL SAMPLES; CHEMICAL ACTIVATION; FISCHER-344 RATS; LIVER CARCINOGEN AB The non-steroidal anti-estrogen tamoxifen is used as an adjunct chemotherapeutic agent for the treatment of all stages of breast cancer and more recently as a chemoprotective agent in women with elevated risk of developing breast cancer. While beneficial for the treatment of breast cancer, tamoxifen increases the risk of endometrial cancer. In addition, it has been shown to induce liver and endometrial tumors in rats. Tamoxifen is genotoxic in rat liver, as indicated by the formation of DNA adducts, through a metabolic pathway involving the alpha -hydroxylation of tamoxifen and N-desmethyltamoxifen. Since the contribution of these cc-hydroxy metabolites of tamoxifen to the induction of endometrial tumors is presently unknown, we compared the extent of DNA adduct formation in liver and selected non-hepatic tissues of female Sprague-Dawley rats treated by gavage with tamoxifen, alpha -hydroxytamoxifen, N-desmethyltamoxifen, alpha -hydroxy-N-desmethyltamoxifen and N,N-didesmethyltamoxifen, or intraperitoneal injection with tamoxifen, alpha -hydroxytamoxifen, 3-hydroxytamoxifen and 4-hydroxytamoxifen. In addition, spleen lymphocytes from rats treated by gavage with tamoxifen or alpha -hydroxytamoxifen were assayed for the induction of mutants in the hypoxanthine phosphoribosyl transferase (Hprt) gene. The relative levels of binding in rats treated by gavage were alpha -hydroxytamoxifen > tamoxifen approximate to N-desmethyltamoxifen approximate to alpha -hydroxy-N-desmethyltamoxifen > N,N-didesmethyltamoxifen. In rats dosed intraperitoneally, the relative order of binding was alpha -hydroxytamoxifen > tamoxifen > 3-hydroxytamoxifen approximate to 4-hydroxytamoxifen. None of the compounds resulted in an increase in DNA adducts in uterus, spleen, thymus or bone marrow DNA from rats treated by gavage or in uterus DNA from rats injected intraperitoneally. Neither tamoxifen nor alpha -hydroxy-tamoxifen increased the Hprt mutant frequency in spleen T-lymphocytes. These results confirm previous observations that tamoxifen is activated to a genotoxic agent in rat liver through alpha -hydroxylation, and also suggest that endometrial tumors in rats do not arise from the formation of tamoxifen-DNA adducts. C1 Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. Univ Tecn Lisboa, Ctr Quim Estrutural, Inst Super Tecn, P-1049001 Lisbon, Portugal. RP Beland, FA (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. EM fbeland@nctr.fda.gov RI Marques, M. Matilde/E-2535-2012 OI Marques, M. Matilde/0000-0002-7526-4962 NR 72 TC 33 Z9 33 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD AUG PY 2001 VL 22 IS 8 BP 1307 EP 1315 PG 9 WC Oncology SC Oncology GA 463HV UT WOS:000170471800026 ER PT J AU Thai, SF Allen, JW DeAngelo, AB George, MH Fuscoe, JC AF Thai, SF Allen, JW DeAngelo, AB George, MH Fuscoe, JC TI Detection of early gene expression changes by differential display in the livers of mice exposed to dichloroacetic acid SO CARCINOGENESIS LA English DT Article ID STEAROYL-COA DESATURASE-1; MALE B6C3F1 MOUSE; MESSENGER-RNA; ALPHA-1-ANTITRYPSIN DEFICIENCY; IDENTIFICATION; CLONING; METABOLISM; INDUCTION; CARCINOGENICITY; SPECIFICITY AB Dichloroacetic acid (DCA) is a major by-product of water disinfection by chlorination. Several studies have demonstrated the hepatocarcinogenicity of DCA in mice when administered in drinking water. The mechanism of DCA carcinogenicity is not clear and we speculate that changes in gene expression may be important. In order to analyze early changes in gene expression induced by DCA treatment we used the differential display method. Mice were treated with 2 g/l DCA in drinking water for 4 weeks. Total RNAs were obtained from livers of both control and treated mice for analysis. Of similar to 48 000 bands on the differential display gels representing an estimated 96% of RNA species, 381 showed differences in intensity. After cloning and confirmation by both reverse-northern and northern analyses, six differentially expressed genes were found. The expression of five of these genes was suppressed in the DCA-treated mice while one was induced. After sequencing, four genes were identified and two were matched to expressed sequence tags through the BLAST program. These genes are alpha-1 protease inhibitor, cytochrome b5, stearoyl-CoA desaturase and carboxylesterase. Stearoyl-CoA desaturase was induced similar to3-fold in the livers of DCA-treated mice and the other three genes were suppressed approximately 3-fold. Stearoyl-CoA desaturase, cytochrome b5 and carboxylesterase are endoplasmic reticulum membrane-bound enzymes involved in fatty acid metabolism. The expression pattern of four of these genes was similar in DCA-induced hepatocellular carcinomas and the 4 week DCA-treated mouse livers. The expression of stearoyl-CoA desaturase and one of the unidentified genes returned to control levels in the carcinomas. Understanding the roles and interactions between these genes may shed light on the mechanism of DCA carcinogenesis. C1 US EPA, Natl Hlth & Environm Effects Res Lab, Div Environm Carcinogenesis, Res Triangle Pk, NC 27711 USA. RP Fuscoe, JC (reprint author), Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, HFT-120,3900 NCTR Rd, Jefferson, AR 72079 USA. NR 41 TC 29 Z9 30 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD AUG PY 2001 VL 22 IS 8 BP 1317 EP 1322 DI 10.1093/carcin/22.8.1317 PG 6 WC Oncology SC Oncology GA 463HV UT WOS:000170471800027 PM 11470764 ER PT J AU Wray-Cahen, D Caperna, TJ Steele, NC AF Wray-Cahen, D Caperna, TJ Steele, NC TI Methyl-beta-cyclodextrin: an alternative carrier for intravenous infusion of palmitate during tracer studies in swine (Sus scrofa domestica) SO COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY A-MOLECULAR AND INTEGRATIVE PHYSIOLOGY LA English DT Article DE albumin; fasted; fatty acid oxidation; fed; methyl-beta-cyclodextrin; palmitate; swine; tracer methodology ID HUMAN-SERUM-ALBUMIN; FATTY-ACID; GROWING PIGS; PLASMA; PHARMACOKINETICS; INJECTION; RATS; SOMATOTROPIN; CHOLESTEROL; FORMULATION AB Fatty acid-free albumin has been the standard carrier for intravenous infusion of fatty acids to study in vivo lipid metabolism. However, subjects can have adverse reactions to infusion of albumin. We sought an alternative to albumin as a carrier for intravenous infusion of fatty acids, using the pig as a model. Cyclodextrins are naturally occurring water-soluble molecules that can serve as carriers for lipid-soluble compounds. C-13-palmitate was complexed to either 20% methyl-beta -cyclodextrin, 20% 2-hydroxypropyl-beta -cyclodextrin, or 5% porcine albumin (isotopic purity of infusates: 99.22 +/- 0.66%). C-13-palmitate-albumin was infused under fed conditions and C-13-palmitate-methyl-beta -cyclodextrin was infused under fasted and fed conditions in 50-kg pigs. Palmitate remained in solution at 4 degreesC in methyl-beta -cyclodextrin, but precipitated at 25-30 degreesC in 2-hydroxypropyl-beta -cyclodextrin. Pigs infused with C-13-palmitate-methyl-beta -cyclodextrin maintained normal body temperature and appetite, those infused with C-13-palmitate-albumin became anorexic and exhibited other negative side effects to albumin. Palmitate oxidation rates under fed conditions were similar using either C-13-palmitate-methyl-beta -cyclodextrin or C-13-palmitate-albumin complexes. Fasting increased C-13-palmitate-methyl-beta -cyclodextrin oxidation by approximately eight-fold. These data suggest that methyl-beta -cyclodextrin may be a suitable substitute for albumin in fatty acid metabolism studies in swine. (C) 2001 Published by Elsevier Science Inc. C1 USDA ARS, Inst Livestock & Poultry Sci, Growth Biol Lab, Beltsville, MD 20705 USA. RP Wray-Cahen, D (reprint author), US FDA, CDRH, OST Lab Large Anim Res, HFV-500,8401 Muirkirk Rd, Laurel, MD 20708 USA. NR 37 TC 5 Z9 5 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 1095-6433 J9 COMP BIOCHEM PHYS A JI Comp. Biochem. Physiol. A-Mol. Integr. Physiol. PD AUG PY 2001 VL 130 IS 1 BP 55 EP 65 DI 10.1016/S1095-6433(01)00369-5 PG 11 WC Biochemistry & Molecular Biology; Physiology; Zoology SC Biochemistry & Molecular Biology; Physiology; Zoology GA 463JC UT WOS:000170472500006 PM 11672683 ER PT J AU Beaucage, SL AF Beaucage, SL TI Strategies in the preparation of DNA oligonucleotide arrays for diagnostic applications SO CURRENT MEDICINAL CHEMISTRY LA English DT Review ID GENE-EXPRESSION PATTERNS; LIGHT-DIRECTED SYNTHESIS; FIBER OPTIC BIOSENSOR; GOLD SURFACES; DEOXYNUCLEOSIDE PHOSPHORAMIDITES; GLASS SUPPORTS; COVALENT IMMOBILIZATION; POLYPROPYLENE SUPPORTS; FLUOROMETRIC DETECTION; FLUORESCENCE ANALYSIS AB This report emphasizes the interfacial chemistry that is required to ensure proper attachment of oligonucleotides onto the surface of microarrays. For example, strategies for the covalent attachment of presynthesized oligonucleotides to glass slides, gold films, polyacrylamide gel pads, polypyrrole films, and optical fibers are surveyed in an attempt to better define the parameters for optimal formation and detection of DNA hybrids. These parameters include among others, the nature and length of the linkers attaching oligonucleotides to the arrays, and the surface density of oligonucleotides required for unhindered hybridization with DNA targets. Sensitive detection methods such as the use of light-scattering techniques, molecular beacons, surface plasmon resonance, attenuated total internal reflection-FTIR, and the evanescent field excitation of fluorescence from surface-bound fluorophores have been developed to study the kinetics and specificity of hybridization events. Finally, the synthesis of oligonucleotides directly on glass surfaces and polypropylene sheets has been investigated to enable DNA sequencing by hybridization and achieve oligonucleotide densities of ca. 10(6) sequences per cm(2) on DNA chips. 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. NR 94 TC 104 Z9 109 U1 3 U2 36 PU BENTHAM SCIENCE PUBL LTD PI HILVERSUM PA PO BOX 1673, 1200 BR HILVERSUM, NETHERLANDS SN 0929-8673 J9 CURR MED CHEM JI Curr. Med. Chem. PD AUG PY 2001 VL 8 IS 10 BP 1213 EP 1244 PG 32 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 452RM UT WOS:000169872600006 PM 11472237 ER PT J AU Erickson, BD Campbell, WL Cerniglia, CE AF Erickson, BD Campbell, WL Cerniglia, CE TI A rapid method for determining the tuberculocidal activity of liquid chemical germicides SO CURRENT MICROBIOLOGY LA English DT Article ID MYCOBACTERIUM-TUBERCULOSIS; TRANSMISSION; BRONCHOSCOPE AB A rapid, quantitative method has been developed for determining the tuberculocidal activity of liquid chemical germicides. In this method, a test strain of Mycobacterium bovis that carries the firefly luciferase gene is exposed to a,germicide, and the surviving bacteria are detected by bioluminescence. The tuberculocidal activities of five commercially available glutaraldehyde-based disinfectants were tested, and all reduced the number of surviving mycobacteria by greater than five orders of magnitude. In contrast, a phenol-based disinfectant with tuberculocidal claims gave less than one order of magnitude reduction of the test organism. With this method for determining tuberculocidal activity, results can be obtained in less than one day, compared with weeks or months for the standard tuberculocidal assays. C1 US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. RP US FDA, Natl Ctr Toxicol Res, Div Microbiol, HFT-250,3900 NCTR Rd, Jefferson, AR 72079 USA. EM berickson@nctr.fda.gov NR 13 TC 3 Z9 3 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0343-8651 EI 1432-0991 J9 CURR MICROBIOL JI Curr. Microbiol. PD AUG PY 2001 VL 43 IS 2 BP 79 EP 82 DI 10.1007/s002840010264 PG 4 WC Microbiology SC Microbiology GA 442XT UT WOS:000169310800001 PM 11391467 ER PT J AU Jinneman, KC Hill, WE AF Jinneman, KC Hill, WE TI Listeria monocytogenes lineage group classification by MAMA-PCR of the listeriolysin gene SO CURRENT MICROBIOLOGY LA English DT Article ID VIRULENCE-ASSOCIATED GENES; POLYMORPHIC DNA; STRAINS; IDENTIFICATION; AMPLIFICATION; SEQUENCE AB Nucleotide sequence differences within several virulence genes, including the listeriolysin O (hly) gene, are associated with three evolutionary lineage groups of Listeria monocytogenes. Because the ability of L. monocytogenes to cause disease may vary by evolutionary lineage group, rapid discrimination among the three lineage types may be important for estimating pathogenic potential. A Mismatch Amplification Mutation Assay (MAMA) was developed and used to rapidly screen and characterize L. monocytogenes isolates with regard to lineage type. A standard PCR amplified a 446-bp region within the hly gene with all three L. monocytogenes lineage genotypes. MAMA primers to four different sites within this region of the hly gene were designed to amplify under the same PCR conditions and generated amplicons, the size of which depended on the isolate genotype. Ninety-seven L. monocytogenes isolates were screened. All isolates, except ATCC 19116, could be classified by MAMA PCR as one of the three hly genotypes. Overall, 56, 36, and 4 of the 97 isolates tested were type 1, 2, or 3 respectively. Among the 26 patient isolates, 85%, 15%, and 0% were type 1, 2, or 3 respectively; for the 60 food isolates, 54% were type 1, 43% were type 2, and 3% were type 3. The combination of these MAMA PCR analyses provides a rapid method to screen and categorize L. monocytogenes isolates because of conserved nucleotide differences within the hly gene. C1 US FDA, Seafood Prod Res Ctr, Pacific Reg Lab NW, Bothell, WA 98021 USA. RP Jinneman, KC (reprint author), USDA, Food Safety & Inspect Serv, OPHS, Aerosp Ctr 344, 1400 Independence Ave SW, Washington, DC 20250 USA. NR 15 TC 36 Z9 36 U1 0 U2 3 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0343-8651 J9 CURR MICROBIOL JI Curr. Microbiol. PD AUG PY 2001 VL 43 IS 2 BP 129 EP 133 DI 10.1007/s002840010274 PG 5 WC Microbiology SC Microbiology GA 442XT UT WOS:000169310800011 PM 11391477 ER PT J AU Carbone, KM Rubin, SA Nishino, Y Pletnikov, MV AF Carbone, KM Rubin, SA Nishino, Y Pletnikov, MV TI Borna disease: virus-induced neurobehavioral disease pathogenesis SO CURRENT OPINION IN MICROBIOLOGY LA English DT Review ID INFECTED-RATS; LABORATORY STRAINS; NERVOUS-SYSTEM; SCHWANN-CELLS; HUMAN-ORIGIN; LEWIS RATS; BRAIN; EXPRESSION; PERSISTENT; ASTROCYTES AB Studies of the pathogenesis of neurobehavioral diseases following Boma disease virus infections have been increasing rapidly over the past ten years. Recent major advances have included a report of vertical transmission of the virus in its natural host, the horse, and a report of isolation of a novel variant, No/98, in that same species. In rats infected neonatally with the Boma disease virus that lack blood-borne inflammation in the brain, evidence of an 'endogenous' brain inflammatory response is abundant, with elevated expression of cytokine and chemokine mRNA. Infection in these rats is also associated with abnormal levels of neurotransmitters, including serotonin and norepinephrine. Data and debate continue to be forthcoming about the role of Boma disease virus in human infection and psychiatric disease. C1 US FDA, Lab Pediat & Resp Viral Dis, CBER, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Psychiat, Baltimore, MD 21205 USA. RP Carbone, KM (reprint author), US FDA, Lab Pediat & Resp Viral Dis, CBER, HFM 460,8800 Rockville Pike, Bethesda, MD 20892 USA. FU NIMH NIH HHS [R01 MH48948] NR 49 TC 18 Z9 18 U1 1 U2 2 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1369-5274 J9 CURR OPIN MICROBIOL JI Curr. Opin. Microbiol. PD AUG PY 2001 VL 4 IS 4 BP 467 EP 475 DI 10.1016/S1369-5274(00)00237-X PG 9 WC Microbiology SC Microbiology GA 463BY UT WOS:000170458000019 PM 11495813 ER PT J AU Hutzler, JM Frye, RF Korzekwa, KR Branch, RA Huang, SM Tracy, TS AF Hutzler, JM Frye, RF Korzekwa, KR Branch, RA Huang, SM Tracy, TS TI Minimal in vivo activation of CYP2C9-mediated flurbiprofen metabolism by dapsone SO EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article DE dapsone; flurbiprofen; activation; metabolism; CYP2C9 ID CYTOCHROME-P450 2C9; N-HYDROXYLATION; DISPOSITION; BINDING; 4'-HYDROXYLATION; PLASMA; URINE; DRUGS AB Dapsone has been shown to activate flurbiprofen 4'-hydroxylation by expressed CYP2C9 enzyme and in human liver microsomes. It has been suggested that this observation is due to substrate cooperativity on enzyme activity however, the in vivo relevance of this observation is unknown. Thus. the purpose of this Study was to evaluate whether dapsone can act cooperatively with flurbiprofen to activate the in vivo metabolism of flurbiprofen to 4'-hydroxyflurbiprofen. Twelve healthy subjects received single-dose flurbiprofen 50 mg on three occasions: alone (visit A): 2 h after a single dapsone 100-mg dose (visit B); and 2 h after the seventh daily dose of dapsone 100 mg (visit C). Concentrations of flurbiprofen and 4'-hydroxy flurbiprofen in plasma and urine and dapsone and N-acetyldapsone in plasma were determined by HPLC. Flurbiprofen pharmacokinetic parameters for the three visits were estimated by non-compartmental methods and compared in the absence and presence of dapsone. Flurbiprofen apparent oral clearance was increased by similar to 11% (P<0.02) after dapsone 100 mg for 7 days. Dapsone plasma concentrations averaged 52 muM after a single dose and 11 +/-4 muM after seven daily 100 mg doses. These dapsone plasma concentrations were within the range of concentrations producing activation of flurbiprofen metabolism by CYP2C9 in vitro. These results are consistent with the hypothesis that dapsone does influence flurbiprofen metabolism in vivo in a cooperative way to enhance metabolism. However, the magnitude of effect is substantially less than observed in vitro. (C) 2001 Elsevier Science BY All rights reserved. C1 W Virginia Univ, Sch Pharm, Dept Basic Pharmaceut Sci, Morgantown, WV 26506 USA. Sch Pharm, Dept Pharmaceut Sci, Pittsburgh, PA USA. Univ Pittsburgh, Ctr Clin Pharmacol, Pittsburgh, PA USA. US FDA, Rockville, MD 20857 USA. RP Tracy, TS (reprint author), W Virginia Univ, Sch Pharm, Dept Basic Pharmaceut Sci, HSN POB 9530, Morgantown, WV 26506 USA. OI Frye, Reginald/0000-0002-1841-1401 FU NCRR NIH HHS [5M01 RR00056] NR 25 TC 35 Z9 37 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0928-0987 J9 EUR J PHARM SCI JI Eur. J. Pharm. Sci. PD AUG PY 2001 VL 14 IS 1 BP 47 EP 52 DI 10.1016/S0928-0987(01)00144-0 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 458EQ UT WOS:000170180600006 PM 11457649 ER PT J AU Collins, TFX Sprando, RL Black, TN Shackelford, ME Olejnik, N Ames, MJ Rorie, JI Ruggles, DI AF Collins, TFX Sprando, RL Black, TN Shackelford, ME Olejnik, N Ames, MJ Rorie, JI Ruggles, DI TI Developmental toxicity of sodium fluoride measured during multiple generations SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article DE sodium fluoride; reproduction; developmental toxicity; rat ID AFFECT SPERMATOGENESIS; RATS AB Sodium fluoride (NaF) has been used to fluoridate drinking water in the United States since the mid 1940s. Because of the lack of reliable studies on the multigeneration effects of the compound, NaF (0, 25. 100, 175 or 250 ppm in drinking water) was given to rats continuously during three generations. Parental (F0) generation rats were treated for 10 weeks and mated within groups. At gestation day 20, caesarean sections were performed and eight F0 females per group and their litters (F1) were observed for implant status, fetal weight and length, sex and morphological development. The remaining F0 females (29-32 per group) were allowed to litter. F1 offspring (36 of each sex per group) were mated within groups, and caesarean sections were performed at gestation day 20. The F1 females and their litters (F2) were observed for implant status. fetal weight and length, sex and morphological development. In addition, F2 fetuses were evaluated for internal (soft-tissue) and skeletal development, Decreased fluid consumption for F0 and F1 dams at 175 and 250 ppm was attributed to decreased palatability of the solution. No dose-related effects in feed consumption or mean body weight gain were observed in either F0 or F1 females. Numbers of corpora lutea, implants, viable fetuses and fetal morphological development were similar in all groups. No dose-related anomalies in internal organs were observed in F2 Fetuses. Ossification of the hyoid bone of F2 fetuses was significantly decreased at 250 ppm. Because of the decreased ossification of the hyoid bone, 250 ppm is considered the effect level. Published by Elsevier Science Ltd. C1 US FDA, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. RP Collins, TFX (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 8301 Muirkirk Rd, Laurel, MD 20708 USA. NR 20 TC 18 Z9 22 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 AUG PY 2001 VL 39 IS 8 BP 867 EP 876 DI 10.1016/S0278-6915(01)00033-3 PG 10 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA 453HW UT WOS:000169911300011 PM 11434994 ER PT J AU Slikker, W Desai, VG Duhart, H Feuers, R Imam, SZ AF Slikker, W Desai, VG Duhart, H Feuers, R Imam, SZ TI Hypothermia enhances bcl-2 expression and protects against oxidative stress-induced cell death in Chinese hamster ovary cells SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE hypothermia; oxidative stress; glutathione peroxidase; gene expression; apoptosis; free radicals ID HYDROGEN-PEROXIDE; INDUCED APOPTOSIS; GLUTATHIONE-PEROXIDASE; DNA; METHAMPHETAMINE; CYTOTOXICITY; ANTIOXIDANT; GENERATION; ISCHEMIA; PROTEINS AB Oxidative stress is one of the major causes of cellular injury. Various reactive oxygen (ROS) and nitrogen (RNS) species such as superoxide, hydroxyl radical, peroxynitrite, and nitric oxide are involved in the manifestations of different types of organ toxicity and the resultant syndromes, symptoms, or diseases. Hypothermic conditions have been reported to reduce the oxidative stress in various in vitro and in vivo studies. In the present study, we sought to determine the effect of lowered temperatures on oxidative stress-induced cell death in Chinese hamster ovary (CHO) cells. We also investigated the oxidative stress-induced alterations in the expression of anti-apoptotic protein, bcl-2, in CHO cells at lowered temperatures. CHO cells were incubated at four different temperatures of 30, 32, 35, and 37 degreesC (control temperature) from 1 to 4 d. In another set, the cells were incubated with 100 muM hydrogen peroxide (H2O2) for 30 min before harvesting at different time points. The cells were harvested at 1, 2, 3, and 4 d. Cell survival was significantly higher at 30 degreesC as compared to 37 degreesC over 4 d of incubation. In cells incubated with H2O2, significantly higher cell viability was observed at lower temperatures as compared to the cells incubated at 37 degreesC. The activity of glutathione peroxidase (GSH-Px) also increased significantly at lower temperatures. Lowered temperature also provided a significant increase in the expression of anti-apoptotic protein, bcl-2 after 4 d of incubation. These data suggest that hypothermic conditions lowers the risk of oxidative stress-induced cellular damage and programmed cell death by increasing the activity of GSH-Px and by the induction in the expression of the anti-apoptotic protein, bcl-2. (C) 2001 Elsevier Science Inc. C1 US FDA, Natl Ctr Toxicol Res, Neurochem Lab, Div Neurotoxicol, Jefferson, AR 72079 USA. US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. RP Imam, SZ (reprint author), US FDA, Natl Ctr Toxicol Res, Neurochem Lab, Div Neurotoxicol, HFT-132,3900 NCTR Dr, Jefferson, AR 72079 USA. NR 30 TC 42 Z9 46 U1 0 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD AUG 1 PY 2001 VL 31 IS 3 BP 405 EP 411 DI 10.1016/S0891-5849(01)00593-7 PG 7 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 460AP UT WOS:000170283900015 PM 11461779 ER PT J AU McGowen, MM Vionnet, J Vann, WF AF McGowen, MM Vionnet, J Vann, WF TI Elongation of alternating alpha 2,8/2,9 polysialic acid by the Escherichia coli K92 polysialyltransferase SO GLYCOBIOLOGY LA English DT Article DE E. coli; polysialic acid; polysialyltransferase ID CAPSULAR POLYSACCHARIDE PRODUCTION; BACTERIA; SIALYLTRANSFERASE; BIOSYNTHESIS; EXPRESSION; GENETICS; K1 AB We have chosen E. coli K92, which produces the alternating structure alpha (2-8)neuNAc alpha (2-9)neuNAc as a model system for studying bacterial polysaccharide biosynthesis. We have shown that the polysialyltransferase encoded by the K92 neuS gene can synthesize both alpha (2-8) and alpha (2-9) neuNAc linkages in vivo by C-13-nuclear magnetic resonance analysis of polysaccharide isolated from a heterologous strain containing the K92 neuS gene. The K92 polysialyltransferase is associated with the membrane in lysates of cells harboring the neuS gene in expression vectors. Although the enzyme can transfer sialic acid to the nonreducing end of oligosaccharides with either linkage, it is unable to initiate chain synthesis without exogenously added polysialic acid. Thus, the polysialyltransferase encoded by neuS is not sufficient for de novo synthesis of polysaccharide but requires another membrane component for initiation. The acceptor specificity of this polysialyltransferase was studied using sialic acid oligosaccharides of various structures as exogenous acceptors. The enzyme can transfer to the nonreducing end of all bacteria polysialic acids, but has a definite preference for alpha (2-8) acceptors. Gangliosides containing neuNAc oc(2-8)neuNAc are elongated, whereas monsialylated gangliosides are not. Disialylgangliosides are better acceptors than short oligosaccharides, suggesting a lipid-linked oligosaccharide may be preferred in the elongation reaction. These studies show that the K92 polysialyltransferase catalyzes an elongation reaction that involves transfer of sialic acid from CMP-sialic acid to the nonreducing end of two different acceptor substrates. C1 Ctr Biol Evaluat & Res, Lab Bacterial Toxins, Div Bacterial Parasit & Allergen Prod, Bethesda, MD 20892 USA. RP Vann, WF (reprint author), Ctr Biol Evaluat & Res, Lab Bacterial Toxins, Div Bacterial Parasit & Allergen Prod, 8800 Rockville Pike, Bethesda, MD 20892 USA. NR 21 TC 30 Z9 30 U1 0 U2 2 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 AUG PY 2001 VL 11 IS 8 BP 613 EP 620 DI 10.1093/glycob/11.8.613 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 461DH UT WOS:000170349300002 PM 11479272 ER PT J AU Bernstein, ML Reaman, GH Hirschfeld, S AF Bernstein, ML Reaman, GH Hirschfeld, S TI Developmental therapeutics in childhood cancer - A perspective from the Children's Oncology Group and the US Food and Drug Administration SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article ID PHASE-I TRIAL; REFRACTORY SOLID TUMORS; ACUTE LYMPHOBLASTIC-LEUKEMIA; EVERY 3 WEEKS; PEDIATRIC-ONCOLOGY; ANTITUMOR-ACTIVITY; CONTINUOUS-INFUSION; SYSTEMIC EXPOSURE; PHARMACOKINETIC PK; MYELOID-LEUKEMIA AB New agents are required for the treatment of childhood cancer. Current therapies fail to cure approximately 30% of children with malignancies. The toxicity is high, with serious short-term and long-term side effects. The number of children with cancer is small, with only approximately I child in 315 affected by age 20 years. Approximately 12,500 new cases are diagnosed in the United States each year.(66) A variety of histologic subtypes, mostly different from adult cancers, are represented. The pharmacokinetics of drugs in children often are different from those in adults, with children frequently eliminating drug more rapidly. The pharmacodynamics also may be different. Children less than age 10 years are more susceptible to pseudotumor cerebri induced by retinoids than are older children or adults,(81) As a consequence, specific studies of pharmacokinetics; and pharmacodynamics are needed in children. Because the number of children affected is small, most studies are multicentric, to enable a sufficiently large group to be accrued. This is especially true of new agent studies. This article briefly reviews the strategy for selecting promising agents for study, including efforts by the U.S. Food and Drug Administration (FDA) to increase the availability of agents in early development. Study design and recent and planned developmental therapeutics studies are described, with an emphasis on Children's Oncology Group (COG) studies of cytotoxic agents. For an additional review of the general issues involved in phase I trials in children with cancer, see Smith et al.(80) C1 Hop St Justine, Div Hematol Oncol, Serv Hematol Oncol, Montreal, PQ H3T 1C5, Canada. Univ Montreal, Dept Pediat, Montreal, PQ H3C 3J7, Canada. George Washington Univ, Sch Med & Hlth Sci, Dept Pediat, Washington, DC 20052 USA. Childrens Natl Med Ctr, Div Hematol Oncol, Washington, DC 20010 USA. Childrens Oncol Grp, Arcadia, CA USA. US FDA, Ctr Drug Evaluat & Res, Div Oncol Drug Prod, Rockville, MD 20857 USA. NCI, Bethesda, MD 20892 USA. RP Bernstein, ML (reprint author), Hop St Justine, Div Hematol Oncol, Serv Hematol Oncol, 3175 Cote St Catherine,2nd Floor,Block 4, Montreal, PQ H3T 1C5, Canada. RI Hirschfeld, Steven/E-2987-2016 OI Hirschfeld, Steven/0000-0003-0627-7249 NR 99 TC 3 Z9 3 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0889-8588 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD AUG PY 2001 VL 15 IS 4 BP 631 EP + DI 10.1016/S0889-8588(05)70240-9 PG 26 WC Oncology; Hematology SC Oncology; Hematology GA 482BR UT WOS:000171555400004 PM 11676277 ER PT J AU Kodell, RL AF Kodell, RL TI U-shaped dose-response relationships for mutation and cancer SO HUMAN AND ECOLOGICAL RISK ASSESSMENT LA English DT Article DE adaptive repair; background additivity; genotoxicity; hormesis; initiation; point mutation ID CHEMICAL CARCINOGENESIS; MODEL; INITIATION; THRESHOLDS; PROMOTION; EXPOSURE AB A biologically based mutation model that can be parameterized to reflect U-shaped behavior at low doses of genotoxic substances is derived. The U-shaped behavior results from an efficient, adaptive DNA repair process, by which some endogenous DNA damage that would not be repaired in the absence of the genotoxic substance is repaired when low levels of the substance are present. Hence, the model embodies a type of hormesis. The dose response is U shaped even though the genotoxic mechanism is additive to an existing background mutation process. The risk-assessment implications regarding possible hormetic effects, instead of the generally expected low-dose-linear effects, for agents that are both genotoxic and additive to background are discussed. C1 US FDA, Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. RP Kodell, RL (reprint author), US FDA, Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, 3900 NCTR Rd, Jefferson, AR 72079 USA. NR 32 TC 2 Z9 2 U1 0 U2 3 PU CRC PRESS LLC PI BOCA RATON PA 2000 CORPORATE BLVD NW, JOURNALS CUSTOMER SERVICE, BOCA RATON, FL 33431 USA SN 1080-7039 J9 HUM ECOL RISK ASSESS JI Hum. Ecol. Risk Assess. PD AUG PY 2001 VL 7 IS 4 BP 909 EP 919 DI 10.1080/20018091094727 PG 11 WC Biodiversity Conservation; Environmental Sciences SC Biodiversity & Conservation; Environmental Sciences & Ecology GA 469DJ UT WOS:000170798200020 ER PT J AU Joshi, MB Gam, AA Boykins, RA Kumar, S Sacci, J Hoffman, SL Nakhasi, HL Kenney, RT AF Joshi, MB Gam, AA Boykins, RA Kumar, S Sacci, J Hoffman, SL Nakhasi, HL Kenney, RT TI Immunogenicity of well-characterized synthetic Plasmodium falciparum multiple antigen peptide conjugates SO INFECTION AND IMMUNITY LA English DT Article ID YOELII CIRCUMSPOROZOITE PROTEIN; LIVER-STAGE ANTIGEN-1; T-CELL EPITOPES; MALARIA VACCINE; B-CELL; SPOROZOITE VACCINE; IMMUNE-RESPONSE; ANTIBODIES; DESIGN; MICE AB Given the emerging difficulties with malaria drug resistance and vector control, as well as the persistent lack of an effective vaccine, new malaria vaccine development strategies are needed. We used a novel methodology to synthesize and fully characterize multiple antigen peptide (MAP) conjugates containing protective epitopes from Plasmodium falciparum and evaluated their immunogenicity in four different strains of mice. A di-epitope MAP (T3-T1) containing two T-cell epitopes of liver stage antigen-1 (LSA-1), a di-epitope MAP containing T-cell epitopes from LSA-1 and from merozoite surface protein-1, and a tri-epitope MAP (T3-CS-T1) containing T3-T1 and a potent B-cell epitope from the circumsporozoite protein central repeat region were tested in this study. Mice of all four strains produced peptide-specific antibodies; however, the magnitude of the humoral response indicated strong genetic restriction between the different strains of mice. Anti-MAP antibodies recognized stage-specific proteins on the malaria parasites in an immunofluorescence assay. In addition, serum from hybrid BALB/cJ x A/J CAF1 mice that had been immunized with the tri-epitope MAP T3-CS-T1 successfully inhibited the malaria sporozoite invasion of hepatoma cells in vitro. Spleen cells from immunized mice also showed a genetically restricted cellular immune response when stimulated with the immunogen in vitro. This study indicates that well-characterized MAPS combining solid-phase synthesis and conjugation chemistries are potent immunogens and that this approach can be utilized for the development of subunit vaccines. C1 US FDA, Lab Parasit Biol & Biochem, Off Vaccine Res & Review, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. US FDA, Div Emerging & Transfus Transmitted Dis, Off Blood Res & Review, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. USN, Malaria Program, Med Res Ctr, Silver Spring, MD USA. RP Kenney, RT (reprint author), IOMAI Corp, 20 Firstfield Rd,Suite 250, Gaithersburg, MD 20878 USA. NR 52 TC 26 Z9 33 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 AUG PY 2001 VL 69 IS 8 BP 4884 EP 4890 DI 10.1128/IAI.69.8.4884-4890.2001 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 456UP UT WOS:000170100900024 PM 11447164 ER PT J AU Hauck, WW Parekh, A Lesko, LJ Chen, ML Williams, RL AF Hauck, WW Parekh, A Lesko, LJ Chen, ML Williams, RL TI Limits of 80%-125% for AUC and 70%-143% for C(max) - What is the impact on bioequivalence studies? SO INTERNATIONAL JOURNAL OF CLINICAL PHARMACOLOGY AND THERAPEUTICS LA English DT Article DE bioequivalence; confidence intervals; sample size ID EQUIVALENCE AB Objective: The US Food and Drug Administration (FDA) currently uses bioequivalence (BE) limits for fasting BE studies that are based on the 90% confidence interval for the ratio of difference of the test and reference products C(max) and AUC failing within 80% to 125%. The FDA has also proposed that BE limits be used similarly for AUC and Cma, measurements from fed BE studies. In some cases, regulatory agencies have considered a wider BE limit for C(max), because of the typically higher variability of C(max) compared to AUC. We investigated the consequences of changing from an 80%/125% limit for both pharmacokinetic measures to one that uses a limit of 80%/125% for AUC and 70%/143% for C(max). Methods: We computed the sample sizes required for BE studies using 80%/125% for AUC and 70%/143% for C(max) as BE limits. We also determined the range of the ratios Of Cmax and AUC values in a study that could meet the 70%/143% and 80%/125% BE limits. Results: The sample size for the study, in order to have adequate power with 80%/125% for AUC and 70%/143% for C(max) will be determined primarily by the intrasubject variability of AUC, though with a substantial proportion of studies (about one third) still determined by the variability Of C(max) The ratio of mean C(max) values that can pass a wider 70%/143% BE limit could easily be as high as 128%. Conclusion: Without further scientific or clinical rationale, we find it difficult to justify widening the bioequivalence limit for C(max) to 70%/143% for either fasting or fed BE studies. C1 Thomas Jefferson Univ, Div Clin Pharmacol, Biostat Sect, Philadelphia, PA 19107 USA. US FDA, Off Pharmaceut Sci, Off Clin Pharmacol & Biopharmaceut, Rockville, MD 20857 USA. US FDA, Ctr Drug Evaluat & Res, Off Pharmaceut Sci, Rockville, MD 20857 USA. US Pharmacopeia, Rockville, MD USA. RP Hauck, WW (reprint author), Thomas Jefferson Univ, Div Clin Pharmacol, Biostat Sect, 125 S 9th St,402, Philadelphia, PA 19107 USA. EM whauck@lac.jci.tju.edu NR 11 TC 20 Z9 22 U1 0 U2 0 PU DUSTRI-VERLAG DR KARL FEISTLE PI DEISENHOFEN-MUENCHEN PA BAHNHOFSTRASSE 9 POSTFACH 49, D-82032 DEISENHOFEN-MUENCHEN, GERMANY SN 0946-1965 J9 INT J CLIN PHARM TH JI Int. J. Clin. Pharmacol. Ther. PD AUG PY 2001 VL 39 IS 8 BP 350 EP 355 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 493PX UT WOS:000172232900005 PM 11515710 ER PT J AU Schwetz, BA AF Schwetz, BA TI New device for procedures on diseased bypass grafts SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT News Item C1 US FDA, Off Commissioner, Rockville, MD 20857 USA. RP Schwetz, BA (reprint author), US FDA, Off Commissioner, HF-1,Room 14-71,5600 Fishers Ln, Rockville, MD 20857 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD AUG 1 PY 2001 VL 286 IS 5 BP 527 EP 527 DI 10.1001/jama.286.5.527 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 458HE UT WOS:000170188300004 PM 11476645 ER PT J AU Schwetz, BA AF Schwetz, BA TI New weight-reduction system SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT News Item C1 US FDA, Off Commissioner, Rockville, MD 20857 USA. RP Schwetz, BA (reprint author), US FDA, Off Commissioner, HF-1,Room 14-71,5600 Fishers Ln, Rockville, MD 20857 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD AUG 1 PY 2001 VL 286 IS 5 BP 527 EP 527 DI 10.1001/jama.286.5.527 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 458HE UT WOS:000170188300005 PM 11476645 ER PT J AU Schwetz, BA AF Schwetz, BA TI New oral contraceptive SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT News Item C1 US FDA, Off Commissioner, Rockville, MD 20857 USA. RP Schwetz, BA (reprint author), US FDA, Off Commissioner, HF-1,Room 14-71,5600 Fishers Ln, Rockville, MD 20857 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD AUG 1 PY 2001 VL 286 IS 5 BP 527 EP 527 DI 10.1001/jama.286.5.527 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 458HE UT WOS:000170188300003 PM 11476645 ER PT J AU Yedavalli, RV Loth, F Yardimci, A Pritchard, WF Oshinski, JN Sadler, L Charbel, F Alperin, N AF Yedavalli, RV Loth, F Yardimci, A Pritchard, WF Oshinski, JN Sadler, L Charbel, F Alperin, N TI Construction of a physical model of the human carotid artery based upon in vivo magnetic resonance images SO JOURNAL OF BIOMECHANICAL ENGINEERING-TRANSACTIONS OF THE ASME LA English DT Article ID BIFURCATION; REPLICAS AB A method is described for construction of an in vitro flow model based on in vivo measurements of the lumen geometry of the human carotid bifurcation. A large-scale physical model of the vessel lumen it-as constructed using fused deposition modeling (a rapid prototyping technique) based oil magnetic resonance (MR) images of the carotid bifurcation acquired in it healthy volunteer. The lumen negative was then used to construct a flow model for experimental studies that examined the hemodynamic environment of subject-specific geometry and flow conditions. The physical model also supplements physician insight into the three-dimensional geometry of the arterial segment, complementing the two-dimensional images obtained by MR. Study of the specific geometry and flow conditions in patients with vascular disease may contribute to our understanding of the relationship between their hemodynamic environment and conditions that lead to the development and progression of arterial disease. C1 Univ Illinois, Coll Med, Chicago, IL 60607 USA. Univ Illinois, Dept Mech Engn, Chicago, IL 60607 USA. Univ Illinois, Dept Bioengn, Chicago, IL 60607 USA. Baxter Int, Adv Engn Design Ctr, Round Lake, IL 60073 USA. US FDA, Rockville, MD 20852 USA. Emory Univ, Dept Radiol & Biomed Engn, Atlanta, GA 30322 USA. Visible Prod Inc, Ft Collins, CO 80524 USA. Univ Illinois, Dept Neurosurg, Chicago, IL 60612 USA. Univ Illinois, Dept Radiol, Chicago, IL 60612 USA. Univ Illinois, Dept Bioengn, Chicago, IL 60612 USA. RP Yedavalli, RV (reprint author), Univ Illinois, Coll Med, Chicago, IL 60607 USA. RI Loth, Francis/C-1177-2008; YARDIMCI, Ahmet/B-9568-2016 NR 15 TC 28 Z9 28 U1 0 U2 2 PU ASME-AMER SOC MECHANICAL ENG PI NEW YORK PA THREE PARK AVE, NEW YORK, NY 10016-5990 USA SN 0148-0731 J9 J BIOMECH ENG-T ASME JI J. Biomech. Eng.-Trans. ASME PD AUG PY 2001 VL 123 IS 4 BP 372 EP 376 DI 10.1115/1.1385845 PG 5 WC Biophysics; Engineering, Biomedical SC Biophysics; Engineering GA 468NF UT WOS:000170763200011 PM 11563764 ER PT J AU Zuppardo, AB DePaola, A Bowers, JC Schully, KL Gooch, JA Siebeling, RJ AF Zuppardo, AB DePaola, A Bowers, JC Schully, KL Gooch, JA Siebeling, RJ TI Heterogeneity of environmental, retail, and clinical isolates of Vibrio vulnificus as determined by lipopolysaccharide-specific monoclonal antibodies SO JOURNAL OF FOOD PROTECTION LA English DT Article ID FIELD GEL-ELECTROPHORESIS; ESCHERICHIA-COLI; SEROLOGICAL IDENTIFICATION; YERSINIA-ENTEROCOLITICA; STRAINS; ANTIGEN; OYSTERS; ANGUILLARUM; SALMONELLA; SEROGROUPS AB The opportunistic pathogen Vibrio vulnificus expresses lipopolysaccharide (LPS) antigens on its outer membrane surface. A serological typing system was developed for these antigens, utilizing the discriminatory recognition of monoclonal antibodies (MAb) by ELISA. MAb were used to recognize five unique types of LPS-associated antigens for examination of clinical, environmental, and retail isolates of V. vulnificus. The overall serotype profile of the clinical isolates was significantly different (P < 0.05) from that of the environmental and retail isolates. A higher percentage of clinical isolates were typable (61%) compared to the environmental isolates (41%) and retail isolates (44%). In particular, the percentage of serotype 1/5 among clinical isolates (33%), compared to that of environmental (9%) and retail (4%), was highly significant (P < 0.0001). Among the environmental Gulf Coast isolates, there were differences in the prevalence of serotypes 2 and 3 (P < 0.05), depending on whether isolates were obtained from Louisiana or Alabama harvest sites. There were no statistically significant differences between the serotype profiles of Gulf and Atlantic Coast retail isolates despite the absence of serotype 1/5 from the Atlantic Coast. While some serotype diversity was detected in V. vulnificus isolated during different seasons, from different geographic locations, and at retail versus at harvest, there was no apparent concordance between any of the serotype distributions obtained from oysters versus that isolated clinically. The heterogeneity of environmental isolates and relative homogeneity among clinical isolates suggest that human risk may not be predicted on quantitative exposure alone. C1 US Dept Commerce, NOAA, NOS, Ctr Coastal Environm Hlth & Biomol Res, Charleston, SC 29412 USA. US FDA, Div Math & Stat, Washington, DC 20204 USA. US FDA, Gulf Coast Seafood Lab, Dauphin Isl, AL 36528 USA. Louisiana State Univ, Dept Biol Sci, Baton Rouge, LA 70803 USA. RP Zuppardo, AB (reprint author), Florida Dept Hlth, Bur Labs, POB 210, Jacksonville, FL 32231 USA. NR 40 TC 7 Z9 7 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 AUG PY 2001 VL 64 IS 8 BP 1172 EP 1177 PG 6 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 460UH UT WOS:000170326600013 PM 11510655 ER PT J AU Huang, LY Sousa, CR Itoh, Y Inman, J Scott, DE AF Huang, LY Sousa, CR Itoh, Y Inman, J Scott, DE TI IL-12 induction by a Th1-inducing adjuvant in vivo: Dendritic cell subsets and regulation by IL-10 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CD4+ T-CELLS; INTERLEUKIN-10 PROTECTS MICE; IMMUNITY IN-VIVO; BRUCELLA-ABORTUS; IFN-GAMMA; INTRACELLULAR INFECTION; TOXOPLASMA-GONDII; LIPOPOLYSACCHARIDE; MACROPHAGES; EXPRESSION AB IL-12 induction is critical for immune responses against many viruses and intracellular bacterial pathogens. Recent studies suggest that IL-12-secreting dendritic cells (DC) are potent Th1-inducing APC. However, controversy exists concerning the function of DC subsets. Murine studies have suggested that CD8(+) DC preferentially induce Th1 responses, whereas CD8(-) DC induce Th2 development; in this model, different DC subsets prime different responses. Alternatively, the propensity of DC subsets to prime a Th1 response could depend upon the type of initial stimulus. We used a prototypic Th1-inducing adjuvant, heat-killed Brucella abortus (HKBA) to assess stimulation of DC subsets, relationship between Ag burden and IL-12 production, and down-regulation of DC subset IL-12 production by IL-10. In this study, we show that DC were sole producers of IL-12, although most HKBA uptake was by splenic macrophages and granulocytes. More CD8(-) than CD8(+) DC produced IL-12 after HKBA challenge, whereas only CD8(+) DC produced IL-12 after injection of another Th1-promoting microbial substance, soluble Toxoplasma gondii Ags. Studies in IL-10-deficient mice revealed that IL-10 down-regulates frequency and duration of IL-12 production by both DC subsets. In the absence of IL-10, IL-12 expression is enabled in CD11c(low) cells, but not in macrophages or granulocytes. These findings support the concept of DC as the major IL-12 producers in spleens, but challenge the notion that CD8(+) and CD8(-) DC are destined to selectively induce Th1 or Th2 responses, respectively. Thus, the nature of the stimulating substance is important in determining which DC subsets are activated to produce IL-12. C1 US FDA, Ctr Biol Evaluat & Res, Div Hematol, Lab Plasma Derivat, Bethesda, MD 20892 USA. Imperial Canc Res Fund, Immunobiol Lab, London WC2A 3PX, England. NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Scott, DE (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Hematol, Lab Plasma Derivat, Bldg 29,Room 232,8800 Rockville Pike, Bethesda, MD 20892 USA. NR 47 TC 84 Z9 88 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD AUG 1 PY 2001 VL 167 IS 3 BP 1423 EP 1430 PG 8 WC Immunology SC Immunology GA 471VM UT WOS:000170949400036 PM 11466361 ER PT J AU Hu, RQ Bekisz, J Schmeisser, H McPhie, P Zoon, K AF Hu, RQ Bekisz, J Schmeisser, H McPhie, P Zoon, K TI Human IFN-alpha protein engineering: The amino acid residues at positions 86 and 90 are important for antiproliferative activity SO JOURNAL OF IMMUNOLOGY LA English DT Article ID LYMPHOBLASTOID INTERFERON-ALPHA; 3-DIMENSIONAL CRYSTAL-STRUCTURE; I INTERFERONS; EVOLUTIONARY IMPLICATIONS; CASSETTE MUTAGENESIS; RECEPTOR-BINDING; BETA RECEPTOR; CELLS; CLONING; SITES AB Human IFN-alpha is a family of structurally related proteins that exhibit a wide range of antiproliferative activities. To understand the structural basis for these different antiproliferative activities, eight recombinant human IFN-alpha hybrids (HY) of alpha 21a/alpha 2c (HY-4, HY-5) and mutants (site-directed mutagenesis (SDM)-1, 2 and cassette mutagenesis (CM)-1, 2, 3, and 4) have been expressed, purified, and characterized. The data showed that the amino acid region 81-95 is important for antiproliferative activity. Site-directed mutagenesis and cassette mutagenesis studies showed that if serine (S) 86 and asparagine (N) 90 were replaced by tyrosine (Y), the antiproliferative activity was increased. We have also observed that if Y86 was replaced by isoleucine (I), the antiproliferative activity was comparable. However, if Y86 was replaced by aspartic acid (D), lysine (K), or alanine (A), the antiproliferative activity was substantially decreased. Our results indicate that Y and/or I at position 86 and Y at position 90 are very important in antiproliferative activity of human IFN-alpha. Circular dichroism spectra showed that the amino acid replacements at position 86 did not change the secondary structure. Thus the biological activity changes among those mutants do not appear to be due to conformational changes. The results also suggest that hydrophobic residue(s) at position 86 may be important for the interaction of the molecule with its receptor. The competitive binding data correlated with the antiproliferative activity. The N-terminal region of the molecule and the hydrophobic residues (including Y and I) on the C-helix region at positions 86 and/or 90 are important for binding and antiproliferative activities of human ifn-alphas.. C1 US FDA, Ctr Biol Evaluat & Res, Div Therapeut Prot, Bethesda, MD 20892 USA. NIDDKD, NIH, Bethesda, MD 20892 USA. RP Hu, RQ (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Therapeut Prot, Bethesda, MD 20892 USA. NR 38 TC 19 Z9 22 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD AUG 1 PY 2001 VL 167 IS 3 BP 1482 EP 1489 PG 8 WC Immunology SC Immunology GA 471VM UT WOS:000170949400043 PM 11466368 ER PT J AU Tadokoro, T Kobayashi, N Beer, J Zmudzka, B Hearing, V Korossy, K Ito, S Wakamatsu, K AF Tadokoro, T Kobayashi, N Beer, J Zmudzka, B Hearing, V Korossy, K Ito, S Wakamatsu, K TI DNA damage and melanin production induced by ultraviolet radiation in human skin within various racial/ethnic groups SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. US FDA, CDRH, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD AUG PY 2001 VL 117 IS 2 MA 650 BP 498 EP 498 PG 1 WC Dermatology SC Dermatology GA 466WC UT WOS:000170668300682 ER PT J AU Kushimoto, T Basrur, V Matsunaga, J Vieira, W Muller, J Appella, E Hearing, V AF Kushimoto, T Basrur, V Matsunaga, J Vieira, W Muller, J Appella, E Hearing, V TI Melanosome mapping by purification of early stage melanosomes SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. US FDA, CBER, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD AUG PY 2001 VL 117 IS 2 MA 715 BP 509 EP 509 PG 1 WC Dermatology SC Dermatology GA 466WC UT WOS:000170668300745 ER PT J AU Pershing, L Nelson, J Corlett, J Hare, D Shrivastava, S AF Pershing, L Nelson, J Corlett, J Hare, D Shrivastava, S TI Application of dermatopharmacokinetic approach in the assessment of clinical bioequivalent and bio-inequivalent tretinoin gel products SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Univ Utah, Salt Lake City, UT 84112 USA. US FDA, Off Pharmaceut Sci, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD AUG PY 2001 VL 117 IS 2 MA 948 BP 547 EP 547 PG 1 WC Dermatology SC Dermatology GA 466WC UT WOS:000170668300978 ER PT J AU Smith, JF Rockwell, RJ Parkinson, J Dennis, JE AF Smith, JF Rockwell, RJ Parkinson, J Dennis, JE TI Are you a laser product manufacturer?: Interpretation of the FDA regulations applicable to laser product manufacturers SO JOURNAL OF LASER APPLICATIONS LA English DT Article DE laser; laser products; product safety; standards; compliance; laser manufacturer; CDRH AB Often, companies that manufacture, modify, or integrate laser products find themselves to be uncertain as to whether they are required to comply with the U.S. Federal Laser Product Performance Standard (FLPPS). The FLPPS is a regulation that applies to laser products manufactured on or after August 2, 1976 unless specifically exempted. Many companies make or alter (modify) specific laser products solely for in-house use for widespread applications, including industrial processes and process and product quality control systems. In-house applications may require several units to be built. Often a basic design may be altered for a different end-user within the company. The in-house system may consist of integrating a purchased laser system with handler and process control equipment, or modifying a complete purchased piece of equipment to suit the specific requirements of the in-house user. Other companies purchase existing certified laser products such as bar code reader, position sensor, or micrometer, etc. and incorporate these components into a machine which they manufacture and sell. In these scenarios, the question is often asked: "Am I a laser product "manufacturer" subject to the FLPPS?" The answer in many cases may at first be unclear. Occasionally there is also some confusion on other topics regarding laser product safety. Among them are: the applicability of the FLPPS vs the American National Standard Institute (ANSI) Z136.1 Standard for the safe use of lasers, the question of when has a product been modified; and what is a "manufacturer" in the context of applying the FLPPS. This paper addresses the fore mentioned topics, including history and various scenarios that will help to determine when "manufacturing" has taken place. (C) 2001 Laser Institute of America. C1 Rockwell Laser Ind, Cincinnati, OH 45243 USA. US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Smith, JF (reprint author), Rockwell Laser Ind, Cincinnati, OH 45243 USA. NR 1 TC 2 Z9 2 U1 1 U2 1 PU LASER INST AMER PI ORLANDO PA 13501 INGENUITY DR, SUITE 128, ORLANDO, FL 32826 USA SN 1042-346X J9 J LASER APPL JI J. Laser Appl. PD AUG PY 2001 VL 13 IS 4 BP 150 EP 153 PG 4 WC Materials Science, Multidisciplinary; Optics; Physics, Applied SC Materials Science; Optics; Physics GA 467MN UT WOS:000170708500004 ER PT J AU Stewart, D Reineke, K Ulaszek, J Fu, T Tortorello, M AF Stewart, D Reineke, K Ulaszek, J Fu, T Tortorello, M TI Growth of Escherichia coli O157 : H7 during sprouting of alfalfa seeds SO LETTERS IN APPLIED MICROBIOLOGY LA English DT Article ID BEEF AB Aims: Escherichia coli O157:H7 was monitored daily during sprouting of alfalfa seeds inoculated at high (3.92 log(10) cfu g(-1)) and low (1.86 log(10) cfu g(-1)) levels to assess the extent of pathogen growth during production. Methods and Results: Sprouts and rinse water were tested by direct and membrane filter plating on modified sorbitol MacConkey agar and BCM O157:H7(+) agar; the antibody-direct epifluorescent filter technique; and rapid immunoassays. The pathogen reached maximum populations after one and two days of sprouting seeds inoculated at high and low levels, respectively; in either case, populations of 5-6 log(10) cfu g(-1) were reached. Detection limits of two rapid immunoassays, Reveal and VIP, without enrichment were determined to be 5-7 log(10) cfu ml(-1). Conclusions: These results show the ability of E. coli O157:H7 to grow to high levels during sprouting; however, because these levels may be below detection limits, it is necessary to include enrichment when monitoring sprout production for E. coli O157:H7 by the rapid test kits. Significance and Impact of the Study: The data indicate that sprouts may harbor high levels of pathogens. The appropriate use of rapid test methods for pathogen monitoring during sprouting is indicated. C1 US FDA, Natl Ctr Food Safety & Technol, Summit Argo, IL 60501 USA. IIT, Natl Ctr Food Safety & Technol, Summit Argo, IL 60501 USA. RP Tortorello, M (reprint author), US FDA, Natl Ctr Food Safety & Technol, 6502 S Archer Rd, Summit Argo, IL 60501 USA. NR 7 TC 31 Z9 31 U1 0 U2 4 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0266-8254 J9 LETT APPL MICROBIOL JI Lett. Appl. Microbiol. PD AUG PY 2001 VL 33 IS 2 BP 95 EP 99 DI 10.1046/j.1472-765x.2001.00957.x PG 5 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 456VJ UT WOS:000170102700001 PM 11472514 ER PT J AU Zheng, Q AF Zheng, Q TI On the dispersion index of a Markovian molecular clock SO MATHEMATICAL BIOSCIENCES LA English DT Article DE neutral theory; molecular clock; dispersion index; Markov chain ID NUCLEOTIDE SUBSTITUTIONS; BASE SUBSTITUTIONS; MAMMALIAN GENES; EVOLUTION; SEQUENCES; NUMBER; RATES; DNA; BIASES AB The number of nucleotide substitutions accumulated in a gene or in a lineage is an important random variable in the study of molecular evolution. Of particular interest is the ratio of the variance to the mean of that random variable, often known as the dispersion index. Because nucleotide substitution is most commonly modeled by a continuous-time four-state Markov chain, this paper provides a systematic method of computing the dispersion indices exhibited by a continuous-time four-state Markov chain. Using this method along with computer algebra and Monte Carlo simulation, this paper offers partially proven conjectures that were supported by thorough computer experiments. It is believed that the Tamura model, the equal-input model and the Takahata-Kimura model always exhibit dispersion indices less than 2. It is also believed that a general four-state model can be chosen to exhibit a dispersion index of any desired magnitude, although the chance of a randomly chosen such model exhibiting a dispersion index greater than 2 is as small as about 2%. Relevance of these findings to the neutral theory is discussed. (C) 2001 Published by Elsevier Science Inc. C1 Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. RP Zheng, Q (reprint author), Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, HFT-10,3900 NCTR Dr, Jefferson, AR 72079 USA. NR 35 TC 8 Z9 8 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0025-5564 J9 MATH BIOSCI JI Math. Biosci. PD AUG PY 2001 VL 172 IS 2 BP 115 EP 128 DI 10.1016/S0025-5564(01)00067-0 PG 14 WC Biology; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology GA 471HX UT WOS:000170924900004 PM 11520502 ER PT J AU Ball, R Ball, LK Wise, RP Braun, MM Beeler, JA Salive, ME AF Ball, R Ball, LK Wise, RP Braun, MM Beeler, JA Salive, ME TI Stevens-Johnson syndrome after vaccination - Reply SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Letter C1 US FDA, Ctr Biol Evaluat & Res, Off Biostat & Epidemiol, Rockville, MD 20857 USA. US FDA, Ctr Biol Evaluat & Res, Off Vaccines Res & Review, Rockville, MD 20857 USA. RP Ball, R (reprint author), US FDA, Ctr Biol Evaluat & Res, Off Biostat & Epidemiol, Rockville, MD 20857 USA. NR 6 TC 0 Z9 0 U1 0 U2 0 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 AUG PY 2001 VL 20 IS 8 BP 819 EP 819 PG 1 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA 462TT UT WOS:000170436400029 ER PT J AU Kombo, LA Gerber, MA Pickering, LK Atreya, CD Breiman, RF AF Kombo, LA Gerber, MA Pickering, LK Atreya, CD Breiman, RF TI Intussusception, infection, and immunization Summary of a workshop on rotavirus SO PEDIATRICS LA English DT Article DE rotavirus; intussusception; rhesus rotavirus vaccine tetravalent; workshop ID CHILDREN; LIPOPOLYSACCHARIDE; MICE AB This article summarizes the proceedings of a workshop sponsored by the National Institutes of Health and the National Vaccine Program Office, and held in Bethesda, Maryland, on January 21, 2000. The objective of the meeting was to focus research toward an understanding of the basis for the possible association between intussusception and the reassortant rhesus-human rotavirus vaccine tetravalent (RRV-TV). After numerous reports of intussusception after administration of RRV-TV, the manufacturers of this vaccine voluntarily withdrew it from the United States market. The American Academy of Pediatrics, the Advisory Committee on Immunization Practices, and the American Academy of Family Physicians also withdrew their original recommendations for administration of RRV-TV to children at 2, 4, and 6 months of age. These actions will have global implications for the prevention of morbidity and mortality attributable to rotavirus infection. Benefit-cost ratios for the use of RRV-TV will be substantially different in developing countries compared with developed countries. Therefore, extensive research is needed in both of these settings, to further our understanding of the epidemiology, pathogenesis, and pathology of both rotavirus disease and intussusception to enable optimal prevention. The workshop reviewed the current understanding of the possible association between RRV-TV and intussusception, as well as the possible association between a variety of viral infections and intussusception. The workshop also identified critical areas of research regarding this possible association. This research will be essential not only for the development of safe and effective rotavirus vaccines, but for the development of other oral vaccines as well. C1 Natl Vaccine Program Off, Atlanta, GA 30333 USA. NIAID, NIH, Bethesda, MD 20892 USA. Ctr Dis Control & Prevent, Natl Immunizat Program, Atlanta, GA USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. Ctr Dis Control & Prevent, Natl Ctr Infect Dis, Atlanta, GA USA. RP Kombo, LA (reprint author), Natl Vaccine Program Off, 1600 Clifton Rd NE,MS D-66, Atlanta, GA 30333 USA. NR 29 TC 12 Z9 12 U1 0 U2 1 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD AUG PY 2001 VL 108 IS 2 AR e37 DI 10.1542/peds.108.2.e37 PG 7 WC Pediatrics SC Pediatrics GA 458TZ UT WOS:000170211800018 PM 11483847 ER PT J AU Rodriguez, EM Staffa, JA Graham, DJ AF Rodriguez, EM Staffa, JA Graham, DJ TI The role of databases in drug postmarketing surveillance SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Article; Proceedings Paper CT Mid-Year Symposium of the International-Society-for-Pharmacoepidemiology CY APR, 2000 CL CHAPEL HILL, NORTH CAROLINA SP Int Soc Pharmacoepidemiology DE pharmacoepidemiology; adverse drug reactions; clinical trials; phase IV; consumer product safety; pharmacovigilance AB This paper describes the role of databases used for postmarketing surveillance of drugs at the United States Food and Drug Administration (FDA). First we describe the Adverse Event Reporting System (AERS), the largest database of adverse event reports in the world. Next, we explain the methods we have used for assembling these adverse event reports into a case series and analysing them, as well as techniques for employing drug use databases to construct reporting rates in the evaluation of drug safety issues. Finally, we discuss the FDA's use of the databases it accesses through its Cooperative Agreement Program to conduct high priority studies to support regulatory decision-making. Published in 2001 by John Wiley & Sons, Ltd. C1 US FDA, Div Drug Risk Evaluat 2, Off Postmarketing Drug Risk Assessment, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Rodriguez, EM (reprint author), US FDA, Div Drug Risk Evaluat 2, Off Postmarketing Drug Risk Assessment, Ctr Drug Evaluat & Res, 5600 Fishers Lane,HFD-440, Rockville, MD 20857 USA. NR 6 TC 58 Z9 59 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG-SEP PY 2001 VL 10 IS 5 BP 407 EP 410 DI 10.1002/pds.615 PG 4 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 501UN UT WOS:000172704600011 PM 11802586 ER PT J AU Ellenberg, SS AF Ellenberg, SS TI Safety considerations for new vaccine development SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Article; Proceedings Paper CT Mid-Year Symposium of the International-Society-for-Pharmacoepidemiology CY APR, 2000 CL CHAPEL HILL, NORTH CAROLINA SP Int Soc Pharmacoepidemiology DE vaccine; clinical trials; adverse events; spontaneous reports; post-market surveillance ID REASSORTANT ROTAVIRUS VACCINE; CONTROLLED TRIAL; EFFICACY AB Vaccines are highly effective and extremely safe. Although most known vaccine reactions are minor (e.g. fever, injection site pain or swelling), rare but serious reactions such as vaccine-associated paralytic polio do occur. When large populations are vaccinated, some adverse health events may occur by chance shortly after vaccination. It is difficult to determine whether these are truly coincidental or attributable to the vaccine. The most reliable way to assess causality is in a controlled study, but clinical trials of new vaccines are typically too small to detect rare but serious effects. If the size of these trials were increased, much more could be learned about the safety of a vaccine prior to its exposure to entire populations. This information would increase confidence in the safety of vaccines, would be a valuable resource for assessing spontaneous reports of adverse events after licensure, and would reduce the risk of licensing a new vaccine that had the potential to cause severe injury to a small proportion of vaccinees. Published in 2001 by John Wiley & Sons, Ltd. C1 US FDA, Off Biostat & Epidemiol, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. RP Ellenberg, SS (reprint author), 1401 Rockville Pike, Rockville, MD 20852 USA. NR 16 TC 19 Z9 19 U1 0 U2 2 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG-SEP PY 2001 VL 10 IS 5 BP 411 EP 415 DI 10.1002/pds.616 PG 5 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 501UN UT WOS:000172704600012 PM 11802587 ER PT J AU Chen, JJ Chen, YJ Rice, G Teuschler, LK Hamernik, K Protzel, A Kodell, RL AF Chen, JJ Chen, YJ Rice, G Teuschler, LK Hamernik, K Protzel, A Kodell, RL TI Using dose addition to estimate cumulative risks from exposures to multiple chemicals SO REGULATORY TOXICOLOGY AND PHARMACOLOGY LA English DT Article DE chemical mixture; low-dose extrapolation; relative potency factor (RPF); similar action; toxicity equivalence factor (TEF) ID COMMON MECHANISM; TOXICITY AB The Food Quality Protection Act (FQPA) of 1996 requires the EPA to consider the cumulative risk from exposure to multiple chemicals that have a common mechanism of toxicity. Three methods, hazard index (HI), point-of-departure index (PODI), and toxicity equivalence factor (TEF), have commonly been considered to estimate the cumulative risk. These methods are based on estimates of ED10 (point of departure) and reference doses from the dose-response functions of individual chemicals. They do not incorporate the actual dose-response function of the mixture from multiple chemical exposures. Dose addition is considered to be an appropriate approach to cumulative risk assessment because it assumes that the chemicals of interest act in accordance with a common mode of action (a similar action). This paper proposes a formal statistical procedure to estimate the cumulative risk by fitting the dose-response model of the mixture under dose addition. The relative potency between two chemicals is estimated directly from the joint dose response model of the mixture. An example data set of four drugs representing four chemicals is used to illustrate the proposed procedure and compare it to the HI, PODI, and TEF methods. C1 US FDA, Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. US EPA, Natl Ctr Environm Assessment, Cincinnati, OH 45268 USA. US EPA, Div Hlth Effects, Washington, DC 20460 USA. RP Chen, JJ (reprint author), US FDA, Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. NR 8 TC 14 Z9 15 U1 0 U2 6 PU ACADEMIC PRESS INC 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 AUG PY 2001 VL 34 IS 1 BP 35 EP 41 DI 10.1006/rtph.2001.1485 PG 7 WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology SC Legal Medicine; Pharmacology & Pharmacy; Toxicology GA 467QC UT WOS:000170714400004 PM 11502154 ER PT J AU Kopecko, DJ Hu, L Zaal, KJM AF Kopecko, DJ Hu, L Zaal, KJM TI Campylobacter jejuni - microtubule-dependent invasion SO TRENDS IN MICROBIOLOGY LA English DT Review ID EPITHELIAL-CELL CULTURES; INTRACELLULAR SURVIVAL; CHLAMYDIA-TRACHOMATIS; INTESTINAL-CELLS; HEP-2 CELLS; INTERNALIZATION; INFECTION; CAMPYLOBACTER-JEJUNI-81-176; TRANSLOCATION; PHAGOCYTOSIS AB Campylobacter jejuni is the leading bacterial cause of food-borne illness worldwide and a major cause of Guillain-Barre paralysis. Recent molecular and cellular studies of one well-characterized C. jejuni strain have begun to unravel the details of an unusual microtubule-dependent (actin-filament-independent) gut-invasion mechanism, through which at least some C. jejuni initiate disease. Although responsible for causing a human dysenteric syndrome remarkably similar to that triggered by Shigella spp., current evidence suggests that C. jejuni use some markedly different molecular mechanisms of pathogenesis compared with shigellae. C1 US FDA, Ctr Biol Evaluat & Res, Lab Enter & Sexually Transmitted Dis, Bethesda, MD 20892 USA. NINDS, Cellular Org Unit, Neurobiol Lab, NIH, Bethesda, MD 20892 USA. RP Kopecko, DJ (reprint author), US FDA, Ctr Biol Evaluat & Res, Lab Enter & Sexually Transmitted Dis, Bldg 29-420,NIH Campus, Bethesda, MD 20892 USA. NR 48 TC 58 Z9 59 U1 1 U2 4 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0966-842X J9 TRENDS MICROBIOL JI Trends Microbiol. PD AUG PY 2001 VL 9 IS 8 BP 389 EP 396 DI 10.1016/S0966-842X(01)02107-2 PG 8 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 463DV UT WOS:000170462300010 PM 11514222 ER PT J AU Tsuyuki, S Horvath-Arcidiacono, J Bloom, E AF Tsuyuki, S Horvath-Arcidiacono, J Bloom, E TI Redox modulation of porcine target cells: the combination of nitric oxide and thiol deprivation protects endothelial cells from lysis by IL-2-activated human natural killer (NK) cells SO XENOTRANSPLANTATION LA English DT Meeting Abstract C1 US FDA, CBER, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD AUG PY 2001 VL 8 SU 1 MA 604 BP 118 EP 118 PG 1 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 477XD UT WOS:000171308800321 ER PT J AU Bloom, ET AF Bloom, ET TI New FDA xenotransplantation documents: a proposed rule and a draft guidance SO XENOTRANSPLANTATION LA English DT Editorial Material C1 US FDA, CBER, DCGT, LCI, Bethesda, MD 20892 USA. RP Bloom, ET (reprint author), US FDA, CBER, DCGT, LCI, HFM 518,Bldg 29B,Room 2NN04,8800 Rockville Pike, Bethesda, MD 20892 USA. NR 1 TC 1 Z9 1 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD AUG PY 2001 VL 8 IS 3 BP 153 EP 154 PG 2 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 456NP UT WOS:000170089200006 PM 11472622 ER PT J AU Furumura, M Potter, SB Toyofuku, K Matsunaga, J Muller, J Hearing, VJ AF Furumura, M Potter, SB Toyofuku, K Matsunaga, J Muller, J Hearing, VJ TI Involvement of ITF2 in the transcriptional regulation of melanogenic genes SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID AGOUTI-RELATED PROTEIN; MELANOCYTE-SPECIFIC TRANSCRIPTION; WAARDENBURG SYNDROME; IN-VITRO; SIGNAL PROTEIN; MELANOCORTIN RECEPTORS; TYROSINASE GENE; SPLICE VARIANT; CYCLIC-AMP; E-BOX AB In response to agouti signal protein, melanocytes switch from producing eumelanin to pheomelanin concomitant with the down-regulation of melanogenic gene transcription. We previously reported that a ubiquitous basic helix-loop-helix transcription factor, known as ITF2, is up-regulated during this switch, and we now report that treatment of melanocytes with melanocyte-stimulating hormone down-regulates expression of ITF2. To more fully characterize the involvement of ITF2 in regulating melanogenic gene transcription, ITF2 sense or antisense constructs were introduced into melan-a melanocytes. Gene and protein expression analyses and luciferase reporter assays using promoters from melanogenic genes showed that up-regulation of ITF2 suppressed melanogenic gene expression as well as the expression of Mitf, a melanocyte-specific transcription factor. In addition, stable ITF2 sense transfectants had significant reductions in pigmentation and a less dendritic phenotype compared with mock transfectants. In contrast, ITF2 antisense-transfected melanocytes were more pigmented and more dendritic. These results demonstrate that up-regulation of ITF2 during the pheomelanin switch is functionally significant and reveal that differential expression of a ubiquitous basic helix-loop-helix transcription factor can modulate expression of melanogenic genes and the differentiation of melanocytes. C1 NCI, Pigment Cell Biol Sect, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. US FDA, Div Virol, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Hearing, VJ (reprint author), NCI, Pigment Cell Biol Sect, Cell Biol Lab, NIH, Bldg 37,Rm 1B25, Bethesda, MD 20892 USA. NR 53 TC 30 Z9 31 U1 0 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 27 PY 2001 VL 276 IS 30 BP 28147 EP 28154 DI 10.1074/jbc.M101626200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 456QH UT WOS:000170093400055 PM 11382753 ER PT J AU Patterson, LJ Aberdeen, A Kone, J Haben, M Raymond, M Berkower, I AF Patterson, LJ Aberdeen, A Kone, J Haben, M Raymond, M Berkower, I TI Formation of HIV-1 envelope-hepatitis B core antigen hybrids with high affinity for CD4 SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE HIV vaccine; immunogenicity; gp120; particle assembly ID HUMAN MONOCLONAL-ANTIBODY; VIRUS CORE; NEUTRALIZING ANTIBODIES; GP120; GLYCOPROTEIN; PROTEIN; EPITOPE; DOMAIN; IMMUNOGENICITY; PARTICLES AB We have identified an acceptor site on HIV gp120, where foreign protein sequences can be inserted while retaining the native conformation of gp120. The resulting hybrids showed dual antigenicity, normal glycosylation, and high affinity binding of the CD4 receptor. This site allows insertion of highly immunogenic proteins such as core antigen of hepatitis B virus. By combining the immunogenicity of the carrier protein with the antigenicity of gp120, these hybrids may lead to modified HIV-1 antigens with enhanced immunogenicity. (C) 2001 Academic Press. C1 NIH, Immunoregulat Lab, DVP, Off Vaccine Res & Review,Ctr Biol,US FDA, Bethesda, MD 20892 USA. NCI, Basic Res Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Berkower, I (reprint author), NIH, Immunoregulat Lab, DVP, Off Vaccine Res & Review,Ctr Biol,US FDA, Bldg 29,Room 523,NIH Campus, Bethesda, MD 20892 USA. NR 30 TC 1 Z9 1 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUL 20 PY 2001 VL 285 IS 3 BP 639 EP 643 DI 10.1006/bbrc.2001.5227 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 457HP UT WOS:000170131400011 PM 11453640 ER PT J AU Weisz, A Mazzola, EP Matusik, JE Ito, Y AF Weisz, A Mazzola, EP Matusik, JE Ito, Y TI Preparative separation of isomeric 2-(2-quinolinyl)-1H-indene-1,3(2H)-dione monosulfonic acids of the color additive D&C Yellow No. 10 (Quinoline Yellow) by pH-zone-refining counter-current chromatography SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article DE counter-current chromatography; positional isomers; D&C yellow no. 10; Quinoline Yellow; monosulfonic acids; sulfonic acids; dyes ID PHLOXINE-B; PURIFICATION; COMPONENTS AB The main components of the color additive D&C Yellow No. 10 (Quinoline Yellow, Color Index No. 47005), 2-(2-quinolinyl)-1H-indene-1,3(2H)-dione-6 ' -sulfonic acid (6SA) and 2-(2-quinolinyl)-1H-indene-1,3(2H)-dione-8 ' -sulfonic acid (8SA), were isolated from the dye mixture by pH-zone-refining counter-current chromatography (CCC) in the ion-exchange mode. These positional isomers were separated from a portion of dye using sulfuric acid as the retainer acid and dodecylamine as the ligand (ion exchanger). The added ligand enhanced the partitioning of the hydrophilic components in the organic stationary phase of the two-phase solvent system that consisted of isoamyl alcohol-methyl tert-butyl ether-acetonitrile-water (3:1:1:5). Thus, separation of 1.8 g of D&C Yellow No. 10 using the above method resulted in 0.6 g of 6SA and 0.18 g of 8SA of over 99% purity. The isolated compounds were characterized by mass spectrometry and proton nuclear magnetic resonance with correlated spectroscopy assignments. The study exemplifies a new field of applications for pH-zone-refining CCC, to the separation of positional isomers of strongly hydrophylic compounds containing sulfonic acid groups. Published by Elsevier Science B.V. C1 US FDA, Off Cosmet & Colors, Washington, DC 20204 USA. US FDA, Off Sci Anal & Support, Washington, DC 20204 USA. NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. RP Weisz, A (reprint author), US FDA, Off Cosmet & Colors, Washington, DC 20204 USA. NR 22 TC 26 Z9 28 U1 2 U2 12 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 20 PY 2001 VL 923 IS 1-2 BP 87 EP 96 DI 10.1016/S0021-9673(01)00984-0 PG 10 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 458PM UT WOS:000170203800011 PM 11510564 ER PT J AU La Grenade, L Graham, D Trontell, A AF La Grenade, L Graham, D Trontell, A TI Myocarditis and cardiomyopathy associated with clozapine use in the United States SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 US FDA, Rockville, MD 20857 USA. RP La Grenade, L (reprint author), US FDA, Rockville, MD 20857 USA. NR 3 TC 77 Z9 80 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUL 19 PY 2001 VL 345 IS 3 BP 224 EP 225 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 453JM UT WOS:000169912800027 PM 11463031 ER PT J AU Rexrode, KM Buring, JE Glynn, RJ Stampfer, MJ Youngman, LD Gaziano, JM AF Rexrode, KM Buring, JE Glynn, RJ Stampfer, MJ Youngman, LD Gaziano, JM TI Analgesic use and renal function in men SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; NONNARCOTIC ANALGESICS; COLORECTAL-CANCER; FAILURE; DISEASE; RISK; ASPIRIN; ACETAMINOPHEN; ABUSE AB Context Several case-control studies suggest an association between analgesic use and increased risk of chronic renal disease, but few cohort studies have examined this association. Objective To determine whether analgesic use is associated with risk of renal dysfunction. Design and Setting Cohort study of analgesic use data from the Physicians' Health Study, which lasted 14 years from September 1982 to December 1995 with annual follow-up. Participants A total of 11 032 initially healthy men who provided blood samples and self-report of analgesic use. Main Outcome Measures Elevated creatinine level defined as 1.5 mg/dL (133 mu mol/L) or higher and a reduced creatinine clearance defined as 55 mL/min (0.9 mL/s) or less, and self-reported use of acetaminophen, aspirin, and other nonsteroidal antiinflammatory drugs (never [<12 pills]; 12-1499 pills; 1500-2499 pills; and 2500 pills). Results PI total of 460 men had elevated creatinine levels (4.2%) and 1258 had reduced creatinine clearance (11.4%). Mean creatinine levels and creatinine clearances were similar among men who did not use analgesics and those who did, even at total intakes of 2500 or more pills. In multivariable analyses adjusted for age; body mass index; history of hypertension, elevated cholesterol, and diabetes; occurrence of cardiovascular disease; physical activity; and use of other analgesics, the relative risks of elevated creatinine level associated with intake of 2500 or more pills were 0.83 (95% confidence interval [CI], 0.50-1.39, P for trend =.05) for acetaminophen, 0.98 (95% CI, 0.53-1.81; P for trend =.96) for aspirin, and 1.07 (95% CI, 0.71-1.64; P for trend =.86) for other nonsteroidal anti-inflammatory drugs. Ho association was observed be tween analgesic use and reduced creatinine clearance. Conclusions Moderate analgesic use in this cohort study of initially healthy men was not associated with increased risk of renal dysfunction. C1 Brigham & Womens Hosp, Dept Med, Div Prevent Med, Channing Lab, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. US FDA, Res Off, Laurel, MD USA. Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA. VA Boston Healthcare Syst, Boston, MA USA. RP Gaziano, JM (reprint author), Brigham & Womens Hosp, Dept Med, Div Prevent Med, Channing Lab, 900 Commonwealth Ave, Boston, MA 02215 USA. OI Rexrode, Kathryn/0000-0003-3387-8429 FU NCI NIH HHS [CA-34944, CA-40360]; NHLBI NIH HHS [HL-26490, HL-34595] NR 27 TC 60 Z9 62 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 JUL 18 PY 2001 VL 286 IS 3 BP 315 EP 321 DI 10.1001/jama.286.3.315 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 452QA UT WOS:000169869200022 PM 11466097 ER PT J AU Alayash, AI Summers, AG Wood, F Jia, YP AF Alayash, AI Summers, AG Wood, F Jia, YP TI Effects of glutaraldehyde polymerization on oxygen transport and redox properties of bovine hemoglobin SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE bovine hemoglobin; glutaraldehyde; blood substitutes ID CHLORIDE-BINDING SITES; HYDROGEN-PEROXIDE; BLOOD SUBSTITUTES; FERRYL INTERMEDIATE; DISTAL POCKET; NITRIC-OXIDE; MYOGLOBIN; MECHANISM; CARRIERS; METHEMOGLOBIN AB Crosslinking of bovine Hb (HbBv) with glutaraldehyde produces a mixture of low oxygen affinity (P-50) tetrameric and polymeric Hb species (PolyHbBv). Under physiological conditions the P-50 of HbBv and PolyHbBv were 27 and 35 mmHg, respectively. The dependence of the P-50 on pH and chloride ions and the cooperativity (n(50)) of the protein were diminished as a result of glutaraldehyde modification. Rapid kinetic studies showed greater overall rates of oxygen dissociation (k(off)) with little or no change in the association of CO (k(on)) to the modified protein. The rate of nitric oxide (NO)-induced oxidation of the PolyHbBv was slightly lower than that of HbBv, Autoxidation rate of PolyHbBv was 1.4 times faster than that of HbBv. The reaction of hydrogen peroxide (H2O2) with the ferrous (Fe2+) and ferric (Fe3+) forms of the proteins led to the formation of a more stable ferrylHb (Fe4+) in the case of PolyHbBv. Glutaraldehyde polymerization of HbBv alters its normal allosteric mechanisms, autoxidation kinetics and other related redox properties, which may compromise its function and cause greater toxicity when used as an oxygen transport fluid. (C) 2001 Academic Press. C1 US FDA, Ctr Biol Evaluat & Res, Div Hematol, Lab Plasma Derivat, Bethesda, MD 20892 USA. RP Alayash, AI (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Hematol, Lab Plasma Derivat, Bethesda, MD 20892 USA. NR 39 TC 50 Z9 51 U1 0 U2 8 PU ACADEMIC PRESS INC 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 JUL 15 PY 2001 VL 391 IS 2 BP 225 EP 234 DI 10.1006/abbi.2001.2426 PG 10 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 454TL UT WOS:000169987800010 PM 11437354 ER PT J AU Joshi, BH Plautz, GE Puri, RK AF Joshi, BH Plautz, GE Puri, RK TI Correspondence re: B. H. Joshi et al., interleukin-13 receptor alpha chain: A novel tumor-associated transmembrane protein in primary explants of human malignant gliomas. Cancer Res., 60 : 1168-1172, 2000. Reply SO CANCER RESEARCH LA English DT Letter ID CARCINOMA CELL-LINES; COMMON GAMMA-CHAIN; PSEUDOMONAS EXOTOXIN; INTERLEUKIN-4-PSEUDOMONAS EXOTOXIN; SIGNAL-TRANSDUCTION; (IL)-13 BINDING; IL-4 RECEPTOR; PHOSPHORYLATION; COMPONENT; CLONING C1 US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. Yale Univ, Sch Med, New Haven, CT 06520 USA. RP Joshi, BH (reprint author), US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. NR 27 TC 0 Z9 0 U1 0 U2 0 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 JUL 15 PY 2001 VL 61 IS 14 BP 5661 EP 5662 PG 2 WC Oncology SC Oncology GA 451YN UT WOS:000169830500054 ER PT J AU Sacks, LV AF Sacks, LV TI Some healthy skepticism about inhaled therapy for tuberculosis - Reply SO CLINICAL INFECTIOUS DISEASES LA English DT Letter C1 US FDA, Div Special Pathogens & Immunol Drug Prod, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Sacks, LV (reprint author), Ctr Drug Evaluat & Res, Div Special Pathogens, HFD 590, 9201 Corp Blvd, Rockville, MD 20850 USA. NR 2 TC 0 Z9 0 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 JUL 15 PY 2001 VL 33 IS 2 BP 267 EP 267 DI 10.1086/321824 PG 1 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 444FD UT WOS:000169387700022 ER PT J AU Williams, G Cortazar, P Pazdur, R AF Williams, G Cortazar, P Pazdur, R TI Developing drugs to decrease the toxicity of chemotherapy SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Letter ID DOXORUBICIN-CONTAINING THERAPY; ADVANCED BREAST-CANCER; CARDIOPROTECTION; DEXRAZOXANE C1 US FDA, Rockville, MD 20857 USA. RP Williams, G (reprint author), US FDA, Rockville, MD 20857 USA. NR 4 TC 7 Z9 8 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 15 PY 2001 VL 19 IS 14 BP 3439 EP 3440 PG 2 WC Oncology SC Oncology GA 452DB UT WOS:000169840900020 PM 11454894 ER PT J AU Wang, SJ Hung, HMJ Tsong, Y Cui, L AF Wang, SJ Hung, HMJ Tsong, Y Cui, L TI Group sequential test strategies for superiority and non-inferiority hypotheses in active controlled clinical trials SO STATISTICS IN MEDICINE LA English DT Article ID EQUIVALENCE TEST; SAMPLE-SIZE AB In a group sequential active controlled clinical trial, the study hypothesis may be a superiority hypothesis that an experimental treatment is more effective than the active control therapy or a non-inferiority hypothesis that the treatment is no worse than the active control within some non-inferiority range. When it is necessary to plan for testing the superiority and the non-inferiority hypotheses, we propose an adaptive group sequential closed test strategy by which the sample size is planned for testing superiority and is to be increased for showing non-inferiority given that it is deemed more plausible than superiority based on the observed sample path during the course of the trial. The proposed adaptive test strategy is valid in terms of having the type I error probability maintained at the targeted ct level for both superiority and non-inferiority, It has power advantage or sample size saving over the traditional group sequential test designed for testing either superiority only or non-inferiority only. Copyright (C) 2001 John Wiley & Sons, Ltd. C1 US FDA, Div Biometr 2, OB CDER, Rockville, MD 20857 USA. US FDA, Div Biometr 1, OB CDER, Rockville, MD 20857 USA. RP Wang, SJ (reprint author), US FDA, Div Biometr 2, OB CDER, HFD-715,5600 Fishers Lane, Rockville, MD 20857 USA. NR 22 TC 41 Z9 41 U1 1 U2 4 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 JUL 15 PY 2001 VL 20 IS 13 BP 1903 EP 1912 DI 10.1002/sim.820.abs PG 10 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 446VB UT WOS:000169533900002 PM 11427948 ER PT J AU Imam, SZ Itzhak, Y Cadet, JL Islam, F Slikker, W Ali, SF AF Imam, SZ Itzhak, Y Cadet, JL Islam, F Slikker, W Ali, SF TI Methamphetamine-induced alteration in striatal p53 and bcl-2 expressions in mice SO MOLECULAR BRAIN RESEARCH LA English DT Article DE methamphetamine; gene expression; peroxynitrite; transgenic mouse ID DNA-DAMAGING AGENTS; DOPAMINERGIC NEUROTOXICITY; TRANSGENIC MICE; IN-VITRO; INDUCTION; PROTECTS; ARREST; VIVO AB Methamphetamine (METH)-induced alterations in the expression of p53 and bcl-2 protein were studied in the striatum of wild type, neuronal nitric oxide synthase knockout (nNOS -/-) and copper zinc superoxide dismutase overexpressed (SOD-Tg) mice. METH treatment up-regulated p53 and down-regulated bcl-2 expression in the striatum of wild type mice. No significant alterations were observed in the expression of these proteins in the nNOS -/- or SOD-Tg mice. These data suggest that METH might cause its neurotoxic effects via the production of free radicals and secondary perturbations in the expression of genes known to be involved in apoptosis and cell death machinery. C1 US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Neurochem Lab, Jefferson, AR 72079 USA. Univ Miami, Sch Med, Dept Psychiat & Behav Sci, Miami, FL USA. Natl Inst Drug Abuse, Mol Neuropsychiat Sect, Intramural Res Program, Baltimore, MD USA. Hamdard Univ, Dept Med Elementol & Toxicol, Neurotoxicol Lab, New Delhi, India. RP Ali, SF (reprint author), US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Neurochem Lab, 3900 NCTR Rd,HFT-132, Jefferson, AR 72079 USA. NR 24 TC 13 Z9 13 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD JUL 13 PY 2001 VL 91 IS 1-2 BP 174 EP 178 DI 10.1016/S0169-328X(01)00139-5 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 455ZA UT WOS:000170056600021 ER PT J AU Pethe, K Alonso, S Biet, F Delogu, G Brennan, MJ Locht, C Menozzi, FD AF Pethe, K Alonso, S Biet, F Delogu, G Brennan, MJ Locht, C Menozzi, FD TI The heparin-binding haemagglutinin of M-tuberculosis is required for extrapulmonary dissemination SO NATURE LA English DT Article ID MYCOBACTERIUM-TUBERCULOSIS; HEMAGGLUTININ; GENE; IDENTIFICATION; MACROPHAGES; VIRULENCE; SURVIVAL; COMPLEX; ADHESIN; MICE AB Tuberculosis remains the world's leading cause of death due to a single infectious agent, Mycobacterium tuberculosis, with 3 million deaths and 10 million new cases per year(1). The infection initiates in the lungs and can then spread rapidly to other tissues(2). The availability of the entire M. tuberculosis genome sequence(3) and advances in gene disruption technologies(4) have led to the identification of several mycobacterial determinants involved in virulence(5-8). However, no virulence factor specifically involved in the extrapulmonary dissemination of M. tuberculosis has been identified to date. Here we show that the disruption of the M. tuberculosis or Mycobacterium bovis Bacille Calmette-Guerin (BCG) hbhA gene encoding the heparin-binding haemagglutinin adhesin (HBHA) markedly affects mycobacterial interactions with epithelial cells, but not with macrophage-like cells. When nasally administered to mice, the mutant strains were severely impaired in spleen colonization, but not in lung colonization. Coating wild-type mycobacteria with anti-HBHA antibodies also impaired dissemination after intranasal infection. These results provide evidence that adhesins such as HBHA are required for extrapulmonary dissemination, and that interactions with non-phagocytic cells have an important role in the pathogenesis of tuberculosis. They also suggest that antibody responses to HBHA may add to immune protection against tuberculosis. C1 Inst Pasteur Lille, INSERM, U447, F-59019 Lille, France. US FDA, Ctr Biol Evaluat & Res, Lab Mycobacterial Dis, Bethesda, MD 20892 USA. RP Locht, C (reprint author), Inst Pasteur Lille, INSERM, U447, 1 Rue Prof Calmette, F-59019 Lille, France. RI Pethe, Kevin/D-4505-2011; Delogu, Giovanni/I-3701-2012; Pethe, Kevin/L-1199-2013; Pethe, Kevin/F-9495-2015 OI Delogu, Giovanni/0000-0003-0182-8267; Pethe, Kevin/0000-0003-0297-0150; NR 20 TC 253 Z9 270 U1 1 U2 17 PU MACMILLAN PUBLISHERS LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD JUL 12 PY 2001 VL 412 IS 6843 BP 190 EP 194 DI 10.1038/35084083 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 451AJ UT WOS:000169778700054 PM 11449276 ER PT J AU Oshima, Y Puri, RK AF Oshima, Y Puri, RK TI Suppression of an IL-13 autocrine growth loop in a human Hodgkin/Reed-Sternberg tumor cell line by a novel IL-13 antagonist SO CELLULAR IMMUNOLOGY LA English DT Article DE interleukin-13 (IL-13); IL-13 antagonist; IL-13 cytotoxin; Hodgkin lymphoma; Hodgkin cells; Reed-Sternberg cells; Hodgkin/Reed-Sternberg tumor cells; autocrine; paracrine ID HUMAN GLIOMA-CELLS; PSEUDOMONAS EXOTOXIN; CHIMERIC PROTEIN; CARCINOMA-CELLS; INTERLEUKIN-13 RECEPTORS; SARCOMA-CELLS; CHAIN; BINDING; LYMPHOMA; DISEASE AB IL-13 has been proposed to be an autocrine growth factor for Hodgkin/Reed-Sternberg tumor cells (H/RS cells). Since we have recently identified and produced a novel IL-13 antagonist (IL-13E13K) that can suppress the biological activity of IL-13, here we examined whether IL-13E13K can inhibit growth of Hodgkin lymphoma (HL)-derived cell lines. IL-13E13K not only inhibited the growth of an unstimulated H/RS cell line (L1236) but also cells that were stimulated by exogenous IL-13 in a dose-dependent manner. Several HL-derived cell lines expressed IL-13 message and protein and message for various chains of IL-13R. FURS cell lines expressed mRNA for the IL-13R alpha1, IL-4R alpha, and IL-2R gamma chains. However, none of these cell lines expressed the IL-13R alpha2 chain. An H/R,S cell line (L1236) internalized the ligand-receptor complex after binding to a fusion protein composed of IL-13 and a mutated form of Pseudomonas exotoxin A (IL-13PE38QQR, or IL-13 cytotoxin), as IL-13 cytotoxin was specifically cytotoxic to H/RS cells an vitro. These results indicate that IL-13E13K and IL-13 cytotoxin can effectively suppress growth of a L1236 MRS cell line. Therefore, additional studies should be performed to determine the expression of IL-13 and IL-13R in primary clinical samples of Hodgkin's lymphoma and both agents should be further tested in vitro and an vivo as possible therapeutic agents for HL. C1 US FDA, Ctr Biol Evaluat & Res, Lab Molec Tumor Biol, Div Cellular & Gene Therapies, Bethesda, MD 20892 USA. RP Puri, RK (reprint author), US FDA, Ctr Biol Evaluat & Res, Lab Molec Tumor Biol, Div Cellular & Gene Therapies, 29 Lincoln Dr,NIH Bldg 29B,Room 2NN10, Bethesda, MD 20892 USA. NR 29 TC 17 Z9 18 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD JUL 10 PY 2001 VL 211 IS 1 BP 37 EP 42 DI 10.1006/cimm.2001.1828 PG 6 WC Cell Biology; Immunology SC Cell Biology; Immunology GA 479NY UT WOS:000171411500005 PM 11585386 ER PT J AU Kadlubar, F Coles, B Sweeney, C Nowell, S Lang, N AF Kadlubar, F Coles, B Sweeney, C Nowell, S Lang, N TI Biotransformation of dietary carcinogens and impact of polymorphisms SO TOXICOLOGY LA English DT Meeting Abstract C1 Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Cent Arkansas Vet Healthcare Syst, Little Rock, AR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU 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 JUL 8 PY 2001 VL 164 IS 1-3 SU S BP 6 EP 7 PG 2 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 452ZA UT WOS:000169888500017 ER PT J AU Hattan, D Kahl, L AF Hattan, D Kahl, L TI Current developments in food additive toxicology in the USA SO TOXICOLOGY LA English DT Meeting Abstract C1 US FDA, Washington, DC 20204 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 JUL 8 PY 2001 VL 164 IS 1-3 SU S BP 30 EP 31 PG 2 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 452ZA UT WOS:000169888500089 ER PT J AU Mulligan, LT AF Mulligan, LT TI International harmonization of the assessment of the human food safety of veterinary drugs SO TOXICOLOGY LA English DT Meeting Abstract C1 US FDA, Ctr Vet Med, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 JUL 8 PY 2001 VL 164 IS 1-3 SU S BP 55 EP 55 PG 1 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 452ZA UT WOS:000169888500167 ER PT J AU Tor-Agbidye, J Palmer, VS Spencer, PS AF Tor-Agbidye, J Palmer, VS Spencer, PS TI Cyanide metabolism in sulfur amino acid deficiency: relevance to cassava-related neurodegenerative diseases SO TOXICOLOGY LA English DT Meeting Abstract C1 Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. Third World Med Res Fdn, Portland, OR USA. Oregon Hlth Sci Univ, Ctr Res Occupat & Environm Toxicol, Portland, OR 97201 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 JUL 8 PY 2001 VL 164 IS 1-3 SU S BP 169 EP 170 PG 2 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 452ZA UT WOS:000169888500539 ER PT J AU Kawakami, K Takeshita, F Puri, RK AF Kawakami, K Takeshita, F Puri, RK TI Identification of distinct roles for a dileucine and a tyrosine internalization motif in the interleukin (IL)-13 binding component IL-13 receptor alpha 2 chain SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SIGNAL TRANSDUCER GP130; CARCINOMA CELL-LINES; DI-LEUCINE MOTIF; CYTOPLASMIC DOMAIN; TRANSFERRIN RECEPTOR; PSEUDOMONAS EXOTOXIN; IL-13R-ALPHA-1 CHAIN; JANUS KINASE; GAMMA-CHAIN; IN-VITRO AB Interleukin (IL)-13 receptor alpha2 (IL-13R alpha2) chain is an essential binding component for IL-13-mediated ligand binding. Recently, we have demonstrated that this receptor chain also plays an important role in the internalization of IL-13. To study the mechanism of IL-13 internalization, we generated mutated IL-13R alpha2 chains that targeted trileucine residues (Leu(335), Leu(336), and Leu(337)) in the transmembrane domain and a tyrosine motif (Tyr(343)) in the intracellular domain and transfected these cDNAs in COS-7 cells. Cells that expressed a C-terminally truncated IL-13R alpha2 chain (Delta 335) did not bind IL-13, suggesting that the trileucine region modulates IL-13 binding. Truncation of IL-13R alpha2 chain with a mutation in the trileucine region resulted in significantly decreased internalization compared with wild type IL-13R alpha2 chain transfected cells. COS-7 cells transfected with tyrosine motif mutants exhibited a similar internalization level compared with wild type IL-13R alpha2 chain transfected cells; however, dissociation of cell surface IL-13 was faster compared with wild type IL-13R alpha2 transfectants. These results were further confirmed by determining the cytotoxicity of a chimeric protein composed of IL-13 and a mutated form of Pseudomonas exotoxin (IL13-PE38QQR) to cells that expressed IL-13R alpha2 chain mutants. We further demonstrate that the IL-13R alpha2 chain is not ubiquitinated and that internalization of IL-13R alpha2 did not depend on ubiquitination, Together, our findings suggest that the dileucine motif in the trileucine region and tyrosine motif participate in IL-13R alpha2 internalization in distinct manners. C1 US FDA, NIH, Lab Mol Tumor Biol,Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Retroviral Immunol Sect, Div Viral Prod, Bethesda, MD 20892 USA. RP Puri, RK (reprint author), US FDA, NIH, Lab Mol Tumor Biol,Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Bldg 29B,Rm 2NN10,29 Lincoln Dr,MSC 4555, Bethesda, MD 20892 USA. NR 51 TC 37 Z9 38 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 6 PY 2001 VL 276 IS 27 BP 25114 EP 25120 DI 10.1074/jbc.M100936200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 451KF UT WOS:000169800700092 PM 11352909 ER PT J AU Hammons, GJ Yan-Sanders, Y Jin, B Blann, E Kadlubar, FF Lyn-Cook, BD AF Hammons, GJ Yan-Sanders, Y Jin, B Blann, E Kadlubar, FF Lyn-Cook, BD TI Specific site methylation in the 5 '-flanking region of CYP1A2 - Interindividual differences in human livers SO LIFE SCIENCES LA English DT Article DE CpG methylation; epigenetic regulation; CYP1A2; hypermethylation ID DNA METHYLATION; DEVELOPMENTAL EXPRESSION; SIGNALING PATHWAY; GENE-EXPRESSION; CYP2E1 GENE; CAFFEINE; MICROSOMES; CYTOCHROME-P-450; ENZYMES; RAT AB Human cytochrome P450 1A2 (CYP1A2) is involved in the metabolism of a large number of common drugs and is responsible for the metabolic activation of numerous promutagens and procarcinogens. Large interindividual differences exist in the expression of this enzyme. This variability has important implications for drug efficacy and cancer susceptibility. In this sudy, the methylation status of the CCGG site (bp -2759) located adjacent to an AP-1 site in the 5 ' -flanking region of the CYP1A2 gene was assessed in liver samples from a pool of 55 human donors. DNA methylation is an important epigenetic mechanism controlling gene expression and may be one of the molecular mechanisms underlying the interindividual variation. Analysis was conducted using Hpa II digestion and PCR. Results showed that individual samples varied in the methylation status at this site. The site was found to be hypermethylated in similar to 60% of the samples. To compare methylation status with level of CYP1A2 expression, results were analyzed by median test. In 44% of the samples with expression levels above the median the CCGG site was hypermethylated. However, for those samples with levels below the median hypermethylation of the site was found in 73% of the samples. The difference was statistically significant (p <0.05), These findings indicate that CpG methylation may be involved in controlling the expression of CYP1A2, with hypermethylation reducing expression. Moreover, this approach can be useful in assessing the role of site-specific DNA methylation in interindividual variation of CYP1A2. Analysis of other CpG sites in potentially important regulatory elements of the CYP1A2 gene will continue, (C) 2001 Elsevier Science. All rights reserved. C1 Natl Ctr Toxicol Res, Div Mol Epidemiol, Jefferson, AR 72079 USA. RP Hammons, GJ (reprint author), Natl Ctr Toxicol Res, Div Mol Epidemiol, HFT-100, Jefferson, AR 72079 USA. NR 34 TC 35 Z9 38 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0024-3205 J9 LIFE SCI JI Life Sci. PD JUL 6 PY 2001 VL 69 IS 7 BP 839 EP 845 DI 10.1016/S0024-3205(01)01175-4 PG 7 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 451TR UT WOS:000169817800009 PM 11487095 ER PT J AU Schwetz, BA AF Schwetz, BA TI New treatment for chronic myelogenous leukemia SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT News Item C1 US FDA, Off Commissioner, Rockville, MD 20857 USA. RP Schwetz, BA (reprint author), US FDA, Off Commissioner, HF-1,Room 14-71,5600 Fishers Ln, Rockville, MD 20857 USA. NR 1 TC 8 Z9 8 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUL 4 PY 2001 VL 286 IS 1 BP 35 EP 35 DI 10.1001/jama.286.1.35 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 449GR UT WOS:000169676400005 PM 11434814 ER PT J AU Hungerford, JM Hollingworth, TA Wekell, MM AF Hungerford, JM Hollingworth, TA Wekell, MM TI Automated kinetics-enhanced flow-injection method for histamine in regulatory laboratories: rapid screening and suitability requirements SO ANALYTICA CHIMICA ACTA LA English DT Article; Proceedings Paper CT 8th International Conference on Flow Analysis CY JUN 25-29, 2000 CL WARSAW, POLAND DE histamine; scombroid; kinetics; fluorescence; ruggedness; flow-injection analysis ID BIOGENIC-AMINES; FISH; OXIDASE AB Scombroid poisoning continues to be a leading cause of finfish-borne illness. Histamine found in implicated fish has been traditionally used as a marker, if not the cause, of scombrotoxicity. The most accepted method for detecting histamine in fish meat requires extensive manual manipulations and sample cleanup steps. To address the need for more rapid methodology, an automated, kinetically-enhanced flow injection method for histamine has been used to screen thousands of sub-samples of various fish and seafood products. Selectivity (expressed as molar fluorescence ratios) for histamine versus histidine in the sample matrix is a function of reaction kinetics. Fine-tuning this effect is sufficient to remove the need for ion-exchange sample conditioning. This fine-tuning of reaction kinetics is easily accomplished via control of flow rates, reaction temperature, etc. Method performance is excellent, with detection and quantitation limits near 0.8 and 2.4 mg/kg, and linearity to approximately 340 mg/kg, Each sample produces a response in <1 min. The method is more rapid and more practical than other proposed screening methods including alternative chemistries, HPLC methods, and immunoassays. For widespread use in the regula tory environment, an analytical method must produce similar results in other laboratories. Success requires simplified rugged procedures, a knowledge of which specific variables are important in determining method ruggedness, and demonstration of system suitability. Consistent with the methods' reliance on chemical kinetics, the most important factors are reaction time and temperature, and the condensation reagent concentration. These factors are not so sensitive that they limit ruggedness and practicality. A temperature change of 3 degreesC results in a 4% change in peak height, and a 1 cm change in reactor length results: in a 0.4% difference. These effects are then easily controlled using commercial instrumentation. With no sample cleanup other than extraction and crude filtration, tuna can be screened for histamine with R.S.D. of <3% (N = 5 extracts, five injections/extract). Recoveries at 50 and 100 mg/kg were 97 and 118% (each spike extracted to five replicates, five injections/extract). Agreement with histamine levels using the alternate (official) method is also very good. Published by Elsevier Science B.V. C1 US FDA, Pacific Reg Lab NW, Seafood Prod Res Ctr, Bothell, WA USA. RP Hungerford, JM (reprint author), US FDA, Pacific Reg Lab NW, Seafood Prod Res Ctr, 22201 23rd Dr SE, Bothell, WA USA. NR 14 TC 7 Z9 7 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0003-2670 J9 ANAL CHIM ACTA JI Anal. Chim. Acta PD JUL 3 PY 2001 VL 438 IS 1-2 BP 123 EP 129 DI 10.1016/S0003-2670(01)00985-0 PG 7 WC Chemistry, Analytical SC Chemistry GA 450BH UT WOS:000169721300015 ER PT J AU Temple, R Ellenberg, SS AF Temple, R Ellenberg, SS TI Placebo-controlled trials - Response SO ANNALS OF INTERNAL MEDICINE LA English DT Letter C1 US FDA, Rockville, MD 20857 USA. RP Temple, R (reprint author), US FDA, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD JUL 3 PY 2001 VL 135 IS 1 BP 63 EP 64 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 449JC UT WOS:000169680500013 ER PT J AU McClain, DE Benson, KA Dalton, TK Ejnik, J Emond, CA Hedge, SJ Kalinich, JF Landauer, MA Miller, AC Pellmar, TC Stewart, MD Villa, V Cu, J AF McClain, DE Benson, KA Dalton, TK Ejnik, J Emond, CA Hedge, SJ Kalinich, JF Landauer, MA Miller, AC Pellmar, TC Stewart, MD Villa, V Cu, J TI Biological effects of embedded depleted uranium (DU): summary of Armed Forces Radiobiology Research Institute research SO SCIENCE OF THE TOTAL ENVIRONMENT LA English DT Article; Proceedings Paper CT Conference on Toxicology and Risk Assessment Approaches for the 21st Century CY APR 10-13, 2000 CL KINGS ISL, OHIO SP Tri Serv USAF, USA, USN Toxicol, Natl Ctr Environm Assessment, US EPA, ATSDR, Div Toxicol, Natl Inst Occupat Safety & Hlth, Natl Res Council, Natl Acad Sci DE depleted uranium; uranium; toxicity; health effects ID PELLETS AB The Persian Gulf War resulted in injuries of US Coalition personnel by fragments of depleted uranium (DU). Fragments not immediately threatening the health of the individuals were allowed to remain in place, based on long-standing treatment protocols designed for other kinds of metal shrapnel injuries. However, questions were soon raised as to whether this approach is appropriate for a metal with the unique radiological and toxicological properties of DU, The Armed Forces Radiobiology Research Institute (AFRRI) is investigating health effects of embedded fragments of DU to determine whether current surgical fragment removal policies remain appropriate for this metal. These studies employ rodents implanted with DU pellets as well as cultured human cells exposed to DU compounds. Results indicate uranium from implanted DU fragments distributed to tissues far-removed from implantation sites, including bone, kidney, muscle, and liver. Despite levels of uranium in the kidney that were nephrotoxic after acute exposure, no histological or functional kidney toxicity was observed. However, results suggest the need for further studies of long-term health impact, since DU was found to be mutagenic, and it transformed human osteoblast cells to a tumorigenic phenotype, It also altered neurophysiological parameters in rat hippocampus, crossed the placental barrier, and entered fetal tissue. This report summarizes AFRRI's depleted uranium research to date. Published by Elsevier Science B.V. C1 Armed Forces Radiobiol Res Inst, Bethesda, MD 20889 USA. US FDA, Div Oncol Drug Prod, Rockville, MD 20857 USA. USN, Drug Screening Lab, Great Lakes, IL 60085 USA. Natl Acad Sci, Inst Med, Washington, DC 20418 USA. RP McClain, DE (reprint author), Armed Forces Radiobiol Res Inst, 8901 Wisconsin Ave, Bethesda, MD 20889 USA. NR 14 TC 37 Z9 41 U1 0 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0048-9697 J9 SCI TOTAL ENVIRON JI Sci. Total Environ. PD JUL 2 PY 2001 VL 274 IS 1-3 BP 115 EP 118 DI 10.1016/S0048-9697(01)00734-3 PG 4 WC Environmental Sciences SC Environmental Sciences & Ecology GA 450EH UT WOS:000169728200010 PM 11453287 ER PT J AU Beiden, SV Wagner, RF Campbell, G Metz, CE Jiang, YL AF Beiden, SV Wagner, RF Campbell, G Metz, CE Jiang, YL TI Components-of-variance models for random-effects ROC analysis: The case of unequal variance structures across modalities SO ACADEMIC RADIOLOGY LA English DT Article DE receiver operating characteristic (ROC); components-of-variance; jackknife; bootstrap AB Rationale and Objectives. Several of the authors have previously published an analysis of multiple sources of uncertainty in the receiver operating characteristic (ROC) assessment and comparison of diagnostic modalities. The analysis assumed that the components of variance were the same for the modalities under comparison. The purpose of the present work is to obtain a generalization that does not require that assumption. Materials and Methods. The generalization is achieved by splitting three of the six components of variance in the previous model into modality-dependent contributions. Two distinct formulations of this approach can be obtained from alternative choices of the three components to be split; however, a one-to-one relationship exists between the magnitudes of the components estimated from these two formulations. Results, The method is applied to a study of multiple readers, with and without the aid of a computer-assist modality, performing the task of discriminating between benign and malignant clusters of microcalcifications. Analysis according to the first method of splitting shows large decreases in the reader and reader-by-case components of variance when the computer assist is used by the readers. Analysis in terms of the alternative splitting shows large decreases in the corresponding modality-interaction components. Conclusion. A solution to the problem of multivariate ROC analysis without the assumption of equal variance structure across modalities has been provided. Alternative formulations lead to consistent results related by a one-to-one mapping. A surprising result is that estimates of confidence intervals and numbers of cases and readers required for a specified confidence interval remain the same in the more general model as in the restricted model. C1 US FDA, Ctr Devices & Radiol Hlth, Off Sci & Technol HFZ 142, Rockville, MD 20857 USA. US FDA, Ctr Devices & Radiol Hlth, Off Surveillance & Biometr HFZ 542, Rockville, MD 20857 USA. Univ Chicago, Rossman Labs, Dept Radiol, Chicago, IL 60637 USA. RP Wagner, RF (reprint author), US FDA, Ctr Devices & Radiol Hlth, Off Sci & Technol HFZ 142, Rockville, MD 20857 USA. RI Jiang, Yulei/A-9355-2009 OI Jiang, Yulei/0000-0001-9322-0958 FU NCI NIH HHS [R01-CA62362]; NIGMS NIH HHS [R01-GM57622] NR 18 TC 36 Z9 36 U1 0 U2 1 PU ASSOC UNIV RADIOLOGISTS PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523-2251 USA SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD JUL PY 2001 VL 8 IS 7 BP 605 EP 615 DI 10.1016/S1076-6332(03)80685-2 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 447FP UT WOS:000169561100006 PM 11450961 ER PT J AU Beiden, SV Wagner, RF Campbell, G Chan, HP AF Beiden, SV Wagner, RF Campbell, G Chan, HP TI Analysis of uncertainties in estimates of components of variance in multivariate ROC analysis SO ACADEMIC RADIOLOGY LA English DT Article DE receiver operating characteristic (ROC); components-of-variance; jackknife; bootstrap ID MULTIREADER AB Rationale and Objectives. Solutions have previously been presented to the problem of estimating the components of variance in the general linear model used for multivariate receiver operating characteristic (ROC) analysis. The case where the variance components do not change across the modalities under comparison was first treated, followed by the case where they are permitted to change. No analysis of uncertainties in these estimates has been presented previously. Materials and Methods, For the case where the variance components do not change across modalities, the "jackknife-after-bootstrap" resampling procedure can be used together with conventional linear propagation of variance to solve for the uncertainties in estimates of the components. For the case where the components are permitted to change across modalities, a slight elaboration of this procedure is presented. Results. The approach was validated by Monte Carlo simulations, where uncertainties in estimates of the variance components calculated by the jackknife-after-bootstrap procedure were found to converge in the mean to the Monte Carlo results over many independent trials. The method is exemplified with data from a study of readers-with and without the aid of a computer-assist modality-given the task of discriminating benign from malignant masses in mammography. Conclusion. The present approach is relevant to a broad class of problems where estimates of multiple contributions to the variance observed in ROC assessment of diagnostic modalities are desired, in particular, for the assessment of multiple-reader studies of computer-aided diagnosis in radiology where the variance components may change across reading modalities (eg, unaided vs computer-aided reading). C1 US FDA, Ctr Devices & Radiol Hlth, Off Sci & Technol HFZ 142, Rockville, MD 20857 USA. US FDA, Ctr Devices & Radiol Hlth, Off Surveillance & Biometr HFZ 542, Rockville, MD 20857 USA. Univ Michigan, Dept Radiol, Ann Arbor, MI 48109 USA. RP Wagner, RF (reprint author), US FDA, Ctr Devices & Radiol Hlth, Off Sci & Technol HFZ 142, Rockville, MD 20857 USA. FU NCI NIH HHS [CA 48129] NR 9 TC 31 Z9 31 U1 0 U2 1 PU ASSOC UNIV RADIOLOGISTS PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523-2251 USA SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD JUL PY 2001 VL 8 IS 7 BP 616 EP 622 DI 10.1016/S1076-6332(03)80686-4 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 447FP UT WOS:000169561100007 PM 11450962 ER PT J AU Pogribna, M Melnyk, S Pogribny, I Chango, A Yi, P James, SJ AF Pogribna, M Melnyk, S Pogribny, I Chango, A Yi, P James, SJ TI Homocysteine metabolism in children with Down syndrome: In vitro modulation SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID COULOMETRIC ELECTROCHEMICAL DETECTION; GENE; CHROMOSOME-21; PLASMA; INDIVIDUALS; METHYLATION; TRISOMY-21; HYPOTHESIS; SURVIVAL; DNA AB The gene for cystathionine beta -synthase (CBS) is located on chromosome 21 and is overexpressed in children with Down syndrome (DS), or trisomy 21. The dual purpose of the present study was to evaluate the impact of overexpression of the CBS gene on homocysteine metabolism in children with DS and to determine whether the supplementation of trisomy 21 lymphoblasts in vitro with selected nutrients would shift the genetically induced metabolic imbalance. Plasma samples were obtained from 42 children with karyotypically confirmed full trisomy 21 and from 36 normal siblings (mean age 7.4 years). Metabolites involved in homocysteine metabolism were measured and compared to those of normal siblings used as controls. Lymphocyte DNA methylation status was determined as a functional endpoint. The results indicated that plasma levels of homocysteine, methionine, S-adenosylhomocysteine, and S-adenosylmethionine were all significantly decreased in children with DS and that their lymphocyte DNA was hypermethylated relative to that in normal siblings. Plasma levels of cystathionine and cysteine were significantly increased, consistent with an increase in CBS activity. Plasma glutathione levels were significantly reduced in the children with DS and may reflect an increase in oxidative stress due to the overexpression of the superoxide dismutase gene, also located on chromosome 21. The addition of methionine, folinic acid, methyl-B-12, thymidine, or dimethylglycine to the cultured trisomy 21 lymphoblastoid cells improved the metabolic profile in vitro. The increased activity of CBS in children with DS significantly alters homocysteine metabolism such that the folate-dependent resynthesis of methionine is compromised. The decreased availability of homocysteine promotes the well-established "folate trap," creating a functional folate deficiency that may contribute to the metabolic pathology of this complex genetic disorder. C1 US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. Univ Arkansas Med Sci, Dept Pediat, Little Rock, AR 72205 USA. RP James, SJ (reprint author), US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. NR 38 TC 133 Z9 137 U1 2 U2 4 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD JUL PY 2001 VL 69 IS 1 BP 88 EP 95 DI 10.1086/321262 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 456XM UT WOS:000170108100009 PM 11391481 ER PT J AU Soglia, JR Turesky, RJ Paehler, A Vouros, P AF Soglia, JR Turesky, RJ Paehler, A Vouros, P TI Quantification of the heterocyclic aromatic amine DNA adduct N-(deoxyguanosin-8-yl)-2-amino-3-methylimidazo[4,5-f]quinoline in livers of rats using capillary liquid chromatography/microelectrospray mass spectrometry: a dose-response study SO ANALYTICAL CHEMISTRY LA English DT Article ID FOOD MUTAGEN 2-AMINO-3-METHYLIMIDAZO<4,5-F>QUINOLINE; P-32 POSTLABELING ASSAY; NONHUMAN-PRIMATES; CARCINOGEN 2-AMINO-3-METHYLIMIDAZO<4,5-F>QUINOLINE; ENVIRONMENTAL CARCINOGENS; CHEMICAL CARCINOGENESIS; BORNE CARCINOGEN; N-2 ATOMS; IDENTIFICATION; CHROMATOGRAPHY AB Capillary liquid chromatography/microelectrospray-mass spectrometry (capillary LC/mu ESI-MS) was used to quantify DNA adducts of the heterocyclic aromatic amine 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) in livers of male Fischer-344 rats. Animals received a single oral dose of either 0.05, 0.50, 1.0, or 10 mg/kg IQ and were sacrificed 24 h following treatment. The major lesion identified at all doses was N-(deoxyguanosine-8-yl)-2-amino-3-methylimidazo[4,5-f]quinoline (dG-C8-IQ), The capillary LC/mu ESI-MS method provided the means for quantifying 17.5 fmol of dG-C8-IQ (2.0 adducts in 10(8) nucleosides) (S/N 10) in 300 mug of liver DNA with an intra- and interday precision of 3.5 and 6.6% (RSD), respectively, dG-C8-IQ was quantified with a mean intra-and interday accuracy of 105 +/- 26 and 106 +/- 28 (SD) based on back-calculated adduct masses from five standard curves analyzed over a four-week period. This is the first report on development of a capillary LC/mu ESI-MS method to quantify dG-CS-IQ adducts in liver DNA of rats following dosing with IQ at different levels. Furthermore, the ability to accurately and precisely quantify dG-C8-IQ at a level of 2.0 adducts in 108 nucleosides in vivo makes this method well suited for use in future studies relating carcinogen exposure to risk in humans. C1 Northeastern Univ, Barnett Inst, Boston, MA 02115 USA. Northeastern Univ, Dept Chem, Boston, MA 02115 USA. Natl Ctr Toxicol Res, Div Chem, Jefferson, AR 72079 USA. Nestec Ltd, Nestle Res Ctr, CH-1000 Lausanne 26, Switzerland. RP Vouros, P (reprint author), Northeastern Univ, Barnett Inst, Boston, MA 02115 USA. FU NCI NIH HHS [1R01CA69390-05] NR 54 TC 39 Z9 39 U1 0 U2 7 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0003-2700 J9 ANAL CHEM JI Anal. Chem. PD JUL 1 PY 2001 VL 73 IS 13 BP 2819 EP 2827 DI 10.1021/ac010218j PG 9 WC Chemistry, Analytical SC Chemistry GA 448ZP UT WOS:000169660100010 PM 11467522 ER PT J AU Yamaguchi, K Sawada, T Yamane, S Haga, S Ikeda, K Igata-Yi, R Yoshiki, K Matsuoka, M Okabe, H Horii, Y Nawa, Y Waltrip, RW Carbone, KM AF Yamaguchi, K Sawada, T Yamane, S Haga, S Ikeda, K Igata-Yi, R Yoshiki, K Matsuoka, M Okabe, H Horii, Y Nawa, Y Waltrip, RW Carbone, KM TI Synthetic peptide-based electrochemiluminescence immunoassay for anti-Borna disease virus p40 and p24 antibodies in rat and horse serum SO ANNALS OF CLINICAL BIOCHEMISTRY LA English DT Article ID PERIPHERAL-BLOOD MONONUCLEAR; GENOMIC ORGANIZATION; AFFECTIVE-DISORDERS; CELLS; SCHIZOPHRENIA; RNA AB Borna disease virus (BDV) is a neurotropic pathogen that infects a wide variety of vertebrates. We have developed a new electrochemiluminescence immunoassay (ECLIA) for the detection of antibodies to BDV, using three synthetic peptides corresponding to the amino acid residues 3 20 and 338 358 of p40 and 59-79 of p24 peptide of BDV. Using the ECLIA, we examined serum samples for the presence of anti-BDV antibodies in 20 rats (experimentally BDV-infected and uninfected) and 38 horses (13 US horses. experimentally infected and uninfected, and 25 Japanese horses, feral and domestic). The ECLIA, performed in a double-blind manner. detected anti-BDV antibodies in rats with a history of BDV infection. giving results that were in agreement with indirect immunofluorescence assay Lind, or Western blot (WB) analysis. The ECLIA also correctly identified all three experimentally infected horses and four domestic American horses that were seropositive for BDV antibodies by WB. Among the Japanese horses, at least two out of 10 feral and Six Out Of 15 domestic horses were seropositive for BDV. In most of these cases. the specificity of immunoreactivity was verified by blocking with Soluble p40 and p24 peptides. C1 Kumamoto Univ, Sch Med, Blood Transfus Serv, Kumamoto 8608556, Japan. Eisai Tsukuba Res Labs, Div Diagnost, Tsukuba, Ibaraki, Japan. Tokyo Inst Psychiat, Dept Ultrastruct & Histochem, Tokyo, Japan. Natl Kikuchi Hosp, Kumamoto, Japan. Miyazaki Univ, Fac Agr, Dept Vet Internal Med, Miyazaki 88921, Japan. Miyazaki Med Coll, Dept Parasitol, Miyazaki 88916, Japan. Univ Maryland, Sch Med, Maryland Psychiat Res Ctr, Baltimore, MD 21201 USA. US FDA, Div Viral Prod, Washington, DC 20204 USA. RP Yamaguchi, K (reprint author), Kumamoto Univ, Sch Med, Blood Transfus Serv, Honjo 1-1-1, Kumamoto 8608556, Japan. OI Matsuoka, Masao/0000-0002-0473-754X NR 19 TC 7 Z9 9 U1 0 U2 3 PU ROYAL SOC MEDICINE PRESS LTD PI LONDON PA 1 WIMPOLE STREET, LONDON W1M 8AE, ENGLAND SN 0004-5632 J9 ANN CLIN BIOCHEM JI Ann. Clin. Biochem. PD JUL PY 2001 VL 38 BP 348 EP 355 DI 10.1258/0004563011900867 PN 4 PG 8 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 502TE UT WOS:000172758200008 PM 11471876 ER PT J AU Hoff, PM Saad, ED Ravandi-Kashani, F Czerny, E Pazdur, R AF Hoff, PM Saad, ED Ravandi-Kashani, F Czerny, E Pazdur, R TI Phase I trial of i.v. administered tirapazamine plus cyclophosphamide SO ANTI-CANCER DRUGS LA English DT Article DE cyclophosphamide; hypoxia; phase I trial; solid tumors; tirapazamine ID FSAIIC MURINE FIBROSARCOMA; SR-4233 TIRAPAZAMINE; BIOREDUCTIVE AGENT; TUMOR HYPOXIA; SOLID TUMORS; BLOOD-FLOW; CISPLATIN; CANCER; CELLS; CHEMOTHERAPY AB Our objective was to determine the maximum tolerated doses of tirapazamine and cyclophosphamide given i.v., in combination. Eligible patients had advanced solid tumors refractory to conventional treatment. Tirapazamine (escalated from 80 to 390 mg/m(2)) was given i.v. over 2 h rind followed by cyclophosphamide over 1 h, The cyclophosphamide dose was fixed at 1000 mg/m(2) until the tirapazamine dose of 390 mg/m(2) was reached. Once that dose of tirapazamine was reached, the cyclophosphamide dose was escalated to 1250 and 1500 mg/m(2), Twenty-eight patients were enrolled. The dose-limiting toxicity was granulocytopenia. One patient had transient deafness for 2 days. Four other patients had grade 1 ototoxicity, Grade 1 and 2 muscle cramps were observed at all dose levels, Other toxic effects observed included fatigue, nausea, vomiting, headache, diarrhea, drug fever, elevated transaminases and elevated creatine phosphokinase, Three patients had stable disease and the longest time to progression was 5 months. The combination of tirapazamine and cyclophosphamide is feasible, and the dose-limiting toxicity is granulocytopenia. The use of growth factors could possibly allow escalation of tirapazamine doses in future phase II trials. Without growth factor support, the recommended doses of tirapazamine and cyclophosphamide when administered in this schedule are 260 and 1000 mg/m(2), respectively. [(C) 2001 Lippincott Williams & Wilkins.]. C1 Univ Texas, MD Anderson Canc Ctr, Dept Gastrointestinal Med Oncol, Houston, TX 77030 USA. Sanofi Res Div, Malvern, PA 19355 USA. US FDA, Div Oncol Drug Prod, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Hoff, PM (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Gastrointestinal Med Oncol, 1515 Holcombe Blvd,Box 426, Houston, TX 77030 USA. NR 32 TC 4 Z9 4 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4973 J9 ANTI-CANCER DRUG JI Anti-Cancer Drugs PD JUL PY 2001 VL 12 IS 6 BP 499 EP 503 DI 10.1097/00001813-200107000-00002 PG 5 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 454RZ UT WOS:000169986700002 PM 11459995 ER EF