FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Davis, C Heath, A Best, S Hewlett, I Lelie, N Schuurman, R Holmes, H AF Davis, C Heath, A Best, S Hewlett, I Lelie, N Schuurman, R Holmes, H TI Calibration of HIV-1 working reagents for nucleic acid amplification techniques against the 1st international standard for HIV-1 RNA SO JOURNAL OF VIROLOGICAL METHODS LA English DT Article DE HIV-1 RNA; NAT; calibration; working reagents; International Standard ID PLASMA; TRANSFUSION; INFECTION; SAFETY; RISK; NAT AB Many laboratories use working reagents/run controls to monitor the performance of their nucleic acid amplification techniques (NAT) for the measurement of HIV-1 RNA. A collaborative study was carried out in order to calibrate seven internationally available working reagents, QC105 (National Serology Reference Laboratory [NRL], Australia), B5 and B10 (Center for Biological Evaluation and Research [CBER], USA), Pelispy (Central Laboratory of the Netherlands Blood Transfusion Service [CLB], The Netherlands), PWS-1 and PWS-3 (National Institute for Biological Standards and Control [NIBSC], UK) and IRC (Virology Networks [VN], The Netherlands) against the 1st International Standard for HIV-1 RNA (code 97/656). Twenty-one laboratories from 12 different countries participated in the collaborative study and from the results it was determined that QC105 contained 4.0 log(10) International Units (IU)/ml, B5 2.2 log(10) IU/ml, B10 3.8 log(10) IU/ml, Pelispy 4.4 log(10) IU/ml, PWS-1 3.6 log(10) IU/ml, PWS-3 2.7 log(10) IU/ml and IRC 4.3 log(10) IU/ml. The seven working reagents calibrated in this international study may be used to validate and standardise the large number of qualitative and quantitative, commercial and in-house NAT assays that are currently being applied in the fields of blood safety and patient management. They will also help laboratories to comply with the sensitivity requirements that may be brought in by the regulatory authorities and may contribute to further harmonisation of guidelines on NAT published by organisations such as the European Medicines Evaluation Agency (EMEA), Paul-Ehrlich Institute and CBER, FDA. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Natl Inst Biol Stand & Controls, Div Retrovirol, Potters Bar EN6 3QG, Herts, England. Natl Inst Biol Stand & Controls, Div Informat, Potters Bar EN6 3QG, Herts, England. Natl Serol Reference Lab, Fitzroy, Vic 3065, Australia. Food & Drug Adm, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. Sanquin CLB Diagnost Div, VQC Lab, NL-1867 CT Alkmaar, Netherlands. Univ Utrecht Hosp, Dept Virol, NL-3584 CX Utrecht, Netherlands. RP Holmes, H (reprint author), Natl Inst Biol Stand & Controls, Div Retrovirol, Blanche Lane, Potters Bar EN6 3QG, Herts, England. NR 12 TC 20 Z9 23 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-0934 J9 J VIROL METHODS JI J. Virol. Methods PD JAN PY 2003 VL 107 IS 1 BP 37 EP 44 AR PII S0166-0934(02)00187-8 DI 10.1016/S0166-0934(02)00187-8 PG 8 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Virology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Virology GA 633BA UT WOS:000180258300006 PM 12445936 ER PT J AU Wilson, CA Laeeq, S Ritzhaupt, A Colon-Moran, W Yoshimura, FK AF Wilson, CA Laeeq, S Ritzhaupt, A Colon-Moran, W Yoshimura, FK TI Sequence analysis of porcine endogenous retrovirus long terminal repeats and identification of transcriptional regulatory regions SO JOURNAL OF VIROLOGY LA English DT Article ID MURINE LEUKEMIA-VIRUS; HUMAN FOAMY VIRUS; HUMAN-CELLS; DISEASE SPECIFICITY; MINIATURE SWINE; ENVELOPE GENE; SARCOMA-VIRUS; C VIRUSES; 3' END; ENHANCER AB Porcine cells express endogenous retroviruses, some of which are infectious for human cells. To better understand the replication of these porcine endogenous retroviruses (PERVs) in cells of different types and animal species, we have performed studies of the long terminal repeat (LTR) region of known gammaretroviral isolates of PERV. Nucleotide sequence determination of the LTRs of PERV-NIH, PERV-C, PERV-A, and PERV-B revealed that the PERV-A and PERV-B LTRs are identical, whereas the PERV-NIH and PERV-C LTRs have significant sequence differences in the U3 region between each other and with the LTRs of PERV-A and PERV-B. Sequence analysis revealed a similar organization of basal promoter elements compared with other gammaretroviruses, including the presence of enhancer-like repeat elements. The sequences of the PERV-NIH and PERV-C repeat element are similar to that of the PERV-A and PERV-B element with some differences in the organization of these repeats. The sequence of the PERV enhancer-like repeat elements differs significantly from those of other known gammaretroviral enhancers. The transcriptional activities of the PERV-A, PERV-B, and PERV-C LTRs relative to each other were similar in different cell types of different animal species as determined by transient expression assays. On the other hand, the PERV-NIH LTR was considerably weaker in these cell types. The transcriptional activity of all PERV LTRs was considerably lower in porcine ST-IOWA cells than in cell lines from other species. Deletion mutant analysis of the LTR of a PERV-NIH isolate identified regions that transactivate or repress transcription depending on the cell type. C1 Wayne State Univ, Dept Immunol & Microbiol, Detroit, MI 48201 USA. Wayne State Univ, Karmanos Ctr Inst, Detroit, MI 48201 USA. US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Bethesda, MD 20892 USA. Inst Monitoring Data Management Biometr & Med Wri, Cologne, Germany. RP Yoshimura, FK (reprint author), Wayne State Univ, Dept Immunol & Microbiol, 6255 Scott Hall, Detroit, MI 48201 USA. NR 55 TC 25 Z9 25 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 JAN PY 2003 VL 77 IS 1 BP 142 EP 149 DI 10.1128/JVI.77.1.142-149.2003 PG 8 WC Virology SC Virology GA 626CU UT WOS:000179855400015 PM 12477819 ER PT J AU Thomson, M Nascimbeni, M Havert, MB Major, M Gonzales, S Alter, H Feinstone, SM Murthy, KK Rehermann, B Liang, TJ AF Thomson, M Nascimbeni, M Havert, MB Major, M Gonzales, S Alter, H Feinstone, SM Murthy, KK Rehermann, B Liang, TJ TI The clearance of hepatitis C virus infection in chimpanzees may not necessarily correlate with the appearance of acquired immunity SO JOURNAL OF VIROLOGY LA English DT Article ID T-CELL RESPONSE; MOLECULAR CLONE; VIRAL CLEARANCE; CDNA CLONE; GENOTYPE 1B; PERSISTENCE; TRANSCRIPTS; STABILITY; RECOVERY; SEQUENCE AB Clearance of hepatitis C virus (HCV) infection in humans and chimpanzees is thought to be associated with the induction of strong T-cell responses. We studied four chimpanzees infected with HCV derived from an infectious full-length HCV genotype 1b cDNA. Two of the chimpanzees cleared the infection to undetectable levels for more than 12 months of follow-up; the other two became persistently infected. Detailed analyses of HCV-specific immune responses were performed during the courses of infection in these chimpanzees. Only weak and transient T helper responses were detected during the acute phase in all four chimpanzees. A comparison of the frequency of gamma interferon (IFN-gamma)-producing CD4(+) and CD8(+) T cells in peripheral blood by ELISpot assay did not reveal any correlation between viral clearance and T-cell responses. In addition, analyses of IFN-gamma, IFN-alpha, and interleukin-4 mRNA levels in liver biopsies, presumably indicative of intrahepatic T-cell responses, revealed no distinct pattern in these chimpanzees with respect to infection outcome. The present study suggests that the outcome of HCV infection in chimpanzees is not necessarily attributable to HCV sequence variation and that chimpanzees may recover from HCV infection by mechanisms other than the induction of readily detectable HCV-specific T-cell responses. C1 NIDDK, Liver Dis Sect, Bethesda, MD 20892 USA. SW Fdn Biomed Res, Dept Virol & Immunol, San Antonio, TX 78227 USA. US FDA, Ctr Biol Evaluat & Res, Lab Hepatitis Viruses, Div Viral Prod, Bethesda, MD 20892 USA. NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. RP Liang, TJ (reprint author), NIDDK, Liver Dis Sect, NIH Bldg 10,Rm 9B16,10 Ctr Dr, Bethesda, MD 20892 USA. FU NHLBI NIH HHS [N01-HB-27091, N01HB27091] NR 31 TC 66 Z9 69 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 JAN PY 2003 VL 77 IS 2 BP 862 EP 870 DI 10.1128/JVI.77.2.862-870.2003 PG 9 WC Virology SC Virology GA 631KH UT WOS:000180166600006 PM 12502802 ER PT J AU Whitehead, SS Falgout, B Hanley, KA Blaney, JE Markoff, L Murphy, BR AF Whitehead, SS Falgout, B Hanley, KA Blaney, JE Markoff, L Murphy, BR TI A live, attenuated dengue virus type 1 vaccine candidate with a 30-nucleotide deletion in the 3 ' untranslated region is highly attenuated and immunogenic in monkeys SO JOURNAL OF VIROLOGY LA English DT Article ID SECONDARY STRUCTURE; 3'-UNTRANSLATED REGION; CONSTRUCTION; INFECTION; SEQUENCES; STRAINS; HUMANS; FEVER AB The Delta30 deletion mutation, which was originally created in dengue virus type 4 (DEN4) by the removal of nucleotides 172 to 143 from the 3' untranslated region (3' UTR), was introduced into a homologous region of wild-type (wt) dengue virus type 1 (DEN1). The resulting virus, rDEN1Delta30, was attenuated in rhesus monkeys to a level similar to that of the rDEN4Delta30 vaccine candidate. rDEN1Delta30 was more attenuated in rhesus monkeys than the previously described vaccine candidate, rDEN1mutF, which also contains mutations in the 3' UTR, and both vaccines were highly protective against challenge with wt DEN1. Both rDEN1Delta30 and rDEN1mutF were also attenuated in HuH-7-SCID mice. However, neither rDEN1Delta30 nor rDEN1mutF showed restricted replication following intrathoracic inoculation in the mosquito Toxorhynchites splendens. The ability of the Delta30 mutation to attenuate both DEN1 and DEN4 viruses suggests that a tetravalent DEN vaccine could be generated by introduction of the Delta30 mutation into wt DEN viruses belonging to each of the four serotypes. C1 Natl Inst Allergy & Infect Dis, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Lab Vector Borne Virus Dis, Bethesda, MD 20892 USA. RP Whitehead, SS (reprint author), Natl Inst Allergy & Infect Dis, Infect Dis Lab, NIH, Bldg 50mRm 6515,50 S Dr, Bethesda, MD 20892 USA. NR 22 TC 89 Z9 96 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 JAN PY 2003 VL 77 IS 2 BP 1653 EP 1657 DI 10.1128/JVI.77.2.1653-1657.2003 PG 5 WC Virology SC Virology GA 631KH UT WOS:000180166600089 PM 12502885 ER PT J AU Zha, H Raffeld, M Charboneau, L Pittaluga, S Liotta, LA Petricoin, E Kwak, LW Jaffe, ES AF Zha, H Raffeld, M Charboneau, L Pittaluga, S Liotta, LA Petricoin, E Kwak, LW Jaffe, ES TI Investigation of pro-survival pathways by reverse phase protein microarray in follicular lymphoma SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol C1 NCI, Bethesda, MD 20892 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 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2003 VL 83 IS 1 MA 1190 BP 261A EP 261A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 641EU UT WOS:000180732501203 ER PT S AU Waynant, RW Ilev, IK Mitra, K AF Waynant, RW Ilev, IK Mitra, K BE Bass, LS Kollias, N Malek, RS Katzir, A Shah, UK Wong, BJF Trowers, EA Woodward, TA DeRiese, WTW Robinson, DS Reidenbach, HD Paulsen, KD Gregory, KW TI A concept for early cancer detection and therapy SO LASERS IN SURGERY: ADVANCED CHARACTERIZATION, THERAPEUTICS, AND SYSTEMS XIII SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Conference on Lasers in Surgery - Advanced Characterization, Therapeutics and Systems XIII CY JAN 25-26, 2003 CL SAN JOSE, CA SP SPIE DE early detection; high-resolution x-ray; optical biopsy; waveguide-delivered therapy AB Early detection and treatment of breast cancer is least costly in terms of dollars, morbidity and mortality. With new early detection x-ray technology, tumors can be found, diagnosed and treated at a much smaller size than is currently possible. This paper proposes the development of a high resolution, high quality imaging system. It is a laser-driven x-ray system with time-gated detection that removes scattering noise in the image and produces resolution on the order of 10 mum. This higher resolution and higher image quality will enable the detection of one or two millimeter tumors hopefully detecting them before metastasis. We also propose that tumor detection should be followed by an immediate needle-directed, optical fiber biopsy to instantly determine if cancer is present and, if present, the tumor should immediately be given a lethal treatment of laser or x-radiation through the same needle using fiber optics or hollow waveguides. This technology will help prevent multiple interventions resulting in both the lowest overall cost and a more efficacious therapy. The approach can be stopped at the first negative (benign) indication and will help forestall repeated examination as well as reduce patient anxiety. C1 US FDA, Elect Opt Branch, Rockville, MD 20857 USA. RP Waynant, RW (reprint author), US FDA, Elect Opt Branch, 12725 Twinbrook Pkwy, Rockville, MD 20857 USA. RI Mitra, Kunal/C-6560-2016 OI Mitra, Kunal/0000-0002-7277-4908 NR 9 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-4749-8 J9 P SOC PHOTO-OPT INS PY 2003 VL 4949 BP 425 EP 432 DI 10.1117/12.476526 PG 8 WC Engineering, Biomedical; Optics; Surgery SC Engineering; Optics; Surgery GA BX17B UT WOS:000184498100055 ER PT J AU Pfefer, TJ Paithankar, DY Poneros, JM Schomacker, KT Nishioka, NS AF Pfefer, TJ Paithankar, DY Poneros, JM Schomacker, KT Nishioka, NS TI Temporally and spectrally resolved fluorescence spectroscopy for the detection of high grade dysplasia in Barrett's esophagus SO LASERS IN SURGERY AND MEDICINE LA English DT Article DE laser-induced fluorescence; fluorophore lifetime; precancer detection; esophagus ID LASER-INDUCED FLUORESCENCE; GASTROINTESTINAL-DISEASES; EXCITATION WAVELENGTHS; COLONIC DYSPLASIA; CANCER-DIAGNOSIS; VIVO; AUTOFLUORESCENCE; ENDOSCOPY; TISSUE; SYSTEM AB Background and Objectives: Temporal and spectral fluorescence spectroscopy can identify adenomatous colonic polyps accurately. In this study, these techniques were examined as a potential means of improving the surveillance of high grade dysplasia (HGD) in Barrett's esophagus (BE). Study Design/Materials and Methods: Using excitation wavelengths of 337 and 400 nm, 148 fluorescence spectra, and 108 transient decay profiles (at 550 20 nm) were obtained endoscopically in 37 patients. Corresponding biopsies were collected and classified as carcinoma, HGD, or low risk tissue (LRT) [non-dysplastic BE, indefinite for dysplasia (IFD), and low grade dysplasia (LGD)]. Diagnostic algorithms were developed retrospectively using linear discriminant analysis (LDA) to separate LRT from HGD. Results: LDA produced diagnostic algorithms based solely on spectral data. Moderate levels of sensitivity (Se) and specificity (Sp) were obtained for both 337 nm (Se = 74%, Sp = 67%) and 400 nm (Se = 74%, Sp = 85%) excitation. Conclusions: In the diagnosis of HGD in BE, steady-state fluorescence was more effective than time-resolved data, and excitation at 400 nm excitation was more effective than 337 nm. While fluorescence-targeted biopsy is approaching clinical usefulness, increased sensitivity to dysplastic changes-possibly through modification of system parameters-is needed to improve accuracy levels. (C) 2003 Wiley-Liss, Inc. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. RP Pfefer, TJ (reprint author), US FDA, CDRH, HFZ-134,12725 Twinbrook Pkwy,201, Rockville, MD 20857 USA. RI Pfefer, Josh/I-9055-2012 NR 39 TC 60 Z9 62 U1 0 U2 4 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PY 2003 VL 32 IS 1 BP 10 EP 16 DI 10.1002/lsm.10136 PG 7 WC Dermatology; Surgery SC Dermatology; Surgery GA 639QF UT WOS:000180640200003 PM 12516065 ER PT J AU Waynant, RW AF Waynant, RW TI Laser (light) therapy: Future research directions SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract CT 23rd Annual Meeting of the American-Society-for-Laser-Medicine-and-Surgery CY APR 09-13, 2003 CL ANAHEIM, CALIFORNIA SP American Soc Laser Med Surg C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PY 2003 SU 15 MA 141 BP 40 EP 40 PG 1 WC Dermatology; Surgery SC Dermatology; Surgery GA 661FK UT WOS:000181880400136 ER PT J AU Byrnes, KR Waynant, RW Ilev, IK Johnson, B Pollard, H Srivastava, M Eidelman, O Huang, W Anders, JJ AF Byrnes, KR Waynant, RW Ilev, IK Johnson, B Pollard, H Srivastava, M Eidelman, O Huang, W Anders, JJ TI Alteration in gene expression following spinal cord injury and photo-biomodulation SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract CT 23rd Annual Meeting of the American-Society-for-Laser-Medicine-and-Surgery CY APR 09-13, 2003 CL ANAHEIM, CALIFORNIA SP American Soc Laser Med Surg 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 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 2003 SU 15 MA 144 BP 41 EP 41 PG 1 WC Dermatology; Surgery SC Dermatology; Surgery GA 661FK UT WOS:000181880400139 ER PT J AU Lee, HS Coates, GA AF Lee, HS Coates, GA TI Effect of thermal pasteurization on Valencia orange juice color and pigments SO LEBENSMITTEL-WISSENSCHAFT UND-TECHNOLOGIE-FOOD SCIENCE AND TECHNOLOGY LA English DT Article DE pasteurization; orange juice; color; carotenoid ID CAROTENOID-PIGMENTS AB Changes in carotenoid pigment content and juice color due to thermal pasteurization of Valencia orange juices were studied. Total carotenoid pigment content loss was significant (P<0.05) after thermal pasteurization at 90&DEG;C for 30s. Thermal effects on carotenoid pigment contents, especially on violaxanthin (-46.4%) and antheraxanthin (-24.8%), were clearly observed. With the loss of violaxanthin and antheraxanthin, lutein became the major carotenoid, followed by zeaxanthin, in pasteurized Valencia orange juice. There was perceptible color change after orange juice pasteurization, which led to juice color becoming lighter and more saturated. Decreases in CIE a* value and increases in CIE L*, b*, h*, and C* are the major color changes after pasteurization. Overall increases in reflected light might also influence the perception of color to a great extent in pasteurized orange juice. Total color differences (&UDelta;E*) compared to the fresh juice was 2.92 +/- 0.97 (P < 0.05). (C) 2003 Published by Elsevier Science Ltd. on behalf of Swiss Society of Food Science and Technology. C1 Florida Dept Citrus, Ctr Citrus Res & Educ, Lake Alfred, FL 33850 USA. RP Lee, HS (reprint author), FDA, CFSAN, OFAS, College Pk, MD 20740 USA. NR 17 TC 103 Z9 106 U1 4 U2 10 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0023-6438 J9 LEBENSM-WISS TECHNOL JI Lebensm.-Wiss. Technol.-Food Sci. Technol. PY 2003 VL 36 IS 1 BP 153 EP 156 DI 10.1016/S0023-6438(02)00087-7 PG 4 WC Food Science & Technology SC Food Science & Technology GA 656PP UT WOS:000181616400018 ER PT J AU Snyder, RV Gibbs, PDL Palacios, A Abiy, L Dickey, R Lopez, JV Rein, KS AF Snyder, RV Gibbs, PDL Palacios, A Abiy, L Dickey, R Lopez, JV Rein, KS TI Polyketide synthase genes from marine dinoflagellates SO MARINE BIOTECHNOLOGY LA English DT Article DE polyketide; polyketide synthase; toxin; dinotlagellate; biosynthesis ID PROROCENTRUM-LIMA; ENGINEERED BIOSYNTHESIS; GONYAULAX-POLYEDRA; OKADAIC ACID; BACTERIA; MICROORGANISMS; STREPTOMYCES; METABOLITES; TOXICITY; SEQUENCE AB Rapidly developing techniques for manipulating the pathways of polyketide biosynthesis at the genomic level have created the demand for new pathways with novel biosynthetic capability. Polyketides derived from dinoflagellates are among the most complex and unique structures identified thus far, yet no studies of the biosynthesis of dinoflagellate-derived polyketides at the genomic level have been reported. Nine strains representing 7 different species of dinoflagellates were screened for the presence of type I and type II polyketide synthases (PKSs) by polymerase chain reaction (PCR) and reverse transcriptase PCR. Seven of the 9 strains yielded products that were homologous with known and putative type I PKSs. Unexpectedly, a PKS gene was amplified from cultures of the dinoflagellate Gymnodinium catenatum, a saxitoxin producer, which is not known to produce a polyketide. In each case the presence of a PKS gene was correlated with the presence of bacteria in the cultures as identified by amplification of the bacterial 16S ribosomal RNA gene. However, amplification from polyadenylated RNA, the lack of PKS expression in light-deprived cultures, residual phylogenetic signals, resistance to methylation-sensitive restriction enzymes, and the lack of hybridization to bacterial isolates support a dinoflagellate origin for most of these genes. C1 Florida Int Univ, Dept Chem, Miami, FL 33199 USA. Univ Miami, Rosenstiel Sch Marine & Atmospher Sci, NIEHS, Marine & Freshwater Biomed Sci Ctr, Miami, FL 33149 USA. US FDA, Gulf Coast Seafood Lab, Dauphin Isl, AL 36528 USA. Harbor Branch Oceanog Inst Inc, Div Biomed Marine Res, Ft Pierce, FL 34946 USA. RP Rein, KS (reprint author), Florida Int Univ, Dept Chem, 11200 SW 8th St, Miami, FL 33199 USA. EM reink@fiu.edu RI Lopez, Jose/F-8809-2011 OI Lopez, Jose/0000-0002-1637-4125 FU NIEHS NIH HHS [P30 ES05705]; NIGMS NIH HHS [GM 61347, R21 GM60012-01] NR 41 TC 58 Z9 62 U1 0 U2 13 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1436-2228 J9 MAR BIOTECHNOL JI Mar. Biotechnol. PD JAN-FEB PY 2003 VL 5 IS 1 BP 1 EP 12 DI 10.1007/s10126-002-0077-y PG 12 WC Biotechnology & Applied Microbiology; Marine & Freshwater Biology SC Biotechnology & Applied Microbiology; Marine & Freshwater Biology GA 651QZ UT WOS:000181333200001 PM 12925913 ER PT S AU Gallas, BD AF Gallas, BD BE Chakraborty, DP Krupinski, EA TI Variance of the channelized-Hotelling observer from a finite number of trainers and testers SO MEDICAL IMAGING 2003: 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 2003 Conference CY FEB 17-20, 2003 CL SAN DIEGO, CA SP SPIE, Amer Assoc Phys Med, Amer Physiol Soc, Ctr Devices & Radiol Hlth, Soc Imaging Sci & Technol, Natl Elect Mfg Assoc, Diagnost Imaging & Therapy Syst Div, Radiol Soc N Amer, Soc Comp Appl Radiol DE bias; variance; signal detection; classifier; channel; Hotelling; observer; bootstrap; shuffle ID COMPUTER-AIDED DIAGNOSIS; SAMPLE-SIZE; CLASSIFIER PERFORMANCE; ROC ANALYSIS; COMPONENTS; DESIGN AB In this paper we analyze the bootstrap and shuffle methods for estimating the mean and variance of the performance of the channelized-Hotelling observer given a finite number of images for training and testing. This background is needed to understand the role of the bootstrap and shuffle methods in new and more complicated models of bias and variance. We assess the accuracy and precision of the bootstrap and shuffle estimates by comparing them to Monte Carlo estimates. The comparisons show that the shuffle estimate of the mean and the bootstrap estimate of the variance are unbiased. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Gallas, BD (reprint author), US FDA, Ctr Devices & Radiol Hlth, HFZ-142,12720 Twinbrook Pkwy, Rockville, MD 20857 USA. OI Gallas, Brandon/0000-0001-7332-1620 NR 16 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 0-8194-4835-4 J9 P SOC PHOTO-OPT INS PY 2003 VL 5034 BP 100 EP 111 DI 10.1117/12.480334 PG 12 WC Optics; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BW91Q UT WOS:000183593100014 ER PT S AU Wagner, RF Beiden, SV Campbell, G Metz, CE Sacks, WM AF Wagner, RF Beiden, SV Campbell, G Metz, CE Sacks, WM BE Chakraborty, DP Krupinski, EA TI Contemporary issues for experimental design in assessment of medical Imaging and computer-assist systems SO MEDICAL IMAGING 2003: 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 2003 Conference CY FEB 17-20, 2003 CL SAN DIEGO, CA SP SPIE, Amer Assoc Phys Med, Amer Physiol Soc, Ctr Devices & Radiol Hlth, Soc Imaging Sci & Technol, Natl Elect Mfg Assoc, Diagnost Imaging & Therapy Syst Div, Radiol Soc N Amer, Soc Comp Appl Radiol ID OF-VARIANCE MODELS; OBSERVER-PERFORMANCE; ROC ANALYSIS; COMPONENTS; RADIOLOGISTS; VARIABILITY; METHODOLOGY; MODALITIES; POPULATION; IMAGES C1 US FDA, CDRH, Off Sci & Technol, Rockville, MD 20857 USA. RP Wagner, RF (reprint author), US FDA, CDRH, Off Sci & Technol, 12720 Twinbrook Pkwy, Rockville, MD 20857 USA. NR 41 TC 6 Z9 6 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 0-8194-4835-4 J9 P SOC PHOTO-OPT INS PY 2003 VL 5034 BP 213 EP 224 DI 10.1117/12.480094 PG 12 WC Optics; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BW91Q UT WOS:000183593100025 ER PT S AU Wagner, RF Beam, CA Beiden, SV AF Wagner, RF Beam, CA Beiden, SV BE Chakraborty, DP Krupinski, EA TI A study of the propagation of reader variability in mammography to the variable expected benefit over the population SO MEDICAL IMAGING 2003: 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 2003 Conference CY FEB 17-20, 2003 CL SAN DIEGO, CA SP SPIE, Amer Assoc Phys Med, Amer Physiol Soc, Ctr Devices & Radiol Hlth, Soc Imaging Sci & Technol, Natl Elect Mfg Assoc, Diagnost Imaging & Therapy Syst Div, Radiol Soc N Amer, Soc Comp Appl Radiol DE technology assessment; mammography; ROC analysis; multiple-reader studies; expected benefit analysis C1 US FDA, Ctr Devices & Radiol Hlth, Off Sci & Technol, Rockville, MD 20850 USA. RP Wagner, RF (reprint author), US FDA, Ctr Devices & Radiol Hlth, Off Sci & Technol, Rockville, MD 20850 USA. NR 7 TC 1 Z9 1 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-4835-4 J9 P SOC PHOTO-OPT INS PY 2003 VL 5034 BP 238 EP 241 DI 10.1117/12.480328 PG 4 WC Optics; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BW91Q UT WOS:000183593100028 ER PT S AU Hadjiiski, L Chan, HP Sahiner, B Helvie, MA Roubidoux, M Blane, C Paramagul, C Petrick, N Bailey, J Klein, K Foster, M Patterson, S Adler, D Nees, A Shen, J AF Hadjiiski, L Chan, HP Sahiner, B Helvie, MA Roubidoux, M Blane, C Paramagul, C Petrick, N Bailey, J Klein, K Foster, M Patterson, S Adler, D Nees, A Shen, J BE Sonka, M Fitzpatrick, JM TI ROC study: Effects of computer-aided diagnosis on radiologists' characterization of malignant and benign breast masses in temporal pairs of mammograms SO MEDICAL IMAGING 2003: IMAGE PROCESSING, PTS 1-3 SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Medical Imaging 2003 Conference CY FEB 17-20, 2003 CL SAN DIEGO, CA SP SPIE, Amer Assoc Phys Med, Amer Physiol Soc, Ctr Devices & Radiol Hlth, Soc Imaging Sci & Technol, Natl Elect Mfg Assoc, Diagnost Imaging & Therapy Syst Div, Radiol Soc N Amer, Soc Comp Appl Radiol DE computer-aided diagnosis; interval changes; ROC observer study; classification; mammography; breast cancer ID DIGITIZED MAMMOGRAMS; TEXTURE ANALYSIS; CLASSIFICATION; IMPROVEMENT; FEATURES; CANCER; MICROCALCIFICATIONS; LESIONS AB We conducted an observer performance study using receiver operating characteristic (ROC) methodology to evaluate the effects of computer-aided diagnosis (CAD) on radiologists' performance for characterization. of masses on serial mammograms. The automated CAD system, previously developed in our laboratory, can classify masses as malignant or benign based on interval change information on serial mammograms. In this study, 126 temporal image pairs (73 malignant and 53 benign) from 52 patients containing masses on serial mammograms were used. The corresponding masses on each temporal pair were identified by an experienced radiologist and automatically segmented by the CAD program. Morphological, texture, and spiculation features of the mass on the current and the prior mammograms were extracted. The individual features and the difference between the corresponding current and prior features formed a multidimensional feature space. A subset of the most effective features that contained the current, prior, and interval change information was selected by a stepwise procedure and used as input predictor variables to a linear discriminant classifier in a leave-one-case-out training and testing resampling scheme. The linear discriminant classifier estimated the relative likelihood of malignancy of each mass. The classifier achieved a test A, value of 0.87. For the ROC study, 4 MQSA radiologists and I breast imaging fellow assessed the masses on the temporal pairs and provided estimates, of the likelihood of malignancy without and with CAD. The average A, value for the likelihood of malignancy estimated by the radiologists was 0.79 without CAD and improved to 0.87 with CAD. The improvement was statistically significant (p=0.0003). This preliminary result indicated that CAD using interval change analysis can significantly improve radiologists' accuracy in classification of masses and thereby may increase the positive predictive value of mammography. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Hadjiiski, L (reprint author), US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. NR 25 TC 3 Z9 3 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 0-8194-4833-8 J9 P SOC PHOTO-OPT INS PY 2003 VL 5032 BP 94 EP 101 DI 10.1117/12.483549 PN 1-3 PG 8 WC Engineering, Biomedical; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BW90V UT WOS:000183561900010 ER PT S AU Jennings, RJ Badano, A AF Jennings, RJ Badano, A BE Yaffe, MK Antonuk, LE TI Effect on DQE of screen energy weighting in mammography SO MEDICAL IMAGING 2003: PHYSICS OF MEDICAL IMAGING, PTS 1 AND 2 SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Medical Imaging 2003 Conference CY FEB 17-20, 2003 CL SAN DIEGO, CA SP SPIE, Amer Assoc Phys Med, Amer Physiol Soc, Ctr Devices & Radiol Hlth, Soc Imaging Sci & Technol, Natl Elect Mfg Assoc, Diagnost Imaging & Therapy Syst Div, Radiol Soc N Amer, Soc Comp Appl Radiol DE mammography; detective quantum efficiency; x-ray spectrum; screen ID DETECTIVE QUANTUM EFFICIENCY; DEVICES AB Our work investigates the effect on the zero-spatial-frequency DQE of indirect mammographic image receptors of the combined effects of x-ray,beam hardening and light photon transport within the x-ray sensitive medium of the image receptor. Beam hardening,,in this context, refers to the preferential absorption of low-energy x-ray photons at the surface of the detector on which the x-ray beam is incident, with deeper layers of the detector absorbing higher and higher average energies. The light photon transport properties of both powder and crystalline/columnar phosphors favor the collection at the light-sensitive element of the detector of light photons generated closest to that element. The net result of these two effects is to perform a weighting of the detected x-ray spectrum. For the standard back-screen configuration used in conventional mammography, low-energy x rays are more heavily weighted, matching the energy dependence of the signal to be detected. For a front-screen configuration, used in-all existing indirect-detection digital mammographic systems, just the opposite is true. We have used the optical Monte Carlo simulation code DETECT-II to determine average light collection efficiency and optical pulse distributions for a Min-R screen in both front- and back-screen configurations, and for two thicknesses of CsI, as a function of x-ray energy. These data, along with appropriately hardened x-ray spectra for several anode and filter combinations and a range of tube voltages, were used as input to the task-dependent DQE theory of Tapiovaara and Wagner. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Jennings, RJ (reprint author), US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. OI badano, aldo/0000-0003-3712-6670 NR 17 TC 7 Z9 7 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 0-8194-4831-1 J9 P SOC PHOTO-OPT INS PY 2003 VL 5030 BP 319 EP 326 DI 10.1117/12.480198 PG 8 WC Engineering, Biomedical; Optics; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Optics; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BX07Z UT WOS:000184199600031 ER PT S AU Petrick, N Badano, A Chan, HP Sahiner, B Hadjiiski, LM AF Petrick, N Badano, A Chan, HP Sahiner, B Hadjiiski, LM BE Yaffe, MK Antonuk, LE TI Digital indirect detection x-ray imagers with microlens focusing: Effects of Fresnel reflections from the microlens layer SO MEDICAL IMAGING 2003: PHYSICS OF MEDICAL IMAGING, PTS 1 AND 2 SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Medical Imaging 2003 Conference CY FEB 17-20, 2003 CL SAN DIEGO, CA SP SPIE, Amer Assoc Phys Med, Amer Physiol Soc, Ctr Devices & Radiol Hlth, Soc Imaging Sci & Technol, Natl Elect Mfg Assoc, Diagnost Imaging & Therapy Syst Div, Radiol Soc N Amer, Soc Comp Appl Radiol DE digital x-ray imaging; digital radiography; microlen array; indirect detection imaging; light collection; fill factor; flat-panel imager ID LIGHT COLLECTION; MAMMOGRAPHY; PROTOTYPE AB We have been investigating whether a microlens layer placed between the phosphor and the photodetector can improve indirect detection x-ray imagers. Using a simulation study, we analyzed the light collection properties of the proposed imager taking into account Fresnel reflection and transmission properties of the lenses and the screen. A digital x-ray imager combining an 82-mum-thick Gd2O2S:Tb phosphor screen, a fused silica microlens layer, and a 127-mum pixel pitch photodetector (optical fill factor of 57%) were modeled. The light collection for. the prototypes varied from 53% to 69% for lens thicknesses ranging from 10 to 56 mum. The full-width half-maximum (FWHM) of the light spread function ranged from 177-192 mum. 4-8% of the light was reflected back into the phosphor screen when correctly taking into account Fresnel reflections for these prototype imagers. In comparison, 56% of the light was collected and the FWHM of the light spread function was 174 mum for a conventional imager with the screen in direct contact with the photodetector. We observed that the light collection was overestimated by 6-9% but the spread functions were basically unaffected when the Fresnel assumption was not utilized in the simulations.. This study shows that a properly designed microlens layer can more than offset Fresnel losses, thereby producing an improved digital x-ray imager. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20904 USA. RP Petrick, N (reprint author), US FDA, Ctr Devices & Radiol Hlth, 12720 Twinbrook Pkwy, Rockville, MD 20904 USA. OI badano, aldo/0000-0003-3712-6670 NR 13 TC 1 Z9 1 U1 1 U2 1 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-4831-1 J9 P SOC PHOTO-OPT INS PY 2003 VL 5030 BP 504 EP 510 DI 10.1117/12.479995 PG 7 WC Engineering, Biomedical; Optics; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Optics; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BX07Z UT WOS:000184199600048 ER PT S AU Wear, KA Laib, A AF Wear, KA Laib, A BE Walker, WF Insana, MF TI Relationship between ultrasonic backscatter and trabecular thickness in human calcaneus: Theory and experiment SO MEDICAL IMAGING 2003: ULTRASONIC IMAGING AND SIGNAL PROCESSING SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Medical Imaging 2003 Conference CY FEB 17-20, 2003 CL SAN DIEGO, CA SP SPIE, Amer Assoc Phys Med, Amer Physiol Soc, Ctr Devices & Radiol Hlth, Soc Imaging Sci & Technol, Natl Elect Mfg Assoc, Diagnost Imaging & Therapy Syst Div, Radiol Soc N Amer, Soc Comp Appl Radiol ID FREQUENCY-DEPENDENCE; CANCELLOUS BONE; MODEL AB Trabecular thickness within cancellous bone is an important determinant of osteoporotic fracture risk. Noninvasive assessment of trabecular thickness could potentially yield useful diagnostic information. Faran's theory of elastic scattering from a cylindrical object immersed in a fluid has been employed to predict the dependence of ultrasonic backscatter on trabecular thickness. Methodology to test this theory has been validated in experiments using nylon fishing lines spanning a wide range of diameters. In the case of bone, Faran's theory predicts that, in the range of morphological and material properties expected for trabecular bone, the backscatter coefficient at 500 kHz should be approximately proportional to trabecular thickness to the power of 2.9. Experimental measurements of backscatter coefficient were performed on 43 human calcaneus samples in vitro. Mean trabecular thicknesses on the 43 samples were assessed using micro computed tomography. A power law fit to the data showed that the backscatter coefficient empirically varied as trabecular thickness to the 2.8 power. The 95% confidence interval for this exponent was 1.7 to 3.9. The square of the correlation coefficient for the linear regression to the log transformed data was 0.40. This suggests that 40% of variations in backscatter may be attributed to variations in trabecular thickness. These results (1) reinforce previous studies that offered validation for the Faran cylinder model for prediction of scattering properties of cancellous bone, and (2) provide added evidence for the potential diagnostic utility of the backscatter measurement. C1 FDA, Rockville, MD 20852 USA. RP Wear, KA (reprint author), FDA, 12720 Twinbrook Pkwy, Rockville, MD 20852 USA. NR 11 TC 0 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 0-8194-4836-2 J9 P SOC PHOTO-OPT INS PY 2003 VL 5035 BP 109 EP 114 DI 10.1117/12.479898 PG 6 WC Engineering, Electrical & Electronic; Optics; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Optics; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BW91R UT WOS:000183593400013 ER PT S AU Wear, KA Garra, BS Pinet, MC Felker, S Mai, J AF Wear, KA Garra, BS Pinet, MC Felker, S Mai, J BE Walker, WF Insana, MF TI Measurements of ultrasonic backscattered spectral centroid shift from spine in vivo - Methodology and preliminary results SO MEDICAL IMAGING 2003: ULTRASONIC IMAGING AND SIGNAL PROCESSING SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Medical Imaging 2003 Conference CY FEB 17-20, 2003 CL SAN DIEGO, CA SP SPIE, Amer Assoc Phys Med, Amer Physiol Soc, Ctr Devices & Radiol Hlth, Soc Imaging Sci & Technol, Natl Elect Mfg Assoc, Diagnost Imaging & Therapy Syst Div, Radiol Soc N Amer, Soc Comp Appl Radiol AB We have developed a technique to measure backscattered ultrasound from lumbar vertebrae using a commercial ultrasound scanner. The spectral centroid shift between the spine and reference phantom data is an index of attenuation within the spine. From measurements from 11 vertebrae, we found a correlation coefficient of r = -0.61 between spectral centroid shift and bone mineral density (BMD). This negative correlation is expected as denser, more highly attenuating bone would be expected to produce greater downshifts in spectral centroid. This is the first technique performing quantitative ultrasound measurements on trabecular bone in the spine. This study shows that 1) acquisition of ultrasonic backscatter data from human spine in vivo is feasible, and 2) spectral centroid shift exhibits a moderate negative correlation with BMD in accordance with expectations. C1 US FDA, Rockville, MD 20852 USA. RP Wear, KA (reprint author), US FDA, 12720 Twinbrook Pkwy, Rockville, MD 20852 USA. NR 2 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 0-8194-4836-2 J9 P SOC PHOTO-OPT INS PY 2003 VL 5035 BP 411 EP 413 DI 10.1117/12.479899 PG 3 WC Engineering, Electrical & Electronic; Optics; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Optics; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BW91R UT WOS:000183593400044 ER PT S AU Badano, A Gallas, BD Myers, KJ Burgess, AE AF Badano, A Gallas, BD Myers, KJ Burgess, AE BE Galloway, RL TI Effect of viewing angle on visual detection in liquid crystal displays SO MEDICAL IMAGING 2003: 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 2003 Conference CY FEB 17-20, 2003 CL SAN DIEGO, CA SP SPIE, Amer Assoc Phys Med, Amer Physiol Soc, Ctr Devices & Radiol Hlth, Soc Imaging Sci & Technol, Natl Elect Mfg Assoc, Diagnost Imaging & Therapy Syst Div, Radiol Soc N Amer, Soc Comp Appl Radiol DE AMLCD; viewing angle; Lambertian; luminance; psychophysics; model observer; AFC AB Display devices for medical diagnostic. workstations should have a diffuse emission with apparent luminance independent of viewing angle. Such-displays are called Lambertian, or they obey Lambert's law. Actual display devices are never truly Lambertian; the-luminance of a pixel depends on the viewing angle. In active-matrix liquid crystal displays (AMLCD), the departure from the Lambertian profile depends on the gray level and complex pixel designs having multiple domains, in-plain switching or vertically-aligned technology. Our previous measurements established that the largest deviation from the desired Lambertian distribution occurs in the low luminance range, for the diagonal viewing direction. Our purpose in this work is to determine the effect that non-uniform changes of the angular emission have on the detection of low-contrast signals in noisy backgrounds. We used a sequential two-alternative forced choice (2AFC) approach with test images displayed at the center of the screen. The observer location was fixed at different viewing angles: on-axis and off-axis. The results are expressed in terms of percent-correct for each observer and for each experimental condition (viewing angle and luminance). Our results show that for the test images used in this experiment with human observers, the changes in detectability between on-axis and off-axis viewing are smaller than the observer variability. Model observers are consistent with these results but also indicate that different background and signal levels can lead to meaningful performance differences between on-axis and off-axis viewing. 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 16 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 0-8194-4830-3 J9 P SOC PHOTO-OPT INS PY 2003 VL 5029 BP 474 EP 483 DI 10.1117/12.479766 PG 10 WC Engineering, Biomedical; Optics; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Optics; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BW93R UT WOS:000183701400049 ER PT J AU Zha, H Raffeld, M Charboneau, L Pittaluga, S Liotta, LA Petricoin, E Kwak, LW Jaffe, ES AF Zha, H Raffeld, M Charboneau, L Pittaluga, S Liotta, LA Petricoin, E Kwak, LW Jaffe, ES TI Investigation of pro-survival pathways by reverse phase protein microurray in follicular lymphoma SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol C1 NCI, Bethesda, MD 20892 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 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2003 VL 16 IS 1 MA 1190 BP 261A EP 261A PG 1 WC Pathology SC Pathology GA 640ZY UT WOS:000180720101200 ER PT J AU Boucher, PE Maris, AE Yang, MS Stibitz, S AF Boucher, PE Maris, AE Yang, MS Stibitz, S TI The response regulator BvgA and RNA polymerase a subunit C-terminal domain bind simultaneously to different faces of the same segment of promoter DNA SO MOLECULAR CELL LA English DT Article ID ESCHERICHIA-COLI ADA; BORDETELLA-PERTUSSIS; ALPHA-SUBUNIT; SIGMA-SUBUNIT; FHA PROMOTER; MINOR-GROOVE; BETA-SUBUNIT; TRANSCRIPTION; ACTIVATION; PROTEIN AB Examination of the binding of FeBABE-conjugated BvgA to the fha promoter of Bordetella pertussis has revealed that three dimers, formed by head-to-head association of monomers, bind one face of the DNA helix from the inverted-heptad primary binding site to the -35 region. The orientation of BvgA monomers within the dimers is the same as that recently demonstrated by X-ray crystallographic methods for a dimer of the C-terminal domain of NarL bound to DNA. Use of FeBABE conjugates of RNAP alpha subunit C-terminal domain showed that binding of this domain is linearly coincident with binding of the BvgA dimers, but to a different helical face. These results reveal a previously undescribed mode of interaction between RNAP alpha-CTD and a transcriptional activator. C1 US FDA, Ctr Biol Evaluat & Res, Div Bacterial Parasit & Allergen Prod, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Dept Chem & Biochem, Los Angeles, CA 90095 USA. RP Boucher, PE (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Bacterial Parasit & Allergen Prod, 8800 Rockville Pike, Bethesda, MD 20892 USA. RI Meares, Claude/A-8345-2011 NR 29 TC 42 Z9 42 U1 1 U2 3 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD JAN PY 2003 VL 11 IS 1 BP 163 EP 173 DI 10.1016/S1097-2765(03)00007-8 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 643EL UT WOS:000180848900019 PM 12535530 ER PT J AU Dobrovolsky, VN Bucci, T Heflich, RH Desjardins, J Richardson, FC AF Dobrovolsky, VN Bucci, T Heflich, RH Desjardins, J Richardson, FC TI Mice deficient for cytosolic thymidine kinase gene develop fatal kidney disease SO MOLECULAR GENETICS AND METABOLISM LA English DT Article DE thymidine kinase; kidney glomerulus; sublingual salivary gland ID BASEMENT-MEMBRANE DISEASE; DNA ALKYLATING-AGENTS; MOUSE LYMPHOMA-CELLS; DECREASED TTP POOLS; GOODPASTURES-SYNDROME; MOLECULAR-CLONING; FOLIC-ACID; EXPRESSION; MUTATION; ADENINE AB The thymidine kinase (Tk) gene codes for a cytosolic protein involved in the pyrimidine nucleotide salvage pathway. A functional Tk gene is not necessary for cells in culture, and a naturally occurring Tk deficient phenotype has not been described in humans or animal models. In order to determine the biological significance of the Tk gene, we created Tk(-/-) knockout (KO) mice through homologous recombination in mouse embryonic stem cells. Tk KO mice have shortened life spans compared with their wild-type or Tk heterozygous (HET) siblings. All Tk KO mice develop sclerosis of kidney glomeruli and die before one year of age of kidney failure. Among other changes in KO animals, the most consistent is a switch from exclusively mucous secretion to predominantly serous secretion in the sublingual salivary gland. HET parents can produce KO mice at a frequency approaching Mendelian inheritance. Other observations in KO animals include an elevated level of serum thymidine, a significant decrease in the cloning efficiency of splenic lymphocytes, an increase in the frequency of hypoxanthine guanine phosphoribosyl transferase gene mutant lymphocytes, and histological alteration in the lymphoid structure of the spleen. In addition, KO animals sporadically exhibit inflammation of the arteries, which taken together with the lymphocyte and spleen abnormalities, suggest an abnormal immune system. Alterations in Tk KO mice indicate that the pyrimidine nucleotide salvage pathway is indispensable in vivo. (C) 2002 Elsevier Science (USA). All rights reserved. C1 Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Pathol Associates Int, Jefferson, AR USA. OSI Pharmaceut Inc, Boulder, CO USA. RP Dobrovolsky, VN (reprint author), Div Genet & Reprod Toxicol, 3900 NCTR Rd,HFT-120, Jefferson, AR 72079 USA. NR 55 TC 35 Z9 36 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD JAN PY 2003 VL 78 IS 1 BP 1 EP 10 DI 10.1016/S1096-7192(02)00224-X PG 10 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 645YP UT WOS:000181008300001 PM 12559842 ER PT S AU Bryan, WW AF Bryan, WW BE Bromberg, MB TI MUNE as an endpoint in clinical trials SO MOTOR UNIT NUMBER ESTIMATION (MUNE), PROCEEDINGS SE SUPPLEMENTS TO CLINICAL NEUROPHYSIOLOGY LA English DT Proceedings Paper CT 1st International Symposium on Motor Unit Number Estimation (MUNE) CY JUL 13-15, 2001 CL SNOWBIRD, UT ID CONDUCT C1 United States Food & Drug Adm, Ctr Biol Evaluat & Res, Off Therapeut Res & Review, Div Clin Trial Design & Anal, Rockville, MD 20852 USA. RP Bryan, WW (reprint author), United States Food & Drug Adm, Ctr Biol Evaluat & Res, Off Therapeut Res & Review, Div Clin Trial Design & Anal, 1401 Rockville Pike,Rm 230N, Rockville, MD 20852 USA. NR 6 TC 4 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1567-424X BN 0-444-50723-X J9 SUPPL CLIN NEUROPHYS PY 2003 VL 55 BP 324 EP 328 DI 10.1016/S1567-424X(03)00039-4 PG 5 WC Neurosciences SC Neurosciences & Neurology GA BX77E UT WOS:000186383000039 ER PT J AU Kotenko, SV Gallagher, G Baurin, VV Lewis-Antes, A Shen, ML Shah, NK Langer, JA Sheikh, F Dickensheets, H Donnelly, RP AF Kotenko, SV Gallagher, G Baurin, VV Lewis-Antes, A Shen, ML Shah, NK Langer, JA Sheikh, F Dickensheets, H Donnelly, RP TI IFN-lambda s mediate antiviral protection through a distinct class II cytokine receptor complex SO NATURE IMMUNOLOGY LA English DT Article ID INTERFERON-GAMMA RECEPTOR; INTERLEUKIN-10 RECEPTOR; SIGNAL-TRANSDUCTION; ALPHA; IDENTIFICATION; ACTIVATION; CHAIN; BETA; EXPRESSION; PROTEINS AB We report here the identification of a ligand-receptor system that, upon engagement, leads to the establishment of an antiviral state. Three closely positioned genes on human chromosome 19 encode distinct but paralogous proteins, which we designate interferon-lambda1 (IFN-lambda1), IFN-lambda2 and IFN-lambda3 (tentatively designated as IL-29, IL- 28A and IL-28B, respectively, by HUGO). The expression of IFN-lambda mRNAs was inducible by viral infection in several cell lines. We identified a distinct receptor complex that is utilized by all three IFN-lambda proteins for signaling and is composed of two subunits, a receptor designated CRF2-12 (also designated as IFN-lambdaR1) and a second subunit, CRF2-4 (also known as IL-10R2). Both receptor chains are constitutively expressed on a wide variety of human cell lines and tissues and signal through the Jak-STAT (Janus kinases-signal transducers and activators of transcription) pathway. This receptor-ligand system may contribute to antiviral or other defenses by a mechanism similar to, but independent of, type I IFNs. C1 Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Biochem & Mol Biol, Newark, NJ 07103 USA. Univ Med & Dent New Jersey, New Jersey Dent Sch, Dept Oral Biol, Newark, NJ 07103 USA. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Microbiol Mol Genet & Immunol, Piscataway, NJ 08854 USA. US FDA, Ctr Biol Evaluat & Res, Div Therapeut Prot, Bethesda, MD 20892 USA. RP Kotenko, SV (reprint author), Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Biochem & Mol Biol, Newark, NJ 07103 USA. FU NIAID NIH HHS [R01 AI051139, R01 AI51139] NR 44 TC 940 Z9 1048 U1 2 U2 37 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD JAN PY 2003 VL 4 IS 1 BP 69 EP 77 DI 10.1038/ni875 PG 9 WC Immunology SC Immunology GA 629MG UT WOS:000180053000017 PM 12483210 ER PT J AU Anderson, HA Maylock, CA Williams, JA Paweletz, CP Shu, HJ Shacter, E AF Anderson, HA Maylock, CA Williams, JA Paweletz, CP Shu, HJ Shacter, E TI Serum-derived protein S binds to phosphatidylserine and stimulates the phagocytosis of apoptotic cells SO NATURE IMMUNOLOGY LA English DT Article ID MACROPHAGE RECOGNITION; VITRONECTIN RECEPTOR; BLOOD-COAGULATION; GENERAL FEATURE; CLEARANCE; GAS6; LYMPHOCYTES; EXPOSURE; ANTIBODIES; INHIBITION AB Rapid phagocytosis of apoptotic cells is thought to limit the development of inflammation and autoimmune disease. Serum enhances macrophage phagocytosis of apoptotic cells. Here we identified protein S as the factor responsible for serum-stimulated phagocytosis of apoptotic cells. Protein S is best known for its anti-thrombotic activity, serving as a cofactor for protein C. Purified protein S was equivalent to serum in its ability to stimulate macrophage phagocytosis of apoptotic lymphoma cells, and immunodepletion of protein S eliminated the prophagocytic activity of serum. Protein S acted by binding to phosphatidylserine expressed on the apoptotic cell surface. Protein S is thus a multifunctional protein that can facilitate clearance of early apoptotic cells in addition to regulating blood coagulation. C1 US FDA, Biochem Lab, Ctr Biol Evaluat & Res, Div Therapeut Prot, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Dept Pediat, Bethesda, MD 20815 USA. NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. Univ Texas, Dept Pharmacol, SW Med Ctr, Dallas, TX 75390 USA. RP Shacter, E (reprint author), US FDA, Biochem Lab, Ctr Biol Evaluat & Res, Div Therapeut Prot, Bethesda, MD 20892 USA. NR 42 TC 213 Z9 220 U1 0 U2 1 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD JAN PY 2003 VL 4 IS 1 BP 87 EP 91 DI 10.1038/ni871 PG 5 WC Immunology SC Immunology GA 629MG UT WOS:000180053000019 PM 12447359 ER PT J AU Molzon, J AF Molzon, J TI The common technical document: the changing face of the new drug application SO NATURE REVIEWS DRUG DISCOVERY LA English DT Article C1 US FDA, Ctr Drug Evaluat & Res, Int Program, Rockville, MD 20857 USA. RP Molzon, J (reprint author), US FDA, Ctr Drug Evaluat & Res, Int Program, 5600 Fishers Lane, Rockville, MD 20857 USA. NR 0 TC 7 Z9 7 U1 2 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-1776 J9 NAT REV DRUG DISCOV JI Nat. Rev. Drug Discov. PD JAN PY 2003 VL 2 IS 1 BP 71 EP 74 DI 10.1038/nrd990 PG 4 WC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA 634QY UT WOS:000180353000017 PM 12509761 ER PT S AU Paule, MG Fogle, CM Allen, RR Pearson, EC Hammond, TG Popke, EJ AF Paule, MG Fogle, CM Allen, RR Pearson, EC Hammond, TG Popke, EJ BE Slikker, W Andrews, RJ Trembly, B TI Chronic exposure to NMDA receptor and sodium channel blockers during development in monkeys and rats - Long-term effects on cognitive function SO NEUROPROTECTIVE AGENTS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 6th International Conference on Neuroprotective Agents CY SEP 15-19, 2002 CL HILTON HEAD ISL, SOUTH CAROLINA DE operant behavior; rhesus monkey; nonhuman primate; excitatory amino acids; cognition; development; learning; auditory and visual discrimination; motivation; short-term memory; MK-801; remacemide; phenytoin ID BEHAVIORAL-TEST BATTERY; NONHUMAN-PRIMATES; RHESUS-MONKEYS; PERFORMANCE; ANTAGONISTS; CHILDREN; BRAIN AB The effects of chronic administration of MK-801 (NMDA-receptor antagonist) and remacemide (sodium channel blocker) on monkey learning of several brain function tasks was assessed in juveniles (nine months old). Low (LO) and high (HI) doses of both drugs were given orally each day for 18 months. There were no adverse effects of any treatment on tests of short-term memory or motivation. HI doses of both MK-801 and remacemide delayed acquisition of a visual discrimination task (the remacemide effect was much greater). HI doses of remacemide alone severely disrupted learning task acquisition and this effect lasted for several months after dosing. Thus, in monkeys, chronic blockade of NMDA receptors is relatively well tolerated, whereas blockade of sodium channels (perhaps in conjunction with NMDA receptor blockade) has long-term-perhaps permanent-consequences. To further explore the roles of NMDA receptors and sodium channels in these effects, MK-801, phenytoin (sodium channel blocker), or both were administered to rats and the acquisition of tasks similar to those used in the monkey study were assessed. Dosing began at weaning and continued for nine months. Throughout the study, HI MK-801 subjects exhibited impaired performance in all tasks. Some effects of MK-801 were blocked completely by phenytoin. In the rat, blockade of sodium channels was well tolerated but blockade of NMDA receptors had significant and long-term (permanent?) adverse consequences. These data contrast markedly with those obtained for the monkey and suggest, at least for some drug classes, that the rat might not be a good predictor of effects in primates. C1 US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. Peak Stat Serv, Evergreen, CO USA. AstraZeneca Safety Assessment, Loughborough, Leics, England. RP Paule, MG (reprint author), US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. NR 18 TC 12 Z9 13 U1 0 U2 3 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-468-4 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2003 VL 993 BP 116 EP 122 PG 7 WC Multidisciplinary Sciences; Neurosciences SC Science & Technology - Other Topics; Neurosciences & Neurology GA BX10T UT WOS:000184303000014 PM 12853303 ER PT S AU Hashemi, RR Bahar, M Tang, N Tyler, AA Hinson, W AF Hashemi, RR Bahar, M Tang, N Tyler, AA Hinson, W BE Slikker, W Andrews, RJ Trembly, B TI Prediction of experimental data for an independent variable using the experimental data collected for other independent variables in a study of skin cancer caused by exposure to UV radiation SO NEUROPROTECTIVE AGENTS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 6th International Conference on Neuroprotective Agents CY SEP 15-19, 2002 CL HILTON HEAD ISL, SOUTH CAROLINA DE data prediction; independent variable; skin cancer; UV radiation AB In this study, two algorithms (ONE and TWO) are introduced to determine the position of the t-distribution of variable V-i (with 95% confidence) in the treated group in reference to the t-distribution of variable V-i (with 95% confidence) in the control group of an experimental study involving UV radiation exposure of a group of rodents. The outcome of applying the two algorithms is two discretized files. A reduct of each file is generated using the rough sets methodology and then the measurements for one independent variable are predicted using the measurements of the other independent variables in the same reduct. The rough sets methodology and the fuzzy-rough classifier are used for this prediction. The results reveal that (1) algorithm TWO is the best, (2) the values for non-core variables are predicted with minimum accuracy of 87%, and (3) the prediction of values for core variables is not successful. C1 Univ Arkansas, Dept Comp Sci, Little Rock, AR 72204 USA. Teachers Training Univ, Dept Phys, Tehran, Iran. Natl Univ Ireland Univ Coll Cork, Sch Med, Cork, Ireland. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Hashemi, RR (reprint author), Univ Arkansas, Dept Comp Sci, Little Rock, AR 72204 USA. NR 9 TC 1 Z9 1 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-468-4 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2003 VL 993 BP 146 EP 157 PG 12 WC Multidisciplinary Sciences; Neurosciences SC Science & Technology - Other Topics; Neurosciences & Neurology GA BX10T UT WOS:000184303000018 PM 12853307 ER PT S AU Slikker, W Duhart, H Gaylor, D Imam, S AF Slikker, W Duhart, H Gaylor, D Imam, S BE Slikker, W Andrews, RJ Trembly, B TI Neuroprotection or neurotoxicity - Impact of discontinuous dose-response curves on risk assessment SO NEUROPROTECTIVE AGENTS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 6th International Conference on Neuroprotective Agents CY SEP 15-19, 2002 CL HILTON HEAD ISL, SOUTH CAROLINA DE neuroprotection; neurotoxicity; dose-response curves; risk assessment C1 US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. Gaylor & Associates LLC, Little Rock, AR USA. RP Slikker, W (reprint author), US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-468-4 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2003 VL 993 BP 158 EP 158 PG 1 WC Multidisciplinary Sciences; Neurosciences SC Science & Technology - Other Topics; Neurosciences & Neurology GA BX10T UT WOS:000184303000019 PM 12853308 ER PT S AU Virmani, A Gaetani, F Imam, S Binienda, Z Ali, S AF Virmani, A Gaetani, F Imam, S Binienda, Z Ali, S BE Slikker, W Andrews, RJ Trembly, B TI Possible mechanism for the neuroprotective effects of L-carnitine on methamphetamine-evoked neurotoxicity SO NEUROPROTECTIVE AGENTS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 6th International Conference on Neuroprotective Agents CY SEP 15-19, 2002 CL HILTON HEAD ISL, SOUTH CAROLINA DE L-carnitine; acetyl-L-carnitine; mitochondria; methamphetamine; free radicals; oxidative phosphorylation; respiratory chain; mitochondrial permeability pores; voltage dependent anion channels; mitochondrial permeability transition pores (mPTP); cyclosporin-dependent mPTP; adenine nucleotide translocase; reactive oxygen species; cell death switch ID INDUCED DOPAMINERGIC NEUROTOXICITY; ACETYL-L-CARNITINE; MITOCHONDRIAL DYSFUNCTION; INDUCED APOPTOSIS; ACID; BRAIN; 7-NITROINDAZOLE; PEROXYNITRITE; INHIBITOR; INCREASES AB Some of the damage to the CNS that is observed following amphetamine and methamphetamine (METH) administration is known to be linked to increased formation of free radicals. This increase could be, in part, related to mitochondrial dysfunction and/or cause damage to the mitochondria, thereby leading to a failure of cellular energy metabolism and an increase in secondary excitotoxicity. The actual neuronal damage that occurs with METH-induced toxicity seems to affect dopaminergic cells in particular. METH-induced toxicity is related to an increase in the generation of both reactive oxygen (hydroxyl, superoxide, peroxide) and nitrogen (nitric oxide) species. Peroxynitrite (ONOO-), which is a reaction product of either superoxide or nitric oxide, is the most damaging radical. It can be reduced by antioxidants such as selenium, melatonin, and the selective nNOS inhibitor, 7-nitroindazole. METH-induced toxicity has been previously shown to increase production of the peroxynitrite stress marker, 3-nitrotyrosine (3-NT), in vitro, in cultured PC12 cells, and also in vivo, in the striatum of adult male mice. Pre- and post-treatment of mice with L-carnitine (LC) significantly attenuated the production of 3-NT in the striatum after METH exposure. LC is a mitochondriotropic compound in that it carries long-chain fatty acyl groups into mitochondria for beta-oxidation. It was shown also to play a protective role against various mitochondrial toxins, such as 3-nitropropionic acid. The protective effects of LC against METH-induced toxicity could be related to its prevention of possible metabolic compromise produced by METH and the resulting energy deficits. In particular, LC may be maintaining the mitochondrial permeability transition (MPT) and modulating the activation of the mitochondrial permeability transition pores (mPTP), especially the cyclosporin-dependent mPTP. The possible neuroprotective mechanism of LC against METH-toxicity and the role of the mitochondrial respiratory chain and the generation of free radicals and their subsequent action on the MPT and mPTP are also being examined using an in vitro model of NGF-differentiated pheochromocytoma cells (PC12). In preliminary experiments, the pretreatment of PC12 cells with LC (5mM), added 10min before METH (500muM), indicated that LC enhances METH-induced DA depletion. The role of LC in attenuating METH-evoked toxicity is still under investigation and promises to reveal information regarding the underlying mechanisms and role of mitochondria in the triggering of cell death. C1 Sigma Tau Hlth Sci, Res & Dev, I-00040 Pomezia, Italy. US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. RP Virmani, A (reprint author), Sigma Tau Hlth Sci, Res & Dev, I-00040 Pomezia, Italy. NR 23 TC 39 Z9 41 U1 1 U2 3 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-468-4 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2003 VL 993 BP 197 EP 207 PG 11 WC Multidisciplinary Sciences; Neurosciences SC Science & Technology - Other Topics; Neurosciences & Neurology GA BX10T UT WOS:000184303000025 PM 12853314 ER PT S AU Binienda, ZK AF Binienda, ZK BE Slikker, W Andrews, RJ Trembly, B TI Neuroprotective effects of L-carnitine in induced mitochondrial dysfunction SO NEUROPROTECTIVE AGENTS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 6th International Conference on Neuroprotective Agents CY SEP 15-19, 2002 CL HILTON HEAD ISL, SOUTH CAROLINA DE 3-nitropropionic acid; succinate dehydrogenase; mitochondrial dysfunction; L-carnitine; neuroprotection ID TOXIN 3-NITROPROPIONIC ACID; ENERGY-METABOLISM; RAT-BRAIN; NEUROTOXICITY; HYPOTHERMIA; INHIBITION; APOPTOSIS; NECROSIS; STRIATUM; LESIONS AB The neuroprotective action Of L-carnitine (LC) in the rat model of 3-nitropropionic acid (3-NPA)-induced mitochondrial dysfunction was examined. 3-NPA is known to produce decreases in neuronal ATP levels via inhibition of the succinate dehydrogenase (SDH) at complex 11 of the mitochondrial electron transport chain. SDH is involved in reactions of the Krebs cycle and oxidative phosphorylation, and its inhibition leads to both necrosis and apoptosis. LC enhances mitochondrial metabolism and, together with its acetylated form, acetyl-L-carnitine (ALC), via the LC-ALC-mediated transfer of acetyl groups, plays an important modulatory role in neurotransmitter signal transduction pathways and gene expression in neuronal cells. In the study described here, adult male Sprague-Dawley rats were injected with 3-NPA alone or treated with LC prior to 3-NPA administration. Pretreatment with LC totally prevented the 3-NPA-induced decrease in brain temperature measured using temperature probes implanted intracranially. It appears that the protective effects of LC against 3-NPA-induced neurotoxicity are achieved via compensatory enhancement of several pathways of mitochondrial energy metabolism. The results of this and previous studies conducted by our division in the 3-NPA model of mitochondrial dysfunction demonstrate that 3-NPA may be employed in vivo to evaluate enhancers of mitochondrial function that might exert neuroprotective effects. C1 Natl Ctr Toxicol Res, FDA, Div Neurotoxicol, Jefferson, AR 72079 USA. RP Binienda, ZK (reprint author), Natl Ctr Toxicol Res, FDA, Div Neurotoxicol, HFT-1 32, Jefferson, AR 72079 USA. NR 20 TC 35 Z9 36 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-468-4 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2003 VL 993 BP 289 EP 295 PG 7 WC Multidisciplinary Sciences; Neurosciences SC Science & Technology - Other Topics; Neurosciences & Neurology GA BX10T UT WOS:000184303000031 PM 12853320 ER PT S AU Scallet, AC Haley, RL Scallet, DM Duhart, HM Binienda, ZK AF Scallet, AC Haley, RL Scallet, DM Duhart, HM Binienda, ZK BE Slikker, W Andrews, RJ Trembly, B TI 3-nitropropionic acid inhibition of succinate dehydrogenase (complex II) activity in cultured chinese hamster ovary cells - Antagonism by L-carnitine SO NEUROPROTECTIVE AGENTS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 6th International Conference on Neuroprotective Agents CY SEP 15-19, 2002 CL HILTON HEAD ISL, SOUTH CAROLINA DE 3-nitropropionic acid; inhibition; succinate dehydrogenase activity; Chinese hamster ovary; L-carnitine ID MITOCHONDRIAL DYSFUNCTION; ELECTRON-TRANSPORT; RAT-BRAIN; IN-VITRO; NEUROTOXICITY; METABOLISM; NEURONS; DAMAGE; ASTROCYTES; DISORDERS AB 3-Nitropropionic acid (3-NPA) is an inhibitor of the mitochondrial enzyme succinate dehydrogenase (SDH, a part of complex 11) that links the tricarboxylic acid (TCA) cycle to the respiratory electron transport chain. 3-NPA inactivates SDH by covalently and irreversibly binding to its active site. We previously examined the effects of 3-NPA on the histochemical activity of SDH in vivo, by using the reduction of a yellow tetrazolium dye (nitro blue tetrazolium) to a blue formazan as an indicator. In studies of cultured cells, the related dye methylthiazoletetrazolium (MTT) has commonly been used as an indicator of the presence and number of viable cells; that is cells that are capable of producing energy via the TCA cycle. Here we observed that doses of 3-NPA as low as 10(-8)M inhibited formazan production in an in vitro model system using CHO cells. This effect was antagonized by L-carnitine, which greatly increased the production of formazan, indicating a considerable improvement in energy production by the cultured cells. CHO cells appear to be a convenient model for the evaluation of therapeutic compounds that may modulate cellular bioenergetics. C1 USFDA, Div Neurotoxicol, Natl Ctr Toxicol Res, Expt Neuropathol Lab, Jefferson, AR 72079 USA. RP Scallet, AC (reprint author), USFDA, Div Neurotoxicol, Natl Ctr Toxicol Res, Expt Neuropathol Lab, 3900 NCTR Dr, Jefferson, AR 72079 USA. NR 31 TC 11 Z9 11 U1 0 U2 3 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-468-4 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2003 VL 993 BP 305 EP 312 PG 8 WC Multidisciplinary Sciences; Neurosciences SC Science & Technology - Other Topics; Neurosciences & Neurology GA BX10T UT WOS:000184303000033 PM 12853322 ER PT S AU Imam, SZ Oetinger, M Skinner, JT Slikker, W Ali, SF AF Imam, SZ Oetinger, M Skinner, JT Slikker, W Ali, SF BE Slikker, W Andrews, RJ Trembly, B TI The role of caspase III inhibition in methamphetamine-induced alterations in p53 and bcl-2 expression - Correlation with dopaminergic neurotoxicity SO NEUROPROTECTIVE AGENTS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 6th International Conference on Neuroprotective Agents CY SEP 15-19, 2002 CL HILTON HEAD ISL, SOUTH CAROLINA DE caspase III inhibition; methamphetamine-induced alterations; p53 expression; bcl-2 expression C1 US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Neurochem Lab, Jefferson, AR 72079 USA. RP Imam, SZ (reprint author), US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Neurochem Lab, Jefferson, AR 72079 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-468-4 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2003 VL 993 BP 350 EP 350 PG 1 WC Multidisciplinary Sciences; Neurosciences SC Science & Technology - Other Topics; Neurosciences & Neurology GA BX10T UT WOS:000184303000038 PM 12853327 ER PT S AU Imam, SZ Duhart, HM Skinner, JT Ali, SF AF Imam, SZ Duhart, HM Skinner, JT Ali, SF BE Slikker, W Andrews, RJ Trembly, B TI Cocaine induces a dose-dependent alteration in the expression of immediate early genes c-fos and SP-1 and in nuclear factor NF-kappa beta in PC12 cells SO NEUROPROTECTIVE AGENTS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 6th International Conference on Neuroprotective Agents CY SEP 15-19, 2002 CL HILTON HEAD ISL, SOUTH CAROLINA DE cocaine; c-fos; nuclear factor NF-kappa beta; PC12 cells C1 US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. RP Imam, SZ (reprint author), US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-468-4 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2003 VL 993 BP 362 EP 362 PG 1 WC Multidisciplinary Sciences; Neurosciences SC Science & Technology - Other Topics; Neurosciences & Neurology GA BX10T UT WOS:000184303000040 PM 12853329 ER PT S AU Delongchamp, RR Harris, AJ Bowyer, JF AF Delongchamp, RR Harris, AJ Bowyer, JF BE Slikker, W Andrews, RJ Trembly, B TI A statistical approach in using cDNA array analysis to determine modest changes in gene expression in several brain regions after neurotoxic insult SO NEUROPROTECTIVE AGENTS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 6th International Conference on Neuroprotective Agents CY SEP 15-19, 2002 CL HILTON HEAD ISL, SOUTH CAROLINA DE statistical approach; cDNA array analysis; gene expression; brain regions; neurotoxic insult ID NEURONAL DEGENERATION; MICROARRAY DATA; METHAMPHETAMINE; EXPOSURE; SEIZURE; DESIGN; INJURY; TESTS AB Modest changes in gene expression of three-fold or less might be expected after mild to moderate neurotoxic exposure to classes of compounds, such as the substituted amphetamines, or at time points that are weeks after more severe neurotoxic exposures. When many genes appear to change expression by less than two-fold, it is crucial to run several pairs of arrays and use statistical analysis to determine which genes are really changing. This limits the number of genes that have to undergo the time consuming task of performing RT-PCR to validate change in expression levels. We describe here methods for statistically determining which genes are being expressed above background levels. These methods are used to compare expression differences among the striatum, parietal cortex, posterior lateral amygdaloid nucleus, and substantia nigra brain regions, all of which differ significantly in their gene expression profiles. In these comparisons, it was possible to distinguish differences among hundreds of genes with manageable estimated false discovery rates. The effect of amphetamine treatment on gene expression in posterior lateral amygdaloid nucleus was also evaluated. The expression data indicate that many genes have changed, but in this case it is more difficult to separate affected genes from false positives. The optimum list has 50 genes, of which 32% are expected to be false positives. C1 US FDA, Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. RP Delongchamp, RR (reprint author), US FDA, Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, 3900 NCTR Rd, Jefferson, AR 72079 USA. NR 29 TC 10 Z9 10 U1 0 U2 0 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-468-4 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2003 VL 993 BP 363 EP 376 PG 14 WC Multidisciplinary Sciences; Neurosciences SC Science & Technology - Other Topics; Neurosciences & Neurology GA BX10T UT WOS:000184303000041 PM 12853330 ER PT S AU Imam, SZ AF Imam, SZ BE Slikker, W Andrews, RJ Trembly, B TI Molecular mechanisms of dopaminergic neurodegeneration - Genetic and environmental basis SO NEUROPROTECTIVE AGENTS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 6th International Conference on Neuroprotective Agents CY SEP 15-19, 2002 CL HILTON HEAD ISL, SOUTH CAROLINA DE molecular mechanism; dopaminergic neurodegeneration C1 US FDA, Div Neurotoxicol, Jefferson, AR USA. RP Imam, SZ (reprint author), US FDA, Div Neurotoxicol, Jefferson, AR USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-468-4 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2003 VL 993 BP 377 EP 377 PG 1 WC Multidisciplinary Sciences; Neurosciences SC Science & Technology - Other Topics; Neurosciences & Neurology GA BX10T UT WOS:000184303000042 PM 12853331 ER PT S AU Wulfkuhle, JD Paweletz, CP Steeg, PS Petricoin, EF Liotta, L AF Wulfkuhle, JD Paweletz, CP Steeg, PS Petricoin, EF Liotta, L BE LlombartBosch, A Felipo, V TI Proteomic approaches to the diagnosis, treatment, and monitoring of cancer SO NEW TRENDS IN CANCER FOR THE 21ST CENTURY SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT International Cancer Symposium on New Trends in Cancer for the 21st Century CY NOV 10-13, 2002 CL VALENCIA, SPAIN ID 2-DIMENSIONAL GEL-ELECTROPHORESIS; LASER CAPTURE MICRODISSECTION; PHOSPHORYLATED PROTEINS; FUNCTIONAL PROTEOMICS; MASS-SPECTROMETRY; MICROARRAYS; IDENTIFICATION; DISEASE; TARGETS; SERUM AB The field of proteomics holds promise for the discovery of new biomarkers for the early detection and diagnosis of disease, molecular targets for therapy and markers for therapeutic efficacy and toxicity. A variety of proteomics approaches may be used to address these goals. Two-dimensional gel electrophoresis (2D-PAGE) is the cornerstone of many discovery-based proteomics studies. Technologies such as laser capture microdissection (LCM) and highly sensitive MS methods are currently being used together to identify greater numbers of lower abundance proteins that are differentially expressed between defined cell populations. Newer technologies such as reverse phase protein arrays will enable the identification and profiling of target pathways in small biopsy specimens. Surface-enhanced laser desorption/ionization time-of-flight (SELDI-TOF) analysis enables the high throughput characterization of lysates from very few tumor cells or body fluids and may be best suited for diagnosis and monitoring of disease. Such technologies are expected to supplement our arsenal of mRNA-based assays, and we believe that in the., future, entire cellular networks and not just a single deregulated protein will be the target of therapeutics and that we will soon be able to monitor the status of these pathways in diseased cells before, during and after therapy. C1 NCI, FDA, Clin Proteom Prog, Pathol Lab,Ctr Canc Res, Bethesda, MD 20892 USA. NCI, Womens Canc Sect, Pathol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Clin Proteom Program, NCI, Bethesda, MD 20892 USA. RP Wulfkuhle, JD (reprint author), CBER, FDA, Bldg 29A-2B20,HFM 535,8800 Rockville Pike, Bethesda, MD 20892 USA. NR 36 TC 75 Z9 82 U1 1 U2 5 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0065-2598 BN 0-306-47762-9 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2003 VL 532 BP 59 EP 68 PG 10 WC Oncology; Medicine, Research & Experimental SC Oncology; Research & Experimental Medicine GA BX19E UT WOS:000184568400007 PM 12908550 ER PT J AU Sun, HH Collins, JM Mangner, TJ Muzik, O Shields, AF AF Sun, HH Collins, JM Mangner, TJ Muzik, O Shields, AF TI Imaging [F-18]FAU [1-(2 '-deoxy-2 '-fluoro-beta-D-arabinofuranosyl)uracil] in dogs SO NUCLEAR MEDICINE AND BIOLOGY LA English DT Article DE FAU; PET; thymidine kinase ID INTRA-ARTERIAL; THYMIDINE; PET; PHARMACOKINETICS; TUMORS AB We have studied the biodistribution of [F-18]FAU [(1-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)uracil], which previous work has shown is incorporated into DNA and functions as an inhibitor of DNA synthesis. It is being tested as a potential antineoplastic agent and imaging agent for PET. We have produced [F-18]FAU and injected the tracer into 3 normal dogs and imaged them for up to 4 hours and removed tissues along with blood and urine samples for HPLC and activity analysis. The result, showed that [F-18]FAU evenly distributed to most of organs. In sharp contrast to our prior experience with thymidine and its analogs, marrow had less retention of [F-18]FAU than the non-proliferating tissues. (C) 2002 Elsevier Science Inc. All rights reserved. C1 Wayne State Univ, Karmanos Canc Inst, Dept Med, Detroit Med Ctr, Detroit, MI 48202 USA. Wayne State Univ, Karmanos Canc Inst, Dept Radiol, Detroit Med Ctr, Detroit, MI USA. US FDA, Bethesda, MD 20014 USA. RP Shields, AF (reprint author), Wayne State Univ, Karmanos Canc Inst, Dept Med, Detroit Med Ctr, Detroit, MI 48202 USA. FU NCI NIH HHS [CA 82645, CA 83131] NR 10 TC 11 Z9 12 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0969-8051 J9 NUCL MED BIOL JI Nucl. Med. Biol. PD JAN PY 2003 VL 30 IS 1 BP 25 EP 30 AR PII S0969-8051(02)00376-1 DI 10.1016/S0969-8051(02)00376-1 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 631BN UT WOS:000180147200003 PM 12493539 ER PT J AU Hussain, M Banerjee, M Sarkar, FH Djuric, Z Pollak, MN Doerge, D Fontana, J Chinni, S Davis, J Forman, J Wood, DP Kucuk, O AF Hussain, M Banerjee, M Sarkar, FH Djuric, Z Pollak, MN Doerge, D Fontana, J Chinni, S Davis, J Forman, J Wood, DP Kucuk, O TI Soy isoflavones in the treatment of prostate cancer SO NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL LA English DT Article; Proceedings Paper CT AACR Special Meeting on Prostate Cancer CY DEC, 2001 CL Naples, FL SP AACR ID LOW-DENSITY-LIPOPROTEIN; OXIDATIVE DNA-DAMAGE; KAPPA-B ACTIVATION; GENISTEIN; CELLS; MEN; GROWTH; PHYTOESTROGENS; ANGIOGENESIS; INHIBITION AB Epidemiological studies suggest an inverse association between soy intake and prostate cancer (Pca) risk. We have previously observed that soy isoflavone genistein induces apoptosis and inhibits growth of both androgen-sensitive and androgen-independent Pca cells in vitro. To determine the clinical effects of soy isoflavones on Pca we conducted a pilot study in patients with Pca who had rising serum prostate-specific antigen (PSA) levels. Patients with Pca were enrolled in the study if they had either newly diagnosed and untreated disease under watchful waiting with rising PSA (group I) or had increasing serum PSA following local therapy (group II) or while receiving hormone therapy (group III). The study intervention consisted of 100 mg of soy isoflavone (Novasoy(R)) taken by mouth twice daily for a minimum of 3 or maximum of 6 mo. Forty-one patients were enrolled (4 in group 1, 18 in group II, and 19 in group III) and had a median PSA level of 13.3 ng/ml. Thirty-nine patients could be assessed for response. Soy isoflavone supplementation was given for a median of 5.5 (range 0.8-6) mo per patient. Although there were no sustained decreases in PSA qualifying for a complete or partial response, stabilization of the PSA occurred in 83% of patients in hormone-sensitive (group II) and 35% of hormone-refractory (group III) patients. There was a decrease in the rate of the rise of serum. PSA in the whole group (P = 0.01) with rates of rise decreasing from 14 to 6% in group II (P = 0.21) and from 31 to 9% in group III (P = 0.05) following the soy isoflavone intervention. Serum genistein and daidzein levels increased during supplementation from 0.11 to 0.65 muM (P = 0.00002) and from 0.11 to 0.5 muM (P = 0.00001), respectively. No significant changes were observed in serum levels of testosterone, IGF-1, IGFBP-3, or 5-OHmdU. These data suggest that soy isoflavones may benefit some patients with Pca. C1 Karmanos Canc Inst, Detroit, MI 48201 USA. Wayne State Univ, Vet Adm Med Ctr, Detroit, MI 48201 USA. Ctr Healthcare Effectiveness Res, Detroit, MI 48201 USA. Wayne State Univ, Dept Pathol, Detroit, MI 48201 USA. McGill Univ, Dept Med, Montreal, PQ, Canada. Jewish Gen Hosp, Montreal, PQ, Canada. US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. Wayne State Univ, Dept Radiat Oncol, Detroit, MI 48201 USA. Wayne State Univ, Dept Urol, Detroit, MI 48201 USA. Wayne State Univ, Div Hematol & Oncol, Detroit, MI 48201 USA. RP Kucuk, O (reprint author), Karmanos Canc Inst, 4100 John R,HWCRC 4th Floor, Detroit, MI 48201 USA. EM kucuko@karmanos.org RI Pollak, Michael/G-9094-2011; Djuric, Zora/H-5147-2013; OI Pollak, Michael/0000-0003-3047-0604; Djuric, Zora/0000-0002-8886-8853; Fontana, Joseph/0000-0003-3829-3358 FU NCI NIH HHS [P30-CA22453-20] NR 31 TC 96 Z9 96 U1 1 U2 6 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 2003 VL 47 IS 2 BP 111 EP 117 DI 10.1207/s15327914nc4702_1 PG 7 WC Oncology; Nutrition & Dietetics SC Oncology; Nutrition & Dietetics GA 816WY UT WOS:000221141200001 PM 15087261 ER PT J AU Dingley, KH Ubick, EA Chiarappa-Zucca, ML Nowell, S Abel, S Ebeler, SE Mitchell, AE Burns, SA Steinberg, FM Clifford, AJ AF Dingley, KH Ubick, EA Chiarappa-Zucca, ML Nowell, S Abel, S Ebeler, SE Mitchell, AE Burns, SA Steinberg, FM Clifford, AJ TI Effect of dietary constituents with chemopreventive potential on adduct formation of a low dose of the heterocyclic amines PhIP and IQ and phase II hepatic enzymes SO NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL LA English DT Article ID GLUTATHIONE S-TRANSFERASES; INDUCED MAMMARY CARCINOGENESIS; DNA-ADDUCT; 2-AMINO-1-METHYL-6-PHENYLIMIDAZO<4,5-B>PYRIDINE PHIP; BREAST-CANCER; UDP-GLUCURONOSYLTRANSFERASES; PHENETHYL ISOTHIOCYANATE; METABOLIZING-ENZYMES; ANTIOXIDANT ENZYMES; COLORECTAL-CANCER AB We conducted a study to evaluate dietary chemopreventive strategies to reduce genotoxic effects of the carcinogens 2-amino-l-methyl-6-phenyl-imidazo[4,5-b]pyridine (PhIP) and 2-amino-3-methylimidazo[4,5-f]quinoline (IQ). PUP and IQ are heterocyclic amines (HCAs) that are found in cooked meat and may be risk factors for cancer Typical chemoprevention studies have used carcinogen doses many thousand-fold higher than usual human daily intake. Therefore, we administered a low dose of [C-14] PhIP and [H-3]IQ and utilized accelerator mass spectrometry to quantify PhIP adducts in the liver colon,prostate, and blood plasma and IQ adducts in the liver and blood plasma with high sensitivity. Diets supplemented with phenethylisothiocyanate (PEITC), genistein, chlorophyllin, or lycopene were evaluated for their ability to decrease adduct formation of [C-14]PhIP and [H-3]IQ in rats. We also examined the effect of treatments on the activity of the phase II detoxification enzymes glutathione S-transferase (GST), UDP-glucuronyltransferase (UGT), phenol sulfotransferase (SULT) and quinone reductase (QR). PEITC and chlorophyllin significantly decreased PhIP-DNA adduct levels in all tissues examined, which was reflected by similar changes in PhIP binding to albumin in the blood. In contrast, genistein and lycopene tended to increase PhIP adduct levels. The treatments did not significantly alter the level of IQ-DNA or -protein adducts in the liver With the exception of lycopene, the treatments had some effect on the activity of one or more hepatic phase II detoxification enzymes. We conclude that PEITC and chlorophyllin are protective of PhIP-induced genotoxicity after a low exposure dose of carcinogen, possibly through modification of HCA metabolism. C1 Lawrence Livermore Natl Lab, Biol & Biotechnol Res Program, Livermore, CA 94551 USA. Lawrence Livermore Natl Lab, Ctr Accelerator Mass Spectrometry, Livermore, CA 94551 USA. Lawrence Livermore Natl Lab, Chem Biol & Nucl Div, Chem & Mat Sci Directorate, Livermore, CA 94551 USA. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Univ Calif Davis, Dept Vegetable Crops, Davis, CA 95616 USA. Univ Calif Davis, Dept Viticulture & Enol, Davis, CA 95616 USA. Univ Calif Davis, Dept Food Sci & Technol, Davis, CA 95616 USA. Univ Calif Davis, Dept Nutr, Davis, CA 95616 USA. RP Dingley, KH (reprint author), Lawrence Livermore Natl Lab, Biol & Biotechnol Res Program, L-452, Livermore, CA 94550 USA. OI Ebeler, Susan/0000-0002-8394-6736 FU NCI NIH HHS [CA55861]; NCRR NIH HHS [RR13461]; NIDDK NIH HHS [DK45939] NR 81 TC 63 Z9 63 U1 1 U2 9 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 2003 VL 46 IS 2 BP 212 EP 221 DI 10.1207/S15327914NC4602_15 PG 10 WC Oncology; Nutrition & Dietetics SC Oncology; Nutrition & Dietetics GA 750FN UT WOS:000186980800015 PM 14690798 ER PT J AU Cohen, MH Williams, GA Sridhara, R Chen, G Pazdur, R AF Cohen, MH Williams, GA Sridhara, R Chen, G Pazdur, R TI FDA drug approval summary: Gefitinib (ZD1839) (Iressa (R)) tablets SO ONCOLOGIST LA English DT Article DE gefitinib; Iressa (R); non-small cell lung cancer, metastatic; third-line treatment AB On May 5, 2003, gefitinib (Iressa((R)), ZD1839) 250-mg tablets received accelerated approval by the US. Food and Drug Administration as monotherapy treatment for patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) after failure of both platinum-based and docetaxel chemotherapies. Information provided in this summary includes efficacy and safety results of relevant clinical trials. Effectiveness was demonstrated in a randomized, double-blind, phase 11, multicenter trial comparing two oral doses of gefitinib (250 mg/day versus 500 mg/day). Two hundred sixteen patients were enrolled. The 142 patients who were refractory to or intolerant of a platinum and docetaxel comprised the evaluable population for the efficacy analysis. A partial tumor response occurred in 14% (9 of 66) of patients receiving gefitinib 250 mg/day and in 8% (6 of 76) of patients receiving gefitinib 500 mg/day. The overall objective response rate for both doses combined was 10.6% (15 of 142 patients) (95% confidence interval 6.0%-16.8%). Responses were more frequent in females and in nonsmokers. The median duration of response was 7.0 months (range 4.6-18.6+ months). Other submitted data included the results of two large trials conducted in chemotherapy-naive, stage III and IV NSCLC patients. Patients were randomized to receive gefitinib (250 mg or 500 mg daily) or placebo, in combination with either gemcitabine plus cisplatin (n = 1,093) or carboplatin plus paclitaxel (n = 1,037). Results from those studies showed no benefit (response rate, time to progression, or survival) from adding gefitinib to chemotherapy. Consequently, gefinitib is only recommended for use as monotherapy. Common adverse events associated with gefitinib treatment included diarrhea, rash, acne, dry skin, nausea, and vomiting. Most toxicities were Common Toxicity Criteria grade I or 2. Interstitial lung disease (ILD) has been observed in patients receiving gefitinib. Worldwide, the incidence of ILD is about 1% (2% in the Japanese postmarketing experience and about 0.3% in a U.S. expanded access program). Approximately one-third of the cases were fatal. Physicians should promptly evaluate new or worsening pulmonary symptoms. If ILD is confirmed, appropriate management includes discontinuation of gefitinib. Gefitinib was approved under accelerated approval regulations on the basis of a surrogate end point response rate. No controlled gefitinib trials, to date, demonstrate a clinical benefit, such as improvement in disease-related symptoms or greater survival. Accelerated approval regulations require the sponsor to conduct further studies to verify that gefitinib therapy produces such a benefit. C1 US FDA, Ctr Drug Evaluat & Res, Div Oncol Drug Prod, Rockville, MD 20857 USA. RP Cohen, MH (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Oncol Drug Prod, HFD-150,5600 Fishers Lane, Rockville, MD 20857 USA. NR 0 TC 278 Z9 310 U1 3 U2 22 PU ALPHAMED PRESS PI MIAMISBURG PA ONE PRESTIGE PLACE, STE 290, MIAMISBURG, OH 45342-3758 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2003 VL 8 IS 4 BP 303 EP 306 DI 10.1634/theoncologist.8-4-303 PG 4 WC Oncology SC Oncology GA 707GG UT WOS:000184502000002 PM 12897327 ER PT J AU Kane, RC Bross, PF Farrell, AT Pazdur, R AF Kane, RC Bross, PF Farrell, AT Pazdur, R TI Velcade((R)): USFDA approval for the treatment of multiple myeloma progressing on prior therapy SO ONCOLOGIST LA English DT Editorial Material DE multiple myeloma; bortezomib; Velcade((R)); accelerated approval ID PHASE-I TRIAL; COMBINATION CHEMOTHERAPY; SURVIVAL; TRANSPLANTATION; MALIGNANCIES AB Bortezomib (formerly PS-341), a promising new drug for the treatment of multiple myeloma, recently received accelerated approval from the U.S. Food and Drug Administration (FDA) for the therapy of patients with progressive myeloma after previous treatment. Two phase II studies of bortezomib used the same schedule of twice-weekly i.v. dosing for the first 2 weeks of each 3-week cycle. In a randomized study of 54 patients, two doses were compared (1.0 and 1.3 mg/m(2)) and objective responses occurred at both dose levels (23% versus 35%), including one complete response in each arm. In the other phase II study, 202 heavily pretreated patients (median of six prior therapies) all received the same schedule at 1.3 mg/m(2). Of 188 evaluable patients, complete responses occurred in five (3%) and partial responses occurred in 47 (25%). The median duration of response was 365 days. The most clinically relevant adverse events were asthenic conditions, nausea, vomiting, diarrhea, thrombocytopenia, and a peripheral neuropathy that often was painful. This report highlights the FDA analysis supporting the accelerated approval. C1 US FDA, Ctr Drug Evaluat & Res, Div Oncol Drug Prod, Rockville, MD 20857 USA. RP Kane, RC (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Oncol Drug Prod, HFD-150,5600 Fishers Lane, Rockville, MD 20857 USA. NR 20 TC 300 Z9 312 U1 1 U2 12 PU ALPHAMED PRESS PI MIAMISBURG PA ONE PRESTIGE PLACE, STE 290, MIAMISBURG, OH 45342-3758 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2003 VL 8 IS 6 BP 508 EP 513 DI 10.1634/theoncologist.8-6-508 PG 6 WC Oncology SC Oncology GA 748LG UT WOS:000186862900004 PM 14657528 ER PT S AU Ilev, IK Waynant, RW Gorman, E Luedtke, R Byrnes, KR Anders, J AF Ilev, IK Waynant, RW Gorman, E Luedtke, R Byrnes, KR Anders, J BE Gannot, I TI Combined fiber-optic confocal microscopy for noninvasive optical sensing SO OPTICAL FIBERS AND SENSORS FOR MEDICAL APPLICATIONS III SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Conference on Optical Fibers and Sensors for Medical Applications III CY JAN 25-28, 2003 CL SAN JOSE, CA SP SPIE DE confocal microscopy; fiber-optic sensors; noninvasive optical sensing; refractive-index ID REFRACTIVE-INDEX; THICKNESS AB A novel and simple noninvasive sensor technique for simultaneous measurement of refractive-index and thickness of both optically transparent and non-transparent media is presented. It is a fiber-optic confocal-microscope-type sensor technique based on either a single-confocal or a combined dual-confocal fiber-optic design. The single-confocal design is a single-fiber, intensity sensing arrangement that provides precise spatial location of the backreflecting sample surfaces and bi-parameter measurements. The combined dual-confocal design includes two independent confocal channels consisting of two identical apertureless fiber-optic-type confocal microscopes constructed by use of a single 2x2 fiber coupler. This sensor arrangement provides direct measurement in absolute unites of refractive-index and thickness of optically transparent and non-transparent media. C1 US FDA, Ctr Devices & Radiol Hlth, Electro Opt Branch, Rockville, MD 20857 USA. RP Ilev, IK (reprint author), US FDA, Ctr Devices & Radiol Hlth, Electro Opt Branch, HFZ-134, Rockville, MD 20857 USA. OI Byrnes, Kimberly/0000-0002-7501-7734 NR 11 TC 1 Z9 1 U1 1 U2 1 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-4757-9 J9 P SOC PHOTO-OPT INS PY 2003 VL 4957 BP 23 EP 28 DI 10.1117/12.488652 PG 6 WC Engineering, Biomedical; Instruments & Instrumentation; Optics SC Engineering; Instruments & Instrumentation; Optics GA BX31Y UT WOS:000184939100003 ER PT S AU Pfefer, TJ Matchette, LS Ross, AM Ediger, MN AF Pfefer, TJ Matchette, LS Ross, AM Ediger, MN BE Gannot, I TI Influence of fiberoptic probe geometry on the origin of detected fluorescence: Experimental validation of computational results SO OPTICAL FIBERS AND SENSORS FOR MEDICAL APPLICATIONS III SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Conference on Optical Fibers and Sensors for Medical Applications III CY JAN 25-28, 2003 CL SAN JOSE, CA SP SPIE DE fluorescence spectroscopy; fiberoptics; laser-tissue interaction ID TISSUE; SPECTROSCOPY; PROPAGATION; ENDOSCOPY; LIGHT AB Prior computational investigations indicate that the origin of signals detected during fluorescence spectroscopy is highly dependent on illumination-collection geometry. The present study was undertaken to provide experimental validation of trends noted in these prior studies. Two-layered tissue phantoms were constructed using agarose gels doped with Intralipid and either Fluorescein or Rhodamine to achieve biologically relevant levels of scattering and easily measurable levels of fluorescence. The effect of fiber diameter, fiber-sample spacing, and illumination-collection fiber spacing were investigated using single and multi-fiber probes. Increases in diameter and fiber-sample spacing for single fiber probes resulted in improved detection of the deeper fluorophore layer, as did an increase in illumination-collection fiber spacing in multi-fiber probes. As multi-fiber probe-sample spacing was increased, an increase in relative contribution from the superficial layer, followed by a subsequent reversal of this trend, was measured. Each of these results is in qualitative agreement with prior simulations, thus providing further evidence of the utility of numerical modeling as a tool for elucidating light-tissue interactions and device design. Furthermore, the trends noted here have the potential to form the basis of systems which determine the spatial distribution of tissue fluorophores and/or target specific tissue layers, thus leading to improvements in the efficacy of optical diagnostics. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Pfefer, TJ (reprint author), US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. NR 13 TC 0 Z9 0 U1 0 U2 3 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-4757-9 J9 P SOC PHOTO-OPT INS PY 2003 VL 4957 BP 142 EP 148 DI 10.1117/12.478055 PG 7 WC Engineering, Biomedical; Instruments & Instrumentation; Optics SC Engineering; Instruments & Instrumentation; Optics GA BX31Y UT WOS:000184939100018 ER PT J AU Abramson, JS Baker, CJ Baltimore, RS Bocchini, JA Long, SS McMmillan, JA Meissner, HC Powell, KR Prober, CG Rennels, MB Saari, TN Weiner, LB Swanson, J Embree, J Fischer, MA Mahoney, M Gellin, BG Makhene, M Orenstein, WA Pratt, DR Starke, JR Pickering, LK Ledbetter, EO Cook, M AF Abramson, JS Baker, CJ Baltimore, RS Bocchini, JA Long, SS McMmillan, JA Meissner, HC Powell, KR Prober, CG Rennels, MB Saari, TN Weiner, LB Swanson, J Embree, J Fischer, MA Mahoney, M Gellin, BG Makhene, M Orenstein, WA Pratt, DR Starke, JR Pickering, LK Ledbetter, EO Cook, M CA Comm Infect Dis TI Recommended childhood and adolescent immunization schedule - United States, 2003 SO PEDIATRICS LA English DT Article C1 Amer Acad Pediat, Comm Infect Dis, Elk Grove Village, IL 60007 USA. Amer Acad Pediat, Pediat Practice Act Grp, Elk Grove Village, IL 60007 USA. Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. Amer Acad Family Phys, Leawood, KS 66211 USA. Natl Vaccine Program Off, Atlanta, GA USA. NIH, Bethesda, MD 20892 USA. US FDA, Washington, DC 20204 USA. Amer Thorac Soc, New York, NY 10019 USA. RP Abramson, JS (reprint author), Amer Acad Pediat, Comm Infect Dis, Elk Grove Village, IL 60007 USA. NR 3 TC 11 Z9 11 U1 0 U2 0 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD JAN PY 2003 VL 111 IS 1 BP 212 EP 212 PG 1 WC Pediatrics SC Pediatrics GA 630XC UT WOS:000180135200051 ER PT J AU Shah, VP Elkins, J Shaw, S Hanson, R AF Shah, VP Elkins, J Shaw, S Hanson, R TI In vitro release: Comparative evaluation of vertical diffusion cell system and automated procedure SO PHARMACEUTICAL DEVELOPMENT AND TECHNOLOGY LA English DT Article DE in vitro release; vertical diffusion cell; automated procedure ID DERMATOLOGICAL DRUG PRODUCTS AB In vitro release for topical drug products is carried out using a vertical diffusion cell system and a synthetic support membrane. The improvements in vertical diffusion cell design and automated procedures have been carefully studied and evaluated to establish their reproducibility and ruggedness of the experimental procedure. The data were analyzed using 90% confidence interval procedure developed and published by the US Food and Drug Administration in SUPAC-SS (Start Up and Post Approval Changes-Semi Solid) guidance. C1 US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. Hanson Res Corp, Chatsworth, CA USA. RP Elkins, J (reprint author), 6742 St Anne, Dallas, TX 75247 USA. NR 6 TC 10 Z9 10 U1 0 U2 0 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 2003 VL 8 IS 1 BP 97 EP 102 DI 10.1081/PDT-120017528 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 657JE UT WOS:000181662100011 PM 12665202 ER PT J AU Ray, WA MacDonald, TM Solomon, DH Graham, DJ Avorn, J AF Ray, WA MacDonald, TM Solomon, DH Graham, DJ Avorn, J TI COX-2 selective non-steroidal anti-inflammatory drugs and cardiovascular disease SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Editorial Material ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; GASTROINTESTINAL TOXICITY; MYOCARDIAL-INFARCTION; RHEUMATOID-ARTHRITIS; CYCLOOXYGENASE-2; CELECOXIB C1 Vanderbilt Univ, Sch Med, MCN, Nashville, TN 37232 USA. Univ Dundee, Ninewells Hosp & Med Sch, Dept Clin Pharmacol & Therapeut, MEMO, Dundee DD1 9SY, Scotland. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. US FDA, Rockville, MD 20857 USA. RP Ray, WA (reprint author), Vanderbilt Univ, Sch Med, MCN, A-1124, Nashville, TN 37232 USA. NR 19 TC 13 Z9 14 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 2003 VL 12 IS 1 BP 67 EP 70 DI 10.1002/pds.798 PG 4 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 642TE UT WOS:000180819900009 PM 12616850 ER PT B AU Dietz, J AF Dietz, J BE Vasil, IK TI FDA's policy on food biotechnology SO PLANT BIOTECHNOLOGY 2002 AND BEYOND LA English DT Proceedings Paper CT 10th IAPTC&B Congress CY JUN 23-28, 2002 CL ORLANDO, FL SP Univ Florida, Genet Inst, Univ Florida, Inst Food & Agr Sci, Univ Florida, Interdisciplinary Ctr Biotechnol Res, Univ Florida, Off Provost, Univ Florida, Technol & Grad Educ, Danone Grp, Monsanto, Pioneer Hi Bred, Soc Vitro Biol, Plant Sect, ProfiGen, Syngenta, Canadian IAPTC&B Chapter, Epicyte Pharmaceut Inc, Exelixis Plant Sci, NASA, Plant Biotechnol Inst, Scotts Co, USA IAPTC&B Chapter, ArborGen LLC, Epcot, Land Walt Disney World Resort, RiceTec Inc, UNESCO, Council Biotechnol Informat, Kluwer Acad Publ, Nestle, Paradigm Genet, ProdiGene, Weyerhaeuser, Phytomedics DE biotechnology; food; laws; regulations C1 US FDA, College Pk, MD 20740 USA. RP Dietz, J (reprint author), US FDA, HFS-255,5100 Paint Branch Pkwy, College Pk, MD 20740 USA. NR 4 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS BN 1-4020-1126-1 PY 2003 BP 575 EP 578 PG 4 WC Biotechnology & Applied Microbiology; Plant Sciences SC Biotechnology & Applied Microbiology; Plant Sciences GA BW37K UT WOS:000181781600119 ER PT J AU Seo, KH Holt, PS Vaughn, LE Gast, RK Stone, HD AF Seo, KH Holt, PS Vaughn, LE Gast, RK Stone, HD TI Detection of Salmonella enteritidis - Specific immunoglobulin A antibodies in crop samples from chickens infected with Salmonella enteritidis SO POULTRY SCIENCE LA English DT Article DE mucosal immunity; immunoglobulin A; Salmonella; crop; poultry immunity ID LYMPHOID-TISSUES; COLONIZATION; HENS AB The crop (ingluvies), an organ for food storage in most avian species when the proventriculus is full, is located at the base of the esophagus. Little is known about any immunological capacity in the crop, and the current study was conducted to determine whether any antibodies to SE could be found in crop flushes taken from White Leghorn hens following infection with this organism. Surprisingly, an exceptionally strong IgA anti-SE response could be detected in the crops of hens 17 d postchallenge, and a comparison at Day 22 of crop vs: intestinal IgA anti-SE responses showed a good correlation between anti-SE antibody levels in the two regions. Histologic examination of crop tissues revealed development of lymphoid aggregates in the crop walls following challenge with SE. These results indicate that the crop may serve a role in immune protection in addition to its capacity as a food storage organ. C1 ARS, USDA, SE Poultry Res Lab, Athens, GA 30605 USA. US FDA, Ctr Food Safety & Appl Nutr, OPDEF HFS300, Washington, DC 20204 USA. RP Holt, PS (reprint author), ARS, USDA, SE Poultry Res Lab, 934 Coll Stn Rd, Athens, GA 30605 USA. NR 14 TC 12 Z9 12 U1 0 U2 0 PU POULTRY SCIENCE ASSOC INC PI SAVOY PA 1111 NORTH DUNLAP AVE, SAVOY, IL 61874-9604 USA SN 0032-5791 J9 POULTRY SCI JI Poult. Sci. PD JAN PY 2003 VL 82 IS 1 BP 67 EP 70 PG 4 WC Agriculture, Dairy & Animal Science SC Agriculture GA 638RF UT WOS:000180583500011 PM 12580247 ER PT B AU Weininger, S AF Weininger, S BE Reisman, S Foulds, R Mantilla, B TI Systems engineering and software devopment for the NIH fetal saturation (FOX) trial SO PROCEEDINGS OF THE IEEE 29TH ANNUAL NORTHEAST BIOENGINEERING CONFERENCE LA English DT Proceedings Paper CT IEEE 29th Annual Northeast Bioengineering Conference CY MAR 22-23, 2003 CL NJ INST TECHNOL, NEWARK, NJ SP Schering Plough, Becton Dickinson, Boston Sci, Reva Med, Vyteris, Whitaker Fdn, NJIT Pre Coll Programs, NJIT Student Senate, NJIT Grad Student Assoc HO NJ INST TECHNOL DE fetal saturation; fetal heart rate; signal acquisition; data acquisition; software development AB NIH-NICHD plans to analyze electronic fetal monitoring signals and data recorded from 10 000 pregnant women to assess the efficacy of the fetal oxygen saturation modality. The FOX project involves a systems engineering effort to determine the necessary fetal monitor configurations and interfaces, and a software development effort to design and implement an application to manage the study and collect the physiologic data from the monitors and store it on a PC. Major activities were the development of a project requirements document, a test plan, a requirements/design specification, a functioning prototype and final product, and to perform design reviews. Milestones included the delivery of a project requirements document and requirements specification, a prototype, completion of user acceptance testing on the final design, and beta site and full site deployments. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Weininger, S (reprint author), US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 0-7803-7767-2 PY 2003 BP 231 EP 232 PG 2 WC Computer Science, Artificial Intelligence; Engineering, Biomedical; Instruments & Instrumentation; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Instruments & Instrumentation; Radiology, Nuclear Medicine & Medical Imaging GA BX14C UT WOS:000184414900114 ER PT B AU Goldberger, MJ AF Goldberger, MJ BE Knobler, SL Lemon, SM Najafi, M Burroughs, T TI Antibiotic resistance: Encouraging the development of new therapies, preserving the usefulness of current therapies SO RESISTANCE PHENOMENON IN MICROBES AND INFECTIOUS DISEASE VECTORS: IMPLICATIONS FOR HUMAN HEALTH AND STRATEGIES FOR CONTAINMENT LA English DT Proceedings Paper CT Workshop Forum on Emerging Infections CY FEB 06-07, 2002 CL WASHINGTON, D.C. SP US Dept HHS, NIH, Ctr Dis Control & Prevent, US FDA, US Dept Def, US Dept State, US Dept Vet Affairs, USDA, Amer Soc Microbiol, Burroughs Wellcome Fund, Eli Lilly & Co, Pfizer, GlaxoSmithKline, Wyeth Ayerst Labs C1 US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Goldberger, MJ (reprint author), US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATL ACADEMIES PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE, WASHINGTON, DC 20418 USA BN 0-309-08854-2 PY 2003 BP 206 EP 210 PG 5 WC Public, Environmental & Occupational Health; Infectious Diseases; Microbiology SC Public, Environmental & Occupational Health; Infectious Diseases; Microbiology GA BY20U UT WOS:000188244000020 ER PT S AU Jiang, J Temenak, JJ Richards, AL AF Jiang, J Temenak, JJ Richards, AL BE Hechemy, KE AvsicZupanc, T Childs, JE Raoult, DA TI Real-time PCR duplex assay for Rickettsia prowazekii and Borrelia recurrentis SO RICKETTSIOLOGY: PRESENT AND FUTURE DIRECTIONS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT International Conference on Rickettsiae and Rickettsial Diseases CY SEP 04-07, 2002 CL LJUBLJANA, SLOVENIA SP Amer Soc Rickettsiol, DADE Behring, European Soc Clin Microbiol & Infect Dis, FOCUS Technol, Inst Mikrobiol Imunol, KEMOMED d o o, KRKA D D, LEK D D, Med Fakulteta Ljubljana, MEDILINE D O O, MINIST ZA SOLSTVO ZNANOST SPORT RS, PANIBIO Inc, Prirodoslovini Muzej Slovenije DE typhus; Rickettsia prowazekii; Borrelia recurrentis; human body louse ID POLYMERASE-CHAIN-REACTION; RELAPSING-FEVER; MOLECULAR BEACONS; EPIDEMIC TYPHUS; GENOTYPIC IDENTIFICATION; DIAGNOSIS; DISEASES AB Rickettsia prowazekii, the etiologic agent for epidemic typhus, and Borrelia recurrentis, the etiologic agent of relapsing fever, both utilize the same vector, the human body louse (Pediculus humanus), to transmit human disease. We have developed an assay to detect both bacterial pathogens in a single tube utilizing real-time PCR. Assays for both agents are specific. The R. prowazekii and B. recurrentis assays do not detect nucleic acid from R. typhi, R. canada, or any of eight spotted fever rickettsiae. In addition they did not react with Neorickettsia risticii, N. sennetsu, Franciscella persica, Bartonella quintana, Legionella pneumophila, Proteus mirabilis, Salmonella enterica, Escherichia coli, and Staphylococcus aureus. Moreover, the B. recurrentis assay did not detect B. duttonii, B. coriaceae, B. afzelii, B. garinii, B. hermsii, or B. burgdorferi nucleic acid. Both assays detected repeatedly only R. prowazekii or B. recurrentis either when tested alone or together in one test tube. C1 USN, Med Res Ctr, Rickettsial Dis Dept, Silver Spring, MD 20910 USA. Henry M Jackson Fdn, Rockville, MD USA. US FDA, Rockville, MD 20857 USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. RP Richards, AL (reprint author), USN, Med Res Ctr, Rickettsial Dis Dept, 503 Robert Grant Ave, Silver Spring, MD 20910 USA. NR 16 TC 14 Z9 18 U1 0 U2 4 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-444-7 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2003 VL 990 BP 302 EP 310 PG 9 WC Genetics & Heredity; Immunology; Infectious Diseases; Multidisciplinary Sciences SC Genetics & Heredity; Immunology; Infectious Diseases; Science & Technology - Other Topics GA BX09Q UT WOS:000184284900051 PM 12860643 ER PT S AU Ge, H Chuang, YE Zhao, S Temenak, JJ Ching, WM AF Ge, H Chuang, YE Zhao, S Temenak, JJ Ching, WM BE Hechemy, KE AvsicZupanc, T Childs, JE Raoult, DA TI Genomic studies of Rickettsia prowazekii virulent and avirulent strains SO RICKETTSIOLOGY: PRESENT AND FUTURE DIRECTIONS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT International Conference on Rickettsiae and Rickettsial Diseases CY SEP 04-07, 2002 CL LJUBLJANA, SLOVENIA SP Amer Soc Rickettsiol, DADE Behring, European Soc Clin Microbiol & Infect Dis, FOCUS Technol, Inst Mikrobiol Imunol, KEMOMED d o o, KRKA D D, LEK D D, Med Fakulteta Ljubljana, MEDILINE D O O, MINIST ZA SOLSTVO ZNANOST SPORT RS, PANIBIO Inc, Prirodoslovini Muzej Slovenije DE epidemic typhus; Rickettsia prowazekii; DNA microarray; virulence ID AGROBACTERIUM-TUMEFACIENS; LEGIONELLA-PNEUMOPHILA; ESCHERICHIA-COLI; CELL-DIVISION; VIRB4 ATPASE; FTSK; PROTEIN; RESOLUTION; SEGREGATION; GENE C1 USN, Med Res Ctr, Silver Spring, MD 20910 USA. NCI, NIH, Gaithersburg, MD 20877 USA. US FDA, Rockville, MD 20852 USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. RP Ching, WM (reprint author), USN, Med Res Ctr, 503 Robert Grant Ave, Silver Spring, MD 20910 USA. NR 17 TC 6 Z9 6 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-444-7 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2003 VL 990 BP 671 EP 677 PG 7 WC Genetics & Heredity; Immunology; Infectious Diseases; Multidisciplinary Sciences SC Genetics & Heredity; Immunology; Infectious Diseases; Science & Technology - Other Topics GA BX09Q UT WOS:000184284900113 PM 12860705 ER PT S AU Woods, TO AF Woods, TO BE Winters, GL Nutt, MJ TI MRI safety and compatibility of implants and medical devices SO STAINLESS STEELS FOR MEDICAL AND SURGICAL APPLICATIONS SE AMERICAN SOCIETY FOR TESTING AND MATERIALS SPECIAL TECHNICAL PUBLICATION LA English DT Proceedings Paper CT Symposium on Stainless Steels for Medical and Surgical Applications CY MAY 06-07, 2002 CL PITTSBURGH, PA SP ASTM Comm F04 DE MRI; MRI safety; MRI compatibility; implants; medical devices ID ANEURYSM CLIP AB Since MRI (magnetic resonance imaging) scanners became available in the 1980's, they have rapidly become one of the most common clinical imaging tools. The MR environment produces unique safety and compatibility issues for materials used in implants and medical devices. The principal issues for MR safety and compatibility are magnetically induced displacement force and torque, radio frequency (RF) heating, and image artifact. This paper defines and discusses the potential hazards produced by implants and devices in the MR environment, with an emphasis on stainless steels. It also describes MR safety and compatibility test methods developed by ASTM and summarizes ongoing MR standards development work. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. RP Woods, TO (reprint author), US FDA, Ctr Devices & Radiol Hlth, 9200 Corp Blvd,HFZ-150, Rockville, MD 20850 USA. NR 22 TC 3 Z9 3 U1 0 U2 0 PU AMERICAN SOCIETY TESTING AND MATERIALS PI W CONSHOHOCKEN PA 100 BARR HARBOR DRIVE, W CONSHOHOCKEN, PA 19428-2959 USA SN 1040-1695 BN 0-8031-3459-2 J9 AM SOC TEST MATER PY 2003 VL 1438 BP 82 EP 90 DI 10.1520/STP11156S PG 9 WC Instruments & Instrumentation; Metallurgy & Metallurgical Engineering; Materials Science, Biomaterials; Materials Science, Characterization & Testing SC Instruments & Instrumentation; Metallurgy & Metallurgical Engineering; Materials Science GA BW53S UT WOS:000182321300008 ER PT S AU Mannila, M Lang, QY Wai, CM Cui, YY Ang, CYW AF Mannila, M Lang, QY Wai, CM Cui, YY Ang, CYW BE Gopalan, AS Wai, CM Jacobs, HK TI Supercritical fluid extraction of bioactive components from St. John's Wort (hypericum perforatum L.) and Ginkgo biloba SO SUPERCRITICAL CARBON DIOXIDE: SEPARATIONS AND PROCESSES SE ACS SYMPOSIUM SERIES LA English DT Article; Proceedings Paper CT Symposium on Separations and Processes Using Supercritical Carbon Dioxide held at the 223rd American-Chemical-Society National Meeting CY APR 07-11, 2002 CL ORLANDO, FLORIDA SP Petr Res Fund, Amer Chem Soc, Div Ind & Engn Chem ID PERFORMANCE LIQUID-CHROMATOGRAPHY; ENRICHED CO2 EXTRACT; ANTIDEPRESSANT ACTIVITY; METHANOLIC EXTRACT; HYPERFORIN; LEAVES; OPTIMIZATION; DEPRESSION; SEPARATION; STABILITY AB Supercritical fluid extraction (SFE) offers an attractive alternative to solvent-based methods for extraction and manufacturing of herbal products. In addition to being a "green" solvent, supercritical CO2 can also be selective for extraction and separation of active ingredients from certain herbs. The main active constituents in St. John's wort are hyperforin and adhyperforin, which can be effectively extracted with neat CO2 under mild conditions (30 degreesC and 80 atm). Furthermore, extraction of hyperforin and adhyperforin from St. John's wort with neat CO2 is selective, resulting in a fairly enriched and stable extract of these compounds. A successful supercritical. CO2 extraction of terpene trilactones (bilobalide and ginkgolides A, B and Q from Ginkgo biloba leaves can be achieved at an elevated temperature (100 degreesC) and high pressure (350 atm; 0.72 g/ml density) with a small amount of ethanol/acetic acid (9:1) as a modifier. SFE of bilobalide and ginkgolides under these conditions resulted in an approximately 10% higher yield compared with traditional solvent based extractions. C1 Univ Idaho, Dept Chem, Moscow, ID 83844 USA. US FDA, Natl Ctr Toxicol Res, Div Chem, Jefferson, AR 72079 USA. RP Mannila, M (reprint author), Univ Idaho, Dept Chem, Moscow, ID 83844 USA. NR 45 TC 5 Z9 5 U1 1 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 SIXTEENTH ST NW, WASHINGTON, DC 20036 USA SN 0097-6156 BN 0-8412-3836-7 J9 ACS SYM SER PY 2003 VL 860 BP 130 EP 144 PG 15 WC Chemistry, Multidisciplinary SC Chemistry GA BX55A UT WOS:000185657900009 ER PT S AU Grajkowski, A Cieslak, J Chmielewski, MK Marchan, V Phillips, LR Wilk, A Beaucage, SL AF Grajkowski, A Cieslak, J Chmielewski, MK Marchan, V Phillips, LR Wilk, A Beaucage, SL BE ChoChung, YS Gewirtz, AM Stein, CA TI Conceptual "heat-driven" approach to the synthesis of DNA oligonucleotides on microarrays SO THERAPEUTIC OLIGONUCLEOTIDES: ANTISENSE, RNAI, TRIPLE-HELIX, GENE REPAIR, ENHANCER DECOYS, CPG AND DNA CHIPS SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT 6th NIH Symposium on Therapeutic Oligonucleotides CY DEC 16-17, 2002 CL Bethesda, MD SP NIH Therapeut Oligonucleotides Interest Grp, NCI, Doris Duke Charitable Fdn, Genta Inc, NIH Interest Grp Fdn DE deoxyribonucleoside cyclic N-acylphosphoramidites; deoxyribonucleoside phosphoramidites; solid-phase oligonucleotide synthesis; heat-sensitive phosphate protecting groups; nucleobase protection; 5 '-hydroxyl protection; 3 '-O-acetylthymidine 5 '-O-carbonates; cyclodeesterification; cyclodecarbonation; thermolytic deprotection; microarrays ID PHOSPHATE/THIOPHOSPHATE PROTECTING GROUP; PHASE OLIGODEOXYRIBONUCLEOTIDE SYNTHESIS; GENE-EXPRESSION PATTERNS; LIGHT-DIRECTED SYNTHESIS; ARRAYS; HYBRIDIZATION; DISCOVERY AB The discovery of deoxyribonucleoside cyclic N-acylphosphoramidites, a novel class of phosphoramidite monomers for solid-phase oligonucleotide synthesis, has led to the development of a number of phosphate protecting groups that can be cleaved from DNA oligonucleotides under thermolytic neutral conditions. These include the 2-(N-formyl-N-methyl) amino ethyl, 4-oxopentyl, 3-(N-tert-butyl)carboxamido-1-propyl, 3-(2-pyridyl)-1-propyl, 2-[N-methyl-N-(2-pyridyl)]aminoethyl, and 4-methythiobutyl groups. When used for 5'-hydroxyl protection of nucleosides, the analogous 1-phenyl-2-[N-methyl-N-(2-pyridyl)]aminoethyloxycarbonyI group exhibited excellent thermolytic properties, which may permit an iterative "heat-driven" synthesis of DNA oligonucleotides on microarrays. In this regard, progress has been made toward the use of deoxyribonucleoside cyclic N-acylphosphoramidites in solid-phase oligonucleotide syntheses without nucleobase protection. Given that deoxyribonucleoside cyclic N-acylphosphoramidites produce oligonucleotides with heat-sensitive phosphate protecting groups, blocking the 5'-hydroxyl of these monomers with, for example, the thermolabile 1-phenyl-2-[N-methyl-N-(2pyridyl)]aminoethyloxycarbonyl group may provide a convenient thermocontrolled method for the synthesis of oligonucleotides on microarrays. C1 US FDA, Ctr Biol Evaluat & Res, Div Therapeut Prot, Bethesda, MD 20892 USA. NCI, Biol Testing Branch, Dev Therapeut Program, Frederick, MD 21701 USA. US Pharmacopeia, Rockville, MD 20852 USA. RP US FDA, Ctr Biol Evaluat & Res, Div Therapeut Prot, 8800 Rockville Pike, Bethesda, MD 20892 USA. EM beaucage@cber.fda.gov RI Marchan, Vicente/K-9751-2014 OI Marchan, Vicente/0000-0002-1905-2156 NR 26 TC 11 Z9 11 U1 0 U2 4 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-470-6 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2003 VL 1002 BP 1 EP 11 DI 10.1196/annals.1281.003 PG 11 WC Biotechnology & Applied Microbiology; Oncology; Medicine, Research & Experimental; Multidisciplinary Sciences SC Biotechnology & Applied Microbiology; Oncology; Research & Experimental Medicine; Science & Technology - Other Topics GA BY69H UT WOS:000189440400001 PM 14751818 ER PT S AU Klinman, DM Zeuner, R Yamada, H Gursel, M Currie, D Gursel, I AF Klinman, DM Zeuner, R Yamada, H Gursel, M Currie, D Gursel, I BE ChoChung, YS Gewirtz, AM Stein, CA TI Regulation of CpG-induced immune activation by suppressive oligodeoxynucleotides SO THERAPEUTIC OLIGONUCLEOTIDES: ANTISENSE, RNAI, TRIPLE-HELIX, GENE REPAIR, ENHANCER DECOYS, CPG AND DNA CHIPS SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT 6th NIH Symposium on Therapeutic Oligonucleotides CY DEC 16-17, 2002 CL Bethesda, MD SP NIH Therapeut Oligonucleotides Interest Grp, NCI, Doris Duke Charitable Fdn, Genta Inc, NIH Interest Grp Fdn DE synthetic oligonucleotides; CpG motifs; immune activation ID BACTERIAL-DNA; IN-VIVO; IMMUNOSTIMULATORY DNA; DENDRITIC CELLS; KINASE-ACTIVITY; CUTTING EDGE; B-CELLS; MOTIFS; OLIGONUCLEOTIDES; GAMMA AB Bacterial DNA and synthetic oligodeoxynucleotides (ODN) containing unmethylated "CpG motifs" stimulate an innate immune response characterized by the production of cytokines, chemokines, and polyreactive Igs that promote host survival following infectious challenge. Yet CpG-driven immune activation can have deleterious consequences, such as increasing the host's susceptibility to autoimmune disease. The immunomodulatory activity of CpG DNA can be blocked by DNA containing "suppressive" motifs. This work explores the rules governing cellular recognition of stimulatory and suppressive motifs, and the resultant modulation of the immune system. Results suggest that both CpG and suppressive ODN may find use as therapeutic agents. C1 US FDA, Ctr Biol Evaluat & Res, Sect Retroviral Res, Bethesda, MD 20892 USA. RP US FDA, Ctr Biol Evaluat & Res, Sect Retroviral Res, Bldg 29A,Rm 3 D10, Bethesda, MD 20892 USA. EM Klinman@cber.fda.gov RI Gursel, Mayda /H-1812-2012; OI Gursel, Ihsan/0000-0003-3761-1166; Gursel, Mayda/0000-0003-0044-9054 NR 39 TC 26 Z9 29 U1 0 U2 0 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-470-6 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2003 VL 1002 BP 112 EP 123 DI 10.1196/annals.1281.023 PG 12 WC Biotechnology & Applied Microbiology; Oncology; Medicine, Research & Experimental; Multidisciplinary Sciences SC Biotechnology & Applied Microbiology; Oncology; Research & Experimental Medicine; Science & Technology - Other Topics GA BY69H UT WOS:000189440400012 PM 14751829 ER PT J AU Hollingworth, RM Bjeldanes, LF Bolger, M Kimber, I Meade, BJ Taylor, SL Wallace, KB AF Hollingworth, RM Bjeldanes, LF Bolger, M Kimber, I Meade, BJ Taylor, SL Wallace, KB CA SOT Ad Hoc Working Grp TI The safety of genetically modified foods produced through biotechnology SO TOXICOLOGICAL SCIENCES LA English DT Article ID EOSINOPHILIA-MYALGIA-SYNDROME; FEEDING VALUE; CORN POLLEN; EQUIVALENT; SOYBEANS; IMPACT; GENE; IDENTIFICATION; METHYLATION; POPULATIONS C1 Michigan State Univ, E Lansing, MI 48824 USA. Univ Calif Berkeley, Berkeley, CA 94720 USA. US FDA, Rockville, MD 20857 USA. NIOSH, Cincinnati, OH 45226 USA. Univ Nebraska, Lincoln, NE 68583 USA. Univ Minnesota, Minneapolis, MN 55455 USA. RP Hollingworth, RM (reprint author), Michigan State Univ, E Lansing, MI 48824 USA. NR 47 TC 41 Z9 42 U1 1 U2 23 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 2003 VL 71 IS 1 BP 2 EP 8 PG 7 WC Toxicology SC Toxicology GA 634VT UT WOS:000180363000001 PM 12520069 ER PT J AU McDonald, LJ Loberg, LI McCormick, DL Gauger, JR Savage, RE Zhu, H Lotz, WG Mandeville, R Owen, RD Cress, LW Desta, AB AF McDonald, LJ Loberg, LI McCormick, DL Gauger, JR Savage, RE Zhu, H Lotz, WG Mandeville, R Owen, RD Cress, LW Desta, AB TI Ornithine decarboxylase activity in tissues from rats exposed to 60 Hz magnetic fields, including harmonic and transient field characteristics SO TOXICOLOGY MECHANISMS AND METHODS LA English DT Article DE intermittent exposures; in vivo; multilaboratory analysis; ODC ID CARCINOMA CELLS; COHERENCE TIME; ODC ACTIVITY; POLYAMINE; INDUCTION; MICE; SUPERPOSITION; MICROWAVES; PROMOTER; PROTEIN AB Ornithine decarboxylase (ODC) activity is used widely as a biomarker for tumor promotion in animal model systems. Several previous studies have reported increases in ODC activity in tissues of rats exposed to 60 Hz magnetic fields. The goals of this study were to confirm these findings and to determine whether ODC activity is increased in tissues of animals exposed to magnetic fields containing complex metrics. Three experiments were conducted in male F344 rats. Each study included a sham control group and a group exposed to pure continuous 60 Hz fields (0.2 mT). Additional groups included animals exposed to randomly time-varying 60 Hz fields (range of 0.02 to 0.2 mT); intermittent 60 Hz fields (2 mT) with on-off cycles ranging from 5 s to 5 min; pure continuous 180 Hz fields (2 mT); 60 Hz fields with a superimposed 3rd harmonic (total field strength, 2 mT); 60 Hz fields with superimposed third, fifth, and seventh harmonics (total field strength, 2 mT); 60 Hz fields (2 mT) with superimposed transients; and randomly time-varying 60 Hz fields (range of 0.02 to 0.2 mT) with superimposed transients. After 4 weeks of exposure (18.5 h/day), eight animals per group were euthanized within 1 h of magnetic field deactivation. Homogenates of liver, kidneys, spleen, and brain were prepared from each animal, quick-frozen, and shipped for analysis by four independent laboratories. No consistent pattern of differences in the ODC activity among experimental groups was found either within a laboratory or among laboratories. The results do not support the hypothesis that exposure to extremely low frequency magnetic fields stimulates ODC activity. C1 NIOSH, DART, Cincinnati, OH 45226 USA. Mem Sloan Kettering Canc Ctr, Cellular Biochem & Biophys Project, New York, NY 10021 USA. IIT, Res Inst, Life Sci Res Sect, Chicago, IL 60616 USA. IIT, Res Inst, Electromagnet & Elect Syst Sect, Chicago, IL 60616 USA. Biophage Inc, Montreal, PQ, Canada. US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Savage, RE (reprint author), NIOSH, DART, MS C-27,4676 Columbia Pkwy, Cincinnati, OH 45226 USA. NR 31 TC 0 Z9 0 U1 2 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1537-6524 J9 TOXICOL MECH METHOD JI Toxicol. Mech. Methods PD JAN-MAR PY 2003 VL 13 IS 1 BP 31 EP 38 DI 10.1080/15376520390178148 PG 8 WC Toxicology SC Toxicology GA 637JZ UT WOS:000180509100004 PM 20021180 ER PT J AU Glynn, SA Williams, AE Nass, CC Bethel, J Kessler, D Scott, EP Fridey, J Kleinman, SH Schreiber, GB AF Glynn, SA Williams, AE Nass, CC Bethel, J Kessler, D Scott, EP Fridey, J Kleinman, SH Schreiber, GB CA Retrovirus Epidemiology Donor Stud TI Attitudes toward blood donation incentives in the United States: implications for donor recruitment SO TRANSFUSION LA English DT Article ID CHI-SQUARED TESTS; TABLES AB BACKGROUND: The potential effectiveness of various donation incentive programs may vary by demographics, first-time or repeat status, and collection site. STUDY DESIGN AND METHODS: Attitudes toward future incentives were obtained from a 1998 anonymous survey sent to 92,581 US blood donors. Responses (encouraged, discouraged, no difference) to incentives were compared within demographic groups, donations sites, and between first-time and repeat community whole-blood (WB) donors using chi-square tests and logistic regressions adjusted for sample design. RESULTS: Incentives most likely to encourage donation return among all 45,588 WB respondents were blood credits (61%), cholesterol screening (61%), and prostate-specific antigen (PSA) screening (73% of men). Younger donors (less than or equal to25 years old) were 4 to 5 times more likely to be encouraged to donate if offered compensatory incentives (tickets to events, discounts or lottery and/or raffle tickets), gifts, or a token of appreciation than were those donors older than 55. This age effect influenced positive attitudes toward incentives in first-time donors and in donors giving at schools, universities, or military sites. Among all donors, up to 7 to 9 percent reported they would be discouraged to return if offered compensatory incentives. CONCLUSIONS: Blood credits and cholesterol and PSA screening would be well received at all donation sites. Gifts, compensatory incentives, and tokens of appreciation appeal more to younger donors. These data may allow blood centers to optimize recruitment by tailoring limited incentive resources more effectively. C1 WESTAT Corp, Rockville, MD 20850 USA. US FDA, CBER, Off Blood Res & Review, Rockville, MD 20857 USA. Amer Red Cross, Blood Serv, Baltimore, MD USA. New York Blood Ctr, New York, NY 10021 USA. Blood Bank San Bernardino & Riverside Counties, San Bernardino, CA USA. RP Glynn, SA (reprint author), WESTAT Corp, WB 280,1441 W Montgomery Ave, Rockville, MD 20850 USA. FU NHLBI NIH HHS [N01-HB-97079, N01-HB-47114, N01-HB-97077, N01-HB-97078, N01-HB-97080, N01-HB-97081, N01-HB-97082] NR 28 TC 59 Z9 67 U1 2 U2 5 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD JAN PY 2003 VL 43 IS 1 BP 7 EP 16 DI 10.1046/j.1537-2995.2003.00252.x PG 10 WC Hematology SC Hematology GA 634BY UT WOS:000180321200003 PM 12519425 ER PT J AU Kotewicz, ML Brown, EW LeClerc, JE Cebula, TA AF Kotewicz, ML Brown, EW LeClerc, JE Cebula, TA TI Genomic variability among enteric pathogens: the case of the mutS-rpoS intergenic region SO TRENDS IN MICROBIOLOGY LA English DT Review ID ESCHERICHIA-COLI; HORIZONTAL TRANSFER; EVOLUTION; SEQUENCE; REPAIR; RECOMBINATION; BACTERIA; ORIGIN; GENES AB The mutS-rpoS intergenic region of enteric bacteria ranges in size from 88 bp in Yersinia to > 12 000 bp in Salmonella. We interpret this expansion as the result of the horizontal transfer of segments of DNA from diverse origins. Both comparative genomic analysis and selective sequencing of a variety of Escherichia coli pathogens have provided additional evidence for reassortment of segments within this region. C1 US FDA, Div Mol Biol, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. RP Cebula, TA (reprint author), US FDA, Div Mol Biol, Ctr Food Safety & Appl Nutr, MOD-1,8301 Muirkirk Rd, Laurel, MD 20708 USA. NR 31 TC 25 Z9 27 U1 0 U2 0 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0966-842X J9 TRENDS MICROBIOL JI Trends Microbiol. PD JAN PY 2003 VL 11 IS 1 BP 2 EP 6 AR PII S0966-842X(02)00005-7 DI 10.1016/S0966-842X(02)00005-7 PG 5 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 640GY UT WOS:000180681400001 PM 12526846 ER PT J AU Brennan, MJ Morris, SL Orme, IM AF Brennan, MJ Morris, SL Orme, IM TI Obituary - Frank Miles Collins (March 30, 1928 November 2, 2002) SO TUBERCULOSIS LA English DT Biographical-Item C1 US FDA, Lab Mycobacterial Dis & Cell Immunol, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. Colorado State Univ, Ft Collins, CO 80523 USA. RP Brennan, MJ (reprint author), US FDA, Lab Mycobacterial Dis & Cell Immunol, Ctr Biol Evaluat & Res, Bldg 29,Room 503,HFM 431,29 Lincoln Dr, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 1472-9792 J9 TUBERCULOSIS JI Tuberculosis PY 2003 VL 83 IS 4 BP 271 EP 272 DI 10.1016/S1472-9792(03)00046-5 PG 2 WC Immunology; Microbiology; Respiratory System SC Immunology; Microbiology; Respiratory System GA 715FB UT WOS:000184959000005 ER PT S AU Cerniglia, CE AF Cerniglia, CE BE Sasek, V Glaser, JA Baveye, P TI Recent advances in the biodegradation of polycyclic aromatic hydrocarbons by Mycobacterium species SO UTILIZATION OF BIOREMEDIATION TO REDUCE SOIL CONTAMINATION: PROBLEMS AND SOLUTIONS SE NATO Science Series IV Earth and Environmental Sciences LA English DT Proceedings Paper CT NATO Advanced Research Workshop on the Utilization of Bioremediation to Reduce Soil Contamination CY JUN 14-19, 2000 CL PRAGUE, CZECH REPUBLIC SP NATO ID SP STRAIN PYR-1; ANAEROBIC NAPHTHALENE DEGRADATION; PYRENE-DEGRADING BACTERIUM; RING FISSION-PRODUCTS; MICROBIAL-METABOLISM; CONTAMINATED SOILS; PHENANTHRENE DEGRADATION; CATALASE-PEROXIDASE; REDUCING CONDITIONS; MINERALIZATION AB Polycyclic aromatic hydrocarbons (PAHs) constitute a class of organic compounds containing two or more fused benzene rings in linear, angular, and cluster arrangements. The environmental fate of these ubiquitous contaminants is of concern because of the mutagenicity, ecotoxicity, and carcinogenic potential of high-molar-mass PAHs. A variety of bacterial species have been isolated that have the ability to degrade PAHs with two rings (naphthalene) and three rings (anthracene and phenanthrene). Most of the research on the degradative biochemical pathways, the genes involved in PAH metabolism, and genetic regulation has been on Pseudomonas, Sphingomonas, Burkholderia, and Comamonas strains. Recent reports have shown that various Mycobacteritum, Nocardia, and Rhodococcus species have the ability to degrade PAHs containing more than three rings (such as pyrene, fluoranthene, and benzo[alpha]pyrene). Mycobacterium sp. PYR-1 (reclassified as Mycobacterium van-baalenii strain PYR-1), which was originally isolated from oil-contaminated estuarine and marine sediments, is capable of mineralizing PAHs, such as naphthalene, pyrene, fluoranthene, phenanthrene, anthracene and benzo[alpha]pyrene. Biodegradation pathways have been elucidated which suggest that Mycobacterium sp. PYR-1 metabolizes PAHs through similar and unique catabolic pathways compared to that reported for Gram-negative bacteria. Mycobacterium sp. PYR-1 enhanced the degradation of four different aromatic ring classes of PAHs when inoculated into microcosms containing sediment and water from estuarine and freshwater environments. Molecular techniques to detect the Mycobacterium indicated that it survived and performed well in mixed-sediment microbial populations. Analysis of protein expression in Mycobacterium sp. PYR-1 using 2-dimensional polyacrylamide gel electrophoresis. enabled detection of several major proteins whose activity was increased after induction by PAHs. The cloning and sequence analysis of some of the genes encoding PAH degradation have been conducted. These studies demonstrate the bioremediation potential of Mycobacterium species to degrade PAHs in aquatic and terrestrial environments. C1 US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. RP Cerniglia, CE (reprint author), US FDA, Natl Ctr Toxicol Res, Div Microbiol, 3900 NCTR Rd, Jefferson, AR 72079 USA. NR 82 TC 3 Z9 3 U1 1 U2 14 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 1568-1238 BN 1-4020-1141-5 J9 NATO SCI S SS IV EAR JI NATO Sci. Series IV Earth Environ. Sciences PY 2003 VL 19 BP 51 EP 73 PG 23 WC Engineering, Environmental; Environmental Sciences; Soil Science; Toxicology SC Engineering; Environmental Sciences & Ecology; Agriculture; Toxicology GA BW49V UT WOS:000182216400004 ER PT J AU Thorpe, SJ Sands, D Fox, B Behr-Gross, ME Schaffner, G Yu, MW AF Thorpe, SJ Sands, D Fox, B Behr-Gross, ME Schaffner, G Yu, MW TI A global standard for anti-D immunoglobulin: international collaborative study to evaluate a candidate preparation SO VOX SANGUINIS LA English DT Article DE anti-D immunoglobulin; global standardization; potency ID QUANTITATION; PRODUCTS; ASSAY AB Background and Objectives The aim of the study was to evaluate a lyophilized anti-D immunoglobulin preparation to serve as a global standard for potency assays of anti-D immunoglobulin products. Materials and Methods The candidate global standard, 01/572, was calibrated against the World Health Organization (WHO) International Reference Preparation (IRP) for anti-D immunoglobulin, human (68/419), along with two reserve candidate reference preparations, in an international collaborative study involving 25 laboratories in 15 countries. The United States Food and Drug Administration (US-FDA) Center for Biologics Evaluation and Research (CBER) Standard for anti-D immunoglobulin, Lot 3, was included for comparison. Most laboratories (20/25) performed AutoAnalyser methodology, competitive enzyme-linked immunoassay (EIA) and/or flow cytometry. Results The overall mean potency of the candidate global standard, 01/572, was 284.5 international units (IU)/ampoule, with an interlaboratory variability, expressed as a percentage geometric coefficient of variation (% gcv), of 9.7. The mean potency of the US Standard was 859.4 IU/ml with an interlaboratory variability of 9.5% gcv, excluding an outlier. The mean potencies of the reserve preparations per ampoule/vial were 110.6 IU and 106.7 IU when calibrated against the IRP, and 112.2 IU and 106.6 IU when calibrated against 01/572, respectively, with interlaboratory % gcv values of 9.6-18.3 (excluding outliers). Conclusions Preparation 01/572 proved more suitable for use as a global standard than the reserve candidate preparations and was established, with an assigned potency of 285 IU/ampoule, by the WHO as the 2nd International Standard for anti-D immunoglobulin; by FDA-CBER as the Standard for anti-D immunoglobulin, Lot 4; and by the European Directorate for the Quality of Medicines (EDQM) as the 1st Biological Reference Preparation for anti-D immunoglobulin. C1 Natl Inst Biol Stand & Controls, Potters Bar EN6 3QG, Herts, England. European Directorate Qual Med, Strasbourg, France. Paul Ehrlich Inst, D-6070 Langen, Germany. Ctr Biol Evaluat & Res, Bethesda, MD USA. RP Thorpe, SJ (reprint author), Natl Inst Biol Stand & Controls, Blanche Lane,S Mimms, Potters Bar EN6 3QG, Herts, England. RI Thorpe, Susan/E-1808-2013; Fox, Bernard/E-2523-2013 NR 16 TC 5 Z9 5 U1 1 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. PY 2003 VL 85 IS 4 BP 313 EP 321 DI 10.1111/j.0042-9007.2003.00367.x PG 9 WC Hematology SC Hematology GA 747GE UT WOS:000186796200009 PM 14633258 ER PT J AU Bloom, ET AF Bloom, ET TI Xenotransplantation - Federal regulatory considerations SO XENO-TRANSPLANTATION SE CURRENT TOPICS IN MICROBIOLOGY AND IMMUNOLOGY LA English DT Review ID PORCINE ENDOGENOUS RETROVIRUS; LIVER SUPPORT-SYSTEM; BIOARTIFICIAL LIVER; HUMAN-CELLS; INFECTION AB Xenotransplantation may offer benefits to individual patients, but may also pose significant risks, to the recipient and to the public at large. The United States Food and Drug Administration endeavors to meet the challenge of regulating xenotransplantation to allow its development while safeguarding the public health. The approach includes using the existing FDA regulatory framework, publishing xenotransplantation-specific guidance documents, obtaining public input, and collaborating with other public: health agencies and international bodies in order to develop and maintain a safe and rational program for the regulation of xenotransplantation. C1 US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Lab Immunol & Virol, Rockville, MD 20852 USA. RP Bloom, ET (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Lab Immunol & Virol, HFM-518,1401 Rockville Pike, Rockville, MD 20852 USA. NR 20 TC 11 Z9 12 U1 2 U2 2 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0070-217X J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 2003 VL 278 BP 239 EP 251 PG 13 WC Immunology; Microbiology SC Immunology; Microbiology GA BX55Q UT WOS:000185672800009 PM 12934947 ER PT J AU Sweeney, C Coles, BF Nowell, S Lang, NP Kadlubar, FF AF Sweeney, C Coles, BF Nowell, S Lang, NP Kadlubar, FF TI Novel markers of susceptibility to carcinogens in diet: associations with colorectal cancer SO TOXICOLOGY LA English DT Article; Proceedings Paper CT 9th International Congress of Toxicology (ICT IX) CY JUL 08-12, 2001 CL QUEENSLAND, AUSTRALIA DE cytochrome P450 2A6; caffeine phenotype; glutathione S-transferase A1; colorectal cancer ID GLUTATHIONE S-TRANSFERASES; POLYMORPHISM; PHENOTYPES; CAFFEINE; RISK; MEAT AB Red meats cooked at high temperatures generate mutagenic heterocyclic amines, which undergo metabolic activation by hepatic cytochrome P450 1A2 and N-acetyltransferase-2. A primary detoxification pathway involves glutathione S-transferase A1 (GSTA1), which catalyzes the reduction of the carcinogenic N-acetoxy derivative back to the parent amine. Recently, we described a polymorphism in the GSTA1 proximal promoter; the variant (GSTA1*B) allele significantly lowers enzyme expression. In a case-control study, GSTA1*B/*B genotype was associated with an increased risk of colorectal cancer, particularly among consumers of well-done meat. Dietary nitrosamines, which are bioactivated by CYP2A6, represent another potential etiologic factor for colorectal cancer. CYP2A6 converts the caffeine metabolite 1,7-dimethylxanthine (17X) to 1,7-dimethyluric acid (17U); we investigated CYP2A6 activity using the 17U/17X urinary metabolite ratio from case-control subjects who completed a caffeine phenotype assay. The distribution of CYP2A6 activity was significantly different between CRCa cases and controls, with subjects in the medium and high activity groups having an increased risk (P for trend = 0.001). GSTA1 genotype and CYP2A6 phenotype should be evaluated as markers of susceptibility to dietary carcinogens in future studies. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved. C1 Natl Ctr Toxicol Res, Div Mol Epidemiol, Jefferson, AR 72079 USA. Cent Arkansas Vet Hlth Care Syst, Little Rock, AR USA. Univ Arkansas Med Sci, Dept Surg, Little Rock, AR 72205 USA. RP Kadlubar, FF (reprint author), Natl Ctr Toxicol Res, Div Mol Epidemiol, Jefferson, AR 72079 USA. OI Sweeney, Carol/0000-0003-1113-7160 FU NCI NIH HHS [R01CA55751] NR 12 TC 34 Z9 36 U1 1 U2 5 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0300-483X J9 TOXICOLOGY JI Toxicology PD DEC 27 PY 2002 VL 181 BP 83 EP 87 AR PII S0300-483X(02)00259-7 DI 10.1016/S0300-483X(02)00259-7 PG 5 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 639TX UT WOS:000180646400014 PM 12505289 ER PT J AU Hattan, DG Kahl, LS AF Hattan, DG Kahl, LS TI Current developments in food additive toxicology in the USA SO TOXICOLOGY LA English DT Article; Proceedings Paper CT 9th International Congress of Toxicology (ICT IX) CY JUL 08-12, 2001 CL QUEENSLAND, AUSTRALIA DE biotechnology testing policy; alternative toxicologic test methods; food additive toxicology AB A recently published proposal (Fed. Reg. 66 (2001) 4706) for mandatory submission of information on all plant-derived bioengineered foods fed to humans or animals will be reviewed. Under this proposal, information such as data on identity, level and function of the introduced substance(s); an estimate of dietary exposure; allergenic potential of the protein; data relevant to other safety issues that may be associated with the substance; selection of a comparable food; historic uses of comparable food; composition and characteristics of bioengineered food versus those of the comparable food should be provided. In addition, characterization of the parent plant; construction of the transformation vector and introduced genetic material along with number of insertion sites and genes; data on the genetic material and any newly inserted genes for antibiotic resistance should be submitted with the notification. The Interagency Coordinating Committee for Validation of Alternative Methods (ICCVAM) was identified by the U.S. Congress as the organization to review and validate new alternative toxicological test methods for 14 U.S. government agencies. Validated and accepted alternative toxicity tests will be incorporated into toxicity testing recommendations for regulatory agencies. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved. C1 US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. RP Hattan, DG (reprint author), 5126 Beavertbrook Rd, Columbia, MD 21044 USA. NR 8 TC 4 Z9 4 U1 0 U2 5 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0300-483X J9 TOXICOLOGY JI Toxicology PD DEC 27 PY 2002 VL 181 BP 417 EP 420 AR PII S0300-483X(02)00482-1 DI 10.1016/S0300-483X(02)00482-1 PG 4 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 639TX UT WOS:000180646400070 PM 12505345 ER PT J AU Weber, DJ McFarland, RD Irony, I AF Weber, DJ McFarland, RD Irony, I TI Selected food and drug administration review issues for regulation of allogeneic islets of Langerhans as somatic cell therapy SO TRANSPLANTATION LA English DT Article ID GRAFT-SURVIVAL; CYCLOSPORINE-A; RAPAMYCIN; TRANSPLANTATION; PROLONGATION; SIROLIMUS; FK506; RAT AB The Food and Drug Administration has seen a significant increase in investigational new drug (IND) applications for the use of allogeneic islets of Langerhans to treat type 1 diabetes mellitus. The current regulatory framework for clinical use of allogeneic islets of Langerhans is described. In addition, expectations and considerations for information to be included in the manufacturing, preclinical, and clinical sections of an IND for allogeneic islets of Langerhans to treat type 1 diabetes mellitus are discussed. C1 US FDA, Div Cellular & Gene Therapies, Off Cellular Tissue & Gene Therpies, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. US FDA, Div Clin Evaluat & Pharmacol Toxicol, Off Cellular Tissue & Gene Therpies, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. US FDA, Div Clin Trial Design & Anal, Off Therapeut Res & Review, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Weber, DJ (reprint author), US FDA, Div Cellular & Gene Therapies, Off Cellular Tissue & Gene Therpies, Ctr Biol Evaluat & Res, 1401 Rockville Pike,HFM-700, Rockville, MD 20852 USA. NR 31 TC 17 Z9 17 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 2002 VL 74 IS 12 BP 1816 EP 1820 DI 10.1097/01.TP.0000038291.03671.E3 PG 5 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 629HJ UT WOS:000180044000034 PM 12499908 ER PT J AU Jakab, RL Bowyer, JF AF Jakab, RL Bowyer, JF TI Parvalbumin neuron circuits and microglia in three dopamine-poor cortical regions remain sensitive to amphetamine exposure in the absence of hyperthermia, seizure, and stroke SO BRAIN RESEARCH LA English DT Article DE amphetamine neurotoxicity; somatosensory 'barrel-field'; limbic system; striatum; hypothermia; hyperthermia ID METHAMPHETAMINE-INDUCED NEUROTOXICITY; TYROSINE-HYDROXYLASE ACTIVITY; SUBSTITUTED AMPHETAMINES; SOMATOSENSORY CORTEX; GLUTAMATE RELEASE; C57BL/6J MOUSE; RAT STRIATUM; DEGENERATION; BRAIN; IMMUNOREACTIVITY AB The dopamine-releasing and depleting substance amphetamine (AMPH) can make cortical neurons susceptible to damage, and the prevention of hyperthermia, seizures and stroke is thought to block these effects. Here we report a 2-day AMPH treatment paradigm which affected only interneurons in three cortical regions with average or below-average dopamine input. AMPH (six escalating doses/day ranging from 5 to 30 mg/kg for 2 days) was given at 17-18 degreesC ambient temperature (T) to adult male rats. During the 2-day AMPH treatment, peak body T stayed below 38.9 degreesC in 40% of the AMPH treated rats. In 60% of the rats, deliberate cooling suppressed (<39.5 degreesC) or minimized (<40.0 degreesC) hyperthermia. Escalation of stereotypes to seizure-like behaviors was rare and post-mortem morphological signs of stroke were absent. Neurons labeled with the anionic, neurodegeneration-marker dye Fluoro-Jade (F-J) were seen I day after dosing, peaked 3 days later, but were barely detectable 14 days after dosing. Only nonpyramidal neurons in layer IV of the somatosensory barrel cortex and in layer II of the piriform cortex and posterolateral cortical amygdaloid nucleus were labeled with Fluoro-Jade. Isolectin B-labeled activated microglia were only detected in their neighborhood. F-J labeled neurons were extremely rare in cortical regions rich in dopamine (e.g. cingulate cortex), and Were absent in cortical regions with no dopamine (e.g. visual cortex). Parvalbumin was seen in some Fluoro-Jade-labeled neurons and parvalbumin immunostaining in local axon plexuses intensified. This AMPH paradigm affected fewer cortical regions, and caused smaller reduction in striatal tyrosine hydroxylase (TH) immunoreactivity than previous 1-day AMPH regimens generating seizures or severe (above 40 degreesC) hyperthermia. Correlation between peak or mean body T and the extent of neurodegeneration or microgliosis was below statistical significance. Astrogliosis (elevated levels of the astroglia-marker, glial fibrillary acidic protein (GFAP)) was detected in many brain regions. In the striatum and midbrain, F-J labeled neurons and activated microglia were absent, but astrogliosis, decreased TH immunolabel, and swollen TH fibers were detected. In sum, after this AMPH treatment, cortical pyramidal neurons were spared, but astrogliosis was brain-wide and some interneurons and microglia in three cortical regions with average or below-average dopamine input remained sensitive to AMPH exposure. Published by Elsevier Science B.V. C1 US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. RP Bowyer, JF (reprint author), US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, HFT-132,3900 NCTR Rd, Jefferson, AR 72079 USA. NR 68 TC 25 Z9 25 U1 2 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD DEC 20 PY 2002 VL 958 IS 1 BP 52 EP 69 AR PII S0006-8993(02)03439-X DI 10.1016/S0006-8993(02)03439-X PG 18 WC Neurosciences SC Neurosciences & Neurology GA 624RV UT WOS:000179775500007 PM 12468030 ER PT J AU Friedman, MA AF Friedman, MA TI Strengthening the FDA SO SCIENCE LA English DT Editorial Material C1 Pharmacia Corp, Peapack, NJ 07977 USA. US FDA, Rockville, MD 20857 USA. RP Friedman, MA (reprint author), Pharmacia Corp, Peapack, NJ 07977 USA. EM Michael.a.friedman@pharmacia.com NR 5 TC 0 Z9 0 U1 1 U2 3 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD DEC 20 PY 2002 VL 298 IS 5602 BP 2332 EP 2332 DI 10.1126/science.1080416 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 627DG UT WOS:000179915900035 PM 12493898 ER PT J AU Hussain, S Ali, SF AF Hussain, S Ali, SF TI Zinc potentiates 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine induced dopamine depletion in caudate nucleus of mice brain SO NEUROSCIENCE LETTERS LA English DT Article DE 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; zinc; dopamine; mice ID PARKINSONS-DISEASE; OXIDATIVE STRESS; FREE-RADICALS; MPTP; METALLOTHIONEIN; NEUROTOXICITY; MECHANISMS; TOXICITY; PROTEINS; MOUSE AB Present study describes the effect of zinc (Zn) on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced dopamine depletion in mice brain. MPTP is a known neurotoxicant primarily causing marked depletion of dopamine (DA) levels in nigrostriatal dopaminergic system. Adult Male C57-mice were intraperitonially injected with 25 mg/kg MPTP in the presence or absence of zinc acetate. Twenty-four hours after treatment animals were sacrificed and DA levels were determined by high performance liquid chromatography in caudate nucleus of control and treated mice. The results showed that there was a marked depletion of DA in MPTP treated mice, whereas no change was observed in DA levels in mice treated with Zn when compare to controls. Interestingly, mice receiving MPTP in conjunction with Zn showed significantly lower DA levels in brain when compare to animals receiving MPTP alone. In summary the data suggest that Zn treatment potentiates depletion of dopamine in MPTP treated mice. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved. C1 US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Neurochem Lab, Jefferson, AR 72079 USA. Univ Arkansas Med Sci, Dept Biochem & Mol Biol & Neurol, Little Rock, AR 72205 USA. RP Hussain, S (reprint author), USAF, Res Lab, POB 31009, Dayton, OH 45431 USA. NR 27 TC 4 Z9 4 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD DEC 19 PY 2002 VL 335 IS 1 BP 25 EP 28 AR PII S0304-3940(02)01158-8 DI 10.1016/S0304-3940(02)01158-8 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 625AY UT WOS:000179795700007 PM 12457734 ER PT J AU Anderson, SM Verchick, L Sowadsky, R Civen, R Mohle-Boetani, JC Werner, SB Starr, M Abbott, S Gutierrez, M Palumbo, M Farrar, J Shillam, P Umland, E Tanuz, M Sewell, M Cato, J Keene, W Goldoft, M Hofmann, J Kobayashi, J Waller, P Braden, C Djomand, G Reller, M Chege, W AF Anderson, SM Verchick, L Sowadsky, R Civen, R Mohle-Boetani, JC Werner, SB Starr, M Abbott, S Gutierrez, M Palumbo, M Farrar, J Shillam, P Umland, E Tanuz, M Sewell, M Cato, J Keene, W Goldoft, M Hofmann, J Kobayashi, J Waller, P Braden, C Djomand, G Reller, M Chege, W TI Multistate outbreaks of Salmonella serotype Poona infections associated with eating cantaloupe from Mexico - United States and Canada, 2000-2002 (Reprinted from MMWR, vol 51, pg 1044-1047, 2002) SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Reprint C1 Arizona Dept Hlth Serv, Phoenix, AZ 85007 USA. Clark Cty Hlth Dept, Las Vegas, NV USA. Nevada State Hlth Div, Carson City, NV 89701 USA. Calif Dept Hlth Serv, Berkeley, CA 94704 USA. Colorado Dept Hlth, Denver, CO 80220 USA. New Mexico Dept Hlth, Santa Fe, NM USA. Oregon Dept Human Serv, Salem, OR 97310 USA. Washington State Dept Hlth, Olympia, WA 98504 USA. US FDA, Ctr Food Safety & Appl Nutr, Rockville, MD 20857 USA. US FDA, Off Regulatory Affairs, Rockville, MD 20857 USA. CDC, Div Bacterial & Mycot Dis, Natl Ctr Infect Dis, Atlanta, GA 30333 USA. RP Anderson, SM (reprint author), Arizona Dept Hlth Serv, Phoenix, AZ 85007 USA. NR 9 TC 1 Z9 1 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD DEC 18 PY 2002 VL 288 IS 23 BP 2967 EP 2969 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 626CG UT WOS:000179854200015 ER PT J AU Xu, XM Carlson, BA Grimm, TA Kutza, J Berry, MJ Arreola, R Fields, KH Shanmugam, I Jeang, KT Oroszlan, S Combs, GF Marx, PA Gladyshev, VN Clouse, KA Hatfield, DL AF Xu, XM Carlson, BA Grimm, TA Kutza, J Berry, MJ Arreola, R Fields, KH Shanmugam, I Jeang, KT Oroszlan, S Combs, GF Marx, PA Gladyshev, VN Clouse, KA Hatfield, DL TI Rhesus monkey simian immunodeficiency virus infection as a model for assessing the role of selenium in AIDS SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE immunodeficiency diseases; AIDS; molecular biology; selenium; HIV ID SELENOCYSTEINE TRANSFER RNASEC; HIV-1 TAT PROTEIN; GLUTATHIONE-PEROXIDASE; TRANSFER-RNA; T-CELLS; SERUM SELENIUM; DEFICIENCY; REPLICATION; BLOOD; SUPPLEMENTATION AB The objective of this study was to determine whether simian immunodeficiency virus (SIV) infection of rhesus macaques could be used as a model system to assess the role of selenium in AIDS. Plasma and serum selenium levels were determined by standard assays in monkeys before and after inoculation of SIV. SIV-infected cells or cells expressing the HIV Tat protein were labeled with Se-75, and protein extracts were prepared and electrophoresed to analyze selenoprotein expression. Total tRNA was isolated from CEMx174 cells infected with SIV or from KK1 cells infected with HIV, and selenocysteine tRNA isoforms were characterized by reverse phase chromatography. SIV-infected monkeys show a decrease in blood selenium levels similar to that observed in AIDS with development of SAIDS. Cells infected with SIV in vitro exhibit reduced selenoprotein levels and an accumulation of small molecular weight selenium compounds relative to uninfected cells. Examination of the selenocysteine tRNA isoforms in HIV-infected KK1 cells or SIV-infected CEMx174 cells reveals an isoform distribution characteristic of selenium-deficient cells. Furthermore, transfection of Jurkat E6 cells with the Tat gene selectively altered selenoprotein synthesis, with GPX4 and Sep 15 being the most inhibited and TR1 the most enhanced. Taken together, the data show that monkeys infected with SIV in vivo and cells infected with SIV in vitro will provide appropriate models for investigating the mechanism(s) responsible for reduced selenium levels that accompany the progression of AIDS in HIV disease. C1 NCI, Sect Mol Biol Selenium, Basic Res Lab, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Monoclonal Antibodies, Rockville, MD 20857 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Thyroid, Boston, MA 02115 USA. NIAID, Mol Virol Sect, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. NCI, HIV Drug Resistance Program, Ctr Canc Res, Frederick, MD 21701 USA. Cornell Univ, Div Nutr Sci, Dept Nutr, Ithaca, NY 14853 USA. Tulane Univ, Hlth Sci Ctr, Sch Publ Hlth & Trop Med, Covington, LA USA. Tulane Natl Primate Res Ctr, Covington, LA USA. Univ Nebraska, Dept Biochem, Lincoln, NE 68583 USA. RP Hatfield, DL (reprint author), NCI, Sect Mol Biol Selenium, Basic Res Lab, NIH, Bldg 37,Room 2D09, Bethesda, MD 20892 USA. RI Jeang, Kuan-Teh/A-2424-2008; Gladyshev, Vadim/A-9894-2013 FU NCRR NIH HHS [P51 RR 000164]; NIAID NIH HHS [R01 AI 41952] NR 39 TC 10 Z9 11 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS JI JAIDS PD DEC 15 PY 2002 VL 31 IS 5 BP 453 EP 463 PG 11 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 624TA UT WOS:000179776100001 PM 12473832 ER PT J AU Kawakami, K Kawakami, M Puri, RK AF Kawakami, K Kawakami, M Puri, RK TI IL-13 receptor-targeted cytotoxin cancer therapy leads to complete eradication of tumors with the aid of phagocytic cells in nude mice model of human cancer SO JOURNAL OF IMMUNOLOGY LA English DT Article ID INTERLEUKIN-13 RECEPTOR; PSEUDOMONAS EXOTOXIN; CARCINOMA-CELLS; ALPHA CHAIN; SIGNAL-TRANSDUCTION; SYSTEMIC DELIVERY; IN-VIVO; PROTEIN; BINDING; GENE AB Tumor-directed therapeutic approaches require unique or overexpressed specific Ag or receptor as a target to achieve selective tumor killing. However, heterogeneous expression of these targets on tumor cells limits the efficacy of this form of therapy. In this study, we forced abundant expression of IL-13Ralpha2 chain by plasmid-mediated gene transfer in head and neck, as well as prostate tumors to provide a potential target. This was followed by successfully treating xenograft tumor-bearing nude mice with IL-13R-directed cytotoxin (IL13-PE38QQR). Although we did not observe an indirect cytotoxic bystander effect conveyed to nontransduced tumor cells in vitro, our approach in vivo led to a complete regression of established tumors transfected with IL-13Ralpha12 chain in most animals. We found that the tumor eradication was achieved in part by infiltration of macrophages and NK cells, assessed by immunohistochemistry. Moreover, head and neck tumors xenografted in macrophage-depleted nude mice were less sensitive to the antitumor effect of IL-13 cytotoxin. Because we did not observe vector-related toxicity in any vital organs, our novel combination strategy of gene transfer of IL-13Ralpha2 chain and receptor-directed cytotoxin therapy may be a useful approach for the treatment of localized cancer. C1 US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Lab Mol Tumor Biol, Bethesda, MD 20892 USA. RP Puri, RK (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Lab Mol Tumor Biol, NIH Bldg 29B,Room 2NN10,29 Lincoln Dr MSC 4555, Bethesda, MD 20892 USA. NR 35 TC 19 Z9 19 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 DEC 15 PY 2002 VL 169 IS 12 BP 7119 EP 7126 PG 8 WC Immunology SC Immunology GA 624MN UT WOS:000179763600058 PM 12471149 ER PT J AU Howard, PC Couch, LH Patton, RE Eppley, RM Doerge, DR Churchwell, MI Marques, MM Okerberg, CV AF Howard, PC Couch, LH Patton, RE Eppley, RM Doerge, DR Churchwell, MI Marques, MM Okerberg, CV TI Comparison of the toxicity of several fumonisin derivatives in a 28-day feeding study with female B6C3F(1) mice SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE fumonisin; mice; hepatotoxicity; sphinganine ID SPRAGUE-DAWLEY RATS; FUSARIUM-MONILIFORME; SPHINGOLIPID BIOSYNTHESIS; N-(CARBOXYMETHYL)FUMONISIN B-1; MAIZE HYBRIDS; MYCOTOXINS; LIVER; CORN; CULTURES; CARCINOGENESIS AB Fumonisin mycotoxins are produced by Fusaria fungi that grow worldwide primarily on corn. Fumonisin B-1 the most predominant form in corn samples, is a renal carcinogen in male F344/N rats and a hepatocarcinogen in female B6C3F(1) mice when fed at concentrations higher than 50 ppm (70 mumol/kg) in the diet for 2 years. We sought to determine the relative toxicities of several naturally occurring fumonisin derivatives when included in the diet of female B6C3F(1) mice. Mice were fed diets containing fumonisin B-1 fumonisin B-2, fumonisin B-3, fumonisin P1, hydrolyzed-fumonisin B-1, N-(acetyl)fumonisin B-1, or N-(carboxymethyl)fumonisin B-1 (approximately 0, 14, 70, and 140 mumol/kg diet) for 28 days. None of the doses used caused a decrease in body weight gain over the 28 days. Serum levels of total bile acids, cholesterol, and alkaline phosphatase were increased only in mice receiving 72 and 143 mumol/kg fumonism B-1, suggesting that only fumonisin B-1 was hepatotoxic in the mice. Corroborating this observation, the liver weight, relative to body weight, was decreased only in the mice that consumed 143 mumol/kg fumonisin B-1. Consistent with fumonisin B-1 inhibition of ceramide synthase, the liver sphinganine-to-sphingosine ratio was increased and the liver ceramide levels were decreased only in the mice receiving 72 and 143 mumol/kg fumonisin B-1. Increased hepatocellular apoptosis, hepatocellular hypertrophy, Kupffer cell hyperplasia, and macrophage pigmentation were detected in the mice consuming 72 and 143 mumol/kg fumonisin B-1. The other fumonisin derivatives did not alter serum analytes, organ weights, or hepatic structure. These results suggest that, of the naturally occurring fumonisins, fumonisin B-1 is the principal hepatotoxic derivative in the B6C3F(1) mouse. (C) 2002 Elsevier Science (USA). C1 US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Pathol Associates Int, Jefferson, AR 72079 USA. US FDA, Div Nat Prod, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. Univ Tecn Lisboa, Ctr Quim Estrutural, Inst Super Tecn, P-1049001 Lisbon, Portugal. RP Howard, PC (reprint author), US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, HFT-110,3900 NCTR Rd, Jefferson, AR 72079 USA. EM Phoward@nctr.fda.gov RI Marques, M. Matilde/E-2535-2012 OI Marques, M. Matilde/0000-0002-7526-4962 NR 64 TC 50 Z9 50 U1 1 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0041-008X EI 1096-0333 J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD DEC 15 PY 2002 VL 185 IS 3 BP 153 EP 165 DI 10.1006/taap.2002.9529 PG 13 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 629RD UT WOS:000180061900001 PM 12498732 ER PT J AU Pogribny, IP James, SJ AF Pogribny, IP James, SJ TI De novo methylation of the p16(INK4A) gene in early preneoplastic liver and tumors induced by folate/methyl deficiency in rats SO CANCER LETTERS LA English DT Article DE p16 gene; DNA methylation; hepatocarcinogenesis; rat folate/methyl deficiency ID DNA METHYLATION; HEPATOCELLULAR-CARCINOMA; CPG ISLANDS; LUNG-TUMORS; CANCER; HEPATOCARCINOGENESIS; EXPRESSION; CHROMATIN AB Previous studies have established that chronic dietary insufficiency of the lipotropic nutrients choline and methionine with or without chemical initiation is hepatocarcinogenic in the rat and certain mouse strains. In the present study, the folate/methyl-deficient model of multistage hepatocarcinogenesis was used to evaluate progressive in vivo changes in p16 promoter methylation in both preneoplastic and tumor tissues. Previous studies using this model have demonstrated stage-dependent alterations in genome-wide and p53 gene-specific methylation. In the present study, we used highly sensitive methylation specific PCR (MSP) to determine time of appearance of methylated sequences within p16 promoter. In addition, methylation-sensitive single nucleotide primer extension methodology was applied to determine methylation status of the remaining CpG sites within amplified methylated alleles. Using this approach, extensive methylation in p16 promoter was found in 100% of tumors, but the pattern of methylation varied depending on tumor type. The incidence and extent of de novo methylation in the CpG island of the p16 promoter increased with tumor progression. To further explore the evolution of p16 gene hypermethylation, we examined the appearance and progression of site-specific de novo methylation during early preneoplasia. Our data show that site-specific de novo methylation of 5' CpG island of p16 gene precedes tumor development and undergoes dynamic expansion during tumor progression. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved. C1 US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Pogribny, IP (reprint author), US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. NR 23 TC 67 Z9 70 U1 0 U2 3 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD DEC 10 PY 2002 VL 187 IS 1-2 BP 69 EP 75 AR PII S0304-3835(02)00408-1 DI 10.1016/S0304-3835(02)00408-1 PG 7 WC Oncology SC Oncology GA 618NP UT WOS:000179424400010 PM 12359353 ER PT J AU Schwerin, MR Walsh, DL Richardson, DC Kisielewski, RW Kotz, RM Routson, LB Lytle, CD AF Schwerin, MR Walsh, DL Richardson, DC Kisielewski, RW Kotz, RM Routson, LB Lytle, CD TI Biaxial flex-fatigue and viral penetration of natural rubber latex gloves before and after artificial aging SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH LA English DT Article DE latex; fatigue; flexing; accelerated aging; viral penetration AB Barrier integrity of unaged and oven-aged (at 70 degreesC) natural rubber latex examination gloves was assessed with a biaxial flex-fatigue method where failure was detected electronically, and by live viral penetration testing performed according to a modified version of ASTM F1671-97a. When no change in barrier properties was detected during flex testing, no virus passage was found after viral challenge. Conversely, when a change in the barrier properties was indicated by the electrical signal, virus passage was found in 74% of the specimens. Flex-fatigue results indicated that unaged test specimens from powdered (PD) and powder-free (PF) nonchlorinated gloves had significantly longer fatigue lives than powder-free chlorinated (CL) gloves from the same manufacturer. Biaxial flexing of oven-aged glove specimens showed a marginal increase in fatigue life for the PF gloves, but no increase for the PD gloves. The fatigue life of the CL gloves was observed to increase significantly after oven aging. However, this appears to be due to a design feature of the test apparatus, wherein peak volume displacement of the worked specimen is held constant. An aging-induced change in the viscoelastic properties of the CL gloves-permanent deformation of the specimens early in the fatigue test-relieves the stress magnitude applied as the test progresses. Thus, permanent deformation acts as a confounding factor in measuring durability of latex gloves by fixed displacement flex-fatigue. (C) 2002 Wiley Periodicals, Inc. C1 US FDA, CDRH, OST, DMMS, Rockville, MD 20850 USA. US FDA, Ctr Devices & Radiol Hlth, Off Surveillance & Biometr, Rockville, MD 20852 USA. RP Schwerin, MR (reprint author), US FDA, CDRH, OST, DMMS, HFR-150,9200 Corp Blvd, Rockville, MD 20850 USA. NR 21 TC 7 Z9 7 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0021-9304 J9 J BIOMED MATER RES JI J. Biomed. Mater. Res. PD DEC 5 PY 2002 VL 63 IS 6 BP 739 EP 745 DI 10.1002/jbm.10467 PG 7 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 617QQ UT WOS:000179372700009 PM 12418018 ER PT J AU Liu, T Muller, J Ye, ZP AF Liu, T Muller, J Ye, ZP TI Association of influenza virus matrix protein with ribonucleoproteins may control viral growth and morphology SO VIROLOGY LA English DT Article ID FILAMENTOUS PARTICLE FORMATION; A VIRUS; M1 PROTEIN; NUCLEAR TRANSPORT; RNA; MEMBRANE; HEMAGGLUTININ; EXPORT; FORMS AB The matrix protein (M1) of influenza virus plays a central role in viral replication. In relation to viral growth and morphology, we studied the RNP-binding activity of M1s from high-growth strain A/Puerto Rico/8/34 (A/PR8/34) and the relatively low-growth wild-type strain A/Nanchang/933/95. The RNP-binding strength of M1 was studied by disruption of M1 from M1/RNP complexes with salt and acidic condition. Our results indicated that binding of M1 of high-growth A/PR8/34 was more difficult to break than the binding of M1 of low-growth A/Nanchang/933/95. Consistent with the presence of M1 in A/PR8/34, binding of M1 of Resvir-9, a reassortant containing P, M, and NS genes from A/PR8/34 and the rest of genes from A/Nanchang/933/95 and retaining relative high-growth characteristic, was relatively difficult to break than the binding of M1 of A/Nanchang/933/95. Physical properties of morphological features of these viruses were studied by velocity sucrose gradient centrifugation and transmission electron microscopy of purified viral particles, and by immunofluorescence staining of hemagglutinin expressed on the surface of infected cells. The results demonstrated that high-growth strains, A/PR8/34, and a relative high-growth reassortant, Resvir-9, had characteristics associated predominantly with spherical particles, while the low-growth strain, A/Nanchang/933/95, had characteristics of filamentous particles. These studies indicate that the binding between M1 and RNP complex might determine viral growth and morphology. (C) 2002 Elsevier Science (USA). C1 US FDA, Ctr Biol & Evaluat & Res, Lab Pediat & Resp Viral Dis, Bethesda, MD 20982 USA. US FDA, Ctr Biol Evaluat & Res, Lab Vector Borne Viral Dis, Div Viral Prod,Off Vaccines Res & Review, Bethesda, MD 20982 USA. RP Ye, ZP (reprint author), US FDA, Ctr Biol & Evaluat & Res, Lab Pediat & Resp Viral Dis, Bldg 29A,Room 2B17,8800 Rockville Pike, Bethesda, MD 20982 USA. NR 32 TC 26 Z9 27 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD DEC 5 PY 2002 VL 304 IS 1 BP 89 EP 96 DI 10.1006/viro.2002.1669 PG 8 WC Virology SC Virology GA 628GM UT WOS:000179984800009 PM 12490406 ER PT J AU McClellan, MB AF McClellan, MB TI New 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 McClellan, MB (reprint author), US FDA, Off Commissioner Food & Drugs, HF-1,Room 14-71,5600 Fishers Ln, Rockville, MD 20857 USA. NR 0 TC 4 Z9 4 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 4 PY 2002 VL 288 IS 21 BP 2678 EP 2678 DI 10.1001/jama.288.21.2678-b PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 620UA UT WOS:000179549800009 ER PT J AU McClellan, MB AF McClellan, MB TI Proposed change of patent rules 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 McClellan, MB (reprint author), US FDA, Off Commissioner Food & Drugs, HF-1,Room 14-71,5600 Fishers Ln, Rockville, MD 20857 USA. NR 0 TC 4 Z9 4 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 4 PY 2002 VL 288 IS 21 BP 2678 EP 2678 DI 10.1001/jama.288.21.2678-b PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 620UA UT WOS:000179549800008 ER PT J AU McClellan, MB AF McClellan, MB TI Two drugs for opioid dependence 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 McClellan, MB (reprint author), US FDA, Off Commissioner Food & Drugs, HF-1,Room 14-71,5600 Fishers Ln, Rockville, MD 20857 USA. NR 0 TC 4 Z9 4 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 4 PY 2002 VL 288 IS 21 BP 2678 EP 2678 DI 10.1001/jama.288.21.2678-b PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 620UA UT WOS:000179549800010 ER PT J AU Iyasu, S Randall, LL Welty, TK Hsia, J Kinney, HC Mandell, F McClain, M Randall, B Habbe, D Wilson, H Willinger, M AF Iyasu, S Randall, LL Welty, TK Hsia, J Kinney, HC Mandell, F McClain, M Randall, B Habbe, D Wilson, H Willinger, M TI Risk factors for sudden infant death syndrome among Northern Plains Indians SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID NURSE HOME VISITATION; CONFIDENTIAL INQUIRY; RANDOMIZED TRIAL; ALCOHOL; STILLBIRTHS; ENVIRONMENT; PREGNANCY; OUTCOMES; SMOKING; GROWTH AB Context Sudden infant death syndrome (SIDS) is a leading cause of postneonatal mortality among American Indians, a group whose infant death rate is consistently above the US national average. Objective To determine Prenatal and postnatal risk factors for SIDS among American Indians. Design, Setting, and Participants Population-based case-control study of 33 SIDS infants and 66 matched living controls among American Indians in South Dakota, North Dakota, Nebraska, and Iowa enrolled from December 1992 to November 1996 and investigated using standardized parental interview, medical record abstraction', autopsy protocol, and infant death review. Main Outcome Measures Association of SIDS with maternal socioeconomic and behavioral factors, health care utilization, and infant care practices. Results The proportions of case and control infants who were usually placed prone to sleep (15.2% and 13.6%, respectively), who shared a bed with parents (59.4% and 55.4%), or whose mothers smoked during pregnancy (69.7% and 54.6%) were similar. However, mothers of 72.7% of case infants and 45.5% of control infants engaged in binge drinking during pregnancy. Conditional logistic regression revealed significant associations between SIDS and 2 or more layers of clothing on the infant (adjusted odds ratio [aOR], 6.2; 95% confidence interval [CI], 1.4-26.5), any visits by a public health nurse (aOR, 0.2; 95% Cl, 0.1-0.8), periconceptional maternal alcohol use (aOR, 6.2; 95% Cl, 1.6-23.3), and maternal first-trimester binge drinking (aOR, 8.2; 95% Cl, 1.9-35.3). Conclusions Public health nurse visits, maternal alcohol use during the periconceptional period and first trimester, and layers of clothing are important risk factors for SIDS among Northern Plains Indians. Strengthening public health nurse visiting programs and programs to reduce alcohol consumption among women of childbearing age could potentially reduce the high rate of SIDS. C1 Ctr Dis Control & Prevent, Div Reprod Hlth, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA USA. Aberdeen Area Indian Hlth Serv, Rapid City, SD USA. Harvard Univ, Childrens Hosp, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts SIDS Ctr, Boston, MA USA. LCM Pathologists PC, Sioux Falls, SD USA. Clin Lab Black Hills, Rapid City, SD USA. Providence Mem Hosp, Dept Pathol, El Paso, TX USA. NICHHD, NIH, Bethesda, MD 20892 USA. RP Iyasu, S (reprint author), US FDA, Div Pediat, Off Counter Terrorism & Pediat Drug Dev, Ctr Drug Evaluat & Res, 5A-33,HFD-960,5600 Fishers Ln, Rockville, MD 20857 USA. NR 30 TC 99 Z9 102 U1 0 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD DEC 4 PY 2002 VL 288 IS 21 BP 2717 EP 2723 DI 10.1001/jama.288.21.2717 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 620UA UT WOS:000179549800031 PM 12460095 ER PT J AU Palmai, M Buchanan, RL AF Palmai, M Buchanan, RL TI The effect of Lactococcus lactis on the growth characteristics of Listeria monocytogenes in alfalfa sprout broth SO ACTA ALIMENTARIA LA English DT Article DE Listeria monocytogenes; competition; pH; alfalfa sprouts ID ESCHERICHIA-COLI O157-H7; PSEUDOMONAS-FLUORESCENS; MICROBIAL COMPETITION; SODIUM-CHLORIDE; RADISH SPROUTS; ACID BACTERIA; BEAN-SPROUTS; TEMPERATURE; VEGETABLES; SALMONELLA AB Lactic acid bacteria isolated from commercially produced alfalfa sprouts were screened for activity against Listeria monocytogenes F4258. Most active isolates were identified as Lactococcus lactis subsp. lactis. The isolates fell into two categories, strains that inhibited by acid production only, and strains that appeared to have additional inhibitory activity. An acid-only isolate, SP26, was used to evaluate the effect of initial pH (5, 6, 7, 8) and temperature (10, 20, and 30 degreesC) on the interaction between the lactic acid bacterium and L monocytogenes using "sprout juice" as a model system. The model system was inoculated with an initial level of approx. 10(3) CFU ml(-1) L monocytogenes in both mono-culture controls and the co-cultures and the co-cultures with L. lactis (10(3)-10(4) CFU ml(-1)). The primary inhibitory effect attributable to L lactis was a 2 to 3 log cycle decrease in the maximum population density obtained by L monocytogenes. The extent of the inhibition was decreased at 10 degreesC, but was only slightly affected by pH in the range of 6.0 to 8.0. L monocytogenes did not grow in the sprout broth at pH 5.0 at any of the incubation temperatures. C1 Natl Inst Food Hyg & Nutr, Dept Food Microbiol & Food Hyg, H-1476 Budapest, Hungary. US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Palmai, M (reprint author), Natl Inst Food Hyg & Nutr, Dept Food Microbiol & Food Hyg, POB 52, H-1476 Budapest, Hungary. NR 29 TC 8 Z9 8 U1 1 U2 4 PU AKADEMIAI KIADO PI BUDAPEST PA PO BOX 245, H-1519 BUDAPEST, HUNGARY SN 0139-3006 J9 ACTA ALIMENT HUNG JI Acta Aliment. PD DEC PY 2002 VL 31 IS 4 BP 379 EP 392 DI 10.1556/AAlim.31.2002.4.7 PG 14 WC Food Science & Technology; Nutrition & Dietetics SC Food Science & Technology; Nutrition & Dietetics GA 636DX UT WOS:000180440200007 ER PT J AU Wang, SJ Winchell, CJ McCormick, CG Nevius, SE O'Neill, RT AF Wang, SJ Winchell, CJ McCormick, CG Nevius, SE O'Neill, RT TI Short of complete abstinence: An analysis exploration of multiple drinking episodes in alcoholism treatment trials SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE multiple event times; heavy drinking day; safe drinking day; any drinking day; alcoholism treatment clinical trial ID FAILURE TIME DATA; REGRESSION-ANALYSIS; RECURRENT EVENTS; NALTREXONE; THERAPY; DEPENDENCE; MODEL AB Background: In alcoholism treatment clinical trials, conventional analysis of efficacy outcomes often focuses on the time to a first event, where the event may be "any drinking", "safe (or low risk) drinking", "moderate drinking" or "heavy drinking," in addition to multiple outcomes such as frequency of drinking days, percent abstinence days, etc. Methods: We consider the multivariate failure time analytic methods. In alcoholism treatment trials, the naturalistic course of drinking behavior during treatment intervention often presents with a gradual change in drinking before the emergence of a more stable drinking or abstinence pattern. Thus, for each subject, evaluation of all drinking events, and incorporating the event times over a defined duration, may give a more comprehensive description of his/her drinking pattern. As a consequence, the efficacy of a new treatment for alcoholism may be elevated with greater statistical sensitivity. Results: The utility of the multiple failure time method is demonstrated via a real case study for evaluation of alcoholism treatments. The multiple event time analyses showed that the risk of having "any drinking days" or "heavy drinking days" during the entire duration of the study was significantly lower with experimental treatment than with placebo. Further explorations showed that the treatment effect was primarily observed in the later relapse events and not the first event with respect to relapse to any drinking episodes. Such effect would have missed using the traditional time to first event analysis approach. The observed effect of treatment with respect to relapse to multiple heavy drinking episodes was shown not only in the first event but also in the later events. Conclusion:The multiple failure time approach may be applicable when 'drinking failure' is variously defined as a single drink, one at-risk drinking day, one heavy drinking day, or one alcohol-related social, occupational or medical problem. If "a drinking episode" is properly defined and the design gains statistical efficiency, the multiple event analytic strategy should provide improved statistical power to detect treatment effects. C1 US FDA, CDER, OPaSS, OB,Div Biometr 2,PKLN, Rockville, MD 20857 USA. US FDA, CDER, Div Anesthet Crit Care & Addit Drug Prod, Rockville, MD 20857 USA. US FDA, CDER, OPaSS, Off Biostat, Rockville, MD 20857 USA. RP Wang, SJ (reprint author), US FDA, CDER, OPaSS, OB,Div Biometr 2,PKLN, 9B07,5600 Fishers Lane, Rockville, MD 20857 USA. NR 36 TC 18 Z9 18 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD DEC PY 2002 VL 26 IS 12 BP 1803 EP 1809 DI 10.1097/01.ALC.0000042009.07691.12 PG 7 WC Substance Abuse SC Substance Abuse GA 631LP UT WOS:000180169500006 PM 12500103 ER PT J AU Fetsch, PA Simone, NL Bryant-Greenwood, PK Marincola, FM Filie, AC Petricoin, EF Liotta, LA Abati, A AF Fetsch, PA Simone, NL Bryant-Greenwood, PK Marincola, FM Filie, AC Petricoin, EF Liotta, LA Abati, A TI Proteomic evaluation of archival cytologic material using SELDI affinity mass spectrometry - Potential for diagnostic applications SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article; Proceedings Paper CT 90th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 03-09, 2001 CL ATLANTA, GEORGIA SP US & Canadian Acad Pathol DE proteomics; SELDI; protein fingerprint; protein biochip; archival cytologic samples; melanoma; clear cell sarcoma; renal cell carcinoma; reactive mesothelial cells ID LASER CAPTURE MICRODISSECTION; CANCER-RESEARCH; CELL CARCINOMA; BREAST-CANCER; TISSUE; MELANOMA; IDENTIFICATION; TECHNOLOGIES; PROGRESSION; BIOMARKERS AB Proteomic studies of cells via surface-enhanced laser desorption/ionization spectrometry (SELDI) analysis have enabled rapid, reproducible protein profiling directly from crude samples. We applied this technique to archival cytology material to determine whether distinct, reproducible protein fingerprints could be identified for potential diagnostic purposes in blinded specimens. Rapid Romanowsky-stained cytocentrifuged specimens from fine-needle aspirates of metastatic malignant melanoma (with both known cutaneous primary and unknown primary sites), clear cell sarcoma, and renal cell card. noma and reactive effusions were examined using the SELDI technology. A unique characteristic fingerprint was identified for each disease entity. Fifteen "blinded" unknown samples then were analyzed. When the protein profile fingerprints were plotted against the known fingerprints for the aforementioned diagnoses, the appropriate match or diagnosis was obtained in 13 (87%) of 15 cases. These preliminary findings suggest a substantial potential for SELDI applications to specific pathologic diagnoses. C1 NCI, Cytophathol Sect, NIH, Pathol Lab, Bethesda, MD 20892 USA. NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. US FDA, Clin Prote Program, Bethesda, MD 20014 USA. RP Abati, A (reprint author), NCI, Cytophathol Sect, NIH, Pathol Lab, Bldg 10,Room 2A19, Bethesda, MD 20892 USA. NR 32 TC 55 Z9 59 U1 0 U2 1 PU AMER SOC CLINICAL PATHOLOGY PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD DEC PY 2002 VL 118 IS 6 BP 870 EP 876 DI 10.1092/HCRY7A2X09D9GYYA PG 7 WC Pathology SC Pathology GA 619JA UT WOS:000179471800008 PM 12472280 ER PT J AU van der Heijde, D Braun, J McGonagle, D Siegel, J AF van der Heijde, D Braun, J McGonagle, D Siegel, J TI Treatment trials in ankylosing spondylitis: current and future considerations SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Article; Proceedings Paper CT Ankylosing Spondylitis Workshop CY JAN 18-19, 2002 CL BERLIN, GERMANY ID NONSTEROIDAL ANTIINFLAMMATORY DRUG; ERYTHROCYTE SEDIMENTATION-RATE; C-REACTIVE PROTEIN; FUNCTIONAL INDEX; RHEUMATOID-ARTHRITIS; DISEASE-ACTIVITY; SCORING METHODS; SPINE SCORE; PLACEBO; SPONDYLOARTHROPATHIES AB Emerging treatment options in ankylosing spondylitis (AS) are giving new hope to patients with this chronic and potentially disabling disease. Clinical development of new treatments requires that rigorous and well controlled trials be conducted to demonstrate safety and efficacy. A number of classification systems have been developed in recent years as a result of enhanced understanding of the pathogenesis of AS. Although new outcome measures have been developed and a consensus has been reached on the use of assessment instruments in clinical trials, there is still need for improvement and implementation. The Assessments in Ankylosing Spondylitis (ASAS) Working Group has addressed some of these dilemmas by establishing a core set of domains for the evaluation of AS and by selecting specific assessment methods for each domain. They have also published improvement criteria for assessing short term improvement with symptom modifying antirheumatic drugs and are presently in the process of developing response criteria for disease controlling antirheumatic treatment. Various experts are also currently examining discrepancies and inadequacies of classification systems for AS. Imaging studies, magnetic resonance imaging, in particular, may Provide better classification criteria in the near future. In addition to consensus on outcome assessment and classification of AS, lessons learnt from clinical trials in rheumatoid arthritis (RA) may serve as a template for AS. Guidance provided by the United States Food and Drug Administration for clinical trials in RA may be of particular use. The FDA has defined the claims that sponsors can receive for RA products and the clinical trial data that would be expected to be submitted to support such claims. C1 Univ Hosp Maastricht, Div Rheumatol, Dept Internal Med, NL-6202 AZ Maastricht, Netherlands. US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. Univ Leeds, Dept Rheumatol, Leeds, W Yorkshire, England. Free Univ Berlin, Dept Gastroenterol & Rheumatol, D-1000 Berlin, Germany. Rheumazentrum Ruhrgebiet, Herne, Germany. RP van der Heijde, D (reprint author), Univ Hosp Maastricht, Div Rheumatol, Dept Internal Med, POB 5800, NL-6202 AZ Maastricht, Netherlands. NR 46 TC 16 Z9 16 U1 2 U2 2 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD DEC PY 2002 VL 61 SU 3 BP 24 EP 32 PG 9 WC Rheumatology SC Rheumatology GA 619RE UT WOS:000179489500005 ER PT J AU Simjee, S White, DG Wagner, DD Meng, J Qaiyumi, S Zhao, S McDermott, PF AF Simjee, S White, DG Wagner, DD Meng, J Qaiyumi, S Zhao, S McDermott, PF TI Identification of vat(E) in Enterococcus faecalis isolates from retail poultry and its transferability to Enterococcus faecium SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID QUINUPRISTIN-DALFOPRISTIN; RESISTANT ENTEROCOCCI; GENTAMICIN RESISTANCE; ENCODING RESISTANCE; STREPTOGRAMIN-A; UNITED-KINGDOM; FOOD-ANIMALS; SATA GENE; STRAIN AB Sixteen isolates of Enterococcus faecalis were recovered from retail poultry samples (seven chickens and nine turkeys) purchased from grocery stores in the greater Washington, D.C., area. PCR for known streptogramin resistance genes identified vat(E) in five E. faecalis isolates (three isolates from chickens and two isolates from turkeys). The vat(E) gene was transmissible on a ca. 70-kb plasmid, along with resistance to erythromycin, tetracycline, and streptomycin, by conjugation to E. faecalis and Enterococcus faecium recipient strains. DNA sequencing showed little variation between E. faecalis vat(E) genes from the chicken samples; however, one E. faecalis vat(E) gene from a turkey sample possessed 5 nucleotide changes that resulted in four amino acid substitutions. None of these substitutions in the vat(E) allele have previously been described. This is the first report of vat(E) in E. faecalis and its transferability to E. faecium, which indicates that E. faecalis can act as a reservoir for the dissemination of vat(E)-mediated streptogramin resistance to E. faecium. C1 US FDA, Ctr Vet Med, Laurel, MD 20708 USA. Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA. RP Simjee, S (reprint author), US FDA, Ctr Vet Med, 8401 Muirkirk Rd, Laurel, MD 20708 USA. NR 23 TC 25 Z9 28 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD DEC PY 2002 VL 46 IS 12 BP 3823 EP 3828 DI 10.1128/AAC.46.12.3823-3828.2002 PG 6 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 617TB UT WOS:000179376000020 PM 12435683 ER PT J AU Wang, HL Mann, CK Vickers, TJ AF Wang, HL Mann, CK Vickers, TJ TI Effect of powder properties on the intensity of Raman scattering by crystalline solids SO APPLIED SPECTROSCOPY LA English DT Article DE Raman; powders; particle size ID PROBE DESIGNS; SPECTROSCOPY; ABSORPTION AB The effect of particle size on Raman intensity has been measured for a number of crystalline solids with a fiber-optic-based Raman spectrometer. Particle sizes ranged from 76 to 605 mum. Materials examined were sodium nitrate, sodium chlorate, sodium bromate, potassium ferrocyanide, potassium ferricyanide, and copper(II) sulfate. Raman intensity was found to decrease with increasing particle size. The factors responsible for this trend are discussed. We conclude that the major factor is diffuse reflectance that enhances the overlap between the excitation and collection beams. The depth of sample contributing to the Raman signal has been examined for both powders and tablets as a function of powder particle size. Materials examined in this study were sodium nitrate, sodium sulfate, sodium chlorate, sodium bromate, potassium ferrocyanide, potassium ferricyanide, and copper(II) sulfate. For nonabsorbing powders, the depth of sample contributing to the signal exceeded 15 mm. The effect of the pressure used in forming tablets on the Raman signal strength and reproducibility has been examined for sodium nitrate. The Raman intensity was found to decrease with increasing pressure until a tablet of constant density was formed. The effect of particle size and particle size mismatch on the sodium nitrate Raman signal in binary mixtures with potassium chloride, potassium bromide, and potassium iodide has been examined. Good reproducibility was found to require matching of component particle sizes. C1 Florida State Univ, Dept Chem & Biochem, Tallahassee, FL 32306 USA. US FDA, CBER, HRM406, Rockville, MD 20852 USA. RP Vickers, TJ (reprint author), Florida State Univ, Dept Chem & Biochem, Tallahassee, FL 32306 USA. NR 13 TC 32 Z9 32 U1 0 U2 12 PU SOC APPLIED SPECTROSCOPY PI FREDERICK PA 201B BROADWAY ST, FREDERICK, MD 21701 USA SN 0003-7028 J9 APPL SPECTROSC JI Appl. Spectrosc. PD DEC PY 2002 VL 56 IS 12 BP 1538 EP 1544 DI 10.1366/000370202321115779 PG 7 WC Instruments & Instrumentation; Spectroscopy SC Instruments & Instrumentation; Spectroscopy GA 628TB UT WOS:000180011700005 ER PT J AU Brown, SL Greene, MH Gershon, SK Edwards, ET Braun, MM AF Brown, SL Greene, MH Gershon, SK Edwards, ET Braun, MM TI Tumor necrosis factor antagonist therapy and lymphoma development - Twenty-six cases reported to the Food and Drug Administration SO ARTHRITIS AND RHEUMATISM LA English DT Article ID INFLAMMATORY-BOWEL-DISEASE; EPSTEIN-BARR-VIRUS; RHEUMATOID-ARTHRITIS; LYMPHOPROLIFERATIVE DISORDERS; CROHNS-DISEASE; FACTOR-ALPHA; MONOCLONAL-ANTIBODY; HODGKINS-DISEASE; METHOTREXATE; RISK AB Objective. Etanercept and infliximab are tumor necrosis factor (TNF) antagonists that have been recently approved for the treatment of rheumatoid arthritis (RA) and Crohn's disease (CD). This study was undertaken to investigate the occurrence of lymphoproliferative disorders in patients treated with these agents. Methods. Relevant data in the MedWatch post-market adverse event surveillance system run by the US Food and Drug Administration were reviewed. Results. We identified 26 cases of lymphoproliferative disorders following treatment with etanercept (18 cases) or infliximab (8 cases). The majority of cases (81%) were non-Hodgkin's lymphomas. The interval between initiation of therapy with etanercept or infliximab and the development of lymphoma was very short (median 8 weeks). In 2 instances (I infliximab, 1 etanercept), lymphoma regression was observed following discontinuation of anti-TNF treatment, in the absence of specific cytotoxic therapy directed toward the lymphoma. Conclusion. Although data from a case series such as this cannot establish a clear causal relationship between exposure to these medications and the risk of lymphoproliferative disease, the known predisposition of patients with RA and CD to lymphoma, the known excess of lymphoma in other immunosuppressed populations, and the known immunosuppressive effects of the anti-TNF drugs provide a biologic basis for concern and justification for the initiation of additional epidemiologic studies to formally evaluate this possible association. C1 US FDA, Div Epidemiol, Off Biostat & Epidemiol, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. NCI, Rockville, MD USA. RP Braun, MM (reprint author), US FDA, Div Epidemiol, Off Biostat & Epidemiol, Ctr Biol Evaluat & Res, 1401 Rockville Pike,HFM-210, Rockville, MD 20852 USA. NR 45 TC 397 Z9 414 U1 0 U2 8 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 2002 VL 46 IS 12 BP 3151 EP 3158 DI 10.1002/art.10679 PG 8 WC Rheumatology SC Rheumatology GA 624HJ UT WOS:000179754000005 PM 12483718 ER PT J AU Stokes, WS Schechtman, LM Hill, RN AF Stokes, WS Schechtman, LM Hill, RN TI The Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM): A review of the ICCVAM test method evaluation process and current international collaborations with the European Centre for the Validation of Alternative Methods (ECVAM) SO ATLA-ALTERNATIVES TO LABORATORY ANIMALS LA English DT Article; Proceedings Paper CT ECVAM Status Seminar CY JUN 04-06, 2002 CL EUROPEAN COMMISS JOINT RES CTR AMPHITHEATRE, ISPRA, ITALY HO EUROPEAN COMMISS JOINT RES CTR AMPHITHEATRE DE alternative method; animal welfare; ECVAM; ICCVAM; NICEATM; regulatory acceptance; validation ID TOXICITY; WORKSHOP AB Over the last decade, national authorities in the USA and Europe have launched initiatives to validate new and improved toxicological test methods. In the USA, the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM), and its supporting National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM), were established by the Federal Government to work with test developers and Federal agencies to facilitate the validation, review, and adoption of new scientifically sound test methods, including alternatives that can reduce, refine, and replace animal use. In Europe, the European Centre for the Validation of Alternative Methods (ECVAM) was established to conduct validation studies on alternative test methods. Despite differences in organisational structure and processes, both organisations seek to achieve the adoption and use of alternative test methods. Accordingly, both have adopted similar validation and regulatory acceptance criteria, Collaborations and processes have also evolved to facilitate the international adoption of new test methods recommended by ECVAM and ICCVAM. These collaborations involve the sharing of expertise and data for test-method workshops and independent scientific peer reviews, and the adoption of processes to expedite the consideration of test methods already reviewed by the other organisation. More recently, NICEATM and ECVAM initiated a joint international validation study on in vitro methods for assessing acute systemic toxicity. These collaborations are expected to contribute to accelerated international adoption of harmonised new test methods that will support improved public health and provide for reduced and more-humane use of laboratory animals. C1 NIEHS, Natl Toxicol Program, Interagcy Ctr Evaluat Alternat Toxicol Methods, Environm Toxicol Program, Res Triangle Pk, NC 27709 USA. US FDA, Natl Ctr Toxicol Res, Rockville, MD 20857 USA. US EPA, Off Prevent Pesticides & Tox Subst, Washington, DC 20460 USA. RP Stokes, WS (reprint author), NIEHS, Natl Toxicol Program, Interagcy Ctr Evaluat Alternat Toxicol Methods, Environm Toxicol Program, Mail Code EC-17,POB 12233, Res Triangle Pk, NC 27709 USA. NR 33 TC 16 Z9 16 U1 0 U2 0 PU FRAME PI NOTTINGHAM PA RUSSELL & BURCH HOUSE 96-98 NORTH SHERWOOD ST, NOTTINGHAM NG1 4EE, NOTTS, ENGLAND SN 0261-1929 J9 ATLA-ALTERN LAB ANIM JI ATLA-Altern. Lab. Anim. PD DEC PY 2002 VL 30 SU 2 BP 23 EP 32 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 640BY UT WOS:000180667700005 PM 12513648 ER PT J AU Schechtman, LM Stokes, WS AF Schechtman, LM Stokes, WS TI ECVAM-ICCVAM: Prospects for future collaboration SO ATLA-ALTERNATIVES TO LABORATORY ANIMALS LA English DT Article; Proceedings Paper CT ECVAM Status Seminar CY JUN 04-06, 2002 CL EUROPEAN COMMISS JOINT RES CTR AMPHITHEATRE, ISPRA, ITALY HO EUROPEAN COMMISS JOINT RES CTR AMPHITHEATRE DE alternative method; animal welfare; collaboration; ECVAM; ESAC; ICCVAM; NICEATM; regulatory acceptance; SACATM; validation ID ALTERNATIVE METHODS AB The level and complexity of testing for hazard and risk assessment of marketed products and environmental agents has increased substantially over time, resulting in the use of greater numbers of both animals and humans for testing. Today, industry and regulatory bodies worldwide face increasing pressures to demonstrate responsible utilisation of laboratory animals, to limit their use, and to employ alternative non-animal tests. Institutions have also been established to identify, encourage the development of, conduct research on, and validate new, improved, and surrogate test methods that will reduce and replace animal use. Two such organisations are ECVAM and the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM). As the evolutionary changes occurring in the field of toxicology result in an unprecedented increase in the introduction of alternative methodologies, these will strain the capacities of such alternative-methods institutions, That realisation is causing a shift in thinking and is creating an impetus to seek approaches by which to collaborate and develop more-efficient operational procedures for the validation and regulatory acceptance of alternative methods. Similarities in objectives, functions, scientific standards, and commitment to the principles of validation and animal welfare support the value of a cooperative arrangement between ECVAM and ICCVAM, to minimise duplication of effort, maximise productivity, and influence the international adoption of alternative tests. Opportunities for ECVAM-ICCVAM collaboration are discussed, which illustrate the feasibility and potential benefits of such a partnership. C1 US FDA, Natl Ctr Toxicol Res, Rockville, MD 20857 USA. NIEHS, Environm Toxicol Program, NIH, Res Triangle Pk, NC 27709 USA. RP Schechtman, LM (reprint author), US FDA, Natl Ctr Toxicol Res, Rockville, MD 20857 USA. NR 13 TC 5 Z9 5 U1 0 U2 0 PU FRAME PI NOTTINGHAM PA RUSSELL & BURCH HOUSE 96-98 NORTH SHERWOOD ST, NOTTINGHAM NG1 4EE, NOTTS, ENGLAND SN 0261-1929 J9 ATLA-ALTERN LAB ANIM JI ATLA-Altern. Lab. Anim. PD DEC PY 2002 VL 30 SU 2 BP 227 EP 236 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 640BY UT WOS:000180667700040 PM 12513682 ER PT J AU Cha, CJ Kim, SJ Kim, YH Stingley, R Cerniglia, CE AF Cha, CJ Kim, SJ Kim, YH Stingley, R Cerniglia, CE TI Molecular cloning, expression and characterization of a novel class glutathione S-transferase from the fungus Cunninghamella elegans SO BIOCHEMICAL JOURNAL LA English DT Article DE fungal enzyme; overexpression; sequence analysis; substrate specificity ID POLYCYCLIC AROMATIC-HYDROCARBONS; ESCHERICHIA-COLI; ANOPHELES-GAMBIAE; CRYSTAL-STRUCTURE; IDENTIFICATION; METABOLISM; GENE; PURIFICATION; RESISTANCE; ENZYMES AB The structural gene for glutathione S-transferase (CeGST1-1) in the fungus Cunninghamella elegans was cloned by screening a cDNA library using a degenerate oligonucleotide probe based on the N-terminal sequence of the purified protein. Open reading frame analysis indicated that the cegst1 gene encodes a protein of 210 amino acid residues. The deduced amino acid sequence showed 25 % sequence identity with the sequence of the Pi-class GST from Danio rerio (zebrafish). Similarity was also shown with the Alpha-class GST from Fasciola hepatica (liver fluke; 23 % identity), the Mu class from Mus musculus (22 %) and the Sigma class from Ommastrephes sloani (squid; 21 %). Further screening of a cDNA library with the cegst1 gene probe revealed the presence of another GST isoenzyme (CeGST2-2) in this fungus, which shows 84 % sequence identity with CeGST1-1 at the amino acid level. Reverse transcription PCR revealed that cegst2 was also expressed at the mRNA level in the fungus C. elegans. Both cegst genes were overexpressed in Escherichia coli using the expression vector pQE51, displaying specific activities with 1-chloro-2,4-dinitrobenzene of 2.04 and 0.75 mumol/min per mg of protein respectively. Both enzymes exhibited a similar substrate specificity and inhibition profile, indicating that CeGST1-1 and CeGST2-2 belong to the same GST class. Mutagenesis analysis revealed that Tyr(10) in the N-terminal region is essential for catalysis of CeGST1-1. We propose from these results that the CeGSTs are novel Gamma-class GSTs and designated as GSTG1-1 and GSTG2-2 respectively. C1 US FDA, Div Microbiol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Cerniglia, CE (reprint author), US FDA, Div Microbiol, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. NR 49 TC 12 Z9 13 U1 3 U2 5 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON W1N 3AJ, ENGLAND SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD DEC 1 PY 2002 VL 368 BP 589 EP 595 DI 10.1042/BJ20020400 PN 2 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 624RX UT WOS:000179775700021 PM 12196209 ER PT J AU Gundberg, CM Looker, AC Nieman, SD Calvo, MS AF Gundberg, CM Looker, AC Nieman, SD Calvo, MS TI Patterns of osteocalcin and bone specific alkaline phosphatase by age, gender, and race or ethnicity SO BONE LA English DT Article DE osteocalcin; bone specific alkaline phosphatase; race/ethnicity; bone turnover; National Health and Nutrition Examination Survey; aging ID BIOCHEMICAL MARKERS; HIP FRACTURE; WHITE WOMEN; POSTMENOPAUSAL WOMEN; RACIAL-DIFFERENCES; FEMORAL-NECK; SERUM; TURNOVER; METABOLISM; MEN AB A variety of biochemical markers of bone turnover that assess bone formation or resorption are now available for research and clinical application. However, our understanding of the usual pattern of these measures over age in the general population is limited. Therefore, values of two bone formation markers, serum osteocalcin (Oc) and bone specific alkaline phosphatase (bone ALP), were compared by age, gender, and race or ethnicity using serum obtained from a subsample of blacks, whites, and Mexican Americans from the third National Health and Nutrition Examination Survey (NHANES). In all racial and ethnic groups, mean values of both serum Oc and bone ALP were lower in women than in men <50 years old. In individuals greater than or equal to50 years of age, Oc was significantly higher in women than in men. When analyzed in these two broad age groups, Oc was lower in older black men than in white or Mexican American men, but bone ALP was not different among the groups. In women, Oc levels tended to be lower in the black women than in white or Mexican American women. In contrast, bone ALP tended to be lower in white women than in black or Mexican American women. On the other hand, when analyzed by decade, patterns differed between the two markers in both men and women. In women, both Oc and bone ALP rose postmenopausally. However, bone ALP plateaued in the sixth through eighth decades, whereas Oc levels tended to increase further. In men, Oc was highest in the 20-29 year age group, declined and stabilized, then increased again in the seventh decade. In contrast, mean bone ALP did not differ by decade in men. Our data document differences in levels of circulating Oc and bone ALP by age, gender, and race/ethnicity. The age patterns reflected by the two markers are not concordant and distinctions are most evident in the latter decades. Our findings suggest that the specific osteoblast activity reflected by these markers responds differently to the physiologic changes that occur later in life. (C) 2002 by Elsevier Science Inc. All rights reserved. C1 Yale Univ, Sch Med, Dept Orthopaed & Rehabil, New Haven, CT 06510 USA. Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Hyattsville, MD 20782 USA. US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. RP Gundberg, CM (reprint author), Yale Univ, Sch Med, Dept Orthopaed, 789 Howard St,TMP-509, New Haven, CT 06510 USA. FU NIAMS NIH HHS [AR38460] NR 53 TC 74 Z9 80 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 8756-3282 J9 BONE JI Bone PD DEC PY 2002 VL 31 IS 6 BP 703 EP 708 AR PII S8756-3282(02)00902-X DI 10.1016/S8756-3282(02)00902-X PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 630MG UT WOS:000180111300010 PM 12531565 ER PT J AU Divi, RL Beland, FA Fu, PP Von Tungeln, LS Schoket, B Camara, JE Ghei, M Rothman, N Sinha, R Poirier, MC AF Divi, RL Beland, FA Fu, PP Von Tungeln, LS Schoket, B Camara, JE Ghei, M Rothman, N Sinha, R Poirier, MC TI Highly sensitive chemiluminescence immunoassay for benzo[a]pyrene-DNA adducts: validation by comparison with other methods, and use in human biomonitoring SO CARCINOGENESIS LA English DT Article ID HYDROCARBON-DNA ADDUCTS; POLYCYCLIC AROMATIC-HYDROCARBONS; WHITE BLOOD-CELLS; FED COAL-TAR; LUNG-CANCER; MOUSE EPIDERMIS; BREAST-TISSUE; BENZO(A)PYRENE; ASSOCIATION; MCL-5 AB A chemiluminescence immunoassay (CIA) utilizing antiserum elicited against DNA modified with (+/-)-7beta, 8alpha-dihydroxy-9alpha,10alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]- pyrene (BPDE) has been developed and validated to study the formation of polycyclic aromatic hydrocarbon (PAH)-DNA adducts in human tissues. Advantages include a low limit of detection for 10b-(deoxyguanosin-N-2-yl)-7beta,8alpha,9alpha-trihydroxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPdG, similar to1.5 adducts/10(9) nucleotides using 20 mug DNA) and a high signal-to-noise ratio (greater than or equal to100). The CIA BPDE-DNA standard curve gave 50% inhibition at 0.60 +/- 0.08 fmol BPdG (mean +/- SE, n = 30), which was a 10-fold increase in sensitivity compared with the dissociation-enhanced lanthanide fluoroimmunoassay (DELFIA). Calf thymus DNA modified with [1,3-H-3]BPDE was assayed by radiolabeling, P-32-postlabeling, DELFIA and CIA, and all assays gave similar values. Liver DNAs from mice exposed to 0.5 and 1.0 mg [7,8-H-3]benzo[a]pyrene (BP) were assayed by the same four assays and a dose-response was obtained with all assays. The BPDE-DNA CIA was further validated in MCL-5 cells exposed to 4 muM BP for 24 h, where nuclear and mitochondrial DNA adduct levels were associated with an increase in DNA tail length measured by the Comet assay. Human peripheral blood cell (buffy coat) DNA samples (n = 43) obtained from 25 individuals who were either colorectal adenocarcinoma patients or controls were assayed by BPDE-DNA CIA. Three samples (7%) were non-detectable, and the remaining 40 samples had values between 0.71 and 2.21 PAH-DNA adducts/10(8) nucleotides. The intra-assay coefficient of variation (CV), for four wells on the same microtiter plate, was 1.85%. Sufficient DNA for two assays, on separate plates, was available for 38 of the 43 samples, and the PAH-DNA adduct values obtained were highly correlated (r(2) = 0.95). Coded duplicate DNA samples from 15 individuals were assayed four times gave an inter-assay CV of 13.8%. C1 NCI, Carcinogen DNA Interact Sect, NIH, Bethesda, MD 20892 USA. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Jozef Fordor Natl Ctr Publ Hlth, H-1097 Budapest, Hungary. RP Poirier, MC (reprint author), NCI, Carcinogen DNA Interact Sect, NIH, Bldg 37,Room 4032,37 Convent Dr,MSC-4255, Bethesda, MD 20892 USA. NR 40 TC 53 Z9 56 U1 1 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD DEC PY 2002 VL 23 IS 12 BP 2043 EP 2049 DI 10.1093/carcin/23.12.2043 PG 7 WC Oncology SC Oncology GA 632YM UT WOS:000180252500008 PM 12507927 ER PT J AU Wein, LM Wu, JT Ianculescu, AG Puri, RK AF Wein, LM Wu, JT Ianculescu, AG Puri, RK TI A mathematical model of the impact of infused targeted cytotoxic agents on brain tumours: implications for detection, design and delivery SO CELL PROLIFERATION LA English DT Article ID CONVECTION-ENHANCED DELIVERY; GLIOMA GROWTH; INTERLEUKIN-4; TISSUE; DIFFUSION; EXOTOXIN; THERAPY; TUMORS; TOXIN; MICROINFUSION AB Motivated by the recent development of highly specific agents for brain tumours, we develop a mathematical model of the spatio-temporal dynamics of a brain tumour that receives an infusion of a highly specific cytotoxic agent (e.g. IL-4-PE, a cytotoxin comprised of IL-4 and a mutated form of Pseudomonas exotoxin). We derive an approximate but accurate mathematical formula for the tumour cure probability in terms of the tumour characteristics (size at time of detection, proliferation rate, diffusion coefficient), drug design (killing rate, loss rate and convection constants for tumour and tissue), and drug delivery (infusion rate, infusion duration). Our results suggest that high specificity is necessary but not sufficient to cure malignant gliomas; a nondispersed spatial profile of pretreatment tumour cells and/or good drug penetration are also required. The most important levers to improve tumour cure appear to be earlier detection, higher infusion rate, lower drug clearance rate and better convection into tumour, but not tissue. In contrast, the tumour cure probability is less sensitive to a longer infusion duration and enhancements in drug potency and drug specificity. C1 MIT, Sloan Sch Management, Cambridge, MA 02142 USA. US FDA, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. RP Wein, LM (reprint author), MIT, Sloan Sch Management, 30 Wadsworth St,E53-343, Cambridge, MA 02142 USA. RI Kipke, Daryl/A-2167-2009 NR 25 TC 12 Z9 12 U1 2 U2 4 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0960-7722 J9 CELL PROLIFERAT JI Cell Prolif. PD DEC PY 2002 VL 35 IS 6 BP 343 EP 361 DI 10.1046/j.1365-2184.2002.00246.x PG 19 WC Cell Biology SC Cell Biology GA 621DW UT WOS:000179574100003 PM 12427253 ER PT J AU Contrera, JF AF Contrera, JF TI Estimating the carcinogenic potential of pharmaceuticals using structural similarity clustering and MDL-QSAR electropological descriptors SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Meeting Abstract CT Meeting of the American-Chemical-Society Division of Chemical Toxicology of the 224th ACS National Meeting CY AUG 18-22, 2002 CL BOSTON, MASSACHUSETTS SP Amer Chem Soc, Div Chem Toxicol C1 US FDA, Ctr Drug Evaluat & Res, Informat & Computat Safety Anal Staff, Off Pharmaceut Sci, 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 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD DEC PY 2002 VL 15 IS 12 MA 28 BP 1658 EP 1658 PG 1 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 627VU UT WOS:000179957500048 ER PT J AU Houghton, PJ Adamson, PC Blaney, S Fine, HA Gorlick, R Haber, M Helman, L Hirschfeld, D Hollingshead, MG Israel, MA Lock, RB Maris, JM Merlino, G Patterson, W Reynolds, CP Shannon, K Yu, A Yu, J Smith, MA AF Houghton, PJ Adamson, PC Blaney, S Fine, HA Gorlick, R Haber, M Helman, L Hirschfeld, D Hollingshead, MG Israel, MA Lock, RB Maris, JM Merlino, G Patterson, W Reynolds, CP Shannon, K Yu, A Yu, J Smith, MA TI Testing of new agents in childhood cancer preclinical models: Meeting summary SO CLINICAL CANCER RESEARCH LA English DT Review ID ACUTE LYMPHOBLASTIC-LEUKEMIA; ANTIVIRAL PROTEIN IMMUNOTOXIN; NEUROBLASTOMA-CELL-LINES; TOPOISOMERASE-I INHIBITOR; CHRONIC MYELOID-LEUKEMIA; SYSTEM TUMOR XENOGRAFTS; TRANSGENIC MOUSE MODEL; MEDULLOBLASTOMA XENOGRAFTS; ANTITUMOR-ACTIVITY; NEUROFIBROMATOSIS TYPE-1 AB A workshop on pediatric preclinical testing, sponsored by the National Cancer Institute and the Children's Oncology Group Phase 1 Consortium, was held on June 26-27, 2001 in Bethesda, Maryland. Drs. Peter Adamson, Peter Houghton, and Malcolm Smith organized and hosted the meeting. There were 20 participants from 12 institutions. The primary objectives of the workshop included: (a) development of a working inventory of available preclinical models (including human tumor xenografts in immunodeficient mice, transgenic and syngeneic tumors, and selected in vitro models), with a basic understanding of the strengths and weaknesses of each as possible components of a preclinical testing program; (b) identification of the key scientific issues related to establishment of a program for preclinical testing of new agents for their applicability to childhood cancers; and (c) identification of the key infrastructure requirements for a program for preclinical testing of new agents for their applicability to childhood cancers. This report is a synthesis of the workshop's presentations and discussions. C1 St Jude Childrens Res Hosp, Memphis, TN 38101 USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. Texas Childrens Canc Ctr, Houston, TX 77024 USA. Neurol Oncol Branch, Bethesda, MD 20892 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ New S Wales, Childrens Canc Inst Australia Med Res, Kensington, NSW 2033, Australia. Sydney Childrens Hosp, Childrens Canc Inst Australia Med Res, Randwick, NSW, Australia. NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. US FDA, Rockville, MD 20852 USA. NCI, Biol Testing Branch, Frederick, MD 21702 USA. Dartmouth Coll Sch Med, Norris Cotton Canc Ctr, Lebanon, NH 03756 USA. NCI, Mol Genet Sect, Bethesda, MD 20892 USA. NCI, Technol Transfer Branch, Bethesda, MD 20892 USA. Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. Univ Calif San Francisco, Sch Med, San Francisco, CA 94143 USA. Univ Calif San Diego, Med Ctr, San Diego, CA 92103 USA. Scripps Res Inst, La Jolla, CA 92037 USA. NCI, Canc Therapy Evaluat Program, Pediat Sect, Bethesda, MD 20892 USA. RP Smith, MA (reprint author), NCI, Canc Therapy Evaluat Program, Pediat Sect, 6130 Execut Blvd,Room 7025, Bethesda, MD 20892 USA. EM smithm@ctep.nci.nih.gov RI Houghton, Peter/E-3265-2011; YU, JOHN/G-8954-2012; Lock, Richard/G-4253-2013; Hirschfeld, Steven/E-2987-2016 OI Hirschfeld, Steven/0000-0003-0627-7249 NR 109 TC 42 Z9 42 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC PY 2002 VL 8 IS 12 BP 3646 EP 3657 PG 12 WC Oncology SC Oncology GA 622XR UT WOS:000179673400002 PM 12473573 ER PT J AU Weaver, JP Sullivan, EJ Karwoski, C Beitz, J AF Weaver, JP Sullivan, EJ Karwoski, C Beitz, J TI Intensive care unit outbreaks of Burkholderia cepacia pneumonia from contamination of multi-dose bottles of albuterol inhalation solution: Cases from two hospitals reported to The Food and Drug Administration SO CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT 32nd Critical Care Congress CY JAN 28-FEB 02, 2003 CL SAN ANTONIO, TEXAS SP Soc Crit Care Med C1 US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD DEC PY 2002 VL 30 IS 12 SU S MA 476 BP A116 EP A116 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA 633RM UT WOS:000180296300394 ER PT J AU Yuan, R Madani, S Wei, XX Reynolds, K Huang, SM AF Yuan, R Madani, S Wei, XX Reynolds, K Huang, SM TI Evaluation of cytochrome P450 probe substrates commonly used by the pharmaceutical industry to study in vitro drug interactions SO DRUG METABOLISM AND DISPOSITION LA English DT Article ID HUMAN-LIVER-MICROSOMES; PHENACETIN O-DEETHYLATION; INHIBITORY MONOCLONAL-ANTIBODIES; IN-VITRO; S-MEPHENYTOIN; TOLBUTAMIDE HYDROXYLATION; COUMARIN 7-HYDROXYLATION; KINETIC CHARACTERIZATION; CAUCASIAN POPULATIONS; CATALYTIC ACTIVITY AB Pharmaceutical industry investigators routinely evaluate the for a new drug to modify cytochrome P450 ( P450) by determining the effect of the drug on in vitro probe that represent activity of specific P450 enzymes. The in vitro obtained with one probe substrate are usually extrapolated the compound's potential to affect all substrates of the enzyme. Due to this practice, it is important to use the right substrate and to conduct the experiment under optimal Surveys conducted by reviewers in CDER indicated that the common in vitro probe reactions used by industry include the following: phenacetin O-deethylation for CYP1A2, 7-hydroxylation for CYP2A6,7-ethoxy-4-trifluoromethyl O-dealkylation for CYP2B6, tolbutamide 4'-hydroxylation CYP2C9, S-mephenytoin 4-hydroxylation for CYP2C19, 1'-hydroxylation for CYP2D6, chlorzoxazone 6-hydroxylation CYP2E1, and testosterone 6beta-hydroxylation for CYP3A4. We reviewed the validation information in the literature on these reactions and other frequently used reactions, including caffeine N3-demethylation for CYP1A2, S-mephenytoin N-demethylation for CYP2B6, S-warfarin 7'-hydroxylation for CYP2C9, dextromethorphan O-demethylation for CYP2D6, and midazolam 1'-hydroxylation for CYP3A4. The available information indicates that we need to continue the search for better probe substrates for some enzymes. For CYP3A4-based drug interactions it may be necessary to evaluate two or more probe substrates. In many cases, the probe reaction represents a particular enzyme activity only under specific experimental conditions. Investigators must consider appropriateness of probe substrates and experimental conditions when conducting in vitro drug interaction studies and when extrapolating the results to in vivo situations. C1 US FDA, Off Clin Pharmacol & Biopharmaceut, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Yuan, R (reprint author), 3401 Hillview Ave,A2-264, Palo Alto, CA 94304 USA. NR 83 TC 219 Z9 249 U1 1 U2 23 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 DEC PY 2002 VL 30 IS 12 BP 1311 EP 1319 DI 10.1124/dmd.30.12.1311 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 615KK UT WOS:000179244200003 PM 12433797 ER PT J AU Schroeder, CM Meng, JH Zhao, SH DebRoy, C Torcolini, J Zhao, CW McDermott, PF Wagner, DD Walker, RD White, DG AF Schroeder, CM Meng, JH Zhao, SH DebRoy, C Torcolini, J Zhao, CW McDermott, PF Wagner, DD Walker, RD White, DG TI Antimicrobial resistance of Escherichia coli O26, O103, O111, O128, and O145 from animals and humans SO EMERGING INFECTIOUS DISEASES LA English DT Article ID HEMOLYTIC-UREMIC SYNDROME; ANTIBIOTIC-RESISTANCE; MULTIPLEX PCR; TOXIN GENES; STRAINS; FOOD; PREVALENCE; O157-H7; INFECTIONS; PATTERNS AB Susceptibilities to fourteen antimicrobial agents important in clinical medicine and agriculture were determined for 752 Escherichia coli isolates of serotypes O26, O103, O111, O128, and O145. Strains of these serotypes may cause urinary tract and enteric infections in humans and have been implicated in infections with Shiga toxin-producing E. coli (STEC). Approximately 50% of the 137 isolates from humans were resistant to ampicillin, sulfamethoxazole, cephalothin, tetracycline, or streptomycin, and approximately 25% were resistant to chloramphenicol, trimethoprim-sulfamethoxazole, or amoxicillin-clavulanic acid. Approximately 50% of the 534 isolates from food animals were resistant to sulfamethoxazole, tetracycline, or streptomycin. Of 195 isolates with STEC-related virulence genes, approximately 40% were resistant to sulfamethoxazole, tetracycline, or streptomycin. Findings from this study suggest antimicrobial resistance is widespread among E coli O26, O103, O111, O128, and O145 inhabiting humans and food animals. C1 Univ Maryland, College Pk, MD 20742 USA. Penn State Univ, University Pk, PA 16802 USA. US FDA, Ctr Vet Med, Laurel, MD 20708 USA. RP White, DG (reprint author), US FDA, Ctr Vet Med, Laurel, MD 20708 USA. NR 35 TC 66 Z9 71 U1 1 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 DEC PY 2002 VL 8 IS 12 BP 1409 EP 1414 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 625UQ UT WOS:000179834300008 PM 12498656 ER PT J AU Papaconstantinou, AD Fisher, BR Umbreit, TH Brown, KM AF Papaconstantinou, AD Fisher, BR Umbreit, TH Brown, KM TI Increases in mouse uterine heat shock protein levels are a sensitive and specific response to uterotrophic agents SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE bisphenol A; coumestrol; dexamethasone; endocrine disruptors; estrogen; heat shock proteins; methoxychlor; medroxyprogesterone; tamoxifen; uterotrophism ID EPITHELIAL-CELL PROLIFERATION; ESTROGEN-RECEPTOR-ALPHA; GROWTH-FACTOR RECEPTORS; IN-VIVO INTERACTIONS; BISPHENOL-A; DEXAMETHASONE INHIBITION; GENE-EXPRESSION; ANTIPROGESTERONE COMPOUNDS; OVARIECTOMIZED RATS; REPRODUCTIVE-TRACT AB There is increasing consensus that the uterotrophic estrogenicity assay should be coupled with other morphometric or molecular end points that might enhance its sensitivity. We have previously shown that bisphenol A (BPA), similarly to 17beta-estradiol (E-2), increases levels of uterine heat shock proteins (hsps), mainly hsp90alpha and glucose-regulated protein (grp) 94. In this study we investigated whether increases in uterine lisp levels are a specific response of estrogens or estrogen mimics. We therefore examined the ability of a) E-2 diethylstilbestrol (DES), and tamoxifien (TAM); b) the xenoestrogens coumestrol (CM), methoxychlor (MXC), BPA, and dibutyl phthalate (DBP); c) the progestin medroxyprogesterone (MED); d) the glucocorticoid dexamethasone (DEX); and e) phytol (PHY), a precursor to a retinoid X and peroxisome proliferator-activating receptor agonist, to increase uterine weights and alter uterine morphology and lisp levels. We showed that DES, TAM, CM, MXC, and BPA significantly increased uterine weights and uterine hsp90alpha and grp94 levels. Even though the doses of CM, MXC, and BPA used were much higher than the E-2 dose, those treatments resulted in lower increases in uterine weight. On the other hand, increases in grp94 levels were equal to those induced by E-2 treatment. Treatments with MED, DEX, DBP, or PHY did not significantly alter uterine weight or morphology and had no significant effects on uterine hsp levels. The results of this study suggest that only the estrogens increase uterine hsp90alpha and grp94 levels, and that this lisp effect is a more sensitive uterotrophic response than uterine weight increase. C1 George Washington Univ, Dept Biol Sci, Washington, DC 20052 USA. US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Brown, KM (reprint author), George Washington Univ, Dept Biol Sci, 332 Lisner Hall,2023 G St NW, Washington, DC 20052 USA. NR 73 TC 12 Z9 12 U1 0 U2 3 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD DEC PY 2002 VL 110 IS 12 BP 1207 EP 1212 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 625HG UT WOS:000179810600023 PM 12460799 ER PT J AU Osborne, CD Noblet, GP Enongene, EN Bacon, CW Riley, RT Voss, KA AF Osborne, CD Noblet, GP Enongene, EN Bacon, CW Riley, RT Voss, KA TI Host resistance to Trypanosoma cruzi infection is enhanced in mice fed Fusarium verticillioides (= F-moniliforme) culture material containing fumonisins SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article DE fumonisin; Fusarium verticillioides; host resistance; macrophage; nitric oxide; Trypanosoma cruzi ID HUMAN ESOPHAGEAL CANCER; NITRIC-OXIDE SYNTHASE; NECROSIS-FACTOR-ALPHA; CHICKEN MACROPHAGE; B-1; CORN; MECHANISM; TOXICITY; EXPOSURE; RATS AB Fumonisins, metabolites of Fusarium verticillioides (=F. moniliforme) and related fungi that occur naturally on corn, elicit various organ- and species-specific toxicities. However, immunologic effects of fumonisins are not well characterized. BALB/c mice were fed diets containing F. verticillioides culture material (CM) providing 50 (LD) or 150 (HD) ppm fumonisins (FB1 + FB2) beginning I week before and continuing 5 weeks after challenge with the myotropic Brazil strain of T. cruzi. A control group (ZD) was fed a diet lacking CM. The LD and HD diets caused increases in tissue sphinganine/sphingosine ratios and minimum to mild hepatotoxicity, both of which are typically induced by fumonisins. Nitric oxide (NO) production by peritoneal macrophages from HD mice was significantly higher than by peritoneal macrophages from ZD mice on day 14 after challenge. NO production also was stimulated in macrophages from ZD mice, but the peak response did not occur until day 26 after challenge. Compared with ZD mice, LD and HD mice exhibited reduced parasitemia and decreased numbers of pseudocysts in cardiac muscle. Thus, the CM increased host resistance to T. cruzi by accelerating NO production by macrophages or otherwise enhancing the immune response. The findings provide additional evidence that fumonisins modulate immune function. Published by Elsevier Science Ltd. C1 Dept Biol Sci, Clemson, SC 29634 USA. US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. ARS, USDA, Toxicol & Mycotoxin Res Unit, Athens, GA 30604 USA. RP Noblet, GP (reprint author), Dept Biol Sci, Clemson, SC 29634 USA. NR 44 TC 3 Z9 3 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 DEC PY 2002 VL 40 IS 12 BP 1789 EP 1798 AR PII S0278-6915(02)00182-5 PG 10 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA 621PT UT WOS:000179599000008 ER PT J AU Mermelstein, NH Fennema, OR Batt, CA Goff, HD Griffiths, MW Hoover, DG Hsieh, FH Juneja, VK Kroger, M Lund, DB Miller, DD Min, DB Murphy, PA Palumbo, SA Rao, MA Ryser, ET Schneeman, BO Singh, H Stone, H Whiting, R Wu, JSB Yousef, AE BeMiller, JN Dennis, C Doyle, MP Escher, FE Klaenhammer, T Knorr, D Kokini, JL Iwaoka, W Chism, GW Dong, FM Hartel, R Reitmeier, C Schmidt, SJ Wrolstad, RE AF Mermelstein, NH Fennema, OR Batt, CA Goff, HD Griffiths, MW Hoover, DG Hsieh, FH Juneja, VK Kroger, M Lund, DB Miller, DD Min, DB Murphy, PA Palumbo, SA Rao, MA Ryser, ET Schneeman, BO Singh, H Stone, H Whiting, R Wu, JSB Yousef, AE BeMiller, JN Dennis, C Doyle, MP Escher, FE Klaenhammer, T Knorr, D Kokini, JL Iwaoka, W Chism, GW Dong, FM Hartel, R Reitmeier, C Schmidt, SJ Wrolstad, RE TI Food research trends - 2003 and beyond SO FOOD TECHNOLOGY LA English DT Editorial Material C1 Univ Wisconsin, Dept Food Sci, Madison, WI 53706 USA. Univ Guelph, Dept Food Sci, Guelph, ON N1G 2W1, Canada. Ludwig Inst Canc Res Partnership, Ithaca, NY USA. Cornell Univ, Dept Food Sci, Ithaca, NY USA. Nanobiotechnol Ctr, Ithaca, NY USA. Univ Guelph, Dept Food Sci, Chair Dairy Microbiol, Guelph, ON N1G 2W1, Canada. Univ Guelph, Dept Food Sci, Canadian Res Inst Food Safety, Guelph, ON N1G 2W1, Canada. Univ Delaware, Dept Anim & Food Sci, Newark, DE USA. Univ Missouri, Columbia, MO USA. USDA ARS, Eastern Reg Res Ctr, Microbial Food Safety Res Unit, Wyndmoor, PA USA. Penn State Univ, Dept Food Sci, University Pk, PA 16802 USA. Ohio State Univ, Dept Food Sci & Technol, Columbus, OH 43210 USA. Iowa State Univ, Dept Food Sci & Human Nutr, Ames, IA USA. Natl Ctr Food Safety & Technol, Summit Argo, IL USA. Cornell Univ, Dept Food Sci & Technol, Geneva, NY 14456 USA. Michigan State Univ, Dept Food Sci & Human Nutr, E Lansing, MI 48824 USA. Univ Calif Davis, Dept Nutr, Davis, CA 95616 USA. Massey Univ, Inst Food Nutr & Human Hlth, Palmerston North, New Zealand. Tragon Corp, Redwood City, CA USA. US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. Natl Taiwan Univ, Inst Food Technol, Taipei 10764, Taiwan. Purdue Univ, Whistler Ctr Carbohydrate Res, W Lafayette, IN 47907 USA. Campden & Chorleywood Food Res Assoc, Chipping Campden, Glos, England. Univ Georgia, Ctr Food Safety, Griffin, GA USA. Swiss Fed Inst Technol, Inst Food Sci & Nutr, ETH, Zurich, Switzerland. N Carolina State Univ, SE Dairy Foods Res Ctr, Raleigh, NC 27695 USA. Berlin Univ Technol, Dept Food Biotechnol & Food Proc Engn, Berlin, Germany. Univ Delaware, Newark, DE USA. Rutgers State Univ, Ctr Adv Food Technol, New Brunswick, NJ USA. Rutgers State Univ, Dept Food Sci, New Brunswick, NJ USA. Univ Illinois, Dept Food Sci & Human Nutr, Urbana, IL 61801 USA. Univ Illinois, Dept Food Sci & Human Nutr, Champaign, IL 61820 USA. Oregon State Univ, Corvallis, OR 97331 USA. RP Mermelstein, NH (reprint author), Univ Wisconsin, Dept Food Sci, 1605 Linden Dr, Madison, WI 53706 USA. NR 0 TC 2 Z9 2 U1 2 U2 3 PU INST FOOD TECHNOLOGISTS PI CHICAGO PA 525 WEST VAN BUREN, STE 1000, CHICAGO, IL 60607-3814 USA SN 0015-6639 J9 FOOD TECHNOL-CHICAGO JI Food Technol. PD DEC PY 2002 VL 56 IS 12 BP 30 EP + PG 18 WC Food Science & Technology SC Food Science & Technology GA 626JD UT WOS:000179867300007 ER PT J AU Schmeisser, F Donohue, M Weir, JP AF Schmeisser, F Donohue, M Weir, JP TI Tetracycline-regulated gene expression in replication-incompetent herpes simplex virus vectors SO HUMAN GENE THERAPY LA English DT Article ID IMMEDIATE-EARLY GENES; NERVE GROWTH-FACTOR; THYMIDINE KINASE; MAMMALIAN-CELLS; TRANSGENE EXPRESSION; GANGLION NEURONS; TYPE-1; INFECTION; SYSTEM; BRAIN AB Although herpes simplex virus (HSV) vectors appear to have great potential as gene delivery vectors both in vitro and in vivo, the expression of foreign genes in such vectors cannot be easily regulated. Of the known eukaryotic regulatory systems, the tetracycline-inducible gene expression system is perhaps the most widely used because of its induction characteristics and because of the well-known pharmacological properties of tetracycline (Tet) and analogs such as doxycycline. Here, we describe the adaptation of the Tet-inducible system for use in replication-incompetent HSV vectors. HSV vectors were constructed that contained several types of Tet-inducible promoters for foreign gene expression. These promoters contained a tetracycline response element (TRE) linked to either a minimal cytomegalovirus (CMV) immediate-early promoter, a minimal HSV ICP0 promoter, or a truncated HSV ICP0 promoter containing one copy of the HSV TAATGARAT cis-acting immediate-early regulatory element ( where R represents a prime base). All three promoter constructs were regulated appropriately by doxycycline, as shown by the expression of the marker gene lacZ in cell lines engineered to express Tet transactivators. The ICP0 promoter constructs expressed the highest and most sustained levels of lacZ, but the CMV promoter construct had the highest relative level of induction, suggesting their use in different applications. To extend the utility of Tet-regulated HSV vectors, vectors were constructed that coexpressed an inducible Tet transactivator in addition to the inducible lacZ marker gene. This modification resulted in tetracycline-inducible gene expression that was not restricted to specific cell lines, and this vector was capable of inducible expression in irreversibly differentiated NT2 cells (NT-neurons) for several days. Finally, HSV vectors were constructed that expressed modified Tet transactivators, resulting in improved induction properties and indicating the flexibility of the Tet-regulated system for regulation of foreign gene expression in HSV vector-infected cells. C1 US FDA, Lab DNA Viruses, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Weir, JP (reprint author), Ctr Biol Evaluat & Res, Div Viral Prod, HFM-457,1401 Rockville Pike, Rockville, MD 20852 USA. EM weirj@cber.fda.gov NR 52 TC 16 Z9 21 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD DEC PY 2002 VL 13 IS 18 BP 2113 EP 2124 DI 10.1089/104303402320987815 PG 12 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 766CP UT WOS:000188328100001 PM 12542843 ER PT J AU Simjee, S White, DG Meng, J Wagner, DD Qaiyumi, S Zhao, S Hayes, JR McDermott, PF AF Simjee, S White, DG Meng, J Wagner, DD Qaiyumi, S Zhao, S Hayes, JR McDermott, PF TI Prevalence of streptogramin resistance genes among Enterococcus isolates recovered from retail meats in the Greater Washington DC area SO JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY LA English DT Article DE Enterococcus faecium; quinupristin-dalfopristin; resistance ID QUINUPRISTIN-DALFOPRISTIN; ANTIMICROBIAL RESISTANCE; STAPHYLOCOCCAL GENE; ENCODING RESISTANCE; UNITED-KINGDOM; FOOD-ANIMALS; FAECIUM; VIRGINIAMYCIN; SATA; SUSCEPTIBILITY AB The prevalence of streptogramin resistance genes in enterococci recovered from retail poultry in the Greater Washington DC area was examined. Forty-three chicken and 32 turkey retail samples were analysed. Thirty-one non-Enterococcus faecalis enterococcal strains were isolated that displayed MICs of quinupristin-dalfopristin and virginiamycin of greater than or equal to4 mg/L. These included Enterococcus faecium (turkey n = 4, chicken n = 23), Enterococcus gallinarum (turkey n = 2, chicken n = 1) and Enterococcus hirae (chicken n = 1). The presence of streptogramin resistance genes was examined by PCR in all non-E. faecalis isolates. The vat(E) gene was detected in 10/23 chicken E. faecium and from 2/4 turkey E. faecium. No other streptogramin resistance genes were detected by PCR. In addition, erm(B) was detected in all the E. faecium and E. gallinarum found in turkeys and in 7/23 E. faecium found in chickens. The vat(E) gene was transferable by conjugation from only two of the 12 E. faecium isolates (one from chicken and one from turkey). This study suggests that there is a high prevalence of low-level streptogramin resistance among enterococci found in retail poultry and that other, yet to be identified, mechanisms operate in these isolates that confer streptogramin resistance in enterococci. C1 US FDA, Ctr Vet Med, Laurel, MD 20708 USA. Univ Maryland, Dept Cell Biol & Mol Genet, College Pk, MD 20742 USA. RP Simjee, S (reprint author), US FDA, Ctr Vet Med, 8401 Muirkirk Rd, Laurel, MD 20708 USA. NR 24 TC 31 Z9 33 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-7453 J9 J ANTIMICROB CHEMOTH JI J. Antimicrob. Chemother. PD DEC PY 2002 VL 50 IS 6 BP 877 EP 882 DI 10.1093/jac/dkf236 PG 6 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA 622VY UT WOS:000179668900015 PM 12461007 ER PT J AU Schmitt, MP AF Schmitt, MP TI Analysis of a DtxR-like metalloregulatory protein, MntR, from Corynebacterium diphtheriae that controls expression of an ABC metal transporter by an Mn2+-dependent mechanism SO JOURNAL OF BACTERIOLOGY LA English DT Article ID TOXIN REPRESSOR DTXR; STREPTOCOCCUS-GORDONII; BACILLUS-SUBTILIS; SEQUENCE-ANALYSIS; CRYSTAL-STRUCTURE; IRON ACQUISITION; BINDING; GENE; IDENTIFICATION; MANGANESE AB The DtxR protein is a global iron-dependent repressor in Corynebacterium diphtheriae that regulates transcription from multiple promoters. A search of the partially completed C. diphtheriae genome identified a gene, mntR, whose predicted product has significant homology with the DtxR repressor protein. The mntR gene is the terminal gene in a five-gene operon that also carries the mnUBCD genes, whose predicted products are homologous to ABC metal transporters. Transcription of this genetic system, as measured by expression of an mntA-lacZ reporter fusion, is strongly repressed by Mn2+. The divalent metals Fe2+, Cu2+, and Zn2+ did not repress expression of the mntA-lacZ construct. A mutation in the mntR gene abolished Mn2+-dependent repression of the nmtA-lacZ fusion, demonstrating that MntR is essential for the Mn2+-dependent regulation of this promoter. Footprinting experiments showed that MntR protects from DNase I digestion an approximately 73-bp AT-rich region that includes the entire mntA promoter. This large region protected from DNase I suggests that as many as three MntR dimer pairs may bind to this region. Binding studies also revealed that DtxR failed to bind to the MntR binding site and that MntR exhibited weak and diffuse binding at the DtxR binding site at the tox promoter. A C. diphtheriae mntA mutant grew as well as the wild type in a low-Mn2+ medium, which suggests that the mntABCD metal transporter is not required for growth in a low-Mn2+ medium and that additional Mn2+ transport systems may be present in C diphtheriae. This study reports the characterization of MntR, a Mn2+-dependent repressor, and the second member of the family of DtxR-like metalloregulatory proteins to be identified in C. diphtheriae. C1 US FDA, Ctr Biol Evaluat & Res, Lab Bacterial Toxins, Div Bacterial Allergen & Parasit Prod, Bethesda, MD 20892 USA. RP Schmitt, MP (reprint author), US FDA, Ctr Biol Evaluat & Res, Lab Bacterial Toxins, Div Bacterial Allergen & Parasit Prod, Bldg 29,Rm 108,8800 Rockville Pike, Bethesda, MD 20892 USA. NR 55 TC 27 Z9 28 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD DEC PY 2002 VL 184 IS 24 BP 6882 EP 6892 DI 10.1128/JB.184.24.6882-6892.2002 PG 11 WC Microbiology SC Microbiology GA 620JA UT WOS:000179529200016 PM 12446639 ER PT J AU Simjee, S White, DG McDermott, PF Wagner, DD Zervos, MJ Donabedian, SM English, LL Hayes, JR Walker, RD AF Simjee, S White, DG McDermott, PF Wagner, DD Zervos, MJ Donabedian, SM English, LL Hayes, JR Walker, RD TI Characterization of Tn1546 in vancomycin-resistant Enterococcus faecium isolated from canine urinary tract infections: Evidence of gene exchange between human and animal enterococci SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID VANA GLYCOPEPTIDE RESISTANCE; LEVEL GENTAMICIN RESISTANCE; MOLECULAR ANALYSIS; UNITED-STATES; FARM-ANIMALS; FAECALIS; ELEMENTS; PLASMID; IDENTIFICATION; STRAIN AB Thirty-five enterococcal isolates were recovered from dogs diagnosed with urinary tract infections at the Michigan State University Veterinary Teaching Hospital over a 2-year period (1996 to 1998). Isolated species included Enterococcus faecium (n = 13), Enterococcus faecalis (n = 7), Enterococcus gallinarum (n = 11), and Enterococcus casseliflavus (n = 4). Antimicrobial susceptibility testing revealed several different resistance phenotypes, with the majority of the enterococcal isolates exhibiting resistance to three or more antibiotics. One E. faecium isolate, CVM1869, displayed high-level resistance to vancomycin (MIC > 32 mug/ml) and gentamicin (MIC > 2,048 mug/ml). Molecular analysis of this isolate revealed the presence of Tn1546 (vanA), responsible for high-level vancomycin resistance, and Tn5281 carrying aac6'-aph2", conferring high-level aminoglycoside resistance. Pulsed-field gel electrophoresis analysis revealed that CVM1869 was a canine E. faecium clone that had acquired Tn1546, perhaps from a human vancomycin-resistant E. faecium. Transposons Tn5281 and Tn1546 were located on two different conjugative plasmids. Sequence analysis revealed that in Tn1546, ORF1 had an 889-bp deletion and an IS1216V insertion at the 5' end and an IS1251 insertion between vanS and vanH. To date, this particular form of Tn1546 has only been described in human clinical vancomycin-resistant enterococcus isolates unique to the United States. Additionally, this is the first report of a vancomycin-resistant E. faecium isolated from a companion animal in the United States. C1 US FDA, Ctr Vet Med, Laurel, MD 20708 USA. William Beaumont Hosp, Royal Oak, MI 48073 USA. Univ Maryland, Dept Cell Biol & Mol Genet, College Pk, MD 20742 USA. RP Simjee, S (reprint author), US FDA, Ctr Vet Med, 8401 Muirkirk Rd, Laurel, MD 20708 USA. NR 42 TC 55 Z9 59 U1 2 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 2002 VL 40 IS 12 BP 4659 EP 4665 DI 10.1128/JCM.40.12.4659-4665.2002 PG 7 WC Microbiology SC Microbiology GA 622DP UT WOS:000179631500042 PM 12454168 ER PT J AU Volokhov, D Rasooly, A Chumakov, K Chizhikov, V AF Volokhov, D Rasooly, A Chumakov, K Chizhikov, V TI Identification of Listeria species by microarray-based assay SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID VIRULENCE-ASSOCIATED GENES; POLYMERASE-CHAIN-REACTION; MULTIPLEX PCR; RAPID DETECTION; MONOCYTOGENES; FRAGMENT; PROBE; MILK; HYBRIDIZATION; PATHOGENESIS AB We have developed a rapid microarray-based assay for the reliable detection and discrimination of six species of the Listeria genus: L. monocytogenes, L. ivanovii, L. innocua, L. welshimeri, L. seeligeri, and L. grayi. The approach used in this study involves one-tube multiplex PCR amplification of six target bacterial virulence factor genes (iap, hly, inlB, plcA, plcB, and clpE), synthesis of fluorescently labeled single-stranded DNA, and hybridization to the multiple individual oligonucleotide probes specific for each Listeria species and immobilized on a glass surface. Results of the microarray analysis of 53 reference and clinical isolates of Listeria spp. demonstrated that this method allowed unambiguous identification of all six Listeria species based on sequence differences in the iap gene. Another virulence factor gene, hly, was used for detection and genotyping all L. monocytogenes, all L. ivanovii, and 8 of 11 L. seeligeri isolates. Other members of the genus Listeria and three L. seeligeri isolates did not contain the hly gene. There was complete agreement between the results of genotyping based on the hly and iap gene sequences. All L. monocytogenes isolates were found to be positive for the inlB, plcA, plcB, and clpE virulence genes specific only to this species. Our data on Listeria species analysis demonstrated that this microarray technique is a simple, rapid, and robust genotyping method that is also a potentially valuable tool for identification and characterization of bacterial pathogens in general. C1 US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20895 USA. RP Chizhikov, V (reprint author), US FDA, Ctr Biol Evaluat & Res, Lab Method Dev, HFM-470,1401 Rockville Pike, Rockville, MD 20852 USA. NR 48 TC 149 Z9 179 U1 0 U2 13 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD DEC PY 2002 VL 40 IS 12 BP 4720 EP 4728 DI 10.1128/JCM.40.12.4720-4728.2002 PG 9 WC Microbiology SC Microbiology GA 622DP UT WOS:000179631500052 PM 12454178 ER PT J AU Fu, PP Yang, YC Xia, QS Chou, MW Cui, YY Lin, G AF Fu, PP Yang, YC Xia, QS Chou, MW Cui, YY Lin, G TI Pyrrolizidine alkaloids - Tumorigenic components in Chinese herbal medicines and dietary supplements SO JOURNAL OF FOOD AND DRUG ANALYSIS LA English DT Review DE pyrrolizidine alkaloids; Chinese herbal medicines; tumorigenecity ID VENO-OCCLUSIVE DISEASE; PERFORMANCE LIQUID-CHROMATOGRAPHY; FLAVIN-CONTAINING MONOOXYGENASE; DNA CROSS-LINKING; RAT-LIVER; ACUTE TOXICITY; GUINEA-PIG; IN-VITRO; CARCINOGENIC ACTIVITY; MASS-SPECTROMETRY AB Traditional Chinese medicine (TCM) has long been used for treating illness in China and other Asian countries, and recently used by the Western countries in several different ways, either for new drug development, or as functional foods and dietary supplements. However, quality assurance and health adverse effects of the herbal plants have not been well studied. Pyrrolizidine alkaloids, a class of hepatotoxic and tumorigenic compounds, have been detected in herbal plants and dietary supplements. In this review, the sources of the pyrrolizidine alkaloid-containing Chinese herbal plants in China and the toxicity, genotoxicity, and, tumorigenicity of these compounds are discussed. The metabolic pathways, particularly the activation pathways leading to genotoxicity, are discussed. Recent mechanistic studies indicate that pyrrolizidine alkaloids induce tumors via a genotoxic mechanism mediated by 6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine (DHP)-derived DNA adduct formation. This mechanism may be general to most carcinogenic pyrrolizidine alkaloids. Perspectives are included for suggestion of directions of future research. C1 Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Chinese Univ Hong Kong, Dept Pharmacol, Shatin, Hong Kong, Peoples R China. NR 122 TC 71 Z9 71 U1 2 U2 18 PU NATL LABORATORIES FOODS DRUGS PI NANKANG, TAIPEI PA DEPT HEALTH, EXECUTIVE YUAN, 161-2 KUEN YANG ST DR. ERICK T. SUEN, DEPUTY DIR., NANKANG, TAIPEI, TAIWAN SN 1021-9498 J9 J FOOD DRUG ANAL JI J. Food Drug Anal. PD DEC PY 2002 VL 10 IS 4 BP 198 EP 211 PG 14 WC Food Science & Technology; Pharmacology & Pharmacy SC Food Science & Technology; Pharmacology & Pharmacy GA 643XP UT WOS:000180888900002 ER PT J AU Howard, PC Sams, RL Bucher, JR Allaben, WT AF Howard, PC Sams, RL Bucher, JR Allaben, WT TI Phototoxicology and photocarcinogenesis at the US Food and Drug Administration's National Center for Toxicological Research SO JOURNAL OF FOOD AND DRUG ANALYSIS LA English DT Article DE phototoxicology; photocarcinogenesis; simulated solar light; SKH-1 hairless mice ID GLYCOLIC ACID; HAIRLESS MICE; PHOTOAGED SKIN; RADIATION; CANCER AB Ultraviolet radiation (UVR) causes skin cancer in humans and can induce skin cancer in test animals. The interaction of UVR with many drugs has been reported, however, there is a paucity of data concerning the carcinogenesis of cosmetic ingredients and environmental contaminants in combination with UVR. A research center has been developed at the U.S. Food and Drug Administration's National Center for Toxicological Research to quantify the potential carcinogenicity of combined exposure to chemicals and UVR. The chemicals tested in this facility are nominated to, and approved by, the National Toxicology Program. In this paper we describe the nomination of chemicals, test animals, source of UVR, dosimetry, and test paradigm that are used. This unique test facility is being used to protect public health through quantifying the photocarcinogenicity of chemicals to which the public is exposed. C1 US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Natl Toxicol Program Ctr Phototoxicol, Jefferson, AR 72079 USA. NIEHS, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA. NR 31 TC 8 Z9 8 U1 1 U2 1 PU NATL LABORATORIES FOODS DRUGS PI NANKANG, TAIPEI PA DEPT HEALTH, EXECUTIVE YUAN, 161-2 KUEN YANG ST DR. ERICK T. SUEN, DEPUTY DIR., NANKANG, TAIPEI, TAIWAN SN 1021-9498 J9 J FOOD DRUG ANAL JI J. Food Drug Anal. PD DEC PY 2002 VL 10 IS 4 BP 252 EP 257 PG 6 WC Food Science & Technology; Pharmacology & Pharmacy SC Food Science & Technology; Pharmacology & Pharmacy GA 643XP UT WOS:000180888900007 ER PT J AU Howard, PC Sams, RL Dennis, DA Wamer, WG AF Howard, PC Sams, RL Dennis, DA Wamer, WG TI Alpha-hydroxy acids: Consideration of the biological effects and possible role in photococarcinogenesis SO JOURNAL OF FOOD AND DRUG ANALYSIS LA English DT Article DE alpha-hydroxy acids; glycolic acid; phototoxicity; simulated solar light; SKH-1 hairless mice ID GLYCOLIC ACID; PHOTOAGED SKIN; PROLIFERATION; MICE AB The U.S. Food and Drug Administration nominated topically applied alpha-hydroxy acids to the U.S. National Toxicology Program for toxicological studies. The alpha-hydroxy acids are present at significant concentrations in many cosmetic products and are marketed as products to correct photoaging of skin. In this paper, we review the current knowledge concerning the effect of topical treatment of mice with creams containing alpha-hydroxy acids and the effect of ultraviolet radiation on treated and untreated mouse skin. C1 US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Natl Toxicol Program Ctr Phototoxicol, Jefferson, AR 72079 USA. US FDA, Ctr Food Safety & Appl Nutr, Off Cosmet & Colors, College Pk, MD 20740 USA. NR 26 TC 2 Z9 2 U1 1 U2 1 PU NATL LABORATORIES FOODS DRUGS PI NANKANG, TAIPEI PA DEPT HEALTH, EXECUTIVE YUAN, 161-2 KUEN YANG ST DR. ERICK T. SUEN, DEPUTY DIR., NANKANG, TAIPEI, TAIWAN SN 1021-9498 J9 J FOOD DRUG ANAL JI J. Food Drug Anal. PD DEC PY 2002 VL 10 IS 4 BP 258 EP 261 PG 4 WC Food Science & Technology; Pharmacology & Pharmacy SC Food Science & Technology; Pharmacology & Pharmacy GA 643XP UT WOS:000180888900008 ER PT J AU Fu, PP Howard, PC Culp, SJ Xia, QS Webb, PJ Blankenship, LR Wamer, WG Bucher, JR AF Fu, PP Howard, PC Culp, SJ Xia, QS Webb, PJ Blankenship, LR Wamer, WG Bucher, JR TI Do topically applied skin creams containing retinyl palmitate affect the photocarcinogenecity of simulated solar light? SO JOURNAL OF FOOD AND DRUG ANALYSIS LA English DT Article DE retinyl palmitate; photocarcinogenicity; SKH-1 mice ID ALL-TRANS-RETINOL; MOUSE SKIN; VITAMIN-A; ACID; METABOLISM; INHIBITION AB Retinyl palmitate (all-trans-retinyl palmitate; RP) was nominated in 2001 by the U.S. Food and Drug Administration's Center for Food Safety and Applied Nutrition (CFSAN) to the National Toxicology Program (NTP) as a high priority compound for phototoxicity and photocarcinogenicity studies at the National Center for Toxicological Research (NCTR). Studies with SKH-1 hairless mice are required to test whether topical application of RP enhances the phototoxicity and photocarcinogenicity of simulated solar light and UV light. Mechanistic studies are needed to provide insight into the disposition of RP in vitro and on the skin of mice, and to test thoroughly whether genotoxic damage by UV-induced radicals may participate in any toxicity of topically applied RP in the presence of UV light. C1 US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. US FDA, Ctr Food Safety & Appl Nutr, Off Cosmet & Colors, College Pk, MD 20740 USA. NIEHS, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA. NR 43 TC 8 Z9 8 U1 0 U2 0 PU NATL LABORATORIES FOODS DRUGS PI NANKANG, TAIPEI PA DEPT HEALTH, EXECUTIVE YUAN, 161-2 KUEN YANG ST DR. ERICK T. SUEN, DEPUTY DIR., NANKANG, TAIPEI, TAIWAN SN 1021-9498 J9 J FOOD DRUG ANAL JI J. Food Drug Anal. PD DEC PY 2002 VL 10 IS 4 BP 262 EP 268 PG 7 WC Food Science & Technology; Pharmacology & Pharmacy SC Food Science & Technology; Pharmacology & Pharmacy GA 643XP UT WOS:000180888900009 ER PT J AU Cook, DW Bowers, JC DePaola, A AF Cook, DW Bowers, JC DePaola, A TI Density of total and pathogenic (tdh+) Vibrio parahaemolyticus in Atlantic and Gulf coast molluscan shellfish at harvest SO JOURNAL OF FOOD PROTECTION LA English DT Article ID UNITED-STATES; INFECTIONS; OYSTERS; GENE AB The densities of total and pathogenic Vibrio parahaemolyticus in 671 samples of molluscan shellfish harvested in 1999 and 2000 from 14 sites in seven Gulf and Atlantic coast states were determined at 2-week intervals over a period of 12 to 16 months in each state. Changes in V. parahaemolyticus densities in shellfish between harvest and sample analysis were minimized with time and temperature controls. Densities were measured by direct plating techniques, and gene probes were used for identification. Total and pathogenic V. parahaemolyticus organisms were identified with probes for the thermolabile direct hemolysin (tlh) gene and the thermostable direct hemolysin (tdh) gene, respectively. An enrichment procedure involving 25 g of shellfish was also used for the recovery of pathogenic V parahaemolyticus. The densities of V. parahaemolyticus in shellfish from all harvest sites were positively correlated with water temperature. Shellfish from the Gulf Coast typically bad higher densities of V. parahaemolyticus than did shellfish harvested from the North Atlantic or mid-Atlantic coast. Vibrio parahaemolyticus counts exceeded 1,000 CFU/g for only 5% of all samples. Pathogenic (tdh+) V. parahaemolyticus was detected in approximately 6% of all samples by both procedures, and 61.5% of populations in the positive samples from the direct plating procedure were at the lower limit of detection (10 CFU/g). The frequency of detection of pathogenic V. parahaemolyticus was significantly related to water temperature and to the density of total V. parahaemolyticus. The failure to detect pathogenic V. parahaemolyticus in shellfish more frequently was attributed to the low numbers and uneven distribution of the organism. C1 US FDA, Gulf Coast Seaford Lab, Dauphin Isl, AL 36528 USA. US FDA, Div Math & Stat, Washington, DC 20204 USA. RP Cook, DW (reprint author), US FDA, Gulf Coast Seaford Lab, POB 158,1 Iberville Dr, Dauphin Isl, AL 36528 USA. NR 18 TC 72 Z9 80 U1 1 U2 8 PU INT ASSOC FOOD PROTECTION PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD DEC PY 2002 VL 65 IS 12 BP 1873 EP 1880 PG 8 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 624HQ UT WOS:000179754600006 PM 12495004 ER PT J AU Lapham, CK Romantseva, T Petricoin, E King, LR Manischewitz, J Zaitseva, MB Golding, H AF Lapham, CK Romantseva, T Petricoin, E King, LR Manischewitz, J Zaitseva, MB Golding, H TI CXCR4 heterogeneity in primary cells: possible role of ubiquitination SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE monocytes; lymphocytes; chemokine receptor HIV-1 ID IMMUNODEFICIENCY-VIRUS TYPE-1; PROTEIN-COUPLED RECEPTOR; DELTA-OPIOID RECEPTORS; ENDOPLASMIC-RETICULUM; CHEMOKINE RECEPTORS; GEL-ELECTROPHORESIS; MEMBRANE-FUSION; BETA-ARRESTIN; HIV-1 ENTRY; DEGRADATION AB The chemokine receptor CXCR4 is a primary coreceptor for the HIV-1 virus. The predicted molecular weight (MW) of glycosylated CXCR4 is 45-47 kDa. However, immunoblots of whole cell lysates from human lymphocytes, monocytes, macrophages, and the Jurkat T-lymphocyte line revealed multiple MW isoforms of CXCR4. Three of the bands could be precipitated by anti-CXCR4 monoclonal antibodies (101 and 47 kDa) or coprecipitated with CD4 (62 kDa). Expression of these isoforms was enhanced by infection with a recombinant vaccinia virus encoding CXCR4. In immunoblots of two-dimensional gels, antiubiquitin antibodies reacted with the 62-kDa CXCR4 species from monocytes subsequent to coprecipitation with anti-CD4 antibodies. Culturing of monocytes and lymphocytes with lactacystin enhanced the amount of the 101-kDa CXCR4 isoform in immunoblots by three- to sevenfold. In lymphocytes, lactacystin also increased cell-surface expression of CXCR4, which correlated with enhanced fusion with HIV-1 envelope-expressing cells. Similar increases in the intensity of the 101-kDa isoform were seen after treatment with the lysosomal inhibitors monensin and ammonium chloride. Antiubiquitin antibodies reacted with multiple proteins above 62 kDa, which were precipitated with anti-CXCR4 antibodies. Our data indicate that ubiquitination may contribute to CXCR4 heterogeneity and suggest roles for proteasomes and lysosomes in the constitutive turnover of CXCR4 in primary human cells. C1 US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. US FDA, Div Cytokine Biol, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Golding, H (reprint author), US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Bldg 29B,Room 4NN04,HFM 454, Bethesda, MD 20892 USA. NR 37 TC 31 Z9 33 U1 0 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD DEC PY 2002 VL 72 IS 6 BP 1206 EP 1214 PG 9 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 629QX UT WOS:000180061300016 PM 12488503 ER PT J AU Jones, RR Steffe, JF Harte, JB AF Jones, RR Steffe, JF Harte, JB TI Sensory firmness scale based on gelatin gels SO JOURNAL OF TEXTURE STUDIES LA English DT Article ID TEXTURE; BEEF AB A series of gelatin gels was produced and scaled to resemble the firmness of typical meat samples used in texture evaluation. The maximum force required to cut through the gel sample was determined with a Warner-Bratzler instrument and a TA. TX2 Model Texture Analyzer. Samples were scaled depending on the shear force required to force a blade through the material. An untrained sensory panel of 30 people, and a trained panel of 12, confirmed the sensory scale using a triangle test and unstructured scales. Untrained panelists were able to distinguish a difference between gels in three tenderness categories (P less than or equal to 0.001) in three consecutive tests. Trained panelists detected significant differences between scaled standards. Results suggest that scaled firmness standards based on gelatin gels provide a good model for meat tenderness sensory training. C1 Michigan State Univ, US FDA, E Lansing, MI 48824 USA. Michigan State Univ, Dept Agr Engn, E Lansing, MI 48824 USA. Michigan State Univ, Dept Food Sci & Human Nutr, E Lansing, MI 48824 USA. RP Steffe, JF (reprint author), Michigan State Univ, US FDA, 209 Farrall Hall, E Lansing, MI 48824 USA. NR 20 TC 0 Z9 0 U1 1 U2 2 PU FOOD NUTRITION PRESS INC PI TRUMBULL PA 6527 MAIN ST, P O BOX 374, TRUMBULL, CT 06611 USA SN 0022-4901 J9 J TEXTURE STUD JI J. Texture Stud. PD DEC PY 2002 VL 33 IS 6 BP 543 EP 558 DI 10.1111/j.1745-4603.2002.tb01366.x PG 16 WC Food Science & Technology SC Food Science & Technology GA 653PW UT WOS:000181446700005 ER PT J AU O'Brien, WD Abbott, JG Stratmeyer, ME Harris, GR Schafer, ME Siddiqi, TA Merritt, CRB Duck, FA Bendick, PJ AF O'Brien, WD Abbott, JG Stratmeyer, ME Harris, GR Schafer, ME Siddiqi, TA Merritt, CRB Duck, FA Bendick, PJ TI Acoustic output upper limits proposition - Should upper limits be retained? SO JOURNAL OF ULTRASOUND IN MEDICINE LA English DT Editorial Material C1 Univ Illinois, Dept Elect & Comp Engn, Bioacoust Res Lab, Urbana, IL 61801 USA. Philips Med Syst Ultrasound, Bothell, WA USA. US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. Son Tech Inc, Ft Washington, PA USA. Univ Cincinnati, Coll Med, Dept Obstet & Gynecol, Cincinnati, OH 45267 USA. Thomas Jefferson Univ Hosp, Philadelphia, PA 19107 USA. Royal United Hosp, Dept Med Phys, Bath BA1 3NG, Avon, England. William Beaumont Hosp, Peripheral Vasc Diagnost Ctr, Royal Oak, MI 48072 USA. RP O'Brien, WD (reprint author), Univ Illinois, Dept Elect & Comp Engn, Bioacoust Res Lab, 405 N Mathews, Urbana, IL 61801 USA. NR 6 TC 14 Z9 14 U1 0 U2 0 PU AMER INST ULTRASOUND MEDICINE PI LAUREL PA SUBSCRIPTION DEPT, 14750 SWEITZER LANE, STE 100, LAUREL, MD 20707-5906 USA SN 0278-4297 J9 J ULTRAS MED JI J. Ultrasound Med. PD DEC PY 2002 VL 21 IS 12 BP 1335 EP 1341 PG 7 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA 623GX UT WOS:000179695900002 PM 12494975 ER PT J AU Liu, T Ye, ZP AF Liu, T Ye, ZP TI Restriction of viral replication by mutation of the influenza virus matrix protein SO JOURNAL OF VIROLOGY LA English DT Article ID RNA-BINDING DOMAINS; M1 PROTEIN; A VIRUS; NUCLEAR EXPORT; INFECTED-CELLS; RIBONUCLEOPROTEINS; MEMBRANE; LOCALIZATION; HEMAGGLUTININ; ASSOCIATION AB The matrix protein (M1) of influenza virus plays an essential role in viral assembly and has a variety of functions, including association with influenza virus ribonucleoprotein (RNP). Our previous studies show that the association of M1 with viral RNA and nucleoprotein not only promotes formation of helical RNP but also is required for export of RNP from the nucleus during viral replication. The RNA-binding domains of M1 have been mapped to two independent regions: a zinc finger motif at amino acid positions 148 to 162 and a series of basic amino acids (RKLKR) at amino acid positions 101 to 105, which is also involved in RNP-binding activity. To further understand the role of the RNP-binding domain of M1 in viral assembly and replication, mutations in the coding sequences of RKLKR and the zinc finger motif of M1 were constructed using a PCR technique and introduced into wild-type influenza virus by reverse genetics. Altering the zinc finger motif of M1 only slightly affected viral growth. Substitution of Arg with Ser at position 101 or 105 of RKLKR did not have a major impact on nuclear export of RNP or viral replication. In contrast, deletion of RKLKR or substitution of Lys with Asn at position 102 or 104 of RKLKR resulted in a lethal mutation. These results indicate that the RKLKR domain of M1 protein plays an important role in viral replication. C1 US FDA, Ctr Biol Evaluat & Res, Off Vaccines Res & Review, Div Viral Prod,Lab Pediat & Resp Viral Dis, Bethesda, MD 20892 USA. RP Ye, ZP (reprint author), US FDA, Lab Pediat & Resp Viral Dis, Div Viral Prod, Bldg 29A,Rm 2B17,8800 Rockville Pike, Bethesda, MD 20982 USA. NR 43 TC 33 Z9 35 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 2002 VL 76 IS 24 BP 13055 EP 13061 DI 10.1128/JVI.76.24.13055-13061.2002 PG 7 WC Virology SC Virology GA 617DE UT WOS:000179344800066 PM 12438632 ER PT J AU Petricoin, EF Hackett, JL Lesko, LJ Puri, RK Gutman, SI Chumakov, K Woodcock, J Feigal, DW Zoon, KC Sistare, FD AF Petricoin, EF Hackett, JL Lesko, LJ Puri, RK Gutman, SI Chumakov, K Woodcock, J Feigal, DW Zoon, KC Sistare, FD TI Medical applications of microarray technologies: a regulatory science perspective SO NATURE GENETICS LA English DT Editorial Material ID DENSITY OLIGONUCLEOTIDE ARRAYS; BENIGN PROSTATIC HYPERPLASIA; GENE-EXPRESSION PATTERNS; CDNA MICROARRAY; DNA MICROARRAY; MOLECULAR CLASSIFICATION; PROTEIN MICROARRAYS; MUTATION DETECTION; COMPLEMENTARY-DNA; CANCER AB The potential medical applications of microarrays have generated much excitement, and some skepticism, within the biomedical community. Some researchers have suggested that within the decade microarrays will be routinely used in the selection, assessment, and quality control of the best drugs for pharmaceutical development, as well as for disease diagnosis and for monitoring desired and adverse outcomes of therapeutic interventions. Realizing this potential will be a challenge for the whole scientific community, as breakthroughs that show great promise at the bench often fail to meet the requirements of clinicians and regulatory scientists. The development of a cooperative framework among regulators, product sponsors, and technology experts will be essential for realizing the revolutionary promise that microarrays hold for drug development, regulatory science, medical practice and public health. C1 US FDA, Div Therapeut Prod, Off Therapeut Res & Review, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. Ctr Devices & Radiol Hlth, Div Clin Lab Devices, Off Device Evaluat, Rockville, MD 20850 USA. US FDA, Off Clin Pharmacol & Biopharmaceut, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. US FDA, Div Cell & Gene Therapy, Off Therapeut Res & Review, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. US FDA, Div Viral Prod, Off Vaccines Res & Review, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. US FDA, Off Director, Ctr Drug Evaluat & Res, Rockville, MD 20852 USA. US FDA, Off Director, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. US FDA, Off Director, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. US FDA, Div Appl Pharmacol Res, Off Testing & Res, Ctr Drug Evaluat & Res, Laurel, MD 20708 USA. RP Petricoin, EF (reprint author), US FDA, Div Therapeut Prod, Off Therapeut Res & Review, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. NR 65 TC 149 Z9 153 U1 1 U2 11 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD DEC PY 2002 VL 32 SU S BP 474 EP 479 DI 10.1038/ng1029 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 624CN UT WOS:000179742900006 PM 12454641 ER PT J AU Hurrell, R Bothwell, T Cook, JD Dary, O Davidsson, L Fairweather-Tait, S Hallberg, L Lynch, S Rosado, J Walter, T Whittaker, P AF Hurrell, R Bothwell, T Cook, JD Dary, O Davidsson, L Fairweather-Tait, S Hallberg, L Lynch, S Rosado, J Walter, T Whittaker, P TI The usefulness of elemental iron for cereal flour fortification: A SUSTAIN task force report SO NUTRITION REVIEWS LA English DT Review DE elemental iron; iron bioavailability; cereal fortification; wheat flour fortification ID DEFICIENCY ANEMIA; INFANT CEREALS; CARBONYL IRON; NUTRITIONAL-ANEMIA; BIOAVAILABILITY; ABSORPTION; FOODS; PRODUCTIVITY; INDONESIA; PREGNANCY AB Fortification of cereal flours may be a useful public health strategy to combat iron deficiency. Cereal flours that are used shortly after production (e.g., baking flour) can be fortified with soluble iron compounds, such as ferrous sulfate, whereas the majority of flours stored for longer periods is usually fortified with elemental iron powders to avoid unacceptable sensory changes. Elemental iron powders are less well absorbed than soluble iron compounds and they vary widely in their absorption depending on manufacturing method and physicochemical characteristics. Costs vary with powder type, but elemental iron powders are generally less expensive than ferrous sulfate. This review evaluates the usefulness of the different elemental iron powders based on results from in vitro studies, rat assays, human bioavailability studies, and efficacy studies monitoring iron status in human subjects. It concludes that, at the present time, only electrolytic iron powder can be recommended as an iron fortificant. Because it is only approximately half as well absorbed as ferrous sulfate, it should be added to provide double the amount of iron. C1 Swiss Fed Inst Technol, Zurich, Switzerland. Univ Witwatersrand, Johannesburg, South Africa. Univ Kansas, Med Ctr, Kansas City, KS 66103 USA. MOST, Micronutrient USAID Program, Arlington, VA USA. Inst Food Res, Norwich NR4 7UA, Norfolk, England. Univ Gothenburg, Gothenburg, Sweden. Eastern Virginia Med Sch, Norfolk, VA 23501 USA. Inst Med Sci & Nutr, Mexico City, DF, Mexico. Inst Nutr & Food Technol, Santiago, Chile. US FDA, Washington, DC 20204 USA. RP Hurrell, R (reprint author), Swiss Fed Inst Technol, Zurich, Switzerland. RI Fairweather-Tait, Susan/K-4251-2012 NR 69 TC 60 Z9 62 U1 0 U2 4 PU INT LIFE SCIENCES INST PI LAWRENCE PA 810 EAST 10TH ST SUBSCRIPTION OFFICE, LAWRENCE, KS 66044 USA SN 0029-6643 J9 NUTR REV JI Nutr. Rev. PD DEC PY 2002 VL 60 IS 12 BP 391 EP 406 DI 10.1301/002966402320964061 PG 16 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 631CA UT WOS:000180148500001 PM 12521144 ER PT J AU Jackson, Y Dietz, WH Sanders, C Kolbe, LJ Whyte, JJ Wechsler, H Schneider, BS McNally, LA Charles-Azure, J Vogel-Taylor, M Starke-Reed, P Hubbard, VS Johnson-Taylor, WL Troiano, RP Donato, K Yanovski, S Kuczmarski, RJ Haverkos, L McMurry, K Wykoff, RF Woo, V Noonan, AS Rowe, J McCarty, K Spain, CB AF Jackson, Y Dietz, WH Sanders, C Kolbe, LJ Whyte, JJ Wechsler, H Schneider, BS McNally, LA Charles-Azure, J Vogel-Taylor, M Starke-Reed, P Hubbard, VS Johnson-Taylor, WL Troiano, RP Donato, K Yanovski, S Kuczmarski, RJ Haverkos, L McMurry, K Wykoff, RF Woo, V Noonan, AS Rowe, J McCarty, K Spain, CB TI Summary of the 2000 Surgeon General's listening session: Toward a national action plan on overweight and obesity SO OBESITY RESEARCH LA English DT Article DE schools; worksites; media; family and community; health care ID UNITED-STATES AB Objective: To provide insight into discussions at the Surgeon General's Listening Session, "Toward a National Action Plan on Overweight and Obesity," and to complement The Surgeon General's Call to Action to Prevent and Decrease Overweight and Obesity. Research Methods and Procedures: On December 7 and 8, 2000, representatives from federal, state, academic, and private sectors attended the Surgeon General's Listening Session and were given an opportunity to recommend what to include in a national plan to address overweight and obesity. The public was invited to comment during a corresponding public comment period. The Surgeon General's Listening Session was also broadcast on the Internet, allowing others to view the deliberations live or access the archived files. Significant discussion points from the Listening Session have been reviewed by representatives of the federal agencies and are the basis of this complementary document. Results: Examples of issues, strategies, and barriers to change are discussed within five thematic areas: schools, health care, family and community, worksite, and media. Suggested cooperative or collaborative actions for preventing and decreasing overweight and obesity are described. An annotated list of some programmatic partnerships is included. Discussion: The Surgeon General's Listening Session provided an opportunity for representatives from family and community groups, schools, the media, the health-care environment, and worksites to become partners and to unite around the common goal of preventing and decreasing overweight and obesity. The combination of approaches from these perspectives offers a rich resource of opportunity to combat the public health epidemic of overweight and obesity. C1 NIH, Div Nutr Res Coordinat, DHHS, Bethesda, MD 20892 USA. Adm Aging, US Dept HHS, Washington, DC USA. Ctr Dis Control & Prevent, Div Nutr & Phys Act, DHHS, Atlanta, GA USA. Ctr Dis Control & Prevent, Div Adolescent & Sch Hlth, DHHS, Atlanta, GA USA. Ctr Medicare & Medicaid Serv, Agcy Healthcare Res & Qual, DHHS, Baltimore, MD USA. US FDA, DHHS, Rockville, MD 20857 USA. US Hlth Resources & Serv Adm, DHHS, Rockville, MD 20857 USA. Indian Hlth Serv, US Dept HHS, Rockville, MD USA. NIH, Off Director, DHHS, Bethesda, MD 20892 USA. NCI, NIH, DHHS, Bethesda, MD 20892 USA. NHLBI, NIH, DHHS, Bethesda, MD 20892 USA. NIDDKD, NIH, DHHS, Bethesda, MD 20892 USA. NICHHD, NIH, DHHS, Bethesda, MD 20892 USA. Off Dis Prevent & Hlth Promot, DHHS, Washington, DC USA. Off Surg Gen, DHHS, Washington, DC USA. Off Womens Hlth, DHHS, Washington, DC USA. Presidents Council Phys Fitness & Sports, Off Publ Hlth & Sci, DHHS, Washington, DC USA. RP Johnson-Taylor, WL (reprint author), NIH, Div Nutr Res Coordinat, DHHS, 2 Democracy Plaza,Room 640,6707 Democracy Blvd,MS, Bethesda, MD 20892 USA. OI Troiano, Richard/0000-0002-6807-989X NR 12 TC 22 Z9 22 U1 0 U2 0 PU NORTH AMER ASSOC STUDY OBESITY PI SILVER SPRING PA 8630 FENTON ST, SUITE 918, SILVER SPRING, MD 20910 USA SN 1071-7323 J9 OBES RES JI Obes. Res. PD DEC PY 2002 VL 10 IS 12 BP 1299 EP 1305 DI 10.1038/oby.2002.176 PG 7 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 625MY UT WOS:000179821300014 PM 12490675 ER PT J AU Pool, V Braun, MM Kelso, JM Mootrey, G Chen, RT Yunginger, JW Jacobson, RM Gargiullo, PM AF Pool, V Braun, MM Kelso, JM Mootrey, G Chen, RT Yunginger, JW Jacobson, RM Gargiullo, PM CA VAERS Team TI Prevalence of anti-gelatin IgE antibodies in people with anaphylaxis after measles-mumps-rubella vaccine in the United States SO PEDIATRICS LA English DT Article DE anaphylaxis; gelatin; measles-mumps-rubella vaccine; VAERS; vaccine adverse reactions ID IMMEDIATE-TYPE REACTIONS; REPORTING-SYSTEM VAERS; ADVERSE EVENTS; VARICELLA VACCINE; NEOMYCIN ALLERGY; EGG ALLERGY; CHILDREN; IMMUNIZATION; DIPHTHERIA; JAPAN AB Objective. Anaphylaxis after immunization, although rare, is serious and potentially life-threatening. Understanding risk factors for this reaction is therefore important. Gelatin is added to many vaccines as a heat stabilizer. Japanese researchers have demonstrated a strong association between immediate hypersensitivity reactions to measles, mumps, rubella, varicella, and Japanese encephalitis immunizations and subsequent detection of anti-gelatin immunoglobulin E (IgE) antibodies. They suggested that previous receipt by these patients of diphtheria-tetanus-acellular pertussis vaccines with trace amounts of gelatin was responsible for the sensitization. We aimed to assess whether a similar association exists for vaccinees in the United States who reported anaphylaxis after receipt of measles-mumps-rubella (MMR) or measles vaccines and to review recent trends in reporting of hypersensitivity reactions. Methods. We conducted a retrospective case-control study. Cases of anaphylaxis that met a predefined case definition were identified from the US Vaccine Adverse Event Reporting System (VAERS). Mayo Clinic patients who received MMR vaccine uneventfully served as controls. The study subjects were interviewed to obtain the history of allergies. Sera from study subjects and their matched controls were tested for IgE antibodies to gelatin, whole egg, and vaccine viral antigens using solid-phase radioimmunoassay. Data from the Biologics Surveillance System on annual numbers of doses of MMR and varicella vaccines distributed in the United States were used to evaluate possible changes in reporting of selected allergic adverse events. Results. Fifty-seven study subjects were recruited into the study and interviewed. Of these, 22 provided serum samples for IgE testing. Twenty-seven subjects served as a comparison group and provided a sample for IgE testing; 21 of these completed an allergy history questionnaire. Self-reported history of food allergies was present more frequently in the interviewed study subjects than in the controls, whereas the proportions of people with other characteristics were similar in both groups. None of the interviewed people had a history of food allergy to gelatin. The level of anti-gelatin IgE antibodies was significantly higher among study subjects than among controls, whereas the levels of IgE antibodies against egg and all 3 viral antigens did not differ significantly. Of 22 study subjects, 6 (27%) tested positive for anti-gelatin IgE, whereas none of the 27 controls did. The rate of anaphylactic reactions reported to VAERS after measles virus-containing immunization in the United States between 1991 and 1997 is 1.8 per 1 million doses distributed. No substantial increase in the number of reported allergic events after frequently used gelatin containing MMR and varicella vaccines could be observed during the first 4 years (1997-2000) since the introduction of diphtheria-tetanus-acellular pertussis vaccines for use in infancy. Conclusion. Anaphylactic reactions to MMR in the United States are rare. The reporting rate has the same order of magnitude as estimates from other countries. Almost one fourth of patients with reported anaphylaxis after MMR seem to have hypersensitivity to gelatin in the vaccine. They may be at higher risk of developing anaphylaxis to subsequent doses of other gelatin-containing vaccines. These people should seek an allergy evaluation before such immunization. C1 CDCP, Epidemiol & Surveillance Div, Natl Immunizat Program, Atlanta, GA 30333 USA. US FDA, Div Epidemiol, Off Biostat & Epidemiol, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. USN, Dept Internal Med, Div Allergy, Med Ctr, San Diego, CA 92152 USA. Mayo Clin & Mayo Fdn, Allerg Dis Res Lab, Rochester, MN 55905 USA. Mayo Clin & Mayo Fdn, Mayo Vaccine Res Grp, Rochester, MN 55905 USA. CDCP, Div Canc Prevent & Control, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA USA. RP Pool, V (reprint author), CDCP, Vaccine Safety & Dev Activ, Natl Immunizat Program, Mail Stop E-61,1600 Clifton Rd, Atlanta, GA 30333 USA. NR 30 TC 56 Z9 59 U1 0 U2 2 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD DEC PY 2002 VL 110 IS 6 AR e71 DI 10.1542/peds.110.6.e71 PG 9 WC Pediatrics SC Pediatrics GA 620TU UT WOS:000179549200006 PM 12456938 ER PT J AU Dhawan, S AF Dhawan, S TI Design and construction of novel molecular conjugates for signal amplification (I): conjugation of multiple horseradish peroxidase molecules to immunoglobulin via primary amines on lysine peptide chains SO PEPTIDES LA English DT Article DE peptide; lysine; signal amplification; enzyme conjugates ID VIRUS; IMMUNOASSAY; EPITOPES; ELISA AB Immunoconjugates are widely used for indirect detection of analytes (such as antibodies or antigens) in a variety of immunoassays. However, the availability of functional groups such as primary amines or free sulfhydryls in an immunoglobulin molecule is the limiting factor for optimal conjugation and, therefore, determines the sensitivity of an assay. In the present study, an N-terminal bromoacetylated 20 amino acid peptide containing 20 lysine residues was conjugated to N-succinimidyl-S-acetylthioacetate (SATA)-modified IgG or free sulfhydryl groups on 2-mercaptoethylamine (2-MEA)-reduced IgG molecules via a thioether (S-CH(2)CONH) linkage to introduce multiple reactive primary amines per IgG. These primary amines were then covalently coupled with maleimide-activated horseradish peroxidase (HRP). The poly-HRP-antibody conjugates thus generated demonstrated greater than 15-fold signal amplification upon reaction with orthophenyldiamine substrate. The poly-HRP-antibody conjugates efficiently detected human immunodeficiency virus (HIV)-1 antibodies in plasma specimens with significantly higher sensitivity than conventionally prepared HRP-antibody conjugates in an HIV-1 solid-phase enzyme immunoassay and Western blot analysis. The signal amplification techniques reported here could have the potential for development of highly sensitive immunodiagnostic assay systems. (C) 2002 Elsevier Science Inc. All rights reserved. C1 US FDA, Mol Virol Lab, Immunopathogenesis Sect, Div Emerging & Transfus Transmitted Dis,Ctr Biol, Rockville, MD 20852 USA. RP Dhawan, S (reprint author), US FDA, Mol Virol Lab, Immunopathogenesis Sect, Div Emerging & Transfus Transmitted Dis,Ctr Biol, 1401 Rockville Pike,HFM-315, Rockville, MD 20852 USA. EM dhawan@cber.fda.gov NR 23 TC 15 Z9 17 U1 5 U2 15 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-9781 J9 PEPTIDES JI Peptides PD DEC PY 2002 VL 23 IS 12 BP 2091 EP 2098 AR PII S0196-9781(02)00250-4 DI 10.1016/S0196-9781(02)00250-4 PG 8 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA 641WJ UT WOS:000180769800003 PM 12535687 ER PT J AU Dhawan, S AF Dhawan, S TI Design and construction of novel molecular conjugates for signal amplification (II): use of multivalent polystyrene microparticles and lysine peptide chains to generate immunoglobulinhorseradish peroxidase conjugates SO PEPTIDES LA English DT Article DE peptide; microparticle; signal amplification; enzyme conjugates; diagnostic assays ID LINKED-IMMUNOSORBENT-ASSAY; LATEX IMMUNOASSAY; ANTIBODIES; SYSTEM; ELISA; IGM AB Spherical polystyrene microparticles expressing a large number of highly reactive functional groups were chemically engineered to generate antibody-enzyme conjugates as novel signal amplification systems. Chemically modified goat anti-human IgG and horseradish peroxidase (HRP) were combined in a 1:5 ratio and attached to 0.44 mum streptavidin microparticles or N-succinimidyl-S-acetylthioacetate (SATA)-activated 0.29 mum amino microparticles with highly reactive free sulfhydryl groups on their surface. The numbers of HRP molecules/microparticle were further increased by coupling HRP to primary amines on N-terminal biotinylated or bromoacetylated polypeptides containing 20 lysine residues prior to conjugation with streptavidin or sulfhydryl groups-containing microparticles. The antibody-poly-HRP immunoconjugates contained an estimated number of 10(5) HRP/streptavidin microparticle and 10(6) HRP/amino microparticle, respectively. These microparticle immunoconjugates efficiently bound to plasma anti-HIV-1 antibodies that had been captured by HIV antigens on 5 mum carboxyl magnetic microparticles and, upon reaction with orthophenyldiamine substrate, produced a detection signal with 5-8 times more sensitivity as compared to conventional HRP-conjugated goat anti-human IgG. The signal amplification technique by microparticle immunoconjugates may provide potentially novel tools for the development of highly sensitive diagnostic systems. (C) 2002 Elsevier Science Inc. All rights reserved. C1 US FDA, Mol Virol Lab, Immunopathogenesis Sect, Div Emerging & Transfus Transmitted Dis,Ctr Biol, Rockville, MD 20852 USA. RP Dhawan, S (reprint author), US FDA, Mol Virol Lab, Immunopathogenesis Sect, Div Emerging & Transfus Transmitted Dis,Ctr Biol, 1401 Rockville Pike,HFM-315, Rockville, MD 20852 USA. NR 17 TC 11 Z9 12 U1 1 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-9781 J9 PEPTIDES JI Peptides PD DEC PY 2002 VL 23 IS 12 BP 2099 EP 2110 AR PII S0196-9781(02)00253-X DI 10.1016/S0196-9781(02)00253-X PG 12 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA 641WJ UT WOS:000180769800004 PM 12535688 ER PT J AU Wise, RP Braun, MM Seward, JF Mootrey, GT Shields, KE Salive, ME Krause, PR AF Wise, RP Braun, MM Seward, JF Mootrey, GT Shields, KE Salive, ME Krause, PR TI Pharmacoepidemiologic implications of erroneous varicella vaccinations in pregnancy through confusion with Varicella zoster immune globulin SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Article DE varicella vaccine; pregnancy registry; safety surveillance; medical error; product confusion ID INFECTION AB A series of case reports to the varicella vaccine Pregnancy Registry described inadvertent administrations during pregnancy of this live virus product instead of the intended Varicella zoster immune globulin. Cases continued to accrue despite an early publication about the pattern. The persistent problem warrants specific educational efforts to prevent further repetitions. It also has more general implications for medical product safety surveillance. First, this problem's original detection depended on the Pregnancy Registry's open-ended collection of information about pregnancy exposures. It could have escaped recognition through surveillance limited to pre specified potential risks. This need for unrestricted reporting and human vigilance to sift through case stories has particular relevance for efforts to re-think methods to monitor gestational drug exposures. In addition, the problem's persistence despite initial publicity suggests that diligent surveillance may require continued follow-up of identified safety issues. Periodic reassessments of selected preventable problems might strengthen efforts to minimize product risks. Copyright (C) 2002 John Wiley Sons, Ltd. C1 US FDA, Div Epidemiol, Off Biostat & Epidemiol, CBER, Rockville, MD 20852 USA. US FDA, Lab DNA Viruses, Div Viral Prod, Off Vaccines Res & Review,CBER, Rockville, MD 20852 USA. Merck Res Labs, Worldwide Prod Safety & Epidemiol, W Point, PA USA. CDC, Vaccine Safety & Div Act, Div Epidemiol & Surveillance, NIP, Atlanta, GA 30333 USA. CDC, Child Vaccine Preventable Dis Branch, Div Epidemiol & Surveillance, Natl Immunizat Program, Atlanta, GA 30333 USA. RP Wise, RP (reprint author), US FDA, Div Epidemiol, Off Biostat & Epidemiol, CBER, HFM-225,1401 Rockville Pike, Rockville, MD 20852 USA. OI Krause, Philip/0000-0002-1045-7536 NR 15 TC 5 Z9 5 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 DEC PY 2002 VL 11 IS 8 BP 651 EP 654 DI 10.1002/pds.749 PG 4 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 627LD UT WOS:000179933900005 PM 12512240 ER PT J AU Whittaker, P Ali, SF Imam, SZ Dunkel, VC AF Whittaker, P Ali, SF Imam, SZ Dunkel, VC TI Acute toxicity of carbonyl iron and sodium iron EDTA compared with ferrous sulfate in young rats SO REGULATORY TOXICOLOGY AND PHARMACOLOGY LA English DT Article DE iron; carbonyl iron; NaFeEDTA; acute iron toxicity; rats ID EXPOSURE SURVEILLANCE SYSTEM; FOOD FORTIFICATION; BIOAVAILABILITY AB According to the American Association of Poison Control Centers, exposures to excessive doses of iron supplements still occur in children less than 6 years of age. Since 1998, there has been one death among U.S. children in this age group. Exposures, including adverse events, to iron supplements and iron-containing vitamins for the years 1999 and 2000 were 23,215 and 24,249, respectively. To reduce the potential seriousness of such exposures, carbonyl iron (Fe-o) has been suggested as a possible replacement for ferrous sulfate (FeSO4). Carbonyl Fe is a unique form of elemental iron because of its small particle size. It is highly bioavailable when used to correct iron deficiency anemia. There is also current interest in using sodium iron(III) ethylenediaminetetraacetate (NaFeEDTA) for food fortification. In this study both NaFeEDTA and carbonyl Fe were compared with FeSO4, the most common form of iron for dietary supplements, to obtain information relevant to the acute toxicological profile in young rats. With FeSO4 and NaFeEDTA, total liver nonheme iron increased with increasing dose, but the response was approximately 50% lower with NaFeEDTA compared with FeSO4. Serum iron peaked at approximately 0.5 to 1 h for both FeSO4 and carbonyl Fe, while NaFeEDTA was elevated up to 4 h. FeSO4 had an LD50 of 1.1 g Fe/kg and was approximately 45 times more toxic than carbonyl Fe, which had an LD50 greater then 50 g Fe/kg. NaFeEDTA had an LD50 of 1.3 g Fe/kg and, when compared with FeSO4, had approximately the same level of toxicity. C1 US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Whittaker, P (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. NR 23 TC 20 Z9 21 U1 0 U2 8 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0273-2300 J9 REGUL TOXICOL PHARM JI Regul. Toxicol. Pharmacol. PD DEC PY 2002 VL 36 IS 3 BP 280 EP 286 DI 10.1006/rtph.2002.1577 PG 7 WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology SC Legal Medicine; Pharmacology & Pharmacy; Toxicology GA 622BR UT WOS:000179627100006 PM 12473412 ER PT J AU Adams, J Bittner, P Buttar, HS Chambers, CD Collins, TFX Daston, GP Filkins, K Flynn, TJ Graham, JM Jones, KL Kimmel, C Lammer, E Librizzi, R Mitala, J Polifka, JE AF Adams, J Bittner, P Buttar, HS Chambers, CD Collins, TFX Daston, GP Filkins, K Flynn, TJ Graham, JM Jones, KL Kimmel, C Lammer, E Librizzi, R Mitala, J Polifka, JE TI Statement of the public affairs committee of the teratology society on the fetal alcohol syndrome SO TERATOLOGY LA English DT Article ID PRENATAL EXPOSURE; BIRTH-DEFECTS; WESTERN-CAPE; CHILDREN; RECOGNITION; WOMEN; DEFICITS; ETHANOL; FAS C1 Univ Massachusetts, Dept Psychol, Boston, MA 02125 USA. US Consumer Prod Safety Commiss, Bethesda, MD 20814 USA. Therapeut Prod Directorate, Ottawa, ON, Canada. Univ Calif San Diego, Sch Med, Dept Pediat, San Diego, CA 92103 USA. US FDA, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. Procter & Gamble Co, Miami Valley Labs, Cincinnati, OH 45245 USA. Univ Calif Los Angeles, Sch Med, Dept Obstet & Gynecol, Los Angeles, CA 90095 USA. Cedars Sinai Med Ctr, Los Angeles, CA 90095 USA. Univ Calif San Diego, Sch Med, Dept Pediat, La Jolla, CA 92093 USA. US EPA, NCEA, ORD, Washington, DC 20460 USA. Childrens Hosp, Div Med Genet, Oakland, CA 94609 USA. Thomas Jefferson Univ, Sch Med, Dept Obstet & Gynecol, Philadelphia, PA 19107 USA. Johnson & Johnson LLC, Pharmaceut Res & Dev, Raritan, NJ 08837 USA. Univ Washington, Sch Med, TERIS, Dept Pediat, Seattle, WA 98105 USA. RP Chambers, CD (reprint author), Univ Calif San Diego, Med Ctr, Dept Pediat, Div Dysmorphol Teratol, 8446,200 W Arbor Dr, San Diego, CA 92103 USA. OI Flynn, Thomas/0000-0002-7248-0643 NR 35 TC 12 Z9 12 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0040-3709 J9 TERATOLOGY JI Teratology PD DEC PY 2002 VL 66 IS 6 BP 344 EP 347 DI 10.1002/tera.10118 PG 4 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 630EB UT WOS:000180093600012 PM 12486768 ER PT J AU Stirling, D Junod, S AF Stirling, D Junod, S TI Arnold J. Lehman - Profiles in toxicology SO TOXICOLOGICAL SCIENCES LA English DT Editorial Material C1 Intertox Inc, Seattle, WA 98121 USA. US FDA, Hist Off, Rockville, MD 20857 USA. RP Stirling, D (reprint author), Intertox Inc, 2819 Elliott Ave,Suite 201, Seattle, WA 98121 USA. NR 8 TC 1 Z9 1 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD DEC PY 2002 VL 70 IS 2 BP 159 EP 160 DI 10.1093/toxsci/70.2.159 PG 2 WC Toxicology SC Toxicology GA 621XB UT WOS:000179615300002 PM 12441360 ER PT J AU Petricoin, EF Liotta, LA AF Petricoin, EF Liotta, LA TI Proteomic analysis at the bedside: early detection of cancer SO TRENDS IN BIOTECHNOLOGY LA English DT Review ID LASER CAPTURE MICRODISSECTION; IMMOBILIZED PH GRADIENTS; OVARIAN-CANCER; 2-DIMENSIONAL ELECTROPHORESIS; PROTEIN BIOCHIP; PROSTATE; EXPRESSION; TECHNOLOGY; DISCOVERY; TISSUE AB Proteomic technologies promise to accelerate rapidly a new era in molecular medicine, especially in the detection and discovery of disease-related biomarkers. These technologies have no bigger impact than in the field of human cancer research. Beyond lifestyle-associated prevention strategies, early detection of cancer has the most profound impact on the ultimate course of the disease: the earlier the cancer is detected, the better the prognosis. Today, new proteomic technologies are being used to discover new diagnostic and prognostic biomarkers for the early detection and treatment of cancer that will have important implications at the bedside. C1 US FDA, Ctr Biol Evaluat & Res, Div Therapeut Prot, FDA NCI Clin Prote Program, Bethesda, MD 20892 USA. NCI, CCr, Pathol Lab, FDA NCI Clin Prote Program,NIH, Bethesda, MD 20892 USA. RP Petricoin, EF (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Therapeut Prot, FDA NCI Clin Prote Program, Bethesda, MD 20892 USA. NR 40 TC 5 Z9 9 U1 0 U2 2 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0167-7799 J9 TRENDS BIOTECHNOL JI Trends Biotechnol. PD DEC PY 2002 VL 20 IS 12 SU S BP S30 EP S34 AR PII S0167-7799(02)02092-9 DI 10.1016/S1471-1931(02)00204-5 PG 5 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 617HT UT WOS:000179356800007 PM 12570157 ER PT J AU Santos, N Volotao, EM Soares, CC Carolina, M Albuquerque, M da Silva, FM Chizhikov, V Hoshino, Y AF Santos, N Volotao, EM Soares, CC Carolina, M Albuquerque, M da Silva, FM Chizhikov, V Hoshino, Y TI VP7 gene polymorphism of serotype G9 rotavirus strains and its impact on G genotype determination by PCR SO VIRUS RESEARCH LA English DT Article DE rotavirus; PCR G genotyping; VP7 gene polymorphism; gastroenteritis ID POLYMERASE CHAIN-REACTION; GROUP-A ROTAVIRUS; MOLECULAR CHARACTERIZATION; REVERSE TRANSCRIPTION; ACUTE GASTROENTERITIS; VACCINE DEVELOPMENT; BRAZILIAN CHILDREN; UNITED-STATES; NUCLEIC-ACID; IDENTIFICATION AB Rotaviruses are the single most important etiologic agents of severe diarrhea of infants and young children worldwide. Surveillance of rotavirus serotypes/genotypes (both VP7[G] and VP4[P]) is in progress globally in which polymerase chain reaction (PCR) has been the assay of choice. We investigated polymorphism of the VP7 gene of serotype G9 rotavirus strains and its impact on the determination of VP7 gene genotype by PCR assay. By VP7 gene sequence analysis, we and others have previously shown that the G9 rotavirus strains belong to one of three VP7 gene lineages. By PCR assay using three different sets of commonly used primers specific for G1-4, 8 and 9, 23 Brazilian G9 strains and 5 well-characterized prototype G9 strains which collectively represented all three VP7 gene lineages were typed as: (i) G3; (ii) G4; (iii) G9; (iv) G3 and G9; or (v) G9 and G4 depending on a primer pool employed. This phenomenon appeared to be due to: (i) a VP7 gene lineage-specific polymorphism, more specifically mutation(s) in the primer binding region of the VP7 gene of G9 strain; and (ii) the magnitude of difference in nucleotide homology at respective primer binding site between homotypic (G9) and heterotypic (G3 or G4) primers present in a primer pool employed. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Univ Fed Rio de Janeiro, Inst Microbiol, Dept Virol, Ilha Fdn, BR-21941590 Rio De Janeiro, Brazil. US FDA, Ctr Biol Evaluat & Res, Kensington, MD 20895 USA. NIH, Infect Dis Lab, Bethesda, MD 20892 USA. RP Santos, N (reprint author), Univ Fed Rio de Janeiro, Inst Microbiol, Dept Virol, Ilha Fdn, Cidade Univ,CCS Bl 1, BR-21941590 Rio De Janeiro, Brazil. RI Santos, Norma/H-6986-2015 OI Santos, Norma/0000-0002-5123-9172 NR 61 TC 12 Z9 12 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-1702 J9 VIRUS RES JI Virus Res. PD DEC PY 2002 VL 90 IS 1-2 BP 1 EP 14 AR PII S0168-1702(02)00106-5 DI 10.1016/S0168-1702(02)00106-5 PG 14 WC Virology SC Virology GA 629QL UT WOS:000180060300001 PM 12457958 ER PT J AU Bolger, PM Schwetz, BA AF Bolger, PM Schwetz, BA TI Mercury and health SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 US FDA, College Pk, MD 20740 USA. RP Bolger, PM (reprint author), US FDA, College Pk, MD 20740 USA. NR 0 TC 69 Z9 70 U1 0 U2 6 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 NOV 28 PY 2002 VL 347 IS 22 BP 1735 EP 1736 DI 10.1056/NEJMp020139 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 619GU UT WOS:000179468600001 PM 12456847 ER PT J AU Schmitt, TC AF Schmitt, TC TI Determination of chloral hydrate and its metabolites in blood plasma by capillary gas chromatography with electron capture detection SO JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES LA English DT Article DE chloral hydrate ID MICE; MUTAGENICITY; SINGLE; MOUSE AB A sensitive, accurate, and reliable method is described for the quantitative determination of chloral hydrate (CH) and its metabolites in blood plasma of mice and rats. Metabolites of CH include trichloroacetic acid (TCA), trichloroethanol (TCE), and trichloroethanol glucuronide (TCE-Glu). This new method uses capillary gas chromatography with electron-capture detection (GC/ECD). Procedures for improving sample stability and quality assurance are also described that were not mentioned in previous literature. Rat or mouse plasma (50 mul) is acidified (or treated enzymatically for TCE-Glu determination) and extracted with peroxide free methyl t-butyl ether. Distilled diazomethane (CH2N2) is added to derivatize TCA to its methyl ester. Detection limits were estimated at 0.2 mug/ml for CH and TCE, and 0.1 mug/ml for TCA. Detector response to TCA and TCE were shown to be linear in the range of 3.125-200 mug/ml (r greater than or equal to 0.9996). For CH, the response fits a second-order equation in this same range (r = 0.99994). (C) 2002 Elsevier Science B.V. All rights reserved. C1 US FDA, Natl Ctr Toxicol Res, Dept Hlth & Human Serv, Div Chem, Jefferson, AR 72079 USA. RP Schmitt, TC (reprint author), US FDA, Natl Ctr Toxicol Res, Dept Hlth & Human Serv, Div Chem, HFT-230,3900 NCTR Rd, Jefferson, AR 72079 USA. NR 18 TC 7 Z9 8 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1570-0232 J9 J CHROMATOGR B JI J. Chromatogr. B PD NOV 25 PY 2002 VL 780 IS 2 BP 217 EP 224 AR PII S1570-0232(02)00371-9 DI 10.1016/S1570-0232(02)00371-9 PG 8 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 613KT UT WOS:000179132000002 PM 12401346 ER PT J AU Fu, TT Abbott, UR Hatzos, C AF Fu, TT Abbott, UR Hatzos, C TI Digestibility of food allergens and nonallergenic proteins in simulated gastric fluid and simulated intestinal fluid - A comparative study SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE digestive stability; food allergens; simulated gastric fluid; simulated intestinal fluid; allergenicity assessment ID SAFETY ASSESSMENT; IN-VITRO; EXPRESSED PROTEIN; ATOPIC-DERMATITIS; SOYBEAN GLYCININ; POTATO-TUBERS; IDENTIFICATION; PEANUT; STABILITY; TOMATOES AB Information on the comparative digestibility of food allergens and nonallergenic proteins is crucial when stability to digestion is to be used as a criterion to assess the allergenic potential of novel proteins. In this work, we compared the digestive stability of a number of food allergens and proteins of unproven allergenicity and examined whether allergens possess a higher stability than nonallergenic proteins of similar cellular functions, and whether there is a correlation between protein digestibility and allergenicity. The stability of groups of storage proteins,. plant lectins, contractile proteins, and enzymes, both allergens and proteins with unproven allergenicity, in a standard simulated gastric fluid and a standard simulated intestinal fluid was measured. Food allergens were not necessarily more resistant to digestion than nonallergenic proteins. There was not a clear relationship between digestibility measured in vitro and protein allergenicity. C1 US FDA, Summit Argo, IL 60501 USA. IIT, Natl Ctr Food Safety & Technol, Summit Argo, IL 60501 USA. RP Fu, TT (reprint author), US FDA, Summit Argo, IL 60501 USA. EM tfu@cfsan.fda.gov FU FDA HHS [FD000431] NR 39 TC 209 Z9 218 U1 6 U2 61 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0021-8561 EI 1520-5118 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD NOV 20 PY 2002 VL 50 IS 24 BP 7154 EP 7160 DI 10.1021/jf020599h PG 7 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 615UU UT WOS:000179266000036 PM 12428975 ER PT J AU Louch, HA Buczko, ES Woody, MA Venable, RM Vann, WF AF Louch, HA Buczko, ES Woody, MA Venable, RM Vann, WF TI Identification of a binding site for ganglioside on the receptor binding domain of tetanus toxin SO BIOCHEMISTRY LA English DT Article ID NEUROTOXIN TYPE-A; H-C FRAGMENT; CRYSTAL-STRUCTURE; EXPRESSION; RESOLUTION; SEQUENCES; HOMOLOGY; PROTEINS AB The carboxyl-terminal region of the tetanus toxin heavy chain (H-C fragment) binds to di- and trisialylgangliosides on neuronal cell membranes. To determine which amino acids in tetanus toxin are involved in ganglioside binding, homology modeling was performed using recently resolved X-ray crystallographic structures of the tetanus toxin H-c fragment. On the basis of these analyses, two regions in tetanus toxin that are structurally homologous with the binding domains of other sialic acid and galactose-binding proteins were targeted for mutagenesis. Specific amino acids within these regions were altered using site-directed mutagenesis. The amino acid residue tryptophan 1288 was found to be critical for binding of the Hc fragment to ganglioside GT1b. Docking of GD1b within this region of the toxin suggested that histidine 1270 and aspartate 1221 were within hydrogen bonding distance of the ganglioside. These two residues were mutagenized and found also to be important for the binding of the tetanus toxin H-c fragment to ganglioside GT1b. In addition, the H-c fragments mutagenized at these residues have reduced levels of binding to neurites of differentiated PC-12 cells. These studies indicate that the amino acids tryptophan 1288, histidine 1270, and aspartate 1221 are components of the GT1b binding site on the tetanus toxin H-c fragment. C1 US FDA, Lab Bacterial Toxins, Div Bacterial Parasit & Allergen Prod, OVRR,CBER, Bethesda, MD 20892 USA. US FDA, Biophys Lab, Div Bacterial Parasit & Allergen Prod, OVRR,CBER, Bethesda, MD 20892 USA. RP Vann, WF (reprint author), US FDA, Lab Bacterial Toxins, Div Bacterial Parasit & Allergen Prod, OVRR,CBER, 8800 Rockville Pike, Bethesda, MD 20892 USA. NR 28 TC 27 Z9 28 U1 1 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD NOV 19 PY 2002 VL 41 IS 46 BP 13644 EP 13652 DI 10.1021/bi020291j PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 615FY UT WOS:000179236200020 PM 12427026 ER PT J AU Evans, DR Huang, MS Fettinger, JC Williams, TL AF Evans, DR Huang, MS Fettinger, JC Williams, TL TI Synthesis and characterization of diametrically substituted tetra-O-n-butylcalix[4]arene ligands and their chelated complexes of titanium, molybdenum, and palladium SO INORGANIC CHEMISTRY LA English DT Article ID PHOSPHATE DIESTER TRANSESTERIFICATION; NONLINEAR-OPTICAL PROPERTIES; UPPER-RIM; MOLECULAR-STRUCTURE; STRUCTURAL CHARACTERIZATION; FUNCTIONALIZED CALIXARENES; RECOGNITION PROPERTIES; REACTION COORDINATE; ANION RECOGNITION; METAL-COMPLEXES AB The ligation properties of three new upper-rim-substituted calix[4]arene ligands, 5,17-bis(hydroxymethyl)-tetra-n-butoxycalix-[4]arene ((HOCH2)(2)-(n)Bu(4)Clx, 7), 5,17-bis((diphenylphosphinito)methoxy)-tetra-n-butoxycalix[4]arene ((PPh2OCH2)(2)-(n)Bu(4)Clx, 8), and 5,17-bis((diphenylphosphino)methyl)-tetra-n-butoxycalix[4]arene ((PPh2CH2)(2)-(n)Bu(4)Clx, 10) are reported herein. The newly prepared compounds differ from previously reported diametrically substituted calix[4]arene derivatives in that the lower-rim substituent was n-butyl. The presence of this lower-rim substituent did not reduce the inherent crystallinity of these complexes as purification of all materials occurred via simple crystallizations. The key precursor for the syntheses of 8 and 10 was 7, acquisition of which occurred in six steps starting from tetra-tert-butylcalix[4]arene, 1. Calix[4]arene derivatives include, tetra-n-butoxycalix[4]arene ((n)Bu(4)Clx, 3), 5,11,17,23-tetrabromo-tetra-n-butoxycalix[4]arene (Br-4-(n)Bu(4)Clx, 4), 5,17-dibromo-tetra-n-butoxycalix[4]arene (Br-2-(n)Bu(4)Clx, 5), 5,17-bis(formyl)-tetra-n-butoxycalix[4]arene ((CHO)(2)-(n)Bu(4)Clx, 6), and 5,17-bis(chloromethyl)-tetra-n-butoxycalix[4]arene ((CICH2)(2)-(n)Bu(4)Clx, 9), all of which were synthesized using modifications of existing procedures. Characterization of all compounds occurred, when possible, using H-1, C-13, and P-31 NMR, elemental analyses, FAB-MS, ESI-MS, FT-IR, and X-ray crystallography. The solid-state structures of all calix[4]arene intermediates and ligands showed that the annulus adopted the pinched-cone conformation in which the average C(5)C-. . .(17) intraannular separation was 4.5 +/- 0.4 Angstrom. Reaction of 7 with CpTiMe3 yielded the cis-chelate, CpTi(Me)[(OCH2)(2)-(n)Bu(4)Clx] (11), quantitatively. Data obtained using ESI-MS (positive-ion mode) confirmed the monomer formulation showed above, and 1H NMR spectra provided sufficient information to deduce the nature of the Ti coordination sphere. Reaction of 8 with Cis-CI2Pd(NCPh)(2) in refluxing benzene afforded cis-Cl2Pd[(PPh2OCH2)(2)-(n)Bu(4)Clx] (2) in good yields. The monomeric identity of this compound was verified by both X-ray crystallography and positive-ion ESI-MS. The cis-bidentate calix[4]arene ligand did not undergo any noticeable contortion upon chelation of the PdCl2 fragment. Acid-promoted decomposition of 12 occurred in the presence of adventitious HCI and gaseous HCI, and the products of this decomposition were 9 and [mu(2)-ClPd(PPh2OH)(PPh2O)](2). In addition, chelates of 8 that contained Mo(CO)(3)L (L = NCMe (14a), NCEt (14b), and CO (14c)) showed that the mode of coordination was relatively insensitive to the identity of the metal. X-ray crystallography afforded views of the solid-state structures of 14b,c and, like 12, showed that the Mo(CO)3L fragment resided above the pinched-cone of the calix[4]arene. H-1 NMR revealed that C-H/pi interactions existed between L (14a,b) and a phenyl ring of the coordinated phosphinite. Finally, the bis(diphenylphosphine)calix[4]arene ligand (10) readily coordinated the Mo(CO)(3)L species, but the reaction did not go to completion, as evidenced by H-1 NMR, even after a 5 day reaction time. Data suggest that the product is similar to that observed for 12 and 14, but the incomplete reaction complicated attempts to obtain pure material and prohibited definitive assignment of the coordination array. C1 Univ Maryland, Dept Chem & Biochem, College Pk, MD 20742 USA. US FDA, Ctr Food Safety & Nutr, College Pk, MD 20741 USA. RP Evans, DR (reprint author), Univ Maryland, Dept Chem & Biochem, College Pk, MD 20742 USA. EM de44@umail.umd.edu NR 71 TC 22 Z9 22 U1 0 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0020-1669 J9 INORG CHEM JI Inorg. Chem. PD NOV 18 PY 2002 VL 41 IS 23 BP 5986 EP 6000 DI 10.1021/ic020446b PG 15 WC Chemistry, Inorganic & Nuclear SC Chemistry GA 614JE UT WOS:000179184200013 PM 12425624 ER PT J AU Simak, J Holada, K Risitano, AM Zivny, JH Young, NS Vostal, JG AF Simak, J Holada, K Risitano, AM Zivny, JH Young, NS Vostal, JG TI Elevated counts of circulating endothelial membrane microparticles in patients with paroxysmal nocturnal hemoglobinuria. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 US FDA, Ctr Biol Evaluat & Res, Lab Cellular Hematol, Bethesda, MD USA. NHLBI, NIH, Hematol Branch, Bethesda, MD 20892 USA. RI Simak, Jan/C-1153-2011 NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 202 BP 56A EP 57A PN 1 PG 2 WC Hematology SC Hematology GA 614JK UT WOS:000179184700203 ER PT J AU Castilho, L Rios, M Rodrigues, A Pellegrino, J Costa, FF AF Castilho, L Rios, M Rodrigues, A Pellegrino, J Costa, FF TI Occurrence of partial D in polytransfused patients: Implications for transfusion practice. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 UNICAMP, Hemoctr, Campinas, SP, Brazil. US FDA, CBER, DETTD, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 4029 BP 136B EP 137B PN 2 PG 2 WC Hematology SC Hematology GA 614JL UT WOS:000179184800572 ER PT J AU Castilho, L Rios, M Pellegrino, J Saad, STO Costa, FF AF Castilho, L Rios, M Pellegrino, J Saad, STO Costa, FF TI The use of DNA-typing for detection of an alloantibody anti-Do(a) in a polytransfused patient with beta thalassemia. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 UNICAMP, Hemoctr, Campinas, SP, Brazil. US FDA, CBER, DETTD, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 4030 BP 137B EP 137B PN 2 PG 1 WC Hematology SC Hematology GA 614JL UT WOS:000179184800573 ER PT J AU Zivny, JH Graciasova, R Holada, K Simak, J Vostal, J AF Zivny, JH Graciasova, R Holada, K Simak, J Vostal, J TI Cellular prion protein (PrPc) expression in erythroid differentiation. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 US FDA, Ctr Biol Evaluat & Res, Lab Cellular Hematol, Bethesda, MD 20014 USA. Charles Univ, Fac Nat Sci, Dept Zool, Prague, Czech Republic. RI Stopkova, Romana/A-8011-2010; 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 2002 VL 100 IS 11 MA 4135 BP 161B EP 161B PN 2 PG 1 WC Hematology SC Hematology GA 614JL UT WOS:000179184800678 ER PT J AU Zha, HB Raffeld, M Charboneau, L Pittaluga, S Liotta, LA Petricoin, E Kwak, L Jaffe, ES AF Zha, HB Raffeld, M Charboneau, L Pittaluga, S Liotta, LA Petricoin, E Kwak, L Jaffe, ES TI Phosphorylation of Akt and Bad in follicular lymphomas (FL) analyzed by reverse phase protein microarrays. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 NCI, Pathol Lab, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 747 BP 199A EP 199A PN 1 PG 1 WC Hematology SC Hematology GA 614JK UT WOS:000179184700748 ER PT J AU Carmel, R Melnyk, S James, SJ AF Carmel, R Melnyk, S James, SJ TI Abnormalities of homocysteine metabolism associated with neurologic dysfunction due to cobalamin deficiency. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 New York Methodist Hosp, Dept Med, Brooklyn, NY USA. Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 850 BP 226A EP 226A PN 1 PG 1 WC Hematology SC Hematology GA 614JK UT WOS:000179184700851 ER PT J AU Hegde, U White, T Stetler-Stevenson, M Marti, G Janik, J Pittaluga, S Kingma, D Steinberg, S Cheson, B Jaffe, ES Wilson, WH AF Hegde, U White, T Stetler-Stevenson, M Marti, G Janik, J Pittaluga, S Kingma, D Steinberg, S Cheson, B Jaffe, ES Wilson, WH TI Phase I study of combination rituximab (CD20) and apolizumab (Hu1D10) monoclonal antibody therapy in previously treated B-cell lymphoma and chronic lymphocytic leukemia. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 NCI, Ctr Canc Res, Bethesda, MD 20892 USA. US FDA, Bethesda, MD 20014 USA. Georgetown Univ Hosp, Div Hematol Oncol, Washington, DC 20007 USA. NR 0 TC 6 Z9 6 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 2002 VL 100 IS 11 MA 1389 BP 358A EP 358A PN 1 PG 1 WC Hematology SC Hematology GA 614JK UT WOS:000179184701390 ER PT J AU Rachel, JM Zucker, ML Plapp, FV Fox, CM Marti, GE Abbasi, F Menitove, JE AF Rachel, JM Zucker, ML Plapp, FV Fox, CM Marti, GE Abbasi, F Menitove, JE TI B cell monoclonal lymphocytosis in blood donors. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 St Lukes Hosp, Kansas City, MO USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. Community Blood Ctr Greater Kansas City, Kansas City, MO USA. NR 0 TC 6 Z9 6 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 2002 VL 100 IS 11 MA 2321 BP 590A EP 590A PN 1 PG 1 WC Hematology SC Hematology GA 614JK UT WOS:000179184702323 ER PT J AU Kay, NE Bone, ND Pittner, BT Jelinek, DF Leland, P Frank, DA Battle, TE Puri, RK AF Kay, NE Bone, ND Pittner, BT Jelinek, DF Leland, P Frank, DA Battle, TE Puri, RK TI Plasma membrane IL-4 receptors can be targeted to eliminate B-chronic lymphocytic leukemia B cells. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PA SP Amer Soc Hematol C1 Mayo Clin, Div Hematol, Rochester, MN USA. Dana Farber Canc Inst, Boston, MA 02115 USA. CBER, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 2324 BP 591A EP 591A PN 1 PG 1 WC Hematology SC Hematology GA 614JK UT WOS:000179184702326 ER PT J AU von Kries, R Toschke, AM Koletzko, B Slikker, W AF von Kries, R Toschke, AM Koletzko, B Slikker, W TI Maternal smoking during pregnancy and childhood obesity SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE child; obesity; pregnancy; risk factors; smoking ID BODY-MASS INDEX; SELF-REPORTED SMOKING; PRESCHOOL-CHILDREN; PHYSICAL-ACTIVITY; CIGARETTE-SMOKING; YOUNG-CHILDREN; OVERWEIGHT; PREVALENCE; EXPOSURE; WEIGHT AB A recent cohort study suggested that maternal smoking during pregnancy might be a risk factor for childhood obesity. Data from the obligatory school entry health examination in six Bavarian (Germany) public health offices in 1999-2000 were used to assess the relation between maternal smoking during pregnancy and childhood obesity (n = 6,483 German children aged 5.00-6.99 years). A body mass index greater than the 90th percentile was defined as overweight, and a body mass index greater than the 97th percentile was defined as obesity. The main exposure was maternal smoking during pregnancy. The prevalences of overweight and obesity, expressed as percentages, increased in the following order: never smoked (overweight: 8.1, 95% confidence interval (CI): 7.2, 9.0; obesity: 2.2, 95% CI: 1.7, 2.7); less than 10 cigarettes daily (overweight: 14.1, 95% CI: 11.1, 17.7; obesity: 5.7, 95% CI: 3.7, 8.2); and 10 or more cigarettes daily (overweight: 17.0, 95% CI: 10.1, 26.2; obesity: 8.5, 95% CI: 3.7, 16.1). The adjusted odds ratios for maternal smoking during pregnancy were 1.43 (95% CI: 1.07, 1.90) for overweight and 2.06 (95% CI: 1.31, 3.23) for obesity. A dose-dependent association between overweight/obesity and maternal smoking during pregnancy was observed that could not be explained by a wide range of confounders, suggesting that intrauterine exposure to inhaled smoke products rather than lifestyle factors associated with maternal smoking accounts for this finding. C1 Univ Munich, Inst Social Pediat & Adolescent Med, Dept Pediat Epidemiol, D-81377 Munich, Germany. Univ Munich, Dr von Haunersch Kinderspital, Munich, Germany. US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. RP von Kries, R (reprint author), Univ Munich, Inst Social Pediat & Adolescent Med, Dept Pediat Epidemiol, Heiglhofstr 63, D-81377 Munich, Germany. EM ag.epi@LRZ.uni-muenchen.de RI Toschke, Andre/A-8848-2010 NR 52 TC 212 Z9 217 U1 0 U2 15 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 NOV 15 PY 2002 VL 156 IS 10 BP 954 EP 961 DI 10.1093/aje/kwf128 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 616LW UT WOS:000179306100008 PM 12419768 ER PT J AU Hobbs, CA Cleves, MA Lauer, RM Burns, TL James, SJ AF Hobbs, CA Cleves, MA Lauer, RM Burns, TL James, SJ TI Preferential transmission of the MTHFR 677 T allele to infants with Down syndrome: Implications for a survival advantage SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE trisomy 21; cystathionine beta synthase; DNA methylation; folic acid; transmission disequilibrium test; MTHFR ID MATERNAL RISK-FACTORS; METHYLENETETRAHYDROFOLATE REDUCTASE; FOLATE METABOLISM; GENE; NONDISJUNCTION; POLYMORPHISMS; MUTATION; DISEASE AB We have examined the transmission frequencies of the methylenetetrahydrofolate reductase (MTHFR) 677 T and C alleles from heterozygous parents to children with Down syndrome (trisomy 21) in 202 Caucasian families. Our results indicated that the MTHFR 677T allele was transmitted to children with Down syndrome at a significantly higher rate than would be expected based on Mendelian inheritance patterns, and the C allele was transmitted at a significantly lower rate (P < 0.009). Transmission frequencies were also examined independently for maternally and paternally transmitted alccleles to assess potential parent-of-origin effects. Because the vast majority of conceptions with trisomy 21 end in pregnancy loss, we questioned whether the observed preferential transmission of the T allele to this population of liveborn infants with Down syndrome could reflect a survival advantage. A plausible biochemical interpretation of these results is presented based on a maternal-fetal MTHFR 677T allele interaction in the context of the constitutive overexpression of three copies of the cystathionine beta synthase gene in the trisomy 21 fetus. Published 2002 Wiley-Liss, Inc. C1 US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. Univ Iowa Hosp & Clin, Dept Pediat, Iowa City, IA 52242 USA. Univ Arkansas Med Sci, Arkansas Ctr Birth Defects Res & Prevent, Arkansas Childrens Hosp, Little Rock, AR USA. RP James, SJ (reprint author), US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. FU NHLBI NIH HHS [HL 62178-01]; NICHD NIH HHS [HD 39054-01, R01 HD24605] NR 22 TC 24 Z9 25 U1 1 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD NOV 15 PY 2002 VL 113 IS 1 BP 9 EP 14 DI 10.1002/ajmg.10704 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 607QQ UT WOS:000178802600003 PM 12400059 ER PT J AU Li, W Boykins, RA Backlund, PS Wang, GY Chen, HC AF Li, W Boykins, RA Backlund, PS Wang, GY Chen, HC TI Identification of phosphoserine and phosphothreonine as cysteic acid and beta-methylcysteic acid residues in peptides by tandem mass spectrometric sequencing SO ANALYTICAL CHEMISTRY LA English DT Article ID AFFINITY-CHROMATOGRAPHY; PHOSPHORYLATION SITES; PROTEIN-PHOSPHORYLATION; SELECTIVE DETECTION; SUBSTITUTED SERYL; THREONYL RESIDUES; COMPLEX-MIXTURES; PHOSPHOPEPTIDES; PHOSPHOPROTEINS; ELIMINATION AB Tandem mass spectrometry has long been an intrinsic tool to determine phosphorylation sites in proteins. However, loss of the phosphate moiety from both phosphoserine and phosphothreonine residues in low-energy collision-induced dissociation is a common phenomenon, which makes identification of P-Ser and P-Thr residues complicated. A method for direct sequencing of the Ser and Thr phosphorylation sites by ESI tandem mass spectrometry followingbeta-elimination/sulfite addition to convert -HPO4 to SO3 has been studied. Five model phosphopeptides, including three synthetic P-Ser-, P-Thr-, or P-Ser- and P-Thr-containing peptides; a protein kinases C-phosphorylated peptide; and a phosphopeptide derived from,beta-casein trypsin digests were modified and then sequenced using an ESI-quadrupole ion trap mass spectrometer. Following incubation of P-Ser- or P-Thr-containing peptides with Na2SO3/NaOH, 90% P-Ser and 80% P-Thr was converted to cysteic acid and beta-methylcysteic acid, respectively, as revealed by amino acid analysis. The conversion can be carried out at I muM concentration of the peptide. Both cysteic acid and beta-methylcysteic acid residues in the sequence were shown to be stable and easily identifiable under general conditions for tandem mass spectrometric sequencing applicable to common peptides. C1 NICHHD, Endocrinol & Reprod Res Branch, Lab Cell & Mol Biophys, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Biophys Lab, Div Bacterial Parasit & Allergen Prod, Bethesda, MD 20892 USA. RP Chen, HC (reprint author), NICHD, NIH, Bldg 49,Room 6A36,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 30 TC 27 Z9 28 U1 0 U2 3 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 NOV 15 PY 2002 VL 74 IS 22 BP 5701 EP 5710 DI 10.1021/ac020259v PG 10 WC Chemistry, Analytical SC Chemistry GA 616VH UT WOS:000179323700002 PM 12463352 ER PT J AU Williams, TL Leopold, P Musser, S AF Williams, TL Leopold, P Musser, S TI Automated postprocessing of electrospray LC/MS data for profiling protein expression in bacteria SO ANALYTICAL CHEMISTRY LA English DT Article ID ASSISTED-LASER-DESORPTION/IONIZATION; FLIGHT MASS-SPECTROMETRY; PERFORMANCE LIQUID-CHROMATOGRAPHY; NONPOROUS RP HPLC; RAPID IDENTIFICATION; WHOLE CELLS; PHASE; MICROORGANISMS; REPRODUCIBILITY; SEPARATIONS AB We describe an integrated approach for automating protein analysis of bacterial cell extracts. The method uses electrospray LC/MS to generate chromatographic profiles of proteins present in an extract, along with a software program that automates the data analysis. The software program, Retana, automates the sequential summing, centroiding, and deconvolution of multiply charged proteins present in consecutive scans of the LC/MS analysis. This procedure generates a concise, single spectrum of proteins present in the extract, along with their retention time and relative abundance. A comparison of the method with "whole cell" MALDI analysis demonstrates improved mass resolution and mass accuracy, along with the appearance of a greater number of proteins. Additionally, it is possible to compare protein expression among strains of bacteria by normalizing the relative abundance of similar proteins in each analysis. C1 US FDA, Instrumentat & Biophys Branch, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. BioAnalyte Inc, Portland, ME 04101 USA. RP Williams, TL (reprint author), US FDA, Instrumentat & Biophys Branch, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy,HFS-717, College Pk, MD 20740 USA. NR 33 TC 35 Z9 37 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 NOV 15 PY 2002 VL 74 IS 22 BP 5807 EP 5813 DI 10.1021/ac0258958 PG 7 WC Chemistry, Analytical SC Chemistry GA 616VH UT WOS:000179323700015 PM 12463365 ER PT J AU Dixon, AM Venable, RM Pastor, RW Bull, TE AF Dixon, AM Venable, RM Pastor, RW Bull, TE TI Micelle-bound conformation of a hairpin-forming peptide: Combined NMR and molecular dynamics study SO BIOPOLYMERS LA English DT Article DE NMR; molecular dynamics; CD; simulated annealing; peptide; micelle; hairpin turn ID NUCLEAR-MAGNETIC-RESONANCE; OCTYL GLUCOSIDE MICELLES; BETA-HAIRPIN; DODECYLPHOSPHOCHOLINE MICELLES; STRUCTURAL CHARACTERIZATION; SECONDARY STRUCTURE; AQUEOUS-SOLUTIONS; INFLUENZA-VIRUS; SPECTROSCOPY; SIMULATIONS AB A peptide fragment from a protein hairpin turn region was modified by addition of isoleucine residues to both ends to enhance binding to lipid micelles; the resulting peptide (I-1-I-2-C-3-N-4-N-5-P-6-H-7-I-8-I-9) contains the core sequence I-C-N-N-P-H from an antibody-binding region of hemagglutinin A. Nuclear magnetic resonance (NMR) diffusion measurements indicated partial binding (43-65%) of the peptide to micelles of n-octylglucoside and significantly stronger binding (85%) to dodecylphosphocholine (DPC) micelles. Simulated annealing and conformational analysis using nuclear Overhauser enhancement restraints revealed a type I or III hairpin turn between residues N-5 and I-8 of the DPC-bound peptide. Amide exchange experiments support the possibility that a hydrogen bond forms between A, and I, stabilizing the turn. In contrast, no discernable structure was observed,for the peptide in aqueous solution by either NMR or circular dichroism. Molecular dynamics simulations of DPC micelles and peptide-micelle complexes suggested that the peptide lies flat on the micelle surface and showed rapid rearrangement of the lipids to accommodate the bound peptide. According to a search performed using the basic local alignment search tool (BLAST), the sequences N-P-H-I and N-P-H-V are present as hairpin turns in eight of the nine proteins whose crystal structures were available. The addition of isoleucine residues and the use of lipid micelles to stabilize hairpin conformations equivalent to those found in proteins generates new possibilities for reproducing biologically important hairpin turns from short, linear peptides. (C) 2002 Wiley Periodicals, Inc. C1 US FDA, Biophys Lab, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Bull, TE (reprint author), US FDA, Biophys Lab, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RI Dixon, Ann/I-3696-2012 OI Dixon, Ann/0000-0002-5261-304X NR 63 TC 14 Z9 14 U1 0 U2 5 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0006-3525 J9 BIOPOLYMERS JI Biopolymers PD NOV 15 PY 2002 VL 65 IS 4 BP 284 EP 298 DI 10.1002/bip.10249 PG 15 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 607EV UT WOS:000178779400006 PM 12382289 ER PT J AU Chen, JJZ Gokden, N Greene, GF Mukunyadzi, P Kadlubar, FF AF Chen, JJZ Gokden, N Greene, GF Mukunyadzi, P Kadlubar, FF TI Extensive somatic mitochondrial mutations in primary prostate cancer using laser capture microdissection SO CANCER RESEARCH LA English DT Article ID DNA MUTATIONS; TUMORS; HETEROPLASMY; SUBSTITUTION; PATTERN; REGION; MTDNA AB Prostate cancer is the second leading cause of cancer deaths among men in the United States, but the precise molecular events leading to prostate carcinogenesis are not well understood. We isolated histologically defined cell populations from prostate cancer and its preinvasive lesions using laser capture microdissection, and performed genetic analysis on the mitochondrial genome, a sensitive cytoplasmic DNA. An extremely high incidence of somatic mutation (90% of prostatectomy cancer specimens) was found in the control region (the displacement loop) of mitochondrial DNA. The massive induction of lesion-associated mutations suggests active mitochondrial mutagenesis in both prostate cancer and its preinvasive lesions. Inspection of these mutations provides new insights into prostate cancer genetics and reveals unique patterns of somatic mutations in prostatic neoplastic lesions. C1 Natl Ctr Toxicol Res, Div Mol Epidemiol, US FDA, Jefferson, AR 72079 USA. Univ Arkansas Med Sci, Dept Pathol, Little Rock, AR 72205 USA. Univ Arkansas Med Sci, Dept Urol, Little Rock, AR 72205 USA. RP Chen, JJZ (reprint author), Natl Ctr Toxicol Res, Div Mol Epidemiol, US FDA, 3900 NCTR Rd, Jefferson, AR 72079 USA. NR 21 TC 75 Z9 82 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 NOV 15 PY 2002 VL 62 IS 22 BP 6470 EP 6474 PG 5 WC Oncology SC Oncology GA 616QV UT WOS:000179315200025 PM 12438238 ER PT J AU Wulfkuhle, JD Sgroi, DC Krutzsch, H McLean, K McGarvey, K Knowlton, M Chen, S Shu, HJ Sahin, A Kurek, R Wallwiener, D Merino, MJ Petricoin, EF Zhao, YM Steeg, PS AF Wulfkuhle, JD Sgroi, DC Krutzsch, H McLean, K McGarvey, K Knowlton, M Chen, S Shu, HJ Sahin, A Kurek, R Wallwiener, D Merino, MJ Petricoin, EF Zhao, YM Steeg, PS TI Proteomics of human breast ductal carcinoma in situ SO CANCER RESEARCH LA English DT Article ID SURGICAL-ADJUVANT-BREAST; TRANS-GOLGI NETWORK; IN-SITU; LOCAL RECURRENCE; HYDROGEN-PEROXIDE; FOLLOW-UP; CONSERVING THERAPY; ESTROGEN-RECEPTOR; HORMONE RECEPTORS; TUMOR PROGRESSION AB We report the first proteomic analysis of matched normal ductal/ lobular units and ductal carcinoma in situ (DCIS) of the human breast. An understanding of the transition from normal epithelium to the first definable stage of cancer at the functional level of protein expression is hypothesized to contribute to improved detection, prevention, and treatment. Ten sets of two-dimensional gels were evaluated, containing either matched normal ductal/lobular units or DCIS from either whole tissue sections or up to 100,000 laser capture microdissected epithelial cells. Differential protein expression was confirmed by image analysis. Protein spots (315) were excised and subjected to mass spectrometry sequencing. Fifty-seven proteins were differentially expressed between normal ductal/ lobular units and DCIS. Differences in overall protein expression levels and posttranslational processing were evident. Ten differentially expressed proteins were validated in independent DCIS specimens, and 14 of 15 proteomic trends from two-dimensional gel analyses were confirmed by standard inummohistochemical analysis using a limited independent tumor cohort. Many of the proteins identified were previously unconnected with breast cancer, including proteins regulating the intracellular trafficking of membranes, vesicles, cancer preventative agents, proteins, ions, and fatty acids. Other proteomic identifications related to cytoskeletal architecture, chaperone function, the microenvironment, apoptosis, and genomic instability. Proteomic analysis of DCIS revealed differential expression patterns distinct from previous nucleic acid-based studies and identified new facets of the earliest stage of breast cancer progression. C1 NCI, Womens Canc Sect, Pathol Lab, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Mol Pathol Unit, Boston, MA 02129 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02129 USA. NCI, Pathol Lab, Bethesda, MD 20892 USA. Univ Texas, SW Med Ctr, Dept Biochem, Dallas, TX 75390 USA. Univ Texas, MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA. Univ Tubingen, Dept Obstet & Gynecol, D-72076 Tubingen, Germany. US FDA, Ctr Biol Evaluat & Res, NCI, Clin Proteom Program,Div Therapeut Prot, Bethesda, MD 20892 USA. RP Steeg, PS (reprint author), NCI, Womens Canc Sect, Pathol Lab, Bldg 10,Room 2A33, Bethesda, MD 20892 USA. FU NCI NIH HHS [CA 85146] NR 69 TC 188 Z9 200 U1 2 U2 6 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 2002 VL 62 IS 22 BP 6740 EP 6749 PG 10 WC Oncology SC Oncology GA 616QV UT WOS:000179315200062 PM 12438275 ER PT J AU Zhu, PX Tsai, CM Frasch, CE AF Zhu, PX Tsai, CM Frasch, CE TI Immunologic and genetic characterization of lipooligosaccharide variants in a Neisseria meningitidis serogroup C strain SO FEMS IMMUNOLOGY AND MEDICAL MICROBIOLOGY LA English DT Article DE lipooligosaccharide; immunotype; glycosyltransferase; lgt; Neisseria ID OUTER-MEMBRANE PROTEIN; TERMINAL LIPOPOLYSACCHARIDE STRUCTURE; PHASE-VARIABLE GENES; ANTIGENIC VARIATION; GONORRHOEAE LIPOOLIGOSACCHARIDE; PATHOGENIC NEISSERIAE; POLYACRYLAMIDE GELS; BETA-CHAIN; BIOSYNTHESIS; EXPRESSION AB Neisseria meningitidis shows great variation in expression of structurally different lipooligosaccharides (LOS) on its cell surface. To better understand the LOS diversity that may occur within an individual strain, a group C wild-type strain, BB305-Tr4, and two stable isogenic LOS variants, Tr5 and Tr7. were selected for this study. SDS-PAGE analysis showed a size reduction of Tr5 and Tr7 LOS compared to that of Tr4. Immunoblotting showed that parental Tr4 LOS reacted with L1, L2 and L3,7 antibodies. variant Tr5 LOS with L1 and L6 antibodies, while Tr7 LOS was non-typeable. Genetic analysis showed that the gene organization at the Igt-1 locus in the three strains was lgtZ,C,A.B,H4 in Tr4. lgtZ,C,A,H4 in Tr5 and IgtZ,C,A,H9 in Tr7. The genetic differences in the three strains were consistent with their phenotypic changes. Sequence comparison revealed two independent recombination events. The first was the recombination of repeated DNA fragments in the flanking regions to delete lgtB in Tr5. The second was the recombination of a fragment of two genes, lgtB and lgtH4. to create an inactive lgtH9 allele with a mosaic structure in Tr7. These Findings suggest that besides phase variation, homologous recombination can contribute to the genetic diversity of the lgt locus and to the generation of LOS variation in A meningitidis. (C) 2002 Federation of European Microbiological Societies. Published by Elsevier Science B.V. All rights reserved. C1 US FDA, Ctr Biol Evaluat & Res, Lab Bacterial Polysaccharides, Bethesda, MD 20892 USA. RP Zhu, PX (reprint author), OVRR, Div Bacterial Prod, 1401 Rockville Pike,HFM-428, Rockville, MD 20852 USA. NR 42 TC 3 Z9 3 U1 0 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 NOV 15 PY 2002 VL 34 IS 3 BP 193 EP 200 AR PII S0928-8244(02)00379-6 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 616BR UT WOS:000179282300005 PM 12423771 ER PT J AU Cui, YY Gurley, B Ang, CYW Leakey, J AF Cui, YY Gurley, B Ang, CYW Leakey, J TI Determination of hyperforin in human plasma using solid-phase extraction and high-performance liquid chromatography with ultraviolet detection SO JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES LA English DT Article DE hyperforin; St. John's wort ID ST-JOHNS-WORT; HYPERICUM-PERFORATUM; MASS-SPECTROMETRY; CLINICAL-TRIALS; ARRAY DETECTION; DEPRESSION; CONSTITUENTS; METAANALYSIS; STABILITY AB Hyperforin is one of the most important active components in St. John's wort (Hypericum perforatum), a botanical dietary supplement used as an alternative treatment modality for mild to moderate depression. A solid-phase extraction (SPE) and an isocratic high-performance liquid chromatography (HPLC) analysis with ultraviolet (UV) detection were developed to determine hyperforin in human plasma samples. Benzo[k]fluoranthene was used as an internal standard. The absolute recovery for hyperforin was more than 89% for plasma concentrations ranging from 25 to 500 ng/ml. The linearity of calibration curves, inter-day and infra-day. relative standard deviations were investigated. The limit of detection (LOD) of hyperforin was 4 ng/ml in plasma and the limit of quantitation (LOQ) was 10 ng/ml. Hyperforin concentrations in human plasma following St. John's wort administration were analyzed. The result suggests that this method is rapid, sensitive, reproducible and capable of quantitative analysis of hyperforin plasma concentrations. Published by Elsevier Science B.V. C1 US FDA, Natl Ctr Toxicol Res, Div Chem, Jefferson, AR 72079 USA. Univ Arkansas Med Sci, Coll Pharm, Dept Pharmaceut Sci, Little Rock, AR 72205 USA. RP Ang, CYW (reprint author), US FDA, Natl Ctr Toxicol Res, Div Chem, HFT-230,3900 NCTR Rd, Jefferson, AR 72079 USA. NR 22 TC 21 Z9 21 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1570-0232 J9 J CHROMATOGR B JI J. Chromatogr. B PD NOV 15 PY 2002 VL 780 IS 1 BP 129 EP 135 AR PII S1570-0232(02)00439-7 DI 10.1016/S1570-0232(02)00439-7 PG 7 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 613BF UT WOS:000179110200015 PM 12383488 ER PT J AU Zhang, L Lizzio, EF Gubina, E Chen, T Mostowski, H Kozlowski, S AF Zhang, L Lizzio, EF Gubina, E Chen, T Mostowski, H Kozlowski, S TI Organ-specific cytokine polarization induced by adoptive transfer of transgenic T cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID LYMPHOCYTES-T; IMMUNE PRIVILEGE; SELF-TOLERANCE; IN-VIVO; RECEPTOR; MICE; TH2; IL-4; INFECTION; RESPONSES AB There are two distinct phenotypes of T cell cytokine responses that lead to different effector functions and different outcomes in disease processes. Although evidence suggests a possible role of the local microenvironment in the differentiation or localization of T cells with these phenotypes, there are no examples of divergent T cell cytokine phenotypes with the same Ag specificity concurrently existing in different tissue compartments. Using a CD8(+) T cell adoptive transfer model for graft-vs-host disease, we demonstrate that a potent type 2 cytokine response develops in the spleen while a potent type 1 cytokine response simultaneously develops in the testis. These experiments demonstrate for the first time that cytokine production can be oppositely polarized in different organs of the same individual. This may have important implications for organ-specific pathology in infection or autoimmunity: infections or autoimmune diseases that affect multiple organs may have heterogeneity in tissue cytokine responses that is not revealed in systemic lymphocyte cytokine responses. Therefore, attempts to modulate the immune response phenotype may ameliorate pathology in one organ while exacerbating pathology in another. C1 US FDA, Ctr Biol Evaluat & Res Food & Drug Adm, Div Monoclonal Antibodies, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res Food & Drug Adm, Div Cell & Gene Therapy, Bethesda, MD 20892 USA. RP Kozlowski, S (reprint author), US FDA, Ctr Biol Evaluat & Res Food & Drug Adm, Div Monoclonal Antibodies, Bldg 29B,Rm 3NN08,HFM-561,29 Lincoln Dr, Bethesda, MD 20892 USA. EM Kozlowski@cber.fda.gov NR 49 TC 6 Z9 6 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 15 PY 2002 VL 169 IS 10 BP 5514 EP 5521 PG 8 WC Immunology SC Immunology GA 614CG UT WOS:000179170300020 PM 12421927 ER PT J AU Yamada, H Gursel, I Takeshita, F Conover, J Ishii, KJ Gursel, M Takeshita, S Klinman, DM AF Yamada, H Gursel, I Takeshita, F Conover, J Ishii, KJ Gursel, M Takeshita, S Klinman, DM TI Effect of suppressive DNA on CpG-induced immune activation SO JOURNAL OF IMMUNOLOGY LA English DT Article ID EXPRESSION IN-VIVO; BACTERIAL-DNA; IMMUNOSTIMULATORY DNA; CUTTING EDGE; B-CELLS; MOTIFS; OLIGODEOXYNUCLEOTIDES; GAMMA; PROTECTION; INHIBITION AB Bacterial DNA and synthetic oligodeoxynucleotides (ODN) containing unmethylated CpG motifs stimulate a strong innate immune response. This stimulation can be abrogated by either removing the CpG DNA or adding inhibitory/suppressive motifs. Suppression is dominant over stimulation and is specific for CpG-induced immune responses (having no effect on LPS- or Con A-induced activation). Individual cells noncompetitively internalize both stimulatory and suppressive ODN. Studies using ODN composed of both stimulatory and suppressive motifs indicate that sequence recognition proceeds in a 5'-->3' direction, and that a 5' motif can block recognition of immediately 3' sequences. These findings contribute to our understanding of the immunomodulatory activity of DNA-based products and the rules that govern immune recognition of stimulatory and suppressive motifs. 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 3D10, Bethesda, MD 20892 USA. RI Gursel, Mayda /H-1812-2012; Ishii, Ken/B-1685-2012; OI Ishii, Ken/0000-0002-6728-3872; Gursel, Ihsan/0000-0003-3761-1166 NR 37 TC 83 Z9 87 U1 0 U2 4 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 15 PY 2002 VL 169 IS 10 BP 5590 EP 5594 PG 5 WC Immunology SC Immunology GA 614CG UT WOS:000179170300029 PM 12421936 ER PT J AU Cao, SJ Liu, JG Chesi, M Bergsagel, PL Ho, IC Donnelly, RP Ma, XJ AF Cao, SJ Liu, JG Chesi, M Bergsagel, PL Ho, IC Donnelly, RP Ma, XJ TI Differential regulation of IL-12 and IL-10 gene expression in macrophages by the basic leucine zipper transcription factor c-Maf fibrosarcoma SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NF-KAPPA-B; INTERLEUKIN-12 P40 PROMOTER; NUCLEAR ONCOPROTEIN; MULTIPLE-MYELOMA; ACTIVATION; PROTEINS; JUN; FOS; CELLS; SITE AB IL-12 is a principal activator of both innate and adaptive immunity against infections agents and malignancies. Regulation of proinflammatory IL-12 gene expression in phagocytes by the anti-inflammatory cytokine IL-10 represents a major homeostatic process underlying host-pathogen and host-self interactions. Delineation of the signaling pathway of IL-10 is crucial to the understanding of immunological regulatory networks. In this study, we report that IL-10 and c-musculoaponeurotic fibrosarcoma (Maf) induce their mutual expression in inflammatory macrophages. We demonstrate that c-Maf is one of the physiological mediators of IL-10's immunosuppressive activities. When overexpressed, c-Maf selectively inhibits transcriptional activation of IL-12 p40 and p35 genes while potently activating IL-10 and IL-4 expression, potentially contributing to the development of A state of anti-inflammation and dichotomy of immunologic polarization. c-Maf induces changes in nuclear DNA-binding activities at multiple sites including the et, GA-12, NF-kappaB, C/EBP, and AP-1 elements. Nonetheless, the essential c-Maf-responsive element appears to be located elsewhere. Inhibition of IL-12 p40 gene expression by c-Maf requires the N-terminal transactivation domain, suggesting an indirect mechanism of transcriptional inhibition involving the induction of an unidentified, repressor. In c-Maf-deficient murine macrophages, IL-10 production is impaired. However, IL-10-mediated inhibition of IL-12 production remains intact, indicating the existence of alternative mediators in the absence of c-Maf, consistent with the observation that a functional AP-1 is required for this pathway. C1 Cornell Univ, Weill Med Coll, Dept Microbiol & Immunol, New York, NY 10021 USA. Cornell Univ, Weill Med Coll, Dept Med, New York, NY 10021 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. US FDA, Ctr Biol Evaluat & Res, Div Therapeut Prot, Bethesda, MD 20892 USA. RP Ma, XJ (reprint author), Cornell Univ, Weill Med Coll, Dept Microbiol & Immunol, 1300 York Ave, New York, NY 10021 USA. RI Bergsagel, Peter/A-7842-2011 OI Bergsagel, Peter/0000-0003-1523-7388 FU NCI NIH HHS [CA 79772]; NIAID NIH HHS [AI 45899] NR 46 TC 74 Z9 75 U1 1 U2 4 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 15 PY 2002 VL 169 IS 10 BP 5715 EP 5725 PG 11 WC Immunology SC Immunology GA 614CG UT WOS:000179170300044 PM 12421951 ER PT J AU Choudhury, BK Wild, JS Alam, R Klinman, DM Boldogh, I Dharajiya, N Mileski, WJ Sur, S AF Choudhury, BK Wild, JS Alam, R Klinman, DM Boldogh, I Dharajiya, N Mileski, WJ Sur, S TI In vivo role of p38 mitogen-activated protein kinase in mediating the anti-inflammatory effects of CpG oligodeoxynucleotide in murine asthma SO JOURNAL OF IMMUNOLOGY LA English DT Article ID INDUCED AIRWAY HYPERRESPONSIVENESS; INDUCED EOSINOPHIL RECRUITMENT; ALLERGIC LUNG INFLAMMATION; CD4+ T-CELLS; INTERFERON-GAMMA; PRESENTING CELLS; BACTERIAL-DNA; MUCOSAL IL-12; CUTTING EDGE; INTERLEUKIN-12 AB DNA containing unmethylated CpG motifs is intrinsically immunostimulatory, inducing the production of a variety of cytokines and chemokines by immune cells. The strong Th1 response triggered by CpG oligodeoxynucleotide (ODN) inhibits the development of Th2-mediated allergic asthma in mice. This work documents that CpG ODN-induced IL-12 production plays a critical role in this process, because intrapulmonary CpG ODN inhibits allergic inflammation in wild-type but not IL-12(-/-) mice. CpG ODN rapidly localized to alveolar macrophages (AM), thereby triggering the phosphorylation of p38 mitogen-activated protein kinase (MAP kinase). AM cultured with CpG but not control ODN up-regulated IL-12 p40 expression and release, and these effects were blocked by the highly specific p38 MAP kinase inhibitor SB202190. Intrapulmonary administration of this inhibitor blocked the ability of CpG ODN to produce IL-12 in the lungs and reversed the anti-inflammatory effects of CpG ODN on allergic lung inflammation. These findings indicate that IL-12 production by AM is stimulated by intrapulmonary CpG ODN administration through a p38 MAP kinase-dependent process, and IL-12 is a key cytokine that mediates CpG ODN-induced protection against allergic lung inflammation. C1 Univ Texas, Med Branch, Dept Internal Med, Div Allergy & Immunol, Galveston, TX 77555 USA. Univ Texas, Med Branch, NIH, Asthma & Allerg Dis Res Ctr, Galveston, TX 77555 USA. Univ Texas, Med Branch, Dept Microbiol & Immunol, Galveston, TX 77555 USA. Univ Texas, Med Branch, Dept Surg, Galveston, TX 77555 USA. US FDA, Sect Retroviral Res, Bethesda, MD 20014 USA. RP Sur, S (reprint author), Univ Texas, Med Branch, Dept Internal Med, Div Allergy & Immunol, Med Res Bldg 8-104, Galveston, TX 77555 USA. FU NIAID NIH HHS [K08 AI 01539, P01 AI 46004]; NIEHS NIH HHS [ES 06676] NR 38 TC 37 Z9 40 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 15 PY 2002 VL 169 IS 10 BP 5955 EP 5961 PG 7 WC Immunology SC Immunology GA 614CG UT WOS:000179170300074 PM 12421981 ER PT J AU Collins, JM AF Collins, JM TI Idiosyncratic drug toxicity SO CHEMICO-BIOLOGICAL INTERACTIONS LA English DT Editorial Material C1 US FDA, CDER, Lab Clin Pharmacol, Rockville, MD 20857 USA. RP Collins, JM (reprint author), US FDA, CDER, Lab Clin Pharmacol, HFD-902,NLRC,5600 Fishers Lane, Rockville, MD 20857 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0009-2797 J9 CHEM-BIOL INTERACT JI Chem.-Biol. Interact. PD NOV 10 PY 2002 VL 142 IS 1-2 BP 3 EP 6 AR PII S0009-2797(02)00050-9 DI 10.1016/S0009-2797(02)00050-9 PG 4 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology GA 616QJ UT WOS:000179314200002 PM 12399151 ER PT J AU Hartman, NR Cysyk, RL Bruneau-Wack, C Thenot, JP Parker, RJ Strong, JM AF Hartman, NR Cysyk, RL Bruneau-Wack, C Thenot, JP Parker, RJ Strong, JM TI Production of intracellular S-35-glutathione by rat and human hepatocytes for the quantification of xenobiotic reactive intermediates SO CHEMICO-BIOLOGICAL INTERACTIONS LA English DT Article DE adducts; glutathione; hepatocytes; acetaminophen; reactive intermediates; metabolism ID LIQUID-CHROMATOGRAPHY; COVALENT BINDING; GLUTATHIONE; PARACETAMOL; ACETAMINOPHEN; SPECTROMETRY; METABOLISM; TOXICITY; LIVER; DNA AB The quantification and identification of xenobiotic reactive intermediates is difficult in the absence of highly radiolabeled drug. We have developed a method for identifying these intermediates by measuring the formation of adducts to intracellularly generated radiolabeled glutathione (GSH). Freshly isolated adherent rat and human hepatocytes were incubated overnight in methionine and cystine-free ('thio-free') medium. They were then exposed to 100 muM methionine and 10 muCi S-35-labeled methionine in otherwise thio-free medium to replete Cellular GSH pools with intracellularly generated S-35-labeled GSH. After 3 h, acetaminophen was added as a test compound and the cells were incubated for an additional 24 h. Intracellular GSH and its specific activity were quantified after reaction with monobromobimane followed by HPLC analysis with fluorescence and radiochemical detection. Radiolabeled GSH as detectable at 3 h and maintained high specific activity and physiological concentrations for up to 24 h. Incubation medium from acetaminophen treated and nontreated hepatocytes were analyzed for radiolabeled peaks by HPLC using radiochemical detection, Radiolabeled peaks not present in nontreated hepatocytes were identified as acetaminophen GSH adducts by LC-MS. Formation of acetaminophen S-35-GSH adducts by rat hepatocytes containing endogenously synthesized S-35-GSH was increased with acetaminophen concentrations ranging from 500 to 2 mM. Published by Elsevier Science Ireland Ltd. C1 US FDA, Ctr Drug Evaluat & Res, Off Testing & Res, Lab Clin Pharmacol, Laurel, MD USA. NCI, Basic Res Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. Sanofi Synthelabo Rech, Pharmacokinet & Metab, F-91380 Chilly Mazarin, France. RP Strong, JM (reprint author), Room 2017,Mod-1,8301 Muirkirk Rd, Laurel, MD 20708 USA. NR 18 TC 14 Z9 14 U1 0 U2 2 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0009-2797 J9 CHEM-BIOL INTERACT JI Chem.-Biol. Interact. PD NOV 10 PY 2002 VL 142 IS 1-2 BP 43 EP 55 AR PII S0009-2797(02)00053-4 DI 10.1016/S0009-2797(02)00053-4 PG 13 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology GA 616QJ UT WOS:000179314200005 PM 12399154 ER PT J AU Kapetanovic, IM Torchin, CD Strong, JM Yonekawa, WD Lu, C Li, AP Dieckhaus, CM Santos, WL Macdonald, TL Sofia, RD Kupferberg, HJ AF Kapetanovic, IM Torchin, CD Strong, JM Yonekawa, WD Lu, C Li, AP Dieckhaus, CM Santos, WL Macdonald, TL Sofia, RD Kupferberg, HJ TI Reactivity of atropaldehyde, a felbamate metabolite in human liver tissue in vitro SO CHEMICO-BIOLOGICAL INTERACTIONS LA English DT Article DE reactive metabolites; aldehyde dehydrogenase; glutathione transferase; atropaldehyde; glutathione; hepatocytes ID GLUTATHIONE S-TRANSFERASES; IN-VITRO; MERCAPTURIC ACIDS; OXIDATIVE STRESS; HUMAN URINE; RAT; TOXICITY; IDENTIFICATION; ACROLEIN; DETOXIFICATION AB Antiepileptic therapy with a broad spectrum drug felbamate (FBM) has been limited due to reports of hepatotoxicity and aplastic anemia associated with its use. It was proposed that a bioactivation of FBM leading to formation of alpha,beta-unsaturated aldehyde, atropaldehyde (ATPAL) could be responsible for toxicities associated with the parent drug. Other members of this class of compounds, acrolein and 4-hydroxynonenal (HNE), are known for their reactivity and toxicity. It has been proposed that the bioactivation of FBM to ATPAL proceeds though a more stable cyclized product, 4-hydroxy-5-phenyltetrahydro-1.3-oxazin-2-one (CCMF) whose formation has been shown recently. Aldehyde dehydrogenase (ALDH) and glutathione transferase (GST) are detoxifying enzymes and targets for reactive aldehydes. This study examined effects of ATPAL and its precursor, CCMF on ALDH, GST and cell viability in liver, the target tissue for its metabolism and toxicity. A known toxin, HNE, which is also a substrate for ALDH and GST, was used for comparison. Interspecies difference in metabolism of FBM is well documented, therefore, human tissue was deemed most relevant and used for these studies. ATPAL inhibited ALDH and GST activities and led to a loss of hepatocyte viability. Several fold greater concentrations of CCMF were necessary to demonstrate a similar degree of ALDH inhibition or cytotoxicity as observed with ATPAL. This is consistent with CCMF requiring prior conversion to the more proximate toxin, ATPAL. GSH was shown to protect against ALDH inhibition by ATPAL. In this context. ALDH and GST are detoxifying pathways and their inhibition would lead to an accumulation of reactive species from FBM metabolism and/or metabolism of other endogenous or exogenous compounds and predisposing to or causing toxicity. Therefore, mechanisms of reactive aldehydes toxicity could include direct interaction with critical cellular macromolecules or indirect interference with cellular detoxification mechanisms. Published by Elsevier Science Ireland Ltd. C1 US FDA, CDER, Lab Clin Pharmacol, MOD1, Laurel, MD 20708 USA. NINDS, NIH, Bethesda, MD 20892 USA. In Vitro Technol, Baltimore, MD 21227 USA. Univ Virginia, Dept Chem, Charlottesville, VA 22901 USA. Wallace Labs, Cranbury, NJ 08512 USA. RP Kapetanovic, IM (reprint author), NCI, Div Canc Prevent, Chemoprevent Agent Dev Res Grp, NIH, 6130 Execut Blvd,Suite 2116,MSC 7322, Bethesda, MD 20892 USA. OI Santos, Webster/0000-0002-4731-8548; Li, Albert/0000-0001-5772-6265 NR 30 TC 18 Z9 18 U1 0 U2 3 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0009-2797 J9 CHEM-BIOL INTERACT JI Chem.-Biol. Interact. PD NOV 10 PY 2002 VL 142 IS 1-2 BP 119 EP 134 AR PII S0009-2797(02)00058-3 DI 10.1016/S0009-2797(02)00058-3 PG 16 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology GA 616QJ UT WOS:000179314200010 PM 12399159 ER PT J AU Shapira-Nahor, O Maayan, S Peden, KWC Rabinowitz, R Schlesinger, M Alian, A Panet, A AF Shapira-Nahor, O Maayan, S Peden, KWC Rabinowitz, R Schlesinger, M Alian, A Panet, A TI Replication of HIV-1 deleted Nef mutants in chronically immune activated human T cells SO VIROLOGY LA English DT Article DE HIV-1 replication; Nef gene mutants; T cell activation ID HUMAN-IMMUNODEFICIENCY-VIRUS; NF-KAPPA-B; BLOOD MONONUCLEAR-CELLS; TYPE-1 INFECTION; HUMAN-LYMPHOCYTES; DOWN-REGULATION; PLASMA-LEVELS; IN-VITRO; PROTEIN; CD4 AB Lymphocytes (PBMC) obtained from blood of HIV-sera negative Ethiopian immigrants (ETH) were highly susceptible to HIV-1 infection in vitro with no need for stimulation by mitogens. As the HIV nef gene product has been shown to enhance viral replication in stimulated primary lymphocytes, we investigated in this work the role of Nef in viral replication in the ETH cells. Lymphocytes obtained from ETH individuals supported high replication of wild-type HIV-1 and low but significant replication level of the two deleted Nef mutants (encode truncated Nef proteins consisting only of either the first 35 or the first 86 amino acids of Nef). In contrast, no replication was observed in nonactivated cells obtained from non-ETH individuals. After activation of the PBMC from ETH individuals with PHA, replication of both wild-type strains and the two deleted Nef mutant viruses further increased. The CD4(+) T cells of ETH individuals exhibited elevated levels of the surface activation markers CD45RO and HLA-DR, compared with T cells derived from non-ETH group. Likewise, expression of the chemokine receptors CCR5 and CXCR4 on these cells was higher in the ETH group than in the non-ETH group. Replication of HIV-1 wild-type and the isogenic-deleted Nef mutants was significantly correlated with the proportion of ETH cells expressing CD45RO and the chemokine receptors. This study suggests that HIV-1 may respond differently to several activation states characteristic of T cells. One activation state, defined by chronically activated lymphocytes from ETH individuals, is permissive to the wild-type HIV-1 and, to a lesser degree, to the Nef mutants. Further activation of these cells by exogenous stimuli enhances replication of the virus. Our results support the notion that Nef enhances the basal level of T cell activation and consequently, viral replication. (C) 2002 Elsevier Science (USA). C1 Hebrew Univ Jerusalem, Hadassah Med Sch, Dept Virol, IL-91120 Jerusalem, Israel. Hebrew Univ Jerusalem, Hadassah Med Sch, Hubert H Humphrey Ctr Expt Med & Canc Res, IL-91120 Jerusalem, Israel. Hadassah Hebrew Univ Hosp, IL-91120 Jerusalem, Israel. US FDA, Ctr Biol Evaluat & Res, Lab Retrovirus Res, Bethesda, MD 20892 USA. RP Shapira-Nahor, O (reprint author), Hebrew Univ Jerusalem, Hadassah Med Sch, Dept Virol, POB 12272, IL-91120 Jerusalem, Israel. OI Alian, Akram/0000-0003-1901-3832 NR 58 TC 4 Z9 4 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD NOV 10 PY 2002 VL 303 IS 1 BP 138 EP 145 DI 10.1006/viro.2002.1643 PG 8 WC Virology SC Virology GA 625RF UT WOS:000179828800013 PM 12482665 ER PT J AU Von Tungeln, LS Yi, P Bucci, TJ Samokyszyn, VM Chou, MW Kadlubar, FF Fu, PP AF Von Tungeln, LS Yi, P Bucci, TJ Samokyszyn, VM Chou, MW Kadlubar, FF Fu, PP TI Tumorigenicity of chloral hydrate, trichloroacetic acid, trichloroethanol, malondialdehyde, 4-hydroxy-2-nonenal, crotonaldehyde, and acrolein in the B6C3F(1) neonatal mouse SO CANCER LETTERS LA English DT Article DE neonatal B6C3F(1) mouse; lipid peroxidation; chloral hydrate ID BIOASSAY; METABOLISM; MICE; DNA; CHROMATOGRAPHY; ADDUCT AB The tumorigenicity of chloral hydrate (CH), trichloroacetic acid (TCA), trichloroethanol (TCE), malondialdehyde (MDA), crotonaldehyde, acrolein, and 4-hydroxy-2-nonenal (HNE) was tested in the 1360171 neonatal mouse. Mice were administered i.p. injections of CH (1000, 2000, 2500, and 5000 nmol per animal), TCA (1000 and 2000 nmol), TCE (1000 and 2000 nmol), MDA (1500 and 3000 nmol), crotonaldehyde (1500 and 3000 nmol), acrolein (75 and 150 nmol), and HNE (750 and 1500 nmol) at 8 and 15 days of age. At 12 months, only male mice treated with the positive control chemicals, 4-aminobiphenyl (500 and 1000 nmol) and benzo[a]pyrene (150 and 300 nmol), had incidences of tumors in the liver significantly higher than the solvent control. Additional male mice were dosed as described above and their livers were excised at 24, 48 h, and 7 days after the final dose. Liver DNA was isolated and analyzed by P-32-postlabeling/high-performance liquid chromatography (HPLC) and HPLC/electrochemical detection for MDA-derived adduct (M(1)G) and 8-oxo-2'-deoxyguanosine (8-OHdG) formation, respectively. At 24 and 48 It after the final dose, CH- and TCA-treated mice exhibited significantly higher M(1)G levels than the controls. 8-OHdG formation was also induced by CH, TCA, and MDA. These results suggest that under these experimental conditions the B6C3F(1) neonatal mouse is not sensitive to carcinogens that induce an increase in endogenous DNA adduct formation through lipid peroxidation or oxidative stress. Published by Elsevier Science Ireland Ltd. C1 Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. Natl Ctr Toxicol Res, Pathol Associates Int Inc, Jefferson, AR 72079 USA. Univ Arkansas Med Sci, Dept Pharmacol, Little Rock, AR 72205 USA. RP Fu, PP (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. NR 17 TC 11 Z9 11 U1 1 U2 7 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 NOV 8 PY 2002 VL 185 IS 1 BP 13 EP 19 AR PII S0304-3835(02)00231-8 DI 10.1016/S0304-3835(02)00231-8 PG 7 WC Oncology SC Oncology GA 599GY UT WOS:000178326800002 PM 12142074 ER PT J AU Nowell, S Sweeney, C Winters, M Stone, A Lang, NP Hutchins, LF Kadlubar, FF Ambrosone, CB AF Nowell, S Sweeney, C Winters, M Stone, A Lang, NP Hutchins, LF Kadlubar, FF Ambrosone, CB TI Association between sulfotransferase 1A1 genotype and survival of breast cancer patients receiving tamoxifen therapy SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID HUMAN CYTOSOLIC SULFOTRANSFERASES; PHENOL SULFOTRANSFERASES; ESTRONE SULFATE; DEHYDROEPIANDROSTERONE; POLYMORPHISM; METABOLISM AB Background: Human sulfotransferase 1A1 (SULT1A1) catalyzes the sulfation of a variety of phenolic and estrogenic compounds, including 4-hydroxytamoxifen (4-OH TAM), the active metabolite of tamoxifen. A functional polymorphism in exon 7 of the SULT1A1 gene (SULT1A1*2) has been described that generates an enzyme that has approximately twofold lower activity and is less thermostable than that of the common allele SULT1A1*1. We investigated the hypothesis that that high sulfation activity would increase the elimination of 4-OH TAM by examining whether the presence of this polymorphism affects the efficacy of tamoxifen therapy. Methods: We examined the relationship between the SULT1A1*2 allele and survival in a cohort of 337 women with breast cancer who received tamoxifen (n = 160) or who did not (n = 177). SULT1A1 genotype was determined by restriction fragment polymorphism analysis. Patient survival was evaluated according to SULT1A1 genotype using Kaplan-Meier survival functions. Hazard ratios (HRs) were calculated from adjusted Cox proportional hazards modeling. All statistical tests were two-sided. Results: Among tamoxifen-treated patients, those who were homozygous for the SULT1A1*2 low-activity allele had approximately three times the risk of death (HR = 2.9, 95% confidence interval [CI] = 1.1 to 7.6) as those who were homozygous for the common allele or those who were heterozygous (SULT1A1*1/*2). Among patients who did not receive tamoxifen, there was no association between survival and SULTIAI genotype (HR = 0.7, 95% CI = 0.3 to 1.5). Conclusions: Sulfation of 4-OH TAM provides a previously unanticipated benefit, possibly due to alterations in the bio-availability of the active metabolite or to undefined estrogen receptor-mediated events. These data alternatively suggest that variability in the metabolism of tamoxifen may affect its efficacy. C1 Natl Ctr Toxicol Res, Div Mol Epidemiol, Jefferson, AR 72079 USA. Univ Arkansas Med Sci, Dept Pharmacol & Toxicol, Little Rock, AR 72205 USA. Univ Minnesota, Div Epidemiol, Minneapolis, MN 55455 USA. Univ Arkansas Med Sci, Cent Arkansas Vet Hlth Care Syst, Little Rock, AR 72205 USA. Univ Arkansas Med Sci, Dept Surg Oncol, Little Rock, AR 72205 USA. Arkansas Canc Res Ctr, Little Rock, AR USA. Mt Sinai Sch Med, Ruttenberg Canc Ctr, New York, NY USA. RP Nowell, S (reprint author), Natl Ctr Toxicol Res, Div Mol Epidemiol, 3900 NCTR Dr,HFT 100, Jefferson, AR 72079 USA. OI Sweeney, Carol/0000-0003-1113-7160 NR 13 TC 98 Z9 103 U1 1 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD NOV 6 PY 2002 VL 94 IS 21 BP 1635 EP 1640 PG 6 WC Oncology SC Oncology GA 611YG UT WOS:000179045100011 PM 12419790 ER PT J AU Brorson, K de Wit, C Hamilton, E Mustafa, M Swann, PG Kiss, R Taticek, R Polastri, G Stein, KE Xu, Y AF Brorson, K de Wit, C Hamilton, E Mustafa, M Swann, PG Kiss, R Taticek, R Polastri, G Stein, KE Xu, Y TI Impact of cell culture process changes on endogenous retrovirus expression SO BIOTECHNOLOGY AND BIOENGINEERING LA English DT Article DE cell culture process changes; retrovirus expression; quantitave PCR; viral safety ID REVERSE-TRANSCRIPTASE ASSAY; MURINE LEUKEMIA-VIRUS; SODIUM-BUTYRATE; ENHANCE PRODUCTION; MAMMALIAN-CELLS; CHO CELLS; C VIRUSES; SEQUENCES; DNA; SUPPRESSION AB Cell culture process changes (e.g., changes in scale, medium formulation, operational conditions) and cell line changes are common during the development life cycle of a therapeutic protein. To ensure that the impact of such process changes on product quality and safety is minimal, it is standard practice to compare critical product quality and safety attributes before and after the changes. One potential concern introduced by cell culture process improvements is the possibility of increased endogenous retrovirus expression to a level above the clearance capability of the subsequent purification process. To address this, retrovirus expression was measured in scaled down and full production scaled Chinese hamster ovary (CHO) cell cultures of four monoclonal antibodies and one recombinant protein before and after process changes. Two highly sensitive, quantitative (Q)-PCR-based assays were used to measure endogenous retroviruses. It is shown that cell culture process changes that primarily alter media components, nutrient feed volume, seed density, cell bank source (i.e., master cell bank vs. working cell bank), and vial size, or culture scale, singly or in combination, do not impact the rate of retrovirus expression to an extent greater than the variability of the Q-PCR assays (0.2-0.5 log(10)). Cell culture changes that significantly alter the metabolic state of the cells and/or rates of protein expression (e.g., pH and temperature shifts, NaButyrate addition) measurably impact the rate of retrovirus synthesis (up to 2 log(10)). The greatest degree of variation in endogenous retrovirus expression was observed between individual cell lines (up to 3 log(10)). These data support the practice of measuring endogenous retrovirus output for each new cell line introduced into manufacturing or after process changes that significantly increase product-specific productivity or alter the metabolic state, but suggest that reassessment of retrovirus expression after other process changes may be unnecessary. (C) 2002 Wiley Periodicals, Inc. C1 Genentech Inc, San Francisco, CA 94080 USA. US FDA, Ctr Biol Evaluat & Res, Div Monoclonal Antibodies, Bethesda, MD 20892 USA. RP Xu, Y (reprint author), Genentech Inc, 1 DNA Way, San Francisco, CA 94080 USA. NR 55 TC 23 Z9 24 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0006-3592 J9 BIOTECHNOL BIOENG JI Biotechnol. Bioeng. PD NOV 5 PY 2002 VL 80 IS 3 BP 257 EP 267 DI 10.1002/bit.10366 PG 11 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 600TQ UT WOS:000178408000003 PM 12226857 ER PT J AU Cote, TR Kalra, S Gershon, S Brinker, A Lu, S Proestel, S Rihal, C John, B Braun, MM Bell, M AF Cote, TR Kalra, S Gershon, S Brinker, A Lu, S Proestel, S Rihal, C John, B Braun, MM Bell, M TI Severe pulmonary Hemorrhage among recipients of platelet glycoprotein IIb/IIIa inhibitors SO CIRCULATION LA English DT Meeting Abstract CT American-Heart-Association Abstracts From Scientific Sessions CY NOV 17-20, 2002 CL CHICAGO, ILLINOIS SP Amer Heart Assoc C1 Ctr Biol Evaluat & Res, Rockville, MD USA. US FDA, Rockville, MD 20857 USA. Mayo Clin, Rochester, MN 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 NOV 5 PY 2002 VL 106 IS 19 SU S MA 2213 BP 445 EP 445 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 613QJ UT WOS:000179142702251 ER PT J AU Delatour, T Richoz, J Vouros, P Turesky, RJ AF Delatour, T Richoz, J Vouros, P Turesky, RJ TI Simultaneous determination of 3-nitrotyrosine and tyrosine in plasma proteins of rats and assessment of artifactual tyrosine nitration SO JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES LA English DT Article DE nitration; nitrotyrosine; tyrosine; proteins ID MASS-SPECTROMETRIC QUANTIFICATION; NITRIC-OXIDE SYNTHASE; IN-VIVO; FERRIC NITRILOTRIACETATE; PEROXYNITRITE FORMATION; LIQUID-CHROMATOGRAPHY; OXIDATIVE DAMAGE; RENAL CARCINOGEN; NITROTYROSINE; INFLAMMATION AB A sensitive and specific isotope dilution liquid chromatography-electrospray tandem mass spectrometry method was developed for the determination of the 3-nitrotyrosine residue levels in rat plasma proteins. The assay is based on the cleavage of proteins with concentrated hydrochloric acid to release both 3-nitrotyrosine and tyrosine. To control the potential artifactual nitration of tyrosine residues during the proteolysis, samples are spiked with C-13(9)-labeled tyrosine and the level of C-13(9)-labeled 3-nitrotyrosine is measured. The clean-up process entails hydrolysate fortification with 2,5,643-3-nitrotyrosine, followed. by solid-phase extraction on octadecylsilyl (to isolate tyrosine) and aminopropylsilyl (to isolate 3-nitrotyrosine) cartridges. Tyrosine and 3-nitrotyrosine fractions are mixed in an appropriate ratio prior to the analysis. The method was applied to animals exposed to ferric nitrilotriacetate to induce oxidative stress. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Nestec Ltd, Nestle Res Ctr, CH-1000 Lausanne 26, Switzerland. Northeastern Univ, Boston, MA 02115 USA. Natl Ctr Toxicol Res, Div Chem, Jefferson, AR 72079 USA. RP Delatour, T (reprint author), Nestec Ltd, Nestle Res Ctr, Vers Chez Les Blanc, CH-1000 Lausanne 26, Switzerland. NR 32 TC 24 Z9 25 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1570-0232 J9 J CHROMATOGR B JI J. Chromatogr. B PD NOV 5 PY 2002 VL 779 IS 2 BP 189 EP 199 AR PII S1570-0232(02)00370-7 DI 10.1016/S1570-0232(02)00370-7 PG 11 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 609ZR UT WOS:000178936700004 PM 12361733 ER PT J AU Wagner, RF Beiden, SV Campbell, G Metz, CE Sacks, WM AF Wagner, RF Beiden, SV Campbell, G Metz, CE Sacks, WM TI Assessment of medical imaging and computer-assist systems: Lessons from recent experience SO ACADEMIC RADIOLOGY LA English DT Article DE computers, diagnostic aid; diagnostic radiology, observer performance; receiver operating characteristic curve (ROC) ID OPERATING CHARACTERISTIC ANALYSIS; MONTE-CARLO VALIDATION; DISCRETE RATING DATA; OF-VARIANCE MODELS; ROC ANALYSIS; OBSERVER-PERFORMANCE; AIDED DETECTION; SCREENING MAMMOGRAPHY; EXPERIMENTAL-DESIGN; DIGITAL MAMMOGRAPHY AB In the last 2 decades major advances have been made in the field of assessment methods for medical imaging and computer-assist systems through the use of the paradigm of the receiver operating characteristic (ROC) curve. In the most recent decade this methodology was extended to embrace the complication of reader variability through advances in the multiple-reader, multiple-case (MRMC) ROC measurement and analysis paradigm. Although this approach has been widely adopted by the imaging research community, some investigators appear averse to it, possibly from concern that it could place a greater burden on the scarce resources of patient cases and readers compared to the requirements of alternative methods. The present communication argues, however, that the MRMC ROC approach to assessment in the context of reader variability may be the most resource-efficient approach available. Moreover, alternative approaches may also be statistically uninterpretable with regard to estimated summary measures of performance and their uncertainties. The authors propose that the MRMC ROC approach be considered even more widely by the larger community with responsibilities for the introduction and dissemination of medical imaging technologies to society. General principles of study design are reviewed, and important contemporary clinical trials are used as examples. C1 US FDA, Ctr Devices & Radiol Hlth, Off Sci & Technol, Rockville, MD 20857 USA. US FDA, Ctr Devices & Radiol Hlth, Off Surveillance & Biometr, Rockville, MD 20857 USA. US FDA, Ctr Devices & Radiol Hlth, Off Device Evaluat, Rockville, MD 20857 USA. Univ Chicago, Dept Radiol, Rossmann Labs, Chicago, IL 60637 USA. RP US FDA, Ctr Devices & Radiol Hlth, Off Sci & Technol, 12720 Twinbrook Pkwy,Rm T153, Rockville, MD 20857 USA. FU NCI NIH HHS [R01-CA62362]; NIGMS NIH HHS [R01-GM57622] NR 84 TC 55 Z9 55 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1076-6332 EI 1878-4046 J9 ACAD RADIOL JI Acad. Radiol. PD NOV PY 2002 VL 9 IS 11 BP 1264 EP 1277 DI 10.1016/S1076-6332(03)80560-3 PG 14 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 611NB UT WOS:000179023000005 PM 12449359 ER PT J AU Chango, A Mircher, C James, SJ Rethore, MO Nicolas, JP AF Chango, A Mircher, C James, SJ Rethore, MO Nicolas, JP TI One carbon metabolism and trisomy 21: analysis of the impact of genetic polymorphism SO ANNALES DE BIOLOGIE CLINIQUE LA French DT Review DE folate; methylation; one carbon; trisomy 21; Down syndrome; genetic polymorphism ID METHYLENETETRAHYDROFOLATE REDUCTASE GENE; CYSTATHIONINE BETA-SYNTHASE; MATERNAL RISK-FACTORS; NEURAL-TUBE DEFECTS; DOWN-SYNDROME; HOMOCYSTEINE METABOLISM; COMMON MUTATION; FOLATE STATUS; S-ADENOSYLMETHIONINE; PLASMA HOMOCYSTEINE AB Trisomy 21 is the most common chromosome abnormality characterized by the presence of three copies of chromosome 21 in the genome. The clinical disorder attributed to trisomy 21 is Down syndrome. Patients with Down syndrome are heterogeneous in their phenotypic expression. Due to the location of the cystathionine beta-synthase gene on chromosome 21, and its involvement in one carbon metabolism, homocysteine levels have been found to be decreased in children with Down syndrome. The study of the regulation of one carbon metabolism in Down syndrome becomes important in light of possible normalization of the metabolic imbalance and the detection of increased sensitivity to therapeutic interventions. Thus, the importance of evaluating single nucleotide polymorphisms in genes involved in one carbon metabolism need to be addressed in individuals with trisomy 21. This review offers an analysis of the impact of these polymorphisms in Down syndrome and their possible implications for phenotypic heterogeneity. C1 ISAB, Dept Sci Nutr & Sante, F-60026 Beauvais, France. US FDA, NCTR, Div Biochem Toxicol, Rockville, MD 20857 USA. Ctr Med Jerome Lejeune, Paris, France. Fac Med, Lab Biochim Med & Pediat, Vandoeuvre Les Nancy, France. RP Chango, A (reprint author), ISAB, Dept Sci Nutr & Sante, BP 30313, F-60026 Beauvais, France. NR 50 TC 2 Z9 2 U1 0 U2 1 PU JOHN LIBBEY EUROTEXT LTD PI MONTROUGE PA 127 AVE DE LA REPUBLIQUE, 92120 MONTROUGE, FRANCE SN 0003-3898 J9 ANN BIOL CLIN-PARIS JI Ann. Biol. Clin. PD NOV-DEC PY 2002 VL 60 IS 6 BP 647 EP 653 PG 7 WC Medical Laboratory Technology; Medicine, Research & Experimental SC Medical Laboratory Technology; Research & Experimental Medicine GA 619YX UT WOS:000179506500003 PM 12446228 ER PT J AU Furst, DE Cush, J Kaufmann, S Siegel, J Kurth, R AF Furst, DE Cush, J Kaufmann, S Siegel, J Kurth, R TI Preliminary guidelines for diagnosing and treating tuberculosis in patients with rheumatoid arthritis in immunosuppressive trials or being treated with biological agents SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Article; Proceedings Paper CT 4th International Symposium on Advances in Targeted Therapies CY APR 28-MAY 01, 2002 CL MANDELIEU, FRANCE C1 Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. Presbyterian Med Ctr, Dallas, TX USA. Koch Inst, Berlin, Germany. US FDA, Washington, DC 20204 USA. RP Furst, DE (reprint author), 1000 Vet Ave Rehab Ctr,Rn 32-59, Los Angeles, CA 90095 USA. NR 2 TC 51 Z9 56 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD NOV PY 2002 VL 61 SU 2 BP 62 EP 63 PG 2 WC Rheumatology SC Rheumatology GA 609KZ UT WOS:000178903900015 ER PT J AU Simon, LS AF Simon, LS TI Pharmacovigilance: towards a better understanding of the benefit to risk ratio SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Article; Proceedings Paper CT 4th International Symposium on Advances in Targeted Therapies CY APR 28-MAY 01, 2002 CL MANDELIEU, FRANCE ID DRUG C1 US FDA, CDER, ODEV, Div Analges Antiflammatory & Ophthalmol, Rockville, MD 20850 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Simon, LS (reprint author), US FDA, CDER, ODEV, Div Analges Antiflammatory & Ophthalmol, 9201 Corporated Blvd,Room N-314,HFD 550, Rockville, MD 20850 USA. NR 6 TC 10 Z9 11 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD NOV PY 2002 VL 61 SU 2 BP 88 EP 89 PG 2 WC Rheumatology SC Rheumatology GA 609KZ UT WOS:000178903900024 ER PT J AU Rasooly, A Weisz, A AF Rasooly, A Weisz, A TI In vitro antibacterial activities of phloxine B and other halogenated fluoresceins against methicillin-resistant Staphylococcus aureus SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID REFINING COUNTERCURRENT CHROMATOGRAPHY; PREPARATIVE SEPARATION; SYNTHETIC MIXTURE; PURIFICATION; COMPONENTS AB Fluorescein dyes in which the benzoic acid moiety has been tetrachlorinated (50 to 100 mug/ml) inhibit in vitro Staphylococcus aureus growth (MIC, 25 mug/ml). Specifically, under standard room illumination, phloxine B at a concentration of 100 mug/ml killed 99% of the cultures (mid-log phase). It also reduced S. aureus CFU by 10(4). Structure-activity analysis revealed that the activity against S. aureus increases with the increase in the number of the substituting halogens in the hydroxyxanthene moiety. C1 US FDA, Ctr Food Safety & Appl Nutr, Off Cosmet & Colors, Washington, DC 20204 USA. US FDA, Off Plant & Dairy Foods & Beverages, College Pk, MD 20740 USA. RP Weisz, A (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Cosmet & Colors, HFS-126,200 C St SW, Washington, DC 20204 USA. NR 21 TC 15 Z9 15 U1 0 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 NOV PY 2002 VL 46 IS 11 BP 3650 EP 3653 DI 10.1128/AAC.46.11.3650-3653.2002 PG 4 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 606BK UT WOS:000178712800052 PM 12384384 ER PT J AU Lee, MD Sanchez, S Zimmer, M Idris, U Berrang, ME McDermott, PF AF Lee, MD Sanchez, S Zimmer, M Idris, U Berrang, ME McDermott, PF TI Class 1 integron-associated tobramycin-gentamicin resistance in Campylobacter jejuni isolated from the broiler chicken house environment SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID BETA-LACTAMASE; GENE CASSETTES; AMINOGLYCOSIDE 6'-N-ACETYLTRANSFERASE; ESCHERICHIA-COLI; DNA; EPIDEMIOLOGY; ELEMENTS; RECOMBINATION; TRIMETHOPRIM; PLASMID AB Using PCR, we screened 105 isolates of poultry-associated Campylobacter jejuni for the presence of class 1 integrons. Of those isolates, 21% (22 of 105) possessed the integrase gene, but only 5 isolates produced an amplicon in a 5'-3' conserved sequence PCR directed toward amplification of the resistance cassettes. DNA sequencing demonstrated that all five isolates possessed the aminoglycoside resistance gene, aacA4. C1 Univ Georgia, Dept Med Microbiol & Parasitol, Athens, GA 30602 USA. Univ Georgia, Athens Diagnost Lab, Athens, GA 30602 USA. Univ Georgia, Dept Environm Hlth Sci, Athens, GA 30602 USA. USDA, Poultry Prod & Meat Qual, Athens, GA 30604 USA. US FDA, Ctr Vet Med, Laurel, MD 20708 USA. RP Lee, MD (reprint author), Univ Georgia, Dept Med Microbiol & Parasitol, Athens, GA 30602 USA. NR 33 TC 39 Z9 44 U1 1 U2 6 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 2002 VL 46 IS 11 BP 3660 EP 3664 DI 10.1128/AAC.46.11.3660-3664.2002 PG 5 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 606BK UT WOS:000178712800055 PM 12384387 ER PT J AU Sau, S Bassen, HI Krauthamer, V AF Sau, S Bassen, HI Krauthamer, V TI Method for evaluating optical characteristics of endoscopes for recording fluorescence-related cardiac electrical activity SO APPLIED OPTICS LA English DT Article ID HEART AB Nondestructive methods were used to evaluate marketed fiber-optic endoscopes (intended for simple viewing) for fluorescence recording. Our application is for optical recording from the heart. For one angioscope, we measured a focal length of 0.33 mm, a field of view of 45degrees, an aperture of 0.26 mm, and an efficiency of 43%. We calculated that the angioscope would give a signal-to-noise ratio of 1.0 for a cardiac action potential, if its field of view were divided into a nine-pixel array (for safe continuous illumination). Our methods are useful in designing and evaluating fluorescence fiber-optic systems with superior signal quality and spatial resolution. (C) 2002 Optical Society of America. C1 Duke Univ, Dept Biomed Engn, Durham, NC 27708 USA. US FDA, Electrophys Branch HFZ133, Ctr Devices & Radiol Hlth, Rockville, MD 20852 USA. RP Sau, S (reprint author), Duke Univ, Dept Biomed Engn, Durham, NC 27708 USA. EM vik@cdrh.fda.gov NR 12 TC 2 Z9 2 U1 0 U2 0 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1559-128X EI 2155-3165 J9 APPL OPTICS JI Appl. Optics PD NOV 1 PY 2002 VL 41 IS 31 BP 6725 EP 6730 DI 10.1364/AO.41.006725 PG 6 WC Optics SC Optics GA 608LJ UT WOS:000178847600021 PM 12412663 ER PT J AU Ng, C Losso, JN Marshall, WE Rao, RM AF Ng, C Losso, JN Marshall, WE Rao, RM TI Freundlich adsorption isotherms of agricultural by-product-based powdered activated carbons in a geosmin-water system SO BIORESOURCE TECHNOLOGY LA English DT Article DE activated carbon; pecan shells; sugarcane bagasse; geosmin; Freundlich model; adsorption isotherm ID DRINKING-WATER; ORGANIC POLLUTANTS; OFF-FLAVORS; METHYLISOBORNEOL; REMOVAL; CATFISH; MIB AB The present study was designed to model the adsorption of geosmin from water under laboratory conditions using the Freundlich isotherm model. This model was used to compare the efficiency of sugarcane bagasse and pecan shell-based powdered activated carbon to the efficiency of a coal-based commercial activated carbon (Calgon Filtrasorb 400). When data were generated from Freundlich isotherms, Calgon Filtrasorb 400 had greater geosmin adsorption at all geosmin concentrations studied than the laboratory produced steam-activated pecan shell carbon, steam-activated bagasse carbon, and the CO(-)activated pecan shell carbon. At geosmin concentrations < 0.07 mug/l for the phosphoric acid-activated pecan shell carbon and below 0.08 mug/l for a commercially produced steam-activated pecan shell carbon obtained from Scientific Carbons, these two carbons had a higher calculated geosmin adsorption than Filtrasorb 400. While the commercial carbon was more efficient than some laboratory prepared carbons at most geosmin concentrations, the results indicate that when the amount of geosmin was below the threshold level of human taste (about 0.1 mug/l), the phosphoric acid-activated pecan shell carbon and the Scientific Carbons sample were more efficient than Filtrasorb 400 at geosmin removal. (C) 2002 Elsevier Science Ltd. All rights reserved. C1 Louisiana State Univ, Ctr Agr, Dept Food Sci, Baton Rouge, LA 70820 USA. Dept Hlth & Human Serv, Food & Drug Adm, Lenexa, KS 66285 USA. USDA ARS, So Reg Res Ctr, New Orleans, LA 70179 USA. RP Losso, JN (reprint author), Louisiana State Univ, Ctr Agr, Dept Food Sci, 111 Food Sci Bldg, Baton Rouge, LA 70820 USA. NR 23 TC 115 Z9 118 U1 2 U2 29 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0960-8524 J9 BIORESOURCE TECHNOL JI Bioresour. Technol. PD NOV PY 2002 VL 85 IS 2 BP 131 EP 135 AR PII S0960-8524(02)00093-7 DI 10.1016/S0960-8524(02)00093-7 PG 5 WC Agricultural Engineering; Biotechnology & Applied Microbiology; Energy & Fuels SC Agriculture; Biotechnology & Applied Microbiology; Energy & Fuels GA 586LX UT WOS:000177586400005 PM 12227536 ER PT J AU Palom, Y Kumar, GS Tang, LQ Paz, MM Musser, SM Rockwell, S Tomasz, M AF Palom, Y Kumar, GS Tang, LQ Paz, MM Musser, SM Rockwell, S Tomasz, M TI Relative toxicities of DNA cross-links and monoadducts: New insights from studies of decarbamoyl mitomycin C and mitomycin C SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID MAMMARY-TUMOR CELLS; REDUCTIVE ACTIVATION; CYTOSINE METHYLATION; SEQUENCE SPECIFICITY; HYPOXIC CONDITIONS; MINOR-GROOVE; ADDUCTS; ALKYLATION; GUANINE; REPAIR AB Mitomycin C (MC), a cytotoxic anticancer drug and bifunctional DNA DNA alkylating agent, induces cross-linking of the complementary strands of DNA. The DNA interstrand cross-links (ICLs) are thought to be the critical cytotoxic lesions produced by MC. Decarbamoyl mitomycin C (DMC) has been regarded as a monofunctional mitomycin, incapable of causing ICLs. Paradoxically, DMC is slightly more toxic than MC to hypoxic EMT6 mouse mammary tumor cells as well as to CHO cells. To resolve this paradox, EMT6 cells were treated with MC or DMC under hypoxia at equimolar concentrations and the resulting DNA adducts were analyzed using HPLC and UV detection. MC treatment generated both intrastrand And interstrand cross-link adducts and four monoadducts, as shown previously. DMC generated two stereoisomeric monoadducts and two stereoisomeric ICL adducts, all of which were structurally characterized; one was identical with that formed with MC, the other was new and unique to DMC. Overall, adduct frequencies were strikingly higher (20-30-fold) with DMC than with MC. Although DMC monoadducts greatly exceeded DMC cross-link adducts (similar to 10: 1 ratio), the latter were equal or higher in number than the cross-link adducts from MC. DMC displayed a much higher monoadduct:cross-link ratio than MC. The similar cytotoxicities of the two drug show a correlation with their similar DNA cross-link adduct frequencies, but not with their total adduct or monoadduct frequencies. This provides specific experimental evidence that the ICLs rather than the monoadducts are critical factors in the cell death induced by MC. In vitro, overall alkylation of calf thymus DNA by DMC was much less efficient than by MC. Nevertheless, ICLs formed with DMC were clearly detectable. The chemical pathway of the cross-linking was shown to be analogous to that occurring with MC. These results also suggest that the differential sensitivity of Fanconi's Anemia cells to MC and DMC is related to factors other than a selective defect in cross-link repair. C1 CUNY Hunter Coll, Dept Chem, New York, NY 10021 USA. Yale Univ, Sch Med, Dept Therapeut Radiol, New Haven, CT 06520 USA. US FDA, College Pk, MD 20740 USA. RP Tomasz, M (reprint author), CUNY Hunter Coll, Dept Chem, New York, NY 10021 USA. RI Paz, Manuel/F-2732-2011; Rockwell, Sara/B-8458-2009 OI Paz, Manuel/0000-0002-5734-1266; FU NCI NIH HHS [CA28681, CA71961]; NCRR NIH HHS [RR03037] NR 47 TC 59 Z9 60 U1 1 U2 10 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD NOV PY 2002 VL 15 IS 11 BP 1398 EP 1406 DI 10.1021/tx020044g PG 9 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 617TT UT WOS:000179377500007 PM 12437330 ER PT J AU Reed, GF Lynn, F Meade, BD AF Reed, GF Lynn, F Meade, BD TI Use of coefficient of variation in assessing variability of quantitative assays SO CLINICAL AND DIAGNOSTIC LABORATORY IMMUNOLOGY LA English DT Article ID IMMUNOSORBENT AB We have derived the mathematical relationship between the coefficient of variation associated with repeated measurements from quantitative assays and the expected fraction of pairs of those measurements that differ by at least some given factor, i.e., the expected frequency of disparate results that are due to assay variability rather than true differences. Knowledge of this frequency helps determine what magnitudes of differences can be expected by chance alone when the particular coefficient of variation is in effect. This frequency is an operational index of variability in the sense that it indicates the probability of observing a particular disparity between two measurements under the assumption that they measure the same quantity. Thus the frequency or probability becomes the basis for assessing if an assay is sufficiently precise. This assessment also provides a standard for determining if two assay results for the same subject, separated by an intervention such as vaccination or infection, differ by more than expected from the variation of the assay, thus indicating an intervention effect. Data from an international collaborative study are used to illustrate the application of this proposed interpretation of the coefficient of variation, and they also provide support for the assumptions used in the mathematical derivation. C1 NEI, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Rockville, MD USA. RP Reed, GF (reprint author), NEI, NIH, 31 Ctr Dr,MSC 2510,Bldg 31,room 6A52, Bethesda, MD 20892 USA. NR 5 TC 162 Z9 163 U1 1 U2 25 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1071-412X J9 CLIN DIAGN LAB IMMUN JI Clin. Diagn. Lab. Immunol. PD NOV PY 2002 VL 9 IS 6 BP 1235 EP 1239 DI 10.1128/CDLI.9.6.1235-1239.2002 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 615WV UT WOS:000179271100014 PM 12414755 ER PT J AU Kawakami, M Kawakami, K Stepensky, VA Maki, RA Robin, H Muller, W Husain, SR Puri, RK AF Kawakami, M Kawakami, K Stepensky, VA Maki, RA Robin, H Muller, W Husain, SR Puri, RK TI Interleukin 4 receptor on human lung cancer: A molecular target for cytotoxin therapy SO CLINICAL CANCER RESEARCH LA English DT Article ID CIRCULARLY PERMUTED INTERLEUKIN-4; RECOMBINANT HUMAN INTERLEUKIN-4; BREAST-CARCINOMA CELLS; COMMON GAMMA-CHAIN; PSEUDOMONAS EXOTOXIN; ANTITUMOR-ACTIVITY; CHIMERIC PROTEIN; FUSION PROTEIN; IL-4 RECEPTORS; IN-VITRO AB Previous studies have demonstrated that human lung tumor cell lines express interleukin 4 (IL-4) receptors, and IL-4 can mediate modest to moderate antiproliferative activity in vitro and in vivo in animal models of human lung tumors. On the basis of these studies, IL-4 was tested in clinical trials; however, it showed little antitumor activity in lung cancer patients. In the present study, we examined the expression of IL-4 receptors (IL-41ts) in lung tumor samples and normal lung tissues and tested whether an IL-4R targeted agent will have better antitumor activity in vitro and in vivo compared with IL-4. IL-4R expression was tested by immunohistochemistry in 54 lung tumor samples and normal lung tissues in a tissue array, by reverse-transcription PCR and Northern blot analyses in lung tumor cell lines. Cytotoxic activity of IL-4 cytotoxin [IL-4(38-37)-PE38KDEL], composed of a circular permuted IL-4 and a mutated form of Pseudomonas exotoxin (PE38KDEL) was tested by protein synthesis inhibition and clonogenic assays in seven lung tumor cell lines. Antitumor activity of IL-4 cytotoxin was tested in vitro and in immunodeficient animal models of human lung tumors. We observed that IL-4Rs are expressed at higher levels in situ in lung tumor samples compared with normal lung tissues and IL-4 cytotoxin is highly and specifically cytotoxic to lung tumor cell lines in vitro. Intratumoral and i.p. administration of IL-4 cytotoxin to immunodeficient mice with s.c. established human lung H358 non-small cell lung cancer tumors mediated considerable antitumor activity in a dose-dependent manner with the higher dose producing durable complete responses. On the other hand, H460 non-small cell lung cancer tumors expressing low levels of IL-4R did not respond to IL-4 cytotoxin therapy. Because IL-4 cytotoxin mediates its antitumor activity through IL-4R, and a variety of lung tumors expressed high levels of IL-4R, we propose testing the safety of this agent in patients with lung cancer. C1 US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Lab Mol Tumor Biol,NIH, Bethesda, MD 20892 USA. Neurosci Biosci Inc, San Diego, CA 92121 USA. Sharp Mem Hosp & Rehabil Ctr, San Diego, CA 90034 USA. RP Puri, RK (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Lab Mol Tumor Biol,NIH, Bldg 29B,Room 2NN10,29 Lincoln Dr MSC 4555, Bethesda, MD 20892 USA. NR 32 TC 30 Z9 31 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 2002 VL 8 IS 11 BP 3503 EP 3511 PG 9 WC Oncology SC Oncology GA 615UY UT WOS:000179266400027 PM 12429641 ER PT J AU Moody, JD Freeman, JP Fu, PP Cerniglia, CE AF Moody, JD Freeman, JP Fu, PP Cerniglia, CE TI Biotransformation of mirtazapine by Cunninghamella elegans SO DRUG METABOLISM AND DISPOSITION LA English DT Article ID STEREOSELECTIVE FUNGAL METABOLISM; IN-VIVO; ANTIDEPRESSANT AB The fungus Cunninghamella elegans was used as a microbial model of mammalian metabolism to biotransform the tetracyclic antidepressant drug mirtazapine, which is manufactured as a racemic mixture of R(-)- and S(+)-enantiomers. In 168 h, C. elegans transformed 91% of the drug into the following seven metabolites: 8-hydroxymirtazapine, N-desmethyl-8-hydroxymirtazapine, N-desmethylmirtazapine, 13-hydroxymirtazapine, mirtazapine N-oxide, 12-hydroxymirtazapine, and N-desmethyl-13-hydroxymirtazapine. Circular dichroism spectral analysis of unused mirtazapine indicated that it was slightly enriched with the R(-)- enantiomer. When the fungus was treated with the optically pure forms of the drug, the S(+)-enantiomer produced all seven metabolites whereas the R(-)- enantiomer produced only 8-hydroxymirtazapine, N-desmethyl-8-hydroxymirtazapine, N-desmethylmirtazapine, and mirtazapine N-oxide. C. elegans produced five mammalian and two novel metabolites and is therefore a suitable microbial model for mirtazapine metabolism. C1 Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. Natl Ctr Toxicol Res, Div Chem, Jefferson, AR 72079 USA. Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Cerniglia, CE (reprint author), Natl Ctr Toxicol Res, Div Microbiol, HFT-250, Jefferson, AR 72079 USA. NR 24 TC 25 Z9 27 U1 1 U2 8 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 NOV PY 2002 VL 30 IS 11 BP 1274 EP 1279 DI 10.1124/dmd.30.11.1274 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 604VL UT WOS:000178641700019 PM 12386135 ER PT J AU Weinstein, JN Reinhold, WC Bussey, K Nishizuka, S Kane, D Gray, J Petricoin, E Liotta, L Kirsch, I Buetow, K AF Weinstein, JN Reinhold, WC Bussey, K Nishizuka, S Kane, D Gray, J Petricoin, E Liotta, L Kirsch, I Buetow, K TI An integrated approach to the pharmacogenomics and pharmacoproteomics of cancer SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT 14th EORTC/NCI/AACR Symposium on Molecular Targets and Cancer Therapeutics CY NOV 19-22, 2002 CL FRANKFURT, GERMANY ID MOLECULAR PHARMACOLOGY; EXPRESSION DATABASE; CELL-LINES; INFORMATION; PATTERNS C1 US Natl Canc Inst, Bethesda, MD USA. SRA Int, Fairfax, VA USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. US FDA, Bethesda, MD 20014 USA. NR 11 TC 0 Z9 0 U1 1 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD NOV PY 2002 VL 38 SU 7 MA 310 BP S94 EP S95 PG 2 WC Oncology SC Oncology GA 626VZ UT WOS:000179895700312 ER PT J AU Wear, KA AF Wear, KA TI A Gaussian framework for modeling effects of frequency-dependent attenuation, frequency-dependent scattering, and gating SO IEEE TRANSACTIONS ON ULTRASONICS FERROELECTRICS AND FREQUENCY CONTROL LA English DT Article ID ACOUSTIC BACKSCATTER COEFFICIENTS; NORMAL RENAL PARENCHYMA; HUMAN TRABECULAR BONE; ULTRASONIC BACKSCATTER; SPEED MEASUREMENTS; SPECTRUM ANALYSIS; DATA REDUCTION; TISSUE; ANISOTROPY; BLOOD AB For a wide range of applications in medical ultrasound, power spectra of received signals are approximately Gaussian. It has been established previously that an ultrasound beam with a Gaussian spectrum propagating through a medium with linear attenuation remains Gaussian. In this paper, Gaussian transformations are derived to model the effects of scattering (according to a power law, as is commonly applicable in soft tissues, especially over limited frequency ranges) and gating (with a Hamming window, a commonly used gate function). These approximations are shown to be quite accurate even for relatively broad band systems with fractional bandwidths approaching 100%. The theory is validated by experiments in phantoms consisting of glass particles suspended in agar. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20852 USA. RP Wear, KA (reprint author), US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20852 USA. NR 42 TC 15 Z9 18 U1 0 U2 2 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 USA SN 0885-3010 J9 IEEE T ULTRASON FERR JI IEEE Trans. Ultrason. Ferroelectr. Freq. Control PD NOV PY 2002 VL 49 IS 11 BP 1572 EP 1582 DI 10.1109/TUFFC.2002.1049739 PG 11 WC Acoustics; Engineering, Electrical & Electronic SC Acoustics; Engineering GA 615AR UT WOS:000179224100013 PM 12484480 ER PT J AU Cerveny, KE DePaola, A Duckworth, DH Gulig, PA AF Cerveny, KE DePaola, A Duckworth, DH Gulig, PA TI Phage therapy of local and systemic disease caused by Vibrio vulnificus in iron-dextran-treated mice SO INFECTION AND IMMUNITY LA English DT Article ID OYSTERS CRASSOSTREA-VIRGINICA; FIELD GEL-ELECTROPHORESIS; ESCHERICHIA-COLI DIARRHEA; EXTRACELLULAR CYTOLYSIN; PHENOTYPIC EVALUATION; HUMAN-SERUM; BACTERIOPHAGES; VIRULENCE; PATHOGENESIS; INFECTIONS AB Vibrio vulnificus is a gram-negative bacterium that contaminates filter-feeding shellfish such as oysters. After ingestion of contaminated oysters, predisposed people may experience highly lethal septicemia. Contamination of wounds with the bacteria can result in devastating necrotizing fasciitis, which can progress to septicemia. The extremely rapid progression of these diseases can render antibiotic treatment ineffective, and death is a frequent outcome. In this study, we examined the potential use of bacteriophages as therapeutic agents against V. vulnificus in an iron-dextran-treated mouse model of V. vulnificus infection. Mice were injected subcutaneously with 10 times the lethal dose of V. vulnificus and injected intravenously, either simultaneously or at various times after infection, with phages. Treatment of mice with phages could prevent death; systemic disease, as measured by CFU per gram of liver and body temperature; and local disease, as measured by CFU per gram of lesion material and histopathologic analysis. Two different phages were effective against three different V. vulnificus strains with various degrees of virulence, while a third phage that required the presence of seawater to lyse bacteria in vitro was ineffective at treating mice. Optimum protection required that the phages be administered within 3 It of bacterial inoculation at doses as high as 10(8) PFU. One of the protective phages had a half-life in blood of over 2 h. These results demonstrate that bacteriophages have therapeutic potential for-both localized and systemic infections caused by V. vulnificus in animals. This model should be useful in answering basic questions regarding phage therapy. C1 Univ Florida, Coll Med, Dept Mol Genet & Microbiol, Gainesville, FL 32610 USA. US FDA, Gulf Coast Seafood Lab, Dauphin Isl, AL 36528 USA. RP Gulig, PA (reprint author), Univ Florida, Coll Med, Dept Mol Genet & Microbiol, Box 100266, Gainesville, FL 32610 USA. NR 46 TC 85 Z9 92 U1 2 U2 11 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD NOV PY 2002 VL 70 IS 11 BP 6251 EP 6262 DI 10.1128/IAI.70.11.6251-6262.2002 PG 12 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 605JQ UT WOS:000178675100041 PM 12379704 ER PT J AU Xue, HH Fink, DW Zhang, XL Qin, J Turck, CW Leonard, WJ AF Xue, HH Fink, DW Zhang, XL Qin, J Turck, CW Leonard, WJ TI Serine phosphorylation of Stat5 proteins in lymphocytes stimulated with IL-2 SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE cytokine; mass spectrometry; retroviral transduction; signal transduction; T lymphocyte ID MAMMARY-GLAND; ACTIVATION; TYROSINE; TRANSACTIVATION; INTERLEUKIN-2; TRANSCRIPTION; EXPRESSION; REQUIRES; PATHWAY; FAMILY AB Tyrosine phosphorylation regulates cytokine-induced dimerization of STAT proteins. Serine phosphorylation has also been found to occur in a number of STAT proteins, including Stat1, Sat3, Stat4, Stat5a, Stat5b and Stat6, and was shown to be important for maximal transcriptional activation mediated by Stat1, Stat3 and Stat4, but not for Stat5a or Stat5b. As these latter proteins were studied in transiently transfected COS-7 cells stimulated with prolactin, we sought to further investigate the significance of their serine phosphorylation in a more physiologically based system in response to IL-2. Both Stat5a and Stat5b were rapidly phosphorylated on serine in response to IL-2 and the phosphorylation site in Stat5a was mapped to Ser780, which is not conserved in Stat5b. In vitro studies with reporter constructs, and experiments in which wild-type and mutant Stat5a retroviruses were used to transduce Stat5a-deficient splenocytes revealed that the serine mutant constructs were not diminished in their ability to mediate IL-2 signaling and if anything exhibited augmented proliferative capability. Thus, in contrast to the apparent importance of serine phosphorylation for transcriptional activation by Stat1, Stat3 and Stat4 in response to IFN, IL-6 and IL-12 respectively, serine phosphorylation of Stat5a does not enhance Stat5a-mediated signaling in response to IL-2. C1 NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. US FDA, CBER, Lab Stem Cell Biol Neurotroph Factors, Rockville, MD 20825 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94143 USA. RP Leonard, WJ (reprint author), NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. EM wjl@helix.nih.gov NR 30 TC 14 Z9 15 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD NOV PY 2002 VL 14 IS 11 BP 1263 EP 1271 DI 10.1093/intimm/dxf101 PG 9 WC Immunology SC Immunology GA 611TP UT WOS:000179034100004 PM 12407017 ER PT J AU D'Antonio, A Losito, S Pignata, S Grassi, M Perrone, F De Luca, A Tambaro, R Bianco, C Gullick, WJ Johnson, GR Iaffaioli, VR Salomon, DS Normanno, N AF D'Antonio, A Losito, S Pignata, S Grassi, M Perrone, F De Luca, A Tambaro, R Bianco, C Gullick, WJ Johnson, GR Iaffaioli, VR Salomon, DS Normanno, N TI Transforming growth factor alpha, amphiregulin and cripto-1 are frequently expressed in advanced human ovarian carcinomas SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE cripto-1; amphiregulin; TGF alpha; ovarian cancer; prognosis ID FACTOR-RELATED PROTEINS; EGF SUPERGENE FAMILY; BREAST-CANCER CELLS; FACTOR RECEPTOR; ANTISENSE OLIGONUCLEOTIDES; IMMUNOHISTOCHEMICAL DETECTION; HUMAN MALIGNANCIES; EPITHELIAL-CELLS; MESSENGER-RNA; COLON AB The expression of transforming growth factor alpha (TGFalpha), amphiregulin (AR) and cripto-1 (CR-1) was assessed by immunohistochemistry in 83 specimens (59 primary ovarian tumors and 24 extra-ovarian carcinomas) that were obtained from 68 ovarian carcinoma patients. Within the 59 primary tumors, 54 (92%) expressed immunoreactive TGFalpha, 45 (76%) expressed AR, and 28 (47%) expressed CR-1. The expression of AR and CR-1 mRNAs in the ovarian carcinomas was also demonstrated by RT-PCR analysis. Seventeen extra-ovarian specimens (71%) were found to express CR-1, whereas AR and TGFalpha were expressed respectively in 21 (87%) and 22 (92%) extra-ovarian tissues. In 15 cases for whom both ovarian and extra-ovarian tissues were available, a statistically significant higher expression of CR-1 was found in extra-ovarian specimens. A statistically significant correlation was found between AR expression in the ovarian carcinomas and both low grade and low proliferative activity. Finally, expression of TGFalpha was predictive of longer progression-free survival. These data strongly suggest that the EGF-related peptides might be involved in the pathogenesis and outcome of human ovarian cancer. C1 ITN Fdn Pascale, Serv Oncol Spimentale D, I-80131 Naples, Italy. ITN Fdn Pascale, Serv Anat Patol, I-80131 Naples, Italy. ITN Fdn Pascale, Div Oncol Med B, I-80131 Naples, Italy. ITN Fdn Pascale, Ufficio Sperimentaz Clin Controllate, I-80131 Naples, Italy. AORN Cardarelli, Naples, Italy. NCI, Tumor Growth Factor Sect, Basic Res Lab, NIH, Bethesda, MD 20892 USA. Univ Kent, Dept Biosci, Canterbury CT2 7NJ, Kent, England. US FDA, DTP, Bethesda, MD 20892 USA. RP Normanno, N (reprint author), ITN Fdn Pascale, Serv Oncol Spimentale D, I-80131 Naples, Italy. RI De Luca, Antonella/J-8737-2016; OI De Luca, Antonella/0000-0001-5762-447X; Normanno, Nicola/0000-0002-7158-2605 NR 32 TC 53 Z9 54 U1 1 U2 3 PU PROFESSOR D A SPANDIDOS PI ATHENS PA 1, S MERKOURI ST, EDITORIAL OFFICE,, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD NOV PY 2002 VL 21 IS 5 BP 941 EP 948 PG 8 WC Oncology SC Oncology GA 603RX UT WOS:000178574600003 PM 12370739 ER PT J AU Khan, AA Kim, SJ Paine, DD Cerniglia, CE AF Khan, AA Kim, SJ Paine, DD Cerniglia, CE TI Classification of a polycyclic aromatic hydrocarbon-metabolizing bacterium, Mycobacterium sp strain PYR-1, as Mycobacterium vanbaalenii sp nov. SO INTERNATIONAL JOURNAL OF SYSTEMATIC AND EVOLUTIONARY MICROBIOLOGY LA English DT Article DE Mycobacterium vanbaalenii; rapidly growing bacteria; polycyclic aromatic hydrocarbon metabolizing bacteria; 16S rDNA; fatty acid analysis ID PYRENE-DEGRADING BACTERIUM; NUCLEOTIDE-SEQUENCE; DEGRADATION; PHENANTHRENE; MINERALIZATION; FLUORANTHENE; BENZOPYRENE; IDENTIFICATION; EXPRESSION; ANTHRACENE AB A polycyclic aromatic hydrocarbon (PAH)-utilizing Mycobacterium strain, PYR-1(T), was isolated from petroleum-contaminated estuarine sediments and has been shown by 16S rRNA gene sequencing to be closely related to Mycobacterium aurum ATCC 23366(T) and Mycobacterium vaccae ATCC 15438(T). In this investigation, the 16S rDNA, fatty acid methyl esters, DNA-DNA hybridization, PFGE analysis of restriction-digested total genomic DNA and biochemical tests were used to determine the taxonomic relationship of strain PYR-1(T) to other closely related Mycobacterium species. The sequence of the 16S rRNA gene of strain PYR-1(T) was similar to that of Mycobacterium austroafricanum ATCC 33464(T), except for one gap at position 43. Fatty acid methyl ester analysis also showed similarity to M. austroafricanum ATCC 33464(T); however, the Euclidean distance was greater than 4.0, indicating that these strains were not identical. Dot-blot DNA-DNA hybridization of strain PYR-1(T) with M. austroafricanum indicated less than 40% relatedness. When the total chromosomal DNA of M. aurum ATCC 23366(T), M. austroafricanum ATCC 33464(T) and strain PYR-1(T) was digested with restriction enzyme XbaI and analysed by PFGE, all three organisms gave different restriction patterns. Previous studies from our laboratory have shown that the reverse-phase HPLC elution profiles of mycolic acids of strain PYR-1(T) and M. austroafricanum ATCC 33464(T) have different patterns. Based on phylogenetic analysis using 16S rRNA gene sequences, fatty acid analysis, DNA-DNA hybridization and PFGE analysis and physiological and chemotaxonomic characteristics, it is concluded that strain PYR-1(T) (= DSM 7251(T) = NRRL B-24157(T)) represents a novel species of the genus Mycobacterium, for which the name Mycobacterium vanbaalenii sp. nov. is proposed. 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, 3900 NCTR Rd, Jefferson, AR 72079 USA. NR 45 TC 61 Z9 62 U1 0 U2 12 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 1466-5026 J9 INT J SYST EVOL MICR JI Int. J. Syst. Evol. Microbiol. PD NOV PY 2002 VL 52 BP 1997 EP 2002 DI 10.1099/ijs.0.02163-0 PN 6 PG 6 WC Microbiology SC Microbiology GA 625WG UT WOS:000179838100012 PM 12508859 ER PT J AU Khachik, F de Moura, FF Zhao, DY Aebischer, CP Bernstein, PS AF Khachik, F de Moura, FF Zhao, DY Aebischer, CP Bernstein, PS TI Transformations of selected carotenoids in plasma, liver, and ocular tissues of humans and in nonprimate animal models SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article; Proceedings Paper CT 13th International Carotenoid Symposium CY JAN 07-11, 2002 CL HONOLULU, HAWAII ID MACULAR DEGENERATION; STRUCTURAL ELUCIDATION; TECHNICAL PROCEDURES; OXIDATION-PRODUCTS; VISUAL PIGMENTS; OIL DROPLETS; HUMAN RETINA; ZEAXANTHIN; IDENTIFICATION; LUTEIN AB PURPOSE. To determine the stereochemistry of carotenoids in human ocular tissues in comparison with plasma and liver and to elucidate the possible transformations of dietary (3R,3'R,6'R)-lutein and (3R,3'R)-zeaxanthin in the eye. Similarly, to characterize the carotenoid profiles in the eye tissues, plasma, and liver of quails and frogs to determine whether these can serve as appropriate nonprimate animal models for metabolic studies. METHODS. Configurational isomers of carotenoids and their nondietary by-products from pooled human plasma, liver, retinal pigment epithelium (RPE-choroid), ciliary body, iris, and lens were characterized and quantified by high-performance liquid chromatography (HPLC) on a chiral column. Carotenoids and their nondietary by-products in pooled extracts from quail and frog plasma, liver, retina, RPE-choroid, iris, and lens were similarly characterized and quantified. RESULTS. (3R,3'R,6'R)-lutein, ORSR)-zeaxanthin, (3R,3'S; meso)-zeaxanthin, (3R,3'S,6'R)-lutein (3'-epilutein), 3-hydroxy-beta,epsilon-carotene-3'-one, and 5Z- and all-E-lycopene were detected in nearly all human ocular tissues examined. (3R,3'S; meso)zeaxanthin was not detected in the human plasma and liver but was present in human macula, retina, and RPE-choroid. (3S,3'S)-zeaxanthin was detected in human macula in minute quantities. The carotenoid profiles in quail and frog ocular tissues were somewhat similar to those in humans, with the exception that lycopene was absent. Frog retina, plasma, and liver revealed the presence of (3S,3'S)-zeaxanthin. C1 Univ Maryland, Dept Chem & Biochem, Joint Inst Food Safety & Appl Nutr, College Pk, MD 20742 USA. Univ Utah, Sch Med, Dept Ophthalmol & Visual Sci, Salt Lake City, UT USA. Roche Vitamins Ltd, Basel, Switzerland. RP Khachik, F (reprint author), Univ Maryland, Dept Chem & Biochem, Joint Inst Food Safety & Appl Nutr, Bldg 091, College Pk, MD 20742 USA. RI Khachik, Frederick/C-5055-2009 FU NEI NIH HHS [EY11600] NR 44 TC 126 Z9 134 U1 1 U2 4 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD NOV PY 2002 VL 43 IS 11 BP 3383 EP 3392 PG 10 WC Ophthalmology SC Ophthalmology GA 609AB UT WOS:000178879500005 PM 12407147 ER PT J AU Creticos, PS Adams, WR Petty, BG Lewis, LD Singh, GJP Khattignavong, AP Molzon, JA Martinez, MN Lietman, PS Williams, RL AF Creticos, PS Adams, WR Petty, BG Lewis, LD Singh, GJP Khattignavong, AP Molzon, JA Martinez, MN Lietman, PS Williams, RL TI A methacholine challenge dose-response study for development of a pharmacodynamic bioequivalence methodology for albuterol metered-dose inhalers SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE asthma; albuterol metered-dose inhaler; bioequivalence; dose-response; methacholine challenge ID IN-VIVO BIOEQUIVALENCE; INHALATION AEROSOLS; P-PHARM; HISTAMINE; ASTHMA; BRONCHOPROVOCATION; PHARMACOKINETICS; METAPROTERENOL; VENTOLIN; BIOASSAY AB Background: With the expiration of the patent on albuterol metered-dose inhalers (MDIs) in 1989, methods to assess in vivo bioequivalence of generic formulations required investigation. Objective: In an effort to develop a sensitive method to document bioequivalence, bronchoprovocation with methacholine chloride was used to assess the dose-response relationship of albuterol as delivered by MDI. Sensitivity was assessed in terms of magnitudes of ED50, the estimated albuterol dose required to achieve 50% of the fitted maximal value of the pharmacodynamic effect above baseline, and change in response as a function of dose, with emphasis on 1 and 2 actuations. Methods: On separate study days, 15 nonsmokers with mild asthma received randomized nominal albuterol doses of 0 to 576 mug by using specially manufactured MDI canisters. FEV1 was measured 15 minutes after MDI dosing. Serially increasing doses of methacholine were administered, and FEV1 was measured after each methacholine dose until a 20% decrease in FEV1 (PD20) was achieved. Results: Mean PD20 values after use of each of the albuterol-containing MDIs were significantly greater than either mean screening or mean placebo PD20 values (P < .05). Mean responses and most individual subject responses to 1 and 2 actuations (90 and 180 mug) of albuterol MDI were within the sensitive region of the dose-response curve. The mean estimated ED50 value on the basis of nonlinear mixed effect modeling was 119.2 mug (range, 33.3-337.1 mug), with an intersubject percentage coefficient of variation of 69.0%. Conclusions: The methacholine bronchoprovocation model is safe and useful in the study of albuterol MDI dose-response in Asthmatic subjects. Bronchoprovocation studies may be used for determination of bioequivalence of multisource albuterol MDI products. C1 Johns Hopkins Univ, Sch Med, Dept Med, Div Clin Immunol, Baltimore, MD 21205 USA. US FDA, Ctr Drug Evaluat & Res, Off Pharmaceut Sci, Off Gener Drugs, Rockville, MD 20857 USA. Johns Hopkins Sch Med, Dept Med, Div Clin Pharmacol, Baltimore, MD USA. RP Creticos, PS (reprint author), Johns Hopkins Asthma & Allergy Ctr, 5501 Bayview Circle, Baltimore, MD 21224 USA. NR 37 TC 16 Z9 16 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 NOV PY 2002 VL 110 IS 5 BP 713 EP 720 DI 10.1067/mai.2002.129036 PG 8 WC Allergy; Immunology SC Allergy; Immunology GA 612NN UT WOS:000179082500005 PM 12417879 ER PT J AU Clark, SB O'Rangers, JJ Rowe, WD Madson, MR Hurlbut, JA Sofos, JN Fuerst, B James, G Griffith, S Readnour, RS AF Clark, SB O'Rangers, JJ Rowe, WD Madson, MR Hurlbut, JA Sofos, JN Fuerst, B James, G Griffith, S Readnour, RS TI Interlaboratory comparison of methods for the determination of incurred tilmicosin residues in bovine liver SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID LIQUID-CHROMATOGRAPHY; MASS-SPECTROMETRY; TISSUES; MUSCLE; CATTLE; SWINE AB The objective of this study was to compare 2 methods for the determination of tilmicosin residues in bovine liver samples. Three laboratories participated in the comparison of the 2 methods. The first method was described in a New Animal Drug Application (NADA 140-929), and the second was a modification of that method in which hexane was substituted for carbon tetrachloride in one cleanup step. Each of the 3 laboratories analyzed subsamples of 10 bovine livers containing incurred tilmicosin. Residues ranged from 2.3 to 81 ppm tilmicosin in the 10 liver samples with an 11.8% relative standard deviation obtained by using both methods. In addition, fortified-control liver tissue samples were analyzed concurrently with tissues containing incurred residues by using the modified method in one of the laboratories. The fortification levels ranged from 0.3 to 112 ppm, with recoveries ranging from 76 to 92%. The results from the 3 laboratories were comparable, indicating that the modified method was not only as effective as the original NADA method, but also more desirable because of the change to a less hazardous solvent. C1 US FDA, Denver, CO 80225 USA. US FDA, Ctr Vet Med, Rockville, MD 20855 USA. Western Washington Univ, Dept Chem, Bellingham, WA 98225 USA. Colorado State Univ, Dept Anim Sci, Ft Collins, CO 80523 USA. USDA, Food Safety & Inspect Serv, St Louis, MO 63120 USA. Elanco Anim Hlth, Greenfield, IN 46140 USA. RP Clark, SB (reprint author), US FDA, POB 25087, Denver, CO 80225 USA. NR 8 TC 2 Z9 2 U1 0 U2 0 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD NOV-DEC PY 2002 VL 85 IS 6 BP 1260 EP 1267 PG 8 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 620GB UT WOS:000179524700007 PM 12477187 ER PT J AU Roybal, JE Walker, CC Pfenning, AP Turnipseed, SB Storey, JM Gonzales, SA Hurlbut, JA AF Roybal, JE Walker, CC Pfenning, AP Turnipseed, SB Storey, JM Gonzales, SA Hurlbut, JA TI Concurrent determination of four fluoroquinolones in catfish, shrimp, and salmon by liquid chromatography with fluorescence detection SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID PRIMARY METABOLITE CIPROFLOXACIN; CHICKEN TISSUES; ANIMAL-TISSUES; ENROFLOXACIN; MILK; RESIDUES; MUSCLE; PHARMACOKINETICS; QUINOLONES; DIFLOXACIN AB A liquid chromatographic (LC) method with fluorescence detection was developed for concurrent determination of 4 fluoroquinolones: ciprofloxacin (CIPRO), enrofloxacin (ENRO), sarafloxacin (SARA), and difloxacin (DIFLX) in catfish, shrimp, and salmon. The procedure consists of extraction from fish tissue with acidified ethanol, isolation and retention on a cation exchange solid-phase extraction column, elution with basic methanol, and LC analysis with fluorescence detection. LC is performed by isocratic elution with acetonitrile-2% acetic acid (16 + 84) mobile phase, and a PLRP-S polymer column with fluorescence detection, excitation 278 nm and emission 450 nm. A target level of 20 ppb for each of the 4 fluoroquinolones has been established for this method. Fortified and incurred fish sample results are based on a 5-point standard curve calculation (10-160 ppb). Overall percent recoveries (% relative standard deviation) from fortified catfish were 78 (10), 80 (11), 70 (9.4), and 78 (10); from fortified shrimp, 69 (5.9), 85 (4.9), 79 (5.9), and 90 (4.5); and from fortified salmon, 56 (15), 93 (5.6), 61 (11), and 87 (5.0) for CIPRO, ENRO, SARA, and DIFLX, respectively. Data from the analysis of fluoroquinolone-incurred catfish, shrimp, and salmon are presented. C1 US FDA, Anim Drugs Res Ctr, Denver Fed Ctr, Denver, CO 80225 USA. RP Roybal, JE (reprint author), US FDA, Anim Drugs Res Ctr, Denver Fed Ctr, POB 25087, Denver, CO 80225 USA. NR 24 TC 24 Z9 27 U1 1 U2 5 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD NOV-DEC PY 2002 VL 85 IS 6 BP 1293 EP 1301 PG 9 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 620GB UT WOS:000179524700011 PM 12477191 ER PT J AU Rupp, HS AF Rupp, HS TI Determination of deoxynivalenol in whole wheat flour and wheat bran SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID CHROMATOGRAPHY-MASS-SPECTROMETRY; ELECTRON-CAPTURE DETECTION; GAS-CHROMATOGRAPHY; LIQUID-CHROMATOGRAPHY; FUSARIUM MYCOTOXINS; TRICHOTHECENE MYCOTOXINS; CEREALS; CLEANUP; QUANTIFICATION; NIVALENOL AB A liquid chromatographic (LC) method was developed for determining deoxynivalenol (DON) in whole wheat flour and wheat bran. A 15 g test sample was extracted with acetonitrile-water (84 + 16, v/v) and applied to a Romer MycoSep cleanup column. The eluate was dried and then reconstituted in a 0.1 M phosphate buffer, pH 7.0, and applied to a Vicam DONtest-LC cleanup column. The methanol eluate was chromatographed with a methanol-water (17 + 83, v/v) mobile phase on a C-18 column with UV detection at 220 nm. Five replicates at each of 5 fortification levels (0.25, 0.50, 1.0, 2.0, and 4.0 ppm), plus 5 controls, were determined for both whole wheat flour and wheat bran. For flour, the average recoveries were 72.2-91.5% with relative standard deviations (RSDs) of 4.9-18.4%. The intra-assay flour recovery was 82.4% with 9.8% RSD. A 5 replicate sample of naturally incurred wheat had an average of 1.1 ppm DON with 6.7% RSD. For bran, average recoveries of fortified samples were 69.5-99.7% with RSDs of 1.7-18.8%. The intra-assay bran recovery was 81.5% with 8.9% RSD. The limit of detection (about 3x noise) for the method is 0.05 ppm; the correlation coefficient (linearity) was >0.9995. The DON peak was clearly identified and easily integrated in the chromatograms. C1 US FDA, Pacific Reg Lab NW, Bothell, WA 98021 USA. RP Rupp, HS (reprint author), US FDA, Pacific Reg Lab NW, 22201 23rd Dr SE, Bothell, WA 98021 USA. NR 22 TC 6 Z9 7 U1 0 U2 1 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD NOV-DEC PY 2002 VL 85 IS 6 BP 1355 EP 1359 PG 5 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 620GB UT WOS:000179524700019 PM 12477199 ER PT J AU Ang, CYW Cui, YY Chang, HC Luo, WH Heinze, TM Lin, LJ Mattia, A AF Ang, CYW Cui, YY Chang, HC Luo, WH Heinze, TM Lin, LJ Mattia, A TI Determination of St. John's wort components in dietary supplements and functional foods by liquid chromatography SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID HYPERICUM-PERFORATUM L; PHOTODIODE-ARRAY DETECTION; FORCED SWIMMING TEST; MASS-SPECTROMETRY; ANTIDEPRESSANT ACTIVITY; HYPERFORIN; EXTRACTS; CONSTITUENTS; STABILITY; HERB AB St. John's wort (Hypericum perforatum L.) preparations, a top-selling botanical dietary supplement used primarily as an antidepressant, has recently been used as an ingredient in some food products sold as functional foods. A rapid extraction technique followed by a liquid chromatographic (LC) method was developed to determine 4 characteristic bioactive compounds (pseudohypericin, hypericin, hyperforin, and adhyperforin) from St. John's wort in dietary supplements and functional foods to which it was added. Solid samples, including dried leaf/flower mixture, dietary supplement capsules, tea bags, puff and snack bar, were extracted with methanol by sonication. Noncarbonated, fruit-flavored drinks were centrifuged and mixed with methanol. Compounds were then determined by isocratic, reversed-phase LC with UV detection at 2 wavelengths and further identified or confirmed by photodiode array spectra and LC/mass spectrometry. Within-laboratory method variations (% RSD) were satisfactory. Very low amounts, if any, of the 4 components were found in drink and puff samples, and none was found in the snack-bar. The methods developed provide a useful means for the determination of St. John's wort components in dietary supplements and functional foods. C1 US FDA, Natl Ctr Toxicol Res, Div Chem, Jefferson, AR 72079 USA. US FDA, Ctr Food Safety & Appl Nutr, Off Food Addit Safety, Div Petit Review, College Pk, MD 20740 USA. RP Ang, CYW (reprint author), US FDA, Natl Ctr Toxicol Res, Div Chem, HFT-230,3900 NCTR Rd, Jefferson, AR 72079 USA. NR 23 TC 21 Z9 23 U1 1 U2 9 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD NOV-DEC PY 2002 VL 85 IS 6 BP 1360 EP 1369 PG 10 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 620GB UT WOS:000179524700020 PM 12477200 ER PT J AU Bolger, PM Egan, K Jensen, E Canady, R AF Bolger, PM Egan, K Jensen, E Canady, R TI Persistent organic pollutants exposure assessment using the US Total Diet Study SO JOURNAL OF EPIDEMIOLOGY AND COMMUNITY HEALTH LA English DT Article AB The assessment presented in the core paper of this debate by Schafer and Kegley does not adequately describe the computational methodology or sources of data that were used to estimate exposures. While it is difficult to determine from the article, the exposure estimates seem to be very dependent on action levels, rather than on empirically derived data. There is no adequate presentation of analytical methods, limits of detection, or the significance of non-detects in deriving estimates of exposure. C1 US FDA, Div Risk Assessment, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Bolger, PM (reprint author), US FDA, Div Risk Assessment, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. NR 3 TC 2 Z9 2 U1 0 U2 2 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0143-005X J9 J EPIDEMIOL COMMUN H JI J. Epidemiol. Community Health PD NOV PY 2002 VL 56 IS 11 BP 818 EP 819 DI 10.1136/jech.56.11.818 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 607EE UT WOS:000178778000008 PM 12388567 ER PT J AU Lamb, JL Gogley, JM Thompson, MJ Solis, DR Sen, S AF Lamb, JL Gogley, JM Thompson, MJ Solis, DR Sen, S TI Effect of low-dose gamma irradiation on Staphylococcus aureus and product packaging in ready-to-eat ham and cheese sandwiches SO JOURNAL OF FOOD PROTECTION LA English DT Article ID ESCHERICHIA-COLI O157-H7; LISTERIA-MONOCYTOGENES; IONIZING-RADIATION; MICROBIAL QUALITY; GROUND-BEEF; MEAT; INACTIVATION; ELIMINATION; FOOD; SALMONELLA AB Staphylococcus aureus is a common pathogen that causes foodborne illness. Traditional methods for controlling S. aureus do not address postprocess contamination. Low-dose gamma irradiation is effective in reducing pathogens in a variety of foods and may be effective in reducing S. aureus in ready-to-eat foods. The effects of gamma irradiation on product packaging should also be considered. The objective of this study was to determine the effects of gamma irradiation on product packaging and on S. aureus in ready-to-eat ham and cheese sandwiches. The effects of refrigerated storage on irradiated and nonirradiated sandwiches were also investigated. Ham and cheese sandwiches were inoculated with 10(6) or 10(7) CFU of S. aureus per g, frozen, irradiated, and analyzed by a standard plate count method. D-10-values, the amount of irradiation needed to elicit a 1-log(10) reduction of bacteria, were calculated. In addition, irradiated sandwiches were analyzed after 1, 13, 27, and 39 days of storage at 4degreesC. The integrity of postirradiated packaging material was analyzed using Fourier transform infrared (FTIR) spectroscopy. Two experiments yielded D-10-values of 0.62 and 0.63. During refrigerated storage, sandwiches irradiated with 5.9 kGy showed no S. aureus growth at any time; sandwiches irradiated with 3.85 kGy showed a 6.18-log reduction in S. aureus after 13 days; and nonirradiated sandwiches showed a 0.53-log increase in S. aureus after 39 days. FTIR spectroscopy showed that the label side and the bulge side were composed of polyethylene terephthalate and nylon 6, respectively. No significant change in the packaging due to irradiation was detected. In this study, low-dose gamma irradiation was shown to be an effective method for reducing S. aureus in ready-to-eat ham and cheese sandwiches and proved to be more efficacious than refrigeration alone. Additionally, package integrity was not adversely affected by gamma irradiation. C1 US FDA, Pacific Reg Lab SW, Microbiol Branch, Los Angeles, CA 90015 USA. US FDA, Pacific Reg Lab SW, Drug Chem Branch, Los Angeles, CA 90015 USA. RP Lamb, JL (reprint author), US FDA, Pacific Reg Lab SW, Microbiol Branch, Los Angeles, CA 90015 USA. NR 30 TC 11 Z9 12 U1 1 U2 7 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 2002 VL 65 IS 11 BP 1800 EP 1805 PG 6 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 612UE UT WOS:000179093200023 PM 12430707 ER PT J AU Aidoo, A Bishop, ME Shelton, S Lyn-Cook, L Delclos, B Chen, T Manjanatha, MG AF Aidoo, A Bishop, ME Shelton, S Lyn-Cook, L Delclos, B Chen, T Manjanatha, MG TI Effect of dietary intake of estrogenic isoflavones genistein and daidzein on a carcinogen-induced mutation in ovariectornized transgenic rats SO JOURNAL OF NUTRITION LA English DT Meeting Abstract CT International Research Conference on Food, Nutrition and Cancer CY JUL 11-12, 2002 CL WASHINGTON, D.C. SP BASF Aktiengesell, California Dried Plum Board, Campbell Soup Co, Danisco Cultor, Galileo Labs Inc, Mead Johnson Nutr, Roche Vitamins Inc, Yamanouchi, Shaklee, INOBYS C1 US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD NOV PY 2002 VL 132 IS 11 SU S BP 3555S EP 3555S PG 1 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 614PU UT WOS:000179199200082 ER PT J AU Furlong, LA AF Furlong, LA TI Ectopic pregnancy risk when contraception fails - A review SO JOURNAL OF REPRODUCTIVE MEDICINE LA English DT Review DE pregnancy; ectopic; contraception; contraceptive agents; female AB OBJECTIVE: To alert clinicians to the risk of ectopic pregnancy when certain contraceptive methods fail byg als reviewed by the U.S. Food and and Drug administration (FDA). STUDY DESIGN: The review focuses on 7 contraceptive drug products with an increased risk of ectopic pregnancy when the method fails. Data were extracted from reviews of clinical trials submitted to the FDA to support marketing applications and medical from the medical literature. Data on 6 other contraceptive drug products and published data for tubal ligations are used for comparison.This review does not include medroxyprogesterone acetate injections because the FDA reviews for this method did not include any pregnancy outcome information. RESULTS: The results are presented in a table and are compared to postmarketing surveillance reports and published literature, when available. The proportion of ectopic pregnancies among all ranged pregnancies ranged from 1:2 to 1:21 for intrauterine devices, tubal ligations, progestin-only implants and progestin-only oral contraceptives. Although the confidence intervals for the proportions were large in trials with few pregnancies, both postmarketing surveillance reports and published literature support proportions calculated from clinical trial data. CONCLUSION: Pregnancies in women using progestin-only oral contraceptives, progestin-only implants, intrauterine devices and tubal ligations are more likely to be ectopic than pregnancies in the general population. C1 US FDA, Rockville, MD 20857 USA. RP Furlong, LA (reprint author), US FDA, HFD-580,5600 Fishers Lane, Rockville, MD 20857 USA. NR 8 TC 30 Z9 30 U1 0 U2 4 PU SCI PRINTERS & PUBL INC PI ST LOUIS PA PO DRAWER 12425 8342 OLIVE BLVD, ST LOUIS, MO 63132 USA SN 0024-7758 J9 J REPROD MED JI J. Reprod. Med. PD NOV PY 2002 VL 47 IS 11 BP 881 EP 885 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 622UV UT WOS:000179666200001 PM 12497674 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 ID POPULATION; RUPTURE; WOMEN C1 US FDA, Ctr Devices & Radiol Hlth, Off Surveillance & Biometr, Rockville, MD 20857 USA. RP Brown, SL (reprint author), US FDA, Ctr Devices & Radiol Hlth, Off Surveillance & Biometr, Rockville, MD 20857 USA. NR 3 TC 0 Z9 0 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 NOV PY 2002 VL 29 IS 11 BP 2469 EP 2470 PG 2 WC Rheumatology SC Rheumatology GA 611XL UT WOS:000179043100043 ER PT J AU Papaconstantinou, AD Umbreit, TH Goering, PL Brown, KM AF Papaconstantinou, AD Umbreit, TH Goering, PL Brown, KM TI Effects of 17 alpha-methyltestosterone on uterine morphology and heat shock protein expression are mediated through estrogen and androgen receptors SO JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY LA English DT Article DE uterotrophism; 17 alpha-methyltestosterone; flutamide; androgen; anti-estrogen; heat shock proteins; hsp90 alpha; hsp72; grp94 ID HORMONE-BINDING GLOBULIN; POSTMENOPAUSAL WOMEN; GENE-EXPRESSION; BISPHENOL-A; RAT UTERUS; TESTOSTERONE; LOCALIZATION; STEROIDS; METHYLTESTOSTERONE; OVEREXPRESSION AB Testosterone and the synthetic androgen, 17alpha-methyltestosterone (MT), have been shown to increase uterine weights and alter uterine morphology. However, whereas the mechanism of action of testosterone in the uterus has been studied, it is not known if the actions of MT are mediated through androgen (AR) or estrogen (ER) receptors. In the present study, we have shown that MT, at 0.5 or 10 mg/kg per day, increases uterine weight and alters uterine morphology in a dose-dependent manner. Co-administration of the anti-androgen, flutamide, or the anti-estrogen, ICI 182,780, with NIT revealed that the effects of the low dose of NIT are mediated through the ER, whereas those of the high dose are mediated through both the ER and AR. In addition, we have studied the effects of MT on uterine heat shock proteins (hsps), a group of estrogen-regulated proteins whose levels increase in response to growth signals and protein damage. NIT increased levels of hsp90alpha, hsp72, and grp94. All effects on uterine hsp levels were antagonized by the anti-estrogen and not the anti-androgen. Collectively, the results of the present study indicate that the effects of MT in the uterus are mediated through the AR and ER. Published by Elsevier Science Ltd. C1 George Washington Univ, Dept Biol Sci, Washington, DC 20052 USA. US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Brown, KM (reprint author), George Washington Univ, Dept Biol Sci, 332 Lisner Hall,2023 St NW, Washington, DC 20052 USA. NR 41 TC 17 Z9 19 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-0760 J9 J STEROID BIOCHEM JI J. Steroid Biochem. Mol. Biol. PD NOV PY 2002 VL 82 IS 4-5 BP 305 EP 314 AR PII S0960-0760(02)00221-2 DI 10.1016/S0960-0760(02)00221-2 PG 10 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 653AB UT WOS:000181412100005 PM 12589937 ER PT J AU Brinker, A Trontell, A Beitz, J AF Brinker, A Trontell, A Beitz, J TI Pregnancy and pregnancy rates in association with isotretinoin (Accutane) SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Letter C1 US FDA, Off Drug Risk Safety, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Brinker, A (reprint author), US FDA, Off Drug Risk Safety, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. NR 4 TC 6 Z9 6 U1 0 U2 2 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 NOV PY 2002 VL 47 IS 5 BP 798 EP 799 DI 10.1067/mjd.2002.124700 PG 2 WC Dermatology SC Dermatology GA 609FM UT WOS:000178893000029 PM 12399783 ER PT J AU Lenert, LA Burstin, H Connell, L Gosbee, J Phillips, G AF Lenert, LA Burstin, H Connell, L Gosbee, J Phillips, G TI Federal patient safety initiatives panel summary SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Editorial Material C1 Univ Calif San Diego, San Diego, CA 92103 USA. Agcy Healthcare Res & Qual, Rockville, MD USA. NASA, Ames Res Ctr, Moffett Field, CA 94035 USA. Dept Vet Affairs Natl Ctr Patient Safety, Ann Arbor, MI USA. US FDA, Rockville, MD 20857 USA. RP Lenert, LA (reprint author), Univ Calif San Diego, San Diego, CA 92103 USA. NR 3 TC 3 Z9 3 U1 0 U2 0 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PD NOV-DEC PY 2002 VL 9 IS 6 SU S BP S8 EP S10 DI 10.1197/jamia.M1217 PG 3 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Information Science & Library Science; Medical Informatics SC Computer Science; Information Science & Library Science; Medical Informatics GA 611FK UT WOS:000179005600003 PM 12386172 ER PT J AU Ritzhaupt, A van der Laan, LJW Salomon, DR Wilson, CA AF Ritzhaupt, A van der Laan, LJW Salomon, DR Wilson, CA TI Porcine endogenous retrovirus infects but does not replicate in nonhuman primate primary cells and cell lines SO JOURNAL OF VIROLOGY LA English DT Article ID CROSS-SPECIES TRANSMISSION; MURINE LEUKEMIA-VIRUS; ENDOTHELIAL-CELLS; IN-VITRO; HOST-RANGE; PRODUCTIVE INFECTION; NO EVIDENCE; DNA; XENOTRANSPLANTATION; PERV AB Porcine endogenous retroviruses (PERV) can infect human cell lines in vitro; hence, there is a presumed risk of viral exposure to a recipient when pig cells are transplanted into humans (xenotransplantation). Nonhuman primates (NHP) are considered a potential permissive animal model to study the risk of in vivo infection of PERV after xenotransplantation. We set out to determine whether PERV can infect and replicate in NHP primary cells or established cell lines from African green monkey, rhesus macaque, and baboon. We confirm that the NHP cell lines under investigation were infected with PERV as measured by detection of viral DNA and RNA by PCR and reverse transcription (RT)-PCR, respectively, indicating that a functional receptor must be present on the cell surface. However, the load of detectable viral DNA in infected NHP cells declined over time, and the cells never had detectable reverse transcriptase activity. Utilizing quantitative real-time TaqMan PCR we found detectable levels of unintegrated DNA intermediates, but the levels were approximately 100-fold lower compared to HEK 293 cells infected with PERV. Virions released from infected NHP cells could productively infect naive human cell lines, HEK 293 and HeLa, as shown by RT-PCR and RT assay. However, naive NHP cells remained negative in RT-PCR and RT assay after exposure to virions from infected NHP cells. Together our data demonstrate that NHP cells are not permissive to productive replication by PERV, presumably due to inefficient cell entry and replication. In light of these observations, the appropriateness of NHP as suitable animal models to study PERV infection in vivo needs to be reevaluated. C1 US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Lab Immunol & Virol, Bethesda, MD 20892 USA. Scripps Res Inst, Dept Mol & Expt Med, La Jolla, CA 92037 USA. RP Wilson, CA (reprint author), Bldg 29B,Room 2NN11,8800 Rockville Pike, Bethesda, MD 20892 USA. RI Salomon, Daniel/E-9380-2012; OI van der Laan, Luc/0000-0002-0651-5334 FU NIAID NIH HHS [R01 AI045494] NR 40 TC 39 Z9 41 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD NOV PY 2002 VL 76 IS 22 BP 11312 EP 11320 DI 10.1128/JVI.76.22.11312-11320.2002 PG 9 WC Virology SC Virology GA 608AF UT WOS:000178822400015 PM 12388691 ER PT J AU Turturro, A Duffy, P Hass, B Kodell, R Hart, R AF Turturro, A Duffy, P Hass, B Kodell, R Hart, R TI Survival characteristics and age-adjusted disease incidences in C57BL/6 mice fed a commonly used cereal-based diet modulated by dietary restriction SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID LIFE-SPAN; CALORIC RESTRICTION; BODY-WEIGHT; FOOD RESTRICTION; MIDDLE-AGE; CANCER INCIDENCE; TUMOR-INCIDENCE; B6C3F1 MICE; LONGEVITY; RATS AB Studies of C57BL/6 mice are often restricted to one sex, with limited characterization of pathology as a function of age. As part of the National Institute on Aging/National Center for Toxicological Research Collaboration on Biomarkers, over 3000 males and 1500 females of this strain were raised, maintained, and used to evaluate longevity under specific pathogen-free conditions. A diet commonly used in testing the impact of agents was fed ad libitum or was restricted to 60% of normal consumption, starting when the mice were 14-16 weeks of age. Cardiac, renal, and central nervous system pathologies were significantly inhibited by dietary restriction (DR), as were bone degeneration, inflammation, hyperplasia, amyloid induction, and atrophy of secretory organs. Hematological disorders and tumors were among the most common problem in this strain, and they were ameliorated by DR. In males, for other neoplasms, adrenal adenomas, liver tumors, and hemangiomas combined with hemangiosarcomas were decreased by DR, variably in onset and progression. In females, DR decreased pituitary tumors, mammary tumors, and alveolar carcinomas, again variably in onset and progression. C1 NCTR, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. NCTR, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. Toxicol & Ind Hlth, Little Rock, AR USA. RP Turturro, A (reprint author), NCTR, Div Biometry & Risk Assessment, HFT-20,3900 NCTR Rd, Jefferson, AR 72079 USA. NR 71 TC 51 Z9 52 U1 0 U2 2 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD NOV PY 2002 VL 57 IS 11 BP B379 EP B389 PG 11 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 614PQ UT WOS:000179198900001 PM 12403793 ER PT J AU Ge, Y Jensen, T James, SJ Becton, DL Massey, GV Weinstein, HJ Ravindranath, Y Matherly, LH Taub, JW AF Ge, Y Jensen, T James, SJ Becton, DL Massey, GV Weinstein, HJ Ravindranath, Y Matherly, LH Taub, JW TI High frequency of the 844ins68 cystathionine-beta-synthase gene variant in Down syndrome children with acute myeloid leukemia SO LEUKEMIA LA English DT Letter ID MATERNAL RISK-FACTORS; PLASMA HOMOCYSTEINE; FOLATE METABOLISM; POLYMORPHISMS; MUTATION C1 Barbara Ann Karmanos Canc Inst, Expt & Clin Therapeut Program, Detroit, MI USA. US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. Univ Arkansas, Fayetteville, AR 72701 USA. Univ Virginia, Charlottesville, VA 22903 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Childrens Hosp Michigan, Div Pediat Hematol Oncol, Detroit, MI 48201 USA. Wayne State Univ, Sch Med, Dept Pediat, Detroit, MI 48201 USA. Wayne State Univ, Sch Med, Dept Pharmacol, Detroit, MI 48201 USA. RP Taub, JW (reprint author), Childrens Hosp Michigan, 3901 Beaubien Blvd, Detroit, MI 48201 USA. FU NCI NIH HHS [R01 CA92308] NR 8 TC 18 Z9 18 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD NOV PY 2002 VL 16 IS 11 BP 2339 EP 2341 DI 10.1038/sj.leu.2402705 PG 3 WC Oncology; Hematology SC Oncology; Hematology GA 614MF UT WOS:000179193400027 PM 12399985 ER PT J AU Chang, I Beard, B AF Chang, I Beard, B TI Precision test apparatus for evaluating the heating pattern of radiofrequency ablation devices SO MEDICAL ENGINEERING & PHYSICS LA English DT Article DE radiofrequency ablation; measurement techniques ID CATHETER ABLATION; DIELECTRIC-PROPERTIES; TEMPERATURE; ELECTRODE; ENDOCARDIUM; BIOPHYSICS; IMPEDANCE; MICROWAVE; TISSUES; LESION AB Radiofrequency has established itself as a useful technique for managing cardiac arrhythmias and treating soft tissue tumors. However, despite its pervasive use. many of the biophysical principals needed to fully understand and optimize the radiofrequency ablation technique have not been explored. We have designed a test rig that is useful for studying the heat transfer mechanisms that affect the outcome of radiofrequency ablation devices. Using both solid and liquid phantom materials, which simulate body tissues and blood, the test rig is designed for systematic testing of the effects of predictable flow patterns on the temperature profiles generated within the solid phantom. The test rig consists of a custom built thermistor array, a linear test chamber, and a radiofrequency generator. We calibrate the flow of a liquid phantom material to demonstrate that predictable laminar flow profiles are generated. To demonstrate the performance of the ablation system, we present preliminary data attained using a commercially available cardiac ablation catheter. The advantages of this test system are its flexibility, its reproducibility. its precision, and its low cost. Thus, it is ideally suited for studying a variety of complex ablation problems involving multiple tissues types and complex blood flow geometries. Published by Elsevier Science Ltd on behalf of IPEM. C1 US FDA, Rockville, MD 20852 USA. RP US FDA, 12725 Twinbrook Pkwy,HFZ-133, Rockville, MD 20852 USA. EM iac@cdrh.fda.gov OI Beard, Brian/0000-0001-6480-0857 NR 25 TC 6 Z9 7 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1350-4533 EI 1873-4030 J9 MED ENG PHYS JI Med. Eng. Phys. PD NOV PY 2002 VL 24 IS 9 BP 633 EP 640 AR PII S1350-4533(02)00044-9 DI 10.1016/S1350-4533(02)00044-9 PG 8 WC Engineering, Biomedical SC Engineering GA 611EN UT WOS:000179003600008 PM 12376050 ER PT J AU Palmieri, D Suchar, A Henkel, V Wulfkuhle, JD Petricoin, EF Steeg, PS AF Palmieri, D Suchar, A Henkel, V Wulfkuhle, JD Petricoin, EF Steeg, PS TI Altered expression of lipid and vesicle trafficking proteins in human breast ductal carcinoma in situ SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 NCI, Pathol Lab, Womens Canc Sect, Bethesda, MD 20892 USA. NCI, Pathol Lab, Clin Proteom Program, Bethesda, MD 20892 USA. NCI, US FDA, CBER, Clin Proteom Program, Bethesda, MD 20892 USA. RI Palmieri, Diane/B-4258-2015 NR 0 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 2002 VL 13 MA 509 BP 91A EP 91A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569100509 ER PT J AU Selvapandiyan, A Debrabant, A Duncan, R Salotra, P Nakhasi, H AF Selvapandiyan, A Debrabant, A Duncan, R Salotra, P Nakhasi, H TI Functional analysis of Leishmania donovani centrin and its role in parasite virulence SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 US FDA, Ctr Biol Evaluat & Res, DETTD, Lab Bacterial Parasit & Unconvent Agents, Bethesda, MD USA. Indian Council Med Res, Inst Pathol, New Delhi, India. NR 0 TC 0 Z9 0 U1 0 U2 1 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 2002 VL 13 MA 1706 BP 303A EP 304A PG 2 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569101705 ER PT J AU Goyal, N Duncan, R Salotra, P Akopyant, N Klutch, M Rastogi, A Beverly, S Nakhasi, H AF Goyal, N Duncan, R Salotra, P Akopyant, N Klutch, M Rastogi, A Beverly, S Nakhasi, H TI Identification and characterization of Leishmania donovani stage specific genes using genomic microarray SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 Cent Drug Res Inst, Div Biochem, Lucknow 226001, Uttar Pradesh, India. US FDA, Ctr Biol Evaluat & Res, DETTD, Lab Bacterial Parasit & Unconvent Agents, Bethesda, MD USA. Inst Pathol, Mol Biol Lab, New Delhi, India. Washington Univ, St Louis, MO 63130 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 2002 VL 13 MA 2937 BP 521A EP 522A PG 2 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569102936 ER PT J AU Trucksess, MW Pohland, AE AF Trucksess, MW Pohland, AE TI Methods and method evaluation for mycotoxins SO MOLECULAR BIOTECHNOLOGY LA English DT Review DE aflatoxin; AOAC Official Methods; deoxynivalenol; fumonisins; horwitz equation; HORRAT; Horwitz Horn; method validation; ochratoxin ID DEOXYNIVALENOL; WHEAT AB Mycotoxins are metabolites of molds frequently found on and in agricultural commodities, food and feeds. Owing to their demonstrated acute, sub.-acute and, in some cases, chronic toxicity, an effort has been made, worldwide, to control human and animal exposure to these toxic chemicals. This effort depends upon the availability of validated analytical methods for their detection and quantitation. This paper outlines the methodology available, and the procedures used to validate, i.e. evaluate, these methods based on the use of interlaboratory collaborative studies and the application of the HORRAT. C1 US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20204 USA. AOAC Int, Gaithersburg, MD 20877 USA. NR 24 TC 5 Z9 6 U1 1 U2 4 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1073-6085 J9 MOL BIOTECHNOL JI Mol. Biotechnol. PD NOV PY 2002 VL 22 IS 3 BP 287 EP 292 DI 10.1385/MB:22:3:287 PG 6 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 609EH UT WOS:000178890300006 PM 12448882 ER PT J AU Migueles, SA Laborico, AC Shupert, WL Sabbaghian, MS Rabin, R Hallahan, CW Van Baarle, D Kostense, S Miedema, F McLaughlin, M Ehler, L Metcalf, J Liu, SY Connors, M AF Migueles, SA Laborico, AC Shupert, WL Sabbaghian, MS Rabin, R Hallahan, CW Van Baarle, D Kostense, S Miedema, F McLaughlin, M Ehler, L Metcalf, J Liu, SY Connors, M TI HIV-specific CD8(+) T cell proliferation is coupled to perforin expression and is maintained in nonprogressors SO NATURE IMMUNOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; LONG-TERM NONPROGRESSORS; ANTIRETROVIRAL THERAPY; LYMPHOCYTE RESPONSES; CYTOKINE PRODUCTION; TYPE-1 INFECTION; IMMUNE-RESPONSES; EFFECTOR; MEMORY; HLA AB It is unclear why immunological control of HIV replication is incomplete in most infected individuals. We examined here the CD8(+)T cell response to HIV-infected CD4(+)T cells in rare patients with immunological control of HIV. Although high frequencies of HIV-specific CD8(+)T cells were present in nonprogressors and progressors, only those of nonprogressors maintained a high proliferative capacity. This proliferation was coupled to increases in perforin expression. These results indicated that nonprogressors were differentiated by increased proliferative capacity of HIV-specific CD8(+)T cells linked to enhanced effector function. In addition,the relative absence of these functions in progressors may represent a mechanism by which HIV avoids immunological control. C1 NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20205 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. CLB Sanquin, Dept Clin Viroimmunol, Amsterdam, Netherlands. RP Connors, M (reprint author), NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20205 USA. NR 49 TC 659 Z9 677 U1 0 U2 12 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD NOV PY 2002 VL 3 IS 11 BP 1061 EP 1068 DI 10.1038/ni845 PG 8 WC Immunology SC Immunology GA 612KE UT WOS:000179073000013 PM 12368910 ER PT J AU Sams, RL Couch, LH Miller, BJ Okerberg, CV Warbritton, AR Wamer, WG Beer, JZ Howard, PC AF Sams, RL Couch, LH Miller, BJ Okerberg, CV Warbritton, AR Wamer, WG Beer, JZ Howard, PC TI Effects of alpha- and beta-hydroxy acids on the edemal response induced in female SKH-1 mice by simulated solar light SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE glycolic acid; salicylic acid; edema; simulated solar light; ultraviolet light; SKH-1 hairless mice; epidermis ID GLYCOLIC ACID; ULTRAVIOLET-RADIATION; CELL-PROLIFERATION; STRATUM-CORNEUM; PHOTOAGED SKIN; MURINE SKIN; MOUSE AB alpha- and beta-Hydroxy acids have been used extensively in cosmetic and dermatological formulations. At present, there is an inadequate amount of information with which to assess the safety of topical applications of alpha- and beta-hydroxy acids in conjunction with exposure to ultraviolet light. In the present study, we examined changes in the epidermal basal cell proliferation and the edemal response using skin thickness measurements elicited in SKH-1 mice following exposure to simulated solar light (SSL) with or without topical treatment with creams containing alpha- (glycolic) and beta-hydroxy (salicylic) acids. The dose of SSL light required to induce measurable edema (MEDBIOL) in naive, free-moving SKH-1 mice was determined to be 90 mJ (.) CIE/cm(2). Pretreating the mice with daily (5 days/week) exposures of 14 mJ (.) CIE/cm(2) for 6 weeks resulted in a doubling of the MEDBiol to 180 mJ (.) CIE/cm2. Topical application of control cream (pH 3.5), or creams containing glycolic acid (10%, pH 3.5) or salicylic acid (4%, pH 3.5) for 6 weeks (5 days/week) increased the MEDBIOL to 137 mJ - CIE/cm(2). Daily treatments with SSL (14 mJ (.) CIE/cm(2)) and control cream (pH 3.5), glycolic (10%, pH 3.5) or salicylic (4%, pH 3.5) acid-containing creams for 6 weeks (5 days/week) resulted in an MEDBIOL value of 180 mJ (.) CIE/cm(2), which was the same as treatment with light alone for 6 weeks. These data indicate that a 6-week treatment of mouse skin with a representative skin cream, with or without representative alpha- and beta-hydroxy acids (glycolic and salicylic acid, respectively), changes the UV light sensitivity; however, treatment with the cream, with or without the acids, does not contribute to the UV sensitivity of mice cotreated with low doses of UV light. (C) 2002 Elsevier Science (USA). C1 US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. A Charles River Co, Pathol Associates Int, Jefferson, AR 72079 USA. US FDA, Off Cosmet & Colors, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. US FDA, Off Sci & Technol, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Howard, PC (reprint author), US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, HFT-110,3900 NCTR Rd, Jefferson, AR 72079 USA. FU NIA NIH HHS [IAG 224-93-0001] NR 41 TC 7 Z9 7 U1 1 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD NOV 1 PY 2002 VL 184 IS 3 BP 136 EP 143 DI 10.1006/taap.20029498 PG 8 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 615HL UT WOS:000179239700002 PM 12460741 ER PT J AU Tsuyuki, S Kono, M Bloom, ET AF Tsuyuki, S Kono, M Bloom, ET TI Cloning and potential utility of porcine Fas ligand: overexpression in porcine endothelial cells protects them from attack by human cytolytic cells SO XENOTRANSPLANTATION LA English DT Article DE cell surface molecules; cytotoxicity; endothelial cells; T cells; transplantation ID NATURAL-KILLER-CELLS; HUMAN NK CELLS; IMMUNODEFICIENT MOUSE HOSTS; CYTOTOXIC T-LYMPHOCYTES; ANTI-PIG CYTOTOXICITY; XENOGRAFT REJECTION; TARGET-CELLS; IN-VITRO; MEDIATED CYTOTOXICITY; MONONUCLEAR-CELLS AB Endothelial cells (EC) are primary targets of the recipient's immune response to transplanted organs and constitutively express Fas (CD95) ligand (FasL) on their surface. We investigated the role of porcine FasL in the generation of the human anti-pig response in vitro. Porcine aortic endothelial cells (PAEC) lysed a Fas(+) human T-cell line, Jurkat. Anti-human Fas monoclonal antibody (mAb) specifically inhibited this killing in a dose-dependent manner, suggesting that porcine FasL recognizes and binds human Fas to induce apoptosis of human Fas(+) cells. We next cloned porcine FasL, identifying an open reading frame of 849 base pairs predicting a protein of 282 amino acids. The predicted amino acid sequence was 85, 76, and 75% homologous to the predicted amino acid sequences of human, mouse, and rat, respectively, and found that PAEC expressed both FasL mRNA and protein. Transient transfection was used to increase or induce porcine FasL expression in PAEC or COS-7 cells. Transfection of PAEC with a plasmid encoding porcine FasL increased their ability to induce apoptosis in Jurkat cells, fresh human T cells activated with IL-2 and anti-CD3, and fresh IL-2-activated human (natural killer) NK cells. Moreover, porcine Fas L-transfected COS-7 cells induced significant apoptosis in Jurkat cells compared with that induced by mock-transfected COS-7 cells. Finally, the overexpression of porcine FasL in PAEC reduced their susceptibility as target cells to lysis by activated human NK or T cells. These findings suggest that porcine FasL overexpression in EC of vascularized xenografts may provide protection from cellular xenograft rejection. C1 US FDA, CBER, Div Cellular & Gene Therapies, Lab Immunol & Virol, Bethesda, MD 20892 USA. NIDDKD, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. RP Bloom, ET (reprint author), US FDA, CBER, Div Cellular & Gene Therapies, Lab Immunol & Virol, HFM-518,8800 Rockville Pike, Bethesda, MD 20892 USA. NR 60 TC 11 Z9 13 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD NOV PY 2002 VL 9 IS 6 BP 410 EP 421 DI 10.1034/j.1399-3089.2002.01114.x PG 12 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 601YP UT WOS:000178477200009 PM 12371937 ER PT J AU Meyerhoff, A Murphy, D AF Meyerhoff, A Murphy, D TI Guidelines for treatment of anthrax SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 US FDA, Off Commissioner, Rockville, MD 20857 USA. US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Meyerhoff, A (reprint author), US FDA, Off Commissioner, Rockville, MD 20857 USA. NR 2 TC 3 Z9 3 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 16 PY 2002 VL 288 IS 15 BP 1848 EP 1848 DI 10.1001/jama.288.15.1848 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 604EU UT WOS:000178604200019 PM 12377082 ER PT J AU Shvartsburg, AA AF Shvartsburg, AA TI DMSO complexes of trivalent metal ions: First microsolvated trications outside of group 3 SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID ELECTROSPRAY MASS-SPECTROMETRY; DIMETHYL-SULFOXIDE REDUCTASE; DENSITY-FUNCTIONAL THEORY; M = MG; GAS-PHASE; ALKALINE-EARTH; GOLD(II) COMPLEXES; BINDING-ENERGIES; CHARGED IONS; CHEMISTRY AB The advent of electrospray ionization source opened the door to generation of multiply charged metal ions complexed with organic molecules. A significant amount of work on ligated dications has appeared over the past decade. In contrast, only several microsolvated tripositive ions have been reported, involving solely the few rare earths with the lowest third ionization energies (IEs) of all elements (<23 eV). Here trications of numerous trivalent metals outside of group 3 are shown to coordinate dimethyl sulfoxide (DMSO), an eminent aprotic solvent. These include both main group elements (Al, Ga, In, Bi) and transition metals (V, Fe, Cr) with the third IE up to 31 eV, which is 22 eV above the IIE of DMSO. Fragmentation of M3+(DMSO)(n) for these metals (plus La, Yb, and Sc) has been characterized in detail using collision-induced dissociation (CID). A rich, highly element specific dissociation chemistry is observed, including the homolytic C-S cleavage in (+3) charge state and various charge-reduction processes, such as dissociative electron and proton transfer and heterolytic S=O cleavage with and without a concomitant proton transfer. Characteristic sizes for the charge reduction in M3+(DMSO)(n) and M2+(DMSO)(n) have been measured as a function of the relevant elemental IE. These reveal no intrinsic gap between the stabilities of dication and trication complexes, once the IE is adjusted for. This, in particular, suggests that even microsolvated tetracations may exist. C1 Natl Ctr Toxicol Res, Div Chem, Jefferson, AR 72079 USA. RP Shvartsburg, AA (reprint author), Natl Ctr Toxicol Res, Div Chem, HFT-233,3900 NCTR Rd, Jefferson, AR 72079 USA. NR 35 TC 47 Z9 47 U1 1 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD OCT 16 PY 2002 VL 124 IS 41 BP 12343 EP 12351 DI 10.1021/ja020637d PG 9 WC Chemistry, Multidisciplinary SC Chemistry GA 602PY UT WOS:000178514700057 PM 12371878 ER PT J AU Petricoin, EF Ornstein, DK Paweletz, CP Ardekani, A Hackett, PS Hitt, BA Velassco, A Trucco, C Wiegand, L Wood, K Simone, CB Levine, PJ Linehan, WM Emmert-Buck, MR Steinberg, SM Kohn, EC Liotta, LA AF Petricoin, EF Ornstein, DK Paweletz, CP Ardekani, A Hackett, PS Hitt, BA Velassco, A Trucco, C Wiegand, L Wood, K Simone, CB Levine, PJ Linehan, WM Emmert-Buck, MR Steinberg, SM Kohn, EC Liotta, LA TI Serum proteomic patterns for detection of prostate cancer SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID PROTEIN BIOCHIP; ANTIGEN AB Pathologic states within the prostate may be reflected by changes in serum proteomic patterns. To test this hypothesis, we analyzed serum proteomic mass spectra with a bioinformatics tool to reveal the most fit pattern that discriminated the training set of sera of men with a histopathologic diagnosis of prostate cancer (serum prostate-specific antigen [PSA] greater than or equal to 4 ng/mL) from those men without prostate cancer (serum PSA level < 1 ng/mL). Mass spectra of blinded sera (N = 266) from a test set derived from men with prostate cancer or men without prostate cancer were matched against the discriminating pattern revealed by the training set. A predicted diagnosis of benign disease or cancer was rendered based on similarity to the discriminating pattern discovered from the training set. The proteomic pattern correctly predicted 36 (95%, 95% confidence interval [CI] = 82% to 99%) of 38 patients with prostate cancer, while 177 (78%, 95% CI = 72% to 83%) of 228 patients were correctly classified as having benign conditions. For men with marginally elevated PSA levels (4-10 ng/mL; n = 137), the specificity was 71%. If validated in future series, serum proteomic pattern diagnostics may be of value in deciding whether to perform a biopsy on a man with an elevated PSA level. C1 US FDA, NCI, CBER, Dept Therapeut,Clin Proteom Program, Bethesda, MD USA. Univ N Carolina, Div Urol, Chapel Hill, NC USA. NCI, US FDA, Clin Proteom Program, Dept Therapeut Prot,CBER,NIH, Bethesda, MD USA. NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD USA. Georgetown Univ, Dept Chem, Washington, DC 20057 USA. Correl Syst Inc, Bethesda, MD USA. Catholic Univ Chile, Dept Urol, Santiago, Chile. Simone Protect Canc Inst, Lawrenceville, NJ USA. NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. NCI, Biostat & Data Management Sect, CCR, NIH, Bethesda, MD 20892 USA. RP Petricoin, EF (reprint author), Bldg 29A,Rm 2D12,8800 Rockville Pike, Bethesda, MD 20892 USA. NR 8 TC 501 Z9 535 U1 3 U2 18 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD OCT 16 PY 2002 VL 94 IS 20 BP 1576 EP 1578 PG 3 WC Oncology SC Oncology GA 603MF UT WOS:000178562900013 PM 12381711 ER PT J AU Everman, DB Bartels, CF Yang, Y Yanamandra, N Goodman, FR Mendoza-Londono, JR Savarirayan, R White, SM Graham, JM Gale, RP Svarch, E Newman, WG Kleckers, AR Francomano, CA Govindaiah, V Singh, L Morrison, S Thomas, JT Warman, ML AF Everman, DB Bartels, CF Yang, Y Yanamandra, N Goodman, FR Mendoza-Londono, JR Savarirayan, R White, SM Graham, JM Gale, RP Svarch, E Newman, WG Kleckers, AR Francomano, CA Govindaiah, V Singh, L Morrison, S Thomas, JT Warman, ML TI The mutational spectrum of brachydactyly type C SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE brachydactyly type C; growth/differentiation factor 5; cartilage-derived morphogenetic protein 1 ID TGF-BETA-SUPERFAMILY; LOCUS HETEROGENEITY; MEMBERS; BONE; PROTEIN-1; CDMP1 AB Growth/differentiation factor-5 (GDF5), also known as cartilage-derived morphogenetic protein-1 (CDMP-1), is a secreted signaling molecule that participates in skeletal morphogenesis. Heterozygous mutations in GDF5, which maps to human chromosome 20, occur in individuals with autosomal dominant brachydactyly type C (BDC). Here we show that BDC is locus homogeneous by reporting a GDF5 frameshift mutation segregating with the phenotype in a family whose trait was initially thought to map to human chromosome 12. We also describe heterozygous mutations in nine additional probands/families with BDC and show nonpenetrance in a mutation carrier. Finally, we show that mutant GDF5 polypeptides containing missense mutations in their active domains do not efficiently form disulfide-linked dimers when expressed in vitro. These data support the hypothesis that BDC results from functional haploinsufficiency for GDF5. (C) 2002 Wiley-Liss, Inc. C1 Case Western Reserve Univ, Dept Genet, Cleveland, OH 44106 USA. Univ Hosp Cleveland, Ctr Human Genet, Cleveland, OH 44106 USA. Univ Illinois, Coll Med, Peoria, IL 61656 USA. Inst Child Hlth, Mol Med Unit, London, England. Baylor Coll Med, Dept Genet, Houston, TX 77030 USA. Univ Melbourne, Dept Paediat, Melbourne, Vic, Australia. Cedars Sinai Med Ctr, Dept Med Genet, Ahmanson Dept Pediat, Steven Spielberg Pediat Res Ctr,Burns & Allen Res, Los Angeles, CA 90048 USA. Univ Calif Los Angeles, Dept Pediat, Los Angeles, CA 90024 USA. Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, London, England. Inst Hematol & Immul, Havana, Cuba. St Marys Hosp, Dept Clin Genet, Manchester M13 0JH, Lancs, England. NIA, Genet Lab, Baltimore, MD 21224 USA. Ctr DNA Finger Printing & Diagnost, Hyderabad, Andhra Pradesh, India. Ctr Cellular & Mol Biol, Hyderabad 500007, Andhra Pradesh, India. Cleveland Clin Fdn, Cleveland, OH 44195 USA. US FDA, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. Case Western Reserve Univ, Dept Pediat, Cleveland, OH 44106 USA. RP Warman, ML (reprint author), Case Western Reserve Univ, Dept Genet, Room BRB-719,2109 Adelbert Rd, Cleveland, OH 44106 USA. OI Mendoza-Londono, Roberto/0000-0003-3542-8106; Newman, William/0000-0002-6382-4678 FU NIAMS NIH HHS [AR 45687]; NICHD NIH HHS [HD 07104, HD 07518, HD22657]; NIGMS NIH HHS [GM08243] NR 28 TC 56 Z9 60 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 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD OCT 15 PY 2002 VL 112 IS 3 BP 291 EP 296 DI 10.1002/ajmg.10777 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 599DH UT WOS:000178318500009 PM 12357473 ER PT J AU Earley, MC Vogt, RF Shapiro, HM Mandy, FF Kellar, KL Bellisario, R Pass, KA Marti, GE Stewart, CC Hannon, WH AF Earley, MC Vogt, RF Shapiro, HM Mandy, FF Kellar, KL Bellisario, R Pass, KA Marti, GE Stewart, CC Hannon, WH TI Report from a workshop on multianalyte microsphere assays SO CYTOMETRY LA English DT Article DE luminex; microbeads; suspension array assays ID IMMUNOASSAY AB Multiplexed assays using fluorescent microspheres is an exciting technique that has been gaining popularity among researchers, particularly those in the public health field. Part of its popularity is due to its flexibility, as both immunoassays and oligonucleotide hybridization assays can be developed on this platform. This report summarizes a workshop held by the Centers for Disease Control and Prevention that discussed issues surrounding these assays and the Luminex 100 xMAP instrument. Topics included instrumentation, assay design, sample matrix and volume, quality control, and development of commercial applications. C1 CDCP, Natl Ctr Environm Hlth, Div Environm Hlth Lab Sci, Clin Biochem Branch, Atlanta, GA 30341 USA. Cytometry Lab, W Newton, MS USA. Hlth Canada, Natl Lab HIV Immunol, Ottawa, ON K1A 0L2, Canada. Ctr Dis Control & Prevent, Sci Resources Program, Natl Ctr Infect Dis, Atlanta, GA USA. New York State Dept Hlth, Wadsworth Ctr, Div Genet Disorders, Albany, NY USA. US FDA, Div Cell & Gene Therapy, Bethesda, MD 20014 USA. Roswell Pk Canc Inst, Div Pathol & Lab Med, Buffalo, NY 14263 USA. RP Earley, MC (reprint author), CDCP, Natl Ctr Environm Hlth, Div Environm Hlth Lab Sci, Clin Biochem Branch, MS F-19,4770 Buford Highway NE, Atlanta, GA 30341 USA. NR 5 TC 58 Z9 70 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0196-4763 J9 CYTOMETRY JI Cytometry PD OCT 15 PY 2002 VL 50 IS 5 BP 239 EP 242 DI 10.1002/cyto.10140 PG 4 WC Biochemical Research Methods; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 603KR UT WOS:000178559000001 PM 12360572 ER PT J AU D'Agnillo, F Alayash, AI AF D'Agnillo, F Alayash, AI TI A role for the myoglobin redox cycle in the induction of endothelial cell apoptosis SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE myoglobin; cell cycle; apoptosis; hydrogen peroxide; rhabdomyolysis; vascular injury; oxidative stress; free radicals ID HYDROGEN-PEROXIDE; OXIDATIVE STRESS; ISCHEMIA-REPERFUSION; RENAL-FAILURE; MYOCARDIAL-INFARCTION; LIPID-PEROXIDATION; NITRIC-OXIDE; HEME IRON; RAT-HEART; RHABDOMYOLYSIS AB This study investigates the potential role of the ferric/ferryl redox cycle of myoglobin (Mb) in the development of endothelial cell injury. Bovine aortic endothelial cells were incubated with ferric Mb (0.5-100 muM) in the presence or absence of low steady states of H2O2 (3-4 muM) generated by glucose oxidase (GOX). The reaction of ferric Mb with H2O2 generated ferryl Mb as monitored spectrophotometrically. Ferryl Mb formation correlated with the induction of apoptosis as indicated by morphological criteria, caspase 3 activation, phosphatidylserine (PS) externalization, and nuclear condensation by Hoechst 33342 staining. The addition of ascorbate or catalase inhibited the formation of ferryl Mb and the onset of apoptosis, whereas apoptosis was enhanced in cells depleted of intracellular glutathione by pretreatment with buthionine sulfoximine. Mb and Mb/GOX suppressed cell cycle progression, but only Mb/GOX produced significant cell loss revealed by the accumulation of sub G1 events. These results suggest a role for the Mb redox cycle in the induction of endothelial cell apoptosis, which may be relevant in the pathophysiology of diseases characterized by the release of Mb from damaged muscle. Published by Elsevier Science, Inc. C1 US FDA, Ctr Biol Evaluat & Res, Div Hematol, Lab Plasma Derivat, Bethesda, MD 20892 USA. RP D'Agnillo, F (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Hematol, Lab Plasma Derivat, 8800 Rockville Pike,Bldg 29,Room 112, Bethesda, MD 20892 USA. NR 48 TC 26 Z9 26 U1 0 U2 4 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 OCT 15 PY 2002 VL 33 IS 8 BP 1153 EP 1164 AR PII S0891-5849(02)01007-9 DI 10.1016/S0891-5849(02)01007-9 PG 12 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 603NM UT WOS:000178566000015 PM 12374627 ER PT J AU Meseda, CA Elkins, KL Merchlinsky, MJ Weir, JP AF Meseda, CA Elkins, KL Merchlinsky, MJ Weir, JP TI Prime-boost immunization with DNA and modified vaccinia virus Ankara vectors expressing herpes simplex virus-2 glycoprotein D elicits greater specific antibody and cytokine responses than DNA vaccine alone SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT BSA Annual Medical Sociology Conference CY 2000 CL YORK, ENGLAND SP BSA ID IMMUNE-RESPONSES; PROTECTIVE EFFICACY; GENITAL HERPES; INDUCTION; MUCOSAL; TYPE-2; CELL; DISEASE; MICE; IMMUNOGENICITY AB Several reports have indicated that prime-boost strategies of vaccination can enhance the level of specific immunity induced by nucleic acid vaccines. The present report describes such a strategy with herpes simplex virus (HSV)-2 glycoprotein D (gD), using combinations of plasmid vector that expresses gD (pgD2) and a recombinant modified vaccinia virus Ankara vector that expresses gD (MVA-gD2). The IgG antibody response to gD and the HSV-2 neutralizing antibody response were greatest when the MVA-gD2 vector was used as the priming immunization and then was boosted with either pgD2 or MVA-gD2. Determination of the isotype profile of MVA-gD2-primed mice revealed a much broader distribution of isotypes than that seen after DNA vaccination. In addition, antigen-stimulated spleen cells from mice primed with MVA-gD2 and boosted with either MVA-gD2 or pgD2 produced higher levels of interleukin-2 and interferon-gamma than did those from pgD2-primed mice, indicating that a prime-boost immunization strategy that uses the MVA and plasmid DNA vector dramatically enhances and diversifies the humoral and cellular immune response to HSV-2 gD. C1 US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Lab DNA Viruses, Rockville, MD 20852 USA. RP Weir, JP (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Lab DNA Viruses, HFM-457,1401 Rockville Pike, Rockville, MD 20852 USA. NR 35 TC 38 Z9 38 U1 0 U2 3 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 2002 VL 186 IS 8 BP 1065 EP 1073 DI 10.1086/344234 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 598YK UT WOS:000178304800002 PM 12355355 ER PT J AU O'Neill, RT AF O'Neill, RT TI Regulatory perspectives on data monitoring SO STATISTICS IN MEDICINE LA English DT Article; Proceedings Paper CT 9th International Symposium on Long-Term Clinical Trials CY JUN 19-20, 2000 CL LONDON, ENGLAND DE data monitoring committee; interim analysis; International Conference on Harmonization; safety assessment; visual graphics; event charts ID CLINICAL-TRIALS; BOUNDARIES AB Data monitoring is a critical component of the conduct of clinical trials that provide the evidence of efficacy and safety of investigational drugs. These trials may be conducted either by a pharmaceutical sponsor or by the government, especially those large trials that assess the impact of therapies on serious morbidity and/or mortality. While not extensive, I will review a regulatory history of FDA's evolving concerns and positions on data monitoring. I will review the key aspects of data monitoring and interim analysis of clinical trials contained in the recently published International Conference on Harmonization's statistical guidance as well as some other issues being considered for a draft guidance on data monitoring. Finally, some suggestions for improving and enhancing tools and statistical methods for monitoring clinical trials for safety assessment will be offered. This latter area deserves more consideration by statisticians than it has received to date. Published in 2002 by John Wiley Sons, Ltd. C1 US FDA, CDER, HFD700, Rockville, MD 20857 USA. RP O'Neill, RT (reprint author), US FDA, CDER, HFD700, Room 15B-45,5600 Fishers Lane, Rockville, MD 20857 USA. NR 19 TC 17 Z9 17 U1 0 U2 0 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 15 PY 2002 VL 21 IS 19 BP 2831 EP 2842 DI 10.1002/sim.1287 PG 12 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 599WG UT WOS:000178357700008 PM 12325099 ER PT J AU Fleming, TR Ellenberg, S DeMets, DL AF Fleming, TR Ellenberg, S DeMets, DL TI Monitoring clinical trials: issues and controversies regarding confidentiality SO STATISTICS IN MEDICINE LA English DT Article; Proceedings Paper CT 9th International Symposium on Long-Term Clinical Trials CY JUN 19-20, 2000 CL LONDON, ENGLAND DE data monitoring committee; confidentiality; blinding; interim data ID CYTOMEGALOVIRUS DISEASE; ORAL GANCICLOVIR; ZALCITABINE; DIDANOSINE; ZIDOVUDINE; PLACEBO; SAFETY; AIDS AB During phase III clinical trials in life-threatening disease settings, it is important to ensure that the Data Monitoring Committee (DMC) has exclusive access to the interim efficacy and safety data generated by the data analysis centre, in order to minimize the risk of widespread prejudgement of unreliable trial results based on limited data. This prejudgement could adversely impact rates of patient accrual, continued adherence to trial regimens and ability to obtain unbiased and complete assessment of trial outcome measures. This also could result in publications of early results that might be very inconsistent with final study data on the benefit-to-risk profile of the study interventions. Circumstances arise only rarely in which unblinding of interim data beyond the DMC would enhance the ability of the trial to provide reliable results. However, to address the ethical imperative to protect the interests of study participants, the DMC itself should have access to unblinded efficacy and safety results. Copyright (C) 2002 John Wiley Sons, Ltd. C1 Univ Washington, Dept Biostat, Seattle, WA 98195 USA. US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. Univ Wisconsin, Dept Biostat & Med Informat, Madison, WI 53705 USA. RP Fleming, TR (reprint author), Univ Washington, Dept Biostat, Box 357232, Seattle, WA 98195 USA. NR 15 TC 24 Z9 24 U1 0 U2 3 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD OCT 15 PY 2002 VL 21 IS 19 BP 2843 EP 2851 DI 10.1002/sim.1288 PG 9 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 599WG UT WOS:000178357700009 PM 12325100 ER PT J AU Temple, R AF Temple, R TI Policy developments in regulatory approval SO STATISTICS IN MEDICINE LA English DT Article; Proceedings Paper CT 9th International Symposium on Long-Term Clinical Trials CY JUN 19-20, 2000 CL LONDON, ENGLAND DE placebo controls; surrogate endpoints; single study; non-inferiority studies ID PLACEBO-CONTROLLED TRIALS; ACTIVE-CONTROL TRIALS; ISSUES AB Although radical changes in drug regulation are rare (e.g., the Federal Food, Drug and Cosmetic Act of 1938 and the 1962 amendment to the Act creating an effectiveness requirement), regulations and guidance do evolve significantly in the face of new problems and accumulating experience. Recent changes have been driven by the Food and Drug Administration Modernization Act (FDAMA), user fee legislation, the International Conference on Harmonization, recent safety related drug withdrawals, and concerns about trial ethics and investigator conflict of interest. FDAMA and guidance developed in response to it has helped circumstances in which FDA would rely on a single study to support effectiveness and the circumstances in which surrogate endpoints could support approval. An ICH Document 'Choice of control group and related design issues in clinical trials' focussed attention on the ethics of placebo controls (acceptable, even if there is existing therapy, when the placebo-treated patient will suffer no irreversible injury) and the design of 'equivalence' or,non-inferiority' trials. There has been greatly increased attention to obtaining good dose-response information and to assessing need for modifying treatment in demographic (age, gender, race) and concomitant disease (renal or hepatic function abnormalities) subgroups, and in assessing drug-drug interactions. Other important trends are increasing reliance on non-U.S. data, increasing numbers of FDA-industry meetings during drug development, and new focus on risk assessment and risk management. Published in 2002 by John Wiley Sons, Ltd. C1 US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Temple, R (reprint author), US FDA, Ctr Drug Evaluat & Res, 5600 Fishers Lane,HFD-101-WOC 2-6014, Rockville, MD 20857 USA. NR 10 TC 22 Z9 22 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 OCT 15 PY 2002 VL 21 IS 19 BP 2939 EP 2948 DI 10.1002/sim.1298 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 599WG UT WOS:000178357700019 PM 12325110 ER PT J AU Doerge, DR Twaddle, NC Banks, EP Jefferson, WN Newbold, RR AF Doerge, DR Twaddle, NC Banks, EP Jefferson, WN Newbold, RR TI Pharmacokinetic analysis in serum of genistein administered subcutaneously to neonatal mice SO CANCER LETTERS LA English DT Article DE genistein; soy; pharmacokinetics; mass spectrometry; phytoestrogen; uterine cancer ID SPRAGUE-DAWLEY RATS; UDP-GLUCURONOSYLTRANSFERASE; UTERINE ADENOCARCINOMA; ISOFLAVONE GENISTEIN; HUMAN-LIVER; SOY; GLUCURONIDATION; ESTROGENS; DIETARY; MODEL AB Genistein, the principal soy isoflavone, was Previously shown to induce uterine adenocarcinomas by 18 months of age in female CD-1 mice following administration by subcutaneous injections on postnatal days 1-5. A serum pharmacokinetic analysis of genistein in male and female mice treated identically showed that: maximal concentrations of total (conjugated + aglycone) genistein in females (6.8 +/- 1.4 muM) and males (3.8 +/- 1.1 muM, mean +/- SD) were comparable to those previously reported from dietary exposures in adult rats or in human infants consuming soy formulas; the average fraction present as active aglycone (31%) was similar to those in fetal and neonatal rats from placental and lactational exposures; and elimination half-times were longer than those in rats (three- to seven-fold) and adult humans (two- to three-fold). These results are consistent with a diminished capacity for enzymatic conjugation of genistein, based on the ontogeny, as an important determinant of estrogenicity in neonatal mice. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved. C1 Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. NIEHS, Dev Endocrinol Sect, Mol Toxicol Lab, Environm Toxicol Program, Res Triangle Pk, NC 27709 USA. RP Doerge, DR (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. NR 23 TC 46 Z9 46 U1 0 U2 4 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 8 PY 2002 VL 184 IS 1 BP 21 EP 27 AR PII S0304-3835(02)00200-8 DI 10.1016/S0304-3835(02)00200-8 PG 7 WC Oncology SC Oncology GA 595WB UT WOS:000178130600004 PM 12104044 ER PT J AU Vandermeeren, Y De Volder, A Bastings, E Thonnard, JL Duque, J Grandin, C Sebire, G Olivier, E AF Vandermeeren, Y De Volder, A Bastings, E Thonnard, JL Duque, J Grandin, C Sebire, G Olivier, E TI Functional relevance of abnormal fMRI activation pattern after unilateral schizencephaly SO NEUROREPORT LA English DT Article DE corticospinal pathways; functional magnetic resonance imaging; motor cortex; transcranial magnetic stimulation ID TRANSCRANIAL MAGNETIC STIMULATION; HEMIPLEGIC CEREBRAL-PALSY; CENTRAL MOTOR; BRAIN INJURY; CORTEX; MRI; REORGANIZATION; MALFORMATIONS; PLASTICITY; CHILDREN AB Brain plasticity was investigated in a child with a hemiplegia due to unilateral schizencephaly involving the sensorimotor cortex. This focal lesion led to a dramatic functional reorganization of the undamaged hemisphere, as evidenced by the unusual pattern of fMRI activation during paretic finger movements. The functional relevance of the activation in the undamaged motor cortex was supported by the finding that TMS of this area yielded a response in the paretic hand, indicating that it controls both hands. However, this reorganization was not restricted to the primary motor cortex, but also concerned other structures involved in the control of movements, as shown by the activation of contralesional SMA and thalamus. In contrast, the fMRI activation in the damaged sensorimotor cortex during paretic hand movements appears functionally irrelevant. C1 Univ Catholique Louvain, Sch Med, Neurophysiol Lab, B-1200 Brussels, Belgium. Univ Catholique Louvain, Sch Med, Positron Emmiss Tomog Unit, B-1200 Brussels, Belgium. Univ Catholique Louvain, Sch Med, Dept Phys Med, B-1200 Brussels, Belgium. Univ Catholique Louvain, Sch Med, Rehabil Unit, B-1200 Brussels, Belgium. Univ Catholique Louvain, Sch Med, Paediat Neurol Serv, B-1200 Brussels, Belgium. US FDA, Div Neuropharmacol Drug Prod, Washington, DC 20204 USA. RP Olivier, E (reprint author), Univ Catholique Louvain, Sch Med, Neurophysiol Lab, 54 Ave Hippocrate, B-1200 Brussels, Belgium. NR 25 TC 19 Z9 19 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 7 PY 2002 VL 13 IS 14 BP 1821 EP 1824 DI 10.1097/00001756-200210070-00027 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 613XK UT WOS:000179156600027 PM 12395132 ER PT J AU Martinez, M Augsburger, L Johnston, T Jones, WW AF Martinez, M Augsburger, L Johnston, T Jones, WW TI Applying the Biopharmaceutics Classification System to veterinary pharmaceutical products Part I: Biopharmaceutics and formulation considerations SO ADVANCED DRUG DELIVERY REVIEWS LA English DT Review DE veterinary oral dosage forms; Biopharmaceutics Classification System; solubility; dissolution; in vivo/in vitro correlation ID DRUG ABSORPTION; GASTROINTESTINAL TRANSIT; ORAL BIOAVAILABILITY; VIVO BIOAVAILABILITY; SAFETY ASSESSMENT; DOSAGE FORMS; RELEASE; VITRO; PERMEABILITY; DISSOLUTION AB The complexity of multiple species approvals continues throughout the life of a product as post-approval manufacturing changes, as well as all generic versions of approved products, are evaluated for each of the approved target animal species. In comparing product bioavailability across animal species, it is not unusual to observe marked interspecies differences. For many compounds, these differences reflect species-specific presystemic metabolism. However, a host of other variables must also be considered, including in vivo drug solubility, gastric transit time, intestinal permeability, diet, and species-by-formulation interactions. To predict potential species-by-formulation interactions, one must consider the solubility and intestinal permeability of the drug entity, the type of formulation, nature of the excipients, and the physiological characteristics of the animal recipient. In this paper, we examine manufacturing and formulation variables that can affect drug bioavailability, and the potential for species-specific differences in the responses to these formulations. (C) 2002 Elsevier Science B.V. All rights reserved. C1 US FDA, Off New Anim Drug Evaluat, Rockville, MD 20855 USA. Univ Maryland, Baltimore, MD 21201 USA. Univ Missouri, Kansas City, MO 64110 USA. RP Martinez, M (reprint author), US FDA, Off New Anim Drug Evaluat, Rockville, MD 20855 USA. NR 88 TC 46 Z9 46 U1 0 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-409X J9 ADV DRUG DELIVER REV JI Adv. Drug Deliv. Rev. PD OCT 4 PY 2002 VL 54 IS 6 BP 805 EP 824 AR PII S0169-409X(02)00070-4 DI 10.1016/S0169-409X(02)00070-4 PG 20 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 608PH UT WOS:000178855100004 PM 12363432 ER PT J AU Martinez, M Amidon, G Clarke, L Jones, WW Mitra, A Riviere, J AF Martinez, M Amidon, G Clarke, L Jones, WW Mitra, A Riviere, J TI Applying the biopharmaceutics classification system to veterinary pharmaceutical products Part II. Physiological considerations SO ADVANCED DRUG DELIVERY REVIEWS LA English DT Review DE biopharmaceutics classification system; interspecies differences; veterinary oral drug absorption; animal models; food effects; lymphatic uptake ID DEPENDENT INTESTINAL-ABSORPTION; LYMPHATIC DRUG TRANSPORT; ORAL BIOAVAILABILITY; GASTROINTESTINAL TRANSIT; IN-VITRO; DOSAGE FORMS; P-GLYCOPROTEIN; BEAGLE DOGS; CROHNS-DISEASE; SPECIES-DIFFERENCES AB in comparing product bioavailability across animal species, it is not unusual to observe marked interspecies differences. For many compounds, these differences reflect presystemic drug metabolism. However, a host of other variables must also be considered such as in vivo drug solubility, gastric transit time, intestinal permeability, diet, and species-by-formulation interactions. By combining information on drug solubility and intestinal permeability with an understanding of the interrelationship between pH, product dissolution and gastrointestinal physiology, we attempt to define those conditions under which in vitro dissolution data may be used as a surrogate for data on in vivo bioavailability. We consider the likely physiological causes for species-related differences in the absolute and relative bioavailability of orally administered pharmaceuticals, and examine the potential for these normal interspecies differences to reflect bioavailability changes that can occur with various human pathologies. (C) 2002 Elsevier Science B.V. All rights reserved. C1 US FDA, Off New Anim Drug Evaluat, Rockville, MD 20855 USA. Univ Michigan, Ann Arbor, MI 48109 USA. Univ Missouri, Kansas City, MO 64110 USA. Univ Missouri, Columbia, MO 65212 USA. N Carolina State Univ, Raleigh, NC 27606 USA. RP Martinez, M (reprint author), US FDA, Off New Anim Drug Evaluat, Rockville, MD 20855 USA. NR 157 TC 56 Z9 57 U1 1 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-409X J9 ADV DRUG DELIVER REV JI Adv. Drug Deliv. Rev. PD OCT 4 PY 2002 VL 54 IS 6 BP 825 EP 850 AR PII S0169-409X(02)00071-6 DI 10.1016/S0169-409X(02)00071-6 PG 26 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 608PH UT WOS:000178855100005 PM 12363433 ER PT J AU Xu, Z Seidler, FJ Cousins, MM Slikker, W Slotkin, TA AF Xu, Z Seidler, FJ Cousins, MM Slikker, W Slotkin, TA TI Adolescent nicotine administration alters serotonin receptors and cell signaling mediated through adenylyl cyclase SO BRAIN RESEARCH LA English DT Article DE adenylyl cyclase; adolescence; beta-adrenergic receptor; depression; nicotine; serotonin receptor ID RAT-BRAIN REGIONS; POSITRON-EMISSION-TOMOGRAPHY; MAJOR DEPRESSION; CEREBRAL-CORTEX; CHOLINERGIC RECEPTORS; CIGARETTE-SMOKING; 5-HT1A RECEPTOR; GENE-EXPRESSION; FETAL NICOTINE; DENTATE GYRUS AB Nicotine is a neuroteratogen that targets synaptic function during critical developmental stages and recent studies indicate that CNS vulnerability extends into adolescence, the age at which smoking typically commences. We administered nicotine to adolescent rats via continuous minipump infusions from PN30 to PN47.5, using 6 mg/kg/day, a dose rate that replicates the plasma nicotine levels found in smokers, and examined 5HT receptors and related cell signaling during nicotine administration (PN45) and in the post-treatment period (PN50, 60, 75). Adolescent nicotine decreased 5HT(2) receptor binding in brain regions containing 5HT projections (hippocampus and cerebral cortex), with selectivity for females in the cerebral cortex; regions containing 5HT cell bodies showed either an increase (midbrain in males) or no change (brainstem). In contrast, there were no significant changes in 5HT(1A) receptors; however, the ability of the receptors to signal through adenylyl cyclase (AC) showed a switch from stimulatory to inhibitory effects in females during the post-treatment period. There were also transient alterations in AC responses to beta-adrenergic receptor stimulation, as well as pronounced induction of the AC response to the non-receptor-mediated stimulant, forskolin. Our results indicate that adolescent nicotine exposure alters the concentrations and functions of postsynaptic 5HT receptors in a manner commensurate with impaired 5HT synaptic function. The direction of change, emergence of defects after the cessation of nicotine administration, and sex-preference for effects in females, all support a relationship of impaired 5HT function to the higher incidence of depression seen in adolescent smokers. (C) 2002 Elsevier Science B.V. 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 72205 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, Box 3813, Durham, NC 27710 USA. FU NIDA NIH HHS [DA 14247] NR 79 TC 58 Z9 59 U1 2 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD OCT 4 PY 2002 VL 951 IS 2 BP 280 EP 292 AR PII S0006-8993(02)03174-8 DI 10.1016/S0006-8993(02)03174-8 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 602TB UT WOS:000178519600016 PM 12270507 ER PT J AU Liu, MJ Reimschuessel, R Hassel, BA AF Liu, MJ Reimschuessel, R Hassel, BA TI Molecular cloning of the fish interferon stimulated gene, 15 kDa (ISG15) orthologue: a ubiquitin-like gene induced by nephrotoxic damage SO GENE LA English DT Article DE interferon-stimulated gene; ubiquitin-like protein; goldfish; kidney injury ID DOUBLE-STRANDED-RNA; PROTEIN; SYSTEM; TRANSCRIPTION; ALIGNMENT; INDUCTION; NEPHRONS; GOLDFISH; INNATE; MODEL AB In mammals, the response to nephrotoxicant-induced renal injury is limited to repair of the proximal tubule by surviving epithelial cells. In contrast, bony fish are capable of both repair, and de novo production of nephrons in response to renal damage. Importantly, toxicant-induced nephron neogenesis in goldfish (Carassius auratus) parallels nephron development in the mammalian embryo, providing a vertebrate model for kidney development. We utilized this model system to identify genes induced by the renal toxicant, gentamicin, that may function in nephron neogenesis. A novel ubiquitin-like (UBL) gene, 40.1, was identified by differential display analysis of control and gentamicin-treated goldfish kidney. 40.1 was induced dramatically 3-7 days following a sublethal dose of gentamicin, and returned to basal level by 14 days post-treatment. The induction of 40.1 coincided with early renal injury in the proximal tubules of gentamicin-injected fish; however, expression was not restricted to the kidney, suggesting that 40.1 induction may be a more general response to cell injury. Sequence analysis revealed that 40.1 contains tandem UBL domains, and shares homology with ISG15, a 15 kD interferon-(IFN) stimulated UBL found in mammals. Analysis of the genome database for the pufferfish, Fugu rubrides, identified a goldfish ISGI5 (gfIG15) homologue with an IFN-stimulated response element in the promoter region, providing further evidence that gfISG15 is the true teleost ISG15 orthologue. Zebrafish and catfish ISGI5 genes were subsequently identified by sequence analysis. Consistent with its predicted function as a UBL, gfISGI5 formed conjugates with cellular proteins in vitro and in transient transfections. Similar to the induction of mammalian ISG15 by microbial challenge, gfISG15 was induced in the spleen of mycobacteria-infected fish. These studies identified the first teleost ISG15 orthologue. The induction of gfISG15 as an early genetic event in response to a renal toxicant, and its conserved, stress-associated, expression in higher vertebrates suggests that ISG15 is an important component of the host response to diverse stress stimuli. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Univ Maryland, Mol & Cellular Biol Program, Baltimore, MD 21201 USA. US FDA, Ctr Vet Med, Laurel, MD 20708 USA. Univ Maryland, Greenebaum Canc Ctr, Baltimore, MD 21201 USA. RP Hassel, BA (reprint author), Univ Maryland, Mol & Cellular Biol Program, 108 N Greene St, Baltimore, MD 21201 USA. FU NIDDK NIH HHS [DK 53700] NR 30 TC 59 Z9 64 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD OCT 2 PY 2002 VL 298 IS 2 BP 129 EP 139 AR PII S0378-1119(02)00932-0 DI 10.1016/S0378-1119(02)00932-0 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 618UN UT WOS:000179435800003 PM 12426101 ER PT J AU Crawford, LM AF Crawford, LM TI Advisory on clinical holds 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 Crawford, LM (reprint author), US FDA, Off Commissioner Food & Drugs, HF-1,Room 14-71,5600 Fishers Ln, Rockville, MD 20857 USA. NR 0 TC 3 Z9 3 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 2 PY 2002 VL 288 IS 13 BP 1579 EP 1579 DI 10.1001/jama.288.13.1579-c PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 599BJ UT WOS:000178314000007 PM 12350176 ER PT J AU Crawford, LM AF Crawford, LM TI FDA statement on Prempro 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 Crawford, LM (reprint author), US FDA, Off Commissioner Food & Drugs, HF-1,Room 14-71,5600 Fishers Ln, Rockville, MD 20857 USA. NR 0 TC 3 Z9 3 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 2 PY 2002 VL 288 IS 13 BP 1579 EP 1579 DI 10.1001/jama.288.13.1579-c PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 599BJ UT WOS:000178314000006 PM 12350176 ER PT J AU Crawford, LM AF Crawford, LM TI Device for young diabetics 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 Crawford, LM (reprint author), US FDA, Off Commissioner Food & Drugs, HF-1,Room 14-71,5600 Fishers Ln, Rockville, MD 20857 USA. NR 0 TC 3 Z9 3 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 2 PY 2002 VL 288 IS 13 BP 1579 EP 1579 DI 10.1001/jama.288.13.1579-c PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 599BJ UT WOS:000178314000004 PM 12350176 ER PT J AU Crawford, LM AF Crawford, LM TI Pharmacy compounding guidance 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 Crawford, LM (reprint author), US FDA, Off Commissioner Food & Drugs, HF-1,Room 14-71,5600 Fishers Ln, Rockville, MD 20857 USA. NR 0 TC 3 Z9 3 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 2 PY 2002 VL 288 IS 13 BP 1579 EP 1579 DI 10.1001/jama.288.13.1579-c PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 599BJ UT WOS:000178314000005 PM 12350176 ER PT J AU Saad, ED Kraut, EH Hoff, PM Moore, DF Jones, D Pazdur, R Abbruzzese, JL AF Saad, ED Kraut, EH Hoff, PM Moore, DF Jones, D Pazdur, R Abbruzzese, JL TI Phase II study of dolastatin-10 as first-line treatment for advanced colorectal cancer SO AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS LA English DT Article DE colorectal cancer; dolastatin-10; phase II trial ID ADVANCED SOLID TUMORS; CELL LUNG-CANCER; NSC-376128; AGENTS AB Dolastatin-10 is a potent inhibitor of microtubule assembly derived from the sea hare, which displayed significant antitumor activity in preclinical models. We conducted a phase II study of dolastatin-10 in patients with advanced colorectal cancer and no prior chemotherapy for metastatic disease, Fourteen patients received doses ranging from 300 mug/m(2) to 450 mug/m(2) as an intravenous push every 21 days. There were no major objective responses, Toxicity was mainly hematologic. with grade III or IV granulocytopenia occurring in 9 of 42 treatment courses. Other toxic effects were generally mild. Dolastatin-10 lacks clinically significant activity in advanced colorectal cancer when used in this dose and schedule. C1 Univ Texas, MD Anderson Canc Ctr, Dept Gastrointestinal Med Oncol, Houston, TX 77030 USA. Ohio State Univ, Columbus, OH 43210 USA. Wichita Clin Community Oncol Program, Wichita, KS USA. US FDA, Div Oncol Drug Prod, Rockville, MD 20857 USA. RP Hoff, PM (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Gastrointestinal Med Oncol, 1515 Holcombe Blvd,Box 78, Houston, TX 77030 USA. FU NCI NIH HHS [UO1 CA70172] NR 12 TC 34 Z9 38 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-3732 J9 AM J CLIN ONCOL-CANC JI Am. J. Clin. Oncol.-Cancer Clin. Trials PD OCT PY 2002 VL 25 IS 5 BP 451 EP 453 DI 10.1097/00000421-200210000-00005 PG 3 WC Oncology SC Oncology GA 603EY UT WOS:000178546900005 PM 12393982 ER PT J AU Kawakami, K Kawakami, M Husain, SR Puri, RK AF Kawakami, K Kawakami, M Husain, SR Puri, RK TI Pancreatic cancer therapy by intratumoral gene transfer of IL-13R alpha 2 chain followed by IL-13R-targeted bacterial cytotoxin administration in animal models. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT 52nd Annual Meeting of the American-Society-of-Human-Genetics CY OCT 15-19, 2002 CL BALTIMORE, MARYLAND SP Amer Soc Human Genet, NICHHD, NCI, NIMH, Affymetrix Inc, Gentra Syst, NIDCD C1 US FDA, Ctr Biol Evaluat & Res, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, Bethesda, MD USA. NR 0 TC 0 Z9 0 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 OCT PY 2002 VL 71 IS 4 SU S MA 2404 BP 580 EP 580 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 594AC UT WOS:000178025802391 ER PT J AU Jakubzick, C Kunkel, SL Joshi, BH Puri, RK Hogaboam, CM AF Jakubzick, C Kunkel, SL Joshi, BH Puri, RK Hogaboam, CM TI Interleukin-13 fusion cytotoxin arrests Schistosoma mansoni egg-induced pulmonary granuloma formation in mice SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID MONOCYTE CHEMOATTRACTANT PROTEIN-1; HUMAN LUNG FIBROBLASTS; PSEUDOMONAS EXOTOXIN; IL-13 RECEPTOR; CYTOKINE EXPRESSION; SIGNAL-TRANSDUCTION; IFN-GAMMA; TH2 CELLS; T-CELLS; HEPATIC-FIBROSIS AB Schistosoma mansoni egg-induced lung pathology requires the actions of interleukin (IL)-4 and IL-13. Because receptors for IL-4 and IL-13 share chains, we examined the effect of a fusion protein comprised of IL-13 and Pseudomonas exotoxin (IL13-PE) on the development of pulmonary granulomas in mice. At day 8 after an intravenous injection of live S. mansoni eggs, whole lung samples from IL13-PE-treated mice exhibited significantly lower IL-4 and IL-13 gene expression, smaller granulomas, decreased collagen levels, and increased IL-13 receptor alpha2 gene expression compared to controls. The therapeutic effects of IL13-PE were also observed at day 16 despite the termination of IL13-PE treatment at day 8. These studies demonstrate that targeting IL-4- and IL-13- responsive cells with IL13-PE effectively arrests S. mansoni egg granuloma formation. C1 Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI 48109 USA. US FDA, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. RP Hogaboam, CM (reprint author), Univ Michigan, Sch Med, Dept Pathol, 301 Catherine Rd, Ann Arbor, MI 48109 USA. RI hogaboam, cory /M-3578-2014 NR 72 TC 17 Z9 17 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD OCT PY 2002 VL 161 IS 4 BP 1283 EP 1297 DI 10.1016/S0002-9440(10)64405-7 PG 15 WC Pathology SC Pathology GA 601NQ UT WOS:000178453000021 PM 12368202 ER PT J AU Baldwin, AL Wiley, EB Alayash, AI AF Baldwin, AL Wiley, EB Alayash, AI TI Comparison of effects of two hemoglobin-based O-2 carriers on intestinal integrity and microvascular leakage SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE blood substitutes; fluorescence microscopy; venular leakage; electron microscopy ID CROSS-LINKED HEMOGLOBIN; BLOOD SUBSTITUTES; REDOX PROPERTIES; RAT MESENTERY; POLYMERIZATION; GENERATION; TOXICITY; EFFICACY; CELLS AB Two "blood substitutes," a diaspirin cross-linked human hemoglobin [bis(3,5 dibromosalicyl)fumarate, DBBF-Hb] and a bovine polymerized hemoglobin (PolyHbBv), advanced to clinical trials, are used in this study. Previously, we have shown that injection of DBBF-Hb into the rat circulation produces venular leakage and intestinal epithelial disruption. The purpose of this study was to determine whether PolyHbBv, currently approved for veterinary use in the United States, shows similar effects. In anesthetized Sprague-Dawley rats, the mesenteric microvasculature was perfused with DBBF-Hb (n = 6), PolyHbBv (n = 5), cyanomet Hb (CNmet-DBBF-Hb), or HEPES-buffered saline with 0.5% bovine serum albumin (HBS-BSA) (controls, n = 7) for 10 min, followed by FITC-albumin for 3 min, and then fixed for microscopy. For DBBF-Hb, the mean leak number per micrometer venule length [2.41 +/- 0.33 (+/-SE) x 10(-3)] was significantly greater than for PolyHbBv (0.53 +/- 0.14 x 10(-3)), CNmet-DBBF-Hb (0.36 +/- 0.14 x 10(-3)), and HBS-BSA (0.12 +/- 0.08 x 10(-3))( P < 0.01). Corresponding quantities for leak area were 0.10 +/- 0.03, 0.010 +/- 0.003, 0.005 +/- 0.003, and 0.02 +/- 0.02 μm(2)/μm. In rats injected with DBBF-Hb (n = 8), intestinal epithelial integrity was significantly compromised compared with those injected with PolyHbBv (n = 5) or saline (n = 6). These results indicate that intravascular PolyHbBv produces significantly less disruption of the intestinal exchange barrier than does DBBF-Hb, probably because the heme is not so easily oxidized. C1 Univ Arizona, Coll Med, Dept Physiol, Tucson, AZ 85724 USA. US FDA, Lab Plasma Derivat, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Baldwin, AL (reprint author), Univ Arizona, Coll Med, Dept Physiol, Tucson, AZ 85724 USA. FU NHLBI NIH HHS [HL-53047] NR 29 TC 27 Z9 30 U1 1 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD OCT PY 2002 VL 283 IS 4 BP H1292 EP H1301 DI 10.1152/ajpheart.00221.2002 PG 10 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 594DY UT WOS:000178034500003 PM 12234778 ER PT J AU Hanes, DE Orlandi, PA Burr, DH Miliotis, MD Robl, MG Bier, JW Jackson, GJ Arrowood, MJ Churey, JJ Worobo, RW AF Hanes, DE Orlandi, PA Burr, DH Miliotis, MD Robl, MG Bier, JW Jackson, GJ Arrowood, MJ Churey, JJ Worobo, RW TI Inactivation of Cryptosporidium parvum oocysts in fresh apple cider by UV irradiation (vol 68, pg 4168, 2002) SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Correction C1 US FDA, Ctr Food Safety & Appl Nutr, Laurel, MD USA. US FDA, Washington, DC 20204 USA. Cornell Univ, New York State Agr Expt Stn, Dept Food Sci & Technol, Geneva, NY 14456 USA. Ctr Dis Control & Prevent, Div Parasit Dis, Atlanta, GA USA. RP Hanes, DE (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Laurel, MD USA. RI Worobo, Randy/D-8779-2014 NR 1 TC 2 Z9 2 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0099-2240 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD OCT PY 2002 VL 68 IS 10 BP 5208 EP 5208 DI 10.1128/AEM.68.10.5208.2002 PG 1 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 600FX UT WOS:000178380900073 ER PT J AU Lee, JH Slifman, NR Gershon, SK Edwards, ET Schwieterman, WD Siegel, JN Wise, RP Brown, SL Udall, JN Braun, MM AF Lee, JH Slifman, NR Gershon, SK Edwards, ET Schwieterman, WD Siegel, JN Wise, RP Brown, SL Udall, JN Braun, MM TI Life-threatening histoplasmosis complicating immunotherapy with tumor necrosis factor alpha antagonists infliximab and etanercept SO ARTHRITIS AND RHEUMATISM LA English DT Article; Proceedings Paper CT 65th Annual Scientific Meeting of the American-College-of-Rheumatology CY NOV, 2001 CL SAN FRANCISCO, CALIFORNIA SP Amer Coll Rheumatol ID LOW-DOSE METHOTREXATE; TNF-ALPHA; CAPSULATUM; INFECTION; IMMUNITY; THERAPY; PLAYS AB Objective. Two tumor necrosis factor alpha (TNFalpha) antagonists were recently licensed in the US. Infliximab was licensed in 1998 for the treatment of Crohn's disease (CD), and since 1999, it has been licensed in combination with methotrexate for treatment of rheumatoid arthritis (RA). Etanercept was licensed in 1998 for treatment of RA and, more recently, for juvenile RA and psoriatic arthritis. Because of potential immunosuppression related to use of anti-TNFalpha agents, we sought to identify postlicensure cases of opportunistic infection, including histoplasmosis, in patients treated with these products. Methods. The US Food and Drug Administration's (FDA) passive surveillance database for monitoring postlicensure adverse events was reviewed to identify all reports received through July 2001 of histoplasmosis in patients treated with either infliximab or etanercept. Results. Ten cases of Histoplasma capsulatum (HC) infection were reported: 9 associated with infliximab and 1 associated with etanercept. In patients treated with infliximab, manifestations of histoplasmosis occurred within 1 week to 6 months after the first dose and typically included fever, malaise, cough, dyspnea, and interstitial pneumonitis. Of the 10 patients with histoplasmosis, 9 required treatment in an intensive care unit, and 1 died. All patients had received concomitant immunosuppressive medications in addition to infliximab or etanercept, and all resided in HC-endemic regions. Conclusion. Postlicensure surveillance suggests that acute life-threatening histoplasmosis may complicate immunotherapy with TNFalpha antagonists, particularly infliximab. Histoplasmosis should be considered early in the evaluation of patients who reside in HC-endemic areas in whom infectious complications develop during treatment with infliximab or etanercept. C1 US FDA, Div Epidemiol, Off Biostat & Epidemiol, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. Louisiana State Univ, Hlth Sci Ctr, New Orleans, LA USA. RP Braun, MM (reprint author), US FDA, Div Epidemiol, Off Biostat & Epidemiol, Ctr Biol Evaluat & Res, 1401 Rockville Pike,HFM-220, Rockville, MD 20852 USA. NR 21 TC 283 Z9 290 U1 1 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD OCT PY 2002 VL 46 IS 10 BP 2565 EP 2570 DI 10.1002/art.10583 PG 6 WC Rheumatology SC Rheumatology GA 604QX UT WOS:000178633500004 ER PT J AU Seo, KH Holt, PS Brackett, RE Gast, RK Stone, HD AF Seo, KH Holt, PS Brackett, RE Gast, RK Stone, HD TI Mucosal humoral immunity to experimental salmonella enteritidis infection in the chicken crop SO AVIAN DISEASES LA English DT Article DE mucosal; sIgAs; Salmonella enteritidis; crop; bile ID EGG-YOLK; ANTIBODIES; HENS AB In this report, we show that chickens, infected with Salmonella enteritidis (SE) by oral gavage, produce secretory immunoglobulin As (sIgAs) that specifically bind to numerous SE antigens. Chickens infected with SE showed strong slgA response against flagella in both bile and crop. The optical density values of enzyme-linked immunosorbent assay (ELISA) tests in positive bile and crop were 1.17 and 0.38, respectively, and were significantly different from those of negative samples. Western immunoblotting revealed that similar to13.5-, similar to56, similar to62-, similar to80, and similar to143-kD polypeptides were immunodominant proteins in bile, whereas similar to56, similar to62-, and similar to80-kD polypeptides were found to be strong antigens in crop. These results indicate that the crop may function as another site for mucosal immunity, and the SE flagella-based ELISA of crop samples can provide a useful screening test of SE exposure in chickens. C1 FDA CFSAN OPDFB HFS 300, College Pk, MD 20740 USA. USDA ARS, SE Poultry Res Lab, Athens, GA 30605 USA. RP Holt, PS (reprint author), FDA CFSAN OPDFB HFS 300, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. NR 16 TC 17 Z9 17 U1 0 U2 1 PU AMER ASSOC AVIAN PATHOLOGISTS PI KENNETT SQ PA UNIV PENN, NEW BOLTON CENTER, KENNETT SQ, PA 19348-1692 USA SN 0005-2086 J9 AVIAN DIS JI Avian Dis. PD OCT-DEC PY 2002 VL 46 IS 4 BP 1015 EP 1020 DI 10.1637/0005-2086(2002)046[1015:MHITES]2.0.CO;2 PG 6 WC Veterinary Sciences SC Veterinary Sciences GA 624AG UT WOS:000179736700030 PM 12495067 ER PT J AU Lyn-Cook, BD Taylor, S Goobsy, N Hammons, G AF Lyn-Cook, BD Taylor, S Goobsy, N Hammons, G TI Indole-3-carbinol (I3C) inhibits cell growth, induces apoptosis and up-regulates DT-diaphorase in pancreatic cancer cells SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT Conference on Frontiers in Cancer Prevention Research CY OCT 14-18, 2002 CL BOSTON, MASSACHUSETTS SP Amer Assoc Canc Res C1 NCTR, FDA, Jefferson, AR USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD OCT PY 2002 VL 11 IS 10 MA D125 BP 1218S EP 1218S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 604RE UT WOS:000178634200318 ER PT J AU Elespuru, RK Garrett-Young, R Chen, FS AF Elespuru, RK Garrett-Young, R Chen, FS TI Molecular epidemiology approach to cancer etiology using the LARC p53 human tumor database SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT Conference on Frontiers in Cancer Prevention Research CY OCT 14-18, 2002 CL BOSTON, MASSACHUSETTS SP Amer Assoc Canc Res C1 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 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD OCT PY 2002 VL 11 IS 10 MA D140 BP 1221S EP 1221S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 604RE UT WOS:000178634200333 ER PT J AU Kadlubar, FF AF Kadlubar, FF TI Pathways of metabolism of chemopreventive agents and the impact of genetic polymorphisms. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT Conference on Frontiers in Cancer Prevention Research CY OCT 14-18, 2002 CL BOSTON, MASSACHUSETTS SP Amer Assoc Canc Res C1 Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD OCT PY 2002 VL 11 IS 10 BP 1238S EP 1238S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 604RE UT WOS:000178634200401 ER PT J AU Feng, ZH Hu, WW Rom, WN Beland, FA Tang, MS AF Feng, ZH Hu, WW Rom, WN Beland, FA Tang, MS TI 4-aminobiphenyl is a major etiological agent of human bladder cancer: evidence from its DNA binding spectrum in human p53 gene SO CARCINOGENESIS LA English DT Article ID HUMAN URINARY-BLADDER; HOT-SPOTS; MUTATIONAL HOTSPOTS; HEMOGLOBIN ADDUCTS; LUNG; CHROMATOGRAPHY; SMOKERS; QUANTITATION; NONSMOKERS; CARCINOMA AB 4-Aminobiphenyl (4-ABP) is a major etiological agent of human bladder cancer, and its metabolites are able to form DNA adducts that may induce mutation and initiate bladder carcinogenesis. Thirty to sixty percent of human bladder cancer has a mutation in the p53 gene, and the mutational spectrum bears two characteristics: compared with other cancers, the pattern of mutations is more evenly distributed along the p53 gene, and the mutational hotspots occur at both CpG sites, such as codons 175, 248 and 273, and non-CpG sites, such as codons 280 and 285, the latter two being unique mutational hotspots for bladder and other urinary tract cancers. These findings raise the possibility that the special p53 mutational features in human bladder cancer are due to the unique binding spectrum of metabolically activated 4-ABP in bladder cells. To address this question, here we have mapped the 4-ABP-DNA adduct distribution in the p53 gene at the nucleotide sequence level in human bladder cells. We found that, unlike benzo[a]pyrene trans7,8-dihydrodiol-9,10-epoxide-DNA adduction, which preferentially occurs at CpG sites, 4-ABP-DNA adduction is not biased for CpG sites, and the adducts are more evenly distributed along the p53 gene; nonetheless, the p53 mutational hotspots in bladder cancer at codons 175, 248, 280 and 285 are also the preferential sites for 4-ABP adduct formation. These results strongly suggest that the unique binding spectrum of 4-ABP contributes greatly to the unique mutational spectrum in the p53 gene of human bladder cancer, and provide further molecular evidence to directly link 4-ABP to bladder cancer. C1 NYU, Sch Med, Dept Environm Med, Tuxedo Pk, NY 10987 USA. NYU, Sch Med, Dept Med, Tuxedo Pk, NY 10987 USA. NYU, Sch Med, Dept Pathol, Tuxedo Pk, NY 10987 USA. Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Tang, MS (reprint author), NYU, Sch Med, Dept Environm Med, Tuxedo Pk, NY 10987 USA. FU NCI NIH HHS [UO1CA86137]; NIEHS NIH HHS [ES10344, ES03124, ES00260, ES08389]; PHS HHS [M0100096] NR 40 TC 53 Z9 55 U1 1 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD OCT PY 2002 VL 23 IS 10 BP 1721 EP 1727 DI 10.1093/carcin/23.10.1721 PG 7 WC Oncology SC Oncology GA 607QG UT WOS:000178801800021 PM 12376482 ER PT J AU Chen, T da Costa, GG Marques, MM Shelton, SD Beland, FA Manjanatha, MG AF Chen, T da Costa, GG Marques, MM Shelton, SD Beland, FA Manjanatha, MG TI Mutations induced by alpha-hydroxytamoxifen in the lacI and cII genes of Big Blue transgenic rats SO CARCINOGENESIS LA English DT Article ID ENDOGENOUS HPRT GENE; DNA ADDUCT FORMATION; MOLECULAR ANALYSIS; BREAST-CANCER; TAMOXIFEN; LIVER; TISSUE; CELLS; MICE; SULFOTRANSFERASE AB The antiestrogen tamoxifen is widely used for the treatment of breast cancer and more recently for the prevention of breast cancer. A concern over the use of tamoxifen as a chemopreventive agent is its carcinogenicity in rat liver, through a genotoxic mechanism involving alpha-hydroxylation, esterification, and DNA adduct formation, primarily by reaction with dG. In a recent study [Gamboa da Costa et al., Cancer Lett., 176, 37-45 (2002)], we demonstrated a significant increase in the mutant frequency in the lacI gene of Big Blue rats treated with tamoxifen, and a further increase in rats administered alpha-hydroxytamoxifen. In the present study, we have assessed mutation induction by tamoxifen and a-hydroxytamoxifen in the liver cII gene of Big Blue rats and have characterized the types of mutations induced by a-hydroxytamoxifen in the liver lacI and cII genes. The mutant frequencies in the liver W gene were 80 +/- 13 x 10(-6) in the control, 112 +/- 13 x 10(-6) in the tamoxifen-treated group (P < 0.01 vs. control), and 942 +/- 114 x 10(-6) in the a-hydroxytamoxifen-treated animals (P < 0.001 vs. control; P < 0.001 vs. tamoxifen). Molecular analysis of the mutants indicated that the alpha-hydroxytamoxifen-induced mutational spectrum differed significantly from the control spectrum, but was very similar to the spectrum induced by tamoxifen for both the lacI and W genes [Davies et al, Environ. Mol. Mutagen., 28, 430-433 (1996); Davies et al., Carcinogenesis, 20, 13511356 (1999)]. G:C -> T:A transversion was the major type of mutation induced by alpha-hydroxytamoxifen and tamoxifen, while G: C -> A:T transition was the main type of mutation in the control. These results support the hypothesis that alpha-hydroxytamoxifen is a major proximate tamoxifen metabolite causing the initiation of tumors in the liver of rats treated with tamoxifen. C1 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. Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Chen, T (reprint author), Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, HFT 130,3900 NCTR Rd, Jefferson, AR 72079 USA. EM tchen@nctr.fda.gov RI Marques, M. Matilde/E-2535-2012 OI Marques, M. Matilde/0000-0002-7526-4962 NR 36 TC 17 Z9 17 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD OCT PY 2002 VL 23 IS 10 BP 1751 EP 1757 DI 10.1093/carcin/23.10.1751 PG 7 WC Oncology SC Oncology GA 607QG UT WOS:000178801800025 PM 12376486 ER PT J AU Yu, SJ Keenan, SM Tong, W Welsh, WJ AF Yu, SJ Keenan, SM Tong, W Welsh, WJ TI Influence of the structural diversity of data sets on the statistical quality of three-dimensional quantitative-activity relationship (3D-QSAR) models: Predicting the estrogenic activity of xenoestrogens SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID LIGAND-BINDING DOMAINS; NUCLEAR RECEPTOR SXR; ANDROGEN RECEPTOR; PROSTATE-CANCER; GENE-MUTATIONS; RECOGNITION; QSAR AB Federal legislation has resulted in the two-tiered in vitro and in vivo screening of some 80 000 structurally diverse chemicals for possible endocrine disrupting effects. To maximize efficiency and minimize expense, prioritization of these chemicals with respect to their estrogenic disrupting potential prior to this time-consuming and labor-intensive screening process is essential. Computer-based quantitative structure-activity relationship (QSAR) models, such as those obtained using comparative molecular field analysis (CoMFA), have been demonstrated as useful for risk assessment in this application. In general, however, CoMFA models to predict estrogenicity have been developed from data sets with limited structural diversity. In this study, we constructed CoMFA models based on biological data for a structurally diverse set of compounds spanning eight chemical families. We also compared two standard alignment schemes employed in CoMFA, namely, atom-fit and flexible field-fit, with respect to the predictive capabilities of their respective models for structurally diverse data sets. The present analysis indicates that flexible field-fit alignment fares better than atom-fit alignment as the structural diversity of the data set increases. Values of log(RP), where RP = relative potency, predicted by the final flexible field-fit CoMFA models are in good agreement with the corresponding experimental values. These models should be effective for predicting the endocrine disrupting potential of existing chemicals as well as prospective and newly prepared chemicals before they enter the environment. C1 Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Pharmacol, Piscataway, NJ 08854 USA. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Welsh, WJ (reprint author), Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Pharmacol, 675 Hoes Lane, Piscataway, NJ 08854 USA. NR 30 TC 36 Z9 42 U1 1 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD OCT PY 2002 VL 15 IS 10 BP 1229 EP 1234 DI 10.1021/tx0255875 PG 6 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 607TX UT WOS:000178807800003 PM 12387618 ER PT J AU Churchwell, MI Beland, FA Doerge, DR AF Churchwell, MI Beland, FA Doerge, DR TI Quantification of multiple DNA adducts formed through oxidative stress using liquid chromatography and electrospray tandem mass spectrometry SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID BASE ADDUCTS; DAMAGE; ASSAY; 8-OXO-7,8-DIHYDRO-2'-DEOXYGUANOSINE; 1,N-6-ETHENODEOXYADENOSINE; PYRIMIDOPURINONE; MALONDIALDEHYDE; MUTAGENICITY; HEPATITIS; REPAIR AB Damage to DNA can arise through covalent modification of bases by reaction with oxidants and products of lipid peroxidation derived through normal aerobic metabolism. Such premutagenic lesions, including 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG), pyrimido[1,2alpha]purine-10(3H)one-2'-deoxyribose (M1-dG), etheno-2'-deoxyadenosine (epsilon-dA), and etheno-2'-deoxycytidine (epsilon-dC), are believed to be important in the development of human cancers related to diet, disease states, and lifestyle. We report the development of a method for concurrent quantification of these four adducts in DNA hydrolysates of 100 mug or less using on-line sample preparation coupled with liquid chromatography and tandem mass spectrometry. The sensitive detection permitted adduct quantification at levels below one adduct in 10(8) normal nucleotides and measurement of these adducts in DNA from untreated rodent liver and normal human liver samples. This methodology should prove useful in hypothesis-driven studies of cancer etiology in laboratory animals and humans. C1 Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Doerge, DR (reprint author), Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 26 TC 44 Z9 45 U1 0 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD OCT PY 2002 VL 15 IS 10 BP 1295 EP 1301 DI 10.1021/tx0101595 PG 7 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 607TX UT WOS:000178807800013 PM 12387628 ER PT J AU Tu, XM Geesaman, E Wang, K Compadre, CM Buzatu, DA Darsey, JA AF Tu, XM Geesaman, E Wang, K Compadre, CM Buzatu, DA Darsey, JA TI Prediction of the partition coefficient of dillapiol and its derivatives by the use of molecular simulation and artificial neural networks SO CHIMICA OGGI-CHEMISTRY TODAY LA English DT Article AB It is well known that the outer orbitals of a molecule are responsible for its major physical and chemical properties, and consequently responsible for its biological and pharmacological activity. Thus, some extremely useful information could be derived from the various molecular orbital parameters obtained using ab initio quantum mechanics calculations. In this research we studied the inhibition of cytochrome P450 CY3A4 by a set of 26 derivatives of dillapiol molecule, which is a major constituent of dill (1). This enzyme is responsible for the oxidation of many commonly used drugs. The dipole moments, the energies of the lowest 15 unoccupied molecular orbitals, and the energies of the 15 highest occupied molecular orbitals were calculated using Gaussian 94 program at the 3-21G basis level. Those parameters were correlated with the inhibitory activity of the dillapiol molecules using a three-layered back-propagation Artificial Neural Network. The network was trained on 26 dillapiol derivatives. This procedure was followed until all molecules were used in the testing set. C1 Univ Arkansas, Dept Chem, Little Rock, AR 72204 USA. Univ Arkansas Med Sci, Biomed Visualizat Ctr, Little Rock, AR 72205 USA. Natl Ctr Toxicol Res, Div Chem, Jefferson, AR 72079 USA. RP Darsey, JA (reprint author), Univ Arkansas, Dept Chem, Little Rock, AR 72204 USA. NR 9 TC 0 Z9 0 U1 0 U2 0 PU TEKNOSCIENZE PUBL PI MILAN PA VIA AURELIO SAFFI 23, 20123 MILAN, ITALY SN 0392-839X J9 CHIM OGGI JI Chim. Oggi-Chem. Today PD OCT PY 2002 VL 20 IS 10 BP 51 EP 54 PG 4 WC Biotechnology & Applied Microbiology; Chemistry, Multidisciplinary SC Biotechnology & Applied Microbiology; Chemistry GA 626AQ UT WOS:000179848600026 ER PT J AU Schwartz, RS Edelman, ER AF Schwartz, RS Edelman, ER CA Consensus Comm TI Drug-eluting Stents in preclinical studies - Recommended evaluation from a consensus group SO CIRCULATION LA English DT Article ID PORCINE CORONARY-ARTERIES; RESTENOSIS; DELIVERY; MODEL; PATHOLOGY; INJURY; IMPLANTATION; HYPERPLASIA; PACLITAXEL; DESIGNS C1 Minneapolis Heart Inst Fdn, Minnesota Cardiovasc Res Inst, Minneapolis, MN 55407 USA. Minnesota Cardiovasc Res Inst, Minneapolis, MN USA. Harvard Univ, MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. Providence Healthcare Syst, Portland, OR USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Atlanta Cardiovasc Res Inst, Atlanta, GA USA. Washington Hosp Ctr, Washington, DC 20010 USA. Columbia Univ, New York, NY USA. Univ Penn, Hlth Syst, Philadelphia, PA 19104 USA. Armed Forces Inst Pathol, Bethesda, MD USA. US FDA, Rockville, MD 20857 USA. RP Schwartz, RS (reprint author), Minneapolis Heart Inst Fdn, Minnesota Cardiovasc Res Inst, Minneapolis, MN 55407 USA. NR 28 TC 199 Z9 212 U1 0 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 1 PY 2002 VL 106 IS 14 BP 1867 EP 1873 DI 10.1161/01.CIR.0000033485.20594.6F PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 600HZ UT WOS:000178385700024 PM 12356643 ER PT J AU Dagher, R Cohen, M Williams, G Rothmann, M Gobburu, J Robbie, G Rahman, A Chen, G Staten, A Griebel, D Pazdur, R AF Dagher, R Cohen, M Williams, G Rothmann, M Gobburu, J Robbie, G Rahman, A Chen, G Staten, A Griebel, D Pazdur, R TI Approval summary: Imatinib mesylate in the treatment of metastatic and/or unresectable malignant gastrointestinal stromal tumors SO CLINICAL CANCER RESEARCH LA English DT Article ID C-KIT; MUTATIONS AB Purpose: Imatinib mesylate (Gleevec; Novartis, East Hanover, NJ) is a receptor tyrosine kinase inhibitor approved previously in 2001 by the United States Food and Drug Administration for the treatment of chronic myelogenous leukemia in blast crisis, accelerated phase, or in chronic phase after failure of IFN-alpha therapy. We review herein the clinical profile of this drug and the regulatory review leading to the approval of a supplemental New Drug Application for the treatment of metastatic and/or unresectable malignant gastrointestinal stromal tumors (GISTs). Experimental Design: We discuss the efficacy and side effects of imatinib mesylate in a Phase II trial of 147 patients with metastatic and/or unresectable malignant GISTs, the basis for marketing approval, and postmarketing commitments by the drug's manufacturer. Results: Imatinib was assessed in a single, open-label trial involving one European center and three centers in the United States. Seventy-three patients were randomly allocated to receive 400 mg of imatinib daily, and 74 patients received 600 mg daily. At the study report cutoff date, an objective response was confirmed in 56 patients; the overall response rate for the combined study arms was 38% (95% confidence interval, 30-46%). These responses were all partial responses. There was no statistically significant difference in response rates between the two dose groups. Adverse events included edema, fluid retention, nausea, vomiting, diarrhea, myalgias, skin rash, bone marrow suppression, bleeding, and elevations in aspartate aminotransferase, alanine aminotransferase, or bilirubin. Bleeding into the gastrointestinal tract or intratumoral sites occurred in 7 patients (5%) and was not correlated with thrombocytopenia or tumor bulk. The pharmacokinetics of imatinib in GIST patients were similar to those of chronic myelogenous leukemia patients. Conclusions: On February 1, 2001, imatinib mesylate was approved by the United States Food and Drug Administration for the treatment of malignant metastatic and/or unresectable GISTs. The recommended dose is 400 or 600 mg daily. C1 US FDA, Div Oncol Drug Prod, Rockville, MD 20857 USA. US FDA, Div Pharmaceut Evaluat 1, Rockville, MD 20857 USA. US FDA, Div Biometr 1, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Dagher, R (reprint author), US FDA, Div Oncol Drug Prod, HFD-150,5600 Fishers Lane, Rockville, MD 20857 USA. NR 17 TC 261 Z9 272 U1 0 U2 10 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD OCT PY 2002 VL 8 IS 10 BP 3034 EP 3038 PG 5 WC Oncology SC Oncology GA 603EB UT WOS:000178544900002 PM 12374669 ER PT J AU Rider, LG Schiffenbauer, AS Zito, M Lim, KL Ahmed, A Zemel, LS Rennebohm, RM Passo, MH Summers, RM Hicks, JE Lachenbruch, PA Heyes, MP Miller, FW AF Rider, LG Schiffenbauer, AS Zito, M Lim, KL Ahmed, A Zemel, LS Rennebohm, RM Passo, MH Summers, RM Hicks, JE Lachenbruch, PA Heyes, MP Miller, FW CA Juvenile Dermatomyositis Dis Activ TI Neopterin and quinolinic acid are surrogate measures of disease activity in the juvenile idiopathic inflammatory myopathies SO CLINICAL CHEMISTRY LA English DT Article ID SYSTEMIC LUPUS-ERYTHEMATOSUS; MUSCLE-FIBERS; TNF-ALPHA; DERMATOMYOSITIS; DIAGNOSIS; QUANTIFICATION; ENZYMES; CELLS; BLOOD; BRAIN AB Objective: We evaluated the utility of neopterin and quinolinic acid (QUIN) as surrogate measures of disease activity in juvenile idiopathic inflammatory myopathies (IIMS). Methods: Plasma and first morning void urine samples were measured for neopterin and QUIN using commercial ELISA, HPLC, or gas chromatography-mass spectrometry in 45 juvenile IIM patients and 79 healthy controls. Myositis disease activity assessments were obtained. Results: Plasma and urine neopterin and QUIN concentrations were increased in juvenile IIM patients compared with healthy controls (P < 0.017). Urine neopterin and QUIN highly correlated with each other (r(s) = 0.73; P < 0.0001). Urine neopterin and QUIN correlated moderately with myositis disease activity assessments, including physician and parent global activity assessments, muscle strength testing, functional assessments (Childhood Myositis Assessment Scale, Childhood Health Assessment Questionnaire), skin global activity, and edema on magnetic resonance imaging (r(s) = 0.42-0.62; P < 0.05), but generally not with muscle-associated enzymes in serum. Urine neopterin or QUIN, in combination with either serum lactate dehydrogenase (LD) or aspartate aminotransferase (AST), significantly predicted global disease activity (R-2 = 0.40-0.56; P < 0.002), and both were more sensitive to change than these serum enzymes (standardized response means, -0.41 to -0.48). Conclusions: Urinary neopterin and QUIN are candidate measures of disease activity in juvenile IIM patients and add significantly to the prediction of global disease activity in combination with serum LD or AST values. Measurement of these markers in first morning void urine specimens appears to be as good as, or possibly better than, measurements of their concentrations in plasma. (C) 2002 American Association for Clinical Chemistry. C1 NIEHS, Environm Autoimmun Grp, NIH, Bethesda, MD 20892 USA. US FDA, Lab Mol & Dev Immunol, Div Monoclonal Antibodies, CBER, Bethesda, MD 20892 USA. NIAMSD, Arthrit & Rheumatism Branch, NIH, Bethesda, MD 20892 USA. NIMH, Lab Neurotoxicol, NIH, Bethesda, MD 20892 USA. Univ Glasgow, Glasgow Royal Infirm, Dept Med & Rheumatol, Glasgow G31 2ER, Lanark, Scotland. Sherwood Forest Hosp, NHS Trust, Kings Mill Ctr, Nottingham NG17 4JL, England. Specialty Labs, Santa Monica, CA 90404 USA. Univ Connecticut, Connecticut Childrens Med Ctr, Hartford, CT 06106 USA. Ohio State Univ, Columbus Childrens Hosp, Columbus, OH 43205 USA. Univ Cincinnati, Childrens Hosp, Cincinnati, OH 45229 USA. NIH, Dept Radiol, Ctr Clin, Bethesda, MD 20892 USA. NIH, Dept Rehabil Med, Ctr Clin, Bethesda, MD 20892 USA. US FDA, Div Biostat, CBER, Rockville, MD 20852 USA. Curagen Inc, Branford, CT 06405 USA. RP Rider, LG (reprint author), NIEHS, Environm Autoimmun Grp, NIH, 9 Mem Dr,Room 1W101,MSC 0958, Bethesda, MD 20892 USA. OI Schiffenbauer, Adam/0000-0001-9964-9966; Rider, Lisa/0000-0002-6912-2458; Miller, Frederick/0000-0003-2831-9593 NR 29 TC 15 Z9 16 U1 0 U2 3 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 2002 VL 48 IS 10 BP 1681 EP 1688 PG 8 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 597UA UT WOS:000178238100007 PM 12324484 ER PT J AU Frankel, SK Sullivan, EJ Brown, KK AF Frankel, SK Sullivan, EJ Brown, KK TI Vasculitis: Wegener granulomatosis, Churg-Strauss syndrome, microscopic polyangiitis, polyarteritis nodosa, and Takayasu arteritis SO CRITICAL CARE CLINICS LA English DT Review ID ANTINEUTROPHIL CYTOPLASMIC ANTIBODIES; TERM FOLLOW-UP; RHEUMATOLOGY 1990 CRITERIA; SMALL-VESSEL VASCULITIS; SYNDROME ALLERGIC GRANULOMATOSIS; SYSTEMIC LUPUS-ERYTHEMATOSUS; ANCA-ASSOCIATED VASCULITIS; PULMONARY-RENAL SYNDROME; HEPATITIS-B VIRUS; DISEASE-ACTIVITY AB Identification, diagnosis, and management of the primary vasculitides and their attendant complications is a challenging task for the critical care physician. The primary vasculitides are rare, and their signs and symptoms overlap with vastly more common clinical entities. However, with appropriate therapy, the morbidity and mortality of these diseases can be markedly reduced. Common ICU presentations; general principles of evaluation and management; and key clinical, laboratory, radiologic, and pathologic components of the primary vasculitides are reviewed. C1 Natl Jewish Med & Res Ctr, Interstitial Lung Dis Program, Dept Med, Denver, CO 80206 USA. Univ Colorado, Hlth Sci Ctr, Dept Med, Div Pulm Sci & Crit Care Med, Denver, CO 80262 USA. US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20847 USA. RP Brown, KK (reprint author), Natl Jewish Med & Res Ctr, Interstitial Lung Dis Program, Dept Med, Denver, CO 80206 USA. FU NHLBI NIH HHS [HL67671] NR 150 TC 14 Z9 17 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 0749-0704 J9 CRIT CARE CLIN JI Crit. Care Clin. PD OCT PY 2002 VL 18 IS 4 BP 855 EP + AR PII S0749-0704(02)00031-3 DI 10.1016/S0749-0704(02)00031-3 PG 26 WC Critical Care Medicine SC General & Internal Medicine GA 612TY UT WOS:000179092600009 PM 12418444 ER PT J AU Hutter, JC Do Luu, HM Schroeder, LW AF Hutter, JC Do Luu, HM Schroeder, LW TI A biological model of tamponade gases following pneumatic retinopexy SO CURRENT EYE RESEARCH LA English DT Article DE detached retina; intraocular gas ID SURGERY; RATES AB Purpose. Predict the persistence and expansion of intraocular tamponade gases used in retinal detachment surgery. Quantify factors that contribute to elevations in the intraocular pressure. Methods. We developed a non-equilibrium physiological model of intraocular gas transfer in vitreoretinal surgery. The model was calibrated using published volumetric decay measurements for four perfluorocarbon gases (CF4, C2F6, C3F8, C4F10) injected into the New Zealand red rabbit. We validated the model by comparing predicted and experimental results at different conditions in the rabbit. Using the rabbit results, the model was scaled up to humans. Results. Predictions of gas expansion, half-life, and intraocular pressure in humans were found to correlate very well with clinical results. Gas transfer in the eye was controlled by diffusion through plasma and membranes. Although intraocular pressure depended on several complicating factors such as the physiological condition of the eye as wet as the medications being used, prediction of conditions that favor elevations in intraocular pressure were identified based on the transport and thermodynamic properties of the gases. Conclusions. The biological model accurately predicted the dynamics of intraocular gases in the human eye. The major factor affecting the intraocular pressure was the aqueous humor dynamics, which is highly dependent on the physiological conditions in the eye. However, for long duration gases such as perfluoropropane, elevations in intraocular pressure are possible following an increase in volume and/or purity of the injected gas. By injecting a mixture of air with an expansive gas, it is possible to reduce elevations in intraocular pressure in patients with the trade off of a reduced longevity of the gas bubble. For gases that diffuse faster than perfluoropropane, there are minimal effects on intraocular pressure due to these changes. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20852 USA. RP Hutter, JC (reprint author), US FDA, Ctr Devices & Radiol Hlth, 12725 Twinbrook Pkwy HFZ-150, Rockville, MD 20852 USA. NR 26 TC 5 Z9 5 U1 2 U2 2 PU SWETS ZEITLINGER PUBLISHERS PI LISSE PA P O BOX 825, 2160 SZ LISSE, NETHERLANDS SN 0271-3683 J9 CURR EYE RES JI Curr. Eye Res. PD OCT PY 2002 VL 25 IS 4 BP 197 EP 206 PG 10 WC Ophthalmology SC Ophthalmology GA 654TC UT WOS:000181511300001 PM 12658552 ER PT J AU Poirier, LA Vlasova, TI AF Poirier, LA Vlasova, TI TI The prospective role of abnormal methyl metabolism in cadmium toxicity SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article; Proceedings Paper CT 3rd International Meeting on the Molecular Mechanisms of Metal Toxicity and Carcinogenicity CY SEP 02-06, 2001 CL STINTINO, ITALY DE Cd; Zn; carcinogenesis; DNA methyltransferase; methyl deficiency ID DNA METHYLTRANSFERASE; CELL-PROLIFERATION; DEFICIENCY; EXPRESSION; PROTEINS; DOMAIN; METALS C1 US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Poirier, LA (reprint author), US FDA, Natl Ctr Toxicol Res, NFT 140, Jefferson, AR 72079 USA. NR 16 TC 58 Z9 63 U1 1 U2 4 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD OCT PY 2002 VL 110 SU 5 BP 793 EP 795 PG 3 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 612FQ UT WOS:000179064200023 PM 12426133 ER PT J AU Hendry, WJ Sheehan, DM Khan, SA May, JV AF Hendry, WJ Sheehan, DM Khan, SA May, JV TI Developing a laboratory animal model for perinatal endocrine disruption: The hamster chronicles SO EXPERIMENTAL BIOLOGY AND MEDICINE LA English DT Review DE endocrine disruption; diethylstilbestrol; estrogen; cheek pouch; transplantation ID FEMALE REPRODUCTIVE-TRACT; ESTROGEN-RECEPTOR-ALPHA; NEONATAL DIETHYLSTILBESTROL TREATMENT; GROWTH FACTOR-ALPHA; HUMAN ENDOMETRIUM; NUCLEAR-BODIES; MENSTRUAL-CYCLE; MOUSE UTERUS; CELL-DEATH; POLYOVULAR FOLLICLES AB At the biomedical, regulatory, and public level, considerable concern surrounds the concept that inappropriate exposure to endocrine-disrupting chemicals, especially during the prenatal and/or neonatal period, may disrupt normal reproductive tract development and adult function. The intent of this review was to 1. Describe some unique advantages of the hamster for perinatal endocrine disruptor (ED) studies, 2. Summarize the morphological and molecular consequences of exposure to the established perinatal ED, diethylstilbestrol, in the female and male hamster, 3. Present some new, histomorphological insight into the process of neonatal diethylstilbestrol-Induced disruption in the hamster uterus, and 4. Introduce recent efforts and future plans to evaluate the potency and mechanism of action of other putative EDs in the hamster experimental system. Taken together, the findings Indicate that the hamster represents a unique and sensitive In vivo system to probe the phenomenon of endocrine disruption. The spectrum of candidate endpoints includes developmental toxicity, neoplasia, and more subtle endpoints of reproductive dysfunction. C1 Wichita State Univ, Dept Biol Sci, Wichita, KS 67260 USA. Univ Kansas, Sch Med, Womens Res Inst, Wichita, KS 67208 USA. Univ Kansas, Sch Med, Dept Obstet & Gynecol, Wichita, KS 67208 USA. Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. Texas Tech Univ, Hlth Sci Ctr, Univ Med Ctr, Dept Biochem & Cell Biol, Lubbock, TX 79430 USA. Texas Tech Univ, Hlth Sci Ctr, Univ Med Ctr, SW Canc Ctr, Lubbock, TX 79430 USA. RP Hendry, WJ (reprint author), Wichita State Univ, Dept Biol Sci, 1845 Fairmount, Wichita, KS 67260 USA. FU NCI NIH HHS [CA60250]; NICHD NIH HHS [HD37835, HD37971]; NIEHS NIH HHS [ES10232] NR 120 TC 17 Z9 19 U1 0 U2 2 PU SOC EXPERIMENTAL BIOLOGY MEDICINE PI MAYWOOD PA 195 WEST SPRING VALLEY AVE, MAYWOOD, NJ 07607-1727 USA SN 1535-3702 J9 EXP BIOL MED JI Exp. Biol. Med. PD OCT PY 2002 VL 227 IS 9 BP 709 EP 723 PG 15 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 595TB UT WOS:000178123900004 PM 12324652 ER PT J AU Snapp, KR Heitzig, CE Marth, JD Goodman, JL AF Snapp, KR Heitzig, CE Marth, JD Goodman, JL TI Structural modifications of PSGL-1 required for adhesion and entry of the causative agent of human granulocytic ehrlichiosis (HGE) SO GLYCOBIOLOGY LA English DT Meeting Abstract CT 7th Annual Conference of the Society-for-Glycobiology CY NOV 09-12, 2002 CL BOSTON, MASSACHUSETTS SP Soc Glycobiol C1 Northwestern Univ, Sch Med, Dept Microbiol Immunol, Chicago, IL 60611 USA. Univ Calif San Diego, Howard Hughes Med Inst, La Jolla, CA 92093 USA. Univ Calif San Diego, Dept Cellular Mol Med, La Jolla, CA 92093 USA. US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 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 2002 VL 12 IS 10 MA 16 BP 646 EP 646 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 601LT UT WOS:000178448200024 ER PT J AU Vionnet, J Vann, WF AF Vionnet, J Vann, WF TI Initiation and elongation of polymer chains in polysialic acid biosynthesis SO GLYCOBIOLOGY LA English DT Meeting Abstract CT 7th Annual Conference of the Society-for-Glycobiology CY NOV 09-12, 2002 CL BOSTON, MASSACHUSETTS SP Soc Glycobiol C1 US FDA, Lab Bacterial Toxins, Ctr Biol Evaluat & Res, Bethesda, MD 20892 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 2002 VL 12 IS 10 MA 184 BP 703 EP 704 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 601LT UT WOS:000178448200189 ER PT J AU Sundaram, AK Vann, WF AF Sundaram, AK Vann, WF TI Biosynthesis of hyaluronic acid in Bacillus authracis SO GLYCOBIOLOGY LA English DT Meeting Abstract CT 7th Annual Conference of the Society-for-Glycobiology CY NOV 09-12, 2002 CL BOSTON, MASSACHUSETTS SP Soc Glycobiol C1 US FDA, Lab Bacterial Toxins, CBER, Bethesda, MD 20892 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 2002 VL 12 IS 10 MA 197 BP 708 EP 708 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 601LT UT WOS:000178448200202 ER PT J AU Graham, DJ Green, L Senior, JR AF Graham, DJ Green, L Senior, JR TI Hyperacute liver failure induced by troglirazone: What did we learn and what do we need to learn? SO HEPATOLOGY LA English DT Meeting Abstract CT 53rd Annual Meeting of the Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 01-05, 2002 CL BOSTON, MASSACHUSETTS SP Amer Assoc Study Liver Dis C1 US FDA, Off Drug Safety, Rockville, MD 20857 USA. NR 0 TC 2 Z9 2 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 2002 VL 36 IS 4 SU S MA 5 BP 168A EP 168A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 598XK UT WOS:000178301700006 ER PT J AU Guang, G Stuver, S Okayama, A Tsubouchi, H Mueller, N Tabor, E AF Guang, G Stuver, S Okayama, A Tsubouchi, H Mueller, N Tabor, E TI The minimum number of clones necessary to sequence in order to obtain the maximum information about Hepatitis C virus quasispecies: A comparison of cases with and without liver cancer. SO HEPATOLOGY LA English DT Meeting Abstract CT 53rd Annual Meeting of the Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 01-05, 2002 CL BOSTON, MASSACHUSETTS SP Amer Assoc Study Liver Dis C1 US FDA, CBER, Rockville, MD 20857 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Miyazaki Med Coll, Kiyotake, Miyazaki, Japan. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 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 2002 VL 36 IS 4 SU S MA 155 BP 205A EP 205A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 598XK UT WOS:000178301700155 ER PT J AU Nascimbeni, M Mizukoshi, E Bosmann, M Major, M Mihalik, M Rice, C Feinstone, S Rehermann, B AF Nascimbeni, M Mizukoshi, E Bosmann, M Major, M Mihalik, M Rice, C Feinstone, S Rehermann, B TI Differential regulation of CD4+ and CD8+ memory T cells during HCV rechallenge of chimpanzees. SO HEPATOLOGY LA English DT Meeting Abstract CT 53rd Annual Meeting of the Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 01-05, 2002 CL BOSTON, MASSACHUSETTS SP Amer Assoc Study Liver Dis C1 NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 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 2002 VL 36 IS 4 SU S MA 237 BP 226A EP 226A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 598XK UT WOS:000178301700238 ER PT J AU Apte, UM Limaye, PB Devi, SS Bucci, TJ Mehendale, HM AF Apte, UM Limaye, PB Devi, SS Bucci, TJ Mehendale, HM TI Role of pro-mitogenic signaling stimulated by cytokines and growth factors in enhanced liver regeneration in moderately caloric restricted rats upon toxic challenge. SO HEPATOLOGY LA English DT Meeting Abstract CT 53rd Annual Meeting of the Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 01-05, 2002 CL BOSTON, MASSACHUSETTS SP Amer Assoc Study Liver Dis C1 NE Louisiana Univ, Monroe, LA 71209 USA. Pathol Associates Int, A Charles River Co, NCTR, Jefferson, AR 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 2002 VL 36 IS 4 SU S MA 296 BP 237A EP 237A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 598XK UT WOS:000178301700280 ER PT J AU Shankar, K Vaidya, VS Manautou, JE Ronis, MJ Bucci, TJ Corton, JC Mehendale, HM AF Shankar, K Vaidya, VS Manautou, JE Ronis, MJ Bucci, TJ Corton, JC Mehendale, HM TI Activation of PPAR-alpha is pivotal in diabetes-induced resistance against acetaminophen hepatotoxicity: Understanding mechanisms via microarray analyses. SO HEPATOLOGY LA English DT Meeting Abstract CT 53rd Annual Meeting of the Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 01-05, 2002 CL BOSTON, MASSACHUSETTS SP Amer Assoc Study Liver Dis C1 Univ Louisiana, Dept Toxicol, Monroe, LA USA. Univ Connecticut, Dept Pharmaceut Sci, Storrs, CT USA. Arkansas Childrens Hosp, Inst Res, Little Rock, AR 72202 USA. Pathol Associates Intl, Natl Ctr Toxicol Res, 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 2002 VL 36 IS 4 SU S MA 677 BP 332A EP 332A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 598XK UT WOS:000178301700659 ER PT J AU Momosaki, S Yano, H Ogasawara, S Akiba, J Kojiro, M AF Momosaki, S Yano, H Ogasawara, S Akiba, J Kojiro, M TI Interferon-alpha resistance in hepatocellular carcinoma is associated with defective expression and activation of signal transducers. SO HEPATOLOGY LA English DT Meeting Abstract CT 53rd Annual Meeting of the Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 01-05, 2002 CL BOSTON, MASSACHUSETTS SP Amer Assoc Study Liver Dis C1 Kurume Univ, Kurume, Fukuoka 830, Japan. US FDA, Bethesda, MD 20014 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2002 VL 36 IS 4 SU S MA 1061 BP 428A EP 428A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 598XK UT WOS:000178301701042 ER PT J AU Raker, CA Tabor, E Okayama, A Yu, MYW Kohara, M Mueller, NE Tsubouchi, H Stuver, SO AF Raker, CA Tabor, E Okayama, A Yu, MYW Kohara, M Mueller, NE Tsubouchi, H Stuver, SO TI Hepatitis C virus (HCV) in the serum of anti-HCV-positive individuals: Detection of HCV core protein and HCV RNA. SO HEPATOLOGY LA English DT Meeting Abstract CT 53rd Annual Meeting of the Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 01-05, 2002 CL BOSTON, MASSACHUSETTS SP Amer Assoc Study Liver Dis C1 Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. US FDA, Bethesda, MD 20014 USA. Miyazaki Med Coll, Miyazaki 88916, Japan. Tokyo Metropolitan Inst Med Sci, Tokyo, Japan. 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 2002 VL 36 IS 4 SU S MA 1619 BP 568A EP 568A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 598XK UT WOS:000178301701601 ER PT J AU Toraason, M Andersen, M Bogdanffy, MS Dankovic, D Faustman, E Foster, P Frederick, C Haber, L Kimmel, CA Lewis, S McClellan, R Melnick, R Mirer, F Morgan, K Schaeffer, V Silbergeld, E Slikker, W Swenberg, J Vainio, H AF Toraason, M Andersen, M Bogdanffy, MS Dankovic, D Faustman, E Foster, P Frederick, C Haber, L Kimmel, CA Lewis, S McClellan, R Melnick, R Mirer, F Morgan, K Schaeffer, V Silbergeld, E Slikker, W Swenberg, J Vainio, H TI Improving risk assessment: Toxicological research needs SO HUMAN AND ECOLOGICAL RISK ASSESSMENT LA English DT Article DE susceptibility; life stages; pharmacokinetics; dose response; exposure assessment; genomics ID GLUTATHIONE-S-TRANSFERASE; DEVELOPMENTAL TOXICITY; BREAST-MILK; LUNG-CANCER; EXPOSURE; SUSCEPTIBILITY; EXPRESSION; HEALTH; CYP1A1; POLYMORPHISMS AB A workshop convened to define research needs in toxicology identified several deficiencies in data and methods currently applied in risk assessment. The workshop panel noted that improving the link between chemical exposure and toxicological response requires a better understanding of the biological basis for inter- and intra-human variability and susceptibility. This understanding will not be complete unless all life stages are taken into consideration. Because animal studies serve as a foundation for toxicological assessment, proper accounting for cross-species extrapolation is essential. To achieve this, adjustments for dose-rate effects must be improved, which will aid in extrapolating toxicological responses to low doses and from short-term exposures. Success depends on greater use of validated biologically based dose-response models that include pharmacokinetic and pharmacodynamic data. Research in these areas will help define uncertainty factors and reduce reliance on underlying default assumptions. Throughout the workshop the panel recognized that biomedical science and toxicology in particular is on the verge of a revolution because of advances in genomics and proteomics. Data from these high-output technologies are anticipated to greatly improve risk assessment by enabling scientists to better define and model the elements of the relationship between exposure to biological hazards and health risks in populations with differing susceptibilities. C1 NIOSH, Cincinnati, OH 45226 USA. DuPont Co Inc, Newark, DE 19714 USA. NIOSH, Cincinnati, OH 45226 USA. Univ Washington, Seattle, WA 98195 USA. Chem Ind Inst Toxicol, Res Triangle Pk, NC 27709 USA. Rohm & Haas Co, Spring House, PA 19477 USA. Toxicol Excellence Risk Assessment, Cincinnati, OH USA. US EPA, Washington, DC 20460 USA. Exxon Mobile, Annandale, NJ USA. NIEHS, Res Triangle Pk, NC 27709 USA. UAW, Int Union, Detroit, MI USA. Glaxo Wellcome Inc, Res Triangle Pk, NC 27709 USA. US Occupat Safety & Hlth Adm, Washington, DC USA. Univ Maryland, Baltimore, MD 21201 USA. US FDA, Jefferson, AR USA. Univ N Carolina, Chapel Hill, NC USA. Int Agcy Res Canc, F-69372 Lyon, France. RP Toraason, M (reprint author), NIOSH, MSc23,C23,4676 Columbia Pkwy, Cincinnati, OH 45226 USA. EM mtoraason@cdc.gov OI Andersen, Melvin/0000-0002-3894-4811 NR 47 TC 2 Z9 2 U1 0 U2 3 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1080-7039 J9 HUM ECOL RISK ASSESS JI Hum. Ecol. Risk Assess. PD OCT PY 2002 VL 8 IS 6 BP 1405 EP 1419 DI 10.1080/20028091057439 PG 15 WC Biodiversity Conservation; Environmental Sciences SC Biodiversity & Conservation; Environmental Sciences & Ecology GA 612VB UT WOS:000179095200016 ER PT J AU Zeise, L Hattis, D Andersen, M Bailer, AJ Bayard, S Chen, C Clewell, H Conolly, R Crump, K Dunson, D Finkel, A Haber, L Jarabek, AM Kodell, R Krewski, D Thomas, D Thorslund, T Wassell, JT AF Zeise, L Hattis, D Andersen, M Bailer, AJ Bayard, S Chen, C Clewell, H Conolly, R Crump, K Dunson, D Finkel, A Haber, L Jarabek, AM Kodell, R Krewski, D Thomas, D Thorslund, T Wassell, JT TI Improving risk assessment: Research opportunities in dose response modeling to improve risk assessment SO HUMAN AND ECOLOGICAL RISK ASSESSMENT LA English DT Article DE interindividual variability; injury risk; Bayesian analysis; latent variables; Markov Chain Monte Carlo analysis ID HUMAN INTERINDIVIDUAL VARIABILITY; OCCUPATIONAL FATAL INJURY; MULTISTEP CARCINOGENESIS; PHARMACOKINETIC MODEL; GENETIC ALTERATIONS; TUMOR PROMOTION; LIFETIME RISK; UNITED-STATES; CANCER RISKS; UNCERTAINTY AB Substantial improvements in dose response modeling for risk assessment may result from recent and continuing advances in biological research, biochemical techniques, biostatistical/mathematical methods and computational power. This report provides a ranked set of recommendations for proposed research to advance the state of the art in dose response modeling. The report is the result of a meeting of invited workgroup participants charged with identifying five areas of research in dose response modeling that could be incorporated in a national agenda to improve risk assessment methods. Leading topics of emphasis are interindividual variability, injury risk assessment modeling, and procedures to incorporate distributional methods and mechanistic considerations into now-standard methods of deriving a reference dose (RfD), reference concentration (RfC), minimum risk level (MRL) or similar dose-response parameter estimates. C1 Calif Environm Protect Agcy, Off Environm Hlth Hazard Assessment, Oakland, CA USA. Clark Univ, Marsh Inst, Worcester, MA 01610 USA. Colorado State Univ, Ft Collins, CO 80523 USA. Miami Univ, Oxford, OH 45056 USA. US Occupat Safety & Hlth Adm, Washington, DC USA. US EPA, Off Res & Dev, Natl Ctr Environm Assessment, Washington, DC 20460 USA. ICF Consulting, KS Crump Grp, Ruston, LA USA. CIIT Ctr Hlth Res, Res Triangle Pk, NC USA. NIEHS, Res Triangle Pk, NC 27709 USA. US Occupat Safety & Hlth Adm, Washington, DC USA. Toxicol Excellence Risk Assessment, Cincinnati, OH USA. US EPA, Off Res & Dev, Natl Ctr Environm Assessment, Res Triangle Pk, NC 27711 USA. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Univ Ottawa, Ottawa, ON, Canada. Univ So Calif, Los Angeles, CA USA. NIOSH, Morgantown, WV USA. RP Zeise, L (reprint author), Calif Environm Protect Agcy, Off Environm Hlth Hazard Assessment, Oakland, CA USA. EM dhattis@aol.com OI Andersen, Melvin/0000-0002-3894-4811 NR 90 TC 7 Z9 7 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1080-7039 J9 HUM ECOL RISK ASSESS JI Hum. Ecol. Risk Assess. PD OCT PY 2002 VL 8 IS 6 BP 1421 EP 1444 DI 10.1080/20028091057448 PG 24 WC Biodiversity Conservation; Environmental Sciences SC Biodiversity & Conservation; Environmental Sciences & Ecology GA 612VB UT WOS:000179095200017 ER PT J AU Bhandoola, A Tai, XG Eckhaus, M Auchincloss, H Mason, K Rubin, SA Carbone, KM Grossman, Z Rosenberg, AS Singer, A AF Bhandoola, A Tai, XG Eckhaus, M Auchincloss, H Mason, K Rubin, SA Carbone, KM Grossman, Z Rosenberg, AS Singer, A TI Peripheral expression of self-MHC-II influences the reactivity and self-tolerance of mature CD4(+) T cells: Evidence from a lymphopenic T cell model SO IMMUNITY LA English DT Article ID POSITIVE SELECTION; HOMEOSTATIC PROLIFERATION; ACTIVATION THRESHOLD; PEPTIDE LIGANDS; SURVIVAL; THYMUS; COMPLEX; MOLECULES; ANTIGENS; MOUSE AB While intrathymic MHC expression influences the specificity of developing thymocytes, we considered that peripheral MHC expression might influence the reactivity of postthymic T cells. We now report for CD4(+) T cells that peripheral MHC-II expression does influence their reactivity and self-tolerance. Upon transfer into MHC-II-deficient lymphopenic hosts, mature CD4(+) T cells were found to acquire an activated memory phenotype and to become: (1) autoreactive against syngeneic MHC-II+ skin grafts, (2) hyperreactive against third-party MHC-II+ skin grafts, and (3) functionally dysregulated, resulting in a lymphoproliferative disorder characterized by intraepithelial infiltrations. Peripheral MHC-II expression appeared to influence CD4+ T cell reactivity by two complementary mechanisms: maintenance of CD4(+)CD25(+) regulatory T cells ("suppression") and direct dampening of CD4(+) T cell reactivity ("tuning"). C1 NCI, Expt Immunol Branch, Bethesda, MD 20892 USA. NIH, Vet Resources Program, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Transplantat Unit, Boston, MA 02114 USA. US FDA, Div Therapeut Prot, Bethesda, MD 20892 USA. US FDA, Lab Pediat & Resp Viral Dis, Bethesda, MD 20892 USA. Tel Aviv Univ, Dept Physiol & Pharmacol, IL-69978 Tel Aviv, Israel. NIAID, Immunol Lab, Bethesda, MD 20892 USA. RP Singer, A (reprint author), NCI, Expt Immunol Branch, Bldg 10, Bethesda, MD 20892 USA. RI Grossman, Zvi/A-9643-2008 NR 40 TC 68 Z9 68 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD OCT PY 2002 VL 17 IS 4 BP 425 EP 436 DI 10.1016/S1074-7613(02)00417-X PG 12 WC Immunology SC Immunology GA 605FQ UT WOS:000178667100004 PM 12387737 ER PT J AU Hastings, KL AF Hastings, KL TI Implications of the new FDA/CDER immunotoxicology guidance for drugs SO INTERNATIONAL IMMUNOPHARMACOLOGY LA English DT Article DE FDA/CDER; immunotoxicity; drugs ID RESPIRATORY ALLERGENS; IDENTIFICATION; CHEMICALS; TOXICOLOGY; PROFILES; ASSAY; MICE AB Although it has long been recognized that drugs, like other xenobiotics, could have adverse effects on immune function, historically, the assessment of the immunotoxic potential of pharmaceuticals has been undertaken in a haphazard fashion. Typically, studies have been conducted either after adverse effects were observed in clinical trials or if obvious signs of immunotoxicity were seen in nonclinical studies. This situation is changing with the promulgation of new guidances and guidelines by various regulatory agencies, especially in those countries involved in the ICH process. It is anticipated that studies conducted to comply with these regulatory requirements will result in a much better understanding of the immunotoxic potential of pharmaceuticals. In addition, new methods are likely to be developed for detecting drug-induced adverse immune effects. In particular, better methods need to be developed for the prospective identification of drugs which have the potential to induce allergic reactions. In this review, the essential points of the new FDA/CDER guidance document will be discussed, especially with respect to promotion of research into issues such as drug allergy. C1 US FDA, Ctr Drug Evaluat & Res, Dept Special Pathogen & Immunol Drug Prod, Off New Drugs, Rockville, MD 20857 USA. RP Hastings, KL (reprint author), US FDA, Ctr Drug Evaluat & Res, Dept Special Pathogen & Immunol Drug Prod, Off New Drugs, 5600 Fishers Lane, Rockville, MD 20857 USA. NR 40 TC 14 Z9 14 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1567-5769 J9 INT IMMUNOPHARMACOL JI Int. Immunopharmacol. PD OCT PY 2002 VL 2 IS 11 BP 1613 EP 1618 AR PII S1567-5769(02)00061-9 DI 10.1016/S1567-5769(02)00061-9 PG 6 WC Immunology; Pharmacology & Pharmacy SC Immunology; Pharmacology & Pharmacy GA 612VG UT WOS:000179095700011 PM 12433062 ER PT J AU Debrabant, A Lee, N Pogue, GP Dwyer, DM Nakhasi, HL AF Debrabant, A Lee, N Pogue, GP Dwyer, DM Nakhasi, HL TI Expression of calreticulin P-domain results in impairment of secretory pathway in Leishmania donovani and reduced parasite survival in macrophages SO INTERNATIONAL JOURNAL FOR PARASITOLOGY LA English DT Article DE Leishmania; chaperone; calreticulin; folding; macrophage; secretion ID PROTEIN-DISULFIDE-ISOMERASE; ENDOPLASMIC-RETICULUM; ACID-PHOSPHATASE; TRYPANOSOMATID PARASITES; QUALITY-CONTROL; GENE; CHAPERONES; IDENTIFICATION; PROMASTIGOTES; GLYCOPROTEINS AB The secretory proteins of Leishmania are thought to be involved in the parasite survival inside the insect vector or mammalian host. It is clear from studies in higher eukaryotes that proper folding in the endoplasmic reticulum and targeting out of the endoplasmic reticulum is critical for the function of secretory proteins. The endoplasmic reticulum chaperones such as calreticulin play an important role in the quality control of secretory proteins. However, very little is known about the secretory pathway of trypanosomatid parasites such as Leishmania. In the present study, we show that overexpression of the P-domain of Leishmania donovani calreticulin in transfected L donovani resulted in a significant reduction in the secretion of the parasite secretory acid phosphatases. This effect is associated with an intracellular accumulation of active enzyme in these transfected parasites. In addition, parasites expressing the P-domain calreticulin showed a significant decrease in survival inside human macrophages. This study suggests that altering the function of an endoplasmic reticulum chaperone such as calreticulin in Leishmania may affect the targeting of proteins that are associated with the virulence of the parasite during their trafficking through the parasite secretory pathway. (C) 2002 Australian Society for Parasitology Inc. Published by Elsevier Science Ltd. All rights reserved. C1 US FDA, Div Emerging & Transfus Transmitted Dis, LBPUA, OBRR,CBER, Bethesda, MD 20892 USA. Large Scale Biol, Vacaville, CA USA. NIAID, Cell Biol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Debrabant, A (reprint author), US FDA, Div Emerging & Transfus Transmitted Dis, LBPUA, OBRR,CBER, Bldg 29,Room 425,HFM-310,8800 Rockville Pike, Bethesda, MD 20892 USA. NR 42 TC 26 Z9 28 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0020-7519 J9 INT J PARASITOL JI Int. J. Parasit. PD OCT PY 2002 VL 32 IS 11 BP 1423 EP 1434 AR PII S0020-7519(02)00134-0 DI 10.1016/S0020-7519(02)00134-0 PG 12 WC Parasitology SC Parasitology GA 612KK UT WOS:000179073800009 PM 12350377 ER PT J AU Ge, B Bodeis, S Walker, RD White, DG Zhao, S McDermott, PF Meng, JH AF Ge, B Bodeis, S Walker, RD White, DG Zhao, S McDermott, PF Meng, JH TI Comparison of the Etest and agar dilution for in vitro antimicrobial susceptibility testing of Campylobacter SO JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY LA English DT Article DE Campylobacter; Etest; agar dilution; antimicrobial susceptibility ID JEJUNI SUBSP JEJUNI; RESISTANT CAMPYLOBACTER; ANTIBIOTIC-RESISTANCE; HUMANS; COLI; EMERGENCE; STRAINS; ANIMALS; QUINOLONE; BACTERIA AB The performance of the Etest and agar dilution for in vitro antimicrobial susceptibility of Campylobacter spp. was evaluated using a quality control strain Campylobactor jejuni ATCC 33560, and 81 C. jejuni and 54 Campylobacter coli isolates recovered from retail raw meats. Seven antimicrobial agents: chloramphenicol, ciprofloxacin, doxycycline, erythromycin, gentamicin, nalidixic acid and tetracycline, were tested using the two methods, whereas azithromycin was tested using the Etest only. The correlation between the Etest and agar dilution MICs varied greatly depending on the antimicrobial agents tested. The overall agreement of MICs (+/-1 log(2) dilution) between the two methods was 61.9%, ranging from 21.4% for nalidixic acid to 92.6% for gentamicin. MICs obtained using the Etest were generally lower than those by agar dilution regardless of the species of organism tested. MIC50 and/or MIC90 values were at least one dilution lower for the Etest than for agar dilution when testing chloramphenicol, ciprofloxacin, doxycycline, erythromycin and nalidixic acid. Based on the agar dilution MICs, the resistant rate of the 135 Campylobacter isolates was highest for tetracycline (82.2%), followed by doxycycline (78.5%), nalidixic acid (21.5%), ciprofloxacin (20.7%) and erythromycin (17.0%). None of the isolates demonstrated resistance to chloramphenicol or gentamicin. The study indicated that the Etest results were not in complete agreement with the agar dilution test. Although the Etest has been proven to be a satisfactory testing method, its use for Campylobacter susceptibility testing requires further standardization. The study also showed that C. jejuni and C. coli isolates resistant to antimicrobials used for treating campylobacteriosis were common in retail raw meats. C1 Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA. US FDA, Div Anim & Food Microbiol, Res Off, Ctr Vet Med, Laurel, MD 20708 USA. RP Meng, JH (reprint author), Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA. NR 35 TC 58 Z9 59 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-7453 J9 J ANTIMICROB CHEMOTH JI J. Antimicrob. Chemother. PD OCT PY 2002 VL 50 IS 4 BP 487 EP 494 DI 10.1093/jac/dkf162 PG 8 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA 608DU UT WOS:000178830500007 PM 12356792 ER PT J AU Beger, RD Buzatu, DA Wilkes, JG AF Beger, RD Buzatu, DA Wilkes, JG TI Combining NMR spectral and structural data to form models of polychlorinated dibenzodioxins, dibenzofurans, and biphenyls binding to the AhR SO JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN LA English DT Article DE 3D-QSDAR; aryl hydrocarbon receptor (AhR); C-13 NMR; CoSA; CoSASA; CoSCoSA; dioxin; furan; PCB ID RELATIONSHIP QSDAR MODELS; P-DIOXINS; RECEPTOR-BINDING; CHEMICAL-SHIFTS; MECHANISM; QSAR; TOXICOLOGY; AFFINITY; INVITRO; INVIVO AB A three-dimensional quantitative spectrometric data-activity relationship (3D-QSDAR) modeling technique which uses NMR spectral and structural information that is combined in a 3D-connectivity matrix has been developed. A 3D-connectivity matrix was built by displaying all possible assigned carbon NMR chemical shifts, carbon-to-carbon connections, and distances between the carbons. Two-dimensional C-13-C-13 COSY and 2D slices from the distance dimension of the 3D-connectivity matrix were used to produce a relationship among the 2D spectral patterns for polychlorinated dibenzofurans, dibenzodioxins, and biphenyls (PCDFs, PCDDs, and PCBs respectively) binding to the aryl hydrocarbon receptor (AhR). We refer to this technique as comparative structural connectivity spectral analysis (CoSCoSA) modeling. All CoSCoSA models were developed using forward multiple linear regression analysis of the predicted C-13 NMR structure-connectivity spectral bins. A CoSCoSA model for 26 PCDFs had an explained variance (r(2)) of 0.93 and an average leave-four-out cross-validated variance (q(4)(2)) of 0.89. A CoSCoSA model for 14 PCDDs produced an r(2) of 0.90 and an average leave-two-out cross-validated variance (q(2)(2)) of 0.79. One CoSCoSA model for 12 PCBs gave an r(2) of 0.91 and an average q(2)(2) of 0.80. Another CoSCoSA model for all 52 compounds had an r(2) of 0.85 and an average q(4)(2) of 0.52. Major benefits of CoSCoSA modeling include ease of development since the technique does not use molecular docking routines. C1 US FDA, Div Chem, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Beger, RD (reprint author), US FDA, Div Chem, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 33 TC 16 Z9 16 U1 0 U2 11 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0920-654X J9 J COMPUT AID MOL DES JI J. Comput.-Aided Mol. Des. PD OCT PY 2002 VL 16 IS 10 BP 727 EP 740 DI 10.1023/A:1022479510524 PG 14 WC Biochemistry & Molecular Biology; Biophysics; Computer Science, Interdisciplinary Applications SC Biochemistry & Molecular Biology; Biophysics; Computer Science GA 646NE UT WOS:000181040500003 PM 12650590 ER PT J AU Dolan, SP Capar, SG AF Dolan, SP Capar, SG TI Multi-element analysis of food by microwave digestion and inductively coupled plasma-atomic emission spectrometry SO JOURNAL OF FOOD COMPOSITION AND ANALYSIS LA English DT Article DE microwave digestion; inductively coupled plasma; atomic emission spectrometry; food; multi-element analysis ID STANDARD REFERENCE MATERIALS; TOTAL DIET; ABSORPTION SPECTROMETRY; TRACE-ELEMENTS; PLANT-MATERIAL; SAMPLES; CADMIUM; LEAD; COPPER; BORON AB A microwave digestion procedure for multi-elemental analysis of food was developed using one program to digest a variety of food matrices at the same time. A single program was enabled by an analytical portion mass based on the food's energy content calculated from macronutrient data (fat, protein and carbohydrate). The procedure allows a maximum mass to be analyzed for each food matrix without adjustment of the microwave digestion program to compensate for the variable reactivity of food matrices. Inductively coupled plasma-atomic emission spectrometry with ultrasonic nebulization was used to determine aluminum, arsenic, boron, barium, calcium, cadmium, cobalt, chromium, copper, iron, potassium, magnesium, manganese, molybdenum, sodium, nickel, phosphorus, lead, selenium, strontium, thallium, vanadium, and zinc. Method validation was performed on seven certified reference materials and 20 foods. Element fortification recovery of foods was acceptable (88-113%) and, a majority of available comparisons to reference materials indicated agreement except for aluminum, chromium, and selenium. Published by Elsevier Science Ltd. C1 US FDA, Ctr Food Safety & Appl Nutr, Elemental Res Branch HFS338, College Pk, MD 20740 USA. RP Capar, SG (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Elemental Res Branch HFS338, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. NR 31 TC 67 Z9 72 U1 2 U2 22 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0889-1575 J9 J FOOD COMPOS ANAL JI J. Food Compos. Anal. PD OCT PY 2002 VL 15 IS 5 BP 593 EP 615 DI 10.1006/jfca.2002.1064 PG 23 WC Chemistry, Applied; Food Science & Technology SC Chemistry; Food Science & Technology GA 608MA UT WOS:000178849100006 ER PT J AU Petricoin, EF Paweletz, CP Liotta, LA AF Petricoin, EF Paweletz, CP Liotta, LA TI Clinical applications of proteomics: Proteomic pattern diagnostics SO JOURNAL OF MAMMARY GLAND BIOLOGY AND NEOPLASIA LA English DT Article DE proteomics; patterns diagnostics; nipple fluid; breast cancer; mass spectrometry; genetic algorithms ID NIPPLE ASPIRATE FLUID; BREAST-CANCER RISK; ARTIFICIAL NEURAL NETWORKS; PROTEIN BIOCHIP TECHNOLOGY; PROSTATE-SPECIFIC ANTIGEN; SELDI MASS-SPECTROMETRY; CARCINOEMBRYONIC ANTIGEN; OVARIAN-CANCER; SERUM; IDENTIFICATION AB Clinical proteomics is an exciting new subdiscipline of proteomics that involves bedside application of proteomic technologies. A new and potentially revolutionary technology and approach for early disease detection, surveillance, and monitoring is proteomic pattern diagnostics. Using this approach, high throughput mass spectrometry generates a proteomic fingerprint of a given body fluid, such as serum or nipple fluid aspirants (NAF), in less than 30 s. This information archive is then used by new types of bioinformatic pattern recognition algorithms to identify patterns of protein changes that can discriminate cancer from healthy and unaffected individuals. This entire process can take place in less than a minute and requires only a droplet of blood, NAF, or ductal lavage washings. The new concept that is introduced by this platform is that the underlying identities of the proteins that comprise the patterns are not known and do not need to be known; the pattern itself becomes the diagnostic. C1 US FDA, FDA NCI Clin Proteom Program, Div Therapeut Prot, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. NCI, FDA NCI Clin Proteom Program, Pathol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. RP Petricoin, EF (reprint author), US FDA, FDA NCI Clin Proteom Program, Div Therapeut Prot, Ctr Biol Evaluat & Res, Bldg 29A,Room 2D12,8800 Rockville Pike, Bethesda, MD 20892 USA. NR 40 TC 59 Z9 59 U1 0 U2 1 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1083-3021 J9 J MAMMARY GLAND BIOL JI J. Mammary Gland Biol. Neoplasia PD OCT PY 2002 VL 7 IS 4 BP 433 EP 440 DI 10.1023/A:1024042200521 PG 8 WC Oncology; Endocrinology & Metabolism; Physiology SC Oncology; Endocrinology & Metabolism; Physiology GA 685GY UT WOS:000183255100008 PM 12882527 ER PT J AU Weisz, A Andrzejewski, D Fales, HM Mandelbaum, A AF Weisz, A Andrzejewski, D Fales, HM Mandelbaum, A TI Attachment of neutrals during tandem mass spectrometry of sulfonic acid dyes and intermediates in an ion trap SO JOURNAL OF MASS SPECTROMETRY LA English DT Article DE ion-neutral attachment; tandem mass spectrometry; ion trap; collision-induced dissociation; triple-stage quadrupole; electrospray mass spectrometry; atmospheric pressure chemical ionization; Quinoline Yellow; naphthaleneaminosulfonic acids ID FRAGMENT IONS; GAS-PHASE; ELECTROSPRAY; CHROMATOGRAPHY; COMPLEXES; WATER AB Several positional isomers of 2-(2-quinolinyl)-1H-indene-1,3(2H)-dione mono- and disulfonic acids prepared as reference materials for development of analytical methods involved in FDA certification of D&C Yellow No. 10 (Quinoline Yellow) were found consistently to show [MH + 14](+) ions when their electrospray- or atmospheric pressure chemical ionization-prepared MH+ ions were subjected to collisional activation. The source of these ions was found to be the methanol used as solvent in these procedures which combined with their [MH - H2O](+) ions under chemical ionization conditions. The reaction was found to be sensitive to their isomeric and chemical structures and other examples of this process are reviewed. Copyright (C) 2002 John Wiley Sons, Ltd. 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 12 TC 11 Z9 11 U1 0 U2 2 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 OCT PY 2002 VL 37 IS 10 BP 1025 EP 1033 DI 10.1002/jms.357 PG 9 WC Biophysics; Chemistry, Organic; Spectroscopy SC Biophysics; Chemistry; Spectroscopy GA 607WM UT WOS:000178813800002 PM 12375276 ER PT J AU Schenck, FJ Lehotay, SJ Vega, V AF Schenck, FJ Lehotay, SJ Vega, V TI Comparison of solid-phase extraction sorbents for cleanup in pesticide residue analysis of fresh fruits and vegetables SO JOURNAL OF SEPARATION SCIENCE LA English DT Article DE solid-phase extraction; cleanup; pesticide residues; analysis; fruits; vegetables ID CHROMATOGRAPHY/TANDEM MASS-SPECTROMETRY; ENHANCEMENT AB Sample extracts of various commodities, obtained using the US Food and Drug Administration (acetone extraction) and Canadian Pest Management Regulatory Agency (acetonitrile extraction) methods for pesticides were subjected to cleanup with solid phase extraction (SPE) columns. Graphitized carbon black (GCB), octadecylsilyl (C-18), strong anion exchange (SAX), aminopropyl (-NH2), and primary secondary amine (PSA) SPE columns were evaluated. The relative sample cleanup provided by these SPE columns was evaluated using gas chromatography with electron capture, flame photometric, and mass spectrometric detection. The -NH2 and PSA columns were found to provide the most effective cleanup, removing the greatest number of sample matrix interferences. The GCB columns removed most of the visible plant pigment in the extracts, but did little to eliminate the fatty acid matrix interferences "seen" by the detectors. Likewise, the C-18 and SAX columns did little to eliminate matrix interferences. Using an acetone extraction followed by a PSA cleanup, both polar and nonpolar pesticides present in samples at 1.0 ng/g could be recovered. C1 US FDA, SRL, Atlanta, GA 30309 USA. USDA ARS, Eastern Reg Res Ctr, Wyndmoor, PA USA. RP Schenck, FJ (reprint author), US FDA, SRL, 60 8th St NE, Atlanta, GA 30309 USA. NR 11 TC 81 Z9 87 U1 1 U2 27 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1615-9314 J9 J SEP SCI JI J. Sep. Sci. PD OCT PY 2002 VL 25 IS 14 BP 883 EP 890 DI 10.1002/1615-9314(20021001)25:14<883::AID-JSSC883>3.0.CO;2-7 PG 8 WC Chemistry, Analytical SC Chemistry GA 614TU UT WOS:000179207500004 ER PT J AU Shaikh, B O'Driscoll, JL Cullison, R AF Shaikh, B O'Driscoll, JL Cullison, R TI Depletion of residues of furosemide, a loop diuretic, in lactating dairy cows SO JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS LA English DT Article C1 US FDA, Ctr Vet Med, Res Off, Laurel, MD 20708 USA. RP Shaikh, B (reprint author), FOA CVM, 8401 Muirkirk Rd, Laurel, MD 20708 USA. NR 3 TC 0 Z9 1 U1 0 U2 1 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0140-7783 J9 J VET PHARMACOL THER JI J. Vet. Pharmacol. Ther. PD OCT PY 2002 VL 25 IS 5 BP 387 EP 388 DI 10.1046/j.1365-2885.2002.00426.x PG 2 WC Pharmacology & Pharmacy; Veterinary Sciences SC Pharmacology & Pharmacy; Veterinary Sciences GA 613AG UT WOS:000179107500011 PM 12423231 ER PT J AU Argaw, T Ritzhaupt, A Wilson, CA AF Argaw, T Ritzhaupt, A Wilson, CA TI Development of a real time quantitative PCR assay for detection of porcine endogenous retrovirus SO JOURNAL OF VIROLOGICAL METHODS LA English DT Article DE porcine endogenous retrovirus; xenotransplantation; TaqMan PCR; real time quantitative PCR; RT-PCR ID POLYMERASE-CHAIN-REACTION; HUMAN-CELLS; MINIATURE SWINE; NO EVIDENCE; HOST-RANGE; PIG; INFECTION; TRANSMISSION; XENOTRANSPLANTATION; IDENTIFICATION AB Real time PCR technology was applied to the development of assays for detection and quantitation of porcine endogenous retrovirus (PERV) RNA and DNA sequences in tissues and cells of human or animal origin. A plasmid construct encoding the PERV-pol gene or the in vitro transcribed RNA derived from the plasmid (cRNA) serves as a standard template for amplification of a 178 bp fragment. This study showed that the detection of this target sequence was linear over a range from 20 copies to 2 million copies of the plasmid and from 100 copies to I million copies of the cRNA. In addition, amplification of the target sequence was not inhibited by the presence of exogenous genomic DNA. These results demonstrate that a real time (TaqMan-based) PCR or RT-PCR assay can provide a sensitive, reproducible, and robust method for detecting and quantifying PERV DNA or RNA sequences in samples of human or guinea pig origin. Published by Elsevier Science B.V. C1 US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Lab Immunol & Virol, Bethesda, MD 20892 USA. RP Wilson, CA (reprint author), Bldg 29B,Room 2NN11,8800 Rockville Pike, Bethesda, MD 20892 USA. NR 28 TC 28 Z9 33 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-0934 J9 J VIROL METHODS JI J. Virol. Methods PD OCT PY 2002 VL 106 IS 1 BP 97 EP 106 AR PII S0166-0934(02)00140-4 DI 10.1016/S0166-0934(02)00140-4 PG 10 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Virology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Virology GA 611ZK UT WOS:000179048200011 PM 12367734 ER PT J AU Yang, M Coles, BF Delongchamp, R Lang, NP Kadlubar, FF AF Yang, M Coles, BF Delongchamp, R Lang, NP Kadlubar, FF TI Effects of the ADH3, CYP2E1, and GSTP1 genetic polymorphisms on their expressions in Caucasian lung tissue SO LUNG CANCER LA English DT Article DE ADH3; CYP2E1; GSTP1; acetaldehyde-DNA adducts; lung ID ORAL CAVITY; GENOTYPE; CANCER; RISK; EPIDEMIOLOGY; PHENOTYPE; ADDUCTS; SMOKING AB Individual differences in lung cancer susceptibility should be considered for effective lung cancer prevention. We investigated the CYP2E1, ADH3, and GSTP1 genetic polymorphisms that biotransform xenobiotic carcinogens, and variations of their enzyme activity in Caucasian lung tissues (N = 28), and found a variant distribution in pulmonary ADH and CYP2E1 activity. The ADH3*1/*1 subjects (N = 8) showed significantly higher ADH activity than ADH3*2/*2 (N = 3) subjects (P < 0.01). On the other hand, we found a 5-fold variation in the pulmonary CYP2E1 activity using a sensitive HLPC/EC based technique. A subject with the CYP2E1 -c/t allele showed 2-fold higher CYP2E1 activity than subjects with the c/c allele (N = 14). GSTP1 expression comprised 83% of the total pulmonary GSTs. However, neither the GSTP1 polymorphism, nor other lifestyle factors, such as age, gender, smoking status, were found to be associated with pulmonary GST expression. In conclusion, subjects with the ADH3*1 allele showed higher ADH activity and acetaldehyde-DNA adducts in lung than other subjects; thus, the ADH3*1 allele could be considered a risk factor for lung cancer. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved. C1 Seoul Natl Univ, Coll Med, Canc Res Inst, Dept Prevent Med,Chongno Gu, Seoul 110799, South Korea. Natl Ctr Toxicol Res, Div Mol Epidemiol, Jefferson, AR 72079 USA. Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. Cent Arkansas Vet Hlth Care Syst, Little Rock, AR 72205 USA. RP Yang, M (reprint author), Seoul Natl Univ, Coll Med, Canc Res Inst, Dept Prevent Med,Chongno Gu, 28 Yongon Dong, Seoul 110799, South Korea. NR 21 TC 17 Z9 19 U1 0 U2 2 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0169-5002 J9 LUNG CANCER-J IASLC JI Lung Cancer PD OCT PY 2002 VL 38 IS 1 BP 15 EP 21 AR PII S0169-5002(02)00150-2 DI 10.1016/S0169-5002(02)00150-2 PG 7 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 613MB UT WOS:000179135100003 PM 12367788 ER PT J AU Wang, RF Kim, SJ Robertson, LH Cerniglia, CE AF Wang, RF Kim, SJ Robertson, LH Cerniglia, CE TI Development of a membrane-array method for the detection of human intestinal bacteria in fecal samples SO MOLECULAR AND CELLULAR PROBES LA English DT Article DE membrane-array method; microarray; human intestinal bacteria; PCR; 16S rDNA amplification ID 16S RIBOSOMAL-RNA; PCR DETECTION; MICROFLORA; COMMUNITIES; ENVIRONMENT; REVEALS; COLON; FLORA; GENES AB A membrane-array method was developed for the detection of human intestinal bacteria in fecal samples without using the expensive microarray-arrayer and laser-scanner. The 16S rDNA sequences of 20 predominant human intestinal bacterial species were used to design oligonucleotide probes. Three 40-mer oligonucleotides specific for each bacterial species (total 60 probes) were synthesized and applied to nitrocellulose membranes. Digoxigenin (DIG)-labeled 16S rDNAs were amplified by polymerase chain reaction (PCR) from human fecal samples or pure cultured bacteria using two universal primers, and were hybridized to the membrane-array. Hybridization signals were read by NBT/BCIP color development. The 20 intestinal bacterial species tested were Bacteroides thetaiotaomicron, B. vulgatus, B. fragilis, B. distasonis, Clostridium clostridiiforme, C leptum, Fusobacterium prausnitzii, Peptostreptococcus productus, Ruminococcus obeum, R. bromii, R. callidus, R. albus, Bifidobacterium longum, B. adolescentis, B. infantis, Eubacterium biforme, E. aerofaciens, Lactobacillus acidophilus, Escherichia coli, and Enterococcus faecium. The two universal primers were able to amplify full size 16S rDNA from all of the 20 bacterial species tested. The hybridization results indicated that the membrane-array method is a reliable technique for the detection of,predominant human intestinal bacteria in the fecal samples. The result was also confirmed by using specific PCR methods for these bacteria. Published by Elsevier Science Ltd. C1 US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. RP Wang, RF (reprint author), US FDA, Natl Ctr Toxicol Res, Div Microbiol, 3900 NCTR Rd, Jefferson, AR 72079 USA. NR 28 TC 29 Z9 39 U1 1 U2 3 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 OCT PY 2002 VL 16 IS 5 BP 341 EP 350 DI 10.1006/mcpr.2002.0432 PG 10 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Cell Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Cell Biology GA 621ZN UT WOS:000179621600004 PM 12477438 ER PT J AU Kawakami, M Kawakami, K Puri, RK AF Kawakami, M Kawakami, K Puri, RK TI Intratumor administration of interleukin 13 receptor-targeted cytotoxin induces apoptotic glioma tumor xenografts SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID NITRIC-OXIDE SYNTHASE; CYTOCHROME-C; CANCER-CELLS; MITOCHONDRIAL DYSFUNCTION; CASPASE ACTIVATION; ALPHA CHAIN; THERAPY; PROTEIN; RELEASE; DEATH AB Apoptosis is not only essential for homeostasis in normal cells but also in cancer cells, in which it is associated with cell death mechanisms caused by novel therapeutics. We have previously reported that interleukin-13 receptors (IL-13R) are constitutively overexpressed on a majority of human malignant glioma cell lines and primary cell cultures. In addition, we have reported that IL-13 cytotoxin, comprised of human IL-13 and a mutated form of Pseudomonas exotoxin, is highly and specifically cytotoxic to these cells and can lead to pronounced antitumor activity in malignant glioma tumors in animal models. However, the molecular mechanisms of tumor cytotoxicity induced by IL-13 cytotoxin are poorly understood. In this study, we demonstrate that glioma tumors undergo apoptotic cell death on intratumoral administration of IL-13 cytotoxin. This conclusion was made based on (a) time-dependent induction of several proapoptotic molecules, such as caspases (caspase-3, -8, and -9) in tumors; (b) cleavage of procaspase-3 and poly(ADP-ribose) polymerase (PARP); and (c) the release of cytochrome c from mitochondria to the cytosol on injection of IL-13 cytotoxin in U251 glioblastoma tumors established in immunodeficient animals. These indicators of two major pathways of apoptosis were detected in tumors even though IL-13 cytotoxin was no longer present in tumors. In addition, we found that inducible nitric oxide was expressed in tumors in a time-dependent manner with primary localization in infiltrating phagocytes after treatment with IL-13 cytotoxin. These studies demonstrate that IL-13 cytotoxin mediates apoptotic death of glioma cells, resulting in regression of established tumors. Our studies will help unravel the molecular pathways of cell death associated with tumor regression and provide additional insight and define apoptosis as possible surrogate marker of tumor response. C1 US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Lab Mol Tumor Biol, Bethesda, MD 20892 USA. RP Puri, RK (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Lab Mol Tumor Biol, NIH Bldg 29B,Room 2NN10,29 Lincoln Dr,MSC4555, Bethesda, MD 20892 USA. NR 34 TC 39 Z9 42 U1 2 U2 3 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD OCT PY 2002 VL 1 IS 12 BP 999 EP 1007 PG 9 WC Oncology SC Oncology GA 607BQ UT WOS:000178770900003 PM 12481422 ER PT J AU Sambandamurthy, VK Wang, XJ Chen, B Russell, RG Derrick, S Collins, FM Morris, SL Jacobs, WR AF Sambandamurthy, VK Wang, XJ Chen, B Russell, RG Derrick, S Collins, FM Morris, SL Jacobs, WR TI A pantothenate auxotroph of Mycobacterium tuberculosis is highly attenuated and protects mice against tuberculosis SO NATURE MEDICINE LA English DT Article ID BCG VACCINES; VIRULENCE; PERSISTENCE; MACROPHAGES; GENE; ACID AB With the advent of HIV and the widespread emergence of drug-resistant strains of Mycobacterium tuberculosis, newer control strategies in the form of a better vaccine could decrease the global incidence of tuberculosis. A desirable trait in an effective live attenuated vaccine strain is an ability to persist within the host in a limited fashion in order to produce important protective antigens in vivo(1,2). Attenuated M. tuberculosis vaccine candidates have been constructed by deleting genes required for growth in mice(3-5). These candidate vaccines did not elicit adequate protective immunity in animal models, due to their inability to persist sufficiently long within the host tissues. Here we report that an auxotrophic mutant of M. tuberculosis defective in the de novo biosynthesis of pantothenic acid (vitamin B5) is highly attenuated in immunocompromised SCID mice and in immunocompetent BALB/c mice. SCID mice infected with the pantothenate auxotroph survived significantly longer (250 days) than mice infected with either bacille Calmette-Guerin (BCG) vaccine or virulent M. tuberculosis (77 and 35 days, respectively). Subcutaneous immunization with this auxotroph conferred protection in C57BL/6J mice against an aerosol challenge with virulent M. tuberculosis, which was comparable with that afforded by BCG vaccination. Our findings highlight the importance of de novo pantothenate biosynthesis in limiting the intracellular survival and pathogenesis of M. tuberculosis without reducing its immunogenicity in vaccinated mice. C1 Albert Einstein Coll Med, Howard Hughes Med Inst, Bronx, NY 10467 USA. Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10467 USA. Albert Einstein Coll Med, Dept Pathol, Bronx, NY 10467 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. RP Jacobs, WR (reprint author), Albert Einstein Coll Med, Howard Hughes Med Inst, Bronx, NY 10467 USA. NR 23 TC 197 Z9 204 U1 1 U2 9 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD OCT PY 2002 VL 8 IS 10 BP 1171 EP 1174 DI 10.1038/nm765 PG 4 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 599AN UT WOS:000178311000046 PM 12219086 ER PT J AU Haffner, ME Whitley, J Moses, M AF Haffner, ME Whitley, J Moses, M TI Two decades of orphan product development SO NATURE REVIEWS DRUG DISCOVERY LA English DT Article AB Over the past 20 years, incentives of the Orphan Drug Act (ODA), the largest single source of extramural clinical grants at the US Food and Drug Administration, have had a substantial impact on public health. ODA incentives have contributed to the development of many innovative biotechnology products, and as our understanding of the human genome evolves, it is anticipated that pharmacogenomics will result in the identification of more 'orphan diseases'. C1 US FDA, Off Orphan Prod Dev, Rockville, MD 20857 USA. RP Haffner, ME (reprint author), US FDA, Off Orphan Prod Dev, Room 15A08,5600 Fishers Lane, Rockville, MD 20857 USA. NR 4 TC 71 Z9 76 U1 2 U2 8 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-1776 J9 NAT REV DRUG DISCOV JI Nat. Rev. Drug Discov. PD OCT PY 2002 VL 1 IS 10 BP 821 EP 825 DI 10.1038/nrd919 PG 5 WC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA 607RF UT WOS:000178804000018 PM 12360259 ER PT J AU Ilev, IK Waynant, RW Byrnes, KR Anders, JJ AF Ilev, IK Waynant, RW Byrnes, KR Anders, JJ TI Dual-confocal fiber-optic method for absolute measurement of refractive index and thickness of optically transparent media SO OPTICS LETTERS LA English DT Article ID MICROSCOPE AB We present a novel noncontact optical method for absolute measurement of refractive index and thickness of optically transparent media. The method is based on a simple dual-confocal fiber-optic sensor design. It includes two independent confocal channels consisting of two identical apertureless fiber-optic-type confocal microscopes constructed by use of a single 2 x 2 fiber coupler. A geometrical-ray model is used to obtain the analytical dependence between the sample's refractive index and its thickness. The measurement method provides high accuracy in spatially locating the specific imaging points that correspond to the backreflected intensity peaks of the confocal responses. Thus, a simultaneous measurement of the sample refractive index and thickness is achieved. (C) 2002 Optical Society of America. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. Uniformed Serv Univ Hlth Sci, Dept Anat Physiol & Genet, Bethesda, MD 20814 USA. RP Ilev, IK (reprint author), US FDA, Ctr Devices & Radiol Hlth, HFZ-134, Rockville, MD 20857 USA. OI Byrnes, Kimberly/0000-0002-7501-7734 NR 12 TC 28 Z9 29 U1 1 U2 10 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 0146-9592 J9 OPT LETT JI Opt. Lett. PD OCT 1 PY 2002 VL 27 IS 19 BP 1693 EP 1695 DI 10.1364/OL.27.001693 PG 3 WC Optics SC Optics GA 598RF UT WOS:000178289800009 PM 18033338 ER PT J AU Nayak, R Kenney, PB AF Nayak, R Kenney, PB TI Screening of Salmonella isolates from a turkey production facility for antibiotic resistance SO POULTRY SCIENCE LA English DT Article DE Salmonella; turkey production; antibiotic resistance; preharvest sources ID UNITED-STATES; ANTIMICROBIAL RESISTANCE; BROILER-CHICKENS; DRUG-RESISTANCE; HUMAN-BEINGS; ANIMALS; TYPHIMURIUM; POULTRY; PATHOGENS; PLASMIDS AB An ecological survey was conducted from April 1997 to June 1999 on four turkey flocks (F1 to F4). Turkey cecal contents, litter, waterers, feed, feeders, and environmental swabs were analyzed. Presence of Salmonella was determined using conventional microbiological screening techniques and con-firmed by serology. Positive isolates were serotyped and screened for antibiotic resistance. From a total of 69 Salmonella isolates 25% were resistant to one or more antibiotics including gentamicin (G), spectinomycin (SP), streptomycin (S), tetracycline (T), tobramycin (TO), and trimethoprim/sulfamethoxazole. Isolates included 45 S. heidelberg, 13 S. senftenberg, 7 S. muenster, 2 S. anatum, and 2 S. worthington. Resistance to antibiotic(s) was highest among waterer isolates (55%) followed by environmental swabs (43%), feeder content samples (33%), turkey cecal contents (26%), and litter samples (5%). Frequencies of antibiotic-resistant Salmonella in F1, F2, and F4 were 27, 13, and 40%, respectively. Salmonella was undetected in F3. In. F1, S. heidelberg from cecal content and waterer samples was resistant to G, SP, S, and T, whereas S. anatum from waterer samples was resistant to T and S. In F2, S. worthington from litter and feeder content samples was resistant to T, and in F4, S. muenster from environmental swabs was resistant to TO, S, SP, and G. Identifying preharvest sources and characterizing serotype and antibiotic-resistance profile can assist poultry producers and integrators in tracking movement of Salmonella on turkey farms. C1 W Virginia Univ, Div Anim & Vet Sci, Morgantown, WV 26506 USA. US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. RP Kenney, PB (reprint author), W Virginia Univ, Div Anim & Vet Sci, Morgantown, WV 26506 USA. NR 31 TC 15 Z9 15 U1 0 U2 1 PU POULTRY SCIENCE ASSOC INC PI SAVOY PA 1111 NORTH DUNLAP AVE, SAVOY, IL 61874-9604 USA SN 0032-5791 J9 POULTRY SCI JI Poult. Sci. PD OCT PY 2002 VL 81 IS 10 BP 1496 EP 1500 PG 5 WC Agriculture, Dairy & Animal Science SC Agriculture GA 604NF UT WOS:000178627100010 PM 12412915 ER PT J AU Lozier, JN Dutra, A Pak, E Zhou, N Zheng, ZL Nichols, TC Bellinger, DA Read, M Morgan, RA AF Lozier, JN Dutra, A Pak, E Zhou, N Zheng, ZL Nichols, TC Bellinger, DA Read, M Morgan, RA TI The Chapel Hill hemophilia A dog colony exhibits a factor VIII gene inversion SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID VONWILLEBRAND DISEASE; RNA REPAIR; CANIS-FAMILIARIS; SEQUENCE; MUTATION; PROTEIN; EFFICIENCY; THERAPY; MODEL AB In the Chapel Hill colony of factor VIII-deficient dogs, abnormal sequence (ch8, for canine hemophilia 8, GenBank no. AF361485) follows exons 1-22 in the factor VIII transcript in place of exons 23-26. The canine hemophilia 8 locus (ch8) sequence was found in a 140-kb normal dog genomic DNA bacterial artificial chromosome (BAC) clone that was completely outside the factor VIII gene, but not in BAC clones containing the factor VIII gene. The BAC clone that contained ch8 also contained a homologue of F8A (factor 8 associated) sequence, which participates in a common inversion that causes severe hemophilia A in humans. Fluorescence in situ hybridization analysis indicated that exons 1-26 normally proceed sequentially from telomere to centromere at Xq28, and ch8 is telomeric to the factor VIII gene. The appearance of an "upstream" genomic sequence element (ch8) at the end of the aberrant factor VIII transcript suggested that an inversion of genomic DNA replaced factor VIII exons 22-26 with ch8. The F8A sequence appeared also in overlapping normal BAC clones containing factor VIII sequence. We hypothesized that homologous recombination between copies of canine F8A inside and outside the factor VIII gene had occurred, as in human hemophilia A. High-resolution fluorescent in situ hybridization on hemophilia A dog DNA revealed a pattern consistent with this inversion mechanism. We also identified a Hindill restriction fragment length polymorphism of F8A fragments that distinguished hemophilia A, carrier, and normal dogs' DNA. The Chapel Hill hemophilia A dog colony therefore replicates the factor VIII gene inversion commonly seen in humans with severe hemophilia A. C1 US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. Univ N Carolina, Dept Pathol, Francis Owen Blood Res Lab, Chapel Hill, NC 27516 USA. NCI, Surg Branch, Bethesda, MD 20892 USA. NHGRI, Bethesda, MD 20892 USA. RP Lozier, JN (reprint author), US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. FU NHLBI NIH HHS [HL63098, R24 HL063098] NR 31 TC 58 Z9 59 U1 0 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 1 PY 2002 VL 99 IS 20 BP 12991 EP 12996 DI 10.1073/pnas.192219599 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 600LK UT WOS:000178391700090 PM 12242334 ER PT J AU Itzhak, Y Martin, JL Ali, SF AF Itzhak, Y Martin, JL Ali, SF TI Methamphetamine-induced dopaminergic neurotoxicity in mice - Long-lasting sensitization to the locomotor stimulation and desensitization to the rewarding effects of methamphetamine SO PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY LA English DT Review DE conditioned place preference (CPP); dopaminergic neurotoxicity; psychomotor stimulation ID TYROSINE-HYDROXYLASE ACTIVITY; TRANSPORTER KNOCKOUT MICE; NITRIC-OXIDE SYNTHASE; INCENTIVE-SENSITIZATION; COCAINE; DEPLETION; ADDICTION; STRIATUM; RAT AB High doses of methamphetamine (METH) cause the depletion of striatal dopaminergic markers however, little is known about the behavioral consequences of METH-induced neurotoxicity. In the present study, the authors investigated the effect of a neurotoxic dose of METH (5 mg/kg; every 3 h x 3) on the subsequent response of Swiss Webster mice to (a) the psychomotor-stimulating effect of METH and (b) the acquisition and maintenance of conditioned place preference (CPP) by METH, The latter is a paradigm for the assessment of the rewarding properties of abused substances. The administration of the high dose of METH resulted in significant depletion of dopamine (DA) and its metabolites and dopamine transporter (DAT) binding sites in the striatum. The dopaminergic markers were below control levels until the 95th day after METH administration. METH-pretreated mice were sensitized to the psychomotor-stimulating effect of METH (1 mg/kg) as determined on Days 3 and 74 after the initial exposure to the neurotoxic dose of METH. However, the acquisition of CPP by METH (0.5 mg/kg) was markedly reduced in the mice pretreated with the neurotoxic dose of METH compared with the control group, The CPP was maintained for 8 weeks in the control group but not in the METH group. A priming injection of METH (0.5 mg/kg) caused marked reinstatement of place preference in the control group; this response was maintained for three additional weeks. However, the priming injection of METH resulted in diminished place preference in the METH group and the conditioned response dissipated within 3 weeks. These findings suggest that METH-induced striatal dopaminergic neurotoxicity is associated with two opposing and long-lasting behavioral outcomes: (a) sensitization to the psychomotor-stimulating effect of the drug and (b) desensitization to the rewarding properties of the drug. These consequences may be relevant to the psychopathology of METH abuse. (C) 2002 Elsevier Science Inc. All rights reserved. C1 Univ Miami, Sch Med, Dept Psychiat & Behav Sci R629, Miami, FL 33136 USA. US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Itzhak, Y (reprint author), Univ Miami, Sch Med, Dept Psychiat & Behav Sci R629, Gautier Bldg Room 503,1011 NW 15th St, Miami, FL 33136 USA. FU NIDA NIH HHS [DA08584, DA12867] NR 24 TC 35 Z9 35 U1 1 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0278-5846 J9 PROG NEURO-PSYCHOPH JI Prog. Neuro-Psychopharmacol. Biol. Psychiatry PD OCT PY 2002 VL 26 IS 6 BP 1177 EP 1183 AR PII S0278-5846(02)00257-9 DI 10.1016/S0278-5846(02)00257-9 PG 7 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 608LA UT WOS:000178846700023 PM 12452543 ER PT J AU Akkoyunlu, M AF Akkoyunlu, M TI Elimination of erythrocytes from blood prior to DNA extraction improves the sensitivity of anaplasma phagocytophila PCR SO SCANDINAVIAN JOURNAL OF INFECTIOUS DISEASES LA English DT Letter ID HUMAN GRANULOCYTIC EHRLICHIOSIS; AGENT C1 US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Akkoyunlu, M (reprint author), US FDA, Ctr Biol Evaluat & Res, HFM-428,1401 Rockville Pike, Rockville, MD 20852 USA. RI Akkoyunlu, Mustafa/I-5712-2012 NR 3 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS AS PI OSLO PA CORT ADELERSGT 17, PO BOX 2562, SOLLI, 0202 OSLO, NORWAY SN 0036-5548 J9 SCAND J INFECT DIS JI Scand. J. Infect. Dis. PD OCT 1 PY 2002 VL 34 IS 10 BP 788 EP 788 DI 10.1080/00365540210147949 PG 1 WC Infectious Diseases SC Infectious Diseases GA 611TT UT WOS:000179034400021 PM 12477341 ER PT J AU Apte, UM Limaye, PB Ramaiah, SK Vaidya, VS Bucci, TJ Warbritton, A Mehendale, HM AF Apte, UM Limaye, PB Ramaiah, SK Vaidya, VS Bucci, TJ Warbritton, A Mehendale, HM TI Upregulated promitogenic signaling via cytokines and growth factors: Potential mechanism of robust liver tissue repair in calorie-restricted rats upon toxic challenge SO TOXICOLOGICAL SCIENCES LA English DT Article; Proceedings Paper CT 40th Annual Meeting of the Society-of-Toxicology CY MAR 24-29, 2001 CL SAN FRANCISCO, CALIFORNIA SP Soc Toxicol DE epidermal growth factor receptor; EGFR; hepatocyte growth factor; HGF; IL-6; TGF-alpha; thioacetamide; tissue repair; TNF-alpha ID ALPHA TGF-ALPHA; DIETARY RESTRICTION; PARTIAL-HEPATECTOMY; FACTOR RECEPTOR; IMMUNOHISTOCHEMICAL LOCALIZATION; DNA-REPLICATION; REGENERATION; INJURY; THIOACETAMIDE; NECROSIS AB Previously we reported that moderate calorie restriction or diet restriction (DR, calories reduced by 35% for 21 days) in male Sprague-Dawley rats protects from a lethal dose of thioacetamide (TA). DR rats had 70% survival compared with 10% in rats fed ad libitum (AL) because of timely and adequate compensatory liver cell division and tissue repair in the DR rats. Further investigation of the mechanisms indicate that enhanced promitogenic signaling plays a critical role in this stimulated tissue repair. Expression of stimulators of promitogenic signaling interleukin-6 (IL-6), inducible nitric oxide synthase (iNOS), hepatocyte growth factor (HGF), transforming growth factor-alpha (TGF-alpha), and epidermal growth factor receptor (EGFR) were studied during liver tissue repair after TA-induced liver injury. Plasma IL-6 was significantly higher in the DR rats, with 6-fold higher expression at 48 h after TA administration. Immunohistochemical localization revealed significantly higher expression of IL-6 in the hepatic sinusoidal endothelium of DR rats. Expression of TGF-alpha and HGF was consistently higher in the livers of DR rats from 36 to 72 h. EGFR, which serves as a receptor for TGF-alpha, was higher in DR rats before TA administration and remained higher till 48 h after TA intoxication. DR-induced 2-fold increase in hepatic iNOS activity is consistent with early cell division in DR rats after TA challenge. These data suggest that the reason behind the higher liver tissue repair after TA-induced hepatotoxicity in DR rats is timely and higher expression of the growth stimulatory cytokines and growth factors. It appears that the physiological effects of DR make the liver cells vigilant and prime the liver tissue promptly for liver regeneration through promitogenic signaling upon toxic challenge. C1 Univ Louisiana Monroe, Coll Pharm, Dept Toxicol, Monroe, LA 71209 USA. Natl Ctr Toxicol Res, Pathol Associates Int, Jefferson, AR 72079 USA. RP Mehendale, HM (reprint author), Univ Louisiana Monroe, Coll Pharm, Dept Toxicol, 700 Univ Ave,Sugar Hall 306B, Monroe, LA 71209 USA. FU NIEHS NIH HHS [ES 09870] NR 49 TC 35 Z9 37 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD OCT PY 2002 VL 69 IS 2 BP 448 EP 459 DI 10.1093/toxsci/69.2.448 PG 12 WC Toxicology SC Toxicology GA 603KW UT WOS:000178559500019 PM 12377994 ER PT J AU Marques, MM da Costa, GG Blankenship, LR Culp, SJ Beland, FA AF Marques, MM da Costa, GG Blankenship, LR Culp, SJ Beland, FA TI The effect of deuterium and fluorine substitution upon the mutagenicity of N-hydroxy-2,6-dimethylaniline SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article; Proceedings Paper CT 8th International Conference on Carcinogenic/Mutagenic N-Substituted Aryl Compounds CY NOV 12-14, 2001 CL WASHINGTON, D.C. SP NCI, US FDA, Natl Ctr Toxicol Res, Toronto Res Chem Inc, Nestle Res Ctr, Oregon State Univ, Linus Pauling Inst DE 2,6-dimethylaniline; mutagenesis; DNA adducts; Salmonella typhimurium ID NASAL CARCINOGENESIS MODEL; AROMATIC-AMINES; DNA-ADDUCTS; CIGARETTE-SMOKE; TOBACCO-SMOKE; 2,6-DIMETHYLANILINE; LIDOCAINE; METABOLISM; LIVER; RATS AB 2,6-Dimethylaniline (2,6-DMA) is an intermediate in the manufacture of several products, including pesticides, dyestuffs, and synthetic resins. It is also present in nanogram amounts in tobacco smoke, and is a major metabolite of the potent anesthetic and antiarrhythmic drug lidocame, as well as a nasal carcinogen in rats. As with other aromatic amines, 2,6-DMA can undergo metabolic activation through cytochrome P450-mediated N-hydroxylation, followed by O-esterification to a reactive derivative capable of forming DNA adducts. We have recently characterized four DNA adducts resulting from this metabolic pathway. Three of the adducts arose from reaction of the exocyclic heteroatoms of deoxyadenosine and deoxyguanosine with the carbon para to the arylamine nitrogen. The fourth adduct resulted from reaction of the 2,6-DMA nitrogen with the C8 atom of deoxyguanosine. In order to investigate the relative contribution of the exocyclic heteroatom adducts as compared to the C8-deoxyguanosine adduct to the toxicities elicited by 2,6-DMA, we synthesized and compared the mutagenicity of N-hydroxy-2,6-DMA, N-hydroxy-4-deutero-2,6-DMA, 2,6-dimethylnitrosobenzene, 4-deutero-2,6-dimethylnitrosobenzene, and N-hydroxy-4-fluoro-2,6-DMA. In Salmonella typhimurium TA100, the two deuterated compounds and their non-deuterated analogues gave similar mutagenic responses (similar to25 revertants/nmol). Likewise in S. typhimurium TA98, a similar mutant frequency (similar to0.7 revertants/nmol) was obtained with the four compounds. With N-hydroxy-4-fluoro-2,6-DMA, the mutant frequency was reduced by similar to90% in S. typhimurium TA100 and similar to50% in S. typhimurium TA98. The results suggest that multiple adducts contribute to base substitution mutations detected by S. typhimurium TA100 while the C8-deoxyguanosine adduct is primarily responsible for the frameshift mutations detected by S. typhimurium TA98. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Univ Tecn Lisboa, Ctr Quim Estrutural, Inst Super Tecn, P-1049001 Lisbon, Portugal. Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Marques, MM (reprint author), Univ Tecn Lisboa, Ctr Quim Estrutural, Inst Super Tecn, Complexo I,Av Rovisco Pais, P-1049001 Lisbon, Portugal. EM matilde.marques@ist.utl.pt RI Marques, M. Matilde/E-2535-2012 OI Marques, M. Matilde/0000-0002-7526-4962 NR 34 TC 4 Z9 4 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 30 PY 2002 VL 506 SI SI BP 41 EP 48 AR PII S0027-5107(02)00150-1 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 602PJ UT WOS:000178513400005 ER PT J AU Culp, SJ Beland, FA Heflich, RH Benson, RW Blankenship, LR Webb, PJ Mellick, PW Trotter, RW Shelton, SD Greenlees, KJ Manjanatha, MG AF Culp, SJ Beland, FA Heflich, RH Benson, RW Blankenship, LR Webb, PJ Mellick, PW Trotter, RW Shelton, SD Greenlees, KJ Manjanatha, MG TI Mutagenicity and carcinogenicity in relation to DNA adduct formation in rats fed leucomalachite green SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article; Proceedings Paper CT 8th International Conference on Carcinogenic/Mutagenic N-Substituted Aryl Compounds CY NOV 12-14, 2001 CL WASHINGTON, D.C. SP NCI, US FDA, Natl Ctr Toxicol Res, Toronto Res Chem Inc, Nestle Res Ctr, Oregon State Univ, Linus Pauling Inst DE leucomalachite green; malachite green; lacl; mutagenicity; carcinogenicity; transgenic rats ID MALACHITE GREEN; IN-VIVO; TRANSGENIC MICE; 7,12-DIMETHYLBENZANTHRACENE; MUTATION AB Leucomalachite green is a persistent and prevalent metabolite of malachite green, a triphenylmethane dye that has been used widely as an antifungal agent in the fish industry. Concern over the use of malachite green is due to the potential for consumer exposure, evidence suggestive of tumor promotion in rodent liver, and suspicion of carcinogenicity based on structure-activity relationships. Our previous study indicated that feeding rodents malachite or leucomalachite green resulted in a dose-related increase in liver DNA adducts, and that, in general, exposure to leucomalachite green caused an increase in the number and severity of changes greater than was observed following exposure to malachite green. To characterize better the genotoxicity of leucomalachite green, female Big Blue(R) rats were fed leucomalachite green at doses of 0, 9, 27, 91, 272, or 543 ppm for up to 32 weeks. The livers were analyzed for lacI mutations at 4, 16, and 32 weeks and DNA adducts at 4 weeks. Using a P-32-postlabeling assay, we observed a dose-related DNA adduct in the livers of rats fed 91, 272, and 543 ppm leucomalachite green. A similar to3-fold increase in lacI mutant frequency was found in the livers of rats fed 543 ppm leucomalachite green for 16 weeks, but significant increases in mutant frequencies were not found for any of the other doses or time points assayed. We also conducted 2-year tumorigenesis bioassays in female and male F344 rats using 0, 91, 272, and 543 ppm leucomalachite, green. Preliminary results indicate an increasing dose trend in lung adenoma's in male rats treated with leucomalachite green, but no increase in the incidence of liver tumors in either sex of rat. These results suggest that the DNA adduct formed in the livers of rats fed leucomalachite green has little mutagenic or carcinogenic consequence. Published by Elsevier Science B.V. C1 US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. A Charles River Co, Pathol Associates, Jefferson, AR 72079 USA. US FDA, Ctr Vet Med, Rockville, MD 20855 USA. RP Culp, SJ (reprint author), US FDA, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. NR 22 TC 42 Z9 48 U1 2 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0027-5107 J9 MUTAT RES-FUND MOL M JI Mutat. Res.-Fundam. Mol. Mech. Mutagen. PD SEP 30 PY 2002 VL 506 SI SI BP 55 EP 63 AR PII S0027-5107(02)00152-5 DI 10.1016/S0027-5107(02)00152-5 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 602PJ UT WOS:000178513400007 PM 12351145 ER PT J AU Nowell, S Coles, B Sinha, R MacLeod, S Ratnasinghe, DL Stotts, C Kadlubar, FF Ambrosone, CB Lang, NP AF Nowell, S Coles, B Sinha, R MacLeod, S Ratnasinghe, DL Stotts, C Kadlubar, FF Ambrosone, CB Lang, NP TI Analysis of total meat intake and exposure to individual heterocyclic amines in a case-control study of colorectal cancer: contribution of metabolic variation to risk SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article; Proceedings Paper CT 8th International Conference on Carcinogenic/Mutagenic N-Substituted Aryl Compounds CY NOV 12-14, 2001 CL WASHINGTON, D.C. SP NCI, US FDA, Natl Ctr Toxicol Res, Toronto Res Chem Inc, Nestle Res Ctr, Oregon State Univ, Linus Pauling Inst DE colorectal cancer; heterocyclic amines (HCA); glutathione S-transferase A1; sulfotransferase 1A1; cytochrome P450 2A6; genotype; caffeine phenotype ID GLUTATHIONE S-TRANSFERASES; CYTOCHROME P4501A2; POSSIBLE MECHANISM; VARYING DEGREES; UNITED-STATES; COLON-CANCER; DNA-ADDUCTS; WELL-DONE; RED MEAT; PHIP AB A case-control study of colorectal cancer, consisting of 157 cases and 380 controls matched by sex, ethnicity, decade of age and county of residence was performed to explore the associations between environmental exposure, metabolic polymorphisms and cancer risk. Participants were required to provide a blood sample, undergo caffeine phenotyping and complete an in-person interview that evaluated meat consumption, cooking methods and degree of doneness. A color atlas of foods cooked to different degrees of doneness was used to estimate food preparation techniques and food models were used to estimate serving portion sizes. Data was analyzed using a reference database of heterocyclic amine (HCA) exposure based on the food preferences chosen from the atlas. Data regarding individual food items cooked to different levels of doneness, as well as summary variables of foods and of food groups cooked to different degrees of doneness were also evaluated in a univariate analysis for association with colorectal cancer case status. Three measures of metabolic variation, hGSTA1 genotype, SULT1A1 genotype and the phenotype for CYP2A6 were also evaluated for possible association with colon cancer. While higher exposure to HCAs was strongly associated with colorectal cancer risk, increased consumption of five red meats cooked well done or very well done produced comparable odds ratios (OR) for colorectal cancer risk (OR = 4.36, 95% CI 2.08-9.60) for the highest quartile of exposure. Similarly, individuals in the most rapid CYP2A6 phenotype quartile showed an odds ratio (OR = 4.18, 95 % CI 2.03-8.90). The ORs for the low activity hGSTA1 and low activity SULT1A1 alleles were 2.0, 95% CI 1.0-3.7 and 0.6, 95% CI 0.3-1.1, respectively. Individual measures of specific HCAs provided little improvement in risk assessment over the measure of meat consumption, suggesting that exposure to other environmental or dietary carcinogens such as nitrosamines or undefined HCAs may contribute to colorectal cancer risk. Published by Elsevier Science B.V. C1 Cent Arkansas Vet Hlth Care Syst, Little Rock, AR 72205 USA. Arkansas Canc Res Ctr, Little Rock, AR 72205 USA. Univ Arkansas Med Sci, Dept Pharmacol & Toxicol, Little Rock, AR 72205 USA. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. Univ Tennessee, Ctr Hlth Sci, Memphis, TN 38163 USA. Mt Sinai Sch Med, New York, NY USA. RP Lang, NP (reprint author), Cent Arkansas Vet Hlth Care Syst, 4300 W 7th St, Little Rock, AR 72205 USA. RI Sinha, Rashmi/G-7446-2015 OI Sinha, Rashmi/0000-0002-2466-7462 FU NCI NIH HHS [R01CA55751]; NIA NIH HHS [R01AG15722] NR 42 TC 93 Z9 98 U1 1 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 SEP 30 PY 2002 VL 506 SI SI BP 175 EP 185 AR PII S0027-5107(02)00164-1 DI 10.1016/S0027-5107(02)00164-1 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 602PJ UT WOS:000178513400019 PM 12351157 ER PT J AU Turesky, RJ Guengerich, FP Guillouzo, A Langouet, S AF Turesky, RJ Guengerich, FP Guillouzo, A Langouet, S TI Metabolism of heterocyclic aromatic amines by human hepatocytes and cytochrome P4501A2 SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article; Proceedings Paper CT 8th International Conference on Carcinogenic/Mutagenic N-Substituted Aryl Compounds CY NOV 12-14, 2001 CL WASHINGTON, D.C. SP NCI, US FDA, Natl Ctr Toxicol Res, Toronto Res Chem Inc, Nestle Res Ctr, Oregon State Univ, Linus Pauling Inst DE cytochrome P4501A2; hepatocytes; xenobiotic metabolism ID ADDUCT FORMATION; 2-AMINO-3,8-DIMETHYLIMIDAZO<4,5-F>QUINOXALINE MEIQX; LIVER-MICROSOMES; ACTIVATION; 1A2; 2-AMINO-1-METHYL-6-PHENYLIMIDAZO<4,5-B>PYRIDINE; GLUCURONIDATION; INHIBITION; URINE; PHIP AB The metabolism of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and 2-atnino-1-methyl-6-phenylimidazo [4,5-b]pyridine (PhIP) was investigated in primary human and rat hepatocytes. The genotoxic metabolites 2-(hydroxyamino)3,8-dimethylimidazo[4,5-f]quinoxaline (HONH-MeIQx) and 2-(hydroxyamino)-1-methyl-6-phenylimidazo[4,5-b]pyridine (HONH-PhIP), which are formed by cytochrome P4501 A2 (CYP1A2), were detected as stable N-2-glucuronide and N-2-and N-3-glucuronide conjugates, respectively. These products accounted for as much as 10% of the amount of MeIQx and 60% of PhIP added to human hepatocytes. Significantly lower amounts of these products were formed in rat hepatocytes. The phase II conjugates N-2-(3,8-dimethylimidazo[4,5-f]quinoxalin-2-yl-sulfamic acid (MeIQx-N-2-SO3H) and N-2-(beta-1-glucosiduronyl)-2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx-N-2-Gl), as well as the 7-oxo derivatives of MeIQx and-N-desmethyl-MeIQx, 2-amino-3,8-dimethyl-6-hydro-7H-imidazo[4,5-f]quinoxalin-7-one (7-oxo-MeIQx), and 2-amino-6-hydro-8-methyl-7H-imidazo[4,5-f]quinoxalin-7-one (N-desmethyl-7-oxo-MeIQx) were also identified. A novel CYP1A2-derived metabolite was characterized as 2-amino-3-methylimidazo[4,5-f]quinoxaline-8-carboxylic acid (IQx-8-COOH) and was the predominant metabolite formed in human hepatocytes exposed to MeIQx at levels approaching human exposure. Unlike human hepatocytes, rat cell preparations, even following pretreatment with the potent CYP1A1/CYP1A2 inducer 3-methylcholanthrene (3-MC) did not produce IQx-8-COOH but did catalyze the formation of 2-amino-3,8-dimethyl-5-hydroxyimidazo[4,5-f]quinoxaline (5-HO-MeIQx) as a major CYP-mediated detoxication product. In the case of PhIP, direct glucuronidation of the N-2 and N-3 positions also occurred in human and rat hepatocytes. Glucuronide and sulfate conjugates of 2-amino-4'-hydroxy-1-methyl-6-phenylimidazo[4,5-b]pyridine (4'-HO-PhIP) were detected as relatively minor metabolites in human hepatocytes but were the major products formed in rat hepatocytes, accounting for up to 50% of the metabolism. Rat CYP1A2, but not the human ortholog, significantly contributes to 4'-hydroxylation of PhIP. Important differences exist between human and rat liver enzymes in catalytic activity and regioselectivity of MeIQx and PhIP metabolism. Some human hepatocyte preparations are more active at transforming MeIQx and PhIP to a genotoxic species than rat hepatocytes pretreated with potent inducer 3-MC. These pronounced interspecies differences in metabolism of MeIQx and PhIP may affect the biological activity of these mutagens and must be considered when assessing human health risk. Published by Elsevier Science B.V. C1 Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Vanderbilt Univ, Sch Med, Dept Biochem, Ctr Mol Toxicol, Nashville, TN 37232 USA. Univ Rennes 1, INSERM, U456, Fac Pharm, F-35043 Rennes, France. RP Turesky, RJ (reprint author), Natl Ctr Toxicol Res, 3900 NCTR Dr,HFT 100, Jefferson, AR 72079 USA. RI Langouet, Sophie/I-2776-2015 NR 21 TC 57 Z9 58 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0027-5107 J9 MUTAT RES-FUND MOL M JI Mutat. Res.-Fundam. Mol. Mech. Mutagen. PD SEP 30 PY 2002 VL 506 SI SI BP 187 EP 195 AR PII S0027-5107(02)00165-3 DI 10.1016/S0027-5107(02)00165-3 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 602PJ UT WOS:000178513400020 PM 12351158 ER PT J AU Anderson, KE Sinha, R Kulldorff, M Gross, M Lang, NP Barber, C Harnack, L DiMagno, E Bliss, R Kadlubar, FF AF Anderson, KE Sinha, R Kulldorff, M Gross, M Lang, NP Barber, C Harnack, L DiMagno, E Bliss, R Kadlubar, FF TI Meat intake and cooking techniques: associations with pancreatic cancer SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article; Proceedings Paper CT 8th International Conference on Carcinogenic/Mutagenic N-Substituted Aryl Compounds CY NOV 12-14, 2001 CL WASHINGTON, D.C. SP NCI, US FDA, Natl Ctr Toxicol Res, Toronto Res Chem Inc, Nestle Res Ctr, Oregon State Univ, Linus Pauling Inst DE epidemiology; pancreas cancer; meat intake; cooking practices ID HETEROCYCLIC AMINES HCAS; PAST MEDICAL HISTORY; RISK-FACTORS; DIET; FOOD; MUTAGENS; ALCOHOL; HABITS; COFFEE; BEEF AB Heterocyclic amines (HCAs), and polycyclic aromatic hydrocarbons (PAHs), formed in temperature and time-dependent manners during cooking of meat, may increase the risk of certain cancers. As these compounds could be carcinogenic for the pancreas, we assessed meat intake, preparation methods, and doneness preferences as risk factors for exocrine pancreatic cancer. In a case-control study (cases = 193, controls = 674), subjects provided information on their usual meat intake and how it was cooked, e.g. fried, grilled or barbecued (BBQ), etc. Meat doneness preferences were measured using photographs that showed internal doneness and external brownness with a numerical scale. Data were analyzed with unconditional logistic regression. Odds ratios (ORs) increased with increased intake of grilled/BBQ red meat in an analysis adjusted for age, sex, smoking, education, race, and diabetes. Based on amount of BBQ meat consumed, the OR and 95% confidence interval (0) for the fifth quintile relative to the reference group (quintiles 1 and 2) was 2.19 (1.4, 3.4). Findings were not substantively changed by further adjustment for calories, total fat, fruit and vegetables, or alcohol consumption (from a food frequency questionnaire (FFQ)). Other meat variables did not show statistically significant associations with risk nor did they substantively alter the findings for BBQ. These included total meat, processed meat, total red meat, total white meat, total broiled meat, total fried meat, or total meat cooked by means other than grilling. We conclude that grilled red meat intake is a risk factor for pancreatic cancer and that method of meat preparation in addition to total intake is important in assessing the effects of meat consumption in epidemiologic studies. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Univ Minnesota, Minneapolis, MN 55454 USA. NCI, Rockville, MD 20852 USA. Univ Connecticut, Sch Med, Farmington, CT 06030 USA. Univ Arkansas Med Sci, Little Rock, AR 72205 USA. Mayo Clin, Rochester, MN 55905 USA. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Anderson, KE (reprint author), Univ Minnesota, Minneapolis, MN 55454 USA. RI Kulldorff, Martin/H-4282-2011; Sinha, Rashmi/G-7446-2015; OI Sinha, Rashmi/0000-0002-2466-7462; Kulldorff, Martin/0000-0002-5284-2993 FU NCI NIH HHS [R01-CA58697] NR 35 TC 83 Z9 84 U1 3 U2 17 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 30 PY 2002 VL 506 SI SI BP 225 EP 231 AR PII S0027-5107(02)00169-0 DI 10.1016/S0027-5107(02)00169-0 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 602PJ UT WOS:000178513400024 PM 12351162 ER PT J AU Masciotra, S Owen, SM Rudolph, D Yang, CF Wang, B Saksena, N Spira, T Dhawan, S Lal, RB AF Masciotra, S Owen, SM Rudolph, D Yang, CF Wang, B Saksena, N Spira, T Dhawan, S Lal, RB TI Temporal relationship between V1V2 variation, macrophage replication, and coreceptor adaptation during HIV-1 disease progression SO AIDS LA English DT Article DE HIV-1; V1V2 extension; disease progression ID IMMUNODEFICIENCY-VIRUS TYPE-1; SYNCYTIUM-INDUCING PHENOTYPE; ENVELOPE GLYCOPROTEIN; IN-VIVO; RECEPTOR-BINDING; V2 DOMAIN; HOST DETERMINANTS; VARIABLE LOOPS; V1/V2 REGION; SOLUBLE CD4 AB Background: Specific mutations in VPR and V2 potentially restrict HIV-1 replication in macrophages. Such restriction could potentially limit HIV replication in long-term non-progressors (LTNP), thus accounting for low viral load and delayed progression to AIDS. Objective: To examine whether a specific VPR phenotype (truncated versus non-truncated) correlates with disease progression and whether elongated V2 restricts viral replication in macrophages or alters viral tropism. Methods: Sequence analysis was carried for VPR and V1-V3 env from four rapid progressors (RPs), six late progressors (LPs), and three LTNPs in cohort of HIV-1-infected homosexual men. The replication kinetics of sequential isolates was examined in primary CD4 cells and macrophages and coreceptor usage was determined by GHOST infection assays. Results: No differences were found in the VPR protein from RP and LTNP isolates. Analysis of the V2 region revealed that all RPs maintained similar V2 lengths (40 aa), whereas LPs and LTNPs acquired additional amino acids (2-13 aa) in the V2 region. Coreceptor specificity revealed that RP switch from CCR5 to multiple coreceptor usage, whereas LTNPs maintained R5 viruses. Sequential isolates from each group revealed comparable replication efficiencies in both T-cells and macrophages, regardless of the V2 length or coreceptor utilization. In addition, cross-section analysis of six LTNPs from Australia revealed extended V2 with consistent usage of CCR5 coreceptor. Conclusion: The present results suggest that acquisition of a V2 extension over time in HIV-1-infected LPs/LTNPs appears to correlate with maintenance of CCR5 usage among LTNPs. These findings may be important for a better understanding of the host interactions and disease progression. (C) 2002 Lippincott Williams Wilkins. C1 Ctr Dis Control & Prevent, Natl Ctr Infect Dis, HIV Immunol & Diagnost Branch, Div AIDS, Atlanta, GA USA. Univ Sydney, Retroviral Genet Lab, Ctr Virus Res, Westmead Millennium Inst & Res Ctr, Sydney, NSW 2006, Australia. US FDA, Ctr Biol Evaluat & Res, Mol Virol Lab, Bethesda, MD USA. RP Lal, RB (reprint author), CDC, NCID, DASTLR, HIV Immunol & Diagnost Branch, Atlanta, GA 30333 USA. RI Yang, Chunfu/G-6890-2013 NR 50 TC 41 Z9 41 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD SEP 27 PY 2002 VL 16 IS 14 BP 1887 EP 1898 DI 10.1097/00002030-200209270-00005 PG 12 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 611WE UT WOS:000179040100005 PM 12351948 ER PT J AU Yan-Sanders, Y Hammons, GJ Lyn-Cook, BD AF Yan-Sanders, Y Hammons, GJ Lyn-Cook, BD TI Increased expression of heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNP) in pancreatic tissue from smokers and pancreatic tumor cells SO CANCER LETTERS LA English DT Article DE pancreatic cancer; hnRNP gene expression; smokers ID LUNG-CANCER; DETECTION MARKER; MESSENGER-RNA; RISK; IDENTIFICATION; PROTEIN-A1; BIOMARKER; B1 AB Pancreatic cancer is a major cause of deaths in the United States, and has one of the lowest 5-year survival rates. Early diagnosis has not been possible due to the lack of reliable early tumor markers. The heterogeneous nuclear ribonucleoprotein A1/B2 (hnRNP) was recently shown to be up-regulated in the early stage of lung cancer. This protein plays an important role in biogenesis and transport of mRNA. Up-regulation of hnRNP usually precedes morphological differentiation and is considered a good biomarker in the early stages of cancer development. Because smoking is a high risk factor for pancreatic cancer, this study examined the expression of hnRNP in human pancreatic tissues from smokers and non-smokers. A two-fold increase in expression of hnRNP was found overall in smokers when compared to non-smokers and smokers who quit (P < 0.05). The increase in expression of hnRNP was higher in female smokers compared to female non-smokers. High levels of expression was also shown in a limited number of human pancreatic adenocarcinomas and two pancreatic tumor cell lines, HPAF-11 and SU 86.86. HP-8, a normal primary pancreatic cell line, did not express hnRNP. These results strongly suggest that up-regulation of hnRNP may be a good candidate for early screening for pancreatic cancer because of its activation in pancreatic tissue from smokers and activation in pancreatic adenocarcinomas. Over-expression of hnRNP has been suggested as evidence that normal transcriptional regulation is altered. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved. C1 Natl Ctr Toxicol Res, Div Mol Epidemiol, Jefferson, AR 72079 USA. RP Lyn-Cook, BD (reprint author), Natl Ctr Toxicol Res, Div Mol Epidemiol, Jefferson, AR 72079 USA. NR 28 TC 49 Z9 51 U1 0 U2 1 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 SEP 26 PY 2002 VL 183 IS 2 BP 215 EP 220 AR PII S0304-3835(02)00168-4 DI 10.1016/S0304-3835(02)00168-4 PG 6 WC Oncology SC Oncology GA 586KT UT WOS:000177583700013 PM 12065097 ER PT J AU Siegel, JP AF Siegel, JP TI Assessing the use of activated protein c in the treatment of severe sepsis. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Siegel, JP (reprint author), Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. NR 6 TC 90 Z9 97 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD SEP 26 PY 2002 VL 347 IS 13 BP 1030 EP 1034 DI 10.1056/NEJMsb021512 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 596RD UT WOS:000178178400013 PM 12324563 ER PT J CA Florida Dept Hlth Georigia Div Publ Hlth Food & Drug Adm CDC TI West Nile virus infection in organ donor and transplant recipients - Georgia and Florida, 2002 (Reprinted from MMWR, vol 51, pg 790, 2002) SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Reprint C1 Florida Dept Hlth, Tallahassee, FL 32399 USA. Georgia Div Publ Hlth, Atlanta, GA 30303 USA. US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. CDC, Div Healthcare Qual Promot, Div Vector Borne Infect Dis, Natl Ctr Infect Dis, Atlanta, GA 30333 USA. RP Florida Dept Hlth, Tallahassee, FL 32399 USA. NR 1 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 SEP 25 PY 2002 VL 288 IS 12 BP 1465 EP 1466 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 596AT UT WOS:000178142000008 ER PT J AU Twaddle, NC Churchwell, MI Doerge, DR AF Twaddle, NC Churchwell, MI Doerge, DR TI High-throughput quantification of soy isoflavones in human and rodent blood using liquid chromatography with electrospray mass spectrometry and tandem mass spectrometry detection SO JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES LA English DT Article DE isoflavones ID TISSUE DISTRIBUTION; BREAST-CANCER; IN-VITRO; GENISTEIN; DAIDZEIN; ALPHA; CELLS AB Soy-containing foods and dietary supplements are widely consumed for putative health benefits (e.g., cancer chemoprevention, beneficial effects on serum lipids associated with cardiovascular health, reduction of osteoporosis, relief of menopausal symptoms). However, studies of soy isoflavones in experimental animals suggest possible adverse effects as well (e.g., enhancement of reproductive organ cancer, modulation of endocrine function, anti-thyroid effects). This paper describes the development and validation of a sensitive high throughput method for quantifying isoflavones in blood from experimental animal and human studies. Serum samples containing genistein, daidzein, and equol were processed using reverse phase solid-phase extraction in the 96-well format for subsequent LC-ES/MS/MS or LC-ES/MS analysis using isotope dilution in conjunction with labeled internal standards. The method was validated by repetitive analysis of spiked blank serum and the intra-day and inter-day accuracy (88-99%) and precision (relative standard deviations from 3 to 13%) of measurement determined. The lower limit of quantification for all isoflavones was approximately 0.005 muM using MS/MS detection, and 0.03 muM using MS for genistein and daidzein. The degree of method performance, with respect to throughput, sensitivity and selectivity, makes this approach practical for analysis of large sample sets generated from mechanistic animal studies and human clinical trials of soy isoflavones. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Doerge, DR (reprint author), Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 11 TC 58 Z9 58 U1 1 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1570-0232 J9 J CHROMATOGR B JI J. Chromatogr. B PD SEP 25 PY 2002 VL 777 IS 1-2 BP 139 EP 145 AR PII S1570-0232(02)00275-1 DI 10.1016/S1570-0232(02)00275-1 PG 7 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 609ZM UT WOS:000178936300012 PM 12270207 ER PT J AU Dalu, A Blaydes, BS Bryant, CW Latendresse, JR Weis, CC Delclos, KB AF Dalu, A Blaydes, BS Bryant, CW Latendresse, JR Weis, CC Delclos, KB TI Estrogen receptor expression in the prostate of rats treated with dietary genistein SO JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES LA English DT Article DE estrogen receptor expression; prostate; genistein ID SPRAGUE-DAWLEY RATS; SOY ISOFLAVONE GENISTEIN; NEONATAL EXPOSURE; ANDROGEN RECEPTOR; GROWTH-FACTOR; ADULT-RAT; MALE-MICE; ENVIRONMENTAL ESTROGENS; REPRODUCTIVE PHENOTYPES; TISSUE DISTRIBUTION AB Steroid hormones and their receptors play critical roles in the growth, development, and maintenance of the male reproductive tract. Genistein, a naturally occurring isoflavonoid primarily found in soybeans, interacts with estrogen receptors alpha and beta (ERalpha and beta), with preferential affinity for ERbeta. This is one mechanism whereby genistein may affect growth and development and potentially alter susceptibility to carcinogenesis. Previous studies have indicated effects of soy and/or genistein in the male rodent reproductive tract under certain exposure conditions. The current study was undertaken to determine if modulation of the expression of ERalpha and ERbeta by dietary genistein may contribute to those effects. Rats in a two-generation study were fed 0, 5, 100, or 500 ppm genistein prior to mating and through pregnancy and lactation. At weaning, male pups were selected in each of the F-1 and F-2 generations and half of the pups continued on the same diet as their dams (G/G, continuous exposure) while their litter mates were placed on control chow (G/C, gestational and lactational exposure) until sacrifice on PND 140. Male reproductive organ weights, serum levels of testosterone and dihydrotestosterone (DHT), and ERalpha and ERbeta protein levels in the ventral and dorsolateral prostate were the endpoints measured. Prostate sections were also evaluated microscopically. Statistically significant elevations in testosterone and DHT were observed in PND 140 animals from the F-1 generation, but they were not accompanied by organ weight changes. Body weight in the continuously dosed 500 ppm F-1 PND 140 animals was depressed relative to control, but organ weights in animals of either generation showed few treatment-related effects. While estrogen receptor levels were quite variable, levels of ERbeta in the dorsolateral prostate were significantly depressed in all dose groups in the G/C exposure and the high dose group of the G/G exposure in F-1 rats, but not in F-2 rats. Given the growing body of knowledge on the significance of ERbeta in the prostate, the evidence for apparent down regulation of this receptor by genistein may have implications for reproductive toxicity and carcinogenesis that warrant further investigation. Published by Elsevier Science B.V. C1 US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. Pathol Associates Int Inc, Jefferson, AR 72079 USA. RP Delclos, KB (reprint author), US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. RI Latendresse, John/A-9215-2009 NR 74 TC 16 Z9 17 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1570-0232 J9 J CHROMATOGR B JI J. Chromatogr. B PD SEP 25 PY 2002 VL 777 IS 1-2 BP 249 EP 260 AR PII s1570-0232(02)00346-X DI 10.1016/S1570-0232(02)00346-X PG 12 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 609ZM UT WOS:000178936300022 PM 12270217 ER PT J AU Doerge, DR Chang, HC AF Doerge, DR Chang, HC TI Inactivation of thyroid peroxidase by soy isoflavones, in vitro and in vivo SO JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES LA English DT Review DE reviews; soy; isoflavones; thyroid peroxidase ID CHROMATOGRAPHY-MASS-SPECTROMETRY; SPRAGUE-DAWLEY RATS; ANTITHYROID ACTION; IN-VITRO; GENISTEIN; MECHANISM; FORMULA; INHIBITION; DAIDZEIN; HYPOTHYROIDISM AB Soy-containing foods and dietary supplements are widely consumed for putative health benefits (e.g. cancer chemoprevention, beneficial effects on serum lipids associated with cardiovascular health, reduction of osteoporosis, relief of menopausal symptoms). However, studies of soy isoflavones in experimental animals suggest possible adverse effects as well (e.g. enhancement of reproductive organ cancer, modulation of endocrine function, anti-thyroid effects). This paper reviews the evidence in humans and animals for anti-thyroid effects of soy and its principal isoflavones, genistein and daidzein. Published by Elsevier Science B.V. C1 Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Doerge, DR (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. NR 56 TC 70 Z9 75 U1 0 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1570-0232 J9 J CHROMATOGR B JI J. Chromatogr. B PD SEP 25 PY 2002 VL 777 IS 1-2 BP 269 EP 279 AR PII S1570-0232(02)00214-3 DI 10.1016/S1570-0232(02)00214-3 PG 11 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 609ZM UT WOS:000178936300024 PM 12270219 ER PT J AU Kessler, LG Andersen, MR Etzioni, R AF Kessler, LG Andersen, MR Etzioni, R TI Much ado about mammography variability SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID BREAST-CANCER C1 Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. US FDA, Ctr Devices & Radiol Hlth, Off Surveillance & Biometr, Rockville, MD 20857 USA. RP Andersen, MR (reprint author), Fred Hutchinson Canc Res Ctr, 1100 Fairview Ave N,MP 900, Seattle, WA 98109 USA. NR 12 TC 5 Z9 5 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD SEP 18 PY 2002 VL 94 IS 18 BP 1346 EP 1347 PG 2 WC Oncology SC Oncology GA 593VZ UT WOS:000178016300002 PM 12237274 ER PT J AU Morinobu, A Gadina, M Strober, W Visconti, R Fornace, A Montagna, C Feldman, GM Nishikomori, R O'Shea, JJ AF Morinobu, A Gadina, M Strober, W Visconti, R Fornace, A Montagna, C Feldman, GM Nishikomori, R O'Shea, JJ TI STAT4 serine phosphorylation is critical for IL-12-induced IFN-gamma production but not for cell proliferation SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ACTIVATED PROTEIN-KINASE; P38 MAP KINASE; T-CELLS; TYROSINE PHOSPHORYLATION; TRANSCRIPTIONAL ACTIVITY; SIGNAL TRANSDUCER; IL-12 RECEPTOR; T(H)1 CELLS; DNA-BINDING; TH2 CELLS AB T helper 1 (T(H)1) differentiation and IFN-gamma production are crucial in cell-mediated immune responses. IL-12 is an important regulator of this process and mediates its effects through signal transducer and activator of transcription 4 (STAT4). IFN-gamma production is also regulated by the p38 mitogen-activated kinase pathway, although the mechanisms are ill-defined. We show here that GADD45-beta and GADD45-gamma can induce STAT4 S721 phosphorylation via the MKK6/p38 pathway. Thus, STAT4 could be a target that accounts for the defects in cell-mediated immunity associated with perturbations in the p38 pathway. To investigate the biological significance of STAT4 S721 phosphorylation, we reconstituted primary spleen cells from STAT4-deficient mice with wild-type and mutated STAT4, by using a retroviral gene transduction. We demonstrated that expression of wild-type STAT4, but not the S721A mutant, restored normal THII differentiation and IFN-gamma synthesis. The inability of STAT4 S721 to restore IFN-gamma production was not caused by decreased IL-12R expression because the STAT4 S721 mutant also failed to restore IFN-gamma production in STAT4-deficient IL-12Rbeta2 transgenic cells. Importantly, STAT4 S721A-transduced cells showed normal proliferative response to IL-12, illustrating that serine phosphorylation is not required for IL-12-induced proliferation. Additionally, the results imply the existence of STAT4 serine phosphoryiation-dependent and -independent target genes. We conclude that phosphorylation of STAT4 on both tyrosine and serine residues is important in promoting normal TH1 differentiation and IFN-gamma secretion. C1 NIAMSD, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD 20892 USA. NIAID, Mucosal Immun Sect, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. NCI, Div Basic Sci, NIH, Bethesda, MD 20892 USA. NCI, Genet Branch, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Monoclonal Antibodies, Bethesda, MD 20892 USA. RP Morinobu, A (reprint author), NIAMSD, Mol Immunol & Inflammat Branch, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. RI Fornace, Albert/A-7407-2008; Visconti, Roberta/C-5299-2009 OI Fornace, Albert/0000-0001-9695-085X; NR 53 TC 97 Z9 100 U1 1 U2 6 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 17 PY 2002 VL 99 IS 19 BP 12281 EP 12286 DI 10.1073/pnas.182618999 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 596VK UT WOS:000178187000053 PM 12213961 ER PT J AU Tamminga, CA Nemeroff, CB Blakely, RD Brady, L Carter, CS Davis, KL Dingledine, R Gorman, JM Grigoriadis, DE Henderson, DC Innis, RB Killen, J Laughren, TP McDonald, WM Murphy, GM Paul, SM Rudorfer, MV Sausville, E Schatzberg, AF Scolnick, EM Suppes, T AF Tamminga, CA Nemeroff, CB Blakely, RD Brady, L Carter, CS Davis, KL Dingledine, R Gorman, JM Grigoriadis, DE Henderson, DC Innis, RB Killen, J Laughren, TP McDonald, WM Murphy, GM Paul, SM Rudorfer, MV Sausville, E Schatzberg, AF Scolnick, EM Suppes, T TI Developing novel treatments for mood disorders: Accelerating discovery SO BIOLOGICAL PSYCHIATRY LA English DT Article DE depression bipolar disorder research resources; government/industry collaboration ID SEROTONIN TRANSPORTER GENE; ANTIDEPRESSANT-INDUCED MANIA; ELECTROCONVULSIVE-THERAPY; ELECTRODE PLACEMENT; MAJOR DEPRESSION; PHARMACOLOGICAL PROFILE; ENDOGENOUS-DEPRESSION; REFRACTORY DEPRESSION; PSYCHOTIC DEPRESSION; REUPTAKE INHIBITORS AB This review was generated from discussions by the Pharmacologic and Somatic Treatments Section of the National Institute of Mental Health Strategic Plan for Mood Disorders Committee on advancing novel pharmacologic and somatic treatments for mood disorders. The opening section of the article summarizes in broad strokes, current pharmacologic treatments, and new directions in the field. Thereafter the topics focus on specific research initiatives that could advance the current therapeutics for mood disorders including new basic and clinical research in vivo human imaging procedures, somatic therapeutics, and the vast new area of pharmacogenetics. New scientific and technical opportunities exist today based on advances in basic neuroscience, opportunities in clinical testing, industry interest in advancing central nervous system therapeutics, and on active consumer advocacy groups. The question of how to bring all of these positive forces together to accelerate discovery in mood disorder therapeutics is the topic of this article. C1 Univ Maryland, Sch Med, Dept Psychiat, Maryland Psychiat Res Ctr, Baltimore, MD 21228 USA. Emory Univ, Sch Med, Dept Psychiat & Behav Sci, Atlanta, GA USA. Emory Univ, Dept Pharmacol, Atlanta, GA 30322 USA. Emory Univ, Dept Psychiat, Atlanta, GA 30322 USA. Vanderbilt Univ, Sch Med, Dept Pharmacol, Nashville, TN 37212 USA. NIMH, Neuropharmacol Program, Mol & Cellular Neurosci Res Branch, Bethesda, MD 20892 USA. NIMH, Drug Discovery Program, Mol & Cellular Neurosci Res Branch, Bethesda, MD 20892 USA. NIMH, Clin Therapeut Program, Mol & Cellular Neurosci Res Branch, Bethesda, MD 20892 USA. NIMH, Mol Imaging Branch, Bethesda, MD 20892 USA. Univ Pittsburgh, Western Psychiat Inst & Clin, Dept Psychiat, Pittsburgh, PA 15213 USA. Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. Columbia Univ, Coll Phys & Surg, New York State Psychiat Inst, Dept Psychiat, New York, NY USA. Neurocrine Biosci Inc, San Diego, CA USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NIAID, Div AIDS, NIH, Bethesda, MD 20892 USA. US FDA, Rockville, MD 20857 USA. Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. Eli Lilly & Co, Lilly Res Labs, Indianapolis, IN 46285 USA. NCI, Div Canc Treatment & Diag, Dev Therapeut Program, Rockville, MD USA. Merck Res Labs, W Point, PA USA. Univ Texas, SW Med Ctr, Dept Psychiat, Dallas, TX USA. RP Tamminga, CA (reprint author), Univ Maryland, Sch Med, Dept Psychiat, Maryland Psychiat Res Ctr, POB 21247, Baltimore, MD 21228 USA. RI dingledine, Ray/F-5173-2011 NR 83 TC 52 Z9 55 U1 3 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD SEP 15 PY 2002 VL 52 IS 6 BP 589 EP 609 AR PII S0006-3223(02)01470-1 DI 10.1016/S0006-3223(02)01470-1 PG 21 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 598VK UT WOS:000178297000008 PM 12361670 ER PT J AU Hewlett, IK Li, XX Epstein, JS AF Hewlett, IK Li, XX Epstein, JS TI Discrepant results of 2 screening tests for Anti-HIV antibody - Reply SO CLINICAL INFECTIOUS DISEASES LA English DT Letter C1 US FDA, Off Blood Res & Review, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Hewlett, IK (reprint author), US FDA, Off Blood Res & Review, Ctr Biol Evaluat & Res, 1401 Rockville Pike, Rockville, MD 20852 USA. NR 3 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 SEP 15 PY 2002 VL 35 IS 6 BP 774 EP 775 DI 10.1086/341986 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 589MQ UT WOS:000177763200022 ER PT J AU Schwartsmann, G Ratain, MJ Cragg, GM Wong, JE Saijo, N Parkinson, DR Fujiwara, Y Pazdur, R Newman, DJ Dagher, R Di Leone, L AF Schwartsmann, G Ratain, MJ Cragg, GM Wong, JE Saijo, N Parkinson, DR Fujiwara, Y Pazdur, R Newman, DJ Dagher, R Di Leone, L TI Anticancer drug discovery and development throughout the world SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 38th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 18-21, 2002 CL ORLANDO, FL SP Amer Soc Clin Oncol ID NATURAL-PRODUCTS; CANCER; PHARMACOGENETICS; THERAPY AB This year's American Society of Clinical Oncology International Symposium devoted 2 hours to a lively discussion of various aspects of anticancer drug discovery and development throughout the world. The scientific program started with an overview of efforts directed toward promoting international collaboration in natural product-derived anticancer drug discovery. This was followed by a discussion on the importance of interethnic differences and pharmacogenetics in anticancer drug development. Thereafter, this part of the program was completed by a description of the activities of the newly created Singapore-Hong Kong-Australia Drug Development Consortium and an overview of the contribution of Japan to anticancer drug development. The logistics and regulatory aspects of clinical trials with new anticancer agents in different parts of the world were then presented, with an emphasis on Europe, North America, and Japan. The program was completed with a panel discussion of the efforts to harmonize the exchange of clinical data originating from one region of the globe with other territories, with input from official representatives of the United States Food and Drug Administration and the Medical Devices Evaluation Center of Japan. C1 Univ Luterana Brasil, Ctr Comprehens Canc, S Amer Off Anticanc Drug Dev, Canoas, Brazil. Univ Fed Rio Grande do Sul, Postgrad Course Med, Porto Alegre, RS, Brazil. Univ Chicago, Dept Med, Comm Clin Pharmacol & Pharmacogenom, Chicago, IL 60637 USA. Univ Chicago, Canc Res Ctr, Chicago, IL 60637 USA. NCI, Nat Prod Branch, Dev Therapeut Program, Div Canc Treatment & Diag, Frederick, MD 21701 USA. Natl Univ Singapore, Dept Hematol Oncol, Singapore 117548, Singapore. Natl Canc Ctr, Div Med Oncol, Tokyo, Japan. Minist Hlth Labor & Welf, Natl Inst Hlth Sci, Pharmaceut & Med Devices Evaluat Ctr, Tokyo, Japan. Novartis Oncol, Translat Dev, Clin Res, E Hanover, NJ USA. US FDA, Div Oncol Drug Prod, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Schwartsmann, G (reprint author), Univ Luterana Brasil, Ctr Comprehens Canc, S Amer Off Anticanc Drug Dev, Campus Cent ULBRA,Predio 22-5 Andar, Canoas, Brazil. EM gschwart.ez@terra.com.br RI Schwartsmann, Gilberto/G-4256-2016 OI Schwartsmann, Gilberto/0000-0002-7850-1644 NR 27 TC 36 Z9 39 U1 0 U2 3 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP 15 PY 2002 VL 20 IS 18 SU S BP 47S EP 59S DI 10.1200/JCO.2002.07.122 PG 13 WC Oncology SC Oncology GA 597HH UT WOS:000178215800007 PM 12235225 ER PT J AU Cortez, K Murphy, BR Almeida, KN Beeler, J Levandowski, RA Gill, VJ Childs, RW Barrett, AJ Smolskis, M Bennett, JE AF Cortez, K Murphy, BR Almeida, KN Beeler, J Levandowski, RA Gill, VJ Childs, RW Barrett, AJ Smolskis, M Bennett, JE TI Immune-globulin prophylaxis of respiratory syncytial virus infection in patients undergoing stem-cell transplantation SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID ANTIBODY; CHILDREN; INFANTS AB Thirty-two patients undergoing allogeneic hematopoietic stem-cell transplantation were given respiratory syncytial virus (RSV) immune globulin (RSVIG) at the time of transplantation and again 3 weeks later. Antibody titers to RSV, human parainfluenza virus 3, measles, and influenza H1N1, H3N2, and B were measured prior to administration of RSVIG and 6 more times over the course of the subsequent 6 weeks. Baseline antiviral titers and increases in antibody after administration of RSVIG were extremely variable for all the viruses. In 18 patients in whom the baseline titers of antibody titers to RSV-F protein were 1:640-1:2048, there was a 7.7-fold initial increase in these titers after the first dose of RSVIG, compared with a 2.1-fold increase in 14 patients with baseline titers of 1:4096-1:20,840; increases in titers of antibody against the other viruses after the first dose of RSVIG reflected similar variability. The subset of patients with the lowest titers appear to receive the greatest benefit from administration of RSVIG. C1 NIAID, Clin Mycol Sect, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. NHLBI, Microbiol Serv, Dept Lab Med, Warren Grant Magnuson Clin Ctr,NIH, Bethesda, MD 20892 USA. NHLBI, Stem Cell Allotransplant Unit, Hematol Branch, Warren Grant Magnuson Clin Ctr,NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Lab Pediat & Resp Virus Dis, Div Viral Prod, Bethesda, MD USA. RP Cortez, K (reprint author), NIAID, Clin Mycol Sect, Clin Invest Lab, NIH, Rm 11C304,10 Ctr Dr, Bethesda, MD 20892 USA. NR 15 TC 22 Z9 23 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 SEP 15 PY 2002 VL 186 IS 6 BP 834 EP 838 DI 10.1086/342412 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 588GY UT WOS:000177694800015 PM 12198619 ER PT J AU Schmued, LC AF Schmued, LC TI The progression of neuronal, myelin, astrocytic, and immunological changes in the rat brain following exposure to aurothioglucose SO BRAIN RESEARCH LA English DT Article DE circumventricular organ; gold thioglucose; gold therapeutics; neuropathology; blood-brain barrier AB Aurothioglucose (ATG) is presently employed both by clinicians in the treatment of advanced rheumatoid arthritis and by neuroscience researchers to generate lesions around the circumventricular organs (CVOs) of rodent brains, resulting in obese animals. Although the existence of such lesions is well documented, there is relatively little information concerning the changes over time of the different cell types in the regions surrounding the CVOs. To address this question, specific markers allowing identification of four distinct cellular populations were used to characterize respective changes over time. Generally, regions adjacent to the CVOs were more vulnerable than the CVOs themselves, while more caudal structures were more frequently lesioned than more anterior CVO regions. Vascular and glial cells appeared to be the initial targets of ATG, while neuronal cell death occurred subsequent to the inflammatory response. The results of this study help resolve the mechanism of ATG toxicity as reflected by a cascade of pathologies that is consistent with disparate cell types exhibiting specific changes at specific times. Published by Elsevier Science B.V. C1 Natl Ctr Toxicol Res, FDA, Dept Neurotoxicol, Jefferson, AR 72079 USA. RP Schmued, LC (reprint author), Natl Ctr Toxicol Res, FDA, Dept Neurotoxicol, Jefferson, AR 72079 USA. NR 14 TC 4 Z9 4 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 SEP 13 PY 2002 VL 949 IS 1-2 BP 171 EP 177 AR PII S0006-8993(02)02978-5 DI 10.1016/S0006-8993(02)02978-5 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 599CQ UT WOS:000178316900020 PM 12213313 ER PT J AU Crawford, LM AF Crawford, LM TI First drug for women with constipation-predominant IBS 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 Crawford, LM (reprint author), US FDA, Off Commissioner Food & Drugs, HF-1,Room 14-71,5600 Fisshers 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 11 PY 2002 VL 288 IS 10 BP 1225 EP 1225 DI 10.1001/jama.288.10.1225 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 592BW UT WOS:000177917700007 PM 12215114 ER PT J AU Crawford, LM AF Crawford, LM TI Nominations for device panels 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 Crawford, LM (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 11 PY 2002 VL 288 IS 10 BP 1225 EP 1225 DI 10.1001/jama.288.10.1225 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 592BW UT WOS:000177917700008 PM 12215114 ER PT J AU Crawford, LM AF Crawford, LM TI Drug for colorectal 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 Crawford, LM (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 11 PY 2002 VL 288 IS 10 BP 1225 EP 1225 DI 10.1001/jama.288.10.1225 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 592BW UT WOS:000177917700005 PM 12215114 ER PT J AU Crawford, LM AF Crawford, LM TI Needlestick injury data needed 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 Crawford, LM (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 11 PY 2002 VL 288 IS 10 BP 1225 EP 1225 DI 10.1001/jama.288.10.1225 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 592BW UT WOS:000177917700006 PM 12215114 ER PT J AU Nayak, R Khan, SA Watson, RH Cerniglia, CE AF Nayak, R Khan, SA Watson, RH Cerniglia, CE TI Influence of growth media on vancomycin resistance of Enterococcus isolates and correlation with resistance gene determinants SO FEMS MICROBIOLOGY LETTERS LA English DT Article DE vancomycin-resistant enterococcus; plating medium; van gene; antibiotic susceptibility testing method ID SUSCEPTIBILITY; LEVEL AB The effect of Mueller-Hinton (MH), MH+blood or brain heart infusion medium (agar or broth) on 13 Enterococcus isolates was determined, when testing their antibiotic susceptibility. Disk diffusion and Vitek methods were used to determine vancomycin resistance, while broth dilution and E-test methods were used to measure the minimum inhibitory concentration. The data were correlated with the presence of vancomycin resistance genes. A definite correlation pattern could not be established between the presence of van genes and vancomycin resistance in any plating medium, when tested by the disk diffusion assay. The broth dilution, irrespective of the plating medium, and Vitek methods were more reliable than the E-test method in testing isolates with vanA or vanB genes. However, for vanC2/C3 genotypes, the E-test method, irrespective of the plating medium, tested better than the broth dilution assay. (C) 2002 Federation of European Microbiological Societies. Published by Elsevier Science B.V. All rights reserved. C1 US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. RP Khan, SA (reprint author), US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. NR 14 TC 4 Z9 6 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 10 PY 2002 VL 214 IS 2 BP 159 EP 163 AR PII S0378-1097(02)00885-6 PG 5 WC Microbiology SC Microbiology GA 601UV UT WOS:000178467500003 PM 12351224 ER PT J AU Baylor, NW Egan, W Richman, P AF Baylor, NW Egan, W Richman, P TI Aluminum salts in vaccines - US perspective (vol 20, pg S18, 2002) SO VACCINE LA English DT Correction C1 US FDA, Ctr Biol Evaluat & Res, Off Vaccines Res & Review, Bethesda, MD 20014 USA. RP Baylor, NW (reprint author), US FDA, Ctr Biol Evaluat & Res, Off Vaccines Res & Review, Bethesda, MD 20014 USA. NR 1 TC 1 Z9 1 U1 1 U2 6 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 10 PY 2002 VL 20 IS 27-28 BP 3428 EP 3428 AR PII S0264-410X(02)00307-9 DI 10.1016/S0264-410X(02)00307-9 PG 1 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 602CB UT WOS:000178486700024 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 3-(N-tert-butylcarboxamido)-1-propyl group as an attractive phosphate/thiophosphate protecting group for solid-phase oligodeoxyribonucleotide synthesis SO JOURNAL OF ORGANIC CHEMISTRY LA English DT Article ID SULFUR-TRANSFER REAGENT; OLIGONUCLEOTIDE SYNTHESIS; 3H-1,2-BENZODITHIOL-3-ONE 1,1-DIOXIDE; DEOXYNUCLEOSIDE PHOSPHORAMIDITES; DEPROTECTION; MONOMERS; DNA; AMINOLYSIS; CHEMISTRY; LACTONES AB Among the various phosphate/thiophosphate protecting groups suitable for solid-phase oligonucleotide synthesis, the 3-(N-tent-butylcarboxamido)-1-propyl group is one of the most convenient, as it can be readily removed, as needed, under thermolytic conditions at neutral pH. The deprotection reaction proceeds rapidly (t(1/2) similar to100 s) through an intramolecular cyclodeesterification reaction involving the amide function and the release of the phosphate/thiophosphate group as a 2-(tert-butylimino)tetrahydrofuran salt. Incorporation of the 3-(N-tent-butylcarboxamido)-1-propyl group into the deoxyribonucleoside phosphoramidites 1a-d is achieved using inexpensive raw materials. The coupling efficiency of 1a-d in the solid-phase synthesis of d(ATCCGTAGCTAAGGTCATGC) and its phosphorothioate analogue is comparable to that of commercial 2-cyanoethyl deoxyribonucleoside phosphoramidites. These oligonucleotides were phosphate/thiophosphate-deprotected within 30 min upon heating at 90 degreesC in Phosphate-Buffered Saline (PBS buffer, pH 7.2). Since no detectable nucleobase modification or significant phosphorothioate desulfurization occurs, the 3-(N-tert-butylcarboxamido)-1-propyl group represents an attractive alternative to the 2-cyanoethyl group toward the large-scale preparation of therapeutic oligonucleotides. C1 US FDA, Ctr Biol Evaluat & Res, Div Therapeut Prot, Bethesda, MD 20892 USA. NCI, Biol Testing Branch, Dev Therapeut Program, Frederick, MD 21701 USA. RP Beaucage, SL (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Therapeut Prot, 8800 Rockville Pike, Bethesda, MD 20892 USA. NR 31 TC 28 Z9 28 U1 2 U2 7 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-3263 J9 J ORG CHEM JI J. Org. Chem. PD SEP 6 PY 2002 VL 67 IS 18 BP 6430 EP 6438 DI 10.1021/jo0258608 PG 9 WC Chemistry, Organic SC Chemistry GA 591LE UT WOS:000177880900020 PM 12201764 ER PT J AU Feng, ZH Wang, TG Li, DD Fung, P Wilson, BC Liu, B Ali, SF Langenbach, R Hong, JS AF Feng, ZH Wang, TG Li, DD Fung, P Wilson, BC Liu, B Ali, SF Langenbach, R Hong, JS TI Cyclooxygenase-2-deficient mice are resistant to 1-methyl-4-phenyl1,2,3,6-tetrahydropyridine-induced damage of dopaminergic neurons in the substantia nigra SO NEUROSCIENCE LETTERS LA English DT Article DE Parkinson's disease; cyclooxygenase-2; tyrosine hydroxylase; 1-methyl-4-phenyl1, 2, 3, 6-tetrahydropyridine; dopamine ID PARKINSONS-DISEASE; MULTIPLE-SCLEROSIS; REACTIVE OXYGEN; GENE DISRUPTION; MPTP TOXICITY; IN-VIVO; EXPRESSION; NEUROTOXICITY; 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE; MICROGLIA AB Cyclooxygenases (COX), key enzymes in prostanoid biosynthesis, may represent important therapeutic targets in various neurodegenerative diseases. In the present study, we explored the role of COX in Parkinson's disease (PD) by using 1-methyl-4-phenyl1, 2, 3, 6-tetrahydropyridine (MPTP) as a tool to create a rodent Parkinsonian model. MPTP (20 mg/kg, subcutaneously) was injected daily into COX-1- and COX-2-deficient mice and wild-type (WT) controls for five consecutive days. Immunocytochemical analysis of tissues collected 7 days after the final MPTP treatment showed that MPTP significantly decreased the number of tyrosine hydroxylase-immunoreactive (TH-ir) neurons in the substantia nigra pars compacta (SNc) of WT(40% decrease) and COX-1(-/-) (45% decrease) mutants. However, a much smaller loss of TH-ir neurons in COX-2(-/-) mutants (20% decrease) was observed. Furthermore, electrochemical analysis revealed a more than 70% decrease in the levels of dopamine and its metabolites (3,4-dihydroxyphenylacetic acid and homovanillic acid) in the striatum of the WT control COX-1(-/-) and COX-2(-/-) mutant mice. These results indicate that loss of COX-2 activity reduces MPTP-induced damage to the dopaminergic neurons of the SNc, but does not alter the levels of dopamine and its metabolites in the striatum. Interestingly, MPTP caused the same degree of loss of dopaminergic neurons in both COX-2(+/-) and COX-2(-/-) mice (20% loss). The results of this study indicate an important role of COX-2 in MPTP-induced neuronal degeneration and suggest the possibility that manipulation of the COX-2 could be an important target for therapeutic interventions in PD. (C) 2002 Published by Elsevier Science Ireland Ltd. C1 NIEHS, Neuropharmacol Sect, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. Univ Hong Kong, Queen Mary Hosp, Univ Dept Med, Hong Kong, Hong Kong, Peoples R China. US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Neurochem Lab, Jefferson, AR 72079 USA. NIEHS, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Hong, JS (reprint author), NIEHS, Neuropharmacol Sect, Lab Pharmacol & Chem, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. RI liu, Bin/A-7695-2009 NR 36 TC 107 Z9 117 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD SEP 6 PY 2002 VL 329 IS 3 BP 354 EP 358 AR PII S0304-3940(02)00706-8 DI 10.1016/S0304-3940(02)00704-8 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 595JA UT WOS:000178104400024 PM 12183047 ER PT J 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 TI Independent versus sequential reading in ROC studies of computer-assist modalities: Analysis of components of variance SO ACADEMIC RADIOLOGY LA English DT Article DE computers, diagnostic aid; diagnostic radiology, observer performance; receiver operating characteristic curve (ROC) ID AIDED DIAGNOSIS; NODULES; MODELS; INDEX AB Rationale and Objectives. The authors analyzed two methods for arranging the temporal sequencing of unaided versus computer-assisted reading in multiple-reader, multiple-case receiver operating characteristic studies of detection of solitary pulmonary nodules on chest radiographs. In the "independent" mode the readings are separated by about 1 month; in the "sequential" mode, the computer-assisted reading immediately follows the unassisted reading. Materials and Methods. The authors used the method of Beiden, Wagner, and Campbell (BWC) to decompose the components of variance of receiver operating characteristic accuracy measures into those that are correlated and those that are uncorrelated across reading conditions. Only the latter contribute to uncertainty in estimates of the difference in accuracy measures across reading conditions (unaided vs aided). This method was used to analyze data from two independent studies of the detection of solitary pulmonary nodules on chest radiographs. Results. In the sequential reading mode the components that were Correlated across reading conditions increased compared to the independent reading mode, as might be expected. What was not anticipated was the fact that the total reader variance was approximately the same for the two reading modes. The results were remarkably similar across the two independent studies analyzed. Conclusion. The sequential reading mode may thus be the more sensitive probe of the difference between unassisted and computer-assisted reading, if the mean effect is unperturbed (as here). It is also the least demanding on the logistics and investment of reader time. (C) AUR, 2002. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. Univ Chicago, Dept Radiol, Kurt Rossman Labs, Chicago, IL 60637 USA. Georgetown Univ, ISIS Ctr, Washington, DC USA. Deus Technol, Rockville, MD USA. RP Wagner, RF (reprint author), US FDA, Ctr Devices & Radiol Hlth, HFZ-142, Rockville, MD 20857 USA. OI Nishikawa, Robert/0000-0001-7720-9951 FU NCI NIH HHS [CA 62625] NR 19 TC 25 Z9 25 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 SEP PY 2002 VL 9 IS 9 BP 1036 EP 1043 DI 10.1016/S1076-6332(03)80479-8 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 590AV UT WOS:000177795800006 PM 12238545 ER PT J AU Wagner, R AF Wagner, R TI In memoriam - Richard G. Swensson SO ACADEMIC RADIOLOGY LA English DT Biographical-Item C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Wagner, R (reprint author), US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC UNIV RADIOLOGISTS PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523-2251 USA SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD SEP PY 2002 VL 9 IS 9 BP 1074 EP 1075 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 590AV UT WOS:000177795800018 ER PT J AU Cooper, WO Staffa, JA Renfrew, JW Graham, DJ Ray, WA AF Cooper, WO Staffa, JA Renfrew, JW Graham, DJ Ray, WA TI Oral corticosteroid use among children in TennCare SO AMBULATORY PEDIATRICS LA English DT Article DE asthma; Medicaid; respiratory illness; steroid use ID ALTERNATE-DAY PREDNISONE; PEDIATRIC-PATIENTS; MEDICAID PROGRAM; FATAL VARICELLA; THERAPY; ASTHMA; TERM; CARE; HOSPITALIZATION; MEDICATIONS AB Background.-Lack of information about medication effects and use in children is a long-standing and troublesome policy issue. Documenting patterns of use for medications with potential for suboptimal use and adverse effects, such as oral corticosteroids, would be useful. Objective.-To describe the use of oral corticosteroids among children enrolled in TennCare, Tennessee's managed care program for Medicaid enrollees and uninsured individuals. Design.-A retrospective cohort study. Drug Exposure.-Children enrolled in TennCare who had prescriptions filled in their name for oral corticosteroids during 1998 were identified. Descriptive information included age, race, sex, and county of residence. We identified possible indications for corticosteroid use for new users by searching encounter files for encounters temporally related to the index prescription. Subsequent use of corticosteroids was measured in the 365 days after the index prescription. Results.-Of 400 724 children continuously enrolled in TennCare during the study period, 29 362 (7327 per 100 000) children had a prescription filled for an oral corticosteroid. Steroid prescription filling was more common among young children and male children and less common among black children. Children in rural counties had oral corticosteroid prescriptions filled at a higher rate than children residing in urban counties. Nearly 75% of corticosteroid users filled only 1 prescription during the study period; 1319 children filled 4 or more prescriptions. Asthma was the most common indication for oral corticosteroid use (16%), whereas 1 in 5 users (22%) had an unknown indication for oral corticosteroid use. Conclusions.-A large number of children enrolled in TennCare had a prescription for oral corticosteroids filled in 1998. Further population-based studies describing the development of adverse effects in users of corticosteroids would be important. C1 Vanderbilt Univ, Sch Med, Div Gen Pediat, Dept Pediat, Nashville, TN 37232 USA. Vanderbilt Univ, Dept Prevent Med, Div Pharmacoepidemiol, Nashville, TN 37232 USA. Vanderbilt Univ, Vanderbilt Inst Publ Policy Studies, Nashville, TN 37232 USA. US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Cooper, WO (reprint author), Vanderbilt Univ, Sch Med, Div Gen Pediat, Dept Pediat, Suite 5028 MCE, Nashville, TN 37232 USA. FU AHRQ HHS [1U18 HS 10384-01] NR 59 TC 7 Z9 7 U1 0 U2 0 PU ALLIANCE COMMUNICATIONS GROUP DIVISION ALLEN PRESS PI LAWRENCE PA 810 EAST 10TH STREET, LAWRENCE, KS 66044 USA SN 1530-1567 J9 AMBUL PEDIATR JI Ambul. Pediatr. PD SEP-OCT PY 2002 VL 2 IS 5 BP 375 EP 381 DI 10.1367/1539-4409(2002)002<0375:OCUACI>2.0.CO;2 PG 7 WC Pediatrics SC Pediatrics GA 599KC UT WOS:000178332800005 PM 12241133 ER PT J AU Jia, YP Alayash, AI AF Jia, YP Alayash, AI TI Stopped-flow fluorescence method for the detection of heme degradation products in solutions of chemically modified hemoglobins and peroxide SO ANALYTICAL BIOCHEMISTRY LA English DT Article ID BLOOD SUBSTITUTES; HYDROGEN-PEROXIDE; TOXICITY C1 US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Alayash, AI (reprint author), US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. NR 11 TC 8 Z9 8 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD SEP 1 PY 2002 VL 308 IS 1 BP 186 EP 188 AR PII S0003-2697(02)00233-6 DI 10.1016/S0003-2697(02)00233-6 PG 3 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 602PX UT WOS:000178514600025 PM 12234481 ER PT J AU Kwon, HJ Cote, TR Cuffe, MS Kramer, JM Braun, MM AF Kwon, HJ Cote, TR Cuffe, MS Kramer, JM Braun, MM TI Heart failure following the use of licensed tumor necrosis factor antagonists. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 66th Annual Scientific Meeting of the American-College-of-Rheumatology/37th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 24-29, 2002 CL NEW ORLEANS, LOUISIANA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 US FDA, CBER, Rockville, MD 20857 USA. Duke Clin Res Inst, Ctr Educ & Res Therapeut, Durham, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2002 VL 46 IS 9 SU S BP S572 EP S573 PG 2 WC Rheumatology SC Rheumatology GA 600ZN UT WOS:000178421801568 ER PT J AU Manadan, AM Mohan, AK Cote, TR Siegel, JN Sequeira, W Block, JA AF Manadan, AM Mohan, AK Cote, TR Siegel, JN Sequeira, W Block, JA TI Tuberculosis and etanercept treatment. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 66th Annual Scientific Meeting of the American-College-of-Rheumatology/37th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 24-29, 2002 CL NEW ORLEANS, LOUISIANA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Rush Med Coll, Chicago, IL 60612 USA. FDA, Rockville, MD USA. NR 0 TC 13 Z9 13 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2002 VL 46 IS 9 SU S BP S166 EP S166 PG 1 WC Rheumatology SC Rheumatology GA 600ZN UT WOS:000178421800389 ER PT J AU Mohan, N Edwards, ET Capps, TR Slifman, NR Braun, MM Lee, JH Siegel, JN AF Mohan, N Edwards, ET Capps, TR Slifman, NR Braun, MM Lee, JH Siegel, JN TI Leukocytoclastic vasculitis associated with anti-tumor necrosis factor (TNF) therapy. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 66th Annual Scientific Meeting of the American-College-of-Rheumatology/37th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 24-29, 2002 CL NEW ORLEANS, LOUISIANA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Georgetown Univ, Ctr Med, Washington, DC USA. US FDA, Ctr Biol Evaluat & Res, Rockville, MD 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 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2002 VL 46 IS 9 SU S BP S165 EP S165 PG 1 WC Rheumatology SC Rheumatology GA 600ZN UT WOS:000178421800387 ER PT J AU Rider, L Schiffenbauer, A Villalba, M Adams, E Joe, G Harris-Love, M James-Newton, L Hicks, J Pilkington, C Isenberg, D Lachenbruch, P Miller, F AF Rider, L Schiffenbauer, A Villalba, M Adams, E Joe, G Harris-Love, M James-Newton, L Hicks, J Pilkington, C Isenberg, D Lachenbruch, P Miller, F CA the JDM Disease Activity Coll TI Extramuscular disease activity is frequent in adult and juvenile idiopathic inflammatory myopathies (IIM) and does not correlate with other myositis activity measures. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 66th Annual Scientific Meeting of the American-College-of-Rheumatology/37th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 24-29, 2002 CL NEW ORLEANS, LA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 NIEHS, NIH, Bethesda, MD USA. US FDA, CDER, Rockville, MD 20857 USA. NIAID, NIH, Bethesda, MD 20892 USA. NIH, Ctr Clin, Bethesda, MD 20892 USA. Inst Child Hlth, London, England. UCL, London, England. NR 0 TC 3 Z9 3 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD SEP PY 2002 VL 46 IS 9 SU S BP S612 EP S613 PG 2 WC Rheumatology SC Rheumatology GA 600ZN UT WOS:000178421801681 ER PT J AU Rider, LG Schiffenbauer, AS Zito, M Lim, KL Ahmed, A Zemel, LS Rennebohm, RM Passo, MH Hicks, JE Lachenbruch, PA Heyes, MP Miller, FW AF Rider, LG Schiffenbauer, AS Zito, M Lim, KL Ahmed, A Zemel, LS Rennebohm, RM Passo, MH Hicks, JE Lachenbruch, PA Heyes, MP Miller, FW TI Neopterin and quinolinic acid are surrogate measures of disease activity in the juvenile idiopathic inflammatory myopathies. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 66th Annual Scientific Meeting of the American-College-of-Rheumatology/37th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 24-29, 2002 CL NEW ORLEANS, LOUISIANA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 NIEHS, NIH, Bethesda, MD USA. NIMH, NIH, Bethesda, MD 20892 USA. Univ Glasgow, Glasgow Royal Infirm, Glasgow G31 2ER, Lanark, Scotland. Specialty Labs, Santa Monica, CA USA. Connecticut Childrens Med Ctr, Hartford, CT USA. Childrens Hosp, Columbus, OH 43205 USA. Childrens Hosp, Cincinnati, OH 45229 USA. NIH, Dept Rehabil Med, Bethesda, MD 20892 USA. US FDA, CBER, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2002 VL 46 IS 9 SU S BP S305 EP S305 PG 1 WC Rheumatology SC Rheumatology GA 600ZN UT WOS:000178421800799 ER PT J AU Sieber, WK Petersen, MR Stayner, LT Malkin, R Mendell, MJ Wallingford, KM Wilcox, TG Crandall, MS Reed, L AF Sieber, WK Petersen, MR Stayner, LT Malkin, R Mendell, MJ Wallingford, KM Wilcox, TG Crandall, MS Reed, L TI HVAC characteristics and occupant health SO ASHRAE JOURNAL LA English DT Article C1 NIOSH, Cincinnati, OH 45226 USA. US FDA, Washington, DC 20204 USA. MS Crandall Grp, Cincinnati, OH USA. RP Sieber, WK (reprint author), NIOSH, Cincinnati, OH 45226 USA. NR 3 TC 0 Z9 0 U1 1 U2 3 PU AMER SOC HEATING REFRIGERATING AIR-CONDITIONING ENG, INC, PI ATLANTA PA 1791 TULLIE CIRCLE NE, ATLANTA, GA 30329 USA SN 0001-2491 J9 ASHRAE J JI ASHRAE J. PD SEP PY 2002 VL 44 IS 9 BP 49 EP + PG 4 WC Thermodynamics; Construction & Building Technology; Engineering, Mechanical SC Thermodynamics; Construction & Building Technology; Engineering GA 592DL UT WOS:000177921400012 ER PT J AU Sierra-Honigmann, AM Krause, PR AF Sierra-Honigmann, AM Krause, PR TI Live oral poliovirus vaccines and simian cytomegalovirus SO BIOLOGICALS LA English DT Article ID DNA AB Live oral poliovirus vaccines (OPV) are often produced in primary Cercopithecus monkey kidney (CMK) cells. The kidneys of these monkeys are often latently infected with simian cytomegalovirus (SCMV), and CMK cultures are frequently contaminated with SCMV We tested human, monkey and rabbit tissue culture systems, and found that MRC-5 cells are most sensitive for detection of SCMV To address the question of whether OPV could be contaminated with infectious SCMV, we inoculated MRC-5 cells with neutralized OPV manufactured in the United States be tween 1972 and 1998. Infectious SCMV was not found in any of the vaccine lots tested. We also used the polymerase chain reaction (PCR) to search for SCMV DNA in live oral poliovirus vaccines; SCMV DNA sequences were found in several of the vaccine lots manufactured prior to 1992. Published by Elsevier Science Ltd on behalf of The International Association for Biologicals. C1 US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Krause, PR (reprint author), US FDA, Ctr Biol Evaluat & Res, Bldg 29A,Rm 1C16,29 Lincoln Dr, Bethesda, MD 20892 USA. OI Krause, Philip/0000-0002-1045-7536 NR 8 TC 2 Z9 2 U1 0 U2 0 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1045-1056 J9 BIOLOGICALS JI Biologicals PD SEP PY 2002 VL 30 IS 3 BP 167 EP 174 DI 10.1006/biol.2002.0325 PG 8 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA 598LD UT WOS:000178276600001 PM 12217341 ER PT J AU Hagedorn, M Lance, SL Fonseca, DM Kleinhans, FW Artimov, D Fleischer, R Hoque, ATMS Hamilton, MB Pukazhenthi, BS AF Hagedorn, M Lance, SL Fonseca, DM Kleinhans, FW Artimov, D Fleischer, R Hoque, ATMS Hamilton, MB Pukazhenthi, BS TI Altering fish embryos with aquaporin-3: An essential step toward successful cryopreservation SO BIOLOGY OF REPRODUCTION LA English DT Article DE embryo ID BRACHYDANIO-RERIO EMBRYOS; WATER CHANNEL PROTEINS; PERMEABILITY BARRIER; OSMOMETRIC BEHAVIOR; ZEBRAFISH EMBRYOS; XENOPUS OOCYTES; EXPRESSION; GLYCEROL; FAMILY; CELLS AB Fish populations are globally threatened by over-harvesting and habitat degradation. The ability to bank fish embryos by cryopreservation could be crucial for preserving species diversity, for aquaculture (allowing circannual fish farming), and for managing fish models used in human biomedical research. However, no nonmammalian embryo has ever been successfully cryopreserved. For fish, low membrane permeability prevents cryoprotectants from entering the yolk to prevent cryodamage. Here, we present evidence of a membrane mechanism hindering cryopreservation of fish and propose a novel solution to this obstacle. Zebrafish (Danio rerio) embryos have rectifying membranes that allow water to leave but not to reenter readily. This feature may be an evolutionary trait that allows freshwater embryos to grow in hypo-osmotic environments without osmoregulatory organs. However, this trait may also prevent successful fish embryo cryopreservation because both water and cryoprotectants must move into and out of cells. As a solution, we injected zebrafish embryos with mRNA for the aquaporin-3 water channel protein and demonstrated increased membrane permeability to water and to a cryoprotectant. Modeling indicates that sufficient cryoprotectant enters aquaporin-3-expressing zebrafish embryos to allow cryopreservation. C1 Smithsonian Inst, Natl Zool Pk, Dept Reprod Sci, Washington, DC 20008 USA. Smithsonian Inst, Conservat & Res Ctr, Washington, DC 20008 USA. Walter Reed Army Inst Res, Dept Entomol, Silver Spring, MD 20910 USA. Indiana Univ Purdue Univ, Dept Phys, Indianapolis, IN 46202 USA. Johns Hopkins Univ, Sch Med, Dept Radiol, Baltimore, MD 21205 USA. Smithsonian Inst, Natl Zool Pk, Dept Zool Res, Washington, DC 20008 USA. Smithsonian Inst, Natl Zool Pk, Mol Genet Lab, Washington, DC 20008 USA. US FDA, Ctr Biol Evaluat & Res, Lab Plasma Derivat, Div Hematol, Bethesda, MD 20892 USA. Georgetown Univ, Dept Biol, Washington, DC 20057 USA. RP Hagedorn, M (reprint author), Smithsonian Inst, Natl Zool Pk, Dept Reprod Sci, 3001 Connecticut Ave NW, Washington, DC 20008 USA. EM hagedornm@nzp.si.edu RI Lance, Stacey/K-9203-2013; OI Lance, Stacey/0000-0003-2686-1733; Fonseca, Dina/0000-0003-4726-7100 FU NCRR NIH HHS [K01 RR00135, R01 RR08769] NR 38 TC 54 Z9 59 U1 2 U2 10 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PD SEP PY 2002 VL 67 IS 3 BP 961 EP 966 DI 10.1095/biolreprod.101.002915 PG 6 WC Reproductive Biology SC Reproductive Biology GA 587WZ UT WOS:000177668200036 PM 12193408 ER PT J AU Adebowale, A Du, JP Liang, ZM Leslie, JL Eddington, ND AF Adebowale, A Du, JP Liang, ZM Leslie, JL Eddington, ND TI The bioavailability and pharmacokinetics of glucosamine hydrochloride and low molecular weight chondroitin sulfate after single and multiple doses to beagle dogs SO BIOPHARMACEUTICS & DRUG DISPOSITION LA English DT Article DE glucosamine; chondroitin sulfate; bioavailability; disaccharides ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; PERFORMANCE LIQUID-CHROMATOGRAPHY; AGAROSE-GEL ELECTROPHORESIS; DISACCHARIDE ANALYSIS; MANGANESE ASCORBATE; KNEE OSTEOARTHRITIS; PLASMA; EFFICACY; SODIUM AB Objective-The purpose of this study was to determine the oral bioavailability and pharmacokinetics of a glucosamine (GL) and the disaccharides of chondroitin sulfate (CS) after single and multiple-dosing of a GL/CS combination (Cosamin(R)*, Cosequin(R)*). Methods-Male beagle dogs (n = 8, 12 kg) received the following treatments: (1) IV GL (500 mg)/CS (400 mg), (2) p.o. GL (1500mg)/CS (1200mg), (3) p.o. GL (2000mg)/CS (1600mg), (4) p.o. GL (1500mg)/CS (1200mg) QD for days 1-7 and p.o. GL (3000mg)/CS (2400mg) from days 8 to 14. Blood samples were collected over 24h and glucosamine and the disaccharides of chondroitin sulfate were determined. Pharmacokinetic analysis was performed on glucosamine and total chondroitin sulfate disaccharides and parameters were compared across treatments using ANOVA with post hoc analysis. Result-After the IV administration, glucosamine declined rapidly in a bi-exponential fashion with a mean (+/-S.D.) elimination t(1/2) of 0.52 (0.25) h. GL absorption was relatively fast (C-max = 8.95 mug/ml, and T-max 1.5 h after 1500 mg dose) and the mean bioavailability of glucosamine after single dosing was approximately 12%. The extent of absorption of chondroitin sulfate as indicated by the mean C-max (21.5 mug/ml) and mean AUC (187 mug/ml h) of total disaccharides after dosing (1600 mg) provides evidence that chondroitin sulfate is absorbed orally. The bioavailability of CS ranged from 4.8 to 5.0% after single dosing and 200-278% upon multiple dosing. Conclusion-The results of this study show that both glucosamine and chondroitin sulfate (measured as total disaccharides) are bioavailable after oral dosing. in addition, the low molecular weight chondroitin sulfate used in this study displays significant accumulation upon multiple dosing. Copyright (C) 2002 John Wiley Sons, Ltd. C1 Univ Maryland, Sch Pharm, Dept Pharmaceut Sci, Pharmacokinet Biopharmaceut Lab, Baltimore, MD 21201 USA. US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. Eli Lilly & Co, Indianapolis, IN 46285 USA. RP Eddington, ND (reprint author), Univ Maryland, Sch Pharm, Dept Pharmaceut Sci, Pharmacokinet Biopharmaceut Lab, 100 Penn St,AHB 540C, Baltimore, MD 21201 USA. NR 25 TC 80 Z9 85 U1 3 U2 21 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0142-2782 J9 BIOPHARM DRUG DISPOS JI Biopharm. Drug Dispos. PD SEP PY 2002 VL 23 IS 6 BP 217 EP 225 DI 10.1002/bdd.315 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 595YB UT WOS:000178134900001 PM 12214321 ER PT J AU Yoon, SO Hirata, RDC da Silva, ACR Nguyen, NY Hirata, MH AF Yoon, SO Hirata, RDC da Silva, ACR Nguyen, NY Hirata, MH TI Cloning and expression of soluble recombinant protein comprising the extracellular domain of the human type I interferon receptor 2c subunit (IFNAR-2c) in E-coli SO BIOTECHNOLOGY LETTERS LA English DT Article DE chaperones; recombinant soluble protein; type I interferon receptor 2c subunit ID ALPHA-BETA RECEPTOR; ESCHERICHIA-COLI; CHAPERONES; PURIFICATION; GROEL; FOLD; FORM AB An optimized procedure was developed for production of the extracellular domain encoding amino acids 1-243 of the human type I interferon receptor 2c subunit (IFNAR-2c) as a fusion protein with glutathione S-transferase (GST-IFNAR2cEC) in E. coli to obtain active, soluble protein. Induction of protein expression at 37 degreesC resulted in a formation of inclusion body. Co-expression with bacterial chaperones, GroEL and GroES, failed to support the folding of GST-IFNAR2cEc under IPTG induction at 37 degreesC. Expression induced at 25 degreesC decreased the inclusion body formation up to 62% and cell disruption by a French press provided higher recovery of the recombinant protein than cell disruption by sonication. C1 Univ Sao Paulo, Dept Clin & Toxicol Anal, Fac Pharmaceut Sci, BR-05508900 Sao Paulo, Brazil. Univ Sao Paulo, Dept Biochem, Inst Chem, BR-05508900 Sao Paulo, Brazil. US FDA, Ctr Biol Evaluat & Res, Facil Biotechnol Resources, Bethesda, MD USA. RP Hirata, MH (reprint author), Univ Sao Paulo, Dept Clin & Toxicol Anal, Fac Pharmaceut Sci, BR-05508900 Sao Paulo, Brazil. RI Hirata, Rosario/A-7284-2011; Hirata, Mario/C-9718-2013 NR 14 TC 4 Z9 5 U1 0 U2 2 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0141-5492 J9 BIOTECHNOL LETT JI Biotechnol. Lett. PD SEP PY 2002 VL 24 IS 17 BP 1443 EP 1448 DI 10.1023/A:1019879305232 PG 6 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 586GL UT WOS:000177576200012 ER PT J AU Nathwani, AC Davidoff, AM Hanawa, H Hu, YN Hoffer, FA Nikanorov, A Slaughter, C Ng, CYC Zhou, JF Lozier, JN Mandrell, TD Vanin, EF Nienhuis, AW AF Nathwani, AC Davidoff, AM Hanawa, H Hu, YN Hoffer, FA Nikanorov, A Slaughter, C Ng, CYC Zhou, JF Lozier, JN Mandrell, TD Vanin, EF Nienhuis, AW TI Sustained high-level expression of human factor IX (hFIX) after liver-targeted delivery of recombinant adeno-associated virus encoding the hFIX gene in rhesus macaques SO BLOOD LA English DT Article ID COAGULATION-FACTOR-IX; CANINE HEMOPHILIA-B; T-CELL-ACTIVATION; NONHUMAN-PRIMATES; IMMUNE-RESPONSES; VIRAL VECTORS; IN-VIVO; CYSTIC-FIBROSIS; CLINICAL-TRIAL; NULL MUTATION AB The feasibility, safety, and efficacy of liver-directed gene transfer was evaluated in 5 male macaques (aged 2.5 to 6.5 years) by using a recombinant adeno-associated viral (rAAV) vector (rAAV-2 CAGG-hFIX) that had previously mediated persistent therapeutic expression of human factor IX (hFIX; 6%- 10% of physiologic levels) in murine models. A dose of 4 x 10(12) vector genomes (vgs)/kg of body weight was administered through the hepatic artery or portal vein. Persistence of the rAAV vgs as circular monomers and dimers and high-molecular-weight concatamers was documented in liver tissue by Southern blot analysis for periods of up to 1 year. Vector particles were present in plasma, urine, or saliva for several days after Infusion (as shown by polymerase chain reaction analysis), and the vgs were detected in spleen tissue at low copy numbers. An enzyme-linked immunosorption assay capable of detecting between 1% and 25% of normal levels of hFIX in rhesus plasma was developed by using hyperimmune serum from a rhesus monkey that had received an adenoviral vector encoding hFIX. Two macaques having 3 and 40 rAAV genome equivalents/cell, respectively, in liver tissue had 4% and 8% of normal physiologic plasma levels of hFIX, respectively. A level of hFIX that was 3% of normal levels was transiently detected in one other macaque, which had a genome copy number of 25 before abrogation by a neutralizing antibody (inhibitor) to hFIX. This nonhuman-primate model will be useful in further evaluation and development of rAAV vectors for gene therapy of hemophilia B. (C) 2002 by The American Society of Hematology. C1 St Jude Childrens Res Hosp, Dept Surg, Div Exptl Hematol Diagnost Imagin, Memphis, TN 38105 USA. St Jude Childrens Res Hosp, Hartwell Ctr Bioinformat & Biotechnol, Memphis, TN 38105 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. Univ Tennessee, Ctr Hlth Sci, Dept Comparat Med, Memphis, TN 38163 USA. UCL, Dept Haematol, London, England. Natl Blood Author, Watford, England. RP Nienhuis, AW (reprint author), St Jude Childrens Res Hosp, Dept Surg, Div Exptl Hematol Diagnost Imagin, 332 N Lauderdale St, Memphis, TN 38105 USA. EM arthur.nienhuis@stjude.org NR 44 TC 115 Z9 117 U1 0 U2 5 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD SEP 1 PY 2002 VL 100 IS 5 BP 1662 EP 1669 DI 10.1182/blood-2002-02-0589 PG 8 WC Hematology SC Hematology GA 587WU UT WOS:000177667700025 PM 12176886 ER PT J AU Yao, L Pike, SE Pittaluga, S Cherney, B Gupta, G Jaffe, ES Tosato, G AF Yao, L Pike, SE Pittaluga, S Cherney, B Gupta, G Jaffe, ES Tosato, G TI Anti-tumor activities of the angiogenesis inhibitors interferon-inducible protein-10 and the calreticulin fragment vasostatin SO CANCER IMMUNOLOGY IMMUNOTHERAPY LA English DT Article DE angiogenesis; calreticulin; chemokine; endothelium; IP-10 ID X-C CHEMOKINE; IN-VIVO; GROWTH-FACTORS; ENDOGENOUS INHIBITOR; ENDOTHELIAL-CELLS; INTERLEUKIN-12; CANCER; REGRESSION; RECEPTOR; IP-10 AB Tumor growth depends upon an adequate supply of oxygen and nutrients achieved through angiogenesis and maintenance of an intact tumor vasculature. Therapy with individual agents that target new vessel formation or existing vessels has suppressed experimental tumor growth, but rarely resulted in the eradication of tumors. We therefore tested the combined anti-tumor activity of vasostatin and interferon-inducible protein-10 (IP-10), agents that differently target the tumor vasculature. Vasostatin, a selective and direct inhibitor of endothelial cell proliferation, significantly reduced Burkitt tumor growth and tumor vessel density. IP-10, an "angiotoxic" chemokine, caused vascular damage and focal necrosis in Burkitt tumors. When combined, vasostatin plus IP-10 reduced tumor growth more effectively than each agent alone, but complete tumor regression was not observed. Microscopically, these tumors displayed focal necrosis and reduction in vessel density. Combination therapy with the inhibitors of angiogenesis vasostatin and IP-10 is effective in reducing the rate of tumor growth but fails to induce tumor regression, suggesting that curative treatment may require supplemental drugs targeting directly the tumor cells. C1 NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA. NCI, Hematopathol Sect, Pathol Lab, NIH, Bethesda, MD 20892 USA. Ctr Biol Evaluat & Res, Rockville, MD USA. RP Yao, L (reprint author), NCI, Expt Transplantat & Immunol Branch, NIH, Bldg 10,Room 12N226 MSC 1907,10 Ctr Dr, Bethesda, MD 20892 USA. NR 57 TC 32 Z9 36 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0340-7004 J9 CANCER IMMUNOL IMMUN JI Cancer Immunol. Immunother. PD SEP PY 2002 VL 51 IS 7 BP 358 EP 366 DI 10.1007/s00262-002-0294-2 PG 9 WC Oncology; Immunology SC Oncology; Immunology GA 591GP UT WOS:000177871600002 PM 12192535 ER PT J AU Rubinstein, DB Stortchevoi, A Boosalis, M Ashfaq, R Guillaume, T AF Rubinstein, DB Stortchevoi, A Boosalis, M Ashfaq, R Guillaume, T TI Overexpression of DNA-binding protein B gene product in breast cancer as detected by in vitro-generated combinatorial human immunoglobulin libraries SO CANCER RESEARCH LA English DT Article ID PHAGE ANTIBODY LIBRARY; SINGLE-CHAIN FV; HUMAN MONOCLONAL-ANTIBODIES; MOBILITY-GROUP PROTEINS; TUMOR-ANTIGENS; CELL-LINES; SELECTION; DISPLAY; TISSUE; EXPRESSION AB Molecules differentially expressed or overexpressed by malignant cells can serve in detecting and tracking of tumor. Additionally, they potentially can be applied in histologic-specific antitumor therapy. Few breast cancer-associated candidate molecules have been identified. Here we describe the use of combinatorial immunoglobulin [antigen-binding fragment of immunoglobulin molecule (Fab) fragment] phage libraries generated from patients with breast carcinoma to identify, cancer-associated gene expression. The libraries were enriched for tumor-binding Fab by 3 logs and yielded a group of antibodies against DNA-binding protein B (DbpB), a 35-kDa thrombin-inducible nuclear factor and member of the Y-box family of proteins, which are known to act both negatively in selective gene suppression and positively as promoters of gene transcription. Sequencing of the anti-DbpB showed a degree of heterogeneity, and bp substitutions suggesting that the Fabs selected from the combinatorial library represented a varied anti-DbpB immune response and did not simply arise from in vitro amplification by PCR of a single or limited numbers of immunoglobulin genes. Sequencing of the DbpB molecule expressed in malignant breast cancer showed no evidence of tumor-specific mutations. Evaluation of levels of DbpB gene product expression however showed the molecule to be constitutively expressed in normal nonmalignant breast tissues but to have consistently differentially higher expression in breast cancer. Immunohistological staining revealed DbpB to be present both intracellularly and on the cell surface, which suggests it may be a means whereby malignant cells repair and replicate DNA in a selectively advantageous manner as compared with nonmalignant cells. DbpB expression in breast cancer may, advance the basic understanding of the role of Y-box binding proteins as regulatory agents, and in defining malignant cell phenotypes. In addition, DbpB and the antibodies generated against it may have direct application in tumor detection and in molecule-targeted immunotherapy. C1 Boston Univ, Sch Med, Hematol Oncol Sect, Boston, MA 02118 USA. Boston Univ, Sch Med, Ctr Canc Res, Boston, MA 02118 USA. Univ Texas, SW Med Ctr, Div Cytopathol, Dept Surg Pathol, Dallas, TX USA. Univ Catholique Louvain, Expt Oncol Lab, B-1200 Brussels, Belgium. RP Rubinstein, DB (reprint author), US FDA, Ctr Biol Evaluat & Res, 1401 Rockville Pike, Rockville, MD 20857 USA. NR 54 TC 17 Z9 18 U1 1 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 SEP 1 PY 2002 VL 62 IS 17 BP 4985 EP 4991 PG 7 WC Oncology SC Oncology GA 591TW UT WOS:000177897200023 PM 12208750 ER PT J AU Von Tungeln, LS Hamilton, LP Dobrovolsky, VN Bishop, ME Shaddock, JG Heflich, RH Beland, FA AF Von Tungeln, LS Hamilton, LP Dobrovolsky, VN Bishop, ME Shaddock, JG Heflich, RH Beland, FA TI Frequency of Tk and Hprt lymphocyte mutants and bone marrow micronuclei in B6C3F(1)/Tk(+/-) mice treated neonatally with zidovudine and lamivudine SO CARCINOGENESIS LA English DT Article ID IMMUNODEFICIENCY-VIRUS INFECTION; MATERNAL-INFANT TRANSMISSION; DNA-POLYMERASE-GAMMA; REVERSE-TRANSCRIPTASE; 3'-AZIDO-3'-DEOXYTHYMIDINE; CELLS; 3'-AZIDO-2',3'-DIDEOXYTHYMIDINE; PHOSPHORYLATION; HETEROZYGOSITY; GENOTOXICITY AB Mother-to-child transmission of the human immunodeficiency virus is substantially reduced by prenatal and postnatal treatment with anti-retroviral nucleoside analogues; however, the long-term consequences of these drug interventions are not known. The nucleoside analogue zidovudine (3'-azido-2',3'-dideoxythymidine; AZT) is carcinogenic in mice when administered transplacentally or neonatally, and this may be due to a genotoxic mechanism. Since single-drug treatment with AZT is being superseded by multidrug combinations, we have investigated the induction of mutations and micronuclei in mice treated neonatally with AZT, lamivudine (3'-thia-2',3'-dideoxycytidine; 3TC), or a combination of the two drugs. B6C3F(1)/Tk +/- mice were treated daily from days 1-8 of age with 200 mg AZT/kg/day, 200 mg 3TC/kg/day, or a mixture of 200 mg AZT + 200 mg 3TC/kg/day (AZT/3TC). One and 2 days after the last dose, bone marrow was collected to assess the induction of micronuclei in polychromatic erythrocytes; 3 weeks following treatment, the induction of mutants was determined in the hypoxanthine-guanine phosphoribosyltransferase (Hprt) and thymidine kinase (Tk) genes of spleen lymphocytes. AZT and AZT/3TC, but not 3TC, caused a significant increase in micronuclei, with the response being greatest one day after the last dose. None of the drugs induced mutations in the Hprt gene, while AZT and AZT/3TC, but not 3TC, caused a significant increase in the Tk mutant frequency. The increase in Tk mutants by AZT and AZT/3TC was associated with loss of the wild-type (Tk(+)) allele (loss of heterozygosity). These data suggest that AZT, but not 3TC, is genotoxic in neonatal mice, and that 3TC does not alter significantly the responses observed with AZT alone. C1 Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. RP Beland, FA (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, HFT-110, Jefferson, AR 72079 USA. NR 33 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 SEP PY 2002 VL 23 IS 9 BP 1427 EP 1432 DI 10.1093/carcin/23.9.1427 PG 6 WC Oncology SC Oncology GA 586NT UT WOS:000177590600003 PM 12189183 ER PT J AU Lunning, MA Stetler-Stevenson, M Silberstein, PT Zenger, V Marti, GE AF Lunning, MA Stetler-Stevenson, M Silberstein, PT Zenger, V Marti, GE TI Spontaneous (pathological) splenic rupture in a blastic variant of mantle cell lymphoma: A case report and literature review SO CLINICAL LYMPHOMA LA English DT Article DE blastic transformation; chronic lymphocytic leukemia; splenomegaly; splenic infarct; cyclin D1 ID ACUTE LYMPHOBLASTIC-LEUKEMIA; CHRONIC LYMPHOCYTIC-LEUKEMIA; INITIAL MANIFESTATION; SPLEEN; PHASE AB Spontaneous (pathological) splenic rupture (SPSR) in hematological malignancies is rare. This report describes a 71-year-old male diagnosed with mantle cell lymphoma-blastic variant (MCL-BV) who experienced an SPSR a few days before the initial diagnosis. The patient underwent a splenectomy and recovered without incident. Partial remission was seen following several cycles of CHOP (cyclophosphamide/doxorubicin/vincristine/prednisone). However, relapse was rapid, with leukemic meningitis occurring several months later. It was successfully treated by intrathecal methotrexate and cranial spinal radiation. A progressive lymphocytosis developed, which responded to rituximab. Lymphadenopathy and skin involvement ensued, followed by pneumonia and death. The literature on SPSR in patients with MCL-BV and other lymphoproliferative disorders showed similar clinical and postoperative findings. Clinical presentation included Kehr's sign and acute abdominal pain. Postoperative findings included blood in the peritoneal cavity, multiple splenic hematomas, splenic infarcts, and splenic necrosis. Most strikingly, the majority of the patients reviewed appeared to have undergone some type of blastic transformation. One or any combination of these findings that has been noted above in addition to a bleeding diathesis could be the foundation to SPSR. We recommend consideration of splenic rupture in patients with a lymphoproliferative disorder coupled with rapid progression of marked or massive splenomegaly. C1 US FDA, CBER,Flow & Image Cytometry Sect, Lab Stem Cell Biol, Div Cell & Gene Therapies,NIH, Bethesda, MD 20892 USA. Mercy Canc Ctr, Mason City, IA USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. RP Marti, GE (reprint author), US FDA, CBER,Flow & Image Cytometry Sect, Lab Stem Cell Biol,, Div Cell & Gene Therapies,NIH, Bldg 29B,Room 2,NN08 8800 Rockville Pike, Bethesda, MD 20892 USA. NR 31 TC 4 Z9 4 U1 1 U2 2 PU CANCER INFORMATION GROUP, LP PI DALLAS PA 3535 WORTH ST, SAMMONS TOWER, STE 4802, DALLAS, TX 75246 USA SN 1526-9655 J9 CLIN LYMPHOMA JI Clin. Lymphoma PD SEP PY 2002 VL 3 IS 2 BP 117 EP 120 DI 10.3816/CLM.2002.n.018 PG 4 WC Oncology SC Oncology GA 609RE UT WOS:000178917700008 PM 12435285 ER PT J AU Williams, RL Chen, ML Hauck, WW AF Williams, RL Chen, ML Hauck, WW TI Equivalence approaches SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Editorial Material ID INDIVIDUAL BIOEQUIVALENCE; CONFIDENCE-INTERVALS; TRIALS; BIOAVAILABILITY; CRITERION; ISSUES; TESTS C1 US FDA, Ctr Drug Evaluat & Res, Off Pharmaceut Sci, Rockville, MD 20852 USA. US Pharmacopeia, Rockville, MD USA. Thomas Jefferson Univ, Div Clin Pharmacol, Biostat Sect, Philadelphia, PA 19107 USA. RP Chen, ML (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Pharmaceut Sci, HFD-350,Woodmont Off Complex 2,Room 3005,1451 Roc, Rockville, MD 20852 USA. NR 38 TC 40 Z9 43 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD SEP PY 2002 VL 72 IS 3 BP 229 EP 237 DI 10.1067/mcp.2002.126705 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 597RY UT WOS:000178235600001 PM 12235443 ER PT J AU Gurley, BJ Gardner, SF Hubbard, MA Williams, DK Gentry, WB Cui, Y Ang, CYW AF Gurley, BJ Gardner, SF Hubbard, MA Williams, DK Gentry, WB Cui, Y Ang, CYW TI Cytochrome P450 phenotypic ratios for predicting herb-drug interactions in humans SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID ST-JOHNS-WORT; PERFORMANCE LIQUID-CHROMATOGRAPHY; METABOLIZING-ENZYMES; DIETARY-SUPPLEMENTS; DIALLYL SULFIDE; HUMAN CYP3A; PHARMACOKINETICS; CHLORZOXAZONE; MIDAZOLAM; PRODUCTS AB Objectives: Phytochemical-mediated modulation of cytochrome P450 (CYP) activity may underlie many herb-drug interactions. Single-time point phenotypic metabolic ratios were used to determine whether long-term supplementation of St John's wort, garlic oil, Panax ginseng, and Ginkgo biloba affected CYP1A2, CYP2D6, CYP2E1, or CYP3A4 activity. Methods: Twelve healthy volunteers (6 females) were randomly assigned to receive either St John's wort, garlic oil, P ginseng, or G biloba for 28 days. For each subject, a 30-day washout period was interposed between each supplementation phase. Probe-drug cocktails of midazolam, caffeine, chlorzoxazone, and debrisoquin (INN, debrisoquine) were administered before supplementation (baseline) and at the end of supplementation. Presupplementation and postsupplementation phenotypic trait measurements were determined for CYP3A4, CYP1A2, CYP2E1, and CYP2D6 with the use of 1-hydroxymidazolam/midazolam serum ratios (1-hour sample), paraxanthine/caffeine serum ratios (6-hour sample), 6-hydroxychlorzoxazone/chlorzoxazone serum ratios (2-hour sample), and debrisoquin urinary recovery ratios (8-hour collection), respectively. Results: Comparisons of presupplementation and postsupplementation ratios indicated that St John's wort significantly induced the activity of CYP2E1 and CYP3A4 (P < .0001). Among female subjects, St John's wort produced significantly greater increases in CYP3A4 phenotypic ratios that appeared to be unrelated to body mass index. This finding is suggestive of a sexual dimorphism in CYP3A4 inducibility. Garlic oil reduced CYP2E1 activity by 39% (P = .030), whereas no significant effect on CYP activity was observed for P ginseng and G biloba. Conclusions: Single-time point phenotypic metabolic ratios may provide a practical means of predicting CYP-mediated herb-drug interactions in humans. C1 Univ Arkansas Med Sci, Coll Pharm, Dept Pharmaceut Sci, Little Rock, AR 72205 USA. Univ Arkansas Med Sci, Coll Pharm, Dept Pharm Practice, Little Rock, AR 72205 USA. Univ Arkansas Med Sci, Coll Med, Dept Biometry, Little Rock, AR 72205 USA. Univ Arkansas Med Sci, Coll Med, Dept Anesthesiol, Little Rock, AR 72205 USA. Natl Ctr Toxicol Res, Div Chem, Jefferson, AR 72079 USA. RP Gurley, BJ (reprint author), Univ Arkansas Med Sci, Coll Pharm, Dept Pharmaceut Sci, Little Rock, AR 72205 USA. NR 65 TC 215 Z9 226 U1 5 U2 17 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 2002 VL 72 IS 3 BP 276 EP 287 DI 10.1067/mcp.2002.126913 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 597RY UT WOS:000178235600006 PM 12235448 ER PT J AU Lazarus, E AF Lazarus, E TI Adoptive immunotherapy, the Food and Drug Administration and you: a regulatory approach to donor lymphocytes SO CYTOTHERAPY LA English DT Article C1 US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. RP Lazarus, E (reprint author), US FDA, Ctr Biol Evaluat & Res, 1401 Rockville Pike, Rockville, MD 20852 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS AS PI OSLO PA CORT ADELERSGT 17, PO BOX 2562, SOLLI, 0202 OSLO, NORWAY SN 1465-3249 J9 CYTOTHERAPY JI Cytotherapy PD SEP 1 PY 2002 VL 4 IS 5 BP 449 EP 449 DI 10.1080/146532402320776152 PG 1 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology; Hematology; Medicine, Research & Experimental SC Cell Biology; Biotechnology & Applied Microbiology; Hematology; Research & Experimental Medicine GA 612LQ UT WOS:000179077500018 PM 12473222 ER PT J AU Keane-Moore, M AF Keane-Moore, M TI Adoptive immunotherapy - the Food and Drug Administration and you: a regulatory framework for manipulated cellular products SO CYTOTHERAPY LA English DT Article C1 US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. RP Keane-Moore, M (reprint author), US FDA, Ctr Biol Evaluat & Res, 1401 Rockville Pike, Rockville, MD 20852 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS AS PI OSLO PA CORT ADELERSGT 17, PO BOX 2562, SOLLI, 0202 OSLO, NORWAY SN 1465-3249 J9 CYTOTHERAPY JI Cytotherapy PD SEP 1 PY 2002 VL 4 IS 5 BP 451 EP 452 DI 10.1080/146532402320776161 PG 2 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology; Hematology; Medicine, Research & Experimental SC Cell Biology; Biotechnology & Applied Microbiology; Hematology; Research & Experimental Medicine GA 612LQ UT WOS:000179077500019 PM 12473223 ER PT J AU Badano, A Flynn, MJ Kanicki, J AF Badano, A Flynn, MJ Kanicki, J TI Accurate small-spot luminance measurements SO DISPLAYS LA English DT Article DE veiling glare; electronic crosstalk; display contrasts; display measurements ID LIGHT-SCATTERING; DISPLAY DEVICES; CROSSTALK; GLARE AB It has been reported recently that conventional methods for measuring the contrast ratio of display devices using small dark spots can provide inaccurate data if flare in lenses and other optical components is not taken into account. In this paper, we describe a method for reliable measurements of small-spot contrast ratios based on a collimated probe specially designed and constructed to minimize the signal contamination to less than 10(-4) of the bright field. We show that this method can be used to measure the luminance of small circular targets to characterize the veiling glare of cathode-ray tubes. We compare ring response functions obtained for monochrome and color monitors and explain the differences between them in terms of the relative weight of the electron back-scattering and optical components of veiling glare. The method is also useful for characterizing crosstalk in large size active-matrix liquid crystal displays, by measuring luminance changes in small square targets due to variations in the background intensity. Our results suggest that even for medium size arrays, a difference of 1% can be found in the luminance of the small target due to changes in the background luminance. (C) 2002 Elsevier Science B.V. All rights reserved. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. Henry Ford Hlth Syst, Dept Diagnost Radiol, Detroit, MI 48202 USA. Univ Michigan, Dept Nucl Engn & Radiol Sci, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Elect Engn & Comp Sci, Ann Arbor, MI 48109 USA. RP Badano, A (reprint author), US FDA, Ctr Devices & Radiol Hlth, 12720 Twinbrook Pkwy,Mail Stop HFZ-142,Room 167, Rockville, MD 20857 USA. RI Kanicki, Jerzy/E-2753-2016; OI Kanicki, Jerzy/0000-0002-3649-8360; badano, aldo/0000-0003-3712-6670 NR 20 TC 8 Z9 8 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0141-9382 J9 DISPLAYS JI Displays PD SEP PY 2002 VL 23 IS 4 BP 177 EP 182 AR PII S0141-9382(02)00036-7 DI 10.1016/S0141-9382(02)00036-7 PG 6 WC Computer Science, Hardware & Architecture; Engineering, Electrical & Electronic; Instruments & Instrumentation; Optics SC Computer Science; Engineering; Instruments & Instrumentation; Optics GA 595XK UT WOS:000178133700003 ER PT J AU Kodell, RL Kang, SH Chen, JJ AF Kodell, RL Kang, SH Chen, JJ TI Statistical models of health risk due to microbial contamination of foods SO ENVIRONMENTAL AND ECOLOGICAL STATISTICS LA English DT Article DE dose-response; food-borne pathogen; food safety initiative; host susceptibility; low-dose extrapolation; risk assessment ID DOSE-RESPONSE MODELS; PATHOGENS AB Between 6 million and 33 million cases of food-related illness are estimated to occur in the United States each year, with about 5000 episodes resulting in death. Growing concerns about the safety of food prompted the National Food Safety Initiative of 1997, the goal of which is to reduce the incidence of illness caused by food-borne pathogens. A key component of the food safety initiative is the improvement of farm-to-table risk assessment capabilities, including the development of improved dose-response models for estimating risk. When sufficient data are available, allowable contamination levels of specific micro-organisms in food are established using dose-response models to predict risk at very low doses based on experimental data at much higher doses. This necessitates having reliable models for setting allowable exposures to food-borne pathogens. While only limited data on relatively few micro-organisms that occur in food are available at present for dose-response modeling and risk estimation, still none of the two-parameter models proposed so far, including the popular Beta-Poisson (BP) model, appears to be completely satisfactory for describing and fitting all of the present data (Holcomb et al., 1999). The Weibull-Gamma (WG) model is the only three-parameter model that has been proposed to date. In this paper, new competitive three-parameter models are derived, using a formulation that can be parametized to represent statistical variation with respect to the dose of micro-organism received by the host and the host's susceptibility to infection. Parameters of the models are estimated using the maximum likelihood method. Experimental data on several common microbial contaminants in food are used to illustrate the methodology. C1 Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. Ewha Womans Univ, Dept Stat, Seoul 120750, South Korea. RP Kodell, RL (reprint author), Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, 3900 NCTR Rd, Jefferson, AR 72079 USA. NR 14 TC 10 Z9 10 U1 1 U2 5 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1352-8505 J9 ENVIRON ECOL STAT JI Environ. Ecol. Stat. PD SEP PY 2002 VL 9 IS 3 BP 259 EP 271 DI 10.1023/A:1016240210061 PG 13 WC Environmental Sciences; Mathematics, Interdisciplinary Applications; Statistics & Probability SC Environmental Sciences & Ecology; Mathematics GA 572ZM UT WOS:000176804900003 ER PT J AU Gursel, M Verthelyi, D Klinman, DM AF Gursel, M Verthelyi, D Klinman, DM TI CpG oligodeoxynucleotides induce human monocytes to mature into functional dendritic cells SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE CpG oligodeoxynucleotide; monocyte; dendritic cell; maturation; human ID BACTERIAL-DNA; IN-VITRO; IMMUNE ADJUVANTS; INTERFERON-ALPHA; BLOOD MONOCYTES; ACTIVATION; MOTIFS; ANTIGEN; MATURATION; VIVO AB Dendritic cells (DC) excel at presenting antigen to T cells and thus make a key contribution to the induction of primary and secondary immune responses. DC matured in vitro and pulsed with antigen show promise for the immunotherapy of cancer and infectious diseases. Synthetic oligonucleotides (ODN) expressing immunomodulatory "CpG motifs" were found to boost APC function in mice. Current results demonstrate that the recently identified "D" type of CpG ODN stimulate human peripheral blood monocytes to mature into functionally active DC over 2-4 days. The transition from monocyte to DC is characterized by the upregulation of CD83, CD86, CD80, CD40 and the down-regulation of CD14. These DC support antigen-specific humoral and cellular responses in vitro and in vivo. The differentiation of these monocytes is mediated by plasmacytoid DC, which respond to D type ODN by secreting IFN-alpha. Since D type CpG motifs are present in bacterial and viral DNA, the maturation of monocytes into functional DC may reflect a physiologic response that can be harnessed therapeutically through the use of CpG ODN. C1 US FDA, Sect Retroviral Immunol, Ctr Biol Evaluat & Res, 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. RI Gursel, Mayda /H-1812-2012 NR 36 TC 65 Z9 74 U1 0 U2 5 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD SEP PY 2002 VL 32 IS 9 BP 2617 EP 2622 DI 10.1002/1521-4141(200209)32:9<2617::AID-IMMU2617>3.0.CO;2-F PG 6 WC Immunology SC Immunology GA 596BX UT WOS:000178144900025 PM 12207346 ER PT J AU Takamatsu, N Welage, LS Hayashi, Y Yamamoto, R Barnett, JL Shah, VP Lesko, LJ Ramachandran, C Amidon, GL AF Takamatsu, N Welage, LS Hayashi, Y Yamamoto, R Barnett, JL Shah, VP Lesko, LJ Ramachandran, C Amidon, GL TI Variability in cimetidine absorption and plasma double peaks following oral administration in the fasted state in humans: correlation with antral gastric motility (vol 53, pg 37, 2002) SO EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS LA English DT Correction C1 Univ Michigan, Coll Pharm, Ann Arbor, MI 48109 USA. Yamanouchi Pharmaceut Co Ltd, Shizuoka, Japan. Nagoya City Univ, Aichi, Japan. Ono Phamaceut Co Ltd, Osaka, Japan. Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. US FDA, Rockville, MD 20857 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0939-6411 J9 EUR J PHARM BIOPHARM JI Eur. J. Pharm. Biopharm. PD SEP PY 2002 VL 54 IS 2 BP 255 EP 255 AR PII S0939-6411(02)00058-9 DI 10.1016/S0939-6411(02)00058-9 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 599JN UT WOS:000178331000021 ER PT J AU Xin, KQ Ooki, T Mizukami, H Hamajima, K Okudela, K Hashimoto, K Kojima, Y Jounai, N Kumamoto, Y Sasaki, S Klinman, D Ozawa, K Okuda, K AF Xin, KQ Ooki, T Mizukami, H Hamajima, K Okudela, K Hashimoto, K Kojima, Y Jounai, N Kumamoto, Y Sasaki, S Klinman, D Ozawa, K Okuda, K TI Oral administration of recombinant adeno-associated virus elicits human immunodeficiency virus-specific immune responses SO HUMAN GENE THERAPY LA English DT Article ID CYTOTOXIC T-LYMPHOCYTES; ADENOASSOCIATED VIRUS; DENDRITIC CELLS; GENE-TRANSFER; FACTOR-IX; 2-MEDIATED TRANSDUCTION; PROTECTIVE IMMUNITY; HIV VACCINES; IN-VIVO; VECTORS AB Oral vaccines can induce both systemic and mucosal immunity. Mucosal immunity, especially regional cell-mediated immunity, plays an important role in protecting individuals from infectious diseases such as acquired immunodeficiency syndrome. In this study, a recombinant adeno-associated virus vector expressing human immunodeficiency virus type 1 env gene (AAV-HIV) was orally administered to BALB/c mice. Systemic and regional immunity was induced in the mice. Furthermore, the immunization significantly reduced viral load after an intrarectal challenge with a recombinant vaccinia virus expressing HIV env gene. Moreover, we also show that dendritic cells might contribute to the AAV-HIV vector- induced immune responses. C1 Yokohama City Univ, Sch Med, Dept Bacteriol, Kanazawa Ku, Yokohama, Kanagawa 236, Japan. Jichi Med Sch, Div Genet Therapeut, Ctr Mol Med, Minami Kawachi, Tochigi 3290498, Japan. Yokohama City Univ, Sch Med, Dept Pathol, Yokohama, Kanagawa 2360004, Japan. Natl Inst Infect Dis, Leprosy Res Ctr, Dept Bioregulat, Tokyo 1890002, Japan. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Okuda, K (reprint author), Yokohama City Univ, Sch Med, Dept Bacteriol, Kanazawa Ku, 3-9 Fukuura, Yokohama, Kanagawa 236, Japan. RI Mizukami, Hiroaki/D-7674-2013 OI Mizukami, Hiroaki/0000-0001-8954-874X NR 45 TC 47 Z9 51 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD SEP PY 2002 VL 13 IS 13 BP 1571 EP 1581 DI 10.1089/10430340260201662 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 588YX UT WOS:000177730800004 PM 12228012 ER PT J AU Dong, SM Wang, SG Stewart, G Hwang, HM Fu, PP Yu, HT AF Dong, Shiming Wang, Shuguang Stewart, Gernerique Hwang, Huey-Min Fu, Peter P. Yu, Hongtao TI Effect of Organic Solvents and Biologically Relevant Ions on the Light-Induced DNA Cleavage by Pyrene and Its Amino and Hydroxy Derivatives SO INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES LA English DT Article DE PAHs; 1-aminopyrene; 1-hydroxypyrene; pyrene; solvents; photo-induced DNA damages; biologically relevant ions. AB Polycyclic aromatic hydrocarbons (PAHs) are a class of carcinogenic compounds that are both naturally and artificially produced. Many PAHs are pro-carcinogens that require metabolic activation. Recently, it has been shown that PAH can induce DNA single strand cleavage and formation of PAH-DNA covalent adduct upon irradiation with UVA light. The light-induced DNA cleavage parallels phototoxicity in one instance. The DNA photocleavage efficiency depends on the structure of the PAHs. This article reports the effect of both organic solvents and the presence of biologically relevant ions, Na+, Mg2+, Ca2+, K+, Fe3+, Cu2+, Zn+2, Mn2+, and I-, on the light-induced DNA cleavage by pyrene, 1-hydroxypyrene and 1-aminopyrene. Since both 1-hydroxypyrene (0.6 mu M) and 1-aminopyrene (6 mu M) dissolve well in the minimum organic solvents used (2% methanol, dimethylsulfoxide, and dimethylformamide), increasing the amount of the organic solvent resulted in the decrease of the amount of DNA single strand cleavage caused by the combination effect of 1-hydroxy or 1-aminopyrene and UVA light. The result with the less water-soluble pyrene shows that increase of the amount of the organic solvent can increase the amount of DNA single strand DNA photocleavage cause by the combination of pyrene and UVA light. Therefore, there are two effects by the organic solvents: (i) to dissolve PAH and (ii) to quench DNA photocleavage. The presence of Fe3+ and Zn2+ enhances, while the presence of Ca2+ and Mn2+ inhibits the DNA photocleavage caused by 1-aminopyrene and UVA light. Other metal ions have minimal effect. This means that the effect of ions on DNA photocleavage by PAHs is complex. The presence of KI enhances DNA photocleavage. This indicates that the triplet-excited state of 1-aminopyrene is involved in causing DNA cleavage. C1 [Dong, Shiming; Wang, Shuguang; Stewart, Gernerique; Yu, Hongtao] Jackson State Univ, Dept Chem, Jackson, MS 39217 USA. [Hwang, Huey-Min] Jackson State Univ, Dept Biol, Jackson, MS 39217 USA. [Fu, Peter P.] Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Yu, HT (reprint author), Jackson State Univ, Dept Chem, Jackson, MS 39217 USA. EM yu@jsums.edu FU National Institutes of Health [NIH-RCMI G12RR13459-01, NIH-SCORE S06GM08047]; Army Research Office [DAAD 19-01-1-0733] FX This research was supported by the National Institutes of Health through generous grants: NIH-RCMI G12RR13459-01 and NIH-SCORE S06GM08047 and the Army Research Office: DAAD 19-01-1-0733 to JSU. NR 28 TC 8 Z9 8 U1 0 U2 3 PU MDPI AG PI BASEL PA POSTFACH, CH-4005 BASEL, SWITZERLAND SN 1422-0067 J9 INT J MOL SCI JI Int. J. Mol. Sci. PD SEP PY 2002 VL 3 IS 9 BP 937 EP 947 DI 10.3390/i3090937 PG 11 WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary SC Biochemistry & Molecular Biology; Chemistry GA V33IB UT WOS:000209011400003 ER PT J AU Fu, PP Xia, QS Lin, G Chou, MW AF Fu, Peter P. Xia, Qingsu Lin, Ge Chou, Ming W. TI Genotoxic Pyrrolizidine Alkaloids - Mechanisms Leading to DNA Adduct Formation and Tumorigenicity SO INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES LA English DT Article DE Pyrrolizidine alkaloids; tumorigenicity; riddelliine; DNA adducts; genotoxic mechanism AB Plants that contain pyrrolizidine alkaloids are widely distributed in the world. Although pyrrolizidine alkaloids have been shown to be genotoxic and tumorigenic in experimental animals, the mechanisms of actions have not been fully understood. The results of our recent mechanistic studies suggest that pyrrolizidine alkaloids induce tumors via a genotoxic mechanism mediated by 6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine (DHP)-derived DNA adduct formation. This mechanism may be general to most carcinogenic pyrrolizidine alkaloids, including the retronecine-, heliotridine-, and otonecine-type pyrrolizidine alkaloids. It is hypothesized that these DHP-derived DNA adducts are potential biomarkers of pyrrolizidine alkaloid tumorigenicity. The mechanisms that involve the formation of DNA cross-linking and endogenous DNA adducts are also discussed. C1 [Fu, Peter P.; Xia, Qingsu; Chou, Ming W.] Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Lin, Ge] Chinese Univ Hong Kong, Dept Pharmacol, Shatin, Hong Kong, Peoples R China. RP Fu, PP (reprint author), Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM pfu@nctr.fda.gov NR 75 TC 47 Z9 48 U1 1 U2 6 PU MDPI AG PI BASEL PA POSTFACH, CH-4005 BASEL, SWITZERLAND SN 1422-0067 J9 INT J MOL SCI JI Int. J. Mol. Sci. PD SEP PY 2002 VL 3 IS 9 BP 948 EP 964 DI 10.3390/i3090948 PG 17 WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary SC Biochemistry & Molecular Biology; Chemistry GA V33IB UT WOS:000209011400004 ER PT J AU Wu, YS Fang, GC Moody, J Von Tungeln, LS Fu, PP Hwang, HM Yu, HT AF Wu, Yuh-Shen Fang, Guor-Cheng Moody, Joanna Von Tungeln, Linda S. Fu, Peter P. Hwang, Huey-Min Yu, Hongtao TI In Vitro Metabolism of Dibenzo[a,l]pyrene, 2-Chlorodibenzo[a,l]pyrene and 10-Chlorodibenzo[a,l]pyrene - Effects of Chloro Substitution SO INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES LA English DT Article DE Microsomal metabolism; dibenzo[a,l]pyrene; 2-chlorodibenzo[a,l] pyrene; 10-chlorodibenzo[a,l]pyrene AB Stereoselective metabolism of dibenzo[a,l]pyrene (DB[a,l]P), 2-chlorodibenzo[a,l]pyrene (2-Cl-DB[a,l]P) and 10-chlorodibenzo[a,l]pyrene (10-Cl-DB[a,l]P) by rat liver microsomes was studied and effects of the chloro substituent on the metabolism were determined. All three compounds produced trans-8,9-dihydrodiol, trans-11,12-dihydrodiol, and the 7-hydroxyl derivative as major metabolic products and several other phenolic derivatives as minor metabolites. The trans-8,9- and 11,12-dihydrodiols of DB[a,l]P and 2-Cl-DB[a,l]P preferentially adopted a quasidiequatorial conformation, whereas 10-Cl-DB[a,l]P trans-8,9- and 11,12-dihydrodiols preferentially adopted a quasidiaxial conformation. The yields of the trans-11,12-dihydrodiol metabolites are: DB[a,l]P trans-11,12-dihydrodiol > 2-Cl-DB[a,l]P trans-11,12-dihydrodiol >> 10-Cl-DB[a,l]P trans-11,12-dihydrodiol. Circular dichroism (CD) spectral analysis indicates that the trans-8,9-dihydrodiol and trans-11,12-dihydrodiol metabolites from DB[a, l] P, 2-Cl-DB[a,l]P, and 10-Cl-DB[a,l]P are optically active. Furthermore, the major enantiomeric DB[a,l]P trans-11,12-dihydrodiol and 2-Cl-DB[a,l]P trans-11,12-dihydrodiol had R, R absolute configuration. Based on the fact that DB[a,l]P trans-11,12-dihydrodiol is the proximate tumorigenic metabolite of DB[a,l]P, our results suggest that DB[a,l]P exhibits the highest tumorigenic potency followed by 2-Cl-DB[a,l]P, and 10-Cl-DB[a,l]P exhibits the lowest tumorigenicity. C1 [Wu, Yuh-Shen; Fang, Guor-Cheng] Hungkuang Inst Technol, Taichung, Taiwan. [Moody, Joanna; Von Tungeln, Linda S.; Fu, Peter P.] Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Hwang, Huey-Min] Jackson State Univ, Dept Biol, Jackson, MS 39217 USA. [Yu, Hongtao] Jackson State Univ, Dept Chem, Jackson, MS 39217 USA. RP Wu, YS (reprint author), Hungkuang Inst Technol, Taichung, Taiwan. EM ycwu@sunrise.hkc.edu.tw; yu@ccaix.jsums.edu FU Hungkuang Institute of Technology of Humanities and Science Council [HKHSC-89-01]; National Institute of Health [NIH-RCMI G12RR12459] FX This research was partly supported by the Hungkuang Institute of Technology of Humanities and Science Council, through a research contract HKHSC-89-01 and by the National Institute of Health through a generous grant NIH-RCMI G12RR12459. NR 26 TC 2 Z9 2 U1 0 U2 0 PU MDPI AG PI BASEL PA POSTFACH, CH-4005 BASEL, SWITZERLAND SN 1422-0067 J9 INT J MOL SCI JI Int. J. Mol. Sci. PD SEP PY 2002 VL 3 IS 9 BP 1008 EP 1018 DI 10.3390/i30901008 PG 11 WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary SC Biochemistry & Molecular Biology; Chemistry GA V33IB UT WOS:000209011400008 ER PT J AU Yan, J Nichols, J Yang, YC Fu, PP Chou, MW AF Yan, Jian Nichols, Jasyl Yang, Ya-Cheng Fu, Peter P. Chou, Ming W. TI Detection of Riddelliine-Derived DNA Adducts in Blood of Rats Fed Riddelliine SO INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES LA English DT Article DE Pyrrolizidine alkaloids; riddelliine; dehydroretronecine; P-32-postlabeling/HPLC; rat blood DNA adducts AB We have previously shown that riddelliine, a naturally occurring genotoxic pyrrolizidine alkaloid, induces liver tumors in rats and mice through a genotoxic mechanism mediated by the formation of a set of eight 6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine (DHP)-derived DNA adducts. In this study we report the formation of these DHP-derived DNA adducts in blood DNA of rats fed riddelliine. In an adduct formation and removal experiment, male and female F344 rats (8 weeks of age) were administered riddelliine by gavage at a single dose of 10.0 mg/kg body weight in 0.1 M phosphate buffer. At 8, 24, 48, and 168 hrs after dosing, the levels of DHP-derived DNA adduct in blood and liver were determined by P-32-postlabeling/HPLC. Maximum DNA adduct formation occurred at 48 hr after treatment. From 48 to 168 hours, the adduct levels in female rat blood were 4-fold greater than those in male rats. In a dose response experiment, female rats were gavaged 0.1 and 1.0 mg/kg doses of riddelliine for three consecutive days and the DHP-derived DNA adducts in blood DNA were assayed. The levels of the DHP-derived DNA adducts in blood of rats receiving 0.1 and 1.0 mg/kg doses were 12.9 and 51.8 adducts/10(7) nucleotides. These results suggest that: (i) leucocyte DNA can bind with DHP to form a set of DHP-derived DNA adducts generated in liver; (ii) DHP-derived DNA adducts in blood can serve as a potential non-invasive biomarkers for assessing the exposure to riddelliine. C1 [Yan, Jian; Nichols, Jasyl; Fu, Peter P.; Chou, Ming W.] Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. [Yang, Ya-Cheng] Inst Technol, Dept Fooyin, Kaohsiung, Taiwan. RP Chou, MW (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. EM jchen@nctr.fda.gov NR 19 TC 11 Z9 11 U1 0 U2 1 PU MDPI AG PI BASEL PA POSTFACH, CH-4005 BASEL, SWITZERLAND SN 1422-0067 J9 INT J MOL SCI JI Int. J. Mol. Sci. PD SEP PY 2002 VL 3 IS 9 BP 1019 EP 1026 DI 10.3390/i30901019 PG 8 WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary SC Biochemistry & Molecular Biology; Chemistry GA V33IB UT WOS:000209011400009 ER PT J AU Ng, C Bansode, RR Marshall, WE Losso, JN Rao, RM AF Ng, C Bansode, RR Marshall, WE Losso, JN Rao, RM TI Process description and product cost to manufacture sugarcane bagasse-based granular activated carbon SO INTERNATIONAL SUGAR JOURNAL LA English DT Article ID AGRICULTURAL BY-PRODUCTS; CANE BAGASSE; BINDERS; METALS AB Process flow diagrams and manufacturing costs were developed to convert sugarcane bagasse to granular activated carbon. Unit operations in the conversion process consisted of milling, pelletization, pyrolysis/activation, washing with acid and water, and drying/screening/collecting of the final product. Process parameters were calculated for a production facility processing 10,000 kg/day of bagasse and 4,000 kg/day of sugarcane molasses used as a binder. Final product yield for steam activation of the bagasse/binder pellets was 20% or 2,000 kg of activated carbon produced per day. Material losses were incurred during milling (20%), pyrolysis/activation (80%), acid/water washing (15%), and sieving the final product (5%). Based on an annual production cost of $1.94 million and an annual production of 621,000 kg of carbon, steam-activated bagasse carbon would cost $3.12/kg. C1 Louisiana State Univ, Ctr Agr, Dept Food Sci, Baton Rouge, LA 70803 USA. US FDA, Dept Hlth & Human Serv, Lenexa, KS 66285 USA. USDA ARS, So Reg Res Ctr, New Orleans, LA 70179 USA. RP Rao, RM (reprint author), Louisiana State Univ, Ctr Agr, Dept Food Sci, Food Sci Bldg, Baton Rouge, LA 70803 USA. RI Bansode, Rishipal/E-9293-2010 OI Bansode, Rishipal/0000-0001-7826-2711 NR 16 TC 2 Z9 2 U1 0 U2 0 PU INT SUGAR JOURNAL LTD PI KENT PA 80 CALVERLEY, TUNBRIDGE WELLS, KENT TN1 2UN, WALES SN 0020-8841 J9 INT SUGAR J JI Int. Sugar J. PD SEP PY 2002 VL 104 IS 1245 BP 401 EP + PG 6 WC Agronomy; Food Science & Technology SC Agriculture; Food Science & Technology GA 596YU UT WOS:000178194700003 ER PT J AU Clark, SB Turnipseed, SB Nandrea, GJ Madson, MR Hurlbut, JA Sofos, JN AF Clark, SB Turnipseed, SB Nandrea, GJ Madson, MR Hurlbut, JA Sofos, JN TI Confirmation of phenylbutazone residues in bovine kidney by liquid chromatography/mass spectrometry SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; SOLID-PHASE EXTRACTION; MASS-SPECTROMETRY; PLASMA; OXYPHENBUTAZONE; URINE; MILK AB A confirmatory method is described for phenylbutazone (1313) residues in bovine kidney tissue. Ground kidney tissue is diluted with water, and the mixture is made basic with 25% ammonium hydroxide in water; the lipids are extracted with ethyl and petroleum ethers. The ether layer is discarded, and the tissue is acidified with 6N HCl. 1213 residues are extracted with tetrahydrofuran-hexane (1 + 4). The extract is passed through a silica solid-phase extraction column, and the eluate is evaporated to dryness. The residue is dissolved in acidified acetonitrile-water-acetic acid (50 + 49.4 + 0.6). A single quadrupole mass spectrometer coupled to a liquid chromatograph with an electrospray interface is used to confirm the identity of the PB residues in the kidney extract. Negative-ion detection with selected-ion monitoring of 4 ions is used. Sets of control and fortified-control kidney tissues (at 50, 100, and 200 ppb PB) and several kidney tissue field samples were analyzed for method validation. The method was tested further during the course of a survey to determine the incidence of PB residues in bovine kidney samples obtained from slaughterhouses across the country. In addition, the method was tested for use with an ion-trap mass spectrometer coupled to a liquid chromatograph, which allowed confirmation of PB at lower levels (5-10 ppb) in kidney tissue. C1 US FDA, Denver Fed Ctr, Denver, CO 80225 USA. Western Washington Univ, Dept Chem, Bellingham, WA 98225 USA. Colorado State Univ, Dept Anim Sci, Ft Collins, CO 80523 USA. RP Clark, SB (reprint author), US FDA, Denver Fed Ctr, Bldg 20,6th & Kipling, Denver, CO 80225 USA. NR 14 TC 15 Z9 16 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 SEP-OCT PY 2002 VL 85 IS 5 BP 1009 EP 1014 PG 6 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 598KB UT WOS:000178274000002 PM 12374396 ER PT J AU Craven, KE Ferreira, JL Harrison, MA Edmonds, P AF Craven, KE Ferreira, JL Harrison, MA Edmonds, P TI Specific detection of Clostridium botulinum types A, B, E, and F using the polymerase chain reaction SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID NUCLEOTIDE-SEQUENCE; NEUROTOXIN; GENE; PROBE; FOOD; PCR AB Clostridium botulinum organisms generally produce 1 of 4 neurotoxin types (A, B, E, and F) associated with human illness. Neurotoxin type determination is important in identification of the bacterium. A polymerase chain reaction (PCR) method was developed to identify 24 h botulinal cultures as potential types A, 13, E, and F neurotoxin producers as well as other clostridial species which also produce neurotoxins. Components of the PCR and amplification conditions were adjusted for optimal amplification of toxin gene target regions to enable simultaneous testing for types A, 13, E, and F in separate tubes using a single thermal cycler. Each primer set was specific for its corresponding toxin type. A DNA extraction procedure was also included to remove inhibitory substances that may affect amplification. This procedure is rapid, sensitive, and specific for identification of toxigenic C. botulinum. C1 US FDA, SE Reg Lab, Atlanta, GA 30309 USA. Univ Georgia, Dept Food Sci & Technol, Athens, GA 30602 USA. Georgia Inst Technol, Sch Biol, Atlanta, GA 30332 USA. RP Craven, KE (reprint author), US FDA, SE Reg Lab, 60 8th St,NE, Atlanta, GA 30309 USA. NR 16 TC 6 Z9 7 U1 2 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 SEP-OCT PY 2002 VL 85 IS 5 BP 1025 EP 1028 PG 4 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 598KB UT WOS:000178274000005 PM 12374399 ER PT J AU Shieh, YC Baric, RS AF Shieh, YC Baric, RS TI Detection of enteroviruses in shellfish by fluorogenic polymerase chain reaction integrated with 96-well microplate scanning SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID HEPATITIS-A VIRUS; REVERSE TRANSCRIPTION-PCR; ENTERIC VIRUSES; DNA; OYSTERS; HYBRIDIZATION; RECOVERY; SEWAGE AB A one-step procedure was developed to confirm viral targets by using a fluorometric 96-well microplate scanner following polymerase chain reaction (PCR). The fluorogenic PCR, integrated with fluorometric scanning, measured the end point fluorescence of viral PCR amplicon/probe hybrids and permitted the use of nonfluorogenic PCR conditions with addition of a Cy3 fluorophore-labeled linear probe for viruses. This linear probe generated higher ratios of viral signal-to-noise than a comparative beacon probe. Detection efficiency with a Cy3/quencher linear probe was comparable with Southern analysis at the level greater than or equal to0.27 plaque-forming units (PFU) of poliovirus/PCR. For the reaction containing <0.27 PFU, the fluorometric measurements of the first-round PCR viral amplicon were not as sensitive as Southern analysis; however, equivalent sensitivities were achieved with fiuorogenic nested PCR. Concentrates of 11 oyster samples exposed to municipal sewage were tested for enteroviruses; the fluorogenic detection correlated 100% with Southern analysis. This method using fluorometric scanning of viral amplicon is simple; it requires neither continuously monitoring equipment nor redesigning PCR primers; and it accurately detects enteroviruses in oyster sample concentrates in less time than classic spectrophotometry or Southern analysis. C1 US FDA, Gulf Coast Seafood Lab, Dauphin Isl, AL 36528 USA. Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27599 USA. RP Shieh, YC (reprint author), US FDA, Gulf Coast Seafood Lab, POB 158, Dauphin Isl, AL 36528 USA. NR 22 TC 2 Z9 2 U1 0 U2 0 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD SEP-OCT PY 2002 VL 85 IS 5 BP 1045 EP 1051 PG 7 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 598KB UT WOS:000178274000008 PM 12374402 ER PT J AU Sundaresan, PR AF Sundaresan, PR TI Simultaneous determination of vitamin A and beta-carotene in dietary supplements by liquid chromatography SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID FAT-SOLUBLE VITAMINS; REVERSE PHASE HPLC; RETINYL PALMITATE; MULTIVITAMIN TABLETS; SEPARATION; ISOMERS; FOODS; TOCOPHEROLS; ACETATE AB Several liquid chromatography (LC) methods for analysis of vitamin A in foods and feeds have been previously reported but only a few have been applied in non-food matrixes. A validated LC method is needed for determination of vitamin A and beta-carotene in the various matrixes presented by dietary supplements. The performance of a reversed-phase method with methanol-isopropanol gradient elution was evaluated with standard retinyl derivatives and beta-carotene. The reversed-phase method is capable of separating retinol from other derivatives such as retinyl acetate, retinyl palmitate, and beta-carotene. Two types of extraction were used to extract the analytes from the dietary supplements: a hexane-methylene chloride extraction for soft-gel capsules containing beta-carotene, and a direct solvent extraction for dietary supplements in tablet form. The direct solvent extraction consisted of treatment with ethanol and methylene chloride following addition of hot water (55degreesC). Results with the reversed-phase method for vitamin A and beta-carotene in the products examined (n = 8) indicated excellent method performance. The main form of vitamin A or beta-carotene in dietary supplements was the all-trans isomer. The reversed-phase method avoids saponification and is rapid, accurate, precise, and suitable for simultaneous determination of retinyl derivatives and beta-carotene in dietary supplements. C1 US FDA, Ctr Food Safety & Appl Nutr, Div Res & Appl Technol, Off Nutr Prod Labeling & Dietary Supplements, College Pk, MD 20740 USA. RP Sundaresan, PR (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Div Res & Appl Technol, Off Nutr Prod Labeling & Dietary Supplements, College Pk, MD 20740 USA. NR 32 TC 7 Z9 8 U1 0 U2 8 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 2002 VL 85 IS 5 BP 1127 EP 1135 PG 9 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 598KB UT WOS:000178274000019 PM 12374413 ER PT J AU Schenck, FJ Callery, P Gannett, PM Daft, JR Lehotay, SJ AF Schenck, FJ Callery, P Gannett, PM Daft, JR Lehotay, SJ TI Comparison of magnesium sulfate and sodium sulfate for removal of water from pesticide extracts of foods SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID LIQUID-CHROMATOGRAPHY; VEGETABLES; RESIDUES; CLEANUP; FRUITS; AGRICULTURE; PRODUCE AB Water-miscible solvents, such as acetone and acetonitrile, effectively extract both polar and nonpolar pesticide residues from nonfatty foods. The addition of sodium chloride to the resulting acetonitrile-water or acetone-water extract (salting out) results in the separation of the water from the organic solvent. However, the organic solvent layer (pesticide extract) still contains some residual water, which can adversely affect separation procedures that follow, such as solid-phase extraction and/or gas chromatography. Drying agents, such as sodium sulfate or magnesium sulfate, are used to remove the water from the organic extracts. In the present study, we used nuclear magnetic resonance spectroscopy to study the composition of the phases resulting from salting out and to compare the effectiveness of sodium sulfate and magnesium sulfate as drying agents. The study showed that considerable amounts of water remained in the organic phase after phase separation. Sodium sulfate was a relatively ineffective drying agent, removing little or no residual water from the organic solvent. Magnesium sulfate proved to be a much more effective drying agent. C1 US FDA, SE Reg Lab, Atlanta, GA 30309 USA. W Virginia Univ, Dept Basic Pharmaceut Sci, Morgantown, WV 26506 USA. USDA ARS, Wyndmoor, PA 19038 USA. RP Schenck, FJ (reprint author), US FDA, SE Reg Lab, 60 8th St,NE, Atlanta, GA 30309 USA. RI Gannett, Peter/J-3347-2015 OI Gannett, Peter/0000-0002-7859-5468 NR 19 TC 30 Z9 31 U1 1 U2 16 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 2002 VL 85 IS 5 BP 1177 EP 1180 PG 4 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 598KB UT WOS:000178274000024 PM 12374418 ER PT J AU Feldsine, P Abeyta, C Andrews, WH AF Feldsine, P Abeyta, C Andrews, WH TI AOAC INTERNATIONAL Methods Committee guidelines for validation of qualitative and quantitative food microbiological official methods of analysis SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article AB Responding to a need for a guide for conducting Official Method validation studies of microbiological methods, AOAC utilized the experience of three microbiologists who have been active in the field of method validation. In collaboration, a document was prepared which covered the following areas: terms and their definitions associated with the Official Methods program (e.g., reference methods, alternative methods, and ruggedness testing), protocols and validation requirements for qualitative methods versus those for quantitative methods, the concept of the precollaborative study, ruggedness testing, tests for significant differences, performance indicators, and the approval process. After its preparation, this document was reviewed by the members of the Methods Committee on Microbiology and Extraneous Materials and by members of the Official Methods Board. Herein is presented the approved version of that document. C1 BioControl Syst Inc, Bellevue, WA 98005 USA. US FDA, Seafood Prod Res Ctr, Bothell, WA 98021 USA. US FDA, Div Microbiol Studies, College Pk, MD 20740 USA. RP Feldsine, P (reprint author), BioControl Syst Inc, 12822 SE 32nd St, Bellevue, WA 98005 USA. NR 0 TC 87 Z9 95 U1 3 U2 35 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 2002 VL 85 IS 5 BP 1187 EP 1200 PG 14 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 598KB UT WOS:000178274000026 PM 12374420 ER PT J AU Istafanos, P James, L Hunt, J AF Istafanos, P James, L Hunt, J TI Comparison of visual immunoassay and chromogenic culture medium for the presence of Listeria spp. in foods SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID MONOCYTOGENES AB Two rapid screening methods [the TECRA(TM) Listeria Visual Immunoassay (LIS-VIS) kit, an AOAC-approved 48 h visual test, which detects Listeria through colorimetry, and BCM(TM) Listeria isolation and differentiation plating agar] were used to screen U.S. Food and Drug Administration-regulated commodities for the presence of Listeria spp. Seventy-four different food samples were screened for the presence of Listeria spp. by using both protocols. Test results for the TECRA LIS-VIA showed 66 negative samples and 1 false positive, with 4 confirmed as L. monocytogenes and 3 as L. innocua. With the BCM agar, 67 samples were negative, 4 were confirmed as L. monocytogenes, and 3 were confirmed as L. innocua. Both methods showed similar results and were effective screening tools for Listeria spp. in foods. The BCM agar method proved to be a rapid, sensitive, and excellent tool for early screening and differentiation of Listeria spp. present in foods. C1 US FDA, Jamaica, NY 11433 USA. US FDA, Bothell, WA 98021 USA. RP Istafanos, P (reprint author), US FDA, 158-15 Liberty Ave, Jamaica, NY 11433 USA. NR 13 TC 4 Z9 4 U1 0 U2 1 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD SEP-OCT PY 2002 VL 85 IS 5 BP 1201 EP 1203 PG 3 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 598KB UT WOS:000178274000027 PM 12374421 ER PT J AU Wear, KA Garra, BS Pinet, MC Felker, S Mai, J AF Wear, KA Garra, BS Pinet, MC Felker, S Mai, J TI Measurements of ultrasonic backscattered spectral centroid shift from spine in vivo - Methodology & preliminary results. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 24th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 20-24, 2002 CL SAN ANTONIO, TEXAS SP American-Soc-Bone-Mineral-Res C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. Univ Vermont, Dept Radiol, Burlington, ON, Canada. NR 0 TC 3 Z9 3 U1 0 U2 1 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2002 VL 17 SU 1 MA M103 BP S419 EP S419 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 592TK UT WOS:000177952801278 ER PT J AU Wear, KA Laib, A AF Wear, KA Laib, A TI Relationship between ultrasonic backscatter and trabecular thickness in human calcaneus: Theory and experiment. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 24th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 20-24, 2002 CL SAN ANTONIO, TEXAS SP American-Soc-Bone-Mineral-Res C1 US FDA, Rockville, MD 20857 USA. Scanco Med AG, Bassersforf, Switzerland. NR 0 TC 3 Z9 3 U1 0 U2 1 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2002 VL 17 SU 1 MA M102 BP S419 EP S419 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 592TK UT WOS:000177952801277 ER PT J AU Beger, RD Buzatu, DA Wilkes, JG Lay, JO AF Beger, RD Buzatu, DA Wilkes, JG Lay, JO TI Comparative structural connectivity spectra analysis (CoSCoSA) models of steroid binding to the corticosteroid binding globulin SO JOURNAL OF CHEMICAL INFORMATION AND COMPUTER SCIENCES LA English DT Article ID AUTOMATED STRUCTURE EVALUATION; RELATIONSHIP QSDAR MODELS; CHEMICAL-SHIFTS; NEURAL-NETWORK; NMR; PREDICTION; QSAR; SPECTROSCOPY; INDEX; N-15 AB A three-dimensional quantitative spectrometric data-activity relationship (3D-QSDAR) model was developed that is built by combining NMR spectral information with structural information in a 3D-connectivity matrix. The 3D-connectivity matrix is built by displaying all possible carbon-to-carbon connections with their assigned carbon NMR chemical shifts and distances between the carbons. Selected 2D C-13-C-11 COrrelation SpectroscopY (COSY) (through-bond nearest neighbors) and selected theoretical 2D C-13-C-13 distance connectivity spectral slices from the 3D-connectivity matrix to produce a relationship among the spectral patterns for 30 steroids binding to corticosteroid binding globulin., We call this technique a comparative structural connectivity spectra analysis (CoSCoSA) modeling. A CoSCoSA principal component linear regression model based on the combination of C-13-C-13 COSY and (CC)-C-13-C-13 distance spectra principal components (PCs) had an r(2) of 0.96 and a leave-one-out (LOO) cross-validation q(2) of 0.92, A CoSCoSA parallel distributed artificial neural network (PD-ANN) model based on the combination of (CC)-C-13-C-13 COSY and (CC)-C-13-C-13 distance spectra had an r(2) of 0.96,, a leave-three-out q(3)(2) of 0.78, and a leave-ten-out q(10)(2) of 0.73. CoSCoSA modeling attempts to uniquely combine the quantum mechanics information from the NMR chemical shifts with internal molecular atom-to-atom distances into an accurate modeling technique. The CoSCoSA modeling technique has the flexibility and accuracy to outperform the cross validated variance q(2) of previously published quantitative structure-activity relationship QSAR), quantitative spectral data-activity relationship QSDAR), self-organizing map (SOM), and electrotopological state (E-state) models. 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 38 TC 17 Z9 17 U1 0 U2 1 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 2002 VL 42 IS 5 BP 1123 EP 1131 DI 10.1021/ci025511e PG 9 WC Chemistry, Multidisciplinary; Computer Science, Information Systems; Computer Science, Interdisciplinary Applications SC Chemistry; Computer Science GA 597ZX UT WOS:000178251600015 PM 12376999 ER PT J AU Collins, JM Klecker, RW AF Collins, JM Klecker, RW TI Evaluation of highly bound drugs: Interspecies, intersubject, and related comparisons SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article ID PROTEIN-BINDING AB Free (unbound) drug is generally the pharmacologically relevant parameter for drug exposure. Thus, comparisons among species, among individuals, and in other situations such as cell culture or drug metabolism experiments in vitro should be based on free drug. Although the traditional focus has been on the absolute value for free drug, the applications for the data in this study are primarily comparative. Therefore, the authors evaluated direct dialysis of one plasma sample versus another. At equilibrium, the total concentration of valproate in human plasma was 3-fold higher than in rat plasma. The total concentration of monoacetyl dapsone was 10-fold higher in human plasma than in rat plasma and 18-fold higher in human plasma than in dog plasma. These results confirm predictions derived from conventional dialysis of each plasma sample separately versus buffer. These data can be interpreted directly, without interspecies correction factors for binding, especially for the most important cases-drugs that are highly protein-bound. (C) 2002 the American College of Clinical Pharmacology. C1 US FDA, CDER, Lab Clin Pharmacol, Rockville, MD 20857 USA. RP Collins, JM (reprint author), US FDA, CDER, Lab Clin Pharmacol, 5600 Fishers Lane,HFD-902, Rockville, MD 20857 USA. NR 10 TC 9 Z9 9 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD SEP PY 2002 VL 42 IS 9 BP 971 EP 975 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 586HR UT WOS:000177579000003 PM 12211222 ER PT J AU Lathers, CM AF Lathers, CM TI Risk assessment in regulatory policy-making in human and veterinary public health. SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Meeting Abstract C1 US FDA, Ctr Vet Med, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD SEP PY 2002 VL 42 IS 9 MA 2 BP 1051 EP 1051 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 586HR UT WOS:000177579000013 ER PT J AU Lathers, CM Schraeder, PL AF Lathers, CM Schraeder, PL TI Stress factor in sudden unexpected death in epileptic persons (SUDEP). SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Meeting Abstract C1 US FDA, Ctr Vet Med, Rockville, MD 20857 USA. Albert Einstein Med Ctr, Philadelphia, PA 19141 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD SEP PY 2002 VL 42 IS 9 MA 3 BP 1051 EP 1051 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 586HR UT WOS:000177579000014 ER PT J AU Lathers, CM AF Lathers, CM TI Prion diseases. SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Meeting Abstract C1 US FDA, Ctr Vet Med, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD SEP PY 2002 VL 42 IS 9 MA 1 BP 1051 EP 1051 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 586HR UT WOS:000177579000012 ER PT J AU Piazza-Hepp, T Huang, SM Hepp, P AF Piazza-Hepp, T Huang, SM Hepp, P TI Evaluation of drug-grapefruit interaction labeling at the food and drug administration SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Meeting Abstract C1 US FDA, Ctr Drug Evaluat & Res, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD SEP PY 2002 VL 42 IS 9 MA 49 BP 1062 EP 1062 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 586HR UT WOS:000177579000055 ER PT J AU Subramaniam, V Sokol, GH Zenger, VE Anderson, KR Scott, GR Brown, RE Hoffman, RR Cantilena, LR AF Subramaniam, V Sokol, GH Zenger, VE Anderson, KR Scott, GR Brown, RE Hoffman, RR Cantilena, LR TI Survey of compounded drug products by community pharmacies: Findings from a food and drug adminstration (FDA) study SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Meeting Abstract C1 US FDA, Rockville, MD USA. USUHS, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD SEP PY 2002 VL 42 IS 9 MA 66 BP 1065 EP 1065 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 586HR UT WOS:000177579000070 ER PT J AU Kornegay, CJ Vasilakis-Scaramozza, C Jick, H AF Kornegay, CJ Vasilakis-Scaramozza, C Jick, H TI Incident diabetes associated with antipsychotic use in the United Kingdom General Practice Research Database SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID OLANZAPINE TREATMENT; CLOZAPINE TREATMENT; KETOACIDOSIS; MELLITUS; SCHIZOPHRENIA; HYPERGLYCEMIA; RISPERIDONE AB Background: Recent reports suggest an association between antipsychotic use and development or exacerbation of diabetes. This study evaluated the risk of incident diabetes associated with the use of atypical and conventional antipsychotics. Method: This nested case-control study included all patients in the U.K. General Practice Research Database treated with antipsychotic drugs between January 1994 and December 1998. The main outcome measures were the odds ratios of current (within prior 6 months) or recent (7 to 12 months) antipsychotic exposure among those with (N = 424) compared with those without incident diabetes (N = 1522). Results: The adjusted odds ratio for current use of any antipsychotic drug compared with no use in the past year among those with diabetes was 1.7 (95% confidence interval [CI] = 1.3 to 2.3). The adjusted odds ratio for current use of atypical and conventional antipsychotic drugs compared with no use in the past year among those with diabetes was 4.7 (95% Cl = 1.5 to 14,9) and 1.7 (95% CI = 1.2 to 2.3), respectively. The adjusted odds ratio for recent use of conventional antipsychotic drugs compared with no use in the past year among those with diabetes was 1.0 (95% Cl = 0.6 to 1.6). The odds ratio for recent atypical antipsychotic drug use could not be calculated because no study subjects had this exposure. Conclusion: This study showed an increased risk of incident diabetes among current users of atypical and conventional antipsychotic medications. These results were independent of other established risk factors. The larger association observed for atypical antipsychotic users should be regarded as preliminary given the small number of incident diabetes cases in this group. C1 US FDA, Ctr Drug Evaluat & Res, Off Drug Safety, Rockville, MD 20857 USA. Boston Collaborat Drug Surveillance Program, Lexington, MA USA. RP Kornegay, CJ (reprint author), Div Drug Risk Evaluat, Room 15B-23,HFD-420,5600 Fishers Lane, Rockville, MD 20857 USA. RI Research Datalink, Clinical Practice/H-2477-2013 FU FDA HHS [FD-U-001639] NR 26 TC 62 Z9 63 U1 0 U2 4 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD SEP PY 2002 VL 63 IS 9 BP 758 EP 762 PG 5 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 599PP UT WOS:000178344600002 PM 12363114 ER PT J AU Hubinger, JC AF Hubinger, JC TI A survey of consumer cosmetic products and salon preparations for alpha hydroxy acids SO JOURNAL OF COSMETIC SCIENCE LA English DT Article ID GLYCOLIC ACID; TRICHLOROACETIC-ACID; CHEMICAL PEEL; STRATUM-CORNEUM; SKIN; BARRIER; PHENOL; FACE AB The Food and Drug Administration has completed a survey of consumer and salon/professional cosmetic products for glycolic and lactic acids, and product pH, to determine conformity with recommended levels established by the Cosmetic Ingredient Review (CIR). In twenty-five consumer products, concentrations of glycolic and lactic acid ranged from 1.1% to 8.7%. Two products had pHs lower than the recommended minimum of 3.5. In seventeen salon/professional products, glycolic and lactic acids were found at levels ranging from 0.9% to 28.5%. Two salon products had pHs significantly lower than the 3.0 recommended by the CIR. About half of the products contained either a sunscreen or a recommendation for the use of a sunscreen. C1 US FDA, College Pk, MD 20740 USA. RP Hubinger, JC (reprint author), US FDA, 5100 Point Branch Pkwy, College Pk, MD 20740 USA. NR 36 TC 2 Z9 2 U1 0 U2 0 PU SOC COSMETIC CHEMISTS PI NEW YORK PA 120 WALL STREET, SUITE 2400, NEW YORK, NY 10005-4088 USA SN 0037-9832 J9 J COSMET SCI JI J. Cosmet. Sci. PD SEP-OCT PY 2002 VL 53 IS 5 BP 243 EP 248 PG 6 WC Chemistry, Applied; Dermatology SC Chemistry; Dermatology GA 604UC UT WOS:000178638600001 PM 12384710 ER PT J AU Platek, SF Keisler, MA Ranieri, N Reynolds, TW Crowe, JB AF Platek, SF Keisler, MA Ranieri, N Reynolds, TW Crowe, JB TI A method for the determination of syringe needle punctures in rubber stoppers using stereoscopic light microscopy SO JOURNAL OF FORENSIC SCIENCES LA English DT Article DE forensic science; rubber stopper; septa; syringe; needle; intravenous bags; pharmaceutical bottle; puncture; hole; stereoscopic light microscopy; potassium chloride AB The ability to accurately determine the number of,syringe needle penetration holes through the rubber stoppers in pharmaceutical vials and rubber septa in intravenous (IV) line and bag ports has been a critical factor in a number of forensic cases involving the thefts of controlled substances or suspected homicide by lethal injection. In the early 1990s, the microscopy and microanalysis group of the U.S Food and Drug Administration's Forensic Chemistry Center (FCC) developed and implemented a method (unpublished) to locate needle punctures in rubber pharmaceutical vial stoppers In 1996, as part of a multiple homicide investigation, the Indiana State Police Laboratory (ISPL) contacted the FCC for information on a method to identify and count syringe needle punctures through rubber stoppers in pharmaceutical vials. In a joint project and investigation using, the FCC's needle hole location method and applying a method of puncture site mapping developed by the ISPL, a systematic method was developed to locate. identify, count. and map syringe punctures in rubber bottle stoppers or IV bag ports using microscopic analysis. The method requires documentation of punctures on both sides of the rubber stoppers and microscopic analysis of each Suspect puncture site The final result of an analysis using the method is a detailed diagram of puncture holes on both sides of a questioned stopper and a record of the minimum number of puncture holes through a stopper. C1 US FDA, Forens Chem Ctr, Organ Branch, Cincinnati, OH 45237 USA. Indiana State Police, Gen Headquarters Lab, Indianapolis, IN USA. RP Platek, SF (reprint author), US FDA, Forens Chem Ctr, Organ Branch, 6751 Steger Dr, Cincinnati, OH 45237 USA. NR 3 TC 1 Z9 1 U1 0 U2 1 PU AMER SOC TESTING MATERIALS PI W CONSHOHOCKEN PA 100 BARR HARBOR DR, W CONSHOHOCKEN, PA 19428-2959 USA SN 0022-1198 J9 J FORENSIC SCI JI J. Forensic Sci. PD SEP PY 2002 VL 47 IS 5 BP 986 EP 992 PG 7 WC Medicine, Legal SC Legal Medicine GA 596UY UT WOS:000178185800010 PM 12353585 ER PT J AU Schwetz, BA Dobs, AS AF Schwetz, BA Dobs, AS TI Streamlining the clinical research enterprise SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Editorial Material C1 US FDA, Rockville, MD 20857 USA. Johns Hopkins Univ, Sch Med, Clin Res Unit, Baltimore, MD 21218 USA. RP Schwetz, BA (reprint author), US FDA, 14-71 Parklawn Bldg,5600 Fishers Lane, Rockville, MD 20857 USA. NR 17 TC 2 Z9 2 U1 0 U2 2 PU B C DECKER INC PI HAMILTON PA 20 HUGHSON ST SOUTH, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD SEP PY 2002 VL 50 IS 5 BP 356 EP 360 DI 10.2310/6650.2002.32864 PG 5 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 591KG UT WOS:000177878400017 PM 12227660 ER PT J AU Gao, G Buskell, Z Seeff, L Tabor, E AF Gao, G Buskell, Z Seeff, L Tabor, E TI Drift in the hypervariable region of the hepatitis C virus during 27 years in two patients SO JOURNAL OF MEDICAL VIROLOGY LA English DT Article DE hepatitis C virus; immune globulin; quasispecies ID TO-INFANT TRANSMISSION; NON-B HEPATITIS; IMMUNE-RESPONSE; NON-A; EVOLUTION; INFECTION; NEUTRALIZATION; CHIMPANZEES; MECHANISMS; PERSISTENT AB Serial serum samples were obtained over a 27-year period from a hepatitis C virus (HCV)-infected patient and from a nurse who appeared to become infected by this patient. The hypervariable region 1 (HVR1) and 5' noncoding region (5'NCR) of the HCV genome were amplified from each serum sample by polymerase chain reaction (PCR) and cloned. In the first serum specimen from the patient and the first two serum specimens from the nurse, most of the 20 clones from each serum sample had one common sequence in the HVR1 gene. All later serum samples contained a heterogeneous mixture of HCV quasispecies. The uniformity of the HVR1 sequence in the early samples and the emergence of greater diversity in later serum samples is consistent with the apparent transmission of HCV between the patient and nurse and the eventual emergence of other quasispecies as the virus replicated in the new host. In addition, the immune globulin given to the nurse may have been responsible for some of the HCV quasispecies changes observed in her serum. Published 2002 Wiley-Liss, Inc. C1 US FDA, Off Blood Res & Review, Div Emerging & Transfus Transmitted Dis, Rockville, MD 20852 USA. Vet Adm Med Ctr, Washington, DC 20422 USA. NIDDKD, NIH, Bethesda, MD 20892 USA. RP Tabor, E (reprint author), US FDA, Off Blood Res & Review, Div Emerging & Transfus Transmitted Dis, HFM-300,1401 Rockville Pike, Rockville, MD 20852 USA. NR 22 TC 9 Z9 9 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0146-6615 J9 J MED VIROL JI J. Med. Virol. PD SEP PY 2002 VL 68 IS 1 BP 60 EP 67 DI 10.1002/jmv.10170 PG 8 WC Virology SC Virology GA 579PX UT WOS:000177188000009 PM 12210431 ER PT J AU Krieg, RC Paweletz, CP AF Krieg, RC Paweletz, CP TI Proteome analysis in lymphangiogenesis SO JOURNAL OF MOLECULAR MEDICINE-JMM LA English DT Meeting Abstract C1 NCI, FDA, Pathol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0946-2716 J9 J MOL MED-JMM JI J. Mol. Med. PD SEP PY 2002 VL 80 IS 9 BP B4 EP B4 PG 1 WC Genetics & Heredity; Medicine, Research & Experimental SC Genetics & Heredity; Research & Experimental Medicine GA 602KU UT WOS:000178505100018 ER PT J AU Pereira, FC Imam, SZ Gough, B Newport, GD Ribeiro, CF Slikker, W Macedo, TR Ali, SF AF Pereira, FC Imam, SZ Gough, B Newport, GD Ribeiro, CF Slikker, W Macedo, TR Ali, SF TI Acute changes in dopamine release and turnover in rat caudate nucleus following a single dose of methamphetamine SO JOURNAL OF NEURAL TRANSMISSION LA English DT Article DE methamphetamine; acute dosage; caudate nucleus; microdialysis; catecholamines; dopamine turnover ID CATECHOL-O-METHYLTRANSFERASE; STRIATAL DOPAMINE; NEUROTOXICITY; BRAIN; HYPERTHERMIA; AMPHETAMINE; DECREASE; PROTEIN; EFFLUX; INDUCE AB Acute changes in dopamine (DA) turnover were studied in the caudate nucleus (CN) of adult male rats between 0-24 h after a single injection of Methamphetamine (20mg/kg, ip). A single dose of METH-induced an increase in DA turnover [(DOPAC + HVA)/DA] concomitant with an acute DA release followed by transient DA and DOPAC depletion in the rat CN. C1 US FDA, Natl Ctr Toxicol Res, Neurochem Lab, Div Neurotoxicol, Jefferson, AR 72079 USA. Univ Coimbra, Sch Med, Inst Farmacol & Terapeut, P-3000 Coimbra, Portugal. RP Ali, SF (reprint author), US FDA, Natl Ctr Toxicol Res, Neurochem Lab, Div Neurotoxicol, HFT-132, Jefferson, AR 72079 USA. OI Pereira, Frederico/0000-0002-9381-3320 NR 25 TC 13 Z9 13 U1 1 U2 1 PU SPRINGER-VERLAG WIEN PI VIENNA PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 VIENNA, AUSTRIA SN 0300-9564 J9 J NEURAL TRANSM JI J. Neural Transm. PD SEP PY 2002 VL 109 IS 9 BP 1151 EP 1158 DI 10.1007/s00702-002-0754-z PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 587RX UT WOS:000177657300004 PM 12203042 ER PT J AU Choumenkovitch, SF Selhub, J Wilson, PWF Rader, JI Rosenberg, IH Jacques, PF AF Choumenkovitch, SF Selhub, J Wilson, PWF Rader, JI Rosenberg, IH Jacques, PF TI Folic acid intake from fortification in United States exceeds predictions SO JOURNAL OF NUTRITION LA English DT Article DE folate; folic acid; fortification; folate intake; humans ID NEURAL-TUBE DEFECTS; PLASMA HOMOCYSTEINE; FOOD FORTIFICATION; DIETARY-FOLATE; YOUNG-WOMEN; RISK FACTOR; SUPPLEMENTATION; PREVENTION; QUESTIONNAIRE; PREVALENCE AB In 1996, the U.S. Food and Drug Administration issued a regulation requiring that all enriched cereal-grain products be fortified with folic acid by January 1998. An average increase in folic acid intake of 100 mug/d was projected as a result of this fortification. The objective of the present study was to estimate the effect of this fortification on the intake of folic acid and total folate, and on the prevalence of individuals with inadequate folate intake and with high folic acid intake. We used data on food and nutrient intake from 1480 individuals who participated in the 5th and 6th examinations of the Framingham Offspring Cohort Study. Fortification was instituted during the 6th examination so that 931 participants were examined before its implementation (nonexposed) and 549 after implementation (exposed). Published data on total folate in enriched cereal-grain products were used to correct folate content in these foods to reflect fortification. Among nonsupplement users, folic acid intake increased by a mean of 190 [95% confidence interval (CI): 176, 204] mug/d (P < 0.001) and total folate intake increased by a mean of 323 (95% CI: 296-350) mug dietary folate equivalents (DFE)/d (P < 0.001) in the exposed participants. Similar increases were seen among supplement users exposed to fortification. The prevalence of exposed individuals with total folate intake below the estimated average requirement (320 mug DFE/d) decreased from 48.6% (95% CI: 44.2-53.1%) before fortification to 7.0% (95% CI: 3.1-10.9%) after fortification in individuals who did not use folic acid supplements. This prevalence was similar to1% or less for users of supplements both before and after fortification. Prevalence of individuals with folic acid intake above the upper tolerable intake level (1000 mug folic acid/d) increased only among supplement users exposed to fortification (from 1.3 to 11.3%, P < 0.001). No changes in folic acid intake were observed over time in the nonexposed participants. By these estimations, folic acid fortification resulted in a mean increase in folic acid intake that was approximately twice as large as previously projected. C1 Tufts Univ, Jean Mayer USDA, Human Nutr Res Ctr Aging, Vitamin Metab Lab, Boston, MA 02111 USA. Tufts Univ, Jean Mayer USDA, Human Nutr Res Ctr Aging, Nutr Epidemiol Program, Boston, MA 02111 USA. Boston Univ, Sch Med, Framington Heart Study, Framingham, MA 01701 USA. US FDA, Off Food Labeling, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. RP Jacques, PF (reprint author), Tufts Univ, Jean Mayer USDA, Human Nutr Res Ctr Aging, Vitamin Metab Lab, Boston, MA 02111 USA. FU NHLBI NIH HHS [N01-HC-38038]; NIDDK NIH HHS [1R01 DK 56105-01] NR 37 TC 185 Z9 191 U1 1 U2 7 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD SEP PY 2002 VL 132 IS 9 BP 2792 EP 2798 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 592WK UT WOS:000177959700051 PM 12221247 ER PT J AU Kerr, LN Boivin, WS Chaput, MP Hamilton, SL Mailhot, SA O'Malley, LG Teixeira, JC AF Kerr, LN Boivin, WS Chaput, MP Hamilton, SL Mailhot, SA O'Malley, LG Teixeira, JC TI The effect of simulated clinical use on vinyl and latex exam glove durability SO JOURNAL OF TESTING AND EVALUATION LA English DT Article DE medical gloves; vinyl; latex; exam; durability; simulated clinical use ID INTEGRITY; BARRIER; PERFORATIONS; QUALITY; SURGERY AB A simulated clinical-use study was conducted in order to verify the failure rates found in the literature and to identify the failure modes and typical locations of defects in vinyl and latex exam gloves. A simulated clinical-use protocol consisted of approximately 12 min of manipulating various medical devices. This simulated clinical use created significantly more defects in vinyl cloves (35%) than in latex gloves (9%). The user's dominant hand was significantly associated with defect rate in vinyl gloves (60%) but not in latex gloves (56%). The majority of the defects (74%) in the vinyl gloves were located in the thumb and index finger. The defects in the latex gloves were distributed evenly among the palm/back of hand, thumb, index finger, and cuff. Typical defects consisted of holes, slits, tears, and abrasions. C1 US FDA, Winchester Engn & Analyt Ctr, Winchester, MA 01890 USA. RP Kerr, LN (reprint author), US FDA, Winchester Engn & Analyt Ctr, 109 Holton St, Winchester, MA 01890 USA. NR 17 TC 3 Z9 3 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 SEP PY 2002 VL 30 IS 5 BP 415 EP 420 PG 6 WC Materials Science, Characterization & Testing SC Materials Science GA 603NT UT WOS:000178566500006 ER PT J AU Qiao, GL Riviere, JE AF Qiao, GL Riviere, JE TI Systemic uptake and cutaneous disposition of pentachlorophenol in a sequential exposure scenario: Effects of skin preexposure to benzo[a] pyrene SO JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A LA English DT Article ID POLYCYCLIC AROMATIC-HYDROCARBONS; INVITRO PERCUTANEOUS-ABSORPTION; DNA ADDUCT FORMATION; PARATHION IN-VIVO; MOUSE SKIN; CULTURED KERATINOCYTES; METABOLISM; PENETRATION; OCCLUSION; MODEL AB Characterizing interactions caused by sequential skin exposures to various environmental toxicants can be critical for a meaningful risk assessment. To assess sequential chemical exposure effect on chemical cutaneous disposition and systemic uptake of a toxicant, [C-14] pentachlorophenol (PCP) was topically administered in three porcine skin models ( in vivo, ex vivo, and in vitro) at 40 mug/cm(2) with or without skin preexposure to benzo[ a] pyrene (BaP), a known human carcinogen and cutaneous cytochrome P-450 (CYP450) inducer. In the mass balance studies, BaP skin preexposure was found to enhance C-14 absorption in all three models with detectable in vivo effect during the first several days. Total 8-h absorption was tripled by skin preexposure to BaP in the ex vivo (1.1 to 3.2%) and in vitro ( 0.20 to 0.66%) systems. As seen in the extended in vivo studies, total absorption was 50-57% regardless of exposure conditions, suggesting the prolonged observation period may conceal existing impact of potentially modified disposition processes, such as cutaneous metabolism, on systemic absorption. Skin preexposure to the skin CYP450 inducer BaP largely changed label penetration depth and distribution pattern in cutaneous tissues and decreased C-14 concentration in skin and fat. Additionally, BaP preexposure altered C-14 systemic tissue disposition, suggesting that altered cutaneous PCP disposition may eventually change the toxicity profile (cutaneous vs. systemic risk). The preliminary tissue distribution and systemic absorption data suggested that skin preexposure to BaP may considerably modify cutaneous biotransformation rate and thus deserves further investigation. The dermal model-dependent impacts of expected skin biotransformation manipulation by preexposure to chemicals such as BaP on cutaneous disposition and systemic uptake of environmental toxicants such as PCP need to be considered in risk assessment. C1 NIOSH, Hlth Effect Lab Div, Morgantown, WV USA. N Carolina State Univ, Ctr Chem Toxicol Res & Pharmacokinet, Raleigh, NC 27695 USA. RP Qiao, GL (reprint author), US FDA, Ctr Vet Med, HFV 110, 7500 Standish Pl, Rockville, MD 20855 USA. RI Riviere, Jim/A-9210-2008 OI Riviere, Jim/0000-0001-8412-9650 NR 45 TC 4 Z9 4 U1 1 U2 3 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1528-7394 J9 J TOXICOL ENV HEAL A JI J. TOXICOL. ENV. HEALTH PT A PD SEP PY 2002 VL 65 IS 18 BP 1307 EP 1331 DI 10.1080/00984100290071577 PG 25 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 588YT UT WOS:000177730400002 PM 12227954 ER PT J AU Puig, M Mihalik, K Yu, MYW Feinstone, SM Major, ME AF Puig, M Mihalik, K Yu, MYW Feinstone, SM Major, ME TI Sensitivity and reproducibility of HCV quantitation in chimpanzee sera using TaqMan real-time PCR assay SO JOURNAL OF VIROLOGICAL METHODS LA English DT Article DE HCV; TaqMan RT-PCR; quantitation; chimpanzee ID HEPATITIS-C VIRUS; NON-B-HEPATITIS; INTERNATIONAL STANDARD; BLOOD DONATIONS; NAT ASSAYS; NON-A; RNA; AMPLIFICATION; ANTIBODIES; INFECTION AB The availability of molecular protocols for the detection and quantitation of very low numbers of hepatitis C virus (HCV) particles in biological samples is an issue of interest in both clinical and analytical fields of HCV research. A sensitive and reproducible assay is described for HCV RNA quantitation using the TaqMan PCR fluorogenic real-time detection system to establish the levels of HCV RNA in chimpanzee plasma. Our TaqMan PCR protocol and synthetic full length HCV RNA template show that the threshold of sensitivity for our TaqMan PCR is two copies per reaction. As few as 10 genome copies per reaction could be quantitated maintaining a linear range. The accuracy of the TaqMan PCR test was comparable to commercial bDNA and Amplicor tests. The RNA standards of the laboratory were tested in parallel with a World Health Organization (WHO) International Standard for HCV RNA obtaining ratios of 2.7 +/- 0.7 RNA copies per HCV international unit (IU). Our method using RNA extracted from chimpanzee samples had an estimated sensitivity of 200 RNA copies/ml of plasma (approximately eight copies/reaction or 74 WHO IU/ml). Serial plasma samples from HCV-infected chimpanzees were analyzed using this methodology to evaluate its applicability, and RNA profiles were observed consistent with the evolution of the pathology in each animal. The present study therefore illustrates the high reproducibility, sensitivity and reliability of our TaqMan methodology, providing a useful method for HCV research to consistently detect and quantify viral RNA throughout a range of concentrations. Crown Copyright (C) 2002 Published by Elsevier Science B.V. All rights reserved. C1 US FDA, Ctr Biol Evaluat & Res, Lab Hepatitis Viruses, Div Viral Prod, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Lab Plasma Derivat, Div Hematol, Bethesda, MD 20892 USA. RP Major, ME (reprint author), US FDA, Ctr Biol Evaluat & Res, Lab Hepatitis Viruses, Div Viral Prod, Bldg 29A,Room 1D02,8800 Rockville Pike, Bethesda, MD 20892 USA. NR 17 TC 38 Z9 38 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-0934 J9 J VIROL METHODS JI J. Virol. Methods PD SEP PY 2002 VL 105 IS 2 BP 253 EP 263 AR PII S0166-0934(02)00119-2 DI 10.1016/S0166-0934(02)00119-2 PG 11 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Virology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Virology GA 601GT UT WOS:000178438700007 PM 12270658 ER PT J AU Nishino, Y Kobasa, D Rubin, SA Pletnikov, MV Carbone, KM AF Nishino, Y Kobasa, D Rubin, SA Pletnikov, MV Carbone, KM TI Enhanced neurovirulence of Borna disease virus variants associated with nucleotide changes in the glycoprotein and L polymerase genes SO JOURNAL OF VIROLOGY LA English DT Article ID SEMLIKI-FOREST-VIRUS; STRAND RNA VIRUSES; INFLUENZA-A VIRUS; SINGLE AMINO-ACID; INFECTED-CELLS; HOST RANGE; L-PROTEIN; RATS; MICE; EXPRESSION AB Borna disease virus (BDV) infection produces a variety of clinical diseases, from behavioral illnesses to classical fatal encephalitis (i.e., Borna disease [BD]). Since the genomes of most BDV isolates differ by less than 5%, host factors are believed responsible for much of the reported variability in disease expression. The contribution of BDV genomic differences to variation in BD expression is largely unexplored. Here we compared the clinical outcomes of rats infected with one of two related BDV variants, CRP3 or CRNP5. Compared to rats inoculated with CRP3, adult and newborn Lewis rats inoculated with CRNP5 had more severe and rapidly fatal neurological disease, with increased damage to the hippocampal pyramidal neurons and rapid infection of brain stem neurons. To identify possible virus-specific contributions to the observed variability in disease outcome, the genomes of CRP3 and CRNP5 were sequenced. Compared to CRP3, there were four nucleotide changes in the CRNP5 variant, two each in the G protein and in the L polymerase, resulting in four amino acid changes. These results suggest that small numbers of genomic differences between BDV variants in the G protein and/or L polymerase can contribute to the variability in BD outcomes. C1 US FDA, Lab Pediat & Resp Viral Dis, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. Azabu Univ, Biosci Res Inst, Sagamihara, Kanagawa 2298501, Japan. RP Carbone, KM (reprint author), US FDA, Lab Pediat & Resp Viral Dis, Ctr Biol Evaluat & Res, HFM460,8800 Rockville Pike, Bethesda, MD 20892 USA. FU PHS HHS [R0248948] NR 58 TC 14 Z9 18 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 2002 VL 76 IS 17 BP 8650 EP 8658 DI 10.1128/JVI.76.17.8650-8658.2002 PG 9 WC Virology SC Virology GA 582DR UT WOS:000177334900015 PM 12163584 ER PT J AU Ishibe, N Prieto, DR Hosack, DA Lempicki, RA Goldin, LR Raffeld, M Marti, GE Caporaso, NE AF Ishibe, N Prieto, DR Hosack, DA Lempicki, RA Goldin, LR Raffeld, M Marti, GE Caporaso, NE TI Telomere length and heavy-chain mutation status in familial chronic lymphocytic leukemia SO LEUKEMIA RESEARCH LA English DT Article DE familial CLL; telomere length; V-H mutation ID V-H GENES; B-CLL; EXPRESSION AB We examined whether telomere lengths of peripheral blood mononuclear cells are associated with immunoglobulin gene usage in 21 familial chronic lymphocytic leukemia (CLL) patients. Subjects with unmutated V genes tended to have shorter telomeres than those with somatic mutations, especially after adjusting for age. Unlike V-H mutation status, telomere length was not predictive for survival. Our results suggest that telomere length is associated with V-H gene mutation status and provides further evidence that the biological basis of familial B-CLL is similar to that of sporadic patients. (C) 2002 Elsevier Science Ltd. All rights reserved. C1 NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20892 USA. NIH, Clin Serv Program, SAIC Frederick, Frederick, MD 21702 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Res & Evaluat, Div Cell & Gene Therapies, Flow & Image Cytometry Sect, Bethesda, MD 20852 USA. RP Ishibe, N (reprint author), NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd,MSC 7236, Rockville, MD 20892 USA. RI Lempicki, Richard/E-1844-2012 OI Lempicki, Richard/0000-0002-7059-409X NR 9 TC 16 Z9 16 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0145-2126 J9 LEUKEMIA RES JI Leuk. Res. PD SEP PY 2002 VL 26 IS 9 BP 791 EP 794 AR PII S0145-2126(02)00010-3 DI 10.1016/S0145-2126(02)00010-3 PG 4 WC Oncology; Hematology SC Oncology; Hematology GA 591TJ UT WOS:000177896100004 PM 12127552 ER PT J AU Petricoin, EF Zoon, KC Kohn, EC Barrett, JC Liotta, LA AF Petricoin, EF Zoon, KC Kohn, EC Barrett, JC Liotta, LA TI Clinical proteomics: Translating benchside promise into bedside reality SO NATURE REVIEWS DRUG DISCOVERY LA English DT Review ID TYROSINE KINASE INHIBITOR; IMMOBILIZED PH GRADIENTS; OVARIAN-CANCER; 2-DIMENSIONAL ELECTROPHORESIS; PROTEIN MICROARRAYS; MASS-SPECTROMETER; MYELOID-LEUKEMIA; BREAST-CANCER; END-POINTS; THERAPY AB The ultimate goal of proteomics is to characterize the information flow through protein networks. This information can be a cause, or a consequence, of disease processes. Clinical proteomics is an exciting new subdiscipline of proteomics that involves the application of proteomic technologies at the bedside, and cancer, in particular, is a model disease for studying such applications. Here, we describe proteomic technologies that are being developed to detect cancer earlier, to discover the next generation of targets and imaging biomarkers, and finally to tailor the therapy to the patient. C1 US FDA, FDA NCI Clin Proteom Program, Div Therapeut Prot, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. US FDA, Off Director, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. NCI, Ctr Canc Res, NIH, FDA NCI Clin Proteom Program,Lab Pathol, Bethesda, MD 20892 USA. RP Petricoin, EF (reprint author), US FDA, FDA NCI Clin Proteom Program, Div Therapeut Prot, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. NR 82 TC 366 Z9 391 U1 1 U2 25 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-1776 J9 NAT REV DRUG DISCOV JI Nat. Rev. Drug Discov. PD SEP PY 2002 VL 1 IS 9 BP 683 EP 695 DI 10.1038/nrd891 PG 13 WC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA 607EK UT WOS:000178778500013 PM 12209149 ER PT J AU Bastings, EP Greenberg, JP Good, DC AF Bastings, EP Greenberg, JP Good, DC TI Hand motor recovery after stroke: A transcranial magnetic stimulation mapping study of motor output areas and their relation to functional status SO NEUROREHABILITATION AND NEURAL REPAIR LA English DT Article DE transcranial magnetic stimulation (TMS); brain mapping; stroke; motor recovery; hand ID SPINAL-CORD; REORGANIZATION; CORTEX; BRAIN; ARM; INFARCTION; HUMANS; MAPS; MRI AB The respective contributions of the stroke and undamaged hemispheres to motor recovery after stroke remains controversial. The aim of this article is to evaluate the relationship between location and size of cortical motor areas and outcome after stroke. Twelve controls and 12 stroke patients were studied. Hand cortical motor output areas were determined using transcranial magnetic stimulation. Motor-evoked potentials were recorded simultaneously from both bands. Functional motor abilities were evaluated using well-validated measures. Surface area, weighted surface area, and center of gravity of motor output areas were calculated. Different patterns of motor output areas to the paretic hand were observed; there was no motor output from the stroke hemisphere inpatients with poor outcome, contrasting to large motor output area in the stroke hemisphere in patients with good outcome, regardless of infarct size or location. A significant correlation was found between measures of motor outcome in the stroke-affected upper extremity and both the surface area and weight of the central motor output area in the stroke hemisphere. No ipsilateral motor response was obtained after stimulation of either hemisphere. These data support an association between preservation of cortical motor output area to the paretic band in the stroke hemisphere and good motor outcome. C1 Wake Forest Univ, Baptist Med Ctr, Sticht Ctr Aging & Rehabil, Winston Salem, NC 27157 USA. US FDA, Ctr Drug Evaluat & Res, Div Neuropharmacol Drug Prod, Winston Salem, NC USA. RP Good, DC (reprint author), Wake Forest Univ, Baptist Med Ctr, Sticht Ctr Aging & Rehabil, Med Ctr Blvd, Winston Salem, NC 27157 USA. EM dgood@wfubmc.edu FU NICHD NIH HHS [1P01HD35955-01A1] NR 30 TC 25 Z9 25 U1 0 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1545-9683 J9 NEUROREHAB NEURAL RE JI Neurorehabil. Neural Repair PD SEP PY 2002 VL 16 IS 3 BP 275 EP 282 DI 10.1177/154596802401105207 PG 8 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA 845II UT WOS:000223235300005 PM 12234089 ER PT J AU Cross, J Lee, H Westelinck, A Nelson, J Grudzinskas, C Peck, C AF Cross, J Lee, H Westelinck, A Nelson, J Grudzinskas, C Peck, C TI Postmarketing drug dosage changes of 499 FDA-approved new molecular entities, 1980-1999 SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Article DE drug dosage; label changes; postmarketing changes; dosage changes; new molecular entity AB Purpose Risks and benefits of marketed drugs can be improved by changing their labels to optimize dosage regimens for indicated populations. Such postmarketing label changes may reflect the quality of pre-marketing development, regulatory review, and postmarketing surveillance. We documented dosage changes of FDA-approved new molecular entities (NMEs), and investigated trends over time and across therapeutic groups, on the premise that improved drug development methods have yielded fewer postmarketing label changes over time. Methods We compiled a list of NMEs approved by FDA from 1 January 1980 to 31 December 1999 using FDA's website, Freedom of Information Act request, and PhRMA (Pharmaceutical Research and Manufacturers of America) database. Original labeled dosages and indicated patient populations were tracked in labels in the Physician's Desk Reference(R). Time and covariate-adjusted risks for dosage changes by 5-year epoch and therapeutic groups were estimated by survival analysis. Results Of 499 NMEs, 354 (71%) were evaluable. Dosage changes in indicated populations occurred in 73 NMEs (21%). A total of 58 (79%) were safety-motivated, net dosage decreases. Percentage of NMEs with changes by therapeutic group ranged from 27.3% for neuropharmacologic drugs to 13.6% for miscellaneous drugs. Median time to change following approval fell from 6.5 years (1980-1984) to 2.0 years (1995-1999). Contrary to our premise, 1995-1999 NMEs were 3.15 times more likely to change in comparison to 1980-1984 NMEs (p=0.008, Cox analysis). Conclusions Dosages of one in five NMEs changed, four in five changes were safety reductions. Increasing frequency of changes, independent of therapeutic group, may reflect intensified postmarketing surveillance and underscores the need to improve pre-marketing optimization of dosage and indicated population. Copyright (C) 2002 John Wiley Sons, Ltd. C1 US FDA, Ctr Drug Evaluat & Res, Div Metab & Endocrine Drug Prod, Rockville, MD 20857 USA. Georgetown Univ, Ctr Drug Dev Sci, Washington, DC USA. RP Cross, J (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Metab & Endocrine Drug Prod, HFD-510,5600 Fishers Lane,Rm 14-B-04, Rockville, MD 20857 USA. NR 21 TC 67 Z9 69 U1 0 U2 6 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 SEP PY 2002 VL 11 IS 6 BP 439 EP 446 DI 10.1002/pds.744 PG 8 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 606UA UT WOS:000178751100002 PM 12426927 ER PT J AU Kavlock, R Boekelheide, K Chapin, R Cunningham, M Faustman, E Foster, P Golub, M Henderson, R Hinberg, I Little, R Seed, J Shea, K Tabacova, S Tyl, R Williams, P Zacharewski, T AF Kavlock, R Boekelheide, K Chapin, R Cunningham, M Faustman, E Foster, P Golub, M Henderson, R Hinberg, I Little, R Seed, J Shea, K Tabacova, S Tyl, R Williams, P Zacharewski, T TI NTP Center for the Evaluation of Risks to Human Reproduction: phthalates expert panel report on the reproductive and developmental toxicity of butyl benzyl phthalate SO REPRODUCTIVE TOXICOLOGY LA English DT Article DE butyl benzyl phthalate; reproductive toxicity; developmental toxicity; review; exposure; systemic toxicity; toxicokinetics; risk evaluation ID ESTROGEN-RECEPTOR; IN-VITRO; RECOMBINANT YEAST; RATS; ESTERS; SPERM; EMBRYOLETHALITY; ABSORPTION; CHEMICALS; DIESTERS C1 US EPA, Natl Hlth & Environm Effects Res Lab, Res Triangle Pk, NC 27711 USA. Brown Univ, Providence, RI 02912 USA. NIEHS, Res Triangle Pk, NC 27709 USA. Univ Washington, Seattle, WA 98195 USA. Chem Ind Inst Toxicol, Res Triangle Pk, NC 27709 USA. Calif Environm Protect Agcy, Sacramento, CA USA. Lovelace Resp Res Inst, Albuquerque, NM USA. Hlth Canada, Ottawa, ON K1A 0L2, Canada. US EPA, Off Tox Subst, Washington, DC 20460 USA. Duke Univ, Durham, NC USA. US FDA, Rockville, MD 20857 USA. Res Triangle Inst, Res Triangle Pk, NC 27709 USA. Harvard Univ, Boston, MA 02115 USA. Michigan State Univ, E Lansing, MI 48824 USA. RP Kavlock, R (reprint author), US EPA, Natl Hlth & Environm Effects Res Lab, Res Triangle Pk, NC 27711 USA. OI Chapin, Robert/0000-0002-5997-1261 FU NIEHS NIH HHS [R29 ES007981-05, ES-85425] NR 65 TC 61 Z9 69 U1 3 U2 18 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 2002 VL 16 IS 5 BP 453 EP 487 AR PII S0890-6238(02)00029-1 DI 10.1016/S0890-6238(02)00029-1 PG 35 WC Reproductive Biology; Toxicology SC Reproductive Biology; Toxicology GA 615UL UT WOS:000179265200002 PM 12406492 ER PT J AU Kavlock, R Boekelheide, K Chapin, R Cunningham, M Faustman, E Foster, P Golub, M Henderson, R Hinberg, I Little, R Seed, J Shea, K Tabacova, S Tyl, R Williams, P Zacharewski, T AF Kavlock, R Boekelheide, K Chapin, R Cunningham, M Faustman, E Foster, P Golub, M Henderson, R Hinberg, I Little, R Seed, J Shea, K Tabacova, S Tyl, R Williams, P Zacharewski, T TI NTP Center for the Evaluation of Risks to Human Reproduction: phthalates expert panel report on the reproductive and developmental toxicity of di-n-butyl phthalate SO REPRODUCTIVE TOXICOLOGY LA English DT Article DE di-n-butyl phthalate; reproductive toxicity; developmental toxicity; review; exposure; systemic toxicity; toxicokinetics; risk evaluation ID DI(N-BUTYL) PHTHALATE; ESTROGEN-RECEPTOR; IN-VITRO; MONO(2-ETHYLHEXYL) PHTHALATE; DI(2-ETHYLHEXYL) PHTHALATE; ENVIRONMENTAL CHEMICALS; QUANTITATIVE-EVALUATION; ALTERNATIVE MECHANISMS; RECOMBINANT YEAST; LATE-GESTATION C1 US EPA, Natl Hlth & Environm Effects Res Lab, Res Triangle Pk, NC 27711 USA. Brown Univ, Providence, RI 02912 USA. NIEHS, Res Triangle Pk, NC 27709 USA. Univ Washington, Seattle, WA 98195 USA. Chem Ind Inst Toxicol, Res Triangle Pk, NC 27709 USA. Calif Environm Prot Agcy, Sacramento, CA USA. Lovelace Resp Res Inst, Albuquerque, NM USA. Hlth Canada, Ottawa, ON K1A 0L2, Canada. US EPA, Off Tox Subst, Washington, DC 20460 USA. Duke Univ, Durham, NC USA. US FDA, Rockville, MD 20857 USA. Res Triangle Inst, Res Triangle Pk, NC 27709 USA. Harvard Univ, Boston, MA 02115 USA. Michigan State Univ, E Lansing, MI 48824 USA. RP Kavlock, R (reprint author), US EPA, Natl Hlth & Environm Effects Res Lab, Res Triangle Pk, NC 27711 USA. OI Chapin, Robert/0000-0002-5997-1261 FU NIEHS NIH HHS [ES-85425, R29 ES007981-05] NR 75 TC 88 Z9 112 U1 2 U2 24 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 2002 VL 16 IS 5 BP 489 EP 527 AR PII S0890-6238(02)00033-3 DI 10.1016/S0890-6238(02)00033-3 PG 39 WC Reproductive Biology; Toxicology SC Reproductive Biology; Toxicology GA 615UL UT WOS:000179265200003 PM 12406493 ER PT J AU Kavlock, R Boekelheide, K Chapin, R Cunningham, M Faustman, E Foster, P Golub, M Henderson, R Hinberg, I Little, R Seed, J Shea, K Tabacova, S Tyl, R Williams, P Zacharewski, T AF Kavlock, R Boekelheide, K Chapin, R Cunningham, M Faustman, E Foster, P Golub, M Henderson, R Hinberg, I Little, R Seed, J Shea, K Tabacova, S Tyl, R Williams, P Zacharewski, T TI NTP Center for the Evaluation of Risks to Human Reproduction: phthalates expert panel report on the reproductive and developmental toxicity of di(2-ethylhexyl) phthalate SO REPRODUCTIVE TOXICOLOGY LA English DT Review DE di(2-ethylhexyl) phthalate; reproductive toxicity; developmental toxicity; review; exposure; systemic toxicity; toxicokinetics; risk evaluation ID POLYVINYL-CHLORIDE BAGS; HEPATIC PEROXISOME PROLIFERATION; DIFFERENTIAL PRENATAL TOXICITY; RAT EMBRYONIC-DEVELOPMENT; ACTIVATED RECEPTOR-ALPHA; SUBCHRONIC ORAL TOXICITY; CELL FUNCTION-INVITRO; FISCHER 344 RATS; DI-(2-ETHYLHEXYL) PHTHALATE; DI-2-ETHYLHEXYL PHTHALATE C1 US EPA, Natl Hlth & Environm Effects Res Lab, Res Triangle Pk, NC 27711 USA. Brown Univ, Providence, RI 02912 USA. NIEHS, Res Triangle Pk, NC 27709 USA. Univ Washington, Seattle, WA 98195 USA. Chem Ind Inst Toxicol, Res Triangle Pk, NC USA. Calif Environm Protect Agcy, Sacramento, CA USA. Lovelace Resp Res Inst, Albuquerque, NM USA. Hlth Canada, Ottawa, ON K1A 0L2, Canada. US EPA, Off Tox Subst, Washington, DC 20460 USA. Duke Univ, Durham, NC USA. US FDA, Rockville, MD 20857 USA. Res Triangle Inst, Res Triangle Pk, NC 27709 USA. Harvard Univ, Boston, MA 02115 USA. Michigan State Univ, E Lansing, MI 48824 USA. RP Kavlock, R (reprint author), US EPA, Natl Hlth & Environm Effects Res Lab, Res Triangle Pk, NC 27711 USA. FU NIEHS NIH HHS [ES-85425, R29 ES007981-05] NR 248 TC 191 Z9 208 U1 6 U2 35 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 2002 VL 16 IS 5 BP 529 EP 653 AR PII S0890-6238(02)00032-1 DI 10.1016/S0890-6238(02)00032-1 PG 125 WC Reproductive Biology; Toxicology SC Reproductive Biology; Toxicology GA 615UL UT WOS:000179265200004 PM 12406494 ER PT J AU Kavlock, R Boekelheide, K Chapin, R Cunningham, M Fuastman, E Foster, P Golub, M Henderson, R Hinberg, I Little, R Seed, J Shea, K Tabacova, S Tyl, R Williams, P Zacharewski, T AF Kavlock, R Boekelheide, K Chapin, R Cunningham, M Fuastman, E Foster, P Golub, M Henderson, R Hinberg, I Little, R Seed, J Shea, K Tabacova, S Tyl, R Williams, P Zacharewski, T TI NTP Center for the Evaluation of Risks to Human Reproduction: phthalates expert panel report on the reproductive and developmental toxicity of di-isodecyl phthalate SO REPRODUCTIVE TOXICOLOGY LA English DT Article DE di-isodecyl phthalate; reproductive toxicity; developmental toxicity; review; exposure; systemic toxicity; toxicokinetics; risk evaluation ID ESTROGEN-RECEPTOR; IN-VITRO; RECOMBINANT YEAST; ESTERS; CHEMICALS; ABSORPTION; RATS; PLASTICIZERS; XENOBIOTICS; DIESTERS C1 US EPA, Natl Hlth & Environm Effects Res Lab, Res Triangle Pk, NC 27711 USA. Brown Univ, Providence, RI 02912 USA. NIEHS, Res Triangle Pk, NC 27709 USA. Univ Washington, Seattle, WA 98195 USA. Chem Ind Inst Toxicol, Res Triangle Pk, NC USA. Calif Environm Protect Agcy, Sacramento, CA USA. Lovelace Resp Res Inst, Albuquerque, NM USA. Hlth Canada, Ottawa, ON K1A 0L2, Canada. US EPA, Off Tox Subst, Washington, DC 20460 USA. Duke Univ, Durham, NC USA. US FDA, Rockville, MD 20857 USA. Res Triangle Inst, Res Triangle Pk, NC 27709 USA. Harvard Univ, Boston, MA 02115 USA. Michigan State Univ, E Lansing, MI 48824 USA. RP Kavlock, R (reprint author), US EPA, Natl Hlth & Environm Effects Res Lab, Res Triangle Pk, NC 27711 USA. OI Chapin, Robert/0000-0002-5997-1261 FU NIEHS NIH HHS [ES-85425] NR 43 TC 22 Z9 24 U1 0 U2 10 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 2002 VL 16 IS 5 BP 655 EP 678 AR PII S0890-6238(02)00068-0 DI 10.1016/S0890-6238(02)00068-0 PG 24 WC Reproductive Biology; Toxicology SC Reproductive Biology; Toxicology GA 615UL UT WOS:000179265200005 PM 12406495 ER PT J AU Kavlock, R Boekelheide, K Chapin, R Cunningham, M Faustman, E Foster, P Golub, M Henderson, R Hinberg, I Little, R Seed, J Shea, K Tabacova, S Tyl, R Williams, P Zacharewski, T AF Kavlock, R Boekelheide, K Chapin, R Cunningham, M Faustman, E Foster, P Golub, M Henderson, R Hinberg, I Little, R Seed, J Shea, K Tabacova, S Tyl, R Williams, P Zacharewski, T TI NTP Center for the Evaluation of Risks to Human Reproduction: phthalates expert panel report on the reproductive and developmental toxicity of di-isononyl phthalate SO REPRODUCTIVE TOXICOLOGY LA English DT Article DE di-isononyl phthalate; reproductive toxicity; developmental toxicity; review; exposure; systemic toxicity; toxicokinetics; risk evaluation ID DIFFERENTIAL PRENATAL TOXICITY; ESTROGEN-RECEPTOR; IN-VITRO; RECOMBINANT YEAST; RATS; ESTERS; PLASTICIZERS; ABSORPTION; CHEMICALS; RODENTS C1 US EPA, Natl Hlth & Environm Effects Res Lab, Res Triangle Pk, NC 27711 USA. Brown Univ, Providence, RI 02912 USA. NIEHS, Res Triangle Pk, NC 27709 USA. Univ Washington, Seattle, WA 98195 USA. Chem Ind Inst Toxicol, Res Triangle Pk, NC USA. Calif Environm Protect Agcy, Sacramento, CA USA. Lovelace Resp Res Inst, Albuquerque, NM USA. Hlth Canada, Ottawa, ON K1A 0L2, Canada. US EPA, Off Tox Subst, Washington, DC 20460 USA. Duke Univ, Durham, NC USA. US FDA, Rockville, MD 20857 USA. Res Triangle Inst, Res Triangle Pk, NC 27709 USA. Harvard Univ, Boston, MA 02115 USA. Michigan State Univ, E Lansing, MI 48824 USA. RP Kavlock, R (reprint author), US EPA, Natl Hlth & Environm Effects Res Lab, Res Triangle Pk, NC 27711 USA. OI Chapin, Robert/0000-0002-5997-1261 FU NIEHS NIH HHS [ES-85425] NR 50 TC 50 Z9 53 U1 0 U2 11 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 2002 VL 16 IS 5 BP 679 EP 708 AR PII S0890-6238(02)00034-5 DI 10.1016/S0890-6238(02)00034-5 PG 30 WC Reproductive Biology; Toxicology SC Reproductive Biology; Toxicology GA 615UL UT WOS:000179265200006 PM 12406496 ER PT J AU Kavlock, R Boekelheide, K Chapin, R Cunningham, M Faustman, E Foster, P Golub, M Henderson, R Hinberg, I Little, R Seed, J Shea, K Tabacova, S Tyl, R Williams, P Zacharewski, T AF Kavlock, R Boekelheide, K Chapin, R Cunningham, M Faustman, E Foster, P Golub, M Henderson, R Hinberg, I Little, R Seed, J Shea, K Tabacova, S Tyl, R Williams, P Zacharewski, T TI NTP Center for the Evaluation of Risks to Human Reproduction: phthalates expert panel report on the reproductive and developmental toxicity of di-n-hexyl phthalate SO REPRODUCTIVE TOXICOLOGY LA English DT Article DE di-n-hexyl phthalate; reproductive toxicity; developmental toxicity; review; exposure; systemic toxicity; toxicokinetics; risk evaluation ID ESTROGEN-RECEPTOR; IN-VITRO; ACID ESTERS; CHEMICALS; ABSORPTION; MICE; RATS; DI(2-ETHYLHEXYL)PHTHALATE; DIESTERS; MOUSE C1 US EPA, Natl Hlth & Environm Effects Res Lab, Res Triangle Pk, NC 27711 USA. Brown Univ, Providence, RI 02912 USA. NIEHS, Res Triangle Pk, NC 27709 USA. Univ Washington, Seattle, WA 98195 USA. Chem Ind Inst Toxicol, Res Triangle Pk, NC USA. Calif Environm Protect Agcy, Sacramento, CA USA. Lovelace Resp Res Inst, Albuquerque, NM USA. Hlth Canada, Ottawa, ON K1A 0L2, Canada. US EPA, Off Tox Subst, Washington, DC 20460 USA. Duke Univ, Durham, NC USA. US FDA, Rockville, MD 20857 USA. Res Triangle Inst, Res Triangle Pk, NC 27709 USA. Harvard Univ, Boston, MA 02115 USA. Michigan State Univ, E Lansing, MI 48824 USA. RP Kavlock, R (reprint author), US EPA, Natl Hlth & Environm Effects Res Lab, Res Triangle Pk, NC 27711 USA. OI Chapin, Robert/0000-0002-5997-1261 FU NIEHS NIH HHS [ES-85425] NR 32 TC 25 Z9 28 U1 1 U2 6 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 2002 VL 16 IS 5 BP 709 EP 719 AR PII S0890-6238(02)00030-8 DI 10.1016/S0890-6238(02)00030-8 PG 11 WC Reproductive Biology; Toxicology SC Reproductive Biology; Toxicology GA 615UL UT WOS:000179265200007 PM 12406497 ER PT J AU Kavlock, R Boekelheide, K Chapin, R Cunningham, M Faustman, E Foster, P Golub, M Henderson, R Hinberg, I Little, R Seed, J Shea, K Tabacova, S Tyl, R Williams, P Zacharewski, T AF Kavlock, R Boekelheide, K Chapin, R Cunningham, M Faustman, E Foster, P Golub, M Henderson, R Hinberg, I Little, R Seed, J Shea, K Tabacova, S Tyl, R Williams, P Zacharewski, T TI NTP Center for the Evaluation of Risks to Human Reproduction: phthalates expert panel report on the reproductive and developmental toxicity of di-n-octyl phthalate SO REPRODUCTIVE TOXICOLOGY LA English DT Article DE di-n-octyl phthalate; reproductive toxicity; developmental toxicity; review; exposure; systemic toxicity; toxicokinetics; risk evaluation ID ESTROGEN-RECEPTOR; IN-VITRO; DI(2-ETHYLHEXYL) PHTHALATE; RECOMBINANT YEAST; ACID ESTERS; RAT; CHEMICALS; HYDROLYSIS; DIESTERS; CULTURES C1 US EPA, Natl Hlth & Environm Effects Res Lab, Res Triangle Pk, NC 27711 USA. Brown Univ, Providence, RI 02912 USA. NIEHS, Res Triangle Pk, NC 27709 USA. Univ Washington, Seattle, WA 98195 USA. Chem Ind Inst Toxicol, Res Triangle Pk, NC USA. Calif Environm Protect Agcy, Sacramento, CA USA. Lovelace Resp Res Inst, Albuquerque, NM USA. Hlth Canada, Ottawa, ON K1A 0L2, Canada. US EPA, Off Tox Subst, Washington, DC 20460 USA. Duke Univ, Durham, NC USA. US FDA, Rockville, MD 20857 USA. Res Triangle Inst, Res Triangle Pk, NC 27709 USA. Harvard Univ, Boston, MA 02115 USA. Michigan State Univ, E Lansing, MI 48824 USA. RP Kavlock, R (reprint author), US EPA, Natl Hlth & Environm Effects Res Lab, Res Triangle Pk, NC 27711 USA. OI Chapin, Robert/0000-0002-5997-1261 FU NIEHS NIH HHS [ES-85425] NR 36 TC 49 Z9 54 U1 0 U2 8 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 2002 VL 16 IS 5 BP 721 EP 734 AR PII S0890-6238(02)00031-X DI 10.1016/S0890-6238(02)00031-X PG 14 WC Reproductive Biology; Toxicology SC Reproductive Biology; Toxicology GA 615UL UT WOS:000179265200008 PM 12406498 ER PT J AU Hubbard, AR Sands, D Chang, AC Mazurier, C AF Hubbard, AR Sands, D Chang, AC Mazurier, C TI Standardisation of von Willebrand Factor in therapeutic concentrates: Calibration of the 1st International Standard for von Willebrand Factor concentrate (00/514) SO THROMBOSIS AND HAEMOSTASIS LA English DT Article DE von Willebrand Factor; von Willebrand disease; International Standard; Factor VIII concentrates ID VONWILLEBRAND-FACTOR; FACTOR-VIII; COLLAGEN-BINDING; DISEASE; PLASMA; ASSAY; ELISA AB An international study involving 26 laboratories assayed two candidate von Willebrand Factor (VWF) concentrates (B and C) for VWF:Antigen (VWF:Ag), VWF:Ristocetin Cofactor (VWF:RCo) and VWF:Collagen binding (VWF:CB) relative to the 4th International Standard Factor VIII/VWT Plasma (4th IS Plasma) (97/586). Estimates of VWF:Ag showed good agreement between different methods, for both candidates, and the overall combined means were 11.01 IU/ml with inter-laboratory variability (GCV) of 10.9% for candidate B and 14.01 IU/mI (GCV 11.8%) for candidate C. Estimates of VWF:RCo showed no significant difference between methods for both candidates and gave overall means of 9.38 IU/ml (GCV 23.7%) for candidate B and 10.19 IU/ml (GCV 24.4%) for candidate C. Prior to the calibration of the candidates for VWF:CB it was necessary to calibrate the 4th IS Plasma relative to local frozen normal plasma pools: there was good agreement between different collagen reagents and an overall mean of 0.83 IU per ampoule (GCV 11.8%) was assigned. In contrast, estimates of VWF:CB in both candidates showed large differences between collagen reagents with inter-laboratory GCV's of 40%. Candidate B (00/514) was established as the 1st International Standard von Willebrand Factor Concentrate by the WHO Expert Committee on Biological Standardisation in November 2001 with assigned values for VWF:Ag (11.0 IU/ampoule) and VWF:RCo (9.4 IU/ampoule). Large inter-laboratory variability of estimates precluded the assignment of a value for VWF:CB. C1 Natl Inst Biol Stand & Controls, Div Haematol, Potters Bar EN6 3QG, Herts, England. US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. RP Hubbard, AR (reprint author), Natl Inst Biol Stand & Controls, Div Haematol, Blanche Lane, Potters Bar EN6 3QG, Herts, England. RI Hubbard, Anthony/E-2605-2013 NR 25 TC 19 Z9 19 U1 0 U2 0 PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN PI STUTTGART PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD SEP PY 2002 VL 88 IS 3 BP 380 EP 386 PG 7 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 596AN UT WOS:000178140600003 PM 12353064 ER PT J AU Dugyala, RR Claggett, TW Kimmel, GL Kimmel, CA AF Dugyala, RR Claggett, TW Kimmel, GL Kimmel, CA TI HSP90 alpha, HSP90 beta, and p53 expression following in vitro hyperthermia exposure in gestation day 10 rat embryos SO TOXICOLOGICAL SCIENCES LA English DT Article DE hyperthermia; HSP90; p53; developmental toxicity; rat embryo culture ID HEAT-SHOCK PROTEINS; WILD-TYPE P53; GENE-EXPRESSION; MUTANT P53; MATERNAL HYPERTHERMIA; SIGNAL-TRANSDUCTION; DEVELOPMENT INVITRO; INDUCED APOPTOSIS; CELL-LINE; IN-VITRO AB The studies presented here are aimed at understanding the expression of p53, HSP90alpha, and HSP90beta in gestation day (GD) 10 CD rat embryos. GD 10 rat embryos were exposed in vitro to 37degreesC or 42degreesC for 15 min, then cultured at 37degreesC for 0.5, 1, 3, or 5 h. Immunohistochemistry was performed on formalin-fixed, paraffin embedded, sectioned embryos for p53, HSP90alpha, or HSP90beta expression. p53 expression was minimal in control embryos but was induced with heat exposure. Maximum expression of p53 was observed in rostral tissues, e.g., the optic vesicle, rostral neuroepithelium, and mature (rostral) somites 3 and 5 h after heat exposure. Expression of p53 in the caudal region, such as in mid and caudal neuroepithelium, immature (caudal) somites, and presomitic mesoderm, was moderate compared to rostral areas. No p53 expression was observed in the heart under any condition. The rostral-caudal gradient of p53 expression was not observed for HSP90alpha expression. HSP90alpha was induced in heat-exposed embryos beginning at 1 h, predominantly in neural tube and optic vesicle. Moderate but increased expression was observed in the somites of heat-exposed embryos at 3 and 5 h. Expression of p53 was primarily nuclear while HSP90alpha expression was mostly cytoplasmic. No clear association was observed between heat-induced HSP90alpha and p53 expression. HSP90beta was expressed extensively in control and heat-exposed embryos. Results indicate that heat induces p53 and HSP90alpha expression, but not HSP90beta expression, and that HSP90alpha induction is not likely to be involved in p53 regulation in mammalian embryos. C1 Pathol Associates Inc, Frederick, MD 21701 USA. US EPA, Natl Ctr Environm Assessment, Off Res & Dev, Washington, DC 20460 USA. US FDA, Hlth Sci Branch, Div Life Sci, Off Sci & Technol,Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Kimmel, CA (reprint author), US EPA, NCEAW 8623D, ORD, Ariel Rios Bldg,1200 Penn Ave NW, Washington, DC 20006 USA. NR 36 TC 12 Z9 13 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD SEP PY 2002 VL 69 IS 1 BP 183 EP 190 DI 10.1093/toxsci/69.1.183 PG 8 WC Toxicology SC Toxicology GA 593NC UT WOS:000177996800020 PM 12215673 ER PT J AU Wang, B Busch, MP Nass, C Orton, S Murphy, E Glynn, S AF Wang, B Busch, MP Nass, C Orton, S Murphy, E Glynn, S TI Are donors with a history of transfusion at an increased risk for transfusion-transmitted viral infections? SO TRANSFUSION LA English DT Meeting Abstract CT 55th Annual Meeting of the American-Association-of-Blood-Banks CY OCT 26-29, 2002 CL ORLANDO, FL SP Amer Assoc Blood Banks C1 Westat Corp, Rockville, MD USA. Blood Ctr Pacific, San Francisco, CA USA. Amer Red Cross, Blood Serv Chesapeake & Potomac Region, Baltimore, MD USA. US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. Blood Ctr Pacific, San Francisco, CA USA. NHLBI, Retrovirus Epidemiol Donor Study, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0041-1132 EI 1537-2995 J9 TRANSFUSION JI Transfusion PD SEP PY 2002 VL 42 IS 9 SU S BP 13S EP 13S PG 1 WC Hematology SC Hematology GA 592MP UT WOS:000177941700045 ER PT J AU Holness, L Knippen, M Simmons, L AF Holness, L Knippen, M Simmons, L TI Transfusion-related acute lung injury: An update. SO TRANSFUSION LA English DT Meeting Abstract CT 55th Annual Meeting of the American-Association-of-Blood-Banks CY OCT 26-29, 2002 CL ORLANDO, FLORIDA SP Amer Assoc Blood Banks C1 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 2002 VL 42 IS 9 SU S BP 112S EP 113S PG 2 WC Hematology SC Hematology GA 592MP UT WOS:000177941700415 ER PT J AU Orton, SL Tibbals, M Musavi, F Dodd, RY Trouern-Trend, J Cable, RG Armitage, J Alfreds, S Kessler, D AF Orton, SL Tibbals, M Musavi, F Dodd, RY Trouern-Trend, J Cable, RG Armitage, J Alfreds, S Kessler, D TI Preclonation deferral for travel to the United Kingdom. SO TRANSFUSION LA English DT Meeting Abstract CT 55th Annual Meeting of the American-Association-of-Blood-Banks CY OCT 26-29, 2002 CL ORLANDO, FLORIDA SP Amer Assoc Blood Banks C1 New York Blood Ctr, New York, NY 10021 USA. Amer Red Cross, Dedham, DC USA. Amer Red Cross, Roanoke, VA USA. Amer Red Cross, Farmington, CT USA. Amer Red Cross, Rockville, MD 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 2002 VL 42 IS 9 SU S BP 125S EP 126S PG 2 WC Hematology SC Hematology GA 592MP UT WOS:000177941700458 ER PT J AU Tabor, E Epstein, JS AF Tabor, E Epstein, JS TI NAT screening of blood and plasma donations: evolution of technology and regulatory policy SO TRANSFUSION LA English DT Article ID COMPARATIVE SENSITIVITY; HEPATITIS-B; HBVNAT; HBSAG C1 US FDA, Off Blood Res & Review, Rockville, MD 20852 USA. RP Tabor, E (reprint author), US FDA, Off Blood Res & Review, HFM-300,1401 Rockville Pike, Rockville, MD 20852 USA. NR 16 TC 42 Z9 44 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 2002 VL 42 IS 9 BP 1230 EP 1237 DI 10.1046/j.1537-2995.2002.00183.x PG 8 WC Hematology SC Hematology GA 596XD UT WOS:000178191000022 PM 12430684 ER PT J AU Herman, BA Harris, GR AF Herman, BA Harris, GR TI Models and regulatory considerations for transient temperature rise during diagnostic ultrasound pulses SO ULTRASOUND IN MEDICINE AND BIOLOGY LA English DT Article DE temperature rise; biomedical ultrasound; diagnostic ultrasound; ultrasonic heating; exposure regulation; acoustic output ID ACOUSTIC RADIATION FORCE; OUTPUT; EXPOSURE; INDEXES AB A new diagnostic ultrasound (US) technique, sometimes called radiation force imaging, produces and detects motion in solid tissue or acoustic streaming in fluids via a high-intensity beam. Current models for estimating temperature rise during US exposure calculate the steady-state rise, using time-averaged acoustic output, as the worst case for safety consideration. Although valid for very short pulses, this analysis might not correspond to a worst-case scenario for the longer pulses or pulse bursts, up to hundreds of ms, used by this newer method. Models are presented to calculate the transient temperature rise from these pulse bursts for both the bone at focus and soft tissue situation. It is shown, based on accepted time-temperature dose criteria, that, for the bone at focus case and pulse lengths and intensities utilized by these methods, temperature may increase to levels that raise safety concerns. Also, regulatory aspects of this modality are analyzed in terms of the current FDA acoustic output limits for diagnostic US devices. Published by Elsevier Science Inc. on behalf of World Federation for Ultrasound in Medicine Biology. C1 US FDA, CDRH, Rockville, MD 20850 USA. RP Herman, BA (reprint author), US FDA, CDRH, 9200 Corp Blvd,HFZ-132, Rockville, MD 20850 USA. EM bah@cdrh.fda.gov NR 26 TC 64 Z9 65 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-5629 J9 ULTRASOUND MED BIOL JI Ultrasound Med. Biol. PD SEP PY 2002 VL 28 IS 9 BP 1217 EP 1224 AR PII S0301-5629(02)00558-6 DI 10.1016/S0301-5629(02)00558-6 PG 8 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA 606KB UT WOS:000178732200016 PM 12401393 ER PT J AU Amexis, G Rubin, S Chizhikov, V Pelloquin, F Carbone, K Chumakov, K AF Amexis, G Rubin, S Chizhikov, V Pelloquin, F Carbone, K Chumakov, K TI Sequence diversity of Jeryl Lynn strain of mumps virus: Quantitative mutant analysis for vaccine quality control SO VIROLOGY LA English DT Article DE genetic stability; quasispecies; viral vaccine consistency control; MAPREC; oligonucleotide microarray hybridization ID NUCLEOTIDE-SEQUENCE; ASEPTIC-MENINGITIS; NEUROVIRULENCE; EFFICACY; SAFETY AB The Jeryl Lynn strain of mumps vaccine live (MVL) was developed in 1966 by Merck Co. and has been widely used in the U.S. and other countries since the early 1970s. Partial sequencing has recently shown that the vaccine contains a mixture of two substrains with substantially different nucleotide sequences. We have determined the complete genomic sequences of both substrains and identified 414 nucleotide differences (2.69%), leading to 87 amino acid substitutions (1.67%). We used this information to develop methods for quantification of the substrain components in vaccine samples based on PCR and restriction enzyme cleavage and oligonucleotide microarray hybridization and monitored their dynamics in viral populations propagated in different conditions. Passaging Jeryl Lynn strain in Vero or CEF cell cultures resulted in rapid selection of the major component JL1, while growth in embryonated chicken eggs (ECE) favored accumulation of the minor component JL2. Based on the findings presented here, it is proposed that the substrain composition of Jeryl Lynn vaccine can be monitored as a part of its quality control to ensure consistency of the vaccine. (C) 2002 Elsevier Science (USA). C1 US FDA, CBER, Rockville, MD 20852 USA. Aventis Pasteur Serums & Vaccines, Marcy Letoile, France. RP Chumakov, K (reprint author), US FDA, CBER, 1401 Rockville Pike HFM-470, Rockville, MD 20852 USA. NR 22 TC 29 Z9 33 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD SEP 1 PY 2002 VL 300 IS 2 BP 171 EP 179 DI 10.1006/viro.2002.1499 PG 9 WC Virology SC Virology GA 598BC UT WOS:000178254400001 PM 12350348 ER PT J AU Guan, E Wang, JH Roderiquez, G Norcross, MA AF Guan, E Wang, JH Roderiquez, G Norcross, MA TI Natural truncation of the chemokine MIP-1 beta/CCL4 affects receptor specificity but not Anti-HIV-1 activity SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CD8(+) T-CELLS; CD26/DIPEPTIDYL PEPTIDASE-IV; HUMAN-IMMUNODEFICIENCY-VIRUS; MACROPHAGE-TROPIC HIV-1; C-C CHEMOKINES; CHEMOTACTIC ACTIVITY; BETA-CHEMOKINES; CCR5 EXPRESSION; FACTOR 1-ALPHA; RANTES AB Activated lymphocytes synthesize and secrete substantial amounts of the beta-chemokines macrophage inflammatory protein (MIP)-1alpha/CCL3 and MIP-1beta/CCL4, both of which inhibit infection of cells with human immunodeficiency virus type 1 (HIV-1). The native form of MIP-1beta secreted by activated human peripheral blood lymphocytes (MIP-1beta(3-69)) lacks the two NH2-terminal amino acids of the full-length protein. This truncated form of MIP-1beta has now been affinity-purified from the culture supernatant of such cells, and its structure has been confirmed by mass spectrometry. Functional studies of the purified protein revealed that MIP-1beta(3-69) retains the abilities to induce down-modulation of surface expression of the chemokine receptor CCR5 and to inhibit the CCR5-mediated entry of HIV-1 in T cells. Characterization of the chemokine receptor specificity of MIP-1beta(3-69) showed that the truncated protein not only shares the ability of intact MIP-1beta to induce Ca2+ signaling through CCR5, but unlike the full-length protein, it also triggers a Ca2+ response via CCR1 and CCR2b. These results demonstrate that NH2-terminally truncated MIP-1beta functions as a chemokine agonist with expanded receptor reactivity, which may represent an important mechanism for regulation of immune cell recruitment during inflammatory and antiviral responses. C1 US FDA, CBER, Div Therapeut Prot, Bethesda, MD 20892 USA. RP Guan, E (reprint author), US FDA, CBER, Div Therapeut Prot, Bldg 29B,Rm 4E12,HFM 535,8800 Rockville Pike, Bethesda, MD 20892 USA. NR 41 TC 37 Z9 40 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 30 PY 2002 VL 277 IS 35 BP 32348 EP 32352 DI 10.1074/jbc.M203077200 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 588UB UT WOS:000177718700130 PM 12070155 ER PT J AU Temple, RJ Himmel, MH AF Temple, RJ Himmel, MH TI Postmarketing surveillance and black box warnings - Reply SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Temple, RJ (reprint author), US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. NR 2 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 AUG 28 PY 2002 VL 288 IS 8 BP 958 EP 959 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 587RM UT WOS:000177656400018 ER PT J AU Parshikov, IA Moody, JD Heinze, TM Freeman, JP Williams, AJ Sutherland, JB AF Parshikov, IA Moody, JD Heinze, TM Freeman, JP Williams, AJ Sutherland, JB TI Transformation of cinoxacin by Beauveria bassiana SO FEMS MICROBIOLOGY LETTERS LA English DT Article DE antibacterial agent; Beauveria bassiana; biotransformation; cinoxacin ID FUNGUS MUCOR RAMANNIANUS AB The ability of the fungus Beauveria bassiana ATCC 7159 to transform the antibacterial agent cinoxacin was investigated. Cultures in sucrose-peptone broth were dosed with cinoxacin, grown for 20 days, and then extracted with ethyl acetate, Two metabolites were detected and purified by high-performance liquid chromatography. The major metabolite was identified by mass and proton nuclear magnetic resonance spectra as 1-ethyl-1,4-dihydro-3-(hydroxymethyl)[1,3]dioxolo[4,5-g]cinnolin-4-one and the minor metabolite was identified as 1-ethyl-1,4-diliydro-6,7-diliydroxy-3-(hydroxymethyl)cinnolin-4-one. B, bassiana also reduced quinoline-3-carboxylic acid to 3-(hydroxymethyl)quinoline. (C) 2002 Federation of European Microbiological Societies. Published by Elsevier Science B.V. All rights reserved. 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 17 TC 2 Z9 3 U1 1 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1097 J9 FEMS MICROBIOL LETT JI FEMS Microbiol. Lett. PD AUG 27 PY 2002 VL 214 IS 1 BP 133 EP 136 AR PII S0378-1097(02)00858-3 DI 10.1016/S0378-1097(02)00858-3 PG 4 WC Microbiology SC Microbiology GA 592GT UT WOS:000177929100021 PM 12204384 ER PT J AU Mohan, AK Edwards, ET Cote, TR Siegel, JN Braun, MM AF Mohan, AK Edwards, ET Cote, TR Siegel, JN Braun, MM TI Drug-induced systemic lupus erythematosus and TNF-alpha blockers SO LANCET LA English DT Letter C1 US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Mohan, AK (reprint author), US FDA, Ctr Biol Evaluat & Res, 1401 Rockville Pike,Suite 200S, Rockville, MD 20852 USA. NR 5 TC 53 Z9 57 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 24 PY 2002 VL 360 IS 9333 BP 646 EP 646 DI 10.1016/S0140-6736(02)09800-8 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 586TD UT WOS:000177600400042 PM 12241965 ER PT J AU Fromherz, R Gantefor, G Shvartsburg, AA AF Fromherz, R Gantefor, G Shvartsburg, AA TI Isomer-resolved ion spectroscopy SO PHYSICAL REVIEW LETTERS LA English DT Article ID SILICON CLUSTER ANIONS; PHOTOELECTRON-SPECTROSCOPY; SEMICONDUCTOR CLUSTERS; CARBON CLUSTERS; MOBILITY MEASUREMENTS; SCATTERING; CHAINS; SPECTRA; DENSITY; RINGS AB We demonstrate the isomer-resolved spectroscopy of gas-phase ions, with different geometries separated prior to spectroscopic probe using ion mobility techniques. Specifically, ring and chain isomers of carbon cluster anions with 10-12 atoms have been separated by ion mobility/mass spectrometry and examined by photoelectron spectroscopy. This methodology should also apply to other ion spectroscopies, including IR photodissociation. C1 Natl Ctr Toxicol Res, Div Chem, Jefferson, AR 72079 USA. Univ Konstanz, Fachbereich Phys, D-78457 Constance, Germany. RP Shvartsburg, AA (reprint author), Natl Ctr Toxicol Res, Div Chem, HFT-233, Jefferson, AR 72079 USA. NR 34 TC 20 Z9 20 U1 2 U2 12 PU AMERICAN PHYSICAL SOC PI COLLEGE PK PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA SN 0031-9007 J9 PHYS REV LETT JI Phys. Rev. Lett. PD AUG 19 PY 2002 VL 89 IS 8 AR 083001 DI 10.1103/PhysRevLett.89.083001 PG 4 WC Physics, Multidisciplinary SC Physics GA 582FH UT WOS:000177338700014 PM 12190461 ER PT J AU Varricchio, F AF Varricchio, F TI Medication errors reported to the vaccine adverse event reporting system (VAERS) SO VACCINE LA English DT Article C1 US FDA, Off Biostat & Epidemiol, Div Epidemiol, Ctr Biol Evaluat & Review, Rockville, MD 20852 USA. RP Varricchio, F (reprint author), US FDA, Off Biostat & Epidemiol, Div Epidemiol, Ctr Biol Evaluat & Review, 1401 Rockville Pike, Rockville, MD 20852 USA. NR 8 TC 11 Z9 11 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 AUG 19 PY 2002 VL 20 IS 25-26 BP 3049 EP 3051 AR PII S0264-410X(02)00252-9 DI 10.1016/S0264-410X(02)00252-9 PG 3 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 594XD UT WOS:000178076900002 PM 12163255 ER PT J AU Anderson, DL AF Anderson, DL TI Use of radioanalytical techniques at the US Food and Drug Administration. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Natl Inst Stand & Technol, FDA Lab, Gaithersburg, MD 20899 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 18 PY 2002 VL 224 MA 056-NUCL BP U93 EP U93 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 583RM UT WOS:000177422300486 ER PT J AU Contrera, JF AF Contrera, JF TI Estimating the carcinogenic potential of pharmaceuticals using structural similarity clustering and MDL-QSAR electropological descriptors. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA, Off Pharmaceut Sci, Ctr Drug Evaluat & Res Informat & Computat Safety, 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 18 PY 2002 VL 224 MA 028-TOXI BP U365 EP U365 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 583RL UT WOS:000177422201785 ER PT J AU Das, SS Schroeder, LW AF Das, SS Schroeder, LW TI Shelf life of latex medical gloves by accelerated aging. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA, Ctr Devices & Radiol Hlth, Div Mech & Mat Sci, Off Sci & Technol, Rockville, MD 20850 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 18 PY 2002 VL 224 MA 250-PMSE BP U527 EP U527 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 583RM UT WOS:000177422302889 ER PT J AU Heller, DN AF Heller, DN TI Prescription and process for achieving acceptable methods of confirmation. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA, Ctr Vet Med, Laurel, MD 20708 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 18 PY 2002 VL 224 MA 093-ENVR BP U532 EP U532 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 583RL UT WOS:000177422202709 ER PT J AU Heller, DN Betham, RA AF Heller, DN Betham, RA TI Limits to detection, quantitation, and confirmation: The ongoing process of developing recommendations within the mass spectrometry community. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA, Ctr Vet Med, Laurel, MD 20708 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 18 PY 2002 VL 224 MA 086-ENVR BP U531 EP U531 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 583RL UT WOS:000177422202702 ER PT J AU Jansen, SA Duong, T Rossi, L Becoat, C Henry, Y Hajoway, J AF Jansen, SA Duong, T Rossi, L Becoat, C Henry, Y Hajoway, J TI Analysis of pharmaceutical water products for microbial debris. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Temple Univ, Dept Chem, Philadelphia, PA 19122 USA. US FDA, Philadelphia Pharmaceut Lab, Philadelphia, PA 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 18 PY 2002 VL 224 MA 028-ANYL BP U117 EP U117 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 583RL UT WOS:000177422200453 ER PT J AU Lin, YY Fu, TJ AF Lin, YY Fu, TJ TI Evaluation of a fiber-optic biosensor for the detection of pathogen in fresh produce. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 IIT, Dept Food Safety & Technol, Chicago, IL 60616 USA. Natl Ctr Food Safety & Technol, Summit Argo, IL 60501 USA. US FDA, 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 18 PY 2002 VL 224 MA 277-BIOT BP U244 EP U244 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 583RL UT WOS:000177422201141 ER PT J AU McDermott, MK Schroeder, LW Balsis, SL Paradiso, NA Byrne, ML Briber, RM AF McDermott, MK Schroeder, LW Balsis, SL Paradiso, NA Byrne, ML Briber, RM TI Mechanical properties of polyurethane film exposed to solutions of nonoxynol-9 surfactant and polyethylene glycol. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA, Off Sci & Technol, Div Mech & Mat Sci, Rockville, MD 20850 USA. Marquette Univ, Dept Biomed Engn, Milwaukee, WI 53233 USA. Univ Maryland, Dept Mat & Nucl Engn, College Pk, MD 20742 USA. RI Briber, Robert/A-3588-2012 OI Briber, Robert/0000-0002-8358-5942 NR 0 TC 0 Z9 0 U1 1 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 18 PY 2002 VL 224 MA 209-PMSE BP U521 EP U521 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 583RM UT WOS:000177422302848 ER PT J AU McNeal, TP Komolprasert, V Buchalla, R Begley, TH AF McNeal, TP Komolprasert, V Buchalla, R Begley, TH TI Effects of ionizing radiation on food contact materials. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA, Div Chem Res & Environm Review, College Pk, MD 20740 USA. US FDA, Div Food Prod & Packaging, 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 18 PY 2002 VL 224 MA 132-AGFD BP U84 EP U84 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 583RL UT WOS:000177422200276 ER PT J AU Moulton, KE Peggins, JO Chiesa, OA Chamberlain, PL Von Bredow, J Thomas, MH AF Moulton, KE Peggins, JO Chiesa, OA Chamberlain, PL Von Bredow, J Thomas, MH TI Relationship of drug levels in biological fluids to tissue concentrations in bovine steers. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA, CVM, Div Residue Chem, Laurel, MD 20708 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 18 PY 2002 VL 224 MA 065-AGRO BP U106 EP U106 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 583RL UT WOS:000177422200402 ER PT J AU Paquette, KE AF Paquette, KE TI Irradiation of prepackaged food: Evolution of FDA's regulation of the packaging materials. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA, Off Food Addit Safety, College Pk, MD 20740 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 18 PY 2002 VL 224 MA 131-AGFD BP U84 EP U84 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 583RL UT WOS:000177422200275 ER PT J AU Peggins, JO Idowu, OR DeVeau, I Marino, MT von Bredow, JD Thomas, MH AF Peggins, JO Idowu, OR DeVeau, I Marino, MT von Bredow, JD Thomas, MH TI Pharmacokinetics of four different drugs in beef steers and lactating dairy cows. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA, CVM, Div Residue Chem, Laurel, MD 20708 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 18 PY 2002 VL 224 MA 009-AGRO BP U98 EP U98 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 583RL UT WOS:000177422200346 ER PT J AU Roybal, JE Pfenning, AP Turnipseed, SB Gonzalez, SA AF Roybal, JE Pfenning, AP Turnipseed, SB Gonzalez, SA TI Application of photochemical reaction to the liquid chromatographic post-column photolysis and fluorescence detection of antiparasitic veterinary drugs: Avermectins. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA, Anim Drug Res Ctr, Denver, CO 80225 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 18 PY 2002 VL 224 MA 067-AGRO BP U107 EP U107 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 583RL UT WOS:000177422200404 ER PT J AU Shaikh, B Rummel, NG Gieseker, C Serfling, SG Reimschuessel, R AF Shaikh, B Rummel, NG Gieseker, C Serfling, SG Reimschuessel, R TI Metabolism and residue depletion of albendazole and its metabolites in muscle tissue of rainbow trout and tilapia. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA, Ctr Vet Med, Laurel, MD 20708 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 18 PY 2002 VL 224 MA 005-AGRO BP U97 EP U97 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 583RL UT WOS:000177422200342 ER PT J AU Swann, JP AF Swann, JP TI Formation and early growth of the drug laboratory of the USDA Bureau of Chemistry. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Food & Drug Adm Hist Off, 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 18 PY 2002 VL 224 MA 029-HIST BP U597 EP U597 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 583RL UT WOS:000177422203068 ER PT J AU Watson, MT AF Watson, MT TI FDA's policy on food biotechnology. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA, Ctr Food Safety & Appl Nutr HFS 255, College Pk, MD 20740 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 18 PY 2002 VL 224 MA 143-AGFD BP U86 EP U86 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 583RL UT WOS:000177422200287 ER PT J AU Roach, JAG Mossoba, MM Yurawecz, MP Kramer, JKG AF Roach, JAG Mossoba, MM Yurawecz, MP Kramer, JKG TI Chromatographic separation and identification of conjugated linoleic acid isomers SO ANALYTICA CHIMICA ACTA LA English DT Review DE review; conjugated linoleic acid; CLA; Ag+HPLC; GC-FID; dimethyloxazoline; DMOX; methyltriazolinedione; MTAD; GC-MS; GC-FTIR ID PERFORMANCE LIQUID-CHROMATOGRAPHY; THIN-LAYER CHROMATOGRAPHY; TRANSFORM INFRARED-SPECTROSCOPY; HYDROGENATED SOYBEAN OIL; HUMAN-MILK LIPIDS; FATTY-ACID; GAS-CHROMATOGRAPHY; MASS-SPECTROMETRY; POSITIONAL ISOMERS; CLA ISOMERS AB There are 56 possible geometric and positional isomers of conjugated octadecadienoic acids (18:2), better known as conjugated linoleic acid (CLA). Positive health benefits are ascribed to the consumption of the 9c,11t-18:2 and 10t, 12c-18:2 isomers. The dietary significance of the other isomers is not known. Our understanding of the biological role of these acids relies on their proper identification and quantitation in complex biological extracts. Gas chromatography (GC) alone cannot completely separate the naturally occurring CLA isomers. The combination of silver ion high performance liquid chromatography (Ag+ HPLC) and GC offers the best separation of these isomers with complementary identification by GC-mass spectrometry (GC-MS) and GC-Fourier transform infrared (FTIR) analyses. (C) 2002 Elsevier Science B.V. All rights reserved. C1 US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 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, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. NR 75 TC 65 Z9 78 U1 8 U2 33 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 AUG 16 PY 2002 VL 465 IS 1-2 BP 207 EP 226 AR PII S0003-2670(02)00193-9 DI 10.1016/S0003-2670(02)00193-9 PG 20 WC Chemistry, Analytical SC Chemistry GA 584JK UT WOS:000177463300014 ER PT J AU Crawford, LM AF Crawford, LM TI Limited approval for Lotronex SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material C1 US FDA, Off Commissioner Food & Drugs, Rockville, MD 20857 USA. RP Crawford, LM (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 AUG 14 PY 2002 VL 288 IS 6 BP 688 EP 688 DI 10.1001/jama.288.6.688 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 583KY UT WOS:000177408100005 PM 12169049 ER PT J AU Crawford, LM AF Crawford, LM TI Proposed reporting guidance SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material C1 US FDA, Off Commissioner Food & Drugs, Rockville, MD 20857 USA. RP Crawford, LM (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 AUG 14 PY 2002 VL 288 IS 6 BP 688 EP 688 DI 10.1001/jama.288.6.688 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 583KY UT WOS:000177408100007 PM 12169049 ER PT J AU Crawford, LM AF Crawford, LM TI Xenotransplantation advisory SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material C1 US FDA, Off Commissioner Food & Drugs, Rockville, MD 20857 USA. RP Crawford, LM (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 AUG 14 PY 2002 VL 288 IS 6 BP 688 EP 688 DI 10.1001/jama.288.6.688 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 583KY UT WOS:000177408100004 PM 12169049 ER PT J AU Crawford, LM AF Crawford, LM TI Revision of grant program SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material C1 US FDA, Off Commissioner Food & Drugs, Rockville, MD 20857 USA. RP Crawford, LM (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 AUG 14 PY 2002 VL 288 IS 6 BP 688 EP 688 DI 10.1001/jama.288.6.688 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 583KY UT WOS:000177408100006 PM 12169049 ER PT J AU Tolleson, WH Doerge, DR Churchwell, MI Marques, MM Roberts, DW AF Tolleson, WH Doerge, DR Churchwell, MI Marques, MM Roberts, DW TI Metabolism of biochanin A and formononetin by human liver microsomes in vitro SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE isoflavone metabolism; cytochrome P450; biochanin A; formononetin ID NEONATAL EXPOSURE; RUMEN FLUID; FEMALE RATS; GENISTEIN; ISOFLAVONES; PHYTOESTROGENS; DAIDZEIN; CANCER; URINE; BIOAVAILABILITY AB Biochanin A and formononetin are abundant-in legumes.., These proestrogenic isoflavones can be converied by 4'-O-demethylation to the more potent phytoestrogens genistein and daidzein. Incubation of biochanin A or formononetin with human, liver microsomes resulted in 4'-O-demethylation and the production of additional metabolites. Three new hydroxylated formohonetin derivatives, 6,7-dihydroxy-4'-methoxyisoflavone, 7,8-dihydroxy-4'-methoxyisoflavone, and 7,3'-dihydroxy-4'-methoxyisoflavone, were isolated and characterized. We surveyed the O-demethylase competence of cytochrome P450 isoforms found in human liver. Human cytochrome P450 isoforms 1A2, 2E1, 2C9*1, 2C19, and 2D6*1 catalyzed biochanin A consumption and genistein production. Human cytochrome P450 isoforms 1A2, 2C9*1, 2A6, 2D6*1, and 2C19 catalyzed formononetin consumption and daidzein production. These, isoforms also generated other hydroxylated, metabolites. Although O-demethylation of isoflavones has been attributed to metabolism,by gut microflora, our study, demonstrates that human hepatic microsomal enzymes can perform the same transformation and may play a key role in the conversion of 4'-O-methylated isoflavones to more potent phytoestrogens. C1 Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. Univ Tecn Lisboa, Ctr Quim Estrutural, Inst Super Tecn, P-1049001 Lisbon, Portugal. RP Roberts, DW (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM droberts@nctr.fda.gov RI Marques, M. Matilde/E-2535-2012 OI Marques, M. Matilde/0000-0002-7526-4962 NR 23 TC 76 Z9 80 U1 3 U2 15 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0021-8561 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD AUG 14 PY 2002 VL 50 IS 17 BP 4783 EP 4790 DI 10.1021/jf025549r PG 8 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 582ME UT WOS:000177354400007 PM 12166960 ER PT J AU Weisz, A Mazzola, EP Murphy, CM Ito, Y AF Weisz, A Mazzola, EP Murphy, CM Ito, Y TI Preparative separation of isomeric sulfophthalic acids by conventional and pH-zone-refining counter-current chromatography SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article; Proceedings Paper CT 22nd ACS National Meeting CY AUG 26-30, 2001 CL CHICAGO, ILLINOIS SP ACS DE counter-current chromatography; preparative chromatography; sulfophthalic acids; organosulfur compounds; phthalic acids; D&C Yellow No. 10; dyes ID COIL PLANET CENTRIFUGE; LIQUID-CHROMATOGRAPHY; PURIFICATION; DERIVATIVES; PHASE AB Two modes of high-speed counter-current chromatography (HSCCC) were applied to separate 3- and 4-sulfophthalic acid from a mixture. Conventional HSCCC was useful for the separation of up to several hundred milligram quantities of these positional isomers, while pH-zone-refining CCC was implemented successfully to separations at the multigram level. The conventional HSCCC separations were performed with a standard J-type HSCCC system that has a superior resolution but a lower level of retention of the stationary phase of the biphasic solvent system used (acidified n-butanol-water). The pH-zone-refining CCC separations were performed with an X-type HSCCC system (a cross-axis system) that has a higher capability for retention of the stationary phase. The purified positional isomers (over 99% pure as determined by HPLC) were characterized by H-1 NMR and negative ion electrospray ionization mass spectrometry. Published by Elsevier Science B.V. C1 US FDA, Off Cosmet & Colors, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. US FDA, Off Sci Anal & Support, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. RP Weisz, A (reprint author), US FDA, Off Cosmet & Colors, Ctr Food Safety & Appl Nutr, 200 C St SW, Washington, DC 20204 USA. NR 21 TC 28 Z9 32 U1 3 U2 21 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR A JI J. Chromatogr. A PD AUG 9 PY 2002 VL 966 IS 1-2 BP 111 EP 118 AR PII S0021-9673(02)00695-7 DI 10.1016/S0021-9673(02)00695-7 PG 8 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 582DJ UT WOS:000177334200011 PM 12214685 ER PT J AU Wang, RF Beggs, ML Robertson, LH Cerniglia, CE AF Wang, RF Beggs, ML Robertson, LH Cerniglia, CE TI Design and evaluation of oligonucleotide-microarray method for the detection of human intestinal bacteria in fecal samples SO FEMS MICROBIOLOGY LETTERS LA English DT Article DE oligonucleotide-microarray; human intestinal bacterium; polymerase chain reaction; 16S rDNAs amplification ID 16S RIBOSOMAL-RNA; PCR DETECTION; MICROFLORA; ENVIRONMENT; FLORA; COLON AB An oligonucleotide-microarray method was developed for the detection of intestinal bacteria in fecal samples collected from human subjects. The 16S rDNA sequences of 20 predominant human intestinal bacterial species were used to design oligonucleotide probes. Three 40-mer oligonucleotides specific for each bacterial species (total 60 probes) were synthesized and applied to glass slides. Cyanine5 (CY5)-labeled 16S rDNAs were amplified by polymerase chain reaction (PCR) from human fecal samples or bacterial DNA using two universal primers and were hybridized to the oligo-microarray. The 20 intestinal bacterial species tested were Bacteroides thetaiotaomicron, Bacteroides vulgatus, Bacteroides fragilis, Bacteroides distasonis, Clostridium clostridiiforme, Clostridium leptum, Fusobacterium prausnitzii, Peptostreptococcus productus, Ruminococcus obeum, Ruminococcus bromii, Ruminococcus callidus, Ruminococcus albus, Bifidobacterium longum, Bifidobacterium adolescentis, Bifidobacterium infantis, Eubacterium biforme, Eubacterium aerofaciens, Lactobacillus acidophilus, Escherichia coli, and Enterococcus faecium. The two universal primers were able to amplify full size 16S rDNA from all of the 20 bacterial species tested. The hybridization results indicated that the oligo-microarray method developed in this study is a reliable method for the detection of predominant human intestinal bacteria in the fecal samples. (C) 2002 Federation of European Microbiological Societies. Published by Elsevier Science B.V. All rights reserved. C1 US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. Univ Arkansas Med Sci, Dept Geriatr, Core Microarray Facil, Little Rock, AR 72205 USA. RP Wang, RF (reprint author), US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. NR 26 TC 92 Z9 113 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1097 J9 FEMS MICROBIOL LETT JI FEMS Microbiol. Lett. PD AUG 6 PY 2002 VL 213 IS 2 BP 175 EP 182 AR PII S0378-1097(02)00802-9 DI 10.1111/j.1574-6968.2002.tb11302.x PG 8 WC Microbiology SC Microbiology GA 586LF UT WOS:000177584900005 PM 12167534 ER PT J AU Jensen, V Kimzey, LM Goldberger, MJ AF Jensen, V Kimzey, LM Goldberger, MJ TI FDA's role in responding to drug shortages SO AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY LA English DT Article C1 US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Jensen, V (reprint author), US FDA, Ctr Drug Evaluat & Res, 5600 Fishers Lane, Rockville, MD 20857 USA. NR 2 TC 18 Z9 20 U1 0 U2 2 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 AUG 1 PY 2002 VL 59 IS 15 BP 1423 EP 1425 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 580LW UT WOS:000177236900009 PM 12166041 ER PT J AU Brinker, AD Beitz, J AF Brinker, AD Beitz, J TI Spontaneous reports of thrombocytopenia in association with quinine: Clinical attributes and timing related to regulatory action SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article DE quinine; thrombocytopenia; quinine-associated thrombocytopenia ID TONIC WATER AB Quinine has been marketed in the United States (U.S.) both over-the-counter (OTC) and by prescription for numerous purposes, including malaria and muscle spasms. In 1994 and 1995, the U.S. Food and Drug Administration (FDA) acted to limit the marketing of quinine based on the conclusion that no data supported its safe and efficacious use in these settings. This report includes clinical attributes from the largest case series to date of apparently isolated thrombocytopenia in association with quinine and trends in the receipt of spontaneous adverse event reports to FDA's Center for Drug Evaluation and Research (CDER) for this drug-event combination in relation to regulatory action. In this study, we reviewed reports of spontaneous adverse drug events received by CDER. From 1974 through December 2000, CDER received 397 adverse event reports for quinine. Based on crude, unreviewed counts, 141 (35.5%) of these reports described apparently isolated thrombocytopenia. Reporting for this event peaked in 1995, coincident with regulatory action, and has subsequently declined. After elimination of cases confounded by acute or chronic disease or concomitant drug therapy, 64 reports of quinine-associated thrombocytopenia were used to form a case series. This case series, including 11 cases since January 1996, supports the potential for rapid time-to-onset (median 7 days) and clinical severity (hospitalization reported in 55 of the 64 cases). Although the number of reports since regulatory action is limited, CDER continues to receive reports of thrombocytopenia in association with quinine in use for nocturnal leg cramps. Extrapolation of spontaneous adverse event reports for a product with substantial OTC use precludes estimates of rates/incidence. Therefore, the effect of regulatory actions in 1994/1995 is difficult to measure using this approach. Although reports have decreased since regulatory actions on quinine, quinine remains available in the U.S. by prescription and in food products/dietary supplements. This case series confirms previous smaller series that suggest quinine-associated thrombocytopenia may present rapidly with symptoms of profound thrombocytopenia. Clinicians evaluating patients with new-onset and apparently idiopathic thrombocytopenia should maintain clinical vigilance for ingestion of quinine and elicit a detailed food/dietary supplement history from the patient. Published 2002 Wiley-Liss, Inc.(dagger). C1 US FDA, Ctr Drug Evaluat & Res, Div Drug Risk Evaluat, Off Drug Safety, Rockville, MD 20857 USA. RP Brinker, AD (reprint author), 5600 Fishers Lane,Rm 15B-08, Rockville, MD 20857 USA. NR 22 TC 16 Z9 17 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD AUG PY 2002 VL 70 IS 4 BP 313 EP 317 DI 10.1002/ajh.10148 PG 5 WC Hematology SC Hematology GA 578VH UT WOS:000177141200007 PM 12210813 ER PT J AU Kawakami, K Kawakami, M Puri, RK AF Kawakami, K Kawakami, M Puri, RK TI Cytokine receptor as a sensitizer for targeted cancer therapy SO ANTI-CANCER DRUGS LA English DT Review DE cytotoxin therapy; Fas/CD95; gene transfer; immunotherapy; interleukin-13 receptor; sensitization ID TUMOR-NECROSIS-FACTOR; CARCINOMA CELL-LINES; PERMUTED INTERLEUKIN 4-TOXIN; FAS-MEDIATED CYTOTOXICITY; HUMAN-MALIGNANT GLIOMA; INDUCED APOPTOSIS; GENE-TRANSFER; PSEUDOMONAS EXOTOXIN; ALPHA-CHAIN; SIGNAL-TRANSDUCTION AB Introducing a cytokine receptor as a sensitizer into cancer cells offers a unique opportunity for receptor-targeted cancer therapy. It has been shown that transfection of the tumor necrosis factor (TNF) receptor gene in cancer cells or exposing cancer cells to certain reagents which increase expression of TNF receptors results in enhancement of the cytotoxic effect of TNF. In addition, the literature suggests that Fas/CD95-mediated apoptotic tumor cell killing is augmented by gene transfer of Fas Into cancer cells or treatment of cells with agents like cisplatin and interferon (IFN)-gamma. In contrast to these approaches, we have discovered a new approach to cancer therapy; wherein introduction of a cytokine receptor chain into cancer cells sensitizes them to receptor-directed cytotoxins. We have demonstrated that when interieukin (IL)-13 receptor (IL-13R) alpha2 chain, one of the two known IL-13 binding proteins, is introduced into cancer cells that do not express this chain the cells acquire extreme sensitivity to a chimeric fusion cytotoxin composed of IL-13 and a mutated form of Pseudomonas exotoxin (IL13-PE). Cells that do not express this chain or express low levels show limited sensitivity to IL13-PE. Acquisition of sensitivity to IL13-PE was observed both in vitro and in vivo when IL-13Ralpha2-transtected human tumor cells were implanted in immunodeficient animals followed by systemic or regional IL13-PE therapy. Our third generation experiments suggest that this approach is feasible for clinical situations as intratumor administration of plasmid carrying the IL-13Ralpha2 chain gene sensitized these tumors to systemic or regional IL13-PE therapy. This unique approach comprising gene transfer of cytokine receptor chain and receptor-targeted cytotoxin administration represents a novel strategy for cancer therapy. [(C) 2002 Lippincott Williams Wilkins.]. C1 US FDA, Ctr Biol Evaluat & Res, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, Bethesda, MD 20892 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 77 TC 8 Z9 10 U1 0 U2 4 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 AUG PY 2002 VL 13 IS 7 BP 693 EP 699 DI 10.1097/00001813-200208000-00003 PG 7 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 585FV UT WOS:000177515500003 PM 12187325 ER PT J AU Hanes, DE Worobo, RW Orlandi, PA Burr, DH Miliotis, MD Robl, MG Bier, JW Arrowood, MJ Churey, JJ Jackson, GJ AF Hanes, DE Worobo, RW Orlandi, PA Burr, DH Miliotis, MD Robl, MG Bier, JW Arrowood, MJ Churey, JJ Jackson, GJ TI Inactivation of Cryptosporidium parvum oocysts in fresh apple cider by UV irradiation SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID MICE AB This study evaluated the efficacy of UV irradiation on the inactivation of Cryptosporidium pan,urn oocysts in fresh apple cider. Cider was inoculated with oocysts and exposed to 14.32 mJ of UV irradiation/cm(2). Oocyst viability was assessed with the gamma interferon gene knockout (GKO) mouse and infant BALB/cByJ mouse models. All GKO mice challenged with UV-treated cider demonstrated no morbidity or mortality, and infant BALB/c mice challenged with treated cider were negative for the presence of C. parvum. In contrast, the GKO mice challenged with non-UV-treated inoculated cider died and the parasite was detected in the ileums of all challenged infant mice. This study shows that UV irradiation can be used to inactivate C. par,tan in fresh apple cider. C1 US FDA, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. US FDA, Washington, DC 20204 USA. Cornell Univ, New York State Agr Expt Stn, Dept Food Sci & Technol, Geneva, NY 14456 USA. Ctr Dis Control & Prevent, Div Parasit Dis, Atlanta, GA USA. RP Hanes, DE (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 8301 Muirkirk Rd, Laurel, MD 20708 USA. RI Worobo, Randy/D-8779-2014 NR 27 TC 54 Z9 57 U1 1 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0099-2240 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD AUG PY 2002 VL 68 IS 8 BP 4168 EP 4172 DI 10.1128/AEM.68.8.4168-4172.2002 PG 5 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 580WV UT WOS:000177260500071 PM 12147528 ER PT J AU Pfefer, TJ Schomacker, KT Ediger, MN Nishioka, NS AF Pfefer, TJ Schomacker, KT Ediger, MN Nishioka, NS TI Multiple-fiber probe design for fluorescence spectroscopy in tissue SO APPLIED OPTICS LA English DT Article ID LASER-INDUCED FLUORESCENCE; HUMAN COLON TISSUE; TURBID MEDIA; IN-VIVO; OPTICAL-PROPERTIES; AUTOFLUORESCENCE; DEPTH; MODEL; LIGHT; PROPAGATION AB The fiber-optic probe is an essential component of many quantitative fluorescence spectroscopy systems, enabling delivery of excitation light and collection of remitted fluorescence in a wide variety of clinical and laboratory situations. However, there is little information available on the role of illumination-collection geometry to guide the design of these components. Therefore we used a Monte Carlo model to investigate the effect of multifiber probe design parameters-numerical aperture, fiber diameter, source-collection fiber separation distance, and fiber-tissue spacer thickness-on light propagation and the origin of detected fluorescence. An excitation wavelength of 400 ran and an emission wavelength of 630 nm were simulated. Noteworthy effects included an increase in axial selectivity with decreasing fiber size and a transition with increasing fiber-tissue spacer size from a subsurface peak in fluorophore sensitivity to a nearly monotonic decrease typical of single-fiber probes. We provide theoretical evidence that probe design strongly affects tissue interrogation. Therefore application-specific customization of probe design may lead to improvements in the efficacy of fluorescence-based diagnostic devices. (C) 2002 Optical Society of America. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed, Boston, MA 02114 USA. RP Pfefer, TJ (reprint author), US FDA, Ctr Radiol Hlth, FDS CDRH HFZ-134,12725 Twinbrook Pkwy, Rockville, MD 20857 USA. EM josh@eob.cdrh.fda.gov RI Pfefer, Josh/I-9055-2012 NR 36 TC 70 Z9 70 U1 1 U2 5 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1559-128X EI 2155-3165 J9 APPL OPTICS JI Appl. Optics PD AUG 1 PY 2002 VL 41 IS 22 BP 4712 EP 4721 DI 10.1364/AO.41.004712 PG 10 WC Optics SC Optics GA 579NY UT WOS:000177185800040 PM 12153108 ER PT J AU Zeuner, RA Ishii, KJ Lizak, MJ Gursel, I Yamada, H Klinman, DM Verthelyi, D AF Zeuner, RA Ishii, KJ Lizak, MJ Gursel, I Yamada, H Klinman, DM Verthelyi, D TI Reduction of CpG-induced arthritis by suppressive oligodeoxynucleotides SO ARTHRITIS AND RHEUMATISM LA English DT Article ID 4TH INTERNATIONAL-WORKSHOP; BACTERIAL-DNA; REACTIVE ARTHRITIS; ACTIVATION; MOTIFS; CELLS AB Objective. Bacterial DNA contains immunostimulatory CpG motifs that cause inflammation when injected into the knee joints of normal mice. We examined whether synthetic oligodeoxynucleotides (ODN) that suppress CpG-induced immune responses prevent CpG-induced arthritis. Methods. CpG, suppressive, and/or control ODN were injected into the knees of BALB/c mice. joint swelling and inflammation were evaluated by physical measurement, by histologic analysis of joint tissue, and by magnetic resonance imaging. Results. Immunostimulatory CpG DNA induced local arthritis, characterized by swelling of the knee joints, the presence of inflammatory cell infiltrates, the perivascular accumulation of mononuclear cells, and hyperplasia of the synovial lining. Administering suppressive (but not control) ODN reduced the manifestations and severity of arthritis up to 80%. Conclusion. Suppressive ODN may be useful for the prevention or treatment of arthritis induced by bacterial DNA. C1 US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. NINDS, NIH, Bethesda, MD 20892 USA. Univ Kiel, D-24098 Kiel, Germany. RP Klinman, DM (reprint author), US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, 8800 Rockville Pike,Bldg 29A,Room 3D10, Bethesda, MD 20014 USA. RI Ishii, Ken/B-1685-2012; OI Ishii, Ken/0000-0002-6728-3872; Gursel, Ihsan/0000-0003-3761-1166 NR 15 TC 67 Z9 73 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD AUG PY 2002 VL 46 IS 8 BP 2219 EP 2224 DI 10.1002/art.10423 PG 6 WC Rheumatology SC Rheumatology GA 583WB UT WOS:000177432800031 PM 12209528 ER PT J AU Zaslavsky, B Uthus, EO AF Zaslavsky, B Uthus, EO TI Response of liver and heart trace elements in rats to the interaction between dietary zinc and iron SO BIOLOGICAL TRACE ELEMENT RESEARCH LA English DT Article DE iteraction; zinc; iron; discriminant analysis; analysis of variance ID DEFICIENCY; PARAMETERS AB An analysis of the interaction between dietary iron (Fe) and zinc (Zn) was performed by using data from Sprague-Dawley rats in a 5 x 4 fully crossed factorially arranged experiment. The concentrations of 9 trace elements from the liver and 10 from the heart were determined and subjected to diverse statistical analyses and were classified by their response to the interaction between dietary Fe and Zn. The interaction was studied by using analysis of variance (ANOVA), discriminant analysis, and logistic regression to determine the direction of interaction; that is, did dietary Fe affect dietary Zn or did dietary Zn affect dietary Fe? The use of discriminant analysis allowed for using multiple parameters (rather than a single parameter) to determine possible interactions between Fe and Zn. Thus, two main levels of interaction were studied: the separate response of each tissue mineral and the response of some grouped minerals. The responses studied were the effect of dietary Zn on tissue trace element parameters, the effect of dietary Fe on the parameters, the effect of dietary Zn on combined (grouped) parameters, and the effect of dietary Fe on combined parameters. As determined by ANOVA, only three individual trace elements-liver Fe, Cu, and Mo-were significantly affected by the interaction between Fe and Zn. However, a broader interaction between Fe and Zn is revealed when groups of, rather than single, trace elements are studied. For example, an interaction between dietary Fe and Zn affects the weighted linear combination of heart Ca, Cu, K, Mg, Mn, P, and Zn. This article presents the hypothesis that grouped parameters may be useful as status indicators. The complete dataset can be found at http://www.gfhnrc.ars.usda.gov/fezn. C1 ARS, USDA, Grand Forks Human Nutr Res Ctr, Grand Forks, ND 58202 USA. US FDA, CBER HFM217, Rockville, MD 20852 USA. RP Uthus, EO (reprint author), ARS, USDA, Grand Forks Human Nutr Res Ctr, POB 9034, Grand Forks, ND 58202 USA. NR 13 TC 1 Z9 1 U1 0 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0163-4984 J9 BIOL TRACE ELEM RES JI Biol. Trace Elem. Res. PD AUG PY 2002 VL 88 IS 2 BP 165 EP 183 PG 19 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 594QR UT WOS:000178062700008 PM 12296427 ER PT J AU Dyck, PJ Turner, DW Davies, JL O'Brien, PC Dyck, PJB Rask, CA AF Dyck, PJ Turner, DW Davies, JL O'Brien, PC Dyck, PJB Rask, CA CA rhNGF Grp TI Electronic case-report forms of symptoms and impairments of peripheral neuropathy SO CANADIAN JOURNAL OF NEUROLOGICAL SCIENCES LA English DT Article AB Background and objective: For the conduct of controlled clinical trials, epidemiologic surveys or even of medical practice of varieties of peripheral neuropathy, the usefulness, error rate and cost-effectiveness of scannable case-report forms has not been studied. Materials and methods: The overall performance, the frequency of the problems identified and corrected, and the time saved from use of a standard paper case report form was evaluated in multicenter treatment trials, single center epidemiologic surveys and in our neurologic practice. The paper case report form (Clinical Neuropathy Assessment [CNA]) for pen entry at study medical centers for patient, disease and demographic information (Lower Limb Function [LLF] and Neuropathy Impairment Score [NIS]) can be faxed to a core Reading and Quality Assurance Center where the form and data is electronically and interactively evaluated and corrected, if needed, by participating medical centers before electronic entry into database. Observations and conclusions: 1) The approach provides a standard, scannable paper case report form for pen entry of neuropathy symptoms, impairments and disability at the bedside or in the office which is retained as a source document at the participating medical center but a facsimile can be transferred instantaneously, its data can be programmed, interactively evaluated, modified and stored while maintaining an audit trail; 2) it allowed efficient and accurate reading, transfer, analysis, and storage of data of more than 15,000 forms used in multicenter trials: 3) in 500 consecutive CNA evaluations, software programs identified and facilitated interactive corrections of omissions, discrepancies, and disease and study inconsistencies, introducing only a few readily identified and corrected entry errors; and 4) use of programmed, as compared to non-programmed assessment, was more accurate than double keyboard entry of data and was approximately five times faster. C1 Mayo Clin & Mayo Fdn, Peripheral Neuropathy Res Ctr, Rochester, MN 55905 USA. Mayo Clin & Mayo Fdn, Dept Syst Support Serv, Rochester, MN 55905 USA. Mayo Clin & Mayo Fdn, Biostat Sect, Rochester, MN 55905 USA. US FDA, Rockville, MD 20857 USA. RP Dyck, PJ (reprint author), 200 1st St SW, Rochester, MN 55905 USA. FU NINDS NIH HHS [NS36797] NR 13 TC 19 Z9 19 U1 0 U2 4 PU CANADIAN J NEUROL SCI INC PI CALGARY PA PO BOX 4220, STATION C EDITORIAL & SUBSCRIPTION SERV, CALGARY, AB T2T 5N1, CANADA SN 0317-1671 J9 CAN J NEUROL SCI JI Can. J. Neurol. Sci. PD AUG PY 2002 VL 29 IS 3 BP 258 EP 266 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 582LA UT WOS:000177351300011 PM 12195616 ER PT J AU Rathbone, MJ Martinez, MN AF Rathbone, MJ Martinez, MN TI Modified release drug delivery in veterinary medicine SO DRUG DISCOVERY TODAY LA English DT Review ID ESTRADIOL BIODEGRADABLE MICROSPHERES; GASTRIC RETENTION; OVULATION; PROGESTERONE; MARES; CARCASS; SYSTEMS; ESTRUS; MANAGEMENT; IMPLANT AB To successfully research and develop an animal pharmaceutical dosage form, a diverse array of issues covering basic medicine, pharmacology and technology must be addressed. Societal concerns regarding animal and public health, as well as the rapidly changing farming and economic environments, provide additional challenges that require integration into an already complex web of issues. Here, we examine the drive towards reducing the frequency of administration to animals and the closing of gaps between the human and veterinary drug product development. C1 InterAg, Hamilton, New Zealand. Food & Drug Adm, Ctr Vet Med, HFV 130, Rockville, MD 20855 USA. RP Rathbone, MJ (reprint author), InterAg, 558 Te Rapa Rd,POB 20055, Hamilton, New Zealand. NR 49 TC 13 Z9 13 U1 1 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1359-6446 J9 DRUG DISCOV TODAY JI Drug Discov. Today PD AUG 1 PY 2002 VL 7 IS 15 BP 823 EP 829 AR PII S1359-6446(02)02362-0 DI 10.1016/S1359-6446(02)02362-0 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 578UK UT WOS:000177138600010 PM 12546970 ER PT J AU Ho, AY Lopez, AS Eberhart, MG Levenson, R Finkel, BS da Silva, AJ Roberts, JM Orlandi, PA Johnson, CC Herwaldt, BL AF Ho, AY Lopez, AS Eberhart, MG Levenson, R Finkel, BS da Silva, AJ Roberts, JM Orlandi, PA Johnson, CC Herwaldt, BL TI Outbreak of cyclosporiasis associated with imported raspberries, Philadelphia, Pennsylvania, 2000 SO EMERGING INFECTIOUS DISEASES LA English DT Article ID EXTRACTION AB An outbreak of cyclosporiasis occurred in attendees of a wedding reception held in Philadelphia, Pennsylvania, on June 10, 2000. In a retrospective cohort study, 54 (68.4%) of the 79 interviewed guests and members of the wedding party met the case definition. The wedding cake, which had a cream filling that included raspberries, was the food item most strongly associated with illness (multivariate relative risk, 5.9; 95% confidence interval, 3.6 to 10.5). Leftover cake was positive for Cyclospora DNA by polymerase chain reaction analyses. Sequencing of the amplified fragments confirmed that the organism was Cyclospora cayetanensis. The year 2000 was the fifth year since 1995 that outbreaks of cyclosporiasis definitely or probably associated with Guatemalan raspberries have occurred in the spring in North America. Additionally, this is the second documented U.S. outbreak, and the first associated with raspberries, for which Cyclospora has been detected in the epidemiologically implicated food item. C1 Philadelphia Dept Publ Hlth, Div Dis Control, Philadelphia, PA 19146 USA. Atlanta Res & Educ Fdn, Atlanta, GA USA. Ctr Dis Control & Prevent, Atlanta, GA USA. US FDA, Washington, DC 20204 USA. RP Ho, AY (reprint author), Philadelphia Dept Publ Hlth, Div Dis Control, 500 S Broad St,2nd Floor, Philadelphia, PA 19146 USA. EM Alicc.Ho@phila.gov NR 16 TC 77 Z9 82 U1 1 U2 6 PU CENTERS DISEASE CONTROL PI ATLANTA PA 1600 CLIFTON RD, ATLANTA, GA 30333 USA SN 1080-6040 EI 1080-6059 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD AUG PY 2002 VL 8 IS 8 BP 783 EP 788 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 580NG UT WOS:000177240200005 PM 12141962 ER PT J AU Epstein, SL Tumpey, TM Misplon, JA Lo, CY Cooper, LA Subbarao, K Renshaw, M Sambhara, S Katz, JM AF Epstein, SL Tumpey, TM Misplon, JA Lo, CY Cooper, LA Subbarao, K Renshaw, M Sambhara, S Katz, JM TI DNA vaccine expressing conserved influenza virus proteins protective against H5N1 challenge infection in mice SO EMERGING INFECTIOUS DISEASES LA English DT Article ID A VIRUS; HONG-KONG; HETEROSUBTYPIC IMMUNITY; HETEROLOGOUS PROTECTION; CROSS-PROTECTION; DEFICIENT MICE; T-CELLS; HUMANS; HEMAGGLUTININ; CD8(+) AB Influenza vaccination practice, which is based on neutralizing antibodies, requires being able to predict which viral strains will be circulating. If an unexpected strain, as in the 1997 H5N1 Hong Kong outbreak, or even a pandemic emerges, appropriate vaccines may take too long to prepare. Therefore, strategies based on conserved influenza antigens should be explored. We studied DNA vaccination in mice with plasmids expressing conserved nucleoprotein (NP) and matrix (M) from an H1N1 virus. After vaccination, mice were challenged with A/H5N1 viruses of low, intermediate, and high lethality. A/NP+A/M DNA vaccination reduced replication of A/Hong Kong/486/97 (HK/486), a nonlethal H5N1 strain, and protected against lethal challenge with more virulent A/Hong Kong/156/97 (HK/156). After HK/156 exposure, mice survived rechallenge with A/Hong Kong/483/97 (HK/483), although the DNA vaccination alone protected poorly against this highly virulent strain. In the absence of antigenically matched hemagglutinin-based vaccines, DNA vaccination with conserved influenza genes may provide a useful first line of defense against a rapidly spreading pandemic virus. C1 US FDA, Rockville, MD 20857 USA. United States Dept Agri, Athens, GA USA. Ctr Dis Control & Prevent, Atlanta, GA USA. RP Epstein, SL (reprint author), US FDA, CBER, OTRR, DCGT, 1401 Rockville Pike,HFM-521, Rockville, MD 20852 USA. NR 41 TC 120 Z9 133 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 AUG PY 2002 VL 8 IS 8 BP 796 EP 801 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 580NG UT WOS:000177240200007 PM 12141964 ER PT J AU Luu, HMD Hutter, JC AF Luu, HMD Hutter, JC TI Rebuttal and critical review of Andersen et al.'s D-4 PBPK model SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Letter ID OCTAMETHYLCYCLOTETRASILOXANE; RATS; EXPOSURE; HUMANS; VAPOR C1 US FDA, Ctr Devices & Radiol Hlth, Off Sci & Technol, Rockville, MD 20857 USA. RP Luu, HMD (reprint author), US FDA, Ctr Devices & Radiol Hlth, Off Sci & Technol, Rockville, MD 20857 USA. NR 16 TC 0 Z9 0 U1 0 U2 0 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD AUG PY 2002 VL 110 IS 8 BP A445 EP A448 PG 4 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 583FK UT WOS:000177395900005 ER PT J AU Inoue, H Miyaji, M Kosugi, A Nagafuku, M Okazaki, T Mimori, T Amakawa, R Fukuhara, S Domae, N Bloom, ET Umehara, H AF Inoue, H Miyaji, M Kosugi, A Nagafuku, M Okazaki, T Mimori, T Amakawa, R Fukuhara, S Domae, N Bloom, ET Umehara, H TI Lipid rafts as the signaling scaffold for NK cell activation: tyrosine phosphorylation and association of LAT with phosphatidylinositol 3-kinase and phospholipase C-gamma following CD2 stimulation SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE NK cell; lipid raft; CD2; linker for activation of T cells; cytotoxicity ID NATURAL-KILLER-CELLS; T-CELLS; INHIBITORY RECEPTORS; ADAPTER PROTEINS; KINASE P72(SYK); FC-RECEPTOR; TRANSDUCTION; ANTIGEN; LYMPHOCYTES; BINDING 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. Although it has been well understood that lipid rafts (rafts) and a raft-associated linker for activation of T cells (LAT) plays a central role in TCR signal transduction, there are still great gaps in our knowledge of the molecular events involved in NK cell activation. We show here that CD2 and rafts became polarized to the site of NK cell activation by CD2 cross-linking or target cell binding using confocal microscopy, and LAT and a significant amount of CD2 colocalized in raft fractions of sucrose-density gradient from an NK cell line, NK3.3. CD2 cross-linking strongly induced tyrosine phosphorylation of LAT, resulting in increased association with phosphatidylinositol 3-kinase (PI 3-K) and phospholipase C-gamma1 (PLC-gamma1). In vitro binding studies using glutathione S-transferase fusion proteins demonstrated that a large portion of the association between LAT and PI 3-K or PLC-gamma1 was mediated through their SH2 domains in tyrosine phosphorylation-dependent manner. Furthermore, disruption of lipid rafts by cholesterol depletion from cell membranes using methyl-P-cyclodextrin markedly reduced LAT tyrosine phosphorylation and NK cell functions, including cytotoxicity and granule exocytosis. These results document that modulation of raft integrity by aggregation of NK cell activating receptors, which leads to the formation of complexes of LAT with PI 3-K and PLC-gamma1, is essential for the NK cell lytic mechanisms. C1 Kyoto Univ, Grad Sch Med, Dept Rheumatol & Clin Immunol, Sakyo Ku, Kyoto 6068507, Japan. Osaka Dent Univ, Dept Physiol, Osaka, Japan. Osaka Dent Univ, Dept Internal Med, Osaka, Japan. Kansai Med Univ, Dept Internal Med 1, Osaka, Japan. Osaka Univ, Fac Med, Sch Allied Hlth Sci, Osaka, Japan. Kyoto Univ, Grad Sch Med, Dept Hematol & Oncol, Clin Sci Pathol Organs, Kyoto, Japan. US FDA, Div Cellular & Gene Therapies, HFM 518, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. RP Umehara, H (reprint author), Kyoto Univ, Grad Sch Med, Dept Rheumatol & Clin Immunol, Sakyo Ku, Shogoin Kawahara Cho, Kyoto 6068507, Japan. NR 49 TC 39 Z9 39 U1 0 U2 2 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD AUG PY 2002 VL 32 IS 8 BP 2188 EP 2198 DI 10.1002/1521-4141(200208)32:8<2188::AID-IMMU2188>3.0.CO;2-T PG 11 WC Immunology SC Immunology GA 586VE UT WOS:000177605900011 PM 12209631 ER PT J AU Toschke, AM Koletzko, B Slikker, W Hermann, M von Kries, R AF Toschke, AM Koletzko, B Slikker, W Hermann, M von Kries, R TI Childhood obesity is associated with maternal smoking in pregnancy SO EUROPEAN JOURNAL OF PEDIATRICS LA English DT Article DE Barker's hypothesis; body mass index; epidemiology; Germany; primary prevention ID SELF-REPORTED SMOKING; CIGARETTE-SMOKING; NICOTINE; CHILDREN; VALIDITY; EXPOSURE; WEIGHT; ADULTS AB Overweight and obesity are major public health issues. Childhood obesity often persists throughout adulthood. Recently a higher prevalence of obesity in adults whose mothers smoked during pregnancy was reported. The aim of this study was to assess whether this association is also detectable in pre-school children in a different setting and to identify the critical period for intrauterine exposure to inhaled smoke products in pregnancy. We analysed questionnaire data on early feeding and lifestyle factors of 8,765 German children aged 5.00 to 6.99 years. Obesity was defined as a body mass index > 97th percentile. The prevalence estimates for obesity were: mother never smoked 2.8% (95% CI 2.4%-3.2%), smoked after pregnancy only 1.6% (95%CI 0.4%-4.1%), smoked throughout pregnancy 6.2% (95% Cl 4.5%-8.3%), smoked before pregnancy, but not throughout 4.5% (95%CI 3.6%5.7%). These associations could not be explained by confounding due to a number of constitutional, sociodemographic and lifestyle factors. The unadjusted/adjusted odds ratios were: smoked during pregnancy: 2.32 (95% CI 1.63%-3.30%)/1.92 (95% CI 1.29%-2.86%); smoked before, but not throughout pregnancy: 1.67 (95%CI 1.26%-2.22%)/1.74 (95%CI 1.29%-2.34%). Conclusion: the association of maternal smoking in pregnancy and obesity was also detectable in children at school entry. Since smoking after pregnancy was not associated with childhood obesity, intrauterine exposure rather than family lifestyle factors associated with smoking appears to be instrumental. There appears to be a role for early intrauterine exposure. C1 Univ Munich, Dept Paediat Epidemiol, Inst Social Paediat & Adolescent Med, D-81377 Munich, Germany. Univ Munich, Dr Von Haunersch Childrens Hosp, Munich, Germany. US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. RP von Kries, R (reprint author), Univ Munich, Dept Paediat Epidemiol, Inst Social Paediat & Adolescent Med, Heiglhofstr 63, D-81377 Munich, Germany. RI Toschke, Andre/A-8848-2010 NR 21 TC 120 Z9 124 U1 0 U2 12 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0340-6199 J9 EUR J PEDIATR JI Eur. J. Pediatr. PD AUG PY 2002 VL 161 IS 8 BP 445 EP 448 DI 10.1007/s00431-002-0983-z PG 4 WC Pediatrics SC Pediatrics GA 588YB UT WOS:000177728900008 PM 12172830 ER PT J AU Wu, CG Forgues, M Siddique, S Farnsworth, J Velerie, K Wang, XW AF Wu, CG Forgues, M Siddique, S Farnsworth, J Velerie, K Wang, XW TI SAGE transcript profiles of normal primary human hepatocytes expressing oncogenic hepatitis B virus X protein SO FASEB JOURNAL LA English DT Article DE liver cancer; Megarray; nuclear export signal ID GENE-EXPRESSION; HEPATOCELLULAR-CARCINOMA; TRANSGENIC MICE; SERIAL ANALYSIS; LIVER-CANCER; HEPATOCARCINOGENESIS; INFECTION; LOCALIZATION; ETIOLOGY; COMPLEX AB Hepatitis B virus (HBV) is a major risk factor for hepatocellular carcinoma (HCC). HBV encodes an oncogenic HBx gene that functions as a transcriptional coactivator of multiple cellular genes. To understand the role(s) of HBx in the early genesis of HCC, we systematically analyzed gene expression profiles by serial analysis of gene expression (SAGE) in freshly isolated human primary hepatocytes infected with a replication-defective adenovirus containing HBx. A total of 19,501 sequence tags (representing 1443 unique transcripts) were analyzed, which provide a distribution of a transcriptome characteristic of normal hepatocytes and a profile associated with HBx expression. Examples of the targeted genes were confirmed by the Megarray analysis with a significant correlation between quantitative SAGE and Megarray (r = 0.8, P < 0.005). In HBx-expressing hepatocytes, a total of 57 transcripts (3.9%) were induced, and 46 transcripts (3.3%) were repressed by more than fivefold. Interestingly, most of the HBx-up-regulated transcripts can be clustered into three major classes, including genes that encode ribosomal proteins, transcription factors with zinc-finger motifs, and proteins associated with protein degradation pathways. These results suggest that HBx may function as a major regulator in common cellular pathways that, in turn, regulate protein synthesis, gene transcription, and protein degradation. C1 NCI, Human Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. US FDA, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. Virginia Commonwealth Univ, Med Coll Virginia, Dept Radiat Oncol, Richmond, VA 23298 USA. RP Wang, XW (reprint author), NCI, Human Carcinogenesis Lab, Ctr Canc Res, NIH, 37 Convent Dr,MSC 4255,Bldg 37,Room 2C25, Bethesda, MD 20892 USA. EM xin_wei_wang@nih.gov RI Wang, Xin/B-6162-2009 NR 39 TC 25 Z9 28 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD AUG PY 2002 VL 16 IS 10 BP 1665 EP + DI 10.1096/fj.02-0074fje PG 24 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 590HQ UT WOS:000177814000019 PM 12207007 ER PT J AU Andrews, LS Keys, AM Martin, RL Grodner, R Park, DL AF Andrews, LS Keys, AM Martin, RL Grodner, R Park, DL TI Chlorine dioxide wash of shrimp and crawfish an alternative to aqueous chlorine SO FOOD MICROBIOLOGY LA English DT Article AB This study compared the biocidal effect of chlorine dioxide spray with traditional chlorine wash on shrimp and crawfish tail meat. Treatments included aqueous chlorine (hypochlorite) (10-40) mg l(-1) and chlorine dioxide (10-40) mg l(-1) combined with and without a high-pressure prewash (600 psi). Standard aerobic and psychrotrophic bacteria were evaluated for up to 21 days. Samples treated with chlorine dioxide in both treatment techniques had lower aerobic and psychrotrophic counts (P < 0.001) than any combination of other treatments tested Reductions were from 1 to 4 log(10) (increasing as initial concentration of chlorine dioxide increased). Pressure application increased the effectiveness of both sanitizers and water wash by at least 0.5 log Chlorine residuals of 18-51 mg g(-1) were present in aqueous chlorine treatment of &GE;30 ppm. No chlorine residuals were present following chlorine dioxide treatments. (C) 2002 Elsevier Science Ltd. All rights reserved. C1 Mississippi State Univ, MAFES, Coastal Res & Extens Ctr, Expt Seafood Proc Lab, Biloxi, MS 39531 USA. Louisiana State Univ, Louisiana Agr Expt Stn, Dept Food Sci, Baton Rouge, LA 70803 USA. US FDA, Ctr Food Safety & Nutr, Washington, DC 20204 USA. Natl Fisheries Inst, Arlington, VA USA. RP Andrews, LS (reprint author), Mississippi State Univ, MAFES, Coastal Res & Extens Ctr, Expt Seafood Proc Lab, 2710 Beach Blvd,Suite E, Biloxi, MS 39531 USA. NR 10 TC 12 Z9 21 U1 1 U2 9 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0740-0020 J9 FOOD MICROBIOL JI Food Microbiol. PD AUG PY 2002 VL 19 IS 4 BP 261 EP 267 DI 10.1006/yfmic.493 PG 7 WC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology SC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology GA 591RL UT WOS:000177894000001 ER PT J AU Ravishankar, S Fleischman, GJ Balasubramaniam, VM AF Ravishankar, S Fleischman, GJ Balasubramaniam, VM TI The inactivation of Escherichia coli O157 : H7 during pulsed electric field (PEF) treatment in a static chamber SO FOOD MICROBIOLOGY LA English DT Article ID GELLAN GUM; MICROORGANISMS; FOODS; PASTEURIZATION; MICROSCOPY AB The inactivation of Escherichia coli O157:H7 by pulsed electric field (PEF) processing as a function of electric field strength (15-30 kV cm(-1)), pulse number (1-20), temperature (5-65degrees C) and pH (3.5 and 6.8) was studied using a commercially available pulser a static chamber and gellan gum gel as a suspension medium. The custom-designed static chamber achieved near-isothermal treatment conditions while eliminating flow field effects. Gellan gum gel was used to suspend the bacteria for treatment. It allowed uniform distribution of bacteria and neither inhibited nor promoted bacterial growth. The combination of equipment design and experimental protocol allowed the contribution of electrical (PEF) and thermal energy to be measured separately. In water-based gel a maximum of 3 log reductions were achieved by PEF energy. Greater inactivation was observed at a treatment temperature of 55degrees C, but the additional inactivation was attributable entirely to thermal energy Microbial injury was also observed at this temperature. At 60degrees C and above, complete inactivation was achieved but this was attributable entirely to thermal energy In water-based gellan gum gel adjusted to pH 3.5 again a 3 log reduction was achieved by PEF In gel made from freshly squeezed apple juice naturally having the same pH however a maximum of 1.5 log reduction was observed. Published by Elsevier Science Ltd. C1 IIT, Natl Ctr Foood Safety & Technol, Summit Argo, IL 60501 USA. US FDA, Natl Ctr Foood Safety & Technol, Summit Argo, IL 60501 USA. RP Balasubramaniam, VM (reprint author), IIT, Natl Ctr Foood Safety & Technol, Moffett Campus,6502 S Archer Rd, Summit Argo, IL 60501 USA. RI Balasubramaniam, VM Bala/A-2576-2008 OI Balasubramaniam, VM Bala/0000-0002-1540-4273 NR 23 TC 23 Z9 25 U1 2 U2 8 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0740-0020 J9 FOOD MICROBIOL JI Food Microbiol. PD AUG PY 2002 VL 19 IS 4 BP 351 EP 361 DI 10.1006/yfmic.484 PG 11 WC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology SC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology GA 591RL UT WOS:000177894000010 ER PT J AU Misakian, M Casamento, JP Laug, OB AF Misakian, M Casamento, JP Laug, OB TI Development of emulator for walk-through metal detectors SO IEEE TRANSACTIONS ON ELECTROMAGNETIC COMPATIBILITY LA English DT Article DE EMI; emulator; magnetic fields; metal detector; personal medical device; walk-through AB Because of anecdotal reports that magnetic fields from walk-through metal detectors may interfere with the operation of personal medical devices, interest has grown in the development of emulators that can simulate the magnetic fields produced by these metal detectors. This paper describes a system that can produce linearly polarized magnetic fields that have temporal characteristics such as those generated by some walk-through metal detectors. Because the electronic components are "off-the-shelf" devices and the coil can be readily fabricated, the system could be used by manufacturers of medical devices to conduct their own electromagnetic interference tests. C1 Natl Inst Stand & Technol, Gaithersburg, MD 20899 USA. US FDA, CDRH, Rockville, MD 20850 USA. RP Misakian, M (reprint author), Natl Inst Stand & Technol, Gaithersburg, MD 20899 USA. NR 6 TC 4 Z9 4 U1 0 U2 2 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 USA SN 0018-9375 J9 IEEE T ELECTROMAGN C JI IEEE Trans. Electromagn. Compat. PD AUG PY 2002 VL 44 IS 3 BP 486 EP 489 DI 10.1109/TEMC.2002.801775 PG 4 WC Engineering, Electrical & Electronic; Telecommunications SC Engineering; Telecommunications GA 589GQ UT WOS:000177750800011 ER PT J AU Xu, DQ Cisar, JO Ambulos, N Burr, DH Kopecko, DJ AF Xu, DQ Cisar, JO Ambulos, N Burr, DH Kopecko, DJ TI Molecular cloning and characterization of genes for Shigella sonnei form IO polysaccharide: Proposed biosynthetic pathway and stable expression in a live Salmonella vaccine vector SO INFECTION AND IMMUNITY LA English DT Article ID O-ANTIGEN GENES; ESCHERICHIA-COLI; PSEUDOMONAS-AERUGINOSA; BIVALENT VACCINE; TYPHOID VACCINE; DNA-SEQUENCE; PLASMID; LIPOPOLYSACCHARIDE; STRAIN; CONSTRUCTION AB The gene region for biosynthesis of Shigella sonnei form I O polysaccharide (O-Ps) and flanking sequences, totaling >18 kb, was characterized by deletion analysis to define a minimal construct for development of Salmonella-based live vaccine vector strains. Lipopolysaccharide (LPS) expression and DNA sequence studies of plasmid deletion derivatives indicated form I O-Ps expression from a 12.3-kb region containing a putative promoter and 10 contiguous open reading frames (ORFs), one of which is the transposase of IS630. A detailed binsynthetic pathway, consistent with the predicted functions of eight of the nine essential ORFs and the form I O-Ps structure, is proposed. Further sequencing identified partial IS elements (i.e., IS91 and IS630) and wzz upstream of the form I coding region and a fragment of aqpZ and additional full or partial IS elements (i.e., IS629, IS91, and IS911) downstream of this region. The stability of plasmid-based form I O-Ps expression was greater from low-copy vectors than from high-copy vectors and was enhanced by deletion of the downstream IS91 from plasmid inserts. Both core-linked (i.e., LPS) and non-core-linked (i.e., capsule-like) surface expression of form I O-Ps were detected by Western blotting and silver staining of polyacrylamide gel electrophoresis-separated Shigella and Escherichia coli extracts. However, salmonellae, which have a core that is chemically dissimilar to that of shigellae, expressed only non-core-linked surface-associated form I O-Ps. Finally, attenuated Salmonella enterica serovar Typhi live vaccine vector candidates, containing minimal-sized form I operon constructs, elicited immune protection in mice against virulent S. sonnei challenge, thereby supporting the promise of live, oral vaccines for the prevention of shigellosis. C1 US FDA, Ctr Food Safety & Nutr, Div Virulence Assessment, Laurel, MD 20708 USA. Univ Maryland, Sch Med, Dept Microbiol & Immunol, Baltimore, MD 21201 USA. US FDA, Ctr Biol Evaluat & Res, Lab Enter & Sexually Transmitted Dis, Bethesda, MD 20892 USA. Natl Inst Dent & Craniofacial Res, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. RP Kopecko, DJ (reprint author), US FDA, Ctr Biol Evaluat & Res, Lab Enter & Sexually Transmitted Dis, HFM440,Bldg 29,Rm 420, Bethesda, MD 20892 USA. NR 46 TC 28 Z9 29 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 AUG PY 2002 VL 70 IS 8 BP 4414 EP 4423 DI 10.1128/IAI.70.8.4414-4423.2002 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 574VC UT WOS:000176909400050 PM 12117952 ER PT J AU Chowdhury, BA AF Chowdhury, BA TI Comparative efficacy of levalbuterol and racemic albuterol in the treatment of asthma SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Letter C1 US FDA, CDER, Div Pulm & Allergy Drug Prod, Rockville, MD 20857 USA. RP Chowdhury, BA (reprint author), US FDA, CDER, Div Pulm & Allergy Drug Prod, Mail Code HFD-570, Rockville, MD 20857 USA. NR 6 TC 6 Z9 6 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD AUG PY 2002 VL 110 IS 2 BP 324 EP 324 AR UNSP 1/8/126374 DI 10.1067/mai.2002.126374 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 585DY UT WOS:000177509800020 PM 12170276 ER PT J AU Tomazic-Jezic, VJ Lucas, AD AF Tomazic-Jezic, VJ Lucas, AD TI Protein and allergen assays for natural rubber latex products SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article; Proceedings Paper CT Meeting on Natural Rubber Latex Sensitivity CY FEB 09-10, 2001 CL SAN FRANCISCO, CALIFORNIA SP Malaysian Rubber Res Inst DE natural rubber latex; protein measurement; glove powder; standard test; reference protein ID SKIN PRICK TEST; HEALTH-CARE WORKERS; AMMONIATED LATEX; SPINA-BIFIDA; IGE; SENSITIZATION; EXTRACTS; HEV-B-1; GLOVES; IDENTIFICATION AB The major issues in the efforts to alleviate allergy to natural rubber latex (NRL) proteins are prevention of allergic reactions and decreasing future sensitization. An accurate estimate of the potential allergenicity of NRL products is essential as guidance to manufacturers and users. Development of a reliable in vitro method for the quantitation of NRL allergens has been impeded by (1) limited knowledge of the individual allergens among NRL proteins, (2) variations in the protein profiles among NRL products, and (3) heterogeneity of responses to NRL allergens among sensitized individuals. The current methods include measurement of either the total or the antigenic NRL proteins. Although these methods provide valuable information, all except one have not been validated or standardized. The lack of sensitivity and specificity of this standardized method and poor correlation with the allergenic protein levels have mandated the need for a better assay. In the past year, an immunologic method for the quantitation of all antigenic proteins has been developed as a national standard. The method provides a significant improvement in sensitivity and specificity of NRL protein measurement, but the question of relevance to allergen content remains open. In the last several years, the intensive research aimed at purifying and characterizing individual allergens among NRL proteins resulted in the identification of more than 10 major allergens. On the basis of this knowledge, present efforts are focused on the development of a method for quantitation of relevant allergenic NRL proteins. C1 US FDA, Ctr Devices & Radiol Hlth, Off Sci & Technol, Div Life Sci, Rockville, MD 20852 USA. RP Tomazic-Jezic, VJ (reprint author), US FDA, Ctr Devices & Radiol Hlth, Off Sci & Technol, Div Life Sci, HFZ-112,12709 Twinbrook Pkwy, Rockville, MD 20852 USA. NR 36 TC 6 Z9 6 U1 0 U2 3 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD AUG PY 2002 VL 110 IS 2 SU S BP S40 EP S46 DI 10.1067/mai.2002.125335 PG 7 WC Allergy; Immunology SC Allergy; Immunology GA 586ET UT WOS:000177572200007 PM 12170242 ER PT J AU Ball, R Halsey, N Braun, NM Moulton, LH Gale, AD Rammohan, K Wiznitzer, M Johnson, R Salive, ME AF Ball, R Halsey, N Braun, NM Moulton, LH Gale, AD Rammohan, K Wiznitzer, M Johnson, R Salive, ME CA VAERS Working Grp TI Development of case definitions for acute encephalopathy, encephalitis, and multiple sclerosis reports to the Vaccine Adverse Event Reporting System SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Article DE vaccine; immunization; safety; surveillance; adverse events; encephalitis; encephalopathy; multiple sclerosis ID IMMUNIZATION; VAERS AB The Vaccine Adverse Event Reporting System (VAERS), administered by the FDA and CDC, is the U.S. system for surveillance of vaccine adverse events (AE). Acute encephalopathy age < 18 months (EO < 18), age greater than or equal to 18 months (EO greater than or equal to 18), encephalitis (EI), and multiple sclerosis (MS) after vaccination have been reported to VAERS, but reports often contain insufficient information to validate diagnoses. Standardized case definitions would enhance the utility of VAERS reports for AE surveillance. We developed practical case definitions for classification of VAERS reports, and three neurologists independently applied the definitions to reports submitted in 1993. Inter-observer agreement was assessed, and non-concordant classification,, were reviewed in a follow-up conference call. Reports of EO < 18 (n = 8), EO greater than or equal to 18 (it = 20), EI (n = 15), and MS (77 = 16) were classified as "definite" in 7% to 30% of the cases, while 26% to 51%, of reports were thought to have insufficient information to make a classification. Agreement among reviewers was good to excellent, (kappa: 0.65 to 0,85) except for EO < 18 in for which it was marginal (kappa: 0.37). It is possible to develop reproducible case definitions for acute encephalopathy, encephalitis, and multiple sclerosis using a standardized approach. Application of standardized case definitions to VAERS reports documents the limited information in many reports, specifies data for supplemental collection, and indicates that VAERS reports should be cautiously interpreted. Development and application of case definitions for other adverse events reported after vaccination should enhance the value of vaccine safety databases. Published by Elsevier Science Inc. C1 US FDA, Ctr Biol Evaluat & Res, Off Biostat & Epidemiol, Div Epidemiol, Rockville, MD 20852 USA. Johns Hopkins Univ, Bloomsberg Sch Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD USA. Case Western Reserve Univ, Dept Neurol, Cleveland, OH 44106 USA. Ohio State Univ, Dept Neurol, Columbus, OH 43210 USA. Stanford Univ, Sch Med, Dept Neurol & Neurol Sci, Stanford, CA 94305 USA. Johns Hopkins Univ, Bloomsberg Sch Publ Hlth, Dept Int Hlth, Inst Vaccine Safety, Baltimore, MD USA. RP Ball, R (reprint author), US FDA, Ctr Biol Evaluat & Res, Off Biostat & Epidemiol, Div Epidemiol, 1401 Rockville Pike,HFM-220, Rockville, MD 20852 USA. OI Moulton, Lawrence/0000-0001-7041-7387 NR 20 TC 13 Z9 13 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0895-4356 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD AUG PY 2002 VL 55 IS 8 BP 819 EP 824 AR PII S0895-4356(01)00500-5 DI 10.1016/S0895-4356(01)00500-5 PG 6 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 594FD UT WOS:000178037500012 PM 12384197 ER PT J AU Lathers, CM AF Lathers, CM TI Risk assessment in regulatory policy making for human and veterinary public health SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Review ID ENTERICA SEROTYPE TYPHIMURIUM; MONTE-CARLO TECHNIQUES; ANTIMICROBIAL RESISTANCE; INTESTINAL FLORA; FOOD-ADDITIVES; UNITED-STATES; SALMONELLA; OUTBREAK; FUTURE; PRINCIPLES AB Risk assessment is the method of systematically identifying and assessing factors that influence the probability and consequences of a negative event occurring. One responsibility of veterinary medicine is to protect animal and human health. Food animal production uses antibiotics to enhance production. Regulators evaluate new production technology to ensure animal safety and safe, edible products and to make public policy decisions by assessing risks/benefits. The U.S. Food and Drug Administration, Center for Veterinary Medicine's (CVM's) first risk assessment addressed the potential human health impact of campylobacter effects associated with the use of fluoroquinolines in food-producing animals. CVM used the Monte Carlo method to estimate risk by probability distributions that reflect the uncertainty and variability in the data used for the assessment. Enterococci faecium is a species more likely to be resistant to antibiotics of last resort. Effective control of multidrug-resistant enterococci will require a better understanding of the transfer of E. faecium from animals to humans and the interaction between E. faecium, the hospital environment, and humans; prudent antibiotic use; better contact isolation in hospitals; and better surveillance. CVM will model these factors in a second, more complex risk assessment designed to examine the indirect transfer of resistance from animals to humans. Use of risk assessments allows researchers, the industry, regulatory authorities, and educators to make better policy decisions regarding antimicrobial use in food animals and humans and the development of resistance. Today the question of whether the use of antimicrobials for growth enhancement in food animals should or should not be terminated for the benefit of human health remains unresolved. (C) 2002 American College of Clinical Pharmacology. C1 US FDA, Ctr Vet Med, Off New Anim Drug Evaluat, Rockville, MD 20855 USA. RP Lathers, CM (reprint author), US FDA, Ctr Vet Med, Off New Anim Drug Evaluat, 7500 Standish Pl,Rm 387,HFV-100, Rockville, MD 20855 USA. NR 126 TC 3 Z9 3 U1 3 U2 7 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD AUG PY 2002 VL 42 IS 8 BP 846 EP 866 DI 10.1177/009127002401102768 PG 21 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 577EJ UT WOS:000177048300002 PM 12162467 ER PT J AU Tomazic-Jezic, VJ Woolhiser, MR Beezhold, DH AF Tomazic-Jezic, VJ Woolhiser, MR Beezhold, DH TI ELISA inhibition assay for the quantitation of antigenic protein in natural rubber latex SO JOURNAL OF IMMUNOASSAY & IMMUNOCHEMISTRY LA English DT Article ID SKIN PRICK TEST; SPINA-BIFIDA; AMMONIATED LATEX; RISK-FACTORS; ALLERGEN; EXTRACTS; HYPERSENSITIVITY; SENSITIZATION; GLOVES; LOWRY AB Evaluating allergenicity of natural rubber latex (NRL) products is essential for the successful reduction of the consumer's exposure to potentially allergenic NRL proteins. We have developed an ELISA Inhibition method for the quantitation of extractable proteins from NRL products which has good sensitivity and specificity. The method utilizes rabbit anti-NRL protein serum as a detection mechanism. The source of NRL proteins for immunization and as a reference protein in the assay is ammoniated raw latex (AL). By comparison with the Western blot analysis of the rabbit sera, it appears that the ELISA detects most of the latex proteins present in extracts. To investigate, further, this assumption, we compared the ELISA Inhibition test with two other methods for total protein measurement. We also compared the values generated by the ELISA Inhibition test with other immunological methods for quantitation of antigenic and allergenic proteins. Comparisons were performed with 15 extracts from randomly selected surgical and examination gloves. The samples were coded separately for each test to insure the objectivity of evaluation. The antigenic protein values obtained by the ELISA Inhibition test correlated best with the HPLC amino acid analysis (correlation coefficient (cc)=0.79) and with the LEAP assay (cc=0.97). The antigenic protein levels obtained by the ELISA test were 3-10 times lower than those obtained by the HPLC analysis. A lesser correlation was observed with the Modified Lowry assay (cc= 0.45), which is likely due to chemical interference bias in the Lowry method. Our findings suggest that the antigenic proteins measured by the ELISA Inhibition test described here more closely represent the measure of the total protein content in the extracts. It is important to note that the relative values obtained by this method are lower than the values obtained by other total protein methods, possibly due to a large number of small peptides present in NRL products, that would only be measured by the chemical method. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20852 USA. NIOSH, Morgantown, WV 26505 USA. Guthrie Res Inst, Sayre, PA 18840 USA. RP Tomazic-Jezic, VJ (reprint author), US FDA, Ctr Devices & Radiol Hlth, 12709 Twinbrook Pkwy, Rockville, MD 20852 USA. NR 21 TC 1 Z9 1 U1 0 U2 4 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 1532-1819 J9 J IMMUNOASS IMMUNOCH JI J. Immunoass. Immunoch. PD AUG PY 2002 VL 23 IS 3 BP 261 EP 278 DI 10.1081/IAS-120013026 PG 18 WC Biochemical Research Methods; Immunology; Medical Laboratory Technology SC Biochemistry & Molecular Biology; Immunology; Medical Laboratory Technology GA 591AF UT WOS:000177856700001 PM 12227414 ER PT J AU Tomazic-Jezic, VJ Truscott, W AF Tomazic-Jezic, VJ Truscott, W TI Identification of antigenic and allergenic natural rubber latex proteins by immunoblotting SO JOURNAL OF IMMUNOASSAY & IMMUNOCHEMISTRY LA English DT Article ID HEALTH-CARE WORKERS; SPINA-BIFIDA; AMMONIATED LATEX; IGE; EXTRACTS; DIAGNOSIS AB Quantitation of proteins in finished natural rubber latex (NRL) products is essential in predicting their allergenic potential. The ASTM standard Modified Lowry method for measuring total protein content has been used for several years. Most recently, ASTM published a standard for more sensitive and more specific enzyme immunoassay for quantitation of antigenic NRL proteins. It is an ELISA inhibition assay, using rabbit anti NRL sera. Since the measurement of proteins in this method depends on recognition capacity of rabbit antibodies, the selection of an appropriate protein source for rabbit immunization is crucial for the accuracy of such test. In this study, we evaluated the composition of NRL proteins from ammoniated (AL) and nonammoniated (NAL) raw latex and from finished NRL products, and compared the effectiveness of sera from rabbits immunized with NRL proteins, to react with those extracts. Immune rabbit sera were analyzed by immunoblotting against extracts of several samples of AL, NAL, and glove proteins. In the NAL extracts, we identified 26-28 protein bands by SDS-PAGE. AL samples had between 6 and 9 bands with a great variation in the band positions among the samples, The Western blot analysis showed that anti-AL rabbit serum reacted with 4-9 protein bands in various AL extracts. The highest intensity of reaction was observed with the extract used to immunize the rabbits. Similar reaction was observed with anti-NAL serum. However, when the antisera were blotted against NAL extracts, anti-NAL serum reacted more strongly and with a larger number of proteins than anti-AL serum. In summary, anti-NAL serum recognized an equal number of proteins in AL extract as anti-AL serum. However, anti-AL serum recognized fewer protein molecules in NAL extract than anti-NAL serum. Our findings suggest that NAL extract contains more individual proteins than other extracts, and sera from rabbits immunized with this antigen have a greater capacity to react with a wide spectrum of NRL proteins. This finding may be helpful in selecting the representative reference antigen and antiserum for further efforts in NRL protein quantitation. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. Kimberly Clark Co, Roswell, GA 30075 USA. RP Tomazic-Jezic, VJ (reprint author), US FDA, Ctr Devices & Radiol Hlth, 12709 Twinbrook Pkwy, Rockville, MD 20857 USA. NR 21 TC 2 Z9 2 U1 0 U2 2 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 1532-1819 J9 J IMMUNOASS IMMUNOCH JI J. Immunoass. Immunoch. PD AUG PY 2002 VL 23 IS 3 BP 369 EP 383 DI 10.1081/IAS-120013034 PG 15 WC Biochemical Research Methods; Immunology; Medical Laboratory Technology SC Biochemistry & Molecular Biology; Immunology; Medical Laboratory Technology GA 591AF UT WOS:000177856700008 PM 12227421 ER PT J AU Park, MK Amichay, D Love, P Wick, E Liao, F Grinberg, A Rabin, RL Zhang, HWH Gebeyehu, S Wright, TM Iwasaki, A Weng, YM DeMartino, JA Elkins, KL Farber, JM AF Park, MK Amichay, D Love, P Wick, E Liao, F Grinberg, A Rabin, RL Zhang, HWH Gebeyehu, S Wright, TM Iwasaki, A Weng, YM DeMartino, JA Elkins, KL Farber, JM TI The CXC chemokine murine monokine induced by IFN-gamma (CXC chemokine ligand 9) is made by APCs, targets lymphocytes including activated B cells, and supports antibody responses to a bacterial pathogen in vivo SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TULARENSIS STRAIN LVS; T-CELLS; IN-VIVO; DENDRITIC CELLS; RECEPTOR CXCR3; INTERFERON-GAMMA; INTRACELLULAR PATHOGEN; RHEUMATOID-ARTHRITIS; PROTECTIVE IMMUNITY; ACUTE REJECTION AB Monokine induced by IFN-gamma (Mig; CXC chemokine ligand 9) is an IFN-gamma-inducible CXC chemokine that signals through the receptor CXCR3 and is known to function as a chemotactic factor for human T cells, particularly following T cell activation. The mig gene can be induced in multiple cell types and organs, and Mig has been shown to contribute to T cell infiltration into immune/inflammatory reactions in peripheral tissues in mice. We have investigated the expression and activities of Mig and CXCR3 in mouse cells and the role of Mig in models of host defense in mice. Murine (Mu)Mig functioned as a chemotactic factor for resting memory and activated T cells, both CD4(+) and CD8(+), and responsiveness to MuMig correlated with surface expression of MuCXCR3. Using mig(-/-) mice, we found that MuMig was not necessary for survival after infections with a number of intracellular pathogens. Surprisingly, however, we found that mig(-/-) mice showed reductions of 50-75% in Abs produced against the intracellular bacterium Francisella tularensis live vaccine strain. Furthermore, we found that MuMig induced both calcium signals and chemotaxis in activated B cells, and that B cell activation induced expression of MuCXCR3. In addition, IFN-gamma induced the expression of mumig in APCs, including CD8alpha(+) and CD8alpha(-) dendritic cells. Together, our data suggest that Mig and CXCR3 may be important not only to recruit T cells to peripheral inflammatory sites, but also in some cases to maximize interactions among activated T cells, B cells, and dendritic cells within lymphoid organs to provide optimal Immoral responses to pathogens. C1 NIAID, Clin Invest Lab, Inflammat Biol Sect, NIH, Bethesda, MD 20892 USA. NIAID, Immune Cell Interact Unit, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. Merck Res Labs, Dept Immunol Res, Rahway, NJ 07065 USA. Pfizer Global R&D, Ann Arbor, MI 48105 USA. US FDA, Ctr Biol Evaluat & Res, Div Bacterial Parasit & Allergen Prod, Bethesda, MD 20892 USA. NICHHD, Lab Mammalian Genes & Dev, NIH, Bethesda, MD 20892 USA. RP Farber, JM (reprint author), NIAID, Clin Invest Lab, Inflammat Biol Sect, NIH, Bldg 10,Room 11N228,MSC-1888, Bethesda, MD 20892 USA. NR 60 TC 81 Z9 84 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD AUG 1 PY 2002 VL 169 IS 3 BP 1433 EP 1443 PG 11 WC Immunology SC Immunology GA 576UV UT WOS:000177025100037 PM 12133969 ER PT J AU Ross, SA Poirier, L AF Ross, SA Poirier, L TI Proceedings of the trans-HHS workshop: Diet, DNA methylation processes and health SO JOURNAL OF NUTRITION LA English DT Editorial Material DE DNA methylation; S-adenosylmethionine; diet; cancer; disease ID ACID-DEFINED DIETS; CANCER RISK; FOLATE; DEFICIENCY; REDUCTASE; GENE; HYPOMETHYLATION; MUTATION; LIVERS; BREAST C1 NCI, Nutr Sci Res Grp, Div Canc Prevent, Bethesda, MD 20892 USA. US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Ross, SA (reprint author), NCI, Nutr Sci Res Grp, Div Canc Prevent, Bethesda, MD 20892 USA. NR 24 TC 15 Z9 15 U1 0 U2 1 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD AUG PY 2002 VL 132 IS 8 SU S BP 2329S EP 2332S PG 4 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 583GH UT WOS:000177398500001 PM 12163686 ER PT J AU Poirier, LA AF Poirier, LA TI The effects of diet, genetics and chemicals on toxicity and aberrant DNA methylation: an introduction SO JOURNAL OF NUTRITION LA English DT Article; Proceedings Paper CT Trans-HHS Workshop on Diet, DNA Methylation Processes and Health CY AUG 06-08, 2001 CL BETHESDA, MARYLAND SP Natl Ctr Toxicol Res, Food & Durg Adm, Ctr Canc Res, Div Canc Prevent, NHLBI, NICHHD, NIDDK, NIEHS, Div Nutrit Res Coordinat, Off Dietary Supplements, Amer Soc Nutrit Sci, Int Life Sci Inst N Amer DE diet; carcinogenesis; DNA hypomethylation; toxicology; S-adenosylmethionine ID ACID-DEFINED DIETS; CHOLINE-DEVOID DIET; DEFICIENT DIET; RAT-LIVER; S-ADENOSYLETHIONINE; METHIONINE-DEFICIENT; ZINC-DEFICIENCY; MOUSE-LIVER; C3H MICE; EXPRESSION AB In the early 1930s, the group of Banting and Best showed that the choline moiety of lecithin was responsible for the prevention of the fatty livers produced in pancreatectomized dogs treated with insulin. This was the first study linking abnormal methyl metabolism with disease. Since then, deficiencies of each of the four essential dietary sources of methyl groups (choline, methionine, vitamin B-12 and folic acid) have been associated with increased risk of a number of diseases. Choline-deficient diets were shown to enhance liver tumor formation in rats, and such diets frequently were found to lead to atherosclerosis. Although methionine deficiency per se was not extensively studied in vivo, its metabolic antagonist ethionine did cause liver cancer and pancreatic toxicity in rodents. Deficiencies of vitamin B-12 and of folic acid have long been shown to cause neurological disturbances and birth defects both in humans and in experimental animals. In 1969 inborn errors of metabolism leading to the accumulation of the demethylated metabolite of methionine, homocysteine, were proposed as contributing to the early onset of atherosclerosis. Before 1990, numerous studies described the abnormal methylation of DNA in tumors and transformed cells. Less frequently investigated, however, were the exogenous and endogenous agents leading to such abnormal methylation. These included genetic variants among rodent strains and the methyldeficient diets that caused liver cancer. In addition, several chemicals, particularly carcinogens, were shown to alter DNA methylation. The possible links between chemically induced alterations in DNA methylation and development of other diseases were little explored. However, by 1990, a chain of causality had been established in experimental carcinogenesis linking dietary methyl deficiency with methyl insufficiency in vivo, as well as with the abnormal methylation of DNA and of specific genes. Also during this period, the diminished activity of the enzyme methylenetetrahydrofolate reductase (EC 1.5.1.20), which is responsible for the actual de novo synthesis of methyl groups, was shown to be associated with increased risk of developing atherosclerosis, neurological disorders and birth defects. The exponential rise in studies on methyl metabolism and DNA methylation since then enables us to examine here the extent to which the mechanisms by which abnormal methylation processes seem to exert their toxic effects in one disease may be applicable to other pathologies. C1 US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Poirier, LA (reprint author), US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 51 TC 50 Z9 53 U1 0 U2 7 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD AUG PY 2002 VL 132 IS 8 SU S BP 2336S EP 2339S PG 4 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 583GH UT WOS:000177398500003 PM 12163688 ER PT J AU James, SJ Melnyk, S Pogribna, M Pogribny, IP Caudill, MA AF James, SJ Melnyk, S Pogribna, M Pogribny, IP Caudill, MA TI Elevation in S-adenosylhomocysteine and DNA hypomethylation: Potential epigenetic mechanism for homocysteine-related pathology SO JOURNAL OF NUTRITION LA English DT Article; Proceedings Paper CT Trans-HHS Workshop on Diet, DNA Methylation Processes and Health CY AUG 06-08, 2001 CL BETHESDA, MARYLAND SP Natl Ctr Toxicol Res, Food & Durg Adm, Ctr Canc Res, Div Canc Prevent, NHLBI, NICHHD, NIDDK, NIEHS, Div Nutrit Res Coordinat, Off Dietary Supplements, Amer Soc Nutrit Sci, Int Life Sci Inst N Amer DE homocysteine; S-adenosylhomocysteine; S-adenosylmethionine; DNA methylation ID ADENOSYL-L-HOMOCYSTEINE; METHYLENETETRAHYDROFOLATE REDUCTASE GENE; FOLATE/METHYL-DEFICIENT RATS; PLASMA HOMOCYSTEINE; CARDIOVASCULAR-DISEASE; BIOGENIC-AMINES; STRAND BREAKS; GENOMIC DNA; P53 GENE; METHYLATION AB Chronic nutritional deficiencies in folate, choline, methionine, vitamin B-6 and/or vitamin B-12 can perturb the complex regulatory network that maintains normal one-carbon metabolism and homocysteine homeostasis. Genetic polymorphisms in these pathways can act synergistically with nutritional deficiencies to accelerate metabolic pathology associated with occlusive heart disease, birth defects and dementia. A major unanswered question is whether homocysteine is causally involved in disease pathogenesis or whether homocysteinemia is simply a passive and indirect indicator of a more complex mechanism. S-Adenosylmethionine and S-adenosylhomocysteine (SAH), as the substrate and product of methyltransferase reactions, are important metabolic indicators of cellular methylation status. Chronic elevation in homocysteine levels results in parallel increases in intracellular SAH and potent product inhibition of DNA methyltransferases. SAH-mediated DNA hypomethylation and associated alterations in gene expression and chromatin structure may provide new hypotheses for pathogenesis of diseases related to homocysteinemia. 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. RP James, SJ (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. NR 72 TC 124 Z9 128 U1 1 U2 13 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD AUG PY 2002 VL 132 IS 8 SU S BP 2361S EP 2366S PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 583GH UT WOS:000177398500008 PM 12163693 ER PT J AU Cooney, CA Dave, AA Wolff, GL AF Cooney, CA Dave, AA Wolff, GL TI Maternal methyl supplements in mice affect epigenetic variation and DNA methylation of offspring SO JOURNAL OF NUTRITION LA English DT Article; Proceedings Paper CT Trans-HHS Workshop on Diet, DNA Methylation Processes and Health CY AUG 06-08, 2001 CL BETHESDA, MARYLAND SP Natl Ctr Toxicol Res, Food & Durg Adm, Ctr Canc Res, Div Canc Prevent, NHLBI, NICHHD, NIDDK, NIEHS, Div Nutrit Res Coordinat, Off Dietary Supplements, Amer Soc Nutrit Sci, Int Life Sci Inst N Amer DE diet; methylation; epigenetic; maternal; supplement ID MODERATE FOLATE-DEPLETION; AGOUTI GENE-EXPRESSION; GENOMIC DNA; AD-LIBITUM; TRANSGENIC MICE; X-INACTIVATION; BODY-WEIGHT; MOUSE; METHYLTRANSFERASE; HYPOMETHYLATION AB This study was designed to determine if maternal dietary methyl supplements increase DNA methylation and methylation-dependent epigenetic phenotypes in mammalian offspring. Female mice of two strains were fed two levels of dietary methyl supplement or control diet prior to and during pregnancy. Offspring of these mice vary in phenotype, which is epigenetically determined and affects health and 2-y survival. Phenotype and DNA methylation of a long terminal repeat (LTR) controlling expression of the agouti gene were assayed in the resulting offspring. Methyl supplements increase the level of DNA methylation in the agouti LTR and change the phenotype of offspring in the healthy, longer-lived direction. This shows that methyl supplements have strong effects on DNA methylation and phenotype and are likely to affect long-term health. Optimum dietary supplements for the health and longevity of offspring should be intensively investigated. This should lead to public policy guidance that teaches optimal, rather than minimal, dose levels of maternal supplements. C1 Univ Arkansas Med Sci Hosp, Dept Biochem & Mol Biol, Little Rock, AR 72205 USA. Natl Ctr Toxicol Res, Div Mol Epidemiol, Jefferson, AR 72079 USA. Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Cooney, CA (reprint author), Univ Arkansas Med Sci Hosp, Dept Biochem & Mol Biol, Little Rock, AR 72205 USA. NR 63 TC 193 Z9 206 U1 4 U2 39 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD AUG PY 2002 VL 132 IS 8 SU S BP 2393S EP 2400S PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 583GH UT WOS:000177398500014 ER PT J AU Finnell, RH Spiegelstein, O Wlodarczyk, B Triplett, A Pogribny, IP Melnyk, S James, JS AF Finnell, RH Spiegelstein, O Wlodarczyk, B Triplett, A Pogribny, IP Melnyk, S James, JS TI DNA methylation in Folbp1 knockout mice supplemented with folic acid during gestation SO JOURNAL OF NUTRITION LA English DT Article; Proceedings Paper CT Trans-HHS Workshop on Diet, DNA Methylation Processes and Health CY AUG 06-08, 2001 CL BETHESDA, MARYLAND SP Natl Ctr Toxicol Res, Food & Durg Adm, Ctr Canc Res, Div Canc Prevent, NHLBI, NICHHD, NIDDK, NIEHS, Div Nutrit Res Coordinat, Off Dietary Supplements, Amer Soc Nutrit Sci, Int Life Sci Inst N Amer DE Folbp1; DNA methylation; folinic acid; birth defect; mice ID NEURAL-TUBE DEFECTS; EMBRYONIC-DEVELOPMENT; HOMOCYSTEINE METABOLISM; GENE-EXPRESSION; MOUSE EMBRYO; CPG ISLANDS; FOLATE; 5-AZACYTIDINE; HYPERHOMOCYSTEINEMIA; METHYLTRANSFERASE AB Periconceptional folic acid supplementation has been shown to prevent up to 70% of neural tube and other birth defects in humans; however, the mechanism is still unknown. In this study, we tested whether defective intracellular folate transport, as achieved by inactivation of the murine folate-binding protein 1 (Folbp1), affects global DNA methylation in the liver and brain from gestational day (GD) 15 1/2 embryos. Complete Folbp1 inactivation is embryolethal but can be reversed by maternal folinic acid (FA) supplementation, and thus we also tested the effect of FA supplementation on DNA methylation in Folbp1 fetuses. Overall, the extent of global DNA methylation seems to be similar across all genotypes in unsupplemented control Folbp1 mice; however, explicit conclusions regarding Folbp1(-/-) fetuses were not possible because only a single living unsupplemented fetus was viable at GD 15 1/2. FA supplementation induced global DNA hypomethylation across all genotypes. FA-induced hypomethylation is most likely due to its ability to inhibit the enzyme glycine hydroxymethyltransferase, thereby inhibiting the homocysteine remethylation cycle necessary to regenerate S-adenosylmethionine, the methyl donor for DNA methyltransferases. Our hypothesis was that due to defective folate transport in Folbp1(-/-) embryos and fetuses, DNA would be hypomethylated, thereby altering the temporal expression of critical genes necessary for normal embryonic development. However, these results suggest that an extended examination of changes in DNA methylation prior to GD 15 1/2 is required to unequivocally prove or disprove the hypothesis. C1 Texas A&M Univ Syst, Ctr Environm & Genet Med, Inst Biosci & Technol, Hlth Sci Ctr, Houston, TX 77030 USA. Univ Nebraska, Med Ctr, Ctr Human Mol Genet, Omaha, NE 68198 USA. Natl Inst Vet Res, PL-24100 Pulawy, Poland. Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Finnell, RH (reprint author), Texas A&M Univ Syst, Ctr Environm & Genet Med, Inst Biosci & Technol, Hlth Sci Ctr, Houston, TX 77030 USA. NR 44 TC 37 Z9 38 U1 0 U2 0 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD AUG PY 2002 VL 132 IS 8 SU S BP 2457S EP 2461S PG 5 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 583GH UT WOS:000177398500026 PM 12163711 ER PT J AU Rader, JI AF Rader, JI TI Folic acid fortification, folate status and plasma homocysteine SO JOURNAL OF NUTRITION LA English DT Article; Proceedings Paper CT Trans-HHS Workshop on Diet, DNA Methylation Processes and Health CY AUG 06-08, 2001 CL BETHESDA, MARYLAND SP Natl Ctr Toxicol Res, Food & Durg Adm, Ctr Canc Res, Div Canc Prevent, NHLBI, NICHHD, NIDDK, NIEHS, Div Nutrit Res Coordinat, Off Dietary Supplements, Amer Soc Nutrit Sci, Int Life Sci Inst N Amer DE folate; fortification; folate status; serum folate; homocysteine ID NEURAL-TUBE DEFECTS; FOOD FORTIFICATION; SERUM FOLATE; SUPPLEMENTATION; DISEASE; TRIAL AB Folic acid fortification of enriched cereal-grain products (which became mandatory in the U.S. on January 1, 1998) was intended to increase folate intake among childbearing-aged women to reduce their risk of neural tube birth defect (NTD)-affected pregnancies. Interest now focuses on assessing the effects of fortification on risk of NTDs and on folate intake relative to homocysteine (Hcy) concentrations and risk of vascular disease, although a causal relationship between the latter two has not been demonstrated. Increased serum folate levels were first reported in 1999. Data from the Framingham Offspring Study cohort showed increased mean serum folate in middle-aged and older adults; additionally, the prevalence of high Hcy concentrations had decreased by similar to50% in subjects examined before (1995-1996) and after (1997-1998) fortification. Another analyses of samples collected between 1994 and 1999 identified a trend of increasing serum folate values from 1996 onward with values in 1998 160% of those measured in 1996. Comparisons between 1988-1994 National Health and Nutrition Examination Survey (NHANES) III data and 1999 NHANES showed increased serum and erythrocyte folate concentrations among childbearing-aged women. While recent data show improved folate status in a short period of time, much about long-term effects of the fortification program remains unknown. Interest in the effects of increased folate intakes on risk of NTDs or vascular disease needs to be balanced against concerns about masking the anemia of vitamin B-12 deficiency and the general lack of data about safety of continuous high intakes. Careful monitoring over time is necessary to determine that the program functions as intended. C1 US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. RP Rader, JI (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. NR 23 TC 45 Z9 47 U1 1 U2 5 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD AUG PY 2002 VL 132 IS 8 SU S BP 2466S EP 2470S PG 5 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 583GH UT WOS:000177398500028 PM 12163713 ER PT J AU Mahmood, I Sahajwalla, C AF Mahmood, I Sahajwalla, C TI Interspecies scaling of biliary excreted drugs SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article DE interspecies scaling; CL; biliary excretion ID PHARMACOKINETIC PARAMETERS; CLEARANCE; HUMANS; ANIMALS; RATS; DISPOSITION; METABOLISM; RIFABUTIN; SM-1652 AB The objective of this study is to predict clearance of drugs in humans from animals which are excreted in the bile. Clearance (CL) of eight drugs known to be excreted in the bile were randomly selected from the literature. Scaling of CL was performed using at least three animal species, Using simple allometry, CL (.) mean life-span potential (MLP) or CL x brain weight, CLs of studied drugs were predicted in humans. The choice of one of the methods depended on the 'rule or exponents' as described by Mahmood and Balian, A 'correction factor' was calculated by adjusting bile flow rate based on the species body weight (bile flow - mL/day/kg body weight, or liver weight (bile flow = mL/day/kg liver weight), Using the 'rule of exponents' and combining it with the 'correction factor', the CLs of biliary excreted drug,-; were predicted in humans. Predicted CLs in humans front animals using simple allonletry were several times higher for all eight drugs (% error [range] = 46-1703. Using the 'rule of exponents' and combining it with a 'correction factor' as described in this report provided a substantial improvement (% error [range]= 5-91) in the prediction of CL for biliary excreted drugs. The results of this study indicate that the CL of a biliary excreted drug may be overpredicted in humans and by applying the 'correction factor' employed here, the predictability of drug CL in humans from animal data may be significantly improved. (C) 2002 Wiley-Liss, Inc, and the American Pharmaceutical Association. C1 US FDA, Off Clin Pharmacol & Biopharmaceut, Div Pharmaceut Evaluat 1, Woodmont Off Ctr 2, Rockville, MD 20852 USA. RP Mahmood, I (reprint author), US FDA, Off Clin Pharmacol & Biopharmaceut, Div Pharmaceut Evaluat 1, Woodmont Off Ctr 2, Room 4079,1451 Rockville Pike,HRD-860, Rockville, MD 20852 USA. NR 26 TC 45 Z9 45 U1 0 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0022-3549 J9 J PHARM SCI JI J. Pharm. Sci. PD AUG PY 2002 VL 91 IS 8 BP 1908 EP 1914 DI 10.1002/jps.10174 PG 7 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 578EK UT WOS:000177104300015 PM 12115817 ER PT J AU Altekruse, SF Elvinger, F Lee, KY Tollefson, LK Pierson, FW Eifert, J Sriranganathan, N AF Altekruse, SF Elvinger, F Lee, KY Tollefson, LK Pierson, FW Eifert, J Sriranganathan, N TI Antimicrobial susceptibilities of Escherichia coli strains from a turkey operation SO JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION LA English DT Article ID ANTIBIOTIC-RESISTANCE; SALMONELLA; PREVALENCE; CHICKENS; MEAT AB Objective-To measure minimum inhibitory concentrations (MIC) of 17 antimicrobials for Escherichia coli isolates from a turkey operation and assess whether small samples provide precise estimates of geometric mean MIC. Design-Prospective study. Sample Population-105 clinical isolates from birds and 1,104 fecal isolates from 20 flocks (poults and finisher hens). Procedure-A Mueller-Hinton broth dilution panel was used to measure MIC, and MIC of fecal and clinical isolates were compared. We drew random samples of 5, 10, 15, 20, 25, 30, 35, 40, and 45 isolates from each finisher flock and between 100 and 105 isolates from 5, 7, 10, and 20 flocks. Antimicrobial usage was determined for enrolled flocks. Results-Six of 12 poult and 18 of 20 finisher flocks had been treated with antimicrobials, often for respiratory illnesses consistent with colibacillosis. All birds received gentamicin at the hatchery. More fecal than clinical isolates were resistant to ampicillin; however, more clinical isolates were resistant to ciprofloxacin, gentamicin, and sulfamethoxazole. Precise estimates of geometric mean MIC for flocks were obtained when greater than or equal to 15 fecal isolates were obtained per flock and, for the operation, when 105 isolates were obtained from 7 flocks. Conclusion and Clinical Relevance-Antimicrobial usage was common and may have contributed to the resistance patterns of isolates. With a modest allocation of laboratory resources, producers can monitor antimicrobial susceptibilities of clinical and fecal E coli to manage risks of antimicrobial usage and resistance. C1 Virginia Maryland Reg Coll Vet Med, Dept Large Anim Clin Sci, Blacksburg, VA 24061 USA. Virginia Maryland Reg Coll Vet Med, Dept Biomed Sci & Pathobiol, Blacksburg, VA 24061 USA. Virginia Polytech Inst & State Univ, Coll Agr & Life Sci, Dept Food Sci & Technol, Blacksburg, VA 24061 USA. US FDA, Ctr Vet Med, Rockville, MD 20895 USA. RP Altekruse, SF (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Room 7082 MSC 7234, Rockville, MD 20852 USA. NR 26 TC 19 Z9 21 U1 0 U2 4 PU AMER VETERINARY MEDICAL ASSOC PI SCHAUMBURG PA 1931 N MEACHAM RD SUITE 100, SCHAUMBURG, IL 60173-4360 USA SN 0003-1488 J9 J AM VET MED ASSOC JI J. Am. Vet. Med. Assoc. PD AUG 1 PY 2002 VL 221 IS 3 BP 411 EP 416 DI 10.2460/javma.2002.221.411 PG 6 WC Veterinary Sciences SC Veterinary Sciences GA 577JU UT WOS:000177058400016 PM 12164541 ER PT J AU Kotewicz, ML Li, BG Levy, DD LeClerc, JE Shifflet, AW Cebula, TA AF Kotewicz, ML Li, BG Levy, DD LeClerc, JE Shifflet, AW Cebula, TA TI Evolution of multi-gene segments in the mutS-rpoS intergenic region of Salmonella enterica serovar Typhimurium LT2 SO MICROBIOLOGY-SGM LA English DT Article DE mutS; rpoS; horizontal gene transfer; Escherichia coli ID COMPLETE GENOME SEQUENCE; ESCHERICHIA-COLI K-12; HORIZONTAL TRANSFER; HAEMOPHILUS-INFLUENZAE; PHOSPHATASES PRPA; BACTERIA; CHROMOSOME; REPAIR; ORIGIN; RECOMBINATION AB The nucleotide sequence of the 12.6 kb region between the mutS and rpoS genes of Salmonella enterica serovar Typhimurium LT2 (S. typhimurium) was compared to other enteric bacterial mutS-rpoS intergenic regions. The mutS-rpoS region is composed of three distinct segments, designated HK, O and S, as defined by sequence similarities to contiguous ORFs in other bacteria. Inverted chromosomal orientations of each of these segments are found between the mutS and rpoS genes in related Enterobacteriaceae. The HK segment is distantly related to a cluster of seven ORFs found in Haemophilus influenzae and a cluster of five ORFs found between the mutS and rpoS genes in Escherichia coli K-12. The O segment is related to the mutS-rpoS intergenic region found in E. coli O157:H7 and Shigella dysenteriae type 1. The third segment, S, is common to diverse Salmonella species, but is absent from E. coli. Despite the extensive collinearity and conservation of the overall genetic maps of S. typhimurium and E. coli K-12, the insertions, deletions and inversions in the mutS-rpoS region provide evidence that this region of the chromosome is an active site for horizontal gene transfer and rearrangement. C1 US FDA, Div Mol Biol, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. RP Cebula, TA (reprint author), US FDA, Div Mol Biol, Ctr Food Safety & Appl Nutr, 8301 Muirkirk Rd, Laurel, MD 20708 USA. NR 40 TC 12 Z9 12 U1 0 U2 1 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 1350-0872 J9 MICROBIOL-SGM JI Microbiology-(UK) PD AUG PY 2002 VL 148 BP 2531 EP 2540 PN 8 PG 10 WC Microbiology SC Microbiology GA 585NA UT WOS:000177529800030 PM 12177346 ER PT J AU Chakraborty, AK Hall, RH Ghose, AC AF Chakraborty, AK Hall, RH Ghose, AC TI Purification and characterization of a potent hemolytic toxin with phospholipase A(2) activity from the venom of Indian Russell's viper SO MOLECULAR AND CELLULAR BIOCHEMISTRY LA English DT Article DE antivenom; hemolytic toxin; phospholipase A(2); Russell's viper; Vipera russelli; venom toxin ID SNAKE-VENOM; SIAMENSIS; ANTIBODIES; PULCHELLA; SITES; BITES AB A potent toxin with phospholipase A(2) (PLA(2)) and hemolytic activity in vitro was purified from the Russell's viper venom of eastern India (RVV-EI). The purified protein (RVV-PFIIc') of 15.3 kDa molecular weight, and a lethal toxicity dose (LD50 i.p.) of 0.1 mg/kg body weight, was the most toxic PLA(2) so far reported from the Indian subcontinent. The material also possessed anticoagulant activity as it enhanced the prothrombin induced plasma clotting time in vitro. The PLA(2) toxin (RVV-PFIIc') was shown to be different from other PLA(2)s of RVV in respect to one or more of these parameters e.g. molecular weight, isoelectric pH, in vivo toxicity, specific activity of the enzyme and certain other biological activities. The first 19 amino terminal sequence (NLFQFAEMIVKMTGKEAVH) of RVV-PFIIc' showed variable degree of homology (42.1-94.7%) with those of other RVV-PLA(2)s described in the literature. Antisera raised against RVV-EI or RVV-PFIIc', though completely neutralized the in vivo lethal toxicity of RVV-EI or RVV-PFIIc', failed to inhibit their PLA(2) activity in vitro thereby suggesting that in vivo toxicity and in vitro activity of the enzyme may not be directly related. Apart from RVV-PFIIc', at least two other PLA(2) isozymes were found to be present in RVV-EI that were distinct from RVV-PFIIc' in respect to their molecular, biological as well as serological properties. The significance of these and related data in antivenom therapy is discussed. C1 Bose Inst, Dept Microbiol, Kolkata 700054, W Bengal, India. US FDA, Div Virulence Assessment, Washington, DC 20204 USA. RP Bose Inst, Dept Microbiol, P-1-12,CIT Scheme VIIM, Kolkata 700054, W Bengal, India. EM acghosh@bic.boseinst.ernet.in NR 31 TC 6 Z9 7 U1 1 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0300-8177 EI 1573-4919 J9 MOL CELL BIOCHEM JI Mol. Cell. Biochem. PD AUG PY 2002 VL 237 IS 1-2 BP 95 EP 102 DI 10.1023/A:1016591318855 PG 8 WC Cell Biology SC Cell Biology GA 578VX UT WOS:000177142700011 PM 12236591 ER PT J AU Kawakami, K Husain, SR Kawakami, M Puri, RK AF Kawakami, K Husain, SR Kawakami, M Puri, RK TI Improved anti-tumor activity and safety of interleukin-13 receptor targeted cytotoxin by systemic continuous administration in head and neck cancer xenograft model SO MOLECULAR MEDICINE LA English DT Article ID CARCINOMA CELL-LINES; PSEUDOMONAS EXOTOXIN-A; IL-13 RECEPTOR; ALPHA CHAIN; SIGNAL-TRANSDUCTION; (IL)-13 BINDING; PROTEIN; CLONING; GROWTH; PHOSPHORYLATION AB Background: IL-13 receptor (IL-13R) targeted cytotoxin, IL13-PE38QQR, has been shown to have very potent anti-tumor activity to IL-13R-expressing head and neck tumor cells in vitro and in vivo. However, its effect is limited in aggressive tumors. To further improve the anti-tumor activity and safety of IL-13 cytotoxin, we employed continuous infusion technique in animal model of head and neck cancer. Materials and Methods: We surgically implanted continuous infusion (CI) pump intraperitoneally that released drug for 7 days, and its anti-tumor effect was evaluated. A comparison was made for antitumor activity and safety with intravenously (IV) administered IL-13 cytotoxin in a head and neck (KCCT873 and HN12) subcutaneous (SC) xenograft tumor models in nude mice. Vital organ toxicities were assessed by histologic examinations and blood serum chemistry analyses. Results: The 50 or 75 mug/kg/day for 7 days of IL-13 cytotoxin either by IV or CI administration did not show any difference in safety or anti-tumor activity. IV administration of 150 or 200 mug/kg/day of IL-13 cytotoxin for 7 days was lethal to nude mice, whereas 200 mug/kg/day X 7 days of Cl administration was highly effective in the regression of established tumors without any toxicities. Additionally, CI administration of IL-13 cytotoxin (200 mug/kg/day) showed growth inhibition of larger HN12 tumors in nude mice. Conclusion: With a CI schedule, IL-13 cytotoxin can be systemically administrated at approximately twice the dose otherwise given by daily IV bolus administration. C1 US FDA, Ctr Biol Evaluat & Res, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, Bethesda, MD 20892 USA. RP Puri, RK (reprint author), US FDA, Ctr Biol Evaluat & Res, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, NHI Bldg 29B,Room 2NN10,29 Lincoln Dr MSC 4555, Bethesda, MD 20892 USA. NR 42 TC 23 Z9 23 U1 0 U2 2 PU JOHNS HOPKINS UNIV PRESS PI BALTIMORE PA JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD 21218-4319 USA SN 1076-1551 J9 MOL MED JI Mol. Med. PD AUG PY 2002 VL 8 IS 8 BP 487 EP 494 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 605NX UT WOS:000178684900007 PM 12435859 ER PT J AU Caplen, NJ Zheng, ZL Falgout, B Morgan, RA AF Caplen, NJ Zheng, ZL Falgout, B Morgan, RA TI Inhibition of viral gene expression and replication in mosquito cells by dsRNA-triggered RNA interference SO MOLECULAR THERAPY LA English DT Article DE RNA interference; RNAi; mosquito; dsRNA; Semliki Forest virus; dengue virus; gene silencing ID DOUBLE-STRANDED-RNA; MESSENGER-RNA; CAENORHABDITIS-ELEGANS; VIRUS TRANSMISSION; DROSOPHILA CELLS; AEDES-AEGYPTI; C-ELEGANS; HELICASE; DENGUE; DEGRADATION AB Mosquitoes transmit numerous viral pathogens to humans including dengue virus which affects similar to 50 million individuals per year. Inhibition of viral gene expression within an insect host could be used to block virus replication and subsequent transmission of the pathogen to humans. A naturally occurring gene silencing mechanism triggered by double-stranded RNA (dsRNA), RNA interference (RNAi), has recently been described in a number of species including Drosophila. To ascertain if dsRNA-triggered RNAi is present in mosquito cells, we used Aedes albopictus C6/36 cells, and to investigate the feasibility of blocking viral gene expression and replication, we used two mosquito-borne viruses, Semliki Forest virus (SFV) and the serotype 1 dengue virus (DEN1). We demonstrate that dsRNA can specifically inhibit transgene expression in C6/36 cells from both plasmid and SFV replicons and can significantly modify the kinetics of DEN1 RNA and virus replication. The inhibition mediated by dsRNA was sequence-specific and either equal or superior to that induced by antisense single-stranded RNA (ssRNA). This study demonstrates dsRNA-triggered inhibition of gene expression and virus replication in mosquito cells and suggests that this mechanism could be used to block pathogen replication within an insect host and, thus, block disease transmission. C1 NHGRI, NIH, Bethesda, MD 20892 USA. US FDA, Lab Vector Borne Viral Dis, Off Vaccine Res & Review, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Morgan, RA (reprint author), NHGRI, NIH, Bethesda, MD 20892 USA. RI Caplen, Natasha/H-2768-2016 OI Caplen, Natasha/0000-0002-0001-9460 NR 45 TC 62 Z9 73 U1 0 U2 6 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD AUG PY 2002 VL 6 IS 2 BP 243 EP 251 DI 10.1006/mthe.2002.0652 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 582TX UT WOS:000177368200017 PM 12161191 ER PT J AU Zhang, CJ Imam, SZ Ali, SF Mayeux, PR AF Zhang, CJ Imam, SZ Ali, SF Mayeux, PR TI Peroxynitrite and the regulation of Na+,K+-ATPase activity by angiotensin II in the rat proximal tubule SO NITRIC OXIDE-BIOLOGY AND CHEMISTRY LA English DT Article DE renal proximal tubule; reactive nitrogen species; 3-nitrotyrosine; deferoxamme; uric acid; superoxide dismutase; peroxynitrite ID NITRIC-OXIDE SYNTHASE; OPOSSUM KIDNEY-CELLS; NA+-K+-ATPASE; LIPID-A; INHIBITION; LIPOPOLYSACCHARIDE; GENERATION; NITRATION; INJURY; MICE AB NO reacts spontaneously with superoxide to produce the potent oxidant peroxynitrite. Studies were designed to examine the role of NO-derived oxidants and peroxynitrite on the regulation of Na+,K+-ATPase activity by angiotensin 11 (ANG II) freshly isolated rat proximal tubules. At picomolar concentrations ANG 11 stimulates Na+,K+-ATPase activity, but at nanomolar concentrations stimulation is lost. Superoxide dismutase (SOD) was used to examine the role of superoxide and deferoxamine (DFO) and uric acid (UA) were used to examine the role of peroxynitrite. SOD (200 U/mL, 5-min preincubation) restored the stimulatory effect of ANG 11 (1.31 +/- 0.08-fold; n = 4; P < 0.05 compared to 10(-7) M alone), suggesting a role for superoxide. DFO (100 mum, 5-min preincubation) also restored the stimulatory effect of ANG 11 (1.40 +/- 0.08-fold; n = 4; P < 0.05, compared to 10(-7) M alone), as did UA (1.22 +/- 0.07-fold; n = 5; P < 0.05, compared to 10(-7) M alone). The NO synthesis inhibitor, N-monomethyl-L-arginine (L-NMMA, 2 mM; 5-min preincubation), also unmasked a stimulatory effect of ANG 11 at 10(-7) M (1.4 +/- 0.1-fold; n = 7; P < 0.05, compared to 10(-7) M alone). The generation of peroxynitrite was further evidenced by the formation of 3-nitrotyrosine (3-NT). 3-NT increased 3.5-fold in tubules exposed to ANG 11 (10(-7) M) (0.0054 +/- 0.0019 3-NT/100 tyrosines for control and 0.019 +/- 0.0058 3-NT/100 tyrosines for ANG 11, P < 0.05; n = 4) and L-NMMA prevented the increase. These data suggest that peroxynitrite signaling participates in the regulation of renal of Na+,K+-ATPase activity. (C) 2002 Elsevier Science (USA). All rights reserved. C1 Univ Arkansas Med Sci, Dept Pharmacol & Toxicol, Little Rock, AR 72205 USA. US FDA, Natl Ctr Toxicol Res, 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. FU NIDDK NIH HHS [DK44716] NR 47 TC 24 Z9 24 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 1089-8603 J9 NITRIC OXIDE-BIOL CH JI Nitric Oxide-Biol. Chem. PD AUG PY 2002 VL 7 IS 1 BP 30 EP 35 AR PII S1089-8603(02)00003-4 DI 10.1016/S1089-8603(02)00003-4 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 593MX UT WOS:000177996200005 PM 12175817 ER PT J AU Lam, YWF Gaedigk, A Ereshefsky, L Alfaro, CL Simpson, J AF Lam, YWF Gaedigk, A Ereshefsky, L Alfaro, CL Simpson, J TI CYP2D6 inhibition by selective serotonin reuptake inhibitors: Analysis of achievable steady-state plasma concentrations and the effect of ultrarapid metabolism at CYP2D6 SO PHARMACOTHERAPY LA English DT Article ID EXTENSIVE METABOLIZERS; FLUOXETINE; SERTRALINE; DEXTROMETHORPHAN; DESIPRAMINE; PAROXETINE; QUANTIFICATION; FLUVOXAMINE AB Study Objective. To assess the correlation between plasma concentrations of four commonly administered selective serotonin reuptake inhibitors (SSRIs) and the magnitude of cytochrome P450 (CYP) 2D6 inhibition. Design. Prospective analysis. Setting. University-affiliated research laboratory Patients. Thirty-two healthy, drug-free volunteers. Intervention. Subjects were randomized to four groups and received daily administration of either fluoxetine 60 mg (as a loading dose), fluvoxamine 100 ing, paroxetine 20 mg, or sertraline 100 mg for 8 days. Measurements and Main Results. The urinary concentration ratio of dextromethorphan:dextrorphan (interpreted as an in vivo index of CYP2D6 activity) was determined for each subject before and after the 8 days of receiving SSRIs. Plasma SSRI trough concentrations were measured on days 6-9. The CYP2D6 genotype was determined in a subject with an undetectable paroxetine concentration. Inhibition of CYP2D6 correlated significantly with plasma concentrations of paroxetine and fluoxetine. In contrast, no significant correlations emerged between CYP2D6 inhibition and plasma concentrations of sertraline or fluvoxamine. The subject with an undetectable paroxetine concentration was found to carry at least three functional CYP2D6 genes. Conclusions. For paroxetine and fluoxetine, plasma concentrations and dosage strongly influence the magnitude of enzyme inhibition. The potential of paroxetine (a CYP2D6 substrate) as an inhibitor may be affected by the genotypes and metabolic capacities of individual subjects. C1 Univ Texas, Hlth Sci Ctr, Dept Pharmacol, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Psychiat, San Antonio, TX 78284 USA. Univ Texas, Coll Pharm, San Antonio, TX 78284 USA. Childrens Mercy Hosp, Sect Clin Pharmacol & Expt Therapeut, Kansas City, MO 64108 USA. US FDA, Rockville, MD 20857 USA. Alamo Mental Hlth Grp, San Antonio, TX USA. RP Lam, YWF (reprint author), Univ Texas, Hlth Sci Ctr, Dept Pharmacol, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. NR 24 TC 50 Z9 55 U1 1 U2 8 PU PHARMACOTHERAPY PUBLICATIONS INC PI BOSTON PA NEW ENGLAND MEDICAL CENTER, 806, 750 WASHINGTON ST, BOSTON, MA 02111 USA SN 0277-0008 J9 PHARMACOTHERAPY JI Pharmacotherapy PD AUG PY 2002 VL 22 IS 8 BP 1001 EP 1006 DI 10.1592/phco.22.12.1001.33603 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 580AQ UT WOS:000177212200008 PM 12173784 ER PT J AU Teuschler, L Klaunig, J Carney, E Chambers, J Conolly, R Gennings, C Giesy, J Hertzberg, R Klaassen, C Kodell, R Paustenbach, D Yang, R AF Teuschler, L Klaunig, J Carney, E Chambers, J Conolly, R Gennings, C Giesy, J Hertzberg, R Klaassen, C Kodell, R Paustenbach, D Yang, R TI Support of science-based decisions concerning the evaluation of the toxicology of mixtures: A new beginning SO REGULATORY TOXICOLOGY AND PHARMACOLOGY LA English DT Article ID RISK ASSESSMENT; INDIVIDUAL COMPOUNDS; CHEMICAL-MIXTURES; ORAL TOXICITY; RATS; GROUNDWATER; COMBINATION C1 Virginia Commonwealth Univ, Dept Biostat, Richmond, VA 23298 USA. US EPA, Natl Ctr Environm Assessment, Cincinnati, OH 45268 USA. Indiana Univ, Sch Med, Dept Pharmacol & Toxicol, Indianapolis, IN USA. Dow Chem Co USA, Midland, MI 48674 USA. Mississippi State Univ, Coll Vet Med, Mississippi State, MS 39762 USA. CIIT, Res Triangle Pk, NC USA. Michigan State Univ, E Lansing, MI 48824 USA. Univ Kansas, Med Ctr, Dept Pharmacol & Toxicol, Kansas City, KS 66103 USA. Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. Exponent Environm Grp Inc, Menlo Pk, CA USA. Colorado State Univ, Ctr Environm Toxicol & Technol, Ft Collins, CO 80523 USA. RP Gennings, C (reprint author), Virginia Commonwealth Univ, Dept Biostat, Box 980032, Richmond, VA 23298 USA. NR 24 TC 48 Z9 50 U1 0 U2 9 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0273-2300 J9 REGUL TOXICOL PHARM JI Regul. Toxicol. Pharmacol. PD AUG PY 2002 VL 36 IS 1 BP 34 EP 39 DI 10.1006/rtph.2002.1570 PG 6 WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology SC Legal Medicine; Pharmacology & Pharmacy; Toxicology GA 600UR UT WOS:000178410600004 PM 12383716 ER PT J AU Carrington, CD Bolger, MP AF Carrington, CD Bolger, MP TI An exposure assessment for methylmercury from seafood for consumers in the United States SO RISK ANALYSIS LA English DT Article DE methylmercury; dietary exposure; biomarkers ID FISH; MERCURY; INGESTION; CHILDREN AB An exposure model was developed to relate seafood consumption to levels of methylmercury (reported as mercury) in blood and hair in the U.S. population, and two subpopulations defined as children aged 2-5 and women aged 18-45. Seafood consumption was initially modeled using short-term (three-day) U.S.-consumption surveys that recorded the amount of fish eaten per meal. Since longer exposure periods include more eaters with a lower daily mean intake, the consumption distribution was adjusted by broadening the distribution to include more eaters and reducing the distribution mean to keep total population intake constant. The estimate for the total number of eaters was based on long-term purchase diaries. Levels of mercury in canned tuna, swordfish, and shark were based on FDA survey data. The distribution of mercury levels in other species was based on reported mean levels, with the frequency of consumption of each species based on market share. The shape distribution for the given mean was based on the range of variation encountered among shark, tuna, and swordfish. These distributions were integrated with a simulation that estimated average daily intake over a 360-day period, with 10,000 simulated individuals and 1,000 uncertainty iterations. The results of this simulation were then used as an input to a second simulation that modeled levels of mercury in blood and hair. The relationship between dietary intake and blood mercury in a population was modeled from data obtained from a 90-day study with controlled seafood intake. The relationship between blood and hair mercury in a population was modeled from data obtained from several sources. The biomarker simulation employed 2,000 simulated individuals and 1,000 uncertainty iterations. These results were then compared to the recent National Health and Nutrition Examination Survey (NHANES) that tabulated blood and hair mercury levels in a cross-section of the U.S. population. The output of the model and NHANES results were similar for both children and adult women, with predicted mercury biomarker concentrations within a factor of two or less of NHANES biomarker results. However, the model tended to underpredict blood levels for women and overpredict blood and hair levels for children. C1 US FDA, Ctr Food Safety & Appl Nutr, Off Plants & Dairy Foods & Beverages, Div Risk Assessment, Washington, DC 20204 USA. RP Carrington, CD (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Plants & Dairy Foods & Beverages, Div Risk Assessment, Washington, DC 20204 USA. NR 17 TC 53 Z9 55 U1 3 U2 13 PU BLACKWELL PUBLISHERS PI MALDEN PA 350 MAIN STREET, STE 6, MALDEN, MA 02148 USA SN 0272-4332 J9 RISK ANAL JI Risk Anal. PD AUG PY 2002 VL 22 IS 4 BP 689 EP 699 DI 10.1111/0272-4332.00061 PG 11 WC Public, Environmental & Occupational Health; Mathematics, Interdisciplinary Applications; Social Sciences, Mathematical Methods SC Public, Environmental & Occupational Health; Mathematics; Mathematical Methods In Social Sciences GA 591UT UT WOS:000177899200005 PM 12224743 ER PT J AU Lachenbruch, PA AF Lachenbruch, PA TI Analysis of data with excess zeros SO STATISTICAL METHODS IN MEDICAL RESEARCH LA English DT Review AB This paper is an introduction to a set of papers on two-part models that were presented at the 2000 joint Statistical Meetings of American Statistical Association, International Biometric Society (ENAR), International Biometric Society (WNAR), Institute of Mathematical Statistics, and Statistical Society of Canada. The second part of the paper summarizes results of a study of the size and power of two-part models. It proposes that two-part models are a useful alternative to the t-test and the Wilcoxon test. C1 US FDA, Ctr Biol Res & Review, Off Biostat & Epidemiol, Rockville, MD 20857 USA. RP Lachenbruch, PA (reprint author), 1401 Rockville Pike,HFM-215, Rockville, MD 20852 USA. NR 7 TC 68 Z9 68 U1 4 U2 15 PU ARNOLD, HODDER HEADLINE PLC PI LONDON PA 338 EUSTON ROAD, LONDON NW1 3BH, ENGLAND SN 0962-2802 J9 STAT METHODS MED RES JI Stat. Methods Med. Res. PD AUG PY 2002 VL 11 IS 4 BP 297 EP 302 DI 10.1191/0962280202sm289ra PG 6 WC Health Care Sciences & Services; Mathematical & Computational Biology; Medical Informatics; Statistics & Probability SC Health Care Sciences & Services; Mathematical & Computational Biology; Medical Informatics; Mathematics GA 585WU UT WOS:000177548200001 PM 12197297 ER PT J AU Berk, KN Lachenbruch, PA AF Berk, KN Lachenbruch, PA TI Repeated measures with zeros SO STATISTICAL METHODS IN MEDICAL RESEARCH LA English DT Review ID REGRESSION-ANALYSES; MODEL AB Consider repeated measures data with many zeros. For the case with one grouping factor and one repeated measure, we examine several models, assuming that the nonzero data are roughly lognormal. One of the simplest approaches is to model the zeros as left-censored observations from the lognormal distribution. A random effect is assumed for subjects. The censored model makes a strong assumption about the relationship between the zeros and the nonzero values. To check on this, you can instead assume that some of the zeros are 'true' zeros and model them as Bernoulli. Then the other values are modeled with a censored lognormal. A logistic model is used for the Bernoulli p, the probability of a true nonzero. The fit of the pure left-censored lognormal can be assessed by testing the hypothesis that p is 1, as described by Moulton and Halsey.(1) The model can also be simplified by omitting the censoring, leaving a logistic model for the zeros and a lognormal model for the nonzero values. This is approximately equivalent to modeling the zero and nonzero values separately, a two-part model. In contrast to the censored model, this model assumes only a slight relationship (a covariance component) between the occurrence of zeros and the size of the nonzero values. The models are compared in terms of an example with data from children's private speech. C1 Illinois State Univ, Dept Math, Normal, IL 61790 USA. US FDA, Ctr Biol Res & Review, Rockville, MD 20857 USA. RP Berk, KN (reprint author), Illinois State Univ, Dept Math, Box 4520, Normal, IL 61790 USA. NR 11 TC 49 Z9 50 U1 0 U2 7 PU ARNOLD, HODDER HEADLINE PLC PI LONDON PA 338 EUSTON ROAD, LONDON NW1 3BH, ENGLAND SN 0962-2802 J9 STAT METHODS MED RES JI Stat. Methods Med. Res. PD AUG PY 2002 VL 11 IS 4 BP 303 EP 316 DI 10.1191/0962280202sm293ra PG 14 WC Health Care Sciences & Services; Mathematical & Computational Biology; Medical Informatics; Statistics & Probability SC Health Care Sciences & Services; Mathematical & Computational Biology; Medical Informatics; Mathematics GA 585WU UT WOS:000177548200002 PM 12197298 ER PT J AU Krieg, RC Paweletz, CP Liotta, LA Petricoin, EF AF Krieg, Rene C. Paweletz, Cloud P. Liotta, Lance A. Petricoin, Emanuel F., III TI Clinical Proteomics for Cancer Biomarker Discovery and Therapeutic Targeting SO TECHNOLOGY IN CANCER RESEARCH & TREATMENT LA English DT Article DE SELDI; 2D-PAGE; laser capture microdissection; proteomic pattern diagnostics; protein array AB As we emerge into the post-genome era, proteomics finds itself as the driving force field as we translate the nucleic acid information archive into understanding how the cell actually works and how disease processes operate. Even so, the traditionally held view of proteomics as simply cataloging and developing lists of the cellular protein repertoire of a cell are now changing, especially in the sub-discipline of clinical proteomics. The most relevant information archive to clinical applications and drug development involves the elucidation of the information flow of the cell; the "software" of protein pathway networks and circuitry. The deranged circuitry of the cell as the drug target itself as well as the effect of the drug on not just the target, but also the entire network, is what we now are striving towards. Clinical proteomics, as a new and most exciting sub-discipline of proteomics, involves the bench-to-bedside clinical application of proteomic tools. Unlike the genome, there are potentially thousands of proteomes: each cell type has its own unique proteome. Moreover, each cell type can alter its proteome depending on the unique tissue microenvironment in which it resides, giving rise to multiple permutations of a single proteome. Since there is no polymerase chain reaction equivalent to proteomics- identifying and discovering the "wiring diagram" of a human diseased cell in a biopsy specimen remains a daunting challenge. New micro-proteomic technologies are being and still need to be developed to drill down into the proteomes of clinically relevant material. Cancer, as a model disease, provides a fertile environment to study the application of proteomics at the bedside. The promise of clinical proteomics and the new technologies that are developed is that we will detect cancer earlier through discovery of biomarkers, we will discover the next generation of targets and imaging biomarkers, and we can then apply this knowledge to patient-tailored therapy. C1 [Krieg, Rene C.; Paweletz, Cloud P.; Liotta, Lance A.] NCI, FDA NCI Clin Prote Program, Pathol Lab, NIH, Bethesda, MD 20892 USA. [Petricoin, Emanuel F., III] US FDA, FDA NCI Clin Prote Program, Div Therapeut Prot, CBER, Bethesda, MD 20892 USA. RP Petricoin, EF (reprint author), US FDA, FDA NCI Clin Prote Program, Div Therapeut Prot, CBER, Bethesda, MD 20892 USA. EM petricoin@cber.fda.gov NR 61 TC 25 Z9 27 U1 0 U2 1 PU ADENINE PRESS PI SCHENECTADY PA 2066 CENTRAL AVE, SCHENECTADY, NY 12304 USA SN 1533-0346 J9 TECHNOL CANCER RES T JI Technol. Cancer Res. Treat. PD AUG PY 2002 VL 1 IS 4 BP 263 EP 272 PG 10 WC Oncology SC Oncology GA V28FX UT WOS:000208667800007 PM 12625785 ER PT J AU Zbikowska, HM Soukhareva, N Behnam, R Chang, R Drews, R Lubon, H Hammond, D Soukharev, S AF Zbikowska, HM Soukhareva, N Behnam, R Chang, R Drews, R Lubon, H Hammond, D Soukharev, S TI The use of the uromodulin promoter to target production of recombinant proteins into urine of transgenic animals SO TRANSGENIC RESEARCH LA English DT Article DE human erythropoietin; lacZ gene; transgenic mouse; urine; uromodulin promoter ID MAMMARY-GLAND; MICE; EXPRESSION; GENE; RABBITS; GLYCOPROTEIN; KIDNEY; DNA AB A uromodulin promoter has been isolated, sequenced, and used to generate two sets of transgenic mice for expression of the lacZ marker gene and for production of the human recombinant erythropoietin (rhEPO) in urine. We demonstrated that the 5.6-kb fragment of the uromodulin gene containing the 3.7-kb promoter area and, both the first exon and part of the second exon, were sufficient to provide kidney-specific expression of the lacZ gene. Histological analysis of the lacZ expression pattern revealed beta-galactosidase activity specifically in the thick limb of Henle's loop. However, due to random integration of the transgene, ectopic expression was detected in some transgenic lines. Analysis of the EPO-transgenic mice showed that rhEPO was secreted into the urine of founder mice (up to 6 ng/ml). We were able to breed and analyze only two sublines with a very low expression level of rhEPO (up to 260 pg/ml). All of our transgenic mice expressing rhEPO in urine developed disease symptoms similar to polycythemia in humans. These included a considerable increase in red blood cell counts, hemoglobin concentration, and hematocrit concomitant with severe thrombocytopenia, all of which were detected in the rhEPO-expressing mice. Although our model did not prove to be beneficial for commercial production of rhEPO, we concluded that the uromodulin promoter could be useful for expression of other important therapeutic proteins into the urine of transgenic animals. C1 Amer Red Cross, Holland Lab, Plasma Derivat Dept, Rockville, MD 20855 USA. Clearant Inc, Rockville, MD 20850 USA. US FDA, Div Hematol, OBRR, Rockville, MD 20852 USA. RP Soukharev, S (reprint author), Amer Red Cross, Holland Lab, Plasma Derivat Dept, 15601 Crabbs Branch Way, Rockville, MD 20855 USA. NR 24 TC 18 Z9 21 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0962-8819 J9 TRANSGENIC RES JI Transgenic Res. PD AUG PY 2002 VL 11 IS 4 BP 425 EP 435 DI 10.1023/A:1016312017024 PG 11 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 573GJ UT WOS:000176820700009 PM 12212844 ER PT J AU Chu, PS Wang, RC Chu, HFV AF Chu, PS Wang, RC Chu, HFV TI Liquid chromatographic determination of fluoroquinolones in egg albumen and egg yolk of laying hens using fluorometric detection SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE fluoroquinolones; eggs; HPLC; method; survey ID RESIDUES; SARAFLOXACIN AB A liquid chromatographic method was developed for the determination of ciprofloxacin, enrofloxacin, and sarafloxacin at 10-200 ppb in both egg yolk and egg albumen of laying hens. Egg yolk or albumen was acidified with 1 M phosphoric acid followed by deproteination with acetonitrile and centrifugation. The supernate was pipetted out, and the remaining protein pellet was extracted three times with acetonitrile. The supernates were combined and concentrated at 50 degreesC to <0.7 mL. The final volume was adjusted to 2 mL with 0.02 M potassium phosphate buffer, pH 2.5. Separation of the analytes was achieved using reversed-phase HPLC with fluorometric detection. The recoveries were >80% and coefficients of variation <20%. After validation, the method was applied for use in a national survey for fluoroquinolones in table eggs. Of the 276 eggs assayed, none was found positive for fluoroquinolones. The findings suggest that illegal use of fluoroquinolones in laying hens is not widespread. C1 US FDA, Ctr Vet Med, Laurel, MD 20708 USA. RP Chu, PS (reprint author), US FDA, Ctr Vet Med, 8401 Muirkirk Rd, Laurel, MD 20708 USA. NR 7 TC 36 Z9 38 U1 2 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0021-8561 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD JUL 31 PY 2002 VL 50 IS 16 BP 4452 EP 4455 DI 10.1021/jf0202032 PG 4 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 578GQ UT WOS:000177109400004 PM 12137459 ER PT J AU Yi, P Pogribny, IP James, SJ AF Yi, P Pogribny, IP James, SJ TI Multiplex PCR for simultaneous detection of 677-C -> T and 1298-A -> C polymorphisms in methylenetetrahydrofolate reductase gene for population studies of cancer risk SO CANCER LETTERS LA English DT Article DE methylenetetrahydrofolate reductase; cancer risk; folate; multiplex polymerase chain reaction ID MTHFR POLYMORPHISM; CHINESE POPULATION; COLORECTAL-CANCER; FOLATE METABOLISM; COMMON MUTATION; CARCINOMA; ADENOMA AB Methylenetetrahydrofolate reductase (MTHFR) plays a pivotal role in folate metabolism by regulating the diversion of folate metabolites toward DNA methylation or toward DNA synthesis. Because aberrations in both of these pathways can be tumor promoting, the two common polymorphisms in the MTHFR gene, 677 C --> T and 1298 A --> C, have been implicated as risk factors for several cancers. Homozygosity for the 677 C --> T polymorphism and compound heterozygosity for 677 C --> T and 1298 A --> C polymorphisms both reduce enzyme activity by more than 50% and can promote oncogenic alterations in DNA methylation especially when folate status is low. Thus, rapid identification of both polymorphisms in MTHFR gene would be of importance in understanding the genetics of abnormal folate metabolism as related to human cancer risk. Here we describe a multiplex polymerse chain reaction/restriction fragment length polymorphism procedure in which two sets of primers are used to amplify simultaneously the DNA regions spanning 677 and 1298 loci in one PCR reaction. The amplified products are digested by HinfI or MboII followed by agarose gel electrophoresis for simultaneous detection of the 677 C --> T and 1298 A --> C polymorphisms in the same gel. (C) 2002 Published by Elsevier Science Ireland Ltd. C1 US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP James, SJ (reprint author), US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. NR 15 TC 51 Z9 53 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD JUL 26 PY 2002 VL 181 IS 2 BP 209 EP 213 AR PII S0304-3835(02)00060-5 DI 10.1016/S0304-3835(02)00060-5 PG 5 WC Oncology SC Oncology GA 567WR UT WOS:000176509400008 PM 12175537 ER PT J AU Kojima, Y Xin, KQ Ooki, T Hamajima, K Oikawa, T Shinoda, K Ozaki, T Hoshino, Y Jounai, N Nakazawa, M Klinman, D Okuda, K AF Kojima, Y Xin, KQ Ooki, T Hamajima, K Oikawa, T Shinoda, K Ozaki, T Hoshino, Y Jounai, N Nakazawa, M Klinman, D Okuda, K TI Adjuvant effect of multi-CpG motifs on an HIV-1 DNA vaccine SO VACCINE LA English DT Article DE CpG motif; DNA vaccine; HIV; dendritic cells ID HUMAN-IMMUNODEFICIENCY-VIRUS; CELL-MEDIATED-IMMUNITY; CYTOTOXIC T-LYMPHOCYTES; BACTERIAL-DNA; EXPRESSION PLASMID; IMMUNOSTIMULATORY DNA; DENDRITIC CELLS; RESPONSES; ANTIGEN; ACTIVATION AB Synthetic oligodeoxynucleotides (ODN) containing unmethylated CpG motifs trigger an immune response characterized by the activation of B cells, NK cells and monocytes/macrophages. Based on evidence that the immunogenicity of DNA vaccines can be augmented by the addition of CpG motifs, 5-20 additional CpG motifs were cloned into a pUC-derived plasmid. Treating bone-marrow derived dendritic cells (BM-DCs) with CpG-enriched plasmids in vitro boosted their expressions of MHC class II molecules, the CD40 and CD86 activation markers. Co-administering the CpG-enriched plasmids with a DNA vaccine encoding the envelope glycoprotein of HIV to BALB/c mice significantly increased HIV-specific cell mediated and humoral immunity. A significant boost was observed when the CpG plasmid was administered either 2 or 4 days after DNA vaccination. Plasmids containing 20 CpG copies were the most effective immune enhancers both in vitro and in vivo. These results suggest that plasmids containing multiple CpG motifs may improve the immunogenicity of DNA vaccines. (C) 2002 Elsevier Science Ltd. All rights reserved. C1 Yokohama City Univ, Sch Med, Dept Bacteriol, Yokohama, Kanagawa 2360004, Japan. Yokohama City Univ, Sch Med, Dept Parasitol, Yokohama, Kanagawa 2360004, Japan. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Okuda, K (reprint author), Yokohama City Univ, Sch Med, Dept Bacteriol, Yokohama, Kanagawa 2360004, Japan. NR 39 TC 83 Z9 96 U1 0 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD JUL 26 PY 2002 VL 20 IS 23-24 BP 2857 EP 2865 AR PII S0264-410X(02)00238-4 DI 10.1016/S0264-410X(02)00238-4 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 587PB UT WOS:000177649400004 PM 12126895 ER PT J AU Halsted, CH Villanueva, JA Devlin, AM Niemela, O Parkkila, S Garrow, TA Wallock, LM Shigenaga, MK Melnyk, S James, SJ AF Halsted, CH Villanueva, JA Devlin, AM Niemela, O Parkkila, S Garrow, TA Wallock, LM Shigenaga, MK Melnyk, S James, SJ TI Folate deficiency disturbs hepatic methionine metabolism and promotes liver injury in the ethanol-fed micropig SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ADENOSYL-L-METHIONINE; S-ADENOSYLMETHIONINE SYNTHETASE; PERIVENOUS RAT HEPATOCYTES; CHRONIC-ALCOHOLIC MONKEY; OXIDATIVE STRESS; NITRIC-OXIDE; ELECTROCHEMICAL DETECTION; HOMOCYSTEINE METABOLISM; GLUTATHIONE SYNTHESIS; PLASMA HOMOCYSTEINE AB Alcoholic liver disease is associated with abnormal hepatic methionine metabolism and folate deficiency. Because folate is integral to the methionine cycle, its deficiency could promote alcoholic liver disease by enhancing ethanol-induced perturbations of hepatic methionine metabolism and DNA damage. We grouped 24juvenile micropigs to receive folate-sufficient (IFS) or folate-depleted (FD) diets or the same diets containing 40% of energy as ethanol (FSE and FDE) for 14 wk, and the significance of differences among the groups was determined by ANOVA. Plasma homocysteine levels were increased in all experimental groups from 6 wk onward and were greatest in FIDE. Ethanol feeding reduced liver methionine synthase activity, S-adenosylmethionine (SAM), and glutathione, and elevated plasma malondialdehyde (MDA) and alanine transaminase. Folate deficiency decreased liver folate levels and increased global DNA hypomethylation. Ethanol feeding and folate deficiency acted together to decrease the liver SAM/S-adenosylhomocysteine (SAH) ratio and to increase liver SAH, DNA strand breaks, urinary 8-oxo-2'-deoxyguanosine [oxo(8)dG]/mg of creatinine, plasma homocysteine, and aspartate transaminase by more than 8-fold. Liver SAM correlated positively with glutathione, which correlated negatively with plasma MIDA and urinary oxo(8)dG. Liver SAM/SAH correlated negatively with DNA strand breaks, which correlated with urinary oxo(8)dG. Livers from ethanol-fed animals showed increased centrilobular CYP2E1 and protein adducts with acetaldehyde and MIDA. Steatohepatitis occurred in five of six pigs in FDE but not in the other groups. In summary, folate deficiency enhances perturbations in hepatic methionine metabolism and DNA damage while promoting alcoholic liver injury. C1 Univ Calif Davis, Sch Med, Dept Internal Med, Davis, CA 95616 USA. Tampere Univ, Inst Med Technol, FIN-33101 Tampere, Finland. Univ Illinois, Urbana, IL 61801 USA. Childrens Hosp, Oakland Res Inst, Oakland, CA 94609 USA. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Halsted, CH (reprint author), Univ Calif Davis, Sch Med, Dept Internal Med, TB 156,1 Shields Ave, Davis, CA 95616 USA. FU NIDDK NIH HHS [DK45301, DK52501, P30 DK035747, R01 DK052501, DK35747, R29 DK052501] NR 65 TC 113 Z9 117 U1 2 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUL 23 PY 2002 VL 99 IS 15 BP 10072 EP 10077 DI 10.1073/pnas.112336399 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 577DG UT WOS:000177042400085 PM 12122204 ER PT J AU Pletnikov, MV Rubin, SA Vogel, MW Moran, TH Carbone, KM AF Pletnikov, MV Rubin, SA Vogel, MW Moran, TH Carbone, KM TI Effects of genetic background on neonatal Borna disease virus infection-induced neurodevelopmental damage I. Brain pathology and behavioral deficits SO BRAIN RESEARCH LA English DT Article DE Borna; hippocampus; cerebellum; startle; stereotypy; hyperactivity ID LEWIS RATS; PREPULSE INHIBITION; STRAIN DIFFERENCES; VIRAL-INFECTION; NERVOUS-SYSTEM; DENTATE GYRUS; BDV INFECTION; ADULT RATS; AUTISM; PERSISTENT AB The pathogenic mechanisms of gene-environment interactions determining variability of human neurodevelopmental disorders remain unclear. In the two consecutive papers, we used the neonatal Borna disease virus (BDV) infection rat model of neurodevelopmental damage to evaluate brain pathology, monoamine alterations, behavioral deficits, and responses to pharmacological treatments in two inbred rat strains, Lewis and Fisher344. The first paper reports that despite comparable virus replication and distribution in the brain of both rat strains, neonatal BDV infection produced significantly greater thinning of the neocortex in BDV-infected Fisher344 rats compared to BDV-infected Lewis rats, while no strain-related differences were found in BDV-induced granule cell loss in the dentate gyrus of the hippocampus and cerebellar hypoplasia. Unlike BDV-infected Lewis rats, more severe BDV-induced brain pathology in Fisher344 rats was associated with (1) greater locomotor activity to novelty and (2) impairment of habituation and prepulse inhibition of the acoustic startle response. The present data demonstrate that the same environmental insult can produce differential neuroanatomical and behavioral abnormalities in genetically different inbred rat strains. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. US FDA, Ctr Biol Evaluat & Res, Lab Pediat & Resp Viral Dis, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. Univ Maryland, Maryland Psychiat Res Ctr, Dev Neurobiol Lab, Baltimore, MD 21228 USA. RP Pletnikov, MV (reprint author), Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, 720 Rutland Ave,Ross 618, Baltimore, MD 21205 USA. OI Vogel, Michael/0000-0002-8402-1495 FU NIMH NIH HHS [2R7O1 MH48948-08A1] NR 64 TC 26 Z9 27 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 JUL 19 PY 2002 VL 944 IS 1-2 BP 97 EP 107 AR PII S0006-8993(02)02723-3 DI 10.1016/S0006-8993(02)02723-3 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 580FH UT WOS:000177224100011 PM 12106670 ER PT J AU Pletnikov, MV Rubin, SA Vogel, MW Moran, TH Carbone, KM AF Pletnikov, MV Rubin, SA Vogel, MW Moran, TH Carbone, KM TI Effects of genetic background on neonatal Borna disease virus infection-induced neurodevelopmental damage II. Neurochemical alterations and responses to pharmacological treatments SO BRAIN RESEARCH LA English DT Article DE Borna; monoamine; fluoxetine; 8-OH-DPAT; Lewis; Fisher344 ID VENTRAL TEGMENTAL AREA; LEWIS RATS; DOPAMINE RELEASE; SEROTONIN; RECEPTOR; AUTISM; PSYCHOSTIMULANTS; VULNERABILITY; SENSITIVITY; INHIBITION AB The gene-environment interplay is thought to determine variability in clinical conditions and responses to therapy in human neurodevelopmental disorders. Studying abnormal brain and behavior development in inbred strains of rodents can help in the identification of the complex pathogenic mechanisms of the host-environment interaction. This paper is the second one in a series of the two reports of the use of the Borna disease virus (BDV) infection model of neurodevelopmental damage to characterize effects of genetic background on virus-induced neurodevelopmental damage in inbred rat strains, Lewis and Fisher344. The present data demonstrate that neonatal BDV infection produced regional and strain-related alterations in levels of serotonin, norepinephrine and in levels of serotonin turnover at postnatal day 120. Neonatal BDV infection also induced upregulation of hippocampal 5-HT(1a) and cortical 5-HT(2a) receptors in Lewis rats and downregulation of cortical 5-HT(2a) receptors in Fisher344 rats. BDV-associated regional downregulation of D(2) receptors and dopamine transporter sites were noted in Fisher344 rats. In addition to the neurochemical disturbances, neonatal BDV infection induced differential responses to serotonin compounds. While 8-OH-DPAT suppressed virus-enhanced ambulation in BDV-infected Fisher344, fluoxetine inhibited virus-induced hyperactivity in BDV-infected Lewis rats only. The present data provide new insights into the pathogenic events that lead to differential responses to pharmacological treatments in genetically different animals following exposure to the same environmental challenge. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. US FDA, Ctr Biol Evaluat & Res, Lab Pediat & Resp Viral Dis, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. Univ Maryland, Maryland Psychiat Res Ctr, Dev Neurobiol Lab, Baltimore, MD 21228 USA. RP Pletnikov, MV (reprint author), Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, 720 Rutland Ave,Ross 618, Baltimore, MD 21205 USA. EM pletnikov@cber.fda.gov OI Vogel, Michael/0000-0002-8402-1495 FU NIMH NIH HHS [2R7O1 MH48948-08A1] NR 46 TC 20 Z9 22 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 JUL 19 PY 2002 VL 944 IS 1-2 BP 108 EP 123 AR PII S0006-8993(02)02724-5 DI 10.1016/S0006-8993(02)02724-5 PG 16 WC Neurosciences SC Neurosciences & Neurology GA 580FH UT WOS:000177224100012 PM 12106671 ER PT J AU Chowdhury, BA AF Chowdhury, BA TI Chronic urticaria and angioedema SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID CHRONIC IDIOPATHIC URTICARIA; PLACEBO C1 US FDA, Rockville, MD 20857 USA. RP Chowdhury, BA (reprint author), US FDA, Rockville, MD 20857 USA. NR 5 TC 1 Z9 1 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUL 18 PY 2002 VL 347 IS 3 BP 220 EP 221 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 574BR UT WOS:000176869000023 PM 12124416 ER PT J AU Shvartsburg, AA AF Shvartsburg, AA TI Acetonitrile complexes of triply charged metal ions: are ligated trications intrinsically more prone to charge reduction than dications? SO CHEMICAL PHYSICS LETTERS LA English DT Article ID ELECTROSPRAY MASS-SPECTROMETRY; GAS-PHASE REACTIONS; ALKALINE-EARTH; COORDINATION; IONIZATION; CHEMISTRY; CLUSTERS; MG; CA; BA AB The development of electrospray has enabled the generation of gas-phase solvated multiply charged metal ions. Complexes involving both protic ligands (water, alcohols) and aprotic ones (e.g., ketones, DMSO, acetonitrile) were found for dications, but trications were compatible with aprotic ligands only. Here, to probe this difference in stability, acetonitrile complexes of metal trications were formed by ESI and collisionally fragmented. Proton transfer, electron transfer, and heterolytic cleavage channels previously found for dications were observed. Characteristic sizes for these processes suggest an intrinsic gap in the stability of dication and trication complexes against proton transfer, but not against electron transfer. Published by Elsevier Science B.V. C1 Natl Ctr Toxicol Res, Div Chem, Jefferson, AR 72079 USA. RP Shvartsburg, AA (reprint author), Natl Ctr Toxicol Res, Div Chem, HFT-233,3900 NCTR Rd, Jefferson, AR 72079 USA. NR 27 TC 33 Z9 33 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 JUL 17 PY 2002 VL 360 IS 5-6 BP 479 EP 486 AR PII S0009-2614(02)00889-8 DI 10.1016/S0009-2614(02)00889-8 PG 8 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 580QA UT WOS:000177244200010 ER PT J AU Coles, BF Chen, GP Kadlubar, FF Radominska-Pandya, A AF Coles, BF Chen, GP Kadlubar, FF Radominska-Pandya, A TI Interindividual variation and organ-specific patterns of glutathione S-transferase alpha, mu, and pi expression in gastrointestinal tract mucosa of normal individuals SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE carcinogenesis; colon; duodenum; glutathione S-transferase; GI tract; human; protein expression; small intestine; stomach ID COLORECTAL-CANCER; INTESTINAL-MUCOSA; POLYMORPHISM; RISK; ISOENZYMES; RESISTANCE; MODULATION; ENZYMES; TISSUE; COLON AB Glutathione S-transferase (GST) protein in gastrointestinal (G1) tracts of 16 organ donors, from whom all or substantial portions of the G1 tract (stomach-colon) were available, was quantitated by HPLC and examined for interindividual variability/consistency of organ-specific patterns of expression. GSTP1, GSTA1, and GSTA2 were major components, and GSTM1 and GSTM3 were minor components. Consistent patterns of organ-specific expression were evident despite a high degree of interindividual variation of expression. GSTP1 was expressed throughout the G1 tract and showed a decrease of expression from stomach to colon. GSTA1 and GSTA2 were expressed at high levels in duodenum and small intestine and expression decreased from proximal to distal small intestine. In contrast, GSTA1 and GSTA2 expression in colon and stomach of all subjects was low, particularly for colon where GSTA1 expression was 20- to 800-fold lower than that in corresponding small intestine. These consistent patterns of expression would suggest that compared to duodenum and small intestine, colon and to a lesser extent stomach always have low potential for GST-dependent detoxification of chemical carcinogens and are therefore at greater risk of genotoxic effects, particularly via substrates that are specific for GSTA1. This may be a factor in the greater susceptibility of stomach and colon to cancers compared to duodenum/small intestine. (C) 2002 Elsevier Science (USA). All rights reserved. C1 Natl Ctr Toxicol Res, Div Mol Epidemiol, Jefferson, AR 72079 USA. Univ Arkansas Med Sci, Dept Biochem & Mol Biol, Little Rock, AR 72205 USA. RP Coles, BF (reprint author), Natl Ctr Toxicol Res, Div Mol Epidemiol, Jefferson, AR 72079 USA. NR 27 TC 60 Z9 63 U1 0 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD JUL 15 PY 2002 VL 403 IS 2 BP 270 EP 276 AR PII S0003-9861(02)00226-6 DI 10.1016/S0003-9861(02)00226-6 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 578MX UT WOS:000177122900014 PM 12139976 ER PT J AU Shaffer, D Singer, S Korvick, J Honig, P AF Shaffer, D Singer, S Korvick, J Honig, P TI Concomitant risk factors in reports of Torsades de Pointes associated with macrolide use: Review of the United States Food and Drug Administration Adverse Event Reporting System SO CLINICAL INFECTIOUS DISEASES LA English DT Editorial Material ID QT PROLONGATION; DE-POINTES; CISAPRIDE AB In this case series, we examined concomitant risk factors mentioned in reports of torsades de pointes, a rare ventricular arrhythmia, that occurred in association with administration of macrolide antimicrobials (e. g., azithromycin, clarithromycin, dirithromycin, and erythromycin). Increasing age, female sex, and concomitant diseases and drug administration believed to increase risks for torsades de pointes were commonly reported. C1 US FDA, Off Drug Safety, Rockville, MD 20850 USA. RP Singer, S (reprint author), US FDA, Off Drug Safety, CORP2 S126,9201 Corp Blvd, Rockville, MD 20850 USA. NR 12 TC 65 Z9 73 U1 1 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JUL 15 PY 2002 VL 35 IS 2 BP 197 EP 200 DI 10.1086/340861 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 567FQ UT WOS:000176475100012 PM 12087527 ER PT J AU Ishii, KJ Takeshita, F Gursel, I Gursel, M Conover, J Nussenzweig, A Klinman, DM AF Ishii, KJ Takeshita, F Gursel, I Gursel, M Conover, J Nussenzweig, A Klinman, DM TI Potential role of phosphatidylinositol 3 kinase, rather than DNA-dependent protein kinase, in CpG DNA-induced immune activation SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE toll-like receptors; wortmannin; dendritic cells; innate immunity; cytokines ID BACTERIAL-DNA; V(D)J RECOMBINATION; IMMUNOSTIMULATORY DNA; CELLS; MATURATION; RECOGNITION; 3-KINASES; INNATE; MOTIFS; PKCS AB Unmethylated CpG motifs present in bacterial DNA stimulate a strong innate immune response. There is evidence that DNA-dependent protein kinase (DNA-PK) mediates CpG signaling. Specifically, wortmannin (an inhibitor of phosphatidylinositol 3 kinase [PI3]-kinases including DNA-PK) interferes with CpG-dependent cell activation, and DNA-PK knockout (KO) mice fail to respond to CpG stimulation. Current studies establish that wortmannin actually inhibits the uptake and colocalization of CpG DNA with toll-like receptor (TLR)-9 in endocytic vesicles, thereby preventing CpG-induced activation of the NF-kappaB signaling cascade. We find that DNA-PK is not involved in this process, since three strains of DNA-PK KO mice responded normally to CpG DNA. These results support a model in which CpG signaling is mediated through TLR-9 but not DNA-PK, and suggest that wortmannin-sensitive member(s) of the PI3-kinase family play a critical role in shuttling CpG DNA to TLR-9. C1 US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Sect Retroviral Immunol, Bethesda, MD 20892 USA. NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. RP Klinman, DM (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Sect Retroviral Immunol, Bldg 29A,Rm 3D10, Bethesda, MD 20892 USA. RI Gursel, Mayda /H-1812-2012; Ishii, Ken/B-1685-2012; OI Ishii, Ken/0000-0002-6728-3872; Gursel, Ihsan/0000-0003-3761-1166; Gursel, Mayda/0000-0003-0044-9054 NR 26 TC 108 Z9 112 U1 1 U2 5 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 JUL 15 PY 2002 VL 196 IS 2 BP 269 EP 274 DI 10.1084/jem.20020773 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 576PG UT WOS:000177013200013 PM 12119352 ER PT J AU Zhang, X Cui, SS Wallace, AE Hannesson, DK Schmued, LC Saucier, DM Honer, WG Corcoran, ME AF Zhang, X Cui, SS Wallace, AE Hannesson, DK Schmued, LC Saucier, DM Honer, WG Corcoran, ME TI Relations between brain pathology and temporal lobe epilepsy SO JOURNAL OF NEUROSCIENCE LA English DT Article DE mossy fiber sprouting; neuronal loss; epilepsy/physiopathology; kainic acid; hippocampal/physiopathology; temporal lobe epilepsy ID SPONTANEOUS RECURRENT SEIZURES; KAINIC ACID INJECTION; FIBER SYNAPTIC REORGANIZATION; INDUCED STATUS EPILEPTICUS; GRANULE CELL NEUROGENESIS; INDUCED NEURONAL DAMAGE; KAINATE-TREATED RATS; NEUROPEPTIDE-Y; DENTATE GYRUS; MOSSY FIBERS AB Temporal lobe epilepsy, the most common type of epilepsy in adult humans, is characterized clinically by the progressive development of spontaneous recurrent seizures of temporal lobe origin and pathologically by hippocampal neuronal loss and mossy fiber sprouting. In this study, we sought to test the prominent hypothesis that neuronal loss and mossy fiber sprouting play a critical role in the genesis and progression of temporal lobe epilepsy. Rats receiving a single kainic acid injection experienced a single sustained episode of epileptic status with massive neuronal loss and mossy fiber sprouting, whereas rats receiving triple kainic acid injections experienced two priming episodes and one sustained episode of epileptic status with no detectable neuronal loss and mossy fiber sprouting. Early in the process of chronic seizure development, primed rats that failed to show detectable neuronal loss and mossy fiber sprouting exhibited a starting date and a frequency of spontaneous recurrent seizures similar to those of nonprimed rats that showed massive neuronal loss and mossy fiber sprouting. However, nonprimed rats displayed significantly prolonged episodes of spontaneous recurrent seizures over the whole process of chronic seizure development and more frequent severe seizures later in the process. Similar results were observed in both Fischer-344 and Wistar rats as well as in the rat pilocarpine preparation of temporal lobe epilepsy. These results fail to reveal a relation between neuronal loss-mossy fiber sprouting and the genesis of temporal lobe epilepsy but suggest that neuronal loss, mossy fiber sprouting, or both contribute to the intensification of chronic seizures. C1 Univ Saskatchewan, Dept Psychiat, Neuropsychiat Res Unit, Saskatoon, SK S7N 5E4, Canada. Univ Saskatchewan, Dept Psychol, Saskatoon, SK S7N 5A5, Canada. US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. Univ British Columbia, Dept Psychiat, Vancouver, BC V5Z 1L8, Canada. RP Zhang, X (reprint author), Univ Saskatchewan, Dept Psychiat, Neuropsychiat Res Unit, A114 Med Res Bldg,103 Wiggins Rd, Saskatoon, SK S7N 5E4, Canada. NR 75 TC 113 Z9 120 U1 0 U2 0 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JUL 15 PY 2002 VL 22 IS 14 BP 6052 EP 6061 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 573PR UT WOS:000176840500029 PM 12122066 ER PT J AU Dargatz, DA Fedorka-Cray, PJ Ladely, SR Ferris, KE Green, AL Headrick, ML AF Dargatz, DA Fedorka-Cray, PJ Ladely, SR Ferris, KE Green, AL Headrick, ML TI Antimicrobial susceptibility patterns of Salmonella isolates from cattle in feedlots SO JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION LA English DT Article ID SEROTYPES; FECES; BEEF; COWS AB Objective-To evaluate the antimicrobial susceptibility patterns of Salmonella isolates from feedlot cattle. Design-Cross-sectional study. Sample Population-263 Salmonella isolates. Procedures-Fecal samples were collected from the floor of 2 pens in each of 100 feedlots. Two hundred eighty Salmonella isolates were recovered after bacteriologic culture from 38 pens. Of these, 263 isolates were available for antimicrobial susceptibility testing to 16 antimicrobials, using microbroth dilution breakpoint plates. Results-Less than 5% of isolates were resistant to any of the antimicrobials tested, with the exception of sulfamethoxazole (15; 5.7%) and tetracycline (61; 23.2%). Most isolates (197; 74.9%) were susceptible to all antimicrobials tested, whereas 18 (6.8%) were resistant to 2 or more antimicrobials. The percentage of isolates with resistance to any antimicrobial varied by serotype. The percentage of isolates resistant to various antimicrobials was not related to concurrent use of antimicrobials in the feed. Conclusions and Clinical Relevance-With the exception of tetracycline and sulfamethoxazole, resistance of Salmonella isolates to any of the antimicrobials was uncommon. Most isolates were susceptible to all antimicrobials tested. Antimicrobial resistance was not related to the presence of antimicrobials in the ration being fed at the time of sample collection. C1 APHIS, USDA, Ctr Epidemiol, Ft Collins, CO 80521 USA. APHIS, USDA, Ctr Anim Hlth, Ft Collins, CO 80521 USA. ARS, USDA, Richard Russell Res Ctr, Athens, GA 30605 USA. APHIS, USDA, Natl Vet Serv Labs, Ames, IA 50010 USA. US FDA, Ctr Vet Med, Rockville, MD 20855 USA. RP Dargatz, DA (reprint author), APHIS, USDA, Ctr Epidemiol, Ft Collins, CO 80521 USA. NR 17 TC 21 Z9 22 U1 0 U2 2 PU AMER VETERINARY MEDICAL ASSOC PI SCHAUMBURG PA 1931 N MEACHAM RD SUITE 100, SCHAUMBURG, IL 60173-4360 USA SN 0003-1488 J9 J AM VET MED ASSOC JI J. Am. Vet. Med. Assoc. PD JUL 15 PY 2002 VL 221 IS 2 BP 268 EP 272 DI 10.2460/javma.2002.221.268 PG 5 WC Veterinary Sciences SC Veterinary Sciences GA 571JT UT WOS:000176714800025 PM 12118593 ER PT J AU Williams, L Chou, MW Yan, J Young, JF Chan, PC Doerge, DR AF Williams, L Chou, MW Yan, J Young, JF Chan, PC Doerge, DR TI Toxicokinetics of riddelliine, a carcinogenic pyrrolizidine alkaloid, and metabolites in rats and mice SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE riddelliine; pyrrolizidine alkaloid; mass spectrometry; toxicokinetics ID IN-VIVO AB Riddelliine is a representative pyrrolizidine alkaloid, a class of naturally occurring toxic phytochemicals present in plant species worldwide. Human exposure to pyrrolizidine alkaloids occurs through consumption of herbal dietary supplements, including comfrey, and through contaminated livestock products (e.g., milk). A recently completed 2-year bioassay of riddelliine carcinogenicity showed that male and female rats and male mice, but not female mice, developed liver tumors. The toxicokinetics of riddelliine and two metabolites, the N-oxide and retronecine, were determined in serum following an oral gavage dose in male and female rats and mice using a validated liquid chromatography-electrospray mass spectrometric method. The results are consistent with extensive metabolism of riddelliine and its more polar metabolites prior to excretion. It is concluded that factors other than toxicokinetics are responsible for the observed species/sex specificity of gross toxicity or liver tumor induction in rats and mice. C1 Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NIEHS, Res Triangle Pk, NC 27709 USA. RP Doerge, DR (reprint author), Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 13 TC 18 Z9 20 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD JUL 15 PY 2002 VL 182 IS 2 BP 98 EP 104 DI 10.1006/taap.2002.9441 PG 7 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 580XC UT WOS:000177261200002 PM 12140173 ER PT J AU Petricoin, EF Mills, GB Kohn, EC Liotta, LA AF Petricoin, EF Mills, GB Kohn, EC Liotta, LA TI Proteomic patterns in serum and identification of ovarian cancer - Reply SO LANCET LA English DT Letter C1 US FDA, NIH, Clin Proteom Program, Dept Therapeut Prot,Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. Univ Texas, MD Anderson Canc Ctr, Dept Med Therapeut, Div Canc Med, Houston, TX 77030 USA. NCI, Pathol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. RP Petricoin, EF (reprint author), US FDA, NIH, Clin Proteom Program, Dept Therapeut Prot,Ctr Biol Evaluat & Res, Bldg 29A,Room 2B02,880 Rockville Pike, Bethesda, MD 20892 USA. NR 5 TC 30 Z9 31 U1 0 U2 3 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD JUL 13 PY 2002 VL 360 IS 9327 BP 170 EP 171 DI 10.1016/S0140-6736(02)09391-1 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 573PB UT WOS:000176839100034 ER PT J AU Shvartsburg, AA AF Shvartsburg, AA TI Gas-phase metal trications in protic solvent complexes SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID ELECTROSPRAY MASS-SPECTROMETRY; ALKALINE-EARTH; IONS; CHEMISTRY; LIGANDS; COORDINATION; ASSOCIATION; IONIZATION; ENERGIES; MG2+ C1 Natl Ctr Toxicol Res, Div Chem, Jefferson, AR 72079 USA. RP Shvartsburg, AA (reprint author), Natl Ctr Toxicol Res, Div Chem, HFT-233,3900 NCTR Rd, Jefferson, AR 72079 USA. NR 19 TC 31 Z9 31 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD JUL 10 PY 2002 VL 124 IS 27 BP 7910 EP 7911 DI 10.1021/ja025763w PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 569QA UT WOS:000176612400016 PM 12095329 ER PT J AU Heller, DN Ngoh, MA Donoghue, D Podhorniak, L Righter, H Thomas, MH AF Heller, DN Ngoh, MA Donoghue, D Podhorniak, L Righter, H Thomas, MH TI Identification of incurred sulfonamide residues in eggs: methods for confirmation by liquid chromatography-tandem mass spectrometry and quantitation by liquid chromatography with ultraviolet detection SO JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES LA English DT Article DE sulfonamides ID GAS-CHROMATOGRAPHY; ANIMAL-TISSUES; SULFAMETHAZINE RESIDUES; BOVINE-MILK; MEAT; ANTIBIOTICS; KIDNEY; SULFADIMETHOXINE; ANTIBACTERIALS; CARTRIDGE AB Two complementary methods for identifying and measuring sulfonamide residues in eggs were developed for use in surveying eggs for potential drug residues. The first method uses liquid chromatography-tandem mass spectrometry (LC-MS-MS) to confirm the presence of sulfonamide residues in eggs. During its validation the limit of confirmation was estimated to be 5-10 ng/g (ppb) depending on the drug. Also, a method for measuring residue level by liquid chromatography with ultraviolet detection (LC-UV) was validated using the same extraction procedure as the confirmatory method. The determinative method was validated over the 50-200 ppb range. Samples were prepared by homogenizing whole egg, extracting with acetonitrile, and cleaning up with a C-18 solid-phase extraction cartridge. For confirmation, analytes were separated by gradient LC on a C-18 column, ionized by electrospray ionization (ESI), and detected by MS-MS with an ion trap mass spectrometer. For determination, analytes were separated by a different gradient LC procedure and detected by IUV at 287 nm. Fifteen drugs were dosed individually in laying hens, and residues of parent drug and/or metabolites were found in eggs for all the drugs. Validation was based on repetitive analyses of control samples, control samples fortified at 100 ppb sulfonamides, and samples of blended incurred eggs. @ 2002 Published by Elsevier Science B.V. 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 28 TC 63 Z9 75 U1 2 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1570-0232 J9 J CHROMATOGR B JI J. Chromatogr. B PD JUL 5 PY 2002 VL 774 IS 1 BP 39 EP 52 AR PII S1570-0232(02)00187-3 DI 10.1016/S1570-0232(02)00187-3 PG 14 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 566ZB UT WOS:000176457200005 PM 12052721 ER PT J AU Crawford, LM AF Crawford, LM TI Drugs-herbals workshop SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT News Item C1 US FDA, Rockville, MD 20857 USA. RP Crawford, LM (reprint author), US FDA, 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 JUL 3 PY 2002 VL 288 IS 1 BP 36 EP 36 DI 10.1001/jama.288.1.36 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 568YW UT WOS:000176573400006 PM 12090852 ER PT J AU Crawford, LM AF Crawford, LM TI Commercial speech and public health: Request for comment SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT News Item C1 US FDA, Rockville, MD 20857 USA. RP Crawford, LM (reprint author), US FDA, 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 JUL 3 PY 2002 VL 288 IS 1 BP 36 EP 36 DI 10.1001/jama.288.1.36 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 568YW UT WOS:000176573400005 PM 12090852 ER PT J AU Crawford, LM AF Crawford, LM TI Pulmonary hypertension SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT News Item C1 US FDA, Rockville, MD 20857 USA. RP Crawford, LM (reprint author), US FDA, 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 JUL 3 PY 2002 VL 288 IS 1 BP 36 EP 36 DI 10.1001/jama.288.1.36 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 568YW UT WOS:000176573400007 PM 12090852 ER PT J AU Crawford, LM AF Crawford, LM TI Meetings on drug applications SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT News Item C1 US FDA, Rockville, MD 20857 USA. RP Crawford, LM (reprint author), US FDA, 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 JUL 3 PY 2002 VL 288 IS 1 BP 36 EP 36 DI 10.1001/jama.288.1.36 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 568YW UT WOS:000176573400008 PM 12090852 ER PT J AU Rice, CP Nochetto, CB Zara, P AF Rice, CP Nochetto, CB Zara, P TI Volatilization of trifluralin, atrazine, metolachlor, chlorpyrifos, alpha-endosulfan, and beta-endosulfan from freshly tilled soil SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE volatility; pesticides; atrazine; metolachlor; chlorpyrifos; endosulfan; trifluralin ID MEASURING PESTICIDE EVAPORATION; FIELD; DEGRADATION; MODEL; RATES; FLUX; AIR AB The volatile and soil loss profiles of six agricultural pesticides were measured for 20 days following treatment,to freshly tilled soil at the Beltsville Agricultural Research Center. The volatile fluxes were determined using the Theoretical Profile Shape (TPS) method. Polyurethane foam plugs were used to collect the gas-phase levels of the pesticides at the TPS-defined critical height above a treated field. Surface-soil (0-8 cm) samples were collected on each day of air sampling. The order of the volatile flux losses was trifluralin > alpha-endosulfan > chlorpyrifos > metolachlor > atrazine > beta-enclosulfan. The magnitude of the losses ranged from 14.1% of nominal applied amounts of trifluralin to 2.5% of beta-endosulfan. The daily loss profiles were typical of those observed by others for volatile flux of pesticides from moist soil. Even though heavy rains occurred from the first, to third day,after treatment, the majority of the losses took place within 4 days of treatment, that is, 59% of the total applied atrazine and metolachlor and >78% of the other pesticides. Soil losses generally followed pseudo-first-order kinetics; however, leaching. due to heavy rainfall caused significant errors in these results. The portion of soil losses that were accounted for by the volatile fluxes was ordered as follows: a-endosulfan, 34.5%; trifluralin, 26.5%; chlorpyrifos, 23.3%; beta-endosulfan, 14.5%; metolachlor, 12.4%; and, atrazine, 7.5%. C1 USDA ARS, ANRI, EQL, Beltsville, MD 20705 USA. US FDA, Ctr Vet Med, Laurel, MD 20708 USA. RP Rice, CP (reprint author), USDA ARS, ANRI, EQL, Room 225,Bldg 007,BARC-W, Beltsville, MD 20705 USA. NR 24 TC 46 Z9 48 U1 0 U2 16 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0021-8561 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD JUL 3 PY 2002 VL 50 IS 14 BP 4009 EP 4017 AR UNSP JF011571T DI 10.1021/jf011571t PG 9 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 568PF UT WOS:000176550500021 PM 12083875 ER PT J AU Guo, XA van Iersel, MW Chen, JR Brackett, RE Beuchat, LR AF Guo, XA van Iersel, MW Chen, JR Brackett, RE Beuchat, LR TI Evidence of association of salmonellae with tomato plants grown hydroponically in inoculated nutrient solution SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID ESCHERICHIA-COLI O157-H7; RALSTONIA-SOLANACEARUM; BACTERIAL ENDOPHYTES; RADISH SPROUTS; POPULATIONS; INFECTION; INVASION; ROOTS AB The possibility of uptake of salmonellae by roots of hydroponically grown tomato plants was investigated. Within 1 day of exposure of plant roots to Hoagland nutrient solution containing 4.46 to 4.65 log(10) CFU of salmonellae/ml, the sizes of the pathogen populations were 3.01 CFU/g of hypocotyls and cotyledons and 3.40 log(10) CFU/g of steins for plants with intact root systems (control) and 2.55 log(10) CFU/g of hypocotyls and cotyledons for plants from which portions of the roots had been removed. A population of greater than or equal to3.38 log(10) CFU/g of hypocotyls-cotyledons, stems, and leaves of plants grown for 9 days was detected regardless of the root condition. Additional studies need to be done to unequivocally demonstrate that salmonellae can exist as endophytes in tomato plants grown under conditions that simulate commonly used agronomic practices. C1 Univ Georgia, Ctr Food Safety, Griffin, GA 30223 USA. Univ Georgia, Dept Food Sci & Technol, Griffin, GA 30223 USA. Univ Georgia, Dept Hort, Griffin, GA 30223 USA. US FDA, Off Plant Dairy Foods & Beverages, College Pk, MD 20740 USA. RP Beuchat, LR (reprint author), Univ Georgia, Ctr Food Safety, 1109 Expt Str, Griffin, GA 30223 USA. NR 32 TC 108 Z9 112 U1 2 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 JUL PY 2002 VL 68 IS 7 BP 3639 EP 3643 DI 10.1128/AEM.68.7.3639-3643.2002 PG 5 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 569YV UT WOS:000176631600062 PM 12089054 ER PT J AU Khan, AA Nawaz, MS Khan, SA Steele, R AF Khan, AA Nawaz, MS Khan, SA Steele, R TI Detection and characterization of erythromycin-resistant methylase genes in Gram-positive bacteria isolated from poultry litter SO APPLIED MICROBIOLOGY AND BIOTECHNOLOGY LA English DT Article ID COAGULASE-NEGATIVE STAPHYLOCOCCI; STREPTOGRAMIN-B RESISTANCE; GROWTH PROMOTER; AUREUS; LINCOSAMIDES; MACROLIDES; STREPTOCOCCI; EPIDERMIDIS; FERTILIZER AB The epidemiology of four erythromycin-resistant methylase (erm) genes, ermA, ermB, ermC and msrA, was determined in erythromycin-resistant staphylococci, enterococci and streptococci isolated from poultry litter. All isolates were resistant to multiple antibiotics. Southern hybridization indicated that 4 of the 20 staphylococci contained the ermC gene on plasmids: on a 2.2 kb plasmid in Staphylococcus hominis and S. sciuri, on a 6.0 kb plasmid in S. xylosus, and on a 7.0 kb plasmid in S. lentus. In 16 of the 20 staphylococci, the ermA gene was harbored exclusively on the chromosome, as a double chromosomal insert on 8.0 and 6.2 kb EcoRI fragments. None of the staphylococci harbored the msrA gene. Dot-blot analysis indicated that all enterococci and streptococci hybridized with a biotinylated ermB gene probe. Southern hybridization indicated that only 2 of the 19 erythromycin-resistant enterococci contained the ermB gene on plasmids. The gene was localized on 4.0 kb and 5.9 kb plasmids, respectively, in two Enterococcus faecium isolates. Results from our studies indicate that the patterns of occurrence of erm genes, the sizes of the plasmids and the copy numbers of the inserts were different from the existing information on the presence of erm genes in clinical strains of Staphylococcus spp. C1 US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. RP Nawaz, MS (reprint author), US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. NR 23 TC 22 Z9 24 U1 0 U2 2 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 JUL PY 2002 VL 59 IS 2-3 BP 377 EP 381 DI 10.1007/s00253-002-1013-9 PG 5 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 580QU UT WOS:000177245900037 PM 12111173 ER PT J AU Badano, A AF Badano, A TI Modeling the bidirectional reflectance of emissive displays SO APPLIED OPTICS LA English DT Article AB The reflection properties of a display device influence the available contrast and affect the perception of subtle detail. The display reflection characteristics of flat-panel displays (FPDs) are appropriately described by a six-dimensional bidirectional reflectance distribution function (BRDF). I describe a Monte Carlo method for modeling the bidirectional reflectance of multilayer emissive structures used in electronic display devices. I estimate the complete BRDF using a one-dimensional angular distribution function of the luminance. I apply the method to model typical high-performance cathode-ray tube and FPD structures. I find that, for the BRDF signatures of cathode-ray tubes characterized by a specular and a quasi-Lambertian components, the estimated values for the specular and diffuse reflection coefficients agree well with low-resolution experimental measurements conducted with a rotation arm and a collimated probe. I show that emissive FPDs with thin-film organic layers on reflective substrates can exhibit a predominant specular peak broadened by short-range light scattering. (C) 2002 Optical Society of America. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Badano, A (reprint author), US FDA, Ctr Devices & Radiol Hlth, 12720 Twinbrook Pkwy, Rockville, MD 20857 USA. EM agb@cdrh.fda.gov OI badano, aldo/0000-0003-3712-6670 NR 9 TC 4 Z9 4 U1 0 U2 0 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1559-128X EI 2155-3165 J9 APPL OPTICS JI Appl. Optics PD JUL 1 PY 2002 VL 41 IS 19 BP 3847 EP 3852 DI 10.1364/AO.41.003847 PG 6 WC Optics SC Optics GA 570RR UT WOS:000176671900010 PM 12099591 ER PT J AU Armstrong, TN Reimschuessel, R Bradley, BP AF Armstrong, TN Reimschuessel, R Bradley, BP TI DNA damage, histologial changes and DNA repair in larval Japanese medaka (Oryzias latipes) exposed to ultraviolet-B radiation SO AQUATIC TOXICOLOGY LA English DT Article DE cyclobutane pyrimidine dimer; hyperplasia; necrosis; UV-B; fish; photoreactivation ID CULTURED FISH CELLS; PYRIMIDINE DIMERS; PHOTOREPAIR; SURVIVAL; LIGHT; PHOTOREACTIVATION AB Cyclobutane dimer formation, photorepair capability and histological damage were compared among four differently pigmented strains of larval Japanese medaka (Oryzias latipes) to determine whether pigmentation modifies the level of UV-B radiation (290-320 nm) inducible damage in these fish. One-day post-batch medaka were exposed to one of several UV-B fluence rates with or without photoreactivating light for 5 days for 7 h per day. Their DNA was extracted for analysis by ELISA for cyclobutane pyrimidine dimers or the larvae were processed for histological examination. At the higher UV-B fluence rates tested, wild-type melanophore-containing medaka formed significantly more dimers than at least one of the other strains tested. Wild-type medaka also showed significantly less photorepair capability than the white melanophore-lacking medaka, The wild-type larvae had significantly more necrosis than the orange-red melanophore-lacking larvae at the lower UV-B fluence rate tested and at the higher fluence rate used, the wild-type medaka also exhibited significantly more necrosis than the white melanophore-lacking larvae. Of the 19 medaka observed with cellular hyperplasia, six were wild-type. These six individual larvae showed the greatest degree of cellular hyperplasia. Cellular hyperplasia appeared to be greatest at the lowest UV-B fluence rate used. The presence of melanophores in the wild-type medaka may have contributed to an increased level of tissue damage in this strain when compared to the other strains. (C) 2002 Elsevier Science B.V. All rights reserved. C1 BBL Sci, Annapolis, MD 21403 USA. US FDA, Ctr Vet Med, Res Off, Laurel, MD 20708 USA. Univ Maryland, Dept Biol Sci, UMBC, Baltimore, MD 21250 USA. RP Armstrong, TN (reprint author), BBL Sci, 326 1st St,Suite 200, Annapolis, MD 21403 USA. NR 30 TC 29 Z9 34 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-445X J9 AQUAT TOXICOL JI Aquat. Toxicol. PD JUL PY 2002 VL 58 IS 1-2 BP 1 EP 14 AR PII S0166-445X(01)00212-0 DI 10.1016/S0166-445X(01)00212-0 PG 14 WC Marine & Freshwater Biology; Toxicology SC Marine & Freshwater Biology; Toxicology GA 551DR UT WOS:000175544700001 PM 12062151 ER PT J AU Hur, HG Beger, RD Heinze, TM Lay, JO Freeman, JP Dore, J Rafii, F AF Hur, HG Beger, RD Heinze, TM Lay, JO Freeman, JP Dore, J Rafii, F TI Isolation of an anaerobic intestinal bacterium capable of cleaving the C-ring of the isoflavonoid daidzein SO ARCHIVES OF MICROBIOLOGY LA English DT Article DE isoflavonoids; phytoestrogens; daidzem; anaerobic bacteria; C-ring fission ID POSTMENOPAUSAL WOMEN; DIETARY ISOFLAVONES; GENISTEIN; PHYTOESTROGENS; METABOLITES; SOY; MECHANISMS; FLAVONOIDS; FOODS AB Colonic bacteria were screened for bacteria involved in the conversion of phytoestrogens. A gram-positive anaerobic bacterium, strain HGH 136, capable of conversion of the isoflavonoid daidzein, was isolated and identified as a Clostridium sp. The bacterium cleaved the C-ring of daidzein to produce O-demethylangolensin (O-Dma). This compound was identified by comparison of the HPLC retention time and UV spectrum of the metabolite with chemically synthesized O-Dma. The identity of the metabolite was confirmed by liquid chromatography-mass spectrometry and NMR using synthetic O-Dma as a standard. The bacterium incubated with synthetic dihydrodaidzein also produced O-Dma. After 3 days of incubation, 28% of added daidzein and 12% of added dihydrodaidzein were converted to O-Dma. This is the first study in which an anaerobic bacterium involved in the ring cleavage of daidzein to produce O-Dma has been identified. C1 US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. Seoul Natl Univ, Sch Agr Biotechnol, Suwon, South Korea. US FDA, Natl Ctr Toxicol Res, Div Chem, Jefferson, AR 72079 USA. INRA, Jouy En Josas, France. RP Rafii, F (reprint author), US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. RI Lay, Jackson/G-1007-2011 OI Lay, Jackson/0000-0003-3789-2527 NR 27 TC 72 Z9 80 U1 1 U2 13 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0302-8933 J9 ARCH MICROBIOL JI Arch. Microbiol. PD JUL PY 2002 VL 178 IS 1 BP 8 EP 12 DI 10.1007/s00203-002-0414-6 PG 5 WC Microbiology SC Microbiology GA 572HN UT WOS:000176768500002 PM 12070764 ER PT J AU Hur, HG Beger, RD Heinze, TM Lay, JO Freeman, JP Dore, J Rafii, F AF Hur, HG Beger, RD Heinze, TM Lay, JO Freeman, JP Dore, J Rafii, F TI Isolation of an anaerobic intestinal bacterium capable of cleaving the C-ring of the isoflavonoid daidzein (vol 178, pg 75, 2002) SO ARCHIVES OF MICROBIOLOGY LA English DT Correction C1 US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. Kwangju Inst Sci & Technol, Dept Environm Sci & Engn, Kwangju 500712, South Korea. US FDA, Natl Ctr Toxicol Res, Div Chem, Jefferson, AR 72079 USA. INRA, Jouy En Josas, France. RP Rafii, F (reprint author), US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. NR 1 TC 1 Z9 1 U1 0 U2 4 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0302-8933 J9 ARCH MICROBIOL JI Arch. Microbiol. PD JUL PY 2002 VL 178 IS 1 BP 75 EP 75 DI 10.1007/s00203-002-0437-z PG 1 WC Microbiology SC Microbiology GA 572HN UT WOS:000176768500011 ER PT J AU Shamim, EA Rider, LG Pandey, JP O'Hanlon, TP Jara, LJ Samayoa, EA Burgos-Vargas, R Vazquez-Mellado, J Alcocer-Varela, J Salazar-Paramo, M Kutzbach, AG Malley, JD Targoff, IN Garcia-De La Torre, I Miller, FW AF Shamim, EA Rider, LG Pandey, JP O'Hanlon, TP Jara, LJ Samayoa, EA Burgos-Vargas, R Vazquez-Mellado, J Alcocer-Varela, J Salazar-Paramo, M Kutzbach, AG Malley, JD Targoff, IN Garcia-De La Torre, I Miller, FW TI Differences in idiopathic inflammatory myopathy phenotypes and genotypes between Mesoamerican Mestizos and North American Caucasians - Ethnogeographic influences in the genetics and clinical expression of myositis SO ARTHRITIS AND RHEUMATISM LA English DT Article ID INCLUSION-BODY MYOSITIS; CLASS-II ALLELES; JUVENILE DERMATOMYOSITIS; RHEUMATOID-ARTHRITIS; ETHNIC-GROUPS; AUTOANTIBODIES; ASSOCIATION; DISEASES; ONSET; IMMUNOGENETICS AB Objective. As part of a larger, worldwide study of the ethnogeography of myositis, we evaluated the clinical, serologic, and immunogenetic features of Mestizo (Mexican and Guatemalan) and North American Cancasian patients with idiopathic inflammatory myopathy (IIM). Methods. Clinical manifestations, autoantibodies, HLA-DRB1 and DQA1 alleles, and immunoglobulin Gm/Km allotypes were compared between 138 Mestizos with IIM and 287 Caucasians with IIM, using the same classification criteria and standardized questionnaires. Results. IIM in Mestizo patients was characterized by a higher proportion of dermatomyositis (69% of adult Mestizos versus 35% of adult Caucasians; P < 0.001) and anti-Mi-2 autoantibodies (30% versus 7% of adults, respectively, and 32% versus 4% of children, respectively; P < 0.01). Genetic risk factors also differed in these populations. Whereas Mestizos had no HLA risk factors for IIM, HLA-DRBI*0301, the linked allele DQA1*0501, and DRB1 alleles sharing the first hypervariable region motif (EYSTS13)-E-9 were major risk factors in Caucasian patients with IIM. Furthermore, different HLA-DRB1 and DQA1 alleles were associated with anti-Mi-2 autoantibodies (DRB1*04 and DQA1*03 in Mestizos and DRB1*07 and DQA1*02 in Caucasians). Immunoglobulin gamma-chain allotypes Gm(1), Gm(17) (odds ratio for both 11.3, P = 0.008), and Gm(21) (odds ratio 7.3, P = 0.005) and kappa-chain allotype Km(3) (odds ratio 7.3, P = 0.005) were risk factors for IIM in Mestizos; however, no Gull or Km allotypes were risk or protective factors in Caucasians. In addition, Gull and Km phenotypes were unique risk factors (Gm 1,3,17 5,13,21 and Gm 1,17 23 21 and Km 3,3) or protective factors (Km 1,1) for the development of myositis and anti-Mi-2 autoantibodies (Gm 1,2,3,17 23 5,13,21) in adult Mestizos. Conclusion. IIM in Mesoamerican Mestizos differs from IIM in North American Caucasians in the frequency of phenotypic features and in the immune-response genes predisposing to and protecting from myositis and anti-Mi-2 autoantibodies at 4 chromosomal loci. These and other data suggest the likelihood that the expression of IIM is modulated by different genes and environmental exposures around the world. C1 NIEHS, Environm Autoimmun Grp, Off Clin Res, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. Med Univ S Carolina, Charleston, SC 29425 USA. Hosp Especialidades Ctr Med La Raza, Mexico City, DF, Mexico. Hosp Gen San Juan de Dios, Ssn Juan De Dios, Guatemala. Univ Nacl Autonoma Mexico, Mexico City 04510, DF, Mexico. Hosp Gen Mexico City, Mexico City, DF, Mexico. Inst Nacl Nutr Salvador Zubiran, Mexico City 14000, DF, Mexico. Univ Guadalajara, Guadalajara 44430, Jalisco, Mexico. Hosp Especialidades Ctr Med La Raza, Ctr Med Occidente, Inst Mexicano Seura Social, Unidad Invest Med & Epidemiol, Guadalajara, Jalisco, Mexico. Univ Francisco Marrequin, Guatemala City, Guatemala. NIH, Ctr Informat Technol, Bethesda, MD USA. Univ Oklahoma, Med Sci Ctr, Vet Affairs Med Ctr, Oklahoma City, OK USA. Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USA. Hosp Gen Occidente Secretaria Salud, Guadalajara, Jalisco, Mexico. RP Shamim, EA (reprint author), NIEHS, Environm Autoimmun Grp, Off Clin Res, NIH, 9 Mem Dr,Room 1W101,MSC 0958, Bethesda, MD 20892 USA. OI Rider, Lisa/0000-0002-6912-2458; Miller, Frederick/0000-0003-2831-9593 NR 42 TC 49 Z9 52 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD JUL PY 2002 VL 46 IS 7 BP 1885 EP 1893 DI 10.1002/art.10358 PG 9 WC Rheumatology SC Rheumatology GA 572KK UT WOS:000176773200023 PM 12124873 ER PT J AU Altekruse, SF Elvinger, F DebRoy, C Pierson, FW Eifert, JD Sriranganathan, N AF Altekruse, SF Elvinger, F DebRoy, C Pierson, FW Eifert, JD Sriranganathan, N TI Pathogenic and fecal Escherichia coli strains from turkeys in a commercial operation SO AVIAN DISEASES LA English DT Article DE poultry diseases; Escherichia coli infections ID RESISTANCE; COLIBACILLOSIS; COLISEPTICEMIA; VIRULENCE; DIVERSITY; TSH AB The biochemical phenotypes and antimicrobial susceptibility patterns of 105 clinical Escherichia coli isolates from flocks with colibacillosis in a turkey operation were compared with 1104 fecal E coli isolates from 20 flocks in that operation. Clinical isolates and 194 fecal isolates with biochemical phenotypes or minimum inhibitory concentrations for gentamicin and sulfamethoxazole similar to clinical isolates were tested for somatic antigens and the potential virulence genes hylE, iss, tsh, and K1. The predominant biochemical phenotype of clinical isolates contained 21 isolates including 14 isolates belonging to serogroup 078 with barely detectable P-D-glucuronidase activity. Thirty-five fecal isolates had biochemical phenotypes matching common phenotypes of clinical isolates. Sixty-six (63%) clinical isolates exhibited intermediate susceptibility or resistance to gentamicin and sulfamethoxazole compared with 265 (24%) fecal isolates (P<0.001). Seventy-seven clinical isolates reacted with O-antisera, of which 51 (66%) belonged to the following serogroups: O1, O2, O8, O25, O78, O114, and O119. In comparison, 8 of 35 (23%) fecal isolates subtyped on the basis of biochemical phenotype belonged to these serogroups and four of 167 (2%) fecal isolates subtyped on the basis of their antimicrobial resistance patterns belonged to these serogroups. Iss, K1, and tsh genes were detected more often among clinical isolates than these fecal isolates (P<0.05). In summary, a small subgroup Of E coli strains caused most colibacillosis infections in this operation. These strains existed at low concentration in normal fecal flora of healthy turkeys in intensively raised flocks. The data suggest that colibacillosis in turkey operations may be due to endogenous infections caused by specialized pathogens. C1 US FDA, Ctr Vet Med, Rockville, MD 20895 USA. Virginia Polytech Inst & State Univ, Virginia Maryland Reg Coll Vet Med, Dept Large Anim Clin Sci, Blacksburg, VA 24061 USA. Virginia Polytech Inst & State Univ, Virginia Maryland Reg Coll Vet Med, Dept Biomed Sci & Pathobiol, Blacksburg, VA 24061 USA. Penn State Univ, Gastroenter Dis Ctr, Wiley Lab, University Pk, PA 16802 USA. Virginia Polytech Inst & State Univ, Dept Food Sci & Technol, Blacksburg, VA 24061 USA. RP Altekruse, SF (reprint author), US FDA, Ctr Vet Med, 7500 Standish Pl,HFV-250, Rockville, MD 20895 USA. NR 30 TC 18 Z9 18 U1 0 U2 1 PU AMER ASSOC AVIAN PATHOLOGISTS PI KENNETT SQ PA UNIV PENN, NEW BOLTON CENTER, KENNETT SQ, PA 19348-1692 USA SN 0005-2086 J9 AVIAN DIS JI Avian Dis. PD JUL-SEP PY 2002 VL 46 IS 3 BP 562 EP 569 DI 10.1637/0005-2086(2002)046[0562:PAFECS]2.0.CO;2 PG 8 WC Veterinary Sciences SC Veterinary Sciences GA 594QW UT WOS:000178063100007 PM 12243519 ER PT J AU Calvert, RJ Ramakrishna, G Tepper, S Diwan, BA Anderson, LM Kritchevsky, D AF Calvert, RJ Ramakrishna, G Tepper, S Diwan, BA Anderson, LM Kritchevsky, D TI Alterations in membrane-bound and cytoplasmic K-ras protein levels in mouse lung induced by treatment with lovastatin, cholestyramine, or niacin: effects are highly mouse strain dependent SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE cholesterol; lovastatin; cholestyramine; niacin; mouse lung; K-ras ID A/J MICE; TUMORS; CHOLESTEROL; EXPRESSION; REDUCTASE; CANCER; RATS; LOCALIZATION; INHIBITION; RODENT AB Agents that either increase (cholestyramine, CS) or decrease (lovastatin, Lov) de novo peripheral cholesterol synthesis may increase (CS) or decrease (Lov) ras protein membrane localization by altering protein prenylation, and potentially have pro- or anti-carcinogenic effects. Male A/J, Swiss, and C57/BL6 mice were treated with 2 or 4% CS, 1% dietary niacin, or 25 mg/kg of Lov three times per week (Lov-3X) or five times per week (Lov-5X). After 3 weeks, serum cholesterol and triglycerides were determined enzymatically. Membrane and cytoplasmic K-ras proteins in lung were determined by immunoprecipitation followed by western blotting with a K-ras specific antibody. Results confirmed the hypothesis only in isolated instances. A/J mice had a significant 30% increase in cytoplasmic K-ras and a 40% decrease in membrane K-ras from Lov treatment, as predicted. C57/BL6 mice had a significant 77% increase in membrane K-ras, as expected from CS feeding. At variance with the hypothesis, Swiss mice had increased levels (3-28%) of membrane K-ras with all treatments (including Lov), and C57/BL6 mice treated with Lov had a 58-78% increase in cytoplasmic K-ras without any reduction in the levels of membrane K-ras. Niacin, predicted to have no effect on ras membrane localization, decreased cytoplasmic K-ras in A/J mice, increased both membrane and cytoplasmic K-ras in Swiss mice, and had no effect in C57/BL6 mice. Results may have differed from those predicted because of strain-dependent differences in response to the cholesterol-lowering agents. A difference in response among the mouse strains suggests that individual genetic differences may alter the effect of hypocholesterolemic agents on K-ras membrane localization, and potentially the risk of ras-dependent cancer. Published by Elsevier Science Inc. C1 US FDA, Div Res & Appl Technol, Off Nutr Prod Labeling & Dietary Supplements, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. NCI, Comparat Carcinogenesis Lab, Frederick, MD 21702 USA. Wistar Inst Anat & Biol, Philadelphia, PA 19104 USA. NCI, SAIC, Frederick, MD 21702 USA. RP Calvert, RJ (reprint author), US FDA, Div Res & Appl Technol, Off Nutr Prod Labeling & Dietary Supplements, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. NR 22 TC 3 Z9 3 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD JUL 1 PY 2002 VL 64 IS 1 BP 41 EP 48 AR PII S0006-2952(02)01077-8 DI 10.1016/S0006-2952(02)01077-8 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 578JJ UT WOS:000177113400005 PM 12106604 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 nocturnal hemoglobinuria express cellular prion protein SO BLOOD LA English DT Article ID TRANSMEMBRANE FORM; ANCHORED PROTEINS; APLASTIC-ANEMIA; FLOW-CYTOMETRY; BLOOD-CELLS; DISEASES; FAILURE AB Cellular prion protein (PrPc) is a glycosylphosphatidylinositol (GPI)-anchored membrane glycoprotein that contains a putative membrane-spanning section. Patients with paroxysmal nocturnal hemoglobinuria (PNH) lack GPI proteins on the surface of somatically mutated hematopoietic stem cell and its progeny. Platelet expression of PrPc was studied in 8 PNH patients. Resting PNH (CD55(-)) platelets were devoid of surface PrPc, but activation of platelets resulted in the surface expression of PrPc. Expressed PrPc was detected by 2 monoclonal antibodies (mAbs) against the N-terminal part of the molecule but not by mAb 6H4, which binds at the C-terminus beyond the membrane-spanning section. However, 6H4 detected PrPc on Western blots of PNH platelets, demonstrating that the lack of 6H4 binding was not caused by PrPc truncation. Our results indicate that in the absence of GPI anchor, PrPc can be expressed intracellularly and up-regulated on the platelet membrane, likely in a transmembrane form with the C-terminal part of the molecule inserted into the cytoplasm. C1 US FDA, Lab Cellular Hematol, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Vostal, JG (reprint author), US FDA, Lab Cellular Hematol, Div Hematol, Ctr Biol Evaluat & Res, Bldg 29,Room 323,HFM-335,8800 Rockville Pike, Bethesda, MD 20892 USA. RI Simak, Jan/C-1153-2011 NR 22 TC 17 Z9 18 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JUL 1 PY 2002 VL 100 IS 1 BP 341 EP 343 DI 10.1182/blood.V100.1.341 PG 3 WC Hematology SC Hematology GA 567GQ UT WOS:000176477400047 PM 12070046 ER EF