FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Fostel, J Choi, D Zwickl, C Morrison, N Rashid, A Hasan, A Bao, WJ Richard, A Tong, WD Bushel, PR Brown, R Bruno, M Cunningham, ML Dix, D Eastin, W Frade, C Garcia, A Heinloth, A Irwin, R Madenspacher, J Merrick, BA Papoian, T Paules, R Rocca-Serra, P Sansone, AS Stevens, J Tomer, K Yang, CH Waters, M AF Fostel, J Choi, D Zwickl, C Morrison, N Rashid, A Hasan, A Bao, WJ Richard, A Tong, WD Bushel, PR Brown, R Bruno, M Cunningham, ML Dix, D Eastin, W Frade, C Garcia, A Heinloth, A Irwin, R Madenspacher, J Merrick, BA Papoian, T Paules, R Rocca-Serra, P Sansone, AS Stevens, J Tomer, K Yang, CH Waters, M TI Chemical Effects in Biological Systems-Data Dictionary (CEBS-DD): A compendium of terms for the capture and integration of biological study design description, conventional phenotypes, and 'omics data SO TOXICOLOGICAL SCIENCES LA English DT Article DE Chemical Effects in Biological Systems (CEBS) Knowledgebase; toxicogenomics study protocols; toxicity endpoint data; acetaminophen; phenotypic anchor ID GENE-EXPRESSION AB A critical component in the design of the Chemical Effects in Biological Systems (CEBS) Knowledgebase is a strategy to capture toxicogenomics study protocols and the toxicity endpoint data (clinical pathology and histopathology). A Study is generally an experiment carried out during a period of time for the purpose of obtaining data, and the Study Design Description captures the methods, timing, and organization of the Study. The CEBS Data Dictionary (CEBS-DD) has been designed to define and organize terms in an attempt to standardize nomenclature needed to describe a toxicogenomics Study in a structured yet intuitive format and provide a flexible means to describe a Study as conceptualized by the investigator. The CEBS-DD will organize and annotate information from a variety of sources, thereby facilitating the capture and display of toxicogenomics data in biological context in CEBS, i.e., associating molecular events detected in highly-parallel data with the toxicology/pathology phenotype as observed in the individual Study Subjects and linked to the experimental treatments. The CEBS-DD has been developed with a focus on acute toxicity studies, but with a design that will permit it to be extended to other areas of toxicology and biology with the addition of domain-specific terms. To illustrate the utility of the CEBS-DD, we present an example of integrating data from two proteomics and transcriptomics studies of the response to acute acetaminophen toxicity (A. N. Heinloth et al., 2004, Toxicol. Sci. 80, 193-202). C1 US Natl Ctr Toxicogenom, Res Triangle Pk, NC 27709 USA. LMIT, LIMT, Res Triangle Pk, NC 27709 USA. Lilly Res Lab, Greenfield, IN 46140 USA. Univ Manchester, NERC, Manchester M13 9PL, Lancs, England. Alpha Gamma Technol Inc, Raleigh, NC 27609 USA. US EPA, Res Triangle Pk, NC 27711 USA. US Natl Ctr Toxicogenom Res, Jefferson, AR 72079 USA. Glaxo SmithKline Inc, Res Triangle Pk, NC 27709 USA. US Natl Toxicol Program, Res Triangle Pk, NC 27709 USA. Xybion Inc, Cedar Knolls, NJ USA. EBI, EMBL, Cambridge CB10, England. US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. Leadscope Inc, Columbus, OH 43215 USA. RP Fostel, J (reprint author), US Natl Ctr Toxicogenom, POB 12233 Mail Drop F1-05,111 Alexander Dr, Res Triangle Pk, NC 27709 USA. EM fostel@niehs.nih.gov RI Tomer, Kenneth/E-8018-2013; OI Sansone, Susanna-Assunta/0000-0001-5306-5690 NR 12 TC 29 Z9 31 U1 2 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD DEC PY 2005 VL 88 IS 2 BP 585 EP 601 DI 10.1093/toxsci/kfi315 PG 17 WC Toxicology SC Toxicology GA 983FC UT WOS:000233215700032 PM 16150882 ER PT J AU Gopee, NV Cui, YY Olson, G Warbritton, AR Miller, BJ Couch, LH Wamer, WG Howard, PC AF Gopee, NV Cui, YY Olson, G Warbritton, AR Miller, BJ Couch, LH Wamer, WG Howard, PC TI Response of mouse skin to tattooing: Use of SKH-1 mice as a surrogate model for human tattooing SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE tattoo; skin; lymph node; NF-kappa B; COX-1; COX-2; ODC; IL-1 beta; IL-10 ID NF-KAPPA-B; ORNITHINE DECARBOXYLASE ACTIVITY; TUMOR-NECROSIS-FACTOR; TITANIUM-DIOXIDE; LYMPH-NODES; PROINFLAMMATORY CYTOKINES; SINGLET OXYGEN; MESSENGER-RNA; DNA-DAMAGE; RED TATTOO AB Tattooing is a popular cosmetic practice involving more than 45 trillion US citizens. Since the toxicology of tattoo inks and pigments used to formulate tattoo inks has not been reported, we studied the immunological impact of tattooing and determined recovery time from this trauma. SKH-1 hairless mice were tattooed using commercial tattoo inks or suspensions of titanium dioxide, cadmium sulfide, or iron oxide, and sacrificed at 0.5, 1, 3, 4, 7, or 14 days post-tattooing. Histological evaluation revealed dermal hemorrhage at 0.5 and 1 day. Acute inflammation and epidermal necrosis were initiated at 0.5 day decreasing in incidence by day 14. Dermal necrosis and epidermal hyperplasia were prominent by day 3, reducing in severity by day 14. Chronic active inflammation persisted in all tattooed mice from day 3 to 14 post-tattooing. Inguinal and axillary lymph nodes were pigmented, the inguinal being most reactive as evidenced by lymphoid hyperplasia and polymorphonuclear infiltration. Cutaneous nuclear protein concentrations of nuclear factor-kappa B were elevated between 0.5 and 4 days. Inflammatory and proliferative biomarkers, cyclooxygenase-1, cyclooxygenase-2, and ornithine decarboxylase protein levels were elevated between 0.5 and 4 days ill the skin and decreased to control levels by day 14. Interleukin-1 beta and interleukin-10 were elevated ill the lymph nodes but suppressed in the tattooed skin, with maximal suppression occurring between days 0.5 and 4. These data demonstrate that mice substantially recover front the tattooing insult by 14 days, leaving behind pigment in the dermis and the regional lymph nodes. The response seen in mice is similar to acute injury seen ill humans, Suggesting that the murine model might be a suitable surrogate for investigating the toxicological and phototoxicological properties of ingredients used ill tattooing. (c) 2005 Published by Elsevier Inc. C1 US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. US FDA, NTP Ctr Phototoxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Toxicol Pathol Associates, Jefferson, AR 72079 USA. US FDA, Off Cosmet & Colors, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Howard, PC (reprint author), US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, 3900 NCTR Rd,HFT 110, Jefferson, AR 72079 USA. EM PHoward@nctr.fda.gov NR 93 TC 26 Z9 28 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 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD DEC 1 PY 2005 VL 209 IS 2 BP 145 EP 158 DI 10.1016/j.taap.2005.04.003 PG 14 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 990HB UT WOS:000233732700006 PM 15913690 ER PT J AU Valdez, KE Turzillo, AM AF Valdez, KE Turzillo, AM TI Regulation of nuclear factor-kappa B (NF-kappa B) activity and apoptosis by estradiol in bovine granulosa cells SO MOLECULAR AND CELLULAR ENDOCRINOLOGY LA English DT Article DE bovine granulosa cell; estradiol; NF-kappa B; apoptosis ID FIRST FOLLICULAR WAVE; NECROSIS-FACTOR-ALPHA; X-LINKED INHIBITOR; ESTROUS-CYCLE; STIMULATING-HORMONE; FOLLICLES; EXPRESSION; GROWTH; MESSENGER; DNA AB Although atresia of bovine follicles is associated with apoptosis of granulosa cells, the signals initiating this cell death have not been resolved. NF-kappa B has been implicated as an important regulator of genes controlling apoptosis, and previous studies indicate that estradiol may modulate NF-kappa B activation. We hypothesized that estradiol activates NF-kappa B, and thus, inhibits apoptosis in granulosa cells of dominant follicles. Dominant follicles were collected on Days 4, 6, and 8 of the first follicular wave following ovulation and assayed for NF-kappa B activity. Concentrations of estradiol in follicular fluid decreased on Day 6 compared to Day 4 of the wave. NF-kappa B activity in granulosa cells was lower on Day 8 compared to Days 4 and 6. In vitro, NF-kappa B activity and minimal incidence of apoptosis (<4%), as measured by Annexin V and TUNEL assays, were associated with production of estradiol. However, inhibition of NF-kappa B in vitro led to a suppression of apoptosis. These results indicate that follicular NF-kappa B activation is associated with estradiol production. However, whether NF-kappa B is playing a pro- or anti-apoptotic role in granulosa cells of the dominant bovine follicle remains to be elucidated. (c) 2005 Elsevier Ireland Ltd. All rights reserved. C1 Univ Arizona, Dept Physiol Sci, Tucson, AZ 85724 USA. RP Turzillo, AM (reprint author), US FDA, Ctr Vet Med, 7500 Standish Pl,HFV-153, Rockville, MD 20855 USA. EM adele.turzillo@fda.hhs.gov FU NIGMS NIH HHS [5T32 GM08400] NR 34 TC 4 Z9 4 U1 0 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0303-7207 J9 MOL CELL ENDOCRINOL JI Mol. Cell. Endocrinol. PD NOV 24 PY 2005 VL 243 IS 1-2 BP 66 EP 73 DI 10.1016/j.mce.2005.09.004 PG 8 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 989ZI UT WOS:000233712500009 PM 16225986 ER PT J AU Koturbash, I Pogribny, I Kovalchuk, O AF Koturbash, I Pogribny, I Kovalchuk, O TI Stable loss of global DNA methylation in the radiation-target tissue - A possible mechanism contributing to radiation carcinogenesis? SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE radiation carcinogenesis; radiation-target organs; thymic lymphoma; DNA methylation; DNA damage ID MOUSE THYMIC LYMPHOMAS; TUMOR-SUPPRESSOR GENE; IONIZING-RADIATION; GENOMIC HYPOMETHYLATION; HOMOZYGOUS DELETIONS; INTRAGENIC DELETIONS; CHILDHOOD LEUKEMIA; POINT MUTATIONS; CANCER; MICE AB Radiation-induced lymphomagenesis and leukemogenesis are complex processes involving both genetic and epigenetic changes. Although genetic alterations during radiation-induced lymphoma- and leukemogenesis are fairly well studied, the role of epigenetic changes has been largely overlooked. Rodent models are valuable tools for identifying molecular mechanisms of lymphoma and leukemogenesis. A widely used mouse model of radiation-induced thymic lymphoma is characterized by a lengthy "pre-lymphoma" period. Delineating molecular changes occurring during the pre-lymphoma period is crucial for understanding the mechanisms of radiation-induced leukemia/lymphoma development. In the present study, we investigated the role of radiation-induced DNA methylation changes in the radiation carcinogenesis target organ-thymus, and non-target organ muscle. This study is the first report on the radiation-induced epigenetic changes in radiation-target murine thymus during the pre-lymphoma period. We have demonstrated that acute and fractionated whole-body irradiation significantly altered DNA methylation pattern in murine thymus leading to a massive loss of global DNA methylation. We have also observed that irradiation led to increased levels of DNA strand breaks 6 h following the initial exposure. The majority of radiation-induced DNA strand breaks were repaired I month after exposure. DNA methylation changes, though, were persistent and significant radiation-induced DNA hypomethylation was observed in thymus I month after exposure. In sharp contrast to thymus, no significant persistent changes were noted in the non-target muscle tissue. The presence of stable DNA hypomethylation in the radiation-target tissue, even though DNA damage resulting from initial genotoxic radiation insult was repaired, suggests of the importance of epigenetic mechanisms in the development of radiation-related pathologies. The possible role of radiation-induced DNA hypomethylation in radiation-induced genome instability and aberrant gene expression in molecular etiology of thymic lymphomas is discussed. (c) 2005 Elsevier Inc. All rights reserved. C1 Univ Lethbridge, Dept Biol Sci, Lethbridge, AB T1K 3M4, Canada. Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Kovalchuk, O (reprint author), Univ Lethbridge, Dept Biol Sci, 4401 Univ Dr, Lethbridge, AB T1K 3M4, Canada. EM olga.kovalchuk@uleth.ca NR 60 TC 56 Z9 62 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 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD NOV 18 PY 2005 VL 337 IS 2 BP 526 EP 533 DI 10.1016/j.bbrc.2005.09.084 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 977ZF UT WOS:000232841300019 PM 16202973 ER PT J AU Hilden, JM Dinndorf, PA Meerbaum, SO Sather, H Villaluna, D Heerema, NA McGlennen, R Smith, FO Woods, WG Dryer, Z Reaman, GH AF Hilden, JM Dinndorf, PA Meerbaum, SO Sather, H Villaluna, D Heerema, NA McGlennen, R Smith, FO Woods, WG Dryer, Z Reaman, GH TI CCG 1953: Acute lymphoblastic leukemia in infants: Analysis of prognostic factors: A report from the Children's Oncology Group. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 Cleveland Clin, Childrens Hosp, Cleveland, OH 44106 USA. US FDA, Rockville, MD 20857 USA. Childrens Oncol Grp, Arcadia, CA USA. Childrens Hosp, Columbus, OH 43205 USA. Univ Minnesota, Minneapolis, MN USA. Childrens Hosp & Med Ctr, Cincinnati, OH USA. Childrens Healthcare Atlanta, Atlanta, GA USA. Texas Childrens Canc Ctr, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 7 BP 7A EP 7A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426000008 ER PT J AU Morgan, DA Argaw, T Wilson, CA AF Morgan, DA Argaw, T Wilson, CA TI Umbilical cord blood stem cells induced into myeloid, erythroid, or megakaryocytic pathways are susceptible to infection by porcine endogenous retroviruses (PERV). SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 Drexel Univ, Coll Med, Philadelphia, PA 19104 USA. US FDA, Div Cellular & Gene Therapies, CBER, Bethesda, MD 20014 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 2005 VL 106 IS 11 MA 4189 BP 127B EP 128B PN 2 PG 2 WC Hematology SC Hematology GA 986CG UT WOS:000233426100488 ER PT J AU Wiestner, A Marti, GE Billings, EM Liu, H Lee, E White, T Wilson, WH AF Wiestner, A Marti, GE Billings, EM Liu, H Lee, E White, T Wilson, WH TI Differential gene expression in CLL cells from bone marrow and peripheral blood suggests a role of bone marrow stroma in leukemic cell proliferation. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 NHLBI, Hematol Branch, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. NHLBI, Bioinformat Core Facil, Bethesda, MD 20892 USA. NCI, Ctr Canc Res, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 708 BP 209A EP 209A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426001177 ER PT J AU Wiestner, A Dunleavy, K Rizzatti, EG Liu, H Marti, GE White, T Wilson, W AF Wiestner, A Dunleavy, K Rizzatti, EG Liu, H Marti, GE White, T Wilson, W TI Potent single agent activity and tumor selectivity of bortezomib in mantle cell lymphoma: First impressions from a randomized phase II study of EPOCH-rituximab-bortezomib in untreated mantle cell lymphoma. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 NHLBI, Hematol Branch, Bethesda, MD 20892 USA. NCI, Ctr Canc Res, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. NR 0 TC 2 Z9 2 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 2005 VL 106 IS 11 MA 4744 BP 266B EP 266B PN 2 PG 1 WC Hematology SC Hematology GA 986CG UT WOS:000233426101446 ER PT J AU Gaines, AR AF Gaines, AR TI Disseminated intravascular coagulation associated with acute hemoglobinemia or hemoglobinuria following Rh.(D) immune globulin intravenous administration for immune thrombocytopenic purpura SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 US FDA, Off Biostat & Epidemiol, Ctr Biol Evaluat & Res, 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 2005 VL 106 IS 11 MA 1242 BP 361A EP 362A PN 1 PG 2 WC Hematology SC Hematology GA 986CF UT WOS:000233426002177 ER PT J AU Lozier, JN Zhang, P AF Lozier, JN Zhang, P TI Mapping of genes that control the antibody response to human FVIII in mice. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 US FDA, Ctr Biol Evaluat & Res, Rockville, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 1888 BP 536A EP 536A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426003250 ER PT J AU Gelderman-Fuhrmann, MP Simakova, O Carter, LB Simak, J AF Gelderman-Fuhrmann, MP Simakova, O Carter, LB Simak, J TI Evaluation of immunophenotypes and activities of cell membrane microparticles in apheresis platelets: Impact of seven day storage. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 US FDA, CBER, Rockville, MD USA. USUHS, Sch Med, Bethesda, MD USA. RI Simak, Jan/C-1153-2011 NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 1893 BP 537A EP 538A PN 1 PG 2 WC Hematology SC Hematology GA 986CF UT WOS:000233426003255 ER PT J AU Piper, JT Vostal, JG AF Piper, JT Vostal, JG TI A novel animal model for detecting damage to human platelet transfusion products: In vivo recovery and survival in severe combined immunodeficient mice. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 US FDA, CBER, Div Hematol, Lab Cellular Hematol, Rockville, 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 2005 VL 106 IS 11 MA 1891 BP 537A EP 537A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426003253 ER PT J AU Chen, BZJ Hong, HX Ge, WG Tong, WD Walker, R Alpe, TL Barlogie, B Epstein, J AF Chen, BZJ Hong, HX Ge, WG Tong, WD Walker, R Alpe, TL Barlogie, B Epstein, J TI Surface chemistry proteomics and biomarker discovery in multiple myeloma. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 Univ Arkansas Med Sci, Myeloma Inst Res & Therapy, Little Rock, AR USA. US FDA, Natl Ctr Toxicol Res, Div Bioinformat, Jefferson, AR USA. US FDA, Natl Ctr Toxicol Res, Div Syst Toxicol, Ctr Toxicoinformat, Jefferson, AR USA. Univ Arkansas Med Sci, Dept Radiol, Div Diagnost Radiol, Little Rock, AR USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 2493 BP 700A EP 700A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426004340 ER PT J AU Cokic, VP Bhattacharya, B Puri, RK Alan, N AF Cokic, VP Bhattacharya, B Puri, RK Alan, N TI Developmental and differential changes of gene expression in erythroid progenitor cells. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 Inst Med Res, Lab Expt Hematol, Belgrade, Serbia Monteneg. US FDA, Lab Mol & Tumor Biol, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. NIDDK, Mol Med Branch, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 3648 BP 1015A EP 1016A PN 1 PG 2 WC Hematology SC Hematology GA 986CF UT WOS:000233426006432 ER PT J AU Lozier, JN D'Agnillo, F AF Lozier, JN D'Agnillo, F TI In vitro protection of human endothelial cells from adenovirus vector toxicity by activated protein C. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 US FDA, Ctr Biol Evaluat & Res, Rockville, 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 2005 VL 106 IS 11 MA 3694 BP 1028A EP 1028A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426006478 ER PT J AU Chu, PS Lopez, MI AF Chu, PS Lopez, MI TI Liquid chromatography-tandem mass spectrometry for the determination of protein-bound residues in shrimp dosed with nitrofurans SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE nitrofurans; shrimp; LC-MS/MS; method; bound residues ID CATFISH ICTALURUS-PUNCTATUS; SOLID-PHASE EXTRACTION; CHANNEL CATFISH; FURAZOLIDONE METABOLITE; PIG HEPATOCYTES; MUSCLE TISSUES; SEMICARBAZIDE; 3-AMINO-2-OXAZOLIDINONE; PHARMACOKINETICS; CHAIN AB An analytical method was developed for the determination of bound residues of the nitrofuran drugs furazolidone, nitrofurazone, furaltadone, and nitrofurantoin with a sensitivity of 1 ppb in shrimp. In this procedure, shrimp tissue is prewashed with solvents followed by overnight acid hydrolysis, during which the side chains of the bound residues are released and simultaneously derivatized with 2-nitrobenzaldehyde. After liquid-liquid extraction cleanup, the derivatives are detected and quantitated using liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) with an atmospheric pressure chemical ionization interface. The method was validated using control shrimp fortified with each side-chain analyte at 1, 2, and 4 ppb. Method accuracies were > 80% with coefficients of variation of < 20% for all four analytes. Tissues from dosed shrimp were assayed to demonstrate the effectiveness of the method for recovering bound residues of nitrofurans. In shrimp dosed with nitrofurans, nitrofurantoin exhibited the lowest level of bound residues. 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. EM pak.chu@fda.gov NR 25 TC 32 Z9 38 U1 1 U2 17 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 NOV 16 PY 2005 VL 53 IS 23 BP 8934 EP 8939 DI 10.1021/jf051615o PG 6 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 984LP UT WOS:000233306700010 PM 16277385 ER PT J AU Epstein, SL Kong, WP Misplon, JA Lo, CY Tumpey, TM Xu, L Nabel, GJ AF Epstein, SL Kong, WP Misplon, JA Lo, CY Tumpey, TM Xu, L Nabel, GJ TI Protection against multiple influenza A subtypes by vaccination with highly conserved nucleoprotein SO VACCINE LA English DT Article DE influenza; DNA vaccines; adenovirus vectors; conserved antigens; animal models; H5N1 influenza; heterosubtypic immunity ID CD8(+) T-CELLS; HETEROSUBTYPIC IMMUNITY; VIRUS-INFECTION; DNA VACCINES; IN-VITRO; MICE; HUMANS; IMMUNOGENICITY; REPLICATION; VECTOR AB Influenza epidemic and pandemic strains cannot be predicted with certainty. Current vaccines elicit antibodies effective against specific strains, but new strategies are urgently needed for protection against unexpected strains. DNA vaccines encoding conserved antigens protect animals against diverse subtypes, but their potency needs improvement. We tested DNA prime-recombinant adenoviral boost immunization to nucleoprotein (NP). Strong antibody and T cell responses were induced. Protection against challenge was T cell-dependent and substantially more potent than DNA vaccination alone. Importantly, vaccination protected against lethal challenge with highly pathogenic H5N1 virus. Thus, gene-based vaccination with NP may contribute to protective immunity against diverse influenza viruses through its ability to stimulate cellular immunity. (c) 2005 Elsevier Ltd. All rights reserved. C1 US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Lab Immunol & Dev Biol, Bethesda, MD 20892 USA. NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. Ctr Dis Control & Prevent, Influenza Branch, Div Viral & Rickettsial Dis, Atlanta, GA 30333 USA. RP Epstein, SL (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Lab Immunol & Dev Biol, Bethesda, MD 20892 USA. EM epsteins@cber.fda.gov NR 35 TC 190 Z9 202 U1 0 U2 8 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD NOV 16 PY 2005 VL 23 IS 46-47 BP 5404 EP 5410 DI 10.1016/j.vaccine.2005.04.047 PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 989NL UT WOS:000233680700020 PM 16011865 ER PT J AU Walker, RI Van de Verg, LL Hall, RH Schmitt, CK Woo, K Hale, V AF Walker, RI Van de Verg, LL Hall, RH Schmitt, CK Woo, K Hale, V TI Enteric vaccines for pediatric use - Workshop summary SO VACCINE LA English DT Editorial Material DE pediatric vaccines; enteric pathogens; vaccine development and implementation AB Diarrheal diseases remain a major cause of death in children under 5 in less developed countries (LDCs). Vaccine development and implementation offers the best near-term approach to alleviating this problem. For this reason, a workshop to examine the possibilities for making enteric vaccines available to meet the specific needs of children in LDCs was convened in Virginia on April 24-26, 2004. Discussants considered research and development needs, regulatory and business issues, and previous experiences with enteric vaccine development and implementation. No insurmountable roadblocks to progress in this area were noted, and the possibility currently exists that property supported efforts will enable the realization of enteric vaccines for pediatric use. (c) 2005 Elsevier Ltd. All rights reserved. C1 US FDA, Ctr Biol Evaluat & Res, Div Bacterial Parasit & Allergen Prod, Rockville, MD 20851 USA. NIAID, Enter & Hepat Dis Branch, DMID, NIH, Bethesda, MD 20892 USA. Inst OneWorld Hlth, San Francisco, CA 94104 USA. RP Walker, RI (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Bacterial Parasit & Allergen Prod, 1401 Rockville Pike,HFM-425, Rockville, MD 20851 USA. EM walkerri@cber.fda.gov NR 0 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD NOV 16 PY 2005 VL 23 IS 46-47 BP 5432 EP 5439 DI 10.1016/j.vaccine.2005.01.161 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 989NL UT WOS:000233680700024 PM 16286159 ER PT J AU Cutrone, R Lednicky, J Dunn, G Rizzo, P Bocchetta, M Chumakov, K Minor, P Carbone, M AF Cutrone, R Lednicky, J Dunn, G Rizzo, P Bocchetta, M Chumakov, K Minor, P Carbone, M TI Some oral poliovirus vaccines were contaminated with infectious SV40 after 1961 SO CANCER RESEARCH LA English DT Article ID HUMAN MESOTHELIAL CELLS; HUMAN TUMORS; HUMAN CANCER; MALIGNANT MESOTHELIOMA; VACUOLATING VIRUS; DNA-SEQUENCES; SIMIAN-VIRUS-40; TRANSFORMATION; ASSOCIATION; ASBESTOS AB Some polio vaccines prepared from 1954 to 1961 were contaminated with infectious SV40. It has been assumed that all polio vaccines were SV40 free in the United States after 1961 and in other countries after 1962. Following a WHO requirement that was prompted by the detection of SV40 in some human tumors, we conducted a multilaboratory study to test for SV40 polio vaccines prepared after 1961. Vaccine samples from 13 countries and the WHO seed were initially tested by PCR. The possible presence of intact and/or infectious SV40 DNA in PCR-positive samples was tested by transfection and infection of permissive CV-1 cells. All results were, verified by immunohistochemistry, cloning, and sequencing. All the vaccines were SV40 free, except for vaccines from a major eastern European manufacturer that contained infectious SV40. We determined that the procedure used by this manufacturer to inactivate SV40 in oral poliovirus vaccine seed stocks based on heat inactivation in the presence of MgCl2, did not completely inactivate SV40. These SV40-contaminated vaccines were produced from early 1960s to about 1978 and were used throughout the world. Our findings underscore the potential risks of using primary monkey cells for preparing poliovirus vaccines, because of the possible contamination with SV40 or other monkey viruses, and emphasize the importance of using well-characterized cell substrates that are free from adventitious agents. Moreover, our results indicate possible geographic differences in SV40 exposure and offer a possible explanation for the different percentage of SV40-positive tumors detected in some laboratories. C1 Loyola Univ, Med Ctr, Cardinal Bernardin Canc Ctr, Thorac Oncol Program, Maywood, IL 60153 USA. Loyola Univ, Cardinal Bernardin Canc Ctr, Breast Canc Program, Maywood, IL 60153 USA. Loyola Univ, Virol Lab, Dept Pathol, Maywood, IL 60153 USA. US FDA, Rockville, MD 20857 USA. RP Carbone, M (reprint author), Loyola Univ, Med Ctr, Cardinal Bernardin Canc Ctr, Thorac Oncol Program, Room 205,2160 S 1st Ave, Maywood, IL 60153 USA. EM mcarbon@lumc.edu NR 37 TC 57 Z9 59 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 15 PY 2005 VL 65 IS 22 BP 10273 EP 10279 DI 10.1158/0008-5472.CAN-05-2028 PG 7 WC Oncology SC Oncology GA 985ZV UT WOS:000233418900023 PM 16288015 ER PT J AU Kelloff, GJ Krohn, KA Larson, SM Weissleder, R Mankoff, DA Hoffman, JM Link, JM Guyton, KZ Eckelman, WC Scher, HI O'Shaughnessy, J Cheson, BD Sigman, CC Tatum, JL Mills, GQ Sullivan, DC Woodcock, J AF Kelloff, GJ Krohn, KA Larson, SM Weissleder, R Mankoff, DA Hoffman, JM Link, JM Guyton, KZ Eckelman, WC Scher, HI O'Shaughnessy, J Cheson, BD Sigman, CC Tatum, JL Mills, GQ Sullivan, DC Woodcock, J TI The progress and promise of molecular imaging probes in oncologic drug development SO CLINICAL CANCER RESEARCH LA English DT Review ID POSITRON-EMISSION-TOMOGRAPHY; BLOOD-BRAIN-BARRIER; METASTATIC PROSTATE-CANCER; STEROID-HORMONE RECEPTORS; P-GLYCOPROTEIN TRANSPORT; ADVANCED BREAST-CANCER; NON-HODGKINS-LYMPHOMA; IN-VIVO; ESTROGEN-RECEPTOR; ANNEXIN-V AB As addressed by the recent Food and Drug Administration Critical Path Initiative, tools are urgently needed to increase the speed, efficiency and cost effectiveness of drug development for cancer and other diseases. Molecular imaging probes developed based on recent scientific advances have a great potential as oncological drug development tools. Basic science studies using molecular imaging probes can help to identify and characterize disease-specific targets for oncologic drug therapy. Imaging end points, based on these disease-specific biomarkers, hold great promise to better define, stratify, and enrich study groups and to provide direct biological measures of response. Imaging-based biomarkers also have promise for speeding drug evaluation by supplementing or replacing preclinical and clinical pharmocokinetic and pharmacodynamic evaluations, including target interaction and modulation. Such analysis may be particularly valuable in early comparative studies among candidates designed to interact with the same molecular target. Finally, as response biomarkers, imaging end points that characterize tumor vitality, growth, or apoptosis can also serve as early surrogates of therapy success. this article outlines the scientific basis for oncology imaging probes and presents examples of probes that could facilitate progress. The current regulatory opportunities for new and existing probe development and testing are also reviewed, with a focus on recent Food and Drug Administration guidance to facilitate early clinical development of promising probes. C1 NCI, Canc Imaging Program, Div Canc Treatment & Diagnosis, NIH, Bethesda, MD 20892 USA. Mol Tracer LLC, Bethesda, MD USA. Univ Washington, Dept Radiol, Div Nucl Med, Seattle, WA 98195 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA USA. CCS Associates, Mountain View, CA USA. Baylor Charles A Sammons Canc Ctr, Dallas, TX USA. Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC USA. Off Drug Evaluat, Div Med Imaging & Radiopharmaceut Drug Prod, Rockville, MD USA. US FDA, Off Commissioner, Rockville, MD 20857 USA. RP Kelloff, GJ (reprint author), NCI, Canc Imaging Program, Div Canc Treatment & Diagnosis, NIH, EPN 6130 Execut Blvd,Suite 6058, Bethesda, MD 20892 USA. EM kelloffg@mail.nih.gov RI Mankoff, David/F-9576-2010 FU NCI NIH HHS [P01 CA042045] NR 182 TC 160 Z9 162 U1 2 U2 17 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV 15 PY 2005 VL 11 IS 22 BP 7967 EP 7985 DI 10.1158/1078-0432.CCR-05-1302 PG 19 WC Oncology SC Oncology GA 987HI UT WOS:000233508600003 PM 16299226 ER PT J AU Tournas, VH Katsoudas, E AF Tournas, VH Katsoudas, E TI Mould and yeast flora in fresh berries, grapes and citrus fruits SO INTERNATIONAL JOURNAL OF FOOD MICROBIOLOGY LA English DT Article DE moulds; yeasts; berries; grapes; citrus fruits ID FUNGI AB Fresh fruits are prone to fungal contamination in the field, during harvest, transport, marketing, and with the consumer. It is important to identify fungal contaminants in fresh fruits because some moulds can grow and produce mycotoxins on these commodities while certain yeasts and moulds can cause infections orallergies. In this study, 251 fresh fruit samples including several varieties of grapes, strawberries, blueberries, raspberries, blackberries, and various citrus fruits were surface-disinfected, incubated at room temperature for up to 14 days without supplemental media, and subsequently examined for mould and yeast growth. The level of contamination (percent of contaminated items/sample) varied depending on the type of fruit. All raspberry and blackberry samples were contaminated at levels ranging from 33% to 100%, whereas 95% of the blueberry samples supported mould growth at levels between 10% and 100% of the tested berries, and 97% of strawberry samples showed fungal growth on 33-100% of tested berries. The most common moulds isolated from these commodities were Botrytis cinerea, Rhizopus (in strawberries), Alternaria, Penicillium, Cladosporium and Fusarium followed by yeasts, Trichoderma and Aureobasidium. Thirty-five percent of the grape samples tested were contaminated and supported fungal growth; the levels of contamination ranged from 9% to 80%. The most common fungi spoiling grapes were Alternaria, R. cinerea and Cladosporium. Eighty-three percent of the citrus fruit samples showed fungal growth at levels ranging from 25% to 100% of tested fruits. The most common fungi in citrus fruits were Alternaria, Cladosporium, Penicillium, Fusarium and yeasts. Less common were Trichoderma, Geotrichum and Rhizopus. Published by Elsevier B.V. C1 US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. US FDA, NE Reg Lab, Jamaica, NY 11433 USA. RP Tournas, VH (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM vtournas@cfsan.fda.gov NR 16 TC 100 Z9 110 U1 6 U2 32 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-1605 J9 INT J FOOD MICROBIOL JI Int. J. Food Microbiol. PD NOV 15 PY 2005 VL 105 IS 1 BP 11 EP 17 DI 10.1016/j.ijfoodmicro.2005.05.002 PG 7 WC Food Science & Technology; Microbiology SC Food Science & Technology; Microbiology GA 985AR UT WOS:000233349000002 PM 16023239 ER PT J AU Marks, HS Anderson, CR AF Marks, HS Anderson, CR TI Determination of putrescine and cadaverine in seafood (finfish and shellfish) by liquid chromatography using pyrene excimer fluorescence SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article DE putrescine; cadaverine; histamine; tuna; mahimahi; shrimp; salmon; crab; biogenic amines; 1-pyrenebutanoic acid succinimidyl ester; derivatization; LC; pyrene ID BIOGENIC-AMINES; FLUOROMETRIC-DETERMINATION; FORMING DERIVATIZATION; LABELING REAGENT; HISTAMINE; TUNA; SAMPLES; HISTIDINE; FRESH; ACIDS AB A liquid chromatography (LC) method is described for the easy determination of the biogenic diamines putrescine (PUT) and cadaverine (CAD) in canned tuna, frozen tuna loin, fresh mahimahi fillet, frozen raw shrimp, cooked lump crabmeat, and fresh and cold-smoked salmon. The method is also a useful screen for histamine (HTA). The method involves homogenization of fish tissue, extraction of biogenic amines into borate-trichloroacetic acid solution, centrifugation, and derivatization of supernatant with 1-pyrenebutanoic acid succinimidyl ester. The derivatized diamine species allow for the intramolecular excimer fluorescence of the pyrene moiety at a higher emission wavelength than is possible for the endogenous tissue monoamines, thus providing visual specificity of detection. All seafood species were fortified with 0.5, 1.0, 5.0, 10.0, and 15.0 mu g/g (ppm) of PUT and CAD. Determination was based on standard graphs for PUT and CAD using peak areas with standard solutions equivalent to 0.375, 1.0, 5.0, 10.0, and 20.0 ppm in tissue. A set of five matrix controls (unfortified seafood tissue) were also analyzed; endogenous PUT was found in all samples except the canned tuna, and CAD found only in the shrimp, crab, and cold-smoked salmon. The background amines were thus subtracted prior to determining spike recovery. The intra-assay average recoveries ranged from 71 to 94% across species and spike levels. (c) 2005 Elsevier B.V. All rights reserved. C1 US FDA, Seafood Prod Res Ctr, Pacific Reg Lab NW, Bothell, WA 98021 USA. RP Marks, HS (reprint author), US FDA, Seafood Prod Res Ctr, Pacific Reg Lab NW, 22201 23rd Dr SE, Bothell, WA 98021 USA. EM heidi.marks@fda.gov NR 30 TC 20 Z9 21 U1 1 U2 8 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 NOV 11 PY 2005 VL 1094 IS 1-2 BP 60 EP 69 DI 10.1016/j.chroma.2005.07.088 PG 10 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 982IF UT WOS:000233150600009 PM 16257290 ER PT J AU Moses-Kolko, EL Bogen, D Perel, J Wisner, KL Bregar, A Uhl, K Levin, B AF Moses-Kolko, EL Bogen, D Perel, J Wisner, KL Bregar, A Uhl, K Levin, B TI Neonatal signs after in utero exposure to selective serotonin reuptake inhibitors - Reply SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter ID ANTIDEPRESSANT DRUGS; DEPRESSED MOTHERS; CHILDREN C1 Univ Pittsburgh, Sch Med, Pittsburgh, PA 15213 USA. Princeton Univ, Princeton, NJ 08544 USA. US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Moses-Kolko, EL (reprint author), Univ Pittsburgh, Sch Med, Pittsburgh, PA 15213 USA. EM mosesel@upmc.edu NR 8 TC 1 Z9 1 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 9 PY 2005 VL 294 IS 18 BP 2300 EP 2301 DI 10.1001/jama.294.18.2300-b PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 981LI UT WOS:000233089700020 ER PT J AU Orloff, DG AF Orloff, DG TI Fixed combination drugs for cardiovascular disease risk reduction: Regulatory approach SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article; Proceedings Paper CT Symposium on Combination Therapy for Dyslipidemia in the Metabolic Syndrome CY OCT 26, 2004 CL Venice, ITALY AB The use of combination drug therapy for cardiovascular (CV) disease risk reduction is the established approach to multiple risk factor reduction. The spectrum of rational combination products in CV disease prevention and treatment alone is extremely broad. Development of fixed-dose combination drug products requires information beyond that needed for approval of single active ingredient products. Establishing the rationale and target populations for novel combinations, as well as the contributions of the component drugs to the claimed effects, and characterizing the pharmacokinetics, the pharmacodynamics, and clinical safety and efficacy of the combination are all necessary to support approval. (c) 2005 Elsevier Inc. All rights reserved. C1 US FDA, Rockville, MD 20857 USA. RP Orloff, DG (reprint author), US FDA, 5600 Fishers Lane, Rockville, MD 20857 USA. EM orloffd@cder.fda.gov NR 7 TC 7 Z9 8 U1 1 U2 1 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD NOV 7 PY 2005 VL 96 IS 9A SU S BP 28K EP 33K DI 10.1016/j.amjcard.2005.08.005 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 988DI UT WOS:000233571300005 PM 16291011 ER PT J AU Rosen, JB Breman, JG Manclark, CR Meade, BD Collins, WE Lobel, HO Saliou, P Roberts, JM Campaore, P Miller, MA AF Rosen, JB Breman, JG Manclark, CR Meade, BD Collins, WE Lobel, HO Saliou, P Roberts, JM Campaore, P Miller, MA TI Malaria chemoprophylaxis and the serologic response to measles and diphtheria-tetanus-whole-cell pertussis vaccines SO MALARIA JOURNAL LA English DT Article ID PLACEBO-CONTROLLED TRIAL; MENINGOCOCCAL POLYSACCHARIDE VACCINE; STANDARDIZED VIRAL HEMAGGLUTINATION; PLASMODIUM-FALCIPARUM MALARIA; IMMUNE-RESPONSE; ANTIBODY-RESPONSE; INTERMITTENT TREATMENT; AUTOIMMUNE-DISEASE; TANZANIAN INFANTS; GAMBIAN CHILDREN AB Background: Acute malaria has been associated with a decreased antibody response to tetanus and diphtheria toxoids, meningococcal, salmonella, and Hib vaccines. Interest in giving malaria drug therapy and prevention at the time of childhood immunizations has increased greatly following recent trials of intermittent preventive therapy during infancy (IPTi), stimulating this re-analysis of unpublished data. The effect of malaria chemoprophylaxis on vaccine response was studied following administration of measles vaccines and diphtheria-tetanus-whole cell pertussis (DTP) vaccines. Methods: In 1975, six villages divided into two groups of children = 74 months of age from Burkina Faso, were assigned to receive amodiaquine hydrochloride chemoprophylaxis (CH+) every two weeks for seven months or no chemoprophylaxis (CH-). After five months, children in each group received either one dose of measles or two doses of DTP vaccines. Results: For recipients of the measles vaccine, the seroconversion rates in CH+ and CH- children, respectively, were 93% and 96% (P > 0.05). The seroresponse rates in CH+ and CH- children respectively, were 73% and 86% for diphtheria (P > 0.05) and 77% and 91% for tetanus toxoid (P > 0.05). In a subset analysis, in which only children who strictly adhered to chemoprophylaxis criteria were included, there were, likewise, no significant differences in seroconversion or seroresponse for measles, diphtheria, or tetanus vaccines (P > 0.05). While analysis for pertussis showed a 43% (CH+) and 67% (CH-) response (P < 0.05), analyses using logistic regression to control for sex, age, chemoprophylaxis, weight-for-height Z-score, and pre-vaccination geometric mean titer (GMT), demonstrated that chemoprophylaxis was not associated with a significantly different conversion rate following DTP and measles vaccines. Seven months of chemoprophylaxis decreased significantly the malaria IFA and ELISA GMTs in the CH+ group. Conclusion: Malaria chemoprophylaxis prior to vaccination in malaria endemic settings did not improve or impair immunogenicity of DTP and measles vaccines. This is the first human study to look at the association between malaria chemoprophylaxis and the serologic response to whole-cell pertussis vaccine. C1 NIH, Div Int Epidemiol & Populat Studies, Fogarty Int Ctr, Bethesda, MD 20892 USA. NIH, Howard Hughes Med Inst, Res Program, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Bacterial Prod Allergen & Parasit Prod, Bethesda, MD 20892 USA. Ctr Dis Control & Prevent, Div Parasit Dis, Natl Ctr Infect Dis, Atlanta, GA 30333 USA. Soc Pathol Exot, Paris, France. RP Rosen, JB (reprint author), NIH, Div Int Epidemiol & Populat Studies, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA. EM jennifer.rosen@uhmc.sunysb.edu; bremanj@ficod.fic.nih.gov; crm@manclark.com; meade@cber.FDA.gov; wec1@cdc.gov; lobel@hargray.com; psaliou@pasteur.fr; JMR1@CDC.GOV; traoreap@hotmail.com; millemar@mail.nih.gov NR 60 TC 8 Z9 8 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1475-2875 J9 MALARIA J JI Malar. J. PD NOV 6 PY 2005 VL 4 AR 53 DI 10.1186/1475-2875-4-53 PG 9 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA 992QN UT WOS:000233899000001 PM 16271153 ER PT J AU Allred, CD Twaddle, NC Allred, KF Goeppinger, TS Churchwell, MI Ju, YH Helferich, WG Doerge, DR AF Allred, CD Twaddle, NC Allred, KF Goeppinger, TS Churchwell, MI Ju, YH Helferich, WG Doerge, DR TI Soy processing affects metabolism and disposition of dietary isoflavones in ovariectomized balb/c mice SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE soy; isoflavone; genistein; equol; pharmacokinetics; mass spectrometry ID RAT SMALL-INTESTINE; ESTROGEN-RECEPTOR-ALPHA; CANCER MCF-7 CELLS; IN-VITRO; LIQUID-CHROMATOGRAPHY; URINARY-EXCRETION; MASS-SPECTROMETRY; STIMULATE GROWTH; AMERICAN WOMEN; S-EQUOL AB Soy foods and nutritional supplements are widely consumed for potential health benefits. It was previously shown that isoflavone-supplemented diets, which contained equal genistein equivalents, differentially stimulated mammary tumor growth in athymic mice based on the degree of processing. This paper reports plasma pharmacokinetic analysis and metabolite identification using the parental mouse strain fed the same diets, which contained genistin, mixed isoflavones, Novasoy, soy molasses, or soy flour plus mixed isoflavones. Whereas the degree of soy processing did affect several parameters reflecting isoflavone bioavailability and gut microflora metabolism of daidzein to equol, stimulation of tumor growth correlated significantly with only the plasma concentration of aglycon genistein produced by the diets. This conclusion is consistent with the known estrogen agonist activity of genistein aglycon on mammary tumor growth. Conversely, plasma equol concentration was inversely correlated with the degree of soy processing. Although antagonism of genistein-stimulated tumor growth by equol could explain this result, the very low concentration of aglycon equol in plasma (12-fold lower relative to genistein) is inconsistent with any effect. These findings underscore the importance of food processing, which can remove non-nutritive components from soy, on the pharmacokinetics and pharmacodynamics of isoflavones. Such changes in diet composition affect circulating, and presumably target tissue, concentrations of genistein aglycon, which initiates estrogen receptor-mediated processes required for the stimulation of tumor growth in a mouse model for postmenopausal breast cancer. C1 Univ Illinois, Dept Food Sci & Human Nutr, Urbana, IL 61801 USA. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Helferich, WG (reprint author), Univ Illinois, Dept Food Sci & Human Nutr, Urbana, IL 61801 USA. EM helferic@uiuc.edu; ddoerge@nctr.fda.gov FU NCI NIH HHS [CA 77355]; NIA NIH HHS [P01 AG 024387]; NIEHS NIH HHS [T32 ES 07326] NR 45 TC 43 Z9 45 U1 1 U2 5 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 NOV 2 PY 2005 VL 53 IS 22 BP 8542 EP 8550 DI 10.1021/jf051246w PG 9 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 978YR UT WOS:000232909500020 PM 16248551 ER PT J AU Liang, XJ Taylor, B Cardarelli, C Yin, JJ Annereau, JP Garfield, S Wincovitch, S Szakacs, G Gottesman, MM Aszalos, A AF Liang, XJ Taylor, B Cardarelli, C Yin, JJ Annereau, JP Garfield, S Wincovitch, S Szakacs, G Gottesman, MM Aszalos, A TI Different roles for K+ channels in cisplatin-resistant cell lines argue against a critical role for these channels in cisplatin resistance SO ANTICANCER RESEARCH LA English DT Article DE cisplatin resistance; K plus channels; ion homeostasis; microarray; confocal microscopy ID AMPHOTERICIN-B; MULTIDRUG-RESISTANCE; INDUCED APOPTOSIS; CARCINOMA-CELLS; DNA DAMAGE; CYTOTOXICITY; EXPRESSION; PLATINUM; SYSTEM; DRUGS AB Cisplatin resistance has been associated with altered K+ fluxes. Here, we focused our investigations on the detection of K+ channels in a series of cisplatin-resistant (CP-r) cells with increasing resistance and on the functional relationship of these K+ channels to resistance. Microarray analysis and confocal microscopy indicated that there was overexpression of the ether-a-gogo gene (HERG) and the inwardly rectifying potassium channel gene (TWIK) in a human epidermal KB and human liver BEL-7404 carcinoma cell line series selected for cisplatin resistance. With increased resistance, the plasma membrane potential, but not the mitochondrial membrane potential, also increases in these two series. For these reasons, we conducted cell proliferation studies in the presence of either antibodies directed against the detected K+ channels, omeprazole (a H+ pump inhibitor) or a specific inhibitor of the HERG channel (WAY-123398-A-5). The antibodies and omeprazole influenced cell growth only very slightly. The specific K+ channel blocker did not alter cisplatin resistance. We also observed that manipulation of K+ fluxes with antibodies and the H+ pump with omeprazole resulted in opposite effects on cisplatin resistance in these two cell lines. We conclude that K+ and H+ homeostasis are not critical factors in cisplatin resistance since they affect cisplatin resistance differently in KB and BEL-7404 cells. C1 NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. NCI, FACS Core Facil, NIH, Bethesda, MD 20892 USA. NCI, Expt Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. US FDA, Instrumentat & Biophys Branch, Ctr Food Safety & Appl Nutr, College Pk, MD USA. RP Aszalos, A (reprint author), NCI, Cell Biol Lab, NIH, 37 Convent Dr,Room 2112, Bethesda, MD 20892 USA. EM aszalosa@mail.nih.gov RI Szakacs, Gergely/A-2580-2009; Yin, Jun Jie /E-5619-2014 OI Szakacs, Gergely/0000-0002-9311-7827; FU Intramural NIH HHS NR 31 TC 7 Z9 7 U1 0 U2 1 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD NOV-DEC PY 2005 VL 25 IS 6B BP 4113 EP 4122 PG 10 WC Oncology SC Oncology GA 984BU UT WOS:000233278300048 PM 16309205 ER PT J AU Buehler, PW Alayash, AI AF Buehler, PW Alayash, AI TI Redox biology of blood revisited: The role of red blood cells in maintaining circulatory reductive capacity SO ANTIOXIDANTS & REDOX SIGNALING LA English DT Review ID INDEPENDENT OXIDATIVE DAMAGE; ASCORBIC-ACID; VITAMIN-C; DEHYDROASCORBIC ACID; HUMAN ERYTHROCYTES; ENDOTHELIAL-CELLS; HEMOGLOBIN; METHEMOGLOBIN; MICROCIRCULATION; BIOSYNTHESIS AB There is an increasing recognition of the role of red blood cells (RBCs) in cell signaling above and beyond its oxygen (O-2)-carrying function. A recent forum published in the December 2004 issue of Antioxidants & Redox Signaling focused on redox biology of blood and the intricate signaling pathways of RBCs or its free components, i.e., hemoglobin, with the vasculature. The forum provided an up-to-date source of information on this emerging and exciting area of blood biology and the underlying redox chemistry. In the current short review, we have revisited the topic of redox biology of blood and focused on yet another emerging area of research, which deals with the reductive power of blood and the physiological implications. C1 US FDA, CBER, NIH, Lab Biochem & Vasc Biol,Div Hematol, Bethesda, MD 20892 USA. RP US FDA, CBER, NIH, Lab Biochem & Vasc Biol,Div Hematol, Bldg 29,Room 112,8800 Rockville Pike, Bethesda, MD 20892 USA. EM alayash@cber.fda.gov NR 31 TC 20 Z9 21 U1 1 U2 6 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1523-0864 EI 1557-7716 J9 ANTIOXID REDOX SIGN JI Antioxid. Redox Signal. PD NOV-DEC PY 2005 VL 7 IS 11-12 BP 1755 EP 1760 DI 10.1089/ars.2005.7.1755 PG 6 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 993OD UT WOS:000233962500034 PM 16356136 ER PT J AU Woo, EJ Ball, R Braun, MM AF Woo, EJ Ball, R Braun, MM CA VAERS Working Grp TI Fatal syncope-related fall after immunization SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE LA English DT Editorial Material C1 US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Woo, EJ (reprint author), US FDA, Ctr Biol Evaluat & Res, HFM 222,1401 Rockville Pike, Rockville, MD 20852 USA. EM wooj@cber.fda.gov NR 3 TC 13 Z9 17 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 1072-4710 J9 ARCH PEDIAT ADOL MED JI Arch. Pediatr. Adolesc. Med. PD NOV PY 2005 VL 159 IS 11 BP 1083 EP 1083 DI 10.1001/archpedi.159.11.1083 PG 1 WC Pediatrics SC Pediatrics GA 980XK UT WOS:000233051300018 PM 16275804 ER PT J AU Ressom, HW Varghese, RS Abdel-Hamid, M Eissa, SAL Saha, D Goldman, L Petricoin, EF Conrads, TP Veenstra, TD Loffredo, CA Goldman, R AF Ressom, HW Varghese, RS Abdel-Hamid, M Eissa, SAL Saha, D Goldman, L Petricoin, EF Conrads, TP Veenstra, TD Loffredo, CA Goldman, R TI Analysis of mass spectral serum profiles for biomarker selection SO BIOINFORMATICS LA English DT Article ID OVARIAN-CANCER; PROTEOMIC PATTERNS; SPECTROMETRY; IDENTIFICATION; RESOLUTION; DISCOVERY; CARCINOMA; DIAGNOSIS; SAMPLES; MARKER AB Motivation: Mass spectrometric profiles of peptides and proteins obtained by current technologies are characterized by complex spectra, high dimensionality and substantial noise. These characteristics generate challenges in the discovery of proteins and protein-profiles that distinguish disease states, e.g. cancer patients from healthy individuals. We present low-level methods for the processing of mass spectral data and a machine learning method that combines support vector machines, with particle swarm optimization for biomarker selection. Results: The proposed method identified mass points that achieved high prediction accuracy in distinguishing liver cancer patients from healthy individuals in SELDI-QqTOF profiles of serum. C1 Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC 20057 USA. NHTMRI, Viral Hepatitis Res Lab, Cairo, Egypt. Natl Canc Inst, Cairo, Egypt. NCI, US FDA, Clin Proteom Program, Ctr Biol Evaluat, Bethesda, MD 20892 USA. NCI, SAIC Frederick, Frederick, MD 21701 USA. NCI, Biomed Proteom Program, Frederick, MD 21701 USA. RP Ressom, HW (reprint author), Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC 20057 USA. EM hwr@georgetown.edu RI Varghese, Rency/A-8770-2012 NR 26 TC 54 Z9 59 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD NOV 1 PY 2005 VL 21 IS 21 BP 4039 EP 4045 DI 10.1093/bioinformatics/bti670 PG 7 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 978VM UT WOS:000232901100016 PM 16159919 ER PT J AU Hotchkiss, CE Weis, C Blaydes, B Newbold, R Delclos, KB AF Hotchkiss, CE Weis, C Blaydes, B Newbold, R Delclos, KB TI Multigenerational exposure to genistein does not increase bone mineral density in rats SO BONE LA English DT Article DE genistein; bone development; bone mineral density; endocrine disruptors; rat ID SPRAGUE-DAWLEY RATS; SOY ISOFLAVONE SUPPLEMENTATION; HORMONE-REPLACEMENT THERAPY; POSTMENOPAUSAL WOMEN; OVARIECTOMIZED RATS; IN-VITRO; CONTROLLED-TRIAL; PHYTO-ESTROGENS; DOUBLE-BLIND; AROMATASE DEFICIENCY AB Genistein has been shown to prevent bone loss in ovariectomized adult rats. However, the effects of genistein on bone in developing and reproductively-intact rats have not been examined. A large multigenerational experiment involved feeding 0, 5, 100, or 500 ppm genistein in the diet to intact male and female rats from conception until either weaning, postnatal day 140, or continuously for 2 years. Vertebrae (lumbar and caudal) were collected from these animals at necropsy at 2 years of age and subjected to dual-energy x-ray absorptiometry (DXA) scanning to measure bone mineral density (BMD), bone mineral content (BMC), and bone area. Femurs were collected, and length, cross-sectional area, and cortical bone area were measured directly. Serum was collected for measurement of pyridinoline (PYD) and alkaline phosphatase (ALP). BMD was not affected by genistein in any phase of the experiment. In female rats treated continuously with genistein, BMC and bone area were reduced in the 500 ppm group compared to the 5 ppm group in the lumbar vertebrae, and in all treatment groups compared to control in the caudal vertebrae. In both males and females treated continuously, the cross-sectional area of the femur was reduced in rats treated with 500 ppm compared to those treated with 5 ppm. In female rats treated continuously, PYD was higher in the 100 and 500 ppm groups than in the 0 and 5 ppm groups. In conclusion, the effects of genistein on reproductively-intact rats were not dramatic. High dose of genistein throughout the lifespan resulted in decreased bone size, which may reduce the force required to break the bone. Published by Elsevier Inc. C1 Natl Ctr Toxicol Res, Biomet Corp, Jefferson, AR 72079 USA. RP Hotchkiss, CE (reprint author), Natl Ctr Toxicol Res, Biomet Corp, BIO-915,3900 NCTR Rd, Jefferson, AR 72079 USA. EM chotchkiss@nctr.fda.gov NR 67 TC 13 Z9 14 U1 0 U2 0 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 NOV PY 2005 VL 37 IS 5 BP 720 EP 727 DI 10.1016/j.bone.2005.06.005 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 981FU UT WOS:000233073700014 PM 16098821 ER PT J AU Kaput, J Ordovas, JM Ferguson, L van Ommen, B Rodriguez, RL Allen, L Ames, BN Dawson, K German, B Krauss, R Malyj, W Archer, MC Barnes, S Bartholomew, A Birk, R van Bladeren, P Bradford, KJ Brown, KH Caetano, R Castle, D Chadwick, R Clarke, S Clement, K Cooney, CA Corella, D da Cruz, IBM Daniel, H Duster, T Ebbesson, SOE Elliott, R Fairweather-Tait, S Felton, J Fenech, M Finley, JW Fogg-Johnson, N Gill-Garrison, R Gibney, MJ Gillies, PJ Gustafsson, JA Hartmann, JL He, L Hwang, JK Jais, JP Jang, YS Joost, H Junien, C Kanter, M Kibbe, WA Koletzko, B Korf, BR Kornman, K Krempin, DW Langin, D Lauren, DR Lee, JH Leveille, GA Lin, SJ Mathers, J Mayne, M McNabb, W Milner, JA Morgan, P Muller, M Nikolsky, Y van der Ouderaa, F Park, T Pensel, N Perez-Jimenez, F Poutanen, K Roberts, M Saris, WHM Schuster, G Shelling, AN Simopoulos, AP Southon, S Tai, ES Towne, B Trayhurn, P Uauy, R Visek, WJ Warden, C Weiss, R Wiencke, J Winkler, J Wolff, GL Xi, ZW Zucker, JD AF Kaput, J Ordovas, JM Ferguson, L van Ommen, B Rodriguez, RL Allen, L Ames, BN Dawson, K German, B Krauss, R Malyj, W Archer, MC Barnes, S Bartholomew, A Birk, R van Bladeren, P Bradford, KJ Brown, KH Caetano, R Castle, D Chadwick, R Clarke, S Clement, K Cooney, CA Corella, D da Cruz, IBM Daniel, H Duster, T Ebbesson, SOE Elliott, R Fairweather-Tait, S Felton, J Fenech, M Finley, JW Fogg-Johnson, N Gill-Garrison, R Gibney, MJ Gillies, PJ Gustafsson, JA Hartmann, JL He, L Hwang, JK Jais, JP Jang, YS Joost, H Junien, C Kanter, M Kibbe, WA Koletzko, B Korf, BR Kornman, K Krempin, DW Langin, D Lauren, DR Lee, JH Leveille, GA Lin, SJ Mathers, J Mayne, M McNabb, W Milner, JA Morgan, P Muller, M Nikolsky, Y van der Ouderaa, F Park, T Pensel, N Perez-Jimenez, F Poutanen, K Roberts, M Saris, WHM Schuster, G Shelling, AN Simopoulos, AP Southon, S Tai, ES Towne, B Trayhurn, P Uauy, R Visek, WJ Warden, C Weiss, R Wiencke, J Winkler, J Wolff, GL Xi, ZW Zucker, JD TI The case for strategic international alliances to harness nutritional genomics for public and personal health SO BRITISH JOURNAL OF NUTRITION LA English DT Article DE strategic international alliances; nutrigenomics; gene-nutrient interactions; health diaparities ID DIABETES-RELATED TRAITS; CORONARY-HEART-DISEASE; GENETIC ASSOCIATION; POPULATION STRATIFICATION; CARBOHYDRATE INGESTION; COMPLEX DISEASES; IMMUNE FUNCTION; HAPMAP PROJECT; MESSENGER-RNA; DIETARY FIBER AB Nutrigenomics is the study of how constituents of the diet interact with genes, and their products, to alter phenotype and, conversely, how genes and their products metabolise these constituents into nutrients, antinutrients, and bioactive compounds. Results from molecular and genetic epidemiological studies indicate that dietary unbalance can alter gene-nutrient interactions in ways that increase the risk of developing chronic disease. The interplay of human genetic variation and environmental factors will make identifying causative genes and nutrients a formidable, but not intractable, challenge. We provide specific recommendations for how to best meet this challenge and discuss the need for new methodologies and the use of comprehensive analyses of nutrient-genotype interactions involving large and diverse populations. The objective of the present paper is to stimulate discourse and collaboration among nutrigenomic researchers and stakeholders, a process that will lead to an increase in global health and wellness by reducing health disparities in developed and developing countries. C1 Univ Calif Davis, Ctr Excellence Nutr Genom, Davis, CA 95616 USA. Tufts Univ, USDA, Human Nutr Res Ctr Aging, Nutr & Genom Lab, Boston, MA 02111 USA. Univ Auckland, Natl Ctr Res Excellence Nutrigenom, Auckland 1, New Zealand. TNO Qual Life, NuGO, Zeist, Netherlands. Univ Calif Davis, USDA ARS, Western Human Nutr Res Ctr, Davis, CA 95616 USA. Childrens Hosp Oakland, Res Inst, Oakland, CA 94609 USA. Univ Calif Davis, Dept Food Sci & Technol, Davis, CA 95616 USA. Univ Toronto, Dept Nutr Sci, Toronto, ON, Canada. Univ Alabama Birmingham, Univ Alabama Ctr Nutrient Gene Interact, Birmingham, AL 35294 USA. Univ Illinois, Coll Med, Dept Surg, Lab Nutrigenom Med, Chicago, IL 60612 USA. Ben Gurion Univ Negev, Dept Biotechnol Engn, IL-84105 Beer Sheva, Israel. Nestec Ltd, Nestle Res Ctr, CH-1000 Lausanne, Switzerland. Univ Calif Davis, Seed Biotechnol Ctr, Davis, CA 95616 USA. Univ Calif Davis, Program Int Nutr, Dept Nutr, Davis, CA 95616 USA. Univ Reg Noroeste Estado Rio Grande do Sul, Dept Hlth Sci, Bairro Sao Geraldo Ijui, RS, Brazil. Univ Guelph, Dept Philosophy, Guelph, ON N1G 2W1, Canada. Univ Lancaster, ESRC Ctr Econ & Social Aspects Genom CESAGen, Lancaster LA1 4YG, England. McNeil Nutr, New Brunswick, NJ USA. Univ Paris 06, INSERM Avenir Nutr Dpt Hotel Dieu, Paris, France. Univ Arkansas Med Sci, Dept Biochem & Mol Biol, Little Rock, AR 72205 USA. Univ Valencia, Sch Med, Genet & Mol Epidemiol Unit, Valencia, Spain. Univ Reg Noroeste Estado Rio Grande do Sul, Dept Hlth Sci, Bairro Sao Geraldo Ijui, RS, Brazil. Tech Univ Munich, NuGO, Mol Nutr Unit, D-85350 Freising Weihenstephan, Germany. NYU, Dept Sociol, New York, NY 10003 USA. Univ Calif Berkeley, Inst Study Social Change, Berkeley, CA 94720 USA. Univ Virginia, Sch Med, Dept Neurol Surg, Charlottesville, VA 22908 USA. Inst Food Res, Inst Food Res, Norwich NR4 7UA, Norfolk, England. Lawrence Livermore Natl Lab, Biol & Biotechnol Res Program, Livermore, CA 94550 USA. CSIRO Hlth Sci & Nutr, Adelaide, SA 5000, Australia. AM Todd, Montgomeryville, PA 18936 USA. Life Sci Alliance, Villanova, PA 19085 USA. Sciona Inc, Boulder, CO 80302 USA. Trinity Coll Dublin, NuGO, Nutr Unit, Dept Clin Med, Dublin, Ireland. DuPont Nutr & Hlth, Human Hlth Sci, Newark, DE USA. Penn State Univ, Ctr Excellence Nutrigenom, University Pk, PA USA. Karolinska Inst, Novum, Dept Med Nutr, Ctr Biotechnol, SE-14186 Huddinge, Sweden. Univ Alabama Birmingham, Dept Genet, Birmingham, AL 35294 USA. Chinese Acad Sci, Inst Nutr Sci, SIBS, Shanghai 200031, Peoples R China. Yonsei Univ, Dept Biotechnol, Seoul 120749, South Korea. Univ Paris 05, Hop Necker Enfants Malad, Dept Biostat & Bioinformat, Paris, France. Yonsei Univ, Dept Internal Med, Seoul 120749, South Korea. German Inst Human Nutr, NuGO, Potsdam, Germany. Clin M Lamy, Dept Genet, Hop Necker Enfants Malad, F-75743 Paris, France. Cargill Inc, Wayzata, MN 55305 USA. Northwestern Univ, Sch Med, Ctr Genet Med, Ctr Funct Genom,Robert Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA. Univ Munich, Dr Von Hauner Childrens Hosp, D-80539 Munich, Germany. Interleukin Genet Inc, Waltham, MA 02452 USA. Nutrilite Div Access Business Grp LLC, Buena Pk, CA 90622 USA. Univ Toulouse 3, Obes Res Unit, Inst Louis Bugnard, French Inst Hlth & Med Res,INSERM,Toulouse Univ H, F-31059 Toulouse, France. HortRes Ltd, Hamilton, New Zealand. Yonsei Univ, Dept Food & Nutr, Seoul 120749, South Korea. Food Syst Design, Denville, NJ 07834 USA. Univ Calif Davis, Dept Microbiol, Div Biol Sci, Davis, CA 95616 USA. Univ Newcastle, Human Nutr Res Ctr, NuGO, Newcastle Upon Tyne, Tyne & Wear, England. Natl Res Council Canada, Inst Nutrisci & Hlth, Charlottetown, PE C1A 5T1, Canada. AgResearch, Grassland Res Ctr, Palmerston North, New Zealand. NCI, Nutr Sci Res Grp, Div Canc Prevent, NIH, Bethesda, MD 20892 USA. Rowett Res, Aberystwyth AB21 9SB, Dyfed, Wales. Univ Wageningen & Res Ctr, Wageningen Ctr Food Sci & Nutr, NuGO Dutch Innovat Cluster Nutrigenom, Wageningen, Netherlands. GeneGo Inc, St Joseph, MI 49085 USA. Unilever Corp Res, Sharnbrook MK44 1PY, Beds, England. Yonsei Univ, Dept Food & Nutr, Seoul 120749, South Korea. Inst Nacl Tecnol Agropecuaria, Inst Tecnol Alimentos, Buenos Aires, DF, Argentina. Hosp Univ Reina Sofia, Unidad Lipidos & Arteriosclerosis, Cordoba, Spain. Univ Kuopio, Food & Hlth Res Ctr, FIN-70211 Kuopio, Finland. Purina Nestle, St Louis, MO USA. Univ Maastricht, NuGO Nutr & Toxicol Res Inst NUTRIM, Maastricht, Netherlands. Univ Calif Davis, Dept Nutr, Davis, CA 95616 USA. Univ Auckland, Fac Med & Hlth Sci, Auckland 1, New Zealand. Ctr Genet Nutr & Hlth, Washington, DC 20009 USA. NuGO Inst Food Res, Norwich NR4 7UA, Norfolk, England. Singapore Gen Hosp, Dept Endocrinol, Singapore 169608, Singapore. Wright State Univ, Sch Med, Dept Community Hlth, Dayton, OH 45401 USA. Univ Liverpool, Sch Clin Sci, Liverpool Ctr Nutr Genom, Obes Biol Unit, Liverpool L69 3GA, Merseyside, England. Univ Chile, Inst Nutr & Tecnol Alimentos, Santiago 11, Chile. London Sch Hyg & Trop Med, London WC1, England. Univ Illinois, Coll Med, Dept Internal Med, Urbana, IL 61821 USA. Univ Calif Davis, Div Biol Sci, Neurobiol Physiol & Behav Sect, Davis, CA 95616 USA. Viocare Technol Inc, Princeton, NJ 08542 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. Univ Calif San Francisco, Div Neuroepidemiol, San Francisco, CA 94143 USA. Food & Hlth Res, London N1 7AB, England. US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. BioMarker Pharmaceut Inc, Campbell, CA 95008 USA. Univ Paris 13, EPML CNRS APuces, LIM&BIO, F-93017 Bobigny, France. RP Kaput, J (reprint author), Univ Calif Davis, Ctr Excellence Nutr Genom, Davis, CA 95616 USA. EM jkaput@uic.edu RI JAIS, Jean-Philippe/B-2993-2009; Shelling, Andrew/E-7496-2010; Ferguson, Lynnette/F-5989-2011; Jang, Yang Soo/D-4803-2012; Muller, Michael/B-5795-2008; Fairweather-Tait, Susan/K-4251-2012; da Cruz, Ivana/G-4329-2012; Daniel, Hannelore/B-8982-2009; Joost, Hans-Georg/J-4462-2013; ZUCKER, Jean-Daniel /K-3008-2016; Dawson, Kenneth A./L-2540-2016; Kibbe, Warren/B-2106-2010; OI Tai, E Shyong/0000-0003-2929-8966; Perez Jimenez, Francisco/0000-0001-9808-1280; Mathers, John/0000-0003-3406-3002; Cooney, Craig/0000-0003-4279-557X; Langin, Dominique/0000-0002-2669-7825; Shelling, Andrew/0000-0002-5300-1934; Ordovas, Jose/0000-0002-7581-5680; McNabb, Warren/0000-0003-2514-6551; JAIS, Jean-Philippe/0000-0002-0708-8776; Muller, Michael/0000-0002-5930-9905; da Cruz, Ivana/0000-0003-3008-6899; Joost, Hans-Georg/0000-0002-5860-606X; ZUCKER, Jean-Daniel /0000-0002-5597-7922; Dawson, Kenneth A./0000-0002-0568-6588; Kibbe, Warren/0000-0001-5622-7659; Perez-Jimenez, Francisco/0000-0001-7499-7681 FU NHLBI NIH HHS [HL 54776]; NIMHD NIH HHS [MD 00222] NR 83 TC 95 Z9 98 U1 1 U2 19 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA EDINBURGH BLDG, SHAFTESBURY RD, CB2 8RU CAMBRIDGE, ENGLAND SN 0007-1145 EI 1475-2662 J9 BRIT J NUTR JI Br. J. Nutr. PD NOV PY 2005 VL 94 IS 5 BP 623 EP 632 DI 10.1079/BJN20051585 PG 10 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 981NZ UT WOS:000233096600002 PM 16277761 ER PT J AU Sansbury, LB Ratnasinghe, L Bergen, A Cantwell, MM Wanke, K Caporaso, N Lehman, T Kalindindi, A Modali, R Schatzkin, A Lanza, E AF Sansbury, LB Ratnasinghe, L Bergen, A Cantwell, MM Wanke, K Caporaso, N Lehman, T Kalindindi, A Modali, R Schatzkin, A Lanza, E TI Polymorphisms in ERCC2, ERCC4, OGG1, XRCC1, and XRCC3 genes and their role as effect modifiers of dietary antioxidant intake and risk of colorectal adenoma recurrence. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 4th Annual Conference on Frontiers in Cancer Prevention Research CY OCT 30-NOV 02, 2005 CL Baltimore, MD C1 NCI, Canc Prevent Fellowship Program, Div Canc Prevent, Bethesda, MD 20892 USA. US FDA, Ctr Struct Genom, Little Rock, AR USA. Univ Arkansas, Dept Epidemiol, Little Rock, AR 72204 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. BioServe Biotechnol Ltd, Laurel, MD USA. NCI, Ctr Canc Res, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2005 VL 14 IS 11 SU S BP 2700S EP 2700S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 985BN UT WOS:000233351200082 ER PT J AU Lyn-Cook, BD Word, B Hammons, G Fernandez-Bolanos, J Rasheed, A AF Lyn-Cook, BD Word, B Hammons, G Fernandez-Bolanos, J Rasheed, A TI Hydroxytyrosol modulates STAT3 and NF-kappa B expression in androgen responsive and androgen-unresponsive prostate cancer cells in vitro SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 4th Annual Conference on Frontiers in Cancer Prevention Research CY OCT 30-NOV 02, 2005 CL Baltimore, MD C1 US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Philander Smith Coll, Little Rock, AR USA. CSIC, Inst Grasa, E-41080 Seville, Spain. RI Fernandez-Bolanos, Juan/E-1659-2016 OI Fernandez-Bolanos, Juan/0000-0003-0931-2695 NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2005 VL 14 IS 11 SU S BP 2713S EP 2714S PN 2 PG 2 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 985BN UT WOS:000233351200135 ER PT J AU Kaplan, AV Harvey, ED Kuntz, RE Shiran, H Robb, JF Fitzgerald, P AF Kaplan, AV Harvey, ED Kuntz, RE Shiran, H Robb, JF Fitzgerald, P TI Humanitarian use devices/humanitarian device exemptions in cardiovascular medicine SO CIRCULATION LA English DT Article; Proceedings Paper CT 2nd Dartmouth Drug and Device Development Symposium CY OCT 14-15, 2004 CL Woodstock, VT DE heart disease; catheterization; surgery; catheter AB The Second Dartmouth Device Development Symposium held in October 2004 brought together leaders from the medical device community, including clinical investigators, senior representatives from the US Food and Drug Administration, large and small device manufacturers, and representatives from the financial community to examine difficult issues confronting device development. The role of the Humanitarian Use Device/Humanitarian Device Exemption (HUD/HDE) pathway in the development of new cardiovascular devices was discussed in this forum. The HUD/HDE pathway was created by Congress to facilitate the availability of medical devices for "orphan" indications, ie, those affecting < 4000 individuals within the United States each year. The HUD/HDE pathway streamlines the approval process and permits less well-characterized devices to enter the market. HDE approval focuses primarily on issues of safety and scientific soundness and does not require demonstration of efficacy. In the 7 years since the first device was approved in 1997, a total of 35 HDEs have been granted (23 devices, 6 diagnostic tests). As the costs to gain regulatory approval for commonly used devices increase, companies often seek alternative ways to gain market access, including the HUD/HDE pathway. For a given device, there may be multiple legitimate and distinct indications, including indications that meet the HUD criteria. Companies must choose how and when to pursue each of these indications. The consensus of symposium participants was for the HUD/HDE pathway to be reserved for true orphan indications and not be viewed strategically as part of the clinical development plan to access a large market. C1 Dartmouth Hitchcock Med Ctr, Cardiol Sect, Lebanon, NH 03756 USA. Dartmouth Coll Sch Med, Cardiol Sect, Lebanon, NH USA. US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Stanford Univ, Cardiovasc Med Sect, Stanford, CA 94305 USA. RP Kaplan, AV (reprint author), Dartmouth Hitchcock Med Ctr, Cardiol Sect, 1 Med Ctr Dr, Lebanon, NH 03756 USA. EM aaron.v.kaplan@hitchcock.org NR 5 TC 9 Z9 9 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 1 PY 2005 VL 112 IS 18 BP 2883 EP 2886 DI 10.1161/CIRCULATIONAHA.105.553701 PG 4 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 980BM UT WOS:000232988900020 PM 16267261 ER PT J AU Lee, VHL AF Lee, VHL TI Steve Carney talks to Vincent Lee on the pharma industry, the FDA and public education with respect to drugs and their development SO DRUG DISCOVERY TODAY LA English DT Editorial Material C1 OPS, CDER, FDA, Rockville, MD 20852 USA. RP Lee, VHL (reprint author), OPS, CDER, FDA, Rockwall 2,Room 1023,5515 Secur Lane, Rockville, MD 20852 USA. RI Lee, Vincent/A-9439-2008 OI Lee, Vincent/0000-0001-7708-6269 NR 0 TC 0 Z9 0 U1 0 U2 1 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 NOV 1 PY 2005 VL 10 IS 21 BP 1411 EP 1414 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 974EZ UT WOS:000232575400005 PM 16243258 ER PT J AU Hayward, DG Bolger, PM AF Hayward, DG Bolger, PM TI Tetrachlorodibenzo-p-dioxin in baby food made from chicken produced before and after the termination of ball clay use in chicken feed in the United States SO ENVIRONMENTAL RESEARCH LA English DT Article DE 2,3,7,8-tetrachlorodibenzo-p-dioxin; TCDD; baby food; chicken; whole eggs ID MASS-SPECTROMETRY AB Polychlorodibenzo-p-dioxin/furans were determined in chicken-containing baby foods collected from an annually conducted total diet survey by the US FDA during the last half of fiscal year (FY) 1997 through the first half of FY 1998. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD)was found in 8 of 11 baby food samples. The levels were between 0.025 and 0.28 ngkg(-1) wet wt (0.25-5 ng kg(-1) lipid). The mean TCDD value for chicken-containing baby food with "nondetects" equal to 0 was 1.2 ng kg(-1) lipid, eight times higher than the average level found during a previous survey of chicken lipid TCDD levels in 1996. All other 2,3,7,8-chlorine-substituted dibenzo-p-dioxin congeners were also found with a profile consistent with the use of ball clay in chicken feed. TCDD was not detected in any FY 2000 baby foods made with chicken, with an average limit of detection (LOD) of 0.025 ng kg(-1) wet wt. Whole eggs collected in 1997 from producers that never used ball clay in feed revealed TCDD measurements that were nearly all nondetects and none above the median LOD of 0.015 ng kg(-1) wet wt. The percentage of chickens fed ball clay in their feed was estimated.to be between 2.6% and 3.5% of all chickens produced in the United States in 1997. (c) 2004 Elsevier Inc. All rights reserved. C1 US FDA, College Pk, MD 20740 USA. RP Hayward, DG (reprint author), US FDA, 5100 Paint Branch Pkway, College Pk, MD 20740 USA. EM dhayward@cfsan.fda.gov NR 9 TC 10 Z9 10 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 0013-9351 J9 ENVIRON RES JI Environ. Res. PD NOV PY 2005 VL 99 IS 3 BP 307 EP 313 DI 10.1016/j.envres.2004.11.007 PG 7 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA 993MA UT WOS:000233957000003 PM 16307972 ER PT J AU Karamloo, F Schmid-Grendelmeier, P Kussebi, F Akdis, M Salagianni, M von Beust, BR Reimers, A Zumkehr, J Soldatova, L Housley-Markovic, Z Muller, U Kundig, T Kemeny, DM Spangfort, MD Blaser, K Akdis, CA AF Karamloo, F Schmid-Grendelmeier, P Kussebi, F Akdis, M Salagianni, M von Beust, BR Reimers, A Zumkehr, J Soldatova, L Housley-Markovic, Z Muller, U Kundig, T Kemeny, DM Spangfort, MD Blaser, K Akdis, CA TI Prevention of allergy by a recombinant multi-allergen vaccine with reduced IgE binding and preserved T cell epitopes SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE allergy; T cells; antibodies; antigens/peptides/epitopes; vaccination ID BEE-VENOM PHOSPHOLIPASE-A2; BIRCH POLLEN; ASPERGILLUS-FUMIGATUS; CRYSTAL-STRUCTURE; HONEYBEE VENOM; IMMUNOTHERAPY; RESPONSES; ANTIGEN; MELITTIN; A(2) AB Novel approaches for the prevention of allergy are required, because of the inevitably increasing prevalence of allergic diseases during the last 30 years. Here, a recombinant chimeric protein, which comprises the whole amino acid sequences of three bee venom major allergens has been engineered and used in prevention of bee venom sensitization in mice. Phospholipase A(2) (Api in 1), hyaluronidase (Api m 2) and melittin (Api in 3) fragments with overlapping amino acids were assembled in a different order in the Api in (1/2/3) chimeric protein, which preserved entire T cell epitopes, whereas B cell epitopes of all three allergens were abrogated. Accordingly, IgE cross-linking leading to mast cell and basophil mediator release was profoundly reduced in humans. Supporting these findings, the Api in (1/2/3) induced 100 to 1000 times less type-1 skin test reactivity in allergic patients. Treatment of mice with Api in (1/2/3) led to a significant reduction of specific IgE development towards native allergen, representing a protective vaccine effect in vivo. These results demonstrate a novel prototype of a preventive allergy vaccine, which preserves the entire T cell epitope repertoire, but bypasses induction of IgE against native allergen, and side effects related to mast cell/basophil IgE Fc epsilon;RI cross-linking in sensitized individuals. C1 Swiss Inst Allergy & Asthma Res, CH-7270 Davos, Switzerland. Dept Dermatol, Allergy Unit, Zurich, Switzerland. GKT Sch Med, Rayne Inst, Dept Immunol, London, England. Hosp Berne Ziegler, Div Med, Bern, Switzerland. US FDA, Ctr Drug Evaluat & Res, Bethesda, MD 20014 USA. Univ Basel, Biozentrum, Div Struct Biol, Basel, Switzerland. ALK Abello Inc, Horsholm, Denmark. RP Karamloo, F (reprint author), Swiss Inst Allergy & Asthma Res, Obere Str 22, CH-7270 Davos, Switzerland. EM karamlooflory@compuserve.de; akdisac@siaf.unizh.ch NR 39 TC 50 Z9 53 U1 0 U2 3 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 NOV PY 2005 VL 35 IS 11 BP 3268 EP 3276 DI 10.1002/eji.200425522 PG 9 WC Immunology SC Immunology GA 987MQ UT WOS:000233522400020 PM 16206231 ER PT J AU Shields, AF Briston, DA Chandupatla, S Douglas, KA Lawhorn-Crews, J Collins, JM Mangner, TJ Heilbrun, LK Muzik, O AF Shields, AF Briston, DA Chandupatla, S Douglas, KA Lawhorn-Crews, J Collins, JM Mangner, TJ Heilbrun, LK Muzik, O TI A simplified analysis of [F-18]3'-deoxy-3 '-fluorothymidine metabolism and retention SO EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING LA English DT Article DE FLT; PET; tumor; imaging; proliferation ID POSITRON-EMISSION-TOMOGRAPHY; PROLIFERATION IN-VIVO; IMAGING PROLIFERATION; HUMAN VOLUNTEERS; PHARMACOKINETICS; ZIDOVUDINE; TRACER; CANCER; HUMANS; TUMORS AB Purpose: [F-18]3'-deoxy-3'-fluorothymidine (FLT) is a thymidine analog developed for imaging tumor proliferation with positron emission tomography (PET). To quantitatively assess images, the blood activities of FLT and its glucuronidated metabolite were measured and its kinetics analyzed. This study sought to limit the number of blood samples needed to measure FLT retention. Methods: Total FLT activity was measured from 18 venous samples obtained over the first hour and dynamic imaging performed on 33 patients (average dose 350 MBq/mmol). The 5-, 10-, 30- and 60-min samples were analyzed to measure the fraction of activity in FLT and its glucuronide. HPLC analysis was compared against a two-step column (Sep-Pak) and metabolic rates measured using full and limited sampling. Probenecid (2 g, oral) was given to two patients to determine whether imaging of the liver improved. Results: At 60 min, 74% of the blood activity was unmetabolized (range 57-85%). HPLC and Sep-Pak gave comparable results (r=0.97; average difference 2.1%). For kinetic analysis, eight venous samples were sufficient to accurately measure total activity; for metabolite analysis, a single sample at 60 min yielded data with mean errors of 2.2%. The metabolic rate correlated with average SUV (r(2)=0.85; p=0.0002). An aorta input function gave kinetic results comparable to venous blood (r(2)=0.82). Probenecid did not improve imaging of the liver. Conclusion: Dynamic measurements of FLT retention can be used to calculate metabolic rates using a limited set of samples and correction for metabolites measured in a single sample obtained at 60 min. C1 Karmanos Canc Inst, Detroit, MI 48201 USA. Wayne State Univ, Dept Internal Med, Detroit, MI 48202 USA. US FDA, Rockville, MD 20857 USA. Wayne State Univ, Dept Radiol, Detroit, MI USA. Wayne State Univ, Dept Pediat, Detroit, MI 48202 USA. RP Shields, AF (reprint author), Karmanos Canc Inst, 4100 John R St,4 HWCRC, Detroit, MI 48201 USA. EM ShieldsA@Karmanos.org FU NCI NIH HHS [CA 82645, CA 22453, CA 39566] NR 23 TC 40 Z9 41 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1619-7070 J9 EUR J NUCL MED MOL I JI Eur. J. Nucl. Med. Mol. Imaging PD NOV PY 2005 VL 32 IS 11 BP 1269 EP 1275 DI 10.1007/s00259-005-1813-0 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 983QU UT WOS:000233248000005 PM 15991018 ER PT J AU Whittaker, P San, RHC Clarke, JJ Seifried, HE Dunkel, VC AF Whittaker, P San, RHC Clarke, JJ Seifried, HE Dunkel, VC TI Mutagenicity of chromium picolinate and its components in Salmonella typhimurium and L5178Y mouse lymphoma cells SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article DE mutagenicity; chromium; chromium picolinate; Salmonella typhimurium; mouse lymphoma ID HAMSTER OVARY CELLS; MAMMALIAN-CELLS; DAMAGE; TRIS(PICOLINATE); MECHANISMS; LOCUS; DNA AB Chromium picolinate is one of the most commonly used chromium dietary supplements available in the United States, and it has been marketed to consumers for use in weight loss, increasing muscle mass, and lowering serum cholesterol. Chromium picolinate is a synthetic compound that provides a bioavailable form of Cr(III) that is absorbed better than dietary chromium. However, there are several reports that it can have adverse effects. In order to study the mechanism of observed cellular toxicity and mutagenicity, chromium picolinate and its component compounds, chromium (III) chloride and picolinic acid, were evaluated in Salmonella typhimurium and L5178Y mouse lymphoma cells. Neither chromium picolinate nor chromium chloride induced a mutagenic response in S. typhimurium. However, in the L5178Y mouse lymphoma mutation assay, chromium picolinate induced mutagenic responses without and with the addition of S9. Published by Elsevier Ltd. C1 US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. BioReliance, Rockville, MD USA. NCI, NIH, Bethesda, MD 20892 USA. RP Whittaker, P (reprint author), US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. EM paul.whittaker@cfsan.fda.gov FU NCI NIH HHS [N01-CB-87016] NR 21 TC 33 Z9 36 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0278-6915 J9 FOOD CHEM TOXICOL JI Food Chem. Toxicol. PD NOV PY 2005 VL 43 IS 11 BP 1619 EP 1625 DI 10.1016/j.fct.2005.05.003 PG 7 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA 971ML UT WOS:000232388300004 PM 16040181 ER PT J AU Walls, I Buchanan, RL AF Walls, I Buchanan, RL TI Use of food safety obectives as a tool for reducing foodborne listeriosis SO FOOD CONTROL LA English DT Article; Proceedings Paper CT Workshop on Food Safety Objectives - Role in Microbiological Food Safety Management CY APR, 2003 CL Marseille, FRANCE SP ILSI ID RISK-ASSESSMENT; MONOCYTOGENES; OUTBREAK; GASTROENTERITIS; EXPOSURE AB Listeria monocytogenes is a foodborne pathogen that can cause listeriosis, a rare but severe disease whose invasive form has an estimated fatality rate of 20-30% of those who become ill. Typically, listeriosis occurs in individuals who have one or more underlying conditions that depress immune function, which makes them susceptible to the illness. Risk management strategies are required throughout the food chain to reduce the incidence of foodborne listeriosis. Public health objectives can be established to ensure continuous improvement in the health of the population with respect to a particular hazard and ideally should be based on an assessment of the risk to the population by the hazard. Food safety systems can be based on meeting a specific public health objective, to reduce the burden of foodborne disease. The International Commission on Microbiological Specifications for Foods has proposed the establishment of Food Safety Objectives (FSO) to provide a link between a public health objective and performance objectives and performance criteria that are established to control a foodborne hazard. An FSO can be used as a risk management tool for L. monocytogenes in ready-to-eat foods as the FSO establishes the stringency of the measures being used to control the hazard by specifying the frequency and/or cell number of L. monocytogenes in the food that should not be exceeded at the time of consumption. To establish an FSO based on a public health objective, the level of exposure that meets the public health objective must be determined. This requires an understanding of the risk characterization curve and the dose-response relationship for both the normal and the susceptible populations. This may be difficult, as there is considerable variation in the degree of susceptibility of individuals to L. monocytogenes, depending on their age, whether or not they are pregnant, and the severity of any underlying illness. It is likely that when establishing an FSO for L. monocytogenes both the normal and susceptible subpopulations will have to be considered. If the FSO is being met, there should be a concomitant reduction in illness as long as the main factors influencing the risk at the population level remain within the boundaries of the risk assessment. A reduction in illness can be measured through disease surveillance. Once a public health goal is achieved, new, technologically feasible goals should be considered to foster continuous improvement in reductions of listeriosis. Implementing effective food safety control measures, which ensure that the FSO is being met consistently, is key to reducing foodborne listeriosis. (c) ILSI 2005. Published by Elsevier Ltd. All rights reserved. C1 Risk Sci Inst, Int Life Sci Inst, Washington, DC 20005 USA. Food & Drug Adm, Ctr Food Safety & Appl Nutr, Off Sci, College Pk, MD 20740 USA. RP Walls, I (reprint author), Risk Sci Inst, Int Life Sci Inst, 1 Thomas Circle, Washington, DC 20005 USA. NR 23 TC 15 Z9 17 U1 0 U2 6 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0956-7135 J9 FOOD CONTROL JI Food Control PD NOV PY 2005 VL 16 IS 9 SI SI BP 795 EP 799 DI 10.1016/j.foodcont.2004.10.019 PG 5 WC Food Science & Technology SC Food Science & Technology GA 922WA UT WOS:000228869400002 ER PT J AU Bibb, LA King, ND Kunkle, CA Schmitt, MP AF Bibb, LA King, ND Kunkle, CA Schmitt, MP TI Analysis of a heme-dependent signal transduction system in Corynebactetium diphtheriae: Deletion of the chrA/S genes results in heme sensitivity and diminished heme-dependent activation of the hmuO promoter SO INFECTION AND IMMUNITY LA English DT Article ID IRON SOURCES; PATHOGENIC BACTERIA; TRANSPORT-SYSTEM; IDENTIFICATION; DTXR; ACQUISITION; HEMOGLOBIN; EXPRESSION; OXYGENASE; PROTEINS AB The Corynebacterium diphtheriae hmuO gene encodes a heme oxygenase that is involved in the utilization of heme as an iron source. Transcription of hmuO is activated by heme or hemoglobin and repressed by iron and DtxR. Previous studies with Escherichia coli showed that heme-dependent transcriptional activation of an hmuO promoter-lacZ fusion was dependent on the cloned C. diphtheriae chrA and chrS genes (chrAS), which encode the response regulator and sensor kinase, respectively, of a two-component signal transduction system. In this study, nonpolar deletions in the chrAS genes were constructed on the chromosome of C. diphtheriae. Mutations in chrAS resulted in marked reduction in heme-dependent transcription of hmuO, which indicates that the ChrA/S system is a key regulator at the hmuO promoter. However, low but significant levels of heme-specific transcriptional activity were observed at the hmuO promoter in the chrAS mutants, suggesting that an additional heme-dependent activator is involved in hmuO expression. The chrAS mutants were also sensitive to heme, which was observed only in stationary-phase cultures and correlated with reduced cell viability. The heme sensitivity of the mutants was not due to reduced expression of hmuO, and these results suggest that additional factors controlled by the ChrA/S system may be involved in protection against heme toxicity. Transcriptional analysis of the chrAS operon revealed that it was not autoregulated or affected by iron or heme levels. C1 US FDA, Ctr Biol Evaluat & Res, DBPAP, Lab Bacterial Toxins, Bethesda, MD 20892 USA. RP Schmitt, MP (reprint author), US FDA, Ctr Biol Evaluat & Res, DBPAP, Lab Bacterial Toxins, Bldg 29,Room 108,8800 Rockville Pike, Bethesda, MD 20892 USA. EM schmitt@cber.fda.gov NR 36 TC 27 Z9 29 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD NOV PY 2005 VL 73 IS 11 BP 7406 EP 7412 DI 10.1128/IaAI.73.11.7406-7412.2005 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 977WI UT WOS:000232833800040 PM 16239540 ER PT J AU Hughes, MA Green, CS Lowchyj, L Lee, GM Grippe, VK Smith, MF Huang, LY Harvill, ET Merkel, TJ AF Hughes, MA Green, CS Lowchyj, L Lee, GM Grippe, VK Smith, MF Huang, LY Harvill, ET Merkel, TJ TI MyD88-dependent signaling contributes to protection following Bacillus anthracis spore challenge of mice: Implications for toll-like receptor signaling SO INFECTION AND IMMUNITY LA English DT Article ID EMETIC TOXIN PRODUCTION; NECROSIS-FACTOR-ALPHA; CELL ACTIVATION; CYTOKINE RESPONSE; LETHAL FACTOR; MACROPHAGES; RECOGNITION; PROTEIN; SUSCEPTIBILITY; SPECIFICITY AB Bacillus anthracis is a spore-forming, gram-positive organism that is the causative agent of the disease anthrax. Recognition of Bacillus anthracis by the host innate immune system likely plays a key protective role following infection. In the present study, we examined the role of TLR2, TLR4, and MyD88 in the response to B. anthracis. Heat-killed Bacillus anthracis stimulated TLR2, but not TLR4, signaling in HEK293 cells and stimulated tumor necrosis factor alpha (TNF-alpha) production in C3H/HeN, C3H/HeJ, and C57BL/6J bone marrow-derived macrophages. The ability of heat-killed B. anthracis to induce a TNF-alpha response was preserved in TLR2(-/-) but not in MyD88(-/-) macrophages. In vivo studies revealed that TLR2(-/-) mice and TLR4-deficient mice were resistant to challenge with aerosolized Sterne strain spores but MyD88(-/-) mice were as susceptible as A/J mice. We conclude that, although recognition of B. anthracis occurs via TLR2, additional MyD88-dependent pathways contribute to the host innate immune response to anthrax infection. C1 Univ Virginia, Hlth Sci Syst, Dept Internal Med, Div Infect Dis, Charlottesville, VA 22908 USA. Univ Virginia, Hlth Sci Syst, Dept Internal Med, Div Gastroenterol, Charlottesville, VA 22908 USA. US FDA, Ctr Biol Evaluat & Res, Lab Resp & Special Pathogens, Div Bacterial Parasit & Allergen Prod, Bethesda, MD USA. US FDA, Ctr Biol Evaluat & Res, Lab Plasma Derivat, Div Hematol, Bethesda, MD USA. Penn State Univ, Dept Vet Sci, Immunol Res Labs, University Pk, PA 16802 USA. RP Hughes, MA (reprint author), Univ Virginia, Hlth Sci Syst, Dept Internal Med, Div Infect Dis, POB 800513, Charlottesville, VA 22908 USA. EM mah3x@virginia.edu FU NIAID NIH HHS [K08 AI050804, R01 AI034358, R21 AI056113, R21 AI072469, U54 AI057168] NR 39 TC 36 Z9 37 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD NOV PY 2005 VL 73 IS 11 BP 7535 EP 7540 DI 10.1128/IAI.73.11.7535-7540.2005 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 977WI UT WOS:000232833800056 PM 16239556 ER PT J AU Derrick, SC Yang, AL Morris, SL AF Derrick, SC Yang, AL Morris, SL TI Vaccination with a Sindbis virus-based DNA vaccine expressing antigen 85B induces protective immunity against Mycobacterium tuberculosis SO INFECTION AND IMMUNITY LA English DT Article ID PULMONARY TUBERCULOSIS; T-CELLS; IMMUNOGENICITY; INFECTION; MICE; BCG; IMMUNIZATION; IMMUNOLOGY; PREVENTION; STRATEGIES AB To improve DNA vaccination against Mycobacterium tuberculosis, we evaluated the effectiveness of a Sindbis virus-based DNA construct expressing the tuberculosis antigen 85B (Sin85B).The protective efficacy of Sin85B was initially assessed by aerogenically challenging immunized C57BL/6 mice with virulent Mycobacterium tuberculosis. At 1 and 7 months postinfection, the lung bacterial burdens were considerably reduced and the lung pathology was improved in vaccinated mice compared to naive controls. Furthermore, the mean survival period for Sin85B-immunized mice (305 +/- 9 days) after the tuberculous challenge was extended 102 days relative to the naive mice (203 +/- 13 days) and was essentially equivalent to the survival time of Mycobacterium bovis BCG-vaccinated mice (294 +/- 15 days). The essential role of gamma interferon (IFN-gamma) in Sin85B-mediated protection was established by showing that significantly increased levels of IFN-gamma mRNA were present postinfection in lung cells from vaccinated mice relative to control mice and by demonstrating that IFN-gamma depletion prior to challenge abolished the vaccine-induced protection. The substantial antituberculosis protective responses induced by Sin85B immunization of CD4(-/-) mice strongly suggested that CD8 cells partially mediate Sin85B-induced protective immunity. Interestingly, Sin85B vaccination did not protect RNase L-/- (a key enzyme in the innate antiviral response) mice while significant protection was detected in RNase L-1- mice immunized with either BCG or a conventional DNA plasmid expressing antigen 85B. These data show that immunization with Sin85B offers protection similar to BCG in a marine model of pulmonary tuberculosis and suggest that Sin85B-induced protection is dependent upon both innate and acquired immune mechanisms. C1 US FDA, CBER, Lab Mycobacterial Dis & Cellular Immunol, Bethesda, MD 20892 USA. RP Derrick, SC (reprint author), US FDA, CBER, Lab Mycobacterial Dis & Cellular Immunol, Bldg 29,Room 511,29 Lincoln Dr, Bethesda, MD 20892 USA. EM derrick@cber.fda.gov NR 34 TC 12 Z9 13 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD NOV PY 2005 VL 73 IS 11 BP 7727 EP 7735 DI 10.1128/IAI.73.11.7727-7735.2005 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 977WI UT WOS:000232833800077 PM 16239577 ER PT J AU Smith, MJ Garrett, RH AF Smith, MJ Garrett, RH TI A heretofore undisclosed crux of eosinophilia-myalgia syndrome: compromised histamine degradation SO INFLAMMATION RESEARCH LA English DT Review DE systems analysis; indoleamines; structure-activity relationships; inhibitors; host susceptibility ID L-TRYPTOPHAN INGESTION; SENSITIVE AMINE OXIDASE; HISTIDINE DECARBOXYLASE ACTIVITY; VASCULAR ENDOTHELIAL-CELLS; MANUFACTURED L-TRYPTOPHAN; PLASMA MONOAMINE-OXIDASE; PITUITARY-ADRENAL AXIS; CENTRAL NERVOUS-SYSTEM; 1966 BIRTH COHORT; RAT-LIVER AB In contrast to early epidemiological evidence offering links between eosinophilia-myalgia syndrome (EMS) and microimpurities of L-tryptophan-containing dietary supplements (LTCDS), this account shows why reliance on a finite impurity from one manufacturer is both unnecessary and insufficient to explain the etiology of EMS. Excessive histamine activity has induced blood eosinophilia and myalgia (Greek: mys, muscle + algos, pain). Termination of the multiple actions of histamine is dependent on particular amine oxidases and histamine-N-methyltransferase. Histamine metabolism is rapid when these degradative reactions are operative. The latent effects of incurred histamine can be potentiated and aggravating when these mechanisms are impaired. Overloads of tryptophan supplements cause - among other relevant side-effects - an increased formation of formate and indolyl metabolites, several of which inhibit the degradation of histamine. Moreover, (non-EMS) subjects with hypothalamic-pituitary- adrenal (HPA) axis dysregulation have also manifested greatly increased sensitivities to incurred tryptophan and histamine. A final common pathway for syndromes characterized by eosinophilia with myalgia is now evident. C1 US FDA, Div Nat Prod, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. Univ Virginia, Dept Biol, Charlottesville, VA 22904 USA. RP Smith, MJ (reprint author), US FDA, Div Nat Prod, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkway, College Pk, MD 20740 USA. EM mitchell.smith@cfsan.fda.gov; rhg@virginia.edu NR 354 TC 14 Z9 14 U1 1 U2 1 PU SPRINGER BASEL AG PI BASEL PA PICASSOPLATZ 4, BASEL, 4052, SWITZERLAND SN 1023-3830 EI 1420-908X J9 INFLAMM RES JI Inflamm. Res. PD NOV PY 2005 VL 54 IS 11 BP 435 EP 450 DI 10.1007/s00011-005-1380-7 PG 16 WC Cell Biology; Immunology SC Cell Biology; Immunology GA 987CK UT WOS:000233495800001 PM 16307217 ER PT J AU Chen, T Mittelstaedt, RA Beland, FA Heflich, RH Moore, MM Parsons, BL AF Chen, T Mittelstaedt, RA Beland, FA Heflich, RH Moore, MM Parsons, BL TI 4-aminobiphenyl induces liver DNA adducts in both neonatal and adult mice but induces liver mutations only in neonatal mice SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE genotoxic carcinogen; DNA damage; Big Blue mice; lacl; cll ID N-HYDROXY ARYLAMINES; METABOLIC-ACTIVATION; CARCINOGEN 4-AMINOBIPHENYL; HEPATOCELLULAR-CARCINOMA; AROMATIC-AMINES; TRANSGENIC MICE; MOUSE; CANCER; ASSAY; TUMORIGENESIS AB The mechanisms underlying the susceptibility of neonatal mice to genotoxic carcinogens were investigated by analyzing the DNA adducts and mutations induced in the livers of neonatal and adult Big Blue transgenic mice by 4-aminobiphenyl (4-ABP), a potent human and rodent carcinogen. Neonatal and adult mice were treated with a regimen of 4-ABP known to induce tumors in neonatal mice. Animals were sacrificed 1 day after the last treatment for DNA adduct analysis and 8 weeks after the last treatment for analysis of lacI and cII mutant frequency (MF). N-(Deoxyguanosin-8-yl)-4-ABP was the major DNA adduct identified in the livers of the 4-ABP-treated mice and levels of this adduct were significantly higher in treated animals than in the controls for both the neonates and adults. Adduct levels for adult females (44.0 +/- 4.8 adducts/10(6) nucleotides) were higher than in neonatal females (25.9 +/- 2.2 adducts/10(6) nucleotides), while adduct levels in adult males (13.5 +/- 2.0 addUCts/10(6) nucleotides) were lower than in neonatal males (33.8 +/- 4.1 adducts/10(6) nucleotides). 4-ABP treatment significantly increased the liver cII MFs in both sexes of neonatal mice but not in adult mice. Sequence analysis of cII mutant DNA revealed that 4-ABP induced a unique spectrum of mutations in neonatal mice, characterized by a high frequency of G:C -> T:A transversion, while the mutation spectrum in 4-ABP-treated adults was similar to that of control mice. Our results indicate that DNA adduct formation by 4-ABP depends as much on sex as it does on age, whereas the conversion of DNA adducts into mutations differed with animal age. These observations suggest that neonates are more sensitive than adults to genotoxic carcinogens because the relatively high levels of cell division in the developing animal facilitate the conversion of DNA damage into mutation. Supplementary material for this article can be found on the International Journal, of Cancer website at http://www.interscience. wiley.com/jpages/0020-7136/suppmat/index.html (c) 2005 Wiley-Liss, Inc. C1 US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Chen, T (reprint author), US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM tchen@nctr.fda.gov NR 68 TC 10 Z9 10 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD NOV 1 PY 2005 VL 117 IS 2 BP 182 EP 187 DI 10.1002/ijc.21173 PG 6 WC Oncology SC Oncology GA 968VL UT WOS:000232190900003 PM 15880493 ER PT J AU McMullen, SE Casanova, JA Gross, LK Schenck, FJ AF McMullen, SE Casanova, JA Gross, LK Schenck, FJ TI Ion chromatographic determination of nitrate and nitrite in vegetable and fruit baby foods SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article AB An ion chromatographic method was developed for the determination of nitrate and nitrite in vegetable and fruit baby foods. The introduction of nitrate or nitrite to food may be natural or artificial as a preservative. Because of the higher pH found in babies' stomachs, nitrate can act as a reservoir for the production of nitrite by nitrate-reducing bacteria that can be harbored in the intestinal tract. This problem does not exist in adults because of the lower pH of the adult stomach. Exposure to nitrite by infants can result in methemoglobinernia (blue baby syndrome). There are also indications that carcinogenic nitrosamines can be formed from nitrates at the higher pH. These gastric conditions disappear at approximately 6 months of age. In this method, nitrate and nitrite were separated on a hydroxide-selective anion exchange column using online electrolytically generated high-purity hydroxide eluant and detected using suppressed conductivity detection. Average recoveries of spiked nitrite residue ranged from 91 to 104% and spiked nitrate residue ranged from 87 to 104%. This method and the AOAC Official Method yield comparable results for samples containing incurred nitrate residue. In addition, this method eliminates the hazardous waste associated with the use of cadmium found in the AOAC Official Method. C1 US FDA, SW Reg Lab, Atlanta, GA 30309 USA. RP McMullen, SE (reprint author), US FDA, SW Reg Lab, 60 80th St NE, Atlanta, GA 30309 USA. EM smcmulle@ora.fda.gov NR 13 TC 20 Z9 22 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 NOV-DEC PY 2005 VL 88 IS 6 BP 1793 EP 1796 PG 4 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 990SK UT WOS:000233763300030 PM 16526464 ER PT J AU Cisneros, FJ Gough, BJ Patton, RE Ferguson, SA AF Cisneros, FJ Gough, BJ Patton, RE Ferguson, SA TI Serum levels of albumin, triglycerides, total protein and glucose in rats are altered after oral treatment with low doses of 13-cis-retinoic acid or all-trans-retinoic acid SO JOURNAL OF APPLIED TOXICOLOGY LA English DT Article DE retinoic acid; Accutane; triglycerides; albumin; leptin; adiponectin; glucose; cholesterol; creatine; alanine aminotransferase ID LEPTIN GENE-EXPRESSION; SPRAGUE-DAWLEY RATS; ISOTRETINOIN THERAPY; ACNE-VULGARIS; DIURNAL-VARIATIONS; PLASMA-LIPIDS; VITAMIN-A; LIVER; LIPOPROTEINS; PHARMACOKINETICS AB Currently used to treat severe acne, 13-cis-retinoic acid (13-cis-RA) is under investigation for its anticancer effects as is the isomer, all-trans-retinoic acid (all-trans-RA). Here, the effects of oral 13-cis-RA or all-trans-RA treatment on serum chemistry, leptin and adiponectin levels were evaluated. Adult Sprague-Dawley rats were gavaged once daily for 7 consecutive days with 13-cis-RA (7.5 or 15 mg kg(-1)), all-trans-RA (10 or 15 mg kg(-1)) (n = 24/sex/dose), or soy oil (n = 16/sex) and blood was sampled 30-480 min after the last gavage. The body weight was unaffected; however, the liver/ body weight ratios were increased by both doses of all-trans-RA. Sex differences were noted for levels of cholesterol, creatine, triglycerides, albumin, alanine aminotransferase and total protein. Both doses of all-trans-RA reduced albumin levels to approximate to 90% of the control and total protein levels to approximate to 93% of the control while substantially elevating triglyceride levels to approximate to 66%-99% above the control. Additionally, triglyceride levels of the 15 mg kg(-1) 13-cis RA group were approximate to 62% higher than the controls and total protein levels were approximate to 5% less. Glucose levels were affected by sex and RA treatment in that males treated with 15 mg kg(-1) of 13-cis-RA or 10 mg kg(-1) all-trans-RA had lower (13%-19%) levels than the same- sex controls; however, females were not similarly affected. Neither 13-cis-RA nor all-trans-RA treatment had significant effects on the levels of blood urea nitrogen, aspartate amino transferase, leptin or adiponectin. On a mg kg(-1) basis, alltrans-RA was more potent than 13-cis-RA. These results replicate previous findings of RA-induced increased triglyceride levels. Additionally, several new findings indicate there may be sex-specific effects of RA treatment. Finally, neither treatment appeared to alter the typical diurnal cycles of these endpoints. Copyright (c) 2005 John Wiley & Sons, Ltd. C1 FDA, NCTR, Div Neurotoxicol, Jefferson, AR USA. Charles River Labs, Jefferson, AR USA. RP Cisneros, FJ (reprint author), N Carolina Agr & Tech State Univ, Dept Biol, 1601 E Market St, Greensboro, NC 27411 USA. EM cisneros@ncat.edu NR 39 TC 12 Z9 13 U1 1 U2 2 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0260-437X J9 J APPL TOXICOL JI J. Appl. Toxicol. PD NOV-DEC PY 2005 VL 25 IS 6 BP 470 EP 478 DI 10.1002/jat.1082 PG 9 WC Toxicology SC Toxicology GA 984LS UT WOS:000233307000005 PM 16092084 ER PT J AU Yamada, A Sheikh, F Niimi, T DeMayo, FJ Keegan, AD Donnelly, RP Kimura, S AF Yamada, A Sheikh, F Niimi, T DeMayo, FJ Keegan, AD Donnelly, RP Kimura, S TI Induction of uteroglobin-related protein 2 (Ugrp2) gene expression by the Th2 cytokines IL-4 and IL-13 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID INTERLEUKIN-4-INDUCED TRANSCRIPTION FACTOR; HUMAN-MONOCYTES; INTERFERON-GAMMA; SIGNAL-TRANSDUCTION; IFN-GAMMA; EPITHELIAL-CELLS; RECEPTOR; STAT6; LUNG; MOUSE AB Uteroglobin-related proteins 1 and 2 (UGRP1 and -2) are thought to play important roles in inflammation and immunologic responses in the lung. In this study we demonstrate that IL-4 and IL-13 enhance Ugrp2 gene expression in the mouse transformed Clara cell line, mtCC, in a time- and dose-dependent manner. Addition of actinomycin D abrogated the IL-4- and IL-13-induced increase of Ugrp2 expression, demonstrating that this increase occurs at the transcriptional level. When mtCC cells were pretreated with IFN-gamma before the addition of IL-4 or IL-13, IL-4- and 13-induced Ugrp2 mRNA increase was markedly decreased. IL-4 and IL-13 induced phosphorylation of STAT6 in mtCC cells, which binds to the proximal STAT-binding element (SBE) in the Ugrp2 gene promoter, leading to transcriptional activation of this gene. Mutations of the proximal SBE abrogated the binding of activated STAT6 to this site and the IL-4-induced increase in Ugrp2 gene promoter activity. IFN-gamma-activated STAT1 binds to the same SBE in the Ugrp2 gene promoter to which STAT6 binds and decreases the binding of STAT6 to this site. Furthermore, an IL-4-induced increase in Ugrp2 expression was not observed in primary cultures of lung cells derived from STAT6-deficient mice. These results indicate that Ugrp2 expression is enhanced by IL-4 and IL-13 through STAT6 binding to the proximal SBE located in the Ugrp2 gene promoter. C1 Natl Inst Hlth, Natl Canc Inst, Lab Metab, Bethesda, MD 20892 USA. US FDA, Ctr Drug Evaluat & Res, Div Therapeut Prot, Rockville, MD 20857 USA. Baylor Coll Med, Dept Mol & Cell Biol, Houston, TX 77030 USA. Univ Maryland, Ctr Vasc & Inflammatory Dis, Baltimore, MD 21201 USA. RP Kimura, S (reprint author), Natl Inst Hlth, Natl Canc Inst, Lab Metab, Bldg 37,Room 3112B, Bethesda, MD 20892 USA. EM shioko@helix.nih.gov FU Intramural NIH HHS [Z01 BC010449-06, Z99 CA999999] NR 56 TC 14 Z9 14 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 1 PY 2005 VL 175 IS 9 BP 5708 EP 5715 PG 8 WC Immunology SC Immunology GA 977EW UT WOS:000232786300023 PM 16237061 ER PT J AU Tenbrock, K Kyttaris, VC Ahlmann, M Ehrchen, JA Tolnay, M Melkonyan, H Mawrin, C Roth, J Sorg, C Juang, YT Tsokos, GC AF Tenbrock, K Kyttaris, VC Ahlmann, M Ehrchen, JA Tolnay, M Melkonyan, H Mawrin, C Roth, J Sorg, C Juang, YT Tsokos, GC TI The cyclic AMP response element modulator regulates transcription of the TCR zeta-chain SO JOURNAL OF IMMUNOLOGY LA English DT Article ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; CELL SIGNALING ABNORMALITIES; T-CELLS; DECREASED EXPRESSION; IL-2 PRODUCTION; PROTEIN; PROMOTER; BINDING; ELF-1; PHOSPHORYLATION AB Systemic lupus erythematusus T cells display decreased amounts of TCR zeta mRNA that results in part from limited binding of the transcriptional enhancer Elf-1 to the TCR zeta promoter. We have identified a new cis-binding site for the cAMP response element (CRE) modulator (CREM) on the TCR zeta promoter, centered on the -390 nucleotide. Transfection of T cells with an antisense CREM alpha plasmid reduced the binding of CREM to the TCR zeta promoter, as shown by chromatin and reporter chromatin immunoprecipitation assays, and enhanced the production of TCR zeta mRNA and protein. Mutagenesis of the -390 CRE site prevented the binding of CREM to the TCR zeta promoter. The mechanism of CREM-mediated repression appears to be chromatin dependent, because antisense CREM promotes the acetylation of histones on the TCR zeta promoter. Finally, we established an enhanced binding of CREM to the TCR zeta-chain promoter in systemic lupus erythematosus cells compared with control T cells. Our studies demonstrate that CREM a binds to the TCR zeta promoter and repress its activity. C1 Univ Hosp Munster, Dept Pediat, Div Rheumatol, Inst Expt Dermatol,Interdisciplinary Ctr Clin Res, D-48149 Munster, Germany. Walter Reed Army Inst Res, Dept Cellular Injury, Silver Spring, MD 20910 USA. Childrens Hosp, Rheumatol Sect, Washington, DC 20010 USA. US FDA, Div Monoclonal Antibodies, Rockville, MD 20857 USA. RP Tenbrock, K (reprint author), Univ Hosp Munster, Dept Pediat, Div Rheumatol, Inst Expt Dermatol,Interdisciplinary Ctr Clin Res, Res Grp 5,Roentgenstr 21, D-48149 Munster, Germany. EM ktenbroc@uni-muenster.de NR 16 TC 29 Z9 32 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 1 PY 2005 VL 175 IS 9 BP 5975 EP 5980 PG 6 WC Immunology SC Immunology GA 977EW UT WOS:000232786300053 PM 16237091 ER PT J AU Nimmagadda, S Mangner, TJ Sun, HH Klecker, RW Muzik, O Lawhorn-Crews, JM Douglas, KA Collins, JM Shields, AF AF Nimmagadda, S Mangner, TJ Sun, HH Klecker, RW Muzik, O Lawhorn-Crews, JM Douglas, KA Collins, JM Shields, AF TI Biodistribution and radiation dosimetry estimates of 1-(2 '-deoxy-2 '-F-18-fluoro-1-beta-D-arabinofuranosyl)-5-bromouracil: PET imaging studies in dogs SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE F-18; FBAU; proliferation marker; DNA synthesis; metabolism ID POSITRON-EMISSION-TOMOGRAPHY; IN-VIVO; THYMIDINE KINASE; DNA-SYNTHESIS; FBAU 3',5'-DIBENZOATE; CELLULAR PROLIFERATION; GENE-EXPRESSION; VALIDATION; CANCER; ANALOG AB This study reports on the biodistribution and radiation estimates of 1-(2'-deoxy-2'-F-18-fluoro-1-beta-D-arabinofuranosyl)-5-bromo-uracil (F-18-FBAU), a potential tracer for imaging DNA synthesis. Methods: Three normal dogs were intravenously administered F-18-FBAU and a dynamic PET scan was performed for 60 min over the upper abdomen followed by a whole-body scan for a total of 150 min. Blood samples were collected at stipulated time intervals to evaluate tracer clearance and metabolism. Tissue samples of various organs were analyzed for tracer uptake and DNA incorporation. Dynamic accumulation of the tracer in different organs was derived from reconstructed PET images. The radiation dosimetry of F-18-FBAU was evaluated using the MIRD method. Results: At 60 min after injection, blood analysis found > 90% of the activity in unmetabolized form. At 2 h after injection, F-18-FBAU uptake was highest in proliferating tissues (mean SUVs: marrow, 2.6; small intestine, 4.0), whereas nonproliferative tissues showed little uptake (mean SUVs: muscle, 0.75; lung, 0.70; heart, 0.85; liver, 1.28). Dynamic image analysis over 60 min showed progressive uptake of the tracer in marrow. Extraction studies demonstrated that most of the activity in proliferative tissues was in the acid-insoluble fraction (marrow, 83%; small intestine, 73%), consistent with incorporation into DNA. In nonproliferative tissue, most of the activity was not found in the acid-insoluble fraction (> 84% for heart, muscle, and liver). Conclusion: These results demonstrate that F-18-FBAU was resistant to metabolism, readily incorporated into DNA in proliferating tissues, and showed good contrast between organs of variable DNA synthesis. These findings indicate that F-18-FBAU may find use in measuring DNA synthesis with PET. C1 Wayne State Univ, Karmanos Canc Inst, Detroit, MI 48201 USA. Wayne State Univ, Dept Med, Detroit, MI 48201 USA. Wayne State Univ, Dept Radiol, Detroit, MI 48201 USA. US FDA, Lab Clin Pharmacol, Rockville, MD 20857 USA. Wayne State Univ, Dept Pediat, Detroit, MI 48201 USA. RP Shields, AF (reprint author), Wayne State Univ, Karmanos Canc Inst, 4100 John R St,4HWCRC, Detroit, MI 48201 USA. EM shieldsa@karmanos.org RI Nimmagadda, Sridhar/D-6135-2011 OI Nimmagadda, Sridhar/0000-0002-6413-7191 FU NCI NIH HHS [CA33713, CA83131] NR 31 TC 15 Z9 16 U1 0 U2 2 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD NOV PY 2005 VL 46 IS 11 BP 1916 EP 1922 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 981NR UT WOS:000233095800025 PM 16269607 ER PT J AU Freedman, SB Reed, J Burwen, DR Wise, RP Weiss, A Ball, R AF Freedman, SB Reed, J Burwen, DR Wise, RP Weiss, A Ball, R TI Transient bulging fontanelle after vaccination: Case report and review of the vaccine adverse event reporting system SO JOURNAL OF PEDIATRICS LA English DT Article ID VITAMIN-A SUPPLEMENTATION; CLINICAL-FEATURES; PERTUSSIS-VACCINE; YOUNG INFANTS; IMMUNIZATION; TETANUS; DIPHTHERIA; SAFETY; CHILDREN; TRIAL AB Objective To describe the features of transient bulging fontanelle (TBF) after vaccination. Study design We searched the Vaccine Adverse Event Reporting System database for reports describing bulging fontanelle. We defined a definite TBF case as a patient with a bulging fontanelle, normal neuroimaging and cerebrospinal fluid analysis, and absence of a depressed level of consciousness, focal neurologic findings, or identified cause. Follow-up had to reveal normal development. Probable cases lacked either lumbar puncture or neuroimaging or both but met all other criteria. Results We identified 18 patients with definite or probable TBF. The median age at presentation was 4.5 months, interval from vaccination to symptom onset was 18 hours, and time to resolution was 3 days. Fifteen children were febrile. Conclusions We cannot conclude that vaccines cause TBF. Further controlled studies are necessary. Even if further research verifies TBF as a rare side effect, immunization benefits would still vastly outweigh this hypothetical risk. However, confirmation of a vaccine association could modify the management of infants who develop TBF after immunizations. C1 US FDA, CBER, Off Biostat & Epidemiol, Rockville, MD 20852 USA. Northwestern Univ, Div Neonatol, Feinberg Sch Med, Chicago, IL 60611 USA. RP Wise, RP (reprint author), US FDA, CBER, Off Biostat & Epidemiol, HFM 225,1401 Rockville Pike, Rockville, MD 20852 USA. EM R.P.Wise@cber.fda.gov NR 26 TC 9 Z9 9 U1 1 U2 6 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD NOV PY 2005 VL 147 IS 5 BP 640 EP 644 DI 10.1016/j.jpeds.2005.06.009 PG 5 WC Pediatrics SC Pediatrics GA 987EA UT WOS:000233500000019 PM 16291356 ER PT J AU Shin, EC Protzer, U Untergasser, A Feinstone, SM Rice, CM Hasselschwert, D Rehermann, B AF Shin, EC Protzer, U Untergasser, A Feinstone, SM Rice, CM Hasselschwert, D Rehermann, B TI Liver-directed gamma interferon gene delivery in chronic hepatitis C SO JOURNAL OF VIROLOGY LA English DT Article ID VIRUS-INFECTION; IMMUNE-RESPONSES; VIRAL CLEARANCE; PLUS RIBAVIRIN; T-CELLS; EXPRESSION; REPLICATION; PERSISTENCE; LYMPHOCYTES; CHIMPANZEES AB Gamma interferon (IFN-gamma) has been shown to inhibit replication of subgenomic and genomic hepatitis C virus (HCV) RNAs in vitro and to noncytolytically suppress hepatitis B virus (HBV) replication in vivo. IFN-gamma is also known for its immunomodulatory effects and as a marker of a successful cellular immune response to HCV. Therapeutic expression of IFN-gamma in the liver may therefore facilitate resolution of chronic hepatitis C, an infection that is rarely resolved spontaneously. To analyze immunomodullatory and antiviral effects of liver-specific IFN-gamma expression in vivo, we intravenously injected two persistently HCV-infected chimpanzees twice with a recombinant, replication-deficient HBV vector and subsequently with a recombinant adenoviral vector. These vectors expressed human IFN-gamma under control of HBV- and liver-specific promoters, respectively. Gene transfer resulted in a transient increase of intrahepatic IFN-gamma mRNA, without increase in serum alanine aminotransferase levels. Ex vivo analysis of peripheral blood lymphocytes demonstrated enhanced CD16 expression on T cells and upregulation of the liver-homing marker CXCR3. Moreover, an increased frequency of HCV-specific T cells was detected ex vivo in the peripheral blood and in vitro in liver biopsy-derived, antigen-nonspecifically expanded T-cell lines. None of these immunologic effects were observed in the third chimpanzee injected with an HBV control vector. Despite these immunologic effects of the experimental vector, however, IFN-gamma gene transfer did not result in a significant and long-lasting decrease of HCV titers. In conclusion, liver-directed IFN-gamma gene delivery resulted in HCV-specific and nonspecific activation of cellular immune responses but did not result in effective control of HCV replication. C1 NIDDK, Liver Dis Branch, NIH, DHHS, Bethesda, MD 20892 USA. Univ Cologne, Mol Infektiol Zentrum Mol Med, IMMIH, Cologne, Germany. US FDA, Ctr Biol Evaluat & Res, Lab Hepatatis Viruses, Bethesda, MD 20014 USA. Rockefeller Univ, Ctr Study Hepatitis C, New York, NY 10021 USA. Univ Louisville, New Iberia Res Ctr, New Iberia, LA USA. RP Rehermann, B (reprint author), NIDDK, Liver Dis Branch, NIH, DHHS, 10 Ctr Dr,Room 9B16, Bethesda, MD 20892 USA. EM Rehermann@nih.gov RI Shin, Eui-Cheol/C-1690-2011 FU NCI NIH HHS [CA85883-01, R01 CA085883] NR 42 TC 17 Z9 20 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 2005 VL 79 IS 21 BP 13412 EP 13420 DI 10.1128/JVI.79.21.13412-13420.2005 PG 9 WC Virology SC Virology GA 975MJ UT WOS:000232666300020 PM 16227262 ER PT J AU Yedavalli, VSRK Shih, HM Chiang, YP Lu, CY Chang, LY Chen, MY Chuang, CY Dayton, AI Jeang, KT Huang, LM AF Yedavalli, VSRK Shih, HM Chiang, YP Lu, CY Chang, LY Chen, MY Chuang, CY Dayton, AI Jeang, KT Huang, LM TI Human immunodeficiency virus type 1 Vpr interacts with antiapoptotic mitochondrial protein HAX-1 SO JOURNAL OF VIROLOGY LA English DT Article ID ADENINE-NUCLEOTIDE TRANSLOCATOR; APOPTOSIS-INDUCING FACTOR; PROGRAMMED CELL-DEATH; HIV-1 VPR; T-CELLS; MEMBRANE PERMEABILIZATION; NUCLEAR-LOCALIZATION; VIRAL EXPRESSION; EBNA-LP; CYCLE AB Human immunodeficiency virus type 1 viral protein R (Vpr) is required for viral pathogenesis and has been implicated in T-cell apoptosis through its activation of caspase 3 and caspase 9 and perturbation of mitochondrial membrane potential. To understand better Vpr-mitochondria interaction, we report here the identification of antiapoptotic mitochondrial protein HAX-1 as a novel Vpr target. We show that Vpr and HAX-1 physically associate with each other. Overexpression of Vpr in cells dislocates HAX-1 from its normal residence in mitochondria and creates mitochondrion instability and cell death. Conversely, overexpression of HAX-1 suppressed the proapoptotic activity of Vpr. C1 NIAID, Mol Virol Sect, Mol Microbiol Lab, Bethesda, MD 20892 USA. Natl Taiwan Univ Hosp, Acad Sinica, Inst Biomed Sci, Taipei, Taiwan. Natl Taiwan Univ Hosp, Dept Pediat, Taipei, Taiwan. Natl Taiwan Univ Hosp, Dept Internal Med, Taipei, Taiwan. Food & Drug Adm, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Jeang, KT (reprint author), NIH, Bldg 4,Room 306,9000 Rockville Pike, Bethesda, MD 20892 USA. EM kj7e@nih.gov; lmhuang@ha.mc.ntu RI Jeang, Kuan-Teh/A-2424-2008; OI Chang, Luan-Yin/0000-0003-2632-1956; LU, CHUN-YI/0000-0002-5240-2808; Huang, Li-Min/0000-0002-9291-260X NR 61 TC 57 Z9 61 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 2005 VL 79 IS 21 BP 13735 EP 13746 DI 10.1128/JVI.79.21.13735-13746.2005 PG 12 WC Virology SC Virology GA 975MJ UT WOS:000232666300051 PM 16227293 ER PT J AU Machado, MO Hirata, RDC Sellitti, DF Iotti, R Iotti, A Cusumano, AM Riordan, GP Coschigano, KT Kopchick, JJ Zuhl, I Nguyen, N Hirata, MH Doi, SQ AF Machado, MO Hirata, RDC Sellitti, DF Iotti, R Iotti, A Cusumano, AM Riordan, GP Coschigano, KT Kopchick, JJ Zuhl, I Nguyen, N Hirata, MH Doi, SQ TI Growth hormone promotes glomerular lipid accumulation in bGH mice SO KIDNEY INTERNATIONAL LA English DT Article DE glomerulosclerosis; cholesterol; triglycerides; HMG-CoA reductase; low-density lipoprotein receptor; scavenger receptor; real time RT-PCR ID LOW-DENSITY-LIPOPROTEIN; DIET-INDUCED HYPERCHOLESTEROLEMIA; HUMAN MESANGIAL CELLS; CHRONIC-RENAL-FAILURE; TRANSGENIC MICE; FACTOR-I; FOCAL GLOMERULOSCLEROSIS; CHOLESTEROL-METABOLISM; RECEPTOR EXPRESSION; SCAVENGER RECEPTOR AB Background. Bovine growth hormone (bGH) transgenic mice develop progressive glomerulosclerosis and exhibit abnormalities in hepatic lipid metabolism. We have previously shown that growth hormone up-regulates the low-density lipoprotein (LDL) receptor and 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) in mouse mesangial cells. However, a role of lipid abnormalities in bGH kidney disease has not yet been demonstrated. Methods. Groups of bGH mice (5 and 11 months old) presenting with, respectively, moderate and severe degrees of glomerulosclerosis were compared to age-matched controls. Neutral lipid content in kidney cortex was determined by oil red-O staining, serum cholesterol, and triglycerides by enzymatic assays, relative mRNA expression of LDL receptors, HMGR, and scavenger receptor by real-time reverse transcription-polymerase chain reaction (RT-PCR), and HMGR protein expression by immunoblotting. Two younger (5 and 12 weeks old) groups of mice were used to study scavenger receptor expression at earlier time points. Results. Serum cholesterol was significantly increased in bGH mice at 5 months, but triglycerides were lower than control levels at both 5 and 11 months. Renal cortex HMGR expression was elevated at the mRNA but not at the protein level in the 11-month-old bGH group compared to controls. However, glomerular neutral lipid staining and scavenger receptor mRNA expression were markedly increased in all bGH mice, including those at 5 weeks of age compared to respective controls. Conclusion. The bGH mouse exhibits an increased mesangial lipid content and elevated scavenger receptor mRNA expression as early as at 5 weeks of age, suggesting that an increased kidney uptake of oxidized LDL could play a role in the development of glomerulosclerosis in this mouse model. C1 Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. Univ Sao Paulo, Sch Pharmaceut Sci, Sao Paulo, Brazil. CEMIC, Dept Pathol, Buenos Aires, DF, Argentina. CEMIC, Nephrol Sect, Buenos Aires, DF, Argentina. NIDCD, Sect Struct Cell Biol, NIH, Bethesda, MD USA. Ohio Univ, Edison Biotechnol Inst, Athens, OH 45701 USA. Ohio Univ, Dept Biomed Sci, Coll Osteopath Med, Athens, OH 45701 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. RP Doi, SQ (reprint author), Uniformed Serv Univ Hlth Sci, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM sdoi@usush.mil RI Hirata, Rosario/A-7284-2011; Hirata, Mario/C-9718-2013 NR 51 TC 11 Z9 13 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD NOV PY 2005 VL 68 IS 5 BP 2019 EP 2028 DI 10.1111/j.1523-1755.2005.00656.x PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 971MQ UT WOS:000232388800038 PM 16221202 ER PT J AU O'Hanlon, TP Carrick, DM Arnett, FC Reveille, JD Carrington, M Gao, XJ Oddis, CV Morel, PA Malley, JD Malley, K Dreyfuss, J Shamim, EA Rider, LG Chanock, SJ Foster, CB Bunch, T Plotz, PH Love, LA Miller, FW AF O'Hanlon, TP Carrick, DM Arnett, FC Reveille, JD Carrington, M Gao, XJ Oddis, CV Morel, PA Malley, JD Malley, K Dreyfuss, J Shamim, EA Rider, LG Chanock, SJ Foster, CB Bunch, T Plotz, PH Love, LA Miller, FW TI Immunogenetic risk and protective factors for the idiopathic inflammatory myopathies - Distinct HLA-A, -B, -Cw,-DRB1 and -DQA1 allelic profiles and motifs define clinicopothologic groups in Caucasians SO MEDICINE LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; INCLUSION-BODY MYOSITIS; SYSTEMIC-LUPUS-ERYTHEMATOSUS; GENE-EXPRESSION DATA; RHEUMATOID-ARTHRITIS; AUTOIMMUNE-DISEASE; ETHNIC-GROUPS; HAPLOTYPE; CLASSIFICATION; ASSOCIATION AB The idiopathic inflammatory myopathies (IIM) are systemic connective tissue diseases in which autoimmune pathology is suspected to promote chronic muscle inflammation and weakness. We have performed low to high resolution genotyping to characterize the allelic profiles of HLA-A, -B, -Cw, -DRB1, and -DQA1 loci in a large population of North American Caucasian patients with IIM representing the major clinicopathologic groups (n = 571). We confirmed that alleles of the 8.1 ancestral haplotype were important risk markers for the development of IIM, and a random forests classification analysis suggested that within this haplotype, HLA-B*0801, DRB1*0301 and/or closely linked genes are the principal HLA risk factors. In addition, we identified several novel HLA factors associated distinctly with I or more clinicopathologic groups of IIM. The DQA1*0201 allele and associated peptide-binding Motif ((KLPLFHRL54)-K-47) were exclusive protective factors for the CD8+ T cell-mediated IIM forms of polymyositis (PM) and inclusion body myositis (IBM) (pc < 0.005). In contrast, HLA-A*68 alleles were significant risk factors for dermatomyositis (DM) (pc = 0.0021), a distinct clinical group thought to involve a humorally mediated immunopathology. While the DQA1*0301 allele was detected as a possible risk factor for IIM, PM, and DM patients (p < 0.05), DQA1*03 alleles were protective factors for IBM (pc = 0.0002). Myositis associated with malignancies was the most distinctive group of IIM wherein HLA Class I alleles were the only identifiable susceptibility factors and a shared HLA-Cw peptide-binding motif ((90)AGSHTLQWM(98)) conferred significant risk (pc = 0.019). Together, these data suggest that HLA susceptibility markers distinguish different myositis phenotypes with divergent pathogenetic mechanisms. These variations in associated HLA polymorphisms may reflect responses to unique environmental triggers resulting in the tissue pathospecificity and distinct clinicopathologic syndromes of the IIM. C1 NIEHS, Environm Autoimmun Grp, NIH, DHHS, Bethesda, MD 20892 USA. NIH, Ctr Informat Technol, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NIH, NCI, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NIAMSD, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Univ Texas, Houston Hlth Sci Ctr, Houston, TX USA. SAIC Frederick Natl Canc Inst, Basic Res Program, Frederick, MD USA. Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. Malley Res Programming Inc, Rockville, MD USA. Mayo Clin, Rochester, MN USA. US FDA, Rockville, MD 20857 USA. RP O'Hanlon, TP (reprint author), NIEHS, Environm Autoimmun Grp, NIH, DHHS, 9 Mem Dr,Room 1W101,MSC 0958, Bethesda, MD 20892 USA. EM ohanlont@niehs.nih.gov FU NCI NIH HHS [N01-CO-12400] NR 43 TC 49 Z9 51 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0025-7974 J9 MEDICINE JI Medicine (Baltimore) PD NOV PY 2005 VL 84 IS 6 BP 338 EP 349 DI 10.1097/01.md.0000189818.63141.8c PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 985JJ UT WOS:000233373200002 PM 16267409 ER PT J AU Jones, AM Boucher, PE Williams, CL Stibitz, S Cotter, PA AF Jones, AM Boucher, PE Williams, CL Stibitz, S Cotter, PA TI Role of BvgA phosphorylation and DNA binding affinity in control of Bvg-mediated phenotypic phase transition in Bordetella pertussis SO MOLECULAR MICROBIOLOGY LA English DT Article ID RESPONSE REGULATOR; ESCHERICHIA-COLI; VIRULENCE REGULON; RNA-POLYMERASE; FHA PROMOTER; GENE; NARL; BRONCHISEPTICA; INTERMEDIATE; PHOSPHORELAY AB To investigate the mechanism by which the Bordetella BvgAS phosphorelay controls expression of at least three distinct phenotypic phases, we isolated and characterized two B. pertussis mutants that were able to express Bvg(-) and Bvg(i) phase phenotypes but not Bvg(+) phase phenotypes. In both cases, the mutant phenotype was due to a single nucleotide change in bvgA resulting in a single amino acid substitution in BvgA. In vitro phosphorylation assays showed that BvgA containing the T194M substitution was significantly impaired in its ability to use either BvgS or acetyl phosphate as a substrate for phosphorylation. Binding studies indicated that this mutant protein was able to bind an oligonucleotide containing a high-affinity BvgA binding site in a manner similar to wild-type BvgA, but was defective for binding the fhaB promoter in the absence of RNA polymerase (RNAP). By contrast, BvgA containing the R152H substitution had wild-type phosphorylation properties but was severely defective in its ability to bind either the high-affinity BvgA binding site-containing oligonucleotide or the fhaB promoter by itself. Both mutant BvgA proteins were able to bind the fhaB promoter in the presence of RNAP however, demonstrating the profound effect that RNAP has on stabilizing the ternary complexes between promoter DNA, BvgA and RNAP. Our results are consistent with the hypothesis that BvgAS controls expression of multiple phenotypic phases by adjusting the intracellular concentration of BvgA similar to P and they demonstrate the additive nature of BvgA binding site affinity and protein-protein interactions at different Bvg-regulated promoters. C1 Univ Calif Santa Barbara, Dept Mol Cellular & Dev Biol, Santa Barbara, CA 93109 USA. US FDA, Div Bacterial Parasit & Allergen Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Cotter, PA (reprint author), Univ Calif Santa Barbara, Dept Mol Cellular & Dev Biol, Santa Barbara, CA 93109 USA. EM cotter@lifesci.ucsb.edu FU NIAID NIH HHS [AI43986] NR 34 TC 24 Z9 24 U1 1 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD NOV PY 2005 VL 58 IS 3 BP 700 EP 713 DI 10.1111/j.1365-2958.2005.04875.x PG 14 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 973QG UT WOS:000232537100008 PM 16238621 ER PT J AU Rapoport, AP Stadtmauer, EA Aqui, N Badros, A Cotte, J Chrisley, L Veloso, E Zheng, ZH Westphal, S Mair, R Chi, N Ratterree, B Pochran, MF Natt, S Hinkle, J Sickles, C Sohal, A Ruehle, K Lynch, C Zhang, L Porter, DL Luger, S Guo, CF Fang, HB Blackwelder, W Hankey, K Mann, D Edelman, R Frasch, C Levine, BL Cross, A June, CH AF Rapoport, AP Stadtmauer, EA Aqui, N Badros, A Cotte, J Chrisley, L Veloso, E Zheng, ZH Westphal, S Mair, R Chi, N Ratterree, B Pochran, MF Natt, S Hinkle, J Sickles, C Sohal, A Ruehle, K Lynch, C Zhang, L Porter, DL Luger, S Guo, CF Fang, HB Blackwelder, W Hankey, K Mann, D Edelman, R Frasch, C Levine, BL Cross, A June, CH TI Restoration of immunity in lymphopenic individuals with cancer by vaccination and adoptive T-cell transfer SO NATURE MEDICINE LA English DT Article ID PNEUMOCOCCAL CONJUGATE VACCINE; BONE-MARROW TRANSPLANTATION; PROTECTIVE ANTIBODY-RESPONSES; NON-HODGKIN-LYMPHOMA; ACUTE OTITIS-MEDIA; STEM-CELL; STREPTOCOCCUS-PNEUMONIAE; CLONAL EXPANSION; MULTIPLE-MYELOMA; IMMUNOGENICITY AB Immunodeficiency is a barrier to successful vaccination in individuals with cancer and chronic infection. We performed a randomized phase 1/2 study in lymphopenic individuals after high-dose chemotherapy and autologous hematopoietic stem cell transplantation for myeloma. Combination immunotherapy consisting of a single early post-transplant infusion of in vivo vaccine-primed and ex vivo costimulated autologous T cells followed by post-transplant booster immunizations improved the severe immunodeficiency associated with high-dose chemotherapy and led to the induction of clinically relevant immunity in adults within a month after transplantation. Immune assays showed accelerated restoration of CD4 T-cell numbers and function. Early T-cell infusions also resulted in significantly improved T-cell proliferation in response to antigens that were not contained in the vaccine, as assessed by responses to staphylococcal enterotoxin B and cytomegalovirus antigens ( P < 0.05). In the setting of lymphopenia, combined vaccine therapy and adoptive T-cell transfer fosters the development of enhanced memory T-cell responses. C1 Univ Maryland, Greenebaum Canc Ctr, Baltimore, MD 21201 USA. Univ Maryland, Ctr Vaccine Dev, Baltimore, MD 21201 USA. Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. US FDA, Ctr Biol Evolut & Res, Rockville, MD 20852 USA. RP Rapoport, AP (reprint author), Univ Maryland, Greenebaum Canc Ctr, 22 S Greene St, Baltimore, MD 21201 USA. EM arapoport@umn.edu; cjune@mail.med.upenn.edu RI Levine, Bruce/D-1688-2009; OI Sabins, Nina/0000-0001-7983-8962 FU NCI NIH HHS [R21 CA101356-2]; NIAID NIH HHS [N01-AI-85342] NR 47 TC 202 Z9 208 U1 0 U2 12 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVENUE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD NOV PY 2005 VL 11 IS 11 BP 1230 EP 1237 DI 10.1038/nm1310 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 981VF UT WOS:000233115400036 PM 16227990 ER PT J AU Tamura, Y Hamajima, K Matsui, K Yanoma, S Narita, M Tajima, N Xin, KQ Klinman, D Okuda, K AF Tamura, Y Hamajima, K Matsui, K Yanoma, S Narita, M Tajima, N Xin, KQ Klinman, D Okuda, K TI The F(ab ')(2) fragment of an A beta-specific monoclonal antibody reduces A beta deposits in the brain SO NEUROBIOLOGY OF DISEASE LA English DT Article DE Alzheimer's disease; Tg2576 mouse; beta-amyloid peptide (A beta); F(ab ')(2) fragment; IgG1 isotype; anti-A beta monoclonal antibody; passive immunization; amyloid plaque; microglia ID HUMAN-IMMUNODEFICIENCY-VIRUS; ALZHEIMERS-DISEASE; MOUSE MODEL; TRANSGENIC MICE; MEMORY DEFICITS; IMMUNIZATION; CLEARANCE; PEPTIDE; BARRIER; PROTEIN AB This work examines whether administering the F(ab')(2) fragment of an IgG1 monoclonal antibody (mAb) targeting the N-terminal 1-13 amino acids of the beta-amyloid peptide (A beta mAb) reduces amyloid deposition in Alzheimer's disease (AD). The F(ab')(2) fragment was injected intraperitoneally or intracranially into Tg2576 mice, a murine model of human AD. Both routes of administration significantly reduced A plaque formation in the brain, as determined immunohistochemically and by monitoring levels of A beta(1-40) and A beta(1 -42) peptide. Use of the F(ab')(2) fragment significantly reduced phagocytic infiltration in the CNS when compared to intact mAb. Since IgG1 Abs do not fix complement, these findings suggest that effective in vivo clearance of amyloid deposits can be achieved without stimulation of FcR-reactive phagocytes or activation of the complement cascade. (c) 2005 Elsevier Inc. All rights reserved. C1 Yokohama City Univ, Dept Bacteriol, Grad Sch Med, Yokohama, Kanagawa 2360004, Japan. Nichiiko Pharmaceut Co Ltd, Toyama, Japan. Tokyo Dent Coll, Dept Oral Surg, Chiba, Japan. US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20587 USA. RP Okuda, K (reprint author), Yokohama City Univ, Dept Mol Biodef Res, Grad Sch Med, 3-9 Fukuura, Yokohama, Kanagawa 2360004, Japan. EM kokuda@med.yokohama-cu.ac.jp NR 32 TC 29 Z9 31 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 0969-9961 J9 NEUROBIOL DIS JI Neurobiol. Dis. PD NOV PY 2005 VL 20 IS 2 BP 541 EP 549 DI 10.1016/j.nbd.2005.04.007 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 981OA UT WOS:000233096700037 PM 15908227 ER PT J AU Brorson, K Sofer, G Aranha, H AF Brorson, K Sofer, G Aranha, H TI Nomenclature standardization for 'large pore size' virus-retentive filters SO PDA JOURNAL OF PHARMACEUTICAL SCIENCE AND TECHNOLOGY LA English DT Editorial Material ID MEMBRANE-FILTER; PERFORMANCE; PARTICLES; PR772 C1 US FDA, Div Monoclonal Antibodies, Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. GE Healthcare, Piscataway, NJ 08855 USA. GAEA Resources, Northport, NY 11768 USA. RP Brorson, K (reprint author), US FDA, Div Monoclonal Antibodies, Ctr Drug Evaluat & Res, 29 Lincoln Dr, Bethesda, MD 20892 USA. NR 16 TC 1 Z9 1 U1 1 U2 5 PU PARENTERAL DRUG ASSOC INC PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE 620, BETHESDA, MD 20814 USA SN 1079-7440 J9 PDA J PHARM SCI TECH JI PDA J. Pharm. Sci. Technol. PD NOV-DEC PY 2005 VL 59 IS 6 BP 341 EP 345 PG 5 WC Engineering, Biomedical; Pharmacology & Pharmacy SC Engineering; Pharmacology & Pharmacy GA 000VQ UT WOS:000234490900001 PM 16471421 ER PT J AU Duggirala, HJ Hassig, SE Santana, S Rice, J AF Duggirala, HJ Hassig, SE Santana, S Rice, J TI Evaluation of a hepatitis A immunization program SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Article DE hepatitis A; vaccination; intervention ID COMMUNITY-WIDE OUTBREAK; UNITED-STATES; VACCINATION; CARE AB Background: The purpose of this study was to evaluate the effectiveness of a hepatitis A vaccine requirement targeted at child-care center attendees 2-5 years of age in Maricopa County, AZ. A case-control study conducted before implementation in 1997 found that individuals with hepatitis A were 6 times more likely to have worked in or attended a child-care center than were matched controls, and 40% of hepatitis A cases were attributable to attending or working in a child-care center. Methods: A case-control study was conducted postimplementation in 1999. Cases were individuals reported to surveillance staff between August 1, 1999 and April 30, 2000. Cases were included if they met the Centers for Disease Control and Prevention hepatitis A surveillance case definition. Each case (n = 72) was matched to 2 controls (n = 144) based on age and neighborhood. Results: Cases were more likely to have had contact with a hepatitis A case [odds ratio (OR), 7.04; 95% confidence interval (CI), 1.96, 25.31] than were their matched controls in the unadjusted analysis. Individuals with direct contact with a child-care center (OR 0.221; Cl 0.05, 0.99) were protected against disease. In the multivariate analysis, contact with a hepatitis A case (OR 5.63; CI 1.22, 25.91) was significantly associated with disease, and the protective effect of education (OR 0.19; Cl 0.06, 0.60) remained significant. Conclusion: The results of this study suggest the vaccination requirement had some impact on the epidemiology of hepatitis A in Maricopa County. The risk associated with child-care centers seen in the 1997 study is no longer significantly associated with hepatitis A disease. C1 Tulane Univ, New Orleans, LA 70118 USA. Maricopa Cty Dept Publ Hlth, Phoenix, AZ USA. RP Duggirala, HJ (reprint author), US FDA, Rockville, MD 20857 USA. EM hcj@cdrh.fda.gov NR 15 TC 4 Z9 4 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0891-3668 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD NOV PY 2005 VL 24 IS 11 BP 974 EP 978 DI 10.1097/01.inf.00001837660.75182.01 PG 5 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA 985HP UT WOS:000233368500006 PM 16282932 ER PT J AU Williams, TL Monday, SR Edelson-Mammel, S Buchanan, R Musser, SM AF Williams, TL Monday, SR Edelson-Mammel, S Buchanan, R Musser, SM TI A top-down proteomics approach for differentiating thermal resistant strains of Enterobacter sakazakii SO PROTEOMICS LA English DT Article DE biomarkers; LC/MS; mass spectrometry; microorganisms; pathogen ID 2-DIMENSIONAL GEL-ELECTROPHORESIS; MASS-SPECTROMETRY; INFANT FORMULA; SHOTGUN PROTEOMICS; PROTEIN EXPRESSION; SECRETED PROTEINS; ESCHERICHIA-COLI; POWDERED MILK; IDENTIFICATION; SOLUBILIZATION AB Thermal tolerance has been identified as an important factor relevant to the pathogenicity of Enterobacter sakazakii in human neonates. To identify a biomarker specific for this phenotypic trait, intact protein expression profiles of 12 strains of E. sakazakii were obtained using liquid chromatography mass spectrometry. Proteins were extracted from the bacterial cells, separated by reversed-phase liquid chromatography and mass analyzed. At the end of the chromatography run, the uncharged masses of the multiply charged proteins were determined via automated software routines. The resulting data provided an accurate mass expression profile of the proteins found in the individual strains. From the individual expression profiles, it was possible to identify unique proteins corresponding to strains with thermal resistance. One protein found only in the thermal tolerant strains was sequenced and identified as homologous to a hypothetical protein found in the thermal tolerant bacteria, Methylobacillus flagellatus KT The protein sequence of this protein was then used to reverse-engineer PCR primers for the gene sequence associated with the protein. In all cases, only thermal tolerant strains of E. sakazakii produced amplified PCR products, demonstrating the specificity of this biomarker. C1 US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Williams, TL (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM tracie.williams@cfsan.fda.gov NR 37 TC 38 Z9 40 U1 0 U2 8 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1615-9853 J9 PROTEOMICS JI Proteomics PD NOV PY 2005 VL 5 IS 16 BP 4161 EP 4169 DI 10.1002/pmic.200401263 PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 985IY UT WOS:000233372000012 PM 16196092 ER PT J AU Carman, RJ Simon, MA Petzold, HE Wimmer, RF Batra, MR Fernandez, AH Miller, MA Bartholomew, M AF Carman, RJ Simon, MA Petzold, HE Wimmer, RF Batra, MR Fernandez, AH Miller, MA Bartholomew, M TI Antibiotics in the human food chain: Establishing no effect levels of tetracycline, neomycin, and erythromycin using a chemostat model of the human colonic microflora SO REGULATORY TOXICOLOGY AND PHARMACOLOGY LA English DT Article DE tetracycline; neomycin; erythromycin; microflora; human; intestinal; chemostat; residue; trace; low level; acceptable daily intake; ADI; NOEL ID HUMAN FECAL FLORA; INTESTINAL MICROFLORA; ESCHERICHIA-COLI; BILE-ACIDS; RESISTANCE; OXYTETRACYCLINE; FECES; MICE; CIPROFLOXACIN; COLONIZATION AB A chemostat model of the healthy human large bowel ecosystem was used to establish no effect levels for tetracycline, neomycin, and erythromycin. For each compound, the equivalent to four oral doses (0, 1.5, 15, and 150mg/60kg person/d) was studied. Concentrations of the test compounds in the chemostat medium were intended to simulate fecal levels that might be expected following consumption of food containing antibiotic residue and were based on published oral doses and fecal levels. We monitored the following parameters: short chain fatty acids, bile acids, sulfate reduction, azoreductase and nitroreductase activities, beta-glucosidase and beta-glucuronidase activities, a range of bacterial counts and, lastly, the susceptibility among sentinel bacteria to each test compound. Neomycin and erythromycin reduced bile acid metabolism. Neomycin elevated propionate levels and caused a marginal diminution in azoreductase activity. Based on our results, the no observed effect level (NOEL) of both tetracycline and erythromycin was 15 mg/60 kg person/d. The NOEL for neomycin was 1.5 mg/60 kg person/d. Published by Elsevier Inc. C1 TechLab Inc, Blacksburg, VA 24060 USA. US FDA, Ctr Vet Med, Rockville, MD 20855 USA. RP Carman, RJ (reprint author), TechLab Inc, 2001 Kraft Dr, Blacksburg, VA 24060 USA. EM rjcarman@techlab.com NR 49 TC 16 Z9 17 U1 3 U2 10 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 NOV PY 2005 VL 43 IS 2 BP 168 EP 180 DI 10.1016/j.yrtph.2005.06.005 PG 13 WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology SC Legal Medicine; Pharmacology & Pharmacy; Toxicology GA 979HG UT WOS:000232932400005 PM 16129531 ER PT J AU Jacobs, A AF Jacobs, A TI Prediction of 2-year carcinogenicity study results for pharmaceutical products: How are we doing? SO TOXICOLOGICAL SCIENCES LA English DT Editorial Material DE carcinogenicity; genetic toxicology; drug ID RISK-EVALUATION AB Some have proposed that 2-year carcinogenicity studies may not be necessary if the material is a direct-acting DNA mutagen, induces liver enzymes, causes hyperplasia or toxicity in particular organs, causes cell proliferation, is cytotoxic, causes hormonal perturbations, or if one has QSAR analyses or 'omics information. Safety pharmacology data, pharmacologic activity, metabolism data, and results of 13-week dose ranging studies (with organ weight data, clinical chemistry data, hematologic data, clinical signs and histopathologic findings) were compared with results of 2-year carcinogenicity studies reviewed by the Center for Drug Evaluation and Research (CDER)/FDA. The experience with the ICH genetic toxicology battery and alternative carcinogenicity models was also reviewed. It appears that the information available from short-term studies is not currently sufficient to accurately and reliably predict the outcome of long-term carcinogenicity studies. C1 US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20850 USA. RP Jacobs, A (reprint author), US FDA, Ctr Drug Evaluat & Res, 9201 Corp Blvd,Rm N212, Rockville, MD 20850 USA. EM Abigail.Jacobs@fda.hhs.gov NR 10 TC 33 Z9 33 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD NOV PY 2005 VL 88 IS 1 BP 18 EP 23 DI 10.1093/toxsci/kfi248 PG 6 WC Toxicology SC Toxicology GA 972BH UT WOS:000232428300004 PM 16002477 ER PT J AU Ladics, GS Chapin, RE Hastings, KL Holsapple, MP Makris, SL Sheets, LP Woolhiser, MR Burns-Naas, LA AF Ladics, GS Chapin, RE Hastings, KL Holsapple, MP Makris, SL Sheets, LP Woolhiser, MR Burns-Naas, LA TI Developmental toxicology evaluations - Issues with including neurotoxicology and immunotoxicology assessments in reproductive toxicology studies SO TOXICOLOGICAL SCIENCES LA English DT Editorial Material DE developmental immunotoxicology; DIT; developmental neurotoxicology; DNT; developmental and reproductive toxicology; DART; study design; combination study; hazard identification; panel discussion ID RISK ASSESSMENT; SYSTEM FUNCTION; RATS; WORKSHOP; EXPOSURE; IMMUNE AB Developmental and reproductive toxicology (DART) has routinely been a part of safety assessment. Attention is now focused on the effects of chemicals on the developing nervous and immune systems. This focus on developmental neurotoxicology (DNT) and developmental immunotoxicology (DIT) is based on the premise that children differ from adults in some aspects of their biology and, thus, may also differ in their responses to chemicals. This session's objective was to discuss issues common to DNT and DIT as they relate to DART protocols, including high dose selection and maternal toxicity, adequacy of pup exposure during lactation, use of a different dosing paradigm for DART versus DNT or DIT studies, and whether DIT and DNT endpoints can be incorporated into a single DART study for hazard identification purposes. Consensus was achieved on all topics except the adequacy for risk assessment purposes of the use of a limited number of endpoints for DIT and DNT, with the DNT endpoints being the primary focus of disagreement. Panelists indicated that a combination study design for hazard identification was feasible, though flexibility to meet the scientific needs of the project was emphasized. The adequacy of existing triggers for additional developmental studies was also questioned. Panelists iterated the importance of understanding pup exposure during the various life stages and the use of toxicokinetic data in designing these studies. The group agreed to consider the HESI ACSA Life Stages Task Force recommendations as a next step to address some of the issues and challenges raised during this session. C1 DuPont Co Inc, Haskell Lab Toxicol & Ind Med, Newark, DE 19714 USA. Pfizer Inc, Global Res & Dev, Worldwide Safety Sci, Groton, CT 06340 USA. US FDA, Ctr Drug Evaluat Res, Off New Drugs, Rockville, MD 20857 USA. ILSI Hlth & Environm Sci Inst, Washington, DC 20005 USA. US EPA, Natl Ctr Environm Assessment, Washington, DC 20460 USA. Bayer CropSci LP, Stilwell, KS 66085 USA. Dow Chem Co USA, Toxicol & Environm Res & Consulting, Midland, MI 48674 USA. Pfizer Global Res & Dev, Worldwide Safety Sci, San Diego, CA 92064 USA. RP Ladics, GS (reprint author), DuPont Co Inc, Haskell Lab Toxicol & Ind Med, Box 50, Newark, DE 19714 USA. EM gregory.s.ladics@usa.dupont.com OI Chapin, Robert/0000-0002-5997-1261 NR 26 TC 23 Z9 26 U1 1 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD NOV PY 2005 VL 88 IS 1 BP 24 EP 29 DI 10.1093/toxsci/kfi299 PG 6 WC Toxicology SC Toxicology GA 972BH UT WOS:000232428300005 PM 16120748 ER PT J AU Mei, N Xia, QS Chen, L Moore, MM Fu, PP Chen, T AF Mei, N Xia, QS Chen, L Moore, MM Fu, PP Chen, T TI Photomutagenicity of retinyl palmitate by ultraviolet A irradiation in mouse lymphoma cells SO TOXICOLOGICAL SCIENCES LA English DT Article DE retinyl palmitate; UVA; mouse lymphoma assay; photomutagenicity; loss of heterozygosity; mutant frequency ID CUTANEOUS MALIGNANT-MELANOMA; THYMIDINE KINASE GENE; OXIDATIVE DNA-DAMAGE; ETHYL-N-NITROSOUREA; MUTATIONAL SPECTRA; LIPID-PEROXIDATION; HAIRLESS MICE; SKIN-CANCER; V79 CELLS; VITAMIN-A AB Retinyl palmitate (RP), a storage form of vitamin A, is frequently used as a cosmetic ingredient, with more than 700 RP-containing cosmetic products on the U.S. market in 2004. There are concerns for the possible genotoxicity and carcinogenicity of RP when it is exposed to sunlight. To evaluate the photomutagenicity of RP in cells when exposed to ultraviolet A (UVA) light, L5178Y/Tk(+/-) mouse lymphoma cells were treated with different doses of RP alone/or in the presence of UVA light. Treatment of the cells with RP alone at the dose range of 25-100 mu g/ml did not increase mutant frequencies (MFs) over the negative control, whereas treatment of cells with 1-25 mu g/ml RP under UVA light (82.8 mJ/cm(2)/min for 30 min) produced a dose-dependent mutation induction. The mean induced MF (392 x 10(-6)) for treatment with 25 mu g/ml RP under UVA exposure was about threefold higher than that for UVA alone (122 x 10(-6)), a synergistic effect. To elucidate the underlying mechanism of action, we examined the mutants for loss of heterozygosity (LOH) at four microsatellite loci spanning the entire chromosome 11, on which the Tk gene is located. The mutational spectrum for the RP + UVA treatment was significantly different from the negative control, but not significantly different from UVA exposure alone. Ninety four percent of the mutants from RP + UVA treatment lost the Tk(+) allele, and 91% of the deleted sequences extended more than 6 cM in chromosome length, indicating clastogenic events affecting a large segment of the chromosome. These results suggest that RP is photomutagenic in combination with UVA exposure in mouse lymphoma cells, with a clastogenic mode-of-action. C1 US FDA, Div Genet & Reprod Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Chen, T (reprint author), HFT-130,3900 NCTR Rd, Jefferson, AR 72079 USA. EM pfu@nctr.fda.gov; tchen@nctr.fda.gov RI mei, nan/E-8915-2011 OI mei, nan/0000-0002-3501-9014 NR 36 TC 24 Z9 24 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD NOV PY 2005 VL 88 IS 1 BP 142 EP 149 DI 10.1093/toxsci/kfi291 PG 8 WC Toxicology SC Toxicology GA 972BH UT WOS:000232428300017 PM 16107546 ER PT J AU Doerge, DR Young, JF McDaniel, LP Twaddle, NC Churchwell, MI AF Doerge, DR Young, JF McDaniel, LP Twaddle, NC Churchwell, MI TI Toxicokinetics of acrylamide and glycidamide in Fischer 344 rats SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE acrylamide; glycidamide; Fischer 344 rats AB Acrylamide (AA) is a widely studied industrial chemical that is neurotoxic, mutagenic to somatic and germ cells, and carcinogenic in rodents. The recent discovery of AA at ppm levels in a wide variety of commonly consumed foods has energized research efforts worldwide to define toxic mechanisms, particularly toxicokinetics and bioavailability. This study compares the toxicokinetics of AA and its epoxide metabolite, glycidamide (GA), in serum and tissues of male and female F344 rats following acute exposure by intravenous, gavage, and dietary routes at 0.1 mg/kg AA or intravenous and gavage routes with an equimolar amount of GA. AA was rapidly absorbed after oral dosing, was widely distributed to tissues, was efficiently converted to GA, and produced increased levels of GA-DNA adducts in liver. GA was also rapidly absorbed, widely distributed to tissues, and produced increased liver DNA adduct levels. AA bioavailability after aqueous gavage was 60-98% and from the diet was 32-44%; however, first-pass metabolism or other kinetic change resulted in much higher internal exposures to GA (2- to 7-fold) when compared to the intravenous route. A similar effect on metabolism to GA following oral administration was previously observed under an identical exposure paradigm in mice. Furthermore, DNA adduct formation in rat liver showed the same proportionality with the respective GA AUC value as did mice in the previous study. These findings suggest that as the AA content in food is reduced, species-differences in GA formation and subsequent DNA adduct formation may be minimized. These findings provide additional information needed to assess genotoxic risks from the low levels of AA that are pervasive in the food supply. Published by Elsevier Inc. C1 Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Doerge, DR (reprint author), Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM ddoerge@nctr.fda.gov NR 34 TC 56 Z9 57 U1 1 U2 16 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 2005 VL 208 IS 3 BP 199 EP 209 DI 10.1016/j.taap.2005.03.003 PG 11 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 980ZT UT WOS:000233057400001 PM 16239164 ER PT J AU Muni, N Yue, L AF Muni, N Yue, L TI Use of propensity score methodology in cardiovascular device trials: US Food and Drug Administration perspectives SO VALUE IN HEALTH LA English DT Meeting Abstract C1 US FDA, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1098-3015 J9 VALUE HEALTH JI Value Health PD NOV-DEC PY 2005 VL 8 IS 6 BP A111 EP A111 DI 10.1016/S1098-3015(10)67484-0 PG 1 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 980MD UT WOS:000233021700349 ER PT J AU Klamt, F de Oliveira, MR Moreira, JCF AF Klamt, F de Oliveira, MR Moreira, JCF TI Retinol induces permeability transition and cytochrome c release from rat liver mitochondria SO BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS LA English DT Article DE vitamin A; retinol; oxidative stress; mitochondria; cytochrome c; permeability transition pore; MPT ID SERTOLI-CELLS; OXIDATIVE STRESS; DNA-DAMAGE; VITAMIN-A; APOPTOSIS; PORE; SUPPLEMENTATION; SUPEROXIDE; EXPRESSION; INDUCTION AB Biological actions of retinoids on modulation of cellular gene expression by nuclear receptors are widely known. Recently, extra-nuclear effects of retinoids have been proposed, but remain to be better elucidated. Considering that retinoids induce apoptosis in tumor cells by an unknown mechanism, and that mitochondria play a key role in controlling apoptosis via cytochrome c (cyt c) release, we exposed rat liver mitochondria to 3-40 mu M of retinol (vitamin A), and observed that retinol causes mitochondrial permeability transition (MPT) and cyt c release, in a concentration-dependent pattern. Increased superoxide anion generation and lipoperoxidation were also observed. Cyclosporin A or trolox co-administration reverted all parameters tested. In view of these findings, we conclude that retinol induces mitochondria oxidative damage, leading to MPT and cyt c release by opening of the permeability transition pore, thus suggesting a putative mechanism of apoptosis activation by retinol. (c) 2005 Elsevier B.V. All rights reserved. C1 Univ Fed Rio Grande Sul, ICBS, Dept Bioquim, Ctr Estudos Estresse Oxidativo, Porto Alegre, RS, Brazil. Univ Luterana do Brasil, Dept Biol, Cachoeira do Sul, Brazil. RP Klamt, F (reprint author), US FDA, CBER, 29 Lincoln Dr,Bldg 29A,Room 2A09, Bethesda, MD 20892 USA. EM fklamt@terra.com.br; jcfm@vortex.ufrgs.br RI De Oliveira, Marcos /D-7470-2015 OI De Oliveira, Marcos /0000-0003-2414-6605 NR 35 TC 39 Z9 39 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-4165 J9 BBA-GEN SUBJECTS JI Biochim. Biophys. Acta-Gen. Subj. PD OCT 30 PY 2005 VL 1726 IS 1 BP 14 EP 20 DI 10.1016/j.bbagen.2005.07.016 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 982KJ UT WOS:000233156800002 PM 16202537 ER PT J AU Joner, M Finn, AV Ladich, ER Rittersma, SZ Kolodgie, FD Skorija, K Farb, A Gold, HK Virmani, R AF Joner, M Finn, AV Ladich, ER Rittersma, SZ Kolodgie, FD Skorija, K Farb, A Gold, HK Virmani, R TI Morphologic predictors of drug eluting stent thrombosis SO CIRCULATION LA English DT Meeting Abstract CT 78th Annual Scientific Session of the American-Heart-Association CY NOV 13-16, 2005 CL Dallas, TX SP Amer Heart Assoc C1 CVPATH, Gaithersburg, MD USA. MGH, Boston, MA USA. CVPATH, Gaithersburg, MD USA. Univ Amsterdam, Acad Med Ctr, NL-1105 AZ Amsterdam, Netherlands. US FDA, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 25 PY 2005 VL 112 IS 17 SU S MA 3210 BP U749 EP U749 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956404513 ER PT J AU Churchwell, MI Twaddle, NC Meeker, LR Doerge, DR AF Churchwell, MI Twaddle, NC Meeker, LR Doerge, DR TI Improving LC-MS sensitivity through increases in chromatographic performance: Comparisons of UPLC-ES/MS/MS to HPLC-ES/MS/MS SO JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES LA English DT Article DE UPLC; mass spectrometry; beta-agonists; isoflavones; tamoxifen; ephedra alkaloids ID LIQUID-CHROMATOGRAPHY; MASS-SPECTROMETRY; BETA-AGONISTS; PLASMA; METABOLITES; ISOFLAVONES; SUPPLEMENTS; TAMOXIFEN; GENISTEIN; RETINA AB Recent technological advances have made available reverse phase chromatographic media with a 1.7 mu m particle size along with a liquid handling system that can operate such columns at much higher pressures. This technology, termed ultra performance liquid chromatography (UPLC), offers significant theoretical advantages in resolution, speed, and sensitivity for analytical determinations, particularly when coupled with mass spectrometers capable of high-speed acquisitions. This paper explores the differences in LC-MS performance by conducting a side-by-side comparison of UPLC for several methods previously optimized for HPLC-based separation and quantification of multiple analytes with maximum throughput. In general, UPLC produced significant improvements in method sensitivity, speed, and resolution. Sensitivity increases with UPLC, which were found to be analyte-dependent, were as large as 10-fold and improvements in method speed were as large as 5-fold under conditions of comparable peak separations. Improvements in chromatographic resolution with UPLC were apparent from generally narrower peak widths and from a separation of diastereomers not possible using HPLC. Overall, the improvements in LC-MS method sensitivity, speed, and resolution provided by UPLC show that further advances can be made in analytical methodology to add significant value to hypothesis-driven research. (c) 2005 Elsevier B.V. All rights reserved. C1 US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Waters Corp, Milford, MA USA. RP Doerge, DR (reprint author), US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM ddoerge@nctr.fda.gov FU NIA NIH HHS [P01-AG024387] NR 15 TC 238 Z9 249 U1 3 U2 66 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 OCT 25 PY 2005 VL 825 IS 2 BP 134 EP 143 DI 10.1016/j.jchromb.2005.05.037 PG 10 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 975MV UT WOS:000232667500005 PM 16002352 ER PT J AU Hampshire, VA AF Hampshire, VA TI Evaluation of efficacy of heartworm preventive products at the FDA SO VETERINARY PARASITOLOGY LA English DT Article; Proceedings Paper CT 11th Triennial Symposium of the American-Heartworm-Society CY JUL 23-24, 2004 CL Philadelphia, PA SP Amer Heartworm Soc DE heartworm; Dirofilaria immitis; preventative; adverse event AB The Center for Veterinary Medicine, U.S. Food and Drug Administration (FDA/CVM) has authority under the United States Code 21 under Section 514.80 to monitor for adverse experiences of approved animal products. Although veterinarians voluntarily report suspect drug-related events to manufacturers, firms that market FDA-approved animal products must report serious events to the FDA within 15 working days of the veterinarian or pet-owner's call to them. Under the present regulations, canine heartworm preventatives are approved for 100% efficacy after testing in laboratory and field conditions. The report of lack of efficacy against heartworm larvae is a serious adverse drug event because the resulting condition or the treatment of the condition is life threatening. Information on lack of effect that are deemed possibly, probably, or definitely drug-related available for review under generic product on the FDA/CVM website Surveillance of these reports indicates there are some failures for virtually all heartworm prevention product categories. Most failures have been reported in heartworm-endemic states. At this time, it is unclear whether these are representative of the rare occurrences of failure that have been in existence for a long time, but not reported regularly or promptly, or whether there is a true increase in complaints of ineffectiveness and real variability between products. This paper discusses methods, personnel, and procedures in place in the Division of Surveillance that will aid the FDA to better assess heartworm preventive treatment failures. It discusses scoring paradigms presently utilized by FDA/CVM to assess severity of complaints of lack of efficacy against heartworms, and welcomes audience input as to how to improve existing processes. Results suggest that more comprehensive reporting will provide FDA/CVM more accurate surveillance information regarding efficacy problems. Such practices will permit FDA/CVM to better interpret both incidence and severity of in-effect and possible patterns of emerging resistance and to convey this in any necessary updated labeling. It also indicates that as part of that process, practitioners should return to a more conservative testing schedule. Published by Elsevier B.V. C1 US FDA, Ctr Vet Med, Rockville, MD 20855 USA. RP Hampshire, VA (reprint author), US FDA, Ctr Vet Med, 7519 Standish Pl, Rockville, MD 20855 USA. NR 6 TC 28 Z9 28 U1 1 U2 13 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-4017 J9 VET PARASITOL JI Vet. Parasitol. PD OCT 24 PY 2005 VL 133 IS 2-3 SI SI BP 191 EP 195 DI 10.1016/j.vetpar.2005.04.004 PG 5 WC Parasitology; Veterinary Sciences SC Parasitology; Veterinary Sciences GA 975MD UT WOS:000232665700008 PM 16099105 ER PT J AU LaKind, JS Brent, RL Dourson, ML Kacew, S Koren, G Sonawane, B Tarzian, AJ Uhl, K AF LaKind, JS Brent, RL Dourson, ML Kacew, S Koren, G Sonawane, B Tarzian, AJ Uhl, K TI Human milk biomonitoring data: Interpretation and risk assessment issues SO JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A-CURRENT ISSUES LA English DT Article; Proceedings Paper CT Workshop on Human Milk Surveillance and Research on Environmental Chemicals in the United States CY SEP 24-26, 2004 CL Pennsylvania State Univ, Coll Med, Hershey, PA HO Pennsylvania State Univ, Coll Med ID DRUG-METABOLIZING-ENZYMES; ACID HEPATIC FATALITIES; PREDICT INFANT EXPOSURE; REFERENCE DOSE RFD; HUMAN BREAST-MILK; PHARMACOKINETIC DIFFERENCES; DIFFERENTIAL SENSITIVITY; CHLORAMPHENICOL TOXICITY; ENVIRONMENTAL CHEMICALS; UNCERTAINTY FACTOR AB Biomonitoring data can, under certain conditions, be used to describe potential risks to human health (for example, blood lead levels used to determine children's neurodevelopmental risk). At present, there are very few chemical exposures at low levels for which sufficient data exist to state with confidence the link between levels of environmental chemicals in a person's body and his or her risk of adverse health effects. Human milk biomonitoring presents additional complications. Human milk can be used to obtain information on both the levels of environmental chemicals in the mother and her infant's exposure to an environmental chemical. However, in terms of the health of the mother, there are little to no extant data that can be used to link levels of most environmental chemicals in human milk to a particular health outcome in the mother. This is because, traditionally, risks are estimated based on dose, rather than on levels of environmental chemicals in the body, and the relationship between dose and human tissue levels is complex. On the other hand, for the infant, some information on dose is available because the infant is exposed to environmental chemicals in milk as a "dose" from which risk estimates can be derived. However, the traditional risk assessment approach is not designed to consider the benefits to the infant associated with breastfeeding and is complicated by the relatively short-term exposures to the infant from breastfeeding. A further complexity derives from the addition of in utero exposures, which complicates interpretation of epidemiological research on health outcomes of breastfeeding infants. Thus, the concept of "risk assessment" as it applies to human milk biomonitoring is not straightforward, and methodologies for undertaking this type of assessment have not yet been fully developed. This article describes the deliberations of the panel convened for the Technical Workshop on Human Milk Surveillance and Biomonitoring for Environmental Chemicals in the United States, held at the Hershey Medical Center, Pennsylvania State College of Medicine, on several issues related to risk assessment and human milk biomonitoring. Discussion of these topics and the thoughts and conclusions of the panel are described in this article. C1 LaKind Associates LLC, Catonsville, MD 21228 USA. Penn State Univ, Milton S Hershey Med Ctr, Coll Med, Dept Pediat, Hershey, PA 17033 USA. Thomas Jefferson Univ, AI duPont Hosp Children, Jefferson Med Coll, Wilmington, DE USA. Toxicol Excellence Risk Assessment, Cincinnati, OH USA. Univ Ottawa, Dept Pharmacol, Ottawa, ON, Canada. Univ Western Ontario, Hosp Sick Children Mol Toxicol, Div Clin Pharmacol & Toxicol, London, ON N6A 3K7, Canada. US EPA, Natl Ctr Environm Assessment, Off Res & Dev, Washington, DC 20460 USA. Eth & Res Consultant, Baltimore, MD USA. Univ Maryland, Sch Law, Law & Hlth Care Program, Baltimore, MD 21201 USA. Univ Maryland, Sch Nursing, Baltimore, MD 21201 USA. US FDA, Ctr Drug Evaluat & Res, Off New Drugs, Pregnancy Labeling Team, Rockville, MD 20857 USA. RP LaKind, JS (reprint author), LaKind Associates LLC, 106 Oakdale Ave, Catonsville, MD 21228 USA. EM lakindassoc@comcast.net NR 129 TC 15 Z9 15 U1 0 U2 6 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1528-7394 J9 J TOXICOL ENV HEAL A JI J. Toxicol. Env. Health Part A PD OCT 22 PY 2005 VL 68 IS 20 BP 1713 EP 1769 DI 10.1080/15287390500225724 PG 57 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 969ZV UT WOS:000232275900004 PM 16176917 ER PT J AU Berlin, CM LaKind, JS Fenton, SE Wang, RY Bates, MN Brent, RL Condon, M Crase, BL Dourson, ML Ettinger, AS Foos, B Furst, P Giacoia, GP Goldstein, DA Haynes, SG Hench, KD Kacew, S Koren, G Lawrence, RA Mason, A McDiarmid, MA Moy, G Needham, LL Paul, IM Pugh, LC Qian, ZM Salamone, L Selevan, SG Sonawane, B Tarzian, AJ Tully, MR Uhl, K AF Berlin, CM LaKind, JS Fenton, SE Wang, RY Bates, MN Brent, RL Condon, M Crase, BL Dourson, ML Ettinger, AS Foos, B Furst, P Giacoia, GP Goldstein, DA Haynes, SG Hench, KD Kacew, S Koren, G Lawrence, RA Mason, A McDiarmid, MA Moy, G Needham, LL Paul, IM Pugh, LC Qian, ZM Salamone, L Selevan, SG Sonawane, B Tarzian, AJ Tully, MR Uhl, K TI Conclusions and recommendations of the expert panel: Technical Workshop on Human Milk Surveillance and Biomonitoring for Environmental Chemicals in the United States SO JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A-CURRENT ISSUES LA English DT Article; Proceedings Paper CT Workshop on Human Milk Surveillance and Research on Environmental Chemicals in the United States CY SEP 24-26, 2004 CL Pennsylvania State Univ, Coll Med, Hershey, PA HO Pennsylvania State Univ, Coll Med C1 Penn State Univ, Milton S Hershey Med Ctr, Coll Med, Dept Pediat, Hershey, PA 17033 USA. LaKind Associates LLC, Catonsville, MD USA. US EPA, Natl Hlth & Environm Effects Res Lab, Off Res & Dev, Res Triangle Pk, NC 27711 USA. Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Atlanta, GA USA. Univ Calif Berkeley, Sch Publ Hlth, Div Environm Hlth Sci, Berkeley, CA 94720 USA. AI duPont Hosp Children, Wilmington, DE USA. Univ Maryland, Sch Med, Occupat Hlth Program, Baltimore, MD 21201 USA. Amer Acad Pediat, Div Community Hlth Serv, Breastfeeding Initiat, Elk Grove Village, IL USA. Toxicol Excellence Risk Assessment, Cincinnati, OH USA. Harvard Univ, Sch Publ Hlth, Exposure Epidemiol & Risk Program, Boston, MA 02115 USA. US EPA, Off Childrens Hlth Protect, Washington, DC 20460 USA. Chem & Vet Control Lab, Munster, Germany. NICHHD, Pediat Pharmacol Res Unit Network, NIH, Rockville, MD USA. Monsanto Co, St Louis, MO USA. Dept Hlth & Human Serv, Off Womens Hlth, Washington, DC USA. US PHS, Div Perinatal Syst, Rockville, MD USA. US Hlth Resources & Serv Adm, Womens Hlth Maternal & Child Hlth Bur, Rockville, MD 20857 USA. Univ Ottawa, Dept Pharmacol, Ottawa, ON, Canada. Univ Western Ontario, Hosp Sick Children Mol Toxicol, Div Clin Pharmacol & Toxicol, London, ON N6A 3K7, Canada. Univ Rochester, Breastfeeding & Human Lactat Study Ctr, Golisano Childrens Hosp, Rochester, NY USA. Res Fdn Hlth & Environm Effects, Arlington, VA USA. WHO, CH-1211 Geneva, Switzerland. Penn State Univ, Milton S Hershey Med Ctr, Coll Med, Dept Pediat, Hershey, PA 17033 USA. Penn State Univ, Milton S Hershey Med Ctr, Coll Med, Dept Hlth Evaluat Sci, Hershey, PA 17033 USA. Johns Hopkins Univ, Sch Nursing, Baltimore, MD USA. Amer Chem Council, Hlth Prod & Sci Policy Team, Arlington, VA USA. US EPA, Natl Ctr Environm Assessment, Off Res & Dev, Washington, DC 20460 USA. Eth & Res Consultant, Baltimore, MD USA. Univ Maryland, Sch Law, Law & Hlth Care Program, Baltimore, MD 21201 USA. Univ Maryland, Sch Nursing, Baltimore, MD 21201 USA. Univ N Carolina Hlth Care, N Carolina Womens Hosp, Human Milk Banking Associat N Amer, Chapel Hill, NC USA. US FDA, Ctr Drug Evaluat & Res, Off New Drugs, Pregnancy Labeling Team, Rockville, MD 20857 USA. RP Berlin, CM (reprint author), Penn State Univ, Milton S Hershey Med Ctr, Coll Med, Childrens Hosp,Dept Pediat, MC HO85,POB 850, Hershey, PA 17033 USA. EM cmb6@psu.edu OI Paul, Ian/0000-0002-6344-8609 NR 2 TC 11 Z9 11 U1 0 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1528-7394 J9 J TOXICOL ENV HEAL A JI J. Toxicol. Env. Health Part A PD OCT 22 PY 2005 VL 68 IS 20 BP 1825 EP 1831 DI 10.1080/15287390500226896 PG 7 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 969ZV UT WOS:000232275900007 PM 16176920 ER PT J AU Chandrika, B Schnackenberg, LK Raveendran, P Wallen, SL AF Chandrika, B Schnackenberg, LK Raveendran, P Wallen, SL TI High resolution H-1 NMR structural studies of sucrose octaacetate in supercritical carbon dioxide SO CHEMISTRY-A EUROPEAN JOURNAL LA English DT Article DE carbohydrates; NMR spectroscopy; sucrose; supercritical fluids ID HIGH-PRESSURE NMR; NUCLEAR-MAGNETIC-RESONANCE; SHIFTING HYDROGEN-BONDS; PULSED-FIELD GRADIENTS; QUADRUPOLAR NUCLEI; SPECTROSCOPY; PROTEINS; SOLVENTS; SPECTRA; FLUIDS AB High pressure (HP), high resolution (HR), proton nuclear magnetic resonance (H-1 NMR) spectroscopy has been utilized for the first time to investigate the solution structure of a carbohydrate based system, sucrose octaacetate (SOA), in supercritical CO2. The studies indicate that the average solution state conformation of the alpha-(D)-Glucopyranosyl ring of SOA in scCO(2) medium is consistent with the C-4(1) chair form, while the beta-(D)-fructofuranosyl ring adopts an envelope conformation. The investigations also suggest that scCO(2) is a promising medium to study the solution structure and conformation of acetylated sugar systems. Spectral manifestations of a specific interaction between the acetate methyl protons and CO2 molecules are also presented. C1 Univ N Carolina, Dept Chem, Chapel Hill, NC 27599 USA. Univ N Carolina, NST STC Environmentally Responsible Solvents & Pr, Kenan & Venable Labs, Chapel Hill, NC 27599 USA. US FDA, Div Syst Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Natl Inst Adv Ind Sci & Technol, Supercrit Fluid Res Ctr, Miyagino Ku, Sendai, Miyagi 9838551, Japan. RP Wallen, SL (reprint author), Univ N Carolina, Dept Chem, Chapel Hill, NC 27599 USA. EM ravi@ni.aist.go.jp; wallen@email.unc.edu NR 47 TC 7 Z9 9 U1 2 U2 11 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 0947-6539 J9 CHEM-EUR J JI Chem.-Eur. J. PD OCT 21 PY 2005 VL 11 IS 21 BP 6266 EP 6271 DI 10.1002/chem.200500215 PG 6 WC Chemistry, Multidisciplinary SC Chemistry GA 979QS UT WOS:000232960500016 PM 16078290 ER PT J AU Di Paolo, OA Teitel, CH Nowell, S Coles, BF Kadlubar, FF AF Di Paolo, OA Teitel, CH Nowell, S Coles, BF Kadlubar, FF TI Expression of cytochromes P450 and glutathione S-transferases in human prostate, and the potential for activation of heterocyclic amine carcinogens via acetyl-CoA-, PAPS- and ATP-dependent pathways SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE N-acetyltransferase; carcinogen; cytochrome p450; DNA-adducts; glutathione S-transferase; heterocyclic amines; metabolism; PhIP; prostate ID METABOLIC-ACTIVATION; EPITHELIAL-CELLS; HUMAN PANCREAS; CANCER; DNA; DETOXIFICATION; TISSUE; FOOD; IDENTIFICATION; ASSOCIATION AB Dietary factors appear to be involved in the high incidence of prostate cancer in "Westernized" countries, implicating dietary carcinogens such as heterocyclic amines (HAs) in the initiation of prostate carcinogenesis. We examined 24 human prostate samples with respect to their potential for activation and detoxification of HAs and the presence of DNA adducts formed in vivo. Cytochromes P450 1131, 3A4 and 3A5 were expressed at low levels (< 0.1-6.2 pmol/mg microsomal protein). N-Acetyltransferase (NAT) activities, using p-aminobenzoic acid (NAT1) and sulfamethazine (NAT2) as substrates, were < 5-5,500 and < 5-43 pmol/min/mg cytosolic protein, respectively. Glutathione S-transferases (GSTs) P1, M2 and M3 were expressed at 0.038-1.284, 0.0050.126 and 0.010-0.270 mu g/mg cytosolic protein, respectively; GSTM1 was expressed in all GSTM1-positive samples (0.012-0.291 mu g/mg cytosolic protein); and GSTAI was expressed at low levels (< 0.01-0.11 mu g/mg cytosolic protein). Binding of N-hydroxy-PhIP to DNA in vitro occurred primarily by an AcCoA-dependent process (< 1-54 pmol/mg/DNA), PAPS- and ATP-dependent binding being < 1-7 pmol/mg DNA. In vivo, putative PhIP- or 4-amino- biphenyl,)DNA adducts were found in 4 samples (0.4-0.8 adducts/ putative hydrophobic adducts were found in 6 samples (8-64 adducts/10(8) bases). Thus, the prostate appears to have low potential for N-hydroxylation of HAs but greater potential for activation of N-hydroxy HAs to genotoxic N-acetoxy esters. The prostate has potential for GSTP1-dependent detoxification of ATP-activated N-hydroxy-PhIP but little potential for detoxification of N-acetoxy-PhIP by GSTAI. However, there were no significant correlations between expression/activities and DNA adducts formed in vitro or in vivo, DNA adducts in vivo possibly reflecting carcinogen exposure. (c) 2005 Wiley-Liss, Inc. C1 Natl Ctr Toxicol Res, Div Pharmacogenom & Mol Epidemiol, Jefferson, AR 72079 USA. RP Kadlubar, FF (reprint author), Natl Ctr Toxicol Res, Div Pharmacogenom & Mol Epidemiol, HFT100,3900 NCTR Rd, Jefferson, AR 72079 USA. EM fkadlubar@netr.fda.gov NR 35 TC 32 Z9 33 U1 1 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD OCT 20 PY 2005 VL 117 IS 1 BP 8 EP 13 DI 10.1002/ijc.21152 PG 6 WC Oncology SC Oncology GA 961CG UT WOS:000231638900002 PM 15880531 ER PT J AU Angeles-Boza, AM Bradley, PM Fu, PKL Shatruk, M Hilfiger, MG Dunbar, KR Turro, C AF Angeles-Boza, AM Bradley, PM Fu, PKL Shatruk, M Hilfiger, MG Dunbar, KR Turro, C TI Photocytotoxicity of a new Rh-2(II,II) complex: Increase in cytotoxicity upon irradiation similar to that of PDT agent hematoporphyrin SO INORGANIC CHEMISTRY LA English DT Article ID COMET ASSAY; STACKING INTERACTIONS; DNA PHOTOCLEAVAGE; STATE PROPERTIES; BINDING MODES; CARBOXYLATES; RUTHENIUM(II); RHODIUM(II); APOPTOSIS; PRODUCTS AB A new type of heteroleptic dirhodium complex cis-[Rh-2(mu-O2CCH3)(2)-(bpy)(dppz)](2+) (3) was synthesized and its potential as a photodynamic therapy (PDT) agent was investigated. Although 27% hypochromicity of the absorption of 3 in the near-UV and visible regions is observed in the presence of duplex DNA, relative viscosity measurements reveal that the complex does not intercalate between the DNA bases. The DNA photocleavage with visible light by 3 proceeds via both oxygen dependent and independent mechanisms, and it is more efficient than that of related complexes. The increase in the cytotoxicity of 3 towards human skin cells is similar to that of hematoporphyrin, a key ingredient in a PDT drug currently in use. This feature makes this complex a useful candidate for further PDT studies. C1 Texas A&M Univ, Dept Chem, College Stn, TX 77842 USA. Ohio State Univ, Dept Chem, Columbus, OH 43210 USA. US FDA, College Pk, MD 20740 USA. RP Dunbar, KR (reprint author), Texas A&M Univ, Dept Chem, College Stn, TX 77842 USA. EM dunbar@mail.chem.tamu.edu; turro.1@osu.edu RI Angeles-Boza, Alfredo/C-6563-2008; Dunbar, Kim/B-6488-2015; Turro, Claudia/H-5335-2015 OI Angeles-Boza, Alfredo/0000-0002-5560-4405; Dunbar, Kim/0000-0001-5728-7805; Turro, Claudia/0000-0003-3202-5870 FU NIGMS NIH HHS [R01 GM64040-01] NR 25 TC 47 Z9 48 U1 2 U2 32 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 OCT 17 PY 2005 VL 44 IS 21 BP 7262 EP 7264 DI 10.1021/ic0500715 PG 3 WC Chemistry, Inorganic & Nuclear SC Chemistry GA 974RS UT WOS:000232609700001 PM 16212337 ER PT J AU Bendre, SV Shaddock, JG Patton, RE Dobrovolsky, VN Albertini, RJ Heflich, RH AF Bendre, SV Shaddock, JG Patton, RE Dobrovolsky, VN Albertini, RJ Heflich, RH TI Lymphocyte Hprt mutant frequency and sperm toxicity in C57BL/6 mice treated chronically with Azathioprine SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article DE Azathioprine; Hprt mutation; mutant selection; sperm toxicity ID DEPENDENT DIABETES-MELLITUS; T-CELL CLONES; IN-VIVO; PERIPHERAL-BLOOD; HUMAN-POPULATION; B6C3F1 MICE; MUTATIONS; MOUSE; GENE; METABOLISM AB Many patients undergoing chronic therapy with the purine analogue Azathioprine (Aza) have highly elevated HPRT lymphocyte mutant frequencies (MFs), and it is likely that these increases are due to selection of pre-existing HPRT mutant lymphocytes. A similar selection in germ cells might result in an increased frequency of the Lesch-Nyhan syndrome. In this study, a mouse model for Aza mutant selection was developed and Aza toxicity was evaluated in the germ cells of treated mice. Groups of 20 male C57BL/6 mice were treated by gavage three times/week with 0, 5, 10, 25, 50, or 100 mg/kg Aza, and three to eight mice from each group were sacrificed at various times for up to 23 weeks. Mice treated with 25-100 mg/kg Aza were all dead by 14 weeks of treatment. Hprt lymphocyte MF assays indicated that the treated mice had reduced numbers of spleen lymphocytes. Most treated mice had Hprt MFs similar to those of control mice (2.1 +/- 1.6 x 10(-6)), however, highly elevated MFs were detected in one out of three mice given 5 mg/kg for 10 weeks, one out of three mice given 10 mg/kg for 10 weeks, and one out of eight mice given 10 mg/kg for 23 weeks (e.g., 233 x 10(-6) after 10 weeks of 5 mg/kg). Sequence analysis of Hprt cDNA indicated that all mutant clones from one of these mice had a T -->. A transversion in the initiation codon. Multiplex-PCR on mutant clones from the other two mice indicated that all the clones from one had a deletion of Hprt exons 2 and 3, while most of the mutants from the other had lost all of the Hprt exons. Measurements of testicular weight, and of sperm count, viability, morphology, and motility found that Aza produced low levels of toxicity in sperm, with the most consistent effect being a reduction in the testicular weight. The data suggest that mice chronically treated with 5 and 10 mg/kg Aza (doses similar to those used in humans) have elevated Hprt MFs due to clonal amplification of selected Hprt mutants. The results also suggest that mice treated with these doses of Aza retain reasonable fertility, and will be useful for breeding experiments to examine the possibility of increasing the germ-line transmission of Hprt mutations. Published by Elsevier B.V. C1 Univ Arkansas Med Sci, Dept Pharmacol & Toxicol, Little Rock, AR 72205 USA. US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. Chalk River Labs, Jefferson, AR USA. Univ Vermont, Genet Toxicol Lab, Burlington, VT USA. RP Heflich, RH (reprint author), Univ Arkansas Med Sci, Dept Pharmacol & Toxicol, Little Rock, AR 72205 USA. EM rheflich@nctr.fda.gov NR 59 TC 7 Z9 8 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 OCT 15 PY 2005 VL 578 IS 1-2 BP 1 EP 14 DI 10.1016/j.mrfmmm.2004.09.018 PG 14 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 976QF UT WOS:000232747600001 PM 16107271 ER PT J AU Gusev, PA Cui, C Alkon, DL Gubin, AN AF Gusev, PA Cui, C Alkon, DL Gubin, AN TI Topography of Arc/Arg3.1 mRNA expression in the dorsal and ventral hippocampus induced by recent and remote spatial memory recall: Dissociation of CA3 and CA1 activation SO JOURNAL OF NEUROSCIENCE LA English DT Article DE memory; stress; consolidation; hippocampus; water maze; immediate-early gene; corticosterone ID LONG-TERM-MEMORY; IMMEDIATE-EARLY GENE; RETROGRADE-AMNESIA; PYRAMIDAL CELLS; RAT HIPPOCAMPUS; PLACE CELLS; NMDA RECEPTORS; HEAD DIRECTION; SUBFIELDS CA1; FEAR MEMORY AB The understanding of the mechanisms of memory retrieval and its deficits, and the detection of memory underlying neuronal plasticity, is greatly impeded by a lack of precise knowledge of the brain circuitry that underlies the functions of memory. The specific roles of anatomically distinct hippocampal subdivisions in recent and long-term memory retention and recall are essentially unknown. To address these questions, we mapped the expression of Arc/Arg3.1 mRNA, a neuronal activity marker, in memory retention at multiple rostrocaudal levels of the dentate gyrus, CA3, CA1, subiculum, and lateral and medial entorhinal cortices after a platform search in a water-maze spatial task at 24 h and 1 month compared with swim and naive controls. We found that the entorhinohippocampal neuronal activity underlying the recall of recent and remote spatial memory has an anatomically distributed and time-dependent organization throughout both the dorsal and ventral hippocampus that is subdivision specific. We found a dissociation in the activity of the entorhinal cortex, CA3, and CA1 over a period of memory consolidation. Although CA3, the dorsal hippocampus, and the entorhinal cortex demonstrated the most persistent learning-specific signal during both recent and long-term memory recall, CA1 and the ventral hippocampus displayed the most dramatic signal decline. We determined the coordinates of activity clusters in the hippocampal subdivisions during the platform search and their dynamics over time. Our mapping data suggest that although the level of corticohippocampal interaction is similar during the retrieval of recent and remote spatial memories, the mnemonic function of the hippocampus may have changed, and the activity underlying remote spatial memory could be anatomically segregated within hippocampal subdivisions in small segments. C1 Blanchette Rockefeller Neurosci Inst, Rockville, MD 20850 USA. US FDA, Dev Biol Lab, Bethesda, MD 20892 USA. RP Gusev, PA (reprint author), Blanchette Rockefeller Neurosci Inst, 9601 Med Ctr Dr,Acad & Res Bldg,Room 316, Rockville, MD 20850 USA. EM gusevpa@brni-jhu.org NR 86 TC 49 Z9 50 U1 2 U2 9 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 OCT 12 PY 2005 VL 25 IS 41 BP 9384 EP 9397 DI 10.1523/JNEUROSCI.0832-05.2005 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 973TU UT WOS:000232546300008 PM 16221847 ER PT J AU McLaughlin, JB DePaola, A Bopp, CA Martinek, KA Napolilli, NP Allison, CG Murray, SL Thompson, EC Bird, MM Middaugh, JP AF McLaughlin, JB DePaola, A Bopp, CA Martinek, KA Napolilli, NP Allison, CG Murray, SL Thompson, EC Bird, MM Middaugh, JP TI Outbreak of Vibrio parahaemolyticus gastroenteritis associated with Alaskan oysters SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID THERMOSTABLE DIRECT HEMOLYSIN; UNITED-STATES; ALGINOLYTICUS; GENES; COAST; FOOD AB BACKGROUND Vibrio parahaemolyticus, the leading cause of seafood-associated gastroenteritis in the United States, typically is associated with the consumption of raw oysters gathered from warm-water estuaries. We describe a recognized outbreak of V. parahaemolyticus infection associated with the consumption of seafood from Alaska. METHODS After we received reports of the occurrence of gastroenteritis on a cruise ship, we conducted a retrospective cohort study among passengers, as well as active surveillance throughout Alaska to identify additional cases, and an environmental study to identify sources of V. parahaemolyticus and contributors to the outbreak. RESULTS Of 189 passengers, 132 ( 70 percent) were interviewed; 22 of the interviewees ( 17 percent) met our case definition of gastroenteritis. In our multiple logistic-regression analysis, consumption of raw oysters was the only significant predictor of illness; the attack rate among people who consumed oysters was 29 percent. Active surveillance identified a total of 62 patients with gastroenteritis. V. parahaemolyticus serotype O6: K18 was isolated from the majority of patients tested and from environmental samples of oysters. Patterns on pulsed-field gel electrophoresis were highly related across clinical and oyster isolates. All oysters associated with the outbreak were harvested when mean daily water temperatures exceeded 15.0 degrees C ( the theorized threshold for the risk of V. parahaemolyticus illness from the consumption of raw oysters). Since 1997, mean water temperatures in July and August at the implicated oyster farm increased 0.21 degrees C per year (P< 0.001 by linear regression); 2004 was the only year during which mean daily temperatures in July and August at the shellfish farm did not drop below 15.0 degrees C. CONCLUSIONS This investigation extends by 1000 km the northernmost documented source of oysters that caused illness due to V. parahaemolyticus. Rising temperatures of ocean water seem to have contributed to one of the largest known outbreaks of V. parahaemolyticus in the United States. C1 Alaska Dept Hlth & Social Serv, Div Publ Hlth, Anchorage, AK 99503 USA. Alaska Dept Environm Conservat, Anchorage, AK USA. US FDA, Gulf Coast Seafood Lab, Dauphin Isl, AL USA. Ctr Dis Control & Prevent, Natl Ctr Infect Dis, Atlanta, GA USA. RP McLaughlin, JB (reprint author), Alaska Dept Hlth & Social Serv, Div Publ Hlth, 3601 C St,Suite 540, Anchorage, AK 99503 USA. EM joe_mclaughlin@health.state.ak.us NR 32 TC 207 Z9 222 U1 1 U2 22 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD OCT 6 PY 2005 VL 353 IS 14 BP 1463 EP 1470 DI 10.1056/NEJMoa051594 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 970LZ UT WOS:000232313000006 PM 16207848 ER PT J AU Bhattacharya, B Cai, JL Luo, YQ Miura, T Mejido, J Brimble, SN Zeng, XM Schulz, TC Rao, MS Puri, RK AF Bhattacharya, B Cai, JL Luo, YQ Miura, T Mejido, J Brimble, SN Zeng, XM Schulz, TC Rao, MS Puri, RK TI Comparison of the gene expression profile of undifferentiated human embryonic stem cell lines and differentiating embryoid bodies SO BMC DEVELOPMENTAL BIOLOGY LA English DT Article ID IN-VITRO; MICROARRAY ANALYSIS; HUMAN BLASTOCYSTS; GROWTH-FACTORS; SELF-RENEWAL; IDENTIFICATION; PLURIPOTENCY; CLONING; MOUSE; CARDIOMYOCYTES AB Background: The identification of molecular pathways of differentiation of embryonic stem cells (heSC) is critical for the development of stem cell based medical therapies. In order to identify biomarkers and potential regulators of the process of differentiation, a high quality microarray containing 16,659 seventy base pair oligonucleotides was used to compare gene expression profiles of undifferentiated hESC lines and differentiating embryoid bodies. Results: Previously identified '' stemness '' genes in undifferentiated hESC lines showed down modulation in differentiated cells while expression of several genes was induced as cells differentiated. In addition, a subset of 194 genes showed overexpression of greater than >= 3 folds in human embryoid bodies (hEB). These included 37 novel and 157 known genes. Gene expression was validated by a variety of techniques including another large scale array, reverse transcription polymerase chain reaction, focused cDNA microarrays, massively parallel signature sequencing (MPSS) analysis and immunocytochemisty. Several novel hEB specific expressed sequence tags ( ESTs) were mapped to the human genome database and their expression profile characterized. A hierarchical clustering analysis clearly depicted a distinct difference in gene expression profile among undifferentiated and differentiated hESC and confirmed that microarray analysis could readily distinguish them. Conclusion: These results present a detailed characterization of a unique set of genes, which can be used to assess the hESC differentiation. C1 US FDA, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. Bresagen Inc, Athens, GA USA. NIA, Neurosci Lab, Baltimore, MD 21224 USA. Natl Inst Drug Abuse, NIH, Bethesda, MD 20892 USA. RP Puri, RK (reprint author), US FDA, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. EM Bhattacharya@cber.fda.gov; CaiJi@grc.nia.nih.gov; LuoYo@grc.nia.nih.gov; miurat@grc.nia.nih.gov; jmejido@niaid.nih.gov; sbrimble@novocell.com; Xzeng@intra.nida.nih.gov; tjschulz@novocell.com; raomah@grc.nia.nih.gov; puri@cber.fda.gov NR 44 TC 83 Z9 86 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-213X J9 BMC DEV BIOL JI BMC Dev. Biol. PD OCT 5 PY 2005 VL 5 AR 22 DI 10.1186/1471-213X-5-22 PG 16 WC Developmental Biology SC Developmental Biology GA 997WR UT WOS:000234280000001 PM 16207381 ER PT J AU Amat, A Rigau, J Waynant, RW Ilev, IK Tomas, J Anders, JJ AF Amat, A Rigau, J Waynant, RW Ilev, IK Tomas, J Anders, JJ TI Modification of the intrinsic fluorescence and the biochemical behavior of ATP after irradiation with visible and near-infrared laser light SO JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY LA English DT Article DE ATP; Michaelis-Menten enzymatic kinetics; hexokinase; fluorescence; laser ID HELIUM-NEON LASER; GLUCOKINASE; HEXOKINASE; MECHANISMS; SENSITIVITY; ADENINE; MUSCLE AB In this work, the effects of visible (655 nm) and near-infrared (830 nm) light on ATP in solution were examined. The addition of irradiated ATP to the hexokinase reaction caused significant differences in the reaction rates and in the Michaelis-Menten kinetic parameters, k(m) and v(max)., Irradiated ATP cleavage by hexokinase occurred in less time. Changes were wavelength and dose dependent. Excitation of ATP with a 260 nm wavelength ultraviolet light induced a fluorescence emission that was decreased when Mg2+ was added due to ion binding of the phosphates, which are the structures that modify the fluorescence produced by the adenine dipoles. The irradiation of this ATP (.) Mg2+ solution using 655 and 830 nm light increased the fluorescence by a possible displacement of Mg2+ from the phosphates. In conclusion, visible and near-infrared light modifies the biochemical behavior of ATP in the hexokinase reaction and the fluorescence intensity of the molecule thus altering the Mg2+ binding strength to the oxygen atoms in the phosphate group. (c) 2005 Elsevier B.V. All rights reserved. C1 Univ Rovira & Virgili, Fac Med & Hlth Sci, Histol & Neurobiol Unit, E-43201 Reus, Spain. US FDA, Ctr Devices & Radiol Hlth, Div Phys, Rockville, MD 20857 USA. Uniformed Serv Univ Hlth Sci, Dept Anat Physiol & Genet, Bethesda, MD 20814 USA. RP Amat, A (reprint author), Univ Rovira & Virgili, Fac Med & Hlth Sci, Histol & Neurobiol Unit, C St Llorenc 21, E-43201 Reus, Spain. EM albert.amat@urv.net NR 23 TC 33 Z9 34 U1 0 U2 2 PU ELSEVIER SCIENCE SA PI LAUSANNE PA PO BOX 564, 1001 LAUSANNE, SWITZERLAND SN 1011-1344 J9 J PHOTOCH PHOTOBIO B JI J. Photochem. Photobiol. B-Biol. PD OCT 3 PY 2005 VL 81 IS 1 BP 26 EP 32 DI 10.1016/j.jphotobiol.2005.05.012 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 971LC UT WOS:000232384500004 PM 16107316 ER PT J AU Burns, RE Emerson, JE McElroy, GB AF Burns, RE Emerson, JE McElroy, GB TI An economical and effective spray device for application of liquids to beehives SO AMERICAN BEE JOURNAL LA English DT Article C1 FDACS, Div Plant Ind, Gainesville, FL 32614 USA. RP Burns, RE (reprint author), FDACS, Div Plant Ind, POB 147100, Gainesville, FL 32614 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU DADANT & SONS INC PI HAMILTON PA AMER BEE JOURNAL, HAMILTON, IL 62341 USA SN 0002-7626 J9 AM BEE J JI Am. Bee J. PD OCT PY 2005 VL 145 IS 10 BP 803 EP 804 PG 2 WC Entomology SC Entomology GA 967NW UT WOS:000232098900005 ER PT J AU Busse, WW Wanner, A Adams, K Reynolds, HY Castro, M Chowdhury, B Kraft, M Levine, RJ Peters, SP Sullivan, EJ AF Busse, WW Wanner, A Adams, K Reynolds, HY Castro, M Chowdhury, B Kraft, M Levine, RJ Peters, SP Sullivan, EJ TI Investigative bronchoprovocation and bronchoscopy in airway diseases SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Review DE airway hyperresponsiveness; asthma; bronchoalveolar lavage; chronic obstructive pulmonary disease; lidocaine; methacholine; segmental allergen challenge ID BRONCHOALVEOLAR LAVAGE FLUID; OBSTRUCTIVE PULMONARY-DISEASE; SEGMENTAL ALLERGEN CHALLENGE; LATE ASTHMATIC RESPONSES; CYSTIC-FIBROSIS; FLEXIBLE BRONCHOSCOPY; BRONCHIAL HYPERRESPONSIVENESS; ANTIGEN CHALLENGE; CELL PROFILES; FIBEROPTIC BRONCHOSCOPY AB Rationale: Basic and clinical research strategies used for many lung diseases have depended on volunteer subjects undergoing bronchoscopy to establish access to the airways to collect biological specimens and tissue, perhaps with added bronchoprovocation in asthma syndromes. These procedures have yielded a wealth of important scientific information. Since the last critical review more than a decade ago, some of the techniques and applications have changed, and untoward events have occurred, raising safety concerns and increasing institutional review scrutiny. Objectives and Methods: To reappraise these investigational methods in the context of current knowledge, the National Heart, Lung, and Blood Institute and the National Institute of Allergy and Infectious Diseases of the National Institutes of Health convened a working group to review these procedures used for airway disease research, emphasizing asthma and chronic obstructive pulmonary disease. Main Results: The group reaffirmed the scientific importance of investigative bronchoscopy and bronchoprovocation, even as less invasive technologies evolve. The group also considered the safety of bronchoscopy and bronchoprovocation with methacholine and, antigen to be acceptable for volunteer subjects and patients, but stressed the need to monitor this closely and to emphasize proper training of participating medical research personnel. Issues were raised about vulnerable volunteers, especially children who need surrogates for informed consent. Conclusion: This review of investigative bronchoscopy and bronchoprovocation could serve as the basis for future guidelines for the use of these procedures in the United States. C1 NHLBI, DLD, Bethesda, MD 20892 USA. Univ Wisconsin, Madison, WI USA. NIAID, Bethesda, MD USA. US FDA, Rockville, MD USA. Washington Univ, Sch Med, St Louis, MO USA. Natl Jewish Med & Res Ctr, Denton, CO USA. Yale Univ, Sch Med, New Haven, CT USA. Wake Forest Univ, Hlth Sci, Winston Salem, NC USA. Miami Univ, Sch Med, Miami, FL USA. RP Reynolds, HY (reprint author), NHLBI, DLD, 2 Rockledge Ctr,6701 Rockledge Dr, Bethesda, MD 20892 USA. EM reynoldh@mail.nih.gov NR 111 TC 48 Z9 50 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 61 BROADWAY, FL 4, NEW YORK, NY 10006 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD OCT 1 PY 2005 VL 172 IS 7 BP 807 EP 816 DI 10.1164/rccm.200407-966WS PG 10 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 967UD UT WOS:000232115800006 PM 16020805 ER PT J AU Winthrop, KL Siegel, JN Jereb, J Taylor, Z Iademarco, MF AF Winthrop, KL Siegel, JN Jereb, J Taylor, Z Iademarco, MF TI Tuberculosis associated with therapy against tumor necrosis factor alpha SO ARTHRITIS AND RHEUMATISM LA English DT Editorial Material ID EARLY RHEUMATOID-ARTHRITIS; CONTROLLED-TRIAL; METHOTREXATE; INFLIXIMAB; ETANERCEPT; COMBINATION; MANAGEMENT; INHIBITORS; INFECTION; PLACEBO C1 US FDA, CDER, ODE VI, DTBIMP, Rockville, MD 20857 USA. Ctr Dis Control & Prevent, Atlanta, GA USA. Calif Dept Hlth Serv, Sacramento, CA USA. RP Siegel, JN (reprint author), US FDA, CDER, ODE VI, DTBIMP, HFD-108,5600 Fishers Lane, Rockville, MD 20857 USA. EM siegelj@cber.fda.gov NR 29 TC 68 Z9 71 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD OCT PY 2005 VL 52 IS 10 BP 2968 EP 2974 DI 10.1002/art.21382 PG 7 WC Rheumatology SC Rheumatology GA 973UT UT WOS:000232548800003 PM 16200576 ER PT J AU Lawrence, J AF Lawrence, J TI Some remarks about the analysis of active control studies SO BIOMETRICAL JOURNAL LA English DT Article DE meta-analysis; interim analysis ID TRIALS; DESIGN AB In an active-controlled trial, the experimental treatment can be declared to be non-inferior to the control if the confidence interval for the difference excludes a fixed pre-specified margin. Recently, some articles have discussed an alternative method where the data from the current study and placebo-controlled studies for the active control are combined together into a single test statistic to test whether a fixed fraction of the effect of the active control is preserved. It has been shown that, conditional on nuisance parameters from the active-controlled study, a fixed margin can be defined that will be operationally equivalent to this latter method. In this article, we will discuss statistical properties associated with these approaches. Specifically, the interim monitoring boundaries and level of evidence will be considered. C1 US FDA, Div Biometr 1, OB, CDER, Rockville, MD 20857 USA. RP Lawrence, J (reprint author), US FDA, Div Biometr 1, OB, CDER, HFD-710,15B-45,5600 Fishers Lane, Rockville, MD 20857 USA. EM lawrencej@cder.fda.gov NR 7 TC 11 Z9 11 U1 0 U2 0 PU AKADEMIE VERLAG GMBH PI BERLIN PA PALISADENSTR 40, D-10243 BERLIN, GERMANY SN 0323-3847 J9 BIOMETRICAL J JI Biom. J. PD OCT PY 2005 VL 47 IS 5 BP 616 EP 622 DI 10.1002/bimj.200410145 PG 7 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 979BK UT WOS:000232916900002 PM 16385902 ER PT J AU Bolton, G Cabatingan, M Rubino, M Lute, S Brorson, K Bailey, M AF Bolton, G Cabatingan, M Rubino, M Lute, S Brorson, K Bailey, M TI Normal-flow virus filtration: detection and assessment of the endpoint in bioprocessing SO BIOTECHNOLOGY AND APPLIED BIOCHEMISTRY LA English DT Article DE bioprocessing; log (reduction value); murine minute virus; normal flow virus filtration; pore-plugging model; virus break-through ID MEMBRANE-FILTER; HUMAN-IGG; INACTIVATION; PLASMA; PERFORMANCE; PARTICLES; PROTEINS; REMOVAL; FLUIDS AB The breakthrough of a model virus, bacteriophage, Phi X-174, through normal-flow virus filters was studied using both commercial process fluids and model feedstreams. The results indicate that (i) Phi X-174 is a reasonable model for a mammalian parvovirus [MMV (murine minute virus)] in virus filtration studies; (ii) Phi X-174 LRV [log (reduction value)] shows a better correlation with percentage flow decline compared with volume processed under a variety of conditions; (iii) although the extent of decline in virus LRV is dependent on the mechanism of filter fouling, the fouling mechanisms operative in a viral validation study are representative of those likely to be found under actual production conditions. The mechanism of LRV decline by many process streams was proposed to be due to selective plugging of small pores. A theoretical model as well as a predictive equation for LRV decline versus flow decay was derived; experimental results from filtration studies using pore-plugging feedstocks were consistent with the equation. As protein solutions may vary in their adsorptive versus plugging behaviour during filtration, an evaluation of the LRV-versus-flow-decay relationship on a biopharmaceutical-product-specific basis may be warranted. C1 Eli Lilly & Co, Indianapolis, IN 46285 USA. Millipore Corp, Billerica, MA 01821 USA. US FDA, Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. RP Bolton, G (reprint author), Eli Lilly & Co, 307 E McCarty St, Indianapolis, IN 46285 USA. EM Bailey_mr@lilly.com NR 21 TC 42 Z9 43 U1 0 U2 8 PU PORTLAND PRESS LTD PI LONDON PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND SN 0885-4513 J9 BIOTECHNOL APPL BIOC JI Biotechnol. Appl. Biochem. PD OCT PY 2005 VL 42 BP 133 EP 142 DI 10.1042/BA20050056 PN 2 PG 10 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 974IF UT WOS:000232584100004 PM 15901236 ER PT J AU Anderson, LW Collins, JM Klecker, RW Katki, AG Parchment, RE Boinpally, RR LoRusso, PM Ivy, SP AF Anderson, LW Collins, JM Klecker, RW Katki, AG Parchment, RE Boinpally, RR LoRusso, PM Ivy, SP TI Metabolic profile of XK469 (2(R)-[4-(7-chloro-2-quinoxalinyl)oxyphenoxy]-propionic acid; NSC698215) in patients and in vitro: low potential for active or toxic metabolites or for drug-drug interactions SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE NSC698215; metabolites; drug-drug interactions ID ALDEHYDE OXIDASE ACTIVITY; HUMAN LIVER; BIOLOGICAL EVALUATION; ANTITUMOR AGENT; GUINEA-PIG; RAT-LIVER; ZALEPLON; PHARMACOKINETICS; INHIBITION; OXIDATION AB As part of an ongoing phase 1 study, we studied the excretion of XK469 and its metabolism in patients and in vitro. Five primary metabolites were identified by HPLC/MS/MS. An oxidized product formed by cytosolic aldehyde oxidase was the predominant species both in urine and human hepatocytes in vitro. Conjugates of XK469 with glycine, taurine, and glucuronic acid, as well as the microsomal product, 4-oxo-XK469, were also found in urine and in vitro, but none were major contributors to the mass balance for XK469 elimination. Based upon the relative concentrations circulating in plasma, systemic exposure to parent drug was 100-fold higher than for the metabolites. Thus, both toxicity and efficacy of XK469 are most likely to be produced by the parent molecule, rather than the metabolites. Urinary recovery of parent drug was low (2% of dose in 24 h), partly because of the long half-life of XK469 (approximately 3 days). In addition, the metabolite profile in urine indicates that only 25% of the XK469-derived material was unchanged drug. Thus, urinary excretion was not a major factor in XK469 elimination. Variations in systemic exposure to XK469 will be strongly influenced by factors that alter the activity of aldehyde oxidase, including pharmacogenetics, enzyme inhibition, and enzyme induction, but no specific modifiers have been reported. The multiday half-life of XK469 hampered our ability to obtain a complete mass balance, and the possibility exists that other routes, such as biliary excretion, may also play a substantial role in XK469 disposition. C1 US FDA, Lab Clin Pharmacol, Silver Spring, MD 20993 USA. Wayne State Univ, Karmanos Canc Ctr, Detroit, MI USA. NCI, Canc Therapy Evaluat Program, Rockville, MD USA. RP Anderson, LW (reprint author), US FDA, Lab Clin Pharmacol, WO Bldg 64,Rm 2014,10903 New Hampshire Ave,HFD-90, Silver Spring, MD 20993 USA. EM ANDERSONL@cder.fda.gov FU NCI NIH HHS [U01-CA062487] NR 24 TC 9 Z9 9 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD OCT PY 2005 VL 56 IS 4 BP 351 EP 357 DI 10.1007/s00280-004-0962-3 PG 7 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 950CK UT WOS:000230835000004 PM 15895233 ER PT J AU Beland, FA Marques, MM da Costa, GG Phillips, DH AF Beland, FA Marques, MM da Costa, GG Phillips, DH TI Tamoxifen - DNA adduct formation in human endometrium SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Letter ID ALPHA-HYDROXYTAMOXIFEN; IDENTIFICATION; RAT; EXPLANTS C1 Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. Univ Tecn Lisboa, Ctr Quim Estrutural Complexo 1, Inst Super Tecn, P-1049001 Lisbon, Portugal. Inst Canc Res, Sutton SM2 5NG, Surrey, England. RP Beland, FA (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. RI Marques, M. Matilde/E-2535-2012; OI Marques, M. Matilde/0000-0002-7526-4962; Phillips, David/0000-0001-8509-3485 NR 12 TC 6 Z9 6 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD OCT PY 2005 VL 18 IS 10 BP 1507 EP 1509 DI 10.1021/tx050255w PG 3 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 976NM UT WOS:000232740300002 PM 16533012 ER PT J AU Cohen, MH Johnson, JR Pazdur, R AF Cohen, MH Johnson, JR Pazdur, R TI Food and Drug Administration drug approval summary: Temozolomide plus radiation therapy for the treatment of newly diagnosed glioblastoma multiforme SO CLINICAL CANCER RESEARCH LA English DT Article ID ADJUVANT TEMOZOLOMIDE; MALIGNANT GLIOMA; CHEMOTHERAPY; METAANALYSIS; CONCOMITANT; TRIALS AB On March 15, 2005, the U.S. Food and Drug Administration approved temozolomide (Temodar capsules, Schering-Plough Research Institute) for the treatment of adult patients with newly diagnosed glioblastoma multiforme concomitantly with radiotherapy and then as maintenance treatment. Five hundred seventy-three glioblastoma multiforme patients were randomized to = 287) or radiotherapy alone (n = 286). Patients receive either temozolomicle + radiotherapy (n mg/m(2)) in the temozolomide + radiotherapy arm received concomitant temozolomide (75 once daily for the duration of radiation therapy (42-49 days). This was followed, 4 weeks later, by six mg/m(2) cycles-of temozolomicle, 150 or 200 daily for 5 days, every 4 weeks. Patients in the control arm received radiotherapy only. In both arms, radiotherapy was delivered as 60 Gy/30 fractions to the tumor site with a 2 to 3 cm margin. Pneumocystis carinii pneumonia prophylaxis was required during temozolomide + radiotherapy treatment and was continued until recovery of lymphocytopenia (Common Toxicity Criteria grade < 1). At disease progression, temozolomide salvage treatment was given to 161 of 282 patients (57%) in the radiotherapy alone arm, and to 62 of 277 patients (22%) in the temozolomide + radiotherapy arm. Patients receiving concomitant and maintenance temozolomide + radiotherapy had significantly improved overall survival, The hazard ratio was 0.63 (95% confidence interval, 0.52-0.75; log-rank, P < 0.0001). Median survival was 14.6 months (temozolomicle + radiotherapy) versus 12.1 months (radiotherapy alone). Adverse events during temozolomide treatment included thrombocytopepia, nausea, vomiting, anorexia, constipation, alopecia, headache, fatigue, and convulsions. 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. EM cohenma@cder.fda.gov NR 12 TC 60 Z9 63 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD OCT 1 PY 2005 VL 11 IS 19 BP 6767 EP 6771 DI 10.1158/1078-0432.CCR-05-0722 PN 1 PG 5 WC Oncology SC Oncology GA 969MK UT WOS:000232238100005 PM 16203762 ER PT J AU Chen, ML AF Chen, ML TI Confounding factors for sex differences in pharmacokinetics and pharmacodynamics: Focus on dosing regimen, dosage form, and formulation SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Editorial Material ID SUSTAINED-RELEASE VERAPAMIL; CYTOCHROME-P450 3A ACTIVITY; GENDER-RELATED DIFFERENCES; P-GLYCOPROTEIN; GASTROINTESTINAL TRANSIT; HEALTHY-SUBJECTS; ACETYLSALICYLIC-ACID; TIRILAZAD CLEARANCE; MENSTRUAL-CYCLE; HUMAN LIVER C1 US FDA, Ctr Drug Evaluat & Res, Off Pharmaceut Sci, Rockville, MD 20857 USA. RP Chen, ML (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Pharmaceut Sci, HFD-003,5600 Fishers Ln, Rockville, MD 20857 USA. EM chenme@cder.fda.gov NR 77 TC 15 Z9 18 U1 0 U2 3 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD OCT PY 2005 VL 78 IS 4 BP 322 EP 329 DI 10.1016/j.clpt.2005.06.012 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 971KY UT WOS:000232384100003 PM 16198651 ER PT J AU Seed, J Carney, EW Corley, RA Crofton, KM DeSesso, JM Foster, PMD Kavlock, R Kimmel, G Klaunig, J Meek, ME Preston, RJ Slikker, W Tabacova, S Williams, GM Wiltse, J Zoeller, RT Fenner-Crisp, P Patton, DE AF Seed, J Carney, EW Corley, RA Crofton, KM DeSesso, JM Foster, PMD Kavlock, R Kimmel, G Klaunig, J Meek, ME Preston, RJ Slikker, W Tabacova, S Williams, GM Wiltse, J Zoeller, RT Fenner-Crisp, P Patton, DE TI Overview: Using mode of action and life stage information to evaluate the human relevance of animal toxicity data SO CRITICAL REVIEWS IN TOXICOLOGY LA English DT Review DE developmental window; human relevance framework; noncancer modes of action; risk assessment ID FRAMEWORK AB A complete mode of action human relevance analysis-as distinct from mode of action (MOA) analysis alone-depends on robust information on the animal MOA, as well as systematic comparison of the animal data with corresponding information from humans. In November 2003, the International Life Sciences Institute's Risk Science Institute (ILSI RSI) published a 2-year study using animal and human MOA information to generate a four-part Human Relevance Framework (HRF) for systematic and transparent analysis of MOA data and information. Based mainly on non-DNA-reactive carcinogens, the HRF features a "concordance" analysis of MOA information from both animal and human sources, with a focus on determining the appropriate role for each MOA data set in human risk assessment. With MOA information increasingly available for risk assessment purposes, this article illustrates the further applicability of the HRF for reproductive, developmental, neurologic, and renal endpoints, as well as cancer. Based on qualitative and quantitative MOA considerations, the MOA/human relevance analysis also contributes to identifying data needs and issues essential for the dose-response and exposure assessment steps in the overall risk assessment. C1 US EPA, Washington, DC 20460 USA. Dow Chem Co USA, Midland, MI 48674 USA. Pacific NW Natl Lab, Richland, WA 99352 USA. US EPA, Res Triangle Pk, NC 27711 USA. Mitretek Syst, Falls Church, VA USA. NIEHS, Res Triangle Pk, NC 27709 USA. Indiana Univ, Sch Med, Indianapolis, IN USA. Hlth Canada, Ottawa, ON K1A 0L2, Canada. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. US FDA, Rockville, MD 20857 USA. New York Med Coll, Valhalla, NY 10595 USA. RP Patton, DE (reprint author), ILSI Risk Sci Inst, 1 Thomas Circle NW, Washington, DC 20005 USA. EM dpatton@ilsi.org RI Crofton, Kevin/J-4798-2015 OI Crofton, Kevin/0000-0003-1749-9971 NR 7 TC 48 Z9 50 U1 0 U2 4 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1040-8444 J9 CRIT REV TOXICOL JI Crit. Rev. Toxicol. PD OCT-NOV PY 2005 VL 35 IS 8-9 BP 663 EP 672 DI 10.1080/10408440591007133 PG 10 WC Toxicology SC Toxicology GA 993UH UT WOS:000233980100001 ER PT J AU Slikker, W Xu, ZA Levin, ED Slotkin, TA AF Slikker, W Xu, ZA Levin, ED Slotkin, TA TI Mode of action: Disruption of brain cell replication, second messenger, and neurotransmitter systems during development leading to cognitive dysfunction - Developmental neurotoxicity of nicotine SO CRITICAL REVIEWS IN TOXICOLOGY LA English DT Review DE cell signaling; human relevance; neurobehavioral dysfunction; neuroteratogen; neurotransmission; nicotine; nicotinic cholinergic receptor ID INFANT-DEATH-SYNDROME; C-FOS EXPRESSION; PRENATAL EXPOSURE; FETAL NICOTINE; NEONATAL-RAT; ORNITHINE-DECARBOXYLASE; CATECHOLAMINE SYSTEMS; PROTECTIVE RESPONSES; TRANSDERMAL NICOTINE; DOPAMINERGIC SYSTEM AB Developmental exposure to nicotine in rats results in neurobehavioral effects such as reduced locomotor and cognitive function. Key events in the animal mode of action (MOA) include binding to the nicotinic cholinergic receptor during prenatal and/or early postnatal development. This leads to premature onset of cell differentiation at the expense of cell replication, which leads to brain cell death or structural alterations in regional brain areas. Other events include an initial increase followed by a decrease in adenyl cyclase activity, as well as effects on the noradrenergic, dopaminergic, and serotonergic neurotransmitter systems. Because the nicotine receptor is also present in the developing human brain and the underlying biology for DNA synthesis and cell signaling is comparable, this MOA is likely to be relevant for humans. Although the effects of nicotine exposure in developing humans is not well documented, nicotine exposure as a result of cigarette smoking during pregnancy is associated with several physiological and behavioral outcomes that are reminiscent of the effects of nicotine alone in animal models. As data become available with the advent of the use of the nicotine patch in pregnant humans, the question as to the relative importance of smoking per se versus nicotine alone may be determined. C1 Natl Ctr Toxicol Res, Div Neurotoxicol, FDA, Jefferson, AR 72079 USA. Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC 27706 USA. Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Durham, NC 27706 USA. RP Slikker, W (reprint author), Natl Ctr Toxicol Res, Div Neurotoxicol, FDA, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM wslikker@nctr.fda.gov NR 74 TC 54 Z9 54 U1 4 U2 5 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1040-8444 J9 CRIT REV TOXICOL JI Crit. Rev. Toxicol. PD OCT-NOV PY 2005 VL 35 IS 8-9 BP 703 EP 711 DI 10.1080/10408440591007421 PG 9 WC Toxicology SC Toxicology GA 993UH UT WOS:000233980100005 PM 16417037 ER PT J AU Tabacova, S AF Tabacova, S TI Mode of action: Angiotensin-converting enzyme inhibition - Developmental effects associated with exposure to ACE inhibitors SO CRITICAL REVIEWS IN TOXICOLOGY LA English DT Review DE ACEI fetopathy; animal-human prenatal development; congenital abnormalities; critical exposure timing; human relevance; renin-angiotensin system ID NEONATAL RENAL-FAILURE; UTERINE BLOOD-FLOW; PREGNANCY-INDUCED HYPERTENSION; ENALAPRIL MALEATE; RENIN SECRETION; RHESUS MACAQUES; ADULT SHEEP; FETAL; KIDNEY; RATS AB Relative to species tested in laboratory studies, the human fetus displays higher vulnerability to enalapril and other angiotensin-converting enzyme inhibitors (ACEI) exhibiting a malformative syndrome that does not appear to have a similar counterpart in experimental animals. An important reason for this higher vulnerability is the earlier intrauterine development of the kidney and the renin-angiotensin-aidosterone (RAS) system in humans, organ systems that are specific targets of ACEI's pharmacological effect. In humans, these systems begin developing prior to the onset of skeletal ossification at the end of the first trimester, with continuing vulnerability throughout the pregnancy. In most animal species tested, these target systems develop close to term, when the fetus is relatively more mature and less vulnerable to the effects of developmental toxicants. For this reason, animal studies that follow standard protocols and evaluate developmental toxicity only for exposures during embryogenesis will miss developmental effects arising secondary to disruption of target systems that develop after the period of major organogenesis. Thus, although the animal mode of action (MOA) for enalapril and other ACEI is plausible in humans, differences in the timing of development of critical target organ systems, particularly the renal system and RAS, explain the absence of definitive structural abnormalities in test animals. C1 US FDA, Rockville, MD 20852 USA. RP Tabacova, S (reprint author), US FDA, 1451 Rockville Pike,Room 4047, Rockville, MD 20852 USA. EM tabacovas@cder.fda.gov NR 73 TC 16 Z9 18 U1 1 U2 3 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1040-8444 J9 CRIT REV TOXICOL JI Crit. Rev. Toxicol. PD OCT-NOV PY 2005 VL 35 IS 8-9 BP 747 EP 755 DI 10.1080/10408440591007160 PG 9 WC Toxicology SC Toxicology GA 993UH UT WOS:000233980100010 PM 16417042 ER PT J AU Farshid, M Taffs, RE Scott, D Asher, DM Brorson, K AF Farshid, M Taffs, RE Scott, D Asher, DM Brorson, K TI The clearance of viruses and transmissible spongiform encephalopathy agents from biologicals SO CURRENT OPINION IN BIOTECHNOLOGY LA English DT Review ID ANION-EXCHANGE CHROMATOGRAPHY; PLASMA PRODUCTS; BLOOD-PRODUCTS; TSE AGENTS; INACTIVATION; REMOVAL; PROTEIN; TRANSFUSION; PERFORMANCE; REDUCTION AB The viral and transmissible spongiform encephalopathy (TSE) safety of therapeutics of biological origin (biologicals) is greatly influenced by the nature and degree of variability of the source material and by the mode of purification. Plasma-derived and recombinant DNA products currently have good viral safety records, but challenges remain. In general, large enveloped viruses are easier to remove from biologicals than small 'naked' viruses. Monoclonal antibodies and recombinant DNA biopharmaceuticals are derived from relatively homogeneous source materials and purified by multistep schemes that are robust and amenable to scientific analysis and engineering improvement. Viral clearance is more challenging for blood and cell products, as they are complex and labile. Source selection (e.g. country of origin, deferral for CJD risk factors) currently occupies the front line for ensuring that biologicals are free of TSE agents, but robust methods for their clearance from products are under development. C1 US FDA, Res & Off Biotechnol Prod, Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. US FDA, Off Blood Res & Review, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Brorson, K (reprint author), US FDA, Res & Off Biotechnol Prod, Ctr Drug Evaluat & Res, 29 Lincoln Dr, Bethesda, MD 20892 USA. EM kurt.brorson@fda.hhs.go NR 37 TC 23 Z9 23 U1 0 U2 5 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0958-1669 J9 CURR OPIN BIOTECH JI Curr. Opin. Biotechnol. PD OCT PY 2005 VL 16 IS 5 BP 561 EP 567 DI 10.1016/j.copbio.2005.07.006 PG 7 WC Biochemical Research Methods; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 976FJ UT WOS:000232718000014 PM 16095899 ER PT J AU Misbin, RI AF Misbin, RI TI Evaluating the safety of diabetes drugs - Perspective of a food and drug administration insider SO DIABETES CARE LA English DT Editorial Material ID LACTIC-ACIDOSIS; HEPATIC-FAILURE; HEART-FAILURE; METFORMIN; THIAZOLIDINEDIONES; OUTCOMES C1 US FDA, Div Endocrine & Metab Drug Prod, Rockville, MD 20857 USA. RP Misbin, RI (reprint author), 5727 Crawford Dr, Rockville, MD 20851 USA. EM misbinr@cder.fda.gov NR 30 TC 6 Z9 6 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD OCT PY 2005 VL 28 IS 10 BP 2573 EP 2576 DI 10.2337/diacare.28.10.2573 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 971CO UT WOS:000232358900043 PM 16186303 ER PT J AU Cui, Y Churchwell, MI Couch, LH Doerge, DR Howard, PC AF Cui, Y Churchwell, MI Couch, LH Doerge, DR Howard, PC TI Metabolism of pigment yellow 74 by rat and human microsomal proteins SO DRUG METABOLISM AND DISPOSITION LA English DT Article ID CARCINOGENIC O-ANISIDINE; AZO DYES; DRUG-METABOLISM; TATTOO PIGMENTS; HUMAN SKIN; DNA; CYTOCHROME-P-450; HEPATITIS; LIVER; ACTIVATION AB Pigment Yellow 74 (PY74) is a monoazo pigment that is used in yellow tattoo inks. The metabolism of PY74 was investigated using rat liver and human liver microsomes and expressed human cytochromes P450 (P450s). Two phase I metabolites were isolated and characterized by mass spectrometry and NMR techniques. One metabolite (PY74-M1) was a ring hydroxylation product of PY74, 2-((2-methoxy-4-nitrophenyl) azo)-N-(2-methoxy-4-hydroxyphenyl)3- oxobutanamide. The second metabolite (PY74-M2) was identified as 2-(( 2-hydroxy-4-nitrophenyl) azo)-N-( 2-methoxy-4- hydroxyphenyl)3- oxobutanamide, which is the O-demethylation product of PY74-M1. These metabolites were formed by in vitro incubations of PY74 with 3-methylcholanthrene-induced rat liver microsomes and to a much lesser extent by liver microsomes from untreated or phenobarbital-induced rats. The role for CYP1A in the metabolism of PY74 was confirmed using expressed human P450s. The catalytic ability of the P450s for metabolism of PY74 was CYP 1A2 > CYP 1A1 > CYP 3A4 approximate to CYP 1B1 ( no activity with CYP 2B6, 2C9, 2D6 or 2E1). The metabolism of PY74-M1 to PY74-M2 was catalyzed only by CYP 1A2 and CYP 1A1 ( no activity from CYP 1B1, 2B6, 2C9, 2D6, 2E1, or 3A4). These results demonstrate that the tattoo pigment PY74 is metabolized in vitro by P450 to metabolites that should be available for phase II metabolism and excretion. C1 US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. US FDA, Natl Toxicol Program Ctr Phototoxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, HFT-110,3900 NCTR Rd, Jefferson, AR 72079 USA. EM Phoward@nctr.fda.gov NR 38 TC 8 Z9 8 U1 2 U2 4 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0090-9556 EI 1521-009X J9 DRUG METAB DISPOS JI Drug Metab. Dispos. PD OCT PY 2005 VL 33 IS 10 BP 1459 EP 1465 DI 10.1124/dmd.104.003285 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 964PH UT WOS:000231892500008 PM 16014769 ER PT J AU Cheeseman, MA AF Cheeseman, MA TI Thresholds as a unifying theme in regulatory toxicology SO FOOD ADDITIVES AND CONTAMINANTS LA English DT Article; Proceedings Paper CT 3rd International Symposium on Food Packaging - Ensuring the Safety, Quality and Traceability of Foods CY NOV 17-19, 2005 CL Barcelona, SPAIN SP Public Hlth Agcy Barcelona, Res Inst Engn, Int Life Sci Inst, European Commiss DE threshold of regulation; threshold of regulation (TOR); computational toxicology; genetic toxicity tests; MULTICASE AB The scientific basis for the US Food and Drug Administration (FDA) threshold of regulation is discussed in relation to its toxicological testing recommendations for food contact substances and the existing methods it employs for exposure estimation. A case is made that the FDA's threshold of regulation is a natural extension of its toxicity testing regime. The genetic toxicity tests recommended in the exposure-based toxicological testing framework for food contact substances are examined regarding their ability to predict positively carcinogens of varying potency. In addition, the computational toxicology program MULTICASE v. 3.1 is also examined for its ability to predict positively carcinogens of varying potency. It is concluded that MULTICASE can provide equivalent results to genetic toxicity tests at the lowest dietary concentrations. C1 US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Cheeseman, MA (reprint author), US FDA, Ctr Food Safety & Appl Nutr, HFS 275,5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM Mitchell.Cheeseman@FDA.Gov NR 10 TC 9 Z9 9 U1 0 U2 2 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0265-203X J9 FOOD ADDIT CONTAM JI Food Addit. Contam. PD OCT PY 2005 VL 22 IS 10 BP 900 EP 906 DI 10.1080/02652030500150143 PG 7 WC Chemistry, Applied; Food Science & Technology; Toxicology SC Chemistry; Food Science & Technology; Toxicology GA 984ID UT WOS:000233295600002 PM 16227175 ER PT J AU Begley, TH White, K Honigfort, P Twaroski, ML Neches, R Walker, RA AF Begley, TH White, K Honigfort, P Twaroski, ML Neches, R Walker, RA TI Perfluorochemicals: Potential sources of and migration from food packaging SO FOOD ADDITIVES AND CONTAMINANTS LA English DT Article; Proceedings Paper CT 3rd International Symposium on Food Packaging - Ensuring the Safety, Quality and Traceability of Foods CY NOV 17-19, 2005 CL Barcelona, SPAIN SP Public Hlth Agcy Barcelona, Res Inst Engn, Int Life Sci Inst, European Commiss DE perfluorochemicals; perfluorooctanoic acid; perfluoro telomers; food packaging; migration ID PERFLUOROOCTANOIC ACID; FLUOROCHEMICALS; POPULATION; MECHANISMS; SULFONATE; BLOOD; RATS AB Perfluorochemicals are widely used in the manufacturing and processing of a vast array of consumer goods, including electrical wiring, clothing, household and automotive products. Furthermore, relatively small quantities of perfluorochemicals are also used in the manufacturing of food-contact substances that represent potential sources of oral exposure to these chemicals. The most recognizable products to consumers are the uses of perfluorochemicals in non-stick coatings (polytetrafluoroethylene (PTFE)) for cookware and also their use in paper coatings for oil and moisture resistance. Recent epidemiology studies have demonstrated the presence of two particular perfluorochemicals, perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) in human serum at very low part per billion levels. These perfluorochemicals are biopersistent and are the subject of numerous studies investigating the many possible sources of human exposure. Among the various uses of these two chemicals, PFOS is a residual impurity in some paper coatings used for food contact and PFOA is a processing aid in the manufacture of PTFE used for many purposes including non-stick cookware. Little information is available on the types of perfluoro chemicals that have the potential to migrate from perfluoro coatings into food. One obstacle to studying migration is the difficulty in measuring perfluorochemicals by routine conventional analytical techniques such as GC/MS or LC-UV. Many perfluorochemicals used in food-contact substances are not detectable by these conventional methods. As liquid chromatography-mass spectrometry (LC/MS) develops into a routine analytical technique, potential migrants from perfluoro coatings can be more easily characterized. In this paper, data will be presented on the types of perfluoro chemicals that are used in food packaging and cookware. Additionally, research will be presented on the migration or potential for migration of these chemicals into foods or food simulating liquids. Results from migration tests show mg kg(-1) amounts of perfluoro paper additives/coatings transfer to food oil. Analysis of PTFE cookware shows residual amounts of PFOA in the low mu g kg(-1) range. PFOA is present in microwave popcorn bag paper at amounts as high as 300 mu g kg(-1). C1 US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. Univ Maryland, Dept Chem & Biochem, College Pk, MD 20742 USA. RP Begley, TH (reprint author), US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. EM tbegley@cfsan.fda.gov NR 21 TC 172 Z9 188 U1 16 U2 98 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0265-203X J9 FOOD ADDIT CONTAM JI Food Addit. Contam. PD OCT PY 2005 VL 22 IS 10 BP 1023 EP 1031 DI 10.1080/02652030500183474 PG 9 WC Chemistry, Applied; Food Science & Technology; Toxicology SC Chemistry; Food Science & Technology; Toxicology GA 984ID UT WOS:000233295600015 PM 16227186 ER PT J AU Shin, EC Seifert, U Rice, C Feinstone, S Kloetzel, PM Rehermann, B AF Shin, EC Seifert, U Rice, C Feinstone, S Kloetzel, PM Rehermann, B TI Proteasomal antigen-processing is regulated by cytokines of the innate immune response in acute HCV infection SO HEPATOLOGY LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 11-15, 2005 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 NIDDK, Liver Dis Branch, NIH, Bethesda, MD USA. Humboldt Univ, Charite, Berlin, Germany. Rockefeller Univ, New York, NY 10021 USA. US FDA, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2005 VL 42 IS 4 SU 1 BP 245A EP 245A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 972VC UT WOS:000232480300121 ER PT J AU Senior, JR Guo, T Gelperin, K Temple, R AF Senior, JR Guo, T Gelperin, K Temple, R TI Toward validation of "Hy's law" by analyses of clinical trial data SO HEPATOLOGY LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 11-15, 2005 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 US FDA, HFD 030, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2005 VL 42 IS 4 SU 1 BP 515A EP 516A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 972VC UT WOS:000232480301356 ER PT J AU Donthamsetty, S Bhave, VS Mitra, MS Latendresse, JR Mehendale, HM AF Donthamsetty, S Bhave, VS Mitra, MS Latendresse, JR Mehendale, HM TI Non alcoholic steatohepatitis (NASH) sensitizes liver to hepatotoxicity. SO HEPATOLOGY LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 11-15, 2005 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 Univ Louisiana Monroe, Monroe, LA USA. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RI Latendresse, John/A-9215-2009 NR 0 TC 1 Z9 1 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2005 VL 42 IS 4 SU 1 BP 631A EP 631A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 972VC UT WOS:000232480302163 ER PT J AU Simmonds, P Bukh, J Combet, C Deleage, G Enomoto, N Feinstone, S Halfon, P Inchauspe, G Kuiken, C Maertens, G Mizokami, M Murphy, DG Okamoto, H Pawlotsky, JM Penin, FO Sablon, E Tadasu, SI Stuyver, L Thiel, HJ Viazov, S Weiner, A Widell, A AF Simmonds, P Bukh, J Combet, C Deleage, G Enomoto, N Feinstone, S Halfon, P Inchauspe, G Kuiken, C Maertens, G Mizokami, M Murphy, DG Okamoto, H Pawlotsky, JM Penin, FO Sablon, E Tadasu, SI Stuyver, L Thiel, HJ Viazov, S Weiner, A Widell, A TI Consensus proposals for a unified system of nomenclature of hepatitis C virus genotypes SO HEPATOLOGY LA English DT Article ID ENTIRE NUCLEOTIDE-SEQUENCE; COMPLETE CODING SEQUENCE; FULL-LENGTH SEQUENCE; MAJOR GENETIC GROUPS; LINE PROBE ASSAY; BLOOD-DONORS; PHYLOGENETIC ANALYSIS; PREDOMINANT GENOTYPE; ADDITIONAL SUBTYPES; VIRAL GENOTYPES AB International standardization and coordination of the nomenclature of variants of hepatitis C virus (HCV) is increasingly needed as more is discovered about the scale of HCV-related liver disease and important biological and antigenic differences that exist between variants. A group of scientists expert in the field of HCV genetic variability, and those involved in development of HCV sequence databases, the Hepatitis Virus Database (Japan), euHCVdb (France), and Los Alamos (United States), met to re-examine the status of HCV genotype nomenclature, resolve conflicting genotype or subtype names among described variants of HCV, and draw up revised criteria for the assignment of new genotypes as they are discovered in the future. A comprehensive listing of all currently classified variants of HCV incorporates a number of agreed genotype and subtype name reassignments to create consistency in nomenclature. The paper also contains consensus proposals for the classification of new variants into genotypes and subtypes, which recognizes and incorporates new knowledge of HCV genetic diversity and epidemiology. A proposal was made that HCV variants be classified into 6 genotypes (representing the 6 genetic groups defined by phylogenetic analysis). Subtype name assignment will be either confirmed or provisional, depending on the availability of complete or partial nucleotide sequence data, or remain unassigned where fewer than 3 examples of a new subtype have been described. In conclusion, these proposals provide the framework by which the HCV databases store and provide access to data on HCV, which will internationally coordinate the assignment-of-new genotypes and subtypes in the future. C1 Univ Edinburgh, Ctr Infect Dis, Edinburgh EH9 1QH, Midlothian, Scotland. NIAID, Hepatitis Viruses Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. BioSci Lyon Gerland, Inst Biol & Chin Prot, Pole Bioinformat Lyon, Lyon, France. Univ Yamanashi, Dept Internal Med 1, Yamanashi, Japan. US FDA, Div Viral Prod, Lab Hepatitis Viruses, Bethesda, MD 20014 USA. Lab Alphabio, Marseille, France. CNRS, BioMerieux, Immunotherapie Malad Infect Chron, Lyon, France. Los Alamos Natl Lab, Theoret Biol & Biophys Grp, Los Alamos, NM USA. Innogenet NV, Ghent, Belgium. Nagoya City Univ, Grad Sch Med Sci, Dept Clin Mol Informat Med, Nagoya, Aichi 467, Japan. Inst Natl Sante Publ Quebec, Lab Sante Publ Quebec, Quebec City, PQ, Canada. Jichi Med Sch, Dept Infect & Immun, Div Virol, Minami Kawachi, Tochigi, Japan. Univ Paris, Hop Henri Mondor, INSERM, Dept Virol,U635, Creteil, France. Virco BVBA, Mechelen, Belgium. Univ Giessen, Inst Virol, D-6300 Giessen, Germany. Essen Univ Hosp, Inst Virol, Essen, Germany. Chiron Corp, Emeryville, CA 94608 USA. Lund Univ, Malmo Univ Hosp, Dept Med Microbiol, Malmo, Sweden. RP Simmonds, P (reprint author), Univ Edinburgh, Ctr Infect Dis, Edinburgh EH9 1QH, Midlothian, Scotland. EM Peter.Simmonds@ed.ac.uk RI PENIN, Francois/A-7315-2008; DELEAGE, Gilbert/F-7163-2010; Okamoto, Hiroaki/H-4371-2011 OI Okamoto, Hiroaki/0000-0003-0827-0964 NR 96 TC 939 Z9 1016 U1 8 U2 47 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2005 VL 42 IS 4 BP 962 EP 973 DI 10.1002/hep.20819 PG 12 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 970XB UT WOS:000232344600025 PM 16149085 ER PT J AU Michon, F Moore, SL Kim, J Blake, MS Auzanneau, FI Johnston, BD Johnson, MA Pinto, BM AF Michon, F Moore, SL Kim, J Blake, MS Auzanneau, FI Johnston, BD Johnson, MA Pinto, BM TI Doubly branched hexasaccharide epitope on the cell wall polysaccharide of group A streptococci recognized by human and rabbit antisera SO INFECTION AND IMMUNITY LA English DT Article ID GROUP-SPECIFIC CARBOHYDRATE; FLESH-EATING BACTERIA; CONFORMATIONAL-ANALYSIS; MONOCLONAL-ANTIBODY; RHEUMATIC-FEVER; THROAT SWABS; GROUP-B; OLIGOSACCHARIDES; INFECTIONS; ANTIGEN AB A number of epitope specificities associated with the cell wall polysaccharide antigen of group A streptococci were identified in a polyclonal rabbit antiserum induced in rabbits by whole group A streptococci and in polyclonal convalescent human antisera from children that had recovered from streptococcal A infections. The identification was achieved by using a series of synthetic oligosaccharides, glycoconjugates, and bacterial polysaccharide inhibitors to inhibit the binding of the group A helical pollysaccharide to the polyclonal antisera. The exclusively dominant epitope expressed in the convalescent human antisera was the doubly branched extended helical hexasaccharide with the structure alpha-L-Rhap(1-->2)[beta-D-GlcpNAc(1-->3)]alpha-L-Rhap(1-->3)alpha-L-Rhap(1-->2)[beta-D-GlcpNAc(1-->3)]alpha-L-Rhap. The hexasaccharide epitope also bound with the highest immunoreactivity to the rabbit antiserum. In contrast, the human antisera did not show significant binding to the singly branched pentasaccharide with the structure alpha-L-Rhap(1-->2)alpha-LRhap(1-->3)alpha-L-Rhap(1-->2)[beta-D-GlcpNAc(1-->3)alpha-L-Rhap or the branched trisaccharide alpha-L-Rhap(1-->2)[beta-D-GlcpNAc(1-->3)]alpha-L-Rhap, although both these haptens bound significantly to the same rabbit antiserum, albeit with less immunoreactivity than the hexasaccharide. Inhibition studies using streptococcal group A and B rabbit antisera and the inhibitors indicated above also suggested that the group A carbohydrate, unlike the group B streptococcal polysaccharide, does not contain the disaccharide alpha-L-Rhap(1-->2)alpha-L-Rhap motif at its nonreducing chain terminus, stressing the importance of mapping the determinant specificities of these two important streptococcal subcapsular group polysaccharides to fully understand the serological relationships between group A and group B streptococci. C1 Simon Fraser Univ, Dept Chem, Burnaby, BC V5A 1S6, Canada. Baxter Vaccines, Beltsville, MD 20705 USA. US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20851 USA. RP Pinto, BM (reprint author), Simon Fraser Univ, Dept Chem, Burnaby, BC V5A 1S6, Canada. EM bpinto@sfu.ca RI Auzanneau, France-Isabelle/E-9153-2010 NR 40 TC 8 Z9 8 U1 3 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD OCT PY 2005 VL 73 IS 10 BP 6383 EP 6389 DI 10.1128/IAI.73.10.6383-6389.2005 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 967JN UT WOS:000232087600019 PM 16177309 ER PT J AU Bertholet, S Debrabant, A Afrin, F Caler, E Mendez, S Tabbara, KS Belkaid, Y Sacks, DL AF Bertholet, S Debrabant, A Afrin, F Caler, E Mendez, S Tabbara, KS Belkaid, Y Sacks, DL TI Antigen requirements for efficient priming of CD8(+) T cells by Leishmania major-infected dendritic cells SO INFECTION AND IMMUNITY LA English DT Article ID CUTANEOUS LEISHMANIASIS; CROSS-PRESENTATION; GAMMA-INTERFERON; TRYPANOSOMA-CRUZI; IN-VIVO; IMMUNITY; MACROPHAGES; MICE; RESPONSES; PATHWAY AB CD4(+) and CD8(+) T-cell responses have been shown to be critical for the development and maintenance of acquired resistance to infections with the protozoan parasite Leishmania major. Monitoring the development of immunodominant or clonally restricted T-cell subsets in response to infection has been difficult, however, due to the paucity of known epitopes. We have analyzed the potential of L. major transgenic parasites, expressing the model antigen ovalbumin (OVA), to be presented by antigen-presenting cells to OVA-specific OT-II CD4(+) or OT-I CD8(+) T cells. Truncated OVA was expressed in L. major as part of a secreted or nonsecreted chimeric protein with L. donovani 3' nucleotidase (NT-OVA). Dendritic cells (DC) but not macrophages infected with L. major that secreted NT-OVA could prime OT-I T cells to proliferate and release gamma interferon. A diminished T-cell response was observed when DC were infected with parasites expressing nonsecreted NT-OVA or with heat-killed parasites. Inoculation of mice with transgenic parasites elicited the proliferation of adoptively transferred OT-I T cells and their recruitment to the site of infection in the skin. Together, these results demonstrate the possibility of targeting heterologous antigens to specific cellular compartments in L. major and suggest that proteins secreted or released by L. major in infected DC are a major source of peptides for the generation of parasite-specific CD8(+) T cells. The ability of L. major transgenic parasites to activate OT-I CD8(+) T cells in vivo will permit the analysis of parasite-driven T-cell expansion, differentiation, and recruitment at the clonal level. C1 NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. US FDA, CBER, OBRR, Div Emerging & Transfus Transmitted Dis, Bethesda, MD 20892 USA. RP Sacks, DL (reprint author), NIAID, Parasit Dis Lab, NIH, Bldg 4,Room 126,4 Ctr Dr,MSC 0425, Bethesda, MD 20892 USA. EM dsacks@nih.gov NR 44 TC 33 Z9 33 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD OCT PY 2005 VL 73 IS 10 BP 6620 EP 6628 DI 10.1128/IAI.73.10.6620-6628.2005 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 967JN UT WOS:000232087600048 PM 16177338 ER PT J AU Neaton, JD Gray, G Zuckerman, BD Konstam, MA AF Neaton, JD Gray, G Zuckerman, BD Konstam, MA TI Key issues in end point selection for heart failure trials: Composite end points SO JOURNAL OF CARDIAC FAILURE LA English DT Article DE composite end point; clinical trial; heart failure; medical devices ID VENTRICULAR EJECTION FRACTION; CLINICAL-TRIALS; RANDOMIZED-TRIALS; MYOCARDIAL-INFARCTION; MULTIPLE OUTCOMES; THERAPY; DYSFUNCTION; MILLENNIUM; MORTALITY; ENDPOINTS AB Background: Composite outcomes are commonly used in heart failure trials. The aim of this article is to discuss the advantages and disadvantages of composite outcomes and recommend guidelines for reporting them. Examples are used to illustrate key points. Methods and Results: A workshop jointly planned by the Heart Failure Society of America and the US Food and Drug Administration was convened in April 2004. One of the panel discussions concerned the use of composite outcomes in heart failure trials. With use of composite outcomes, event rates are higher and if it is reasonable to assume that the treatment effect is similar for each component of the composite outcome, sample size will be smaller than using one of the components as the primary end point. Composites end points are difficult to interpret if effects are not similar for all components or if the effect of treatment is primarily oil a more common, less serious component of the composite. Composite outcomes typically only focus oil the first occurring event. This can lead to a substantial loss of information in some trials. When composite end points are used, data collection for all components should continue until the end of the trial so that each component call be separately evaluated. Conclusion: Composite end points should be used with caution. Additional research is need oil optimally weighting components of composite outcomes and to better using the entire event history of patients in heart failure trials. Further analyses of completed trials could be useful in this respect. C1 Univ Minnesota, Sch Publ Hlth, Div Biostat, Minneapolis, MN 55414 USA. US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. Tuft New England Med Ctr, Div Cardiol, Boston, MA USA. RP Neaton, JD (reprint author), Univ Minnesota, Sch Publ Hlth, Div Biostat, 2221 Univ Ave SE,Room 200, Minneapolis, MN 55414 USA. NR 48 TC 53 Z9 56 U1 0 U2 3 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD OCT PY 2005 VL 11 IS 8 BP 567 EP 575 DI 10.1016/j.cardfail.2005.08.350 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 981MR UT WOS:000233093200001 PM 16230258 ER PT J AU Anderson, KC Pazdur, R Farrell, AT AF Anderson, KC Pazdur, R Farrell, AT TI Development of effective new treatments for multiple myeloma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID PROTEASOME INHIBITOR PS-341; PHASE-I TRIAL; MALIGNANCIES; BORTEZOMIB; GROWTH C1 Dana Farber Canc Inst, Div Hematol Neoplasia, Boston, MA 02115 USA. US FDA, Off Oncol Drug Prod, Rockville, MD 20857 USA. US FDA, Div Oncol Drug Prod, Rockville, MD 20857 USA. RP Anderson, KC (reprint author), Dana Farber Canc Inst, Div Hematol Neoplasia, Boston, MA 02115 USA. EM kenneth_anderson@dfci.harvard.edu NR 13 TC 13 Z9 15 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD OCT 1 PY 2005 VL 23 IS 28 BP 7207 EP 7211 DI 10.1200/JCO.2005.02.4950 PG 5 WC Oncology SC Oncology GA 969KC UT WOS:000232232000049 PM 16145064 ER PT J AU Ho, C Jensen, D Lacy, F Muni, N Reilly, S Mallis, E AF Ho, C Jensen, D Lacy, F Muni, N Reilly, S Mallis, E TI Use of standards in the review of medical devices SO JOURNAL OF ELECTROCARDIOLOGY LA English DT Article; Proceedings Paper CT 30th Annual Conference of the International-Society-for-Computerized-Electrocardiology CY APR 12-17, 2005 CL Lihue, HI SP Int Soc Computerized Electrocardiol DE FDA; medical devices; standards; pressure band method AB In keeping with its mandate to provide the least burdensome means of product regulation, the US Food and Drug Administration's (FDA) Center for Devices and Radiological Health uses many different standards to facilitate the review of premarket submissions of medical devices. The benefits of using standards in this manner include providing a set of common requirements and test protocols to the device manufacturer, thus reducing the manufacturer's need to "reinvent the wheel" for each new bench test to ensure safety and effectiveness of the device. With the current trend toward international harmonization of standards, tests performed in accordance with an international standard may be acceptable to several countries. However, there are instances in which the FDA does not agree with certain provisions in a standard. This article aims to clarify the approaches taken by the FDA to balance or resolve issues that arise when there is disagreement regarding the acceptability of a particular standard. One approach begins with the recognition of only some provisions of a standard, or more commonly, excluding those parts of a standard that are unacceptable to the FDA for regulatory or scientific validity reasons. Other approaches include working with the standards development organizations to revise the standard to include language more agreeable to all parties involved. Specific examples will be presented on medical devices, Such as electrocardiogram cables and connectors, and noninvasive blood pressure monitors. (c) 2005 Published by Elsevier Inc. C1 US FDA, Ctr Devices & Radiol Hlth, Dept Hlth & Human Serv, Rockville, MD 20850 USA. RP Ho, C (reprint author), US FDA, Ctr Devices & Radiol Hlth, Dept Hlth & Human Serv, Rockville, MD 20850 USA. NR 0 TC 1 Z9 1 U1 1 U2 2 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0022-0736 J9 J ELECTROCARDIOL JI J. Electrocardiol. PD OCT PY 2005 VL 38 IS 4 SU S BP 171 EP 174 DI 10.1016/j.jelectrocard.2005.06.030 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 982VZ UT WOS:000233191000031 PM 16226095 ER PT J AU Stockbridge, N AF Stockbridge, N TI Points to consider in electrocardiogram waveform extraction SO JOURNAL OF ELECTROCARDIOLOGY LA English DT Article C1 US FDA, Div Cardiorenal Drug Prod, Rockville, MD 20857 USA. RP Stockbridge, N (reprint author), US FDA, Div Cardiorenal Drug Prod, Rockville, MD 20857 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0022-0736 J9 J ELECTROCARDIOL JI J. Electrocardiol. PD OCT PY 2005 VL 38 IS 4 BP 319 EP 320 DI 10.1016/j.jelectrocard.2005.06.090 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 981XH UT WOS:000233120800007 PM 16216603 ER PT J AU Vargas, AM Kim, MS Tao, Y Lefcourt, AM Chen, YR Luo, YG Song, YS Buchanan, R AF Vargas, AM Kim, MS Tao, Y Lefcourt, AM Chen, YR Luo, YG Song, YS Buchanan, R TI Detection of fecal contamination on cantaloupes using hyperspectral fluorescence imagery SO JOURNAL OF FOOD SCIENCE LA English DT Article DE hyperspectral imaging; fluorescence; cantaloupe; fecal contamination; ratio image ID SAFETY AB To determine whether detection of fecal contamination on cantaloupes is possible using fluorescence imaging, hyperspectral images of cantaloupes artificially contaminated with a range of diluted bovine feces were acquired from 425 to 774 nm in responses to ultraviolet-A (320 to 400 run) excitation. Evaluation of images at emission peak wavelengths indicated that 675 nm exhibited the greatest contrast between feces contaminated and untreated surface areas. Two-band ratios compared with the single-band images enhanced the contrast between the feces contaminated spots and untreated cantaloupe surfaces. The 595/655-nm, 655/520-nm, and 555/655-nm ratio images provided relatively high detection rates ranging from 79% to 96% across all feces dilutions. However, both single band and ratio methods showed a number of false positives caused by such features as scarred tissues on cantaloupes. Principal component analysis (PCA) was performed using the entire hyperspectral images data; 2nd and 5th principal component (PC) image exhibited differential responses between feces spots and false positives. The combined use of the 2 PC images demonstrated the detection of feces spots (for example, minimum level of 16-mu g/mL dry fecal matter) with minimal false positives. Based on the PC weighing coefficients, the dominant wavelengths were 465, 487, 531, 607, 643, and 688 nm. This research demonstrated the potential of multispectral-based fluorescence imaging for online applications for detection of fecal contamination on cantaloupes. C1 Univ Maryland, College Pk, MD 20742 USA. USDA ARS, Instrument & Sensing Lab, Beltsville, MD 20705 USA. USDA ARS, Food Qual & Safety Lab, Beltsville, MD USA. US FDA, CFSAN, College Pk, MD USA. US FDA, NCFST, Div Food Proc & Packaging, Summit Argo, IL USA. RP Kim, MS (reprint author), Univ Maryland, College Pk, MD 20742 USA. EM kimm@ba.ars.usda.gov NR 19 TC 32 Z9 33 U1 1 U2 13 PU INST FOOD TECHNOLOGISTS PI CHICAGO PA 525 WEST VAN BUREN, STE 1000, CHICAGO, IL 60607-3814 USA SN 0022-1147 J9 J FOOD SCI JI J. Food Sci. PD OCT PY 2005 VL 70 IS 8 BP E471 EP E476 PG 6 WC Food Science & Technology SC Food Science & Technology GA 978WL UT WOS:000232903600019 ER PT J AU Tomioka, K Peredelchuk, M Zhu, XY Arena, R Volokhov, D Selvapandiyan, A Stabler, K Melliquist-Riemenschneider, J Chizhikov, V Kaplan, G Nakhasi, H Duncan, R AF Tomioka, K Peredelchuk, M Zhu, XY Arena, R Volokhov, D Selvapandiyan, A Stabler, K Melliquist-Riemenschneider, J Chizhikov, V Kaplan, G Nakhasi, H Duncan, R TI A multiplex polymerase chain reaction microarray assay to detect bioterror pathogens in blood SO JOURNAL OF MOLECULAR DIAGNOSTICS LA English DT Article ID FRANCISELLA-TULARENSIS; RESPIRATORY VIRUSES; BACILLUS-ANTHRACIS; DNA MICROARRAY; PCR ASSAY; IDENTIFICATION; INFECTION; BACTERIAL AB Heightened concern about the dangers of bioterrorism requires that measures be developed to ensure the safety of the blood supply. Multiplex detection of such agents using a blood-screening DNA microarray is a sensitive and specific method to screen simultaneously for a number of suspected agents. We have developed and optimized a multiplex polymerase chain reaction microarray assay to screen blood for three potential bioterror bacterial pathogens and a human ribosomal RNA gene internal control. The analytical sensitivity of the assay was demonstrated to be 50 colony-forming units/ml for Bacillus anthracis, Francisella tularensis, and Yersinia pseudotuberculosis (surrogate for Yersinia pestis). The absence of any false-positives demonstrated high analytical specificity. Screening B. anthracis-infected mouse blood samples and uninfected controls demonstrated effectiveness and specificity in a preclinical application. This study represents proof of the concept of microarray technology to screen simultaneously for multiple bioterror pathogens in blood samples. C1 US FDA, Div Emerging & Transfus Transmitted Dis, Off Blood Res & Rev, Ctr Biol Evaluat & Res, Bethesda, MD USA. US FDA, Div Hematol, Off Blood Res & Rev, Ctr Biol Evaluat & Res, Bethesda, MD USA. US FDA, Div Viral Prod, Off Vaccines Res & Rev, Ctr Biol Evaluat & Res, Bethesda, MD USA. RP Duncan, R (reprint author), 1401 Rockville Pk,HFM310, Rockville, MD 20852 USA. EM duncan@cber.fda.gov RI Duncan, Robert/I-8168-2015 OI Duncan, Robert/0000-0001-8409-2501 NR 23 TC 46 Z9 47 U1 0 U2 6 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 1525-1578 J9 J MOL DIAGN JI J. Mol. Diagn. PD OCT PY 2005 VL 7 IS 4 BP 486 EP 494 DI 10.1016/S1525-1578(10)60579-X PG 9 WC Pathology SC Pathology GA 972ED UT WOS:000232436000007 PM 16237218 ER PT J AU Potthast, H Dressman, JB Junginger, HE Midha, KK Oeser, H Shah, VP Vogelpoel, H Barends, DM AF Potthast, H Dressman, JB Junginger, HE Midha, KK Oeser, H Shah, VP Vogelpoel, H Barends, DM TI Biowaiver monographs for immediate release solid oral dosage forms: Ibuprofen SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Editorial Material DE absorption; biopharmaceutics classification system(BCS); ibuprofen; permeability; solubility ID BIOPHARMACEUTICS CLASSIFICATION-SYSTEM; PLASMA-PROTEIN BINDING; IN-VIVO; HEALTHY-VOLUNTEERS; PHARMACOKINETICS; BIOAVAILABILITY; ENANTIOMERS; PERMEABILITY; SINGLE; DRUGS AB Literature data are reviewed on the properties of ibuprofen related to the biopharmaceutics classification system (BCS). lbuprofen was assessed to be a BCS class II drug. Differences in composition and/or manufacturing procedures were reported to have an effect on the rate, but not the extent of absorption; such differences are likely to be detectable by comparative in vitro dissolution tests. Also in view of its therapeutic use, its wide therapeutic index and uncomplicated pharmacokinetic properties, a biowaiver for immediate release (IR) ibuprofen solid oral drug products is scientifically justified, provided that the test product contains only those excipients reported in this paper in their usual amounts, the dosage form is rapidly dissolving (85% in 30 min or less) in buffer pH 6.8 and the test product also exhibits similar dissolution profiles to the reference product in buffer pH 1.2, 4.5, and 6.8. (c) 2005 Wiley-Liss, Inc. C1 Natl Inst Publ Hlth & Environm, RIVM, NL-3720 BA Bilthoven, Netherlands. Fed Inst Drugs & Med Devices, BfArM, Bonn, Germany. Univ Frankfurt, Inst Pharmazeut Technol, Frankfurt, Germany. Leiden Univ, Ctr Drug Res, Div Pharmaceut Technol, Leiden, Netherlands. Univ Saskatchewan, Saskatoon, SK, Canada. Univ Heidelberg, Heidelberg, Germany. US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Barends, DM (reprint author), Natl Inst Publ Hlth & Environm, RIVM, NL-3720 BA Bilthoven, Netherlands. EM Dirk.Barends@RIVM.nl RI Fachbereich14, Dekanat/C-8553-2015 NR 41 TC 99 Z9 103 U1 4 U2 25 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0022-3549 J9 J PHARM SCI-US JI J. Pharm. Sci. PD OCT PY 2005 VL 94 IS 10 BP 2121 EP 2131 DI 10.1002/jps.20444 PG 11 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 969TN UT WOS:000232257800002 PM 16136567 ER PT J AU Prodduturi, S Manek, RV Kolling, WM Stodghill, SP Repka, MA AF Prodduturi, S Manek, RV Kolling, WM Stodghill, SP Repka, MA TI Solid-state stability and characterization of hot-melt extruded poly(ethylene oxide) films SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article DE hot-melt extrusion; solid solutions; polymers; solid state stability; thermal analysis; crystallinity ID BIOADHESIVE PROPERTIES; DRUG-RELEASE; EXTRUSION; TABLETS; CLOTRIMAZOLE; POLYETHYLENE AB Poly(ethylene oxide) (PEO) was used to prepare thin polymer films containing clotrimazole (CT) utilizing hot-melt extrusion (HME) technology. Films containing PEOs of two different molecular weights and the drug were investigated for solid-state characteristics, moisture-sorption, bioadhesivity, mechanical properties, release characteristics, and physical and chemical stability of the drug within the HME films. The solid-state characterization of the drug and the polymer were performed utilizing differential scanning calorimetry and X-ray diffractometry. A Texture analyzer was utilized to study the bioadhesive and mechanical properties of the HME films. Physical and chemical stability of the films, stored at 25 degrees C/60% RH, was studied for up to 12 months. XRD profiles indicated that the drug was physically unstable (recrystallization of the drug occurred) after storage for 3 months at 25 degrees C/60% RH. Based on the DSC studies, it has been proposed that the recrystallization of the drug may be due to the folding (due to HME) and unfolding (upon storage) of the linear PEO chains. Desirable bioadhesive, mechanical, and thermoplastic properties of PEO qualify it as a promising and potential drug carrier. However, further investigation is necessary to enhance the physical stability of these PEO-drug systems. (c) 2005 Wiley-Liss, Inc. C1 Univ Mississippi, Sch Pharm, Dept Pharmaceut, University, MS 38677 USA. Univ Mississippi, Sch Pharm, Natl Ctr Nat Prod Res, University, MS 38677 USA. US FDA, Div Pharmaceut Anal, St Louis, MO 63101 USA. NE Louisiana Univ, Sch Pharm, Dept Basic Pharmaceut Sci, Monroe, LA 71209 USA. RP Repka, MA (reprint author), Univ Mississippi, Sch Pharm, Dept Pharmaceut, University, MS 38677 USA. EM marepka@olemiss.edu FU NIDCR NIH HHS [R43DE15455-01] NR 37 TC 59 Z9 60 U1 1 U2 11 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0022-3549 J9 J PHARM SCI-US JI J. Pharm. Sci. PD OCT PY 2005 VL 94 IS 10 BP 2232 EP 2245 DI 10.1002/jps.20437 PG 14 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 969TN UT WOS:000232257800013 PM 16136579 ER PT J AU Whiting, SJ Calvo, MS AF Whiting, SJ Calvo, MS TI Dietary recommendations to meet both endocrine and autocrine needs of Vitamin D SO JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY LA English DT Article; Proceedings Paper CT Workshop on Vitamin D and Cancer Treatment and Prevention CY NOV 17-19, 2004 CL NIH, Bethesda, MD SP Vitamin D Workshop Inc HO NIH DE Vitamin D; Vitamin D intakes; dietary reference intakes; Vitamin D fortification; supplementation; functional indicators ID 25-HYDROXYVITAMIN D CONCENTRATIONS; UNITED-STATES; D INSUFFICIENCY; WHITE WOMEN; CANCER; CALCIUM; BREAST; YOUNG; SUPPLEMENTATION; FORTIFICATION AB In the most recent revision of the dietary recommendations for Americans and Canadians in 1997, a recommended intake for Vitamin D was set in the absence of an estimation of mean requirements. There are now new data to estimate average requirements; however, there must be consideration of factors affecting need in populations and of total body tissue needs including the prevention and treatment of cancer. A recent study provides dietary dose-response data in the absence of sun exposure, and a mean requirement of 12.5 mu g (500 IU) was found for Caucasian men. A seasonal build up (summer) and waning (winter) of Vitamin D stores implies that the requirement of Vitamin D in complete absence of yearly summertime sun exposure would approach levels of intake that mimic Vitamin D gained from sun exposure. High prevalence of Vitamin D insufficiency and the re-emergence of rickets have been observed worldwide. For many countries without mandatory staple food fortification, Vitamin D intake is often too low to sustain healthy circulating levels of 25 hydroxyvitamin D. Even in some countries that require (mandatory) or allow fortification (optional), Vitamin D intakes are low in some groups due to their unique dietary patterns, such as low milk consumption, vegetarian diet, limited or no use of dietary supplements, or changes away from traditional food consumption. Supplement use can significantly increase Vitamin D intakes across all age and gender groups but the benefit is primarily gained in persons whose intakes are close to adequate. African American men and women have greater prevalence of Vitamin D insufficiency, which may be a factor in their susceptibility to certain cancers. New recommendations for Vitamin D should be made for the otherwise healthy populations in greatest need of dietary Vitamin D due to lack of adequate sun exposure. (c) 2005 Elsevier Ltd. All rights reserved. C1 Univ Saskatchewan, Coll Pharm & Nutr, Saskatoon, SK S7N 5C9, Canada. US FDA, Ctr Food Safety & Appl Nutr, Silver Spring, MD 20910 USA. RP Whiting, SJ (reprint author), Univ Saskatchewan, Coll Pharm & Nutr, 110 Sci Pl, Saskatoon, SK S7N 5C9, Canada. EM susan.whiting@usask.ca NR 28 TC 34 Z9 37 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-0760 J9 J STEROID BIOCHEM JI J. Steroid Biochem. Mol. Biol. PD OCT PY 2005 VL 97 IS 1-2 BP 7 EP 12 DI 10.1016/j.jsbmb.2005.06.022 PG 6 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 987UP UT WOS:000233543100003 PM 16046261 ER PT J AU Drum, B Sternheim, CE AF Drum, B Sternheim, CE TI Response saturation of monochromatic increments on intense achromatic backgrounds: implications for color-opponent organization in human vision SO JOURNAL OF THE OPTICAL SOCIETY OF AMERICA A-OPTICS IMAGE SCIENCE AND VISION LA English DT Article ID LATERAL GENICULATE-NUCLEUS; SPECTRAL SENSITIVITY; GANGLION-CELLS; QUANTITATIVE ASPECTS; RECEPTIVE FIELDS; LIGHT ADAPTATION; ROD MONOCHROMAT; CONE MECHANISMS; DARK ADAPTATION; RHESUS-MONKEY AB We present evidence that steady achromatic adapting fields can produce response saturation in color-opponent pathways. We measured tvi (log increment threshold illuminance versus log background illuminance) functions at four test wavelengths (430, 490, 575, and 660 nm) and nine background illuminances from 4.0 to 5.6 log Td. Foveal, 2 degrees diameter, 1 s duration test stimuli were presented on a concentric, perceptually white (5128 degrees K color temperature), 7 degrees diameter, steady background. Thresholds were obtained by the method of adjustment, after which the test stimulus illuminances were increased 0.6 log unit and the subject estimated percentages of red, yellow, green, blue, and white. Average tvi slopes for two subjects were 2.06 for 430 nm, 1.6 for 490 nm, 1.11 for 575 nm and 1.34 for 660 mn, consistent with the estimated ratios of chromatic to achromatic sensitivity at the same wavelengths. Also, the percentage of white seen in the suprathreshold increments increased with increasing background illuminance despite increases in excitation purity. These findings imply that steady, intense, achromatic backgrounds can produce response saturation in color-opponent mechanisms at wavelengths across the visible spectrum. The saturation was more extreme at short wavelengths than at middle or long wavelengths, producing a tritanopic condition at the highest background illuminances. The tritanopia reduced color space to a predominately red-blue dichromacy, in agreement with previous findings. The results support a multistage opponent-color model in which precortical koniocellular and parvocellular opponent pathways interact to produce the observed red-green and yellow-blue color-opponent channels at a cortical level. (c) 2005 Optical Society of America. C1 US FDA, Ctr Devices & Radiol Hlth, Div Ophthalm & Ear Nose & Throat Devices, Rockville, MD 20850 USA. Univ Maryland, Dept Psychol, College Pk, MD 20742 USA. RP Drum, B (reprint author), US FDA, Ctr Devices & Radiol Hlth, Div Ophthalm & Ear Nose & Throat Devices, Rockville, MD 20850 USA. EM bad@cdrh.fda.gov FU NEI NIH HHS [EY07327] NR 56 TC 0 Z9 0 U1 0 U2 1 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1084-7529 EI 1520-8532 J9 J OPT SOC AM A JI J. Opt. Soc. Am. A-Opt. Image Sci. Vis. PD OCT PY 2005 VL 22 IS 10 BP 2107 EP 2119 DI 10.1364/JOSAA.22.002107 PG 13 WC Optics SC Optics GA 968SM UT WOS:000232182600010 PM 16277281 ER PT J AU Cantalupo, P Doering, A Sullivan, CS Pal, A Peden, KWC Lewis, AM Pipas, JM AF Cantalupo, P Doering, A Sullivan, CS Pal, A Peden, KWC Lewis, AM Pipas, JM TI Complete nucleotide sequence of polyomavirus SA12 SO JOURNAL OF VIROLOGY LA English DT Article ID GOOSE HEMORRHAGIC POLYOMAVIRUS; SIMIAN PAPOVAVIRUS SA12; AMINO-TERMINAL DOMAIN; LARGE T-ANTIGEN; HOST RANGE; BK VIRUS; GENE-EXPRESSION; MESSENGER-RNA; MICRORNAS; IDENTIFICATION AB The Polyomaviridae have small icosahedral virions that contain a genome of approximately 5,000 bp of circular double-stranded DNA. Polyomaviruses infect hosts ranging from humans to birds, and some members of this family induce tumors in test animals or in their natural hosts. We report the complete nucleotide sequence of simian agent 12 (SA12), whose natural host is thought to be Papio ursinus, the chacma baboon. The 5,230-bp genome has a genetic organization typical of polyomaviruses. Sequences encoding large T antigen, small t antigen, agnoprotein, and the viral capsid proteins VP1, VP2, and VP3 are present in the expected locations. We show that, like its close relative simian virus 40 (SV40), SA12 expresses microRNAs that are encoded by the late DNA strand overlapping the 3' end of large T antigen coding sequences. Based on sequence comparisons, SA12 is most closely related to BK virus (BKV), a human polyomavirus. We have developed a real-time PCR test that distinguishes SA12 from BKV and the other closely related polyomaviruses JC virus and SV40. The close relationship between SA12 and BKV raises the possibility that these viruses circulate between human and baboon hosts. C1 Univ Pittsburgh, Dept Biol Sci, Pittsburgh, PA 15260 USA. Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94143 USA. Univ Calif San Francisco, GW Hooper Fdn, Dept Microbiol, San Francisco, CA 94143 USA. Univ Calif San Francisco, GW Hooper Fdn, Dept Med, San Francisco, CA 94143 USA. US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Pipas, JM (reprint author), Univ Pittsburgh, Dept Biol Sci, Pittsburgh, PA 15260 USA. EM pipas@pitt.edu FU NCI NIH HHS [CA40586, R01 CA040586] NR 45 TC 72 Z9 83 U1 1 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 OCT PY 2005 VL 79 IS 20 BP 13094 EP 13104 DI 10.1128/JVI.79.20.13094-13104.2005 PG 11 WC Virology SC Virology GA 969OI UT WOS:000232243200049 PM 16189011 ER PT J AU Pogrlbny, I Koturbash, I Tryndyak, V Hudson, D Stevenson, SML Sedelnikova, O Bonner, W Kovalchuk, O AF Pogrlbny, I Koturbash, I Tryndyak, V Hudson, D Stevenson, SML Sedelnikova, O Bonner, W Kovalchuk, O TI Fractionated low-dose radiation exposure leads to accumulation of DNA damage and profound alterations in DNA and histone methylation in the murine thymus SO MOLECULAR CANCER RESEARCH LA English DT Article ID DOUBLE-STRAND BREAKS; GENOMIC HYPOMETHYLATION; EPIGENETIC REGULATION; DEACETYLASE COMPLEX; CHILDHOOD LEUKEMIA; CANCER; CELLS; MOUSE; MICE; INSTABILITY AB Thymus, an important component of hematopoietic tissue, is a well-documented "target" of radiation carcinogenesis. Both acute and fractionated irradiation result in a high risk of leukemia and thymic lymphoma. However, the exact mechanisms underlying radiation-induced predisposition to leukemia and lymphoma are still unknown, and the contributions of genetic and epigenetic mechanisms in particular have yet to be defined. Global DNA hypomethylation is a well-known characteristic of cancer cells. Recent studies have also shown that tumor cells undergo prominent changes in histone methylation, particularly a substantial loss of trimethylation of histone H4-LyS(20) and demethylation of genomic DNA. These losses are considered a universal marker of malignant transformation. In the present study, we investigated the effect of low-dose radiation exposure on the accumulation of DNA lesions and alterations of DNA methylation and histone H4-LyS20 trimethylation in the thymus tissue using an in vivo murine model. For the first time, we show that fractionated whole-body application of 0.5 Gy X-ray leads to decrease in histone H4-LYS20 trimethylation in the thymus. The loss of histone H4-LYS20 trimethylation was accompanied by a significant decrease in global DNA methylation as well as the accumulation of DNA damage as monitored by persistence of histone gamma H2AX foci in the thymus tissue of mice exposed to fractionated irradiation. Altered DNA methylation was associated with reduced expression of maintenance (DNMT1) and, to a lesser extent, de novo DNA methyltransferase DNMT3a in exposed animals. Expression of another de novo DNA methyltransferase DNMT3b was decreased only in males. Irradiation also resulted in similar to 20% reduction in the levels of methyl-binding proteins MeCP2 and MBD2. Our results show the involvement of epigenetic alterations in radiation-induced responses in vivo. These changes may play a role in genome destabilization that ultimately leads to cancer. C1 Univ Lethbridge, Dept Biol Sci, Lethbridge, AB, Canada. Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. NCI, Mol Pharmacol Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Kovalchuk, O (reprint author), Univ Lethbridge, Dept Biol Sci, 4401 Univ Dr,Lethbridge Dr, Lethbridge, AB, Canada. EM olga.kovalchuk@uleth.ca NR 54 TC 72 Z9 88 U1 0 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1541-7786 J9 MOL CANCER RES JI Mol. Cancer Res. PD OCT PY 2005 VL 3 IS 10 BP 553 EP 561 DI 10.1158/1541-7786.MCR-05-0074 PG 9 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 980OI UT WOS:000233027400003 PM 16254189 ER PT J AU Baker, SC Bauer, SR Beyer, RP Brenton, JD Bromley, B Burrill, J Causton, H Conley, MP Elespuru, R Fero, M Foy, C Fuscoe, J Gao, XL Gerhold, DL Gilles, P Goodsaid, F Guo, X Hackett, J Hockett, RD Ikonomi, P Irizarry, RA Kawasaki, ES Kaysser-Kranich, T Kerr, K Kiser, G Koch, WH Lee, KY Liu, CM Liu, ZL Lucas, A Manohar, CF Miyada, G Modrusan, Z Parkes, H Puri, RK Reid, L Ryder, TB Salit, M Samaha, RR Scherf, U Sendera, TJ Setterquist, RA Shi, LM Shippy, R Soriano, JV Wagar, EA Warrington, JA Williams, M Wilmer, F Wilson, M Wolber, PK Wu, XN Zadro, R AF Baker, SC Bauer, SR Beyer, RP Brenton, JD Bromley, B Burrill, J Causton, H Conley, MP Elespuru, R Fero, M Foy, C Fuscoe, J Gao, XL Gerhold, DL Gilles, P Goodsaid, F Guo, X Hackett, J Hockett, RD Ikonomi, P Irizarry, RA Kawasaki, ES Kaysser-Kranich, T Kerr, K Kiser, G Koch, WH Lee, KY Liu, CM Liu, ZL Lucas, A Manohar, CF Miyada, G Modrusan, Z Parkes, H Puri, RK Reid, L Ryder, TB Salit, M Samaha, RR Scherf, U Sendera, TJ Setterquist, RA Shi, LM Shippy, R Soriano, JV Wagar, EA Warrington, JA Williams, M Wilmer, F Wilson, M Wolber, PK Wu, XN Zadro, R CA External RNA Controls Consortium TI The external RNA controls consortium: a progress report SO NATURE METHODS LA English DT Editorial Material ID DNA AMPLIFICATION; PCR AB Standard controls and best practice guidelines advance acceptance of data from research, preclinical and clinical Laboratories by providing a means for evaluating data quality. The External RNA Controls Consortium (ERCC) is developing commonly agreed-upon and tested controls for use in expression assays, a true industry-wide standard control. C1 Affymetrix Inc, Santa Clara, CA 95051 USA. Illumina Inc, San Diego, CA 92121 USA. US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. Univ Washington, Seattle, WA 98105 USA. Univ Cambridge, CIMR, Addenbrookes Hosp, Cambridge CB2 2XY, England. ViaLogy Corp, Altadena, CA 91001 USA. Appl Biosyst Inc, Foster City, CA 94404 USA. Univ London Imperial Coll, London SW7 2AZ, England. Enzo Life Sci Inc, Farmingdale, NY 11735 USA. US FDA, Ctr Devices & Radiol Hlth, Fed Labs White Oak, Silver Spring, MD 20903 USA. Stanford Univ, Sch Med, Stanford, CA 94305 USA. Lab Govt Chemist, Bio Mol Innovat, Teddington TW11 0LY, Middx, England. US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Atactic Technol Inc, Houston, TX 77054 USA. Merck Sharp Labs, Dept Mol Profiling, West Point, PA 19486 USA. Invitrogen Corp, Carlsbad, CA 92008 USA. US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20852 USA. Affymetrix Inc, Santa Clara, CA 95051 USA. US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. Eli Lilly & Co, Lilly Res Lab, Lilly Corp Ctr, Indianapolis, IN 46285 USA. Amer Type Culture Collect, Manassas, VA 20110 USA. NCI, Ctr Adv Technol, NIH, Baltimore, MD 21205 USA. GE Healthcare, Chandler, AZ 85248 USA. Roche Mol Syst, Pleasanton, CA 94588 USA. USDA, Peoria, IL 61604 USA. Agilent Technol Inc, Santa Clara, CA 95051 USA. Lawrence Livermore Natl Lab Microarray Ctr, Livermore, CA 94550 USA. Genentech Inc, San Francisco, CA 94080 USA. US FDA, NIH, Bethesda, MD 20892 USA. Express Anal, Durham, NC 27713 USA. NIST, Chem Sci & Technol Lab, Gaithersburg, MD 20899 USA. US FDA, Off In Vitro Diagnost Device Evaluat & Safety, Rockville, MD 20850 USA. Ambion Inc, Austin, TX 78744 USA. Amer Type Culture Collect, Manassas, VA 20110 USA. Univ Calif Los Angeles, Clin Labs, Los Angeles, CA 90095 USA. Qiagen Inc, D-40727 Hilden, Germany. Univ Zagreb, Sch Med, Zagreb 10000, Croatia. RP Warrington, JA (reprint author), Affymetrix Inc, 3380 Cent Expressway, Santa Clara, CA 95051 USA. EM janet_warrington@affymetrix.com RI Bauer, Steven/G-5559-2012; Kiser, Gretchen/A-3228-2013; OI Brenton, James/0000-0002-5738-6683; Bauer, Steven/0000-0003-2831-846X NR 8 TC 128 Z9 130 U1 0 U2 9 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1548-7091 J9 NAT METHODS JI Nat. Methods PD OCT PY 2005 VL 2 IS 10 BP 731 EP 734 DI 10.1038/nmeth1005-731 PG 4 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 980FC UT WOS:000232998600009 PM 16179916 ER PT J AU Wolff, GL Whittaker, P AF Wolff, GL Whittaker, P TI Dose-response effects of ectopic agouti protein on iron overload and age-associated aspects of the A(vy)/a obese mouse phenome SO PEPTIDES LA English DT Article DE agouti protein; caloric efficiency; hepatocellular tumors; hyperplasia; iron overload; melanocortin receptor 4; obesity; pancreatic islet cells; pseudoagouti mice; systems biology; age-associated weight loss ID VY F1-HYBRID MICE; GENE-EXPRESSION; YELLOW MICE; BODY-WEIGHT; DIFFERENTIAL EXPRESSION; PHENOBARBITAL PROMOTION; VIABLE YELLOW; HUMAN HOMOLOG; COAT COLOR; GROWTH AB Isogenic and congenic offspring from matings of inbred black ala dams by sibling (or non-sibling from another inbred strain) yellow agouti A(vy)/a sires provide an animal model of obese yellow agouti A(vy)/a and isogenic lean pseudoagouti A(vy)/a mice exhibiting two different in vivo concentrations (high, very low) of ectopic agouti protein (ASP) with congenic lean black ala mice as null controls. This makes it possible to differentiate between the high and very low dose levels of ectopic ASP with respect to interactions with diverse physiological and molecular pathways. Assay of differential responses to 12 or 24 months of carbonyl iron overload assessed the possible suitability of this animal model for the study of hemochromatosis. Agouti A/a B6C3F(1) mice were used as non-congenic null controls. The age-related waxing and waning of body weight, food consumption, and caloric efficiency, as well as associated changes in pancreatic islets and islet cells, and formation of liver tumors were assayed. While the hypothesis that these mice might serve as a tool for investigating hemochromatosis was not confirmed, the data did provide evidence that even the very low levels of ASP in pseudoagouti A(vy)/a mice affect the network of molecular/metabolic/physiological response pathways that comprises the yellow agouti obese phenome. We suggest that the combination of yellow agouti A(vy)/a, pseudoagouti A(vy)/a, and black ala congenic mice provides a practical tool for applying a dose-response systems biology approach to understanding the dysregulatory influence of ectopic ASP on the molecular-physiological matrix of the organism. Published by Elsevier Inc. C1 US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Wolff, GL (reprint author), US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. EM gwolffar@prodigy.net NR 55 TC 3 Z9 3 U1 0 U2 3 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 OCT PY 2005 VL 26 IS 10 BP 1697 EP 1711 DI 10.1016/j.peptides.2004.12.033 PG 15 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA 974TH UT WOS:000232613800003 PM 15982784 ER PT J AU Sadrieh, N Brower, J Yu, L Doub, W Straughn, A Machado, S Pelsor, F Saint Martin, E Moore, T Reepmeyer, J Toler, D Nguyenpho, A Roberts, R Schuirmann, DJ Nasr, M Buhse, L AF Sadrieh, N Brower, J Yu, L Doub, W Straughn, A Machado, S Pelsor, F Saint Martin, E Moore, T Reepmeyer, J Toler, D Nguyenpho, A Roberts, R Schuirmann, DJ Nasr, M Buhse, L TI Stability, dose uniformity, and palatability of three counterterrorism drugs - Human subject and electronic tongue studies SO PHARMACEUTICAL RESEARCH LA English DT Article DE analytical chemistry; chromatographic; drug delivery; oral; formulation; solution; in vitro; in vivo correlations; stability; chemical; stability; solution; stability; suspension ID GENERIC ANTIBIOTIC SUSPENSIONS; COMMON PEDIATRIC DRUGS; TASTE; CHILDREN; CEFPROZIL; BRAND AB Purpose. These studies evaluated the ability of common household food and drink products to mask the bitter taste of three selected anti-terrorism drugs. Methods. Three anti-terrorism drugs (doxycycline, ciprofloxacin hydrochloride, and potassium iodide) were mixed with a variety of common household food and drinks, and healthy adult volunteers evaluated the resulting taste and aftertaste. In parallel, the ASTREE Electronic Tongue was used to evaluate taste combinations. Stability of the mixtures over time was monitored, as was the dosage uniformity across preparations. Results. Foods and drinks were identified that satisfactorily masked the bitter flavor of each drug. Dose uniformity and stability were also acceptable over the range studied, although some combinations were significantly less stable than others. The electronic tongue was able to differentiate between tastes, but ranked masking agents in a different order than human volunteers. Conclusions. Doxycycline, potassium iodide, and ciprofloxacin, which are stockpiled in solid tablet form, can conveniently be prepared into more palatable formulations, using common household foods and drinks. The electronic tongue can be used to perform an initial screening for palatability. C1 US FDA, St Louis, MO 63101 USA. US FDA, Rockville, MD 20852 USA. US FDA, Rockville, MD 20850 USA. Univ Tennessee, Memphis, TN 38163 USA. US FDA, Rockville, MD 20857 USA. Alpha MOS, F-31400 Toulouse, France. US FDA, Silver Spring, MD 20903 USA. RP Doub, W (reprint author), US FDA, 1114 Market St, St Louis, MO 63101 USA. EM doubw@cder.fda.gov RI Bueno, Ligia/P-1359-2014 NR 15 TC 27 Z9 27 U1 0 U2 8 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0724-8741 J9 PHARM RES JI Pharm. Res. PD OCT PY 2005 VL 22 IS 10 BP 1747 EP 1756 DI 10.1007/s11095-005-6387-x PG 10 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 966XW UT WOS:000232057100020 PM 16180133 ER PT J AU Hardman, J Endres, L Fischer, P Jenkins, T Wollet, L Kilpatrick, S Rodvold, K Geller, S Sarto, G Miller, M Fischer, J AF Hardman, J Endres, L Fischer, P Jenkins, T Wollet, L Kilpatrick, S Rodvold, K Geller, S Sarto, G Miller, M Fischer, J TI Pharmacokinetics of labetalol in pregnancy. SO PHARMACOTHERAPY LA English DT Meeting Abstract CT Annual Meeting of the American-College-of-Clinical-Pharmacy CY OCT 23-26, 2005 CL San Francisco, CA SP Amer Coll Clin Pharmacy C1 Univ Illinois, Chicago, IL USA. Univ Wisconsin, Madison, WI USA. FDA, Rockville, MD USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU PHARMACOTHERAPY PUBLICATIONS INC PI BOSTON PA NEW ENGLAND MEDICAL CENTER, 806, 750 WASHINGTON ST, BOSTON, MA 02111 USA SN 0277-0008 J9 PHARMACOTHERAPY JI Pharmacotherapy PD OCT PY 2005 VL 25 IS 10 BP 1493 EP 1494 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 971BP UT WOS:000232356400254 ER PT J AU Moon, H Kim, HJ Chen, JJ Kodell, RL AF Moon, H Kim, HJ Chen, JJ Kodell, RL TI Model averaging using the Kullback information criterion in estimating effective doses for microbial infection and illness SO RISK ANALYSIS LA English DT Article DE benchmark dose; food safety; Kullback information; low-dose extrapolation; model uncertainty ID RISK-ASSESSMENT; RESPONSE MODELS; HEALTH RISK; SELECTION; CONTAMINATION; UNCERTAINTY; PATHOGENS AB Since the National Food Safety Initiative of 1997, risk assessment has been an important issue in food safety areas. Microbial risk assessment is a systematic process for describing and quantifying a potential to cause adverse health effects associated with exposure to microorganisms. Various dose-response models for estimating microbial risks have been investigated. We have considered four two-parameter models and four three-parameter models in order to evaluate variability among the models for microbial risk assessment using infectivity and illness data from studies with human volunteers exposed to a variety of microbial pathogens. Model variability is measured in terms of estimated ED(01)s and ED(10)s, with the view that these effective dose levels correspond to the lower and upper limits of the 1% to 10% risk range generally recommended for establishing benchmark doses in risk assessment. Parameters of the statistical models are estimated using the maximum likelihood method. In this article a weighted average of effective dose estimates from eight two- and three-parameter dose-response models, with weights determined by the Kullback information criterion, is proposed to address model uncertainties in microbial risk assessment. The proposed procedures for incorporating model uncertainties and making inferences are illustrated with human infection/illness dose-response data sets. C1 US FDA, Div Biometry & Risk Assessment, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Truman State Univ, Div Math & Comp Sci, Kirksville, MO 63501 USA. RP Moon, H (reprint author), US FDA, Div Biometry & Risk Assessment, Natl Ctr Toxicol Res, 3900 NCTR Dr, Jefferson, AR 72079 USA. EM hmoon@nctr.fda.gov NR 34 TC 23 Z9 23 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0272-4332 EI 1539-6924 J9 RISK ANAL JI Risk Anal. PD OCT PY 2005 VL 25 IS 5 BP 1147 EP 1159 DI 10.1111/j.1539-6924.2005.00676.x PG 13 WC Public, Environmental & Occupational Health; Mathematics, Interdisciplinary Applications; Social Sciences, Mathematical Methods SC Public, Environmental & Occupational Health; Mathematics; Mathematical Methods In Social Sciences GA 978IS UT WOS:000232867400006 PM 16297221 ER PT J AU Ferguson, SA Cisneros, FJ Gough, B Hanig, JP Berry, KJ AF Ferguson, SA Cisneros, FJ Gough, B Hanig, JP Berry, KJ TI Chronic oral treatment with 13-cis-retinoic acid (isotretinoin) or all-trans-retinoic acid does not alter depression-like behaviors in rats SO TOXICOLOGICAL SCIENCES LA English DT Article DE isotretinoin; 13-cis-retinoic acid; all-trans-retinoic acid; depression; anhedonia; locomotor activity; Forced Swim Test ID CHRONIC MILD STRESS; FORCED-SWIMMING TEST; INTRACRANIAL SELF-STIMULATION; ANIMAL-MODELS; SEX-DIFFERENCES; MAJOR DEPRESSION; HIPPOCAMPAL NEUROGENESIS; ANTIDEPRESSANT DRUGS; ALARM SUBSTANCE; FEMALE RATS AB Oral treatment with the anti-acne drug Accutane (isotretinoin, 13-cis-retinoic acid) has been associated with suicide ideation and depression. Here, depression-like behaviors (i.e., behavioral despair and anhedonia) were quantified in adult Sprague-Dawley rats gavaged daily beginning at postnatal day (PND) 82 with 13-cis-RA (7.5 or 22.5 mg/kg) or all-trans-retinoic acid (10 or 15 mg/kg ). Tested at PND 130-131 in the Forced Swim Test, 7.5 mg/kg 13-cis-RA marginally decreased immobility and slightly increased climb/struggle durations whereas neither all-trans-retinoic acid group differed from controls. Voluntary saccharin solution (0.03%) intake at PND 102-104 and PND 151-153 was not different from controls in any treated group, although all RA-treated groups had lower intakes. Swim speed in a water maze at PND 180 was similar across groups, indicating no RA-induced differences in physical ability. Open field activity was mildly decreased at PND 91 in 7.5 mg/kg-treated males only, but it was within the control range at PND 119, 147, and 175. Thus, at serum levels similar to those in humans receiving the drug, chronic 13-cis-RA treatment did not severely affect depression-like behaviors in rats. These data do not substantiate the hypothesis of 13-cis-RA-induced depression. C1 US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. US FDA, Ctr Drug Evaluat Res, Silver Spring, MD USA. RP Ferguson, SA (reprint author), US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM sferguson@nctr.fda.gov NR 72 TC 26 Z9 27 U1 1 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD OCT PY 2005 VL 87 IS 2 BP 451 EP 459 DI 10.1093/toxsci/kfi262 PG 9 WC Toxicology SC Toxicology GA 962WA UT WOS:000231762500016 PM 16033993 ER PT J AU Sander, M Cadet, J Casciano, DA Galloway, SM Marnett, LJ Novak, RF Pettit, SD Preston, RJ Skare, JA Williams, GM Van Houten, B Gollapudi, BB AF Sander, M Cadet, J Casciano, DA Galloway, SM Marnett, LJ Novak, RF Pettit, SD Preston, RJ Skare, JA Williams, GM Van Houten, B Gollapudi, BB TI Proceedings of a workshop on DNA adducts: Biological significance and applications to risk assessment Washington, DC, April 13-14, 2004 SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE risk assessment; DNA; DNA adducts; DNA damage; workshop report ID ENVIRONMENTAL-POLLUTANT 3-NITROBENZANTHRONE; TANDEM MASS-SPECTROMETRY; A/J MOUSE LUNG; ETHYLENE-OXIDE; IN-VIVO; GENOME REARRANGEMENTS; CARCINOGENIC RISK; SOMATIC MUTATIONS; LIVER-CANCER; HUMAN-CELLS AB In April 2004, the Health and Environmental Sciences Institute, a branch of the International Life Sciences Institute, with support from the National Institute of Environmental Health Sciences, organized a workshop to discuss the biological significance of DNA adducts. Workshop speakers and attendees included leading international experts from government, academia, and industry in the field of adduct detection and interpretation. The workshop initially examined the relationship between measured adduct levels in the context of exposure and dose. This was followed by a discussion on the complex response of cells to deal with genotoxic insult in complex, interconnected, and interdependent repair pathways. One of the major objectives of the workshop was to address the recurring question about the mechanistic and toxicological relevance of low-concentration measured adducts and the presentations in the session entitled "Can low levels of DNA adducts predict adverse outcomes?" served as catalysts for further discussions on this subject during the course of the workshop. Speakers representing the regulatory community and industry reviewed the value, current practices, and limitations of utilizing DNA adduct data in risk assessment and addressed a number of practical questions pertaining to these issues. While no consensus statement emerged on the biological significance of low levels of DNA adducts, the workshop concluded by identifying the need for more experimental data to address this important question. One of the recommendations stemming from this workshop was the need to develop an interim "decision-logic" or framework to guide the integration of DNA adduct data in the risk assessment process. HESI has recently formed a subcommittee consisting of experts in the field and other key stakeholders to address this recommendation as well as to identify specific research projects that could help advance the understanding of the biological significance of low levels of DNA adducts. (c) 2005 Elsevier Inc. All rights reserved. C1 ILSI Hlth & Environm Sci Inst, Washington, DC 20005 USA. Page 1 Editorial Serv, Durham, NC 27707 USA. French Atom Energy Comiss, F-38054 Grenoble, France. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Merck Res Labs, West Point, PA 19486 USA. Vanderbilt Univ, Vanderbilt Inst Chem Biol, Nashville, TN 37235 USA. Wayne State Univ, Inst Chem Toxicol, Detroit, MI 48201 USA. US EPA, Res Triangle Pk, NC 27711 USA. Procter & Gamble Co, Cent Product Safety, Cincinnati, OH 45217 USA. New York Med Coll, Dept Toxicol & Pathol, Valhalla, NY 10595 USA. NIEHS, Res Triangle Pk, NC 27709 USA. Dow Chem Co USA, Toxicol & Environm Res & Consulting, Midland, MI 48674 USA. RP Pettit, SD (reprint author), ILSI Hlth & Environm Sci Inst, 1 Thomas Circle,9th Floor NW, Washington, DC 20005 USA. EM spettit@ilsi.org NR 77 TC 15 Z9 15 U1 0 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD OCT 1 PY 2005 VL 208 IS 1 BP 1 EP 20 DI 10.1016/j.taap.2004.12.012 PG 20 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 972TT UT WOS:000232476800001 PM 16164957 ER PT J AU Wu, C AF Wu, C TI GC-MS detects illegal CO in finish SO TRAC-TRENDS IN ANALYTICAL CHEMISTRY LA English DT News Item C1 US FDA, Seafood Prod Res Ctr, Pacific Reg Lab NW, Washington, DC 20204 USA. RP Wu, C (reprint author), US FDA, Seafood Prod Res Ctr, Pacific Reg Lab NW, Washington, DC 20204 USA. EM cindy.wu@fda.gov NR 1 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0165-9936 J9 TRAC-TREND ANAL CHEM JI Trac-Trends Anal. Chem. PD OCT PY 2005 VL 24 IS 9 BP IV EP VI PG 3 WC Chemistry, Analytical SC Chemistry GA 979UM UT WOS:000232970400004 ER PT J AU Levitin, F Stern, O Weiss, M Gil-Henn, C Ziv, R Prokocimer, Z Smorodinsky, NI Rubinstein, DB Wreschner, DH AF Levitin, F Stern, O Weiss, M Gil-Henn, C Ziv, R Prokocimer, Z Smorodinsky, NI Rubinstein, DB Wreschner, DH TI The MUC1 SEA module is a self-cleaving domain SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN LYSOSOMAL ASPARTYLGLUCOSAMINIDASE; POLYMORPHIC EPITHELIAL MUCIN; CARCINOMA-ASSOCIATED ANTIGEN; RECEPTOR PROTEOLYTIC SITE; N-TERMINAL THREONINE; FC CHIMERIC PROTEINS; CANCER CELL-LINES; BREAST-CANCER; MONOCLONAL-ANTIBODY; SPLICE VARIANTS AB MUC1, a glycoprotein overexpressed by a variety of human adenocarcinomas, is a type I transmembrane protein (MUC1/TM) that soon after its synthesis undergoes proteolytic cleavage in its extracellular domain. This cleavage generates two subunits, alpha and beta, that specifically recognize each other and bind together in a strong noncovalent interaction. Proteolysis occurs within the SEA module, a 120-amino acid domain that is highly conserved in a number of heavily glycosylated mucin-like proteins. Post-translational cleavage of the SEA module occurs at a site similar to that in MUC1 in the glycoproteins IgHepta and MUC3. However, as in the case of other proteins containing the cleaved SEA module, the mechanism of MUC1 proteolysis has not been elucidated. Alternative splicing generates two transmembrane MUC1 isoforms, designated MUC1/Y and MUC1/X. We demonstrated here that MUC1/X, whose extracellular domain is comprised solely of the SEA module in addition to 30 MUC1N-terminal amino acids, undergoes proteolytic cleavage at the same site as the MUC1/TM protein. In contrast, the MUC1/Y isoform, composed of an N-terminally truncated SEA module, is not cleaved. Cysteine or threonine mutations of the MUC1/X serine residue (Ser-63) immediately C-terminal to the cleavage site generated cleaved proteins, whereas mutation of the Ser-63 residue of MUC1/X to any other of 17 amino acids did not result in cleavage. In vitro incubation of highly purified precursor MUC1/X protein resulted in self-cleavage. Furthermore, addition of hydroxylamine, a strong nucleophile, markedly enhanced cleavage. Both these features are signature characteristics of self-cleaving proteins, and we concluded that MUC1 undergoes autoproteolysis mediated by an N-->O-acyl rearrangement at the cleavage site followed by hydrolytic resolution of the unstable ester and concomitant cleavage. It is likely that all cleaved SEA module-containing proteins follow a similar route. C1 Tel Aviv Univ, Dept Cell Res & Immunol, IL-69978 Ramat Aviv, Israel. Tel Aviv Univ, Akec & Myra Marmot Hybridoma Lab, IL-69978 Ramat Aviv, Israel. Assaf Harofeh Med Ctr, Dept Endocrinol, IL-70300 Zerifin, Israel. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20851 USA. RP Wreschner, DH (reprint author), Tel Aviv Univ, Dept Cell Res & Immunol, IL-69978 Ramat Aviv, Israel. EM danielhw@post.tau.ac.il NR 86 TC 103 Z9 114 U1 0 U2 7 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 30 PY 2005 VL 280 IS 39 BP 33374 EP 33386 DI 10.1074/jbc.M506047200 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 966YG UT WOS:000232058100035 PM 15987679 ER PT J AU Zaslavsky, BG AF Zaslavsky, BG TI Assessing equivalence or non-inferiority in screening tests with paired and independent binomial endpoints through confidence intervals for the odds ratio SO STATISTICS IN MEDICINE LA English DT Article DE generalized estimation equations; logistic regression; repeated measures; SAS PROC GENMOD ID PROPORTIONS; DIFFERENCE; DESIGN; NONINFERIORITY; TRIALS AB The confidence interval (CI) on the population average (PA) odds ratio (OR) is a useful measure of agreement among different diagnostic methods when no gold standard is available. It can be calculated by the repeated measures logistic regression procedure (GENMOD, SAS). We compare the width of CIs from paired and independent samples with an identical number of measurements and an identical probability of positive response among them. For two and three diagnostic methods with binomial endpoints, the best performing sampling strategy is analytically described. The asymptotic formulae of the ratio of the CI widths for paired and independent samples are provided. We numerically study the dependence of the width of the CIs on the number of positive concordant outcomes. The width of CIs from independent samples is an increasing function of the sample size with a saturation asymptote and rather weak dependence on the argument. The width of CIs from paired samples is a decreasing function of the sample size with a saturation asymptote and significant dependence on the argument when the sample size is small. If curves for paired and independent samples intersect, a critical sample size exists. At this point, a small change in the sample size can reverse the choice of the best performing sampling policy. We numerically validated the robustness of the critical point to variations of the conditional OR. Published in 2005 by John Wiley & Sons, Ltd. C1 US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Zaslavsky, BG (reprint author), US FDA, Ctr Biol Evaluat & Res, 1401 Rockville Pike,HFM-217, Rockville, MD 20852 USA. EM zaslavsky@cber.fda.gov NR 14 TC 1 Z9 1 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD SEP 30 PY 2005 VL 24 IS 18 BP 2837 EP 2855 DI 10.1002/sim.2152 PG 19 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 967VG UT WOS:000232118700007 PM 16134143 ER PT J AU Bowers, DC McNeil, DE Liu, Y Yasui, Y Stovall, M Gurney, JG Hudson, MM Donaldson, SS Packer, RJ Mitby, PA Kasper, CE Robison, LL Oeffinger, KC AF Bowers, DC McNeil, DE Liu, Y Yasui, Y Stovall, M Gurney, JG Hudson, MM Donaldson, SS Packer, RJ Mitby, PA Kasper, CE Robison, LL Oeffinger, KC TI Stroke as a late treatment effect of Hodgkin's disease: A report from the Childhood Cancer Survivor Study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID EXTERNAL CERVICAL IRRADIATION; CAROTID-ARTERY DISEASE; YOUNG-ADULTS; ISCHEMIC-STROKE; RADIOTHERAPY; RADIATION; NECK; SPLENECTOMY; DOXORUBICIN; MORTALITY AB Purpose The objectives of this report are to examine the incidence of and risk factors for stroke among childhood Hodgkin's disease (HD) survivors. Patients and Methods The Childhood Cancer Survivor Study is a multi-institutional cohort study of more than 5-year cancer survivors diagnosed between 1970 and 1986 and a sibling comparison group. Incidence rates of stroke among HD survivors (n = 1,926) and siblings (n = 3,846) were calculated and compared. Cox proportional hazards models were used to estimate the hazard ratios, reported as relative risks (RR), of developing stroke between HD survivors and siblings. Results Nine siblings reported a stroke, for an incidence of 8.00 per 100,000 person-years (95% Cl, 3.86 to 14.43 per 100,000 person-years). Twenty-four HD survivors reported a stroke. The incidence of late-occurring stroke among HD survivors was 83.6 per 100,000 person-years (95% Cl,2.01 to 9.29; P = .0002). All 24 survivors received mantle radiation exposure (median dose, 40 Gy). The incidence of late-occurring stroke among HD survivors treated with mantle radiation was 109.8 per 100,000 person-years (95% Cl, 70.8 to 161.1 per 100,000 person-years). The RR of late-occurring stroke among HD survivors treated with mantle radiation was 5.62 (95% Cl, 2.59 to 12.25; P < .0001). Conclusion Survivors of childhood HD are at increased risk of stroke. Mantle radiation exposure is strongly associated with subsequent stroke. Potential mechanisms may include carotid artery disease or cardiac valvular disease. C1 Univ Texas, SW Med Ctr, Dallas, TX USA. MD Anderson Canc Ctr, Houston, TX USA. US FDA, Rockville, MD 20857 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Univ Minnesota, Minneapolis, MN USA. Stanford Univ, Sch Med, Stanford, CA USA. St Jude Childrens Res Hosp, Memphis, TN 38105 USA. Childrens Natl Med Ctr, Washington, DC 20010 USA. RP Bowers, DC (reprint author), Dept Pediat, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. EM Daniel.Bowers@utsouthwestern.edu RI Yasui, Yutaka/E-2564-2015 OI Yasui, Yutaka/0000-0002-7717-8638 FU NCI NIH HHS [5U01-CA-55727-05] NR 30 TC 117 Z9 120 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 20 PY 2005 VL 23 IS 27 BP 6508 EP 6515 DI 10.1200/JCO.2005.15.107 PG 8 WC Oncology SC Oncology GA 969KN UT WOS:000232233100012 PM 16170160 ER PT J AU Chen, Q Espey, MG Krishna, MC Mitchell, JB Corpe, CP Buettner, GR Shacter, E Levine, M AF Chen, Q Espey, MG Krishna, MC Mitchell, JB Corpe, CP Buettner, GR Shacter, E Levine, M TI Pharmacologic ascorbic acid concentrations selectively kill cancer cells: Action as a pro-drug to deliver hydrogen peroxide to tissues SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE cell death; ascorbate radical ID RECOMMENDED DIETARY ALLOWANCE; VITAMIN-C PHARMACOKINETICS; ACUTE MYELOID-LEUKEMIA; TERMINAL HUMAN CANCER; SUPPLEMENTAL ASCORBATE; SUPEROXIDE-DISMUTASE; SUPPORTIVE TREATMENT; OXIDATIVE STRESS; SURVIVAL TIMES; LYMPHOMA-CELLS AB Human pharmacokinetics data indicate that i.v. ascorbic acid (ascorbate) in pharmacologic concentrations could have an unanticipated role in cancer treatment. Our goals here were to test whether ascorbate killed cancer cells selectively, and if so, to determine mechanisms, using clinically relevant conditions. Cell death in 10 cancer and 4 normal cell types was measured by using 1-h exposures. Normal cells were unaffected by 20 mM ascorbate, whereas 5 cancer lines had EC50 values of < 4 mM, a concentration easily achievable i.v.Human lymphoma cells were studied in detail because of their sensitivity to ascorbate (EC50 of 0.5 mM) and suitability for addressing mechanisms. Extracellular but not intracellular ascorbate mediated cell death, which occurred by apoptosis and pyknosis/necrosis. Cell death was independent of metal chelators and absolutely dependent on H2O2 formation. Cell death from H2O2 added to cells was identical to that found when H2O2 was generated by ascorbate treatment. H2O2 generation was dependent on ascorbate concentration, incubation time, and the presence of 0.5-10% serum, and displayed a linear relationship with ascorbate radical formation. Although ascorbate addition to medium generated H2O2, ascorbate addition to blood generated no detectable H2O2 and only trace detectable ascorbate radical. Taken together, these data indicate that ascorbate at concentrations achieved only by i.v. administration may be a pro-drug for formation of H2O2, and that blood can be a delivery system of the pro-drug to tissues. These findings give plausibility to i.v. ascorbic acid in cancer treatment, and have unexpected implications for treatment of infections where H2O2 may be beneficial. C1 NIDDKD, Mol & Clin Nutr Sect, NIH, Bethesda, MD 20892 USA. NCI, Radiat Biol Branch, NIH, Bethesda, MD 20892 USA. Univ Iowa, Free Rad & Radiat Biol Program, Iowa City, IA 52242 USA. US FDA, Ctr Biol Evaluat & Res, Biochem Lab, Bethesda, MD 20892 USA. RP Levine, M (reprint author), NIDDKD, Mol & Clin Nutr Sect, NIH, Bldg 10,Room 4D52,MSC-1372, Bethesda, MD 20892 USA. EM markl@mail.nih.gov RI Chen, Qi/D-8278-2015 OI Chen, Qi/0000-0002-7173-8411 FU Intramural NIH HHS; NIDDK NIH HHS [Z01 DK054506] NR 58 TC 353 Z9 368 U1 7 U2 43 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 20 PY 2005 VL 102 IS 38 BP 13604 EP 13609 DI 10.1073/pnas.0506390102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 967TW UT WOS:000232115100046 PM 16157892 ER PT J AU Kioi, M Takahashi, S Kawakami, M Kawakami, K Kreitman, RJ Puri, RK AF Kioi, M Takahashi, S Kawakami, M Kawakami, K Kreitman, RJ Puri, RK TI Expression and targeting of interieukin-4 receptor for primary and advanced ovarian cancer therapy SO CANCER RESEARCH LA English DT Article ID RECOMBINANT HUMAN INTERLEUKIN-4; RENAL-CELL CARCINOMA; PHASE-II TRIAL; GYNECOLOGIC-ONCOLOGY-GROUP; GROWTH-FACTOR; INTRAPERITONEAL CISPLATIN; ANTITUMOR-ACTIVITY; CYTOTOXIN THERAPY; EXOTOXIN; BREAST AB Because the most characteristic property of ovarian cancer is i.p. spread, the majority of patients are diagnosed at an advanced stage, leading to limited availability of options for curative therapies. With an intent to identify targeted therapeutic approaches, we have observed that similar to 60% of 21 ovarian cancer tissue samples express a high density of interleukin-4 receptor (IL-4R), whereas normal ovarian tissues tested (n = 7) expressed no or low levels of IL-4R. To target IL-4R, we have developed IL-4 cytotoxin, in which circular-permuted IL-4 is fused to a mutated form of Pseudomonas exotoxin. This cytotoxin is specifically and highly cytotoxic to PA-1, IGROV-1, and SK-OV3 ovarian carcinoma cell lines in vitro. In addition, it shows remarkable antitumor activities against established s.c. ovarian tumors in immunodeficient animals. i.p. administration of IL-4 cytotoxin in mice with orthotopically implanted ovarian tumors caused regression of established tumors and prevented these animals from tumor metastasis. Continuous i.p. infusion of IL-4 cytotoxin prolonged survival of tumor-bearing mice even with bulky disease. These results indicate that IL-4R-targeted cytotoxin may be a useful agent for the management of patients with ovarian cancer, and further studies need to be done to evaluate its safety, tolerability, and efficacy. C1 US FDA, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res,NIH, Bethesda, MD 20892 USA. NCI, Lab Biosyst & Canc, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Puri, RK (reprint author), US FDA, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res,NIH, Bldg 29B,Room 2NN20,HFM-735,29 Lincoln Dr, Bethesda, MD 20892 USA. EM puri@cber.fda.gov OI Kioi, Mitomu/0000-0002-7981-3340 NR 39 TC 15 Z9 16 U1 1 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 15 PY 2005 VL 65 IS 18 BP 8388 EP 8396 DI 10.1158/0008-5472.CAN-05-1043 PG 9 WC Oncology SC Oncology GA 964AQ UT WOS:000231848800042 PM 16166317 ER PT J AU Johnson, JR Cohen, M Sridhara, R Chen, YF Williams, GM Duan, J Gobburu, J Booth, B Benson, K Leighton, J Hsieh, LS Chidambaram, N Zimmerman, P Pazdur, R AF Johnson, JR Cohen, M Sridhara, R Chen, YF Williams, GM Duan, J Gobburu, J Booth, B Benson, K Leighton, J Hsieh, LS Chidambaram, N Zimmerman, P Pazdur, R TI Approval summary for erlotinib for treatment of patients with locally advanced or metastatic non-small cell lung cancer after failure of at least one prior chemotherapy regimen SO CLINICAL CANCER RESEARCH LA English DT Article ID GROWTH-FACTOR RECEPTOR; MUTATIONS; GEFITINIB AB Purpose: To describe the Food and Drug Administration (FDA) review and approval of erlotinib (Tarceva, OSI Pharmaceuticals, Melville, NY) for treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) after failure of at least one prior chemotherapy regimen. Experimental Design: The FDA reviewed raw data in electronic format from a randomized controlled clinical trial comparing erlotinib with placebo in patients with locally advanced or metastatic NSCLC after failure of at least one prior chemotherapy regimen. Results: Patients were randomized in a 2:1 ratio (erlotinib, n = 488 and placebo, n = 243). Erlotinib was superior to placebo for survival, progression-free survival, and tumor response rate. Exploratory analyses indicate that epidermal growth factor receptor status may be an important predictor of the erlotinib survival effect. Rash (75% versus 17%) and diarrhea (54% versus 18%) in the erlotnib and placebo group respectively were the most common adverse events. Severe rash occurred in 9% and severe diarrhea in 6% of erlotinib-treated patients and each resulted in study discontinuation in 1% of patients. Dose reductions were required for 10% of patients-with rash and 4% of patients with diarrhea. Conclusions: On November 18, 2004, the FDA granted erlotinib regular approval for treatment of patients with locally advanced or metastatic NSCLC,after-failure of at least one prior chemotherapy regimen. The applicant has committed to conduct post-marketing clinical trials to assess further the effect of epidermal growth factor, receptor expression; measured with immunohistochemical staining, on erlotinib treatment effect. C1 US FDA, Ctr Drug Evaluat & Res, Div Oncol Drug Prod HFD150, Rockville, MD 20857 USA. RP Johnson, JR (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Oncol Drug Prod HFD150, HFD 150,5600 Fisheries Lane, Rockville, MD 20857 USA. EM Johnsonj@cder.fda.gov NR 14 TC 135 Z9 144 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD SEP 15 PY 2005 VL 11 IS 18 BP 6414 EP 6421 DI 10.1158/1078-CCR-05-0790 PG 8 WC Oncology SC Oncology GA 966JN UT WOS:000232016100002 PM 16166415 ER PT J AU Wang, WL Golding, B AF Wang, WL Golding, B TI The cytotoxic T lymphocyte response against a protein antigen does not decrease the antibody response to that antigen although antigen-pulsed B cells can be targets SO IMMUNOLOGY LETTERS LA English DT Article DE CTL; antibody response; vaccine; antigen-specific B cells; MHC class I presentation ID IN-VIVO; CROSS-PRESENTATION; EXOGENOUS ANTIGEN; FLOW-CYTOMETRY; CTL; PHENOTYPE; OVALBUMIN; EFFECTOR; SURVIVAL; DIVISION AB The role of activated CD8(+) T cells in shaping the dynamics of in vivo antigen presentation and immune responses is a subject receiving more attention. We studied whether cytotoxic T lymphocyte (CTL) would limit antibody responses by targeting antigen-specific B cells. A modified in vivo CTL assay was developed and used herein to demonstrate cytotoxicity in vivo, and to show that antigen-specific B cells that process exogenous antigen and present peptide in association with MHC class I can be the targets of CD8(+) T cells. B cells from C57BL/6 mice immunized with ovalbumin (OVA)/alum were pulsed with OVA in vitro, and transferred into C57BL/6 recipient mice that had been immunized with vaccinia virus expressing SIINFEKL minigene to generate CD8(+) CTL against K-b/SIINFEKL. OVA-pulsed B220(+) B cells from OVA-immunized mice were killed to a greater extent than B220(+) B cells from naive mice (28 +/- 20% versus 12 +/- 16%, p = 0.0042). However, mice receiving vaccinia-SIINFEKL and generating CTL, did not appear to target endogenous B cells, since both primary and secondary antibody responses to OVA were unaffected. Our findings indicate that CTL responses to the protein antigen do not interfere with endogenous B cell responses, even though exogenous B cells expressing the CTL epitope can be efficiently lysed. Published by Elsevier B.V. C1 Ctr Biol Evaluat & Res, Lab Plasma Derivat, Div Hematol, Off Blood Res & Review,Food & Drug Adm, Bethesda, MD 20892 USA. RP Wang, WL (reprint author), Ctr Biol Evaluat & Res, Lab Plasma Derivat, Div Hematol, Off Blood Res & Review,Food & Drug Adm, 29 Lincoln Dr, Bethesda, MD 20892 USA. EM wangw@cber.fda.gov NR 25 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-2478 J9 IMMUNOL LETT JI Immunol. Lett. PD SEP 15 PY 2005 VL 100 IS 2 BP 195 EP 201 DI 10.1016/j.imlet.2005.04.003 PG 7 WC Immunology SC Immunology GA 971YI UT WOS:000232420500015 PM 15916814 ER PT J AU Huang, LY Ishii, KJ Akira, S Aliberti, J Golding, B AF Huang, LY Ishii, KJ Akira, S Aliberti, J Golding, B TI Th1-like cytokine induction by heat-killed Brucella abortus is dependent on triggering of TLR9 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID PLASMACYTOID DENDRITIC CELLS; TOLL-LIKE RECEPTORS; INDUCED IMMUNE ACTIVATION; CPG-DNA; BACTERIAL-DNA; INNATE IMMUNITY; PROTEIN-KINASE; CUTTING EDGE; T-CELLS; B-CELLS AB In this report we provide evidence, for the first time, that bacterial DNA in the context of heat-killed Brucella abortus (HKBA) engages TLR9 in dendritic cells (DC), resulting in a Th1-like cytokine response. This is based on the findings that HKBA induction of IL-12p4O is: 1) abolished in DC from TLR9(-/-) mice; 2) blocked by suppressive oligodeoxynucleotides; 3) simulated by bacterial DNA derived from HKBA; and 4) abrogated by DNase or methylation of the DNA from HKBA. Furthermore, the effect of HKBA can be inhibited by chloroquine, indicating that endosomal acidification is required and supporting the notion that DNA from HKBA is interacting with TLR9 at the level of the enclosome, as is the case with CpG oligodeoxynucleotides. In addition to DC, HKBA can elicit IL-12p4O secretion from macrophages, in which case the effect is wholly MyD88 dependent but only partially TLR9 dependent. This probably explains why HKBA effects in vivo are only partially reduced in TLR9(-/-), but absent in MyD88(-/-) mice. Because of their intimate interactions with T cells, the DC response is most likely to be critical for linking innate and adaptive immune responses, whereas the macrophage reaction may play a role in enhancing NK cell and bystander immune responses. In addition to IL-12p4O, HKBA induces other Th1-like cytokines, namely, IFN-alpha and IFN-gamma, in a TLR9-dependent manner. These cytokines are important in protection against viruses and bacteria, and their induction enhances HKBA as a potential carrier for vaccines. C1 US FDA, Div Hematol, Off Blood Res & Review, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. Osaka Univ, Exploratory Res Adv Technol, Japan Sci & Technol Agcy, Osaka, Japan. Osaka Univ, Dept Host Def, Inst Microbial Dis, Osaka, Japan. Duke Univ, Med Ctr, Dept Immunol, Durham, NC 27701 USA. RP Golding, B (reprint author), US FDA, Div Hematol, Off Blood Res & Review, Ctr Biol Evaluat & Res, Bldg 29,Room 328,1401 Rockville Pike,HFM-345, Rockville, MD 20852 USA. EM Golding@cber.fda.gov RI Akira, Shizuo/C-3134-2009; Aliberti, Julio/G-4565-2012; Aliberti, Julio/I-7354-2013; Ishii, Ken/B-1685-2012 OI Aliberti, Julio/0000-0003-3420-8478; Ishii, Ken/0000-0002-6728-3872 NR 65 TC 59 Z9 64 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 15 PY 2005 VL 175 IS 6 BP 3964 EP 3970 PG 7 WC Immunology SC Immunology GA 966HN UT WOS:000232010800062 PM 16148144 ER PT J AU Ausin, C Grajkowski, A Cieslak, J Beaucage, SL AF Ausin, C Grajkowski, A Cieslak, J Beaucage, SL TI An efficient reagent for the phosphorylation of deoxyribonucleosides, DNA oligonucleotides, and their thermolytic analogues SO ORGANIC LETTERS LA English DT Article ID SULFUR-TRANSFER REAGENT; TRITYL CATION RELEASE; CHEMICAL 5'-PHOSPHORYLATION; 3H-1,2-BENZODITHIOL-3-ONE 1,1-DIOXIDE; OLIGODEOXYRIBONUCLEOTIDES AB The phosphoramidite 11 was prepared in three steps from methyl 2-mercaptoacetate and demonstrated efficiency in the synthesis of conventional 5'-/3'-phosphate/thiophosphate monoester derivatives of 2'-deoxyribonucleosides and DNA oligonucleotides. Moreover, the use of 11 has enabled the preparation of the dinucleoside phosphorothioate analogue 26 in high yields (> 95%) with minimal cleavage (< 2%) of the thermolytic thiophosphate protecting group. C1 US FDA, Div Therapeut Prot, Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. RP Ausin, C (reprint author), US FDA, Div Therapeut Prot, Ctr Drug Evaluat & Res, 8800 Rockville Pike, Bethesda, MD 20892 USA. EM beaucage@cber.fda.gov NR 17 TC 10 Z9 10 U1 3 U2 9 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1523-7060 J9 ORG LETT JI Org. Lett. PD SEP 15 PY 2005 VL 7 IS 19 BP 4201 EP 4204 DI 10.1021/ol0516263 PG 4 WC Chemistry, Organic SC Chemistry GA 964DE UT WOS:000231858100035 PM 16146387 ER PT J AU Okamura, M Lillehoj, HS Raybourne, RB Babu, US Heckert, RA Tani, H Sasai, K Baba, E Lillehoj, EP AF Okamura, M Lillehoj, HS Raybourne, RB Babu, US Heckert, RA Tani, H Sasai, K Baba, E Lillehoj, EP TI Differential responses of macrophages to Salmonella enterica serovars Enteritidis and Typhimurium SO VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY LA English DT Article DE interferon-gamma; nitric oxide; food poisoning; chicken; egg ID CHICKEN INTERFERON-GAMMA; LYMPHOCYTE-PROLIFERATION; MURINE SALMONELLOSIS; IMMUNE-RESPONSES; IN-VIVO; VACCINE; DEATH; EGGS; PHAGOCYTES; EXPRESSION AB Macrophages are major effectors against Salmonella infection, and also transport bacteria between host tissues and provide a protected site for intracellular bacteria] replication. We hypothesized that differences in chicken macrophage responses to Salmonella enterica serovar Enteritidis (SE) and serovar Typhimurium (ST) played a role in preferential infection of eggs by SE compared with ST. To test this hypothesis, we determined bacterial phagocytosis and intracellular viability and macrophage nitric oxide (NO) production following in vitro infection with SE or ST in the presence or absence of interferon-gamma (IFN-gamma). The effects of bacterial components, lipopolysaccharide (LPS), outer membrane proteins (OMP) and flagella, on NO production were also assessed. Our results showed: (1) in the presence or absence of IFN-gamma, the percentage rnacrophages phagocytizing SE and ST was similar; (2) the number of intracellular viable SE was significantly reduced compared with ST in the presence or absence of IFN-gamma; (3) increased macrophage necrosis was seen in the presence of IFN-gamma and ST; (4) Salmonella infection acted synergistically with IFN-gamma in induction of nitric oxide production; and (5) in the absence of IFN-gamma, macrophages produced significantly greater NO following treatment with SE outer membrane protein or flagella compared with ST OMP or flagella, while in the presence of IFN-gamma significantly less NO was produced following treatment with SE-LPS compared with ST-LPS. These results suggest that differential responses of chicken macrophages to SE versus ST may result in increased macrophage death with ST, which could result in an increased inflammatory response as compared to SE. (c) 2005 Elsevier B.V. All rights reserved. C1 US FDA, Immunol Branch, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. Univ Maryland, Avrum Gudelsky Vet Ctr, College Pk, MD 20742 USA. Osaka Prefecture Univ, Grad Sch Agr & Biol Sci, Dept Vet Internal Med, Div Vet Sci, Sakai, Osaka 5998531, Japan. Univ Maryland, Sch Med, Dept Pediat, Baltimore, MD 21201 USA. RP Lillehoj, HS (reprint author), USDA ARS, Beltsville Agr Res Ctr, Anim Parasit Dis Lab, Anim & Nat Resources Inst, Bldg 1040,BARC E, Beltsville, MD 20705 USA. EM hlilleho@anri.barc.usda.gov NR 34 TC 39 Z9 40 U1 0 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-2427 J9 VET IMMUNOL IMMUNOP JI Vet. Immunol. Immunopathol. PD SEP 15 PY 2005 VL 107 IS 3-4 BP 327 EP 335 DI 10.1016/j.vetimm.2005.05.009 PG 9 WC Immunology; Veterinary Sciences SC Immunology; Veterinary Sciences GA 952JI UT WOS:000230999400013 PM 16023220 ER PT J AU Trontell, AE AF Trontell, AE TI The RADAR project and the FDA SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 US FDA, Off Drug Safety, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Trontell, AE (reprint author), US FDA, Off Drug Safety, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. EM trontella@cder.fda.gov NR 5 TC 8 Z9 8 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD SEP 14 PY 2005 VL 294 IS 10 BP 1206 EP 1206 DI 10.1001/jama.294.10.1206-a PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 963UI UT WOS:000231831200012 PM 16160128 ER PT J AU Lugo-Villarino, G Ito, S Klinman, DM Glimcher, LH AF Lugo-Villarino, G Ito, S Klinman, DM Glimcher, LH TI The adjuvant activity of CpG DNA requires T-bet expression in dendritic cells SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE IFN-gamma; oligodeoxynucleotide; plasmacytoid dendritic cells ID LISTERIA-MONOCYTOGENES INFECTION; IFN-GAMMA PRODUCTION; IN-VIVO; IMMUNE-RESPONSES; NK; OLIGODEOXYNUCLEOTIDES; DEFENSE; ABSENCE; HOST AB Treatment with synthetic oligodeoxynucleotides containing CpG motifs (CpG ODNs) is remarkably protective against otherwise lethal infection. Here, we describe an essential role for the transcription factor T-bet in mediating the protective function of CpG ODNs. Loss of T-bet in conventional CD11c(hi) dendritic cells (DCs) and in plasmacytoid DCs impaired production of IFNs. Strikingly, in contrast to Rag2(-/-) mice, Rag2(-/-) mice that also lacked T-bet (DKO) could not be rescued from lethal Listeria monocytogenes infection by prior treatment with CpG ODN. Rescue was achieved by adoptive transfer of CD11c(hi) DCs from WT, but not T-bet(-/-), CpG ODN-treated donor mice. We conclude that T-bet in DCs is required for the adjuvant activity of CpG ODN in infection, revealing its vital role in innate immunity. C1 Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. US FDA, Div Therapeut Prot, Bethesda, MD 20892 USA. RP Glimcher, LH (reprint author), Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, 665 Huntington Ave, Boston, MA 02115 USA. EM lglimche@hsph.harvard.edu OI Lugo, Geanncarlo/0000-0003-4620-8491 FU NIAID NIH HHS [P01 AI056296, P01AI056296] NR 30 TC 40 Z9 46 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 13 PY 2005 VL 102 IS 37 BP 13248 EP 13253 DI 10.1073/pnas.0506638102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 964YG UT WOS:000231916300044 PM 16135562 ER PT J AU Atkins, R Benbow, W Berley, D Blaufuss, E Coyne, DG DeYoung, T Dingus, BL Dorfan, DE Ellsworth, RW Fleysher, L Fleysher, R Gonzalez, MM Goodman, JA Hays, E Hoffman, CM Kelley, LA Lansdell, CP Linnemann, JT McEnery, JE Mincer, AI Morales, MF Nemethy, P Noyes, D Ryan, JM Samuelson, FW Parkinson, PMS Shoup, A Sinnis, G Smith, AJ Sullivan, GW Williams, DA Wilson, ME Xu, XW Yodh, GB AF Atkins, R Benbow, W Berley, D Blaufuss, E Coyne, DG DeYoung, T Dingus, BL Dorfan, DE Ellsworth, RW Fleysher, L Fleysher, R Gonzalez, MM Goodman, JA Hays, E Hoffman, CM Kelley, LA Lansdell, CP Linnemann, JT McEnery, JE Mincer, AI Morales, MF Nemethy, P Noyes, D Ryan, JM Samuelson, FW Parkinson, PMS Shoup, A Sinnis, G Smith, AJ Sullivan, GW Williams, DA Wilson, ME Xu, XW Yodh, GB TI Constraints on very high energy gamma-ray emission from gamma-ray bursts SO ASTROPHYSICAL JOURNAL LA English DT Article DE gamma rays : bursts; gamma rays : observations ID AIR-SHOWER ARRAY; GRB 970417A; TEV; BATSE; ABSORPTION; SEARCH; GRB-010921; MILAGRITO; COMPONENT; SPECTRUM AB The Milagro Gamma-Ray Observatory employs a water Cerenkov detector to observe extensive air showers produced by high-energy particles interacting in the Earth's atmosphere. Milagro has a wide field of view and high duty cycle, monitoring the northern sky almost continuously in the 100 GeV to 100 TeV energy range. Milagro is thus uniquely capable of searching for very high energy emission from gamma-ray bursts ( GRBs) during the prompt emission phase. Detection of > 100 GeV counterparts would place powerful constraints on GRB mechanisms. Twenty-five satellite-triggered GRBs occurred within the field of view of Milagro between 2000 January and 2001 December. We have searched for counterparts to these GRBs and found no significant emission from any of the burst positions. Due to the absorption of high-energy gamma rays by the extragalactic background light, detections are only expected to be possible for redshifts less than similar to 0.5. Three of the GRBs studied have measured redshifts. GRB 010921 has a redshift low enough ( 0.45) to allow an upper limit on the fluence to place an observational constraint on potential GRB models. C1 Univ Wisconsin, Dept Phys, Madison, WI 53706 USA. Univ Calif Santa Cruz, Inst Particle Phys, Santa Cruz, CA 95064 USA. Univ Maryland, Dept Phys, College Pk, MD 20742 USA. Los Alamos Natl Lab, Grp P23, Los Alamos, NM 87545 USA. George Mason Univ, Dept Phys & Astron, Fairfax, VA 22030 USA. NYU, Dept Phys, New York, NY 10003 USA. Michigan State Univ, Dept Phys & Astron, E Lansing, MI 48824 USA. Univ New Hampshire, Dept Phys, Durham, NH 03824 USA. US FDA, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, Rockville, MD 20850 USA. Univ Calif Irvine, Dept Phys & Astron, Irvine, CA 92697 USA. RP Atkins, R (reprint author), Univ Utah, Dept Phys, 115 South 1400 East, Salt Lake City, UT 84112 USA. RI Hays, Elizabeth/D-3257-2012; OI Dingus, Brenda/0000-0001-8451-7450; Mincer, Allen/0000-0002-6307-1418 NR 31 TC 43 Z9 43 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0004-637X J9 ASTROPHYS J JI Astrophys. J. PD SEP 10 PY 2005 VL 630 IS 2 BP 996 EP 1002 DI 10.1086/432501 PN 1 PG 7 WC Astronomy & Astrophysics SC Astronomy & Astrophysics GA 961LR UT WOS:000231664400030 ER PT J AU Anderson, CR Wu, WH AF Anderson, CR Wu, WH TI Analysis of carbon monoxide in commercially treated tuna (Thunnus spp.) and mahi-mahi (Coryphaena hippurus) by gas chromatography mass spectrometry SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE carbon monoxide; GC/MS; headspace; tuna; mahi-mahi ID MYOGLOBIN; ATMOSPHERE; COLOR; STABILITY; AUTOXIDATION; FLESH; LIFE; BEEF; PORK; MEAT AB A simple and confirmative method for quantitative determination of carbon monoxide in tuna and mahi-mahi tissues using GC/MS, following chemical liberation of CO into headspace, is described. Carbon monoxide in recent years has been employed by the fishery industry to preserve fresh appearance in selected species of finfish during frozen storage, particularly in vacuum-packaged products. Indigenous CO contents of fresh AN tuna and mahi-mahi were examined using the method described in this study and found to be close to or less than 150 and 100 ng/g, respectively. Commercially CO-treated, vacuum-packaged tuna from multiple sources consistently showed CO level near or greater than 1 mu g/g, while CO level in the only CO-treated frozen mahi-mahi sample was in the 500 ng/g range. The difference between untreated and treated specimens was in the range of 1 order of magnitude and thus suggested an easy quantitative and confirmative method of CO using widely available instrumentation that may be potentially useful for regulatory purpose in determining whether a commercially available product has been exposed to CO even if not labeled as such. C1 US FDA, Seafood Prod Res Ctr, Pacific Reg Lab NW, Bothell, WA 98021 USA. RP Wu, WH (reprint author), US FDA, Seafood Prod Res Ctr, Pacific Reg Lab NW, 22201 23rd Dr SE, Bothell, WA 98021 USA. EM cindy.wu@fda.hhs.gov NR 25 TC 18 Z9 21 U1 2 U2 9 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0021-8561 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD SEP 7 PY 2005 VL 53 IS 18 BP 7019 EP 7023 DI 10.1021/jf0514266 PG 5 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 961EC UT WOS:000231643700010 PM 16131105 ER PT J AU Colman, E AF Colman, E TI Anorectics on trial: A half century of federal regulation of prescription appetite suppressants SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID CORONARY-HEART-DISEASE; PRIMARY-PREVENTION TRIAL; HYPERTENSION AB Beginning with the passage of the Federal Food, Drug, and Cosmetic Act in 1938 and escalating with the 1962 Kefauver-Harris amendments, increasing pressure has been placed on pharmaceutical manufacturers to demonstrate that a drug's benefits outweigh its risks. Nowhere has the question of risk versus benefit come under greater scrutiny than with anorectics. After the approval in the 1940s and 1950s of a number of amphetamine and amphetamine-like compounds for the treatment of obesity, the U.S. Food and Drug Administration struggled to define the efficacy and safety of these agents. Labeling restrictions on duration of use and warnings about abuse and addiction ultimately contributed to the reduced use of anorectics. That trend continued until the mid-1990s, when the off-label use of fenfluramine plus phentermine (fen-phen) and the approval of dexfenfluramine gave rise to widespread, long-term use of anorectics to treat obesity. The adverse effects that came to be associated with fenfluramine and dexfenfluramine, leading to their eventual withdrawal from the market, gave pause to regulators, physicians, patients, and drug companies alike. Sibutramine, the latest anorectic to enter the market, is now the focus of a landmark trial that is examining, for the first time, whether drug-induced weight loss reduces the risk for fatal and nonfatal cardiovascular disease. C1 US FDA, Div Metab & Endocrine Drug Prod, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Colman, E (reprint author), US FDA, Div Metab & Endocrine Drug Prod, Ctr Drug Evaluat & Res, HFD-510,5600 Fishers Lane, Rockville, MD 20857 USA. EM colmane@cder.fda.gov NR 48 TC 78 Z9 81 U1 1 U2 4 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD SEP 6 PY 2005 VL 143 IS 5 BP 380 EP 385 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 961TE UT WOS:000231683900007 PM 16144896 ER PT J AU Reepmeyer, JC AF Reepmeyer, JC TI Analysis of the nitrogen mustard mechlorethamine in topical pharmaceutical preparations by high-performance liquid chromatography SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article DE nitrogen mustard; mechlorethamine; ointments; HPLC; topical pharmaceutical ID MYCOSIS-FUNGOIDES; OINTMENT; ALKYLATION; STABILITY; HN2; DNA AB Mechlorethamine in topical pharmaceutical formulations was derivatized with benzenethiol to form the disubstitution product and analyzed by normal-phase HPLC on silica gel using dibutyl phthalate as an internal standard. The derivatization reaction, purification, and isolation were conveniently performed in a single test tube. Analyses were successfully performed on three types of ointment formulations: anhydrous hydrophobic petrolatum-based ointments, anhydrous hydrophilic ointments, and hydrous hydrophilic ointments. Precision for the analysis of mechlorethamine standard or mechlorethamine in ointments ranged from 0.08 to 0.52% RSD (n = 6). Recoveries from ointments spiked with 0.02% mechlorethamine hydrochloride were 98.4-100.4%. The chromatograms were clean, showing minimal or no interference from ointment excipients or reagents. Published by Elsevier B.V. C1 US FDA, Div Pharmaceut Anal, St Louis, MO 63101 USA. RP Reepmeyer, JC (reprint author), US FDA, Div Pharmaceut Anal, St Louis, MO 63101 USA. EM reepmeyerj@cder.fda.gov NR 24 TC 6 Z9 6 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR A JI J. Chromatogr. A PD SEP 2 PY 2005 VL 1085 IS 2 BP 262 EP 269 DI 10.1016/j.chroma.2005.06.057 PG 8 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 952NA UT WOS:000231009600012 PM 16106707 ER PT J AU Banks, D AF Banks, D TI Pharmacists, pharmaceutical manufacturers, and conflicts of interest SO AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY LA English DT Editorial Material ID DIVIDED LOYALTIES; INDUSTRY; GIFTS; PERSPECTIVE; PHYSICIANS C1 US FDA, Off Special Hlth Issues, Rockville, MD 20857 USA. RP Banks, D (reprint author), US FDA, Off Special Hlth Issues, Rockville, MD 20857 USA. NR 47 TC 2 Z9 2 U1 1 U2 1 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 SEP 1 PY 2005 VL 62 IS 17 BP 1827 EP 1832 DI 10.2146/ajhp040504 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 960ZK UT WOS:000231631500019 PM 16120744 ER PT J AU Lee, JI Tracy, L Higgins, K Hernandez, A Cavaille-Coll, M AF Lee, JI Tracy, L Higgins, K Hernandez, A Cavaille-Coll, M TI Analysis of exposure-response relationship in everolimus-cyclosporine combination regimen SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Letter C1 US FDA, Ctr Drug Evaluat & Res, Off Biostat, Rockville, MD 20857 USA. US FDA, Ctr Drug Evaluat & Res, Off Drug Evaluat 4, Rockville, MD 20857 USA. RP Lee, JI (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Biostat, Rockville, MD 20857 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD SEP PY 2005 VL 5 IS 9 BP 2328 EP 2329 DI 10.1111/j.1600-6143.2005.00937.x PG 2 WC Surgery; Transplantation SC Surgery; Transplantation GA 952RR UT WOS:000231023700034 PM 16095519 ER PT J AU McDermott, PF Cullen, P Hubert, SK McDermott, SD Bartholomew, M Simjee, S Wagner, DD AF McDermott, PF Cullen, P Hubert, SK McDermott, SD Bartholomew, M Simjee, S Wagner, DD TI Changes in antimicrobial susceptibility of native Enterococcus faecium in chickens fed virginiamycin SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID QUINUPRISTIN-DALFOPRISTIN; SATA GENE; RESISTANCE; STREPTOGRAMIN; ACETYLTRANSFERASE; VANCOMYCIN; RISKS AB The extent of transfer of antimicrobial resistance from agricultural environments to humans is controversial. To assess the potential hazard posed by streptogramin use in food animals, this study evaluated the effect of virginiamycin exposure on antimicrobial resistance in Enterococcus faecium recovered from treated broilers. Four consecutive broiler feeding trials were conducted using animals raised on common litter. In the first three trials, one group of birds was fed virginiamycin continuously in feed at 20 g/ton, and a second group served as the nontreated control. In the fourth trial, anti microbial-free feed was given to both groups. Fecal samples were cultured 1 day after chickens hatched and then at 1, 3, 5, and 7 weeks of age. Isolates from each time point were tested for susceptibility to a panel of different antimicrobials. Quinupristin/dalfopristin-resistant E. faecium appeared after 5 weeks of treatment in trial 1 and within 7 days of trials 2 to 4. Following removal of virginiamycin in trial 4, no resistant isolates were detected after 5 weeks. PCR failed to detect vat, vgb, or erm(B) in any of the streptogramin-resistant E. faecium isolates, whereas the msr(C) gene was detected in 97% of resistant isolates. In an experimental setting using broiler chickens, continuous virginiamycin exposure was required to maintain a stable streptogramin-resistant population of E. faecium in the animals. The bases of resistance could not be explained by known genetic determinants. C1 US FDA, Res Off, Ctr Vet Med, Div Anim & Food Microbiol, Laurel, MD 20708 USA. US FDA, Ctr Vet Med, Rockville, MD 20857 USA. RP McDermott, PF (reprint author), US FDA, Res Off, Ctr Vet Med, Div Anim & Food Microbiol, 8401 Muirkirk Rd, Laurel, MD 20708 USA. EM Patrick.McDermott@fda.gov NR 24 TC 22 Z9 22 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0099-2240 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD SEP PY 2005 VL 71 IS 9 BP 4986 EP 4991 DI 10.1128/AEM.71.9.4986-4991.2005 PG 6 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 964RE UT WOS:000231897400006 PM 16151077 ER PT J AU Landewe, R van der Heijde, D Siegel, J Spencer-Green, G AF Landewe, R van der Heijde, D Siegel, J Spencer-Green, G TI Adalimumab inihibits radiographic progression in comparison with placebo despite a high level of disease activity as measured by CRP and/or DAS28. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 69th Annual Scientific Meeting of the American-College-of-Rheumatology/40th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 12-17, 2005 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Univ Hosp Maastricht, Maastricht, Netherlands. US FDA, Rockville, MD USA. Abbott Labs, Parsippany, NJ USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD SEP PY 2005 VL 52 IS 9 SU S BP S131 EP S132 PG 2 WC Rheumatology SC Rheumatology GA 969BG UT WOS:000232207800285 ER PT J AU Lories, RJ Tylzanowski, PT Reekmans, K Peeters, J Thomas, TT Luyten, FP AF Lories, RJ Tylzanowski, PT Reekmans, K Peeters, J Thomas, TT Luyten, FP TI sFRP3 knockout mice develop accelerated cartilage breakdown in experimental models of osteoarthritis. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 69th Annual Scientific Meeting of the American-College-of-Rheumatology/40th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 12-17, 2005 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Katholieke Univ Leuven, Louvain, Belgium. US FDA, Rockville, MD 20857 USA. RI Tylzanowski, Przemko/G-8881-2013 NR 1 TC 1 Z9 1 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD SEP PY 2005 VL 52 IS 9 SU S BP S255 EP S255 PG 1 WC Rheumatology SC Rheumatology GA 969BG UT WOS:000232207801149 ER PT J AU Rinaldi, JE Chen, EA Berman, MR AF Rinaldi, JE Chen, EA Berman, MR TI Pediatric circulatory support: An FDA perspective SO ASAIO JOURNAL LA English DT Article; Proceedings Paper CT 1st International Conference on Pediatric Mechanical Circulatory Support Systems and Pediatric Cardiopulmonary Perfusion CY MAY 19-21, 2005 CL Hershey, PA ID CHILDREN; INFANTS AB The Department of Health and Human Services, at the direction of Congress, has recently begun to address concerns regarding the development of medical devices designed specifically for the pediatric population, including devices for pediatric mechanical circulatory support, as evidenced by the National Institutes of Health's (NIH) funding of several development contracts. Food and Drug Administration (FDA) approval for marketing of these devices will typically follow either of two regulatory pathways: the Humanitarian Device Exemption (HDE) or the Premarket Application (PMA). An HIDE is limited both in the extent of clinical use and economic benefit to the manufacturer, but does not require data derived from a clinical trial for market approval. A PMA allows for use in a larger patient population and offers economic benefit for the manufacturer; it does, however, almost always necessitate data derived from a clinical trial. The HDE and PMA require demonstration of a reasonable assurance of safety. in addition, an HDE requires a demonstration of probable benefit, whereas a PMA requires a demonstration of a reasonable assurance of effectiveness. The evidence that can be used to support an HDE or a PMA approval may include both preclinical and clinical data. Types of preclinical tests needed depend upon the device design and its intended use, because circulatory support devices are all unique. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20852 USA. RP Rinaldi, JE (reprint author), US FDA, Ctr Devices & Radiol Hlth, 12725 Twinbrook Pkwy,HFZ-170, Rockville, MD 20852 USA. EM jean.rinaldi@fda.hhs.gov NR 5 TC 8 Z9 9 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1058-2916 J9 ASAIO J JI Asaio J. PD SEP-OCT PY 2005 VL 51 IS 5 BP 533 EP 535 DI 10.1097/01.mat.0000181508.26853.dc PG 3 WC Engineering, Biomedical; Transplantation SC Engineering; Transplantation GA 057HH UT WOS:000238586400017 PM 16322713 ER PT J AU Gaines, AR AF Gaines, AR TI Disseminated intravascular coagulation associated with acute hemoglobinemia or hemoglobinuria following Rh-o(D) immune globulin intravenous administration for immune thrombocytopenic purpura SO BLOOD LA English DT Article ID ACUTE-RENAL-FAILURE; WINRHO ANTI-D; IMMUNOGLOBULIN; HEMOLYSIS; ALLOANTIBODIES; INFUSIONS; SEQUELAE; ITP AB The Food and Drug Administration (FDA) licensed Rho(D) immune globulin intravenous (anti-D IGIV) on March 24, 1995, for treatment of immune thrombocytopenic purpura (ITP). A previous review described data on 15 patients who experienced acute hemoglobinemia or hemoglobinuria following anti-D IGIV administration for ITP or secondary thrombocytopenia. Eleven of those patients also experienced clinically compromising anemia, transfusion with packed red blood cells, renal insufficiency, dialysis, or death. That review suggested that patients receiving anti-D IGIV be monitored for those and other potential complications of hemoglobinemia, particularly disseminated intravascular coagulation (DIC). Through November 30, 2004, the FDA received 6 reports of DIC associated with "acute hemolysis" (or similar terms), 5 of which involved fatalities. The attending or consulting physicians assessed that acute hemolysis or DIC caused or contributed to each death. This review presents the first case series of DIC associated with acute hemoglobinemia or hemoglobinuria following anti-D IGIV administration for ITP. The purpose of this review is to increase awareness among physicians and other health care professionals that DIC may be a rare but potentially severe complication of anti-D IGIV treatment. Increased awareness of DIC as a diagnostic possibility may enable prompt recognition and medical intervention in affected patients. C1 US FDA, Div Biostat & Epidemiol, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. RP Gaines, AR (reprint author), US FDA, Div Biostat & Epidemiol HFM220, Ctr Biol Evaluat & Res, 1401 Rockville Pike, Rockville, MD 20852 USA. EM gaines@cber.fda.gov NR 35 TC 87 Z9 92 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 SEP 1 PY 2005 VL 106 IS 5 BP 1532 EP 1537 DI 10.1182/blood-2004-11-4303 PG 6 WC Hematology SC Hematology GA 959CR UT WOS:000231495000013 PM 15878975 ER PT J AU Marti, GE Rawstron, AC Ghia, P Hillmen, P Houlston, RS Kay, N Schleinitz, TA Caporaso, N AF Marti, GE Rawstron, AC Ghia, P Hillmen, P Houlston, RS Kay, N Schleinitz, TA Caporaso, N TI MBL and MoBL - Response SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Letter DE monoclonal B-cell lymphocytosis; nomenclature ID PLASMID C1 US FDA, Ctr Biol Evaluat & Res, NIH, Bethesda, MD 20014 USA. Leeds Teaching Hosp, NHS Trust, HMDS, Leeds Gen Infirm, Leeds, W Yorkshire, England. Univ Vita Salute San Raffaele, Milan, Italy. Inst Canc Res, Sect Canc Genet, Surrey, England. Mayo Clin Rochester, Div Hematol, Rochester, MN USA. Inst J Paoli I Calmettes, F-13009 Marseille, France. NCI, Div Canc Epidemiol & Genet, Genet Epidemiol Branch, NIH, Bethesda, MD USA. RP Marti, GE (reprint author), US FDA, Ctr Biol Evaluat & Res, NIH, Bethesda, MD 20014 USA. EM gemarti@helix.nih.gov RI Ghia, Paolo/K-7138-2016 OI Ghia, Paolo/0000-0003-3750-7342 NR 4 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD SEP PY 2005 VL 130 IS 5 BP 795 EP 796 DI 10.1111/j.1365-2141.2005.05675.x PG 2 WC Hematology SC Hematology GA 963RW UT WOS:000231824600022 ER PT J AU Junod, SW AF Junod, SW TI Quack, quack, quack: The sellers of nostrums in prints, posters, ephemera, and books. SO BULLETIN OF THE HISTORY OF MEDICINE LA English DT Book Review C1 US FDA, Rockville, MD 20857 USA. RP Junod, SW (reprint author), US FDA, Rockville, MD 20857 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU JOHNS HOPKINS UNIV PRESS PI BALTIMORE PA JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD 21218-4363 USA SN 0007-5140 J9 B HIST MED JI Bull. Hist. Med. PD FAL PY 2005 VL 79 IS 3 BP 597 EP 599 DI 10.1353/bhm.2005.0110 PG 3 WC Health Care Sciences & Services; History & Philosophy Of Science SC Health Care Sciences & Services; History & Philosophy of Science GA 962SA UT WOS:000231751400023 ER PT J AU Anderson, KE Kadlubar, FF Kulldorff, M Harnack, L Gross, M Lang, NP Barber, C Rothman, N Sinha, R AF Anderson, KE Kadlubar, FF Kulldorff, M Harnack, L Gross, M Lang, NP Barber, C Rothman, N Sinha, R TI Dietary intake of heterocyclic amines and benzo(a)pyrene: Associations with pancreatic cancer SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID PAST MEDICAL HISTORY; RISK-FACTORS; VARYING DEGREES; FOOD; MEAT; PRODUCTS; RATS; CARCINOGEN; MUTAGENS; COOKING AB Objective: Heterocyclic amines (HCA) and polycyclic aromatic hydrocarbons, formed in temperature- and time-dependent manners during the cooking of meat, are mutagens and carcinogens. We sought to assess the association between dietary intake of HCA and benzo(a)pyrene [B(a)PI and exocrine pancreatic cancer in a population-based case-control study. Methods: Subjects (193 cases and 674 controls) provided information on their usual meat intake and preparation method, e.g., stewed, fried, or grilled/barbecued, etc. Meat doneness preferences were measured using photographs that showed internal doneness and external brownness. We used a meat-derived HCA, B(a)P, and mutagen database with a questionnaire to estimate intake of PhIP, DiMeIQx, MelQx, B(a)P, and mutagenic activity (revertants/g of daily meat intake). Data were analyzed with unconditional logistic regression. Results: In analyses adjusted for age, sex, smoking, education, race, and diabetes, the odds ratio and 95% confidence interval for the highest compared with the lowest quintile were as follows: PhIP, 1.8 (1.0-3.1); DiMeIQx, 2.0 (1.2-3.5); MeIQx, 1.5 (0.9-2.7); 13(a)P, 2.2 (1.2-4.0); and mutagenic activity, 2.4 (1.3-4.3). Conclusions: HCAs and B(a)P from well-done barbecued and pan-fried meats may be associated with increased risk for pancreatic cancer. C1 Univ Minnesota, Div Epidemiol, Sch Publ Hlth, Minneapolis, MN 55454 USA. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA USA. Harvard Pilgrim Hlth Care, Boston, MA USA. Univ Arkansas Med Sci, Dept Surg, Coll Med, Little Rock, AR 72205 USA. Univ Arkansas Med Sci, Cent Arkansas Vet Healthcare Syst, Little Rock, AR 72205 USA. NCI, Rockville, MD USA. RP Anderson, KE (reprint author), Univ Minnesota, Div Epidemiol, Sch Publ Hlth, 1300 S 2nd St 300, Minneapolis, MN 55454 USA. EM anderson_k@epi.umn.edu 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-CA-58697] NR 51 TC 55 Z9 59 U1 0 U2 10 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD SEP PY 2005 VL 14 IS 9 BP 2261 EP 2265 DI 10.1158/1055-9965.EPI-04-0514 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 965SU UT WOS:000231971400033 PM 16172241 ER PT J AU Bast, RC Lilja, H Urban, N Rimm, DL Fritsche, H Gray, J Veltri, R Klee, G Allen, A Kim, N Gutman, S Rubin, MA Hruszkewycz, A AF Bast, RC Lilja, H Urban, N Rimm, DL Fritsche, H Gray, J Veltri, R Klee, G Allen, A Kim, N Gutman, S Rubin, MA Hruszkewycz, A TI Translational crossroads for biomarkers SO CLINICAL CANCER RESEARCH LA English DT Editorial Material ID PROSTATE-CANCER; TISSUE MICROARRAYS; QUANTITATIVE-ANALYSIS; BREAST-CANCER; ANTIGEN PSA; EXPRESSION; DISEASE AB A group of investigators met at a Specialized Programs of Research Excellence Workshop to discuss key issues in the translation of biomarker discovery to the development of useful laboratory tests for cancer care. Development and approval of several new markers and technologies have provided informative examples that include more specific markers for prostate cancer, more sensitive tests for ovarian cancer, more objective analysis of tissue architecture and an earlier indication of response to treatment in breast cancer. Although there is no clear paradigm for biomarker development, several principles are clear. Marker development should be driven by clinical needs, including early cancer detection, accurate pretreatment staging, and prediction of response to treatment, as well as monitoring disease progression and response to therapy. Development of a national repository that uses carefully preserved, well-annotated tissue specimens will facilitate new marker development. Reference standards will be an essential component of this process. Both hospital-based and commercial laboratories can play a role in developing biomarkers from discovery to test validation. Partnering of academe and industry should occur throughout the process of biomarker development. The National Cancer Institute is in a unique position to bring together academe, industry, and the Food and Drug Administration to (a) define clinical needs for biomarkers by tumor type, (b) establish analytic and clinical paradigms for biomarker development, (c) discuss ways in which markers from different companies might be evaluated in combination, (cl) establish computational methods to combine data from multiple biomarkers, (e) share information regarding promising markers developed in National Cancer Institute -supported programs, and (f) exchange data regarding new platforms and techniques that can accelerate marker development. C1 Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Yale Univ, Sch Med, New Haven, CT USA. Lawrence Livermore Natl Lab, Livermore, CA USA. diaDexus, San Francisco, CA USA. Johns Hopkins Univ Hosp, Baltimore, MD 21205 USA. US FDA, Rockville, MD 20857 USA. Natl Canc Inst, Bethesda, MD USA. Mayo Clin, Rochester, MN USA. Abbott Labs, Abbott Pk, IL 60064 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Bast, RC (reprint author), Univ Texas, MD Anderson Canc Ctr, Box 355,1515 Holcombe Blvd, Houston, TX 77030 USA. EM rbast@mdanderson.org RI Bast, Robert/E-6585-2011; OI Bast, Robert/0000-0003-4621-8462; Lilja, Hans/0000-0001-5871-7846; Rubin, Mark/0000-0002-8321-9950 NR 16 TC 54 Z9 57 U1 1 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD SEP 1 PY 2005 VL 11 IS 17 BP 6103 EP 6108 DI 10.1158/1078-0432.CCR-04-2213 PG 6 WC Oncology SC Oncology GA 962IB UT WOS:000231723600003 PM 16144908 ER PT J AU Gao, LF Zhang, L Hu, JD Li, F Shao, YT Zhao, D Kalvakolanu, DV Kopecko, DJ Zhao, XJ Xu, DQ AF Gao, LF Zhang, L Hu, JD Li, F Shao, YT Zhao, D Kalvakolanu, DV Kopecko, DJ Zhao, XJ Xu, DQ TI Down-regulation of signal transducer and activator of transcription 3 expression using vector-based small interfering RNAs suppresses growth of human prostate tumor in vivo SO CLINICAL CANCER RESEARCH LA English DT Article ID MAMMALIAN-CELLS; GENE-EXPRESSION; CANCER-CELLS; CONSTITUTIVE ACTIVATION; NECK-CANCER; STAT3; INHIBITION; APOPTOSIS; PATHWAY; MICE AB Purpose: Signal transducer and activator of transcription 3 (Stat3) is constitutively activated in a variety of cancers and it is a common feature of prostate cancer. Thus, Stat3 represents a promising molecular target for tumor therapy. We applied a DNA vector - based Stat3-specific RNA interference approach to block Stat3 signaling and to evaluate the biological consequences of Stat3 down-modulation on tumor growth using a mouse model. Experimental Design: To investigate the therapeutic potential of blocking Stat3 in cancer cells, three small interfering RNAs (siRNA; Stat3-1, Stat3-2, and Stat3-3) specific for different target sites on Stat3 mRNA were designed and used with a DNA vector-based RNA interference approach expressing short hairpin RNAs to knockdown Stat3 expression in human prostate cancer cells in vitro as well as in vivo. Results: Of the three equivalently expressed siRNAs, only Stat3-3 and Stat3-2, which target the region coding for the SH2 domain and the coiled-coil domain, respectively, strongly suppressed the expression of Stat3 in PC3 and LNCaP cells. The Stat3-1 siRNA, which targeted the DNA-binding domain, exerted no effect on Stat3 expression, indicating that the gene silencing efficiency of siRNA may be dependent on the local structure of Stat3 mRNA. The Stat3 siRNAs down-regulated the expression of Bcl-2 (an antiapoptotic protein), and cyclin D1 and c-Myc (cell growth activators) in prostate cancer cells, Inhibition of Stat3 and its related genes was accompanied by growth suppression and induction of apoptosis in cancer cells in vitro and in tumors implanted in nude mice. Conclusions: These data indicate that Stat3 signaling is a promising molecular target for prostate cancer therapy and that vedor-based Stat3siRNA may be useful as a therapeutic agent for treatment of prostate cancer. C1 US FDA, Ctr Biol Evaluat & Res, Lab Enter & Sexually Transmitted Dis, Bethesda, MD 20892 USA. Jilin Univ, Basic Sch Med, Dept Pathophysiol, Changchun 130021, Peoples R China. Univ Maryland, Greenebaum Canc Ctr, Dept Microbiol & Immunol, Program Mol Biol,Sch Med, Baltimore, MD 21201 USA. RP Zhao, XJ (reprint author), US FDA, Ctr Biol Evaluat & Res, Lab Enter & Sexually Transmitted Dis, Bethesda, MD 20892 USA. EM pro_2@jlu.edu.cn FU NCI NIH HHS [CA 105005, CA 78282] NR 54 TC 102 Z9 120 U1 1 U2 3 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 SEP 1 PY 2005 VL 11 IS 17 BP 6333 EP 6341 DI 10.1158/1078-0432.CCR-05-0148 PG 9 WC Oncology SC Oncology GA 962IB UT WOS:000231723600033 PM 16144938 ER PT J AU Wyles, DL Patel, A Madinger, N Bessesen, M Krause, PR Weinberg, A AF Wyles, DL Patel, A Madinger, N Bessesen, M Krause, PR Weinberg, A TI Development of herpes simplex virus disease in patients who are receiving cidofovir SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID DNA-POLYMERASE MUTANTS; ACYCLOVIR-RESISTANT; MUCOCUTANEOUS INFECTION; TRANSPLANT RECIPIENTS; CONTROLLED-TRIAL; ANTIVIRAL DRUGS; TYPE-1; (S)-1-(3-HYDROXY-2-PHOSPHONYLMETHOXYPROPYL)CYTOSINE; FOSCARNET AB Background. Cidofovir is a nucleotide analogue with antiviral activity against a wide range of DNA viruses, including herpes simplex virus (HSV). In vitro resistance to cidofovir has been reported with use of laboratory HSV strains; clinical failure of cidofovir therapy for HSV disease has also been reported with an isolate that was susceptible by in vitro testing. Patients and methods. Three patients with HSV disease that was unresponsive to cidofovir therapy had viral isolates obtained and stored; the isolates were analyzed for antiviral susceptibility by an antigen reduction assay (ARA). PCR cloning and automated sequencing were performed for isolates that displayed in vitro resistance. Mutations were identified by comparison with the appropriate HSV consensus sequence. Results. An HSV type 2 (HSV-2) isolate recovered from patient 2 displayed in vitro cidofovir resistance with an inhibitory concentration of 50% (IC50) of 13.06 mu g/mL. HSV type 1 isolates recovered from patients 1 and 3 had elevated IC(50)s to cidofovir (7.32 and 8.23 mu g/mL, respectively); however, these isolates did not meet the cutoff point for resistance according to the ARA. Sequencing of a cidofovir-resistant HSV-2 isolate revealed several DNA polymerase mutations that had not been previously described during in vitro resistance selection. Conclusions. To our knowledge, this is the first report of cidofovir resistance in HSV developing in vivo. The 3 sequenced clones all contained mutations truncating the pol C' end, suggesting that this region may be critical for cidofovir antiviral activity. In addition, the presence of multiple mutations suggests that the altered DNA polymerase of cidofovir-resistant virus may have introduced additional mutations into the viral genome. Introduction of the mutations identified in wild-type HSV strains is needed before the resistance phenotype can be definitively associated with any of the mutations found. Additional studies are needed to delineate the mechanisms of cidofovir resistance in HSV. C1 Univ Calif San Diego, Div Infect Dis, La Jolla, CA 92093 USA. Univ Colorado, Hlth Sci Ctr, Div Infect Dis, Denver, CO USA. Dept Vet Affairs Med Ctr, Denver, CO USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. RP Wyles, DL (reprint author), Univ Calif San Diego, Div Infect Dis, 9500 Gilman Dr,MC 0711, La Jolla, CA 92093 USA. EM dwyles@ucsd.edu OI Bessesen, Mary/0000-0001-9305-1293 FU NIAID NIH HHS [P30 AI27767]; NIDDK NIH HHS [5T32DK007038] NR 15 TC 18 Z9 20 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 1 PY 2005 VL 41 IS 5 BP 676 EP 680 DI 10.1086/432477 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 952HW UT WOS:000230995600014 PM 16080090 ER PT J AU Harper, CC Philip, R Robinowitz, M Gutman, SI AF Harper, CC Philip, R Robinowitz, M Gutman, SI TI FDA perspectives on pharmacogenetic testing SO EXPERT REVIEW OF MOLECULAR DIAGNOSTICS LA English DT Editorial Material DE drug development; FDA; in vitro diagnostics; pharmacogenetics; pharmacogenomics AB The field of pharmacogenetic testing is emerging as a topic of interest for many, due to its potential to improve patient care and optimize therapeutic development. The US Food and Drug Administration is interested in incorporating pharmacogenetics into development activities whenever appropriate to protect and promote public health. This article is intended to reflect the opinions of the Office of In vitro Diagnostic Device Evaluation and Safety in the Center for Devices and Radiological Health on some issues associated with developing in vitro diagnostic devices for use in pharmacogenetics. General points and potential issues related to the analytical and clinical validation of these types of devices will be discussed. C1 US FDA, Ctr Devices & Radiol Hlth, Off In Vitro Diagnost Device Evaluat & Safety, Rockville, MD 20850 USA. RP Harper, CC (reprint author), US FDA, Ctr Devices & Radiol Hlth, Off In Vitro Diagnost Device Evaluat & Safety, HFZ-440,2089 Gaither Rd, Rockville, MD 20850 USA. EM courtney.harpet@fda.hhs.gov; rxp@cdrh.fda.gov; myr@cdrh.fda.gov; sig@cdrh.fda.gov NR 6 TC 3 Z9 5 U1 0 U2 3 PU FUTURE DRUGS LTD PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEYY CENTRAL, LONDON N3 1QB, ENGLAND SN 1473-7159 J9 EXPERT REV MOL DIAGN JI Expert Rev. Mol. Diagn. PD SEP PY 2005 VL 5 IS 5 BP 643 EP 648 DI 10.1586/14737159.5.5.643 PG 6 WC Pathology SC Pathology GA 966LJ UT WOS:000232021100003 PM 16149867 ER PT J AU Imam, SZ Jankovic, J Ali, SF Skinner, JT Xie, WJ Conneely, OM Lee, WD AF Imam, SZ Jankovic, J Ali, SF Skinner, JT Xie, WJ Conneely, OM Lee, WD TI Nitric oxide mediates increased susceptibility to dopaminergic damage in Nurr1 heterozygous mice SO FASEB JOURNAL LA English DT Article DE nitric oxide; dopamine; 3-NT; caspase; transcription; apoptosis ID ORPHAN NUCLEAR RECEPTOR; ISCHEMIC BRAIN-INJURY; ALPHA-SYNUCLEIN; EXPRESSION INCREASES; TRANSCRIPTION FACTOR; NEURONAL APOPTOSIS; CELL-DEATH; METHAMPHETAMINE; NEUROTOXICITY; GENE AB Knocking out of Nurr1 gene, a member of nuclear receptor superfamily, causes selective agenesis of dopaminergic neurons in midbrain. Reduced expression of Nurr1 increases the vulnerability of mesencephalic dopamine neurons to dopaminergic toxins. We evaluated the role of nitric oxide as a possible mechanism for this increased susceptibility. Increased expression of neuronal nitric oxide synthase and increased 3-nitrotyrosine were observed in striatum of Nurr1 heterozygous (Nurr1 +/-) mice as compared with wild-type. Increased cytochrome C activation and consecutive release of Smac/DIABLO were also observed in Nurr1 +/- mice. An induction of active Caspase-3 and p53, cleavage of poly-ADP (RNase) polymerase and reduced expression of bcl-2 were observed in Nurr1 +/- mice. Methamphetamine significantly increased these markers in Nurr1 +/- mice as compared with wild-type. The present data therefore suggest that nitric oxide plays a role as a modulating factor for the increased susceptibility, but not the potentiation, of the dopaminergic terminals in Nurr1 +/- mice. We also report that this increased neuronal nitric oxide synthase expression and increased nitration in Nurr1 +/- mice led to the activation of apoptotic cascade via the differential alterations in the DNA binding activity of transcription factors responsible for the propagation of growth arrest as well as apoptosis. C1 Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA. S Texas Vet Hlth Care Syst, San Antonio, TX USA. UT Hlth Sci, Dept Med, San Antonio, TX USA. US FDA, Neurochem Lab, Div Neurotoxicol, NCTR, Jefferson, AR USA. Baylor Coll Med, Dept Cellular & Mol Biol, Houston, TX 77030 USA. RP Lee, WD (reprint author), Baylor Coll Med, Dept Neurol, NB 205,6501 Fannin St, Houston, TX 77030 USA. EM simam@satx.rr.com; Weidongl@bcm.tmc.edu FU NINDS NIH HHS [NS40370, NS043567] NR 48 TC 18 Z9 18 U1 0 U2 2 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 SEP PY 2005 VL 19 IS 11 BP 1441 EP 1450 DI 10.1096/fj.04-3362com PG 10 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 970NA UT WOS:000232315700037 PM 16126911 ER PT J AU Flynn, KM Delclos, KB Newbold, RR Ferguson, SA AF Flynn, KM Delclos, KB Newbold, RR Ferguson, SA TI Long term dietary methoxychlor exposure in rats increases sodium solution consumption but has few effects on other sexually dimorphic behaviors SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article DE xenoestrogen; sodium preference; endocrine disrupter; developmental; sexually dimorphic; methoxychlor ID MAMMARY-GLAND DEVELOPMENT; REPRODUCTIVE-SYSTEM; SEX-DIFFERENCES; ENDOCRINE DISRUPTORS; GENISTEIN EXPOSURE; OFFSPRING TOXICITY; RESEARCH NEEDS; BISPHENOL-A; SALT INTAKE; ESTROGEN AB Methoxychlor is an insecticide with estrogen-like activity, thus exposure during development might cause sexually dimorphic behavioral alterations. To evaluate this, pregnant rats consumed diets containing 0, 10, 100 or 1000 ppm methoxychlor from gestational day 7, and offspring continued on these diets until postnatal day (PND) 77. Assessments of sexually dimorphic behaviors in offspring indicated that intake of a 3.0% sodium chloride solution was significantly increased (41%) in males and females of the 1000 ppm group. No treatment group differed from controls in open field nor running wheel activity, play behavior, nor 0.3% saccharin solution intake. Offspring of the 1000 ppm. group showed significantly decreased body weight, reaching 17% less than controls at PND 77, but not clearly related to their salt solution intake. During pregnancy, 1000 ppm dams consumed 23% less food and weighed 10% less than controls, but this did not affect litter outcomes. These results indicate that in rodents, developmental and chronic exposure to dietary methoxychlor alters the sexually dimorphic behavior of salt-solution intake in young adults of both sexes. Similar behavioral alterations with other xenoestrogens, and the potential for interactions among xenoestrogens, suggest that this report may minimize the true effects of dietary methoxychlor exposure. (c) 2005 Elsevier Ltd. All rights reserved. C1 US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. Natl Inst Environm Hlth Sci, Toxicol Lab, Environm Toxicol Program, Res Triangle Pk, NC 27709 USA. RP Flynn, KM (reprint author), Adelphi Univ, Dept Biol, 1 S Ave, Garden City, NY 11530 USA. EM flynn@adelphi.edu NR 41 TC 11 Z9 11 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 SEP PY 2005 VL 43 IS 9 BP 1345 EP 1354 DI 10.1016/j.fct.2005.03.009 PG 10 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA 960IH UT WOS:000231583300004 PM 15989973 ER PT J AU Booker, CD White, KL AF Booker, CD White, KL TI Benzo(a)pyrene-induced anemia and splenomegaly in NZB/WF1 mice SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article DE benzo(a)pyrene; autoimmunity; anemia; splenomegaly; extramedullary hematopoiesis ID AUTOIMMUNE-DISEASE; PRONE MICE; EXPOSURE; CELLS; HYDROCARBONS; RNA; IMMUNOSUPPRESSION; ERYTHROCYTES; SUPPRESSION; ANTIBODIES AB Benzo(a)pyrene (BaP), a polycyclic aromatic hydrocarbon, is a known immunomodulator. At high doses, BaP is immunosuppressive but at low doses it can enhance the immune response. Studies were conducted to determine if BaP would exacerbate the development of autoimmune disease in genetically prone NZB/WF1 mice. Five week old female NZBW/F1 mice were exposed dermally to 5, 20 and 40 mg/kg BaP for 30 days. Vehicle mice were exposed to an acetone:olive oil mixture for 30 days. BaP did not increase total IgG, anti-DNP-HSA or anti-dsDNA antibody levels. However, hematological evaluation revealed a decrease in erythrocyte number, hemoglobin and hematocrit and an increase in mean corpuscular volume and red cell distribution width in the 20 and 40 mg/kg dose groups. Liver and spleen weights were increased in the high dose groups; however, an increase in spleen cell number was not observed. Histopathological evaluation revealed splenic red pulp expansion in a mouse treated with 40 mg/kg BaP. An increase in splenic CFU-e production was observed in mice treated with 20 and 40 mg/kg BaP. A decrease in splenic total B cells, total T cells, CD4(+) and CD8(+) T cells was observed in mice treated with 20 and 40 mg/kg BaP. An increase in splenic null cells (non-T, non-B cells) was also observed in the high dose groups, consistent with extramedullary hematopoiesis. Coombs' tests, flow cytometry and an immune-mediated hemolysis assay indicated that the anemia was not autoimmune-mediated. Although no change was observed in the percentage of reticulocytes in these animals, further bone marrow analysis is needed to determine if the anemia is due to bone marrow suppression, possibly caused by BaP exposure, or chemical-induced hemolysis, perhaps contributed to by erythrocyte fragility inherited from a parent strain, NZB, which spontaneously develops autoimmune hemolytic anemia and subsequent splenomegaly. Published by Elsevier Ltd. C1 Virginia Commonwealth Univ, Richmond, VA USA. RP Booker, CD (reprint author), US FDA, Ctr Drug Evaluat & Res, 9201 Corp Blvd, Rockville, MD 20850 USA. EM bookerc@cder.fda.gov NR 46 TC 14 Z9 16 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 SEP PY 2005 VL 43 IS 9 BP 1423 EP 1431 DI 10.1016/j.fct.2005.03.018 PG 9 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA 960IH UT WOS:000231583300013 PM 15936865 ER PT J AU Paule, MG AF Paule, MG TI Chronic drug exposures during development in nonhuman primates: Models of brain dysfunction in humans SO FRONTIERS IN BIOSCIENCE LA English DT Article DE rhesus monkeys; operant behavior; cognitive function; comparative psychology; intelligence; animal-to-human extrapolation; drug exposure during developmental; behavioral toxicology; behavioral teratology; developmental toxicology; central nervous system; review ID PRENATAL COCAINE EXPOSURE; EXTRADIMENSIONAL SHIFT TASKS; NMDA RECEPTOR ANTAGONISTS; OPERANT TEST BATTERY; FETAL RHESUS-MONKEY; PROGRESSIVE RATIO; INFANT OUTCOMES; MARIJUANA SMOKE; MARIHUANA USE; PERFORMANCE AB This review of our work presents three specific examples of how nonhuman primates ( rhesus monkeys, Macaca mulatta) have been used to study the effects of chronic drug exposures on brain function during different stages of development. In all cases, exposure levels similar to those experienced by humans were employed and the focus was on long-term--not acute--effects. In the case of the marijuana studies, exposures occurred during the adolescent period; for the cocaine studies, exposures occurred in binge-like fashion entirely before birth ( in utero); and for the remacemide studies, exposures occurred daily in juveniles, prior to adolescence. An automated battery of behavioral tasks, the National Center for Toxicological Research Operant Test Battery (NCTR OTB), designed to assess aspects of motivation, visual discrimination, time perception, short-term memory, and learning, was used to monitor treatment effects. Chronic marijuana smoke exposure resulted in an 'amotivational' syndrome--even in weekend-only smokers--that resolved within three months of exposure cessation. In utero cocaine exposure was shown to cause behavioral rigidity or lack of plasticity as evidenced by the difficulty of subjects to adjust to rules changes for some OTB tasks. These effects were seen in adult subjects suggesting that the effects of gestational cocaine exposure are long-term or permanent. In addition, animals exposed to cocaine in utero were less sensitive to the behaviorally-disrupting effects of cocaine as adults. Remacemide caused profound and long-lasting, perhaps permanent, changes in learning task performance and because performance of this same task by children is significantly correlated with traditional measures of intelligence ( IQ), these data suggest that such treatment may provide a valuable model of chemically-induced mental retardation. C1 US FDA, Natl Ctr Toxicol Res, Behav Toxicol Labs, Div Neurotoxicol, Jefferson, AR 72079 USA. RP Paule, MG (reprint author), US FDA, Natl Ctr Toxicol Res, Behav Toxicol Labs, Div Neurotoxicol, HFT-132,3900 NCTR Rd, Jefferson, AR 72079 USA. EM mpaule@nctr.fda.gov NR 65 TC 18 Z9 18 U1 1 U2 6 PU FRONTIERS IN BIOSCIENCE INC PI MANHASSET PA C/O NORTH SHORE UNIV HOSPITAL, BIOMEDICAL RESEARCH CENTER, 350 COMMUNITY DR, MANHASSET, NY 11030 USA SN 1093-9946 J9 FRONT BIOSCI JI Front. Biosci. PD SEP 1 PY 2005 VL 10 SU S BP 2240 EP 2249 DI 10.2741/1693 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 970OU UT WOS:000232320300020 PM 15970490 ER PT J AU Woodcock, J AF Woodcock, J TI The FDA and the safety of medical products SO HEALTH AFFAIRS LA English DT Letter C1 US FDA, Rockville, MD 20857 USA. RP Woodcock, J (reprint author), US FDA, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PROJECT HOPE PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD SEP-OCT PY 2005 VL 24 IS 5 BP 1377 EP 1377 DI 10.1377/hlthaff.24.5.1377 PG 1 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 008IL UT WOS:000235033400042 PM 16162588 ER PT J AU Mahajan, B Jani, D Chattopadhyay, R Nagarkatti, R Zheng, H Majam, V Weiss, W Kumar, S Rathore, D AF Mahajan, B Jani, D Chattopadhyay, R Nagarkatti, R Zheng, H Majam, V Weiss, W Kumar, S Rathore, D TI Identification, cloning, expression, and characterization of the gene for Plasmodium knowlesi surface protein containing an altered thrombospondin repeat domain SO INFECTION AND IMMUNITY LA English DT Article ID MALARIAL CIRCUMSPOROZOITE PROTEIN; APICAL MEMBRANE ANTIGEN-1; MELANOMA CELL-ADHESION; FALCIPARUM SPOROZOITES; INHIBITORY ANTIBODIES; ERYTHROCYTE INVASION; BINDING PEPTIDES; HEPARIN-BINDING; GENOME SEQUENCE; BLOOD-STAGE AB Proteins present on the surface of malaria parasites that participate in the process of invasion and adhesion to host cells are considered attractive vaccine targets. Aided by the availability of the partially completed genome sequence of the simian malaria parasite Plasmodium knowlesi, we have identified a 786-bp DNA sequence that encodes a 262-amino-acid-long protein, containing an altered version of the thrombospondin type I repeat domain (SPATR). Thrombospondin type 1 repeat domains participate in biologically diverse functions, such as cell attachment, mobility, proliferation, and extracellular protease activities. The SPATR from P. knowlesi (PkSPATR) shares 61% and 58% sequence identity with its Plasmodium falciparum and Plasmodium yoelii orthologs, respectively. By immunofluorescence analysis, we determined that PkSPATR is a multistage antigen that is expressed on the surface of P. knowlesi sporozoite and erythrocytic stage parasites. Recombinant PkSPATR produced in Escherichia coli binds to a human hepatoma cell line, HepG2, suggesting that PkSPATR is a parasite ligand that could be involved in sporozoite invasion of liver cells. Furthermore, recombinant PkSPATR reacted with pooled sera from P. knowlesi-infected rhesus monkeys, indicating that native PkSPATR is immunogenic during infection. Further efficacy evaluation studies in the P. knowlesi-rhesus monkey sporozoite challenge model will help to decide whether the SPATR molecule should be developed as a vaccine against human malarias. C1 US FDA, Bact & Parasit Dis Sect, Div Emerging & Transfus Transmitted Dis, Ctr Biol Evaluat & Res,Off Blood Res & Review, Rockville, MD 20852 USA. Virginia Polytech Inst & State Univ, Virginia Bioinformat Inst, Blacksburg, VA 24061 USA. USN, Med Res Ctr, Malaria Program, Silver Spring, MD 20903 USA. RP Kumar, S (reprint author), US FDA, Bact & Parasit Dis Sect, Div Emerging & Transfus Transmitted Dis, Ctr Biol Evaluat & Res,Off Blood Res & Review, 1401 Rockville Pike, Rockville, MD 20852 USA. EM kumars@cber.fda.gov NR 37 TC 9 Z9 9 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD SEP PY 2005 VL 73 IS 9 BP 5402 EP 5409 DI 10.1128/IAI.73.9.5402.5409.2005 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 958PK UT WOS:000231460000013 PM 16113256 ER PT J AU Schaecher, K Kumar, S Yadava, A Vahey, M Ockenhouse, CF AF Schaecher, K Kumar, S Yadava, A Vahey, M Ockenhouse, CF TI Genome-wide expression profiling in malaria infection reveals transcriptional changes associated with lethal and nonlethal outcomes SO INFECTION AND IMMUNITY LA English DT Article ID PLASMODIUM-YOELII MALARIA; MURINE MALARIA; GENE-EXPRESSION; SPLENIC CONTROL; BERGHEI-YOELII; BALB/C MICE; SPLEEN; MODEL; ERYTHROPOIESIS; MECHANISMS AB High-density oligonucleotide microarrays are widely used to study gene expression in cells exposed to a variety of pathogens. This study addressed the global genome-wide transcriptional activation of genes in hosts infected in vivo, which result in radically different clinical outcomes. We present an analysis of the gene expression profiles that identified a set of host biomarkers which distinguish between lethal and nonlethal blood stage Plasmodium yoelii malaria infections. Multiple biological replicates sampled during the course of infection were used to establish statistically valid sets of differentially expressed genes. These genes that correlated with the intensity of infection were used to identify pathways of cellular processes related to metabolic perturbations, erythropoiesis, and B-cell immune responses and other innate and cellular immune responses. The transcriptional apparatus that controls gene expression in erythropoiesis was also differentially expressed and regulated the expression of target genes involved in the host's response to malaria anemia. The biological systems approach provides unprecedented opportunities to explore the pathophysiology of host-pathogen interactions in experimental malaria infection and to decipher functionally complex networks of gene and protein interactions. C1 Walter Reed Army Inst Res, Dept Immunol, Silver Spring, MD 20910 USA. Walter Reed Army Inst Res, Div Communicable Dis & Immunol, Silver Spring, MD 20910 USA. Walter Reed Army Inst Res, Div Retrovirol, Silver Spring, MD 20910 USA. US FDA, Div Emerging & Transfus Transmitted Dis, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Ockenhouse, CF (reprint author), Walter Reed Army Inst Res, Dept Immunol, 503 Robert Grant Ave, Silver Spring, MD 20910 USA. EM chris.ockenhouse@na.amedd.army.mil NR 36 TC 24 Z9 28 U1 2 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD SEP PY 2005 VL 73 IS 9 BP 6091 EP 6100 DI 10.1128/IAI.73.9.6091-6100.2005 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 958PK UT WOS:000231460000087 PM 16113330 ER PT J AU Ito, S Pedras-Vasconcelos, J Klinman, DM AF Ito, S Pedras-Vasconcelos, J Klinman, DM TI CpG oligodeoxynucleotides increase the susceptibility of normal mice to infection by Candida albicans SO INFECTION AND IMMUNITY LA English DT Article ID BACTERIAL-DNA; INTERFERON-GAMMA; MOTIFS; MURINE; INTERLEUKIN-12; ADJUVANTS; LEUKEMIA; IL-12 AB Synthetic oligodeoxynucleotides containing CpG motifs trigger an innate immune response that typically increases host resistance to infection. Yet CpG treatment reduces the resistance of normal mice to Candida albicans infection. This effect is mediated by CpG-induced interleukin-12, indicating that CpG-dependent cytokine production may have adverse consequences for the host. C1 US FDA, Ctr Biol Evaluat & Res, Sect Retroviral Immunol, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Therapeut Prot, 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. EM Klinman@CBER.FDA.gov NR 26 TC 16 Z9 17 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD SEP PY 2005 VL 73 IS 9 BP 6154 EP 6156 DI 10.1128/IAI.73.9.6154-6156.2005 PG 3 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 958PK UT WOS:000231460000096 PM 16113339 ER PT J AU Kawakami, K Kawakami, M Liu, Q Puri, RK AF Kawakami, K Kawakami, M Liu, Q Puri, RK TI Combined effects of radiation and interleukin-13 receptor-targeted cytotoxin on glioblastoma cell lines SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE glioblastoma; interleukin-13 receptor; cytotoxin; radiation ID CONVECTION-ENHANCED DELIVERY; PSEUDOMONAS EXOTOXIN; SIGNAL-TRANSDUCTION; MALIGNANT GLIOMA; CARCINOMA-CELLS; IL-13 RECEPTOR; DECOY RECEPTOR; CANCER-CELLS; ALPHA CHAIN; PROTEIN AB Purpose: Interleukin-13 receptor-targeted cytotoxin (IL13-PE38) is highly cytotoxic to human glioblastoma (GBM) cells. Although this molecule is being tested in a multicenter Phase III clinical trial (PRECISE Study) in patients with recurrent disease, the activity of IL13-PE38 when combined with radiation therapy has not been investigated. Methods and Materials: Cytotoxicity of IL13-PE38 to GBM cell lines was assessed by protein synthesis inhibition and clonogenic assays, and the growth of GBM cells receiving radiation was assessed by thymidine uptake assays. Expression of IL-13 receptor alpha 2 (IL-13R alpha 2) messenger ribonucleic acid (mRNA) in GBM cells exposed to radiation was assessed by quantitative reverse transcriptase/polymerase chain reaction (RT-PCR) and IL-13R density by radiolabeled IL-13 binding assays. Results: Prior irradiation of GBM cell lines followed by IL13-PE38 treatment did not enhance cytotoxicity; however, concomitant 5 Gy irradiation and IL13-PE38 treatment was highly cytotoxic to T98G, M059K, A172, and LN-229 cell lines as determined by cell viability assays. There was a statistically significant decrease in number of viable cells in IL13-PE38 and irradiated cells compared with irradiated cells alone (p < 0.05) or IL13-PE38 treated cells alone (p < 0.05). In contrast, U251, SN19, and U87MG cell lines did not show any combined effect. These results were confirmed by clonogenic assays. Although three GBM cell lines-U251, SN19, and A172-showed 2.8- to 13.9-fold upregulation of IL-13R alpha 2 mRNA expression at 6-24 h after exposure to 5 Gy radiation, specific binding of radiolabeled IL-13 to these cell lines did not improve. Conclusions: Our results suggest that concomitant radiation therapy and IL13-PE38 treatment may be beneficial for the treatment of patients with GBM. This strategy may be worth exploring in animal models of human glioma. (c) 2005 Elsevier Inc. C1 US FDA, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Lab Mol Tumor Biol, Bethesda, MD 20892 USA. RP Puri, RK (reprint author), US FDA, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Lab Mol Tumor Biol, NIH Bldg 29B,Room 2NN20,29 Lincoln Dr, Bethesda, MD 20892 USA. EM puri@cber.fda.gov NR 32 TC 4 Z9 4 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD SEP 1 PY 2005 VL 63 IS 1 BP 230 EP 237 DI 10.1016/j.ijrobp.2005.05.017 PG 8 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 956TK UT WOS:000231322500029 PM 16111594 ER PT J AU Andersen, WC Roybal, JE Turnipseed, SB AF Andersen, WC Roybal, JE Turnipseed, SB TI Liquid chromatographic determination of malachite green and leucomalachite green (LMG) residues in salmon with in situ LMG oxidation SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID CATFISH ICTALURUS-PUNCTATUS; MASS-SPECTROMETRY; B6C3F(1) MICE; METABOLITES; TISSUE AB A liquid chromatography (LC) method is presented for the quantitative determination of malachite green (MG) in salmon. MG and leucomalachite green (LMG) residues were extracted from salmon tissue with ammonium acetate buffer and acetonitrile, and then isolated by partitioning into dichloromethane. LMG was quantitatively oxidized to the chromic MG by reaction with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone. Samples were then cleaned up by solid-phase extraction with alumina and propylsulfonic acid phases. Extracts were analyzed for MG by LC with visible detection at 618 nm using isocratic elution and a C18 column. The method was validated. in 35 farm-raised salmon (Salmo salar) tissues fortified at 1, 2, 4, and 10 ng/g (ppb) with an average recovery of 95.4% and a relative standard deviation of +/- 11.1%, and in 5 canned salmon (Oncorhynchus gorbuscha) samples fortified at 10 ng/g with an average recovery of 88.9 +/- 2.6%. This study also included the determination of MG and LMG residues in tissues from salmon that had been treated with MG MG was quantitatively determined at the method detection limit of 1 ng/g. C1 US FDA, Denver Fed Ctr, Anim Drugs Res Ctr, Lakewood, CO 80225 USA. RP Andersen, WC (reprint author), US FDA, Denver Fed Ctr, Anim Drugs Res Ctr, POB 25087, Lakewood, CO 80225 USA. EM wendy.andersen@fda.hhs.gov NR 18 TC 24 Z9 28 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 SEP-OCT PY 2005 VL 88 IS 5 BP 1292 EP 1298 PG 7 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 974GG UT WOS:000232578700005 PM 16385977 ER PT J AU Turnipseed, SB Andersen, WC Roybal, JE AF Turnipseed, SB Andersen, WC Roybal, JE TI Determination and confirmation of malachite green and leucomalachite green residues in salmon using liquid chromatography/mass spectrometry with no-discharge atmospheric pressure chemical ionization SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID TANDEM MASS-SPECTROMETRY; ICTALURUS-PUNCTATUS TISSUE; TRIPHENYLMETHANE DYES; TROUT MUSCLE; METABOLITES; VIOLET AB A liquid chromatography/mass spectrometry (LC/MS) method was developed to quantitate and confirm residues of leucomalachite green (LMG) in salmon tissue after their conversion to chromic malachite green (MG) in the extraction process. The method uses no-discharge atmospheric pressure chemical ionization (APCI) in conjunction with an ion-trap instrument to generate product-ion spectra. In the sample preparation procedure, salmon tissue is extracted with acetonitrile/buffer, the LMG residue is partitioned into methylene chloride, the LMG is converted to MG using an organic oxidizing agent, and the MG is isolated on alumina/propylsulfonic acid solid-phase extraction cartridges. The method was validated by fortifying salmon with different levels of LMG and then detecting the residue as MG The LC/MS conditions, including a comparison of electrospray and no-discharge APCI, were evaluated and optimized. MG was not confirmed in any of the control tissue extracts, and all fortified samples analyzed during validation met the confirmation criteria as described. In addition to providing confirmatory data, this method can provide an alternative method for quantitation of MG in salmon. The recoveries of LMG measured as MG by this LC/MS method, at fortification levels of 1-10 ng/g were very high (86-109%), with low relative standard deviation(RSD) values (6.4-13%). The results agreed very closely with those obtained for the same extracts using an LC/VIS procedure, indicating that matrix suppression was not an issue. The presence of LMG in salmon tissue samples fortified at 0.25 ng/g was confirmed by this method, with an average recovery of 70.1% and an RSD of 12.0%. Sample extracts from fish exposed to MG were also analyzed. C1 US FDA, Anim Drugs Res Ctr, Denver, CO 80225 USA. RP Turnipseed, SB (reprint author), US FDA, Anim Drugs Res Ctr, POB 25087, Denver, CO 80225 USA. EM sherri.turnipseed@fda.hhs.gov NR 21 TC 30 Z9 34 U1 0 U2 3 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD SEP-OCT PY 2005 VL 88 IS 5 BP 1312 EP 1317 PG 6 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 974GG UT WOS:000232578700008 PM 16385980 ER PT J AU DeVries, JW Rader, JI AF DeVries, JW Rader, JI TI Historical perspective as a guide for identifying and developing applicable methods for dietary fiber SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article AB A review is presented describing the nature and evolving definition of dietary fiber. The historical development of the current definition is discussed as are the efforts to develop analytical methods to support food labeling regulations. Also considered are the characterization and quantitation of resistance starch, a dietary starch that does not digest in the small intestine, behaves like dietary fiber and therefore may have potential as a health-related ingredient in foods. The current status of AOAC methodology is discussed along with the possibility of updating the definition of dietary fiber. The potential impacts of changing the dietary fiber definition on analytical issues and on food composition databases are also considered. C1 Gen Mills Inc, Medall Labs, Minneapolis, MN 55427 USA. US FDA, College Pk, MD 20740 USA. RP DeVries, JW (reprint author), Gen Mills Inc, Medall Labs, 9000 Plymouth Ave N, Minneapolis, MN 55427 USA. EM jon.devries@gerimills.com NR 31 TC 22 Z9 22 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 2005 VL 88 IS 5 BP 1349 EP 1366 PG 18 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 974GG UT WOS:000232578700011 PM 16385983 ER PT J AU Vega, VA AF Vega, VA TI Rapid extraction of aflatoxin from creamy and crunchy peanut butter SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article AB A rapid extraction technique was developed for the isolation and subsequent liquid chromatographic determination of aflatoxins B-1, B-2, G(1), and G(2) in creamy and crunchy peanut butter. Peanut butter samples were extracted with a methanol 15% sodium chloride (7 + 3) solution followed by a second extraction with methanol. The extract was subjected to a cleanup using a Vicarn Aflatest (R) immunoaffinity column. Control samples for both smooth and crunchy peanut butter were fortified at 4 different levels for aflatoxin B-1, B-2, G(1), and G(2). The average aflatoxin B-1, B-2, G(1), and G(2) recoveries from smooth peanut buffer were 95.2, 89.9, 94.1, and 62.4%, respectively, and 92.4, 84.3, 85.5, and 53.7%, respectively, from crunchy peanut butter. This extraction method and the official AOAC Method 991.31 produced comparable results for peanut butter samples. This method provides a rapid, specific, and easily controlled assay for the analysis of aflatoxins in peanut butter with minimal solvent usage. Organic solvent consumption was decreased by 85% and hazardous waste production was decreased by 80% in comparison with the AOAC method. Along with the decreased solvent consumption, significant savings in time were observed. C1 US FDA, SE Reg Lab, Atlanta, GA 30309 USA. RP Vega, VA (reprint author), US FDA, SE Reg Lab, 60 8th St,NE, Atlanta, GA 30309 USA. EM vvega@ora.fda.gov NR 0 TC 5 Z9 5 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 2005 VL 88 IS 5 BP 1383 EP 1386 PG 4 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 974GG UT WOS:000232578700014 PM 16385986 ER PT J AU Mercer, GE AF Mercer, GE TI Determination of 112 halogenated pesticides using gas chromatography/mass spectrometry with selected ion monitoring SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID ON-COLUMN INJECTION; VEGETABLES; RESIDUES; EXTRACTION; SPLITLESS; MATRICES; FRUITS; FOOD AB A procedure for the analysis of 112 halogenated pesticides that do not contain phosphorus has been developed. The procedure uses gas chromatography with a mass selective detector (GC-MSD), electron impact ionization, and selected-ion monitoring. This GC-MSD procedure provided lower limits of quantitation and provided increased confirmational data compared to the traditional element-selective GC procedures that are commonly used for the detection of this class of pesticides. These analytical improvements were demonstrated by the 25 pesticides that were detected at <= 50 ng/g levels in a variety of fruit and vegetable matrixes using this procedure that were missed by the traditional element selective GC procedures. Validation of the procedure was performed using 20 representative target pesticides with an acetone extraction and a solid-phase extraction cleanup. These target pesticides were used to demonstrate repeatability and linearity of the chromatographic response and recovery from fruit and vegetable matrixes. C1 US FDA, Pacific Reg Lab NW, Bothell, WA 98021 USA. RP Mercer, GE (reprint author), US FDA, Pacific Reg Lab NW, 22201 23rd Dr SE, Bothell, WA 98021 USA. EM greg.mercer@fda.gov NR 16 TC 14 Z9 19 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 2005 VL 88 IS 5 BP 1452 EP 1462 PG 11 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 974GG UT WOS:000232578700024 PM 16385996 ER PT J AU Schermerhorn, PG Golden, PE Krynitsky, AJ Leimkuehler, WM AF Schermerhorn, PG Golden, PE Krynitsky, AJ Leimkuehler, WM TI Determination of 22 triazole compounds including parent fungicides and metabolites in apples, peaches, flour, and water by liquid chromatography/tandem mass spectrometry SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID DRINKING-WATER; RESIDUES; TEBUCONAZOLE; DISINFECTION; FATE; WINE AB A liquid chromatography/tandem mass spectrometry (LC/MS/MS) method has been developed for the determination of 14 parent triazole fungicides and 8 of their metabolites found in apples, peaches, flour, raw water, and tap water. The triazole fungicides chosen for this multiresidue method development project included propiconazole, fenbuconazole and its RH-9129 and RH-9130 metabolites, cyproconazole, difenoconazole, tebuconazole and its HWG 2061 metabolite, hexaconazole, bromuconazole (both stereoisomers), epoxiconazole, tetraconazole, triticonazole and its RPA-404886 and RPA-406341 metabolites, triadimefon, triadimenol, and myclobutanil. Of special concern to the U.S. Environmental Protection Agency were the metabolites common to all triazole fungicides: free triazole, 1,2,4-triazole (T), and its 2 conjugates: triazolylalanine (TA) and triazolylacetic acid (TAA). These metabolites were the primary focus of this project. All samples we cleaned up by a combination of C18 solid-phase extraction (SPE), mixed-mode cationic SPE, and mixed-mode anionic SIDE columns. A triple-stage quadrupole mass spectrometer, equipped with electrospray ionization in the positive-ion mode, was used to determine the compounds of interest. T, TA, and TAA were quantitated using isotopically labeled internal standards (IS), in which the 1,2,4-triazole ring had been synthesized by using C-13 and N-15 (IS_T, IS_TA, and IS_TAA). These isotopically labeled internal standards were necessary to correct for matrix effects. The T, TA, and TAA metabolites were quantitated at the 25-50 parts-per-billion (ppb) level in food commodities and at 0.50 ppb in water. Recoveries were 70-101% from apples, 60-121% from peaches, 57-118% from flour, 75-99% from raw water, and 79-99% from tap water. C1 US EPA, Off Pesticide Programs, Biol & Econ Anal Div, Analyt Chem Branch, Ft George G Meade, MD 20755 USA. US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. Bayer CropSci, Stilwell, KS 66085 USA. RP Schermerhorn, PG (reprint author), US EPA, Off Pesticide Programs, Biol & Econ Anal Div, Analyt Chem Branch, 701 Mapes Rd, Ft George G Meade, MD 20755 USA. EM schermerhorn.patricia@epa.gov NR 10 TC 33 Z9 37 U1 3 U2 32 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 2005 VL 88 IS 5 BP 1491 EP 1502 PG 12 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 974GG UT WOS:000232578700028 PM 16386000 ER PT J AU McClure, FD Lee, JK AF McClure, FD Lee, JK TI Sample sizes needed for specified margins of relative error in the estimates of the repeatability and reproducibility standard deviations SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article AB Sample size formulas are developed to estimate the repeatability and reproducibility standard deviations (s(r) and S-R) such that the actual error in (s(r) and S-R) relative to their respective true values, sigma(r) and sigma(R), are at predefined levels. The statistical consequences associated with AOAC INTERNATIONAL required sample size to validate an analytical method are discussed. In addition, formulas to estimate the uncertainties of (s(r) and S-R) were derived and are provided as supporting documentation. C1 US FDA, Ctr Food Safety & Appl Nutr, Off Sci Anal & Support, Div Math, College Pk, MD 20740 USA. RP McClure, FD (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Sci Anal & Support, Div Math, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM foster.mcclure@cfsan.fda.gov NR 6 TC 5 Z9 5 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 2005 VL 88 IS 5 BP 1503 EP 1510 PG 8 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 974GG UT WOS:000232578700029 PM 16386001 ER PT J AU Porwollik, S Santiviago, CA Cheng, P Florea, L Jackson, S McClelland, M AF Porwollik, S Santiviago, CA Cheng, P Florea, L Jackson, S McClelland, M TI Differences in gene content between Salmonella enterica serovar enteritidis isolates and comparison to closely related serovars gallinarum and Dublin SO JOURNAL OF BACTERIOLOGY LA English DT Article ID FIELD GEL-ELECTROPHORESIS; UNITED-STATES; SEROTYPE ENTERITIDIS; SUBSPECIES-I; PHAGE TYPES; STRAINS; TYPHIMURIUM; VIRULENCE; IDENTIFICATION; INFECTIONS AB Salmonella enterica serovar Enteritidis is often transmitted into the human food supply through eggs of hens that appear healthy. This pathogen became far more prevalent in poultry following eradication of the fowl pathogen S. enterica serovar Gallinarum in the mid-20th century. To investigate whether changes in serovar Enteritidis gene content contributed to this increased prevalence, and to evaluate genetic heterogeneity within the serovar, comparative genomic hybridization was performed on eight 60-year-old and nineteen 10- to 20-year-old serovar Enteritidis strains from various hosts, using a Salmonella-specific microarray. Overall, almost all the serovar Enteritidis genomes were very similar to each other. Excluding two rare strains classified as serovar Enteritidis in the Salmonella reference collection B, only eleven regions of the serovar Enteritidis phage type 4 (PT4) chromosome (sequenced at the Sanger Center) were absent or divergent in any of the other serovar Enteritidis strains tested. The more recent isolates did not have consistent differences from 60-year-old field isolates, suggesting that no large genomic additions on a whole-gene scale were needed for serovar Enteritidis to become more prevalent in domestic fowl. Cross-hybridization of phage genes on the array with related genes in the examined genomes grouped the serovar Enteritidis isolates into two major lineages. Microarray comparisons of the sequenced serovar Enteritidis PT4 to isolates of the closely related serovars Dublin and Gallinarum (biovars Gallinarum and Pullorum) revealed several genomic areas that distinguished them from serovar Enteritidis and from each other. These differences in gene content could be useful in DNA-based typing and in understanding the different phenotypes of these related serovars. C1 Sidney Kimmel Canc Ctr, San Diego, CA 92121 USA. George Washington Univ, Washington, DC 20052 USA. Ctr Food Safety & Appl Nutr, US FDA, Laurel, MD 20708 USA. RP McClelland, M (reprint author), Sidney Kimmel Canc Ctr, 10835 Rd Cure, San Diego, CA 92121 USA. EM mmcclelland@skcc.org RI McClelland, Michael/A-8583-2011; OI McClelland, Michael/0000-0003-1788-9347 FU NIAID NIH HHS [AI34829, R01 AI034829] NR 39 TC 71 Z9 73 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 SEP PY 2005 VL 187 IS 18 BP 6545 EP 6555 DI 10.1128/JB.18.6545-6555.2005 PG 11 WC Microbiology SC Microbiology GA 965PR UT WOS:000231963200034 PM 16159788 ER PT J AU Mudano, AS Bian, J Elkins, M Briggs, D Neal, A Cope, J Gross, T McGunagle, D Graham, J Ferriter, A Saag, KG AF Mudano, AS Bian, J Elkins, M Briggs, D Neal, A Cope, J Gross, T McGunagle, D Graham, J Ferriter, A Saag, KG TI Characteristics of vertebroplasty patients: An analysis of claims data from a large not-for-profit healthcare insurer SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 27th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 23-27, 2005 CL Nashville, TN SP Amer Soc Bone & Mineral Res C1 Univ Alabama, Ctr Educ & Res Therapeut Musculoskeletal Disorder, Birmingham, AL USA. Blue Cross & Blue Shield Alabama, Hlth Management, Birmingham, AL USA. US FDA, Ctr Devices & Radiol Hlth, Off Surveillance & Biometr, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 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 2005 VL 20 IS 9 SU 1 BP S158 EP S158 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 987FM UT WOS:000233503802047 ER PT J AU Mauldin, J Carbone, K Hsu, H Yolken, R Rubin, S AF Mauldin, J Carbone, K Hsu, H Yolken, R Rubin, S TI Mumps virus-specific antibody titers from pre-vaccine era sera: Comparison of the plaque reduction neutralization assay and enzyme immunoassays SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID LINKED IMMUNOSORBENT ASSAYS; VARICELLA-ZOSTER VIRUS; FIELD EVALUATION; INDUCED IMMUNITY; MEASLES; OUTBREAK; RUBELLA; SWITZERLAND; POPULATION; CHILDREN AB Mumps virus-neutralizing antibodies are believed to be the most predictable surrogate marker of protective immunity. However, assays used to detect neutralizing antibodies, such as the plaque reduction neutralization (PRN) assay, are labor- and time-intensive and consequently are often supplanted by the more rapid and inexpensive enzyme immunoassay (EIA) technique. For virus infections for which international antibody standards exist and are bridged to clinical studies of protection (e.g., measles and rubella), the EIA has been successfully used to determine immune surrogate endpoints, yet no such international reference exists for mumps serology. Since both virus-neutralizing and nonneutralizing antibodies are measured in the EIA, in the absence of a mumps serological standard, the EIA may be prone to yielding false-positive results when utilized for assessing surrogate markers of protective immunity. Moreover, since mumps virus-specific antibody titers are generally low in comparison to antibody levels induced by other viruses and EIA procedures often employ relatively high serum dilution factors, the EIA may be prone to yielding false-negative results. To examine these issues, a PRN assay and two commercially available EIA kits were used to evaluate wild-type mumps virus serological responses in human serum samples from the pre-mumps vaccine era. Our results indicate that the PRN assay is a more sensitive and specific method of measuring serological responses to wild-type mumps virus. C1 US FDA, DVP, OVRR, CBER, Bethesda, MD 20892 USA. Johns Hopkins Univ, Dept Pediat, Baltimore, MD 21218 USA. RP Rubin, S (reprint author), US FDA, DVP, OVRR, CBER, Bldg 29A,Room 1A-21,8800 Rockville Pike, Bethesda, MD 20892 USA. EM rubins@cber.fda.gov NR 33 TC 22 Z9 22 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD SEP PY 2005 VL 43 IS 9 BP 4847 EP 4851 DI 10.1128/JCM.43.9.4847-4851.2005 PG 5 WC Microbiology SC Microbiology GA 966LD UT WOS:000232020400087 PM 16145156 ER PT J AU Duan, JZ AF Duan, JZ TI Applications of population pharmacokinetics in current drug labeling in PDR SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Meeting Abstract CT 34th Annual Meeting of the American-College-of-Clinical-Pharmacology CY SEP 11-13, 2005 CL Rockville, MD SP Amer Coll Clin Pharmacol C1 US FDA, CDER, OCPB, DPEI, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD SEP PY 2005 VL 45 IS 9 MA 80 BP 1086 EP 1086 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 956OO UT WOS:000231309900084 ER PT J AU Haffner, M Bona, J Centeno-Deshields, D Nguyen, T Ott, C Whitley, J AF Haffner, M Bona, J Centeno-Deshields, D Nguyen, T Ott, C Whitley, J TI A review of clinical trial designs of typical orphan drugs approved by the Food and Drug Administration. SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Meeting Abstract CT 34th Annual Meeting of the American-College-of-Clinical-Pharmacology CY SEP 11-13, 2005 CL Rockville, MD SP Amer Coll Clin Pharmacol C1 US FDA, Off Orphan Prod Dev, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD SEP PY 2005 VL 45 IS 9 MA 91 BP 1089 EP 1089 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 956OO UT WOS:000231309900095 ER PT J AU Ramchandani, RP Booth, BP Duan, J Williams, GM Men, A Rahman, NAM Mehta, M Gobburu, JV AF Ramchandani, RP Booth, BP Duan, J Williams, GM Men, A Rahman, NAM Mehta, M Gobburu, JV TI Exposure-response analyses lead to more informed regulatory decisions: The oncology drug experience. SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Meeting Abstract CT 34th Annual Meeting of the American-College-of-Clinical-Pharmacology CY SEP 11-13, 2005 CL Rockville, MD SP Amer Coll Clin Pharmacol C1 US FDA, CDER, OCPB, DPE1, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD SEP PY 2005 VL 45 IS 9 MA 119 BP 1096 EP 1096 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 956OO UT WOS:000231309900121 ER PT J AU Haynes, CT Bronaugh, RL Yourick, JJ AF Haynes, CT Bronaugh, RL Yourick, JJ TI In vitro dermal absorption and metabolism of D&C Red No. 17 SO JOURNAL OF COSMETIC SCIENCE LA English DT Article; Proceedings Paper CT Annual Scientific Semina of the Society-Cosmetic-Chemists CY JUN 02-03, 2005 CL Las Vegas, NV SP Soc Cosmet Chemists C1 Off Cosmet & Colors, Food & Drug Adm, Laurel, MD 20708 USA. RP Haynes, CT (reprint author), Off Cosmet & Colors, Food & Drug Adm, Laurel, MD 20708 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU SOC COSMETIC CHEMISTS PI NEW YORK PA 120 WALL STREET, SUITE 2400, NEW YORK, NY 10005-4088 USA SN 1525-7886 J9 J COSMET SCI JI J. Cosmet. Sci. PD SEP-OCT PY 2005 VL 56 IS 5 BP 376 EP 377 PG 2 WC Chemistry, Applied; Dermatology SC Chemistry; Dermatology GA 006NA UT WOS:000234903000023 ER PT J AU Lee, VHL AF Lee, VHL TI Editorial: A tribute to Professor A.T. Florence for his Life-time Research Achievements SO JOURNAL OF DRUG TARGETING LA English DT Editorial Material C1 US FDA, Off Pharmaceut Sci, Rockville, MD 20852 USA. RP Lee, VHL (reprint author), US FDA, Off Pharmaceut Sci, HFD-03, Rockville, MD 20852 USA. RI Lee, Vincent/A-9439-2008 OI Lee, Vincent/0000-0001-7708-6269 NR 0 TC 1 Z9 1 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1061-186X J9 J DRUG TARGET JI J. Drug Target. PD SEP PY 2005 VL 13 IS 8-9 BP 447 EP 448 DI 10.1080/10611860500410862 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 999JD UT WOS:000234384700002 PM 16332569 ER PT J AU Mathias, NR Wu, SK Kim, KJ Lee, VHL AF Mathias, NR Wu, SK Kim, KJ Lee, VHL TI Nucleoside transport in primary cultured rabbit tracheal epithelial cells SO JOURNAL OF DRUG TARGETING LA English DT Article DE rabbit tracheal epithelial cells; nucleoside uptake; antiviral nucleoside analogs; nucleoside substrate selectivity; nucleoside transporters ID BRUSH-BORDER MEMBRANE; XENOPUS-LAEVIS OOCYTES; NECROSIS-FACTOR-ALPHA; PYRIMIDINE NUCLEOSIDES; PLASMA-MEMBRANE; CHOROID-PLEXUS; HUMAN KIDNEY; RAT; EXPRESSION; VESICLES AB The present study aimed at elucidating the mechanisms of nucleoside transport in primary cultured rabbit tracheal epithelial cells (RTEC) grown on a permeable filter support. Uptake of H-3-uridine, the model nucleoside substrate, from the apical fluid of primary cultured RTEC was examined with respect to its dependence on Na+, substrate concentration, temperature and its sensitivity to inhibitors, other nucleosides and antiviral nucleoside analogs. Apical H-3-uridine uptake in primary cultured RTEC was strongly dependent on an inward Na+ gradient and temperature. Ten micromolar nitro-benzyl-mercapto-purine-ribose (NBMPR) (an inhibitor of es-type nucleoside transport in the nanomolar range) did not further inhibit this process. H-3-uridine uptake from apical fluid was inhibited by basolateral ouabain (10 mu M) and apical phloridzin (100 mu M), indicating that uptake may involve a secondary active transport process. Uridine uptake was saturable with a K-m of 3.4 +/- 1.8 mu M and the V-max of 24.3 +/- 5.2 pmoles/mg protein/30 s. Inhibition studies indicated that nucleoside analogs that have a substitution on the nucleobase competed with uridine uptake from apical fluid, but those with modifications on the ribose sugar including acyclic analogs were ineffective. The pattern of inhibition of apical H-3-uridine, H-3-inosine and H-3-thymidine uptake into RTEC cells by physiological nucleosides was consistent with multiple systems: A pyrimidine-selective transport system (CNT1); a broad nucleoside substrate transport system that excludes inosine (CNT4) and an equilibrative NBMPR-insensitive nucleoside transport system (ei type). These results indicate that the presence of apically located nucleoside transporters in the epithelial cells lining the upper respiratory tract can lead to a high accumulation of nucleosides in the trachea. At least one Na+-dependent, secondary, active transport process may mediate the apical absorption of nucleosides or analogous molecules. C1 Univ So Calif, Dept Pharmaceut Sci, Los Angeles, CA 90089 USA. Univ So Calif, Dept Med, Los Angeles, CA 90089 USA. Univ So Calif, Dept Physiol & Biophys, Los Angeles, CA 90089 USA. Univ So Calif, Dept Mol Pharmacol & Toxicol, Los Angeles, CA 90089 USA. Univ So Calif, Dept Biomed Engn, Los Angeles, CA 90089 USA. Univ So Calif, Will Rogers Inst Pulm Res Ctr, Los Angeles, CA 90089 USA. Univ So Calif, Dept Ophthalmol, Los Angeles, CA 90089 USA. RP Lee, VHL (reprint author), US FDA, 5515 Secur Lane,Room 1023, Rockville, MD 20852 USA. EM leev@cder.fda.gov RI Lee, Vincent/A-9439-2008 OI Lee, Vincent/0000-0001-7708-6269 FU NHLBI NIH HHS [HL64365, HL38658]; NIGMS NIH HHS [GM52812] NR 41 TC 3 Z9 3 U1 0 U2 1 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1061-186X J9 J DRUG TARGET JI J. Drug Target. PD SEP PY 2005 VL 13 IS 8-9 BP 509 EP 519 DI 10.1080/10611860500383937 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 999JD UT WOS:000234384700009 PM 16332576 ER PT J AU Wu, SK Ann, DK Kim, KJ Lee, VHL AF Wu, SK Ann, DK Kim, KJ Lee, VHL TI Fine tuning of rabbit equilibrative nucleoside transporter activity by an alternatively spliced variant SO JOURNAL OF DRUG TARGETING LA English DT Article DE C-terminal variant; rbENT2; MDCK; basolateral nucleoside transport; alternatively spliced variant ID FUNCTIONAL-CHARACTERIZATION; MOLECULAR-CLONING; PURINERGIC RECEPTOR; NITROBENZYLTHIOINOSINE; CELLS; ADENOSINE; EI; SENSITIVITY; ISOFORM; ES AB The full-length cDNA encoding an equilibrative nucleoside transporter (rbENT2) and its novel C-terminal variant, rbENT2A, were isolated from rabbit trachea. Rabbit ENT2 protein consists of 456 amino acid residues; rbENT2A is shorter by 41 residues. Both rbENT2 and rbENT2A transcripts are found in rabbit tissues including intestine, kidney cortex, kidney, and trachea, at varying levels of expression. When transfected in a heterologous expression system - Madin Darby canine kidney (MDCK) epithelial cell line - both rbENT2 and rbENT2A were expressed. rbENT2 had a molecular mass of 49kDa; rbENT2A had a molecular mass of 44 kDa. Clones of both transporters yielded functional proteins that were capable of mediating uridine uptake and efflux without the needing to be coupled to a secondary ion (e.g. Na+). Remarkably, rbENT2A displayed a higher affinity (K-m = 41 mu M) and a lower capacity (V-max = 0.6 nmol/mg protein/5min) towards substrates than rbENT2 (K-m = 272.8 mu M, V-max = 1.26 nmol/mg protein/5 min). Pharmacological profiles showed that nitro-benzyl-mercapto-purine-ribose ( NBMPR) potently inhibited H-3-uridine uptake mediated by rbENT2A, but not uptake mediated by rbENT2. The constitutive splicing, broad expression, markedly different kinetics, and distinct pharmacological characteristics of rbENT2A appear to act in conjunction with the wild type, rbENT2, to fine-tune basolateral nucleoside transport function in rabbit trachea. C1 Univ So Calif, Dept Pharmaceut Sci, Los Angeles, CA 90089 USA. Univ So Calif, Dept Mol Pharmacol, Los Angeles, CA 90089 USA. Univ So Calif, Dept Toxicol, Los Angeles, CA 90089 USA. Univ So Calif, Dept Med, Will Rogers Inst Pulm Res Ctr, Los Angeles, CA 90089 USA. Univ So Calif, Dept Physiol & Biophys, Will Rogers Inst Pulm Res Ctr, Los Angeles, CA 90089 USA. Univ So Calif, Dept Mol Pharmacol & Toxicol, Will Rogers Inst Pulm Res Ctr, Los Angeles, CA 90089 USA. Univ So Calif, Dept Biomed Engn, Will Rogers Inst Pulm Res Ctr, Los Angeles, CA 90089 USA. Univ So Calif, Dept Ophthalmol, Los Angeles, CA 90089 USA. RP Lee, VHL (reprint author), US FDA, 5515 Secur Lane,Room 1023, Rockville, MD 20852 USA. EM leev@cder.fda.gov RI Lee, Vincent/A-9439-2008 OI Lee, Vincent/0000-0001-7708-6269 FU NHLBI NIH HHS [HL38658, HL64365]; NIGMS NIH HHS [GM52812] NR 30 TC 9 Z9 9 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1061-186X J9 J DRUG TARGET JI J. Drug Target. PD SEP PY 2005 VL 13 IS 8-9 BP 521 EP 533 DI 10.1080/10611860500403099 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 999JD UT WOS:000234384700010 PM 16332577 ER PT J AU Edelson-Mammel, SG Porteous, MK Buchanan, RL AF Edelson-Mammel, SG Porteous, MK Buchanan, RL TI Survival of Enterobacter sakazakii in a dehydrated powdered infant formula SO JOURNAL OF FOOD PROTECTION LA English DT Article ID NEONATAL MENINGITIS; INFECTIONS; MILK; CONTAMINATION; OUTBREAK AB A quantity of dehydrated powdered infant formula was prepared to contain Enterobacter sakazakii strain 607 at approximately 10(6) CFU/ml when rehydrated according to the manufacturer's instructions. The survival of the microorganism in the dry formula was followed for 2 years, during which samples periodically were rehydrated and analyzed for viable E. sakazakii. During the initial 5 months of storage at room temperature, viable counts declined approximately 2.4 log cycles. During the subsequent 19 months, the concentration of viable E. sakazakii declined an additional 1.0 log cycle. These results indicate that a small percentage of E. sakazakii cells can survive for extended periods in dehydrated powdered infant formula. C1 USDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. Univ Maryland, Joint Inst Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Buchanan, RL (reprint author), USDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM robert.buchanan@cfsan.fda.gov NR 18 TC 61 Z9 63 U1 1 U2 10 PU INT ASSOC FOOD PROTECTION PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD SEP PY 2005 VL 68 IS 9 BP 1900 EP 1902 PG 3 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 961VV UT WOS:000231690800016 PM 16161690 ER PT J AU Dasenbrock, CO Ciolino, LA Hatfield, CL Jackson, DS AF Dasenbrock, CO Ciolino, LA Hatfield, CL Jackson, DS TI The determination of nicotine and sulfate in supermarket ground beef adulterated with black leaf 40 SO JOURNAL OF FORENSIC SCIENCES LA English DT Article; Proceedings Paper CT 16th Internatioanl Ion Chromatography Symposium CY SEP, 2003 CL San Diego, CA DE forensic science; food tampering; Black Leaf 40 insecticide; nicotine sulfate; ground beef; tissue analysis; high performance liquid chromatography-ultraviolet detection; gas chromatography mass spectrometry; high performance anion exchange chromatography ID LIQUID-CHROMATOGRAPHIC DETERMINATION; COMMERCIAL TOBACCO PRODUCTS; ION CHROMATOGRAPHY; QUANTITATION AB In December 2002, approximately 250 lbs. of ground beef was adulterated with nicotine sulfate by a supermarket employee and subsequently sold to the public. Soon afterward, reports of illness associated with ground beef purchased at a single store were identified. Authorities suspected the ground beef was tainted with Black Leaf 40, a banned pesticide containing approximately 40% nicotine as nicotine sulfate. Ground beef submitted to our laboratory was analyzed in concert by high performance liquid chromatography-ultraviolet detection (HPLC-UV), gas chromatography-mass spectrometry (GC-MS), and high performance anion exchange chromatography with suppressed conductivity detection. GC-MS was used to identify the samples that contained nicotine. The nicotine was confirmed and quantitated by HPLC-UV. The sulfate was identified and quantitated by high performance anion exchange chromatography with suppressed conductivity detection. Our analysis revealed that the raw tainted beef contained about 350 mg/kg nicotine free base, a potentially lethal dose of nicotine per serving for an adult. Additionally, we found elevated sulfate levels in the samples that tested positive for nicotine, providing evidence that nicotine sulfate was the probable adulterant. C1 US FDA, Forens Chem Ctr, Cincinnati, OH 45237 USA. RP Dasenbrock, CO (reprint author), US FDA, Forens Chem Ctr, 6751 Steger Dr, Cincinnati, OH 45237 USA. NR 14 TC 3 Z9 3 U1 0 U2 3 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 2005 VL 50 IS 5 BP 1134 EP 1140 PG 7 WC Medicine, Legal SC Legal Medicine GA 961KE UT WOS:000231660300019 PM 16225221 ER PT J AU Coban, C Ishii, KJ Gursel, M Klinman, DM Kumar, N AF Coban, C Ishii, KJ Gursel, M Klinman, DM Kumar, N TI Effect of plasmid backbone modification by different human CpG motifs on the immunogenicity of DNA vaccine vectors SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE Plasmodium falciparum; oligonucleotides; dendritic cells ID TRANSMISSION-BLOCKING ANTIBODIES; PLASMACYTOID DENDRITIC CELLS; PROTECTIVE IMMUNITY; MALARIA; MICE; IMMUNIZATION; PROTEIN; OLIGODEOXYNUCLEOTIDES; ACTIVATION; INDUCTION AB DNA vaccines, in general, have been found to be poorly immunogenic in nonhuman primates and humans as compared with mice. As the immunogenicity of DNA plasmids relies, to a large extent, on the presence of CpG motifs as built in adjuvants, we addressed the issue of poor immunogenicity by inserting recently identified CpG oligonucleotides (ODN) optimal for human (K-type or D-type CpG ODN) into the backbone of plasmid VR1020. We found that plasmid DNA containing K-type CpG motifs or D-type CpG motifs significantly enhanced the up-regulation of surface molecules and production of interleukin-6 from human peripheral blood mononuclear cells (PBMC) and stimulated monocytes to develop into functionally mature dendritic cells (DC) compared with unmodified plasmid. Monocyte maturation into DC was through plasmacytoid DC present in the culture. It is interesting that the K-type CpG motif-modified plasmid stimulated significant levels of interferon (IFN)-gamma and IFN-alpha from human PBMC. Immunization of mice with D-type CpG motif-modified plasmid, encoding Plasmodium falciparum surface protein 25, yielded enhanced antigen-specific antibodies. Taken together, these results suggest that insertion of immunomodulatory human CpG motifs into plasmid DNA can improve immunogenicity of DNA vaccines. C1 Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Johns Hopkins Malaria Res Inst, Dept Mol Microbiol & Immunol, Baltimore, MD 21205 USA. US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. RP Kumar, N (reprint author), Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Johns Hopkins Malaria Res Inst, Dept Mol Microbiol & Immunol, 615 N Wolfe St, Baltimore, MD 21205 USA. EM nkumar@jhsph.edu RI Gursel, Mayda /H-1812-2012; Coban, Cevayir/B-2129-2012; Ishii, Ken/B-1685-2012; OI Ishii, Ken/0000-0002-6728-3872; Gursel, Mayda/0000-0003-0044-9054 FU NIAID NIH HHS [AI47089] NR 33 TC 43 Z9 45 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 SEP PY 2005 VL 78 IS 3 BP 647 EP 655 DI 10.1189/jlb.1104627 PG 9 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 961TZ UT WOS:000231686000009 PM 15961575 ER PT J AU Cote, TR Mohan, AK Polder, JA Walton, MK Braun, MM AF Cote, TR Mohan, AK Polder, JA Walton, MK Braun, MM TI Botulinum toxin type A injections: Adverse events reported to the US Food and Drug Administration in therapeutic and cosmetic cases SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID CHRONIC ANAL-FISSURE; CEREBRAL-PALSY; TEMPOROMANDIBULAR DISORDERS; INTRAMUSCULAR INJECTION; LIMB SPASTICITY; CHILDREN; BOTOX; HYPERHIDROSIS; ACHALASIA; MUSCLE AB Background: Botulinum toxin type A (BTA) (Botox) received Food and Drug Administration (FDA) approval for therapeutic treatment of strabismus and blepharospasm in 1989, cervical dystoma in 2000, and cosmetic treatment of glabellar wrinkles (Botox Cosmetic) in 2002. In 2002 alone there were approximately 1.1 to 1.6 million patients using cosmetic BTA. Our objective was to review adverse event (AE) reporting to the FDA after BTA administration. Methods: We reviewed all (therapeutic and cosmetic use) serious (per FDA regulations) AEs reported to the FDA for the 13.5 years since licensure of the product (December 1989-May 2003) and nonserious AEs reported from December 2001 to November 2002. AEs are reported to the FDA through the MedWatch system. Results: We reviewed 1437 AE reports; 406 followed therapeutic use of BTA (217 serious and 189 nonserious) and 1031 followed cosmetic use (36 serious and 995 nonserious). Reported AEs Occurred predominantly in female patients, with a median age of 50 years. In the year December 2001 to November 2002, when both serious and nonserious reports were evaluated, the proportion of reports classified as serious was 33-fold higher for therapeutic than for cosmetic cases. The 217 serious AEs reported in therapeutic cases involved a wide spectrum of events and included all 28 reported deaths. Among cosmetic users, no deaths were reported and, of the 36 serious AEs, 30 were included as possible complications in the FDA-approved label. The remaining 6 serious AEs did not display a pattern suggesting a common causal relationship to BTA. Among the 995 cosmetic cases reported to have nonserious AEs, most commonly noted were lack of effect (623, 63%), injection site reaction (190, 19%), and ptosis (111, 11%). Conclusions: Serious AEs were more likely to be reported for therapeutic than for cosmetic use, which may be related to higher closes, complicated underlying diseases, or both. Among cosmetic cases, few serious AEs were reported, and these were predominantly events that were previously recognized in clinical trials of BTA for the labeled use. This study is limited primarily by the incomplete nature of AE reporting by clinicians. numerous departures from FDA-approved recommendations for drug Close, dilution, handling, site of injection, and storage were noted in these AE reports. C1 US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20852 USA. RP Braun, MM (reprint author), US FDA, Ctr Biol Evaluat & Res, OBE 1401 Rockville Pike,HFM-220, Rockville, MD 20852 USA. EM braunm@cber.fda.gov NR 57 TC 121 Z9 126 U1 0 U2 18 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 SEP PY 2005 VL 53 IS 3 BP 407 EP 415 DI 10.1016/j.jaad.2005.06.011 PG 9 WC Dermatology SC Dermatology GA 957WY UT WOS:000231405200003 PM 16112345 ER PT J AU Wear, KA Stiles, TA Frank, GR Madsen, EL Cheng, F Feleppa, EJ Hall, CS Kim, BS Lee, P O'Brien, WD Oelze, ML Raju, BI Shung, KK Wilson, TA Yuan, JR AF Wear, KA Stiles, TA Frank, GR Madsen, EL Cheng, F Feleppa, EJ Hall, CS Kim, BS Lee, P O'Brien, WD Oelze, ML Raju, BI Shung, KK Wilson, TA Yuan, JR TI Interlaboratory comparison of ultrasonic backscatter coefficient measurements from 2 to 9 MHz SO JOURNAL OF ULTRASOUND IN MEDICINE LA English DT Article DE backscatter; interlaboratory comparison; tissue characterization ID ACOUSTIC SCATTERING SOURCES; TISSUE-MIMICKING MATERIALS; NORMAL RENAL PARENCHYMA; FREQUENCY-DEPENDENCE; SPECTRUM ANALYSIS; CROSS-SECTIONS; ATTENUATION; LIVER; SPEED; DIFFERENTIATION AB Objective. As are the attenuation coefficient and sound speed, the backscatter coefficient is a fundamental ultrasonic property that has been used to characterize many tissues. Unfortunately, there is currently far less standardization for the ultrasonic backscatter measurement than for the other two, as evidenced by a previous American Institute of Ultrasound in Medicine (AIUM)-sponsored inter-laboratory comparison of ultrasonic backscatter, attenuation, and speed measurements (J Ultrasound Med 1999; 18:615-631). To explore reasons for these disparities, the AIUM Endowment for Education and Research recently supported this second interlaboratory comparison, which extends the upper limit of the frequency range from 7 to 9 MHz. Methods. Eleven laboratories were provided with standard test objects designed and manufactured at the University of Wisconsin (Madison, WI). Each laboratory was asked to perform ultrasonic measurements of sound speed, attenuation coefficients, and backscatter coefficients. Each laboratory was blinded to the values of the ultrasonic properties of the test objects at the time the measurements were performed. Results. Eight of the 11 laboratories submitted results. The range of variation of absolute magnitude of backscatter coefficient measurements was about 2 orders of magnitude. If the results of 1 outlier laboratory are excluded, then the range is reduced to about 1 order of magnitude. Agreement regarding frequency dependence of backscatter was better than reported in the previous interlaboratory comparison. For example, when scatterers were small compared with the ultrasonic wavelength, experimental frequency-dependent backscatter coefficient data obtained by the participating laboratories were usually consistent with the expected Rayleigh scattering behavior (proportional to frequency to the fourth power). Conclusions. Greater standardization of backscatter measurement methods is needed. Measurements of frequency dependence of backscatter are more consistent than measurements of absolute magnitude. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20852 USA. Univ Wisconsin, Madison, WI 53706 USA. Boston Sci, Fremont, CA USA. Philips Res, New York, NY USA. Riverside Res Inst, New York, NY USA. Univ So Calif, Los Angeles, CA 90089 USA. Univ Illinois, Urbana, IL 61801 USA. Univ Tennessee, Memphis, TN USA. RP Wear, KA (reprint author), US FDA, Ctr Devices & Radiol Hlth, 12720 Twinbrook Pkwy, Rockville, MD 20852 USA. EM kaw@cdrh.fda.gov NR 45 TC 68 Z9 68 U1 0 U2 8 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 SEP PY 2005 VL 24 IS 9 BP 1235 EP 1250 PG 16 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA 959MX UT WOS:000231523100010 PM 16123184 ER PT J AU Kay, NE Bone, ND Lee, YK Jelinek, DF Leland, P Battle, TE Frank, DA Puri, RK AF Kay, NE Bone, ND Lee, YK Jelinek, DF Leland, P Battle, TE Frank, DA Puri, RK TI A recombinant IL-4-Pseudomonas exotoxin inhibits protein synthesis and overcomes apoptosis resistance in human CLL B cells SO LEUKEMIA RESEARCH LA English DT Article DE B-CLL; IL-4; IL-4R ID CHRONIC LYMPHOCYTIC-LEUKEMIA; PSEUDOMONAS EXOTOXIN; CYTOTOXIN THERAPY; IN-VITRO; INTERLEUKIN-4; RECEPTOR; IL-4; EXPRESSION; SURVIVAL; PHOSPHORYLATION AB We have determined that CLL B cells consistently express type 3 membrane receptors for the Th2-derived cytokine IL-4 (IL-4R). Furthermore, when added to CLL B cells, IL-4 induces increased apoptosis resistance, increased protein synthesis in CLL B cells and rapid onset activation of STAT1, STAT5 and STAT6. Since the IL-4-IL-4R pathway is intact in CLL B cells and is related to apoptosis resistance, we considered whether we could target this pathway. A recombinant IL-4 Pseudomonas exotoxin fusion protein (IL-4PE), known to bind to IL-4R, was incubated with CLL B cells. IL-4PE (10 ng/ml) cultured with CLL B cells resulted in an increase of apoptosis/death from mean levels of 46.6 +/- 7.0 of non-exposed cells to 69 +/- 8.6 (n = 6). By measuring in vitro protein synthesis, two predominant patterns of sensitivity were observed. In one, CLL B cell clones (n = 4) were found to be extremely sensitive to IL-4PE (IC50's range = 6-25 ng/ml). In the second, low concentrations of IL-4PE induced agonist activity while increasing concentrations induced cytotoxicity in 6 of 21 patient-derived cells. These studies suggest that the IL-4R, on B-CLL cells, can serve as a unique molecular target for directing cytotoxic agents in the therapy of B-CLL. (c) 2005 Elsevier Ltd. All rights reserved. C1 Mayo Clin & Mayo Fdn, Rochester, MN 55905 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. RP Kay, NE (reprint author), Mayo Clin & Mayo Fdn, Stabile 628,200 1st St SW, Rochester, MN 55905 USA. EM kay.neil@mayo.edu FU NCI NIH HHS [CA91542] NR 38 TC 11 Z9 11 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 2005 VL 29 IS 9 BP 1009 EP 1018 DI 10.1016/j.leukres.2004.11.025 PG 10 WC Oncology; Hematology SC Oncology; Hematology GA 952MN UT WOS:000231007700006 PM 16038727 ER PT J AU Rasooly, A AF Rasooly, A TI Biosensor technologies SO METHODS LA English DT Editorial Material C1 Natl Canc Inst, US FDA, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs,Div Biol Sci,Canc Diagnost Pr, Rockville, MD 20852 USA. RP Rasooly, A (reprint author), Natl Canc Inst, US FDA, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs,Div Biol Sci,Canc Diagnost Pr, 6130 Execut Blvd, Rockville, MD 20852 USA. EM rasoolya@mail.nih.gov NR 3 TC 7 Z9 7 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 1046-2023 J9 METHODS JI Methods PD SEP PY 2005 VL 37 IS 1 BP 1 EP 3 DI 10.1016/j.ymeth.2005.05.004 PG 3 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 979MG UT WOS:000232945500001 PM 16199171 ER PT J AU Hu, L Raybourne, RB Kopecko, DJ AF Hu, L Raybourne, RB Kopecko, DJ TI Ca2+ release from host intracellular stores and related signal transduction during Campylobacter jejuni 81-176 internalization into human intestinal cells SO MICROBIOLOGY-SGM LA English DT Article ID EPITHELIAL-CELLS; SALMONELLA-TYPHIMURIUM; MAMMALIAN-CELLS; FREE CALCIUM; IN-VITRO; INVASION; CALMODULIN; OSCILLATIONS; ENDOCYTOSIS; ACTIVATION AB Campylobacter jejuni is the leading bacterial cause of human diarrhoeal disease in many parts of the world, including the USA. The ability of C. jejuni to invade the host intestinal epithelium is an important determinant of virulence. A common theme among pathogenic invasive micro-organisms is their ability to usurp the eukaryotic cell-signalling systems both to allow for invasion and to trigger disease pathogenesis. Ca2+ is very important in a great variety of eukaryotic cell-signalling processes (e.g. calmodulin-activated enzymes, nuclear transcriptional upregulation, and cytoskeletal rearrangements). This study analyses the effects of Ca2+ availability on invasion of human INT407 intestinal epithelial cells by C. jejuni strain 81-176. The ability of C. jejuni to invade INT407 cells was not blocked by chelation of any remaining extracellular Ca2+ from host cells incubated in Ca2+-free, serum-free media. In contrast, C. jejuni invasion was markedly reduced either by chelating host intracellular Ca2+ with 1,2-bis-(2-)ethane-N,N,N',N'tetraacetic acid acetoxymethyl ester (BAPTA, AM) or by blocking the release of Ca2+ from intracellular stores with clantrolene or U73122. Moreover, Bay K8644, a plasma-membrane Ca2+-channel agonist, was observed to stimulate C. jejuni invasion, presumably by increasing host intracellular free Ca2+ levels. Measurement of host-cell cytosolic Ca2+ via spectrofluorimetry and fluorescence microscopy revealed an increase in Ca2+ from 10 min post-infection. Monolayer pretreatment with either a calmodulin antagonist or a specific inhibitor of protein kinase C was found to cause a marked reduction in C. jejuni invasion, suggesting roles for these Ca2+-activated modulators in signal-transcluction events involved in C. jejuni invasion. These results demonstrate that C. jejuni induces the mobilization of Ca2+ from host intracellular stores, which is an essential step in the invasion of intestinal cells by this pathogen. C1 US FDA, Ctr Biol Evaluat & Res, Lab Enter & Sexually Transmitted Dis, Bethesda, MD 20892 USA. US FDA, Ctr Food Safety & Appl Nutr, Virulence Assessment, Laurel, MD 20708 USA. RP Kopecko, DJ (reprint author), US FDA, Ctr Biol Evaluat & Res, Lab Enter & Sexually Transmitted Dis, 29 Lincoln Dr,Bldg 29-420 HFM 440, Bethesda, MD 20892 USA. EM kopecko@cber.fda.gov NR 38 TC 28 Z9 29 U1 0 U2 0 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 SEP PY 2005 VL 151 BP 3097 EP 3105 DI 10.1099/mic.0.27866-0 PN 9 PG 9 WC Microbiology SC Microbiology GA 967FV UT WOS:000232077800029 PM 16151220 ER PT J AU Scallet, AC Schmued, LC Johannessen, JN AF Scallet, AC Schmued, LC Johannessen, JN TI Neurohistochemical biomarkers of the marine neurotoxicant, domoic acid SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Article; Proceedings Paper CT Symposium on Marine Toxin Impacts on Neurobehavioral Function CY JUN 22-24, 2003 CL Philadelphia, PA DE limbic system; hippocampus; excitotoxins; c-Fos; c-Jun; argyrophilia; fluoro-jade; algal blooms; shellfish toxins; myelin; GFAP; HSP-72; rat; IgG; blood-brain barrier ID MONKEYS MACACA-FASCICULARIS; INDUCED NEURONAL DEGENERATION; KAINIC ACID; FLUORO-JADE; MEDIATED EXCITOTOXICITY; TRANSCRIPTION FACTOR; HIPPOCAMPAL DAMAGE; CRASSOSTREA-GIGAS; HIGH-RESOLUTION; PACIFIC OYSTER AB Domoic acid and its potent excitotoxic analogues glutamic acid and kainic acid, are synthesized by marine algae such as seaweed and phytoplankton. During an algal bloom, domoic acid may enter the food web through its consumption by a variety of marine organisms held in high regard as seafoods by both animals and humans. These seafoods include clams, mussels, oysters, anchovies, sardines, crabs, and scallops, among others. Animals, such as pelicans, cormorants, loons, grebes, sea otters, dolphins, and sea lions, which consume seafood contaminated with domoic acid, suffer disorientation and often death. Humans consuming contaminated seafood may suffer seizures, amnesia and also sometimes death. In addition to analytical measurement of domoic acid exposure levels in algae and/or seafood, it is useful to be able to identify the mode of toxicity through post-mortem evaluation of the intoxicated animal. In the present study, using the rat as an animal model of domoic acid intoxication, we compared histochemical staining of the limbic system and especially the hippocampus with degeneration-selective techniques (Fluoro-Jade and silver), a conventional Nissl stain for cytoplasm (Cresyl violet), a myelin-selective stain (Black-Gold), an astrocyte-specific stain (glial fibrillary acidic protein), early/immediate gene responses (c-Fos and c-Jun), as well as for heat shock protein (HSP-72) and blood-brain barrier integrity (rat IgG). The results demonstrate that the degeneration-selective stains are the biomarkers of domoic acid neurotoxicity that are the most useful and easy to discern when screening brain sections at low magnification. We also observed that an impairment of blood-brain barrier integrity within the piriform cortex accompanied the onset of domoic acid neurotoxicity. (c) 2005 Published by Elsevier Inc. C1 US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. US FDA, Ctr Food Safety & Nutr, Laurel, MD 20708 USA. RP Scallet, AC (reprint author), US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, 3900 NCTR Dr, Jefferson, AR 72079 USA. EM AScallet@nctr.fda.gov NR 75 TC 19 Z9 19 U1 2 U2 7 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0892-0362 J9 NEUROTOXICOL TERATOL JI Neurotoxicol. Teratol. PD SEP-OCT PY 2005 VL 27 IS 5 BP 745 EP 752 DI 10.1016/j.ntt.2005.06.018 PG 8 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA 982ED UT WOS:000233139800008 PM 16203121 ER PT J AU Ben-David, M Ilev, IK Waynant, RW Gannot, I AF Ben-David, M Ilev, IK Waynant, RW Gannot, I TI Pulse dispersion in hollow optical waveguides SO OPTICAL ENGINEERING LA English DT Article DE waveguides; dispersion; pulses ID DELIVERY; PROPAGATION; LASER; FIBERS; TAPER AB A study of laser (near- and mid-infrared) pulse dispersion in hollow waveguides is presented, We developed an analytical model to describe the pulse dispersion in hollow waveguides and compared our theoretical calculations with measurements done by us and also by two other groups. The pulse dispersion was experimentally measured for a short Q-switched Er:YAG laser in the nanosecond range and for femtosecond Ti:sapphire laser pulses transmitted by hollow optical waveguides. For analytical calculation of the pulse dispersion in these waveguides, a refined ray tracing program was developed. This approach took into account roughness of the internal reflecting and refracting inner layers. A comparison analysis between the measurements and calculations conducted at identical parameters demonstrates good correlation between theoretical and experimental results. (c) 2005 society of Photo-Optical Instrumentation Engineers. C1 Tel Aviv Univ, Fac Exact Sci, Dept Appl Phys, IL-69978 Tel Aviv, Israel. US FDA, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. Tel Aviv Univ, Fac Engn, Dept Biomed Engn, IL-69978 Tel Aviv, Israel. Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. RP Ben-David, M (reprint author), Tel Aviv Univ, Fac Exact Sci, Dept Appl Phys, IL-69978 Tel Aviv, Israel. EM moshe@glucon.com NR 19 TC 1 Z9 1 U1 1 U2 4 PU SPIE-INT SOCIETY OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 0091-3286 J9 OPT ENG JI Opt. Eng. PD SEP PY 2005 VL 44 IS 9 AR 095001 DI 10.1117/1.2042967 PG 6 WC Optics SC Optics GA 981NG UT WOS:000233094700025 ER PT J AU Banks, D Woo, EJ Burwen, DR Perucci, P Braun, MM Ball, R AF Banks, D Woo, EJ Burwen, DR Perucci, P Braun, MM Ball, R TI Comparing data mining methods on the VAERS database SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Article DE adverse event; empirical Bayes; proportional reporting ratio; vaccine ID REPORTING-SYSTEM VAERS; SIGNAL-DETECTION; PHARMACOVIGILANCE; EVENTS; DRUGS; VACCINATION/; TABLES AB Purpose Data mining may enhance traditional surveillance of vaccine adverse events by identifying events that are reported more commonly after administering one vaccine than other vaccines. Data mining methods find signals as the proportion of times a condition or group of conditions is reported soon after the administration of a vaccine; thus it is a relative proportion compared across vaccines, and not an absolute rate for the condition. The Vaccine Adverse Event Reporting System (VAERS) contains approximately 150 000 reports of adverse events that are possibly associated with vaccine administration. Methods We studied four data mining techniques: empirical Bayes geometric mean (EBGM), lower-bound of the EBGM's 90% confidence interval (EB05), proportional reporting ratio (PRR), and screened PRR (SPRR). We applied these to the VAERS database and compared the agreement among methods and other performance properties, particularly focusing on the vaccine-event combinations with the highest numerical scores in the various methods. Results The vaccine-event combinations with the highest numerical scores varied substantially among the methods. Not all combinations representing known associations appeared in the top 100 vaccine-event pairs for all methods. Conclusions The four methods differ in their ranking of vaccine-COSTART pairs. A given method may be superior in certain situations but inferior in others. This paper examines the statistical relationships among the four estimators. Determining which method is best for public health will require additional analysis that focuses on the true alarm and false alarm rates using known vaccine-event associations. Evaluating the properties of these data mining methods will help determine the value of such methods in vaccine safety surveillance. Copyright (c) 2005 John Wiley & Sons. C1 US FDA, HFM 22, Off Biostat & Epidemiol, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Woo, EJ (reprint author), US FDA, HFM 22, Off Biostat & Epidemiol, Ctr Biol Evaluat & Res, 1401 Rockville Pike, Rockville, MD 20852 USA. EM wooj@cber.fda.gov NR 21 TC 40 Z9 40 U1 2 U2 6 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD SEP PY 2005 VL 14 IS 9 BP 601 EP 609 DI 10.1002/pds.1107 PG 9 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 964XF UT WOS:000231913600002 PM 15954077 ER PT J AU Mendelsohn, AB Governale, L Trontell, A Seligman, P AF Mendelsohn, AB Governale, L Trontell, A Seligman, P TI Changes in isotretinoin prescribing before and after implementation of the System to Manage Accutane Related Teratogenicity (TM) (SMART (TM)) risk management program SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Article DE isotretinoin; risk management; prescriptions; patients; acne AB Purpose To assess changes in isotretinoin prescribing following the implementation of the System to Manage Accutane Related Teratogenicity (TM) (SMART (TM)) risk management program. Methods Using nationally representative commercial data resources on prescription drug dispensing patterns, surveys of office-based physician practices, and a large, claims database from a pharmacy benefits manager (PBM), we examined the total number of isotretinoin prescriptions (new and refill), prescriber speciality, and patient characteristics (age, gender, severity of acne indication) in the year before (April 2001-March 2002) and the year following (April 2002-March 2003) implementation of the SMART (TM) program. Results In the 12-months prior to SMART (TM), 1508 000 prescriptions were dispensed for isotretinoin, declining approximately 23% to 1160 000 prescriptions in the year following SMART (TM). There was little or no change in prescriber specialty, severity of acne, and patient age and gender. Conclusion SMART (TM) may have lead to a decrease in isotretinoin prescriptions. Further research is needed to determine whether the reduced number of isotretinoin prescriptions reflects appropriate use or inhibited use resulting in loss of access to the product's benefits. Copyright (c) 2005 John Wiley & Sons, Ltd. C1 US FDA, Off Drug Safety, Rockville, MD USA. Ctr Dis Control & Prevent, Epidem Intelligence Serv, Atlanta, GA USA. RP Mendelsohn, AB (reprint author), 5600 Fishers Lane,HFD-410,Rm 15B-23, Rockville, MD 20850 USA. NR 4 TC 11 Z9 11 U1 0 U2 2 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD SEP PY 2005 VL 14 IS 9 BP 615 EP 618 DI 10.1002/pds.1111 PG 4 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 964XF UT WOS:000231913600004 PM 15892175 ER PT J AU Simpkins, F Czechowicz, JA Liotta, L Kohn, EC AF Simpkins, F Czechowicz, JA Liotta, L Kohn, EC TI SELDI-TOF mass spectrometry for cancer biomarker discovery and serum proteomic diagnostics SO PHARMACOGENOMICS LA English DT Article DE biomarker; mass spectrometry; proteomics; SELDI-TOF ID LASER DESORPTION/IONIZATION-TIME; OVARIAN-CANCER; PROSTATE-CANCER; NONCANCER PATIENTS; COLORECTAL-CANCER; PANCREATIC-CANCER; BREAST-CANCER; TREE ANALYSIS; IDENTIFICATION; PATTERNS AB Proteomics is more than the identification of proteins that are altered in expression as a consequence of disease. Among the tools critical for the detection, treatment and monitoring of disease are biomarkers. The necessity for new methods to identify and validate biomarkers is underscored by the increased survival of patients diagnosed at early stages of cancer. Serum proteomic pattern diagnostics is a new technique in which proteomic signatures are used as a diagnostic classifier. Surf ace-enhanced laser desorption/ionization time-of-flight mass spectrometry has shown promise as a modality for biomarker discovery of early-stage cancers. Mass spectrometry-derived protein signatures have been modeled and are now moving into validation. Further sequencing of these key features can lead to new insights into disease etiology and intervention. C1 NCI, Pathol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. NCI, FDA, Clin Proteom Program, Bethesda, MD 20892 USA. RP Kohn, EC (reprint author), NCI, Pathol Lab, Ctr Canc Res, Bldg 10 Rm 12N226,10 Ctr Dr,MSC 1500, Bethesda, MD 20892 USA. EM kohne@mail.nih.gov NR 51 TC 29 Z9 32 U1 0 U2 1 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1462-2416 J9 PHARMACOGENOMICS JI Pharmacogenomics PD SEP PY 2005 VL 6 IS 6 BP 647 EP 653 DI 10.2217/14622416.6.6.647 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 965NV UT WOS:000231958300014 PM 16143004 ER PT J AU Yan, J Xia, QS Cherng, SH Wamer, WG Howard, PC Yu, HT Fu, PP AF Yan, J Xia, QS Cherng, SH Wamer, WG Howard, PC Yu, HT Fu, PP TI Photo-induced DNA damage and photocytotoxicity of retinyl palmitate and its photodecomposition products SO TOXICOLOGY AND INDUSTRIAL HEALTH LA English DT Article DE 5,6-epoxy-retinyl palmitate; anhydroretinol; comet assay; DNA strand cleavage; retinyl palmitate ID IN-VIVO; SKIN; LIGHT; PHOTOTOXICITY; TOXICOLOGY; CLEAVAGE; OXYGEN AB Retinyl palmitate (RP) is an ester of retinol (vitamin A) and the predominant form of retinol found endogenously in the skin. We have previously reported that photoirradiation of RP with UVA light resulted in the formation of anhydroretinol (AR), 5,6-epoxyretinyl palmitate (5,6-epoxy-RP) and other photodecomposition products. While AR was formed through an ionic photodissociation mechanism, 5,6-epoxy-RP was formed through a light-mediated, free radical-initiated chain reaction. In the current study, the phototoxicity of RP, AR and 5,6-epoxy-RP in human skin Jurkat T-cells with and without light irradiation was determined using a fluorescein diacetate assay. Under similar conditions, the Comet assay was used to assess damage to cellular DNA. Nuclear DNA was not significantly damaged when the cells were irradiated by UVA plus visible light in the absence of a retinoid; however, when the cells were illuminated with UVA plus visible light in the presence of either RP, 5,6-epoxy-RP or AR (50, 100, 150 and 200 M), DNA fragmentation was observed. Cell death was observed for retinoid concentrations of 100 mu M or higher. When treated with 150 M of RP, 5,6-epoxy-RP or AR, cell death was 52, 33 and 52%, respectively. These results suggest that RP and its two photodecomposition products, AR and 5,6-epoxy-RP, induce DNA damage and cytotoxicity when irradiated with UVA plus visible light. We also determined that photoirradiation of RP, AR and ,6-epoxy-RP causes single strand breaks in supercoiled Phi X174 plasmid DNA. Using a constant dose of UVA light (50 J/cm(2)), the level of DNA cleavage was highest in the presence of AR, followed by 5,6-epoxy-RP, then RP The induced DNA strand cleavage was inhibited by NaN3. These results suggest that photoirradiation of RP, 5,6-epoxy-RP and AR with UVA light generates free radicals that initiate DNA strand cleavage. C1 Jackson State Univ, Dept Chem, Jackson, MS 39217 USA. US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. RP Yu, HT (reprint author), Jackson State Univ, Dept Chem, Jackson, MS 39217 USA. EM yu@ccaix.jsums.edu FU PHS HHS [2143-0001] NR 18 TC 15 Z9 15 U1 1 U2 2 PU ARNOLD, HODDER HEADLINE PLC PI LONDON PA 338 EUSTON ROAD, LONDON NW1 3BH, ENGLAND SN 0748-2337 J9 TOXICOL IND HEALTH JI Toxicol. Ind. Health PD SEP PY 2005 VL 21 IS 7-8 BP 167 EP 175 DI 10.1191/0748233705th225oa PG 9 WC Public, Environmental & Occupational Health; Toxicology SC Public, Environmental & Occupational Health; Toxicology GA 955ZE UT WOS:000231267900004 PM 16149731 ER PT J AU Dechraoui, MYB Wang, ZH Turquet, J Chinain, M Darius, T Cruchet, P Radwan, FFY Dickey, RW Ramsdell, JS AF Dechraoui, MYB Wang, ZH Turquet, J Chinain, M Darius, T Cruchet, P Radwan, FFY Dickey, RW Ramsdell, JS TI Biomonitoring of ciguatoxin exposure in mice using blood collection cards SO TOXICON LA English DT Article DE ciguatoxins; ciguatera; blood collection cards; marine toxins; monitoring; detection ID CELL-BASED ASSAY; SODIUM-CHANNELS; CARIBBEAN-CIGUATOXINS; RECEPTOR-SITE; INDIAN-OCEAN; GAMBIERDISCUS-TOXICUS; CLINICAL-FEATURES; MYELINATED AXONS; REPORTER GENE; MARINE TOXINS AB Ciguatera is a human food poisoning caused by consumption of tropical and subtropical fish that have, through their diet, accumulated ciguatoxins in their tissues. This study used laboratory mice to investigate the potential to apply blood collection cards to biomonitor ciguatoxin exposure. Quantitation by the neuroblastoma cytotoxicity assay of Caribbean ciguatoxin (C-CTX-1) spiked into mice blood was made with good precision and recovery. The blood collected from mice exposed to a sublethal dose of Caribbean ciguatoxic extract (0.59 ng/g C-CTX-1 equivalents) was analyzed and found to contain detectable toxin levels at least 12 h post-exposure. Calculated concentration varied from 0.25 ng/ml at 30 min post-exposure to 0.12 ng/ml at 12 h. A dose response mice exposure revealed a linear dose-dependent increase of ciguatoxin activity in mice blood, with more polar ciguatoxin congeners contributing to 89% of the total toxicity. Finally, the toxin measurement in mice blood exposed to toxic extracts from the Indian Ocean or from the Pacific Ocean showed that the blood collection card method could be extended to each of the three known ciguatoxin families (C-CTX, I-CTX and P-CTX). The low matrix effect of extracted dried-blood samples (used at 1:10 or 1:20 dilution) and the high sensitivity of the neuroblastoma assay (limit of detection 0.006 ng/ml C-CTX-1), determined that the blood collection card method is suitable to monitor ciguatoxin at sublethal doses in mice and opens the potential to be a useful procedure for fish screening, environmental risk assessment or clinical diagnosis of ciguatera fish poisoning in humans or marine mammals. (c) 2005 Elsevier Ltd. All rights reserved. C1 NOAA, Natl Ocean Serv, Marine Biotoxins Program,Coastal Res Branch, Ctr Coastal Environm Hlth & Biomol Res, Charleston, SC 29412 USA. ARVAM, La Reunion, France. Inst Louis Malarde, Tox Microalgae Lab, Papeete, Tahiti, Fr Polynesia. US FDA, Gulf Coast Seafood Lab, Chem Hazards Res Unit, Dauphin Isl, AL USA. RP Ramsdell, JS (reprint author), NOAA, Natl Ocean Serv, Marine Biotoxins Program,Coastal Res Branch, Ctr Coastal Environm Hlth & Biomol Res, 219 Ft Johnson Rd, Charleston, SC 29412 USA. EM john.ramsdell@noaa.gov RI DARIUS, Helene/J-6163-2015 OI DARIUS, Helene/0000-0002-1184-7034 NR 66 TC 18 Z9 19 U1 1 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0041-0101 J9 TOXICON JI Toxicon PD SEP 1 PY 2005 VL 46 IS 3 BP 243 EP 251 DI 10.1016/j.toxicon.2005.03.014 PG 9 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 957XE UT WOS:000231405900001 ER PT J AU Dechraoui, MYB Tiedeken, JA Persad, R Wang, ZH Granade, HR Dickey, RW Ramsdell, JS AF Dechraoui, MYB Tiedeken, JA Persad, R Wang, ZH Granade, HR Dickey, RW Ramsdell, JS TI Use of two detection methods to discriminate ciguatoxins from brevetoxins: Application to great barracuda from Florida Keys SO TOXICON LA English DT Article DE ciguatera; ciguatoxins; brevetoxins; neurotoxic shellfish poisoning; barracuda; receptor binding assay; cytotoxicity assay ID SENSITIVE SODIUM-CHANNELS; JACK CARANX-LATUS; CARIBBEAN-CIGUATOXINS; CONFORMATIONAL-ANALYSIS; GYMNODINIUM-BREVE; RED TIDE; CIGUATERA; FISH; TOXINS; BLOOD AB In Florida (USA), numerous cases of human ciguatera fish poisoning, as well as neurotoxic shellfish poisoning following consumption of local seafood products, have been reported. By using in parallel, the sodium channel receptor binding assay (RBA), and the ouabain/veratridine-dependent cytotoxicity assay (N2A assay), we established criteria to identify, detect, and quantify ciguatoxins in fish extracts, with a brevetoxin as internal standard. Results showed that the Caribbean ciguatoxin C-CTX-1 exhibited an 8-fold higher potency in the RBA than brevetoxins and, a 440 and 2300-fold higher potency in the N2A assay than PbTx-1 and PbTx-3, respectively. Moreover, a sensitivity comparison between assays revealed that the N2A assay was more sensitive (12-fold) for ciguatoxin analysis, whereas the RBA was more sensitive (3-24-fold) for brevetoxins analysis. Based on the relative potency between toxins and the opposite sensitivity of both assays we have used the RBA and the N2A assay to screen great barracuda (Sphyraena barracuda) collected from the Florida Keys for ciguatoxins and brevetoxins. Fish extract analysis showed a sodium channel-dependent activity consistent with the presence of ciguatoxins, and not brevetoxins. Among 40 barracudas analyzed, 60% contained ciguatoxin levels in their liver measurable by the N2A assay with the most toxic fish containing 2.1 ppb C-CTX-1 equivalents. (c) 2005 Elsevier Ltd. All rights reserved. C1 NOAA, Natl Ocean Serv, Marine Biotoxins Program, Ctr Coastal Environm Hlth & Biomol Res, Charleston, SC 29412 USA. US FDA, Gulf Coast Seafood Lab, Chem Hazards Res Unit, Dauphin Isl, AL USA. RP Ramsdell, JS (reprint author), NOAA, Natl Ocean Serv, Marine Biotoxins Program, Ctr Coastal Environm Hlth & Biomol Res, Charleston, SC 29412 USA. EM john.ramsdell@noaa.gov NR 47 TC 45 Z9 49 U1 1 U2 15 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0041-0101 J9 TOXICON JI Toxicon PD SEP 1 PY 2005 VL 46 IS 3 BP 261 EP 270 DI 10.1016/j.toxicon.2005.04.006 PG 10 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 957XE UT WOS:000231405900003 PM 15982699 ER PT J AU Rios, M Stramer, SL Daniel, S Hewlett, IK AF Rios, M Stramer, SL Daniel, S Hewlett, IK TI West Nile virus adheres to human red blood cells (RBC) in whole blood SO TRANSFUSION LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Association-of-Blood-Banks CY OCT 15-18, 2005 CL Seattle, WA SP Amer Assoc Blood Banks C1 US FDA, Ctr Biol Evaluat & Res, DEETD, OBRR, Bethesda, MD USA. Amer Red Cross, Bethesda, MD USA. EM riosm@cber.fda.gov NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 2005 VL 45 IS 3 SU S BP 3A EP 3A PG 1 WC Hematology SC Hematology GA 963ME UT WOS:000231807600010 ER PT J AU Rios, M Daniel, S Stramer, SL Caglioti, S Wood, O Hewlett, IK AF Rios, M Daniel, S Stramer, SL Caglioti, S Wood, O Hewlett, IK TI West Nile virus NAT-positive human plasma containing WNV-IgM and IgG antibodies can infect Vero cells and human primary macrophages in culture SO TRANSFUSION LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Association-of-Blood-Banks CY OCT 15-18, 2005 CL Seattle, WA SP Amer Assoc Blood Banks C1 US FDA, Ctr Biol Evaluat & Res, DETTD, OBRR, Bethesda, MD USA. Amer Red Cross, Gaithersburg, MD USA. Blood Syst Labs, Tempe, AZ USA. EM riosm@cber.fda.gov NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 2005 VL 45 IS 3 SU S BP 3A EP 3A PG 1 WC Hematology SC Hematology GA 963ME UT WOS:000231807600009 ER PT J AU Grinev, A Daniel, S Stramer, SL Caglioti, S Hewlett, IK Rios, M AF Grinev, A Daniel, S Stramer, SL Caglioti, S Hewlett, IK Rios, M TI Genetic variability in West Nile virus (WNV) isolates from blood donors specimens from 2002, 2003 and 2004 USA epidemics SO TRANSFUSION LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Association-of-Blood-Banks CY OCT 15-18, 2005 CL Seattle, WA SP Amer Assoc Blood Banks C1 US FDA, Ctr Biol Evaluat & Res, DEETD, OBRR, Bethesda, MD 20014 USA. Amer Red Cross, Bethesda, MD USA. Blood Syst Labs, Tempe, AZ USA. EM riosm@cber.fda.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 2005 VL 45 IS 3 SU S BP 4A EP 4A PG 1 WC Hematology SC Hematology GA 963ME UT WOS:000231807600013 ER PT J AU Niu, MT Knippen, MA Simmons, LE Holness, LG AF Niu, MT Knippen, MA Simmons, LE Holness, LG TI Deaths due to transfusion-transmitted Klebsiella pneumoniae, 1995-2004 SO TRANSFUSION LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Association-of-Blood-Banks CY OCT 15-18, 2005 CL Seattle, WA SP Amer Assoc Blood Banks C1 US FDA, CBER, OBRR, DBA, Rockville, MD 20857 USA. US FDA, CBER, OCBQ, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 2005 VL 45 IS 3 SU S BP 50A EP 51A PG 2 WC Hematology SC Hematology GA 963ME UT WOS:000231807600171 ER PT J AU Holness, LG Knippen, MA Simmons, LE AF Holness, LG Knippen, MA Simmons, LE TI Characteristics of donors implicated in fatal transfusion related acute lung injury reactions SO TRANSFUSION LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Association-of-Blood-Banks CY OCT 15-18, 2005 CL Seattle, WA SP Amer Assoc Blood Banks C1 US FDA, CBER, Washington, DC 20204 USA. EM holness@cber.fda.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 2005 VL 45 IS 3 SU S BP 82A EP 82A PG 1 WC Hematology SC Hematology GA 963ME UT WOS:000231807600283 ER PT J AU Baleotti, W Rios, M Reid, ME Fabron, A Pellegrino, J Castilho, L AF Baleotti, W Rios, M Reid, ME Fabron, A Pellegrino, J Castilho, L TI Molecular studies of DO alleles in Brazilians reveal the presence of 898G mutation without HY1 SO TRANSFUSION LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Association-of-Blood-Banks CY OCT 15-18, 2005 CL Seattle, WA SP Amer Assoc Blood Banks C1 US FDA, Ctr Biol Evaluat & Res, DETTD, Bethesda, MD 20014 USA. New York Blood Ctr, New York, NY 10021 USA. UNICAMP, Hemocentro, Campinas, Brazil. Hemocentro, Marilia, Brazil. EM castilho@unicamp.br RI Baleotti, Wilson Jr/C-3558-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 2005 VL 45 IS 3 SU S BP 126A EP 127A PG 2 WC Hematology SC Hematology GA 963ME UT WOS:000231807600445 ER PT J AU Grinev, A Daniel, S Laassari, M Chumakov, K Hewlett, IK Rios, M AF Grinev, A Daniel, S Laassari, M Chumakov, K Hewlett, IK Rios, M TI Development and validation of a microarray-based assay that rapidly detects genetic variability in West Nile Virus specimens SO TRANSFUSION LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Association-of-Blood-Banks CY OCT 15-18, 2005 CL Seattle, WA SP Amer Assoc Blood Banks C1 US FDA, Ctr Biol Evaluat & Res, DEETD, OBRR, Bethesda, MD 20014 USA. US FDA, Ctr Biol Evaluat & Res, OVRR, Bethesda, MD 20014 USA. EM riosm@cber.fda.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 2005 VL 45 IS 3 SU S BP 148A EP 148A PG 1 WC Hematology SC Hematology GA 963ME UT WOS:000231807600520 ER PT J AU Meseda, CA Garcia, AD Kumar, A Mayer, AE Manischewitz, J King, LR Golding, H Merchlinsky, M Weir, JP AF Meseda, CA Garcia, AD Kumar, A Mayer, AE Manischewitz, J King, LR Golding, H Merchlinsky, M Weir, JP TI Enhanced immunogenicity and protective effect conferred by vaccination with combinations of modified vaccinia virus Ankara and licensed smallpox vaccine Dryvax in a mouse model SO VIROLOGY LA English DT Article DE modified vaccinia virus Ankara; Dryvax; vaccine immunogenicity; smallpox vaccination ID OUTER-MEMBRANE PROTEINS; DNA VACCINE; NONHUMAN-PRIMATES; STRAIN MVA; MICE; CHALLENGE; ANTIBODIES; BIOTERRORISM; IMMUNIZATION; PROPAGATION AB Significant adverse events are associated with vaccination with the currently licensed smallpox vaccine. Candidate new-generation smallpox vaccines such as the replication-defective modified vaccinia virus Ankara (MVA) produce very few adverse events in experimental animals and in limited human clinical trials conducted near the end of the smallpox eradication campaign. Efficacy evaluation of such new-generation vaccines will be extraordinarily complex, however, since the eradication of smallpox precludes a clinical efficacy trial and the correlates of protection against smallpox are unknown. A combination of relevant animal efficacy studies along with thorough comparative immunogenicity studies between traditional and new-generation smallpox vaccines will be necessary for vaccine licensure. In the present study, a variety of immune responses elicited by MVA and the licensed smallpox vaccine Dryvax in a murine model were compared, with a focus on mimicking conditions and strategies likely to be employed in human vaccine trials. Immunization of mice with MVA, using several relevant vaccination routes including needle-free delivery, elicited Immoral and cellular immune responses qualitatively similar to those elicited by vaccination with Dryvax. Similar levels of vaccinia-specific IgG and neutralizing antibody were elicited by Dryvax and MVA when higher doses (approximately I log) of MVA were used for immunization. Antibody levels peaked at about 6 weeks post-immunization and remained stable for at least 15 weeks. A booster immunization of either MVA or Dryvax following an initial priming immunization with NIVA resulted in an enhanced IgG titer and neutralizing antibody response. In addition, both Dryvax and various MVA vaccination protocols elicited antibody responses to the extracellular enveloped form of the virus and afforded protection against a lethal intranasal challenge with vaccinia virus WR. Published by Elsevier Inc. C1 US FDA, Lab DNA Viruses, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. US FDA, Lab Retrovirus Res, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Weir, JP (reprint author), US FDA, Lab DNA Viruses, Div Viral Prod, Ctr Biol Evaluat & Res, HFM 457,1401 Rockville Pike, Bethesda, MD 20892 USA. EM weirj@cber.fda.gov NR 39 TC 55 Z9 56 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD SEP 1 PY 2005 VL 339 IS 2 BP 164 EP 175 DI 10.1016/j.virol.2005.06.002 PG 12 WC Virology SC Virology GA 960ZO UT WOS:000231631900003 PM 15993917 ER PT J AU de Jager, LS Perfetti, GA Diachenko, GW AF de Jager, LS Perfetti, GA Diachenko, GW TI APCI-LCMS method for the detection of Ginkgo biloba marker compounds in teas and beverages SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 230th National Meeting of the American-Chemical-Society CY AUG 28-SEP 01, 2005 CL Washington, DC C1 US FDA, Ctr Food Safety & Appl Nutr, Off Food Addit Safety, College Pk, MD 20785 USA. EM ldejager@cfsan.fda.gov 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 28 PY 2005 VL 230 MA 106-AGFD BP U55 EP U56 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 032TJ UT WOS:000236797300106 ER PT J AU DiNovi, MJ Doell, DL Edwards, AJ Mihalov, JJ AF DiNovi, MJ Doell, DL Edwards, AJ Mihalov, JJ TI Estimating intake of flavors: Is there a "better" method? SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 230th National Meeting of the American-Chemical-Society CY AUG 28-SEP 01, 2005 CL Washington, DC C1 US FDA, Ctr Food Safety & Appl Nutr, Div Biotechnol & GRAS Notice Review, Rockville, MD 20857 USA. US FDA, Ctr Food Safety & Appl Nutr, Div Petit Review, Rockville, MD 20857 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 28 PY 2005 VL 230 MA 89-AGFD BP U47 EP U47 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 032TJ UT WOS:000236797300089 ER PT J AU Fu, PKL Liu, Y Yin, JJ Turro, C AF Fu, PKL Liu, Y Yin, JJ Turro, C TI Mechanistic studies on the photosensitizing activities of 2,3 diaminophenazine, a common contaminant in hair dyes SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 230th National Meeting of the American-Chemical-Society CY AUG 28-SEP 01, 2005 CL Washington, DC C1 US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. Ohio State Univ, Dept Chem, Columbus, OH 43210 USA. EM patty.fu@fda.gov RI Yin, Jun Jie /E-5619-2014; Turro, Claudia/H-5335-2015 OI Turro, Claudia/0000-0003-3202-5870 NR 0 TC 0 Z9 0 U1 0 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 28 PY 2005 VL 230 MA 79-TOXI BP U1869 EP U1869 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 032TJ UT WOS:000236797303746 ER PT J AU Glaser, ZR AF Glaser, ZR TI Some considerations dealt with by the speaker while with the center for devices and radiological health (CDRH), FDA SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 230th National Meeting of the American-Chemical-Society CY AUG 28-SEP 01, 2005 CL Washington, DC C1 Johns Hopkins Univ, FDA, Rockville, MD 20853 USA. EM z.glaser@juno.com 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 28 PY 2005 VL 230 MA 455-ANYL BP U393 EP U393 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 032TJ UT WOS:000236797300768 ER PT J AU Heiserman, WM Alam, MR Begley, TH Limm, W Walker, RA AF Heiserman, WM Alam, MR Begley, TH Limm, W Walker, RA TI Properties and 2-D organization of common polymer antioxidant additives SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 230th National Meeting of the American-Chemical-Society CY AUG 28-SEP 01, 2005 CL Washington, DC C1 Univ Maryland, Dept Chem, College Pk, MD 20742 USA. US FDA, Ctr Food Safety & Appl Nutr, Rockville, MD USA. US FDA, Div Chem Res & Environm Review, Rockville, MD USA. EM wendyh@umd.edu RI wenjian, wu/G-7517-2011 NR 0 TC 0 Z9 0 U1 1 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 28 PY 2005 VL 230 MA 191-COLL BP U1129 EP U1129 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 032TJ UT WOS:000236797302271 ER PT J AU Hepp, N AF Hepp, N TI Identification of elements in tattoo inks by X-ray fluorescence spectrometry SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 230th National Meeting of the American-Chemical-Society CY AUG 28-SEP 01, 2005 CL Washington, DC C1 US FDA, Off Colors & Cosmet, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. EM NHepp@cfsan.fda.gov NR 0 TC 0 Z9 0 U1 1 U2 5 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 28 PY 2005 VL 230 MA 145-ANYL BP U244 EP U245 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 032TJ UT WOS:000236797300468 ER PT J AU Icenogle, TB Regnault, WF Antonucci, JM Skrtic, D AF Icenogle, TB Regnault, WF Antonucci, JM Skrtic, D TI Physical and chemical characterization of bioactive polymer composites SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 230th National Meeting of the American-Chemical-Society CY AUG 28-SEP 01, 2005 CL Washington, DC C1 Food & Drug Adm, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. NIST, Div Polymers, Gaithersburg, MD 20899 USA. NIST, Amer Dent Assoc Hlth Fdn, Paffenbarger Res Ctr, Gaithersburg, MD 20899 USA. EM tbi@cdrh.fda.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 28 PY 2005 VL 230 MA 346-POLY BP U4159 EP U4159 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 032TJ UT WOS:000236797308343 ER PT J AU Kim, H Troxell, TC AF Kim, H Troxell, TC TI FDA strategy for perchlorate in food SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 230th National Meeting of the American-Chemical-Society CY AUG 28-SEP 01, 2005 CL Washington, DC C1 US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. EM henry.kim@cfsan.fda.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 28 PY 2005 VL 230 MA 85-ENVR BP U1541 EP U1541 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 032TJ UT WOS:000236797303085 ER PT J AU Klauda, JB Pastor, RW Kucerka, N Brooks, BR AF Klauda, JB Pastor, RW Kucerka, N Brooks, BR TI Refining the structure of lipid bilayers with insight from molecular dynamics simulations SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 230th National Meeting of the American-Chemical-Society CY AUG 28-SEP 01, 2005 CL Washington, DC C1 NHLBI, Lab Computat Biol, NIH, Bethesda, MD 20892 USA. US FDA, Biophys Lab, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. Carnegie Mellon Univ, Dept Phys, Pittsburgh, PA 15213 USA. Carnegie Mellon Univ, Dept Biol Sci, Pittsburgh, PA 15213 USA. EM klauda@helix.nih.gov RI Klauda, Jeffery/A-4345-2008 NR 0 TC 0 Z9 0 U1 1 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 28 PY 2005 VL 230 MA 296-COMP BP U1391 EP U1391 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 032TJ UT WOS:000236797302805 ER PT J AU Krynitsky, AJ Niemann, RA Hopper, ML Williams, AD AF Krynitsky, AJ Niemann, RA Hopper, ML Williams, AD TI Rapid determination of perchlorate anion in foods by ion chromatography-tandem mass spectrometry SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 230th National Meeting of the American-Chemical-Society CY AUG 28-SEP 01, 2005 CL Washington, DC C1 US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. US FDA, Total Diet Pesticide Res Ctr, College Pk, MD 20740 USA. US FDA, SE Reg Lab, College Pk, MD 20740 USA. EM Alex.Krynitsky@cfsan.fda.gov NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 28 PY 2005 VL 230 MA 211-ENVR BP U1604 EP U1604 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 032TJ UT WOS:000236797303211 ER PT J AU Lague, P Pastor, RW AF Lague, P Pastor, RW TI Molecular dynamics simulations of the influenza hemagglutinin fusion peptide in micelles and bilayers: A structural investigation SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 230th National Meeting of the American-Chemical-Society CY AUG 28-SEP 01, 2005 CL Washington, DC C1 Univ Laval, Dept Biochem, Ste Foy, PQ G1K 7P4, Canada. Cornell Univ, Weill Med Coll, Dept Biochem, Ithaca, NY 14853 USA. US FDA, Biophys Lab, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. EM Patrick.Lague@rsvs.ulaval.ca 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 28 PY 2005 VL 230 MA 85-BIOL BP U542 EP U542 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 032TJ UT WOS:000236797301084 ER PT J AU Mai, H Brodie, DL Meyers, MB Baldo, AL Krantz, Z Andrzejewski, D Weisz, A AF Mai, H Brodie, DL Meyers, MB Baldo, AL Krantz, Z Andrzejewski, D Weisz, A TI High-performance liquid chromatographic method for the determination of triiodoresorcinol and other side reaction products and intermediates in the color additive FD&C Red No. 3 (Erythrosine) SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 230th National Meeting of the American-Chemical-Society CY AUG 28-SEP 01, 2005 CL Washington, DC C1 US FDA, Off Cosmet & Colors, College Pk, MD 20740 USA. US FDA, Instrumentat & Biophys Branch, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. EM hmai@cfsan.fda.gov; aweisz@cfsan.fda.gov NR 0 TC 0 Z9 0 U1 0 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 28 PY 2005 VL 230 MA 228-ANYL BP U285 EP U286 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 032TJ UT WOS:000236797300549 ER PT J AU Musser, SM AF Musser, SM TI Development of quantitative LC/MS methods for food safety applications SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 230th National Meeting of the American-Chemical-Society CY AUG 28-SEP 01, 2005 CL Washington, DC C1 US FDA, Instrumentat & Biophys Branch, College Pk, MD 20740 USA. EM Steven.Musser@fda.hhs.org 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 28 PY 2005 VL 230 MA 453-ANYL BP U392 EP U392 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 032TJ UT WOS:000236797300766 ER PT J AU Niemann, RA Krynitsky, AJ AF Niemann, RA Krynitsky, AJ TI Ion chromatographic analysis of food for perchlorate by suppressed conductivity compared to tandem mass spectrometry SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 230th National Meeting of the American-Chemical-Society CY AUG 28-SEP 01, 2005 CL Washington, DC C1 US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. EM rniemann@cfsan.fda.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 28 PY 2005 VL 230 MA 212-ENVR BP U1604 EP U1605 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 032TJ UT WOS:000236797303212 ER PT J AU Nyman, PJ Morehouse, KM McNeal, TP Diachenko, GW AF Nyman, PJ Morehouse, KM McNeal, TP Diachenko, GW TI Determination of furan in foods SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 230th National Meeting of the American-Chemical-Society CY AUG 28-SEP 01, 2005 CL Washington, DC C1 US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. EM pjn@cfsan.fda.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 28 PY 2005 VL 230 MA 97-AGFD BP U51 EP U51 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 032TJ UT WOS:000236797300097 ER PT J AU Parry, JW Moore, J Zhou, KQ Yin, JJ Wang, JY Yu, LL AF Parry, John W. Moore, Jeffrey Zhou, Kequan Yin, Jun-Jie Wang, Jian-Ying Yu, Liangli TI Potential of wheat antioxidants in disease prevention and health promotion SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 230th National Meeting of the American-Chemical-Society CY AUG 28-SEP 01, 2005 CL Washington, DC SP Amer Chem Soc C1 Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA. US FDA, Ctr Food Safety & Appl Nutr, Rockville, MD 20857 USA. Univ Maryland, Sch Med, Dept Surg & Pathol, Baltimore, MD 21201 USA. EM ly5@umail.umd.edu RI Yin, Jun Jie /E-5619-2014 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 28 PY 2005 VL 230 MA 28-AGFD BP U16 EP U17 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 032TJ UT WOS:000236797300029 ER PT J AU Petigara, BR AF Petigara, BR TI Isolation and identification of Sudan I-IV in Worcestershire sauce and chili powder SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 230th National Meeting of the American-Chemical-Society CY AUG 28-SEP 01, 2005 CL Washington, DC C1 US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. US FDA, Off Cosmet & Colours, College Pk, MD 20740 USA. EM BPetigara@cfsan.fda.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 28 PY 2005 VL 230 MA 222-ANYL BP U282 EP U282 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 032TJ UT WOS:000236797300543 ER PT J AU Petigara, BR AF Petigara, BR TI Separation and identification of pigments found in permanent cosmetic/tattoo inks using reversed-phase high performance liquid chromatography and photodiode array detection SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 230th National Meeting of the American-Chemical-Society CY AUG 28-SEP 01, 2005 CL Washington, DC C1 US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. EM BPetigara@cfsan.fda.gov NR 0 TC 0 Z9 0 U1 0 U2 4 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 28 PY 2005 VL 230 MA 221-ANYL BP U281 EP U282 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 032TJ UT WOS:000236797300542 ER PT J AU Wamer, W Fu, PP Falvey, DE AF Wamer, W Fu, PP Falvey, DE TI Hotocytotoxicity of retinol and the role of photooxidative damage SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 230th National Meeting of the American-Chemical-Society CY AUG 28-SEP 01, 2005 CL Washington, DC C1 Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. Univ Maryland, Dept Chem, College Pk, MD 20742 USA. EM wwamer@cfsan.fda.gov RI Falvey, Daniel/B-7817-2009 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 28 PY 2005 VL 230 MA 80-TOXI BP U1869 EP U1870 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 032TJ UT WOS:000236797303747 ER PT J AU Wang, HL AF Wang, HL TI Analysis of protective antigen in final product of human anthrax vaccine SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 230th National Meeting of the American-Chemical-Society CY AUG 28-SEP 01, 2005 CL Washington, DC C1 US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 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 28 PY 2005 VL 230 MA 157-ANYL BP U250 EP U250 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 032TJ UT WOS:000236797300480 ER PT J AU Warner, CR Noonan, GO Hsu, WC Perfetti, GA Begley, TH Diachenko, GW AF Warner, CR Noonan, GO Hsu, WC Perfetti, GA Begley, TH Diachenko, GW TI Investigation of flour tortillas implicated in episodes of illnesses associated with school lunches SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 230th National Meeting of the American-Chemical-Society CY AUG 28-SEP 01, 2005 CL Washington, DC C1 US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. Univ Maryland, Joint Inst Food Safety & Appl Nutr Intern, College Pk, MD 20742 USA. EM Charles.Wamer@cfsan.fda.gov NR 0 TC 0 Z9 0 U1 0 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 28 PY 2005 VL 230 MA 84-AGFD BP U44 EP U45 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 032TJ UT WOS:000236797300084 ER PT J AU Klauda, JB Pastor, RW Brooks, BR AF Klauda, JB Pastor, RW Brooks, BR TI Adjacent gauche stabilization in linear alkanes: Implications for polymer models and conformational analysis SO JOURNAL OF PHYSICAL CHEMISTRY B LA English DT Letter ID MOLECULAR SIMULATIONS; AB-INITIO; ENERGIES AB High-level ab initio quantum mechanical calculations are used to study various gauche conformational energies of n-pentane to n-decane. The destabilizing "pentane effect" (adjacent gauche states of opposite sign) for alkanes is confirmed, but the energies were found to depend slightly on chain length. In contrast, introducing an adjacent gauche of the same sign requires only 0.22-0.37 kcal/mol, approximately half of the single gauche state energy. This adjacent gauche stabilization should be taken into account when formulating or analyzing rotational isomeric models, carrying out conformational analysis, and developing force fields for alkanes, lipids, and related polymers. C1 NHLBI, Lab Computat Biol, NIH, Bethesda, MD 20892 USA. US FDA, Biophys Lab, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Klauda, JB (reprint author), NHLBI, Lab Computat Biol, NIH, Bldg 10, Bethesda, MD 20892 USA. EM klauda@helix.nih.gov RI Klauda, Jeffery/A-4345-2008 FU NHLBI NIH HHS [Z01 HL001051-08] NR 13 TC 42 Z9 43 U1 1 U2 11 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1520-6106 J9 J PHYS CHEM B JI J. Phys. Chem. B PD AUG 25 PY 2005 VL 109 IS 33 BP 15684 EP 15686 DI 10.1021/jp0527608 PG 3 WC Chemistry, Physical SC Chemistry GA 958DX UT WOS:000231426000005 PM 16852989 ER PT J AU Collins, JM AF Collins, JM TI Imaging and other biomarkers in early clinical studies: One step at a time or re-engineering drug development? SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material C1 US FDA, Lab Clin Pharmacol, Rockville, MD 20857 USA. RP Collins, JM (reprint author), US FDA, Lab Clin Pharmacol, Rockville, MD 20857 USA. NR 8 TC 19 Z9 21 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD AUG 20 PY 2005 VL 23 IS 24 BP 5417 EP 5419 DI 10.1200/JCO.2005.05.907 PG 3 WC Oncology SC Oncology GA 957LQ UT WOS:000231371700001 PM 16027435 ER PT J AU Golding, H Khurana, S Yarovinsky, F King, LR Abdoulaeva, G Antonsson, L Owman, C Platt, EJ Kabat, D Andersen, JF Sher, A AF Golding, H Khurana, S Yarovinsky, F King, LR Abdoulaeva, G Antonsson, L Owman, C Platt, EJ Kabat, D Andersen, JF Sher, A TI CCR5 N-terminal region plays a critical role in HIV-1 inhibition by Toxoplasma gondii-derived cyclophilin-18 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; ENVELOPE GLYCOPROTEIN; AMINO-TERMINUS; GASTROINTESTINAL-TRACT; CHEMOKINE RECEPTORS; ENTRY INHIBITORS; GP120 BINDING; CELL-LINE; INFECTION; DOMAIN AB Molecular mimicry of chemokine ligands has been described for several pathogens. Toxoplasma gondii produces a protein, cyclophilin-18 (C-18), which binds to the human immunodeficiency virus (HIV) co-receptor CCR5 and inhibits fusion and infection of T cells and macrophages by R5 viruses but not by X4 viruses. We recently identified structural determinants of C-18 required for anti-HIV activity (Yarovinsky, F., Andersen, J. F., King, L. R., Caspar, P., Aliberti, J., Golding, H., and Sher, A. ( 2004) J. Biol. Chem. 279, 53635 - 53642). Here we have elucidated the fine specificity of CCR5 residues involved in binding and HIV inhibitory potential of C-18. To delineate the regions of CCR5 involved in C-18 binding, we analyzed C-18 inhibition of cells expressing CXCR4/CCR5 chimeric receptors and CCR5 with a truncated N terminus (Delta 2-19). These experiments identified a critical role for the N terminus of CCR5 in C-18 binding and anti-HIV activity. Studies with a large panel of CCR5 N-terminal peptides, including Tyr-sulfated analogues, truncated peptides, and alanine-scanning mutants, suggested that each of the 12 - 17 amino acids in the N terminus of CCR5 are essential for C-18 binding and inhibitory activity. Tyr sulfation did not improve C-18 reactivity. This finding is of interest because the same CCR5 N-terminal region was shown previously to play a key role in binding of HIV-1 envelope glycoproteins. The elucidation of the functional C-18-binding mechanism may help in the rational design of novel antiviral agents against HIV. C1 US FDA, Div Viral Prodat & Res, Bethesda, MD 20892 USA. US FDA, Core Facil, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. Div Mol Neurobiol, SE-22184 Lund, Sweden. Oregon Hlth Sci Univ, Portland, OR 97239 USA. RP Golding, H (reprint author), US FDA, Div Viral Prodat & Res, Bethesda, MD 20892 USA. EM goldingh@cber.FDA.gov NR 40 TC 7 Z9 8 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 19 PY 2005 VL 280 IS 33 BP 29570 EP 29577 DI 10.1074/jbc.M500236200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 954SX UT WOS:000231176200024 PM 15975927 ER PT J AU Calvert, RJ Kammouni, W Kikawa, KD AF Calvert, RJ Kammouni, W Kikawa, KD TI Optimization of a nonradioactive method for consistent and sensitive determination of activated K-ras protein SO ANALYTICAL BIOCHEMISTRY LA English DT Article DE K-ras; lung; activity assay ID ESCHERICHIA-COLI; HEAT-SHOCK; EXPRESSION; CELLS; PURIFICATION; MOUSE; LUNG; REDUCTASE; PATHWAY; CLONING AB Accurate measurement of activity of wild-type K-ras protein is important due to its tumor suppressor action in tissues such as lung. A published method by Taylor and co-workers uses plasmid-containing Escherichia coli cells to produce a glutathione-S-transferase/raf-1 ras binding domain (GST-RBD) fusion protein attached to glutathione beads to isolate activated ras protein. We systematically optimized the method before use on lung tissues. Changing the GST-RBD protein induction temperature from the original 37 to 30 degrees C produced a consistently greater yield of fusion protein. To improve stability of the GST-RBD beads so as to perform large-scale experiments, 0.1% NaN3 was added. NaN3-treated beads retained full affinity for at least 24 days. Sensitivity was improved by using a polyvinylidene difluoride membrane rather than nitrocellulose for immunoblotting. We also compared our GST-RBD beads with two commercial assay kits and found that our beads had both superior sensitivity and reduced variability. In summary, our modification of the GST-RBD affinity method to recover activated K-ras greatly increased the yield of fusion protein, prolonged the useful life of GST-RBD beads to at least 24 days, and enhanced detection sensitivity. Published by Elsevier Inc. C1 US FDA, Off Nutr Prod Labeling & Dietary Supplements, Div Res & Appl Technol, College Pk, MD 20740 USA. NCI, Comparat Carcinogenesis Lab, Frederick, MD 21702 USA. RP Calvert, RJ (reprint author), US FDA, Off Nutr Prod Labeling & Dietary Supplements, Div Res & Appl Technol, College Pk, MD 20740 USA. EM calvert@mail.ncifcrf.gov NR 26 TC 3 Z9 3 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 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD AUG 15 PY 2005 VL 343 IS 2 BP 283 EP 292 DI 10.1016/j.ab.2005.06.008 PG 10 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 954OH UT WOS:000231163900012 PM 16018961 ER PT J AU Koblinski, JE Kaplan-Singer, BR VanOsdol, SJ Wu, M Engbring, JA Wang, SL Goldsmith, CM Piper, JT Vostal, JG Harms, JF Welch, DR Kleinman, HK AF Koblinski, JE Kaplan-Singer, BR VanOsdol, SJ Wu, M Engbring, JA Wang, SL Goldsmith, CM Piper, JT Vostal, JG Harms, JF Welch, DR Kleinman, HK TI Endogenous osteonectin/SPARC/BM-40 expression inhibits MDA-MB-231 breast cancer cell metastasis SO CANCER RESEARCH LA English DT Article ID EXTRACELLULAR-MATRIX PROTEIN; HUMAN-MELANOMA CELLS; SPARC-NULL MICE; GENE-EXPRESSION; ENHANCED GROWTH; BONE METASTASIS; TUMOR-GROWTH; IN-VIVO; OSTEONECTIN; PLATELET AB Skeletal metastases occur with high incidence in patients with breast cancer and cause long-term skeletal morbidity. Osteonectin (SPARC, BM-40) is a bone matrix factor that is an in vitro chemoattractant for breast and prostate cancer cells. Increased expression of osteonectin is found in malignant breast tumors. We infected MDA-231 breast cancer cells with an adenovirus expressing osteonectin to examine the role of osteonectin expression in breast cancer cells and its effect on metastasis, in particular to bone. Expression of osteonectin did not affect MDA-231 cell proliferation, apoptosis, migration, cell aggregation, or protease cleavage of collagen IV. However, in vitro invasion of these osteonectin-infected cells through Matrigel and colony formation on Matrigel was decreased. Interestingly, high osteonectin expression in MDA-231 cells inhibited metastasis in a dose-dependent manner to many different organs including bone. The reduction in metastasis may be due to decreased platelet-tumor cell aggregation, because exogenous osteonectin inhibited platelet aggregation in vitro and the high osteonectin expression in MDA-231 cells reduced tumor cell-induced thrombocytopenia in vivo compared with control-infected cells. These studies suggest that high endogenous expression of osteonectin in breast cancer cells may reduce metastasis via reduced invasive activity and reduced tumor cell-platelet aggregation. C1 Natl Inst Dent & Craniofacial Res, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD 20892 USA. Natl Inst Dent & Craniofacial Res, Genet Therapy & Therapeut Branch, NIH, Bethesda, MD 20892 USA. Capital Univ Med Sci, Fac Stomatol, Beijing, Peoples R China. US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. Penn State Univ, Coll Med, Jake Gittlen Canc Res Inst, Hershey, PA USA. Univ Alabama, Dept Pathol, Ctr Comprehens Canc, Birmingham, AL 35294 USA. RP Kleinman, HK (reprint author), Natl Inst Dent & Craniofacial Res, Craniofacial Dev Biol & Regenerat Branch, NIH, Room 433,Bldg 30,30 Convent Dr, Bethesda, MD 20892 USA. EM hkleinma@mail.nih.gov RI Welch, Danny/B-7310-2009; OI Welch, Danny/0000-0002-1951-4947; Wu, Michael C./0000-0002-3357-6570 FU NCI NIH HHS [CA-91572, CA87728] NR 56 TC 74 Z9 75 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD AUG 15 PY 2005 VL 65 IS 16 BP 7370 EP 7377 DI 10.1158/0008-5472.CAN-05-0807 PG 8 WC Oncology SC Oncology GA 954XK UT WOS:000231188600044 PM 16103089 ER PT J AU Mann, BS Johnson, JR Kelly, R Sridhara, R Williams, G Pazdur, R AF Mann, BS Johnson, JR Kelly, R Sridhara, R Williams, G Pazdur, R TI Letrozole in the extended adjuvant treatment of postmenopausal women with history of early-stage breast cancer who have completed 5 years of adjuvant tamoxifen SO CLINICAL CANCER RESEARCH LA English DT Article ID ONCOLOGY TECHNOLOGY-ASSESSMENT; RANDOMIZED-TRIAL; AROMATASE INHIBITORS; AMERICAN-SOCIETY; DRUG-THERAPY; COMBINATION; EXEMESTANE AB Purpose: To present the basis of the decision of the Food and Drug Administration to grant accelerated approval for letrozole for extended adjuvant treatment of early-stage breast cancer in postmenopausal women after completion of adjuvant tamoxifen. Experimental Design: The Food and Drug Administration reviewed the data from the MA17 trial, a single, multinational, randomized, double-blind, and placebo -controlled trial, submitted by the applicant to support the proposed new indication. Results: MA17 consisted of a core study and Lipid and Bone Mineral Density safety substudies. It enrolled 5,1187 patients. In the core study, median treatment duration was 24 months and median follow-up duration was 27.4 months. Using a conventional definition of disease-free survival, 122 events on letrozole and 193 events on placebo were observed (hazard ratio, 0.62; 95% confidence interval, 0.49-0,78; P = 0.00003). Distant disease-free survival also improved with letrozole, 55 versus 92 events (hazard ratio, 0.61; 95% confidence interval, 0.44-0.84; P = 0.003). No statistically significant improvement in overall survival was observed. Hot flushes, arthralgia/arthritis, myalgia, and new diagnosis of osteoporosis were more common on letrozole. Frequency of fractures and cardiovascular ischemic events was not significantly different. A statistically significant mean decrease in bone mineral density in the hip occurred at 24 months on letrozole. Conclusions: Letrozole administration led to a statistically significant prolongation in disease-free survival. Fractures and cardiovascular events were similar to placebo; however, new diagnoses of osteoporosis were more frequent. Short duration of treatment and follow-up precluded assessment of long-term safety and efficacy. Thus, accelerated approval was granted instead of regular approval. C1 US FDA, Div Oncol Drug Prod, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Mann, BS (reprint author), US FDA, Div Oncol Drug Prod, Ctr Drug Evaluat & Res, HFD-150,5600 Fishers Lane, Rockville, MD 20857 USA. EM mannb@cder.fda.gov NR 19 TC 22 Z9 24 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD AUG 15 PY 2005 VL 11 IS 16 BP 5671 EP 5677 DI 10.1158/1078-0432.CCR-05-0354 PG 7 WC Oncology SC Oncology GA 956SL UT WOS:000231320000005 PM 16115902 ER PT J AU Gulmann, C Espina, V Petricoin, E Longo, DL Santi, M Knutsen, T Raffeld, M Jaffe, ES Liotta, LA Feldman, AL AF Gulmann, C Espina, V Petricoin, E Longo, DL Santi, M Knutsen, T Raffeld, M Jaffe, ES Liotta, LA Feldman, AL TI Proteomic analysis of apoptotic pathways reveals prognostic factors in follicular lymphoma SO CLINICAL CANCER RESEARCH LA English DT Article ID NON-HODGKINS-LYMPHOMA; LASER CAPTURE MICRODISSECTION; PHASE PROTEIN MICROARRAYS; BCL-2 FAMILY-MEMBERS; B-CELL LYMPHOMA; EXPRESSION PATTERNS; PROSTATE-CANCER; OVARIAN-CANCER; SURVIVAL; PHOSPHORYLATION AB Follicular lymphoma (FL) is the second most common non-Hodgkin's lymphoma and generally is incurable. Reliable prognostic markers to differentiate patients who progress rapidly from those who survive for years with indolent disease have not been established. Most cases overexpress Bcl-2, but the pathogenesis of FL remains incompletely understood. To determine whether a proteomic approach could help overcome these obstacles, we procured lymphoid follicles from 20 cases of FL and 15 cases of benign follicular hyperplasia (FH) using laser capture microdissection. Lysates were spotted on reverse-phase protein microarrays and probed with 21 antibodies to proteins in the intrinsic apoptotic pathway, including those specific for posttranslational modifications such as phosphorylation. A panel of three antibodies [phospho-Akt(Ser473), Bcl-2, and cleaved poly (ADP-ribose) polymerase] segregated most cases of FL from FH. Phospho-Akt(Ser473) and Bcl-2 were significantly increased in FL (P=0.001 and P<0.0001, respectively). Additionally, the Bcl-2/Bak ratio completely segregated FL from FH, High ratios of Bcl-2/Bak and Bcl-2/Bax were associated with early death from disease with differences in median survival times of 7.3 years (P=0.0085) and 3.8 years (P=0.018), respectively. Using protein microarrays, we identified candidate proteins that may signify clinically relevant molecular events in FL. This approach showed significant changes at the posttranslational level, including Akt phosphorylation, and suggested new prognostic markers, including the Bcl-2/Bak and Bcl-2/Bax ratios. Proteomic end points should be incorporated in larger, multicenter trials to validate the clinical utility of these protein microarray findings. C1 NCI, Pathol Lab, Food & Drug Adm, Clin Proteom Program, Bethesda, MD 20892 USA. NCI, Genet Branch, Bethesda, MD 20892 USA. US FDA, Tissue Proteom Unit, Div Therapeut Prot, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. NIA, Baltimore, MD 21224 USA. Childrens Natl Med Ctr, Dept Pathol, Washington, DC 20010 USA. RP Feldman, AL (reprint author), NCI, Pathol Lab, Food & Drug Adm, Clin Proteom Program, Room 2A33,Bldg 10,10 Ctr Dr, Bethesda, MD 20892 USA. EM feldmana@mail.nih.gov RI Feldman, Andrew/D-5028-2012; OI Espina, Virginia/0000-0001-5080-5972 NR 50 TC 77 Z9 81 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD AUG 15 PY 2005 VL 11 IS 16 BP 5847 EP 5855 DI 10.1158/1078-0432.CCR-05-0637 PG 9 WC Oncology SC Oncology GA 956SL UT WOS:000231320000028 PM 16115925 ER PT J AU Zubkova, I Mostowski, H Zaitseva, M AF Zubkova, I Mostowski, H Zaitseva, M TI Up-regulation of IL-7, stromal-derived factor-1 alpha, thymus-expressed chemokine, and secondary lymphoid tissue chemokine gene expression in the stromal cells in response to thymocyte depletion: Implication for thymus reconstitution SO JOURNAL OF IMMUNOLOGY LA English DT Article ID T-CELL; DENDRITIC CELLS; ANTIRETROVIRAL THERAPY; IMMUNE RECONSTITUTION; STIMULATING FACTOR; EPITHELIAL-CELLS; HUMAN ADULT; ALPHA-BETA; GM-CSF; MICE AB Three in vivo adult mouse models were established to study which signals are required to restore the postnatal thymus. Single administration of dexamethasone, estradiol, or exposure to sublethal dose of gamma irradiation served as prototype thymus-ablating therapies. In all models, transient thymic atrophy was manifested due to the loss of the predominant portion of CD4(-)CD8(-) double negative and CD4(+)CD8(+) double positive thymocytes and was followed by a complete regeneration of the thymuses. Acute atrophy/regeneration was observed in the dexamethasone and irradiation models; in the estradiol-treated animals, slow kinetics of atrophy and regeneration was observed. Importantly, in both acute and chronic models, high levels of IL-7 mRNA were detected in the thymuses isolated from mice during maximum atrophy. In addition, chemokine gene array analysis of involuted thymuses revealed high levels of mRNA expression of stromal-derived factor-1 alpha (SDF-1 alpha), thymus-expressed chemokine (TECK), and secondary lymphoid tissue chemokine (SLC) but not of other chemokines. The levels of IL-7, SDF-1 alpha, TECK, and SLC mRNA inversely correlated with the kinetics of regeneration. RT-PCR analysis of stromal cells purified from involuted thymuses confirmed increased IL-7, SDF-1 alpha, and SLC gene expression in MHC class II(+)CD45(-) epithelia] cells and increased IL-7 and TECK gene expression in class II(+)CD45(+)CD11c(+) dendritic cells. Thus, our data showed for the first time that expression of IL-7, SDF-1 alpha, TECK, and SLC mRNA is induced in the thymic stroma during T cell depletion and may play an important role in the reconstitution of the adult thymus. C1 US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. US FDA, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Bldg 29B,4NN06,8800 Rockville Pike, Bethesda, MD 20892 USA. EM zaitseva@cber.fda.gov NR 68 TC 44 Z9 45 U1 0 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD AUG 15 PY 2005 VL 175 IS 4 BP 2321 EP 2330 PG 10 WC Immunology SC Immunology GA 966HJ UT WOS:000232010400039 PM 16081802 ER PT J AU Reepmeyer, JC Brower, JF Ye, HP AF Reepmeyer, JC Brower, JF Ye, HP TI Separation and detection of the isomeric equine conjugated estrogens, equilin sulfate and Delta(8,9)-dehydroestrone sulfate, by liquid chromatography-electrospray-mass spectrometry using carbon-coated zirconia and porous graphitic carbon stationary phases SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article DE conjugated estrogens; equilin sulfate; dehydroestrone sulfate; porous graphitic carbon; carbon coated zircona; Zr-CARB ID SILVER-ION CHROMATOGRAPHY; CAROTENOID ISOMERS; ACID ISOMERS; FATTY-ACIDS; SELECTIVITY; STEROLS; RETINOL; URINE; HPLC AB Equilin-3-sulfate and Delta(8.9)-dehydroestrone-3-sulfate are two isomers found in equine conjugated estrogens that differ in structure only were not resolved on a C-18 column during the analysis of by the position of a double bond in the steroid B-ring. These geometric isomers conjugated estrogen drug products by LC-MS using acetonitrile-ammonium acetate buffer as the mobile phase. While no separations of these two isomers were observed on C-18 or other alkyl-bonded silica based phases using a variety of mobile phase conditions, partial separations were achieved on phenyl bonded silica phases with a resolution of 1.5 on a diphenyl phase, and baseline separations were readily achieved on two carbonaceous phases with resolutions routinely exceeding three on graphitic carbon-coated zirconia (Zr-CARB) and resolutions as high as 19 on porous graphitic carbon (Hypercarb). An examination of a selected few conjugated estrogens in the complex drug substance by LC-MS on Hypercarb is presented. Published by Elsevier B.V. C1 US FDA, Div Pharmaceut Anal, St Louis, MO 63101 USA. RP Reepmeyer, JC (reprint author), US FDA, Div Pharmaceut Anal, St Louis, MO 63101 USA. EM reepmeyerj@cder.fda.gov NR 40 TC 20 Z9 21 U1 5 U2 16 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 12 PY 2005 VL 1083 IS 1-2 BP 42 EP 51 DI 10.1016/j.chroma.2005.05.092 PG 10 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 945YH UT WOS:000230538400006 PM 16078686 ER PT J AU Saito, M Murata, T Watanabe, K Kawakami, K Suzuki, M Koji, T Puri, RK Kitazato, K Kobayashi, N AF Saito, M Murata, T Watanabe, K Kawakami, K Suzuki, M Koji, T Puri, RK Kitazato, K Kobayashi, N TI Adenoviral vector-mediated gene transfer of IL-13R alpha 2 chain followed by IL-13 cytotoxin treatment offers potent targeted therapy for cytotoxin-resistant cancers SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE IL-13 cytotoxin; IL-13R alpha 2 chain; adenoviral vector; molecular targeting ID RECEPTOR ALPHA-2 CHAIN; RENAL-CELL CARCINOMA; HUMAN GLIOMA-CELLS; INTERLEUKIN-13 RECEPTOR; PSEUDOMONAS EXOTOXIN; NECK-CANCER; IN-VITRO; REPLICATION-DEFICIENT; SIGNAL-TRANSDUCTION; IMMUNE-RESPONSES AB Previous studies demonstrated that IL-13R alpha 2 chain-overexpressing cancer cells were highly sensitive to IL-13 cytotoxin (IL13-PE38QQR) and could be targeted by cytotoxin treatment. However. the majority of human tumors do not express high levels of IL-13R alpha 2 chain. To expand the IL-13 cytotoxin-mediated cancer targeting therapy, we combined cytotoxin treatment with gene transfer of IL-13R alpha 2 chain. We constructed a recombinant adenoviral vector carrying the human IL-13R alpha 2 gene (Ad-IL-13R alpha 2), which expresses high levels of IL-13R alpha 2 chain on infected cells. Human cancer cell lines A549 and HOS, which originally show no IL-13R alpha 2 expression and little sensitivity to IL-13 cytotoxin, were effectively converted to become sensitive to this cytotoxin after Ad-IL-13R alpha 2 infection. The CC50 of IL-13 cytotoxin for Ad-IL-13R alpha 2-infected A549 cells was < 10 ng/ml, whereas the CC50 for uninfected or control vector-infected cells was > 500 ng/ml. We also examined the antitumor activity of IL-13 cytotoxin in an established xenograft model of cytotoxin-resistant human lung tumor. Only a single i.t. injection of Ad-IL-13R alpha 2 markedly enhanced the sensitivity of established tumors to IL-13 cytotoxin treatment: furthermore, this antitumor effect was significantly sustained I for more than I month after the last treatment with IL-13 cytotoxin. Taken together, these results suggest the combination of adenoviral vector-mediated IL-13R alpha 2 gene transfer and IL-13 cytotoxin administration can be an effective targeting approach for several types of IL-13 cytotoxin-resistant cancers which show no or little expression of IL-13R alpha 2 chain. (c) 2005 Wiley-Liss, Inc. C1 Nagasaki Univ, Grad Sch Biomed Sci, Lab Mol Biol Infect Agents, Dept Mol Microbiol & Immunol, Nagasaki 8528521, Japan. US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Lab Mol Tumor Biol, Bethesda, MD 20014 USA. Yokohama City Univ, Sch Med, Dept Internal Med 1, Yokohama, Kanagawa 232, Japan. Nagasaki Univ, Grad Sch Biomed Sci, Cell Biol & Histol Lab, Dept Dev & Reconstruct Med, Nagasaki 852, Japan. RP Kobayashi, N (reprint author), Nagasaki Univ, Grad Sch Biomed Sci, Lab Mol Biol Infect Agents, Dept Mol Microbiol & Immunol, 1-14 Bunkyomachi, Nagasaki 8528521, Japan. EM nobnob@net.nagasaki-u.ac.jp NR 55 TC 8 Z9 9 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD AUG 10 PY 2005 VL 116 IS 1 BP 1 EP 8 DI 10.1002/ijc.20995 PG 8 WC Oncology SC Oncology GA 935FW UT WOS:000229766100001 PM 15756691 ER PT J AU Wang, YP Yan, J Beger, RD Fu, PP Chou, MW AF Wang, YP Yan, J Beger, RD Fu, PP Chou, MW TI Metabolic activation of the tumorigenic pyrrolizidine alkaloid, monocrotaline, leading to DNA adduct formation in vivo SO CANCER LETTERS LA English DT Article DE monocrotaline; pyrrolizidine alkaloid; DNA adducts ID MEDICINAL-PLANTS; RIDDELLIINE; TOXICITY; LIVER; RATS; DEHYDRORETRONECINE; MICE AB Monocrotaline is a representative naturally occurring genotoxic pyrrolizidine alkaloid. Metabolism of monocrotaline by liver microsomes of F344 female rats generated (+/-)6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine (DHP) and monocrotatine-N-oxide as major metabolites. Metabolism in the presence of triacetyleandomycin, a P450 3A enzyme inhibitor, reduced the formation of DHP by 52% and monocrotaline N-oxide formation by 59%. Dexamethasone significantly induced microsomal monocrotaline metabolizing enzyme activities in rat liver and lung. Previously, we have identified a set of DHP-derived DNA adducts from DHP-modified calf thymus DNA by (32)p-post labeling/HPLC analysis. Metabolism of monocrotaline in the presence of calf thymus DNA resulted in a similar set of DHP-DNA adducts. These DHP-DNA adducts were also found in the liver DNA of rats treated with monocrotaline. The time course of the DHP-derived DNA adduct formation and removal in the liver of rats gavaged with a single dose (10 mg/kg) of monocrotaline was similar to that of rats treated with riddellime. The levels of DHP-DNA adducts in liver DNA of rats treated with monocrotaline were much lower than that of riddelliine-treated rats. Results from this study indicate that (i) DHP is a common reactive metabolite for retronecine-type of pyrrolizidine alkaloids, (ii) the formation of DHP-derived DNA adducts in the liver DNA of rats treated with monocrotaline suggests that monocrotaline-induced tumorigenicity is through a genotoxic mechanism. Published by Elsevier Ireland Ltd. C1 Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Chou, MW (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM mchou@nctr.fda.gov NR 28 TC 41 Z9 44 U1 5 U2 14 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD AUG 8 PY 2005 VL 226 IS 1 BP 27 EP 35 DI 10.1016/j.canlet.2004.11.039 PG 9 WC Oncology SC Oncology GA 949DZ UT WOS:000230766400003 PM 16004930 ER PT J AU Sharma, U Chen, G Kang, JU Ilev, I Waynant, RW AF Sharma, U Chen, G Kang, JU Ilev, I Waynant, RW TI Fiber optic confocal laser Doppler velocimeter using an all-fiber laser source for high resolution measurements SO OPTICS EXPRESS LA English DT Article AB We demonstrate and analyze a novel fiber optic confocal laser Doppler velocimeter using an ultra-narrow linewidth all-fiber laser source centered at around 1550 nm (eye-safe region). The narrow spectral linewidth of the fiber laser (< 10 kHz) is used to achieve an extremely high velocity resolution (similar to 0.0075 m/s), which is an order of magnitude better as compared to the commonly used semiconductor diode lasers or He-Ne lasers based systems. The directional optical circulator based design used in our system is much simpler to implement and is power conserving compared to the conventional Michelson interferometer based designs. We perform Gaussian beam propagation analysis by using the ABCD law to study the performance of the confocal design. The analysis is in good accord with our experimental results. The confocal design is capable of providing ultrahigh spatial resolution (similar to 5 mu m, in both lateral and longitudinal directions) for high-precision velocity distribution measurement applications. (C) 2005 Optical Society of America. C1 Johns Hopkins Univ, Dept Elect & Comp Engn, Baltimore, MD 21218 USA. US FDA, Ctr Devices & Radiol Hlth, Div Phys, Off Sci & Engn Labs, Rockville, MD 20857 USA. RP Sharma, U (reprint author), Johns Hopkins Univ, Dept Elect & Comp Engn, 3400 N Charles St, Baltimore, MD 21218 USA. EM jkang@jhu.edu RI Kang, Jin/A-3228-2010; Agrawal, Amit/C-3728-2009 OI Agrawal, Amit/0000-0001-8230-4603 NR 13 TC 7 Z9 8 U1 1 U2 13 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1094-4087 J9 OPT EXPRESS JI Opt. Express PD AUG 8 PY 2005 VL 13 IS 16 BP 6250 EP 6258 DI 10.1364/OPEX.13.006250 PG 9 WC Optics SC Optics GA 953VP UT WOS:000231109600041 PM 19498637 ER PT J AU Ferguson, SA Gray, EP AF Ferguson, SA Gray, EP TI Aging effects on elevated plus maze behavior in spontaneously hypertensive, Wistar-Kyoto and Sprague-Dawley male and female rats SO PHYSIOLOGY & BEHAVIOR LA English DT Article DE spontaneously hypertensive rat; elevated plus maze; anxiety; aging; Wistar-Kyoto ID ANXIETY-RELATED BEHAVIORS; OVARIAN HORMONES; SEX-DIFFERENCES; ESTROUS-CYCLE; WKY RATS; STRAINS; SHR; AGE; FLUOXETINE; DIAZEPAM AB Male and female spontaneously hypertensive (SHR), Wistar-Kyoto (WKY), and Sprague-Dawley (SD) rats were assessed at one of two ages (postnatal day 74 or 346) for open field locomotor activity and anxiety-related behavior in the elevated plus maze (EPM). In general, the SHR displayed the least anxiety-related behavior, an effect that was magnified with age. At 11 months of age, the SHR more frequently entered and remained longer in the open arms than either the SID or the WKY strains. EPM behavior of the WKY strain was much less affected by age than that of the SD strain which displayed increased anxiety-related behavior with age. At the younger age, the typical sex effects were apparent; specifically, females exhibited a shorter duration in the closed arms. While the SHR were the most active strain in the EPM at both ages, they were more active in the open field only at the older age. In general, age-related changes in open field activity mirrored those of the EPM. These results provide a more comprehensive illustration of aging-related behavioral changes in male and female SHR, WKY and SD rats. (c) 2005 Elsevier Inc. All rights reserved. C1 US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. RP Ferguson, SA (reprint author), US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM sferguson@nctr.fda.gov NR 36 TC 34 Z9 35 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0031-9384 J9 PHYSIOL BEHAV JI Physiol. Behav. PD AUG 7 PY 2005 VL 85 IS 5 BP 621 EP 628 DI 10.1016/j.physbeh.2005.06.009 PG 8 WC Psychology, Biological; Behavioral Sciences SC Psychology; Behavioral Sciences GA 960YL UT WOS:000231629000012 PM 16043200 ER PT J AU Slikker, W Bowyer, JF AF Slikker, W Bowyer, JF TI Biomarkers of adult and developmental neurotoxicity SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article; Proceedings Paper CT International Conference on Biomarkers for Toxicology and Molecular Epidemiology CY MAR 15, 2004 CL Atlanta, GA DE neurotoxicity; nervous system; biomarkers; gene expression; amphetamine ID TYROSINE-HYDROXYLASE ACTIVITY; COMPLEX BRAIN-FUNCTION; GENE-EXPRESSION; METHAMPHETAMINE NEUROTOXICITY; NEURONAL DEGENERATION; RISK ASSESSMENT; CDNA ARRAY; LIMBIC SYSTEM; D-AMPHETAMINE; DOPAMINE AB Neurotoxicity may be defined as any adverse effect on the structure or function of the central and/or peripheral nervous system by a biological, chemical, or physical agent. A multidisciplinary approach is necessary to assess adult and developmental neurotoxicity due to the complex and diverse functions of the nervous system. The overall strategy for understanding developmental neurotoxicity is based on two assumptions: (1) significant differences in the adult versus the developing nervous system susceptibility to neurotoxicity exist and they are often developmental stage dependent; (2) a multidisciplinary approach using neurobiological, including gene expression assays, neurophysiological, neuropathological, and behavioral function is necessary for a precise assessment of neurotoxicity. Application of genomic approaches to developmental studies must use the same criteria for evaluating microarray studies as those in adults including consideration of reproducibility, statistical analysis, homogenous cell populations, and confirmation with non-array methods. A study using amphetamine to induce neurotoxicity supports the following: (1) gene expression data can help define neurotoxic mechanism(s), (2) gene expression changes can be useful biomarkers of effect, and (3) the site-selective nature of gene expression in the nervous system may mandate assessment of selective cell populations. Published by Elsevier Inc. C1 US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. RP Slikker, W (reprint author), US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, HFT-132,3900 NCTR Rd, Jefferson, AR 72079 USA. EM wslikker@nctr.fda.gov NR 55 TC 6 Z9 8 U1 2 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD AUG 7 PY 2005 VL 206 IS 2 BP 255 EP 260 DI 10.1016/j.taap.2004.09.022 PG 6 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 945UP UT WOS:000230528000021 PM 15967216 ER PT J AU Petersen, LR Epstein, JS AF Petersen, LR Epstein, JS TI Problem solved? West Nile virus and transfusion safety SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID BLOOD-TRANSFUSION; UNITED-STATES; TRANSMISSION C1 Ctr Dis Control & Prevent, Natl Ctr Infect Dis, Ft Collins, CO 80522 USA. US FDA, CDER, Rockville, MD 20857 USA. RP Petersen, LR (reprint author), Ctr Dis Control & Prevent, Natl Ctr Infect Dis, Ft Collins, CO 80522 USA. NR 9 TC 31 Z9 34 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD AUG 4 PY 2005 VL 353 IS 5 BP 516 EP 517 DI 10.1056/NEJMe058144 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 951OB UT WOS:000230939000012 PM 16079376 ER PT J AU Martina, Y Kurian, S Cherqui, S Evanoff, G Wilson, C Salomon, DR AF Martina, Y Kurian, S Cherqui, S Evanoff, G Wilson, C Salomon, DR TI Pseudotyping of porcine endogenous retrovirus by xenotropic murine leukemia virus in a pig islet xenotransplantation model SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE pig islets; porcine endogenous retrovirus (PERV); pseudotyping; xenotransplantation; xenotropic MLV AB The potential of porcine endogenous retrovirus (PERV) as a human pathogen, particularly as a public health risk, is a major concern for xenotransplantation.In vitroPERV transmission to human cells is well established. Evidence from human/pig hematopoietic chimeras in immunodeficient mice suggests PERV transmission from pig to human cells in vivo. However, recently Yang et al. demonstrated in such a model that PERV-C, a nonhuman-tropic class, could be transmitted via pseudotyping by xenotropic murine leukemia virus (X-MLV). We developed a mouse pig islet xenotransplant model, where pig and human cells are located in physically separate compartments, to directly assess PERV transmission from a functional pig xenograft. X-MLV efficiently pseudotypes all three classes of PERV, including PERV-A and -B that are known to productively infect human cell lines and PERV-C that is normally not infectious for human cells. Pseudotyping also extends PERV's natural tropism to nonpermissive, nonhuman primate cells. X-MLV is activated locally by the surgical procedure involved in the tissue transplants. Thus, the presence and activation of endogenous X-MLV in immunodeficient mice limits the clinical significance of previous reports of in vivo PERV transmission from pig tissues to human cells. C1 Scripps Res Inst, Dept Mol & Expt Med, La Jolla, CA USA. US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Bethesda, MD USA. RP Salomon, DR (reprint author), Scripps Res Inst, Dept Mol & Expt Med, La Jolla, CA USA. EM dsalomon@scripps.edu RI Salomon, Daniel/E-9380-2012; OI Cherqui, Stephanie/0000-0003-1240-5219 FU NIAID NIH HHS [R01 AI52349-03]; NIDDK NIH HHS [DK07022-25] NR 52 TC 29 Z9 29 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD AUG PY 2005 VL 5 IS 8 BP 1837 EP 1847 DI 10.1111/j.1600-6143.2005.00978.x PG 11 WC Surgery; Transplantation SC Surgery; Transplantation GA 942OK UT WOS:000230291500009 PM 15996230 ER PT J AU Porter, CM Bloom, ET AF Porter, CM Bloom, ET TI Human CD4(+)CD25(+) regulatory T cells suppress anti-porcine xenogeneic responses SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE CD4(+) T cells; cellular rejection; T regulatory cells; tolerance; xenotransplantation AB Due to the shortage of human organs, xenotransplantation is being explored as an alternative to allotransplantation, but immune rejection remains a major hurdle to its implementation. We tested the ability of human CD4(+)CD25(+) T cells (Treg cells) to suppress CD4(+) T cell-mediated anti-porcine xenoresponses usingin vitroassays. Human Treg cells were hyporesponsive to porcine cell stimulation and suppressed the proliferative response of CD4(+)CD25(-) T cells in a dose-dependent manner, and comparison of the allo- and xenoresponses indicated that more Treg cells might be required to suppress the xenogeneic response than the allogeneic response. Stimulation of CD4(+)CD25(-) T cells with porcine cells resulted in secretion of IFN-gamma, TNF-alpha, IL-10, IL-6 and IL-2, and Treg cells suppressed the secretion of these cytokines, as well as the CD4(+)CD25(-) T-cell cytolytic response against porcine cells. These results suggest a potential role for Treg cells in promoting xenograft survival. C1 US FDA, Ctr Biol Evaluat & Res, Lab Immunol & Virol,Off Cellular Tissue & Gene Th, Div Cellular & Gene Therapies, Bethesda, MD 20014 USA. RP Porter, CM (reprint author), US FDA, Ctr Biol Evaluat & Res, Lab Immunol & Virol,Off Cellular Tissue & Gene Th, Div Cellular & Gene Therapies, Bethesda, MD 20014 USA. EM porterc@cber.fda.gov NR 20 TC 25 Z9 26 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD AUG PY 2005 VL 5 IS 8 BP 2052 EP 2057 DI 10.1111/j.1600-6143.2005.00972.x PG 6 WC Surgery; Transplantation SC Surgery; Transplantation GA 942OK UT WOS:000230291500038 PM 15996259 ER PT J AU Rafii, F Park, M AF Rafii, F Park, M TI Effects of gyrase mutation on the growth kinetics of ciprofloxacin-resistant strains of Clostridium perfringens SO ANAEROBE LA English DT Article; Proceedings Paper CT 7th Biennial Congress of the Anaerobe-Society-of-the-Americas CY JUL 19-21, 2004 CL Annapolis, MD SP Anaerobe Soc Amer DE Clostridium perfringens; gyrase; fluoroquinolones; resistance; mutation ID FLUOROQUINOLONE RESISTANCE; GATIFLOXACIN; DIFFICILE; MUTANTS; PLASMID AB To investigate the effect of gyrA mutation on resistance of Clostridium perfringens to fluoroquinolones, a ciprofloxacin-resistant mutant was developed. The mutant had a single substitution in gyrA at position 87 (Asp to Tyr) and no additional mutations in gyrB, parC or parE. The MIC values of gatifloxacin and ciprofloxacin for this strain were 16 and 32-fold higher than those for the wild type, which were 0.125 and 0.250 mu g/mL, respectively. The resistant mutant grew equally well in the presence or absence of 5 mu g/ mL of ciprofloxacin or 1 mu g/mL of gatifloxacin and grew to lower cell densities with up to 30 mu g/mL of ciprofloxacin or 5 mu g/mL of gatifloxacin. Higher concentrations of fluoroquinolones resulted in increases in the time required to reach the end of the exponential phase and in lower cell densities at the end. The efflux pump inhibitor reserpine did not affect susceptibility to fluoroquinolones. The substitution of Asp 87 to Tyr in gyrA may have protected C perfringens from low concentrations of ciprofloxacin and gatifloxacin and enabled survival and growth at higher concentrations. Published by Elsevier Ltd. C1 Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 71602 USA. RP Rafii, F (reprint author), Natl Ctr Toxicol Res, Div Microbiol, 3900 NCTR Rd, Jefferson, AR 71602 USA. EM frafii@nctr.fda.gov NR 16 TC 5 Z9 5 U1 0 U2 0 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1075-9964 J9 ANAEROBE JI Anaerobe PD AUG PY 2005 VL 11 IS 4 BP 201 EP 205 DI 10.1016/j.anaerobe.2005.01.004 PG 5 WC Microbiology SC Microbiology GA 931XI UT WOS:000229518400003 PM 16701569 ER PT J AU Ge, BL McDermott, PF White, DG Meng, JH AF Ge, BL McDermott, PF White, DG Meng, JH TI Role of efflux pumps and topoisomerase mutations in fluoroquinolone resistance in Campylobacter jejuni and Campylobacter coli SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID DNA-SEQUENCE ANALYSIS; ESCHERICHIA-COLI; STAPHYLOCOCCUS-AUREUS; GYRA MUTATIONS; NUCLEOTIDE-SEQUENCE; MOLECULAR CHARACTERIZATION; IN-VITRO; GENE; SUSCEPTIBILITY; STRAINS AB Point mutations in the topoisomerase (DNA gyrase A) gene are known to be associated with fluoroquinolone resistance in Campylobacter. Recent studies have shown that an efflux pump encoded by cmeABC is also involved in decreased susceptibilities to fluoroquinolones, as well as other antimicrobials. Genome analysis suggests that Campylobacter jejuni contains at least nine other putative efflux pumps. Using insertional inactivation and site-directed mutagenesis, we investigated the potential contributions of these pumps to susceptibilities to chloramphenicol, ciprofloxacin, erythromycin, and tetracycline in C. jejuni and Campylobacter coli. Insertional inactivation of cmeB resulted in 4- to 256-fold decreases in the MICs of chloramphenicol, ciprofloxacin, erythromycin, and tetracycline, with erythromycin being the most significantly affected. In contrast, inactivation of all other putative efflux pumps had no effect on susceptibility to any of the four antimicrobials tested. Mutation of gyrA at codon 86 (Thr-Ile) caused 128- and 64-fold increases in the MICs of ciprofloxacin and nalidixic acid, respectively. The replacement of the mutated gyrA with a wild-type gyrA allele resulted in a 32-fold decrease in the ciprofloxacin MIC and no change in the nalidixic acid MIC. Our findings indicate that CmeABC is the only efflux pump among those tested that influences antimicrobial resistance in Campylobacter and that a point mutation (Thr-86-Ile) in gyrA directly causes fluoroquinolone resistance in Campylobacter. These two mechanisms work synergistically in acquiring and maintaining fluoroquinolone resistance in Campylobacter species. C1 Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA. Louisiana State Univ, Dept Food Sci, Baton Rouge, LA 70803 USA. US FDA, Div Anim & Food Microbiol, Res Off, Ctr Vet Med, Laurel, MD USA. RP Meng, JH (reprint author), Univ Maryland, Dept Nutr & Food Sci, 0112 Skinner Bldg, College Pk, MD 20742 USA. EM jmeng@umd.edu NR 52 TC 68 Z9 74 U1 1 U2 7 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 AUG PY 2005 VL 49 IS 8 BP 3347 EP 3354 DI 10.1128/AAC.49.8.3347-3354.2005 PG 8 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 951SI UT WOS:000230950700037 PM 16048946 ER PT J AU Wilkes, JG Rushing, LG Gagnon, JF McCarthy, SA Rafii, F Khan, AA Kaysner, CA Heinze, TM Sutherland, JB AF Wilkes, JG Rushing, LG Gagnon, JF McCarthy, SA Rafii, F Khan, AA Kaysner, CA Heinze, TM Sutherland, JB TI Rapid phenotypic characterization of Vibrio isolates by pyrolysis metastable atom bombardment mass spectrometry SO ANTONIE VAN LEEUWENHOEK INTERNATIONAL JOURNAL OF GENERAL AND MOLECULAR MICROBIOLOGY LA English DT Article DE metastable atom bombardment; principal component-discriminant analysis; pyrolysis mass spectrometry; vibrio ID LASER-DESORPTION/IONIZATION-TIME; ARTIFICIAL NEURAL-NETWORKS; NOSOCOMIAL INFECTION; PATTERN-RECOGNITION; TDH GENE; BACTERIA; PARAHAEMOLYTICUS; IDENTIFICATION; DIFFERENTIATION; MYCOBACTERIA AB Pyrolysis mass spectrometry was investigated for rapid characterization of food-borne bacterial pathogens. Nine isolates of Vibrio parahaemolyticits and one isolate each of Vibrio fluvialis, Vibrio hollisae, and Vibrio vulnificus were analyzed. Pyrolysis mass spectra, generated via an alternative ionization method, metastable atom bombardment, were subject to principal component-discriminant analysis. The spectral patterns were used to distinguish Vibrio isolates differing in species, serotype and expression of the thermostable direct hemolysin gene. The patterns of similarity and dissimilarity amongst spectra in the Vibrio test set generally reflected those associated with species, serotype or hemolysin-producing genes, though the combined influence of these and other variables in the multi-dimensional data did not produce a simple clustering with respect to any one of these characteristics. These results suggested that with enough examples to model the most common combinations, the method should be able to characterize Vibrio isolates according to their phenotypic characteristics. Pyrolysis-mass spectrometry with metastable atom bombardment and pattern recognition appeared suitable for rapid infraspecific comparison of Vibrio isolates. This integrated analytical, pattern-recognition system should be examined further for potential utility in clinical and public health diagnostic contexts. C1 US FDA, Div Syst Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. US FDA, Div Microbiol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Dephy Technol, Montreal, PQ H4E 1A2, Canada. US FDA, Gulf Coast Seafood Lab, Dauphin Isl, AL 36528 USA. US FDA, Seafood Prod Res Ctr, Bothell, WA 98021 USA. RP Wilkes, JG (reprint author), US FDA, Div Syst Toxicol, Natl Ctr Toxicol Res, 3900 NCTR Dr, Jefferson, AR 72079 USA. EM jwilkes@nctr.fda.gov NR 46 TC 8 Z9 9 U1 0 U2 4 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0003-6072 J9 ANTON LEEUW INT J G JI Antonie Van Leeuwenhoek PD AUG PY 2005 VL 88 IS 2 BP 151 EP 161 DI 10.1007/s10482-005-3990-z PG 11 WC Microbiology SC Microbiology GA 967QO UT WOS:000232106500007 PM 16096691 ER PT J AU Tolleson, WH Doss, JC Latendresse, J Warbritton, AR Melchior, WB Chin, L Dubielzig, RR Albert, DM AF Tolleson, WH Doss, JC Latendresse, J Warbritton, AR Melchior, WB Chin, L Dubielzig, RR Albert, DM TI Spontaneous uveal amelanotic melanoma in transgenic Tyr-RAS+ Ink4a/Arf-/- mice SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID INTRAOCULAR MELANOMA; MALIGNANT-MELANOMA; GERMLINE MUTATIONS; CHOROIDAL MELANOMA; RISK-FACTORS; IN-VIVO; TUMORS; MODEL; P16(INK4A); P14(ARF) AB Objective: To characterize a murine model of spontaneous amelanotic melanoma arising in the uvea of transgenic mice bearing a targeted deletion of the Ink4a/Arf tumor suppressor locus (exons 2 and 3) and expressing human H-ras controlled by the human tyrosinase promoter. Methods: Ocular lesions developed in 20 (15.7%) of 127 male albino Tyr-RAS+ Ink4a/Arf-/- transgenic FVB/N mice within 6 months, and were evaluated histologically and ultrastructurally. Results: Uveal melanomas were locally invasive but confined to the eye, with no evidence of metastasis. Tumor cells exhibited epithelioid and spindle-shaped morphological features and closely resembled the human counterpart. Melan-A, SIN and neuron-specific enolase expression were detected immuno his to chemically. Melanosomal structures were detected using electron microscopy. The retinal pigment epithelium was intact above small melanomas, and electron microscopy of the tumors failed to show the presence of basement membrane formation or desmosomes. Conclusion: Spontaneous uveal malignant melanomas occurring in male Tyr-RAS+ Ink4a/Arf-/- transgenic mice arise within the choroid or ciliary body and share histopathological features characteristic of human uveal melanoma. Clinical Relevance: Uveal melanoma research has benefited from xenograft models, but engineered mouse models of spontaneous uveal amelanotic melanoma will undoubtedly further our understanding of the genetic underpinning for this disease. C1 Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. Toxicol Pathol Associates, Jefferson, AR USA. Univ Arkansas Med Sci, Dept Pathol, Little Rock, AR 72205 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Dermatol, Boston, MA 02115 USA. Univ Wisconsin, Sch Vet Med, Madison, WI 53706 USA. Univ Wisconsin, Sch Med, Dept Ophthalmol & Visual Sci, Madison, WI 53706 USA. RP Tolleson, WH (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM wtolleson@nctr.fda.gov FU NCI NIH HHS [R01 CA 93947]; NEI NIH HHS [EY 01917] NR 38 TC 15 Z9 15 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD AUG PY 2005 VL 123 IS 8 BP 1088 EP 1094 DI 10.1001/archopht.123.8.1088 PG 7 WC Ophthalmology SC Ophthalmology GA 955OY UT WOS:000231236900009 PM 16087843 ER PT J AU Goucher, DR Wincovitch, SM Garfield, SH Carbone, KM Malik, TH AF Goucher, DR Wincovitch, SM Garfield, SH Carbone, KM Malik, TH TI A quantitative determination of multi-protein interactions by the analysis of confocal images using a pixel-by-pixel assessment algorithm SO BIOINFORMATICS LA English DT Article ID DECONVOLUTION; MICROSCOPY; OBJECTS; MICE AB Motivation: Recent advances in confocal microscopy have allowed scientists to assess the expression, and to some extent, the interaction/colocalization of multiple molecules within cells and tissues. In some instances, accurately quantifying the colocalization of two or more proteins may be critical. This can require the acquisition of multiple Z plane images (Z stacks) throughout a specimen and, as such, we report here the successful development of a freeware, open-source image analysis tool, IMAJIN_COLOC, developed in PERL (v. 5.8, build 806), using the PERLMagick libraries (ImageMagick). Using a pixel-by-pixel analysis algorithm, IMAJIN_COLOC can analyze images for antigen expression (any number of colors) and can measure all possible combinations of colocalization for up to three colors by analyzing a Z stack gallery acquired for each sample. The simultaneous (i.e. in a single pass) analysis of three-color colocalization, and batch analysis capabilities are distinctive features of this program. Results: A control image, containing known individual and colocalized pixel counts, was used to validate the accuracy of IMAJIN_COLOC. As further validation, pixel counts and colocalization values from the control image were compared to those obtained with the software packaged with the Zeiss laser-scanning microscope (LSM AIM, version 3.2). The values from both programs were found to be identical. To demonstrate the applicability of this program in addressing novel biological questions, we examined the role of neurons in eliciting an immune reaction in response to viral infection. Specifically, we successfully examined expression of the chemokine RANTES in measles virus (MV) infected hippocampal neurons and quantified changes in RANTES production throughout the disease period. The resultant quantitative data were also evaluated visually, using a gif image created during the analysis. Availability: PERL (ActivePerl, version 5.8) is available at activestate.com; the PERLMagick libraries are available at imagemagick.org, and IMAJIN_COLOC, the source code and user documentation can be downloaded from http://www.fda.gov/cber/research/imaging/imageanalysis.htm Contact: Malik@cber.fda.gov C1 US FDA, DVP, OVRR, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. NCI, Expt Carcinogenesis Lab, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Dept Psychiat, Baltimore, MD 21205 USA. Johns Hopkins Univ, Dept Med, Baltimore, MD 21205 USA. RP Malik, TH (reprint author), US FDA, DVP, OVRR, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. EM Malik@cber.fda.gov NR 19 TC 10 Z9 10 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD AUG 1 PY 2005 VL 21 IS 15 BP 3248 EP 3254 DI 10.1093/bioinformatics/bti531 PG 7 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 945OY UT WOS:000230513200007 PM 15947019 ER PT J AU Evans, DL Charney, DS Lewis, L Golden, RN Gorman, JM Krishnan, KRR Nemeroff, CB Bremner, JD Carney, RM Coyne, JC Delong, MR Frasure-Smith, N Glassman, AH Gold, PW Grant, I Gwyther, L Ironson, G Johnson, RL Kanner, AM Katon, WJ Kaufmann, PG Keefe, FJ Ketter, T Laughren, TP Leserman, J Lyketsos, CG McDonald, WM McEwen, BS Miller, AH Musselman, D O'Connor, C Petitto, JM Pollock, BG Robinson, RG Roose, SP Rowland, J Sheline, Y Sheps, DS Simon, G Spiegel, D Stunkard, A Sunderland, T Tibbits, P Valvo, WJ AF Evans, DL Charney, DS Lewis, L Golden, RN Gorman, JM Krishnan, KRR Nemeroff, CB Bremner, JD Carney, RM Coyne, JC Delong, MR Frasure-Smith, N Glassman, AH Gold, PW Grant, I Gwyther, L Ironson, G Johnson, RL Kanner, AM Katon, WJ Kaufmann, PG Keefe, FJ Ketter, T Laughren, TP Leserman, J Lyketsos, CG McDonald, WM McEwen, BS Miller, AH Musselman, D O'Connor, C Petitto, JM Pollock, BG Robinson, RG Roose, SP Rowland, J Sheline, Y Sheps, DS Simon, G Spiegel, D Stunkard, A Sunderland, T Tibbits, P Valvo, WJ TI Mood disorders in the medically ill: Scientific review and recommendations SO BIOLOGICAL PSYCHIATRY LA English DT Review DE mood disorders; medical comorbidity; depression; antidepressant therapy ID CORONARY-ARTERY-DISEASE; PLACEBO-CONTROLLED TRIAL; HUMAN-IMMUNODEFICIENCY-VIRUS; ISCHEMIC-HEART-DISEASE; DOUBLE-BLIND PLACEBO; SEROTONIN REUPTAKE INHIBITORS; METASTATIC BREAST-CANCER; PITUITARY-ADRENAL AXIS; HIV-INFECTED MEN; ACUTE MYOCARDIAL-INFARCTION AB Objective. The purpose of this review is to assess the relationship between mood disorders and development, course, and associated morbidity and mortality of selected medical illnesses, review evidence for treatment, and determine needs in clinical practice and research. Data Sources. Data were culled from the 2002 Depression and Bipolar Support Alliance Conference proceedings and a literature review addressing prevalence, risk factors, diagnosis, and treatment. This review also considered the experience of primary and specialty care providers, policy analysts, and patient advocates. The review and recommendations reflect the expert opinion of the authors. Study Selection/Data Extraction: Reviews of epidemiology and mechanistic studies were included, as were open-label and randomized controlled trials on treatment of depression in patients with medical comorbidities. Data on study design, population, and results were extracted for review of evidence that includes tables of prevalence and pharmacological treatment. The effect of depression and bipolar disorder on selected medical comorbidities was assessed, and recommendations for practice, research, and policy were developed. Conclusions: A growing body of evidence suggests that biological mechanisms underlie a bidirectional link between mood disorders and many medical illnesses. In addition, there is evidence to suggest that mood disorders affect the course of medical illnesses. Further prospective studies are warranted. C1 Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. Washington Univ, St Louis, MO USA. Emory Univ, Atlanta, GA 30322 USA. NCI, NIMH, NHLBI, Bethesda, MD 20892 USA. United States Food & Drug Adm, Rockville, MD USA. Johns Hopkins Univ, Baltimore, MD USA. Univ Pittsburgh, Pittsburgh, PA USA. McGill Univ, Montreal, PQ, Canada. Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada. Columbia Univ, New York, NY USA. Mt Sinai Sch Med, New York, NY USA. Rockefeller Univ, New York, NY 10021 USA. Univ N Carolina, Sch Med, Chapel Hill, NC USA. Duke Univ, Durham, NC USA. Stanford Univ, Stanford, CA 94305 USA. Univ Calif San Diego, San Diego, CA 92103 USA. Univ Miami, Coral Gables, FL 33124 USA. Univ Florida, Gainesville, FL USA. Univ Med & Dent New Jersey, Newark, NJ 07103 USA. St Lukes Hosp, Chicago, IL USA. Univ Washington, Ctr Hlth Studies, Grp Hlth Cooperat, Seattle, WA 98195 USA. Univ Iowa, Iowa City, IA USA. Amer Diabetes Assoc, Alexandria, VA USA. Mended Hearts, Dallas, TX USA. RP Evans, DL (reprint author), Univ Penn, Sch Med, Dept Psychiat, 305 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM psych@mail.med.upenn.edu RI Bremner, James/B-1632-2013 NR 274 TC 509 Z9 523 U1 18 U2 58 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD AUG 1 PY 2005 VL 58 IS 3 BP 175 EP 189 DI 10.1016/j.biopsych.2005.05.001 PG 15 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 953DR UT WOS:000231057100001 PM 16084838 ER PT J AU Marti, GE Rawstron, AC Ghia, P Hillmen, P Houlston, RS Kay, N Schleinitz, TA Caporaso, N AF Marti, GE Rawstron, AC Ghia, P Hillmen, P Houlston, RS Kay, N Schleinitz, TA Caporaso, N CA Int Familial CLL Consortium TI Diagnostic criteria for monoclonal B-cell lymphocytosis SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Review DE monoclonal B-cell lymphocytosis; B cells; early detection; surrogate biomarker; familial chronic lymphocytic leukaemia ID UNDETERMINED SIGNIFICANCE MLUS; NATURAL-HISTORY; WORKING GROUP; LEUKEMIA CLL; EXPRESSION; PROGNOSIS; BLOOD; DIFFERENTIATION; GAMMOPATHIES; IL-1-BETA AB Very low levels of circulating monoclonal B-cell subpopulations can now be detected in apparently healthy individuals using flow cytometry. We propose the term 'monoclonal B-cell lymphocytosis' (MBL) to describe this finding. The aim of this document is to provide a working definition of MBL for future clinical, epidemiological and laboratory studies. We propose that the detection of a monoclonal B-cell population by light chain restriction is sufficient to define this condition in individuals not meeting the diagnostic criteria for other B-lymphoproliferative disorders. The majority of individuals with MBL will have cells that are indistinguishable from chronic lymphocytic leukaemia (CLL). However, this blood cell clonal expansion of CD5(+) or CD5(-) B-lymphocytes is age-dependent and immunophenotypic heterogeneity is common. Longitudinal studies are required to determine whether MBL is a precursor state to CLL or other B-lymphoproliferative disease in a situation analogous to a monoclonal gammopathy of undetermined significance and myeloma. Future studies of MBL should be directed towards determining its relationship to clinical disease, particularly in individuals from families with a genetic predisposition to developing CLL. C1 NIH, Flow & Image Cytometry Sect, LSCB DCGT OCTGT, CBER FDA, Bethesda, MD 20892 USA. Leeds Teaching Hosp NHS Trust, Leeds Gen Infirm, Haematol Malignancy Diagnost Serv, Leeds, W Yorkshire, England. Univ Turin, Dept Oncol Sci, Candiolo, TO, Italy. Ist Ric & Cura Cancro, Lab Canc Immunol, Candiolo, TO, Italy. Canc Res Inst, Sect Canc Genet, Sutton, Surrey, England. Mayo Clin, Div Hematol, Rochester, MN USA. Inst J Paoli I Calmettes, F-13009 Marseille, France. NCI, Dept Med, Div Canc Epidemiol & Genet, Genet Epidemiol Branch,NIH, Bethesda, MD 20892 USA. RP Marti, GE (reprint author), NIH, Flow & Image Cytometry Sect, LSCB DCGT OCTGT, CBER FDA, Bdg 29B,Rm 2NN08,8800 Rockville Pike, Bethesda, MD 20892 USA. RI Ghia, Paolo/K-7138-2016 OI Ghia, Paolo/0000-0003-3750-7342 NR 47 TC 214 Z9 223 U1 0 U2 12 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD AUG PY 2005 VL 130 IS 3 BP 325 EP 332 DI 10.1111/j.1365-2141.2005.05550.x PG 8 WC Hematology SC Hematology GA 948OO UT WOS:000230725800001 PM 16042682 ER PT J AU Beland, FA Churchwell, MI Von Tungeln, LS Chen, SJ Fu, PP Culp, SJ Schoket, B Gyorffy, E Minarovits, J Poirier, MC Bowman, ED Weston, A Doerge, DR AF Beland, FA Churchwell, MI Von Tungeln, LS Chen, SJ Fu, PP Culp, SJ Schoket, B Gyorffy, E Minarovits, J Poirier, MC Bowman, ED Weston, A Doerge, DR TI High-performance liquid chromatography electrospray ionization tandem mass spectrometry for the detection and quantitation of benzo[a]pyrene-DNA adducts SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID HYDROCARBON-DNA ADDUCTS; POLYCYCLIC AROMATIC-HYDROCARBONS; FED COAL-TAR; HUMAN-PLACENTA; HUMAN LUNG; BENZOPYRENE-DNA ADDUCTS; RISK ASSESSMENT; CANCER-RISK; QUANTIFICATION; EXPOSURE AB A method, using HPLC combined with electrospray tandem mass spectrometry (ES-MS/ MS), was developed and validated to detect and quantify the major DNA adduct resulting from exposure to the ultimate tumorigenic benzo[alpha]pyrene (BP) metabolite, trans-7,8-dihydroxyanti-9,10-epoxy-7,8,9,10-tetrahydrobenzo[alpha]pyrene (BPDE). Calf thymus DNA was reacted with BPDE, digested enzymatically to nucleosides, and the major DNA adduct, 10-(deoxyguanosin-N-2-yl)-7,8,9-trihydroxy-7,8,9,10-tetrahydrobenzo[alpha]pyrene (dG-BPDE), was purified by HPLC. Similar procedures were applied to prepare dG-BPDE-d(8) from [1,2,3,4,5,6,11,12(2)H(8)]BPDE for use as an internal standard. The HPLC-ES-MS/MS method was validated using a mixture of hydrolyzed salmon testis DNA (82 mu g) and 10 pg dG-BPDE (analogous to 6.9 adducts/10(8) nucleotides). The results indicated an inter- and intraday accuracy of 99-100% and precision of 1.6-1.7% (relative standard deviation). When applied to a calf thymus DNA sample modified in vitro with [1,3-H-3]BPDE, the method gave a value very similar to those obtained by radiolabeling, P-32-postlabeling, and immunoassay. HPLC-ES-MS/MS analysis of hepatic DNA from mice treated intraperitoneally with 0.5 and 1.0 mg of [7,8-H-3]BP gave values comparable to those determined by P-32-postlabeling and immunoassay. Lung DNA from mice fed a 0.3% coal tar diet (containing approximately 2 mg BP/g coal tar) for one month had 0.6 +/- 0.04 dG-BPDE adducts/10(8) nucleotides. This value is much lower than the 102 14 total DNA adducts/10(8) nucleotides determined by P-32-postlabeling, which suggests that dG-BPDE makes only a minor contribution to the DNA adducts formed in lung tissue of mice administered coal tar. The HPLC-ES-MS/MS method was used to assess human lung DNA samples for the presence of dG-BPDE. Based upon a limit of detection of 0.3 dG-BPDE adducts/10(8) nucleotides, when using 100,mu g of DNA, dG-BPDE was detected in only 1 out of 26 samples. These observations indicate that HPLC-ES-MS/MS is suitable to assess the contribution of BP to DNA damage caused by exposures to polycyclic aromatic hydrocarbon (PAH) mixtures. The results further suggest that dG-BPDE may contribute only a small fraction of the total DNA adducts detected by other DNA adduct methodologies in individuals exposed to PAHs. C1 Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. Jozsef Fodor Natl Ctr Publ Hlth, Natl Inst Environm Hlth, H-1097 Budapest, Hungary. Bela Johan Natl Ctr Epidemiol, H-1529 Budapest, Hungary. NCI, NIH, Bethesda, MD 20892 USA. Natl Inst Occupat Hlth Safety, Ctr Dis Control & Prevent, Morgantown, WV 26505 USA. RP Beland, FA (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. EM fbeland@nctr.fda.gov FU NCI NIH HHS [N02-CO-91012] NR 38 TC 63 Z9 66 U1 0 U2 15 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 AUG PY 2005 VL 18 IS 8 BP 1306 EP 1315 DI 10.1021/tx050068y PG 10 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 955OG UT WOS:000231235000014 PM 16097804 ER PT J AU Finlay, WJJ deVore, NC Dobrovolskaia, EN Gam, A Goodyear, CS Slater, JE AF Finlay, WJJ deVore, NC Dobrovolskaia, EN Gam, A Goodyear, CS Slater, JE TI Exploiting the avian immunoglobulin system to simplify the generation of recombinant antibodies to allergenic proteins SO CLINICAL AND EXPERIMENTAL ALLERGY LA English DT Article DE 2D SDS-PAGE; chicken; ELISA; phage display; scFv; Western blot ID PHAGE-DISPLAY; RAGWEED POLLEN; MAJOR ALLERGEN; IMMUNIZED HENS; ANTIGEN-E; FRAGMENTS; DIABODIES; CLONING; TECHNOLOGY; TRIABODIES AB Background Monoclonal antibodies are a valuable tool in the study of allergens, but the technology used in their generation can be slow and labour-intensive. Therefore, we have examined recombinant antibody development by phage-display against single allergens and protein mixtures. Objective We used the avian immunoglobulin system (generated from single V-H and V-L genes) to provide a rapid method for generating highly specific recombinant antibody fragments from a minimal number of animals. Methods A single-chain antibody fragment (scFv) library was generated from a single chicken immunized with model allergens. ScFvs were isolated by phage-display and their properties investigated by ELISA and Western blot. Results Mono-specific scFvs were generated against recombinant Fel d 1 and native Amb a 1. Pannings against yellow jacket venom extracts only yielded clones that reacted with multiple proteins in the venom extract. The scFvs from each panning type were effectively expressed in Escherichia coli and readily purified. Highly specific and sensitive recognition of Fel d 1 and Amb a 1 was demonstrated in ELISA, with scFvs displaying antibody-concentration-dependent absorbance curves down to picogram levels of antibody. The specificity of selected antibodies for their cognate antigen was further confirmed in Western blot analysis, with scFvs directed to either Fel d 1 or Amb a 1 showing no reactivity for the other antigens used in immunization. Anti-Amb a 1 scFvs also mapped Amb a 1-isoform location in Western blot of ragweed extracts separated by 2D SDS-PAGE. DNA sequence analysis of scFvs showed that multiple different clones had been generated against Fel d 1 and Amb a 1. Using two anti-Fel d 1 scFv for ELISA analysis of Fel d 1 content in crude cat pelt extracts, we could produce data which were highly similar (P=0.33 and 0.89 by paired t-test analysis) to those obtained using conventional assays (radial immunodiffusion). Conclusion Phage-display technology may generate multiple allergen-specific recombinant antibody fragments from a single chicken, to allergens from mammalian, plant and insect sources. The resulting antibody fragments are of demonstrable use in allergen identification and quantification, in comparison with standard immunoassays. C1 USDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. Univ Calif San Diego, Sch Med, San Diego, CA 92103 USA. RP Slater, JE (reprint author), USDA, Ctr Biol Evaluat & Res, 29 Lincoln Dr, Bethesda, MD 20892 USA. EM SlaterJ@cber.fda.gov OI Goodyear, Carl/0000-0001-5926-5941 NR 34 TC 28 Z9 30 U1 1 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0954-7894 J9 CLIN EXP ALLERGY JI Clin. Exp. Allergy PD AUG PY 2005 VL 35 IS 8 BP 1040 EP 1048 DI 10.1111/j.1365-2222.2005.02307.x PG 9 WC Allergy; Immunology SC Allergy; Immunology GA 957UL UT WOS:000231398700009 PM 16120086 ER PT J AU Kraus, CN Zalkikar, J Powers, JH AF Kraus, CN Zalkikar, J Powers, JH TI Levofloxacin and macrolides for treatment of legionnaires disease: Multiple comparisons give few answers SO CLINICAL INFECTIOUS DISEASES LA English DT Letter C1 US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Powers, JH (reprint author), 9201 Corp Blvd,HFD-104, Rockville, MD 20850 USA. EM POWERSJOH@cder.fda.gov NR 7 TC 4 Z9 5 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD AUG 1 PY 2005 VL 41 IS 3 BP 416 EP 416 DI 10.1086/431768 PG 1 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 942TK UT WOS:000230305300029 PM 16007549 ER PT J AU Martinez-Urtaza, J Simental, L Velasco, D DePaola, A Ishibashi, M Nakaguchi, Y Nishibuchi, M Carrera-Flores, D Rey-Alvarez, C Pousa, A AF Martinez-Urtaza, J Simental, L Velasco, D DePaola, A Ishibashi, M Nakaguchi, Y Nishibuchi, M Carrera-Flores, D Rey-Alvarez, C Pousa, A TI Pandemic Vibrio parahalemolyticus O3 : K6, Europe SO EMERGING INFECTIOUS DISEASES LA English DT Letter ID PARAHAEMOLYTICUS; EMERGENCE; STRAINS; CLONE C1 Univ Santiago de Compostela, Inst Acuicultura, Santiago De Compostela 15782, Spain. Complexo Hosp Univ Juan Canalejo, La Coruna, Spain. US FDA, Dauphin Isl, AL USA. Osaka Prefectural Inst Publ Hlth, Osaka 537, Japan. Kyoto Univ, Kyoto, Japan. Conselleria Sanidade, Santiago De Compostela, Spain. RP Martinez-Urtaza, J (reprint author), Univ Santiago de Compostela, Inst Acuicultura, Campus Univ Sur, Santiago De Compostela 15782, Spain. EM ucmjmur@usc.es RI Martinez-Urtaza, Jaime/A-5528-2015 NR 9 TC 90 Z9 94 U1 0 U2 3 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 2005 VL 11 IS 8 BP 1319 EP 1320 PG 2 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 950RL UT WOS:000230874900035 PM 16110585 ER PT J AU Roubinian, N Kirkpatrick, BD Lynn, F Zenilman, J Bash, M AF Roubinian, N Kirkpatrick, BD Lynn, F Zenilman, J Bash, M TI Neisseria meningitidis endotoxin and capsule transmission by transplantation SO EMERGING INFECTIOUS DISEASES LA English DT Letter ID LIVER-TRANSPLANTATION; DONORS C1 US FDA, Lab Bacterial Polysaccharides, Off Vaccines Res & Reviw, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. Univ Vermont, Coll Med, Burlington, VT USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. RP Bash, M (reprint author), US FDA, Lab Bacterial Polysaccharides, Off Vaccines Res & Reviw, Ctr Biol Evaluat & Res, HFM-428,29 Lincoln Dr, Bethesda, MD 20892 USA. EM bash@cber.fda.gov NR 10 TC 0 Z9 0 U1 0 U2 0 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 2005 VL 11 IS 8 BP 1326 EP 1327 PG 2 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 950RL UT WOS:000230874900039 PM 16110590 ER PT J AU Benoit, SR Mendelsohn, AB Nourjah, P Staffa, JA Graham, DJ AF Benoit, SR Mendelsohn, AB Nourjah, P Staffa, JA Graham, DJ TI Risk factors for prolonged QTc among US adults: Third National Health and Nutrition Examination Survey SO EUROPEAN JOURNAL OF CARDIOVASCULAR PREVENTION & REHABILITATION LA English DT Article DE medications; NHANES; QTc prolongation; risk factors; torsades ID CORONARY-HEART-DISEASE; INTERVAL PROLONGATION; CARDIOVASCULAR-DISEASE; QUESTIONNAIRE DATA; DIABETES-MELLITUS; MEDICAL RECORDS; DE-POINTES; ALL-CAUSE; POPULATION; WOMEN AB Background QT interval prolongation can lead to torsades de pointes, a potentially fatal arrhythmia. Although research exists on the relationship between QT prolongation and clinical outcome, few studies have described risk factors for prolonged QT interval in the general population. Methods The Third National Health and Nutrition Examination Survey (NHANES 111) collected electrocardiogram interval data on 8561 subjects over 40 years of age and projected results to the US population. QT was corrected for heart rate using Fridericia's formula. Logistic regression analyses were performed to identify factors independently associated with prolonged QTc interval, defined as being in the upper 5% of the population QTc interval distribution. Analyses were conducted separately for women and men as a result of differences in the QT distribution between the sexes and also because of potential effect modification. Analytical variables included age, race/ethnicity, electrolyte measurements, body mass index, the recent use of QT-prolonging drugs and past medical histories of stroke, thyroid disease, hypertension, diabetes and myocardial infarction. Results Age, female sex, hypocalcemia (men), hypokalemia (women), and a history of thyroid disease and myocardial infarction (men) were associated with a prolonged QTc interval. In addition, taking QT-prolonging medications in the past month was associated with more than a twofold increase in the odds of prolonged QTc interval in both men and women. Conclusions Healthcare practitioners should be aware that a prolonged QTc interval is a potential indicator of cardiovascular risk, and should exercise caution in prescribing potentially QT-prolonging medications to certain patients. C1 US FDA, Rockville, MD 20857 USA. RP Benoit, SR (reprint author), Ctr Dis Control & Prevent, 1600 Clifton Rd NE,MS E-68, Atlanta, GA 30333 USA. EM bvy8@cdc.gov NR 45 TC 63 Z9 67 U1 2 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1741-8267 J9 EUR J CARDIOV PREV R JI Eur. J. Cardiovasc. Prev. Rehabil. PD AUG PY 2005 VL 12 IS 4 BP 363 EP 368 DI 10.1097/01.hjr.0000173110.21851.a9 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 965RJ UT WOS:000231967700009 PM 16079644 ER PT J AU Ishii, KJ Ito, S Tamura, T Hemmi, H Conover, J Ozato, K Akira, S Klinman, DM AF Ishii, KJ Ito, S Tamura, T Hemmi, H Conover, J Ozato, K Akira, S Klinman, DM TI CpG-activated Thy1.2(+) dendritic cells protect against lethal Listeria monocytogenes infection SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE CpG DNA; innate immunity; host protection; Listeria; TLR9 ID TOLL-LIKE RECEPTORS; ANTIGEN-PRESENTING CELLS; IFN-GAMMA-PRODUCTION; BACTERIAL-DNA; IMMUNE-RESPONSE; IN-VIVO; INNATE; OLIGODEOXYNUCLEOTIDES; MOTIFS; EXPRESSION AB Synthetic oligodeoxynucleotides containing CpG motifs (CpG ODN) activate the innate immune system by interacting with Toll-like receptor 9. The resultant immune response increases host resistance to infection by a variety of pathogenic microorganisms, including Listeria monocytogenes. There is a considerable interest in harnessing the immunoprotective properties of CpG ODN, yet little is known of the cell phenotype(s) responsible for mediating this protection. This work demonstrates that treatment of mice with CpG ODN increases the number of Thy1.2(+), CD11c(+) dendritic cells (Thy1.2(+) DC) in the spleen, which are both necessary and sufficient for transferring resistance to infection from CpG-treated donors to naive recipients. These CpG-activated Thy1.2(+) DC are distinct from conventional (CD11c(hi), Thy1.2(-)) or plasmacytoid DC (mPDCA(+)), and secrete IFN-gamma that contributes to protection. These findings suggest that a novel Thy1.2(+) DC subset plays a critical role in mediating the immunoprotective activity of CpG DNA. C1 US FDA, Sect Retroviral Immunol, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. NICHHD, Lab Mol Growth Regulat, NIH, Bethesda, MD 20892 USA. Osaka Univ, ERATO, Japan Sci & Technol Agcy, Akira Innate Immun Project, Osaka, Japan. Osaka Univ, Microbial Dis Res Inst, Dept Host Def, Osaka, Japan. RP Klinman, DM (reprint author), US FDA, Sect Retroviral Immunol, Ctr Biol Evaluat & Res, Bldg 29A,Rm 3D 10, Bethesda, MD 20892 USA. EM klinman@cber.fda.gov RI Akira, Shizuo/C-3134-2009; Ishii, Ken/B-1685-2012 OI Ishii, Ken/0000-0002-6728-3872 NR 31 TC 16 Z9 18 U1 0 U2 0 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 2005 VL 35 IS 8 BP 2397 EP 2405 DI 10.1002/eji.200425795 PG 9 WC Immunology SC Immunology GA 957MK UT WOS:000231373700014 PM 16047338 ER PT J AU Takeshita, F Ishii, KJ Kobiyama, K Kojima, Y Coban, C Sasaki, S Ishii, N Klinman, DM Okuda, K Akira, S Suzuki, K AF Takeshita, F Ishii, KJ Kobiyama, K Kojima, Y Coban, C Sasaki, S Ishii, N Klinman, DM Okuda, K Akira, S Suzuki, K TI TRAF4 acts as a silencer in TLR-mediated signaling through the association with TRAF6 and TRIF SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE TLR; cellular signaling; innate immunity ID INTERFERON-ALPHA INDUCTION; NADPH OXIDASE ACTIVATION; TOLL-LIKE RECEPTOR-9; NF-KAPPA-B; CPG DNA; HUMAN NEUTROPHILS; PROTEIN-KINASE; P47(PHOX); TRANSCRIPTION; PHAGOCYTOSIS AB Toll-like receptors (TLR) and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase play an essential role in intracellular eradication of engulfed pathogens. Here, we demonstrate the physical and functional association between components of the cytosolic NADPH oxidase and TLR-mediated signaling molecules. Cytosolic components of NADPH oxidase suppressed TLR-mediated NF-kappa B activation as well as IFN-beta promoter activation. We demonstrate that TNT-associated factor (TRAF) 4 associates with p47(phox), a component of cytosolic NADPH oxidase, and physically interacts and functionally counteracts with TRAF6 and Toll-IL-1 receptor (TIR) domain-containing adaptor-inducing IFN-beta (TRIF) molecules that critically regulate TLR-mediated signaling. TRAF4 mRNA expression was elicited in RPMI 8226 cells following LPS or CpG DNA treatment. These results suggest that TRAF4 participates in the molecular mechanism underlying silencing of TLR-mediated signaling through the interaction with molecules harboring phagosome/endosome membrane. C1 Yokohama City Univ, Sch Med, Dept Mol Biodef Res, Kanazawa Ku, Yokohama, Kanagawa 2360004, Japan. Japan Sci & Technol Agcy, Akira Innate Immun Program, ERATO, Osaka, Japan. Natl Inst Infect Dis, Leprosy Res Ctr, Dept Host Def, Tokyo, Japan. US FDA, Sect Retroviral Immunol, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. Osaka Univ, Microbial Dis Res Inst, Dept Host Def, Osaka, Japan. Natl Inst Infect Dis, Leprosy Res Ctr, Dept Microbiol, Tokyo, Japan. RP Takeshita, F (reprint author), Yokohama City Univ, Sch Med, Dept Mol Biodef Res, Kanazawa Ku, 3-9 Fukuura, Yokohama, Kanagawa 2360004, Japan. EM takesita@yokohama-cu.ac.jp RI Akira, Shizuo/C-3134-2009; Coban, Cevayir/B-2129-2012; Ishii, Ken/B-1685-2012 OI Ishii, Ken/0000-0002-6728-3872 NR 33 TC 60 Z9 67 U1 0 U2 8 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 2005 VL 35 IS 8 BP 2477 EP 2485 DI 10.1002/eji.200526151 PG 9 WC Immunology SC Immunology GA 957MK UT WOS:000231373700023 PM 16052631 ER PT J AU Varricchio, F AF Varricchio, F TI Vaccine adverse event reporting: the importance of follow-up SO EXPERT REVIEW OF VACCINES LA English DT Editorial Material ID DATA-COLLECTION; CASE-DEFINITION; IMMUNIZATION; SYSTEM; INFORMATION; GUIDELINES C1 US FDA, Div Epidemiol, Off Biostat & Epidemiol, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Varricchio, F (reprint author), US FDA, Div Epidemiol, Off Biostat & Epidemiol, Ctr Biol Evaluat & Res, 1401 Rockville Pike, Rockville, MD 20852 USA. EM Varricchio@comcast.net NR 14 TC 3 Z9 3 U1 0 U2 0 PU FUTURE DRUGS LTD PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1476-0584 J9 EXPERT REV VACCINES JI Expert Rev. Vaccines PD AUG PY 2005 VL 4 IS 4 BP 445 EP 448 DI 10.1586/14760584.4.4.445 PG 4 WC Immunology SC Immunology GA 984JH UT WOS:000233298700001 PM 16117700 ER PT J AU Ferguson, SA Cisneros, FJ Gough, BJ Ali, SF AF Ferguson, SA Cisneros, FJ Gough, BJ Ali, SF TI Four weeks of oral isotretinoin treatment causes few signs of general toxicity in male and female Sprague-Dawley rats SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article DE retinoic acid; toxicity; adult; isotretinoin; dopamine ID 13-CIS RETINOIC ACID; 13-CIS-RETINOIC ACID; ALL-TRANS; ESTROUS-CYCLE; UNITED-STATES; PHASE-II; THERAPY; LIVER; MICE; ACNE AB Despite widespread use of isotretinoin for its anti-acne effects and its current evaluation in clinical trials as a cancer treatment, little is known about its general toxicity in adult nonpregnant animals, particularly after oral administration which mimics the human route. Here, adult male and female Sprague-Dawley rats were gavaged daily with 0 (soy oil), 7.5, or 15 mg/kg isotretinoin for 28 days during which time body weight, food/water intake, and estrous phase were measured. At sacrifice, organ weights were collected and concentrations of dopamine (DA), serotonin and metabolites were measured in frontal cortex, striatum, hippocampus, and diencephalon. Food intake was mildly decreased in both treated groups (approximate to 15% in males and 7% in females); however, body weight and water consumption were unaffected. The estrous cycle appeared slightly affected (i.e., lengthened by 15 mg/kg, and both treated groups appeared to have less time in diestrus and more time in estrus). Kidney/body weight ratio was decreased by 7.5 and 15 mg/kg isotretinoin and spleen/body weight ratio was increased in the 7.5 mg/kg group. Males of the 7.5 mg/kg group exhibited significantly higher gonad/body weight ratios than did same-sex controls. Concentrations of monoamine and metabolites in the frontal cortex and diencephalon were unaffected. Nor were striatal DA and DOPAC concentrations affected; however, there were isolated effects on striatal HVA and 5-HIAA. Hippocampal DA concentrations were marginally increased. These data indicate mild effects resulting from oral isotretinoin treatment at doses which likely produce serum levels within the range of humans. (c) 2005 Elsevier Ltd. All rights reserved. C1 Natl Ctr Toxicol Res, FDA, Div Neurotoxicol, Jefferson, AR 72079 USA. RP Ferguson, SA (reprint author), Natl Ctr Toxicol Res, FDA, Div Neurotoxicol, HFT-132,3900,NCTR Rd, Jefferson, AR 72079 USA. EM sferguson@nctr.fda.gov NR 32 TC 14 Z9 15 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0278-6915 J9 FOOD CHEM TOXICOL JI Food Chem. Toxicol. PD AUG PY 2005 VL 43 IS 8 BP 1289 EP 1296 DI 10.1016/j.fct.205.02.016 PG 8 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA 951ZJ UT WOS:000230970600007 PM 15950819 ER PT J AU Hoke, EM Maylock, CA Shacter, E AF Hoke, EM Maylock, CA Shacter, E TI Desferal inhibits breast tumor growth and does not interfere with the tumoricidal activity of doxorubicin SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE free radicals; breast cancer; chemotherapy; doxorubicin; desferal; iron; oxidants; antioxidants ID RIBONUCLEOTIDE REDUCTASE; INDUCED APOPTOSIS; REACTIVE OXYGEN; ANTHRACYCLINE CARDIOTOXICITY; CARDIOPROTECTIVE AGENT; CANCER-CHEMOTHERAPY; ANTITUMOR-ACTIVITY; RADICAL FORMATION; CARDIAC TOXICITY; IRON-DEFICIENCY AB Desferal is a clinically approved iron chelator used to treat iron overload. Doxorubicin is an anthracycline cancer chemotherapy drug used in the treatment of breast cancer. It can undergo redox cycling in the presence of iron to produce reactive oxygen species. The oxidant-generating activity of doxorubicin is thought to be responsible for the cardiotoxic side effects of the drug, but it is unclear whether it is also required for its anti-tumor activity. To test whether an iron-chelating antioxidant would interfere with the tumor-killing activity of doxorubicin, nude mice were transplanted with xenografts of human breast cancer MDA-MB 231 cells and then treated with doxorubicin and/or desferal. Not only did desferal not interfere with the anti-tumor activity of doxorubicin, it inhibited tumor growth on its own. In vitro studies confirmed that desferal inhibits breast tumor growth. However, it did not induce apoptosis, nor did it induce cell cycle arrest. Instead, desferal caused cytostasis, apparently through iron depletion. The cytostatic activity of desferal was partially ameliorated by pretreatment with iron-saturated transferrin, and transferrin receptor expression on breast cancer cells nearly doubled after exposure to desferal. In contrast to its effect on tumor cells, desferal did not inhibit growth of normal breast epithelial cells. The data indicate that the anti-tumor activity of doxorubicin is not dependent on iron-mediated ROS production. Furthermore, desferal may have utility as an adjunctive chemotherapy due to its ability to inhibit breast tumor growth and cardiotoxic side effects without compromising the tumor-killing activity of an anthracycline chemotherapy drug. Published by Elsevier Inc. C1 US FDA, Ctr Drug Evaluat & Res, Div Therapeut Prot, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Dept Pediat, Bethesda, MD 20815 USA. RP Shacter, E (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Therapeut Prot, Bethesda, MD 20892 USA. EM emily.shacter@fda.gov NR 58 TC 43 Z9 43 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD AUG 1 PY 2005 VL 39 IS 3 BP 403 EP 411 DI 10.1016/j.freeradbiomed.2005.03.029 PG 9 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 949GZ UT WOS:000230774400011 PM 15993339 ER PT J AU Zhang, XM Miao, XP Tan, W Ning, BT Liu, ZH Hong, Y Song, WG Guo, YL Zhang, XY Shen, Y Qiang, BQ Kadlubar, FF Lin, DX AF Zhang, XM Miao, XP Tan, W Ning, BT Liu, ZH Hong, Y Song, WG Guo, YL Zhang, XY Shen, Y Qiang, BQ Kadlubar, FF Lin, DX TI Identification of functional genetic variants in cyclooxygenase-2 and their association with risk of esophageal cancer SO GASTROENTEROLOGY LA English DT Article ID ARACHIDONIC-ACID METABOLISM; SQUAMOUS-CELL CARCINOMA; C-MYB; TRANSCRIPTIONAL REGULATION; TUMOR ANGIOGENESIS; PROMOTER VARIANT; LINKAGE PHASE; EXPRESSION; POLYMORPHISM; HAPLOTYPES AB (Background & Aims) under bar: Overexpression of cyclooxygenase-2 (COX-2) is implicated in many steps of cancer development. Single nucleotide polymorphisms (SNIPS) in the COX-2 promoter might contribute to differential COX-2 expression and subsequent interindividual variability in susceptibility to cancer. This study sought to identify functional SNPs in the COX-2 promoter and evaluated their effects on the risk of developing esophageal squamous cell carcinoma (ESCC). (Methods) under bar: Thirty individual DNA samples were sequenced to search for SNPs, and the function of the SNIPS was examined by a set of biochemical assays. Genotypes and haplotypes were analyzed in :1026 patients and 1270 controls, and odds ratios and 95% confidence intervals (Cls) were estimated by logistic regression. (Results: ) under bar Three SNPs, -1290A -> G, -1195G -> A, and -765G -> C, were identified; the frequencies of variant alleles were 0.04, 0.51, and 0.02, respectively. The -1195G -> A change creates a c-MYB binding site and displays a higher promoter activity. The -1195A-containing haplotypes had significantly increased luciferase expression and COX-2 messenger RNA levels in esophageal tissues compared with the -1195G-containing counterparts. A case-control analysis showed a 1.72-fold (95% Cl, 1.35-2.20) and 2.24-fold (95% Cl, 1.59-3.16) excess risk of developing ESCC for the -1195AA or -765CC genotype carriers compared with noncarriers. A greater risk of developing ESCC was observed for A(-1195)-C-765- containing haplotypes compared with G(-1195)-G(-765)- containing haplotypes, suggesting an interaction between the -1195G -> A and -765G -> C polymorphisms in the context of haplotype. (Conclusions) under bar: These findings indicate that genetic variants in COX-2 may play a role in mediating susceptibility to esophageal cancer. C1 Chinese Acad Med Sci, Inst Canc, Dept Etiol & Carcinogenesis, Beijing 100021, Peoples R China. Chinese Acad Med Sci, Inst Canc, Natl Lab Mol Oncol, Beijing 100021, Peoples R China. Peking Union Med Coll, Beijing, Peoples R China. N China Coal Med Coll, Dept Sci Biol, Tangshan, Hebei, Peoples R China. Natl Ctr Toxicol Res, Div Pharmacogenom & Mol Epidemiol, Jefferson, AR 72079 USA. Tangshan Gongren Hosp, Tangshan, Hebei, Peoples R China. Chinese Natl Human Genome Ctr, Beijing, Peoples R China. RP Lin, DX (reprint author), Chinese Acad Med Sci, Inst Canc, Dept Etiol & Carcinogenesis, Beijing 100021, Peoples R China. EM dlin@public.bta.net.cn RI zhang, xuemei/F-3818-2010; miao, xiaoping/C-4336-2011; Zhang, Xinyu/S-4946-2016 OI miao, xiaoping/0000-0002-6818-9722; Zhang, Xinyu/0000-0001-8154-9334 NR 42 TC 169 Z9 193 U1 2 U2 14 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD AUG PY 2005 VL 129 IS 2 BP 565 EP 576 DI 10.1053/j.gastro.2005.05.003 PG 12 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 953IU UT WOS:000231070600020 PM 16083713 ER PT J AU Han, J Lee, H Nguyen, NY Beaucage, SL Puri, RK AF Han, J Lee, H Nguyen, NY Beaucage, SL Puri, RK TI Novel multiple 5 '-amino-modified primer for DNA microarrays SO GENOMICS LA English DT Article DE microarray; uni-link molecules; novel multiple 5 '-amino-modified primer; signal intensity ID RNA AMPLIFICATION; EXPRESSION; HYBRIDIZATION; FIDELITY; PROBES AB For DNA microarray analysis, total RNA is reverse-transcribed, labeled by incorporating fluorescent dye into the cDNA, and used to hybridize microarray. This protocol requires a minimum of 20 mu g of total RNA. To overcome the sample limitation, an RNA amplification technique has been developed. Although it needs less RNA, this amplification technique is relatively expensive, time consuming, and, unfortunately, has been found to introduce bias. In this study, we designed a novel 5'-amino-modified primer and used it for priming cDNA synthesis. The novel primer has a special structure that contains four Uni-Link molecules with two nucleotide (thymine) residues inserted between them as spacers. This novel primer is used in the reverse-transcription reaction for cDNA synthesis. Using the novel 5'-modified primer combined with indirect labeling method, cDNA probes can be prepared with much less total RNA (5 mu g or less) without amplification producing optimal results after hybridization of arrays. This primer can also be used to label nucleotides for other purposes. Published by Elsevier Inc. C1 Lab Mol Tumor Biol, Div Cellular & Gene Therapies, Bethesda, MD 20892 USA. Facil Biotechnol Resources, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. US FDA, Div Therapeut Prot, Off Biotechnol Prod, Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. RP Puri, RK (reprint author), Lab Mol Tumor Biol, Div Cellular & Gene Therapies, Bethesda, MD 20892 USA. EM puri@cber.fda.gov NR 15 TC 13 Z9 16 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD AUG PY 2005 VL 86 IS 2 BP 252 EP 258 DI 10.1016/j.ygeno.2005.04.009 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 947QU UT WOS:000230662000012 PM 15949917 ER PT J AU Flynn, B Wang, V Sacks, DL Seder, RA Verthelyi, D AF Flynn, B Wang, V Sacks, DL Seder, RA Verthelyi, D TI Prevention and treatment of cutaneous leishmaniasis in primates by using synthetic type D/A oligodeoxynucleotides expressing CpG motifs SO INFECTION AND IMMUNITY LA English DT Article ID INFECTED RHESUS MACAQUES; BACTERIAL-DNA; PROTECTIVE IMMUNITY; DENDRITIC CELLS; INNATE IMMUNITY; MACACA-MULATTA; IN-VIVO; B-CELL; RESISTANCE; VACCINE AB Oligodeoxynucleotides (ODN) containing CpG motifs mimic microbial DNA and are recognized by toll-like receptor 9 on immune cells. The resulting response limits the early spread of infectious organisms and promotes the development of adaptive immunity. In this regard, CpG ODN show promise as immunoprotective agents and as vaccine adjuvants. Previous studies of nonhuman primates showed that administration of CpG ODN type D (also known as type A) at the site of infection 3 days before and after a challenge with Leishmania major enhanced host resistance and reduced the lesion's severity. In this study, we show that systemic administration of D/A ODN limits the size of lesions following an intradermal infection with L. major. Importantly, the reduced morbidity was not associated with a reduction in long-term immunity, as such treated macaques were still protected following a secondary challenge. Finally, administration of D/A ODN to macaques that had established cutaneous lesions reduced the severity of the lesions, suggesting a potential role for CpG ODN in L. major treatment. Together, these findings support the development of clinical studies to assess the use of CpG ODN types D/A as immunoprotective and therapeutic agents. C1 US FDA, Ctr Drug Evaluat & Review, Div Therapeut Prot, Washington, DC 20204 USA. NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Verthelyi, D (reprint author), Bldg 29A Rm 3B19,8800 Rockville Pike, Bethesda, MD 20892 USA. EM Verthelyi@cber.fda.gov NR 30 TC 27 Z9 31 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD AUG PY 2005 VL 73 IS 8 BP 4948 EP 4954 DI 10.1128/IAI.73.8.4948-4954.2005 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 949BT UT WOS:000230760600054 PM 16041009 ER PT J AU Bhagwat, AA Chan, L Han, R Tan, J Kothary, M Jean-Gilles, J Tall, BD AF Bhagwat, AA Chan, L Han, R Tan, J Kothary, M Jean-Gilles, J Tall, BD TI Characterization of enterohemorrhagic Escherichia coli strains based on acid resistance phenotypes SO INFECTION AND IMMUNITY LA English DT Article ID SHIGELLA-FLEXNERI; DECARBOXYLASE SYSTEM; TOLERANCE RESPONSE; ENTERIC BACTERIA; GENE-EXPRESSION; RPOS MUTATIONS; GLUTAMATE; O157-H7; SURVIVAL; STRESS AB Acid resistance is perceived to be an important property of enterohemorrhagic Escherichia coli strains, enabling the organisms to survive passage through the acidic environment of the stomach so that they may colonize the mammalian gastrointestinal tract and cause disease. Accordingly, the organism has developed at least three genetically and physiologically distinct acid resistance systems which provide different levels of protection. The glutamate-dependent acid resistance (GDAR) system utilizes extracellular glutamate to protect cells during extreme acid challenges and is believed to provide the highest protection from stomach acidity. In this study, the GDAR system of 82 pathogenic E. coli isolates from 34 countries and 23 states within the United States was examined. Twenty-nine isolates were found to be defective in inducing GDAR under aerobic growth conditions, while five other isolates were defective in GDAR under aerobic, as well as fermentative, growth conditions. We introduced rpoS on a low-copy-number plasmid into 26 isolates and were able to restore GDAR in 20 acid-sensitive isolates under aerobic growth conditions. Four isolates were found to be defective in the newly discovered LuxR-like regulator GadE (formerly YhiE). Defects in other isolates could be due to a mutation(s) in a gene(s) with an as yet undefined role in acid resistance since GadE and/or RpoS could not restore acid resistance. These results show that in addition to mutant alleles of rpoS, mutations in gadE exist in natural populations of pathogenic E. coli. Such mutations most likely alter the infectivity of individual isolates and may play a significant role in determining the infective dose of enterohemorrhagic E. coli. C1 USDA, Prod Qual & Safety Lab, Henry A Wallace Beltsville Agr Res Ctr, ARS, Beltsville, MD 20705 USA. US FDA, Div Virulence Assessment, Laurel, MD 20708 USA. RP Bhagwat, AA (reprint author), USDA, Prod Qual & Safety Lab, Henry A Wallace Beltsville Agr Res Ctr, ARS, Bldg 002,10300 Baltimore Ave, Beltsville, MD 20705 USA. EM bhagwata@ba.ars.usda.gov OI Tall, Ben/0000-0003-0399-3629 NR 52 TC 43 Z9 46 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD AUG PY 2005 VL 73 IS 8 BP 4993 EP 5003 DI 10.1128/IAI.73.8.4993-5003.2005 PG 11 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 949BT UT WOS:000230760600059 PM 16041014 ER PT J AU Zink, SD Burns, DL AF Zink, SD Burns, DL TI Importance of srtA and srtB for growth of Bacillus anthracis in macrophages SO INFECTION AND IMMUNITY LA English DT Article ID STAPHYLOCOCCUS-AUREUS; SURFACE-PROTEINS; CELL-WALL; SORTASE; PATHOGENESIS; VIRULENCE; TOXIN; GENE; ENVELOPE; BACTERIA AB We examined the effect of mutation of two sortase genes of Bacillus anthracis, srtA and srtB, on the ability of the bacterium to grow in J774A.1 cells, a mouse macrophage-like cell line. While disruption of either srtA or srtB had no effect on the ability of the bacteria to grow in rich culture media, mutations in each of these genes dramatically attenuated growth of the bacterium in J774A.1 cells. Complementation of the mutation restored the ability of bacteria to grow in the cells. Since the initial events in inhalation anthrax are believed to be uptake of B. anthracis spores by alveolar macrophages followed by germination of the spores and growth of the bacteria within the macrophages, these results suggest that two sortases of B. anthracis may be critical in the early stages of inhalation anthrax. C1 US FDA, Lab Resp & Special Pathogens, Bethesda, MD 20892 USA. RP Burns, DL (reprint author), US FDA, CBER, HFM-434,8800 Rockville Pike, Bethesda, MD 20892 USA. EM burns@cber.fda.gov OI Zink, Steven/0000-0002-3271-0192 NR 30 TC 23 Z9 25 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD AUG PY 2005 VL 73 IS 8 BP 5222 EP 5228 DI 10.1128/IAI.73.8.5222-5228.2005 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 949BT UT WOS:000230760600089 PM 16041044 ER PT J AU Wang, Z Orlandi, PA Stenger, DA AF Wang, Z Orlandi, PA Stenger, DA TI Simultaneous detection of four human pathogenic microsporidian species from clinical samples by oligonucleotide Microarray SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID SUBUNIT RIBOSOMAL-RNA; POLYMERASE CHAIN-REACTION; IMMUNODEFICIENCY-VIRUS-INFECTION; INTESTINAL BIOPSY SPECIMENS; ENTEROCYTOZOON-BIENEUSI; STOOL SPECIMENS; ENCEPHALITOZOON-INTESTINALIS; SEPTATA-INTESTINALIS; ELECTRON-MICROSCOPY; DNA EXTRACTION AB Microsporidian species have been rapidly emerging as human enteric pathogens in immunocompromised and immunocompetent individuals in recent years. Routine diagnostic techniques for microsporidia in clinical laboratories are laborious and insensitive and tend to underestimate their presence. In most instances, they are unable to differentiate species of spores due to their small sizes and similar morphologies. In this study, we report the development of another protozoan oligonucleotide microarray assay for the simultaneous detection and identification to the species level of four major microsporidian species: Enterocytozoon bieneusi, Encephalitozoon cuniculi, Encephalitozoon hellem, and Encephalitozoon intestinalis. The 18S small-subunit rRNA gene was chosen as the amplification target, labeled with fluorescence dye, and hybridized to a series of species-specific oligonucleotide probes immobilized on a microchip. The specificity and sensitivity of the microarray were clearly demonstrated by the unique hybridization profiles exhibited by each species of microsporidian tested and its ability to detect as few as 10 spores. In order to assess the applicability of this microarray in a clinical setting, we conducted microarray assays of 20 fecal samples from AIDS patients. Twelve of these samples were positive for the presence of microsporidia and could be confidently identified; 11 of them were positive for more than one species. Our results suggested that this microarray-based approach represents an attractive diagnostic tool for high-throughput detection and identification of microsporidian species in clinical and epidemiological investigations. C1 USN, Res Lab, Ctr Biomol Sci & Engn, Washington, DC 20375 USA. US FDA, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. RP Wang, Z (reprint author), USN, Res Lab, Ctr Biomol Sci & Engn, Code 6910,4555 Overlook Ave SW, Washington, DC 20375 USA. EM zwang@cbmse.nrl.navy.mil NR 39 TC 22 Z9 30 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD AUG PY 2005 VL 43 IS 8 BP 4121 EP 4128 DI 10.1128/JCM.43.8.4121-4128.2005 PG 8 WC Microbiology SC Microbiology GA 954EL UT WOS:000231136800076 PM 16081959 ER PT J AU Temple, RJ AF Temple, RJ TI Enrichment designs: Efficiency in development of cancer treatments SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material 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 7 TC 25 Z9 25 U1 1 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD AUG 1 PY 2005 VL 23 IS 22 BP 4838 EP 4839 DI 10.1200/JCO.2005.02.913 PG 2 WC Oncology SC Oncology GA 952CL UT WOS:000230979300011 PM 15983397 ER PT J AU Grant, MA AF Grant, MA TI Comparison of a new enrichment procedure for Shiga toxin-producing Escherichia coli with five standard methods SO JOURNAL OF FOOD PROTECTION LA English DT Article ID PREVALENCE; O157-H7; SYSTEM; GENES; MEAT AB A new procedure for enrichment of Escherichia coli O157:H7 and other Shiga toxin-producing E. coli was compared to five standard methods: the British Public Health Laboratory Service, International Standard Method, U.S. Department of Agriculture, Canadian Health Products and Food Branch, and U.S. Food and Drug Administration. The new procedure was comparable to the standard methods in its ability to detect target cells inoculated into foods at approximately 1 CFU g(-1). Comparisons were also made of the ability of the six enrichment procedures to detect E coli O157:H7 against a large background of competitor microorganisms. In these experiments the new procedure yielded more target cells than the other five enrichments by two to three orders of magnitude as determined by enumeration on sorbitol MacConkey agar with tellurite and cefixime and Rainbow agar with tellurite and novobiocin and by verification of presumptive colonies by real-time PCR. For example, the population of enterohemorrhagic E coli strain 6341 recovered on sorbitol MacConkey agar with tellurite and cefixime after enrichment with the experimental method was 2.42 X 10(8) CFU ml(-1) and 1.80 X 10(6) CFU ml(-1) after enrichment with the Canadian Health Products and Food Branch method, the second most effective in this experiment. In addition, broth cultures resulting from each of the six enrichment procedures were used to prepare templates for real-time PCR detection of stx(1)/stx(2). Resulting threshold cycle (Ct) values after the experimental enrichment were similar to positive control values, whereas the five standard methods produced delayed Ct values or were not detected. C1 US FDA, Pacific Reg Lab NW, Bothell, WA 98021 USA. RP Grant, MA (reprint author), US FDA, Pacific Reg Lab NW, 23rd Dr SE, Bothell, WA 98021 USA. EM mike.grant@fda.gov NR 23 TC 16 Z9 16 U1 0 U2 1 PU INT ASSOC FOOD PROTECTION PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD AUG PY 2005 VL 68 IS 8 BP 1593 EP 1599 PG 7 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 953BQ UT WOS:000231051200006 PM 21132965 ER PT J AU Ben-Ari, J Etinger, A Weisz, A Mandelbaum, A AF Ben-Ari, J Etinger, A Weisz, A Mandelbaum, A TI Hydrogen-shift isomerism: mass spectrometry of isomeric benzenesulfonate and 2-, 3- and 4-dehydrobenzenesulfonic acid anions in the gas phase SO JOURNAL OF MASS SPECTROMETRY LA English DT Article DE hydrogen-shift isomerism; distonic isomerism; proton transfer; gas-phase anions; deprotonation of diacids; aromatic sulfonic acids; collision induced dissociation (CID); DFT computations ID CHARGED PHENYL RADICALS; BENZYNE NEGATIVE-IONS; CHEMICAL-IONIZATION; 4-DEHYDROANILINIUM ION; PROTONATION PROCESS; DISTONIC ISOMERS; IONIZED ANILINE; ABSOLUTE HEATS; KINETIC NATURE; META-BENZYNE AB The isomeric 3- and 4-dehydrobenzenesulfonic acid anions b and c were prepared by collision induced dissociation (CID) of the [M - H](-) ions of isomeric sulfobenzoic acids obtained by negative electrospray ionization (ESI). The CID spectra (MS3) of anions b and c are different from each other, and both are different from that of the isomeric benzenesulfonate anion a, obtained from benzenesulfonic acid. The stability of ions b and c shows that 1,2-proton transfer does not take place in this system under the conditions of the CID experiment. Density functional (DFT) calculations at B3LYP/6-31+G(2d,p) level of theory show that benzenesulfonate anion a is the most stable isomer, and the energies of isomers b and c are higher by more than 65 kcal mol(-1). The calculated energies of the transition states involved in the 1,2-hydrogen migration leading to the interconversion of the isomeric anions are very high (> 120 kcal mol(-1) relative to ion a, barrier energies > 55 kcal mol(-1)), much higher than those of transition structures leading to fragmentation. This situation does not allow isomerization of ions b and c to a, under the conditions of the CID experiments. The isomeric 2-dehydrobenzenesulfonic acid anion isomerizes to the benzenesulfortate anion a by a facile proton transfer from the SO3H group to the adjacent position 2. The results of this work indicate that the gas phase deprotonation of meta- and para-sulfobenzoic acids is a kinetically controlled process. Copyright (c) 2005 John Wiley & Sons, Ltd. C1 US FDA, Ctr Food Safety & Appl Nutr, Off Cosmet & Colors, College Pk, MD 20740 USA. Technion Israel Inst Technol, Dept Chem, Lise Meitner Minerva Ctr Computat Quantum Chem, IL-32000 Haifa, Israel. RP Weisz, A (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Cosmet & Colors, College Pk, MD 20740 USA. EM aweisz@cfsan.fda.gov NR 38 TC 8 Z9 8 U1 0 U2 7 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1076-5174 J9 J MASS SPECTROM JI J. Mass Spectrom. PD AUG PY 2005 VL 40 IS 8 BP 1064 EP 1071 DI 10.1002/jms.881 PG 8 WC Biophysics; Chemistry, Organic; Spectroscopy SC Biophysics; Chemistry; Spectroscopy GA 961CF UT WOS:000231638800009 PM 15973646 ER PT J AU Itzhak, Y Anderson, KL Ali, SF AF Itzhak, Y Anderson, KL Ali, SF TI Selective role of the nitrergic system in dopamine mediated neurotoxicity of substituted amphetamines SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 20th Biennial Meeting of the International-Society-for-Neurochemistry/European-Society-for-Neurochemi stry CY AUG 21-26, 2005 CL Innsbruck, AUSTRIA SP Int Soc Neurochem, European Soc Neurochem C1 Univ Miami, Sch Med, Dept Psychiat, Miami, FL 33152 USA. NCTR, Div Neurotoxicol, Jefferson, AR USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD AUG PY 2005 VL 94 SU 2 BP 61 EP 61 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 961PD UT WOS:000231673400176 ER PT J AU Trumbo, PR AF Trumbo, PR TI Are there adverse effects of lycopene exposure? SO JOURNAL OF NUTRITION LA English DT Article; Proceedings Paper CT Conference on Promises and Perils of Lycopena/Tomato Supplementation and Cancer Prevention CY FEB 17-18, 2005 CL British Inst Int Comparat Law, Bethesda, MD SP Div Canc Prevent, Div Canc Epidemiol & Genet, Ctr Canc Res, Natl Canc Inst, Natl Inst Hlth, Dept DHHS, Agr Res Serv HO British Inst Int Comparat Law DE lycopene; tomatoes; toxicity; safety ID SYNTHETIC LYCOPENE; ORAL TOXICITY; RATS; PRODUCTS C1 US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Trumbo, PR (reprint author), US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. EM paula.truinbo@fda.hhs.gov NR 12 TC 5 Z9 5 U1 0 U2 0 PU AMER SOCIETY NUTRITIONAL SCIENCE PI BETHESDA PA 9650 ROCKVILLE PIKE, RM L-2407A, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD AUG PY 2005 VL 135 IS 8 BP 2060S EP 2061S PG 2 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 972TQ UT WOS:000232476500042 PM 16046742 ER PT J AU Kortejarvi, H Yliperttula, M Dressman, JB Junginger, HE Midha, KK Shah, VP Barends, DM AF Kortejarvi, H Yliperttula, M Dressman, JB Junginger, HE Midha, KK Shah, VP Barends, DM TI Biowaiver monographs for immediate release solid oral dosage forms: Ranitidine hydrochloride SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article DE absorption; Biopharmaceutics Classification System (BCS); ranitidine; permeability; solubility ID BIOPHARMACEUTICS CLASSIFICATION-SYSTEM; CACO-2 CELL MONOLAYERS; IN-VIVO CORRELATION; GASTROINTESTINAL TRANSIT; H2-RECEPTOR ANTAGONIST; P-GLYCOPROTEIN; PERMEABILITY; DRUGS; BIOAVAILABILITY; ABSORPTION AB Literature and experimental data relevant to the decision to allow a waiver of in vivo bioequivalence testing for the approval of immediate release (IR) solid oral dosage forms containing ranitidine hydrochloride are reviewed. According to the current Biopharmaceutics Classification System (BCS), ranitidine hydrochloride should be assigned to Class Ill. However, based on its therapeutic and therapeutic index, pharmacokinetic properties and data related to the possibility of excipient interactions, a biowaiver can be recommended for IR solid oral dosage forms that are rapidly dissolving and contain only those excipients as reported in this study. (c) 2005 Wiley-Liss, Inc. C1 Natl Inst Publ Hlth & Environm, RIVM, NL-3720 BA Bilthoven, Netherlands. Orion Pharma, Res & Dev, Espoo, Finland. Univ Frankfurt, Inst Pharmazeut Technol, D-6000 Frankfurt, Germany. Leiden Univ, Leiden Amsterdam Ctr Drug Res, Div Pharmaceut Technol, Leiden, Netherlands. Univ Saskatchewan, Saskatoon, SK, Canada. US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Barends, DM (reprint author), Natl Inst Publ Hlth & Environm, RIVM, POB 1, NL-3720 BA Bilthoven, Netherlands. EM dirk.barends@rivm.nl RI Fachbereich14, Dekanat/C-8553-2015 NR 49 TC 48 Z9 53 U1 0 U2 6 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0022-3549 J9 J PHARM SCI-US JI J. Pharm. Sci. PD AUG PY 2005 VL 94 IS 8 BP 1617 EP 1625 DI 10.1002/jps.20392 PG 9 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 952BS UT WOS:000230977300001 PM 15959881 ER PT J AU Gopalakrishnan, M Suarez, S Hickey, AJ Gobburu, J AF Gopalakrishnan, M Suarez, S Hickey, AJ Gobburu, J TI Population pharmacokinetic-pharmacodynamic modeling of subcutaneous and pulmonary insulin in rats SO JOURNAL OF PHARMACOKINETICS AND PHARMACODYNAMICS LA English DT Article DE insulin; glucose; HMAP; population pharmacokinetic-pharmacodynamic modeling; indirect response model ID INHALED HUMAN INSULIN; DIABETES-MELLITUS; ABSORPTION; DELIVERY; BIOAVAILABILITY; PROTEINS; BINDING; RABBIT; AGENTS; EXTENT AB Purpose: To develop a population pharmacokinetic-pharmacodynamic (PKPD) model for insulin in rats. Methods: Rats were administered insulin either subcutaneously (s.c) (0.26,1.3,2.6 U/kg) or by pulmonary route (spray-instillation (s.i)) (0.26,1.3,2.6,13,26 U/kg). Insulin (0.26,1.3,2.6 U/kg) combined with different combinations of hydroxy methyl amino propionic acid (HMAP: 5,10,16,25 mg/kg) was also administered by spray-instillation. Plasma insulin and glucose concentrations at pre-determined time points were measured. Population pharmacokinetic-pharmacodynamic modeling was performed using NONMEM. Results: Insulin exhibited dose-disproportional PK across formulations and routes of administration. The kinetic model suggested monoexponential disposition with simultaneous first order (64%-dimeric form of insulin) - zero order (36%-hexameric form of insulin) absorption. Maximum relative bioavailability (relative to s.c - 0.26 U/kg) of spray-instilled insulin was 46%. Addition of HMAP increased the relative bioavailability of insulin administered via spray-instilled route by 40%. The insulin-glucose relationship was characterized using an indirect response model, wherein, insulin stimulation of glucose uptake into muscle cells was assumed. The basal zero order production rate of glucose (k(G, prod)) was estimated as 0.98 mg/dl/min. The SC50 was fixed at 80 mu U/ml based on literature reports and the S-max was estimated to be 6. Conclusions: The proposed PKPD model satisfactorily describes insulin disposition and glucose concentrations across range of doses with and without HMAP. C1 US FDA, Off Clin Pharmacol & Biopharmaceut, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. Self, Rockville, MD 20852 USA. US FDA, Div Pharmaceut Evaluat 2, Off Clin Pharmacol & Biopharmaceut, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. Univ N Carolina, Chapel Hill, NC 27599 USA. RP Gobburu, J (reprint author), US FDA, Off Clin Pharmacol & Biopharmaceut, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. EM jogarao.gobburu@fda.hhs.gov NR 37 TC 15 Z9 15 U1 0 U2 3 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1567-567X J9 J PHARMACOKINET PHAR JI J. Pharmacokinet. Pharmacodyn. PD AUG PY 2005 VL 32 IS 3-4 BP 485 EP 500 DI 10.1007/s10928-005-0008-4 PG 16 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 990DT UT WOS:000233724100009 PM 16284921 ER PT J AU Mackey, EA Paul, RL Lindstrom, RM Anderson, DL Greenberg, RR AF Mackey, EA Paul, RL Lindstrom, RM Anderson, DL Greenberg, RR TI Sources of uncertainties in prompt gamma activation analysis SO JOURNAL OF RADIOANALYTICAL AND NUCLEAR CHEMISTRY LA English DT Article ID NEUTRON-SCATTERING; HYPERMET-PC; HYDROGEN; SENSITIVITIES AB Two prompt gamma-ray activation analysis (PGAA) facilities at the NIST Center for Neutron Research have been used routinely to perform elemental analyses of a variety of materials. Results from these analyses are usually expressed as mass fraction values with expanded uncertainties. The expanded uncertainty consists of the combined uncertainty multiplied by the appropriate coverage factor (k) required to achieve a 95% confidence interval. The combined uncertainty includes the uncertainties associated with preparation, irradiation, and gamma-ray spectrometry of samples and standards, and corrections for gamma-rays from the background or blanks where necessary. To determine the combined uncertainty, each component of uncertainty associated with each variable and constant in the basic measurement equation is evaluated. In this paper we present the PGAA measurement equation, a description of the potential sources of uncertainty for each component of the equation, and three examples of uncertainty evaluation. The examples are for determination of H in standard reference material (SRM) 2454, hydrogen in titanium alloy using the cold neutron PGAA facility, Cd in SRM 2702 Inorganics in Marine Sediment using the original thermal neutron PGAA facility, and N in SRM 3244 Ephedra-Containing Protein Powder using the recently designed thermal neutron PGAA facility. C1 Natl Inst Stand & Technol, Analyt Chem Div, Gaithersburg, MD 20899 USA. US FDA, Elemental Res Branch, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Mackey, EA (reprint author), Natl Inst Stand & Technol, Analyt Chem Div, Gaithersburg, MD 20899 USA. NR 30 TC 11 Z9 11 U1 0 U2 5 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0236-5731 J9 J RADIOANAL NUCL CH JI J. Radioanal. Nucl. Chem. PD AUG PY 2005 VL 265 IS 2 BP 273 EP 281 DI 10.1007/s10967-005-0820-8 PG 9 WC Chemistry, Analytical; Chemistry, Inorganic & Nuclear; Nuclear Science & Technology SC Chemistry; Nuclear Science & Technology GA 948CD UT WOS:000230692700016 ER PT J AU Wear, KA AF Wear, KA TI The dependencies of phase velocity and dispersion on trabecular thickness and spacing in trabecular bone-mimicking phantoms SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID BOVINE CANCELLOUS BONE; QUANTITATIVE ULTRASOUND MEASUREMENTS; WAVE-PROPAGATION; HIP FRACTURE; STRATIFIED MODEL; MINERAL-CONTENT; BIOT THEORY; OS CALCIS; ATTENUATION; DENSITY AB Frequency-dependent phase velocity was measured in trabecular-bone-mimicking phantoms consisting of two-dimensional arrays of parallel nylon wires (simulating trabeculae) with thicknesses ranging from 152 to 305 mu m and spacings ranging from 700 to 1000 mu m. Phase velocity varied approximately linearly with frequency over the range from 400 to 750 kHz. Dispersion was characterized by the slope of a linear least-squares regression fit to phase velocity versus frequency data. The increase in phase velocity (compared with that in water) at 500 kHz was approximately proportional to the (1) square of trabecular thickness, (2) inverse square of trabecular spacing, and (3) volume fraction occupied by nylon wires. The first derivative of phase velocity with respect to frequency was negative and exhibited nonlinear, monotonically decreasing dependencies on trabecular thickness and volume fraction. The dependencies of phase velocity and its first derivative on volume fraction in the phantoms were consistent with those reported in trabecular bone. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20852 USA. RP Wear, KA (reprint author), US FDA, Ctr Devices & Radiol Hlth, HFZ-142,12720 Twinbrook Pkwy, Rockville, MD 20852 USA. EM kaw@cdrh.fda.gov NR 52 TC 34 Z9 35 U1 0 U2 1 PU ACOUSTICAL SOC AMER AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0001-4966 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD AUG PY 2005 VL 118 IS 2 BP 1186 EP 1192 DI 10.1121/1.1940448 PG 7 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA 955FJ UT WOS:000231210500064 PM 16158673 ER PT J AU Barletta, JM Edelman, DC Highsmith, WE Constantine, NT AF Barletta, JM Edelman, DC Highsmith, WE Constantine, NT TI Detection of ultra-low levels of pathologic prion protein in scrapie infected hamster brain homogenates using real-time immuno-PCR SO JOURNAL OF VIROLOGICAL METHODS LA English DT Article DE BSE; immuno-PCR; IPCR; real-time IPCR; prion; PrPC; PrPSc; scrapie; TSE ID CREUTZFELDT-JAKOB-DISEASE; TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHY; POLYMERASE-CHAIN-REACTION; SENSITIVE ANTIGEN-DETECTION; MUMPS-SPECIFIC IGG; BLOOD-TRANSFUSION; CAPILLARY-ELECTROPHORESIS; ULTRASENSITIVE DETECTION; CYCLIC AMPLIFICATION; VARIANT AB Pathologic prion protein (PrPSc), implicated in transmissible spongiform encephalopathies, is detected by antibody-based tests or bioassays to confirm the diagnosis of prion diseases. Presently, the Western blot or an ELISA is officially used to screen the brain stem in cattle for the presence of PrPSc. The immuno-polymerase chain reaction (IPCR), a technique whereby the exponential amplification ability of PCR is coupled to the detection of proteins by antibodies in an ELISA format, was applied in-a modified real-time IPCR method to detect ultra-low levels of prion protein. Using IPCR, recombinant hamster PrPC was consistently detected at I fg/mL and proteinase K (PK)-digested scrapie infected hamster brain homogenates diluted to 10(-8) (approximately 10-100 infectious units) was detected with a semi-quantitative dose response. This level of detection is I million-fold more sensitive than the levels detected by Western blot or ELISA and poises IPCR as a method capable of detecting PrPSc in the pre-clinical phase of infection. Further, the data indicate that unless complete PK digestion of PrPC in biological materials is verified, ultrasensitive assays such as IPCR may inaccurately classify a sample as positive. (c) 2005 Elsevier B.V. All rights reserved. C1 US FDA, CDER, OPS, Rockville, MD 20857 USA. Univ Maryland, Dept Pathol, Baltimore, MD 21201 USA. Mayo Clin, Div Lab Genet, Dept Lab Med & Pathol, Rochester, MN USA. RP Barletta, JM (reprint author), US FDA, CDER, OPS, Rockville, MD 20857 USA. EM bariettaj@cder.fda.gov; constant@umbi.umd.edu RI Highsmith, William/B-6175-2008 NR 58 TC 38 Z9 40 U1 1 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-0934 J9 J VIROL METHODS JI J. Virol. Methods PD AUG PY 2005 VL 127 IS 2 BP 154 EP 164 DI 10.1016/j.jviromet.2005.04.007 PG 11 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Virology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Virology GA 943LK UT WOS:000230355000007 PM 15921765 ER PT J AU Byrnes, KR Wu, XJ Waynant, RW Ilev, IK Anders, JJ AF Byrnes, KR Wu, XJ Waynant, RW Ilev, IK Anders, JJ TI Low power laser irradiation alters gene expression of olfactory ensheathing cells in vitro SO LASERS IN SURGERY AND MEDICINE LA English DT Article DE BDNF; cellular proliferation; extracellular matrix proteins; GDNF; growth factors; low power laser irradiation; NT3; photobiomodulation; rat ID SPINAL-CORD-INJURY; RAT-LIVER MITOCHONDRIA; CENTRAL-NERVOUS-SYSTEM; HELIUM-NEON LASER; SCHWANN-CELLS; FUNCTIONAL RECOVERY; NEUROTROPHIC FACTOR; MESSENGER-RNA; 660 NM; REGENERATION AB Background and Objectives: Both photobiomodulation (PBM) and olfactory ensheathing cells (OECs) transplantation improve recovery following spinal cord injury. However, neither the combination of these two therapies nor the effect of light on OECs has been reported. The purpose of this study was to determine the effect of light on OEC activity in vitro. Materials and Methods: OECs were purified from adult rat olfactory bulbs and exposed to 810 nm light (150 mW; 0, 0.2, or 68 J/cm(2)). After 7-21 days in vitro, cells underwent immunocytochernistry or RNA extraction and RT-PCR. Results: Analysis of immunolabeling revealed a significant decrease in fibronectin expression in the cultures receiving 68 J/cm(2). Analysis of gene expression revealed a significant (P < 0.05) increase in brain derived neurotrophic factor (BDNF), glial derived neurotrophic factor (GDNF), and collagen expression in the 0.2 j/cm(2) group in comparison to the non-irradiated and 68 J/cm(2) groups. OEC proliferation was also found to significantly increase in both light treated groups in comparison to the control group (P < 0.001). Conclusions: These results demonstrate that low and high dosages of PBM alter OEC activity, including upregulation of a number of neurotrophic growth factors and extracellular matrix proteins known to support neurite outgrowth. Therefore, the application of PBM in conjunction with OEC transplantation warrants consideration as a potential combination therapy for spinal cord injury. C1 Georgetown Univ, Dept Neurosci, Washington, DC 20057 USA. Uniformed Serv Univ Hlth Sci, Dept Anat Physiol & Genet, Bethesda, MD 20814 USA. US FDA, Div Phys, Ctr Devices & Radiol Hlth, HFZ 130, Rockville, MD 20857 USA. RP Byrnes, KR (reprint author), Georgetown Univ, Dept Neurosci, Room EP16A,3970 Reservoir Rd NW, Washington, DC 20057 USA. EM krb27@georgetown.edu OI Byrnes, Kimberly/0000-0002-7501-7734 NR 64 TC 39 Z9 44 U1 0 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PD AUG PY 2005 VL 37 IS 2 BP 161 EP 171 DI 10.1002/lsm.20202 PG 11 WC Dermatology; Surgery SC Dermatology; Surgery GA 961DT UT WOS:000231642800010 PM 16037971 ER PT J AU Li, BG Brown, EW D'Agostino, C LeClerc, JE Cebula, TA AF Li, BG Brown, EW D'Agostino, C LeClerc, JE Cebula, TA TI Structure and distribution of the phosphoprotein phosphatase genes, prpA and prpB, among Shigella subgroups SO MICROBIOLOGY-SGM LA English DT Article ID ENTEROINVASIVE ESCHERICHIA-COLI; COMPLETE GENOME SEQUENCE; LENGTH DIFFERENCE TEST; SALMONELLA-ENTERICA; NATURAL-POPULATIONS; STRAINS; FLEXNERI; PATHOGENICITY; STRATEGIES; MUTATIONS AB Phosphoprotein phosphatases encoded by the prpA and prpB genes function in signal transduction pathways for degradation of misfolded proteins in the extracytoplasmic compartments of Escherichia coli. In order to trace the evolution of prp genes and assess their roles in other enteric pathogens, the structure and distribution of these genes among closely related Shigella subgroups were studied. PCR amplification, probe hybridization studies and DNA sequencing were used to determine the prp genotypes of 58 strains from the four Shigella subgroups, Dysenteriae, Boydii, Sonnei and Flexneri. It was found that the prp alleles among Shigella subgroups were extremely susceptible to gene inactivation and that the mutations involved in prp allele inactivation were varied. They included IS insertions, gene replacement by an IS element, a small deletion within the gene or large deletion engulfing the entire gene region, and base substitutions that generated premature termination codons. As a result, of 58 strains studied, only eight (14%) possessed intact prpA and prpB genes. Of the Shigella strains examined, 76% (44/58) showed at least one of the prp alleles inactivated by one or more IS elements, including IS1, IS4, IS600 and IS629. Phylogenetic analysis revealed that IS elements have been independently acquired in multiple lineages of Shigella, suggesting that loss of functional alleles has been advantageous during Shigella strain evolution. C1 US FDA, Ctr Food Safety & Appl Nutr, Div Mol Biol, Laurel, MD 20708 USA. RP Cebula, TA (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Div Mol Biol, 8301 Muirkirk Rd, Laurel, MD 20708 USA. EM tcebula@cfsan.fda.gov NR 37 TC 3 Z9 3 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 2005 VL 151 BP 2671 EP 2683 DI 10.1099/mic.0.27990-0 PN 8 PG 13 WC Microbiology SC Microbiology GA 958PA UT WOS:000231459000017 PM 16079345 ER PT J AU Gomes, AV Edmondson, RD Zong, C Young, GW Liem, DA Wang, GW Jones, RC Thyparambil, S Zhang, J Pantaleon, D Ping, P AF Gomes, A. V. Edmondson, R. D. Zong, C. Young, G. W. Liem, D. A. Wang, G. W. Jones, R. C. Thyparambil, S. Zhang, J. Pantaleon, D. Ping, P. TI Biochemical and proteomic characterization of the murine cardiac 26S proteasome SO MOLECULAR & CELLULAR PROTEOMICS LA English DT Meeting Abstract C1 [Gomes, A. V.; Zong, C.; Young, G. W.; Liem, D. A.; Wang, G. W.; Zhang, J.; Pantaleon, D.; Ping, P.] Univ Calif Los Angeles, Dept Physiol, Div Cardiol, Los Angeles, CA 90024 USA. [Gomes, A. V.; Zong, C.; Young, G. W.; Liem, D. A.; Wang, G. W.; Zhang, J.; Pantaleon, D.; Ping, P.] Univ Calif Los Angeles, Dept Med, Div Cardiol, Los Angeles, CA 90024 USA. [Edmondson, R. D.; Jones, R. C.; Thyparambil, S.] NCTR, Jefferson, AR USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 1535-9476 J9 MOL CELL PROTEOMICS JI Mol. Cell. Proteomics PD AUG PY 2005 VL 4 IS 8 SU 1 BP S175 EP S175 PG 1 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA V44IB UT WOS:000202995300455 ER PT J AU Xu, Z Cawthon, D McCastlain, KA Duhart, HM Newport, GD Fang, H Patterson, TA Slikker, W Ali, SF AF Xu, Z Cawthon, D McCastlain, KA Duhart, HM Newport, GD Fang, H Patterson, TA Slikker, W Ali, SF TI Selective alterations of transcription factors in MPP+-induced neurotoxicity in PC12 cells SO NEUROTOXICOLOGY LA English DT Article; Proceedings Paper CT 21st International Neurotoxicology Conference CY FEB 10-14, 2004 CL Honolulu, HI DE MPP+; dopamine; cell viability; transcription factor; protein/DNA array; neurotoxicity; differentiated PC12 cells ID NERVE GROWTH-FACTOR; KAPPA-B ACTIVATION; PARKINSONS-DISEASE; DOPAMINERGIC-NEURONS; GENE-EXPRESSION; MPTP MODEL; PHEOCHROMOCYTOMA CELLS; MEMBRANE-PERMEABILITY; INDUCED APOPTOSIS; OXIDATIVE STRESS AB MPP+ (1-methyl-4-phenylpyridinium; the active metabolite of the neurotoxin MPTP (1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine)) depletes dopamine (DA) content and elicits cell death in PC12 cells. However, the mechanism of MPP+-induced neurotoxicity is still unclear In this study, the dose response and time-course of MPP'-induced DA depletion and decreased cell viability were determined in nerve growth factor (NGF)-differentiated PC12 cells. The alteration of transcription factors (TFs) induced by MPP+ from a selected dose level and time point was then evaluated using protein/DNA-binding arrays. K-means clustering analysis identified four pattems of protein/DNA-binding changes. Three of the 28 TFs identified in PC12 cells increased by 100% (p53, PRE, Smad SBE) and 2 decreased by 50% (HSE, RXR(DR1)) of control with MPP+ treatment. In addition, three TFs decreased within the range of 33-50% (TFIID, E2F1, CREB) and two TFs increased within the range of 50-100% (PAX-5, Stat4). An electrophoretic mobility shift assay (EMSA) was used to confirm the changes of p53 and HSE. The observed changes in TFs correlated with the alterations of DA and cell viability. The data indicates that selective transcription factors are involved in MPP'-induced neurotoxicity and it provides mechanistic information that may be applicable to animal studies with MPTP and clinical studies of Parkinson's disease. Published by Elsevier Inc. C1 US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Neurochem Lab, Jefferson, AR 72079 USA. US FDA, Natl Ctr Toxicol Res, Bioinformat Div, Z Tech Corp, Jefferson, AR 72079 USA. RP Ali, SF (reprint author), US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Neurochem Lab, HFT-132,3900 NCTR Rd, Jefferson, AR 72079 USA. EM sali@nctr.fda.gov NR 70 TC 25 Z9 27 U1 2 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0161-813X J9 NEUROTOXICOLOGY JI Neurotoxicology PD AUG PY 2005 VL 26 IS 4 BP 729 EP 737 DI 10.1016/j.neuro.2004.12.008 PG 9 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA 961VH UT WOS:000231689400023 PM 16112330 ER PT J AU Cohen, MH Johnson, JR Chen, YF Sridhara, R Pazdur, R AF Cohen, MH Johnson, JR Chen, YF Sridhara, R Pazdur, R TI FDA drug approval summary: Erlotinib (Tarceva (R)) tablets SO ONCOLOGIST LA English DT Article DE erlotinib (Tarceva (R)) tablets; non-small cell lung cancer; metastatic; second-line treatment ID GROWTH-FACTOR RECEPTOR; CELL LUNG-CANCER; MUTATIONS; GEFITINIB; OSI-774 AB On November 18,2004, erlotinib (Tarceva (R); OSI Pharmaceuticals, Inc., Melville, NY, http://www.osip.com, and Genentech, Inc., South San Francisco, CA, http:// www.gene.com) received regular approval as monotherapy for the treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) after failure of at least one prior chemotherapy regimen. Survival of erlotinib-treated patients was superior to that of placebo-treated patients. The median survival duration of erlotinib-treated patients was 6.67 months, compared with 4.70 months for placebo-treated patients. Exploratory univariate analyses showed a larger survival prolongation in two subsets of patients: those who never smoked and those with epidermal growth factor receptor (EGFR)-positive tumors. Patients who never smoked and were EGFR-positive had a large erlotinib survival benefit. Erlotinib was also superior to placebo for progression-free survival and a response rate of 8.9% versus 0.9%. Skin rash and diarrhea were the most common erlotinib adverse events. Severe rash occurred in 8%, and severe diarrhea occurred in 6% of erlotinib-treated patients. In the first-line treatment of NSCLC, two large, controlled, randomized trials showed no benefit from adding erlotinib to doublet, platinum-based chemotherapy. Therefore, erlotinib is not indicated for use in this setting. C1 US FDA, HFD 150, Div Oncol Drug Prod, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Cohen, MH (reprint author), US FDA, HFD 150, Div Oncol Drug Prod, Ctr Drug Evaluat & Res, 5600 Fishers Lane, Rockville, MD 20857 USA. EM cohenma@cder.fda.gov NR 10 TC 178 Z9 196 U1 2 U2 11 PU ALPHAMED PRESS PI MIAMISBURG PA ONE PRESTIGE PLACE, STE 290, MIAMISBURG, OH 45342-3758 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PD AUG PY 2005 VL 10 IS 7 BP 461 EP 466 DI 10.1634/theoncologist.10-7-461 PG 6 WC Oncology SC Oncology GA 960SP UT WOS:000231613800001 PM 16079312 ER PT J AU Berhane, BT Zong, CG Liem, DA Huang, A Le, S Edmondson, RD Jones, RC Qiao, X Whitelegge, JP Ping, PP Vondriska, TM AF Berhane, BT Zong, CG Liem, DA Huang, A Le, S Edmondson, RD Jones, RC Qiao, X Whitelegge, JP Ping, PP Vondriska, TM TI Cardiovascular-related proteins identified in human plasma by the HUPO Plasma Proteome Project pilot Phase SO PROTEOMICS LA English DT Article DE atherosclerosis; biomaker; biosignature; blood; ischemic heart disease; myocardial infraction ID HEART-FAILURE; GROWTH; RECEPTORS; DISEASE; BIOLOGY AB Proteomic profiling of accessible bodily fluids, such as plasma, has the potential to accelerate biomarker/biosignature development for human diseases. The HUPO Plasma Proteome Project pilot phase examined human plasma with distinct proteomic approaches across multiple laboratories worldwide. Through this effort, we confidently identified 3020 proteins, each requiring a minimum of two high-scoring MS/MS spectra. A critical step subsequent to protein identification is functional annotation, in particular with regard to organ systems and disease. Performing exhaustive literature searches, we have manually annotated a subset of these 3020 proteins that have cardiovascular-related functions on the basis of an existing body of published information. These cardiovascular-related proteins can be organized into eight groups: markers of inflammation and/or cardiovascular disease, vascular and coagulation, signaling, growth and differentiation, cytoskeletal, transcription factors, channels/receptors and heart failure and remodeling. In addition, analysis of the peptide per protein ratio for MS/MS identification reveals group-specific trends. These findings serve as a resource to interrogate the functions of plasma proteins, and moreover, the list of cardiovascular-related proteins in plasma constitutes a baseline proteomic blueprint for the future development of biosignatures for diseases such as myocardial ischemia and atherosclerosis. C1 Univ Calif Los Angeles, Cardiovasc Res Labs, Dept Physiol, Div Cardiol,David Geffen Sch Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Cardiovasc Res Labs, Dept Med, Div Cardiol,David Geffen Sch Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Chem & Biochem, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Vondriska, TM (reprint author), Univ Calif Los Angeles, Cardiovasc Res Labs, Dept Physiol, Div Cardiol,David Geffen Sch Med, Room 1619,MRL Bldg, Los Angeles, CA 90095 USA. EM tvondriska@mednet.ucla.edu OI Ping, Peipei/0000-0003-3583-3881; Berhane, Beniam/0000-0002-1963-376X NR 28 TC 56 Z9 64 U1 0 U2 9 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1615-9853 J9 PROTEOMICS JI Proteomics PD AUG PY 2005 VL 5 IS 13 BP 3520 EP 3530 DI 10.1002/pmic.200401308 PG 11 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 958VZ UT WOS:000231477600027 PM 16052623 ER PT J AU Brynes, SD AF Brynes, SD TI Demystifying 21 CFR Part 556 - Tolerances for residues of new animal drugs in food SO REGULATORY TOXICOLOGY AND PHARMACOLOGY LA English DT Article DE Code of Federal Regulations; 21 CFR 556; animal drug residues; tolerances; safe concentrations AB 21 Code of Federal Regulations Part 556 (Tolerances for Residues of New Animal Drugs in Foods) is one of the Center for Veterinary Medicine's most significant set of regulations. However, in many respects, it is outdated. Subpart A (General Provisions) defines tolerance designations that are obsolete, while Subpart B (Specific Tolerances for Residues of New Animal Drugs) is inconsistent in terminology and often confusing. The purpose of this paper is to define the older terms and update the reader as to current concepts that apply to tolerance-setting for new animal drugs. A list of useful definitions appears at the end of the article. C1 US FDA, Ctr Vet Med, Rockville, MD 20855 USA. RP Brynes, SD (reprint author), US FDA, Ctr Vet Med, 7500 Standish Pl, Rockville, MD 20855 USA. EM sbrynes@cvm.fda.gov NR 0 TC 4 Z9 5 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0273-2300 J9 REGUL TOXICOL PHARM JI Regul. Toxicol. Pharmacol. PD AUG PY 2005 VL 42 IS 3 BP 324 EP 327 DI 10.1016/j.yrtph.2005.05.009 PG 4 WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology SC Legal Medicine; Pharmacology & Pharmacy; Toxicology GA 955EY UT WOS:000231209400008 PM 16006026 ER PT J AU Hong, H Tong, W Xie, Q Fang, H Perkins, R AF Hong, H Tong, W Xie, Q Fang, H Perkins, R TI An in silico ensemble method for lead discovery: decision forest SO SAR AND QSAR IN ENVIRONMENTAL RESEARCH LA English DT Article DE decision forest; lead discovery; classification; estrogen binding; QSAR ID ESTROGEN-RECEPTOR BINDING; PATTERN-RECOGNITION; SET; PREDICTIONS; CHEMICALS; MODELS; SYSTEM AB Recent progress in combinatorial chemistry and parallel synthesis has radically changed the approach to drug discovery in the pharmaceutical industry. At present, thousands of compounds can be made in a short period, creating a need for fast and effective in silico methods to select the most promising lead candidates. Decision forest is a novel pattern recognition method, which combines the results of multiple distinct but comparable decision tree models to reach a consensus prediction. In this article, a decision forest model was developed using a structurally diverse training data set containing 232 compounds whose estrogen receptor binding activity was tested at the U.S. Food and Drug Administration (FDA)'s National Center for Toxicological Research (NCTR). The model was subsequently validated using a test data set of 463 compounds selected from the literature, and then applied to a large data set with 57,145 compounds as a screening example. The results show that the decision forest method is a fast, reliable and effective in silico approach, which could be useful in drug discovery. C1 US FDA, Div Syst Toxicol, Ctr Toxicoinformat, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. US FDA, Div Bioinformat, Z Tech, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Tong, W (reprint author), US FDA, Div Syst Toxicol, Ctr Toxicoinformat, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM wtong@nctr.fda.gov NR 21 TC 28 Z9 28 U1 0 U2 2 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1062-936X J9 SAR QSAR ENVIRON RES JI SAR QSAR Environ. Res. PD AUG PY 2005 VL 16 IS 4 BP 339 EP 347 DI 10.1080/10659360500203022 PG 9 WC Chemistry, Multidisciplinary; Computer Science, Interdisciplinary Applications; Environmental Sciences; Mathematical & Computational Biology; Toxicology SC Chemistry; Computer Science; Environmental Sciences & Ecology; Mathematical & Computational Biology; Toxicology GA 966PE UT WOS:000232032200004 PM 16234175 ER PT J AU Guo, TL Germolec, DR Musgrove, DL Delclos, KB Weis, C White, KL AF Guo, TL Germolec, DR Musgrove, DL Delclos, KB Weis, C White, KL TI Myelotoxicity in genistein-, nonylphenol-, methoxychlor-, vinclozolin- or ethinyl estradiol-exposed F-1 generations of Sprague-Dawley rats following developmental and adult exposures SO TOXICOLOGY LA English DT Article DE endocrine active chemicals; genistem; nonylphenol; ethinyl estradiol; vinclozolin; methoxychlor and developmental myelotoxicity ID ESTROGEN-RECEPTORS ALPHA; PHENOTYPIC MARKER EXPRESSION; DOSE ORAL-CONTRACEPTIVES; FORMING CELL RESPONSE; IN-VITRO; SOY ISOFLAVONES; BETA; PHYTOESTROGENS; MICE; CHEMICALS AB The myelotoxicity of five endocrine active chemicals was evaluated in F, generation of Sprague-Dawley rats following developmental and adult exposures at three concentration levels. Rats were exposed to genistein (GEN: 25, 250 and 1250 ppm), nonylphenol (NPH: 25, 500 and 2000 ppm), methoxychlor (MXC: 10, 100 and 1000 ppm), vinclozolin (VCZ: 10, 150 and 750 ppm) and ethinyl estradiol (EE2: 5, 25 and 200 ppb) gestationally and lactationally through dams from day 7 of gestation and through feed after weaning on postnatal day (PND) 22 to PND 64. The parameters examined included the number of recovered bone marrow cells, DNA synthesis, and colony forming units (CFU) in the presence of granulocyte macrophage-colony stimulating factor (GM-CSF), macrophage colony-stimulating factor (M-CSF) and erythropoietin. Except for the EE2, the concentrations of other individual chemicals in the diet were in an approximate range that allowed for a comparison to be made in terms of myelotoxic potency. Decreases in the DNA synthesis, CFU-GM and CFU-M seemed to be the common findings among the alterations induced by these compounds. Using the numbers of alterations induced by each chemical in the parameters examined as criteria for comparison, the order of myelotoxic potency in F, males was: GEN > MXC > NPH > VCZ; the order in females: GEN > NPH > VCZ. Additionally, some of the functional changes induced by these compounds were gender-specific or dimorphic. Overall, the results demonstrated that developmental and adult exposures of F, rats to these endocrine active chemicals at the concentrations tested had varied degrees of myelotoxicity with GEN being the most potent. Furthermore, the sex-specific effects of these chemicals in F, male and female rats suggest that there may be interactions between these compounds and sex hormone in modulating these responses. (C) 2005 Elsevier Ireland Ltd. All rights reserved. C1 Virginia Commonwealth Univ, Dept Pharmacol & Toxicol, Richmond, VA 23298 USA. NIEHS, Mol Toxicol Lab, Res Triangle Pk, NC 27709 USA. US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Guo, TL (reprint author), Virginia Commonwealth Univ, Dept Pharmacol & Toxicol, POB 980613, Richmond, VA 23298 USA. EM tlguo@hsc.vcu.edu FU NIEHS NIH HHS [ES55094]; PHS HHS [224-93-0001] NR 57 TC 19 Z9 24 U1 1 U2 5 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0300-483X J9 TOXICOLOGY JI Toxicology PD AUG 1 PY 2005 VL 211 IS 3 BP 207 EP 219 DI 10.1016/j.tox.2005.03.008 PG 13 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 934OY UT WOS:000229719300004 PM 15925024 ER PT J AU Burr, DH Rollins, D Lee, LH Pattarini, DL Walz, SS Tian, JH Pace, JL Bourgeois, AL Walker, RI AF Burr, DH Rollins, D Lee, LH Pattarini, DL Walz, SS Tian, JH Pace, JL Bourgeois, AL Walker, RI TI Prevention of disease in ferrets fed an inactivated whole cell Campylobacter jejuni vaccine SO VACCINE LA English DT Article DE Campylobacter; vaccine; diarrhea ID INFECTION; MODEL; ENTERITIS; COLONIZATION; THAILAND; IMMUNITY; CHILDREN AB Ferrets were used to demonstrate the potential of a killed whole cell vaccine prepared from Campylobacter jejuni to protect against disease. C jejuni strain 81-176 was grown in BHI broth, formalin-fixed, and resuspended in PBS to a concentration of 10(10) cells per ml. This vaccine (CWC) or live organisms were delivered orally with a nasogastric tube into anesthetized animals treated to reduce gastric acidity and intestinal motility. When 5 x 10(10) CFU of the vaccine strain (Lior serotype 5) or one of two other serotypes, CGL-7 (Lior 4) or BT44 (Lior 9), was used to challenge the ferrets, all of the animals developed a mucoid diarrhea. If the animals had been challenged with 5 x 109 CFU of the homologous strain I month before challenge with 10(10) CFU, 80-100% protection against disease was seen. This protection was also obtained after an initial exposure to the 81-176 strain followed by challenge with either of the heterologous strains. CWC was used to see if protection demonstrated with the live organisms could be produced with the non-living preparation. When 10(9) cells of CWC was given as two doses 7 days apart with or without 25 mu g of a coadministered mucosal adjuvant, LTR192G, only 40-60% of the animals were protected. If the regimen was changed to four doses given 48 h apart, 80% of the animals were free of diarrhea after subsequent challenge. Increasing the number of cells in the four dose regimen to 10(10) cells did not improve protection. Animals given four doses of 10(10) cells combined with LTR192G were subsequently challenged with 10(10) cells of the homologous strain or the heterologous strain CGL-7. The CWC protected against both strains. Serum IgG antibody titers determined by ELISA showed little increase following the CWC four dose vaccination regimen, compared to animals given one dose of the live organism. On subsequent challenge, however, both CWC vaccinated and live-challenged ferrets showed comparable antibody titer increases above those obtained following the initial challenge or vaccination. Western blots were used to show that the immunodominant antigen in vaccinated animals was a 45 kDa protein, while in ferrets challenged with live organisms the immunodominant antigen was a 62 kDa protein. These data show that the CWC can be used to protect against disease caused by Campylobacter. They also show that protection and serum IgG responses do not depend upon the use of the mucosal adjuvant and that cross protection among some of the major serotypes of Campylobacter responsible for human disease is possible. Published by Elsevier Ltd. C1 US FDA, Laurel, MD 20708 USA. USN, Med Res Ctr, Enter Dis Program, Silver Spring, MD 20910 USA. Antex Biol, Gaithersburg, MD 20879 USA. RP Walker, RI (reprint author), US FDA, Div Bacterial Parasit & Allergen Prod, Ctr Biol Evaluat & Res, 1401 Rockville Pike,HFM-425, Rockville, MD 20851 USA. EM walkerri@cber.fda.gov NR 26 TC 12 Z9 13 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD JUL 29 PY 2005 VL 23 IS 34 BP 4315 EP 4321 DI 10.1016/j.vaccine.2005.03.038 PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 951RG UT WOS:000230947600005 PM 16005742 ER PT J AU Mossoba, MM Al-Khaldi, SF Kirkwood, J Fry, FS Sedman, J Ismail, AA AF Mossoba, MM Al-Khaldi, SF Kirkwood, J Fry, FS Sedman, J Ismail, AA TI Printing microarrays of bacteria for identification by infrared micro spectroscopy SO VIBRATIONAL SPECTROSCOPY LA English DT Article; Proceedings Paper CT 3rd International Conference on Shedding Light on Disease - Optical Diagnostics for the New Millenium (SPEC 2004) CY JUN 19-23, 2004 CL Newark, NJ DE microarray; bacteria identification; infrared; food safety; imaging; FPA-FTIR ID PLANE-ARRAY DETECTOR; VIBRATIONAL SPECTROSCOPY; DISCRIMINATION; MICROORGANISMS AB Fourier transform infrared (FTIR) spectroscopy has been established as a rapid bacteria identification technique. To increase the throughput of this methodology, the feasibility of applying contact deposition microarray technology to print intact bacterial cells as arrayed deposits (150 mu m diameter) on optical substrates and on agar slides was demonstrated for the first time. This contact deposition technology delivers nanoliter (nL) droplets of bacterial suspensions from a microliter plate onto a slide surface. Protocols for printing microarrays of whole-cells on agar and on infrared (IR)-transparent slides were evaluated and optimized for subsequent measurement by IR microspectroscopy and IR imaging. Parameters that were investigated included pin capacity, deposition mode, and spatial distribution of microarrays. Bacteria representing eight genera (Yersinia, Staphylococcus, Salmonella, Listeria, Enterobacter, Citrobacter, Klebsiella, and Escherichia) were used in this proof-of-concept study. The resulting dendrograms generated by hierarchical cluster analysis (HCA) demonstrated clustering of the descendants of the foodborne bacteria investigated into their respective branches. The suitability of microarray printing coupled to focal-plane-array (FPA) FTIR detection for the rapid identification of bacteria was demonstrated. Published by Elsevier B.V. C1 US FDA, Ctr Food Safety & Appl Nutr, Div Gen Sci Support, OSAS, College Pk, MD 20740 USA. US FDA, OPDFB, Div Microbiol Studies, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. McGill Univ, Dept Food Sci & Agr Chem, McGill IR Grp, Montreal, PQ H9X 3V9, Canada. RP Mossoba, MM (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Div Gen Sci Support, OSAS, 5100 Paint Branch Pkway, College Pk, MD 20740 USA. EM magdi.mossoba@fda.hhs.gov NR 18 TC 27 Z9 29 U1 2 U2 14 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-2031 J9 VIB SPECTROSC JI Vib. Spectrosc. PD JUL 29 PY 2005 VL 38 IS 1-2 BP 229 EP 235 DI 10.1016/j.vibspec.2005.04.006 PG 7 WC Chemistry, Analytical; Chemistry, Physical; Spectroscopy SC Chemistry; Spectroscopy GA 952UP UT WOS:000231031300032 ER PT J AU Chowdhury, BA AF Chowdhury, BA TI Treatment of mild asthma SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 US FDA, Rockville, MD 20857 USA. RP Chowdhury, BA (reprint author), US FDA, Rockville, MD 20857 USA. EM chowdhuryb@cder.fda.gov NR 2 TC 0 Z9 0 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUL 28 PY 2005 VL 353 IS 4 BP 424 EP 424 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 949JW UT WOS:000230782800028 PM 16050059 ER PT J AU Jhoo, JW Lo, CY Li, SM Sang, SM Ang, CYW Heinze, TM Ho, CT AF Jhoo, JW Lo, CY Li, SM Sang, SM Ang, CYW Heinze, TM Ho, CT TI Stability of black tea polyphenol, theaflavin, and identification of theanaphthoquinone as its major radical reaction product SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE theaflavin; theanaphthoquinone; oxidation; radical oxidation; pH stability ID GREEN TEA; ANTIOXIDANT MECHANISM; CATECHINS AB In the current study, we have focused on isolation and detection of major radical oxidation products from theaflavin in order to better understand antioxidation mechanisms of this compound. Theanaph-thoquinone was identified as a major oxidation product of theaflavin from two different oxidant model systems: DPPH and peroxidase/hydrogen peroxide. This result indicated that the benzotropolone moiety in theaflavin may play an important role in its antioxidant properties. The stability of theaflavin was studied in varying pH solutions: simulated gastric juice and buffer solutions of pH 5.5, pH 7.4, and pH 8.5. The results indicated that theaflavin is unstable in alkaline conditions, while it was stable in acidic conditions. Theanaphthoquinone was identified as an autoxidation product of theaflavin during its stability study in alkaline conditions. C1 Rutgers State Univ, Dept Food Sci, New Brunswick, NJ 08901 USA. US FDA, Natl Ctr Toxicol Res, Div Chem, Jefferson, AR 72079 USA. RP Ho, CT (reprint author), Rutgers State Univ, Dept Food Sci, 65 Dudley Rd, New Brunswick, NJ 08901 USA. EM ho@aesop.rutgers.edu NR 18 TC 26 Z9 29 U1 0 U2 18 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 JUL 27 PY 2005 VL 53 IS 15 BP 6146 EP 6150 DI 10.1021/jf050662d PG 5 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 948FW UT WOS:000230702400049 PM 16029009 ER PT J AU Wagner, RD Cerniglia, CE AF Wagner, RD Cerniglia, CE TI Antimicrobial susceptibility patterns of competitive exclusion bacteria applied to newly hatched chickens SO INTERNATIONAL JOURNAL OF FOOD MICROBIOLOGY LA English DT Article DE competitive exclusion; antimicrobial susceptibility testing; anaerobic; poultry; antimicrobial drug resistance ID ANTIBIOTIC-RESISTANCE; ENTEROCOCCUS-FAECIUM; ANIMALS; FOOD; ENVIRONMENT; SALMONELLA; POULTRY; ORIGIN AB Competitive exclusion (CE) products are mixtures of obligate and facultative anaerobic bacteria applied to poultry hatchlings for prevention of Salmonella colonization. These mixtures have the potential to introduce bacteria with undesirable antimicrobial drug resistance traits into the human food supply. Antimicrobial drug susceptibilities of 27 obligate and facultative anaerobes isolated from a commercial CE product were evaluated with a microdilution minimal inhibitory concentration (MIC) assay. Bacteroides distasonis and Bacteroides fragilis isolates were resistant to tetracycline and other antimicrobial drugs. An Escherichia coli isolate was resistant to four antimicrobial drugs: erythromycin, penicillin, vancomycin, and tylosin. Erythromycin-resistant enterococci and vancomycin-resistant Lactococcus lactis isolates in the CE product were detected. These findings suggest that more work needs to be done to assess the potential effects of CE product use in poultry on the food supply. (c) 2005 Elsevier B.V. All rights reserved. C1 Natl Ctr Toxicol Res, Microbiol Div, Jefferson, AR 72079 USA. RP Wagner, RD (reprint author), Natl Ctr Toxicol Res, Microbiol Div, 3900 NCTR Rd,HFT-250, Jefferson, AR 72079 USA. EM dwagner@nctr.fda.gov NR 27 TC 5 Z9 5 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-1605 J9 INT J FOOD MICROBIOL JI Int. J. Food Microbiol. PD JUL 25 PY 2005 VL 102 IS 3 BP 349 EP 353 DI 10.1016/j.ijfoodmicro.2004.11.034 PG 5 WC Food Science & Technology; Microbiology SC Food Science & Technology; Microbiology GA 952NF UT WOS:000231010200009 PM 16014302 ER PT J AU Belluco, C Mammano, E Petricoin, E Prevedello, L Calvert, V Liotta, L Nitti, D Lise, M AF Belluco, C Mammano, E Petricoin, E Prevedello, L Calvert, V Liotta, L Nitti, D Lise, M TI Kinase substrate protein microarray analysis of human colon cancer and hepatic metastasis SO CLINICA CHIMICA ACTA LA English DT Article; Proceedings Paper CT International Conference on Laboratory Medicine CY OCT 29, 2002 CL Padua, ITALY SP Int Soc Enzymol DE proteomics; colorectal cancer; metastasis; protein kinases ID ACTIVATION AB Background: Liver metastases represent the major determinant of survival in patients with colorectal cancer (CRC). In cases with unresectable liver disease, more effective agents are needed, since chemotherapy achieves median survival of only 15 months. Protein kinases coordinate complex functions that are often disregulated in cancer and are therefore considered important targets for molecular therapeutics. In this study, we investigated the phosphoproteomic status of different protein kinases in primary CRC and in liver metastases. Methods: The status of 29 key endpoints was evaluated using reverse phase protein array on laser capture microdissected neoplastic cells from five primary CRCs without metastases, three patient-matched primary CRCs and synchronous liver metastases and five CRC metachronous liver metastases. Results: Unsupervised hierarchical two-way clustering analysis showed an entirely different phosphoproteomic profile in primary CRCs compared to liver metastases. This difference was observed also in primary and metastatic patient-matched lesions. Conclusions: Our findings of different signaling pathways between primary and metastatic CRC suggest a possible microenvironment effect, and emphasize the need to perform molecular network analysis of metastatic tissue when molecular targeting is considered. (c) 2005 Elsevier B.V. All rights reserved. C1 Univ Padua, Surg Branch, Dept Oncol & Surg Sci, Padua, Italy. US FDA, Ctr Biol Evaluat & Res, NCI Clin Prote Program, Bethesda, MD 20014 USA. US FDA, Clin Prote Program, Pathol Lab, NCI, Bethesda, MD 20014 USA. RP Belluco, C (reprint author), Univ Padua, Surg Branch, Dept Oncol & Surg Sci, Padua, Italy. EM claudio.belluco@unipd.it OI belluco, claudio/0000-0001-5972-9574 NR 9 TC 30 Z9 32 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0009-8981 J9 CLIN CHIM ACTA JI Clin. Chim. Acta PD JUL 24 PY 2005 VL 357 IS 2 SI SI BP 180 EP 183 DI 10.1016/j.cccn.2005.03.024 PG 4 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 950IN UT WOS:000230850900010 PM 15921671 ER PT J AU Gomes, AV Edmondson, RD Zong, CG Young, G Liem, DA Wang, GW Jones, RC Thyparambil, S Zhang, J Pantaleon, D Ping, PP AF Gomes, AV Edmondson, RD Zong, CG Young, G Liem, DA Wang, GW Jones, RC Thyparambil, S Zhang, J Pantaleon, D Ping, PP TI Biochemical and proteomic characterization of the murine cardiac 26S proteasome SO CIRCULATION RESEARCH LA English DT Meeting Abstract CT 2nd Annual Symposium of the American-Heart-Association-Council-on-Basic-Cardiovascular-Sciences CY JUL 24-27, 2005 CL Keystone, CO SP Amer Heart Assoc Council Basic Cardiovasc Sci, Amer Heart Assoc Interdisciplinary Working Grp Functional Geonom & Translat Biol, Natl Heart, Lung & Blood Inst C1 Univ Calif Los Angeles, Los Angeles, CA 90024 USA. NCTR, Jefferson, AR USA. NR 0 TC 1 Z9 2 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7330 J9 CIRC RES JI Circ.Res. PD JUL 22 PY 2005 VL 97 IS 2 MA 146 BP E36 EP E36 PG 1 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 947TH UT WOS:000230668900152 ER PT J AU Kainz, W Christ, A Kellom, T Seidman, S Nikoloski, N Beard, B Kuster, N AF Kainz, W Christ, A Kellom, T Seidman, S Nikoloski, N Beard, B Kuster, N TI Dosimetric comparison of the specific anthropomorphic mannequin (SAM) to 14 anatomical head models using a novel definition for the mobile phone positioning SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID ENERGY-ABSORPTION; ELECTROMAGNETIC ABSORPTION; CELLULAR TELEPHONES; LIMITING EXPOSURE; 1900 MHZ; 300 GHZ; CHILDREN; GUIDELINES; ANTENNA; DIPOLE AB This paper presents new definitions for obtaining reproducible results in numerical phone dosimetry. Numerous numerical dosimetric studies have been published about the exposure of mobile phone users which concluded with conflicting results. However, many of these studies lack reproducibility due to shortcomings in the description of the phone positioning. The new approach was tested by two groups applying two different numerical program packages to compare the specific anthropomorphic mannequin (SAM) to 14 anatomically correct head models. A novel definition for the positioning of mobile phones next to anatomically correct head models is given along with other essential parameters to be reported. The definition is solely based on anatomical characteristics of the head. A simple up-to-date phone model was used to determine the peak spatial specific absorption rate (SAR) of mobile phones in SAM and in the anatomically correct head models. The results were validated by measurements. The study clearly shows that SAM gives a conservative estimate of the exposure in anatomically correct head models for head only tissue. Depending on frequency, phone position and head size the numerically calculated 10 g averaged SAR in the pinna can be up to 2.1 times greater than the peak spatial SAR in SAM. Measurements in small structures, such as the pinna, will significantly increase the uncertainty; therefore SAM was designed for SAR assessment in the head only. Whether SAM will provide a conservative value for the pinna depends on the pinna SAR limit of the safety standard considered. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20852 USA. ITIS, Fdn Res Informat Technol Soc, CH-8004 Zurich, Switzerland. RP Kainz, W (reprint author), US FDA, Ctr Devices & Radiol Hlth, 12725 Twinbrook Pkwy, Rockville, MD 20852 USA. EM wolfgang.kainz@fda.hhs.gov RI Foundation, IT'IS/B-9559-2008; OI Beard, Brian/0000-0001-6480-0857 NR 29 TC 47 Z9 47 U1 0 U2 6 PU IOP PUBLISHING LTD PI BRISTOL PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD JUL 21 PY 2005 VL 50 IS 14 BP 3423 EP 3445 DI 10.1088/0031-9155/50/14/016 PG 23 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 952ZA UT WOS:000231043800016 PM 16177519 ER PT J AU Miyaji, M Jin, ZX Yamaoka, S Amakawa, R Fukuhara, S Sato, SB Kobayashi, T Domae, N Mimori, T Bloom, ET Okazaki, T Umehara, H AF Miyaji, M Jin, ZX Yamaoka, S Amakawa, R Fukuhara, S Sato, SB Kobayashi, T Domae, N Mimori, T Bloom, ET Okazaki, T Umehara, H TI Role of membrane sphingomyelin and ceramide in platform formation for Fas-mediated apoptosis SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID TYROSINE KINASE P72(SYK); LIPID RAFTS; CELL-SURFACE; PHOSPHATIDYLINOSITOL 3-KINASE; IMMUNOLOGICAL SYNAPSE; OXIDATIVE DAMAGE; LYMPHOID-CELLS; DEATH RECEPTOR; T-CELLS; ACTIVATION AB Engagement of the Fas receptor ( CD95) initiates multiple signaling pathways that lead to apoptosis, such as the formation of death-inducing signaling complex ( DISC), activation of caspase cascades, and the generation of the lipid messenger, ceramide. Sphingomyelin (SM) is a major component of lipid rafts, which are specialized structures that enhance the efficiency of membrane receptor signaling and are a main source of ceramide. However, the functions of SM in Fas-mediated apoptosis have yet to be clearly defined, as the responsible genes have not been identified. After cloning a gene responsible for SM synthesis, SMS1, we established SM synthase-defective WR19L cells transfected with the human Fas gene (WR/Fas-SM(-)), and cells that have been functionally restored by transfection with SMS1 (WR/Fas-SMS1). We show that expression of membrane SM enhances Fas-mediated apoptosis through increasing DISC formation, activation of caspases, efficient translocation of Fas into lipid rafts, and subsequent Fas clustering. Furthermore, WR/Fas-SMS1 cells, but not WR/Fas-SM(-) cells, showed a considerable increase in ceramide generation within lipid rafts upon Fas stimulation. These data suggest that a membrane SM is important for Fas clustering through aggregation of lipid rafts, leading to Fas-mediated apoptosis. C1 Kyoto Univ, Grad Sch Med, Dept Rheumatol & Clin Immunol, Sakyo Ku, Kyoto 6068507, Japan. Kansai Med Univ, Dept Internal Med 1, Moriguchi, Osaka 5708506, Japan. Kanazawa Med Univ, Dept Internal Med, Div Hematol & Immunol, Kanazawa, Ishikawa 9200293, Japan. Tottori Univ, Fac Med, Dept Clin Lab Med Hematol, Yonago, Tottori 6838504, Japan. RIKEN, Wako, Saitama 3510198, Japan. Kyoto Univ, Grad Sch Sci, Dept Biophys, Kyoto 6068502, Japan. Osaka Dent Univ, Dept Med, Hirakata, Osaka 5731121, Japan. US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Bethesda, MD 20892 USA. RP Umehara, H (reprint author), Kyoto Univ, Grad Sch Med, Dept Rheumatol & Clin Immunol, Sakyo Ku, Kyoto 6068507, Japan. EM umehara@kanazawa-med.ac.jp RI Kobayashi, Toshihide/B-6298-2015 OI Kobayashi, Toshihide/0000-0002-4811-7270 NR 57 TC 111 Z9 118 U1 0 U2 2 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 18 PY 2005 VL 202 IS 2 BP 249 EP 259 DI 10.1084/jem.20041685 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 946UE UT WOS:000230597800008 PM 16009715 ER PT J AU Cowley, SC Hamilton, E Frelinger, JA Su, J Forman, J Elkins, KL AF Cowley, SC Hamilton, E Frelinger, JA Su, J Forman, J Elkins, KL TI CD4(-)CD8(-) T cells control intracellular bacterial infections both in vitro and in vivo SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID LIVE VACCINE STRAIN; FRANCISELLA-TULARENSIS; PROTECTIVE IMMUNITY; MYCOBACTERIUM-TUBERCULOSIS; CD4-DEFICIENT MICE; B-CELLS; GENERATION; LVS; RESISTANCE; EFFECTOR AB Memory T cells, including the well-known CD4(+) and CD8(+) T cells, are central components of the acquired immune system and are the basis for successful vaccination. After infection, CD4(+) and CD8(+) T cells expand into effector cells, and then differentiate into long- lived memory cells. We show that a rare population of CD4(-)CD8(-)CD3(+)alpha beta(+)gamma delta(-)NK1.1(-) T cells has similar functions. These cells potently and specifically inhibit the growth of the intracellular bacteria Mycobacterium tuberculosis ( M. tb.) or Francisella tularensis Live Vaccine Strain ( LVS) in macrophages in vitro, promote survival of mice infected with these organisms in vivo, and adoptively transfer immunity to F. tularensis LVS. Furthermore, these cells expand in the spleens of mice infected with M. tb. or F. tularensis LVS, and then acquire a memory cell phenotype. Thus, CD4(-)CD8(-) T cells have a role in the control of intracellular infection and may contribute to successful vaccination. C1 US FDA, Ctr Biol Evaluat & Res, Lab Mycobacterial Dis & Cellular Immunol, Rockville, MD 20852 USA. Univ N Carolina, Dept Microbiol & Immunol, Chapel Hill, NC 27599 USA. Univ Texas, SW Med Ctr, Ctr Immunol, Dallas, TX 75390 USA. RP Elkins, KL (reprint author), US FDA, Ctr Biol Evaluat & Res, Lab Mycobacterial Dis & Cellular Immunol, Rockville, MD 20852 USA. EM elkins@cber.fda.gov NR 48 TC 73 Z9 75 U1 0 U2 3 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD JUL 18 PY 2005 VL 202 IS 2 BP 309 EP 319 DI 10.1084/jem.20050569 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 946UE UT WOS:000230597800013 PM 16027239 ER PT J AU Delongchamp, RR Velasco, C Dial, S Harris, AJ AF Delongchamp, RR Velasco, C Dial, S Harris, AJ TI Genome-wide estimation of gender differences in the gene expression of human livers: Statistical design and analysis SO BMC BIOINFORMATICS LA English DT Article; Proceedings Paper CT 2nd Annual Conference of the MidSouth-Computational-Biology-and-Bioinformatics-Society CY OCT 07-09, 2004 CL Little Rock, AK SP MidSouth Computational Biol Bioinformat Soc ID SITE-SPECIFIC RECOMBINATION; MICROARRAY AB Background: Gender differences in gene expression were estimated in liver samples from 9 males and 9 females. The study tested 31,110 genes for a gender difference using a design that adjusted for sources of variation associated with cDNA arrays, normalization, hybridizations and processing conditions. Results: The genes were split into 2,800 that were clearly expressed ( expressed genes) and 28,310 that had expression levels in the background range ( not expressed genes). The distribution of p-values from the 'not expressed' group was consistent with no gender differences. The distribution of p-values from the 'expressed' group suggested that 8 % of these genes differed by gender, but the estimated fold-changes ( expression in males / expression in females) were small. The largest observed fold-change was 1.55. The 95 % confidence bounds on the estimated fold-changes were less than 1.4 fold for 79.3 %, and few (1.1%) exceed 2-fold. Conclusion: Observed gender differences in gene expression were small. When selecting genes with gender differences based upon their p-values, false discovery rates exceed 80 % for any set of genes, essentially making it impossible to identify any specific genes with a gender difference. C1 Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. Louisiana State Univ, Hlth Sci Ctr, Sch Publ Hlth, New Orleans, LA 70112 USA. Natl Ctr Toxicol Res, Ctr Hepatotox, Jefferson, AR 72079 USA. Ctr Toxicol & Environm Hlth LLC, Little Rock, AR 72201 USA. RP Delongchamp, RR (reprint author), Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. EM rdelongchamp@nctr.fda.gov; cvelas@lsuhsc.edu; sdial@nctr.fda.gov; aharris@cteh.com FU NIDDK NIH HHS [N01-DK-9-2310] NR 14 TC 18 Z9 18 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2105 J9 BMC BIOINFORMATICS JI BMC Bioinformatics PD JUL 15 PY 2005 VL 6 SU 2 AR S13 DI 10.1186/1471-2105-6-S2-S13 PG 9 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA 022NC UT WOS:000236061500013 PM 16026598 ER PT J AU Fang, H Tong, W Perkins, R Shi, L Hong, H Cao, X Xie, Q Yim, SH Ward, JM Pitot, HC Dragan, YP AF Fang, H Tong, W Perkins, R Shi, L Hong, H Cao, X Xie, Q Yim, SH Ward, JM Pitot, HC Dragan, YP TI Bioinformatics approaches for cross-species liver cancer analysis based on microarray gene expression profiling SO BMC BIOINFORMATICS LA English DT Article; Proceedings Paper CT 2nd Annual Conference of the MidSouth-Computational-Biology-and-Bioinformatics-Society CY OCT 07-09, 2004 CL Little Rock, AR SP MidSouth Computat Biol & Bioinformat Soc ID COMPARATIVE GENOMIC HYBRIDIZATION; HEPATOCELLULAR CARCINOMAS; TRANSGENIC MICE; DNA MICROARRAY; BREAST-CANCER; CELL-LINES; HEPATOCARCINOGENESIS; TUMORIGENESIS; MODELS; GROWTH AB Background: The completion of the sequencing of human, mouse and rat genomes and knowledge of cross-species gene homologies enables studies of differential gene expression in animal models. These types of studies have the potential to greatly enhance our understanding of diseases such as liver cancer in humans. Genes co-expressed across multiple species are most likely to have conserved functions. We have used various bioinformatics approaches to examine microarray expression profiles from liver neoplasms that arise in albumin-SV40 transgenic rats to elucidate genes, chromosome aberrations and pathways that might be associated with human liver cancer. Results: In this study, we first identified 2223 differentially expressed genes by comparing gene expression profiles for two control, two adenoma and two carcinoma samples using an F-test. These genes were subsequently mapped to the rat chromosomes using a novel visualization tool, the Chromosome Plot. Using the same plot, we further mapped the significant genes to orthologous chromosomal locations in human and mouse. Many genes expressed in rat 1q that are amplified in rat liver cancer map to the human chromosomes 10, 11 and 19 and to the mouse chromosomes 7, 17 and 19, which have been implicated in studies of human and mouse liver cancer. Using Comparative Genomics Microarray Analysis (CGMA), we identified regions of potential aberrations in human. Lastly, a pathway analysis was conducted to predict altered human pathways based on statistical analysis and extrapolation from the rat data. All of the identified pathways have been known to be important in the etiology of human liver cancer, including cell cycle control, cell growth and differentiation, apoptosis, transcriptional regulation, and protein metabolism. Conclusion: The study demonstrates that the hepatic gene expression profiles from the albumin-SV40 transgenic rat model revealed genes, pathways and chromosome alterations consistent with experimental and clinical research in human liver cancer. The bioinformatics tools presented in this paper are essential for cross species extrapolation and mapping of microarray data, its analysis and interpretation. C1 US FDA, Div Syst Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Z Tech Corp, Div Bioinformat, Jefferson, AR 72079 USA. NCI, Lab Metab, Ctr Canc Res, Bethesda, MD 20892 USA. NCI, Vet & Tumor Pathol Sect, Ctr Canc Res, Ft Detrick, MD 21702 USA. Univ Wisconsin, McArdle Lab Canc Res, Madison, WI 53706 USA. RP Tong, W (reprint author), US FDA, Div Syst Toxicol, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM hfang@nctr.fda.gov; wtong@nctr.fda.gov; rperkins@nctr.fda.gov; lshi@nctr.fda.gov; hhong@nctr.fda.gov; xcao@nctr.fda.gov; qxie@nctr.fda.gov; yims@mail.nih.gov; jeward@niaid.nih.gov; pitot@oncology.wisc.edu; ydragan@nctr.fda.gov NR 42 TC 19 Z9 22 U1 0 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2105 J9 BMC BIOINFORMATICS JI BMC Bioinformatics PD JUL 15 PY 2005 VL 6 SU 2 AR S6 DI 10.1186/1471-2105-6-S2-S6 PG 10 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA 022NC UT WOS:000236061500006 PM 16026603 ER PT J AU Hong, HX Dragan, Y Epstein, J Teitel, C Chen, BZ Xie, Q Fang, H Shi, LM Perkins, R Tong, WD AF Hong, HX Dragan, Y Epstein, J Teitel, C Chen, BZ Xie, Q Fang, H Shi, LM Perkins, R Tong, WD TI Quality control and quality assessment of data from surface-enhanced laser desorption/ionization (SELDI) time-of flight (TOF) mass spectrometry (MS) SO BMC BIOINFORMATICS LA English DT Article; Proceedings Paper CT 2nd Annual Conference of the MidSouth-Computational-Biology-and-Bioinformatics-Society CY OCT 07-09, 2004 CL Little Rock, AK SP MidSouth Computational Biol Bioinformat Soc ID PROSTATE-CANCER; PROTEIN PROFILES; OVARIAN-CANCER; IDENTIFICATION; IONIZATION; DESORPTION; BIOMARKER; SERUM; DISCOVERY; CARCINOMA AB Background: Proteomic profiling of complex biological mixtures by the ProteinChip technology of surface-enhanced laser desorption/ionization time-of-flight (SELDI-TOF) mass spectrometry ( MS) is one of the most promising approaches in toxicological, biological, and clinic research. The reliable identification of protein expression patterns and associated protein biomarkers that differentiate disease from health or that distinguish different stages of a disease depends on developing methods for assessing the quality of SELDI-TOF mass spectra. The use of SELDI data for biomarker identification requires application of rigorous procedures to detect and discard low quality spectra prior to data analysis. Results: The systematic variability from plates, chips, and spot positions in SELDI experiments was evaluated using biological and technical replicates. Systematic biases on plates, chips, and spots were not found. The reproducibility of SELDI experiments was demonstrated by examining the resulting low coefficient of variances of five peaks presented in all 144 spectra from quality control samples that were loaded randomly on different spots in the chips of six bioprocessor plates. We developed a method to detect and discard low quality spectra prior to proteomic profiling data analysis, which uses a correlation matrix to measure the similarities among SELDI mass spectra obtained from similar biological samples. Application of the correlation matrix to our SELDI data for liver cancer and liver toxicity study and myeloma-associated lytic bone disease study confirmed this approach as an efficient and reliable method for detecting low quality spectra. Conclusion: This report provides evidence that systematic variability between plates, chips, and spots on which the samples were assayed using SELDI based proteomic procedures did not exist. The reproducibility of experiments in our studies was demonstrated to be acceptable and the profiling data for subsequent data analysis are reliable. Correlation matrix was developed as a quality control tool to detect and discard low quality spectra prior to data analysis. It proved to be a reliable method to measure the similarities among SELDI mass spectra and can be used for quality control to decrease noise in proteomic profiling data prior to data analysis. C1 US FDA, Div Bioinformat, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. US FDA, Div Syst Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Univ Arkansas Med Sci, Myleoma Inst Res & Therapy, Arkansas Canc Res Ctr, Little Rock, AR 72205 USA. US FDA, Div Mol Epidemiol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Hong, HX (reprint author), US FDA, Div Bioinformat, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM hhong@nctr.fda.gov; ydragan@nctr.fda.gov; EpsteinJoshua@uams.edu; cteitel@nctr.fda.gov; BangzhengChen@uams.edu; qxie@nctr.fda.gov; hfang@nctr.fda.gov; lshi@nctr.fda.gov; rperkins@nctr.fda.gov; wtong@nctr.fda.gov FU NCI NIH HHS [CA-55819, P01 CA055819] NR 23 TC 46 Z9 49 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2105 J9 BMC BIOINFORMATICS JI BMC Bioinformatics PD JUL 15 PY 2005 VL 6 SU 2 AR S5 DI 10.1186/1471-2105-6-S2-S5 PG 11 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA 022NC UT WOS:000236061500005 PM 16026602 ER PT J AU Shi, LM Tong, WD Su, ZQ Han, T Han, J Puri, RK Fang, H Frueh, FW Goodsaid, FM Guo, L Branham, WS Chen, JJ Xu, ZA Harris, SC Hong, HX Xie, Q Perkins, RG Fuscoe, JC AF Shi, LM Tong, WD Su, ZQ Han, T Han, J Puri, RK Fang, H Frueh, FW Goodsaid, FM Guo, L Branham, WS Chen, JJ Xu, ZA Harris, SC Hong, HX Xie, Q Perkins, RG Fuscoe, JC TI Microarray scanner calibration curves: characteristics and implications SO BMC BIOINFORMATICS LA English DT Article; Proceedings Paper CT 2nd Annual Conference of the MidSouth-Computational-Biology-and-Bioinformatics-Society CY OCT 07-09, 2004 CL Little Rock, AK SP MidSouth Computational Biol Bioinformat Soc ID OLIGONUCLEOTIDE ARRAYS; DNA MICROARRAYS; EXPRESSION; SIGNAL; NORMALIZATION; DESIGN; RATIOS; GENES; RANGE AB Background: Microarray-based measurement of mRNA abundance assumes a linear relationship between the fluorescence intensity and the dye concentration. In reality, however, the calibration curve can be nonlinear. Results: By scanning a microarray scanner calibration slide containing known concentrations of fluorescent dyes under 18 PMT gains, we were able to evaluate the differences in calibration characteristics of Cy5 and Cy3. First, the calibration curve for the same dye under the same PMT gain is nonlinear at both the high and low intensity ends. Second, the degree of nonlinearity of the calibration curve depends on the PMT gain. Third, the two PMTs ( for Cy5 and Cy3) behave differently even under the same gain. Fourth, the background intensity for the Cy3 channel is higher than that for the Cy5 channel. The impact of such characteristics on the accuracy and reproducibility of measured mRNA abundance and the calculated ratios was demonstrated. Combined with simulation results, we provided explanations to the existence of ratio underestimation, intensity-dependence of ratio bias, and anti-correlation of ratios in dye-swap replicates. We further demonstrated that although Lowess normalization effectively eliminates the intensity-dependence of ratio bias, the systematic deviation from true ratios largely remained. A method of calculating ratios based on concentrations estimated from the calibration curves was proposed for correcting ratio bias. Conclusion: It is preferable to scan microarray slides at fixed, optimal gain settings under which the linearity between concentration and intensity is maximized. Although normalization methods improve reproducibility of microarray measurements, they appear less effective in improving accuracy. C1 US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20852 USA. Z Tech Corp, Jefferson, AR 72079 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Shi, LM (reprint author), US FDA, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM leming.shi@fda.hhs.gov; weida.tong@fda.hhs.gov; zhenqiang.su@fda.hgs.gov; tao.han@fda.hhs.gov; jing.han@fda.hhs.gov; raj.puri@fda.hhs.gov; hong.fang@fda.hhs.gov; felix.frueh@fda.hhs.gov; federico.goodsaid@fda.hhs.gov; lei.guo@fda.hhs.gov; william.branham@fda.hhs.gov; james.chen@fda.hhs.gov; axu@genelogic.com; stephen.harris@fda.hhs.gov; huixiao.hong@fda.hhs.gov; qian.xie@fda.hhs.gov; roger.perkins@fda.hhs.gov; james.fuscoe@fda.hhs.gov RI Guo, Lei/E-9232-2011; Su, Zhenqiang/H-3914-2012 NR 30 TC 55 Z9 60 U1 0 U2 7 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2105 J9 BMC BIOINFORMATICS JI BMC Bioinformatics PD JUL 15 PY 2005 VL 6 SU 2 AR S11 DI 10.1186/1471-2105-6-S2-S11 PG 14 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA 022NC UT WOS:000236061500011 PM 16026596 ER PT J AU Shi, LM Tong, WD Fang, H Scherf, U Han, J Puri, RK Frueh, FW Goodsaid, FM Guo, L Su, ZQ Han, T Fuscoe, JC Xu, ZA Patterson, TA Hong, HX Xie, Q Perkins, RG Chen, JJ Casciano, DA AF Shi, LM Tong, WD Fang, H Scherf, U Han, J Puri, RK Frueh, FW Goodsaid, FM Guo, L Su, ZQ Han, T Fuscoe, JC Xu, ZA Patterson, TA Hong, HX Xie, Q Perkins, RG Chen, JJ Casciano, DA TI Cross-platform comparability of microarray technology: Intra-platform consistency and appropriate data analysis procedures are essential SO BMC BIOINFORMATICS LA English DT Article; Proceedings Paper CT 2nd Annual Conference of the MidSouth-Computational-Biology-and-Bioinformatics-Society CY OCT 07-09, 2004 CL Little Rock, AK SP MidSouth Computational Biol Bioinformat Soc ID GENE-EXPRESSION MEASUREMENTS; OLIGONUCLEOTIDE MICROARRAYS; PERSPECTIVE; PERFORMANCE; ARRAYS; QA/QC; NOISE; NEED AB Background: The acceptance of microarray technology in regulatory decision-making is being challenged by the existence of various platforms and data analysis methods. A recent report ( E. Marshall, Science, 306, 630 - 631, 2004), by extensively citing the study of Tan et al. ( Nucleic Acids Res., 31, 5676 - 5684, 2003), portrays a disturbingly negative picture of the cross-platform comparability, and, hence, the reliability of microarray technology. Results: We reanalyzed Tan's dataset and found that the intra-platform consistency was low, indicating a problem in experimental procedures from which the dataset was generated. Furthermore, by using three gene selection methods (i.e., p-value ranking, fold-change ranking, and Significance Analysis of Microarrays (SAM)) on the same dataset we found that p-value ranking ( the method emphasized by Tan et al.) results in much lower cross-platform concordance compared to fold-change ranking or SAM. Therefore, the low cross-platform concordance reported in Tan's study appears to be mainly due to a combination of low intra-platform consistency and a poor choice of data analysis procedures, instead of inherent technical differences among different platforms, as suggested by Tan et al. and Marshall. Conclusion: Our results illustrate the importance of establishing calibrated RNA samples and reference datasets to objectively assess the performance of different microarray platforms and the proficiency of individual laboratories as well as the merits of various data analysis procedures. Thus, we are progressively coordinating the MAQC project, a community-wide effort for microarray quality control. C1 US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Z Tech Corp, Jefferson, AR 72079 USA. US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. US FDA, Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. RP Shi, LM (reprint author), US FDA, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM leming.shi@fda.hhs.gov; weida.tong@fda.hhs.gov; hong.fang@fda.hhs.gov; uwe.scherf@fda.hhs.gov; jing.han@fda.hhs.gov; raj.puri@fda.hhs.gov; felix.frueh@fda.hhs.gov; federico.goodsaid@fda.hhs.gov; lei.guo@fda.hhs.gov; zhenqiang.su@fda.hgs.gov; tao.han@fda.hhs.gov; james.fuscoe@fda.hhs.gov; axu@genelogic.com; tucker.patterson@fda.hhs.gov; huixiao.hong@fda.hhs.gov; qian.xie@fda.hhs.gov; roger.perkins@fda.hhs.gov; james.chen@fda.hhs.gov; dan.casciano@fda.hhs.gov RI Guo, Lei/E-9232-2011; Su, Zhenqiang/H-3914-2012 NR 31 TC 124 Z9 130 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2105 J9 BMC BIOINFORMATICS JI BMC Bioinformatics PD JUL 15 PY 2005 VL 6 SU 2 AR S12 DI 10.1186/1471-2105-6-S2-S12 PG 14 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA 022NC UT WOS:000236061500012 PM 16026597 ER PT J AU Wren, JD Slikker, W AF Wren, JD Slikker, W TI Proceedings of the Second Annual Conference of the MidSouth Computational Biology and Bioinformatics Society SO BMC BIOINFORMATICS LA English DT Editorial Material ID GENE-EXPRESSION; MICROARRAY; ALGORITHM; CLUSTERS; CANCER; SET AB The MCBIOS 2004 conference brought together regional researchers and students in biology, computer science and bioinformatics on October 7th-9th 2004 to present their latest work. This editorial describes the conference itself and introduces the twelve peer-reviewed manuscripts accepted for publication in the Proceedings of the MCBIOS 2004 Conference. These manuscripts included new methods for analysis of high-throughput gene expression experiments, EST clustering, analysis of mass spectrometry data and genomic analysis. C1 US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Univ Oklahoma, Dept Bot & Microbiol, Stephenson Res & Technol Ctr, Adv Ctr Genome Technol, Norman, OK 73019 USA. RP Slikker, W (reprint author), US FDA, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM Jonathan.Wren@OU.edu; wslikker@nctr.fda.gov RI Wren, Jonathan/E-5611-2011 OI Wren, Jonathan/0000-0003-2776-3545 NR 16 TC 2 Z9 2 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2105 J9 BMC BIOINFORMATICS JI BMC Bioinformatics PD JUL 15 PY 2005 VL 6 SU 2 AR S1 DI 10.1186/1471-2105-6-S2-S1 PG 4 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA 022NC UT WOS:000236061500001 ER PT J AU Xie, Q Ratnasinghe, LD Hong, HX Perkins, R Tang, ZZ Hu, N Taylor, PR Tong, WD AF Xie, Q Ratnasinghe, LD Hong, HX Perkins, R Tang, ZZ Hu, N Taylor, PR Tong, WD TI Decision forest analysis of 61 single nucleotide polymorphisms in a case-control study of esophageal cancer; a novel method SO BMC BIOINFORMATICS LA English DT Article; Proceedings Paper CT 2nd Annual Conference of the MidSouth-Computational-Biology-and-Bioinformatics-Society CY OCT 07-09, 2004 CL Little Rock, AK SP MidSouth Computational Biol Bioinformat Soc ID ESTROGEN-RECEPTOR BINDING; HAPLOTYPE FREQUENCIES; PREDICTION; MODELS; RISK; CASE/CONTROL; SELECTION; ALCOHOL; SMOKING; DISEASE AB Background: Systematic evaluation and study of single nucleotide polymorphisms ( SNPs) made possible by high throughput genotyping technologies and bioinformatics promises to provide breakthroughs in the understanding of complex diseases. Understanding how the millions of SNPs in the human genome are involved in conferring susceptibility or resistance to disease, or in rendering a drug efficacious or toxic in the individual is a major goal of the relatively new fields of pharmacogenomics. Esophageal squamous cell carcinoma is a high-mortality cancer with complex etiology and progression involving both genetic and environmental factors. We examined the association between esophageal cancer risk and patterns of 61 SNPs in a case-control study for a population from Shanxi Province in North Central China that has among the highest rates of esophageal squamous cell carcinoma in the world. Methods: High-throughput Masscode mass spectrometry genotyping was done on genomic DNA from 574 individuals ( 394 cases and 180 age-frequency matched controls). SNPs were chosen from among genes involving DNA repair enzymes, and Phase I and Phase II enzymes. We developed a novel adaptation of the Decision Forest pattern recognition method named Decision Forest for SNPs (DF-SNPs). The method was designated to analyze the SNP data. Results: The classifier in separating the cases from the controls developed with DF-SNPs gave concordance, sensitivity and specificity, of 94.7%, 99.0% and 85.1%, respectively; suggesting its usefulness for hypothesizing what SNPs or combinations of SNPs could be involved in susceptibility to esophageal cancer. Importantly, the DF-SNPs algorithm incorporated a randomization test for assessing the relevance ( or importance) of individual SNPs, SNP types ( Homozygous common, heterozygous and homozygous variant) and patterns of SNP types ( SNP patterns) that differentiate cases from controls. For example, we found that the different genotypes of SNP GADD45B E1122 are all associated with cancer risk. Conclusion: The DF-SNPs method can be used to differentiate esophageal squamous cell carcinoma cases from controls based on individual SNPs, SNP types and SNP patterns. The method could be useful to identify potential biomarkers from the SNP data and complement existing methods for genotype analyses. C1 US FDA, Div Bioinformat, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. US FDA, Ctr Toxicoinformat, Div syst Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NCI, Genet Epidemiol Branch, DCEG, Rockville, MD 20852 USA. Shanxi Canc Hosp, Taiyuan 030013, Shanxi, Peoples R China. US FDA, Ctr Struct Genom, DPME, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Xie, Q (reprint author), US FDA, Div Bioinformat, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM QXie@nctr.fda.gov; LRatnasinghe@nctr.fda.gov; HHong@nctr.fda.gov; RPerkins@nctr.fda.gov; Zlyyjsi@public.ty.sx.cn; Hun@mail.nih.gov; PTaylor@dcpcepn.nci.nih.gov; WTong@nctr.fda.gov NR 19 TC 29 Z9 30 U1 0 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2105 J9 BMC BIOINFORMATICS JI BMC Bioinformatics PD JUL 15 PY 2005 VL 6 SU 2 AR S4 DI 10.1186/1471-2105-6-S2-S4 PG 9 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA 022NC UT WOS:000236061500004 PM 16026601 ER PT J AU Xu, ZJ Patterson, TA Wren, JD Han, T Shi, LM Duhart, H Ali, SF Slikker, W AF Xu, ZJ Patterson, TA Wren, JD Han, T Shi, LM Duhart, H Ali, SF Slikker, W TI A microarray study of MPP+-treated PC12 cells: Mechanisms of toxicity (MOT) analysis using bioinformatics tools SO BMC BIOINFORMATICS LA English DT Article; Proceedings Paper CT 2nd Annual Conference of the MidSouth-Computational-Biology-and-Bioinformatics-Society CY OCT 07-09, 2004 CL Little Rock, AK SP MidSouth Computational Biol Bioinformat Soc ID GENE-EXPRESSION ANALYSIS; ENDOPLASMIC-RETICULUM STRESS; INDUCED OXIDATIVE STRESS; NERVE GROWTH-FACTOR; INDUCED APOPTOSIS; PARKINSONS-DISEASE; DOPAMINERGIC-NEURONS; CDNA MICROARRAY; INDUCED NEUROTOXICITY; CALCYCLIN S100A6 AB Background: This paper describes a microarray study including data quality control, data analysis and the analysis of the mechanism of toxicity (MOT) induced by 1-methyl-4-phenylpyridinium (MPP+) in a rat adrenal pheochromocytoma cell line ( PC12 cells) using bioinformatics tools. MPP+ depletes dopamine content and elicits cell death in PC12 cells. However, the mechanism of MPP+-induced neurotoxicity is still unclear. Results: In this study, Agilent rat oligo 22K microarrays were used to examine alterations in gene expression of PC12 cells after 500 mu M MPP+ treatment. Relative gene expression of control and treated cells represented by spot intensities on the array chips was analyzed using bioinformatics tools. Raw data from each array were input into the NCTR Array Track database, and normalized using a Lowess normalization method. Data quality was monitored in Array Track. The means of the averaged log ratio of the paired samples were used to identify the fold changes of gene expression in PC12 cells after MPP+ treatment. Our data showed that 106 genes and ESTs ( Expressed Sequence Tags) were changed 2-fold and above with MPP+ treatment; among these, 75 genes had gene symbols and 59 genes had known functions according to the Agilent gene Refguide and Array Track-linked gene library. The mechanism of MPP+-induced toxicity in PC12 cells was analyzed based on their genes functions, biological process, pathways and previous published literatures. Conclusion: Multiple pathways were suggested to be involved in the mechanism of MPP+-induced toxicity, including oxidative stress, DNA and protein damage, cell cycling arrest, and apoptosis. C1 US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Univ Oklahoma, Dept Bot & Microbiol, Adv Ctr Genome Technol, Norman, OK 73019 USA. US FDA, Div Syst Biol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Slikker, W (reprint author), US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM axu@genelogic.com; TPatterson@nctr.fda.gov; Jonathan.Wren@OU.edu; leming.shi@fda.hhs.gov; wslikker@nctr.fda.gov RI Wren, Jonathan/E-5611-2011 OI Wren, Jonathan/0000-0003-2776-3545 NR 91 TC 15 Z9 16 U1 0 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2105 J9 BMC BIOINFORMATICS JI BMC Bioinformatics PD JUL 15 PY 2005 VL 6 SU 2 AR S8 DI 10.1186/1471-2105-6-S2-S8 PG 14 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA 022NC UT WOS:000236061500008 PM 16026605 ER PT J AU Zhang, BL Zhang, YQ Dagher, MC Shacter, E AF Zhang, BL Zhang, YQ Dagher, MC Shacter, E TI Rho GDP dissociation inhibitor protects cancer cells against drug-induced apoptosis SO CANCER RESEARCH LA English DT Article ID HUMAN LYMPHOMA-CELLS; NADPH OXIDASE; PROTEOMIC ANALYSIS; MAMMALIAN-CELLS; GTPASES; ACTIVATION; PROTEINS; RAC1; EXPRESSION; P21 AB Rho GDP dissociation inhibitor (RhoGDI) plays an essential role in control of a variety of cellular functions through interactions with Rho family GTPases, including Rac1, Cdc42, and RhoA. RhoGDI is frequently overexpressed in human tumors and chemoresistant cancer cell lines, raising the possibility that RhoGDI might play a role in the development of drug resistance in cancer cells. We found that overexpression of RhoGDI increased resistance of cancer cells (MDA-MB-231 human breast cancer cells and JLP-119 lymphoma cells) to the induction of apoptosis by two chemotherapeutic agents: etoposide and doxorubicin. Conversely, silencing of RhoGDI expression by DNA vector-mediated RNA interference (small interfering RNA) sensitized MDA-MB-231 cells to drug-induced apoptosis. Resistance to apoptosis was restored by reintroduction of RhoGDI protein expression. The mechanism for the antiapoptotic activity of RhoGDI may derive from its ability to inhibit caspase-mediated cleavage of Rac1 GTPase, which is required for maximal apoptosis to occur in response to cytotoxic drugs. Taken together, the data show that RhoGDI is an antiapoptotic molecule that mediates cellular resistance to these chemotherapy agents. C1 US FDA, Biochem Lab, Div Therapeut Prot, Off Biotechnol Prod,Ctr Drug Evaluat & Res, Bethesda, MD USA. Univ Grenoble 1, CNRS, Lab Biochim & Biophys Syst Integres, Commissariat Energie Atom, Grenoble, France. RP Zhang, BL (reprint author), 29 Lincoln Dr,Bldg 29A,Room 2B-24, Bethesda, MD 20892 USA. EM baolin.zhang@fda.gov NR 35 TC 99 Z9 105 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUL 15 PY 2005 VL 65 IS 14 BP 6054 EP 6062 DI 10.1158/0008-5472.CAN-05-0175 PG 9 WC Oncology SC Oncology GA 947HG UT WOS:000230633400013 PM 16024605 ER PT J AU Ackerman, AH Creed, PA Parks, AN Fricke, MW Schwegel, CA Creed, JT Heitkemper, DT Vela, NP AF Ackerman, AH Creed, PA Parks, AN Fricke, MW Schwegel, CA Creed, JT Heitkemper, DT Vela, NP TI Comparison of a chemical and enzymatic extraction of arsenic from rice and an assessment of the arsenic absorption from contaminated water by cooked rice SO ENVIRONMENTAL SCIENCE & TECHNOLOGY LA English DT Article ID CELL-CULTURE MODEL; ION CHROMATOGRAPHY; FOOD; BANGLADESH; METABOLISM AB Rice is a target food for arsenic speciation based analyses because of its relatively high arsenic concentration and per capita consumption rates. Improved speciation data for rice can be helpful in estimating inorganic arsenic exposures in the U.S. and in endemic populations. The inorganic arsenic exposure for cooked rice should include both the arsenic in raw rice plus the arsenic absorbed from the water used to prepare it. The amount of arsenic absorbed from water by rice during preparation was assessed using five different types of rice cooked in both contaminated drinking water and arsenic-free reagent water. The rice samples were extracted using trifluoroacetic acid (TFA) and speciated using IC-ICP-MS. The TFA procedure was able to extract 84-104% of the arsenic (As) from the five different cooked rice samples. Chromatographic recoveries ranged from 99% to 116%. The dimethylarsinic acid (DMA) and inorganic arsenic concentration ranged from 22 to 270 ng of As/g of rice and from 31 to 108 ng of As/g of rice, respectively, for samples cooked in reagent water. The overall recoveries, which relate the sum of the chromatographic species back to the total digested concentration, ranged from 89% to 117%. The absorption of arsenic by rice from the total volume of water [1:1 to 4:1 (water:rice)] used in cooking was between 89% and 105% for two different contaminated drinking water samples. A comparison of the TFA extraction to an enzymatic extraction was made using the five rice samples and NIST 1568a rice flour. The two extraction procedures produced good agreement for inorganic arsenic DMAI and the overall recovery. Through the use of IC - ESI-MS/ MS with a parent ion of m/z 153 and fragment ions of m/z 138, 123, and 105, the structure dimethylthioarsinic acid was tentatively identified in two of the rice samples using the enzymatic extraction. C1 US EPA, ORD, NERL, Microbiol & Chem Exposure Assessment Res Div, Cincinnati, OH 45268 USA. US FDA, Forens Chem Ctr, Cincinnati, OH 45249 USA. RP Creed, JT (reprint author), US EPA, ORD, NERL, Microbiol & Chem Exposure Assessment Res Div, Cincinnati, OH 45268 USA. EM Creed.Jack@epa.gov RI Creed, John/A-9187-2009 FU PHS HHS [DW-75-93936101] NR 13 TC 95 Z9 97 U1 1 U2 38 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0013-936X J9 ENVIRON SCI TECHNOL JI Environ. Sci. Technol. PD JUL 15 PY 2005 VL 39 IS 14 BP 5241 EP 5246 DI 10.1021/es048150n PG 6 WC Engineering, Environmental; Environmental Sciences SC Engineering; Environmental Sciences & Ecology GA 945XL UT WOS:000230536200022 PM 16082952 ER PT J AU Wokovich, AM Spencer, JA Westenberger, BJ Buhse, LF Jasper, JP AF Wokovich, AM Spencer, JA Westenberger, BJ Buhse, LF Jasper, JP TI Stable isotopic composition of the active pharmaceutical ingredient (API) naproxen SO JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS LA English DT Article DE IRMS; isotope ratio mass Spectrometry; naproxen; APT; active pharmaceutical ingredient; isotope ratio; delta C-13; delta O-18; delta D ID NUCLEAR-MAGNETIC-RESONANCE; RATIO MASS-SPECTROMETRY; GEOGRAPHIC ORIGIN; ANIMAL PRODUCTS; ECSTASY; MEAT AB A survey of the multi-stable isotopic composition of an active pharmaceutical ingredient (API), naproxen, was performed to assess the potential of Isotope Ratio Mass Spectrometry (IRMS) to distinguish the provenance of APIs. Twenty-six lots of naproxen from six manufacturers representing four countries (Italy, India, Ireland, and the USA) were analyzed for three isotope ratios (C-13/C-12, O-18/O-16, and D/H). The samples were analyzed by either Elemental Analyzer/Isotope Ratio Mass Spectrometry (EA/IRMS: carbon (delta(13)C)) or by Thermal Conversion-EA/IRMS (TCEA/IRMS: hydrogen (delta D))s and oxygen (delta(18)O). Bivariate and trivariate isotope ratio graphs for naproxen show marked clustering of the data for five out of the six naproxen manufacturers, suggesting that IRMS may be a plausible means to screen for manufacturer of given APIs. (c) 2005 Elsevier B.V. All rights reserved. C1 US FDA, Ctr Drug Evaluat & Res, Div Pharmaceut Anal, St Louis, MO 63101 USA. Mol Isotope Technol LLC, Niantic, CT 06357 USA. RP Wokovich, AM (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Pharmaceut Anal, St Louis, MO 63101 USA. EM wokovicha@cder.fda.gov NR 15 TC 12 Z9 12 U1 1 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0731-7085 J9 J PHARMACEUT BIOMED JI J. Pharm. Biomed. Anal. PD JUL 15 PY 2005 VL 38 IS 4 BP 781 EP 784 DI 10.1016/j.jpba.2005.02.033 PG 4 WC Chemistry, Analytical; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 948LT UT WOS:000230718000028 PM 15967309 ER PT J AU Heller, DN Peggins, JO Nochetto, CB Smith, ML Chiesa, OA Moulton, K AF Heller, DN Peggins, JO Nochetto, CB Smith, ML Chiesa, OA Moulton, K TI LC/MS/MS measurement of gentamicin in bovine plasma, urine, milk, and biopsy samples taken from kidneys of standing animals SO JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES LA English DT Article DE gentamicin; liquid chromatogaphy-tandem mass spectrometry; residue analysis; quantification; plasma; urine; kidney; milk ID TANDEM-MASS-SPECTROMETRY; LIQUID-CHROMATOGRAPHY; AMINOGLYCOSIDE ANTIBIOTICS; DERIVATIZATION; CONFIRMATION; EXTRACTION; SERUM AB Methods for the measurement of gentamicin concentration in several bovine tissues were developed and validated. A novel liquid chromatographic (LC) technique employed trifluoroacetic acid in the mobile phase so that all gentamicin components co-eluted. Analytes were ionized by positive-ion pneumatically assisted electrospray and detected by selected reaction monitoring (SRM) with an LC-tandem mass spectrometer (LC/MS/MS). Calibration of plasma and urine samples was based on tobramycin internal standard. Calibration of milk and kidney samples was based on external standard, due to variability of tobramycin response in these matrices. The extraction technique employed treatment with aqueous trichloroacetic acid to both precipitate protein and liberate gentamicin from the matrix. Milk samples had to be defatted by centrifugation prior to extraction. Urine samples were further cleaned up with C-18 solid phase extraction (SPE). These methods were validated for use in several residue depletion studies (reported elsewhere) to monitor the depletion of gentamicin in tissues under various dosing conditions. The plasma method was calibrated from 1 to 5000 ng/mL in two ranges, with a limit of quantitation (LOQ) in the low range calculated at 3.3 ng/mL. The milk method was calibrated from 2.5 to 2500 ng/mL with an LOQ calculated at 4.5 ng/mL. The urine method was designed for use at low levels, and was calibrated from 1 to 100 ng/mL with an LOQ of 3.8 ng/mL. The kidney method was primarily designed for analysis of small samples (approximately 100 mg). This method was calibrated from 10 to 50,000 ng/g with an LOQ of 26 ng/g. Published by Elsevier B.V. C1 US FDA, FDA Ctr Vet Med, Laurel, MD 20708 USA. RP Heller, DN (reprint author), US FDA, FDA Ctr Vet Med, 8401 Muirkirk Rd, Laurel, MD 20708 USA. EM david.heller@fda.gov NR 14 TC 55 Z9 60 U1 0 U2 24 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 2005 VL 821 IS 1 BP 22 EP 30 DI 10.1016/j.jchromb.2005.04.015 PG 9 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 935TW UT WOS:000229807300004 PM 15905139 ER PT J AU Lynch, J Guo, L Gelebart, P Chilibeck, K Xu, J Molkentin, JD Agellon, LB Michalak, M AF Lynch, J Guo, L Gelebart, P Chilibeck, K Xu, J Molkentin, JD Agellon, LB Michalak, M TI Calreticulin signals upstream of calcineurin and MEF2C in a critical Ca2+-dependent signaling cascade SO JOURNAL OF CELL BIOLOGY LA English DT Article ID TRANSCRIPTION FACTOR MEF2C; CARDIAC-HYPERTROPHY; ENDOPLASMIC-RETICULUM; GENE-EXPRESSION; NUCLEAR EXPORT; NF-ATC; CALCIUM; PROTEINS; HEART; MOUSE AB e uncovered a new pathway of interplay between calreticulin and myocyte-enhancer factor (MEF) 2C, a cardiac-specific transcription factor. We establish that calreticulin works upstream of calcineurin and MEF2C in a Ca2+-dependent signal transduction cascade that links the endoplasmic reticulum and the nucleus during cardiac development. In the absence of calreticulin, translocation of MEF2C to the nucleus is compromised. This defect is reversed by calreticulin itself or by a constitutively active form of calcineurin. Furthermore, we show that expression of the calreticulin W gene itself is regulated by MEF2C in vitro and in vivo and that, in turn, increased expression of calreticulin affects MEF2C transcriptional activity. The present findings provide a clear molecular explanation for the embryonic lethality observed in calreticulin-deficient mice and emphasize the importance of calreticulin in the early stages of cardiac development. Our study illustrates the existence of a positive feedback mechanism that ensures an adequate supply of releasable Ca2+ is maintained within the cell for activation of calcineurin and, subsequently, for proper functioning of MEF2C. C1 Univ Alberta, Dept Biochem, Edmonton, AB T6G 2H7, Canada. Univ Alberta, Canadian Inst Hlth, Res Grp Mol & Cell Biol Lipds, Edmonton, AB T6G 2H7, Canada. US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Childrens Hosp, Med Ctr, Cincinnati, OH 45229 USA. RP Univ Alberta, Dept Biochem, Edmonton, AB T6G 2H7, Canada. EM marek.michalak@ualberta.ca RI Guo, Lei/E-9232-2011 NR 45 TC 52 Z9 57 U1 0 U2 3 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 950 THIRD AVE, 2ND FLR, NEW YORK, NY 10022 USA SN 0021-9525 EI 1540-8140 J9 J CELL BIOL JI J. Cell Biol. PD JUL 4 PY 2005 VL 170 IS 1 BP 37 EP 47 DI 10.1083/jcb.200412156 PG 11 WC Cell Biology SC Cell Biology GA 943XK UT WOS:000230388700006 PM 15998798 ER PT J AU Powers, JH Cooper, CK Lin, D Ross, DB AF Powers, JH Cooper, CK Lin, D Ross, DB TI Sample size and the ethics of non-inferiority trials SO LANCET LA English DT Letter C1 US FDA, Off Drug Evaluat 4, Ctr Drug Evaluat & Res, Rockville, MD 20850 USA. US FDA, Off Biostat, Ctr Drug Evaluat & Res, Rockville, MD 20850 USA. US FDA, Off Drug Evaluat 6, Ctr Drug Evaluat & Res, Rockville, MD 20850 USA. RP Powers, JH (reprint author), US FDA, Off Drug Evaluat 4, Ctr Drug Evaluat & Res, 9201 Corp Blvd,HFD-104, Rockville, MD 20850 USA. EM POWERSJOH@cder.fda.gov NR 5 TC 6 Z9 6 U1 0 U2 4 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD JUL 2 PY 2005 VL 366 IS 9479 BP 24 EP 25 DI 10.1016/S0140-6736(05)66817-1 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 942JB UT WOS:000230277600021 PM 15993221 ER PT J AU Chang, NS Simone, AF Schultheis, LW AF Chang, NS Simone, AF Schultheis, LW TI From the FDA - What's in a label? A guide for the anesthesia practitioner SO ANESTHESIOLOGY LA English DT Article C1 US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Simone, AF (reprint author), US FDA, Ctr Drug Evaluat & Res, 5600 Fishers Lane,HFD-170, Rockville, MD 20857 USA. EM simonea@cder.fda.gov NR 12 TC 13 Z9 13 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD JUL PY 2005 VL 103 IS 1 BP 179 EP 185 DI 10.1097/00000542-200507000-00026 PG 7 WC Anesthesiology SC Anesthesiology GA 941JZ UT WOS:000230212400025 PM 15983471 ER PT J AU Chhabra, R Krernzner, ME Kiliany, BJ AF Chhabra, R Krernzner, ME Kiliany, BJ TI FDA policy on unapproved drug products: Past, present, and future SO ANNALS OF PHARMACOTHERAPY LA English DT Article DE food and drug administration; compliance; drug efficacy study implementation AB OBJECTIVE: To review the history of drug regulation by the Food and Drug Administration (FDA) as it relates to unapproved drugs and FDA policy, along with the FDA's efforts to avoid future incidents by amending and enforcing those policies that are already in place. DATA SOURCES: Data from FDA history documents, FDA guidances, Code of Federal Regulations Title 21, and presentations by the FDA's Office of Compliance were gathered. STUDY SELECTION AND DATA EXTRACTION: All information identified from the data sources was evaluated, and all information deemed relevant was included for this review. DATA SYNTHESIS: Contrary to popular belief, there are drugs on the market that have not been evaluated for safety or efficacy by the FDA. For almost a century, the FDA has taken action against public health threats posed by unapproved drug products, and today's drugs and vaccines are required to demonstrate both safety and efficacy prior to marketing, The FDA has taken great strides to ensure the welfare of Americans by reacting to disasters that have occurred in the past and being proactive by setting regulations that will prevent such catastrophes from occurring in the future. CONCLUSIONS: The FDA recognizes that drug regulation is an ongoing process and that, although we have come a long way, there is still much to be done. C1 Food & Drug Adm, Div Drug Informat, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Chhabra, R (reprint author), Food & Drug Adm, Div Drug Informat, Ctr Drug Evaluat & Res, 5600 Fishers Ln,HFD-240, Rockville, MD 20857 USA. EM chhabrar@cder.fda.gov NR 9 TC 2 Z9 2 U1 0 U2 3 PU HARVEY WHITNEY BOOKS CO PI CINCINNATI PA PO BOX 42696, CINCINNATI, OH 45242 USA SN 1060-0280 J9 ANN PHARMACOTHER JI Ann. Pharmacother. PD JUL-AUG PY 2005 VL 39 IS 7-8 BP 1260 EP 1264 DI 10.1345/aph1E569 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 941QN UT WOS:000230229400017 PM 15956239 ER PT J AU Sharma, SK Eblen, BS Bull, RL Burr, DH Whiting, RC AF Sharma, SK Eblen, BS Bull, RL Burr, DH Whiting, RC TI Evaluation of lateral-flow clostridium botulinum neurotoxin detection kits for food analysis SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID LINKED-IMMUNOSORBENT-ASSAY; COAGULATION ASSAY; TOXIN; IMMUNOASSAY; ANTIBODIES; SAMPLES; COMPLEXES; PROTEINS; PCR AB The suitability and sensitivity of two in vitro lateral-How assays for detecting Clostridium botulinum neurotoxins (BoNTs) in an assortment of foods were evaluated. Toxin extraction and preparation methods for various liquid, solid, and high-fat-con tent foods were developed. The lateral-flow assays, one developed by the Naval Medical Research Center (Silver Spring, MD) and the other by Allexeter Technologies (Gaithersburg, MD), are based on the immunodetection of BoNT types A, B, and E. The assays were found to be rapid and easy to perform with minimum requirements for laboratory equipment or skills. They can readily detect 10 ng/ml of BoNT types A and B and 20 ng/ml of BoNT type E. Compared to other in vitro detection methods, these assays are less sensitive, and the assessment of a result is strictly qualitative. However, the assay was found to be simple to use and to require minimal training. The assays successfully detected BoNT types A, B, and E in a wide variety of foods, suggesting their potential usefulness as a preliminary screening system for triaging food samples with elevated BoNT levels in the event of a C. botulinum contamination event. C1 US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. Naval Med Res Ctr, Biol Def Res Directorate, Silver Spring, MD 20910 USA. Natl Ctr Food Sci & Technol, Summit Argo, IL 60501 USA. RP Sharma, SK (reprint author), US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. EM Sliashi.Sharma@cfsan.fda.gov NR 33 TC 48 Z9 52 U1 2 U2 11 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0099-2240 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD JUL PY 2005 VL 71 IS 7 BP 3935 EP 3941 DI 10.1128/AEM.71.7.3935-3941.2005 PG 7 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 944RE UT WOS:000230445700068 PM 16000807 ER PT J AU Kim, YH Cerniglia, CE AF Kim, YH Cerniglia, CE TI Influence of erythromycin A on the microbial populations in aquaculture sediment microcosms SO AQUATIC TOXICOLOGY LA English DT Article DE erythromycin A; degradation; erythromycin esterase; microcosm; Pseudomonas; restriction fragment length polymorphism ID GENE CASSETTES; DEGRADATION; MINERALIZATION; DECOMPOSITION; ESTERASE; KINETICS AB Degradation of erythromycin A was studied using two sediment samples obtained from the salmon and trout hatchery sites at Hupp Springs (HS) and Goldendale (GD), Washington, United States. The former site had been treated for 3 years with erythromycin-medicated feed prior to the experiments, and the latter site had not been treated with any antibiotic for at least 6 years. The two sediment microcosms treated with either N-[methyl-C-14]erythromycin A or [1,3,5,7,9,11,13-C-14]erythromycin A showed S-curves for erythromycin A mineralization with a prolonged lag time of 120 days, except for GD microcosms treated with [1,3,5,7,9,11,13-C-14]erythromycin A. We proposed a simplified logistic model to interpret the mineralization curves under the assumption of the low densities of initial populations metabolizing erythromycin A. The model was helpful for knowing the biological potential for erythromycin A degradation in sediments. Although erythromycin A added to the two sediment microcosms did not significantly alter the numbers of total viable aerobic bacteria or erythromycin-resistant bacteria, it affected the bacterial composition. The influence on the bacterial composition appeared to be greater in GD microcosms without pre-exposure to antibiotics. PCR-RFLP and DNA sequence analyses of the 16S ribosomal RNA gene and the erythromycin esterase (ere) gene revealed that ereA type2 (ereA2) was present in potentially erythromycin-degrading Pseudomonas spp. strains GD100, GD200, HS100, HS200 and HS300, isolated from erythromycin-treated and non-treated GD and HS microcosms. Erythromycin A appeared to influence the development and proliferation of strain GD200, possibly via the lateral gene transfer of ereA2. (c) 2005 Elsevier B.V. All rights reserved. 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. EM yhkim660628@hotmail.com; ccerniglia@nctr.fda.gov NR 25 TC 7 Z9 7 U1 1 U2 15 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 1 PY 2005 VL 73 IS 3 BP 230 EP 241 DI 10.1016/j.aquatox.2005.03.013 PG 12 WC Marine & Freshwater Biology; Toxicology SC Marine & Freshwater Biology; Toxicology GA 938HL UT WOS:000229990400002 PM 15935863 ER PT J AU Klontz, KC Lambert, LA Jewell, RE Katz, LM AF Klontz, KC Lambert, LA Jewell, RE Katz, LM TI Adverse effects of cosmetic tattooing: An illustrative case of granulomatous dermatitis following the application of permanent makeup SO ARCHIVES OF DERMATOLOGY LA English DT Letter C1 US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Klontz, KC (reprint author), US FDA, Ctr Food Safety & Appl Nutr, HFS-728,5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM karl.klontz@cfsan.fda.gov NR 2 TC 9 Z9 9 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD JUL PY 2005 VL 141 IS 7 BP 918 EP 919 DI 10.1001/archderm.141.7.918 PG 2 WC Dermatology SC Dermatology GA 944PV UT WOS:000230442100031 PM 16027323 ER PT J AU Ximenes, EA Chen, HZ Kataeva, IA Cotta, MA Felix, CR Ljungdahl, LG Li, XL AF Ximenes, EA Chen, HZ Kataeva, IA Cotta, MA Felix, CR Ljungdahl, LG Li, XL TI A mannanase, ManA, of the polycentric anaerobic fungus Orpinomyces sp strain PC-2 has carbohydrate binding and docking modules SO CANADIAN JOURNAL OF MICROBIOLOGY LA English DT Article DE Orpinomyces; anaerobic fungi; mannanase; cellulose-binding module; cellulosome ID TRICHODERMA-REESEI; CLOSTRIDIUM-THERMOCELLUM; CELLOBIOHYDROLASE-I; GENE DUPLICATION; BETA-MANNANASE; NEOCALLIMASTIX-FRONTALIS; AGARICUS-BISPORUS; ENDOGLUCANASE-I; CELLULOSE; DOMAIN AB The anaerobic fungus Orpinomyces sp. strain PC-2 produces a broad spectrum of glycoside hydrolases, most of which are components of a high molecular mass cellulosomal complex. Here we report about a cDNA (manA) having 1924 bp isolated from the fungus and found to encode a polypeptide of 579 amino acid residues. Analysis of the deduced sequence revealed that it had a mannanase catalytic module, a family 1 carbohydrate-binding module, and a noncatalytic docking module. The catalytic module was homologous to aerobic fungal mannanases belonging to family 5 glycoside hydrolases, but unrelated to the previously isolated mannanases (family 26) of the anaerobic fungus Piromyces. No mannanase activity could be detected in Escherichia coli harboring a manA-containing plasmid. The manA was expressed in Saccharomyces cerevisiae and ManA was secreted into the culture medium in multiple forms. The purified extracellular heterologous mannanase hydrolyzed several types of mannan but lacked activity against cellulose, chitin, or beta-glucan. The enzyme had high specific activity toward locust bean mannan and an extremely broad pH profile. It was stable for several hours at 50 degrees C, but was rapidly inactivated at 60 degrees C. The carbohydrate-binding module of the Man A produced separately in E. coli bound preferably to insoluble lignocellulosic substrates, suggesting that it might play an important role in the complex enzyme system of the fungus for lignocellulose degradation. C1 USDA ARS, Natl Ctr Agr Utilizat Res, Fermentat Biotechnol Res Unit, Peoria, IL 61604 USA. Univ Brasilia, Lab Enzimol, Dept Biol Celular, BR-70910900 Brasilia, DF, Brazil. US FDA, Div Microbiol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Univ Georgia, Dept Biochem & Mol Biol, Athens, GA 30602 USA. Univ Georgia, Ctr Biol Resource Recovery, Athens, GA 30602 USA. RP Li, XL (reprint author), USDA ARS, Natl Ctr Agr Utilizat Res, Fermentat Biotechnol Res Unit, 1815 N Univ St, Peoria, IL 61604 USA. EM lix@ncaur.usda.gov RI Ximenes, Eduardo/G-5323-2013; OI Ximenes, Eduardo/0000-0001-9087-0218; Cotta, Michael/0000-0003-4565-7754 NR 50 TC 8 Z9 10 U1 0 U2 5 PU NATL RESEARCH COUNCIL CANADA PI OTTAWA PA RESEARCH JOURNALS, MONTREAL RD, OTTAWA, ONTARIO K1A 0R6, CANADA SN 0008-4166 J9 CAN J MICROBIOL JI Can. J. Microbiol. PD JUL PY 2005 VL 51 IS 7 BP 559 EP 568 DI 10.1139/W05-033 PG 10 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Immunology; Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Immunology; Microbiology GA 965YB UT WOS:000231985700005 PM 16175204 ER PT J AU Mehendale, S Aung, H Wang, AB Yin, JJ Wang, CZ Xie, JT Yuan, CS AF Mehendale, S Aung, H Wang, AB Yin, JJ Wang, CZ Xie, JT Yuan, CS TI American ginseng berry extract and ginsenoside Re attenuate cisplatin-induced kaolin intake in rats SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE American ginseng; berry; ginsenoside Re; herbal medicine; cisplatin ID CHEMOTHERAPY-INDUCED NAUSEA; RADIATION-INDUCED EMESIS; DRUG-INDUCED EMESIS; INDUCED PICA; MOTION SICKNESS; ANIMAL-MODEL; IN-VITRO; SCUTELLARIA-BAICALENSIS; RECEPTOR ANTAGONISTS; SUNCUS-MURINUS AB Purpose: Cisplatin, a chemotherapeutic agent, causes significant nausea and vomiting. It is postulated that cisplatin-induced oxidant stress may be responsible for these symptoms. We tested whether pretreatment with American ginseng berry extract (AGBE), an herb with potent antioxidant capacity, and one of its active antioxidant constituents, ginsenoside Re, could counter cisplatin-induced emesis using a rat pica model. Methods: In rats, exposure to emetic stimuli such as cisplatin causes significant kaolin intake, a phenomenon called pica. We therefore measured cisplatin-induced kaolin intake as an indicator of the emetic response. Rats were pretreated with vehicle, AGBE ( dose range 50 - 150 mg/kg, IP) or ginsenoside Re ( 2 and 5 mg/kg, IP). Rats were treated with cisplatin ( 3 mg/kg, IP) 30 min later. Kaolin intake, food intake, and body weight were measured every 24 h for 120 h. Additionally, the free radical scavenging activity of AGBE was measured in vitro using ESR spectroscopy. Results: A significant dose-response relationship was observed between increasing doses of pretreatment with AGBE and reduction in cisplatin-induced pica. Kaolin intake was maximally attenuated by AGBE at a dose of 100 mg/kg. Food intake also improved significantly at this dose ( P< 0.05). Pretreatment with ginsenoside Re ( 5 mg/kg) also decreased kaolin intake ( P< 0.05). In vitro studies demonstrated a concentration-response relationship between AGBE and its ability to scavenge superoxide and hydroxyl radicals. Conclusion: Pretreatment with AGBE and its major constituent, Re, attenuated cisplatin-induced pica, and demonstrated potential for the treatment of chemotherapy-induced nausea and vomiting. Significant recovery of food intake further strengthens the conclusion that AGBE may exert an antinausea/antiemetic effect. C1 Univ Chicago, Pritzker Sch Med, Comm Clin Pharmacol & Pharmacogenom, Chicago, IL 60637 USA. Univ Chicago, Pritzker Sch Med, Tang Ctr Herbal Med Res, Chicago, IL 60637 USA. Univ Chicago, Pritzker Sch Med, Dept Anesthesia, Chicago, IL 60637 USA. Univ Chicago, Pritzker Sch Med, Dept Crit Care, Chicago, IL 60637 USA. US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Yuan, CS (reprint author), Univ Chicago, Pritzker Sch Med, Comm Clin Pharmacol & Pharmacogenom, Chicago, IL 60637 USA. EM cyuan@airway.uchicago.edu RI Yin, Jun Jie /E-5619-2014 FU NCCIH NIH HHS [AT00563, AT002176]; NCI NIH HHS [P30 CA14599, R01 CA79042] NR 51 TC 27 Z9 29 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD JUL PY 2005 VL 56 IS 1 BP 63 EP 69 DI 10.1007/s00280-004-0956-1 PG 7 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 924HT UT WOS:000228970400009 PM 15791456 ER PT J AU Lin, J Kadlubar, FF Spitz, MR Zhao, H Wu, XF AF Lin, J Kadlubar, FF Spitz, MR Zhao, H Wu, XF TI A modified host cell reactivation assay to measure DNA repair capacity for removing 4-aminobiphenyl adducts: A pilot study of bladder cancer SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID GENETIC SUSCEPTIBILITY; LUNG-CANCER; SENSITIVITY; DAMAGE AB As DNA repair plays an important role in genetic susceptibility to bladder cancer, assessment of the DNA repair phenotype is critical for the molecular epidemiology of bladder cancer. In this study, we developed and applied an assay using the luciferase (luc) reporter gene in a host-cell reactivation assay to measure DNA repair capacity for DNA damage induced by 4-aminobiphenyl (4-ABP), a well-studied aromatic amine and a known bladder carcinogen. We observed a dose-response relationship for 4-ABP dosage and DNA repair capacity (luc activity). We then applied this assay to measure DNA repair capacity in a pilot study of 89 pairs of bladder cancer patients and healthy controls matched by age, gender, and ethnicity, and we found that DNA repair capacity was significantly lower in cases than in controls (13.0% versus 14.4%; P = 0.006). Poor DNA repair capacity was associated with 3.42-fold increased bladder cancer risk. Further analysis revealed that intermediate and low levels of DNA repair capacity increased bladder cancer risk to 3.43-fold and 4.97-fold, respectively, compared with individuals with the most efficient DNA repair capacity. Moreover, ever. smokers with suboptimal DNA repair capacity exhibited a 6.06-fold increased risk compared with never smokers with normal DNA repair capacity. In conclusion, our results support the hypothesis that deficient DNA repair capacity for 4-ABP induced DNA damage and increases bladder cancer risk. Our assay provides a new tool to specifically quantify DNA repair capacity in bladder cancer studies and, therefore, contributes to our goal of further elucidating bladder carcinogenesis. C1 Univ Texas, MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Wu, XF (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Epidemiol, 1155 Hermann Pressler Blvd,Unit 1340, Houston, TX 77030 USA. EM xwu@mdanderson.org FU NCI NIH HHS [CA 88579, CA 86390, CA 91846, CA 74880] NR 16 TC 14 Z9 14 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JUL PY 2005 VL 14 IS 7 BP 1832 EP 1836 DI 10.1158/1055-9965.EPI-04-0902 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 945TS UT WOS:000230525700039 PM 16030125 ER PT J AU Fang, GC Wu, YS Chen, JC Fu, PPC Chang, CN Ho, TT Chen, MH AF Fang, GC Wu, YS Chen, JC Fu, PPC Chang, CN Ho, TT Chen, MH TI Characteristic study of polycyclic aromatic hydrocarbons for fine and coarse particulates at Pastureland near Industrial Park sampling site of central Taiwan SO CHEMOSPHERE LA English DT Article DE PAHs; pastureland; PM2.5; PM2.5-10; dust storm; GC-MS ID URBAN ATMOSPHERE; PM2.5 AEROSOLS; AIR; CHINA; PM10; PAHS; AREA AB The concentrations of ambient air polycyclic aromatic hydrocarbons were measured in a farm area (Tunghai University Pastureland) between August 2001 and April 2002 in central Taiwan, Taichung. Particle-bound polycyclic aromatic hydrocarbons (PAHs) were collected on quartz filters, the collected sample was extracted with a dichloromethane (DCM)/n-hexane mixture (50/50, v/v) for 24 h, and then the extracts were subjected to gas chromatography-mass spectrometric analysis. The PM2.5 (fine particulate) and PM2.5-10 (coarse particulate) total PAHs concentrations at the Tunghai University Pastureland sampling site were found to be 180.62 ng m(-3) and 164.98 ng m(-3), respectively. In general, the concentrations of polycyclic aromatic hydrocarbons were higher in spring and winter than those of summer and autumn for either PM2.5 or PM2.5-10 in Pastureland in central Taiwan. Moreover, coarse particulates are the dominant species during the dust storm season (March and April) in central Taiwan. (c) 2005 Elsevier Ltd. All rights reserved. C1 Hungkuang Univ, Dept Environm Engn, Taichung 433, Taiwan. Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. Tunghai Univ, Dept Environm Sci, Taichung 407, Taiwan. RP Fang, GC (reprint author), Hungkuang Univ, Dept Environm Engn, Taichung 433, Taiwan. EM gcfang@sunrise.hkc.edu.tw NR 13 TC 24 Z9 27 U1 0 U2 7 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0045-6535 J9 CHEMOSPHERE JI Chemosphere PD JUL PY 2005 VL 60 IS 3 BP 427 EP 433 DI 10.1016/j.chemosphere.2004.12.034 PG 7 WC Environmental Sciences SC Environmental Sciences & Ecology GA 939IU UT WOS:000230066800017 PM 15924963 ER PT J AU Toombs, EL AF Toombs, EL TI Cosmetics in the treatment of acne vulgaris SO DERMATOLOGIC CLINICS LA English DT Article AB This article describes scenarios of patients with acne vulgaris who have tried over-the-counter products and cosmetics, and are disheartened by the persistence of their disease and the resulting scars. They may have seen an aesthetician, plastic surgeon, or even a general practioner before seeing a well-informed skin specialist. Patients perceive the dermatologist to be the skin care expert and seek guidance to obtain otherwise unobtainable results. Therefore, practicing dermatologists should take advantage of the available tools to treat patients aggressively and completely. Appropriately applied cosmetics can play a role in achieving this goal. This article describes scenarios that integrate cosmetics into an anti-acne treatment regimen that is well tolerated by both male and female patients. C1 Aesthet Dermatol Dupont Circle, Washington, DC 20009 USA. US FDA, Off Cosmet & Colors, Washington, DC 20204 USA. RP Toombs, EL (reprint author), Aesthet Dermatol Dupont Circle, 1612 18th St NW, Washington, DC 20009 USA. EM ella.toombs@verizon.net NR 21 TC 5 Z9 5 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 0733-8635 J9 DERMATOL CLIN JI Dermatol. Clin. PD JUL PY 2005 VL 23 IS 3 BP 575 EP + DI 10.1016/j.det.2005.04.001 PG 8 WC Dermatology SC Dermatology GA 955SW UT WOS:000231248900017 PM 16039436 ER PT J AU Batz, MB Doyle, MP Morris, JG Painter, J Singh, R Tauxe, RV Taylor, MR Wong, DMAL AF Batz, MB Doyle, MP Morris, JG Painter, J Singh, R Tauxe, RV Taylor, MR Wong, DMAL CA Food Attribution Working Grp TI Attributing illness to food SO EMERGING INFECTIOUS DISEASES LA English DT Article ID UNITED-STATES; RISK-FACTORS; INFECTION; SITES; SURVEILLANCE; ENTERITIDIS; DENMARK; NETWORK AB Identification and prioritization of effective food safety interventions require an understanding of the relationship between food and pathogen from farm to consumption. Critical to this cause is food attribution, the capacity to attribute cases of foodborne disease to the food vehicle or other source responsible for illness. A wide variety of food attribution approaches and data are used around the world including the analysis of outbreak data, case-control studies, microbial subtyping and source tracking methods, and expert judgment, among others. The Food Safety Research Consortium sponsored the Food Attribution Data Workshop in October 2003 to discuss the virtues and limitations of these approaches and to identify future options for collecting food attribution data in the United States. We summarize workshop discussions and identify challenges that affect progress in this critical component of a risk-based approach to improving food safety. C1 Resources Future Inc, Washington, DC 20036 USA. Univ Georgia, Griffin, GA USA. Univ Maryland, Sch Med, Baltimore, MD 21201 USA. Ctr Dis Control & Prevent, Atlanta, GA USA. US FDA, Laurel, MD USA. Danish Inst Food & Vet Res, Copenhagen, Denmark. RP Batz, MB (reprint author), Resources Future Inc, 1616 P St NW, Washington, DC 20036 USA. EM mbatz@rff.org NR 39 TC 102 Z9 107 U1 1 U2 11 PU CENTER DISEASE CONTROL PI ATLANTA PA ATLANTA, GA 30333 USA SN 1080-6040 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD JUL PY 2005 VL 11 IS 7 BP 993 EP 999 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 939XS UT WOS:000230106600001 PM 16022770 ER PT J AU Perez-Gracia, JL Munoz, M Williams, G Wu, J Carrasco, E Garcia-Ribas, I Peiro, A Lopez-Picazo, JM Gurpide, A Chopitea, A Martin-Algarra, S Garcia-Foncillas, J Blatter, J AF Perez-Gracia, JL Munoz, M Williams, G Wu, J Carrasco, E Garcia-Ribas, I Peiro, A Lopez-Picazo, JM Gurpide, A Chopitea, A Martin-Algarra, S Garcia-Foncillas, J Blatter, J TI Assessment of the value of confirming responses in clinical trials in oncology SO EUROPEAN JOURNAL OF CANCER LA English DT Article DE response assessment; response guidelines; clinical trials ID ADVANCED BREAST-CANCER; INTERNATIONAL-UNION; SWITZERLAND; AGREEMENT; PROGRAM; THERAPY; PROJECT; GENEVA AB The requirement for a second assessment to confirm initial tumour response is required by all response guidelines. Its rationale, however, is not clear. We have conducted this study to compare validity of response rate assessment determined with and without secondary confirmation. Using specified criteria, nine trials of one single cytotoxic drug including 416 patients were selected from a pharmaceutical database. objective response rates were determined by a single determination and by two separate determinations. 81 responses (19.5%, [15.8-23.6%]) were scored by the confirmation method and 97 responses (23.3% [19.3-27.7%]) by the no-confirmation method. The Kappa (K) coefficient of 0.89 indicates good agreement between both methods. This is the first study that systematically compares response rates calculated with and without performing response confirmation. Results show good agreement between both methods. We suggest that assessing response without confirmation may be the preferred method. These results should be confirmed by additional studies in a variety of cancer settings. (c) 2005 Elsevier Ltd. All rights reserved. C1 Univ Navarra Clin, Dept Med Oncol, Pamplona 31008, Spain. Eli Lilly & Co, Dept Clin Res, Madrid, Spain. US FDA, Rockville, MD 20857 USA. Eli Lilly & Co, Dept Clin Res, Indianapolis, IN 46285 USA. Eli Lilly & Co, Dept Clin Res, Frankfurt, Germany. RP Perez-Gracia, JL (reprint author), Univ Navarra Clin, Dept Med Oncol, Avenida Pio 12 36, Pamplona 31008, Spain. EM jlgracia@unav.es RI Garcia-Foncillas, Jesus/E-6857-2010 OI Perez-Gracia, Jose Luis/0000-0003-4941-9075; NR 12 TC 7 Z9 7 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD JUL PY 2005 VL 41 IS 11 BP 1528 EP 1532 DI 10.1016/j.ejca.2005.01.023 PG 5 WC Oncology SC Oncology GA 955AK UT WOS:000231196800014 PM 16026690 ER PT J AU Shah, VP AF Shah, VP TI IV-IVC for topically applied preparations - a critical evaluation SO EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS LA English DT Article; Proceedings Paper CT 5th International Conference and Workshop on Cell Culture and In Vitro Models for Drug Absorption and Delivery CY FEB 25-MAR 05, 2004 CL Saarbrucken Univ, Dept Biopharmaceut & Pharmaceut Technol, Saarbrucken, GERMANY SP Int Assoc Pharmaceut Technol, Controlled Release Soc, Local Chapter Germany, German Pharmaceut Soc, European Federat Pharmaceut Sci, Soc Dermopharm, Zentralstelle Efass & Bewert Ersatz & Erganzungsmethoden Tierversuch Im Rfl, European Assoc Pharma Biotechnol, Stift Europrofess, NanoBioNet, Saarland Univ, Ctr Bioinformat, Univ Saarlandes, Frankreichzentrum, Across Barriers GmbH HO Saarbrucken Univ, Dept Biopharmaceut & Pharmaceut Technol DE in vitro-in vivo correlation; in vitro release; rheological properties; spreadability; dermatopharmacokinctics; DPK; pharmacodynamics ID DERMATOLOGICAL DRUG PRODUCTS; STRATUM-CORNEUM; RELEASE; BIOEQUIVALENCE AB In vitro-in vivo correlation (IV-IVC) is the relationship between an in vitro parameter (drug release or other rheological properties/measurement such as viscosity and spreadability) and an in vivo parameter (pharmacodynamic (PD) or dermatopharmacokinetic (DPK) or other measurement). In a true sense of correlation, in vitro measurement should predict in vivo performance of the product. For topically applied preparations, one of the in vitro measurements is the drug release from the formulation and in vivo measurement is the drug concentration in the stratum corneum, DPK or the PD measurements. The in vitro release of the drug is the property of the dosage form and is a measure of product quality and 'sameness', especially after certain Scale-UP and Post Approval Changes after initial drug approval. To obtain an IV-IVC for a topically applied drug product is a difficult challenge. However, some success has been achieved in showing a relationship between the drug release and PD and/or DPK measurement. Interestingly, one of the in vitro rheological properties was found to relate to the observed PD and DPK response for Clobetasol dipropionate products. Different rheological properties of the two formulation products explained the difference in DPK results obtained by two laboratories for the same tretinoin Gel products. In the scientific arena, it is difficult to obtain a classical IV-IVC even for orally administered products and is more so difficult for topically administered drug products. (c) 2005 Elsevier B.V. All rights reserved. C1 US FDA, Ctr Drug Evaluat & Res, Off Pharmaceut Sci, Rockville, MD 20852 USA. RP Shah, VP (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Pharmaceut Sci, Rockville, MD 20852 USA. EM shahvi@cder.fda.gov NR 12 TC 14 Z9 21 U1 0 U2 2 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 JUL PY 2005 VL 60 IS 2 BP 309 EP 314 DI 10.1016/j.ejpb.2004.09.015 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 941UQ UT WOS:000230240100014 PM 15939242 ER PT J AU Rathore, D McCutchan, TF Sullivan, M Kumar, S AF Rathore, D McCutchan, TF Sullivan, M Kumar, S TI Antimalarial drugs: current status and new developments SO EXPERT OPINION ON INVESTIGATIONAL DRUGS LA English DT Review DE antimalarial; artemisinin; artesunate; atovaquone; chloroquine; lumefantrine; malaria; mefloquine; Plasmodium; protease inhibitors; pyrimethamine; sulfadoxine; triclosan ID PLASMODIUM-FALCIPARUM MALARIA; NONIMMUNE COLOMBIAN SOLDIERS; PLACEBO-CONTROLLED TRIAL; UNCOMPLICATED FALCIPARUM; DOUBLE-BLIND; SULFADOXINE-PYRIMETHAMINE; AFRICAN CHILDREN; IN-VITRO; PEPTIDE DEFORMYLASE; PROTEIN FARNESYLTRANSFERASE AB Malaria continues to be a major threat in the developing world, with > 1 million clinical episodes and 3000 deaths every day. in the last century, malaria claimed between 150 and 300 million lives, accounting for 2 - 5% of all deaths. Currently similar to 40% of the world population resides in areas of active malaria transmission. The disease symptoms are most severe in young children and pregnant women. A total of 90% of the disease-associated mortality occurs in Subsaharan Africa, despite the fact that malaria is indigenous to most tropical regions. A licensed vaccine for malaria has not become a reality and antimalarial drugs are the only available method of treatment. Although chloroquine, the first synthetically developed antimalarial, proved to be an almost magical cure for > 30 years, the emergence and spread of chloroquine-resistant parasites has made it virtually ineffective in most parts of the world. Currently, artemisinin, a plant-derived antimalarial, is the only available drug that is globally effective against the parasite. Although several new drugs have been introduced in the past 30 years, widespread or isolated cases of resistance indicate that their window of effectiveness will be limited. Thus, there is an urgent need to develop new therapeutics and regimens for malaria control. This article presents an overview of the currently available antimalarial chemotherapy options and the efforts being undertaken to develop new drugs based on both the recent technological advances and modifications to the old remedies, and on combination therapies. C1 Ctr Biol Evaluat & Res, Off Blood Res & Review, Div Emerging & Transfus Transmitted Dis, Rockville, MD 20850 USA. Virginia Polytech Inst & State Univ, Virginia Bioinformat Inst, Blacksburg, VA 24061 USA. NIAID, Lab Malaria & Vector Res, Rockville, MD 20850 USA. RP Kumar, S (reprint author), Ctr Biol Evaluat & Res, Off Blood Res & Review, Div Emerging & Transfus Transmitted Dis, Rockville Pike, Rockville, MD 20850 USA. EM KumarS@cber.fda.gov NR 111 TC 40 Z9 42 U1 1 U2 11 PU ASHLEY PUBLICATIONS LTD PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1354-3784 J9 EXPERT OPIN INV DRUG JI Expert Opin. Investig. Drugs PD JUL PY 2005 VL 14 IS 7 BP 871 EP 883 DI 10.1517/13543784.14.7.871 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 950DH UT WOS:000230837300011 PM 16022576 ER PT J AU Chen, HC Wang, G Backlund, PS Boykins, RA AF Chen, HC Wang, G Backlund, PS Boykins, RA TI Phosphorylation and O-glycosylation sites identification in peptides by Ba-hydroxide catalyzed beta-elimination/propanethiol addition and mass spectrometric analyses SO FEBS JOURNAL LA English DT Meeting Abstract CT IUBMB 50th Anniversary Symposium CY JUL 02-07, 2005 CL Budapest, HUNGARY SP Int Union Biochem Molecular Biol C1 NICHD, Endo Repro Res Br, NIH, Bethesda, MD USA. NICHD, Lab Cell & Mol Biophys, NIH, Bethesda, MD USA. US FDA, Ctr Biol Evaluat & Res, Biophys Lab, Bethesda, MD USA. EM chenha@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1742-464X J9 FEBS J JI FEBS J. PD JUL PY 2005 VL 272 SU 1 BP 526 EP 526 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 005MG UT WOS:000234826102610 ER PT J AU Hight, SC Cheng, J AF Hight, SC Cheng, J TI Determination of total mercury in seafood by cold vapor-atomic absorption spectroscopy (CVAAS) after microwave decomposition SO FOOD CHEMISTRY LA English DT Article DE total Hg; seafood; CVAAS; microwave decomposition ID FLOW-INJECTION; POTABLE WATER; ICP-MS; SPECTROMETRIC DETERMINATION; BIOLOGICAL-MATERIALS; SODIUM-BOROHYDRIDE; STABILIZING AGENT; RAPID DIGESTION; GOLD; FISH AB A method was developed for determination of total Hg in seafood using 10% w/v SnCl2 . 2H(2)O and continuous flow CVAAS after microwave decomposition in closed vessels. Seafoods were decomposed with 5 mL HNO3 and 1 mL 1% w/v NaCl at 200 degreesC, transferred to polypropylene tubes containing 3.5 mL HCl, and diluted to 50 mL with H2O, Standards were prepared in diluent containing 10% v/v HNO3, 7% v/v HCl, and 0.02% w/v NaCl. Potential interference by 22 elements was evaluated. Interference by Se and An was observed. Stability of standard solutions in HNO3, HCl and NaCl was evaluated. Stabilizing effect of chloride was demonstrated. Results for six reference materials containing 0.0371-1.59 mg/kg Hg were 86-106% of certificate values. Concentrations in 11 varieties of seafood were 0.015-1.78 mg/kg. Average recoveries of inorganic and organic Hg added to seafood were 102% and 99%, respectively; average recoveries from fortified method blanks were 100% and 97%, respectively. The limits of quantitation were 0.0022 and 0.011 mg/kg in seafoods and reference materials, respectively. Published by Elsevier Ltd. C1 US FDA, Ctr Food Safety & Appl Nutr, Elemental Res Branch, College Pk, MD 20740 USA. RP Hight, SC (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Elemental Res Branch, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM susan.hight@fda.gov; john.cheng@fda.gov NR 33 TC 42 Z9 44 U1 2 U2 19 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0308-8146 J9 FOOD CHEM JI Food Chem. PD JUL PY 2005 VL 91 IS 3 BP 557 EP 570 DI 10.1016/j.foochem.2004.10.024 PG 14 WC Chemistry, Applied; Food Science & Technology; Nutrition & Dietetics SC Chemistry; Food Science & Technology; Nutrition & Dietetics GA 896FR UT WOS:000226920500023 ER PT J AU Lin, CTJ Jensen, KL Yen, ST AF Lin, CTJ Jensen, KL Yen, ST TI Awareness of foodborne pathogens among US consumers SO FOOD QUALITY AND PREFERENCE LA English DT Article DE consumer awareness; foodborne pathogens; multivariate probit ID FOOD SAFETY; MODELS; RISKS AB Each year in the United States, microbial pathogens cause millions of cases of foodborne disease and result in many hospitalizations and deaths. Effective consumer education programs to promote safer food handling practices and other averting behaviors may benefit from consumer awareness of microbial pathogens. This paper investigates US consumers' awareness of four major microbial pathogens (Salmonella, Campylobacter, Listeria and Escherichia coli) as food safety problems, using a multivariate probit model. The awareness varies among pathogens and the variations appear to be related to differences in the number and severity of illnesses associated with these pathogens. Our findings suggest that awareness of microbial pathogens is associated with food safety perceptions, awareness of potentially risky foods and substances associated with potential food safety hazards, food safety related behaviors, and demographics. There are differentiated effects of variables on awareness of the four pathogens. (c) 2004 Elsevier Ltd. All rights reserved. C1 Univ Tennessee, Dept Agr Econ, Knoxville, TN 37996 USA. US FDA, Div Market Studies, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Yen, ST (reprint author), Univ Tennessee, Dept Agr Econ, Knoxville, TN 37996 USA. EM chung-tung.lin@cfsan.fda.gov; kjensen@utk.edu; syen@utk.edu NR 48 TC 24 Z9 25 U1 0 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0950-3293 J9 FOOD QUAL PREFER JI Food. Qual. Prefer. PD JUL PY 2005 VL 16 IS 5 BP 401 EP 412 DI 10.1016/j.foodqual.2004.07.001 PG 12 WC Food Science & Technology SC Food Science & Technology GA 927AW UT WOS:000229165800003 ER PT J AU Stultz, BG Ray, RP Hursh, DA AF Stultz, BG Ray, RP Hursh, DA TI Analysis of the shortvein cis-regulatory region of the decapentaplegic gene of Drosophila melanogaster SO GENESIS LA English DT Article DE decapentaplegic; cis-regulation; shortvein; adult-head capsule formation; Drosophila melanogaster; Bone Morphogenetic Protein ID MIDGUT MORPHOGENESIS; CUBITUS INTERRUPTUS; VISCERAL MESODERM; IMAGINAL DISKS; HOMEOTIC GENE; EXPRESSION; EMBRYO; DPP; ULTRABITHORAX; ELEMENTS AB In mammals, the Transforming Growth Factor-beta (TGF-beta) superfamily controls a variety of developmental processes. In Drosophila, by contrast, a single member of the superfamily, decapentaplegic (dpp) performs most TGF-beta developmental functions. The complexity of dpp functions is reflected in the complex cis-regulatory sequences that flank the gene. Dpp is divided into three regions: Hin, including the protein-coding exons; disk, including 3' cis-regulatory sequences; and shortvein (shv), including noncoding exons and 5' cis-regulatory sequences. We analyzed the cis-regulatory structure of the shortvein region using a nested series of rearrangement breakpoints and rescue constructs. We delimit the molecular regions responsible for three mutant phenotypes: larval lethality, wing venation defects, and head capsule defects. Multiple overlapping elements are responsible for larval lethality and wing venation defects. However, the area regulating head capsule formation is distinct, and resides 5' to these elements. We have demonstrated this by isolating and describing two novel dpp alleles, which affect only the adult head capsule. C1 US FDA, Lab Immunol & Dev Biol, Ctr Biol Evaluat & Res, Div Cell & Gene Therapy, Bethesda, MD 20892 USA. Univ Sussex, Sch Life Sci, Dept Biol & Environm Sci, Brighton, E Sussex, England. RP Hursh, DA (reprint author), US FDA, Lab Immunol & Dev Biol, Ctr Biol Evaluat & Res, Div Cell & Gene Therapy, HFM 730,Bldg 29B,Rm 1E16,8800 Rockville Pike, Bethesda, MD 20892 USA. EM hursh@cber.fda.gov NR 43 TC 8 Z9 8 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1526-954X J9 GENESIS JI Genesis PD JUL PY 2005 VL 42 IS 3 BP 181 EP 192 DI 10.1002/gene.20134 PG 12 WC Developmental Biology; Genetics & Heredity SC Developmental Biology; Genetics & Heredity GA 950CT UT WOS:000230835900006 PM 15986479 ER PT J AU Kent, SLB Dennis, JE AF Kent, SLB Dennis, JE TI FDA's pioneering role in laser safety regulations SO HEALTH PHYSICS LA English DT Meeting Abstract C1 US FDA, Boise, ID 83702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0017-9078 EI 1538-5159 J9 HEALTH PHYS JI Health Phys. PD JUL PY 2005 VL 89 IS 1 SU S BP S37 EP S37 PG 1 WC Environmental Sciences; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA 938FS UT WOS:000229985900097 ER PT J AU Kent, SLB O'Kelley, P AF Kent, SLB O'Kelley, P TI The history of state and federal nonionizing radiation control programs SO HEALTH PHYSICS LA English DT Meeting Abstract C1 US FDA, Boise, ID 83702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0017-9078 EI 1538-5159 J9 HEALTH PHYS JI Health Phys. PD JUL PY 2005 VL 89 IS 1 SU S BP S37 EP S37 PG 1 WC Environmental Sciences; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA 938FS UT WOS:000229985900099 ER PT J AU Kent, SLB Odlaug, MA AF Kent, SLB Odlaug, MA TI The birth and control of X-ray products SO HEALTH PHYSICS LA English DT Meeting Abstract C1 US FDA, Boise, ID 83702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0017-9078 EI 1538-5159 J9 HEALTH PHYS JI Health Phys. PD JUL PY 2005 VL 89 IS 1 SU S BP S36 EP S36 PG 1 WC Environmental Sciences; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA 938FS UT WOS:000229985900095 ER PT J AU Noska, MA Cunningham, WC Yu, C Cheng, JJ Kamboj, S Domotor, S Wallo, A AF Noska, MA Cunningham, WC Yu, C Cheng, JJ Kamboj, S Domotor, S Wallo, A TI Operational guidelines for food products potentially contaminated from a radiological dispersal device incident SO HEALTH PHYSICS LA English DT Meeting Abstract C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. US FDA, Ctr Food Safety & Appl Nutr, Rockville, MD 20857 USA. Argonne Natl Lab, Argonne, IL 60439 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0017-9078 EI 1538-5159 J9 HEALTH PHYS JI Health Phys. PD JUL PY 2005 VL 89 IS 1 SU S BP S25 EP S25 PG 1 WC Environmental Sciences; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA 938FS UT WOS:000229985900063 ER PT J AU Alderman, MH Arnett, DK Bakris, GL Black, HR Boerwinkle, E Califf, RM Cushman, WC Cutler, J Davis, BR Devereux, RB Ferdinand, K Fleg, JL Fournier, A Furberg, CD Giles, TD Gottdiener, JS Grimm, RH Hyman, DJ Jamerson, KA Kostis, JB Krauss, RM Leenen, FHH Levey, AS Levy, D MacMahon, S Oparil, S Probstfield, JL Psaty, BM Roccella, E Salive, M Schwartz, WB Svetkey, L Throckmorton, D Turner, ST Velletri, P Wright, J AF Alderman, MH Arnett, DK Bakris, GL Black, HR Boerwinkle, E Califf, RM Cushman, WC Cutler, J Davis, BR Devereux, RB Ferdinand, K Fleg, JL Fournier, A Furberg, CD Giles, TD Gottdiener, JS Grimm, RH Hyman, DJ Jamerson, KA Kostis, JB Krauss, RM Leenen, FHH Levey, AS Levy, D MacMahon, S Oparil, S Probstfield, JL Psaty, BM Roccella, E Salive, M Schwartz, WB Svetkey, L Throckmorton, D Turner, ST Velletri, P Wright, J CA Natl Heart Lung Blood Inst Working TI Major clinical trials of hypertension - What should be done next? SO HYPERTENSION LA English DT Article DE clinical trials; drug therapy ID CHRONIC HEART-FAILURE; BLOOD-PRESSURE CONTROL; EVIDENCE-BASED PROOF; CARDIOVASCULAR-DISEASE; KIDNEY-DISEASE; RANDOMIZED-TRIAL; ANGIOTENSIN-II; UNITED-STATES; PREVENTION; RISK AB The National Heart, Lung, and Blood Institute assembled an ad hoc working group to evaluate opportunities for new major clinical trials in the field of hypertension. The mandate of this working group was to consider the possible designs of major randomized clinical trials focused on clinical outcomes that might merit significant investment by the National Institutes of Health. The group concluded that the ideal pragmatic clinical trial would have a factorial design and include a population at elevated risk of cardiovascular disease events. Subjects would be randomized to a target of systolic blood pressure <130 versus 130 to 150 mm Hg for adequate separation of means. Initial treatment with thiazide diuretic would be followed by randomization to angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, beta-blocker, calcium channel blocker, or aldosterone antagonist. A third drug could be added according to a protocol. DNA, proteins, and metabolites would be collected in a sample adequate to assess differential impact of treatment on outcome as a function of genotype, proteomic, and metabolomic expression. Subclinical markers and images would also be measured in a sample of patients to develop evidence of ability to predict ultimate effect on clinical outcomes. This ideal trial would take place within a network, funded for at least a decade, aimed at connecting primary care providers with hypertension specialists. Within the network, substudies or independent studies would be coordinated to develop a continuously improving base of knowledge about the effective delivery of hypertension care. C1 Duke Clin Res Inst, Durham, NC 27715 USA. NHLBI, Framingham Heart Study, Bethesda, MD 20892 USA. Albert Einstein Coll Med, Bronx, NY 10467 USA. Univ Minnesota, Minneapolis, MN 55455 USA. Rush Med Univ, Chicago, IL USA. Rush Presbyterian St Lukes Med Ctr, Chicago, IL 60612 USA. Univ Texas, Hlth Sci Ctr, Houston, TX USA. Univ Tennessee, Hlth Sci Ctr, Knoxville, TN 37996 USA. Univ Texas, Sch Publ Hlth, Austin, TX 78712 USA. New York Presbyterian Hosp, New York, NY USA. Xavier Univ, Coll Pharm, New Orleans, LA 70125 USA. Univ Hosp, Dept Nephrol, Amiens, France. Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA. Louisiana State Univ, Sch Med, Baton Rouge, LA 70803 USA. Univ Maryland, Sch Med, Baltimore, MD 21201 USA. Baylor Coll Med, Houston, TX 77030 USA. Univ Michigan, Med Ctr, Ann Arbor, MI 48109 USA. Robert Wood Johnson Med Sch, Piscataway, NJ USA. Childrens Hosp Oakland, Res Inst, Oakland, CA 94609 USA. Univ Ottawa, Inst Heart, Ottawa, ON K1N 6N5, Canada. Tufts Univ, Sch Med, Medford, MA 02155 USA. Univ Sydney, Sydney, NSW 2006, Australia. Univ Alabama Birmingham, Vasc Biol & Hypertens Program, Birmingham, AL USA. Univ Washington, Sch Med, Clin Trials Serv Unit, Seattle, WA 98195 USA. NHLBI, OPEC, Bethesda, MD 20892 USA. Ctr Medicare & Medicaid Serv, Div Med & Surg Serv, Baltimore, MD USA. Tufts Univ New England Med Ctr, Div Nephrol, Boston, MA 02111 USA. Duke Univ, Med Ctr, Durham, NC 27706 USA. US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. US FDA, Div Cardiorenal Drugs, Rockville, MD 20857 USA. Mayo Clin Rochester, Rochester, MN USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. RP Califf, RM (reprint author), Duke Clin Res Inst, POB 17969, Durham, NC 27715 USA. EM Calif001@mc.duke.edu NR 31 TC 16 Z9 18 U1 2 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X EI 1524-4563 J9 HYPERTENSION JI Hypertension PD JUL PY 2005 VL 46 IS 1 BP 1 EP 6 DI 10.1161/01.HYP.0000168924.37091.58 PG 6 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 938OM UT WOS:000230012700001 ER PT J AU Harvill, ET Lee, G Grippe, VK Merkel, TJ AF Harvill, ET Lee, G Grippe, VK Merkel, TJ TI Complement depletion renders C57BL/6 mice sensitive to the Bacillus anthracis Sterne strain SO INFECTION AND IMMUNITY LA English DT Article ID TOXIN; PATHOGENESIS AB Concerns regarding safety and control of virulent Bacillus anthracis have created substantial hurdles to the study of anthrax. The Sterne strain is considered relatively safe to study, but this acapsular strain has a defect in normal mice and is often studied in A/J mice. A/J mice are highly susceptible to the Sterne strain, due to a defect in the Hc locus, which encodes complement factor 5 (C5). Here we show that normally resistant C57/BL/6 mice become highly susceptible to the Sterne strain upon complement depletion with cobra venom factor. This generalizable approach should allow the virulence of anthrax to be studied under relatively safe conditions and using a wide variety of mouse strains. C1 US FDA, DBPAP, CBER, Lab Respiratory & Special Pathogens, Bethesda, MD 20892 USA. Penn State Univ, Dept Vet Sci, Res Labs, University Pk, PA 16802 USA. RP Merkel, TJ (reprint author), US FDA, DBPAP, CBER, Lab Respiratory & Special Pathogens, Bldg 29,Room 418,29 Lincoln Dr, Bethesda, MD 20892 USA. EM merkel@cber.fda.gov NR 12 TC 33 Z9 33 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JUL PY 2005 VL 73 IS 7 BP 4420 EP 4422 DI 10.1128/IAI.73.7.4420-4422.2005 PG 3 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 940NL UT WOS:000230151100075 PM 15972541 ER PT J AU Singh, R Schroeder, CM Meng, JH White, DG McDermott, PF Wagner, DD Yang, HC Simjee, S DebRoy, C Walker, RD Zhao, SH AF Singh, R Schroeder, CM Meng, JH White, DG McDermott, PF Wagner, DD Yang, HC Simjee, S DebRoy, C Walker, RD Zhao, SH TI Identification of antimicrobial resistance and class 1 integrons in Shiga toxin-producing Escherichia coli recovered from humans and food animals SO JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY LA English DT Article DE gene cassettes; food-borne pathogens; STEC ID PREVALENCE; GENES AB Objectives: The objective of this study was to identify antimicrobial resistance and class 1 integrons among Shiga toxin-producing Escherichia coli (STEC). Methods: Two-hundred and seventy-four STEC recovered from poultry, cattle, swine and humans were characterized by antimicrobial susceptibility testing, screened for the presence of class 1 integrons by PCR, and assayed for integron transfer by conjugation. Results: Ninety-three (34%) of the isolates were resistant to streptomycin, followed by 89 (32%) to sulfamethoxazole, 83 (30%) to tetracycline, 48 (18%) to ampicillin, 29 (11%) to cefalothin, 22 (8%) to trimethoprim/sulfamethoxazole, 18 (7%) to gentamicin, 13 (5%) to chloramphenicol and 10 (4%) to cefoxitin. Class 1 integrons were detected in 43 (16%) of the 274 isolates. The adenyl acetyltransferase gene, aadA, which confers resistance to streptomycin, was identified in integrons from 41 (95%) of these 43 isolates, and the dfrA12 gene, which confers resistance to trimethoprim, was identified in integrons from eight (19%) of the isolates. The sat1 gene, which confers resistance to streptothricin, an antimicrobial that has never been approved for use in the United States, was identified in integrons from three (7%) of the isolates. Transfer of integrons by conjugation between strains of E. coli resulted in transfer of antimicrobial-resistant phenotypes for ampicillin, chloramphenicol, cefalothin, gentamicin, tetracycline, trimethoprim, sulfamethoxazole and streptomycin. Conclusions: Antimicrobial resistance is common in STEC. Class 1 integrons located on mobile plasmids have facilitated the emergence and dissemination of antimicrobial resistance among STEC in humans and food animals. C1 US FDA, Ctr Vet Med, Res Off, Div Anim & Food Microbiol, Laurel, MD 20708 USA. Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA. Penn State Univ, Gastroenter Dis Ctr, University Pk, PA USA. RP Zhao, SH (reprint author), US FDA, Ctr Vet Med, Res Off, Div Anim & Food Microbiol, 8401 Muirkirk Rd, Laurel, MD 20708 USA. EM szhao@cvm.fda.gov NR 10 TC 42 Z9 47 U1 1 U2 10 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 JUL PY 2005 VL 56 IS 1 BP 216 EP 219 DI 10.1093/jac/dki161 PG 4 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA 948OE UT WOS:000230724800029 PM 15911552 ER PT J AU Rupp, HS Stuart, JS Hurlbut, JA AF Rupp, HS Stuart, JS Hurlbut, JA TI Liquid chromatography/tandem mass spectrometry analysis of chloramphenicol in cooked crab meat SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID ELECTRON-CAPTURE DETECTION; GAS-CHROMATOGRAPHY; RESIDUES; SHRIMP; THIAMPHENICOL; FLORFENICOL AB A liquid chromatography/tandem mass spectrometry (LC/MS/MS) method is described for the extraction, cleanup, determination, and confirmation of chloramphenicol (CAP) in cooked crab meat. The method involves pulverization of cooked crab meat with dry ice; extraction of the CAP into ethyl acetate (EtOAc); evaporation (by N-2) of the EtOAc; addition of methanol, aqueous NaCl, and heptane; extraction of the lipids into the heptane, followed by extraction of the aqueous phase with MAC; evaporation (by N2) of the MAC; dissolution into methanol-water; filtration; and separation/detection/confirmation using LC/MS/MS. Crab meat was fortified at 0.25, 0.50, and 1.0 ng/g (ppb) chloramphenicol. Average absolute recoveries were 67, 84, and 86 %, respectively, with relative standard deviation values all less than 1 %. Four daughter ions (m/z 152,176,194, and 257) were monitored off the m/z 321 precursor ion. Determination was based on a standard curve using the peak areas of the m/z 152 daughter ion (the base peak) for standard solutions equivalent to 0.10, 0.20, 0.50, and 1.0 ppb in tissue (made with control crab extract). A set of 6 matrix controls (unfortified crab meat) was also analyzed, in which no chloramphenicol was detected. For identification purposes, the ion ratios (of each daughter ion versus the base daughter ion) of the fortified crab versus those of the chloramphenicol standards agreed within 10 % (relative) at fortified chloramphenicol concentrations of 0.25-1.0 ppb. C1 US FDA, Seafood Prod Res Ctr, Bothell, WA 98021 USA. US FDA, Pacific Reg Lab NW, Bothell, WA 98021 USA. RP Rupp, HS (reprint author), US FDA, Seafood Prod Res Ctr, 22201 23rd Dr SE, Bothell, WA 98021 USA. EM heidi.rupp@fda.gov NR 8 TC 7 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 JUL-AUG PY 2005 VL 88 IS 4 BP 1155 EP 1159 PG 5 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 950PT UT WOS:000230870200027 PM 16152935 ER PT J AU Blodgett, RJ AF Blodgett, RJ TI Upper and lower bounds for a serial dilution test SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article AB A Poisson-binomial model estimates the concentration of a target microbe from a serial dilution test. The maximum likelihood procedure gives an equation whose solution equals the estimate of the concentration. This paper gives bounds for the solution to this equation that require only minimal calculations. C1 US FDA, College Pk, MD 20740 USA. RP Blodgett, RJ (reprint author), US FDA, HFS-705,Rm 2D-011,5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM Robert.Blodgett@cfsan.fda.gov NR 5 TC 6 Z9 6 U1 0 U2 3 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD JUL-AUG PY 2005 VL 88 IS 4 BP 1227 EP 1230 PG 4 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 950PT UT WOS:000230870200038 PM 16152945 ER PT J AU Pfefer, TJ Agrawal, A Drezek, RA AF Pfefer, TJ Agrawal, A Drezek, RA TI Oblique-incidence illumination and collection for depth-selective fluorescence spectroscopy SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE fiber optics; fluorescence spectroscopy; Monte Carlo modeling ID RAMAN PROBE DESIGNS; TISSUE FLUORESCENCE; SINGLE-FIBER; GEOMETRY; MODEL AB Optimization of device-tissue interface parameters may lead to an improvement in the efficacy of fluorescence spectroscopy for minimally invasive disease detection. Although illumination-collection geometry has been shown to have a strong influence on the spatial origin of detected fluorescence, devices that deliver and/or collect light at oblique incidence are not well understood. Simulations are performed using a Monte Carlo model of light propagation in homogeneous tissue to characterize general trends in the intensity and spatial origin of fluorescence detected by angled geometries. Specifically, the influence of illumination angle, collection angle, and illumination-collection spot separation distance are investigated for low and high attenuation tissue cases. Results indicate that oblique-incidence geometries have the potential to enhance the selective interrogation of superficial or subsurface fluorophores at user-selectable depths up to about 0.5 mm. Detected fluorescence intensity is shown to increase significantly with illumination and collection angle. Improved selectivity and signal intensity over normal-incidence geometries result from the overlap of illumination and collection cones within the tissue. Cases involving highly attenuating tissue produce a moderate reduction in the depth of signal origin. While Monte Carlo modeling indicates that oblique-incidence designs can facilitate depth-selective fluorescence spectroscopy, optimization of device performance will require application-specific consideration of optical and biological parameters. (C) 2005 Society of Photo-Optical Instrumentation Engineers. C1 US FDA, CDRH, Rockville, MD 20852 USA. Rice Univ, Dept Bioengn, Houston, TX 77251 USA. RP Pfefer, TJ (reprint author), US FDA, CDRH, HFZ-130,12725 Twinbrook Pkwy, Rockville, MD 20852 USA. EM joshua.pfefer@fda.hhs.gov RI Drezek, Rebekah/A-5101-2012; Pfefer, Josh/I-9055-2012 NR 16 TC 22 Z9 22 U1 0 U2 4 PU SPIE-INT SOCIETY OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 J9 J BIOMED OPT JI J. Biomed. Opt. PD JUL-AUG PY 2005 VL 10 IS 4 AR 044016 DI 10.1117/1.1989308 PG 9 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 977JJ UT WOS:000232799200025 PM 16178649 ER PT J AU Wang, AMJ Bender, JE Pfefer, J Utzinger, U Drezek, RA AF Wang, AMJ Bender, JE Pfefer, J Utzinger, U Drezek, RA TI Depth-sensitive reflectance measurements using obliquely oriented fiber probes SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE fiber optic probes; reflectance spectroscopy; epithelial tissue; Monte Carlo ID NEAR-INFRARED SPECTROSCOPY; ILLUMINATION-COLLECTION GEOMETRY; INDUCED FLUORESCENCE-SPECTRA; SOURCE-DETECTOR SEPARATIONS; MONTE-CARLO SIMULATIONS; HIGHLY SCATTERING MEDIA; LASER-DOPPLER FLOWMETRY; SINGLE OPTICAL-FIBER; TURBID MEDIA; IN-VIVO AB Computer simulation is used to facilitate the design of fiber-probe geometries that enable enhanced detection of optical signals arising from specific tissue depths. Obtaining understanding of the relationship between fiber-probe design and tissue interrogation is critical when developing strategies for optical detection of epithelial precancers that originate at known depths from the tissue surface. The accuracy of spectroscopic diagnostics may be enhanced by discretely probing the optical properties of epithelium and underlying stroma, within which the morphological and biochemical features vary as a function of depth. While previous studies have investigated controlling tissue-probing depth for fluorescence-based modalities, in this study we focus on the detection of reflected light scattered by tissue. We investigate how the depth of optical interrogation may be controlled through combinations of collection angles, source-detector separations, and numerical apertures. We find that increasing the obliquity of collection fibers at a given source-detector separation can effectively enhance the detection of superficially scattered signals. Fiber numerical aperture provides additional depth selectivity; however, the perturbations in sampling depth achieved through this means are modest relative to the changes generated by modifying the angle of collection and source-detection separation. (C) 2005 Society of Photo-Optical Instrumentation Engineers. C1 Rice Univ, Dept Bioengn, Houston, TX 77251 USA. US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. Univ Arizona, Biomed Engn Program, Tucson, AZ USA. RP Drezek, RA (reprint author), Rice Univ, Dept Bioengn, POB 1892,MS-142,6100 Main St, Houston, TX 77251 USA. EM drezek@rice.edu RI Drezek, Rebekah/A-5101-2012; Pfefer, Josh/I-9055-2012 FU FDA HHS [BM 08362]; NCI NIH HHS [R01 CA098341, R01 CA098341-01A1, R01 CA098341-02, R01 CA098341-03, R01CA09841-01A1] NR 67 TC 36 Z9 38 U1 0 U2 10 PU SPIE-INT SOCIETY OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 J9 J BIOMED OPT JI J. Biomed. Opt. PD JUL-AUG PY 2005 VL 10 IS 4 AR 044017 DI 10.1117/1.1989335 PG 17 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 977JJ UT WOS:000232799200026 PM 16178650 ER PT J AU Kezirian, GM Drum, B Eydelman, M AF Kezirian, GM Drum, B Eydelman, M TI Systematic evaluation of wavefront-guided outcomes SO JOURNAL OF CATARACT AND REFRACTIVE SURGERY LA English DT Article; Proceedings Paper CT 5th Interantional Congress of Wavefront Sensing and Optimized Refractive Corrections CY FEB 21-24, 2004 CL Whistler, CANADA SP Alcon Lab, Bausch & Lomb Inc, Carl Zeiss Meditec, VISX, Wavelight Laser Technol, Intralase Corp, Lumenis Inc, Nidek Inc, Schwind Eye Tech Solutions ID IN-SITU KERATOMILEUSIS; REFRACTIVE SURGERY; ABERRATIONS; EYES AB Purpose: To present a format for reporting outcomes of aberrometer-guided refractive procedures. Setting: SurgiVision Consultants, Inc., Scottsdale, Arizona, and Food and Drug Administration, Center for Devices and Radiological Health, Rockland, Maryland, USA. Methods: Reports of standard refractive and visual outcomes (uncorrected visual acuity, manifest refractive spherical equivalent, best spectacle-corrected visual acuity) should be provided for any refractive surgery report. Comparison of postoperative uncorrected visual acuity to preoperative best spectacle-corrected visual acuity should be included. Aberration reports should convert 2nd-order terms to refractions (measured in diopters) and use standard refractive reporting methods. Changes in coma, spherical aberration, and root-mean-square changes should be described using statistical methods for aggregate data. Underlying statistics should be reported. Results: Aberration changes are well described by the mean error of the attempted versus achieved outcomes, comparison of the mean changes, and stability overtime. Ancillary plots include histogram representation of the postoperative scores. Additional reports of visual function should be included, as appropriate. Conclusion: Use of standardized tables and graphs permits qualitative and quantitative comparison of outcomes of refractive treatment with wavefront-guided lasers. Modifications of the recommended formats can be expected over time. C1 SurgiVis Consultants Inc, Scottsdale, AZ USA. US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. US FDA, Dept Hlth & Human Serv, Rockville, MD USA. RP Kezirian, GM (reprint author), 28071 N 90th Way, Scottsdale, AZ 85262 USA. EM Guy1000@SurgiVision.net NR 10 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0886-3350 J9 J CATARACT REFR SURG JI J. Cataract. Refract. Surg. PD JUL PY 2005 VL 31 IS 7 BP 1306 EP 1313 DI 10.1016/j.jcrs.2005.01.028 PG 8 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 956ZU UT WOS:000231339700024 PM 16105599 ER PT J AU Adams, AM Ton, MN Wekell, MM MacKenzie, AP Dong, FM AF Adams, AM Ton, MN Wekell, MM MacKenzie, AP Dong, FM TI Survival of Anisakis simplex in arrowtooth flounder (Atheresthes stomia) during frozen storage SO JOURNAL OF FOOD PROTECTION LA English DT Article ID 3RD-STAGE LARVAE; PARASITES AB Survival of naturally occurring larvae of Anisakis simplex in fresh arrowtooth flounder (Atheresthes stomia) was determined after storage for specified periods at four freezing temperatures. All larvae were killed by 96, 60, 12, and 9 h at temperatures of -15, -20, -30, and -40 degrees C, respectively. The average percentages of live larvae per fillet at the next shortest holding time were as follows: 72 h at -15 degrees C, 0 to 3%; 48 h at -20 degrees C, 11 to 30%; 9 h at -30 degrees C, 5%; and 6 h at -40 degrees C, 0 to 3%. Larval survival was directly related to fillet thickness or weight (P <= 0.05). Larval death was directly correlated to freezing temperatures. Holding time necessary to kill larval nematodes decreased as storage temperature decreased. C1 US FDA, Seafood Prod Res Ctr, Bothell, WA 98041 USA. Univ Washington, Sch Aquat & Fishery Sci, Seattle, WA 98105 USA. RP Adams, AM (reprint author), US FDA, Kansas City Dist Lab, 11630 W 80th St, Lenexa, KS 66214 USA. EM aadams@ora.fda.gov NR 16 TC 8 Z9 9 U1 0 U2 5 PU INT ASSOC FOOD PROTECTION PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD JUL PY 2005 VL 68 IS 7 BP 1441 EP 1446 PG 6 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 943CP UT WOS:000230329900018 PM 16013383 ER PT J AU Su, YC Duan, JY Wu, WH AF Su, YC Duan, JY Wu, WH TI Selectivity and specificity of a chromogenic medium for detecting Vibrio parahaemolyticus SO JOURNAL OF FOOD PROTECTION LA English DT Article ID CONSUMPTION; SEAFOOD AB The thiosulfate-citrate-bile salts-sucrose agar (TCBS) used in the most-probable-number method for detecting Vibrio parahaemolyticus cannot differentiate growth of V. parahaemolyticus from Vibrio vulnificus or Vibrio mimicus. This study examined the selectivity and specificity of Bio-Chrome Vibrio medium (BCVM), a chromogenic medium that detects V. parahaemolyticus on the basis of the formation of distinct purple colonies on the medium. A panel consisting of 221 strains of bacteria, including 179 Vibrio spp. and 42 non-Vibrio spp., were examined for their ability to grow and produce colored colonies on BCVM. Growth of Salmonella, Shigella, Escherichia coli, Enterobacter cloacae, Yersinia enterocolitica, and Aeromonas was inhibited by both BCVM and TCBS. All 148 strains of V. parahaemolyticus grew on BCVM, and 145 of them produced purple colonies. The remaining 31 Vibrio spp., except one strain of Vibrio fluvialis, were either unable to grow or produced blue-green or white colonies on BCVM. Bio-Chrome Vibrio medium was capable of differentiating V parahaemolyticus from other species, including V. vulnificus and V. mimicus. Further studies are needed to evaluate the sensitivity and specificity of BCVM for detecting V. parahaemolyticus in foods. C1 Oregon State Univ, OSU Seafood Lab, Astoria, OR 97103 USA. US FDA, Seafood Prod Res Ctr, Pacific Reg Lab NW, Off Regulatory Affairs, Bothell, WA 98021 USA. RP Su, YC (reprint author), Oregon State Univ, OSU Seafood Lab, 2001 Marine Dr,Room 253, Astoria, OR 97103 USA. EM yi-cheng.su@oregonstate.edu NR 14 TC 18 Z9 21 U1 1 U2 5 PU INT ASSOC FOOD PROTECTION PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD JUL PY 2005 VL 68 IS 7 BP 1454 EP 1456 PG 3 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 943CP UT WOS:000230329900021 PM 16013386 ER PT J AU Garland, L Gitlitz, B Ebbinghaus, S Pan, H de Haan, H Puri, RK Von Hoff, D Figlin, R AF Garland, L Gitlitz, B Ebbinghaus, S Pan, H de Haan, H Puri, RK Von Hoff, D Figlin, R TI Phase I trial of intravenous IL-4 Pseudomonas exotoxin protein (NBI-3001) in patients with advanced solid tumors that express the IL-4 receptor SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE phase 1; immunotoxin; renal carcinoma; non-small cell lung carcinoma ID PERMUTED INTERLEUKIN 4-TOXIN; DIRECTED CYTOTOXIN THERAPY; TARGETED CYTOTOXIN; ANTITUMOR-ACTIVITY; CARCINOMA-CELLS; CANCER-CELLS; HUMAN HEAD; TOXIN; XENOGRAFT; TOLERABILITY AB NBI-3001 is a novel immunotoxin of attenuated Pseudomonas exotoxin fused to circularly permutated IL-4, which has shown some antitumor effects in glioblastoma multiforme with intratumoral administration. The authors evaluated the safety and tolerability of NBI-3001 administered intravenously in a dose-escalation design to patients with renal cell and non-small cell lung carcinoma whose tumors showed at least 10% IL-4 receptor expression. Cohorts of three to six patients were treated at dose levels of 0.008, 0.016, and 0.027 mg/m(2) daily X 5 days every 28 days. Neutralizing antibody (NAB)titers, plasma levels of NBI-3001, and patient tolerability were monitored sequentially 14 patients received a total of 36 cycles of NBI-3001 (range 1-6). No dose-limiting toxicities were noted at dose levels 0.008 and 0.016 mg/m(2). At 0.027 mg/m(2), two patients developed self-limiting, grade 3 or 4 transaminase elevation during cycle 1. NAB titers of more than 1: 100 were detected in five of the seven patients treated with at least two cycles; the median titer after cycle I and the median maximum titer in subsequent cycles were 1:50 and approximately 1:1,710, respectively. No objective tumor responses were noted. Eight of 12 evaluable patients with renal cell carcinoma had stable disease; four patients had disease progression. High NAB titers resulted in four patients being withdrawn from the study. The dose-limiting toxicity for intravenous NBI-3001 was transaminase elevation at 0.027 mg/m(2). NBI-3001 at 0.016 mg/m(2) was well tolerated. Low circulating levels of NBI-3001, coupled with rising NAB titers, may have contributed to the lack of response in tumors that express IL-4R. C1 Univ Arizona, Arizona Canc Ctr, Tucson, AZ 85724 USA. Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Los Angeles, CA 90033 USA. Neurocrine Biosci Inc, San Diego, CA USA. US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Lab Mol Tumor Biol,NIH, Bethesda, MD 20014 USA. Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA. RP Garland, L (reprint author), Univ Arizona, Arizona Canc Ctr, 1515 N Campbell Ave,Ste 1969E, Tucson, AZ 85724 USA. EM lgarland@azcc.arizona.edu NR 25 TC 31 Z9 33 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD JUL-AUG PY 2005 VL 28 IS 4 BP 376 EP 381 DI 10.1097/01.cji.0000162782.86008.mL PG 6 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 941MP UT WOS:000230219200013 PM 16000956 ER PT J AU Tock, CL Turner, LR Batra, P Coelho, S Miller, SA Beer, J Radonovich, M Brady, JN Turner, ML Vogel, JC AF Tock, CL Turner, LR Batra, P Coelho, S Miller, SA Beer, J Radonovich, M Brady, JN Turner, ML Vogel, JC TI Transcriptonal profiling of the epidermal response to ultraviolet radiation SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 04-07, 2005 CL St Louis, MO SP Soc Investigat Dermatol C1 NCI, Dermatol Branch, Bethesda, MD 20892 USA. US FDA, CDRH, OST, Rockville, MD USA. Core Microarray Facil, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUL PY 2005 VL 125 IS 1 MA 933 BP A5 EP A5 PG 1 WC Dermatology SC Dermatology GA 943GR UT WOS:000230342000052 ER PT J AU Fuller, J Ashar, BS Carey-Corrado, J AF Fuller, J Ashar, BS Carey-Corrado, J TI Trocar-associated injuries and fatalities: An analysis of 1399 reports to the FDA SO JOURNAL OF MINIMALLY INVASIVE GYNECOLOGY LA English DT Review DE trocar; MAUDE database; laparoscopy; injury ID LITIGATION AB Laparoscopic trocars, medical devices used to gain access into the abdominal cavity, are the most common device named in malpractice injury claims associated with laparoscopic procedures. As part of its ongoing adverse event reporting program, the U.S. Food and Drug Administration (FDA) requires manufacturers and user facilities to file a report whenever a device was or may have been a factor in a death or serious injury. The FDA collects data from these reports in its Manufacturer and User Facility Device Experience (MAUDE) database. This study presents an analysis of fatality and injury data on laparoscopic trocars found in MAUDE reports received from January 1, 1997, through June 30, 2002, including 31 fatal injury cases and 1353 reports on nonfatal injuries. Cholecystectomy was the procedure most frequently associated with both fatal and nonfatal trocar injuries. Most fatalities involved vascular injuries. All fatality reports that identified the trocar design involved either a shielded trocar (which has a retractable shield that covers the trocar blade before and after insertion to help protect abdominal and pelvic organs from inadvertent puncture) or an optical trocar (which allows laparoscopists to view the cutting tip as it penetrates the tissues). Narrative comments cited surgical technique, device problems, and patient characteristics as contributing factors. Among nonfatal injuries, a change in surgical management such as additional surgical procedure-primarily laparotomy-prolonged surgery, or aborted surgery was reported most frequently for vascular and hollow viscus injuries. Many reports did not identify the device model, surgical procedure, or event timing, limiting Food and Drug Administration (FDA) and manufacturer investigations into whether the device contributed to the event. The most common manufacturer conclusions indicated the trocar was not returned, and no conclusions could be drawn about the trocar's contribution to the event. Fatalities occur with procedures in which shielded trocars and optical trocars are used. Further study is needed to evaluate the high proportion of reports associated with laparoscopic cholecystectomy. Laparoscopists should retain for evaluation any devices implicated in patient injuries and should ensure that detailed information on adverse events is provided in adverse event reports to the FDA. The FDA's Manufacturer and User Facility Device Experience (MAUDE) database can be a valuable source for information on adverse outcomes associated with medical devices and, given an understanding of its limitation, provides researchers with a viable adjunct to published literature and litigation surveys for obtaining this information. (c) 2005 AAGL. All rights reserved. C1 US FDA, Off Surveillance & Biometr, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. US FDA, Off Device Evaluat, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Fuller, J (reprint author), 1350 Piccard Dr,HFZ-520,Room 300M, Rockville, MD 20850 USA. EM jyf@cdrh.fda.gov NR 14 TC 64 Z9 69 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1553-4650 J9 J MINIM INVAS GYN L JI J. Mimim. Invasive Gynecol. PD JUL-AUG PY 2005 VL 12 IS 4 BP 302 EP 307 DI 10.1016/j.jmig.2005.05.008 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 952SD UT WOS:000231024900003 PM 16036187 ER PT J AU Kim, YH Pothuluri, JV Cerniglia, CE AF Kim, YH Pothuluri, JV Cerniglia, CE TI Voltammetric investigation of macrolides by an HPLC-coulometric assay SO JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS LA English DT Article DE coulometric assay; HPLC; macrolides; voltammogram ID PERFORMANCE LIQUID-CHROMATOGRAPHY; TANDEM MASS-SPECTROMETRY; ELECTROCHEMICAL DETECTION; ERYTHROMYCIN-A; AQUEOUS-SOLUTION; HUMAN-SERUM; ANTIBIOTICS; AZITHROMYCIN; PHASE; ROXITHROMYCIN AB Voltammograms of macrolides, including anhydroerythromycin A, azithromycin, erythromycin A, erythromycin A enol ether, pseudoerythromycin A enol ether, oleandomycin and tylosin have been investigated using a dual electrode cell in combination with a high-throughput LC method. The half-wave potentials (E-1/2) of the seven macrolides investigated ranged from 0.734 to 0.866 V and the current responses reached the maxima at over 1.0 V. The current response of the downstream electrode displayed a non-linear behavior at high potentials over +0.75 V, probably because of polarization of solvent components, e.g., water. The HPLC-coulometric assay was optimized with the potentials of the upstream and downstream electrodes at +0.65 and +0.85 V, respectively. This method is suitable for detection of 14- and 15-membered macrolides (sensitivity < 0.05 mu g ml(-1)), but not for a 16-membered macrolide, tylosin (sensitivity > 0.1 mu g ml(-1)). The assay shows interferences from biomatrices in rat's blood plasma and serum, and human urine, but they were effectively removed by a cold acetonitrile extraction method. (c) 2005 Elsevier B.V. All rights reserved. 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. EM ccerniglia@nctr.fda.gov NR 30 TC 10 Z9 11 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0731-7085 J9 J PHARMACEUT BIOMED JI J. Pharm. Biomed. Anal. PD JUL 1 PY 2005 VL 38 IS 3 BP 390 EP 396 DI 10.1016/j.jpba.2005.01.028 PG 7 WC Chemistry, Analytical; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 941ST UT WOS:000230235200002 PM 15925238 ER PT J AU Verbeeck, RK Junginger, HE Midha, KK Shah, VP Barends, DM AF Verbeeck, RK Junginger, HE Midha, KK Shah, VP Barends, DM TI Biowaiver monographs for immediate release solid oral dosage forms based on biopharmaceutics classification system (BCS) literature data: Chloroquine phosphate, chloroquine sulfate, and chloroquine hydrochloride SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Editorial Material DE absorption; BCS; chloroquine; permeability; solubility ID PROTEIN-BINDING; PHARMACOKINETICS; DESETHYLCHLOROQUINE; BIOAVAILABILITY; DISPOSITION; METABOLISM; TRANSPORT; CACO-2; DRUGS AB Literature data on the properties of chloroquine phosphate, chloroquine sulfate, and chloroquine hydrochloride related to the Biopharmaceutics Classification System (BCS) are reviewed. The available information indicates that these chloroquine salts can be classified as highly soluble and highly permeable, i.e., BCS class I. The qualitative composition of immediate release (IR) tablets containing these Active Pharmaceutical Ingredients (APIs) with a Marketing Authorization (MA) in Belgium (BE), Germany (DE), Finland (FI), and The Netherlands (NL) is provided. In view of these MA's and the critical therapeutic indication of chloroquine, it is assumed that the registration authorities had evidence that these formulations are bioequivalent to the innovator. It is concluded that IR tablets formulated with these excipients are candidates for a biowaiver. (c) 2005 Wiley-Liss, Inc. and the American Pharmacists Association. C1 Natl Inst Publ Hlth & Environm, RIVM, Lab Qual Control Med, NL-3720 BA Bilthoven, Netherlands. Rhodes Univ, Fac Pharm, ZA-6140 Grahamstown, South Africa. Leiden Univ, Leiden Amsterdam Ctr Drug Res, Div Pharmaceut Technol, Leiden, Netherlands. Univ Saskatchewan, Saskatoon, SK, Canada. US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Barends, DM (reprint author), Natl Inst Publ Hlth & Environm, RIVM, Lab Qual Control Med, POB 1, NL-3720 BA Bilthoven, Netherlands. EM dirk.barends@rivm.nl NR 36 TC 31 Z9 34 U1 3 U2 7 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0022-3549 J9 J PHARM SCI-US JI J. Pharm. Sci. PD JUL PY 2005 VL 94 IS 7 BP 1389 EP 1395 DI 10.1002/jps.20343 PG 7 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 939CT UT WOS:000230050600001 PM 15920763 ER PT J AU Svarstad, BL Mount, JK Tabak, ER AF Svarstad, Bonnie L. Mount, Jeanine K. Tabak, Ellen R. TI Expert and consumer evaluation of patient medication leaflets provided in US pharmacies SO JOURNAL OF THE AMERICAN PHARMACISTS ASSOCIATION LA English DT Article DE patient information; regulation; community and ambulatory pharmacy; consumers AB Objective: Evaluate the distribution and quality of patient medication leaflets provided in U. S. pharmacies. Design: Observational. Setting: United States. Participants: 384 randomly selected community pharmacies in 44 states. Interventions: Professional shoppers ( acting as patients) presented four new prescriptions to study pharmacies. Main Outcome Measures: Medication leaflets obtained by shoppers were evaluated by expert and consumer raters using criteria specified in federal law mandating distribution of useful written information to 95% of individuals receiving new prescriptions by 2006. Results: Leaflets were provided by pharmacies with 89% of 1,536 prescriptions presented by professional shoppers posing as patients. Leaflet quality varied: 95% of leaflets received high ratings on accuracy, but only 19% received high ratings on the specificity of directions. Fewer than 10% of all leaflets met quality criteria regarding contraindications, precautions, and how to avoid harm. One fourth of all leaflets had poor print size, according to the shoppers. Conclusion: Additional efforts are needed to meet federally mandated information distribution and quality goals by 2006. C1 [Svarstad, Bonnie L.; Mount, Jeanine K.] Univ Wisconsin, Sch Pharm, Madison, WI 53705 USA. [Tabak, Ellen R.] US FDA, Off Drug Safety, Div Surveillance Res & Commun Support, Rockville, MD 20857 USA. RP Svarstad, BL (reprint author), Univ Wisconsin, Sch Pharm, 777 Highland Ave, Madison, WI 53705 USA. EM blsvarstad@pharmacy.wisc.edu NR 14 TC 26 Z9 28 U1 0 U2 1 PU AMER PHARMACEUTICAL ASSOC PI WASHINGTON PA 2215 CONSTITUTION AVE NW, WASHINGTON, DC 20037 USA SN 1544-3191 J9 J AM PHARM ASSOC JI J. Am. Pharm. Assoc. PD JUL-AUG PY 2005 VL 45 IS 4 BP 443 EP 451 DI 10.1331/1544345054475586 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA V47JM UT WOS:000203201800008 PM 16128499 ER PT J AU Zarins, CK DeWeese, J Abel, DB White, RA Freischlag, J Fairman, R Makaroun, MS Sicard, G Carpenter, J AF Zarins, CK DeWeese, J Abel, DB White, RA Freischlag, J Fairman, R Makaroun, MS Sicard, G Carpenter, J CA Lifeline Registry EVAR Publication SVS Womens Issues Comm TI Lifeline registry of endovascular aneurysm repair: Long-term primary outcome measures SO JOURNAL OF VASCULAR SURGERY LA English DT Article; Proceedings Paper CT 58th Annual Meeting of the Society-for-Vascular-Surgery CY JUN 03-06, 2004 CL Anaheim, CA SP Soc Vasc Surg ID ABDOMINAL AORTIC-ANEURYSMS; CLINICAL-TRIAL; EUROSTAR EXPERIENCE; STENT GRAFT; RUPTURE; RISK; COMPLICATIONS; SURVEILLANCE; DURABILITY; ENDOLEAK AB Purpose: To determine the long-term outcome after endovascular aneurysm repair (EVAR) of infrarenal abdominal aortic aneurysms (AAA). Methods. Review the primary outcome measures of patients treated with endovascular grafts (EG) in the Lifeline Registry of EVAR. The registry contains data on 2,664 EG patients and 334 open surgical control (SC) patients collected under four multicenter Investigational Device Exemption (IDE) clinical trials that lead to United States Food and Drug Administration (FDA) approval with mandatory 5-year follow-up. Primary outcome measures include operative mortality, AAA-related death, all-cause mortality, aneurysm rupture, and surgical conversion. Results. Pooled data from IDE clinical trials revealed that EG patients were 3 years older (73 +/- 8 years) than,SC patients (70 +/- 8 years, P <.01) and had significantly more cardiac comorbidities before treatment. However, there was no difference in 30-day operative mortality between EG (1.7%) and SC (1.4%) (P =.72). Both EG and SC were successful in preventing rupture, with freedom from aneurysm rupture in 99.8% of EG and 100% of SC patients at 1 year (P =.51). Freedom from rupture remained at 99% in years 1 to 6 after EG, with no increasing risk of late rupture. There was no significant difference in the AAA-related death rate at 1 year between EG (98.2%) and SC (98.6%) (P =.64). Freedom from AAA-related death remained at 98% in years 1 to 6 after EG, with no increasing risk of late AAA-related death. Kaplan-Meier analysis at 6 years revealed freedom from aneurysm rupture in 99%, freedom from AAA-related death in 98%, and freedom from surgical conversion in 95% of EG patients. There was no difference in survival at 4 years between EG (74%) and SC (71%) (P =.49). Overall EG patient survival at 5 years was 66% and at 6 years was 52%. Women had a higher risk of rupture (2.4%) than men (1.2%) (P =.01) and a higher rate of surgical conversion (8.3%) than men (3.8%) (P <.01) but had the same low AAA-related death rate (3.5%) as men (2.1%) (P =.16) at 5 years. Most secondary interventional procedures (85%) were performed <= 30 days after EVAR. Freedom from secondary intervention was 84% at 1 year and 78% at 5 years. Conclusions. Endovascular aneurysm repair using FDA-approved devices is a safe, effective, and durable treatment for anatomically suited patients with infrarenal abdominal aortic aneurysms. C1 New England Res Inst Inc, Registry Data Ctr, Watertown, MA 02472 USA. US FDA, Rockville, MD 20857 USA. RP Zarins, CK (reprint author), New England Res Inst Inc, Registry Data Ctr, 9 Galen St, Watertown, MA 02472 USA. EM zarins@stanford.edu; dcweesepnj@aol.com; dba@cdrh.fda.gov; rawhite@ucla.edu; jfreisc1@jhmi.edu; Ron.fairman@uphs.upenn.edu; makarounms@upc.edu; sicardg@msnotes.wustl.edu; jeffrey.carpenter@uphs.upenn.edu NR 38 TC 76 Z9 77 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD JUL PY 2005 VL 42 IS 1 BP 1 EP 10 DI 10.1016/j.jvs.2005.05.012 PG 10 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 944OD UT WOS:000230437500001 ER PT J AU Momosaki, S Umemura, T Scudamore, CH Kojiro, M Alter, HJ Tabor, E AF Momosaki, S Umemura, T Scudamore, CH Kojiro, M Alter, HJ Tabor, E TI SEN virus infection in patients with hepatocellular carcinoma SO JOURNAL OF VIRAL HEPATITIS LA English DT Article DE hepatocellular carcinoma; SEN virus; 'silent' hepatitis B virus ID LIVER-DISEASE; SURFACE-ANTIGEN; HEPATITIS; BLOOD AB Although most cases of hepatocellular carcinoma (HCC) are associated with either the hepatitis B or C viruses (HBV, HCV), about 10-20% of HCCs occur in patients with chronic hepatitis that is aetiologically undefined. The aim of the present study was to determine the prevalence of the transfusion-transmitted SEN virus (SEN-V) in patients with HCC, including those patients who do not otherwise appear to be infected with HBV or HCV. Fragments of SEN-V subtypes D and H were amplified separately by PCR from the sera of 50 patients with HCC (31 from Canada and 19 from Japan) as well as from HCC and adjacent nontumourous liver tissues from eight of the Canadian patients. SEN-V DNA was found in the serum of 10 of 31 (32%) Canadian patients and eight of 19 (42%) Japanese patients [overall, 18 of 50 (36%) HCC patients]. SEN-V DNA was detected in the serum of 10 of 23 (43%) HCC patients with antibody to HCV (anti-HCV), six of 11 (55%) with hepatitis B surface antigen (HBsAg), and two of 16 (12%) without detectable anti-HCV or HBsAg. Twenty-three HCC patients in this study had 'silent HBV,' characterized by the detection of HBV DNA in the absence of HBsAg; eight of these (35%) also had SEN-V infections. SEN-V DNA was detected in HCC patients most typically in those with coexistent HBV or HCV infection. SEN-V was found in only one of seven HCC patients without HBV (without HBsAg or HBV DNA) or HCV and thus does not appear to be an important cause of 'cryptogenic' HCC. C1 US FDA, Div Emerging & Transfus Dis, Bethesda, MD USA. Kurume Univ, Dept Pathol, Kurume, Fukuoka 830, Japan. NIH, Div Transfus Med, Bethesda, MD USA. Univ British Columbia, Dept Surg, Vancouver, BC V6T 1W5, Canada. RP Tabor, E (reprint author), US FDA, Ctr Biol Evaluat & Res, HFM-300,1401 Rockville Pike, Rockville, MD 20852 USA. EM tabor@cber.fda.gov NR 15 TC 4 Z9 6 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 1352-0504 J9 J VIRAL HEPATITIS JI J. Viral Hepatitis PD JUL PY 2005 VL 12 IS 4 BP 435 EP 438 DI 10.1111/j.1365-2893.2005.00618.x PG 4 WC Gastroenterology & Hepatology; Infectious Diseases; Virology SC Gastroenterology & Hepatology; Infectious Diseases; Virology GA 938MJ UT WOS:000230007200014 PM 15985016 ER PT J AU Hu, Y Hirshfield, I AF Hu, Y Hirshfield, I TI Rapid approach to identify an unrecognized viral agent SO JOURNAL OF VIROLOGICAL METHODS LA English DT Article DE unrecognized viral agents; mRNA; cDNA; subtraction hybridization; long-PCR; nested-PCR; mung bean nuclease; cDNA library ID REPLICATION; CLONING AB For epidemic control, rapid identification and characterization of the responsible unknown agent are crucial. To address this critical question, a method was developed for virus discovery based on a flexible nested-PCR subtraction hybridization. As a positive control, we used hepatitis C virus as a hypothetical unrecognized virus and "discover" it in the sample. Using template-switching universal long-PCR to produce large quantities of cDNA, our nested-PCR-based subtractive hybridization coupled with a single-strand deletion technology removed most of the common cDNA. Following subtraction hybridization, a cDNA library was constructed and displayed by differential reverse dot blot hybridization. This new genomic subtraction hybridization method will be ideally suited to identify rapidly any previously unrecognized viral agent. Published by Elsevier B.V C1 US FDA, NE Reg Lab, Microbiol Sci Branch, Jamaica, NY 11433 USA. St Johns Univ, Jamaica, NY 11439 USA. RP Hu, Y (reprint author), US FDA, NE Reg Lab, Microbiol Sci Branch, 158-15 Liberty Ave, Jamaica, NY 11433 USA. EM yhu@ora.fda.gov NR 16 TC 6 Z9 8 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 JUL PY 2005 VL 127 IS 1 BP 80 EP 86 DI 10.1016/jviromet.2005.02.016 PG 7 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Virology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Virology GA 931AA UT WOS:000229457000011 PM 15893569 ER PT J AU Kim, YH Engesser, KH Cerniglia, CE AF Kim, YH Engesser, KH Cerniglia, CE TI Numerical and genetic analysis of polycyclic aromatic hydrocarbon-degrading mycobacteria SO MICROBIAL ECOLOGY LA English DT Article ID SP STRAIN PYR-1; GROWING MYCOBACTERIA; ESCHERICHIA-COLI; SP-NOV; DEGRADATION; PYRENE; CLASSIFICATION; MINERALIZATION; FLUORANTHENE; PHENANTHRENE AB Ability to degrade high molecular weight polycyclic aromatic hydrocarbons (PAHs) has been found in diverse species of fast-growing mycobacteria. This study included several PAH-degrading mycobacteria from heavily contaminated sites and an uncontaminated humus soil in the Natural Park, Schwabische Alb, Germany. The numerical analysis with a total of 131 tests showed that isolates from humus soil and contaminated sites had similar substrate utilization patterns for primary alcohols from ethanol to pentanol, 1,4-butanediol, benzyl alcohol, hexadecane, ethyl acetate, fluoranthene, phenanthrene, and pyrene as the sole carbon and energy (C/E) sources. Significant differences between the two subgroups isolated from humus soil and contaminated sites were observed in the utilization of polyalcoholic sugars, including adonitol, L-arabitol, erythritol, inositol, rhamnose, sorbitol, and xylitol. Among isolates from humus soil, strain PYR100 showed high similarity in 16S rDNA sequence with M. vanbaalenii strain PYR-1 (=DSM 7251, 100%) and M. austroafricanum ATCC 33464 (99.9%). In addition to the numerical analysis, the 16S-23S intergenic spacer sequence was useful for discriminating between the closely related strains PYR100 and PYR-1 (98% similarity). The patterns of the variable V2 and V3 regions in the ribosomal RNA gene corresponding to Escherichia coli positions 179 to 197 and 1006 to 1023, respectively, were useful for dividing fast-growing and thermosensitive PAH-degrading mycobacteria into ten subgroups consistent with the phylogenetic positions. C1 US FDA, Div Microbiol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Univ Stuttgart, Inst Siedlungswasserbau Wasserguteund Abfallwirts, Abt Biol Abluftreinigung, D-70569 Stuttgart, Germany. RP Kim, YH (reprint author), Seoul Natl Univ, Sch Biol Sci, San 56-1 Shinrim Dong, Seoul 151747, South Korea. EM yhkim660628@hotmail.com NR 47 TC 30 Z9 34 U1 0 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0095-3628 J9 MICROB ECOL JI Microb. Ecol. PD JUL PY 2005 VL 50 IS 1 BP 110 EP 119 DI 10.1007/s00248-004-0126-3 PG 10 WC Ecology; Marine & Freshwater Biology; Microbiology SC Environmental Sciences & Ecology; Marine & Freshwater Biology; Microbiology GA 969WU UT WOS:000232267300012 PM 16132428 ER PT J AU Cao, XH Yu, LX Barbaciru, C Landowski, CP Shin, HC Gibbs, S Miller, HA Amidon, GL Sun, DX AF Cao, Xianhua Yu, Lawrence X. Barbaciru, Catalin Landowski, Christopher P. Shin, Ho-Chul Gibbs, Seth Miller, Heather A. Amidon, Gordon L. Sun, Duxin TI Permeability dominates in vivo intestinal absorption of P-gp substrate with high solubility and high permeability SO MOLECULAR PHARMACEUTICS LA English DT Article DE permeability; P-gp; intestine; gene expression; verapamil; correlation; microarray AB Three purposes are presented in this study: (1) to study the in vivo regional dependent intestinal absorption of a P-gp substrate with high solubility and high permeability, (2) to study the gene expression difference in the various regions of the intestine, and (3) to study the contributions of P-gp or any other transporters for the absorption of a P-gp substrate. The in vivo permeability of verapamil and propranolol were determined by single-pass in situ intestinal perfusion in rat. The gene expression profiles were measured using Affymetrix GeneChip. Correlation analysis between drug in vivo permeability and expression of 3500 genes was performed with nonparametric bootstrap and ANOVA analysis. The permeability of verapamil and propranolol did not demonstrate regional dependency even though significant differences in gene expression were observed in various regions of the intestine. Verapamil permeability significantly correlates with propranolol permeability in both jejunum and ileum, but did not correlate with the permeability of other hydrophilic compounds (valacyclovir, acyclovir, and phenylalanine). Four different regions (duodenum, jejunum, ileum, and colon) showed distinct gene expression patterns with more than 70-499 genes showing at least 5-fold expression differences. Interestingly, P-gp expression is gradually increased by 6-fold from the duodenum to colon. Despite the distinct gene expression patterns in the various regions of the intestine, verapamil permeability did not correlate with any gene expression from 3500 expressed genes in the intestine. A 2-6-fold P-gp expression difference did not seem to associate verapamil permeability in the various intestinal regions in vivo. These data suggest that P-gp plays a minimal role in the in vivo intestinal absorption process of verapamil with high water solubility and high membrane permeability. The intestinal absorption of verapamil in vivo is primarily dominated by its high permeability. However, it is important to note that the findings in this paper do not undermine the importance of P-gp in oral drug bioavailability, drug disposition from the liver, drug efflux from the blood-brain barrier, and drug-drug interaction. C1 [Landowski, Christopher P.; Shin, Ho-Chul; Amidon, Gordon L.] Univ Michigan, Coll Pharm, Dept Pharmaceut Sci, Ann Arbor, MI 48109 USA. [Cao, Xianhua; Gibbs, Seth; Miller, Heather A.; Sun, Duxin] Ohio State Univ, Coll Pharm, Div Pharmaceut, Columbus, OH 43210 USA. [Yu, Lawrence X.] US FDA, Off Gener Drugs, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. [Barbaciru, Catalin] Ohio State Univ, Coll Med & Publ Hlth, Dept Biomed Informat, Columbus, OH 43210 USA. RP Amidon, GL (reprint author), Univ Michigan, Coll Pharm, Dept Pharmaceut Sci, Ann Arbor, MI 48109 USA. EM glamidon@umich.edu OI Landowski, Christopher/0000-0003-1775-8646; Shin, Ho-chul/0000-0001-5500-3901 NR 56 TC 53 Z9 55 U1 1 U2 7 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1543-8384 J9 MOL PHARMACEUT JI Mol. Pharm. PD JUL-AUG PY 2005 VL 2 IS 4 BP 329 EP 340 DI 10.1021/mp0499104 PG 12 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA V52JD UT WOS:000203538900010 PM 16053336 ER PT J AU Lindon, JC Nicholson, JK Holmes, E Keun, HC Craig, A Pearce, JTM Bruce, SJ Hardy, N Sansone, SA Antti, H Jonsson, P Daykin, C Navarange, M Beger, RD Verheij, ER Amberg, A Baunsgaard, D Cantor, GH Lehman-McKeeman, L Earll, M Wold, S Johansson, E Haselden, JN Kramer, K Thomas, C Lindberg, J Schuppe-Koistinen, I Wilson, ID Reily, MD Robertson, DG Senn, H Krotzky, A Kochhar, S Powell, J van der Ouderaa, F Plumb, R Schaefer, H Spraul, M AF Lindon, JC Nicholson, JK Holmes, E Keun, HC Craig, A Pearce, JTM Bruce, SJ Hardy, N Sansone, SA Antti, H Jonsson, P Daykin, C Navarange, M Beger, RD Verheij, ER Amberg, A Baunsgaard, D Cantor, GH Lehman-McKeeman, L Earll, M Wold, S Johansson, E Haselden, JN Kramer, K Thomas, C Lindberg, J Schuppe-Koistinen, I Wilson, ID Reily, MD Robertson, DG Senn, H Krotzky, A Kochhar, S Powell, J van der Ouderaa, F Plumb, R Schaefer, H Spraul, M CA Stand Metab Reporting Struct worki TI Summary recommendations for standardization and reporting of metabolic analyses SO NATURE BIOTECHNOLOGY LA English DT Editorial Material ID SPECTROMETRY; GUIDELINES; STRATEGY; SAMPLES C1 Univ London Imperial Coll Sci Technol & Med, Div Biomed Sci, London SW7 2AZ, England. Univ Wales, Dept Comp Surg, Aberystwyth SY23 3DB, Dyfed, Wales. European Bioinformat Inst, EMBL Outstn, Cambridge CB10 1SD, England. Umea Univ, Chemometr Res Grp, S-90187 Umea, Sweden. Univ Nottingham, Sch Pharm, Ctr Analyt Biosci, Nottingham NG7 2RD, England. Univ London Imperial Coll Sci Technol & Med, MRC, Ctr Clin Sci, Fac Med, London W12 0NN, England. US FDA, Natl Ctr Toxicol Res, Div Syst Toxicol, Ctr Metab, Jefferson, AR 72079 USA. TNO, Pharma, NL-3700 AJ Zeist, Netherlands. Sanofi Aventis, Drug Safety Evaluat, D-65795 Hattersheim, Germany. Novo Nordisk AS, DK-2760 Malov, Denmark. Bristol Myers Squibb Co, Princeton, NJ 08543 USA. Umetr UK Ltd, Winkfield SL4 2DX, Windsor, England. Umetrics, SE-90719 Umea, Sweden. GlaxoSmithKline, Safety Assessment, Ware SG12 0DP, Herts, England. Lilly Dev Ctr, Dept Toxicol & Drug Disposit, B-1348 Louvain, Belgium. AstraZeneca, Sodertalje, Sweden. AstraZeneca, Dept Drug Metab & Pharmacokinet, Macclesfield SK10 4TG, Cheshire, England. Pfizer Global, R&D, Ann Arbor, MI 48105 USA. Hoffmann La Roche Ag, Dept Biostruct Res, CH-4070 Basel, Switzerland. Metan GMBH & Co, D-10589 Berlin, Germany. Nestle Res Ctr, CH-1000 Lausanne, Switzerland. Unilever Res Labs Colworth, Corp Res, Sharnbrook MK44 1LQ, Beds, England. Waters Life Sci R&D Grp, Milford, MA 01757 USA. Bruker BioSpin GMBH, D-76287 Rheinstetten, Germany. RP Lindon, JC (reprint author), Univ London Imperial Coll Sci Technol & Med, Div Biomed Sci, Sir Alexander Fleming Bldg, London SW7 2AZ, England. EM j.lindon@imperial.ac.uk RI Nicholson, Jeremy/B-3395-2012; Jonsson, Par/M-8551-2015; OI Nicholson, Jeremy/0000-0002-8123-8349; Jonsson, Par/0000-0001-8357-5018; Sansone, Susanna-Assunta/0000-0001-5306-5690; Reily, Michael/0000-0003-1179-1525 NR 15 TC 150 Z9 169 U1 7 U2 56 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVENUE SOUTH, NEW YORK, NY 10010-1707 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD JUL PY 2005 VL 23 IS 7 BP 833 EP 838 DI 10.1038/nbt0705-833 PG 6 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 944KT UT WOS:000230427700030 PM 16003371 ER PT J AU Edghill-Smith, Y Golding, H Manischewitz, J King, LR Scott, D Bray, M Nalca, A Hooper, JW Whitehouse, CA Schmitz, JE Reimann, KA Franchini, G AF Edghill-Smith, Y Golding, H Manischewitz, J King, LR Scott, D Bray, M Nalca, A Hooper, JW Whitehouse, CA Schmitz, JE Reimann, KA Franchini, G TI Smallpox vaccine-induced antibodies are necessary and sufficient for protection against monkeypox virus SO NATURE MEDICINE LA English DT Article ID IMMUNODEFICIENCY-VIRUS; MONOCLONAL-ANTIBODY; CYNOMOLGUS MONKEYS; NONHUMAN-PRIMATES; LETHAL MONKEYPOX; ENVELOPE; GENE; CHALLENGE; EXPRESSION; INFECTION AB Vaccination with live vaccinia virus affords long- lasting protection against variola virus, the agent of smallpox. Its mode of protection in humans, however, has not been clearly defined. Here we report that vaccinia- specific B-cell responses are essential for protection of macaques from monkeypox virus, a variola virus ortholog. Antibody- mediated depletion of B cells, but not CD4(+) or CD8(+) T cells, abrogated vaccine- induced protection from a lethal intravenous challenge with monkeypox virus. In addition, passive transfer of human vaccinia-neutralizing antibodies protected nonimmunized macaques from severe disease. Thus, vaccines able to induce long- lasting protective antibody responses may constitute realistic alternatives to the currently available smallpox vaccine (Dryvax). C1 NCI, Anim Models & Retroviral Vaccines Sect, Bethesda, MD 20892 USA. US FDA, Div Viral Prod, Bethesda, MD 20892 USA. US FDA, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. NIAID, Biodef Clin Res Branch, Off Clin Res, Bethesda, MD 20892 USA. So Res Inst, Frederick, MD 21701 USA. USA, Med Res Inst Infect Dis, Div Virol, Ft Detrick, MD 21702 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med,Div Viral Pathogenesis, Boston, MA 02215 USA. RP Franchini, G (reprint author), NCI, Anim Models & Retroviral Vaccines Sect, 41-D804, Bethesda, MD 20892 USA. EM franchig@mail.nih.gov OI Hooper, Jay/0000-0002-4475-0415 FU NCRR NIH HHS [R24 RR016001, RR016001]; NIAID NIH HHS [AI040101] NR 35 TC 182 Z9 182 U1 0 U2 13 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVENUE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD JUL PY 2005 VL 11 IS 7 BP 740 EP 747 DI 10.1038/nm1261 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 942TB UT WOS:000230304200030 PM 15951823 ER PT J AU Kunwar, S Ram, Z Sampson, JH Prados, M Chang, S Lang, FF Piepmeier, JM Gutin, PH Croteau, D Puri, RK AF Kunwar, S Ram, Z Sampson, JH Prados, M Chang, S Lang, FF Piepmeier, JM Gutin, PH Croteau, D Puri, RK TI Peritumoral convection-enhanced delivery (CED) of IL13-PE38QQR (IL13PE): Results of multicenter phase 1 studies in recurrent high grade glioma (HGG) SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 2nd Quadrennial Meeting of the World-Federation-of-Neuro-Oncology/6th Meeting of the European-Association-for-Neur-Oncology CY MAY 05-08, 2005 CL Edinburgh, SCOTLAND SP World Federat Neuro Oncol, European Assoc Neuro Oncol C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. Tel Aviv Univ, IL-69978 Tel Aviv, Israel. Duke Univ, Med Ctr, Durham, NC 27706 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Yale Univ, Sch Med, New Haven, CT 06520 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NeoPharm Inc, Lake Forest, IL USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JUL PY 2005 VL 7 IS 3 MA 114 BP 311 EP 311 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 944XH UT WOS:000230463900118 ER PT J AU Garey, J Ferguson, SA Paule, MG AF Garey, J Ferguson, SA Paule, MG TI Developmental and behavioral effects of acrylamide in Fischer 344 rats SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Article DE acrylamide; rats; development; behavior; neurotoxicity ID SPRAGUE-DAWLEY RATS; ROTAROD PERFORMANCE; NEUROTOXICITY; MICE; DIFLUOROMETHYLORNITHINE; CEREBELLAR; MORPHOLOGY; DAMAGE AB Human exposures to acrylamide (ACR), a known neurotoxicant, can occur via a variety of substances, including cigarette smoke and the ingestion of certain carbohydrate-based foods cooked at high temperatures. In this study, Fischer 344 sperm plug-positive female rats were treated daily with ACR (0, 0.5, 1.0, 2.5, 5.0 or 10.0 mg/kg/day) by gavage beginning on gestation day 7. Dosing of dams ended when litters were bona; pups received daily gavage at the same dose as their dam from postnatal day (PND) 1 through PND22. Pups were tested using a battery of behavioral assessments from PNDs 4-22. Statistically significant decreases in body weight were observed in pups exposed to ACR at doses as low as 1.0 mg/kg/day (treatment x day; repeated measures ANOVA, P < 0.0001). No statistically significant differences among treatment groups were observed in righting reflex, forelimb hang, or open field measures of activity. Statistically significant effects of ACR were observed at the 10 mg/kg/day dose on negative geotaxis performance (P < 0.01) and a linear trend in fall-time latencies on Rotarod performance on PNDs 21-22 (P<0.05), with higher doses producing shorter latencies. These results suggest that ACR exposure produces deficits in development and motor coordination that are observable before weaning. (c) 2005 Elsevier Inc. All rights reserved. C1 Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. RP Garey, J (reprint author), Natl Ctr Toxicol Res, Div Neurotoxicol, HFT-132,3900 NCTR Rd, Jefferson, AR 72079 USA. EM jgarey@nctr.fda.gov NR 28 TC 19 Z9 21 U1 1 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0892-0362 J9 NEUROTOXICOL TERATOL JI Neurotoxicol. Teratol. PD JUL-AUG PY 2005 VL 27 IS 4 BP 553 EP 563 DI 10.1016/j.ntt.2005.03.007 PG 11 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA 958XT UT WOS:000231482200007 PM 16087067 ER PT J AU El-Masri, MM Hammad, TA Fox-Wasylyshyn, SM AF El-Masri, MM Hammad, TA Fox-Wasylyshyn, SM TI Predicting nosocomial bloodstream infections using surrogate markers of injury severity - Clinical and methodological perspectives SO NURSING RESEARCH LA English DT Article DE injury severity; nosocomial bloodstream infection; surrogate markers; trauma patients ID INTENSIVE-CARE-UNIT; TRAUMA PATIENTS; RISK-FACTORS; ATTRIBUTABLE MORTALITY; DIFFERENCE; IMPACT; COSTS; AGE AB Background. Injury severity indices are numerical scores that are utilized to predict nosocomial bloodstream infections (BSI) in critically ill patients. However, surrogate markers of injury severity (SMIS) may be more clinically meaningful than these commonly used numerical injury severity indices with respect to the control and prevention of nosocomial BSI. Objective: The purpose of this study was to demonstrate the clinical and research implications of using the SMIS in predicting nosocomial BSI. Method: A prospective nonexperimental cohort study was conducted on 361 critically ill trauma patients. Three logistic regression models were examined for their clinical relevance and statistical parsimony. The first model included the Injury Severity Score (ISS) and 5 other independent predictors, and excluded the SMIS. The second model included all study variables. The third model excluded the ISS. Results: The analysis suggested that number of blood units transfused, number of central venous catheters inserted, and use of chest tube(s) were the SMIS. The ISS was found to be an independent predictor of nosocomial BSI only when the SMIS were not included in the model. The model that included the SMIS and excluded the ISS explained the highest variance in nosocomial BSI and had the best negative predictive value (93%). Discussion: Clinicians can use knowledge of SMIS to develop interventions that minimize the risk of nosocomial BSI. Hence, the SMIS can serve not only as a prediction tool but also as a way to enhance control and prevention strategies for BSI. C1 Univ Windsor, Fac Nursing, Hlth Educ Ctr, Windsor, ON N9B 3P4, Canada. US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP El-Masri, MM (reprint author), Univ Windsor, Fac Nursing, Hlth Educ Ctr, 401 Sunset,Room 328, Windsor, ON N9B 3P4, Canada. EM melmasri@uwindsor.ca NR 38 TC 5 Z9 5 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-6562 J9 NURS RES JI Nurs. Res. PD JUL-AUG PY 2005 VL 54 IS 4 BP 273 EP 279 PG 7 WC Nursing SC Nursing GA 947OK UT WOS:000230655500010 PM 16027570 ER PT J AU Ning, BT Nowell, S Sweeney, C Ambrosone, CB Williams, S Miao, XP Liang, G Lin, DX Stone, A Ratnasinghe, DL Manjanatha, M Lang, NP Kadlubar, FF AF Ning, BT Nowell, S Sweeney, C Ambrosone, CB Williams, S Miao, XP Liang, G Lin, DX Stone, A Ratnasinghe, DL Manjanatha, M Lang, NP Kadlubar, FF TI Common genetic polymorphisms on the 5 '-flanking region of the SULT1A1 gene: haplotypes and their association with platelet enzymatic activity SO PHARMACOGENETICS AND GENOMICS LA English DT Article DE activity; genotype; haplotype; sulphotransferase ID THERMOSTABLE PHENOL SULFOTRANSFERASE; HUMAN CYTOSOLIC SULFOTRANSFERASES; SULFATION PHARMACOGENETICS; HUMAN MEGAKARYOCYTES; HETEROCYCLIC AMINES; ESTROGEN-RECEPTOR; CANCER RISK; GENOTYPE; RECONSTRUCTION; THERMOLABILE AB SULT1A1 is a phase II detoxification enzyme involved in the biotransformation of a wide variety of endogenous and exogenous phenolic compounds. Human platelet SULT1A1 enzymatic activity shows marked inter-individual variability and a common coding polymorphism, SULT1A1*1/*2, has been described that accounts for a proportion of this variability. We examined the 5'-flanking region of the SULT1A1 gene to determine if genetic variability in this portion of the gene influenced enzymatic activity. Direct sequencing revealed five common genetic polymorphisms (-6246 > C, -396G > A, -358A > C, -341C > G and -294T > C) that were present at different allele frequencies in Caucasian, African-American and Chinese groups. Platelet SULT1A1 enzymatic activity was significantly correlated with individual promoter region polymorphisms and the associations were different between African-Americans and Caucasians. Haplotypes were constructed and platelet enzymatic activity according to haplotype was examined. The haplotypes were also significantly correlated with activity; haplotypes GAACT and GGACT (accounting for 13% and 5% of inter-individual variability in platelet activity, respectively) were important in Caucasians while haplotypes GAACC, GAACT and GGACC (accounting for 8%, 5% and 4% of variability) were significantly associated with activity in African-Americans. The coding region polymorphism, SULT1A1*1/*2 was in linkage disequilibrium with the promoter region polymorphisms and Showed no effect on activity when examined in the coatext of the 5'-flanking region polymorphisms. These studies indicate that variation in the promoter region of the SULT1A1 gene exerts a significant influence on enzymatic activity. C1 Roswell Pk Canc Inst, Buffalo, NY 14263 USA. Natl Ctr Toxicol Res, Dept Pharmacogenom & Mol Epidemiol, Jefferson, AR 72079 USA. Natl Ctr Toxicol Res, Div Genet Toxicol, Jefferson, AR 72079 USA. Univ Utah, Salt Lake City, UT USA. Cent Arkansas Vet Hlth Care Syst, Little Rock, AR USA. Chinese Acad Med Sci, Inst Canc, Dept Etiol & Carcinogenesis, Beijing 100037, Peoples R China. Peking Union Med Coll, Beijing, Peoples R China. Univ Arkansas Med Sci, Coll Med, Dept Surg, Little Rock, AR 72205 USA. RP Nowell, S (reprint author), Roswell Pk Canc Inst, Elm & Carlton St, Buffalo, NY 14263 USA. EM susan.nowell@roswellpark.org RI miao, xiaoping/C-4336-2011 OI miao, xiaoping/0000-0002-6818-9722 NR 40 TC 23 Z9 23 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1744-6872 J9 PHARMACOGENET GENOM JI Pharmacogenet. Genomics PD JUL PY 2005 VL 15 IS 7 BP 465 EP 473 DI 10.1097/01.fpc.0000166823.74378.79 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy GA 949PE UT WOS:000230799800004 PM 15970794 ER PT J AU Godar, DE AF Godar, DE TI UV doses worldwide SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Review ID ULTRAVIOLET-RADIATION EXPOSURE; DIFFERENT OUTDOOR ACTIVITIES; NONMELANOMA SKIN-CANCER; ROBERTSON-BERGER METER; CELL-DEATH MECHANISMS; OZONE DEPLETION; WAVELENGTH DEPENDENCE; SUN EXPOSURE; MALIGNANT-MELANOMA; SOLAR ULTRAVIOLET AB UV radiation affects human health. Human exposure to UV radiation causes a few beneficial health effects like vitamin D-3 formation but it causes many detrimental health effects: sunburn, ocular damage, photoaging, immune suppression, DNA damage and skin cancer. In countries with fair-skinned populations, skin cancer is the most diagnosed of all cancers. In the United States in 2002, there were over one million new skin cancer cases. That means one out of every 285 people got skin cancer. Skin cancer of fair-skinned individuals is increasing at an alarming rate (4-6% per year) around the world and has now reached so-called "pandemic" proportions. Thus, it is important to know what UV doses people around the world get throughout their lives. This review covers how the outdoor UV doses are weighted for different biological effects, the most commonly used measuring devices for terrestrial and personal UV doses, the natural and other effects on terrestrial and personal UV doses, the time people spend outside, their ambient exposures and the terrestrial and personal UV doses of adult outdoor and indoor workers as well as children and adolescents around the world. Overall, outdoor-working adults get about 10%, while indoor-working adults and children get about 3% (2-4%) of the total available annual UV (on a horizontal plane). People's UV doses increase with increasing altitude and decreasing latitude; most indoor-working adult Europeans get 10 000-20 000 J/m(2) per year, Americans get 20000-30 000 J/m(2) per year and Australians are estimated to get 20 000-50 000 J/m(2) per year (excluding vacation, which can increase the dose by 30% or more). C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. RP Godar, DE (reprint author), US FDA, Ctr Devices & Radiol Hlth, 9200 Corp Blvd,HFZ-120, Rockville, MD 20850 USA. EM DEG@CDRH.FDA.GOV OI GODAR, DIANNE/0000-0002-7690-5223 NR 126 TC 132 Z9 135 U1 1 U2 27 PU AMER SOC PHOTOBIOLOGY PI AUGUSTA PA BIOTECH PARK, 1021 15TH ST, SUITE 9, AUGUSTA, GA 30901-3158 USA SN 0031-8655 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD JUL-AUG PY 2005 VL 81 IS 4 BP 736 EP 749 DI 10.1562/2004-09-07-IR-308R.1 PG 14 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 957KB UT WOS:000231367600002 PM 15819599 ER PT J AU McComas, KA Tuite, LS Sherman, LA AF McComas, KA Tuite, LS Sherman, LA TI Conflicted scientists: the "shared pool" dilemma of scientific advisory committees SO PUBLIC UNDERSTANDING OF SCIENCE LA English DT Article; Proceedings Paper CT Annual Conference of the Association-for-Education-in-Journalism-and-Mass-Communication CY 2004 CL Toronto, CANADA SP Assoc Educ Journalism & Mass Commun ID GROUP DECISION-MAKING; PROCEDURAL JUSTICE; PARTICIPATION; SATISFACTION; ANTECEDENTS AB Science advisors play a critical role in government policy making, yet these advisors are often equally attractive to regulated industry. Despite efforts to manage conflicts of interest among science advisors, allegations of conflict frequently plague advisory committee deliberations or outcomes. This article examines what we term the "shared pool" dilemma using data collected from 92 members of I I US Food and Drug Administration advisory committees. The results suggested science advisors were generally positive about their experiences on advisory committees and viewed the committee process as impartial. Written comments suggested that advisors linked the neutrality of the process to the success of the FDA's conflict-of-interest procedures. Even so, the advisors acknowledged the challenges associated with recruiting disinterested and qualified scientists to serve on advisory committees, reflecting the shared pool dilemma. Many advisors seemed more troubled about advisors participating when they lacked expertise than when they had minor conflicts of interest. C1 Cornell Univ, Dept Commun, Ithaca, NY 14853 USA. Univ Maryland, Dept Commun, College Pk, MD 20742 USA. US FDA, Rockville, MD 20857 USA. RP McComas, KA (reprint author), Cornell Univ, Dept Commun, 313 Kennedy Hall, Ithaca, NY 14853 USA. EM kam19@cornell.edu NR 35 TC 6 Z9 6 U1 1 U2 4 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0963-6625 J9 PUBLIC UNDERST SCI JI Public Underst. Sci. PD JUL PY 2005 VL 14 IS 3 BP 285 EP 303 DI 10.1177/096366255052891 PG 19 WC Communication; History & Philosophy Of Science SC Communication; History & Philosophy of Science GA 948QJ UT WOS:000230730500004 ER PT J AU Perrin-Guyomard, A Poul, JM Corpet, DE Sanders, P Fernandez, AH Bartholomew, M AF Perrin-Guyomard, A Poul, JM Corpet, DE Sanders, P Fernandez, AH Bartholomew, M TI Impact of residual and therapeutic doses of ciprofloxacin in the human-flora-associated mice model SO REGULATORY TOXICOLOGY AND PHARMACOLOGY LA English DT Article DE human-flora-associated mouse model; intestinal flora; ciprofloxacin; veterinary drug residues ID FECAL FLORA; COLONIZATION RESISTANCE; INTESTINAL MICROFLORA; ESCHERICHIA-COLI; DIGESTIVE-TRACT; ORAL CIPROFLOXACIN; HEALTHY-VOLUNTEERS; DRUG-RESISTANCE; PHARMACOKINETICS; ECOLOGY AB A study was conducted to evaluate the effects of therapeutic and residual doses of ciprofloxacin on the human intestinal flora implanted into germ-free mice. Ciprofloxacin was administered daily via drinking water at concentrations to provide doses of 0, 0.125, 1.25, and 12.5 mg/kg b.w. Changes in the intestinal flora composition, alteration in bacterial enzyme activities, fecal short chain fatty acid concentration and bacterial cellular fatty acid profiles, overgrowth of resistant bacteria, and disruption of the colonization barrier were the endpoints evaluated in the feces of human-flora-associated (HFA) mice. Ciprofloxacin at all tested doses decreased significantly the aerobic populations and particularly the population of Enterobacteriaceae. Selection of resistant Bacteroides fragilis group was noticed in HFA mice receiving 12.5 mg/kg b.w. In mice challenged with a Salmonella strain, exogenous Salmonella persisted in the feces of all treated mice indicating that the flora responsible for the colonization barrier effect was disturbed by the antibiotic treatment. None of the studied metabolic parameters of the flora were affected by ciprofloxacin at any dose level. Under the experimental conditions of the study, the no-observed-effect level of ciprofloxacin was found to be less than 0.125 mg/kg b.w. Published by Elsevier Inc. C1 Agence Francaise Secur Sanitaire Aliments, Lab Etud & Rech Medicaments Vet & Desinfectants, F-35302 Fougeres, France. INRA, Ecole Natl Vet, Lab Secur Aliments, F-31076 Toulouse, France. US FDA, Ctr Vet Med, Rockville, MD 20855 USA. RP Perrin-Guyomard, A (reprint author), Agence Francaise Secur Sanitaire Aliments, Lab Etud & Rech Medicaments Vet & Desinfectants, BP 90203, F-35302 Fougeres, France. EM a.perrin-guyomard@afssa.fr RI CORPET, Denis/B-3544-2008; OI Corpet, Denis/0000-0003-2119-0504; Sanders, Pascal/0000-0003-4019-480X NR 32 TC 15 Z9 19 U1 1 U2 8 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0273-2300 J9 REGUL TOXICOL PHARM JI Regul. Toxicol. Pharmacol. PD JUL PY 2005 VL 42 IS 2 BP 151 EP 160 DI 10.1016/j.yrtph.2005.03.001 PG 10 WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology SC Legal Medicine; Pharmacology & Pharmacy; Toxicology GA 943DO UT WOS:000230332500002 PM 15963836 ER PT J AU Bailey, AB Chanderbhan, R Collazo-Braier, N Cheeseman, MA Twaroski, ML AF Bailey, AB Chanderbhan, R Collazo-Braier, N Cheeseman, MA Twaroski, ML TI The use of structure-activity relationship analysis in the food contact notification program SO REGULATORY TOXICOLOGY AND PHARMACOLOGY LA English DT Article DE structure-activity relationship; food and drug administration; threshold of regulation; food contact substances; food contact notification; mutagenicity; TD50; MCASE; OnocoLogic; structure alerts ID CHEMICAL-STRUCTURE; RISK ASSESSMENT; CARCINOGENICITY; THRESHOLDS; TOXICITY AB Food contact substances (FCS) include polymers, paper and paperboard, and substances used in their manufacture, that do not impart a technical effect on food. Moreover, FCSs are industrial chemicals generally consumed at dietary concentrations (DC( of less than 1 mg/kg food (ppm), and more commonly at less than 0.05 ppm (50 ppb), in the daily diet. As such, many industrial chemicals have been analyzed for toxicological concern, some of which may share structural similarity with FCSs or their constituents, and the majority of these studies are available in the public domain. The DCs of these compounds lend themselves to using structure-activity relationship (SAR) analysis, as the available "expert systems" and use of analogs allows for prediction and management of potential carcinogens. This paper describes the newly implemented food contact notification (FCN) program, the program by which FDA reviews FCSs for safe use, the administrative review of FCSs, the SAR tools available to FDA, and qualitative and quantitative risk assessments using SAR analysis within the regulatory framework of reviewing the safety of FCSs. Published by Elsevier Inc. C1 US FDA, Ctr Food Safety & Appl Nutr, Off Food Addit Safety, Div Food Contact Notoficat, College Pk, MD 20740 USA. RP Twaroski, ML (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Food Addit Safety, Div Food Contact Notoficat, 5100 Paint Branch Pkwy,HFS-275, College Pk, MD 20740 USA. EM Michelle.Twaroski@cfsan.fda.gov NR 21 TC 51 Z9 51 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 0273-2300 J9 REGUL TOXICOL PHARM JI Regul. Toxicol. Pharmacol. PD JUL PY 2005 VL 42 IS 2 BP 225 EP 235 DI 10.1016/j.yrtph.2005.04.006 PG 11 WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology SC Legal Medicine; Pharmacology & Pharmacy; Toxicology GA 943DO UT WOS:000230332500010 PM 15935536 ER PT J AU Valdez, KE Cuneo, SP Turzillo, AM AF Valdez, KE Cuneo, SP Turzillo, AM TI Regulation of apoptosis in the atresia of dominant bovine follicles of the first follicular wave following ovulation SO REPRODUCTION LA English DT Article ID GRANULOSA-CELL APOPTOSIS; OXIDATIVE STRESS; STIMULATING-HORMONE; SUPEROXIDE-DISMUTASE; ESTROUS-CYCLE; CYTOCHROME-C; LUTEINIZING-HORMONE; OVARIAN FOLLICLES; IN-VIVO; EXPRESSION AB During atresia of bovine follicles, granulosa cells are lost through the controlled form of cell death, apoptosis. The purpose of this study was to characterize the regulation of apoptotic death of granulosa cells in dominant bovine follicles during the first wave of follicular development. Dominant follicles were collected from Holstein heifers on days 4, 6 or 8 of the first follicular wave (n = 5/day). Regulation of apoptosis in granulosa cells was examined by annexin V and propidium iodide staining; measurement of relative levels of mRNA encoding Bcl-2, Bcl-xL and Bax; and activity of caspase-3, -8 and -9. Steady-state levels of mRNA encoding four oxidative stress-response proteins were determined. Compared with day 4, the incidence of apoptotic and nonviable granulosa cells tended to increase on day 6, and numbers of nonviable cells were higher on day 8. The ratios of relative levels of mRNA encoding Bcl-2 to Bax and BcI-xL to Bax were higher on day 6 than days 4 and 8. Activity of caspases-3 and -9 in granulosa cells did not change among the 3 days, while caspase-8 activity decreased on day 8 compared with days 4 and 6. Amounts of GSHPx, MnSOD and Cu/ZnSOD mRNA in granulosa cells were higher on day 8 than day 6. In theca interna, amounts of Cu/ZnSOD mRNA decreased between days 4 and 6. From the decreased production of estradiol and increased numbers of apoptotic and nonviable granulosa cells, we conclude that atresia of the dominant follicle is initiated between days 4 and 6 of the first follicular wave. However, apoptosis of granulosa cells does not appear to be initiated by changes in expression of oxidative stress-response proteins. C1 Univ Arizona, Dept Vet Sci & Microbiol, Tucson, AZ 85724 USA. Univ Arizona, Dept Physiol, Tucson, AZ 85724 USA. RP Turzillo, AM (reprint author), US FDA, Ctr Vet Med, 7500 Standish Pl,HFV 153, Rockville, MD 20855 USA. EM adele.turzillo@fda.hhs.gov FU NIGMS NIH HHS [5T32 GM08400] NR 59 TC 38 Z9 43 U1 1 U2 2 PU BIO SCIENTIFICA LTD PI BRISTOL PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 1470-1626 J9 REPRODUCTION JI Reproduction PD JUL PY 2005 VL 130 IS 1 BP 71 EP 81 DI 10.1530/rep.1.00430 PG 11 WC Developmental Biology; Reproductive Biology SC Developmental Biology; Reproductive Biology GA 947VO UT WOS:000230675600007 PM 15985633 ER PT J AU Silverman, T Aebersold, P Landow, L Lindsey, K AF Silverman, T Aebersold, P Landow, L Lindsey, K TI Regulatory perspectives on clinical trials for trauma, transfusion, and hemostasis SO TRANSFUSION LA English DT Article; Proceedings Paper CT NATA Satellite Symposium CY 2004 CL Athens, GREECE SP NATA ID SEVERE ISOVOLEMIC ANEMIA; SHOCK C1 US FDA, Clin Review Branch, Div Hematol, Off Blood Res & Review,Ctr Biol Evaluat & Review, Rockville, MD 20857 USA. RP Silverman, T (reprint author), US FDA, Clin Review Branch, Div Hematol, Off Blood Res & Review,Ctr Biol Evaluat & Review, Rockville, MD 20857 USA. EM silvermant@cber.fda.gov NR 18 TC 8 Z9 8 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0041-1132 J9 TRANSFUSION JI Transfusion PD JUL PY 2005 VL 45 IS 1 SU S BP 14S EP 21S DI 10.1111/j.1537-2995.2005.00157.x PG 8 WC Hematology SC Hematology GA 943AG UT WOS:000230323400005 PM 15989687 ER PT J AU Akiba, J Umemura, T Alter, HJ Kojiro, M Tabor, E AF Akiba, J Umemura, T Alter, HJ Kojiro, M Tabor, E TI SEN virus: epidemiology and characteristics of a transfusion-transmitted virus SO TRANSFUSION LA English DT Article ID CHRONIC HEPATITIS-C; A-E-HEPATITIS; LIVER-DISEASE; POSTTRANSFUSION HEPATITIS; HEPATOCELLULAR-CARCINOMA; CLINICAL-SIGNIFICANCE; UNKNOWN ETIOLOGY; TT VIRUS; INFECTION; PREVALENCE AB SEN virus (SEN-V) is a blood-borne, single-stranded, nonenveloped DNA virus. Although its prevalence varies by geographic region, it has been detected in as many as 30 percent of postoperative transfusion recipients, compared to 3 percent of postoperative patients who did not receive transfusions. A significant association has been observed between transfusion volume and the occurrence of SEN-V infection. Transmission by transfusion also has been confirmed by the detection of greater than 99 percent homology between SEN-V in donor and recipient sera. Concurrent infections with SEN-V and hepatitis B virus, hepatitis C virus, or human immunodeficiency virus type 1 have been documented, and these observations probably reflect the blood-borne transmission of these viruses as well as SEN-V. Although SEN-V was discovered as part of a search for causes of posttransfusion hepatitis, there is no firm evidence so far that SEN-V infection either causes hepatitis or worsens the course of coexistent liver disease. Nevertheless, SEW V appears to be transmitted by transfusion, and further studies may reveal more about its role in the future. C1 US FDA, Ctr Biol Evaluat & Res, Div Emerging & Transfus Transmitted Dis, Rockville, MD 20852 USA. NIH, Dept Transfus Med, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. Kurume Univ, Sch Med, Dept Pathol, Kurume, Fukuoka 830, Japan. RP Tabor, E (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Emerging & Transfus Transmitted Dis, HFM-300,1401 Rockville Pike, Rockville, MD 20852 USA. EM tabor@cber.fda.gov NR 36 TC 21 Z9 24 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0041-1132 J9 TRANSFUSION JI Transfusion PD JUL PY 2005 VL 45 IS 7 BP 1084 EP 1088 DI 10.1111/j.1537-2995.00209.x PG 5 WC Hematology SC Hematology GA 942UG UT WOS:000230307800008 PM 15987351 ER PT J AU Saldanha, J Heath, A Lelie, N Pisani, G Yu, MY AF Saldanha, J Heath, A Lelie, N Pisani, G Yu, MY CA Collaborative Study Grp TI A World Health Organization International Standard for hepatitis A virus RNA nucleic acid amplification technology assays SO VOX SANGUINIS LA English DT Article DE collaborative study; hepatitis A virus; International Standard; International Units; NAT ID NAT ASSAYS; ESTABLISHMENT; HEMOPHILIACS; INFECTION AB Background and Objectives Sixteen laboratories from 10 different countries participated in an international collaborative study to evaluate candidate materials as the first World Health Organization (WHO) International Standard for hepatitis A virus (HAV) RNA nucleic acid amplification technology (NAT) assays. Materials and Methods Five candidate materials were analysed in this study: materials AA and BB were lyophilized, while materials CC, DD and EE were liquid preparations. Samples were diluted in pooled plasma or in pooled cryo-poor plasma (sample EE). Serial dilutions of the candidate materials were tested by each laboratory in four independent assays and the results were analysed statistically. Results The mean log(10) 'equivalents' per ml were 5.29 for sample AA, 5.07 for sample BB, 4.99 for sample CC, 5.40 for sample DD and 4.08 for sample EE. Conclusions Based on the results of this study, sample AA was established as the first International Standard for HAV RNA NAT assays at the WHO Expert Committee on Biological Standardizaton (ECBS) meeting held in February 2003. The code number of this preparation is 00/560 and the potency, based on the study, is 100 000 International Units (IU)/ml. C1 Natl Inst Biol Stand & Controls, Div Informat, S Mimms, Herts, England. VQC Lab, CLB Diagnost Div, Alkmaar, Netherlands. Ist Super Sanita, Immunol Lab, I-00161 Rome, Italy. OBRR CBER FDA, Div Haematol, Rockville, MD USA. Natl Inst Genet, Los Angeles, CA USA. Univ Edinburgh, Royal Dick Sch Vet Studies, SNBIS PCR Unit, Edinburgh EH9 1QH, Midlothian, Scotland. Paul Ehrlich Inst, Dept Virol, D-6070 Langen, Germany. CLB, Amsterdam, Netherlands. CSL Bioplasma, Broadmeadows, Vic, Australia. Ctr Hosp Univ Nantes, Virol Lab, Nantes 1, France. Octapharma, Frankfurt, Germany. Baxter AG, Vienna, Austria. Japanese Red Cross Plasma Fractionat Ctr, Qual Control Dept, Hokkaido, Japan. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. Natl Inst Infect Dis, Dept Bacterial Blood Prod, Tokyo, Japan. Ist Super Sanita, Immunol Lab, I-00161 Rome, Italy. DRK, Blutspendedienst Hessen, Molek Virusdiagnost, Frankfurt, Germany. Sci Inst Publ Hlth, Brussels, Belgium. Aventis Behring GmbH, Marburg, Germany. RP Saldanha, J (reprint author), Roche Mol Syst Inc, 4300 Hacienda Dr, Pleasanton, CA 94588 USA. EM john.saldanha@roche.com NR 16 TC 19 Z9 21 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0042-9007 J9 VOX SANG JI Vox Sang. PD JUL PY 2005 VL 89 IS 1 BP 52 EP 58 DI 10.1111/j.1423-0410.2005.00633.x PG 7 WC Hematology SC Hematology GA 931NL UT WOS:000229491900008 PM 15938741 ER PT J AU Wysowski, DK Swartz, L AF Wysowski, DK Swartz, L TI Adverse drug event surveillance and drug withdrawals in the United States, 1969-2002 - The importance of reporting suspected reactions SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID GROWTH-HORMONE; BREAST-CANCER; USERS; FOOD; SAFETY; RHABDOMYOLYSIS; TROGLITAZONE; TICLOPIDINE; PHYSICIANS; THERAPY AB Background: The Adverse Event Reporting System is the primary surveillance database used by the Food and Drug Administration for identifying postmarketing drug safety problems. Methods: We analyzed all reports of suspected adverse drug reactions submitted to the Food and Drug Administration from the inception of the Adverse Event Reporting System database in 1969 through December 2002. We documented drug withdrawals and restricted distribution programs based on safety concerns. Results: During the 33-year period from 1969 when adverse drug event reporting was initiated through 2002, about 2.3 million case reports of adverse events for the cumulative number of approximately 6000 marketed drugs were entered in the database. Most reports were for female patients. During this period, numerous drug reactions have been identified and added to the product labeling as boxed warnings, warnings, precautions, contraindications, and adverse reactions. More than 75 drugs/drug products have been removed from the market due to safety problems. In addition, 11 drugs have special requirements for prescriptions or have restricted distribution programs. Drugs withdrawn or restricted represent a small proportion (about 1%) of marketed drugs. Conclusions: The Food and Drug Administration's Adverse Event Reporting System is the primary surveillance database used for the identification of safety problems of marketed drugs. Despite the limitations of underreporting, differential reporting, and uneven quality, submitted reports often allow the identification of serious adverse events that are added to the product labeling information. In rare instances, additional regulations, up to and including market removal, have been required. We encourage physicians, pharmacists, other health care professionals, and patients to continue to report serious suspected and known adverse drug reactions to manufacturers and the Food and Drug Administration. C1 US FDA, Div Drug Risk Evaluat, Rockville, MD 20857 USA. RP Wysowski, DK (reprint author), US FDA, Div Drug Risk Evaluat, HFD-430-5600 Fishers Ln,Parklawn Bldg,Room 15tB-0, Rockville, MD 20857 USA. NR 47 TC 196 Z9 203 U1 0 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD JUN 27 PY 2005 VL 165 IS 12 BP 1363 EP 1369 DI 10.1001/archinte.165.12.1363 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 940BR UT WOS:000230119200005 PM 15983284 ER PT J AU Passerini, AG Shi, CZ Francesco, NM Chuan, PY Manduchi, E Grant, GR Stoeckert, CJ Karanian, JW Wray-Cahen, D Pritchard, WF Davies, PF AF Passerini, AG Shi, CZ Francesco, NM Chuan, PY Manduchi, E Grant, GR Stoeckert, CJ Karanian, JW Wray-Cahen, D Pritchard, WF Davies, PF TI Regional determinants of arterial endothelial phenotype dominate the impact of gender or short-term exposure to a high-fat diet SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE atherosclerosis; regional arterial hemodynamics; microarray; pig; endothelial cell heterogeneity; in vivo; cholesterol ID TRANSCRIPTION PROFILES; GENE-EXPRESSION; ATHEROSCLEROSIS; PATTERNS; HEMODYNAMICS; SWINE AB Regional arterial hemodynamics correlates with distinct endothelial phenotypes that may be modified by risk factors to influence focal and regional susceptibility to atherosclerosis. We compared endothelial transcript profiles from hemodynamically distinct arterial regions in 15 mature pigs: males and females fed a normal diet, and males fed a high-fat diet (15 % lard, 1.5 % cholesterol) for two weeks. Hierarchical clustering analysis showed preferential grouping of arrays by region over risk factor. A set of differentially expressed genes was identified which clearly distinguished regions of disturbed flow from undisturbed flow; however, few differences were observed within the same region based on gender or diet. Consistent with previous results in the absence of risk factors, the balance in gene expression was not inherently pathological at this early time-point. The results implicate regional hemodynamics as a predominant epigenetic determinant of endothelial phenotypic heterogeneity underlying atherosusceptibility in vivo. (c) 2005 Elsevier Inc. All rights reserved. C1 Univ Penn, Inst Med & Engn, Philadelphia, PA 19104 USA. Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. Univ Penn, Dept Bioengn, Philadelphia, PA 19104 USA. Univ Penn, Ctr Bioinformat, Philadelphia, PA 19104 USA. US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Passerini, AG (reprint author), Univ Penn, Inst Med & Engn, Philadelphia, PA 19104 USA. EM passerin@mail.med.upenn.edu; pfd@pobox.upenn.edu FU NHGRI NIH HHS [K25-HG-00052, K25-HG-02296]; NHLBI NIH HHS [T32 HL07954, HL36049, HL62250, HL70128, T32 HL007954] NR 17 TC 9 Z9 9 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 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUN 24 PY 2005 VL 332 IS 1 BP 142 EP 148 DI 10.1016/j.bbrc.2005.04.103 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 929OK UT WOS:000229355200021 PM 15896310 ER PT J AU Neznanov, N Chumakov, KM Neznanova, L Almasan, A Banerjee, AK Gudkov, AV AF Neznanov, N Chumakov, KM Neznanova, L Almasan, A Banerjee, AK Gudkov, AV TI Proteolytic cleavage of the p65-RelA subunit of NF-kappa B during poliovirus infection SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RESPIRATORY SYNCYTIAL VIRUS; ENCODED PROTEASE 3C(PRO); HOST-CELL TRANSCRIPTION; TATA-BINDING PROTEIN; RNA-POLYMERASE-II; IN-VITRO; INDUCED APOPTOSIS; ACTIVATION; EXPRESSION; INHIBITION AB Activation of NF-kappa B during viral infection is one of the critical elements in innate immune response. Several virus-specific factors, such as double-stranded RNA, can trigger host defense mechanisms by inducing NF-kappa B-mediated expression of cytokines and interferons. Early stages of poliovirus infection are also associated with degradation of I kappa B alpha and translocation of NF-kappa B into the nucleus. However, at later stages of poliovirus replication the p65-RelA component of the NF-kappa B complex undergoes a specific cleavage that coincides with the onset of intensive poliovirus protein synthesis and the appearance of the activity of poliovirus protease 3C. Indeed, the p65-RelA amino acid sequence contains the recognition site for 3C, and recombinant protein 3C was shown to be capable of proteolytic cleavage of p65-RelA, generating truncated product similar to that observed during poliovirus infection. Cleavage of p65-RelA occurs during replication of ECHO-1 and rhinovirus 14, suggesting that inactivation of NF-kappa B function by proteolytic cleavage of p65-RelA is the common mechanism by which picornaviruses suppress the innate immune response. C1 Cleveland Clin Fdn, Lerner Res Inst, Dept Mol Genet, Cleveland, OH 44195 USA. Cleveland Clin Fdn, Lerner Res Inst, Dept Canc Biol, Cleveland, OH 44195 USA. US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Neznanov, N (reprint author), Cleveland Clin Fdn, Lerner Res Inst, Dept Mol Genet, 9500 Euclid Ave, Cleveland, OH 44195 USA. EM neznann@ccf.org; Gudkov@ccf.org RI Almasan, Alex/C-2715-2008 FU NCI NIH HHS [CA60730, CA88071] NR 54 TC 75 Z9 77 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 JUN 24 PY 2005 VL 280 IS 25 BP 24153 EP 24158 DI 10.1074/jbc.M502303200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 936UD UT WOS:000229880000089 PM 15845545 ER PT J AU Przybyla-Zawislak, BD Kim, CS Ali, SF Slikker, W Binienda, ZK AF Przybyla-Zawislak, BD Kim, CS Ali, SF Slikker, W Binienda, ZK TI The differential JunB responses to inhibition of succinate dehydrogenase in rat hippocarnpus and liver SO NEUROSCIENCE LETTERS LA English DT Article DE hippocampus; c-fos; junb; krox-20; liver; 3-nitropropionic acid; rat ID C-JUN; TRANSCRIPTION FACTORS; OXIDATIVE STRESS; EXPRESSION; GLUTAMATE; BRAIN; MITOCHONDRIA; ACID; GENE AB The inhibitor of mitochondrial enzyme succinate dehydrogenase, 3-nitropropionic acid (3-NPA), induces cellular energy deficit followed by oxidative stress, secondary excitotoxicity and neuronal degeneration. The fast activation of Jun and Fos proteins and other proteins encoding inducible transcription factors (ITFs) occurs in most tissues upon exposure to a variety of stressors including exposure to mitochondrial inhibitors. However, the consequences of this activation can differ dramatically in different organs. For example, while activation of the same ITFs may lead to apoptosis and necrosis in neurons it may stimulate liver regeneration. Here, we report the alterations in mRNAs levels of c-Fos, JunB, and Krox20 proteins induced in the rat brain and liver by the acute exposure to 3-NPA at 30mg/kg, s.c. While the increase of c-fos transcripts was observed in both the hippocampus and liver, the junb transcript increased in the hippocampus but decreased in the liver. No changes were observed in krox-20 mRNA in the hippocampus. Interestingly, there was a large variation in krox-20 mRNA levels in the liver among animals within the same experimental group. In conclusion, out of the three ITFs transcripts examined here junb may activate different pathways depending on the tissue as indicated by differential responses to mitochondrial inhibition in the hippocampus and liver. © 2005 Elsevier Ireland Ltd. All rights reserved. C1 US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. US FDA, CFSAN, Div Toxicol, Laurel, MD USA. RP Przybyla-Zawislak, BD (reprint author), US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM bzawislak@nctr.fda.gov NR 18 TC 7 Z9 7 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD JUN 24 PY 2005 VL 381 IS 3 BP 354 EP 357 DI 10.1016/j.neulet.2005.02.049 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 932MR UT WOS:000229558300031 PM 15896499 ER PT J AU Starke, PR Weaver, J Chowdhury, BA AF Starke, PR Weaver, J Chowdhury, BA TI Boxed warning added to promethazine labeling for pediatric use SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID SEDATION C1 US FDA, Rockville, MD 20857 USA. RP Starke, PR (reprint author), US FDA, Rockville, MD 20857 USA. EM starkep@cder.fda.gov NR 4 TC 31 Z9 38 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 23 PY 2005 VL 352 IS 25 BP 2653 EP 2653 DI 10.1056/NEJM200506233522522 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 937VJ UT WOS:000229953700029 PM 15972879 ER PT J AU Dobrovolsky, VN Bowyer, JF Pabarcus, MK Heflich, RH Williams, LD Doerge, DR Arvidsson, B Bergquist, J Casida, JE AF Dobrovolsky, VN Bowyer, JF Pabarcus, MK Heflich, RH Williams, LD Doerge, DR Arvidsson, B Bergquist, J Casida, JE TI Effect of arylformamidase (kynurenine formamidase) gene inactivation in mice on enzymatic activity, kynurenine pathway metabolites and phenotype SO BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS LA English DT Article DE arylformamidase; formyl-kynurenine; kynurenine; kynurenic acid; kynurenine formamidase; tryptophan ID PULMONARY INDOLEAMINE 2,3-DIOXYGENASE; INTERFERON-GAMMA; QUINOLINIC ACID; CHICKEN EMBRYOS; TRYPTOPHAN; MOUSE; INHIBITION; INDUCTION; AMINOTRANSFERASE; ORGANOPHOSPHORUS AB The gene coding for arylformamidase (Afmid, also known as kynurenine formamidase) was inactivated in mice through the removal of a shared bidirectional promoter region regulating expression of the Afmid and thymidine kinase (Tk) genes. Afmid/Tk-deficient mice are known to develop sclerosis of glomeruli and to have an abnormal immune system. Afmid-catalyzed hydrolysis of N-fonnyl-kynurenine is a key step in tryptophan metabolism and biosynthesis of kynurenine-derived products including kynurenic acid, quinolinic acid, nicotinamide, NAD, and NADP. A disruption of these pathways is implicated in neurotoxicity and immunotoxicity. In wild-type (WT) mice, Afmid-specific activity (as measured by formyl-kynurenine hydrolysis) was 2-fold higher in the liver than in the kidney. Formyl-kynurenine hydrolysis was reduced by similar to 50% in mice heterozygous (HZ) for Afmid/Tk and almost completely eliminated in Afmid/Tk knockout (KO) mice. However, there was 13% residual formyl-kynurenine hydrolysis in the kidney of KO mice, suggesting the existence of a formamidase other than Afmid. Liver and kidney levels of nicotinamide plus NAD/NADP remained the same in WT, HZ and KO mice. Plasma concentrations of formyl-kynurenine, kynurenine, and kynurenic acid were elevated in KO mice (but not HZ mice) relative to WT mice, further suggesting that there must be enzymes other than Afmid (possibly in the kidney) capable of metabolizing formyl-kynurenine into kynurenine. Gradual kidney deterioration and subsequent failure in KO mice is consistent with high levels of tissue-specific Afmid expression in the kidney of WT but not KO mice. On this basis, the most significant function of the kynurenine pathway and Afmid in mice may be in eliminating toxic metabolites and to a lesser extent in providing intermediates for other processes. Published by Elsevier B.V. C1 Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. Univ Calif Berkeley, Dept Environm Sci Policy & Management, Berkeley, CA 94720 USA. Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. Univ Uppsala, Inst Chem, Dept Analyt Chem, S-75105 Uppsala, Sweden. RP Dobrovolsky, VN (reprint author), Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, 3900 NCTR Rd,HFT-120, Jefferson, AR 72079 USA. EM vdobrovolsky@nctr.fda.gov RI Bergquist, Jonas/C-5894-2015; OI Bergquist, Jonas/0000-0002-4597-041X FU NIEHS NIH HHS [R01 ES08762] NR 35 TC 14 Z9 15 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-4165 J9 BBA-GEN SUBJECTS JI Biochim. Biophys. Acta-Gen. Subj. PD JUN 20 PY 2005 VL 1724 IS 1-2 BP 163 EP 172 DI 10.1016/j.bbagen.2005.03.010 PG 10 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 940YS UT WOS:000230182400018 PM 15866519 ER PT J AU Bleckwenn, NA Golding, H Bentley, WE Shiloach, J AF Bleckwenn, NA Golding, H Bentley, WE Shiloach, J TI Production of recombinant proteins by vaccinia virus in a microcarrier based mammalian cell perfusion bioreactor SO BIOTECHNOLOGY AND BIOENGINEERING LA English DT Article DE vaccinia; bioreactor; microcarrier; ATF; EGFP; gp120 ID BACULOVIRUS EXPRESSION SYSTEM; SF-9 INSECT CELLS; HIV ENVELOPE; MONOCLONAL-ANTIBODY; SUSPENSION-CULTURES; GENE-EXPRESSION; CLINICAL-TRIAL; GROWTH-FACTOR; HELA-CELLS; GLYCOPROTEIN AB The HeLa cell-vaccinia virus expression system was evaluated for the production of recombinant proteins (enhanced green fluorescent protein (EGFP) and HIV envelope coat protein, gp120) using microcarriers in 1.5 L perfused bioreactor cultures. Perfusion was achieved by use of an alternating tangential flow device (ATF), increasing the length of the exponential phase by 50 h compared to batch culture and increasing the maximum cell density from 1.5 x 10(6) to 4.4 x 10(6) cell/mL. A seed train expansion method using cells harvested from microcarrier culture and reseeding onto fresh carriers was developed. EGFP was first used as a model protein to study process parameters affecting protein yield, specifically dissolved oxygen (DO) and temperature during the production phase. The highest level of EGFP, 12 +/- 1.5 mu g/10(6) infected cells, was obtained at 50% DO and 31 degrees C. These setpoints were then used to produce glycoprotein, gp120, which was purified and deglycosylated, revealing a significant amount of N-linked glycosylation. Also, biological activity was assayed, resulting in an ID50 of 3.1 mu g/mL, which is comparable to previous reports. Published 2005 Wiley Periodicals, Inc.(dagger) C1 NIDDK, Biotechnol Unit, DHHS, NIH, Bethesda, MD USA. US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD USA. Univ Maryland, Dept Chem Engn, College Pk, MD 20742 USA. Univ Maryland, Inst Biotechnol, Ctr Biosyst Res, College Pk, MD USA. RP Bleckwenn, NA (reprint author), NIDDK, Biotechnol Unit, DHHS, NIH, Bldg 14A Rm 173,MSC 5522,9000 Rockville Pike, Bethesda, MD USA. EM yossic@nih.gov FU Intramural NIH HHS NR 55 TC 17 Z9 17 U1 2 U2 13 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 JUN 20 PY 2005 VL 90 IS 6 BP 663 EP 674 DI 10.1002/bit.20423 PG 12 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 931CM UT WOS:000229463400001 PM 15858791 ER PT J AU Agol, VI Chumakov, K Ehrenfeld, E Wimmer, E AF Agol, VI Chumakov, K Ehrenfeld, E Wimmer, E TI Don't drop current vaccine until we have new ones SO NATURE LA English DT Letter C1 Russian Acad Med Sci, MP Chumakov Inst Poliomyelitis & Viral Encephalit, Moscow 142782, Russia. US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. NIAID, NIH, Bethesda, MD 20892 USA. SUNY Stony Brook, Sch Med, Dept Mol Genet & Microbiol, Stony Brook, NY 11794 USA. RP Agol, VI (reprint author), Russian Acad Med Sci, MP Chumakov Inst Poliomyelitis & Viral Encephalit, Moscow 142782, Russia. RI Agol, Vadim/E-1941-2013 NR 1 TC 5 Z9 5 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD JUN 16 PY 2005 VL 435 IS 7044 BP 881 EP 881 DI 10.1038/435881b PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 935RN UT WOS:000229799700018 PM 15959489 ER PT J AU Chen, DT Chen, JJ Soong, SJ AF Chen, DT Chen, JJ Soong, SJ TI Probe rank approaches for gene selection in oligonucleotide arrays with a small number of replicates SO BIOINFORMATICS LA English DT Article ID EXPRESSION PROFILES; MODEL; SARCOMA; TISSUE AB Motivation: One major area of interest in analyzing oligonucleotide gene array data is identifying differentially expressed genes. A challenge to biostatisticians is to develop an approach to summarizing probe-level information that adequately reflects the true expression level while accounting for probe variation, chip variation and interaction effects. Various statistical tools, such as MAS and RMA, have been developed to address this issue. In these approaches, the probe level expression data are summarized into gene level data, which are then used for downstream statistical analysis. Since probe variation is often larger than chip variation and there is also a potential interaction effect between probe affinity and treatment effect, strategies such as a gene level analysis, may not be optimal. In this study, we propose a procedure to analyze probe level data for selecting differentially expressed genes under two treatment conditions (groups) with a small number of replicates. The probe level discrepancy between two groups can be measured by a difference of the percentiles of probe perfect-match (PM) ranks or of probe PM weighted ranks. The difference is then compared with a pre-specified threshold to determine differentially expressed genes. The probe level approach takes into account non-homogenous treatment effects and reduces possible cross-hybridization effects across a set of probes. Results: The proposed approach is compared with MAS and RMA using two benchmark gene array datasets. Positive predictivity and sensitivity are used for evaluation. Results show the proposed approach has higher positive predictivity and higher sensitivity. C1 Univ Alabama, Ctr Comprehens Canc, Biostat & Bioinformat Unit, Wallace Tumor Inst 153, Birmingham, AL 35294 USA. US FDA, Div Biometry & Risk Assessment, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Chen, DT (reprint author), Univ Alabama, Ctr Comprehens Canc, Biostat & Bioinformat Unit, Wallace Tumor Inst 153, 1824 6th Ave S, Birmingham, AL 35294 USA. EM dtchen@uab.edu FU NCI NIH HHS [U54 CA100949, 5P30 CA-13148, 1P50 CA89019, P50 CA83591] NR 18 TC 7 Z9 7 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD JUN 15 PY 2005 VL 21 IS 12 BP 2861 EP 2866 DI 10.1093/bioinformatics/bti143 PG 6 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 937OE UT WOS:000229934600012 PM 15814562 ER PT J AU Safar, AM Spencer, H Su, XB Coffey, M Cooney, CA Ratnasinghe, LD Hutchins, LF Fan, CY AF Safar, AM Spencer, H Su, XB Coffey, M Cooney, CA Ratnasinghe, LD Hutchins, LF Fan, CY TI Methylation profiling of archived non-small cell lung cancer: A promising prognostic system SO CLINICAL CANCER RESEARCH LA English DT Article ID PROMOTER HYPERMETHYLATION; DNA METHYLATION; CLINICAL-IMPLICATIONS; MULTIPLE GENES; BREAST-CANCER; SURVIVAL; INACTIVATION; CARCINOMA; ASSAY; HEAD AB Purpose: Enhanced prognostication power is becoming more desirable in clinical oncology. In this study, we explored the prognostic potential of multigene hypermethylation profiling in non-small-cell lung cancer. Experimental Design: We evaluated a panel of eight genes (p16, APC, ATM, hMLH1, MGMT DAPK, ECAD, and RASSF1A) using methylation-specific PCR in 105 archived specimens of non-small-cell lung cancer representing all stages of the illness, We analyzed the effect of gene methylation status on outcome individually in a cumulative manner and in a combinatorial approach using recursive partitioning to identify methylation profiles, which affect overall survival. Results: In this data set, tumors harboring promoter hypermethylation at two or more genes exhibit similar survival trends to others in the cohort. Using recursive partitioning, three genes (APC, ATM, and RASSF1A) emerged as determinants of prognostic groups. This designation retained its statistical significance even when disease stage and age were entered into a multivariate analysis. Using this approach, patients whose tumors were hypermethylated at APC and those hypermethylated at only ATM (not also at APC or RASSF1A) enjoyed substantially longer 1- and 2-year survival than patients in the remaining groups. In 32 adjacent histologically normal lung tissue specimens, we detected similar methylation abnormalities. Conclusion: Assessment of promoter hypermethylation aberrations may facilitate prognostic profiling of lung tumors, but validation in independent data sets is needed to verify these profiles. This system uses material that is abundantly available with linked outcome data and can be used to generate reliable epigenetic determinants. C1 Univ Arkansas Med Sci, Div Hematol & Oncol, Little Rock, AR 72205 USA. Cent Arkansas Vet Healthcare Syst, Little Rock, AR USA. US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Safar, AM (reprint author), Univ Arkansas Med Sci, Div Hematol & Oncol, 4301 W Markham,Slot 508, Little Rock, AR 72205 USA. EM safarahmedm@uams.edu OI Cooney, Craig/0000-0003-4279-557X NR 28 TC 83 Z9 85 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUN 15 PY 2005 VL 11 IS 12 BP 4400 EP 4405 DI 10.1158/1078-0432.CCR-04-2378 PG 6 WC Oncology SC Oncology GA 934RM UT WOS:000229725900019 PM 15958624 ER PT J AU Corby, R Lanni, V Kistler, V Dato, V Weltman, A Yozviak, C Waller, K Nalluswami, K Moll, M Lockett, J Montgomery, S Lynch, M Braden, C Gupta, SK DuBois, A AF Corby, R Lanni, V Kistler, V Dato, V Weltman, A Yozviak, C Waller, K Nalluswami, K Moll, M Lockett, J Montgomery, S Lynch, M Braden, C Gupta, SK DuBois, A CA CDC TI Outbreaks of Salmonella infections associated with eating Roma tomatoes - United States and Canada, 2004 (Reprinted from MMWR, vol 54, pg 325-328, 2005) SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Reprint ID PLANTS C1 Allentown Hlth Bur, Allentown, PA USA. Penn Dept Hlth, Ctr Food Safety & Appl Nutr, Harrisburg, PA 17108 USA. US FDA, Off Crisis Management, Rockville, MD 20857 USA. Ctr Dis Control, Natl Ctr Infect Dis, Div Bacterial & Mycot Dis, Atlanta, GA 30333 USA. CDC, Atlanta, GA 30333 USA. NR 11 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 JUN 15 PY 2005 VL 293 IS 23 BP 2852 EP + PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 935MD UT WOS:000229785500010 ER PT J AU Brinker, A He, RY Desai, M Gelperin, K Robie-Suh, K AF Brinker, A He, RY Desai, M Gelperin, K Robie-Suh, K TI Safety of ximelagatran SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter ID NONVALVULAR ATRIAL-FIBRILLATION; THROMBIN INHIBITOR XIMELAGATRAN; VENOUS THROMBOEMBOLISM; STROKE PREVENTION; RANDOMIZED-TRIAL; WARFARIN C1 US FDA, Off New Drugs, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. US FDA, Off Drug Safety, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Brinker, A (reprint author), US FDA, Off New Drugs, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. EM robiesuh@cder.fda.gov NR 8 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 JUN 15 PY 2005 VL 293 IS 23 BP 2859 EP 2859 DI 10.1001/jama.293.23.2859-a PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 935MD UT WOS:000229785500011 PM 15956625 ER PT J AU Noonan, GO Warner, CR Hsu, W Begley, TH Perfetti, GA Diachenko, GW AF Noonan, GO Warner, CR Hsu, W Begley, TH Perfetti, GA Diachenko, GW TI The determination of semicarbazide (N-Aminourea) in commercial bread products by liquid chromatography-mass spectrometry SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE azodicarbonamide; semicarbazide; method development; bread additive; LC-MS ID PROTEIN-BOUND METABOLITES; FURAZOLIDONE; TISSUE; PLASMA; BLOOD AB Recently, semicarbazide has been found in food in jars sealed with cap liners that were manufactured using azodicarbonamide as a blowing agent. These reports raised the concern that the use of azodicarbonamide-an approved dough conditioner-may result in semicarbazide residues in bread. To answer this question, a method based upon the previously reported liquid chromatography/tandem mass spectrometry determination of the semicarbazone of o-nitrobenzaldehyde was utilized. The method adopted for this work includes an extensive cleanup and reaction with o-nitrobenzaldehyde at pH 3.5, rather than with the widely used 0.1 M HCl;, to form the semicarbazone derivative. A stable isotope dilution assay was used to determine the free semicarbazide present in the bread products. Levels of semicarbazide ranged from 10 to 1200 ppb in commercial bread products with azodicarbonamide listed among their ingredients. C1 US FDA, Off Food Addit Safety, College Pk, MD 20740 USA. Univ Maryland, College Pk, MD 20742 USA. RP Noonan, GO (reprint author), US FDA, Off Food Addit Safety, College Pk, MD 20740 USA. NR 17 TC 23 Z9 28 U1 0 U2 14 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 JUN 15 PY 2005 VL 53 IS 12 BP 4680 EP 4685 DI 10.1021/jf050480j PG 6 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 934PM UT WOS:000229720700005 PM 15941299 ER PT J AU Huque, MF AF Huque, MF TI Introduction SO STATISTICS IN MEDICINE LA English DT Editorial Material ID TRIALS C1 OB OPaSS CDER FDA, Div Biometr 3, Rockville, MD 20853 USA. RP Huque, MF (reprint author), OB OPaSS CDER FDA, Div Biometr 3, 9201 Corp Blvd, Rockville, MD 20853 USA. NR 8 TC 1 Z9 1 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD JUN 15 PY 2005 VL 24 IS 11 BP 1646 EP 1651 DI 10.1002/sim.2017 PG 6 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 929VN UT WOS:000229374800003 ER PT J AU Hartmann, FA White, DG West, SEH Walker, RD DeBoer, DJ AF Hartmann, FA White, DG West, SEH Walker, RD DeBoer, DJ TI Molecular characterization of Staphylococcus intermedius carriage by healthy dogs and comparison of antimicrobial susceptibility patterns to isolates from dogs with pyoderma SO VETERINARY MICROBIOLOGY LA English DT Article DE Staphylococcus intermedius; antimicrobial resistance; pyoderma ID FIELD GEL-ELECTROPHORESIS; ARBITRARILY PRIMED PCR; RESTRICTION PATTERNS; NASAL CARRIAGE; INFECTIONS; POLYMORPHISM; ANTIBIOTICS; FREQUENCY; CARRIERS; STRAINS AB We conducted an epidemiological study of Staphylococcus intermedius using arbitrarily primed PCR (AP-PCR) and antibiograms. One hundred and twenty-five S. intermedius isolates were recovered from the oral cavity and/or cranial hair coat of healthy dogs enrolled in a pet therapy program. Commensal S. intermedius was cultured from 32% of the oral cavity cultures and 13% of the cranial hair coat cultures. We characterized the colonization of the dogs as transient, intermittent, or persistent. For dogs characterized as persistently colonized, 73% of the isolates came from the oral cavity. These isolates were also genotyped by AP-PCR. A single major AP-PCR type was observed in 91% of the dogs (n = 22); minor variations were frequently observed in these major types. Antibiograms of these commensal isolates were compared to antibiograms from 97 historical clinical isolates (1988-1992) obtained from cases of canine pyoderma. Resistance was most often observed to penicillin (64% and 55%) and tetracycline (38% and 38%) among the commensal and clinical isolates, respectively. The commensal isolates were significantly less resistant to erythromycin, clarithromycin, clindamycin, and trimethoprim/sulfamethoxazole. Our data suggests that differences in both genotype and antimicrobial susceptibility phenotypes exist among S. intermedius strains isolated from different anatomic sites from the same dog and supports the opportunistic nature of S. intermedius in canine infections. (c) 2005 Elsevier B.V. All rights reserved. C1 Univ Wisconsin, Clin Pathol Lab, Sch Vet Med, Vet Med Teaching Hosp, Madison, WI 53706 USA. US FDA, Ctr Vet Med, Laurel, MD 20708 USA. Univ Wisconsin, Sch Vet Med, Dept Pathobiol Sci, Madison, WI 53706 USA. Univ Wisconsin, Sch Vet Med, Dept Med, Madison, WI 53706 USA. RP Hartmann, FA (reprint author), Univ Wisconsin, Clin Pathol Lab, Sch Vet Med, Vet Med Teaching Hosp, 2015 Linden Dr, Madison, WI 53706 USA. EM hartmannf@svm.vetmed.wisc.edu NR 31 TC 33 Z9 34 U1 3 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1135 J9 VET MICROBIOL JI Vet. Microbiol. PD JUN 15 PY 2005 VL 108 IS 1-2 BP 119 EP 131 DI 10.1016/j.vetmic.2005.03.006 PG 13 WC Microbiology; Veterinary Sciences SC Microbiology; Veterinary Sciences GA 934UX UT WOS:000229735400013 PM 15917140 ER PT J AU Gollety, C Connors, VA Adams, AM Roumillat, WA de Buron, I AF Gollety, C Connors, VA Adams, AM Roumillat, WA de Buron, I TI Population dynamics of the philometrid nematode Margolisianum bulbosum in the southern flounder Paralichthys lethostigma (Pisces : Paralichthyidae) in South Carolina, USA SO DISEASES OF AQUATIC ORGANISMS LA English DT Article DE nematode; philometridae; population dynamics; southern flounder ID ANGUILLICOLA-CRASSUS; PARASITE; BIOLOGY; CATFISH; HOST AB This is the first report of the philometrid nematode Margolisianum bulbosum Blaylock and Overstreet, 1999 from the southern flounder Paralichthys lethostigma on the east coast of the USA. Observation of adult female worms was used as an indication of the parasite's presence in the fish. Adult females were found only in R lethostigma > 150 mm total length. The overall prevalence was 74%, with a mean intensity of 5 female nematodes per parasitized fish. Infected flounders were found throughout the year with a statistically significant decrease in intensity in the winter months. Neither salinity, water temperature, fish gender nor fish age were found to influence either prevalence or intensity of infection in the flounder. While larvigerous (gravid) females were found throughout the year, the significant decrease in their occurrence during the summer through fall, in concert with an observed decrease in intensity of infection during the winter, indicated that the life cycle of this philometrid species is likely to be annual. C1 Coll Charleston, Dept Biol, Charleston, SC 29401 USA. Univ S Carolina Upstate, Dept Biol, Spartanburg, SC 29301 USA. US FDA, Kansas City Dist Lab, Lenexa, KS 66214 USA. Dept Nat Resources, Charleston, SC 29422 USA. RP de Buron, I (reprint author), Coll Charleston, Dept Biol, 58 Coming St, Charleston, SC 29401 USA. EM deburoni@cofc.edu RI Gollety, Claire/D-6743-2011 NR 22 TC 3 Z9 3 U1 0 U2 2 PU INTER-RESEARCH PI OLDENDORF LUHE PA NORDBUNTE 23, D-21385 OLDENDORF LUHE, GERMANY SN 0177-5103 J9 DIS AQUAT ORGAN JI Dis. Aquat. Org. PD JUN 14 PY 2005 VL 65 IS 1 BP 69 EP 74 DI 10.3354/dao065069 PG 6 WC Fisheries; Veterinary Sciences SC Fisheries; Veterinary Sciences GA 958VE UT WOS:000231475500009 PM 16042045 ER PT J AU Zhang, BL Yang, L Zheng, Y AF Zhang, BL Yang, L Zheng, Y TI Novel intermediate of Rac GTPase activation by guanine nucleotide exchange factor SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE Rho GTPases; guanine nucleotide exchange; reaction mechanism; GTP binding; GDP-dissociation ID STRUCTURAL BASIS; RHO-GTPASES; BINDING PROTEINS; GUANOSINE; MECHANISM; DOMAIN; SWITCH; HYDROLYSIS; CDC42; TRIO AB The biochemical role of guanine nucleotide exchange factors (GEFs) in catalyzing small GTPase GDP- GTP exchange is thought to be twofold: stimulation of GDP dissociation and stabilization of a nucleotide-free GTPase intermediate. Here we report that TrioN, a Dbl family GEF, activates Racl by facilitating GTP binding to, as well as stimulating GDP dissociation from, Racl. The TrioN-catalyzed GDP dissociation is dependent upon the structural nature and the concentration of free nucleotide, and nucleotide binding serves as the rate-limiting step of the GEF reaction. The TrioN-stimulated nucleotide exchange may undergo a novel two nucleotide-one G-protein intermediate involving two cryptic subsites on Racl induced by the GEF, with one subsite contributing to the recognition of the β/γ phosphates of the incoming GTP and another to the binding of the guanine base of the leaving GDP. We propose that the Rac GEF reaction may proceed by competitive displacement of bound GDP by GTP through a transient intermediate of GEF-[GTP-Rac- GDP]. © 2005 Elsevier Inc. All rights reserved. C1 Univ Cincinnati, Childrens Hosp Res Fdn, Div Expt Hematol, Cincinnati, OH 45229 USA. US FDA, Ctr Drug Evaluat & Res, Div Therapeut Prot, Bethesda, MD 20892 USA. RP Zheng, Y (reprint author), Univ Cincinnati, Childrens Hosp Res Fdn, Div Expt Hematol, 3333 Burnet Ave, Cincinnati, OH 45229 USA. EM yi.zheng@chmcc.org RI Zheng, Yi/J-7235-2015 OI Zheng, Yi/0000-0001-7089-6074 FU NIGMS NIH HHS [GM 53943, GM 60523] NR 27 TC 3 Z9 3 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUN 3 PY 2005 VL 331 IS 2 BP 413 EP 421 DI 10.1016/j.bbrc.2005.03.179 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 924EG UT WOS:000228961000007 PM 15850775 ER PT J AU Klamt, F Shacter, E AF Klamt, F Shacter, E TI Taurine chloramine, an oxidant derived from neutrophils, induces apoptosis in human B lymphoma cells through mitochondrial damage SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PERMEABILITY TRANSITION PORE; CYTOCHROME-C RELEASE; HYPOCHLOROUS ACID; OXIDATIVE STRESS; AMINO-ACID; LEUKEMIA-CELLS; CYCLOSPORINE-A; DEATH; RECEPTOR; PHOSPHATIDYLSERINE AB Taurine chloramine (TN-Cl) is one of the most abundant compounds generated by activated neutrophils. In contrast to HOCl, which causes necrosis, TN-Cl is a potent inducer of apoptosis in tumor cells. Here we show that the apoptosis induced by TN-Cl in human B lymphoma cells is dependent upon oxidant-mediated mitochondrial damage, a decrease in mitochondrial membrane potential, and caspase-9 activation. Further, we show that TN-Cl is taken up into the cells and is concentrated in the mitochondria, where it induces opening of the permeability transition pore and mitochondrial swelling. Identical activity is seen upon treatment of isolated mitochondria with TN-Cl and is blocked by the permeability transition pore inhibitors bongkrekic acid and cyclosporin A, as well as by the sulfhydryl-reducing agent tris(2-carboxyethyl)-phosphine. The data suggest that TN-Cl causes apoptosis through direct damage to the mitochondria. C1 US FDA, Biochem Lab, Div Therapeut Prot, CDER, Bethesda, MD 20892 USA. Lutheran Univ Brazil ULBRA, Dept Biol, BR-92450900 Canoas, RS, Brazil. RP Shacter, E (reprint author), US FDA, Biochem Lab, Div Therapeut Prot, CDER, 29 Lincoln Dr,Bldg 29A,Rm 2A-11, Bethesda, MD 20892 USA. EM emily.shacter@fda.gov NR 48 TC 43 Z9 45 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 JUN 3 PY 2005 VL 280 IS 22 BP 21346 EP 21352 DI 10.1074/jbc.M501170200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 930TA UT WOS:000229438800053 PM 15799967 ER PT J AU Roy, S Caillouette, JC Faden, JS Roy, T AF Roy, S Caillouette, JC Faden, JS Roy, T TI The role of an over-the-counter vaginal pH self-test device package insert: Can subjects learn what the device is for and how to use it? SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 71st Annual Meeting of the Central-Association-of-Obstetricians-and-Gynecologists CY OCT 13-16, 2004 CL Washington, DC DE vaginal pH self-test device; vaginitis; over-the-counter; antifungal AB Objective: This study was undertaken to determine whether subjects Could read and understand the package insert of a vaginal pH self-test device to improve self-diagnostic accuracy. Study design: This study was performed at 8 clinic locations with 206 women of varying ages, ethnicity, and education. A package insert explaining the indications and clinical facts associated with the use of a vaginal pH self-test device was used. A 16-item questionnaire was administered to assess comprehension. Results: The cumulative probability of having 12 or more correct answers of 16 was P = .038, significantly different than by chance alone, representing 200 (97.1%) of subjects in this trial. Conclusion: The package insert for the vaginal pH self-test device was read and understood by subjects. Indeed, they correctly understood the role of vaginal pH as an aid in the diagnosis of vaginal symptoms while improving decisions to use an over-the-counter antifungal medication or to see a health care provider. (c) 2005 Elsevier Inc. All rights reserved. C1 Univ So Calif, Dept Obstet & Gynecol, Keck Sch Med, Womens & Childrens Hosp, Los Angeles, CA 90033 USA. US FDA, Washington, DC 20204 USA. RP Roy, S (reprint author), Univ So Calif, Dept Obstet & Gynecol, Keck Sch Med, Womens & Childrens Hosp, 1240 N Mission Rd,Room L1022, Los Angeles, CA 90033 USA. EM subirro@usc.edu NR 4 TC 5 Z9 5 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JUN PY 2005 VL 192 IS 6 BP 1963 EP 1967 DI 10.1016/j.ajog.2005.02.056 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 938XV UT WOS:000230037600048 PM 15970861 ER PT J AU Warfel, JM Steele, AD D'Agnillo, F AF Warfel, JM Steele, AD D'Agnillo, F TI Anthrax lethal toxin induces endothelial barrier dysfunction SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID BACILLUS-ANTHRACIS; INHALATION ANTHRAX; PROTECTIVE ANTIGEN; EDEMA FACTOR; VE-CADHERIN; PATHOLOGY; PATHOGENESIS; RECEPTOR; KINASE; CELLS AB Hemorrhage and pleural effusion are prominent pathological features of systemic anthrax infection. We examined the effect of anthrax lethal toxin (LT), a major virulence factor of Bacillus anthracis, on the barrier function of primary human lung microvascutar endothelial cells. We also examined the distribution patterns of cytoskeletal actin and vascular endothelial-cadherin (VE-cadherin), both of which are involved in barrier function regulation. Endothelial monolayers cultured on porous membrane inserts were treated with the LT components lethal factor (LF) and protective antigen (PA) individually, or in combination. LT induced a concentration- and time-dependent decrease in transendothelial electrical resistance that correlated with increased permeability to fluorescently labeled albumin. LT also produced a marked increase in central actin stress fibers and significantly altered VE-cadherin distribution as revealed by immunofluorescence microscopy and cell surface enzyme-linked inummosorbent assay. Treatment with LF, PA, or the combination of an inactive LF mutant and PA did not alter barrier function or the distribution of actin or VE-cadherin. LT-induced barrier dysfunction was not dependent on endothelial apoptosis or necrosis. The present findings support a possible role for LT-induced barrier dysfunction in the vascular permeability changes accompanying systemic anthrax infection. C1 US FDA, Ctr Biol Evaluat & Res, Div Hematol, Lab Biochem & Vasc Biol, Bethesda, MD 20892 USA. RP D'Agnillo, F (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Hematol, Lab Biochem & Vasc Biol, 29 Lincoln Dr,Bldg 29,Rm 129, Bethesda, MD 20892 USA. EM dagnillo@cber.fda.gov RI Warfel, Jason/D-2557-2011 NR 36 TC 108 Z9 110 U1 0 U2 1 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD JUN PY 2005 VL 166 IS 6 BP 1871 EP 1881 DI 10.1016/S0002-9440(10)62496-0 PG 11 WC Pathology SC Pathology GA 930AC UT WOS:000229387100029 PM 15920171 ER PT J AU Bluhm, L Huang, JM Li, TY AF Bluhm, L Huang, JM Li, TY TI Recent advances in peptide chiral selectors for electrophoresis and liquid chromatography SO ANALYTICAL AND BIOANALYTICAL CHEMISTRY LA English DT Review DE peptide chiral selector; chiral separation; combinatorial library; chiral stationary phase; electrophoresis; chiral chromatography ID TUBULAR CAPILLARY ELECTROCHROMATOGRAPHY; STRUCTURE-ENANTIOSELECTIVITY RELATIONSHIP; MICELLAR ELECTROKINETIC CHROMATOGRAPHY; PARALLEL COMBINATORIAL LIBRARY; AMINO-ACID ORDER; STATIONARY PHASES; SYNTHETIC CYCLOPEPTIDES; MOLECULAR RECOGNITION; SEPARATIONS; RESOLUTION AB The application of peptides in chiral separations using techniques such as capillary electrophoresis (CE), electrokinetic capillary chromatography (EKC) and liquid chromatography is the focus of this review. Methods for finding peptide selectors using combinatorial library approaches are discussed, as well as recent advances in the use of peptides as general chiral selectors for electrophoresis and liquid chromatography. One example shows the effectiveness of polymeric dipeptide surfactants as general chiral selectors for electrophoresis. Another example shows the versatility of oligoproline chiral stationary phases, exhibiting resolution for a number of racemic analytes comparable to other well-established chiral stationary phases. C1 Mississippi State Univ, Dept Chem, Mississippi State, MS 39762 USA. US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Li, TY (reprint author), Mississippi State Univ, Dept Chem, Box 9573, Mississippi State, MS 39762 USA. EM TL45@ra.msstate.edu FU NIGMS NIH HHS [1 R01 GM63812-01] NR 41 TC 25 Z9 25 U1 1 U2 10 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1618-2642 J9 ANAL BIOANAL CHEM JI Anal. Bioanal. Chem. PD JUN PY 2005 VL 382 IS 3 BP 592 EP 598 DI 10.1007/s00216-005-3171-y PG 7 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 932TQ UT WOS:000229576800006 PM 15883787 ER PT J AU Buehler, PW Boykins, RA Jia, YP Norris, S Freedberg, DI Alayash, AI AF Buehler, PW Boykins, RA Jia, YP Norris, S Freedberg, DI Alayash, AI TI Structural and functional characterization of glutaraldehyde-polymerized bovine hemoglobin and its isolated fractions SO ANALYTICAL CHEMISTRY LA English DT Article ID CHLORIDE-BINDING-SITES; OXYGEN-AFFINITY; CROSS-LINKING; MAMMALIAN HEMOGLOBINS; CENTRAL CAVITY; PROTEINS; CARRIERS; 2,3-DIPHOSPHOGLYCERATE; MODULATION AB Glutaraldehyde-polymerized bovine hemoglobin (PolyHbBv, trade name Oxyglobin), is a non-site-specific modified hemoglobin-based oxygen-carrying solution, developed for use in veterinary medicine. PolyHbBv was fractionated into four distinct tetrameric and multiple polytetrameric forms ranging in molecular mass (87.2-502.3 kDa) using size exclusion chromatography (SEC) and verified by laser light scattering. We evaluated the structural modification occurring in the fractionated mixture of PolyHbBv and assessed the functionality and redox stability of each fraction in relation to the mixture as a whole. Intramolecular cross-linking evaluation as performed by MALDI-MS and SEC under dissociating conditions revealed no-site-specific tetramer stabilization within the fractions; Intermolecular cross-linking was highly correlated with lysine and histidine modification as determined by amino acid composition analysis. While native unmodified hemoglobin, HbBv, PolyHbBv, and PolyHbBv fractions (F1-F4) revealed significant methionine oxidation, modification, or both, the critical β Met55 located in the functionally plastic domains (α 1-β 1 interface) of HbBv was unaltered. Moreover, neither of the two β Cys93 located in the highly plastic α 1-β 2 interface were modified in PolyHbBv or in F1-F4. Our structural analysis also revealed that the reported loss in sensitivity to chloride in PolyHbBv could not be attributed to direct alteration of chloride ion binding amino acids. Structural modification imparted by glutaraldehyde resulted in nearly identical functional characteristics of PolyHbBv and its fractions with regard to oxygen equilibrium, ligand binding, and autoxidative kinetics. C1 US FDA, Lab Biochem & Vasc Biol, Div Hematol, Bethesda, MD 20892 USA. US FDA, Biophys Lab, Div Bacterial Parasit & Allergen Prod, CBER, Bethesda, MD 20892 USA. RP Alayash, AI (reprint author), US FDA, Lab Biochem & Vasc Biol, Div Hematol, Bethesda, MD 20892 USA. EM alayash@cber.fda.gov NR 35 TC 46 Z9 46 U1 3 U2 17 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 JUN 1 PY 2005 VL 77 IS 11 BP 3466 EP 3478 DI 10.1021/ac050064y PG 13 WC Chemistry, Analytical SC Chemistry GA 932OA UT WOS:000229561800016 PM 15924377 ER PT J AU Wu, CF Herman, BA Retta, SM Grossman, LW Liu, JS Hwang, NHC AF Wu, CF Herman, BA Retta, SM Grossman, LW Liu, JS Hwang, NHC TI On the closing sounds of a mechanical heart valve SO ANNALS OF BIOMEDICAL ENGINEERING LA English DT Article DE mechanical heart valves; cavitation detection; cavitation noise; impact sound ID IMPACT NOISE; CAVITATION; PREDICTION AB In the 1994 Replacement Heart Valve Guidance of the U.S. Food and Drug Administration (FDA), in-vitro testing is required to evaluate the potential for cavitation damage of a mechanical heart valve (MHV). To fulfill this requirement, the stroboscopic high-speed imaging method is commonly used to visualize cavitation bubbles at the instant of valve closure. The procedure is expensive; it is also limited because not every cavitation event is detected, thus leaving the possibility of missing the whole cavitation process. As an alternative, some researchers have suggested an acoustic cavitation-detection method, based on the observation that cavitation noise has a broadband spectrum. In practice, however, it is difficult to differentiate between cavitation noise and the valve closing sound, which may also contain high-frequency components. In the present study, the frequency characteristics of the closing sound in air of a Bjork-Shiley Convexo-Concave (BSCC) valve are investigated. The occluder closing speed is used as a control parameter, which is measured via a laser sweeping technique. It is found that for the BSCC valve tested, the distribution of the sound energy over its frequency domain changes at different valve closing speeds, but the cut-off frequency remains unchanged at 123.32 +/- 6.12 kHz. The resonant frequencies of the occluder are also identified from the valve closing sound. C1 Florida Atlantic Univ, Coll Engn, Ctr Appl Stochast Res, Boca Raton, FL 33431 USA. US FDA, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Rockville, MD 20852 USA. Natl Hlth Res Inst, Div Med Engn Res, Miaoli, Taiwan. RP Wu, CF (reprint author), Florida Atlantic Univ, Coll Engn, Ctr Appl Stochast Res, 777 Glades Rd, Boca Raton, FL 33431 USA. EM cwu2@fau.edu NR 30 TC 8 Z9 8 U1 0 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0090-6964 EI 1573-9686 J9 ANN BIOMED ENG JI Ann. Biomed. Eng. PD JUN PY 2005 VL 33 IS 6 BP 743 EP 750 DI 10.1007/s10439-005-3237-1 PG 8 WC Engineering, Biomedical SC Engineering GA 939LU UT WOS:000230075100003 PM 16078614 ER PT J AU Siegel, JN Zhen, BG AF Siegel, JN Zhen, BG TI Use of the American College of Rheumatology N(ACR-N) Index of improvement in rheumatoid arthritis - Argument in favor SO ARTHRITIS AND RHEUMATISM LA English DT Article C1 US FDA, CDER, ODE VI, DTBIMP, Rockville, MD 20857 USA. RP Siegel, JN (reprint author), US FDA, CDER, ODE VI, DTBIMP, HFD-108,5600 Fishers Lane, Rockville, MD 20857 USA. EM siegelj@cber.fda.gov NR 9 TC 30 Z9 32 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD JUN PY 2005 VL 52 IS 6 BP 1637 EP 1641 DI 10.1002/art.21243 PG 5 WC Rheumatology SC Rheumatology GA 934PW UT WOS:000229721700005 PM 15934067 ER PT J AU Coecke, S Balls, M Bowe, G Davis, J Gstraunthaler, G Hartung, T Hay, R Merten, OW Price, A Schechtman, L Stacey, G Stokes, W AF Coecke, S Balls, M Bowe, G Davis, J Gstraunthaler, G Hartung, T Hay, R Merten, OW Price, A Schechtman, L Stacey, G Stokes, W TI Guidance on Good Cell Culture Practice - A report of the second ECVAM task force on Good Cell Culture Practice SO ATLA-ALTERNATIVES TO LABORATORY ANIMALS LA English DT Article ID FETAL BOVINE SERUM; MONOCLONAL-ANTIBODY PRODUCTION; CROSS-CONTAMINATION; TISSUE-CULTURE; ORGAN-CULTURE; LINES; RECOMMENDATIONS; ALTERNATIVES; TERMINOLOGY; MYCOPLASMA AB The maintenance of high standards is fundamental to all good scientific practice, and is essential for maximising the reproducibility, reliability, credibility, acceptance and proper application of any results produced. The aim of this Guidance on Good Cell Culture Practice (GCCP) is to promote the maintenance of these standards and to reduce uncertainty in the development and application of animal and human cell and tissue culture procedures and products, by encouraging greater international harmonisation, rationalisation and standardisation of laboratory practices, quality control systems, safety procedures, recording and reporting, and compliance with laws, regulations and ethical principles. The scope of the document has deliberately been broadly defined, to include systems based on cells and tissues obtained from humans and animals, and issues related to the characterisation and maintenance of essential characteristics, as well as quality assurance, recording and reporting, safety, education and training, and ethics. C1 Commiss European Communities, Joint Res Ctr, ECVAM, Inst Hlth & Consumer Protect, I-21020 Ispra, VA, Italy. Bio Prod Lab, Dept Res & Dev, Elstree, Herts, England. FRAME, Nottingham, England. ATCC, Manassas, VA USA. Innsbruck Med Univ, Dept Physiol, A-6010 Innsbruck, Austria. Genethon, Evry, France. US FDA, Natl Ctr Toxicol Res, Rockville, MD 20857 USA. Natl Inst Biol Stand & Controls, Div Cell Biol, Potters Bar EN6 3QG, Herts, England. Natl Inst Biol Stand & Controls, UK Stem Cell Bank, Potters Bar EN6 3QG, Herts, England. Natl Inst Environm Hlth Sci, Evaluat Alternat Toxicol Methods Environm Toxicol, Natl Toxicol Program Interagcy Ctr, Res Triangle Pk, NC USA. RP Coecke, S (reprint author), Commiss European Communities, Joint Res Ctr, ECVAM, Inst Hlth & Consumer Protect, Via Fermi 1, I-21020 Ispra, VA, Italy. EM sandra.coecke@jrc.it NR 94 TC 123 Z9 126 U1 6 U2 21 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 JUN PY 2005 VL 33 IS 3 BP 261 EP 287 PG 27 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 940XZ UT WOS:000230180500011 PM 16180980 ER PT J AU Soukup, M Cho, HJ Lee, JK AF Soukup, M Cho, HJ Lee, JK TI Robust classification modeling on microarray data using misclassification penalized posterior SO BIOINFORMATICS LA English DT Article; Proceedings Paper CT 13th International Conference on Intelligent Systems for Molecular Biology CY JUN 25-29, 2005 CL Detroit, MI SP Int Soc Computat Biol ID GENE-EXPRESSION DATA; CANCER; SELECTION; TUMOR AB Motivation: Genome-wide microarray data are often used in challenging classification problems of clinically relevant subtypes of human diseases. However, the identification of a parsimonious robust prediction model that performs consistently well on future independent data has not been successful due to the biased model selection from an extremely large number of candidate models during the classification model search and construction. Furthermore, common criteria of prediction model performance, such as classification error rates, do not provide a sensitive measure for evaluating performance of such astronomic competing models. Also, even though several different classification approaches have been utilized to tackle such classification problems, no direct comparison on these methods have been made. Results: We introduce a novel measure for assessing the performance of a prediction model, the misclassification-penalized posterior (MiPP), the sum of the posterior classification probabilities penalized by the number of incorrectly classified samples. Using MiPP, we implement a forward step-wise cross-validated procedure to find our optimal prediction models with different numbers of features on a training set. Our final robust classification model and its dimension are determined based on a completely independent test dataset. This MiPP-based classification modeling approach enables us to identify the most parsimonious robust prediction models only with two or three features on well-known microarray datasets. These models show superior performance to other models in the literature that often have more than 40-100 features in their model construction. C1 Univ Virginia, Div Biostat & Epidemiol, Charlottesville, VA 22908 USA. US FDA, Div Biometr 3, Rockville, MD 20850 USA. RP Lee, JK (reprint author), Univ Virginia, Div Biostat & Epidemiol, POB 800717, Charlottesville, VA 22908 USA. EM jaeklee@virginia.edu NR 18 TC 9 Z9 9 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD JUN PY 2005 VL 21 SU 1 BP I423 EP I430 DI 10.1093/bioinformatics/bti1020 PG 8 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 942HH UT WOS:000230273000048 PM 15961487 ER PT J AU Hussain, LA Dickens, SH Bowen, RL AF Hussain, LA Dickens, SH Bowen, RL TI Shear bond strength of experimental methacrylated betacyclodextrin-based formulations SO BIOMATERIALS LA English DT Article DE adhesion; bond strength; collagen; dental adhesive; dentine bonding agent; surface treatment; cyclodextrin methacrylates; polymerization initiators ID HARD TOOTH TISSUES; SURFACE-ACTIVE COMONOMER; DENTIN; THICKNESS; COLLAGEN; RESIN AB Previous studies have shown that methacrylated beta-cyclodextrins (MCDs) can be used as comonomers in resin-based dental composites. These MCDs by virtue of having several polymerizable methacrylate groups and hydrophilic hydroxyl groups, may also promote bonding of dental composites to dentin. This study evaluated MCDs as adhesive comonomers, and optimized comonomer and polymerization initiator concentrations for maximum shear bond strength (SBS). Experimental MCD-based bonding formulations in acetone were prepared by mixing 33 mass fraction % MCDs with (10, 20, 30, 40, or 50) mass fraction % of 2-hydroxyethyl methacrylate (HEMA). The MCD/HEMA-based solutions were activated with varied amounts of camphorquinone (CQ) and ethyl 4-dimethylamino benzoate (4E). Samples for SBS were prepared by bonding a composite resin to acid-etched dentin surfaces of extracted human molars with the experimental bonding solutions. The specimens were immersed in 37 degreesC water for 24 h and bond strengths were determined in shear mode. With increasing HEMA concentration, the SBS values of MCD-bonding solutions increased to 16 MPa at a composition of 33 % MCD, 30% HEMA, and 37% acetone by mass. Also, SBS values of MCD-bonding solutions varied as a function of the CQ and 4E concentrations and passed through a maximum SBS at 21 MPa, which was comparable to that of a commercial control. This preliminary study indicated that nonacidic MCD monomers could be used as an adhesion-promoting comonomer. Additional modification of MCDs having both polymerizable groups and anionic ligand groups, e.g., polymerizable acidic cyclodextrin derivatives should increase the SBS even further, (C) 2004 Elsevier Ltd. All rights reserved. C1 NIST, Amer Dent Assoc Fdn, Paffenbarger Res Ctr, Gaithersburg, MD 20899 USA. RP Hussain, LA (reprint author), US FDA, 7500 Standish Pl,RME 120,Metro Pk N 2,HFD-643, Rockville, MD 20855 USA. EM latiffaitaf@.yahoo.com FU NIDCR NIH HHS [R01-DE05129] NR 26 TC 13 Z9 13 U1 2 U2 6 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0142-9612 J9 BIOMATERIALS JI Biomaterials PD JUN PY 2005 VL 26 IS 18 BP 3973 EP 3979 DI 10.1016/j.biomaterials.2004.10.001 PG 7 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 899KR UT WOS:000227143800021 PM 15626444 ER PT J AU Szarfman, A Tonning, JM Levine, JG Doraiswamy, PM AF Szarfman, A Tonning, JM Levine, JG Doraiswamy, PM TI Risperidone and pituitary tumors: a pharmacovigilance study SO BIPOLAR DISORDERS LA English DT Meeting Abstract CT 6th International Conference on Bipolar Disorder CY JUN 16-18, 2005 CL Pittsburgh, PA DE atypical antipsychotics; adverse events; hyperprolactinemia C1 US FDA, Off Pharmacoepidemiol & Stat Sci, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. US FDA, Immediate Off, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. Duke Univ, Med Ctr, Dept Psychiat, Durham, NC 27706 USA. Duke Univ, Med Ctr, Dept Med, Durham, NC 27706 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD JUN PY 2005 VL 7 SU 2 BP 116 EP 117 PG 2 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 929TO UT WOS:000229369500310 ER PT J AU Harrouk, WA Wheeler, KE Kimmel, GL Hogan, KA Kimmel, CA AF Harrouk, WA Wheeler, KE Kimmel, GL Hogan, KA Kimmel, CA TI Effects of hyperthermia development and boric acid on skeletal in rat embryos SO BIRTH DEFECTS RESEARCH PART B-DEVELOPMENTAL AND REPRODUCTIVE TOXICOLOGY LA English DT Article DE hyperthermia; boric acid; skeleton; segmentation defects; combination exposure; rat; development ID GENE-EXPRESSION DOMAINS; CERVICAL-VERTEBRAE; HEAT EXPOSURE; IN-VITRO; MICE; TRANSFORMATIONS; TERATOGENICITY; TOXICITY; DEFECTS; SHIFTS AB BACKGROUND: The individual effects of boric acid (BA) and hyperthermia on the development of the axial skeleton have been reported previously. Both cause an increased incidence of axial skeletal defects including a decrease in the total number of ribs and vertebrae. Because of the similarity in the effects of the two agents, we examined their interaction when given in combination to pregnant rats on gestational day (GD) 10. METHODS: Dams were treated on GD 10 with BA (0, 250, or 500 mg/kg) and hyperthermia (37, 41, or 42 degrees C) and allowed to deliver their pups. Doses of BA were based on results from a close-finding study. Litters were evaluated on postnatal days (PND) 1 and 3 for number, gender, and weight of pups. On PND3, pups were examined externally and viscerally, and double-stained for skeletal evaluation. RESULTS: A dose-dependent, statistically significant increase in fetal skeletal defects was seen on PND 3 with BA or hyperthermia alone with even greater effects when given in combination. Defects included rib and vertebral fusions, split vertebral centra in the thoracic and lumbar areas, and a decrease in the total number of ribs and vertebrae. CONCLUSIONS: The increased incidence of skeletal defects resulting from combined exposure to hyperthermia and BA was additive for segmentation defects and synergistic for the reduction in numbers of vertebrae. Published 2005 Wiley-Liss, Inc. C1 US FDA, Div Reprod & Urol Drug Prod, CDER, Rockville, MD 20857 USA. Oak Ridge Inst Sci & Engn, Oak Ridge, TN USA. US EPA, Natl Ctr Environm Assessment, Off Res & Dev, Washington, DC 20460 USA. RP Harrouk, WA (reprint author), US FDA, Div Reprod & Urol Drug Prod, CDER, 5600 Fishers Lane,17B-45,Mail Stop HFD-580, Rockville, MD 20857 USA. EM harroukw@cder.fda.gov NR 17 TC 9 Z9 9 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1542-9733 J9 BIRTH DEFECTS RES B JI Birth Defects Res. Part B-Dev. Reprod. Toxicol. PD JUN PY 2005 VL 74 IS 3 BP 268 EP 276 DI 10.1002/bdrb.20047 PG 9 WC Oncology; Genetics & Heredity; Toxicology SC Oncology; Genetics & Heredity; Toxicology GA 942BF UT WOS:000230257200007 PM 15954087 ER PT J AU Nowell, SA Ahn, JY Rae, JM Scheys, JO Trovato, A Sweeney, C MacLeod, SL Kadlubar, FF Ambrosone, CB AF Nowell, SA Ahn, JY Rae, JM Scheys, JO Trovato, A Sweeney, C MacLeod, SL Kadlubar, FF Ambrosone, CB TI Association of genetic variation in tamoxifen-metabolizing enzymes with overall survival and recurrence of disease in breast cancer patients SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE breast cancer; CYP2D6; genetic variation; SULT1A1; tamoxifen; UGT2B15 ID POSTMENOPAUSAL WOMEN; ISOMERS; 4-HYDROXY-N-DESMETHYLTAMOXIFEN; TRANS-4-HYDROXYTAMOXIFEN; GLUCURONIDATION; ISOMERIZATION; EXPRESSION; PHENOTYPE; GENOTYPE; ALLELES AB Tamoxifen has been a mainstay of adjuvant therapy for breast cancer for many years. We sought to determine if genetic variability in the tamoxifen metabolic pathway influenced overall survival in breast cancer patients treated with tamoxifen. We examined functional polymorphisms in CYP2D6, the P450 catalyzing the formation of active tamoxifen metabolites, and UGT2B15, a Phase II enzyme facilitating the elimination of active metabolite in a retrospective study of breast cancer patients. We also examined whether the combination of variant alleles in SULT1A1 and UGT2B15 had more of an impact on overall survival in tamoxifen-treated patients than when the genes were examined separately. We conducted a retrospective study using archived paraffin blocks for DNA extraction and data from pathology reports and hospital tumor registry data for information on clinical characteristics, treatment, and outcomes (162 patients receiving tamoxifen and 175 who did not). Genotypes for CYP2D6 and UGT2B15 were obtained and Cox proportional hazards modeling was performed. After adjusting for age, race, stage of disease at diagnosis, and hormone receptor status, we found no significant association between CYP2D6 genotype and overall survival in either group of breast cancer patients. Tamoxifen-treated patients with UGT2B15 high activity genotypes had increased risk of recurrence and poorer survival. When UGT2B15 and SULT1A1 'at-risk' alleles were combined, women with two variant alleles had significantly greater risk of recurrence and poorer survival than those with common alleles. These studies indicate that genetic variation in Phase II conjugating enzymes can influence the efficacy of tamoxifen therapy for breast cancer. C1 Roswell Pk Canc Inst, Dept Epidemiol, Buffalo, NY 14263 USA. Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI 48109 USA. Merck & Co Inc, Rahway, NJ 07065 USA. Univ Utah, Dept Family & Prevent Med, Salt Lake City, UT USA. Univ Arkansas Med Sci, Little Rock, AR 72205 USA. Natl Ctr Toxicol Res, Div Mol Epidemiol, Jefferson, AR 72079 USA. RP Nowell, SA (reprint author), Roswell Pk Canc Inst, Dept Epidemiol, BSB Room S701,Elm & Carlton St, Buffalo, NY 14263 USA. EM Susan.Nowell@RoswellPark.org OI Sweeney, Carol/0000-0003-1113-7160 FU NIGMS NIH HHS [GM61373] NR 35 TC 189 Z9 194 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD JUN PY 2005 VL 91 IS 3 BP 249 EP 258 DI 10.1007/s10549-004-7751-x PG 10 WC Oncology SC Oncology GA 934WP UT WOS:000229740300005 PM 15952058 ER PT J AU Stevens, EV Raffeld, M Espina, V Kristensen, GB Trope, CG Kohn, EC Davidson, B AF Stevens, EV Raffeld, M Espina, V Kristensen, GB Trope, CG Kohn, EC Davidson, B TI Expression of xeroderma pigmentosum A protein predicts improved outcome in metastatic ovarian carcinoma SO CANCER LA English DT Article DE xeroderma pigmentosum A; nucleotide excision repair; ovarian carcinoma; immunocytochemistry ID NUCLEOTIDE EXCISION-REPAIR; MESSENGER-RNA LEVELS; INDUCED DNA-DAMAGE; GERM-CELL TUMORS; CANCER PATIENTS; CISPLATIN SENSITIVITY; EFFUSION CYTOLOGY; CHEMOTHERAPY; ERCC1; XPA AB BACKGROUND. The nucleotide excision repair (NER) proteins repair DNA adducts due to xenobiotics and cancer chemotherapy. The authors hypothesized that expression of the NER protein xeroderma pigmentosum A (XPA) would be reduced in a clinically significant fashion in metastatic ovarian carcinoma. METHODS. Malignant effusion specimens were studied so that there was a uniform metastatic ovarian carcinoma population for study. XPA protein expression was analyzed by immunocytochemistry in 142 effusion specimens (109 peritoneal specimens, 33 pleural specimens) from 125 patients. Specimens were obtained at diagnosis (n = 76), and at disease recurrence (n = 66). Patients in the latter group received platinum-based chemotherapy. RESULTS. XPA was expressed in cancer cells in 136 of the 142 (96%) effusion specimens. Strongest expression occurred in leukocytes and reactive mesothelial cells. XPA expression did not correlate with treatment status, effusion site, International Federation of Gynecology and Obstetrics stage, histologic grade, or the extent of residual disease. More effusion tumor cells from patients with a complete response to chemotherapy expressed XPA compared with those with a partial or no response (P = 0.03, chi(2) test). Patients with recurrent disease with XPA expressed > 25% of tumor cells had better progression-free survival (PFS) by univariate analysis (median = 0 vs. 11 months, P < 0.001; 95% confidence interval [CI], 1-5, 8-14) and overall survival (OS; median = 24 vs. 34 months, P = 0.04; 95% CI, 17-31, 24-44). XPA was the only predictor of PFS outcome by multivariate analysis (P = 0.03). CONCLUSIONS. The results of the current study showed that XPA was widely expressed in metastatic ovarian carcinoma effusion specimens and in the cells of the effusion microenvironment. Paradoxically, XPA expression was associated with better response to chemotherapy and predicted better PFS and OS. C1 Univ Oslo, Dept Pathol, Norwegian Radium Hosp, N-0310 Oslo, Norway. NCI, Ctr Canc Res, Pathol Lab, Bethesda, MD USA. NCI, Food & Drug Adm Clin Proteom Program, Ctr Canc Res, Bethesda, MD 20892 USA. Univ Oslo, Dept Gynecol Oncol, Norwegian Radium Hosp, Oslo, Norway. RP Davidson, B (reprint author), Univ Oslo, Dept Pathol, Norwegian Radium Hosp, N-0310 Oslo, Norway. EM bend@ulrik.uio.no OI Espina, Virginia/0000-0001-5080-5972 NR 31 TC 20 Z9 21 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD JUN 1 PY 2005 VL 103 IS 11 BP 2313 EP 2319 DI 10.1002/cncr.21031 PG 7 WC Oncology SC Oncology GA 928OS UT WOS:000229282000014 PM 15844177 ER PT J AU Tsuda, H Fukamachi, K Ohshima, Y Ueda, S Matsuoka, Y Hamaguchi, T Ohnishi, T Takasuka, N Naito, A AF Tsuda, H Fukamachi, K Ohshima, Y Ueda, S Matsuoka, Y Hamaguchi, T Ohnishi, T Takasuka, N Naito, A TI High susceptibility of human c-Ha-ras protooncogene transgenic rats to carcinogenesis: A cancer-prone animal model SO CANCER SCIENCE LA English DT Review ID INDUCED MAMMARY CARCINOGENESIS; RICH REPEAT PROTEIN-3; T-ANTIGEN EXPRESSION; N-NITROSOMETHYLBENZYLAMINE; CELL-PROLIFERATION; TRANSITION MUTATIONS; TUMOR DEVELOPMENT; PROMOTER CONTROL; SPRAGUE-DAWLEY; BREAST-CANCER AB Transgenic animals carrying human c-Ha-ras proto-oncogene, v-Ha-ras transgenic mice, pim-1 transgenic mice and several knockout mice deficient of tumor suppressor genes, such as p53, have been shown to exhibit increased carcinogen susceptibility. As a result, studies into practical application and medium-term screening of environmental carcinogens are under way. Given the advantages of rat models characterized by larger organ size, abundant information regarding preneoplasias and virus-free constitution, we have concentrated on the generation of transgenic rats bearing copies of the human c-Ha-ras proto-oncogene and shown the Hras128 strain to be extremely sensitive to the induction of mammary carcinomas, and to a lesser extent, lesions in the urinary bladder, esophagus and skin. In most, if not all, the mammary cancers mutations of the transgene but not the endogenous H-ras gene are present, appearing to occur early in the process of tumorigenesis, which involves proliferation of cells in TEB and intraductal hyperplasia before carcinomas arise. Preliminary findings suggest that this is independent of enclogenous ovarian hormones, although inhibited by soy isoflavones and promoted by atrazine and nonylphenols. Although further studies of the mechanisms are clearly necessary, the model appears to have great potential for screening purposes, not only for modifiers active in the breast, but also other organs where tumors characterized by ras gene mutations develop. C1 Nagoya City Univ, Grad Sch Med Sci, Dept Mol Toxicol, Mizuho Ku, Nagoya, Aichi 4678601, Japan. Kansai Med Univ, Dept Pathol 2, Moriguchi, Osaka 5708506, Japan. Mie Univ, Sch Med, Dept Surg 2, Tsu, Mie 5140001, Japan. Univ Tokushima, Grad Sch, Dept Mol & Environm Pathol, Tokushima 7708503, Japan. Natl Canc Ctr, Res Inst, Canc Prevent Basic Res Project, Tokyo 1040045, Japan. Natl Ctr Toxicol Res, Div Hepatotoxic, Jefferson, AR 72079 USA. RP Tsuda, H (reprint author), Nagoya City Univ, Grad Sch Med Sci, Dept Mol Toxicol, Mizuho Ku, 1 Kawasumi, Nagoya, Aichi 4678601, Japan. EM htsuda@med.nagoya-cu.ac.jp NR 63 TC 21 Z9 22 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1347-9032 J9 CANCER SCI JI Cancer Sci. PD JUN PY 2005 VL 96 IS 6 BP 309 EP 316 DI 10.1111/j.1349-7006.2005.00056.x PG 8 WC Oncology SC Oncology GA 945UW UT WOS:000230528700001 PM 15958052 ER PT J AU Powers, JH Lin, D Ross, D AF Powers, JH Lin, D Ross, D TI FDA evaluation of antimicrobials - Subgroup analysis SO CHEST LA English DT Letter ID NOSOCOMIAL PNEUMONIA; DOUBLE-BLIND; VANCOMYCIN; MULTICENTER C1 US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Powers, JH (reprint author), HFD 104,9201 Corp Blvd, Rockville, MD 20850 USA. EM powersjoh@cder.fda.gov NR 11 TC 18 Z9 18 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD JUN PY 2005 VL 127 IS 6 BP 2298 EP 2299 DI 10.1378/chest.127.6.2298 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 935GI UT WOS:000229767300087 PM 15947370 ER PT J AU Machuca, A Wood, O Lee, S Daniel, S Rios, M Wolfe, ND Carr, JK Eitel, MN Tamoufe, U Torimiro, JN Burke, D Hewlett, IK AF Machuca, A Wood, O Lee, S Daniel, S Rios, M Wolfe, ND Carr, JK Eitel, MN Tamoufe, U Torimiro, JN Burke, D Hewlett, IK TI Seroprevalence of human T cell leukemia virus in HIV antibody negative populations in rural Cameroon SO CLINICAL INFECTIOUS DISEASES LA English DT Editorial Material ID INFECTIONS AB Seven hundred forty-seven serum samples collected from humans in 4 separate rural village areas in Cameroon were examined for antibody to human T cell leukemia viruses (HTLVs) by use of an enzyme immunoassay followed by a Western blot assay. Of the 88 serum samples that the enzyme immunoassay found to be repeatedly reactive, the HTLV status of 49 samples was confirmed by Western blot assay to be HTLV type I, and the status of 6 samples was confirmed to be HTLV type II. C1 US FDA, Mol Virol Lab, OBRR,Div Emerging & Transfus Transmitted Dis, CBER, Rockville, MD 20852 USA. Quim Farmaceut Bayer, Div Diagnost, Madrid, Spain. Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. Johns Hopkins Bloomberg Sch Publ Hlth, Dept Int Hlth, Baltimore, MD USA. Army Hlth Res Ctr, Yaounde, Cameroon. RP Hewlett, IK (reprint author), US FDA, Mol Virol Lab, OBRR,Div Emerging & Transfus Transmitted Dis, CBER, 1401 Rockville Pike HFM-315, Rockville, MD 20852 USA. EM Hewlett@cber.fda.gov OI /0000-0002-5704-8094 NR 7 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JUN 1 PY 2005 VL 40 IS 11 BP 1673 EP 1676 DI 10.1086/429910 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 923AD UT WOS:000228880100016 PM 15889367 ER PT J AU Anand, KJS Aranda, JV Berde, CB Buckman, S Capparelli, EV Carlo, WA Hummel, P Lantos, P Johnston, CC Lehr, VT Lynn, AM Maxwell, LG Oberlander, TF Raju, TNK Soriano, SG Taddio, A Walco, GA AF Anand, KJS Aranda, JV Berde, CB Buckman, S Capparelli, EV Carlo, WA Hummel, P Lantos, P Johnston, CC Lehr, VT Lynn, AM Maxwell, LG Oberlander, TF Raju, TNK Soriano, SG Taddio, A Walco, GA TI Analgesia and anesthesia for neonates: Study design and ethical issues SO CLINICAL THERAPEUTICS LA English DT Article; Proceedings Paper CT Newborns Drug Development Initiative Workshop CY SEP 19-MAR 30, 2003-2004 CL Rockville, MD SP NICHD, FDA DE analgesia; anesthesia; pain; stress; neonate; infant ID BIRTH-WEIGHT INFANTS; INTENSIVE-CARE-UNIT; EXTRACORPOREAL MEMBRANE-OXYGENATION; INDIVIDUALIZED DEVELOPMENTAL CARE; RANDOMIZED CONTROLLED-TRIAL; WEEKS POSTCONCEPTIONAL AGE; PLACEBO-CONTROLLED TRIALS; PATENT DUCTUS-ARTERIOSUS; PAIN REGULATORY SYSTEMS; FORMER PRETERM INFANTS AB Objective: The purpose of this article is to summarize the clinical, methodologic, and ethical considerations for researchers interested in designing future trials in neonatal analgesia and anesthesia, hopefully stimulating additional research in this field. Methods: The MEDLINE, PubMed, EMBASE, and Cochrane register databases were searched using subject headings related to infant, newborn, neonate, analgesia, anesthesia, ethics, and study design. Cross-references and personal files were searched manually. Studies reporting original data or review articles related to these topics were assessed and critically evaluated by experts for each topical area. Data on population demographics, study characteristics, and cognitive and behavioral outcomes were abstracted and synthesized in a systematic manner and refined by group members. Data synthesis and results were reviewed by a panel of independent experts and presented to a wider audience including clinicians, scientists, regulatory personnel, and industry representatives at the Newborn Drug Development Initiative workshop. Recommendations were revised after extensive discussions at the workshop and between committee members. Results: Designing clinical trials to investigate novel or currently available approaches for analgesia and anesthesia in neonates requires consideration of salient study designs and ethical issues. Conditions requiring treatment include pain/stress resulting from invasive procedures, surgical operations, inflammatory conditions, and routine neonatal intensive care. Study design considerations must define the inclusion and exclusion criteria, a rationale for stratification, the confounding effects of comorbid conditions, and other clinical factors. Significant ethical issues include the constraints of studying neonates, obtaining informed consent, making risk-benefit assessments, defining compensation or rewards for participation, safety considerations, the use of placebo controls, and the variability among institutional review boards in interpreting federal guidelines on human research. For optimal study design, investigators must formulate well-defined study questions, choose appropriate trial designs, estimate drug efficacy, calculate sample size, determine the duration of the studies, identify pharmacokinetic and pharmacodynamic parameters, and avoid drug-drug interactions. Specific outcome measures may include scoring on pain assessment scales, various biomarkers and their patterns of response, process outcomes (eg, length of stay, time to extubation), intermediate or long-term outcomes, and safety parameters. Conclusions: Much more research is needed in this field to formulate a scientifically sound, evidence-based, and clinically useful framework for management of anesthesia and analgesia in neonates. Newer study designs and additional ethical dilemmas may be defined with accumulating data in this field. Copyright (c) 2005 Excerpta Medica, Inc. C1 Univ Arkansas Med Sci, Coll Med, Dept Pediat, Little Rock, AR 72205 USA. Univ Arkansas Med Sci, Coll Med, Dept Anesthesiol, Little Rock, AR 72205 USA. Univ Arkansas Med Sci, Coll Med, Dept Neurobiol, Little Rock, AR 72205 USA. Univ Arkansas Med Sci, Coll Med, Dept Pharmacol, Little Rock, AR 72205 USA. Childrens Hosp Michigan, Dept Pediat, Detroit, MI 48201 USA. Childrens Hosp Michigan, Dept Pharmacol, Detroit, MI 48201 USA. Childrens Hosp Michigan, Pharmaceut Sci Network, Detroit, MI 48201 USA. Harvard Univ, Sch Med, Div Pain Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Anesthesia, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. US FDA, Ctr Drug Evaluat & Res, Off Counter Terrorism & Pediat Drug Dev, Rockville, MD 20857 USA. Univ Calif San Diego, Pediat Pharmacol Res Unit, San Diego, CA 92103 USA. Univ Alabama Birmingham, Div Neonatol, Birmingham, AL USA. Loyola Univ, Med Ctr, Dev Follow Up Program, Maywood, IL 60153 USA. Univ Chicago, Dept Pediat, Chicago, IL 60637 USA. Univ Chicago, Dept Med, Chicago, IL 60637 USA. McGill Univ, Sch Nursing, Montreal, PQ, Canada. Wayne State Univ, Eugene Applebaum Sch Pharm & Hlth Sci, Dept Pharm Practice, Detroit, MI USA. Univ Washington, Sch Med, Childrens Hosp & Reg Med Ctr, Dept Anesthesiol, Seattle, WA 98195 USA. Univ Washington, Sch Med, Childrens Hosp & Reg Med Ctr, Dept Pediat, Seattle, WA 98195 USA. Childrens Hosp Philadelphia, Dept Anesthesiol, Philadelphia, PA 19104 USA. British Columbia Childrens Hosp, Div Dev Pediat, Vancouver, BC V6H 3V4, Canada. NICHHD, Pregnancy & Perinatol Branch, Ctr Dev Biol & Perinatal Med, Rockville, MD USA. Childrens Hosp, Dept Anesthesia, Boston, MA 02115 USA. Hosp Sick Children, Populat Hlth Sci Res Inst, Toronto, ON M5G 1X8, Canada. Hosp Sick Children, Dept Pharm, Toronto, ON M5G 1X8, Canada. Hackensack Univ, Med Ctr, Dept Pediat, Hackensack, NJ USA. RP Anand, KJS (reprint author), Arkansas Childrens Hosp, 800 Marshall St, Little Rock, AR 72202 USA. EM anandsunny@uams.edu OI Anand, Kanwaljeet/0000-0001-6498-1483; Maxwell, Lynne/0000-0002-4406-9232 NR 242 TC 31 Z9 33 U1 0 U2 2 PU ELSEVIER PI BRIDGEWATER PA 685 ROUTE 202-206, BRIDGEWATER, NJ 08807 USA SN 0149-2918 EI 1879-114X J9 CLIN THER JI Clin. Ther. PD JUN PY 2005 VL 27 IS 6 BP 814 EP 843 DI 10.1016/j.clinthera.2005.06.021 PG 30 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 945VS UT WOS:000230531000015 PM 16117988 ER PT J AU Choi, Y Ahn, H Chen, JJ AF Choi, Y Ahn, H Chen, JJ TI Regression trees for analysis of count data with extra Poisson variation SO COMPUTATIONAL STATISTICS & DATA ANALYSIS LA English DT Article DE carcinogenicity; generalized linear model; quasi-likelihood; recursive partitioning ID GENERALIZED LINEAR-MODELS; MORTALITY-RATES; CANCER AB This article proposes methods for fitting piecewise loglinear models to count data with an extra-Poisson variation. Both SUPPORT (Statistica Sinica, 4 (1994) 143) and GUIDE (Statistica Sinica, 12 (2002) 361) are used for splitting methods. We developed a new bootstrap resampling method performed at each node of the tree to determine the proper size of a tree. The quasi-likelihood approach is used for fitting an extra-Poisson model at each stratum to take into account the extra variability. An adjusted Anscombe residual for the extra-Poisson model is used in this procedure. Performance of the proposed method is evaluated by a Monte Carlo simulation study. The proposed method is used to investigate geographic variability in mortality rates on lung cancer as well as effects of various demographic variability. (c) 2004 Elsevier B.V. All rights reserved. C1 SUNY Stony Brook, Dept Appl Math & Stat, Stony Brook, NY 11794 USA. Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. Seoul Natl Univ, Dept Prevent Med, Sch Med, Chongro, South Korea. RP Ahn, H (reprint author), SUNY Stony Brook, Dept Appl Math & Stat, Math Tower, Stony Brook, NY 11794 USA. EM hahn@ams.stonybrook.edu NR 27 TC 9 Z9 9 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-9473 J9 COMPUT STAT DATA AN JI Comput. Stat. Data Anal. PD JUN 1 PY 2005 VL 49 IS 3 BP 893 EP 915 DI 10.1016/j.csda.2004.06.011 PG 23 WC Computer Science, Interdisciplinary Applications; Statistics & Probability SC Computer Science; Mathematics GA 934SO UT WOS:000229728900017 ER PT J AU Speer, R Wulfkuhle, JD Liotta, LA Petricoin, EF AF Speer, R Wulfkuhle, JD Liotta, LA Petricoin, EF TI Reverse-phase protein microarrays for tissue-based analysis SO CURRENT OPINION IN MOLECULAR THERAPEUTICS LA English DT Article DE microarrays; protein proteomics; reverse phase; tailored therapy ID PHOSPHORYLATED PROTEINS; CLINICAL PROTEOMICS; KINASE INHIBITORS; PROSTATE-CANCER; BREAST-CANCER; ZD1839 IRESSA; SPECIMENS; MICROENVIRONMENT; TRASTUZUMAB; DIAGNOSIS AB The deciphering of the human genome has elucidated our biological structural design and has generated insights into disease development and pathogenesis. At the same time, knowledge of genetic changes during disease processes has demonstrated the need to move beyond genomics towards proteomics and a systems biology approach to science. Analyzing the proteome comprises more than just a numeration of proteins. In fact, it characterizes proteins within cells in the context of their functional status and interactions in their physiological micro- and macro-environments. As dysregulated signaling often underpins most human diseases, an overarching goal of proteomics is to profile the working state of signaling pathways, to develop 'circuit maps' of normal and diseased protein networks and identify hyperactive, defective or inoperable transduction pathways. Reverse-phase protein microarrays represent a new technology that can generate a multiplex readout of dozens of phosphorylated events simultaneously to profile the state of a signaling pathway target even after the cell is lyzed and the contents denatured. C1 NCI, Ctr Canc Res, FDA NCI Clin Proteom Program, Lab Pathol,NIH, Bethesda, MD 20892 USA. George Mason Univ, Ctr Appl Proteom & Mol Med, Dept Mol & Microbiol, Manassas, VA 20110 USA. RP Petricoin, EF (reprint author), NCI, Ctr Canc Res, FDA NCI Clin Proteom Program, Lab Pathol,NIH, Bethesda, MD 20892 USA. EM epetrico@gmu.edu NR 40 TC 22 Z9 25 U1 2 U2 8 PU CURRENT DRUGS LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1P 6LB, ENGLAND SN 1464-8431 J9 CURR OPIN MOL THER JI Curr. Opin. Mol. Ther. PD JUN PY 2005 VL 7 IS 3 BP 240 EP 245 PG 6 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 933HF UT WOS:000229618800007 PM 15977421 ER PT J AU Cole, D Drum, DJV Stallknecht, DE White, DG Lee, MD Ayers, S Sobsey, M Maurer, JJ AF Cole, D Drum, DJV Stallknecht, DE White, DG Lee, MD Ayers, S Sobsey, M Maurer, JJ TI Free-living Canada Geese and antimicrobial resistance SO EMERGING INFECTIOUS DISEASES LA English DT Article ID UNITED-STATES; SALMONELLA; DISEASES; BIRDS AB We describe antimicrobial resistance among Escherichia coli isolated from free-living Canada Geese in Georgia and North Carolina (USA). Resistance patterns are compared to those reported by the National Antimicrobial Resistance Monitoring System. Canada Geese may be vectors of antimicrobial resistance and resistance genes in agricultural environments. C1 Georgia Div Publ Hlth, Notifiable Dis Sect, Dept Human Resources, Atlanta, GA 30303 USA. Univ Georgia, Athens, GA 30602 USA. US FDA, Laurel, MD USA. Univ N Carolina, Chapel Hill, NC USA. RP Cole, D (reprint author), Georgia Div Publ Hlth, Notifiable Dis Sect, Dept Human Resources, 2 Peachtree St NW,Rm 14-225, Atlanta, GA 30303 USA. EM dacole@dhr.state.ga.us FU NIEHS NIH HHS [ES07018] NR 15 TC 66 Z9 67 U1 0 U2 9 PU CENTER DISEASE CONTROL PI ATLANTA PA ATLANTA, GA 30333 USA SN 1080-6040 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD JUN PY 2005 VL 11 IS 6 BP 935 EP 938 PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 928YG UT WOS:000229307400022 PM 15963291 ER PT J AU Brouwers, FM Petricoin, EF Ksinantova, L Breza, J Rajapakse, V Ross, S Johann, D Mannelli, M Shulkin, BL Kvetnansky, R Eisenhofer, G Walther, MM Hitt, BA Conrads, TP Veenstra, TD Mannion, DP Wall, MR Wolfe, GM Fusaro, VA Liotta, LA Pacak, K AF Brouwers, FM Petricoin, EF Ksinantova, L Breza, J Rajapakse, V Ross, S Johann, D Mannelli, M Shulkin, BL Kvetnansky, R Eisenhofer, G Walther, MM Hitt, BA Conrads, TP Veenstra, TD Mannion, DP Wall, MR Wolfe, GM Fusaro, VA Liotta, LA Pacak, K TI Low molecular weight proteomic information distinguishes metastatic from benign pheochromocytoma SO ENDOCRINE-RELATED CANCER LA English DT Article ID PROSTATE-CANCER; CHROMOSOMES 1P; OVARIAN-CANCER; BREAST-CANCER; SERUM; IDENTIFICATION; PARAGANGLIOMAS; DIAGNOSIS; PROFILES; PATTERNS AB Metastatic lesions occur in up to 36% of patients with pheochromocytorna. Currently there is no way to reliably detect or predict which patients are at risk for metastatic pheochromocytorna. Thus, the discovery of biomarkers that could distinguish patients with benign disease from those with metastatic disease would be of great clinical value. Using surface-enhanced laser desorption ionization protein chips combined with high-resolution mass spectrometry, we tested the hypothesis that pheochromocytorna pathologic states can be reflected as biomarker information within the low molecular weight (LMW) region of the serum proteome. LMW protein profiles were generated from the serum of 67 pheochromocytorna patients from four institutions and analyzed by two different bioinformatics approaches employing pattern recognition algorithms to determine if the LMW component of the circulatory proteome contains potentially useful discriminatory information. Both approaches were able to identify combinations of LMW molecules which could distinguish all metastatic from all benign pheochromocytomas in a separate blinded validation set. In conclusion, for this study set low molecular mass biomarker information correlated with pheochromocytorna pathologic state using blinded validation. If confirmed in larger validation studies, efforts to identify the underlying diagnostic molecules by sequencing would be warranted. In the future, measurement of these biomarkers could be potentially used to improve the ability to identify patients with metastatic disease. C1 NICHHD, Reprod Biol & Med Branch, Bethesda, MD 20892 USA. NCI, FDA Clin Proteom Program, Offf Cell & Gene Therapies, Ctr Biol Evaluat & Res,Food & Drug Adm, Bethesda, MD USA. Slovak Acad Sci, Inst Expt Endocrinol, SK-83306 Bratislava, Slovakia. Komensky Fac Med, Dept Urol, Bratislava, Slovakia. NCI, FDA Clin Proteom Program, Pathol Lab, Ctr Canc Res, Bethesda, MD USA. Univ Florence, Dept Clin Physiopathol, Endocrine Unit, Florence, Italy. St Jude Childrens Res Hosp, Dept Radiol Sci, Memphis, TN 38105 USA. NINDS, Clin Neurocardiol Sect, Bethesda, MD 20892 USA. NCI, Urol Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Correl Syst Inc, Bethesda, MD USA. NCI, Natl Canc Inst Biomed Proteom Program, Analyt Chem Lab, Mass Spect Ctr,SAIC Frederick Inc, Frederick, MD 21701 USA. Predict Diagnost Inc, Vacaville, CA USA. RP Pacak, K (reprint author), NICHD, Unit Clin Neuroendocrinol, NIH, RBMB,Bldg 10,CRC,Room 1E-3140,10 Ctr Dr,MSC-1109, Bethesda, MD 20892 USA. EM karel@mail.nih.gov OI Mannelli, Massimo/0000-0002-8001-9857 NR 36 TC 35 Z9 38 U1 1 U2 1 PU BIOSCIENTIFICA LTD PI BRISTOL PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 1351-0088 J9 ENDOCR-RELAT CANCER JI Endocr.-Relat. Cancer PD JUN PY 2005 VL 12 IS 2 BP 263 EP 272 DI 10.1677/erc.1.00913 PG 10 WC Oncology; Endocrinology & Metabolism SC Oncology; Endocrinology & Metabolism GA 939OT UT WOS:000230083000005 PM 15947101 ER PT J AU Chen, T Hutts, RC Mei, N Liu, XL Bishop, ME Shelton, S Manjanatha, MG Aidoo, A AF Chen, T Hutts, RC Mei, N Liu, XL Bishop, ME Shelton, S Manjanatha, MG Aidoo, A TI Endogenous estrogen status, but not genistein supplementation, modulates 7,12-dimethylbenz[a]anthracene-induced mutation in the liver cll gene of transgenic big blue rats SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article DE DMBA mutagenesis; hepatocellular carcinogenesis; ovariectomy; sex hormones; genistein; Big Blue rats; estrogen ID DNA ADDUCT FORMATION; SPRAGUE-DAWLEY RATS; MAMMARY-TUMOR PROGRESSION; VIVO LACI MUTATIONS; IN-VIVO; HEPATOCELLULAR-CARCINOMA; FEMALE RATS; MOLECULAR ANALYSIS; GREAT-BRITAIN; BREAST-CANCER AB A growing number of studies suggest that isoflavanes found in soybeans have estrogenic activity and may safely alleviate the symptoms of menopause. One of these isoflavones, genistein, is commonly used by postmenopausal women as an alternative to hormone replacement therapy. Although sex hormones have been implicated as an important risk factor for the development of hepatocellular carcinoma, there are limited data on the potential effects of the estrogens, including phytoestrogens, on chemical mutagenesis in liver. Because of the association between mutation induction and the carcinogenesis process, we investigated whether endogenous estrogen and supplemental genistein affect 7,12-dimethylbenz[a]anthracene (DMBA)-induced mutagenesis in rat liver. Intact and ovariectomized female Big Blue rats were treated with 80 mg DMBA/kg body weight. Some of the rats also received a supplement of 1,000 ppm genistein. Sixteen weeks after the carcinogen treatment, the rats were sacrificed, their livers were removed, and mutant frequencies (MFs) and types of mutations were determined in the liver cll gene. DMBA significantly increased the MFs in liver for both the intact and ovariectomized rats. While there was no significant difference in MF between the ovariectomized and intact control animals, the mutation induction by DMBA in the ovariectomized groups was significantly higher than that in the intact groups. Dietary genistein did not alter these responses. Molecular analysis of the mutants showed that DMBA induced chemical-specific types of mutations in the liver cll gene. These results suggest that endogenous ovarian hormones have an inhibitory effect on liver mutagenesis by DMBA, whereas dietary genistein does not modulate spontaneous or DMBA-induced mutagenesis in either intact or ovariectomized rats. Published 2005 Wiley-Liss, Inc. C1 Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Food & Drug Adm, Jefferson, AR 72079 USA. Ctr Toxicol & Environm Hlth, Little Rock, AR USA. Univ Arkansas Med Sci, Dept Pharmacol & Toxicol, Little Rock, AR 72205 USA. RP Chen, T (reprint author), Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Food & Drug Adm, HFT-130,3900 NCTR Rd, Jefferson, AR 72079 USA. EM tchen@nctr.fda.gov RI mei, nan/E-8915-2011 OI mei, nan/0000-0002-3501-9014 NR 71 TC 1 Z9 1 U1 2 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD JUN PY 2005 VL 45 IS 5 BP 409 EP 418 DI 10.1002/em.20102 PG 10 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 937XV UT WOS:000229960800002 PM 15662719 ER PT J AU Verkler, TL Couch, LH Howard, PC Parsons, BL AF Verkler, TL Couch, LH Howard, PC Parsons, BL TI Quantifying levels of p53 mutation in mouse skin tumors SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article DE allele-specific competitive blocker PCR; p53; mutation; allele-specific amplification; skin neoplasm ID SQUAMOUS-CELL CARCINOMAS; COMPETITIVE BLOCKER PCR; HAIRLESS MICE; MUTANT P53; DNA-DAMAGE; UV; GENE; CARCINOGENESIS; SUNLIGHT; METHYLATION AB Allele-specific competitive blocker PCR (ACB-PCR) amplification and quantification was developed for mouse p53 codon 270 CGT -> TGT base substitution and codon 244/245 AAC/CGC -> AAT/ TGC tandem mutation. PCR products corresponding to p53 mutant and wild-type DNA sequences were generated. These DNAs were mixed in known proportions to construct samples with defined mutant fractions and the allele-specific detection of each mutation was systematically optimized. Each assay was used to analyze eight simulated solar light (SSL)-induced tumors. By analyzing mutant fraction (MF) standards in parallel with PCR products generated from tumor samples, p53 mutants could be quantified as subpopulations within the tumors. All eight tumors contained detectable levels of p53 codon 270 CGT -> TGT mutation. Three tumors had p53 MFs between 10(-4) and 10(-3). Five tumors had p53 MFs between 10(-3) and 10(-2). None of the eight mouse skin tumors had measurable levels of p53 codon 244/245 tandem mutation. Frequent detection of p53 codon 270 CGT -> TGT mutation provides additional evidence that a pyrimidine dinucleotide overlapping a methylated CpG site (Pyr(me)CG) is a susceptible target for SSL-induced mutagenesis. The absence of p53 codon 244/ 245 mutation in tumors may be explained by its mutant p53 phenotype and/or indicate that this site is not methylated. These initial results indicate that p53 codon 270 CGT -> TGT mutation may be a sensitive biomarker for SSL- or UV-induced mutagenesis. This mutational endpoint may be useful for evaluating the co-carcinogenicity of compounds administered in combination with UV or SSL. Published 2005 Wiley-Liss, Inc. C1 Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. Natl Ctr Toxicol Res, Natl Toxicol Program, Ctr Phototoxicol, Jefferson, AR 72079 USA. RP Parsons, BL (reprint author), Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, HTF-120,3900 NCTR Rd, Jefferson, AR 72079 USA. EM bparsons@nctr.fda.gov NR 38 TC 5 Z9 5 U1 0 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD JUN PY 2005 VL 45 IS 5 BP 427 EP 434 DI 10.1002/em.20108 PG 8 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 937XV UT WOS:000229960800004 PM 15662716 ER PT J AU Tokatli, F Cinar, A Schlesser, JE AF Tokatli, F Cinar, A Schlesser, JE TI HACCP with multivariate process monitoring and fault diagnosis techniques: application to a food pasteurization process SO FOOD CONTROL LA English DT Article DE multivariate statistical process monitoring; fault diagnosis; HACCP ID STATISTICAL PROCESS-CONTROL; CRITICAL CONTROL POINT; CONTROL STRATEGIES; DYNAMIC PROCESSES; SYSTEMS; LETHALITY; QUALITY AB Multivariate statistical process monitoring (SPM), and fault detection and diagnosis (FDD) methods are developed to monitor the critical control points (CCPs) in a continuous food pasteurization process. Multivariate SPM techniques effectively use information from all process variables to detect abnormal process behavior. Fault diagnosis techniques isolate the source cause of the deviation in process variable(s). The methods developed are illustrated by implementing them to monitor the critical control points and diagnose causes of abnormal operation of a high temperature short time (HTST) pasteurization pilot plant. The detection power of multivariate SPM and FDD techniques over univariate SPM techniques is shown and their integrated use to ensure the product safety and quality in food processes is demonstrated. (C) 2004 Published by Elsevier Ltd. C1 IIT, Dept Chem & Environm Engn, Chicago, IL 60616 USA. US FDA, Natl Ctr Food Safety & Technol, Summit Argo, IL 60501 USA. RP Cinar, A (reprint author), IIT, Dept Chem & Environm Engn, Chicago, IL 60616 USA. EM cinar@iit.edu RI Tokatli, Figen/B-6746-2012; OI Cinar, Ali/0000-0002-1607-9943 NR 32 TC 6 Z9 6 U1 1 U2 8 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0956-7135 J9 FOOD CONTROL JI Food Control PD JUN PY 2005 VL 16 IS 5 BP 411 EP 422 DI 10.1016/j.foodcont.2004.04.008 PG 12 WC Food Science & Technology SC Food Science & Technology GA 900QK UT WOS:000227229200005 ER PT J AU Sung, K Hiett, KL Stern, NJ AF Sung, K Hiett, KL Stern, NJ TI Heat-treated Campylobacter and mRNA stability as determined by reverse transcriptase-polymerase chain reaction SO FOODBORNE PATHOGENS AND DISEASE LA English DT Article ID ESCHERICHIA-COLI; REACTION ASSAY; THERMOPHILIC CAMPYLOBACTER; RT-PCR; JEJUNI; VIABILITY; AMPLIFICATION; CELLS; COLONIZATION; POLYMORPHISM AB The detection method of reverse transcriptase-polymerase chain reaction (RT-PCR), which specifically targets mRNA, was developed and tested for detection of cultivable Campylobacter spp. The expression of four DNA targets-flaA, tkt, porA, and a putative haem-copper oxidase domain-were assayed in heat-inactivated Campylobacter spp. to determine an optimum target for RT-PCR amplification. A diversity of Campylobacter spp. was tested; however, the presented RT-PCR technique was specific for C. jejuni, C. coli, and C. lari. The durability of mRNA species detected by our RT-PCR technique was dependent upon the individual Campylobacter spp. examined, the condition of heat treatment and post-treatment holding time, as well as the transcript targeted. The putative oxidase was determined to be the most stable mRNA species for this assay. The mRNA of the putative oxidase gene was detectable even after Campylobacter spp. had been treated at temperatures of 95-99 degrees C. Using DNA-based PCR, the four DNA targets could be amplified after heat inactivation followed by a 48 h holding time, indicating that the chromosomal DNA was not substantially degraded by the heat treatment. PCR products from the putative oxidase gene were detected at 10(2) to 10(3) C. jejuni CFU per mL, exhibiting the highest level of sensitivity among the genes tested. The results in the present study indicate that mRNA from Campylobacter spp. may persist in a form that is detectable by RT-PCR amplification for an extended period after heat treatment, demonstrating a poor correlation between mRNA detection and cell cultivability. With these results in mind, further investigations are necessary to determine the correlation between RT-PCR amplification and viability. C1 ARS, USDA, Poultry Microbiol Safety Res Unit, Russell Res Ctr, Athens, GA 30604 USA. Univ Georgia, Dept Food Sci & Technol, Athens, GA 30602 USA. Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. RP Hiett, KL (reprint author), ARS, USDA, Poultry Microbiol Safety Res Unit, Russell Res Ctr, POB 5677, Athens, GA 30604 USA. EM khiett@saa.ars.usda.gov NR 32 TC 12 Z9 12 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1535-3141 J9 FOODBORNE PATHOG DIS JI Foodborne Pathog. Dis. PD SUM PY 2005 VL 2 IS 2 BP 130 EP 137 DI 10.1089/fpd.2005.2.130 PG 8 WC Food Science & Technology SC Food Science & Technology GA 052RR UT WOS:000238251700002 PM 15992307 ER PT J AU Zhao, S Fedorka-Cray, PJ Friedman, S McDermott, PF Walker, RD Qaiyumi, S Foley, SL Hubert, SK Ayers, S English, L Dargatz, DA Salamone, B White, DG AF Zhao, S Fedorka-Cray, PJ Friedman, S McDermott, PF Walker, RD Qaiyumi, S Foley, SL Hubert, SK Ayers, S English, L Dargatz, DA Salamone, B White, DG TI Characterization of Salmonella Typhimurium of animal origin obtained from the national antimicrobial resistance monitoring system SO FOODBORNE PATHOGENS AND DISEASE LA English DT Article ID ANTIBIOTIC-RESISTANCE; UNITED-STATES; ESCHERICHIA-COLI; FOOD ANIMALS; ENTERICA TYPHIMURIUM; DT104 INFECTIONS; INTEGRONS; GENES; EMERGENCE; BACTERIA AB Salmonella Typhimurium remains one of the most common causes of salmonellosis in animals and humans in the United States. The emergence of multi-drug resistant Salmonella reduces the therapeutic options in cases of invasive infections, and has been shown to be associated with an increased burden of illness. In this study, 588 S. Typhimurium (including var. Copenhagen) isolates obtained from either animal diagnostic specimens (n = 199) or food animals after slaughter/processing (n = 389) were examined for antimicrobial susceptibility, presence of class-1 integrons, and characterized using pulsed-field gel electrophoresis and phage typing. Seventy-six percent (448/588) of isolates were resistant to at least one antimicrobial. Salmonella isolates displayed resistance most often to streptomycin (63%), tetracycline (61%), ampicillin (61%), and to a lesser extent, chloramphenicol (36%), ceftiofur (15%), gentamicin (9%), and nalidixic acid (4%), with more resistance observed among diagnostic isolates. Salmonella recovered from turkeys (n = 38) exhibited the highest rates of resistance, with 92% of isolates resistant to least one antimicrobial, and 58% resistant to >= 10 antimicrobials. Class 1 integrons were present in 51% of all isolates. Five integron associated resistance genes (aadA, aadB, pse-1, oxa-2 and dhfr) were identified. A total of 311 PFGE patterns were generated using XbaI, indicating a genetically diverse population. The largest PFGE cluster contained 146 isolates, including DT104 isolates obtained from all seven animal species. Results demonstrated a varied spectrum of antimicrobial resistance, including several multidrug resistant clonal groups, among S. Typhimurium and S. Typhimurium var. Copenhagen isolates recovered from both diagnostic and slaughter/processing samples. C1 US FDA, Div Anim & Food Microbiol, Res Off, Ctr Vet Med, Laurel, MD 20708 USA. ARS, USDA, Antimicrobial Resistance Res Unit, Athens, GA USA. Anim & Plant Hlth Inspect Serv, USDA, Vet Serv, Ctr Epidemiol & Anim Hlth, Ft Collins, CO USA. US Food Safety & Inspect Serv, USDA, Zoonot Dis & Residue Surveillance Div, Washington, DC 20250 USA. RP Zhao, S (reprint author), US FDA, Div Anim & Food Microbiol, Res Off, Ctr Vet Med, 8401 Muirkirk Rd, Laurel, MD 20708 USA. EM szhao@cvm.fda.gov NR 45 TC 45 Z9 50 U1 0 U2 4 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1535-3141 J9 FOODBORNE PATHOG DIS JI Foodborne Pathog. Dis. PD SUM PY 2005 VL 2 IS 2 BP 169 EP 181 DI 10.1089/fpd.2005.2.169 PG 13 WC Food Science & Technology SC Food Science & Technology GA 052RR UT WOS:000238251700007 PM 15992312 ER PT J AU Ito, S Ishii, KJ Ihata, A Klinman, DM AF Ito, S Ishii, KJ Ihata, A Klinman, DM TI Contribution of nitric oxide to CpG-mediated protection against Listeria monocytogenes SO INFECTION AND IMMUNITY LA English DT Article ID BACTERIAL-DNA; CUTTING EDGE; INTRACELLULAR BACTERIA; DEPENDENT PROTECTION; CELL-ACTIVATION; INFECTION; OLIGODEOXYNUCLEOTIDES; MURINE; MOTIFS; MICE AB Immunostimulatory CpG oligodeoxynucleotides (ODN) improve host resistance to listeriae. CpG ODN trigger immune cells to produce gamma interferon and "prime" host cells to secrete nitric oxide in response to bacterial exposure. CpG treatment does not protect inducible nitric oxide synthase 2 knockout mice, indicating that NO is critical to CpG-mediated protection against listeriae. C1 FDA, CBER, Bethesda, MD 20892 USA. RP Klinman, DM (reprint author), FDA, CBER, Bldg 29A,Rm 3D10, Bethesda, MD 20892 USA. EM Klinman@CBER.FDA.GOV RI Ishii, Ken/B-1685-2012 OI Ishii, Ken/0000-0002-6728-3872 NR 23 TC 13 Z9 14 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JUN PY 2005 VL 73 IS 6 BP 3803 EP 3805 DI 10.1128/IAI.73.6.3803-3805.2005 PG 3 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 931LD UT WOS:000229485900074 PM 15908417 ER PT J AU McKibben, L Horan, TC Tokars, JI Fowler, G Cardo, DM Pearson, ML Brennan, PJ AF McKibben, L Horan, TC Tokars, JI Fowler, G Cardo, DM Pearson, ML Brennan, PJ CA Healthcare Infection Control TI Guidance on public reporting of healthcare-associated infections: Recommendations of the healthcare infection control practices advisory committee SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Article ID BLOOD-STREAM INFECTIONS; NOSOCOMIAL INFECTIONS; SURVEILLANCE SYSTEM; UNITED-STATES; PREVENTION; RATES C1 Ctr Dis Control & Prevent, Div Healthcare Qual Promot, Natl Ctr Infect Dis, Atlanta, GA 30330 USA. Ctr Dis Control & Prevent, Healthcare Otucomes Branch, Natl Ctr Infect Dis, Div Healthcare Qual Promot, Atlanta, GA 30330 USA. Ctr Dis Control & Prevent, Prevent & Evaluat Branch, Natl Ctr Infect Dis, Div Healthcare Qual Promot, Atlanta, GA 30330 USA. Univ Penn, Sch Med, Div Infect Dis, Philadelphia, PA 19104 USA. Vanderbilt Univ, Med Ctr, Nashville, TN USA. Sharp Mem Hosp & Rehabil Ctr, San Diego, CA USA. Univ Washington, Sch Med, Seattle, WA 98195 USA. Amer Hosp Assoc, Washington, DC USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Duke Univ, Ctr Med, Durham, NC 27706 USA. Univ Minnesota, Minneapolis, MN 55455 USA. Texas Dept Hlth, Austin, TX 78756 USA. Long Beach Mem Med Ctr, Long Beach, CA USA. Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA. Childrens Natl Med Ctr, Washington, DC 20010 USA. Qualis Hlth Boise, Boise, ID USA. Univ Nebraska, Med Ctr, Omaha, NE 68583 USA. Agcy Healthcare Res & Qual, Rockville, MD USA. Assoc PeriOperat Registered Nurses, Denver, CO USA. Assoc Proffes Infect Control & Epidemiol In, Washington, DC USA. Amer Healthcare, Washington, DC USA. Natl Inst Hlth, Bethesda, MD USA. Hlth Serv Resources Adm, Atlanta, GA USA. Ctr Medicare & Medicaid Serv, Baltimore, MD USA. Food & Drug Adm, Rockville, MD USA. Amer Coll Occupat & Environm Med, Arlington Hts, IL USA. CDC, Advisory Comm Eliminat TB, Atlanta, GA 30333 USA. Soc Healthcare Epidemiol Amer Inc, Alexandria, VA USA. Joint Comm Accreditat Healthcare Org, Oak Brook, IL USA. RP Pearson, ML (reprint author), Ctr Dis Control & Prevent, Div Healthcare Qual Promot, Natl Ctr Infect Dis, Mailstop E-68,1600 Clifton Rd,NE, Atlanta, GA 30330 USA. EM mpearson@cdc.gov NR 42 TC 60 Z9 60 U1 0 U2 1 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0899-823X J9 INFECT CONT HOSP EP JI Infect. Control Hosp. Epidemiol. PD JUN PY 2005 VL 26 IS 6 BP 580 EP 587 DI 10.1086/502585 PG 8 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 973QW UT WOS:000232538700015 PM 16018435 ER PT J AU Levine, RA Smith, RE AF Levine, RA Smith, RE TI Sources of variability of acrylamide levels in a cracker model SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE acrylamide; GC-MS; wheat; sodium bicarbonate; baking; crackers ID HEATED FOODSTUFFS; LC-MS/MS; SAFETY; BREAD; DOUGH; ACID AB Surveys determining amounts of acrylamide formed as a byproduct of cooking in frequently consumed fried and baked foods have sometimes found variability in the levels, even when comparing items having similar ingredients and cooking procedures. To better understand the sources of variability, the effects of different ingredients on formation and elimination of acrylamide were studied in a model system based on wheat flour and water, that resembled crackers. It was found that NaHCO3 eliminated acrylamide. To a lesser extent, NH4HCO3, cysteine, sodium bisulfite, and ascorbate also enhanced elimination. Some ingredients, including citric acid, ferulic acid, and NaCl, were found to decrease the amount of acrylamide produced while having little or no effect on elimination. Asparagine, but not reducing sugar, caused a large increase in acrylamide formation. C1 US FDA, Total Diet & Pesticide Res Ctr, Lenexa, KS 66214 USA. Johnson Cty Community Coll, Overland Pk, KS 66210 USA. RP Levine, RA (reprint author), US FDA, Total Diet & Pesticide Res Ctr, 11510 W 80th St, Lenexa, KS 66214 USA. EM RLevine@ora.fda.gov NR 26 TC 45 Z9 52 U1 1 U2 12 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 JUN 1 PY 2005 VL 53 IS 11 BP 4410 EP 4416 DI 10.1021/jf047887t PG 7 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 930GX UT WOS:000229405000016 PM 15913303 ER PT J AU West, RW Kodell, RL AF West, RW Kodell, RL TI Changepoint alternatives to the NOAEL SO JOURNAL OF AGRICULTURAL BIOLOGICAL AND ENVIRONMENTAL STATISTICS LA English DT Article DE onset of trend; profile likelihood ID DOSE-RESPONSE RELATIONSHIPS; MULTIPLE TEST PROCEDURES; SEGMENTED REGRESSION; MODELS; TOXICOLOGY; INFERENCE; RISK AB The onset-of-trend changepoint model is applied to the dose-response setting encountered in regulatory toxicology experiments with continuous responses. An investigation of the least squares criterion over each of the dose intervals provides insights into the distribution of the changepoint estimate for small dose group sample sizes and a simple computational procedure for finding this estimate. A new accessible proof of the consistency of this estimate as dose group size increases is developed. For normally distributed data, an asymptotic procedure is developed for constructing a lower confidence limit on the changepoint. The performance of the changepoint estimate and the lower confidence limit are compared directly to the no-observed-adverse-effect-leveI (NOAEL) via a large simulation study and an example dataset. The lower confidence limit on the changepoint is shown to be a better regulatory quantity than the NOAEL from a statistical perspective. C1 Univ S Carolina, Dept Stat, Columbia, SC 29208 USA. Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. RP West, RW (reprint author), Univ S Carolina, Dept Stat, Columbia, SC 29208 USA. NR 22 TC 2 Z9 2 U1 0 U2 4 PU AMER STATISTICAL ASSOC & INTERNATIONAL BIOMETRIC SOC PI WASHINGTON PA 1444 I ST NW, STE 700, WASHINGTON, DC 20005 USA SN 1085-7117 J9 J AGR BIOL ENVIR ST JI J. Agric. Biol. Environ. Stat. PD JUN PY 2005 VL 10 IS 2 BP 197 EP 211 DI 10.1198/108571105X46525 PG 15 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 933AF UT WOS:000229595500006 ER PT J AU Normand, SLT Rector, TS Neaton, JD Pina, IL Lazar, RM Proestel, SE Fleischer, DJ Cohn, JN Spertus, JA AF Normand, SLT Rector, TS Neaton, JD Pina, IL Lazar, RM Proestel, SE Fleischer, DJ Cohn, JN Spertus, JA TI Clinical and analytical considerations in the study of health status in device trials for heart failure SO JOURNAL OF CARDIAC FAILURE LA English DT Article DE design; endpoints; quality of life; regulatory ID QUALITY-OF-LIFE; MULTIVARIATE INCOMPLETE DATA; LEFT-VENTRICULAR DYSFUNCTION; PATTERN-MIXTURE MODELS; DOUBLE-BLIND; QUESTIONNAIRE; VALIDITY; PLACEBO; PATIENT; CARDIOMYOPATHY AB Background: Measures of health status (including symptoms, functional status, or quality of life) assess patients' experiences of their disease, and may therefore be used to quantify the benefits and risks of treatment. The aim of this article is to provide recommendations to regulatory agencies and research sponsors regarding the use of health status measures in medical device trials. Methods and Results: A workshop jointly planned by the Heart Failure Society of America and the US Food and Drug Administration was convened in October 2003 in Washington, DC. A Working Group to address health status measures initiated its collaboration at the workshop and continued its efforts throughout the next year. The Working Group recommended assessment of health status in all studies of heart failure therapy. Standardized instruments known to be valid, reliable, responsive to changes, and available in the languages of target populations should be used. Minimizing bias may be accomplished by using blinded, independent evaluators; collecting multiple health status measures; using valid statistical methods; and creating a health status resource bank. Conclusion: Assessment of health status should be part of any device trial and should occur regardless of whether the device is intended as destination or bridging therapy. Health status endpoints should be chosen, collected, and analyzed with the same level of scientific rigor as traditional clinical endpoints. Regulatory agencies should require use of analytic methods that handle the complexity of health status data in addition to usual protocol protections. C1 Harvard Univ, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Minneapolis VA Med Ctr, Minneapolis, MN USA. Univ Minnesota, Sch Publ Hlth, Minneapolis, MN USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. Columbia Univ Coll Phys & Surg, New York, NY 10032 USA. US FDA, Rockville, MD 20857 USA. Univ Minnesota, Sch Med, Minneapolis, MN 55455 USA. Mid Amer Heart Inst, Kansas City, MO USA. Univ Missouri, Kansas City, MO 64110 USA. RP Normand, SLT (reprint author), 180 Longwood Ave, Boston, MA 02115 USA. NR 44 TC 12 Z9 12 U1 1 U2 1 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD JUN PY 2005 VL 11 IS 5 BP 396 EP 403 DI 10.1016/j.cardfail.2005.04.002 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 942ED UT WOS:000230264800012 PM 15948091 ER PT J AU Laassri, M Dragunsky, E Enterline, J Eremeeva, T Ivanova, O Lottenbach, K Belshe, R Chumakov, K AF Laassri, M Dragunsky, E Enterline, J Eremeeva, T Ivanova, O Lottenbach, K Belshe, R Chumakov, K TI Genomic analysis of vaccine-derived poliovirus strains in stool specimens by combination of full-length PCR and oligonucleotide microarray hybridization SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID GROUP-A ROTAVIRUSES; 5' NONCODING REGION; UNITED-STATES; SABIN TYPE-3; REVERSE-TRANSCRIPTASE; SMALLPOX VACCINATION; VIRUS EXCRETION; CHAIN-REACTION; FECAL SAMPLES; VIRAL-RNA AB Sabin strains of poliovirus used in the manufacture of oral poliovirus vaccine (OPV) are prone to genetic variations that occur during growth in cell cultures and the organisms of vaccine recipients. Such derivative viruses often have increased neurovirulence and transmissibility, and in some cases they can reestablish chains of transmission in human populations. Monitoring for vaccine-derived polioviruses is an important part of the worldwide campaign to eradicate poliomyelitis. Analysis of vaccine-derived polioviruses requires, as a first step, their isolation in cell cultures, which takes significant time and may yield viral stocks that are not fully representative of the strains present in the original sample. Here we demonstrate that full-length viral cDNA can be PCR amplified directly from stool samples and immediately subjected to genomic analysis by oligonucleotide microarray hybridization and nucleotide sequencing. Most fecal samples from healthy children who received OPV were found to contain variants of Sabin vaccine viruses. Sequence changes in the 5' untranslated region were common, as were changes in the VP1-coding region, including changes in a major antigenic site. Analysis of stool samples taken from cases of acute flaccid paralysis revealed the presence of mixtures of recombinant polioviruses, in addition to the emergence of new sequence variants. Avoiding the need for cell culture isolation dramatically shortened the time needed for identification and analysis of vaccine-derived polioviruses and could be useful for preliminary screening of clinical samples. The amplified full-length viral cDNA can be archived and used to recover live virus for further virological studies. C1 US FDA, CBER, Rockville, MD 20852 USA. Russian Acad Med Sci, MP Chumakov Inst Poliomyelitis, Moscow 142782, Russia. St Louis Univ, St Louis, MO 63103 USA. RP Chumakov, K (reprint author), US FDA, CBER, 1401 Rockville Pike,HFM 470, Rockville, MD 20852 USA. EM chumakov@cber.fda.gov OI Ivanova, O.E./0000-0003-1784-4827 FU NIAID NIH HHS [N01-AI-45251, N01-AI-45250, N01AI45250] NR 54 TC 25 Z9 26 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD JUN PY 2005 VL 43 IS 6 BP 2886 EP 2894 DI 10.1128/JCM.43.6.2886-2894.2004 PG 9 WC Microbiology SC Microbiology GA 936SF UT WOS:000229875000052 PM 15956413 ER PT J AU Prados, M Kunwar, S Lang, FF Ram, Z Westphal, M Barnett, G Sampson, JH Croteau, D Puri, RK AF Prados, M Kunwar, S Lang, FF Ram, Z Westphal, M Barnett, G Sampson, JH Croteau, D Puri, RK TI Final results of phase I/II studies of IL13-PE38QQR administered intratumorally (IT) and/or peritumorally (PT) via convection-enhanced delivery (CED) in patients undergoing tumor resection for recurrent malignant glioma. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Tel Aviv Univ, IL-69978 Tel Aviv, Israel. Univ Hamburg, Hosp Eppendorf, D-20246 Hamburg, Germany. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Duke Univ, Med Ctr, Durham, NC USA. NeoPharm Inc, Lake Forest, IL USA. US FDA, CBER, Bethesda, MD USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2005 VL 23 IS 16 SU S BP 115S EP 115S PN 1 PG 1 WC Oncology SC Oncology GA 943BK UT WOS:000230326600455 ER PT J AU Fernandez, T Pellat-Deceunynck, C Supiot, S Cherel, M Stortchevoi, A Bataille, R Harousseau, JL Rubinstein, DB Guillaume, T AF Fernandez, T Pellat-Deceunynck, C Supiot, S Cherel, M Stortchevoi, A Bataille, R Harousseau, JL Rubinstein, DB Guillaume, T TI Selection of fully human anti-CD138 for detecting and therapy of multiple myeloma from combinatorial libraries and generation of novel anti-myeloma antibodies. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol C1 Univ Nantes, Nantes, France. Yale Univ, New Haven, CT USA. US FDA, Rockville, MD 20857 USA. RI Supiot, Stephane/M-1586-2015; Cherel, Michel/F-8298-2013 OI Supiot, Stephane/0000-0003-2094-1708; NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2005 VL 23 IS 16 SU S BP 178S EP 178S PN 1 PG 1 WC Oncology SC Oncology GA 943BK UT WOS:000230326601126 ER PT J AU Dagher, RN Rosario, LA Morse, DE Pazdur, R AF Dagher, RN Rosario, LA Morse, DE Pazdur, R TI Regulatory considerations for early clinical studies of anti-cancer drugs in healthy volunteers SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol C1 US FDA, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2005 VL 23 IS 16 SU S BP 217S EP 217S PN 1 PG 1 WC Oncology SC Oncology GA 943BK UT WOS:000230326601278 ER PT J AU Saber-Mahloogi, H Timmer, WC Lee, SL Leighton, J Kane, RC Pilaro, A Rahman, A Johnson, G Pazdur, R AF Saber-Mahloogi, H Timmer, WC Lee, SL Leighton, J Kane, RC Pilaro, A Rahman, A Johnson, G Pazdur, R TI The FDA division of oncology initiative with the NCISBIR/STTR programs SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol C1 US FDA, Rockville, MD 20857 USA. NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2005 VL 23 IS 16 SU S BP 234S EP 234S PN 1 PG 1 WC Oncology SC Oncology GA 943BK UT WOS:000230326601347 ER PT J AU Fiorentino, R El-Khoueiry, A Hirschfeld, S AF Fiorentino, R El-Khoueiry, A Hirschfeld, S TI A survey of phase I study designs of cellular, gene therapy and antigenic products for cancer at the US Food & Drug Administration. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol C1 US FDA, Rockville, MD 20857 USA. Univ So Calif, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2005 VL 23 IS 16 SU S BP 536S EP 536S PN 1 PG 1 WC Oncology SC Oncology GA 943BK UT WOS:000230326603367 ER PT J AU Talarico, L Pignatti, F Pazdur, R AF Talarico, L Pignatti, F Pazdur, R TI Registration by the European Agency for the Evaluation of Medicinal products (EMEA) of oncology products approved by the Food and Drug Administration (FDA) under accelerated approval (AA) regulations. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol C1 US FDA, Rockville, MD 20857 USA. European Med Agcy, London, England. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2005 VL 23 IS 16 SU S BP 541S EP 541S PN 1 PG 1 WC Oncology SC Oncology GA 943BK UT WOS:000230326603385 ER PT J AU Liu, K Fiorentino, RP Hirschfeld, S AF Liu, K Fiorentino, RP Hirschfeld, S TI A survey of currently active late-phase oncology studies for cellular, gene therapy and antigenic products regulated by the US Food & Drug Administration, Center for Biologics Evaluation and Research (CBER). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol C1 US FDA, CBER, Rockville, MD USA. RI Hirschfeld, Steven/E-2987-2016 OI Hirschfeld, Steven/0000-0003-0627-7249 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2005 VL 23 IS 16 SU S BP 543S EP 543S PN 1 PG 1 WC Oncology SC Oncology GA 943BK UT WOS:000230326603395 ER PT J AU Mann, BS Dagher, R Williams, G Johnson, J Pazdur, R AF Mann, BS Dagher, R Williams, G Johnson, J Pazdur, R TI Endpoints used by the FDA for new drug approvals for treatment (TT) of advanced (ADV) cancer: Example of hormone refractory prostate cancer (HRPC). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol C1 US FDA, CDER, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2005 VL 23 IS 16 SU S BP 545S EP 545S PN 1 PG 1 WC Oncology SC Oncology GA 943BK UT WOS:000230326603402 ER PT J AU Dunleavy, K White, T Grant, N Shovlin, M Stetler-Stevenson, M Pittaluga, S Jaffe, ES Marti, G Janik, J Wilson, WH AF Dunleavy, K White, T Grant, N Shovlin, M Stetler-Stevenson, M Pittaluga, S Jaffe, ES Marti, G Janik, J Wilson, WH TI Phase I study of combination rituximab with apolizumab in relapsed/refractory B-cell lymphoma and chronic lymphocytic leukemia. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol C1 NCI, Bethesda, MD 20892 USA. US FDA, Bethesda, MD 20014 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2005 VL 23 IS 16 SU S BP 586S EP 586S PN 1 PG 1 WC Oncology SC Oncology GA 943BK UT WOS:000230326603565 ER PT J AU Bowers, DC McNeil, DE Liu, Y Leisenring, W Gurney, J Stovall, M Donaldson, SS Packer, RJ Robison, LL Oeffinger, KC AF Bowers, DC McNeil, DE Liu, Y Leisenring, W Gurney, J Stovall, M Donaldson, SS Packer, RJ Robison, LL Oeffinger, KC TI Risk of stroke among > 5 year survivors of childhood leukemia and brain tumors; a report from the Childhood Cancer Survivor Study. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol C1 Univ Texas, SW Med Ctr, Dallas, TX 75230 USA. US FDA, Rockville, MD 20857 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Univ Minnesota, Minneapolis, MN USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Stanford Univ, Med Ctr, Stanford, CA 94305 USA. Childrens Natl Med Ctr, Washington, DC 20010 USA. NR 0 TC 3 Z9 3 U1 0 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2005 VL 23 IS 16 SU S BP 804S EP 804S PN 1 PG 1 WC Oncology SC Oncology GA 943BK UT WOS:000230326605259 ER PT J AU Helman, LJ Yeung, C Espina, V Eichler, G Krishnan, K Tsokos, M Qualman, S Meyer, W Steinberg, S Petricoin, EF Liotta, LA AF Helman, LJ Yeung, C Espina, V Eichler, G Krishnan, K Tsokos, M Qualman, S Meyer, W Steinberg, S Petricoin, EF Liotta, LA TI Proteomic profiling identifies prognostic subsets in Rhabdomyosarcoma (RMS). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol C1 NCI, NIH, Bethesda, MD USA. Columbus Childrens Hosp, Columbus, OH USA. Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA. US FDA, Bethesda, MD 20014 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2005 VL 23 IS 16 SU S BP 837S EP 837S PN 1 PG 1 WC Oncology SC Oncology GA 943BK UT WOS:000230326605386 ER PT J AU Miller, AJ Hileman, CL Droby, S Paster, N AF Miller, AJ Hileman, CL Droby, S Paster, N TI Science and technology based countermeasures to foodborne terrorism: Introduction SO JOURNAL OF FOOD PROTECTION LA English DT Editorial Material C1 US FDA, Ctr Food Safety & Appl Nutr, US Dept HHS, College Pk, MD 21074 USA. Agr Res Org, Volcani Ctr, IL-50250 Bet Dagan, Israel. RP Miller, AJ (reprint author), US FDA, Ctr Food Safety & Appl Nutr, US Dept HHS, College Pk, MD 21074 USA. EM amiller@cfsan.fda.gov NR 0 TC 4 Z9 4 U1 0 U2 1 PU INT ASSOC FOOD PROTECTION PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD JUN PY 2005 VL 68 IS 6 BP 1253 EP 1255 PG 3 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 935NN UT WOS:000229789100022 PM 15954718 ER PT J AU Sharma, SK Whiting, RC AF Sharma, SK Whiting, RC TI Methods for detection of Clostridium botulinum toxin in foods SO JOURNAL OF FOOD PROTECTION LA English DT Article; Proceedings Paper CT Workshop on Science and Technology Based Countermeasures to Foodborne Terrorism CY JUN 29-JUL 03, 2003 CL Shepherdstown, WV SP Joint Inst Food Safety & Appl Nutr, US & Israel Binat Agr Res & Dev Fund, Edo Chalutz, US Sci Advistory Comm, USDA, Food Safty & Inspect Serv, US Food & Drug Adm, USDA, Anim & Plant Hlth Inspect Serv, USAMY, US Food & Drug Adm Forens Chem Ctr, Int Life Sci Inst ID LINKED-IMMUNOSORBENT-ASSAY; IMMUNOMAGNETIC-ELECTROCHEMILUMINESCENT DETECTION; NONTOXIC-NONHEMAGGLUTININ COMPONENT; ELECTROSPRAY MASS-SPECTROMETRY; NEUROTOXIN PROTEASE ACTIVITY; LASER-DESORPTION IONIZATION; COLORIMETRIC CAPTURE ELISAS; ANTIBODY-BASED IMMUNOASSAY; OPTIC-BASED BIOSENSOR; MOUSE BIOASSAY AB Botulism is a deadly disease caused by ingestion of the preformed neurotoxin produced from the anaerobic spore-forming bacteria Clostridium botulinum. Botulinum neurotoxins are the most poisonous toxins known and have been a concern in the food industry for a long time. Therefore, rapid identification of botulinum neurotoxin using molecular and biochemical techniques is an essential component in the establishment of coordinated laboratory response systems and is the focus of current research and development. Because of the extreme toxicity of botulinum neurotoxin, some confirmatory testing with the mouse bioassay is still necessary, but rapid methods capable of screening large numbers of samples are also needed. This review is focused on the development of several detection methods for botulinum neurotoxins in foods. C1 US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Sharma, SK (reprint author), US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. EM shashi.sharma@cfsan.fda.gov NR 94 TC 44 Z9 45 U1 1 U2 18 PU INT ASSOC FOOD PROTECTION PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD JUN PY 2005 VL 68 IS 6 BP 1256 EP 1263 PG 8 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 935NN UT WOS:000229789100023 PM 15954719 ER PT J AU Bennett, RW AF Bennett, RW TI Staphylococcal enterotoxin and its rapid identification in foods by enzyme-linked immunosorbent assay-based methodology SO JOURNAL OF FOOD PROTECTION LA English DT Article; Proceedings Paper CT Workshop on Science and Technology Based Countermeasures to Foodborne Terrorism CY JUN 29-JUL 03, 2003 CL Shepherdstown, WV SP Joint Inst Food Safety & Appl Nutr, US & Israel Binat Agr Res & Dev Fund, Edo Chalutz, US Sci Advistory Comm, USDA, Food Safty & Inspect Serv, US Food & Drug Adm, USDA, Anim & Plant Hlth Inspect Serv, USAMY, US Food & Drug Adm Forens Chem Ctr, Int Life Sci Inst ID AUREUS; IMMUNOASSAY; INTERMEDIUS; MUSHROOMS; OUTBREAK AB The problem of Staphylococcus aureus and other species as contaminants in the food supply remains significant on a global level. Time and temperature abuse of a food product contaminated with enterotoxigenic staphylococci can result in formation of enterotoxin, which can produce foodborne illness when the product is ingested. Between 100 and 200 ng of enterotoxin can cause symptoms consistent with staphylococcal intoxication. Although humans are the primary reservoirs of contamination, animals, air, dust, and food contact surfaces can serve as vehicles in the transfer of this pathogen to the food supply. Foods may become contaminated during production or processing and in homes or food establishments, where the organism can proliferate to high concentrations and subsequently produce enterotoxin. The staphylococcal enterotoxins are highly heat stable and can remain biologically active after exposure to retort temperatures. Prior to the development of serological methods for the identification of enterotoxin, monkeys (gastric intubation) and later kittens (intravenous injection) were used in assays for toxin detection. When enterotoxins were identified as mature proteins that were antigenic, serological assays were developed for use in the laboratory analysis of foods suspected of containing preformed enterotoxin. More recently developed methods are tracer-labeled immunoassays. Of these methods, the enzyme-linked immunosorbent assays are highly specific, highly sensitive, and rapid for the detection of enterotoxin in foods. C1 US FDA, College Pk, MD 20740 USA. RP Bennett, RW (reprint author), US FDA, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM reginald.bennett@cfsan.fda.gov NR 50 TC 71 Z9 73 U1 1 U2 11 PU INT ASSOC FOOD PROTECTION PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD JUN PY 2005 VL 68 IS 6 BP 1264 EP 1270 PG 7 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 935NN UT WOS:000229789100024 PM 15954720 ER PT J AU Cebula, TA Jackson, SA Brown, EW Goswami, B LeClerc, JE AF Cebula, TA Jackson, SA Brown, EW Goswami, B LeClerc, JE TI Chips and SNPs, bugs and thugs: A molecular sleuthing perspective SO JOURNAL OF FOOD PROTECTION LA English DT Article; Proceedings Paper CT Workshop on Science and Technology Based Countermeasures to Foodborne Terrorism CY JUN 29-JUL 03, 2003 CL Shepherdstown, WV SP Joint Inst Food Safety & Appl Nutr, US & Israel Binat Agr Res & Dev Fund, Edo Chalutz, US Sci Advistory Comm, USDA, Food Safty & Inspect Serv, US Food & Drug Adm, USDA, Anim & Plant Hlth Inspect Serv, USAMY, US Food & Drug Adm Forens Chem Ctr, Int Life Sci Inst ID ESCHERICHIA-COLI O157-H7; POLYMERASE-CHAIN-REACTION; SINGLE-NUCLEOTIDE POLYMORPHISMS; FIELD GEL-ELECTROPHORESIS; HEPATITIS-A VIRUS; VARIABLE-NUMBER; BACILLUS-ANTHRACIS; EXPERIMENTAL POPULATIONS; REVERSE TRANSCRIPTION; EVOLUTIONARY GENOMICS AB Recent events both here and abroad have focused attention on the need for ensuring a safe and secure food supply. Although much has been written about the potential of particular select agents in bioterrorism, we must consider seriously the more mundane pathogens, especially those that have been implicated previously in foodborne outbreaks of human disease, as possible agents of bioterrorism. Given their evolutionary history, the enteric pathogens are more diverse than agents such as Bacillus anthracis, Francisella tularensis, or Yersinia pestis. This greater diversity, however, is a double-edged sword; although diversity affords the opportunity for unequivocal identification of an organism without the need for whole-genome sequencing, the same diversity can confound definitive forensic identification if boundaries are not well defined. Here, we discuss molecular approaches used for the identification of Salmonella enterica, Escherichia coli, and Shigella spp. and viral pathogens and discuss the utility of these approaches to the field of microbial molecular forensics. 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, HFS-025, Laurel, MD 20708 USA. EM tcebula@cfsan.fda.gov NR 100 TC 17 Z9 18 U1 0 U2 1 PU INT ASSOC FOOD PROTECTION PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD JUN PY 2005 VL 68 IS 6 BP 1271 EP 1284 PG 14 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 935NN UT WOS:000229789100025 PM 15954721 ER PT J AU Garber, EAE Eppley, RM Stack, ME McLaughlin, MA Park, DL AF Garber, EAE Eppley, RM Stack, ME McLaughlin, MA Park, DL TI Feasibility of immunodiagnostic devices for the detection of ricin, amanitin, and T-2 toxin in food SO JOURNAL OF FOOD PROTECTION LA English DT Article; Proceedings Paper CT Workshop on Science and Technology Based Countermeasures to Foodborne Terrorism CY JUN 29-JUL 03, 2003 CL Shepherdstown, WV SP Joint Inst Food Safety & Appl Nutr, US & Israel Binat Agr Res & Dev Fund, Edo Chalutz, US Sci Advistory Comm, USDA, Food Safty & Inspect Serv, US Food & Drug Adm, USDA, Anim & Plant Hlth Inspect Serv, USAMY, US Food & Drug Adm Forens Chem Ctr, Int Life Sci Inst ID RIBOSOMAL-RNA; RECOGNITION; ELONGATION AB Qualitative and quantitative comparisons were conducted of commercially available immunodiagnostic devices for the detection of three select agents with oral LD50 values >= 0.1 mg/kg of body weight. Ricin (oral LD50 > 1 mg/kg), amanitin (oral LD50 approximately 0.1 mg/kg), and T-2 toxin (oral LD50 > 1 mg/kg) were spiked into beverages, produce, dairy, and baked goods and assayed using commercially available enzyme-linked immunosorbent assays (ELISAs) and lateral flow devices. In all cases, the commercial diagnostic kits successfully detected all three select agents at concentrations below what might be a health concern. The considerable difference between the limit of detection of the immunodiagnostic devices employed (typically <= 0.020 mu g/g) and the amount of the select agent necessary to pose a health threat in a single serving of food facilitated the design of protocols for the high throughput screening of food samples. These protocols entailed simple extraction methods followed by sample dilution. Lateral flow devices and sandwich ELISAs for the detection of ricin had no significant background problems due to the food matrices. Competitive ELISAs, which typically have unacceptably high background reactions with food samples, successfully detected amanitin and T-2 toxin. C1 US FDA, Ctr Food Safety & Appl Nutr, Off Plant & Dairy Foods, Div Nat Prod, College Pk, MD 20740 USA. RP Garber, EAE (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Plant & Dairy Foods, Div Nat Prod, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM egarber@cfsan.fda.gov NR 21 TC 34 Z9 35 U1 1 U2 2 PU INT ASSOC FOOD PROTECTION PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD JUN PY 2005 VL 68 IS 6 BP 1294 EP 1301 PG 8 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 935NN UT WOS:000229789100027 PM 15954723 ER PT J AU Tadokoro, T Yamaguchi, Y Batzer, J Coelho, SG Zmudzka, BZ Miller, SA Wolber, R Beer, JZ Hearing, VJ AF Tadokoro, T Yamaguchi, Y Batzer, J Coelho, SG Zmudzka, BZ Miller, SA Wolber, R Beer, JZ Hearing, VJ TI Mechanisms of skin tanning in different racial/ethnic groups in response to ultraviolet radiation SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE melanocyte; melanosome; photoprotection; pigmentation; ultraviolet ID MITF; MELANOSOME; TYROSINASE; ERYTHEMA; MODEL; PIGMENTATION; MELANOCYTES; EXPRESSION; PATTERNS; MEDIATOR AB Ultraviolet radiation stimulates pigmentation in human skin, but the mechanism(s) whereby this increase in melanin production (commonly known as tanning) occurs is not well understood. Few studies have examined the molecular consequences of UV on human skin of various racial backgrounds in situ. We investigated the effects of UV on human skin of various races before and at different times after a single 1 minimal erythemal dose UV exposure. We measured the distribution of DNA damage that results, as well as the melanin content/distribution and the expression of various melanocyte-specific genes. The density of melanocytes at the epidermal:dermal junction in different types of human skin are remarkably similar and do not change significantly within 1 wk after UV exposure. The expression of melanocyte-specific proteins (including TYR (tyrosinase), TYRP1 (tyrosinase-related protein 1), DCT (tyrosinase-related protein 2), MART1 (melanoma antigens recognized by T-cells) gp100 (Pmel17/silver), and MITF (micropthalmia transcription factor)) increased from 0 to 7 d after UV exposure, but the melanin content of the skin increased only slightly. The most significant change, however, was a change in the distribution of melanin from the lower layer upwards to the middle layer of the skin, which was more dramatic in the darker skin. These results provide a basis for understanding the origin of different skin colors and responses to UV within different races. C1 NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. Beiersdorf AG, R&D, Skin Res, Hamburg, Germany. US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Hearing, VJ (reprint author), NCI, Cell Biol Lab, NIH, Bldg 37,Room 2132, Bethesda, MD 20892 USA. EM hearingv@nih.gov RI Yamaguchi, Yuji/B-9312-2008 NR 34 TC 112 Z9 114 U1 2 U2 19 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUN PY 2005 VL 124 IS 6 BP 1326 EP 1332 DI 10.1111/j.0022-202X.2005.23760.x PG 7 WC Dermatology SC Dermatology GA 933NC UT WOS:000229636400033 PM 15955111 ER PT J AU Wilkes, JG Rushing, L Nayak, R Buzatu, DA Sutherland, JB AF Wilkes, JG Rushing, L Nayak, R Buzatu, DA Sutherland, JB TI Rapid phenotypic characterization of Salmonella enterica strains by pyrolysis metastable atom bombardment mass spectrometry with multivariate statistical and artificial neural network pattern recognition SO JOURNAL OF MICROBIOLOGICAL METHODS LA English DT Article DE Salmonella; PyMS; MAB; ANN ID TIME-OF-FLIGHT; GRAM-POSITIVE BACTERIA; NOSOCOMIAL INFECTION; ANTIBIOTIC-RESISTANCE; WHOLE CELLS; MALDI-TOF; DIFFERENTIATION; IDENTIFICATION; MYCOBACTERIA; IONIZATION AB Pyrolysis mass spectrometry was investigated for rapid characterization of bacteria. Spectra of Salmonella were compared to their serovars, pulsed-field gel electrophoresis (PFGE) patterns, antibiotic resistance profiles, and MIC values. Pyrolysis mass spectra generated via metastable atom bombardment were analyzed by multivariate principal component-discriminant analysis and artificial neural networks (ANNs). Spectral patterns developed by discriminant analysis and tested with Leave-One-Out (LOO) cross-validation distinguished Salmonella strains by serovar (97% correct) and by PFGE groups (49%). An ANN model of the same PFGE groups was cross-validated, using the LOO rule, with 92% agreement. Using an ANN, thirty previously unseen spectra were correctly classified by serotype (97%) and at the PFGE level (67%). Attempts by ANN to model spectra grouped by resistance profile-but ignoring PFGE or serotype-failed (10% correct), but ANNs differentiating ten samples of the same serotype/PFGE class were more successful. To assess the information content of PyMS data serendipitously associated with or directly related to resistance character, the ten isolates were grouped into four, three, or two categories. The four categories corresponded to four resistance profiles. The four class and three class ANNs showed much improved but insufficient modeling power. The two-class ANN and a corresponding multivariate model maximized inferential power for a coarse antibiotic-resistance-related distinction. They each cross-validated by LOO at 90%. This is the first direct correlation of pyrolysis metastable atom bombardment mass spectrometry with immunological (e.g. serology) or molecular biology (e.g. PFGE) based techniques. (c) 2004 Elsevier B.V. All rights reserved. C1 US FDA, Div Chem, NCTR, Jefferson, AR 72079 USA. RP Wilkes, JG (reprint author), US FDA, Div Chem, NCTR, 3900 NCTR Dr, Jefferson, AR 72079 USA. EM jwilkes@nctr.fda.gov NR 50 TC 15 Z9 16 U1 2 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-7012 J9 J MICROBIOL METH JI J. Microbiol. Methods PD JUN PY 2005 VL 61 IS 3 BP 321 EP 334 DI 10.1016/j.mimet.2004.12.016 PG 14 WC Biochemical Research Methods; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 911SX UT WOS:000228026200003 PM 15767008 ER PT J AU Ivanov, A Dragunsky, E Ivanova, O Rezapkin, G Potapova, S Churnakov, K AF Ivanov, A Dragunsky, E Ivanova, O Rezapkin, G Potapova, S Churnakov, K TI Determination of poliovirus-specific IgA in saliva by ELISA tests SO JOURNAL OF VIROLOGICAL METHODS LA English DT Article DE poliovirus; OPV; saliva; IgA; ELISA; alpha-capture technique ID INACTIVATED POLIOVIRUS; NEUTRALIZING ANTIBODIES; ACELLULAR PERTUSSIS; BINDING-INHIBITION; CONJUGATE VACCINE; UNITED-STATES; ASSAY; IMMUNOGENICITY; POLIOMYELITIS; IMMUNIZATION AB This study describes three ELISA methods for detection of immunoglobulin A (IgA) specific to three types of Sabin strains of poliovirus in saliva taken from 70 children aged 6-7 years vaccinated with a full course of oral poliovirus vaccine (OPV). Of the three ELISA methods (conventional IgA ELISA and two new methods described in this communication, the a-capture ELISA and Inhibition ELISA), a-capture ELISA demonstrated the highest sensitivity, with all saliva samples testing positive for Sabin poliovirus strains specific IgA antibodies of 1-3 types. Of 62 available a-capture ELISA positive saliva samples, all were also positive by the inhibition ELISA, and a significant correlation was found between the results. Fifty-two available saliva samples were screened by the three ELISA tests with positive results, and a significant correlation was found between the a-capture ELISA and the IgA ELISA; the correlation between the IgA ELISA and inhibition ELISA was not significant. The results of this study suggest that determination of Sabin poliovirus-specific IgA in human saliva by the ELISA techniques (especially by the novel α-capture ELISA) can be used reliably for evaluation of mucosal immunity in large groups of people immunized with poliovirus vaccines and for epidemiological studies. © 2005 Elsevier B.V. All rights reserved. C1 US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. Russian Acad Med Sci, MP Chumakov Inst Poliomyelitis & Viral Encephalit, Moscow 142782, Russia. RP Ivanov, A (reprint author), US FDA, Ctr Biol Evaluat & Res, HFM-470,NLRC-B-121,1401 Rockville Pike, Rockville, MD 20852 USA. EM ivanov@cber.fda.gov OI Ivanova, O.E./0000-0003-1784-4827 NR 37 TC 4 Z9 6 U1 0 U2 14 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 JUN PY 2005 VL 126 IS 1-2 BP 45 EP 52 DI 10.1016/j.jviromet.2005.01.030 PG 8 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Virology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Virology GA 924TJ UT WOS:000229003000006 PM 15847918 ER PT J AU Khurana, S Kennedy, M King, LR Golding, H AF Khurana, S Kennedy, M King, LR Golding, H TI Identification of a linear peptide recognized by monoclonal antibody 2D7 capable of generating CCR5-Specific antibodies with human immunodeficiency virus-neutralizing activity SO JOURNAL OF VIROLOGY LA English DT Article ID HIV-1 CORECEPTOR ACTIVITY; CHEMOKINE RECEPTORS; ENTRY INHIBITORS; GP120 BINDING; TROPIC HIV-1; CCR5; TYPE-1; INFECTION; FUSION; GENE AB CCR5 is the major coreceptor for human immunodeficiency virus (HIV) infection. The murine monoclonal antibody (NMb) 2D7, which recognizes a conformation-dependent epitope in the second extracellular loop of CCR5, is one of the most potent inhibitors of R5 virus cell entry. However, attempts to humanize 2D7 for in vivo human use have been unsuccessful so far. A filamentous phage library expressing random peptides was used to identify a peptide mimitope that is recognized by MAb 2D7. A synthetic peptide containing this sequence (2D7-2SK) bound to MAb 2D7 with high affinity and reversed its HIV type 1 (HIV-1) fusion inhibitory activity. The peptide contains sequence homologies to two distal regions of the second extracellular loop of human CCR5, both of which are required for MAb 2D7 binding. Rabbit anti-2D7-mimitope antibodies competed with MAb 2D7 for binding to the 2D7-2SK peptide in Biacore biosensor testing. Importantly, the rabbit anti-2D7-2SK antibodies bound to CCR5 on cells and specifically inhibited R5 (but not X4) envelope-mediated syncytium formation. These antibodies also neutralized infection of human peripheral blood mononuclear cells with R5 HIV isolates comparably to MAb 2D7. In summary, we have identified a novel peptide that closely mimics the MAb 2D7 epitope on CCR5. This peptide could be included as a potential vaccine candidate or to isolate 2D7-like human antibodies as entry inhibitors for R5 viruses. C1 US FDA, Div Viral Prod, CBER, Bethesda, MD 20892 USA. US FDA, Div Hematol, CBER, Bethesda, MD 20892 USA. RP Golding, H (reprint author), US FDA, Div Viral Prod, CBER, Bethesda, MD 20892 USA. EM goldingh@cber.FDA.gov NR 23 TC 32 Z9 32 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUN PY 2005 VL 79 IS 11 BP 6791 EP 6800 DI 10.1128/JVI.79.11.6791-6800.2005 PG 10 WC Virology SC Virology GA 925WY UT WOS:000229085400023 PM 15890918 ER PT J AU Yadava, G Rudin, S Bednarek, D Hoffmann, K Kyprianou, I AF Yadava, G Rudin, S Bednarek, D Hoffmann, K Kyprianou, I TI A total-imaging-systern generalized performance comparison of an x-ray image intensifier and a microangiographic system in neurovascular angiography: Effect of focal spot and scatter SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 24-28, 2005 CL Seattle, WA SP Amer Assoc Physicists Med C1 SUNY Buffalo, Toshiba Stroke Res Ctr, Dept Phys, Buffalo, NY 14260 USA. US FDA, NIBIB, Lab Assessment Med Imaging Syst, Rockville, MD 20857 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2005 VL 32 IS 6 BP 2080 EP 2081 DI 10.1118/1.1998339 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 937EY UT WOS:000229908601248 ER PT J AU Thomas, J Romanyukha, A Chakrabarti, K Kaczmarek, R AF Thomas, J Romanyukha, A Chakrabarti, K Kaczmarek, R TI Impact of room illuminance on black level luminance and contrast detection for off-axis viewing on high resolution normal and high-bright flat panel displays SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 24-28, 2005 CL Seattle, WA SP Amer Assoc Physicists Med C1 USUHS, Potomac, MD USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. ODE, CDRH, FDA, Rockville, MD USA. Ctr Devices & Rad Hlth, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2005 VL 32 IS 6 BP 2110 EP 2111 DI 10.1118/1.1998457 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 937EY UT WOS:000229908601366 ER PT J AU Myers, K Gagne, R Badano, A Gallas, B Kyprianou, I AF Myers, K Gagne, R Badano, A Gallas, B Kyprianou, I TI Non-Fourier concepts in image quality SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 24-28, 2005 CL Seattle, WA SP Amer Assoc Physicists Med C1 US FDA, CDRH, Rockville, MD 20857 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2005 VL 32 IS 6 BP 2135 EP 2135 DI 10.1118/1.1998555 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 937EY UT WOS:000229908601462 ER PT J AU Chakrabarti, K Lin, R Schiller, NI Wang, YP Koubi, D Fan, YX Rudkin, BB Johnson, GR Schiller, MR AF Chakrabarti, K Lin, R Schiller, NI Wang, YP Koubi, D Fan, YX Rudkin, BB Johnson, GR Schiller, MR TI Critical role for kalirin in nerve growth factor signaling through TrkA SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID NUCLEOTIDE-EXCHANGE FACTOR; RECEPTOR TYROSINE KINASE; PLECKSTRIN HOMOLOGY DOMAINS; NEURITE OUTGROWTH; PC12 CELLS; INSULIN-RECEPTOR; NEUROTROPHIN RECEPTORS; REGULATED KINASE; DBL FAMILY; G-PROTEIN AB Kalirin is a multidomain guanine nucleotide exchange factor (GEF) that activates Rho proteins, inducing cytoskeletal rearrangement in neurons. Although much is known about the effects of Kalirin on Rho GTPases and neuronal morphology, little is known about the association of Kalirin with the receptor/signaling systems that affect neuronal morphology. Our experiments demonstrate that Kalirin binds to and colocalizes with the TrkA neurotrophin receptor in neurons. In PC12 cells, inhibition of Kalirin expression using antisense RNA decreased nerve growth factor (NGF)-induced TrkA autophosphorylation and process extension. Kalirin overexpression potentiated neurotrophin-stimulated TrkA autophosphorylation and neurite outgrowth in PC12 cells at a low concentration of NGF. Furthermore, elevated Kalirin expression resulted in catalytic activation of TrkA, as demonstrated by in vitro kinase assays and increased NGF-stimulated cellular activation of Rac, Mek, and CREB. Domain mapping demonstrated that the N-terminal Kalirin pleckstrin homology domain mediates the interaction with TrkA. The effects of Kalirin on TrkA provide a molecular basis for the requirement of Kalirin in process extension from PC12 cells and for previously observed effects on axonal extension and dendritic maintenance. The interaction of TrkA with the pleckstrin homology domain of Kalirin may be one example of a general mechanism whereby receptor/Rho GEF pairings play an important role in receptor tyrosine kinase activation and signal transduction. C1 Univ Connecticut, Ctr Hlth, Dept Neurosci, Farmington, CT 06030 USA. Ecole Normale Super Lyon, CNRS, UMR 5161, INRA,U1237,Lab Biol Mol Cellule,IFR 128, F-69364 Lyon, France. US FDA, Ctr Biol Evaluat & Res, Div Therapeut Prot, Bethesda, MD 20892 USA. RP Schiller, MR (reprint author), Univ Connecticut, Ctr Hlth, Dept Neurosci, 263 Farmington Ave, Farmington, CT 06030 USA. EM schiller@nso.uchc.edu FU NIDDK NIH HHS [R56 DK032948, R01 DK032948, DK32948]; NIMH NIH HHS [MH65567, K01 MH065567] NR 59 TC 32 Z9 32 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JUN PY 2005 VL 25 IS 12 BP 5106 EP 5118 DI 10.1128/MCB.25.12.5106-5118.2005 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 933DZ UT WOS:000229605900027 PM 15923627 ER PT J AU Nayak, R Stewart, TM Nawaz, MS AF Nayak, R Stewart, TM Nawaz, MS TI PCR identification of Campylobacter coli and Campylobacter jejuni by partial sequencing of virulence genes SO MOLECULAR AND CELLULAR PROBES LA English DT Article DE Campylobacter spp.; multiplex PCR; virulence genes ID POLYMERASE-CHAIN-REACTION; GUILLAIN-BARRE-SYNDROME; ASSAY; DIFFERENTIATION; INFECTION AB The objective of this study was to utilize a multiplex PCR assay for concurrent detection of Campylobacter spp. and C. coli or C. jejuni, using probes derived from genes cadF and ceuE and an undefined virulence gene. A total of 97 Campylobacter strains, isolated from turkey litter (n = 74). chicken livers (n = 15) and clinical (n = 8) samples, were speciated using the PCR-based assay. PCR amplification of the isolates identified a 400-bp cadF gene, conserved in Campylobacter species, an 894-bp ceuE gene, specific for C. coli, and a 160-bp oxidoreductase gene. specific for C. jejuni. The similar to 35 kDa cadF adhesion proteins allow Campylobacter to bind to the intestinal epithelial cells and the 37 kDa ceuE lipoproteins are involved in siderophore transport. Sequencing of the 160-bp undefined gene yielded a 67% protein identical match with a gene encoding an oxidoreductase subunit in C. jejuni. The specificity of the assay was validated on 36 non-Campylobacter strains (I I Gram-positive and 25 Gram-negative bacteria). The PCR assay identified 59% of turkey and 47% of chicken isolates as C. jejuni, and 41% of turkey and 53% of chicken isolates as C. coli. All human isolates were identified as C. jejuni. The specificity of this assay to detect C. coli or C. jejuni was 97%. C1 US FDA, Natl Ctr Toxicol Res, Dept Microbiol, Jefferson, AR 72079 USA. RP Nayak, R (reprint author), US FDA, Natl Ctr Toxicol Res, Dept Microbiol, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM rnayak@nctr.fda.gov NR 23 TC 27 Z9 28 U1 0 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 JUN PY 2005 VL 19 IS 3 BP 187 EP 193 DI 10.1016/j.mcp.2004.11.005 PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Cell Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Cell Biology GA 918CG UT WOS:000228515500006 PM 15797819 ER PT J AU Chen, S Zhao, SH McDermott, PF Schroeder, CM White, DG Meng, JH AF Chen, S Zhao, SH McDermott, PF Schroeder, CM White, DG Meng, JH TI A DNA microarray for identification of virulence and antimicrobial resistance genes in Salmonella serovars and Escherichia coli SO MOLECULAR AND CELLULAR PROBES LA English DT Article DE DNA microarray; Salmonella; E. coli; virulence; antimicrobial resistance ID PHAGE TYPE DT104; TYPHIMURIUM DT104; ANTIBIOTIC-RESISTANCE; MOLECULAR EPIDEMIOLOGY; KLEBSIELLA-PNEUMONIAE; MULTIPLEX PCR; ENTERICA; SEROTYPE; INTEGRONS; DISCOVERY AB Characterization of antimicrobial resistance and virulence gene profiles provides important information on the potential pathogenicity of bacteria. This information can be used to facilitate prompt and effective treatment of bacterial infections. We developed and tested a PCR-based microarray platform for detecting virulence and antimicrobial resistance genes in Salmonella serovars and Escherichia coli. Twelve Salmonella and. seven E. coli isolates were screened for the presence of 25 virulence and 23 antimicrobial resistance genes. All S. Typhimuriurn DT104 isolates harbored virulence plasmids. E. coli O157:H7 isolates possessed virulence genes typical of enterohemorrhagic E. coli (EHEC). whereas E. coli 0126 isolates contained virulence genes characteristic of enteropathogenic E. coli (SPEC) and E. coli O111, O78 and O147 isolates had virulence genes characteristic of enterotoxigenic E. coli (ETEC). Correlation between anti microbial resistance phenotype and genotype was observed for each isolate. The aadA, tetA, and sull genes were most commonly detected in bacteria resistant to streptomycin. tetracycline and sulfonamide, respectively. All isolates exhibiting resistance to third generation cephalosporins harbored the bla(CMY-2) and bla(TEM-1) genes. Microarray analysis is an effective method to rapidly screen Salmonella and E. Coli for multiple antimicrobial resistance and virulence genes. (c) 2005 Elsevier Ltd. All rights reserved. C1 Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA. US FDA, Ctr Vet Med, Res Off, Div Anim & Food Microbiol, Laurel, MD USA. RP Meng, JH (reprint author), Univ Maryland, Dept Nutr & Food Sci, 0112 Skinner Bldg, College Pk, MD 20742 USA. EM jmeng@umd.edu OI Chen, Sheng/0000-0003-3526-7808 NR 42 TC 48 Z9 52 U1 1 U2 11 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 JUN PY 2005 VL 19 IS 3 BP 195 EP 201 DI 10.1016/j.mcp.2004.11.008 PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Cell Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Cell Biology GA 918CG UT WOS:000228515500007 PM 15797820 ER PT J AU Achat-Mendes, C Ali, SF Itzhak, Y AF Achat-Mendes, C Ali, SF Itzhak, Y TI Differential effects of amphetamines-induced neurotoxicity on appetitive and aversive Pavlovian conditioning in mice SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE conditioned place preference (CPP); conditioned place aversion (CPA); dopamine; serotonin; associative learning; psychostimulants ID METHAMPHETAMINE-INDUCED NEUROTOXICITY; INDUCED DOPAMINERGIC NEUROTOXICITY; BRAIN-SEROTONIN NEURONS; MDMA ECSTASY USERS; NUCLEUS-ACCUMBENS; 3,4-METHYLENEDIOXYMETHAMPHETAMINE MDMA; PLACE PREFERENCE; COGNITIVE PERFORMANCE; PREFRONTAL CORTEX; METHYLENEDIOXYMETHAMPHETAMINE MDMA AB The abuse of substituted amphetamines such as methamphetamine ( METH) and 3,4-methylenedioxymethamphetamine (MDMA/ Ecstasy) can result in neurotoxicity, manifested as the depletion of dopamine (DA) and 5-hydroxytriptamine (5-HT; serotonin) axon terminal markers in humans and animal models. Human METH and MDMA users exhibit impairments in memory and executive functions, which may be a direct consequence of the neurotoxic potential of amphetamines. The objective of this study was to investigate the influence of amphetamines-induced neurotoxicity on Pavlovian learning. Using mouse models of selective DA neurotoxicity ( METH; 5 mg/kg x 3), selective 5-HT neurotoxicity ( fenfluramine /FEN; 25 mg/kg x 4) and dual DA and 5-HT neurotoxicity (MDMA; 15 mg/ kg x 4), appetitive and aversive conditioning were investigated. Dopaminergic neurotoxicity significantly impaired METH and cocaine conditioned place preference (CPP), but had no effect on LiCl-induced conditioned place aversion (CPA). In contrast, serotonergic neurotoxicity significantly enhanced CPP, and had no effect on CPA. Dual dopaminergic/serotonergic neurotoxicity had no apparent effect on CPP; however, CPA was significantly attenuated. Postmortem analysis revealed that significantly diminished levels of DA and 5-HT markers persisted in the striatum, frontal cortex, hippocampus, and amygdala. These findings suggest that amphetamines-induced dopaminergic and serotonergic neurotoxicity exert opposing influences on the affective state produced by subsequent drug reward, while dual dopaminergic/serotonergic neurotoxicity impairs associative learning of aversive conditioning. Furthermore, results revealed that amphetamines-induced DA and 5-HT neurotoxicity modulates appetitive Pavlovian conditioning similar to other DA and 5-HT neurotoxins. Modulation of Pavlovian conditioning by amphetamines-induced neurotoxicity may be relevant to compulsive drug-seeking behavior in METH and MDMA abusers. C1 Univ Miami, Sch Med, Dept Psychiat & Behav Sci R629, Miami, FL 33136 USA. Univ Miami, Sch Med, Program Neurosci, Miami, FL 33136 USA. US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. RP Itzhak, Y (reprint author), Univ Miami, Sch Med, Dept Psychiat & Behav Sci R629, Gautier Bldg Room 503,1011 NW 15th St, Miami, FL 33136 USA. EM yitzhak@med.miami.edu FU NIDA NIH HHS [R01DA12867] NR 59 TC 29 Z9 30 U1 2 U2 9 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD JUN PY 2005 VL 30 IS 6 BP 1128 EP 1137 DI 10.1038/sj.npp.1300675 PG 10 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 928UQ UT WOS:000229297600011 PM 15688084 ER PT J AU Cohen, MH Johnson, JR Wang, YC Sridhara, R Pazdur, R AF Cohen, MH Johnson, JR Wang, YC Sridhara, R Pazdur, R TI FDA drug approval summary: Pemetrexed for injection (Alimta((R))) for the treatment of non-small cell lung cancer SO ONCOLOGIST LA English DT Article DE pemetrexed for injection; Alimta((R)); non-small cell lung cancer, metastatic; second-line treatment ID PHASE-III TRIAL; CHEMOTHERAPY; DOCETAXEL AB On August 19, 2004, pemetrexed for injection (Alimtao((R)); Eli Lilly and Company, Indianapolis, IN, http:Hwww. lilly.com) received accelerated approval as monotherapy for the treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) who had received prior chemotherapy. Approval was primarily based on a single, controlled, unblinded trial. Five hundred seventy-one protocol-eligible patients were randomized to receive either pemetrexed or docetaxel (Taxotere((R)); Aventis Pharmaceuticals Inc., Bridgewater, NJ, http://www.aventispharmaus.com). The primary efficacy end point was overall survival. The median survival times were 83 months in the pemetrexed arm and 7.9 months in the docetaxel arm. Neither superiority nor noninferiority for overall survival could be demonstrated, the latter because a reliable and consistent survival effect of docetaxell could not be estimated and because of significant crossover of pemetrexed-treated patients to docetaxel after tumor progression. Comparable response rates, 9.1% for pemetrexed and 8.8% for docetaxel, times to progressive disease, and progression-free survival times supported the conclusion that an effect of pemetrexed on survival was reasonably likely, however. In addition, pemetrexed was felt to have a more favorable safety profile than docetaxel. Of greatest importance, pemetrexed caused significantly less neutropenia, febrile neutropenia, neutropenic infections, and need for granulocyte/macrophage colony-stimulating factors. C1 US FDA, Div Oncol Drug Prod, Ctr Drug Evaluat Res, Rockville, MD 20857 USA. RP Cohen, MH (reprint author), US FDA, Div Oncol Drug Prod, Ctr Drug Evaluat Res, HFD-150 5600 Fishers Lane, Rockville, MD 20857 USA. EM cohenma@cder.fda.gov NR 5 TC 56 Z9 63 U1 0 U2 2 PU ALPHAMED PRESS PI MIAMISBURG PA ONE PRESTIGE PLACE, STE 290, MIAMISBURG, OH 45342-3758 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PD JUN-JUL PY 2005 VL 10 IS 6 BP 363 EP 368 DI 10.1634/theoncologist.10-6-363 PG 6 WC Oncology SC Oncology GA 945GB UT WOS:000230489900001 PM 15967829 ER PT J AU Adkins, S Chellemi, D Annamalai, M Baker, C AF Adkins, S. Chellemi, D. Annamalai, M. Baker, C. TI Colombian datura virus diagnosed in Brugmansia spp. in Florida SO PHYTOPATHOLOGY LA English DT Meeting Abstract C1 [Adkins, S.; Chellemi, D.] USDA ARS, Ft Pierce, FL 34945 USA. [Annamalai, M.; Baker, C.] FDACS DPI, Gainesville, FL 32614 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER PHYTOPATHOLOGICAL SOC PI ST PAUL PA 3340 PILOT KNOB ROAD, ST PAUL, MN 55121 USA SN 0031-949X J9 PHYTOPATHOLOGY JI Phytopathology PD JUN PY 2005 VL 95 IS 6 SU S BP S2 EP S2 PG 1 WC Plant Sciences SC Plant Sciences GA V44GO UT WOS:000202991400010 ER PT J AU Irey, M Adkins, S Baker, C AF Irey, M. Adkins, S. Baker, C. TI First report of a virus infection of Ammi majus in Florida SO PHYTOPATHOLOGY LA English DT Meeting Abstract C1 [Irey, M.; Adkins, S.] USDA ARS, USHRL, Ft Pierce, FL USA. [Baker, C.] FDACS DPI, Gainesville, FL USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER PHYTOPATHOLOGICAL SOC PI ST PAUL PA 3340 PILOT KNOB ROAD, ST PAUL, MN 55121 USA SN 0031-949X J9 PHYTOPATHOLOGY JI Phytopathology PD JUN PY 2005 VL 95 IS 6 SU S BP S46 EP S46 PG 1 WC Plant Sciences SC Plant Sciences GA V44GO UT WOS:000202991400283 ER PT J AU Boykins, RA Buehler, PW Jia, YP Venable, R Alayash, AI AF Boykins, RA Buehler, PW Jia, YP Venable, R Alayash, AI TI O-raffinose crosslinked hemoglobin lacks site-specific chemistry in the central cavity: Structural and functional consequences of beta 93Cys modification SO PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS LA English DT Article DE O-raffinose; hemoglobin; blood substitute; mass spectrometry; crosslinking ID POLYMERIZED PYRIDOXYLATED HEMOGLOBIN; OXYGEN CARRIERS; ALLOSTERIC REGULATION; BOVINE HEMOGLOBIN; ADULT HEMOGLOBIN; PROTEIN; HYDRATION; BINDING; WATER; POLYOXYETHYLENE AB Reacting human deoxyHbA(0) with oxidized raffinose (O-raffinose), a trisaccharide, results in a low oxygen affinity "blood substitute," stabilized in a noncooperative T-conformation and possesses readily oxidizable rhombic heme. In this study, we fractionated the O-raffinose-modified HbA(0) heterogeneous polymer (O-R-PolyHbA(0)) into six distinct fractions with a molecular weight distribution ranging from 64 to similar to 600 kDa using size-exclusion chromatography (SEC). Oxygen equilibrium and kinetics binding parameters of all fractions were nearly identical, reflecting a lack of heterogeneity in ligand binding properties among O-R-PolyHbA(0), species (Hill coefficient n equal to 1.0). Several mass spectrometry techniques were used to evaluate undigested and digested HbA(0), O-R-PolyHbA(0), and O-R-PolyHbA(0) fractions. Proposed sites of intramolecular crosslinking (i.e., beta 1Lys82, beta 2Lys82, and beta 1Val1) were not found to be the predominant site of crosslinking within the central cavity. Intermolecular crosslinking with O-raffinose results in no discernible site of amino acids modifications with the exception of beta 93Cys and alpha 104Cys. Based on accessible surface area (ASA) calculations in intact deoxyHbA(0) slight conformational. changes are required to allow for the S on alpha 104Cys to be modified during the reaction with O-raffinose or its partially oxidized product(s). The stabilization of HbA(0) in the T-conformation may not be a direct correlate of O-raffinose induced changes, but an indirect consequence of changing hydration in the water-filled central cavity and/or the distal heme pocket leading in the latter case to accelerated iron oxidation. Structural data presented here when taken together with the oxidative instability of O-R-PolyHbA(0) may provide some basis for the reported toxicity of this oxygen carrier. Published 2005 Wiley-Liss, Inc.* C1 US FDA, Ctr Biol Evaluat & Res, Lab Biochem & Vasc Biol, Div Hematol, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Biophys Lab, Div Bacterial Parasit & Allergen Prod, Bethesda, MD 20892 USA. RP Alayash, AI (reprint author), US FDA, Ctr Biol Evaluat & Res, Lab Biochem & Vasc Biol, Div Hematol, 8800 Rockville Pike,Bldg 29,Rm 112, Bethesda, MD 20892 USA. EM alayash@cber.fda.gov NR 53 TC 22 Z9 22 U1 1 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0887-3585 J9 PROTEINS JI Proteins PD JUN 1 PY 2005 VL 59 IS 4 BP 840 EP 855 DI 10.1002/prot.20453 PG 16 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 927UR UT WOS:000229226500017 PM 15822103 ER PT J AU Fang, GC Wu, YS Chen, JC Fu, PPC Chang, CN Chen, MH AF Fang, GC Wu, YS Chen, JC Fu, PPC Chang, CN Chen, MH TI Metallic elements study on fine and coarse particulates during daytime and nighttime periods at a traffic sampling site SO SCIENCE OF THE TOTAL ENVIRONMENT LA English DT Article DE coarse particulate; daytime; fine particulate; nighttime; traffic; versatile air pollutant system ID CENTRAL TAIWAN; SIZE DISTRIBUTIONS; TRACE-METALS; PM10; MATTER; PM2.5; PARTICLES; URBAN; TAICHUNG; AEROSOLS AB Fine (PM2.5) and coarse (PM2.5-10) particulates were collected simultaneously by using a versatile air pollutant system at a traffic sampling site during daytime and nighttime sampling periods during August 2003 to March 2004. A flame atomic absorption spectrophotometer coupled with hollow cathode lamps were used for chemical analysis. Enrichment factor and principal component analysis were used to compare chemical components and to find the possible emission sources at this traffic sampling site. The variation of metallic element concentrations on fine and coarse particulates during daytime and nighttime was also discussed in this study. Soil dust, traffic exhaust, marine salt and anthropogenic activities were the major pollutant sources at the traffic sampling site in central Taiwan. (c) 2004 Elsevier B.V. All rights reserved. C1 Hungkuang Univ, Dept Environm Engn, Taichung 433, Taiwan. Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. Tunghai Univ, Dept Environm Sci, Taichung 407, Taiwan. RP Fang, GC (reprint author), Hungkuang Univ, Dept Environm Engn, Taichung 433, Taiwan. EM gcfang@sunrise.hk.edu.tw NR 22 TC 1 Z9 1 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0048-9697 J9 SCI TOTAL ENVIRON JI Sci. Total Environ. PD JUN 1 PY 2005 VL 345 IS 1-3 BP 61 EP 68 DI 10.1016/j.scitotenv.2004.10.020 PG 8 WC Environmental Sciences SC Environmental Sciences & Ecology GA 942BO UT WOS:000230258100007 PM 15919528 ER PT J AU Yang, AX Mejido, J Luo, YQ Zeng, XM Schwartz, C Wu, TX Thies, RS Bhattacharya, B Han, J Freed, B Rao, M Puri, RK AF Yang, AX Mejido, J Luo, YQ Zeng, XM Schwartz, C Wu, TX Thies, RS Bhattacharya, B Han, J Freed, B Rao, M Puri, RK TI Development of a focused microarray to assess human embryonic stem cell differentiation SO STEM CELLS AND DEVELOPMENT LA English DT Article ID GENE-EXPRESSION; MOLECULAR SIGNATURE; GROWTH; LINES AB Human embryonic stem cells (hESC) must be differentiated before clinical use. In addition, the extent of contamination of undifferentiated cells and the efficiency of differentiation must also be assessed prior to clinical application. In this manuscript, we describe the development of a focused microarray that may be used to discriminate between hESC and their differentiated progeny. This array contains 755 genes including embryonic stem cell markers as well as markers of differentiation into neural, mesodermal, and endodermal phenotypes. In addition, we have included candidate genes belonging to families of cytokines, chemokines, receptors, signaling pathways, and homeodomain proteins that are likely to be important in the process of differentiation. Testing and validation of the focused array was performed using RNA from hESC, human embryoid body ( hEB) outgrowths, and a human embryonal carcinoma ( hEC) cell line. We have compared gene expression with negative background, GAPDH, beta-actin positive controls, and human universal RNA ( hURNA), showing that such an array can rapidly distinguish between undifferentiated and differentiated hESC-derived cell populations. We expect that the described array will be extremely useful in evaluating the extent of differentiation and the state of the hESC-derived population utilized for therapeutic purposes. C1 US FDA, Lab Mol & Tumor Biol, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. NIA, Neurosci Lab, Gerontol Res Ctr, Baltimore, MD 21224 USA. Natl Inst Drug Abuse, Cellular Neurobiol Branch, Baltimore, MD 21224 USA. Natl Inst Dent & Craniofacial Res, Biostat Core Unit, NIH, Bethesda, MD 20892 USA. Geron Corp, Menlo Pk, CA 94025 USA. Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21218 USA. RP Puri, RK (reprint author), US FDA, Lab Mol & Tumor Biol, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, NIH Bldg 29B,Room 2NN20,29 Lincoln Dr, Bethesda, MD 20892 USA. EM puri@cber.fda.gov NR 14 TC 21 Z9 22 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1547-3287 J9 STEM CELLS DEV JI Stem Cells Dev. PD JUN PY 2005 VL 14 IS 3 BP 270 EP 284 DI 10.1089/scd.2005.14.270 PG 15 WC Cell & Tissue Engineering; Hematology; Medicine, Research & Experimental; Transplantation SC Cell Biology; Hematology; Research & Experimental Medicine; Transplantation GA 940QI UT WOS:000230158600006 PM 15969622 ER PT J AU Haddad, S Leitman, SF Wesley, RA Cecco, S Yau, YY Starling, J Rehak, NN Bolan, CD AF Haddad, S Leitman, SF Wesley, RA Cecco, S Yau, YY Starling, J Rehak, NN Bolan, CD TI Placebo-controlled study of intravenous magnesium supplementation during large-volume leukapheresis in healthy allogeneic donors SO TRANSFUSION LA English DT Article ID IONIZED MAGNESIUM; CALCIUM; CITRATE; PLATELETPHERESIS; DEFICIENCY; SECRETION; RAT AB Background: Marked decreases in ionized magnesium (iMg) levels occur during large-volume leukapheresis (LVL); however, the effect of intravenous (IV) magnesium supplementation in this setting has not been carefully studied. Study Design and Methods: Thirty healthy allogeneic peripheral blood progenitor cell donors receiving citrate anticoagulant with IV calcium prophylaxis were randomized to receive either IV magnesium (0.2 mg Mg per mL acid citrate dextrose-A) or placebo during LVL, with a double-blind design. Results: Thirty subjects underwent 75 LVL pro- cedures, 37 with magnesium and 38 with placebo. Group characteristics were similar for sex, weight, citrate infusion rate (1.36 mg/kg/min vs. 1.37 mg/kg/min), and volume processed (16 L vs. 17 L). Serum iMg levels remained within the reference range with magnesium supplementation, but decreased 39 +/- 11 percent below baseline (p < 10(-10)) after placebo, with greater decreases after consecutive procedures. Subjects receiving magnesium had more vigorous parathyroid hormone responses and higher glucose levels and also tended to have higher serum potassium and ionized calcium levels. Mild paresthesias, coldness, and nausea occurred in 28, 20, and 7 percent of donors, respectively, with no significant differences between groups. Severe symptoms (chest tightness) occurred in only one subject receiving placebo. Conclusion: IV magnesium supplementation exerts a significant impact on serum magnesium levels, but does not reduce the frequency or severity of the relatively mild citrate-related effects observed in LVL performed with continuous IV calcium prophylaxis. C1 NIH, Warren Grant Magnuson Clin Ctr, Dept Transfus Med, Bethesda, MD 20892 USA. NIH, Warren Grant Magnuson Clin Ctr, Biostat Serv, Off Director, Bethesda, MD 20892 USA. NIH, Warren Grant Magnuson Clin Ctr, Dept Lab Med, Bethesda, MD 20892 USA. NIH, Warren Grant Magnuson Clin Ctr, Dept Pharm, Bethesda, MD 20892 USA. Walter Reed Army Inst Res, Silver Spring, MD USA. RP Haddad, S (reprint author), US FDA, Rockville, MD 20857 USA. EM salim.haddad@Fda.hhs.gov NR 23 TC 12 Z9 12 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD JUN PY 2005 VL 45 IS 6 BP 934 EP 944 DI 10.1111/j.1537-2995.2005.04312.x PG 11 WC Hematology SC Hematology GA 927TW UT WOS:000229224400016 PM 15934992 ER PT J AU Wu, CG Mason, B Jong, J Erdman, D McKernan, L Oakley, M Soucie, M Evatt, B Yu, MYW AF Wu, CG Mason, B Jong, J Erdman, D McKernan, L Oakley, M Soucie, M Evatt, B Yu, MYW TI Parvovirus B19 transmission by a high-purity factor VIII concentrate SO TRANSFUSION LA English DT Article ID PLASMA POOLS; BLOOD-PRODUCTS; DNA; INFECTION; HEAT; PCR; IDENTIFICATION; FRACTIONATION; ORGANIZATION; TECHNOLOGY AB Background: Parvovirus B19 (B19) is known to cause a variety of human diseases in susceptible individuals by close contact via the respiratory route or by transfusion of contaminated blood or blood products. In this study, whether a case of B19 transmission was causally related to the infusion of implicated lots of a solvent/detergent (S/D)-treated, immunoaffinity-purified factor VIII concentrate (antihemophilic factor [human][AHF]) was investigated. Study Design and Methods: Anti-B19 (both immunoglobulin M [IgM] and immunoglobulin G [IgG]) and B19 DNA (by a nucleic acid testing [NAT] procedure) were assayed in two implicated product lots, a plasma pool, and a recipient's serum sample. Analysis of the partial B19 sequences obtained from sequencing clones or direct sequencing of the samples was performed. Results: Only one of the two implicated lots was B19 DNA-positive. It contained 1.3 x 10(3) genome equivalents (geq or international units [IU]) per mL. The negative lot was derived from plasma screened for B19 DNA by NAT in a minipool format to exclude high-titer donations, whereas the positive lot was mostly from unscreened plasma. This high-purity AHF product had no detectable anti-B19 IgG. A 4-week postinfusion serum sample from a recipient, who received both lots and became ill, was positive for the presence of B19 antibodies (both IgM and IgG) as well as B19 DNA. The B19 sequences from the positive lot, its plasma pool, and the recipient's serum sample were closely related. Conclusion: These findings and the recipient's clinical history support a causal relationship between the implicated AHF product and B19 infection in this recipient. The seronegative patient became infected after receiving 2 x 10(4) IU (or geq) of B19 DNA, which was present in this S/D-treated, high-purity AHF product. C1 US FDA, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20852 USA. Ctr Dis Control & Prevent, Atlanta, GA USA. Dartmouth Hitchcock Hemophilia Program, Lebanon, NH USA. RP Yu, MYW (reprint author), US FDA, Div Hematol, Ctr Biol Evaluat & Res, HFM-345,Room 303,29 Lincoln Dr, Bethesda, MD 20852 USA. EM yu@cber.fda.gov NR 36 TC 41 Z9 47 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD JUN PY 2005 VL 45 IS 6 BP 1003 EP 1010 DI 10.1111/j.1537-2995.2005.04387.x PG 8 WC Hematology SC Hematology GA 927TW UT WOS:000229224400024 PM 15935000 ER PT J AU Carter, CA Estrin, AJ AF Carter, CA Estrin, AJ TI Opening of China's trade, labour market reform and impact on rural wages SO WORLD ECONOMY LA English DT Article ID ACCESSION; ORGANIZATION; AGRICULTURE; MIGRATION; PRODUCTIVITY; UNEMPLOYMENT C1 US FDA, Rockville, MD 20857 USA. NR 25 TC 0 Z9 0 U1 0 U2 2 PU BLACKWELL PUBL LTD PI OXFORD PA 108 COWLEY RD, OXFORD OX4 1JF, OXON, ENGLAND SN 0378-5920 J9 WORLD ECON JI World Econ. PD JUN PY 2005 VL 28 IS 6 BP 823 EP 839 DI 10.1111/j.1467-9701.2005.00708.x PG 17 WC Business, Finance; Economics; International Relations SC Business & Economics; International Relations GA 934IC UT WOS:000229701500004 ER PT J AU Song, KM Rabin, RL Hill, BJ De Rosa, SC Perfetto, SP Zhang, HH Foley, JF Reiner, JS Liu, J Mattapallil, JJ Douek, DC Roederer, M Farber, JM AF Song, KM Rabin, RL Hill, BJ De Rosa, SC Perfetto, SP Zhang, HH Foley, JF Reiner, JS Liu, J Mattapallil, JJ Douek, DC Roederer, M Farber, JM TI Characterization of subsets of CD4(+) memory T cells reveals early branched pathways of T cell differentiation in humans SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE chemokines; immunologic memory; Th1/Th2 cells ID CHEMOKINE RECEPTOR EXPRESSION; CYTOKINE MESSENGER-RNA; FLOW-CYTOMETRY; L-SELECTIN; EFFECTOR; QUANTIFICATION; LYMPHOCYTES; GENERATION; DIVERSITY; IMMUNITY AB The pathways for differentiation of human CD4(+) T cells into functionally distinct subsets of memory cells in vivo are unknown. The identification of these subsets and pathways has clear implications for the design of vaccines and immune-targeted therapies. Here, we show that populations of apparently naive CD4(+) T cells express the chemokine receptors CXCR3 or CCR4 and demonstrate patterns of gene expression and functional responses characteristic of memory cells. The proliferation history and T cell receptor repertoire of these chemokine-receptor(+) cells suggest that they are very early memory CD4(+) T cells that have "rested down" before acquiring the phenotypes described for "central" or "effector" memory T cells. In addition, the chemokine-receptor(+) "naive" populations contain Th1 and Th2 cells, respectively, demonstrating that Th1/Th2 differentiation can occur very early in vivo in the absence of markers conventionally associated with memory cells. We localized ligands for CXCR3 and CCR4 to separate foci in T cell zones of tonsil, suggesting that the chemokine-receptor(+) subsets may be recruited and contribute to segregated, polarized microenvironments within lymphoid organs. Importantly, our data suggest that CD4(+) T cells do not differentiate according to a simple schema from naive CD45RO(+) noneffector/central memory &RARR; effector/effector memory cells. Rather, developmental pathways branch early on to yield effector/memory populations that are highly heterogeneous and multifunctional and have the potential to become stable resting cells. C1 NIH, Inflammat Biol Sect, Lab Mol Immunol, NIAID,Vaccine Res Ctr, Bethesda, MD 20892 USA. NIH, Sect Human Immunol, Vaccine Res Ctr, Bethesda, MD 20892 USA. NIH, Sect ImmunoTechnol, Vaccine Res Ctr, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Farber, JM (reprint author), NIH, Inflammat Biol Sect, Lab Mol Immunol, NIAID,Vaccine Res Ctr, 10 Ctr Dr,Room 11N-107, Bethesda, MD 20892 USA. EM jfarber@niaid.nih.gov RI Roederer, Mario/G-1887-2011 FU Intramural NIH HHS NR 26 TC 51 Z9 52 U1 1 U2 8 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 31 PY 2005 VL 102 IS 22 BP 7916 EP 7921 DI 10.1073/pnas.0409720102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 932CE UT WOS:000229531000026 PM 15905333 ER PT J AU Kamath, AT Fruth, UL Brennan, MJ Dobbelaer, R Hubrechts, P Ho, MM Mayner, RE Thole, J Walker, KB Liu, M Lambert, PH AF Kamath, AT Fruth, UL Brennan, MJ Dobbelaer, R Hubrechts, P Ho, MM Mayner, RE Thole, J Walker, KB Liu, M Lambert, PH TI New live mycobacterial vaccines: the Geneva consensus on essential steps towards clinical development SO VACCINE LA English DT Article DE Mycobacterium tuberculosis; vaccines; trials ID PANTOTHENATE AUXOTROPH; PUBLISHED LITERATURE; ENHANCED PROTECTION; BCG VACCINES; TUBERCULOSIS; VACCINATION; PREVENTION; VIRULENCE; ANTIGENS; EFFICACY AB As the disease caused by Mycobacterium tuberculosis continues to be a burden, which the world continues to suffer, there is a concerted effort to find new vaccines to combat this problem. Of the various vaccines strategies, one viable option is the development of live mycobacterial vaccines. A meeting with researchers, regulatory bodies, vaccines developers and manufactures was held to consider the challenges and progress, which has been achieved with live mycobacterial vaccines (either modified BCG or attenuated M. tuberculosis). Discussion led to the production of a consensus document of the proposed entry criteria for Phase I clinical trials of candidate live mycobacterial vaccines. The vaccine must be characterised thoroughly to prove identity and consistency, as clinical trial lots are prepared. In pre-clinical studies, greater protective efficacy as well as improved safety potential relative to BCG should be considered when assessing potential vaccine candidates. A standard way to measure the protective efficacy to facilitate comparison between vaccine candidates was suggested. Additional safety criteria and verification of attenuation must be considered for attenuated M. tuberculosis. Two non-reverting independent mutations are recommended for such vaccines. When entering Phase I trials, enrolment should be based upon an acceptable characterisation of the study population regarding mycobacterium status and exclude HIV+ individuals. BCG could be used as a comparator for blinding during the trials and to properly assess vaccine-specific adverse reactions, while assays are being developed to assess immunogenicity of vaccines. The proposed criteria suggested in this consensus document may facilitate the movement of the most promising vaccine candidates to the clinic and towards control of tuberculosis. © 2005 Elsevier Ltd. All rights reserved. C1 Univ Geneva, Dept Pathol & Immunol, Ctr Vaccinol & Neonatal Immunol, CH-1211 Geneva, Switzerland. WHO, Initiat Vaccine Res, CH-1211 Geneva, Switzerland. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. Sci Inst Publ Hlth, Brussels, Belgium. Statens Serum Inst, Qual Control Dept, DK-2300 Copenhagen, Denmark. Natl Inst Biol Stand & Controls, Div Bacteriol, Potters Bar EN6 3QG, Herts, England. Aeras Global TB Vaccine Fdn, Bethesda, MD USA. Anim Sci Grp, Div Infect Dis, Lelystad, Netherlands. Natl Inst Biol Stand & Controls, Div Immunobiol, Potters Bar EN6 3QG, Herts, England. Transgene SA, Strasbourg, France. RP Lambert, PH (reprint author), Univ Geneva, Dept Pathol & Immunol, Ctr Vaccinol & Neonatal Immunol, 1 Rue Michel Servet, CH-1211 Geneva, Switzerland. EM Paul.Lambert@medecine.unige.ch NR 21 TC 75 Z9 77 U1 0 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD MAY 31 PY 2005 VL 23 IS 29 BP 3753 EP 3761 DI 10.1016/j.vaccine.2005.03.001 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 931YT UT WOS:000229522100001 PM 15893612 ER PT J AU Miller, RA Walker, RD Carson, J Coles, M Coyne, R Dalsgaard, I Gieseker, C Hsu, HM Mathers, JJ Papapetropoulou, M Petty, B Teitzell, C Reimschuessel, R AF Miller, RA Walker, RD Carson, J Coles, M Coyne, R Dalsgaard, I Gieseker, C Hsu, HM Mathers, JJ Papapetropoulou, M Petty, B Teitzell, C Reimschuessel, R TI Standardization of a broth microdilution usceptibility testing method to determine minimum inhibitory concentrations of aquatic bacteria SO DISEASES OF AQUATIC ORGANISMS LA English DT Article DE minimum inhibitory concentration; broth microdilution; antimicrobial susceptibility testing; quality control; antibiotic ID DIFFUSION SUSCEPTIBILITY TESTS; FISH-PATHOGENIC BACTERIA; QUALITY-CONTROL LIMITS; AEROMONAS-SALMONICIDA; ANTIMICROBIAL AGENTS; OXOLINIC ACID; FLORFENICOL; PHARMACOKINETICS; CHLORAMPHENICOL; OXYTETRACYCLINE AB A multiple laboratory study was conducted in accordance with the standards established by the Clinical and Laboratory Standards Institute (CLSI), formerly the National Committee for Clinical Laboratory Standards (NCCLS), for the development of quality control (QC) ranges using dilution antimicrobial susceptibility testing methods for bacterial isolates from aquatic animal species. QC ranges were established for Escherichia coli ATCC 25922 and Aeromonas salmonicida subsp. salmonicida ATCC 33658 when testing at 22, 28 and 35 degrees C (E. coli only) for 10 different antimicrobial agents (ampicillin, enrofloxacin, erythromycin, florfenicol, flumequine, gentamicin, ormetoprim/sulfadimethoxine, oxolinic acid, oxytetracycline and trimethoprim/sulfamethoxazole). Minimum inhibitory concentration (MIC) QC ranges were determined using dry- and frozen-form 96-well plates and cation-adjusted Mueller-Hinton broth. These QC ranges were accepted by the CLSI/NCCLS Subcommittee on Veterinary Antimicrobial Susceptibility Testing in January 2004. This broth microdilution testing method represents the first standardized method for determining MICs of bacterial isolates whose preferred growth temperatures are below 35 degrees C. Methods and QC ranges defined in this study will enable aquatic animal disease researchers to reliably compare quantitative susceptibility testing data between laboratories, and will be used to ensure both precision and inter-laboratory harmonization. C1 US FDA, Ctr Vet Med, Res Off, Laurel, MD 20708 USA. Dept Primary Ind Water & Environm, Fish Hlth Unit, Prospect Launceston, Tas 7250, Australia. Univ Prince Edward Isl, Atlantic Vet Coll, Charlottetown, PE C1A 4P3, Canada. Dept Aquaculture, Fish Hlth Div, Inst Marine Res, N-5817 Bergen, Norway. Danish Inst Fisheries Res, Fish Dis Lab, DK-1870 Frederiksberg, Denmark. Univ Wisconsin, Wisconsin Vet Diagnost Lab, Madison, WI 53705 USA. Alpharma, Div Anim Hlth, Chicago Hts, IL 60411 USA. Univ Patras, Sch Med, Publ Hlth Lab, Rion 26500, Greece. Florida Dept Agr & Consumer Serv, Div Anim Ind, Bartow, FL 33830 USA. Washington State Univ, Washington Anim Dis Diagnost Lab, Pullman, WA 99164 USA. RP Miller, RA (reprint author), US FDA, Ctr Vet Med, Res Off, 8401 Muirkirk Rd, Laurel, MD 20708 USA. EM rmiller1@cvm.fda.gov NR 28 TC 27 Z9 30 U1 2 U2 7 PU INTER-RESEARCH PI OLDENDORF LUHE PA NORDBUNTE 23, D-21385 OLDENDORF LUHE, GERMANY SN 0177-5103 J9 DIS AQUAT ORGAN JI Dis. Aquat. Org. PD MAY 30 PY 2005 VL 64 IS 3 BP 211 EP 222 DI 10.3354/dao064211 PG 12 WC Fisheries; Veterinary Sciences SC Fisheries; Veterinary Sciences GA 947PH UT WOS:000230658000004 PM 15997819 ER PT J AU Rathore, D Nagarkatti, R Jani, D Chattopadhyay, R de la Vega, P Kumar, S McCutchan, TF AF Rathore, D Nagarkatti, R Jani, D Chattopadhyay, R de la Vega, P Kumar, S McCutchan, TF TI An immunologically cryptic epitope of Plasmodium falciparum circumsporozoite protein facilitates liver cell recognition and induces protective antibodies that block liver cell invasion SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MALARIA; VACCINE; GENE; HEPARIN; ANTIGEN; REGION; SPOROZOITES; HEPATOCYTES; RECEPTORS; INFECTION AB Circumsporozoite, a predominant surface protein, is involved in invasion of liver cells by Plasmodium sporozoites, which leads to malaria. We have previously reported that the amino terminus region ( amino acids 27 117) of P. falciparum circumsporozoite protein plays a critical role in the invasion of liver cells by the parasite. Here we show that invasion-blocking antibodies are induced by a polypeptide encoding these 91 amino acids, only when it is presented in the absence of the rest of the protein. This suggests that when present in the whole protein, the amino terminus remains immunologically cryptic. A single reactive epitope was identified and mapped to a stretch of 21 amino acids from position 93 to 113. The epitope is configurational in nature, since its recognition was affected by deleting as little as 3 amino acids from either end of the 21-residue peptide. Lysine 104, the only known polymorphic position in the epitope, affected its recognition by the antibodies, and its conversion to leucine in the protein led to a substantial loss of binding activity of the protein to the hepatocytes. This indicated that in the protein, the epitope serves as a binding ligand and facilitates the interaction between sporozoite and hepatic cells. When considered along with the observation that in its native state this motif is immunologically unresponsive, we suggest that hiding functional moieties of the protein from the immune system is an evasion strategy to preserve liver cell binding function and may be of importance in designing anti-sporozoite vaccines. C1 Virginia Polytech Inst & State Univ, Virginia Bioinformat Inst, Blacksburg, VA 24061 USA. NIAID, Growth & Dev Sect, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA. USN, Med Res Ctr, Malaria Program, Silver Spring, MD 20910 USA. US FDA, Div Emerging & Transfus Transmitted Dis, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP McCutchan, TF (reprint author), Virginia Polytech Inst & State Univ, Virginia Bioinformat Inst, Blacksburg, VA 24061 USA. EM Tmccutchan@niaid.nih.gov NR 28 TC 32 Z9 35 U1 0 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 27 PY 2005 VL 280 IS 21 BP 20524 EP 20529 DI 10.1074/jbc.M414254200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 927ZX UT WOS:000229242000046 PM 15781464 ER PT J AU LaPointe, NMA Governale, LA AF LaPointe, NMA Governale, LA TI Outpatient medication use in patients with atrial fibrillation SO CIRCULATION LA English DT Meeting Abstract CT 6th Scientific Forum on Quality of Care and Outcomes Research in Cardiovascular Disease and Stroke CY MAY 14-16, 2005 CL Washington, DC SP Amer Heart Assoc, Qual Care & Outcomes Res Interdiciplinary Working Grp, Councils Cardiovasc Nursing, Councils Cardiovasc Surg & Anesthesia, Councils Clin Cardiol, Councils Epidemiol & Prevent & Stroke, Amer Coll Cardiol Fdn, Ctr Dis Control & Prevent, Dept Vet Affairs C1 Duke Univ, Med Ctr, Durham, NC USA. US FDA, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY 24 PY 2005 VL 111 IS 20 MA P218 BP E353 EP E353 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 929AD UT WOS:000229313000235 ER PT J AU LaPointe, NMA Governale, LA Ricketts, R AF LaPointe, NMA Governale, LA Ricketts, R TI Trends in antiarrhythmic drug use in the ICD era SO CIRCULATION LA English DT Meeting Abstract CT 6th Scientific Forum on Quality of Care and Outcomes Research in Cardiovascular Disease and Stroke CY MAY 14-16, 2005 CL Washington, DC SP Amer Heart Assoc, Qual Care & Outcomes Res Interdiciplinary Working Grp, Councils Cardiovasc Nursing, Councils Cardiovasc Surg & Anesthesia, Councils Clin Cardiol, Councils Epidemiol & Prevent & Stroke, Amer Coll Cardiol Fdn, Ctr Dis Control & Prevent, Dept Vet Affairs C1 Duke Univ, Med Ctr, Durham, NC USA. US FDA, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY 24 PY 2005 VL 111 IS 20 BP E328 EP E328 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 929AD UT WOS:000229313000113 ER PT J AU Struble, K Murray, J Cheng, B Gegeny, T Miller, V Gulick, R AF Struble, K Murray, J Cheng, B Gegeny, T Miller, V Gulick, R TI Antiretroviral therapies for treatment-experienced patients: current status and research challenges SO AIDS LA English DT Review DE antiretroviral therapy; treatment experienced patients; salvage therapy; clinical trial design; HIV drug resistance; pharmacokinetic interactions ID HUMAN-IMMUNODEFICIENCY-VIRUS; STRUCTURED TREATMENT INTERRUPTION; PROTEASE INHIBITOR THERAPY; HIV-INFECTED PATIENTS; DRUG-RESISTANT HIV-1; SOCIETY-USA PANEL; VIROLOGICAL FAILURE; CONTROLLED-TRIAL; HIV-1-INFECTED INDIVIDUALS; RANDOMIZED TRIAL C1 George Washington Univ, Forum Collaborat HIV Res, Washington, DC 20037 USA. US FDA, Rockville, MD 20857 USA. Ctr AIDS, Hope & Remembrance Project, Houston, TX USA. Cornell Univ, New York, NY 14853 USA. RP Miller, V (reprint author), George Washington Univ, Forum Collaborat HIV Res, 2175 K St,NW Suite 700, Washington, DC 20037 USA. EM vmiller@gwu.edu NR 55 TC 39 Z9 40 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 MAY 20 PY 2005 VL 19 IS 8 BP 747 EP 756 DI 10.1097/01.aids.0000168968.34810.ca PG 10 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 930MM UT WOS:000229420100001 PM 15867488 ER PT J AU Anderson, CR Rupp, HS Wu, WH AF Anderson, CR Rupp, HS Wu, WH TI Complexities in tetracycline analysis - chemistry, matrix extraction, cleanup, and liquid chromatography SO JOURNAL OF CHROMATOGRAPHY A LA English DT Review DE tetracycline antibiotics; biological matrix extraction; chromatography ID SOLID-PHASE EXTRACTION; IONIZATION MASS-SPECTROMETRY; FLUORESCENCE DETECTION; ANIMAL-TISSUES; QUANTITATIVE-ANALYSIS; POSTCOLUMN DERIVATIZATION; METAL COMPLEXATION; CHEMICAL-ANALYSIS; THIN-LAYER; OXYTETRACYCLINE AB The extraction and cleanup of commonly used tetracyclines (oxytetracycline, tetracycline, chlortetracycline, and doxycycline) from sample matrix, and their subsequent determination via liquid chromatography can be problematic. Many manuscripts report on various challenges encountered when developing a method for tetracycline antibiotics determination. These complexities often result in less than perfect recoveries or chromatograms and are based on the underlying chemistry associated with tetracyclines. This review compiles, compares, and discusses the results and observations found in published methods, while focusing on chemical principles in order to increase the practicing chemist's understanding of TCs to aid him/her in developing useful analyses. Published by Elsevier B.V. C1 US FDA, Seafood Prod Res Ctr, Pacific Reg Lab NW, Bothell, WA 98021 USA. RP Anderson, CR (reprint author), US FDA, Seafood Prod Res Ctr, Pacific Reg Lab NW, 22201 23rd Dr SE, Bothell, WA 98021 USA. EM collin.anderson@fda.gov; heidi.rupp@fda.gov; cindy.wu@fda.gov NR 71 TC 119 Z9 125 U1 1 U2 28 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 MAY 20 PY 2005 VL 1075 IS 1-2 BP 23 EP 32 DI 10.1016/j.chroma.2005.04.013 PG 10 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 932JU UT WOS:000229550800002 PM 15974114 ER PT J AU Petricoin, EF Bichsel, VE Calvert, VS Espina, V Winters, M Young, L Belluco, C Trock, BJ Lippman, M Fishman, DA Sgroi, DC Munson, PJ Esserman, LJ Liotta, LA AF Petricoin, EF Bichsel, VE Calvert, VS Espina, V Winters, M Young, L Belluco, C Trock, BJ Lippman, M Fishman, DA Sgroi, DC Munson, PJ Esserman, LJ Liotta, LA TI Mapping molecular networks using proteomics: A vision for patient-tailored combination therapy SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID GROWTH-FACTOR RECEPTOR; CELL LUNG-CANCER; GASTROINTESTINAL STROMAL TUMORS; PROTEIN-INTERACTION NETWORKS; ACUTE LYMPHOBLASTIC-LEUKEMIA; TYROSINE KINASE; BREAST-CANCER; ACTIVATING MUTATIONS; SIGNAL-TRANSDUCTION; MASS-SPECTROMETRY AB Mapping tumor cell protein networks in vivo will be critical for realizing the promise of patient-tailored molecular therapy. Cancer can be defined as a dysregulation or hyperactivity in the network of intracellular and extracellular signaling cascades. These protein signaling circuits are the ultimate targets of molecular therapy. Each patient's tumor may be driven by a distinct series of molecular pathogenic defects. Thus, for any single molecular targeted therapy, only a subset of cancer patients may respond. Individualization of therapy, which tailors a therapeutic regimen to a tumor molecular portrait, may be the solution to this dilemma. Until recently, the field lacked the technology for molecular profiling at the genomic and proteomic level. Emerging proteomic technology, used concomitantly with genomic analysis, promises to meet this need and bring to reality the clinical adoption of molecular stratification. The activation state of kinase-driven signal networks contains important information relative to cancer pathogenesis and therapeutic target selection. Proteomic technology offers a means to quantify the state of kinase pathways, and provides post-translational phosphorylation data not obtainable by gene arrays. Case studies using clinical research specimens are provided to show the feasibility of generating the critical information needed to individualize therapy. Such technology can reveal potential new pathway interconnections, including differences between primary and metastatic lesions. We provide a vision for individualized combinatorial therapy based on proteomic mapping of phosphorylation end points in clinical tissue material. (c) 2005 by American Society of Clinical Oncology. C1 NCI, US FDA, Clin Prote Program, Off Cellular & Gene Therapy,CBER, Bethesda, MD 20892 USA. NCI, US FDA, Clin Prote Program, Pathol Lab,Ctr Canc Res,NIH, Bethesda, MD 20892 USA. NIH, Biostat Sect, Math & Stat Comp Lab, Ctr Informat Technol, Bethesda, MD 20892 USA. Johns Hopkins Univ, Dept Urol, Baltimore, MD USA. Univ Padua, Dept Oncol & Surg Sci, Padua, Italy. Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. NYU, Sch Med, Dept Obstet & Gynecol, New York, NY USA. Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. Univ Calif San Francisco, Dept Surg, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94143 USA. RP Petricoin, EF (reprint author), George Mason Univ, Ctr Appl Prote & Mol Med, 10900 Univ Blvd,MS 4E3, Manassas, VA 20110 USA. EM epetrico@gmu.edu OI belluco, claudio/0000-0001-5972-9574; Espina, Virginia/0000-0001-5080-5972 NR 59 TC 116 Z9 124 U1 1 U2 4 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2005 VL 23 IS 15 BP 3614 EP 3621 DI 10.1200/JCO.2005.02.509 PG 8 WC Oncology SC Oncology GA 929NI UT WOS:000229352400043 PM 15908672 ER PT J AU Zhao, SH Maurer, JJ Hubert, S De Villena, JF McDermott, PF Meng, JH Ayers, S English, L White, DG AF Zhao, SH Maurer, JJ Hubert, S De Villena, JF McDermott, PF Meng, JH Ayers, S English, L White, DG TI Antimicrobial susceptibility and molecular characterization of avian pathogenic Escherichia coli isolates SO VETERINARY MICROBIOLOGY LA English DT Article DE fluoroquinolones; DNA gyrase; efflux; antibiotic resistance; avian pathogenic Escherichia coli ID ORGANIC-SOLVENT TOLERANCE; FLUOROQUINOLONE RESISTANCE; POULTRY; CHICKENS; STRAINS; TURKEYS; COLIBACILLOSIS; MUTATIONS; GENES; DNA AB Ninety-five avian pathogenic Escherichia coli (APEC) isolates recovered from diagnosed cases of avian colibacillosis from North Georgia between 1996 and 2000 were serotyped and examined for typical virulence-factors, susceptibility to antimicrobials of human and veterinary significance, and genetic relatedness. Twenty different serotypes were identified, with O78 being the most common (12%). The majority of the avian E. coli isolates (60%), however, were non-typeable with standard O antisera. Eighty-four percent of isolates were PCR positive for the temperature-sensitive hemagglutinin (tsh) gene and 86% positive for the increased serum survival (iss) gene. Multiple antimicrobial-resistant phenotypes (&GE; 3 antimicrobials) were observed in 92% of E. coli isolates, with the majority of isolates displaying resistance to sulfamethoxazole (93%), tetracycline (87%). streptomycin (86%), gentamicin (69%), and nalidixic acid (59%). Fifty-six E. coli isolates displaying resistance to nalidixic acid were co-resistant to difloxacin (57%), enrofloxacin (16%), gatifloxacin (2%), and levofloxacin (2%). DNA sequencing revealed point mutations in gyrA (Ser83-Leu, Asp87-Tyr, Asp87-Gly, Asp87-Ala), gyrB (Glu466-Asp, Asp426-Thr), and parC (Ser80-Ile, Ser80-Arg). No mutations were observed in parE. Twelve of the quinolone-resistant E. coli isolates were tolerant to cyclohexane, a marker for upregulation of the acrAB multi-drug resistance efflux pump. Quinolone-resistant isolates were further genetically characterized via ribotyping. Twenty-two distinct ribogroups were identified, with 61% of isolates clustering into four major ribogroups, indicating that quinolone resistance has emerged among multiple avian pathogenic E. coli serogroups and chromosomal backgrounds. Published by Elsevier B.V. C1 US FDA, Res Off, Ctr Vet Med, Laurel, MD 20708 USA. Univ Georgia, Poultry Diagnost Res Ctr, Athens, GA USA. Univ Georgia, Poultry Diagnost Res Ctr, College Pk, MD USA. Univ Maryland, Dept Nutr & Food Sci, College Pk, MD USA. RP White, DG (reprint author), US FDA, Res Off, Ctr Vet Med, 8401 Muirkirk Rd, Laurel, MD 20708 USA. EM David.White@fda.gov NR 37 TC 60 Z9 62 U1 0 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1135 J9 VET MICROBIOL JI Vet. Microbiol. PD MAY 20 PY 2005 VL 107 IS 3-4 BP 215 EP 224 DI 10.1016/j.vetmic.2005.01.021 PG 10 WC Microbiology; Veterinary Sciences SC Microbiology; Veterinary Sciences GA 926ZE UT WOS:000229161400006 PM 15863280 ER PT J AU Moses-Kolko, EL Bogen, D Perel, J Bregar, A Uhl, K Levin, B Wisner, KL AF Moses-Kolko, EL Bogen, D Perel, J Bregar, A Uhl, K Levin, B Wisner, KL TI Neonatal signs after late in utero exposure to serotonin reuptake inhibitors - Literature review and implications for clinical applications SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Review ID PSYCHOTROPIC MEDICATION EXPOSURE; PAROXETINE WITHDRAWAL SYNDROME; MATERNAL USE; PROZAC TOXICITY; BIRTH OUTCOMES; PREGNANT-WOMEN; FLUOXETINE; DEPRESSION; SYMPTOMS; INFANTS AB Context A neonatal behavioral syndrome linked to in utero serotonin reuptake inhibitor (SRI) exposure during the last trimester of pregnancy has been identified. The US Food and Drug Administration (FDA) and drug manufacturers have recently agreed to a class labeling change for SRIs, which include selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs), to include information about potential adverse events in neonates exposed in utero. Integration of data about the neonatal behavioral syndrome into the management of pregnancy in women who take SRIs is a current challenge for physicians. Objectives To review evidence regarding the SRI-related neonatal syndrome and to help clinicians guide their patients in a risk-benefit decision-making process. Data Sources We searched MEDLINE (1966-February 2005) and PsycINFO (1974-February 2005). All articles related to neonatal signs after in utero SRI exposure were acquired, as well as unpublished data on this topic from the FDA advisory committee meeting of June 2004. References cited in case reports and studies were reviewed. Foreign - language literature was included and translated to English. Study Selection and Data Extraction Studies were included if they had clearly identified maternal SRI exposure for a minimum of the final trimester of pregnancy through delivery and assessed neonatal outcomes. We identified 13 case reports describing a total of 18 cases. Nine cohort studies met criteria. When not included in the published article, relative risks and 95% confidence intervals (CIS) were computed from raw data and summary risk ratios and 95% CIS were determined with Mantel-Haenszel estimates. Data Synthesis Compared with early gestational SRI exposure or no exposure, late SRI exposure carries an overall risk ratio of 3.0 (95% Cl, 2.0-4.4) for a neonatal behavioral syndrome. The most SRI-related neonatal case reports involved fluoxetine and paroxetine exposures. Neonates primarily display central nervous system, motor, respiratory, and gastrointestinal signs that are usually mild and disappear by 2 weeks of age. Medical management has consisted primarily of supportive care in special care nurseries. A severe syndrome that consists of seizures, dehydration, excessive weight loss, hyperpyrexia, or intubation is rare in term infants (1/313 quantifiable cases). There have been no reported neonatal deaths attributable to neonatal SRI exposure. Conclusions Available evidence indicates that in utero exposure to SRIs during the last trimester through delivery may result in a self-limited neonatal behavioral syndrome that can be managed with supportive care. The risks and benefits of discontinuing an SRI during pregnancy need to be carefully weighed for each individual patient. Development and validation of assessment methods and clinical management strategies are critical to advancing this research. C1 Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Sch Med, Dept Pediat, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Sch Med, Dept Clin Pharmacol, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Sch Med, Dept Obstet & Gynecol, Pittsburgh, PA 15213 USA. Princeton Univ, Princeton, NJ 08544 USA. US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Moses-Kolko, EL (reprint author), Univ Pittsburgh, Sch Med, Dept Psychiat, 3811 OHara St, Pittsburgh, PA 15213 USA. EM mosesel@upmc.edu FU NICHD NIH HHS [K12 HD43441-01]; NIMH NIH HHS [K23 MH064561, K23 MH 064561, MH 30915, MH R01 60335] NR 62 TC 276 Z9 280 U1 2 U2 20 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 MAY 18 PY 2005 VL 293 IS 19 BP 2372 EP 2383 DI 10.1001/jama.293.19.2372 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 926JX UT WOS:000229120600025 PM 15900008 ER PT J AU Zhou, KQ Yin, JJ Yu, LL AF Zhou, KQ Yin, JJ Yu, LL TI Phenolic acid, tocopherol and carotenoid compositions, and antioxidant functions of hard red winter wheat bran SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE ESR; wheat; bran; antioxidants; phenolic acid; tocopherol; carotenoid; chelating; radical ID DIFFERENT LOCATIONS; FREE-RADICALS; CEREAL PRODUCTS; EXTRACTS; FRACTIONS; GRAINS; ASSAYS AB An electron spin resonance (ESR) spectrometry study was conducted to examine the free radical scavenging properties of bran extracts of Alliance and Wichita wheat using hydroxyl radical (HO.), 2,2-diphenyl-1-picryhydrazyl radical (DPPH.), and superoxide radical anion (O-2(.-)) and their chelating capacities against Cu2+. Also reported is the radical cation 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS(.+)) scavenging activity, oxygen radical absorbing capacity (ORAC), and chelating property against Fe2+ of the bran extracts measured by the spectrophotometric methods. Significant radical scavenging and chelating capacities were detected in the bran extracts, along with significant levels of phenolic acids, tocopherols, and carotenoids. Ferulic acid, with a concentration range of 130.60-146.38 μ g/g, was the predominant phenolic acid in all of the tested bran samples and accounted for &SIM; 53-67% of total phenolic acids on a weight basis. Total tocopherol concentration ranged from 1.87 to 2.95 μ mol/100 g of bran, whereas total carotenoid level was 0.20-0.33,μ mol/ 100 g of bran. In addition, both wheat variety and growing conditions might significantly alter antioxidant properties and concentrations of beneficial components in wheat bran. C1 Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA. US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Yu, LL (reprint author), Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA. EM LY46@umail.umd.edu RI Yin, Jun Jie /E-5619-2014 NR 28 TC 62 Z9 63 U1 3 U2 19 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0021-8561 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD MAY 18 PY 2005 VL 53 IS 10 BP 3916 EP 3922 DI 10.1021/jf050117c PG 7 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 925JI UT WOS:000229049000025 PM 15884817 ER PT J AU Walker, RI AF Walker, RI TI Considerations for development of whole cell bacterial vaccines to prevent diarrheal diseases in children in developing countries SO VACCINE LA English DT Review DE diarrheal diseases; developing countries; bacterial vaccines ID ENTEROTOXIGENIC ESCHERICHIA-COLI; ORAL CHOLERA VACCINE; HEAT-LABILE ENTEROTOXIN; CAMPYLOBACTER-JEJUNI INFECTION; OUTER-MEMBRANE PROTEINS; GUILLAIN-BARRE-SYNDROME; SHIGELLA-SONNEI LIPOPOLYSACCHARIDE; IMMUNOGLOBULIN-A RESPONSE; MUCOSAL IMMUNE-RESPONSES; ENTERIC-COATED CAPSULES AB Enteric pathogens constitute a major pediatric threat in the developing world through their impact on morbidity and mortality, physical and cognitive development and cause and effect relationship with malnutrition. Although many bacterial pathogens can cause diarrheal diseases, a group of less than 10 including Shigella spp., enterotoxigenic Escherichia coli (ETEC), Vibrio cholerae, and possibly, Campylobacter jejuni account for a significant percentage of these diseases in developing countries. Rotavirus is also a major cause of diarrheal diseases. Vaccines against these agents offer a potentially effective control measure against these diseases, but safe, practical, and effective vaccines for many of these agents have yet to be realized. Many vaccine development approaches are under investigation, but the one that is currently most advanced and that has been most widely applied to enteric pathogens is the use of orally administered live or killed whole pathogen preparations. If inactivated, these vaccines will probably be administered as multiple doses with approximately 10(10) to 10(11) total particles per dose, but they are relatively safe for oral administration. Further, they may not require a buffer for delivery and can be stored in liquid formulations. Fewer doses may be required for some live attenuated pathogen vaccines, but a buffer will most likely be required for oral delivery and the product must be stored in a dried formulation. Also, safety becomes more of a concern with live pathogens depending on the degree of attenuation, host immunocompetence, and the total number and kinds of attenuated pathogens which may be present in a combined agent vaccine. Both live and killed whole pathogen vaccines can be immunogenic and have the possibility to serve as vectors for other antigens. Although many organisms and serotypes are clinically important, by exploiting antigenic cross reactivity and using some pathogen components as vectors for cloned antigens of other pathogens, it could be possible to induce immunity against major enteric pathogens/serotypes with < 10 whole pathogen components in a multi-agent vaccine. Safe and effective mucosal adjuvants may in the future be useful in whole pathogen vaccines, but they do not seem to be essential for immunization. Further, dietary supplements such as zinc, mixed routes of delivery and new regimens are under study which may in the future enhance further the effectiveness of the whole pathogen vaccines which now seem realizable in the near term. For this to happen, however, a coordinated and committed effort is necessary now to address the immunologic, regulatory, manufacturing, testing and implementation issues which will be involved in the realization of this important product to benefit children's health worldwide. Published by Elsevier Ltd. C1 US FDA, Ctr Biol Evaluat & Res, Div Bacterial Parasit & Allergen Prod, Rockville, MD 20851 USA. RP Walker, RI (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Bacterial Parasit & Allergen Prod, 1401 Rockville Pike HFM-425, Rockville, MD 20851 USA. EM walkerri@cber.fda.gov NR 182 TC 44 Z9 46 U1 0 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD MAY 16 PY 2005 VL 23 IS 26 BP 3369 EP 3385 DI 10.1016/j.vaccine.2004.12.029 PG 17 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 927LX UT WOS:000229196500002 PM 15837361 ER PT J AU Sander, LC Sharpless, KE Satterfield, MB Ihara, T Phinney, KW Yen, JH Wise, SA Gay, ML Lam, JW McCooeye, M Gardner, G Fraser, C Sturgeon, R Roman, M AF Sander, LC Sharpless, KE Satterfield, MB Ihara, T Phinney, KW Yen, JH Wise, SA Gay, ML Lam, JW McCooeye, M Gardner, G Fraser, C Sturgeon, R Roman, M TI Determination of ephedrine alkaloids in dietary supplement standard reference materials SO ANALYTICAL CHEMISTRY LA English DT Article ID PERFORMANCE LIQUID-CHROMATOGRAPHY; MASS-SPECTROMETRY; BOTANICALS; PRODUCTS; HUANG AB A suite of five ephedra-containing dietary supplement Standard Reference Materials (SRMs) has been issued by the National Institute of Standards and Technology (NIST) with certified values for ephedrine alkaloids, synephrine, caffeine, and selected toxic trace elements. The materials represent a variety of natural, extracted, and processed sample matrixes that provide different analytical challenges. The constituents have been determined by multiple independent methods with measurements performed by NIST and by three collaborating laboratories. The methods utilized different sample extraction and cleanup steps in addition to different instrumental analytical techniques and approaches to quantification. In addition, food-matrix proximates were determined by National Food Processor Association laboratories for one of the ephedra-containing SRMs. The SRMs are primarily intended for method validation and for use as control materials to support the analysis of dietary supplements and related botanical materials. C1 Natl Inst Stand & Technol, Div Analyt Chem, Gaithersburg, MD 20899 USA. Food & Drug Adm, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. Natl Res Council Canada, Inst Natl Measurement Stand, Ottawa, ON K1A 0R9, Canada. ChromaDex, Clearwater, FL 33706 USA. AIST, Natl Metrol Inst Japan, Tsukuba, Ibaraki, Japan. RP Sander, LC (reprint author), Natl Inst Stand & Technol, Div Analyt Chem, Gaithersburg, MD 20899 USA. EM lane.sander@nist.gov OI McCooeye, Margaret/0000-0001-9424-9111; Lam, Joseph/0000-0001-6402-0535; Sturgeon, Ralph/0000-0001-7304-3034; Sharpless, Katherine/0000-0001-6569-198X NR 20 TC 38 Z9 41 U1 2 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 MAY 15 PY 2005 VL 77 IS 10 BP 3101 EP 3112 DI 10.1021/ac0484530 PG 12 WC Chemistry, Analytical SC Chemistry GA 927PS UT WOS:000229206800010 PM 15889898 ER PT J AU Puri, S Joshi, BH Sarkar, C Mahapatra, AK Hussain, E Sinha, S AF Puri, S Joshi, BH Sarkar, C Mahapatra, AK Hussain, E Sinha, S TI Expression and structure of interleukin 4 receptors in primary meningeal tumors SO CANCER LA English DT Article DE human meningioma; interleukin 4 receptor alpha; interleukin 13 receptors alpha 1 and alpha 2; reverse transcriptase-polymerase chain reaction; quantitative real-time; polymerase chain reaction; in situ immunofluorescence assay ID ENDOTHELIAL GROWTH-FACTOR; CIRCULARLY PERMUTED INTERLEUKIN-4; EXOTOXIN FUSION PROTEIN; KAPOSIS-SARCOMA CELLS; COMMON GAMMA-CHAIN; HUMAN GLIOMA-CELLS; HUMAN BRAIN-TUMORS; PSEUDOMONAS EXOTOXIN; CHIMERIC PROTEIN; IL-4 RECEPTORS AB BACKGROUND. it was reported previously that malignant human tumors, like glioma and medulloblastoma, express high-density interleukin (IL-4) receptor mRNA and protein. Because IL-4 receptors (R) are sensitive targets for targeted therapeutics, knowledge of the expression of these receptors in other central nervous system tumors is of great interest. In this study, the authors examined the expression and subunit composition of IL-4R complex in primary human meningiomas. METHODS. Reverse transcription-polymerase chain reaction (RT-PCR) analysis for IL-13Rα 1, IL-4Rα and IL-2Rγ c was performed on total RNA extracted from 35 meningiomas and a normal human brain tissue sample. Results were confirmed in nine randomly selected tumors by quantitative real-time PCR and in situ immunofluorescence assay. RESULTS. Transcripts for the IL-4Rα and IL-13Rα 1 chains were overexpressed in meningiomas compared with normal brain tissue. The levels of IL-4Rα mRNA appeared to be higher compared with the levels of IL-13Rα 1 mRNA. The results also showed that tumors with higher disease grade tended to have increased mRNA expression for the IL-4Rα chain. This IL-4Rα mRNA overexpression appeared to be more frequent in younger patients (age < 37 years). The transcripts for IL-2Rγ c chain were not detected in any of the tumor samples or in normal brain tissue. Quantitative real-time PCR confirmed the results of the RT-PCR analysis. Meningiomas also demonstrated a bright immunofluorescent staining for the IL-4Rα and IL-13Rα 1 chains but no staining for IL-2Rγ c. CONCLUSIONS. Expression of the 11-4Rα and IL-13Rα 1 chains and absence of IL-2γ c expression established that meningiomas expressed type II IL-4Rs. These receptors may serve as a target for cytotoxin/immunotoxin therapy in patients with meningioma who are not amenable to surgical resection or for recurrent tumors. © 2005 American Cancer Society. C1 All India Inst Med Sci, Dept Biochem, New Delhi 110029, India. Jamia Millia Islamia, Dept Biosci, New Delhi 110025, India. US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Lab Mol Tumor Biol, Bethesda, MD USA. All India Inst Med Sci, Dept Pathol, New Delhi 110029, India. All India Inst Med Sci, Dept Neurosurg, New Delhi, India. RP Sinha, S (reprint author), All India Inst Med Sci, Dept Biochem, New Delhi 110029, India. EM sub_sinha@hotmail.com NR 60 TC 7 Z9 7 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD MAY 15 PY 2005 VL 103 IS 10 BP 2132 EP 2142 DI 10.1002/cncr.21008 PG 11 WC Oncology SC Oncology GA 923WM UT WOS:000228940200019 PM 15830341 ER PT J AU Kaminskas, E Farrell, A Abraham, S Baird, A Hsieh, LS Lee, SL Leighton, JK Patel, H Rahman, A Sridhara, R Wang, YC Pazdur, R AF Kaminskas, E Farrell, A Abraham, S Baird, A Hsieh, LS Lee, SL Leighton, JK Patel, H Rahman, A Sridhara, R Wang, YC Pazdur, R TI Approval summary: Azacitidine for treatment of myelodysplastic syndrome subtypes SO CLINICAL CANCER RESEARCH LA English DT Article ID 5-AZACYTIDINE; LEUKEMIA; DNA; CLASSIFICATION; METHYLATION; P15(INK4B); PROGNOSIS; PATIENT; CANCER; CELLS AB Purpose: This article summarizes data submitted to the U.S. Food and Drug Administration for marketing approval of azacitidine as injectable suspension (Vidaza, Pharmion Corporation, Boulder, CO) for treatment of patients with myelodysplastic syndrome. Experimental Design: In one phase 3 controlled trial, 191 study subjects were randomized to treatment with azacitidine or to observation; an additional 120 patients were treated with azacitidine in two phase 2 single arm studies. The primary efficacy end point was the overall response rate, defined as complete or partial normalization of peripheral blood counts and bone marrow blast percentages for at least 4 weeks. Results: In the controlled trial, the overall response rate was 15.7% in the azacitidine treatment group; there were no responders in the observation group (P < 0.0001). Response rates were similar in the two single arm studies. During response patients stopped being red cell or platelet transfusion dependent. Median duration of responses was at least 9 months. An additional 19% of azacitidine-treated patients had less than partial responses, most becoming transfusion independent. The most common adverse events attributed to azacitidine were gastrointestinal, hematologic, local (injection site), and constitutional. There were no azacitidine-related deaths. Conclusions: On May 19, 2004 the U.S. Food and Drug Administration approved azacitidine as injectable suspension for treatment of patients with the following myelodysplastic syndrome subtypes: refractory anemia or refractory anemia with ringed sideroblasts (if accompanied by neutropenia or thrombocytopenia or requiring transfusions), refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, and chronic myelomonocytic leukemia. Full prescribing information is available at http://www.fda.gov/cder/foi/label/2004/050794lbl.pdf. Azacitidine is the first agent approved for treatment of myelodysplastic syndrome. C1 US FDA, Ctr Drug Evaluat & Res, Div Oncol Drug Prod, Rockville, MD 20857 USA. RP Kaminskas, E (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Oncol Drug Prod, HFD-150,5600 Fishers Lane, Rockville, MD 20857 USA. EM edvardas.kaminskas@fda.hhs.gov NR 30 TC 209 Z9 234 U1 1 U2 10 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAY 15 PY 2005 VL 11 IS 10 BP 3604 EP 3608 DI 10.1158/1078-0432.CCR-04-2135 PG 5 WC Oncology SC Oncology GA 925XJ UT WOS:000229086600002 PM 15897554 ER PT J AU Marcus, KA Johann-Liang, R Powers, JH AF Marcus, KA Johann-Liang, R Powers, JH TI Ribavirin trials and hantavirus - What we should not conclude SO CLINICAL INFECTIOUS DISEASES LA English DT Letter ID INTRAVENOUS RIBAVIRIN C1 US FDA, Div Antiviral Drug Prod, Rockville, MD USA. US FDA, Off Drug Evaluat 4, Ctr Drug Evaluat & Res, Rockville, MD USA. RP Marcus, KA (reprint author), US FDA, Div Antiviral Drug Prod, Rockville, MD USA. EM marcusk@cder.fda.gov NR 5 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 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD MAY 15 PY 2005 VL 40 IS 10 BP 1550 EP 1551 DI 10.1086/429728 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 917MG UT WOS:000228465500029 PM 15844085 ER PT J AU Wang, JH Alvarez, R Roderiquez, G Guan, E Caldwell, Q Wang, J Phelan, M Norcross, MA AF Wang, JH Alvarez, R Roderiquez, G Guan, E Caldwell, Q Wang, J Phelan, M Norcross, MA TI CpG-Independent synergistic induction of beta-chemokines and a dendritic cell phenotype by orthophosphorothioate oligodeoxynucleotides and granulocyte-macrophage colony-stimulating factor in elutriated human primary monocytes SO JOURNAL OF IMMUNOLOGY LA English DT Article ID PERIPHERAL-BLOOD MONOCYTES; ACTIVATED PROTEIN-KINASES; BACTERIAL-DNA; T-CELLS; CUTTING EDGE; PHOSPHOROTHIOATE OLIGODEOXYNUCLEOTIDES; IMMUNE-RESPONSE; CCR5 EXPRESSION; VACCINE; RECEPTORS AB Chemokines attract leukocytes bearing the relevant chemokine receptors and regulate innate immune responses. CpG oligode-oxynucleotides (ODN) and GM-CSF are potent vaccine adjuvants and in combination induce enhanced Th1 responses by mechanisms yet to be determined. We have examined combinations of CpG- or non-CpG-ODN and GM-CSF for effects on the production of chemokines and the differentiation of monocytes to dendritic cells. High levels of the Th1-attracting, HIV-1-inhibitory chemokines, CCL3/MIP-1 alpha and CCL4/MIP-1 beta, were induced in human primary monocytes when CpG- or non-CpG-ODN was combined with GM-CSF, but not with IL-4 or IFN-gamma. The synergistic induction of beta-chemokines by non-CpG-ODN was phosphorothioate (PS) chemistry dependent and inhibited by blocking endosome maturation/acidification and ERK1/2 activation. Chemokine and TLR9 mRNAs were induced by PS-ODN. Cells treated with non-CpG PS-ODN and GM-CSF expressed dendritic cell marker CD83 and high levels of HLA-DR and costimulatory molecules, and were CD14(-) or CD14(dim), consistent with monocyte differentiation into a dendritic cell phenotype. The induction of CD83 and P-chemokines was tyrosine phosphorylation dependent. Secreted CCL3 and CCL4 were detected as a heterodimer. Our results indicate the CpG-independent synergy between PS-ODN and GM-CSF mediated through chemokine and dendritic cell induction. In addition, our observations suggest that PS-ODN plus GM-CSF may be useful as potent ex vivo dendritic cell differentiation/maturation agents for dendritic cell therapy and as vaccine adjuvants for tumor and infectious microorganisms, including HIV-1. C1 US FDA, Off Biotechnol Prod, Off Pharmaceut Sci, Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. RP Wang, JH (reprint author), US FDA, Off Biotechnol Prod, Off Pharmaceut Sci, Ctr Drug Evaluat & Res, Natl Inst Hlth Bldg 29B,Room 4E12,8800 Rockville, Bethesda, MD 20892 USA. EM wangj@cber.fda.gov NR 55 TC 14 Z9 14 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 MAY 15 PY 2005 VL 174 IS 10 BP 6113 EP 6121 PG 9 WC Immunology SC Immunology GA 924DL UT WOS:000228958900027 PM 15879106 ER PT J AU Serrano, CJ Graham, L DeBell, K Rawat, R Veri, MC Bonvini, E Rellahan, BL Reischl, IG AF Serrano, CJ Graham, L DeBell, K Rawat, R Veri, MC Bonvini, E Rellahan, BL Reischl, IG TI A new tyrosine phosphorylation site in PLC gamma 1: The role of tyrosine 775 in immune receptor signaling SO JOURNAL OF IMMUNOLOGY LA English DT Article ID PHOSPHOLIPASE-C-GAMMA; T-CELL LINE; B-CELL; ACTIVATION; C-GAMMA-1; RESIDUES; CALCIUM; STIMULATION; MECHANISM; COMPLEX AB Phospholipase C gamma (PLC gamma) is a ubiquitous gatekeeper of calcium mobilization and diacylglycerol-mediated events induced by the activation of Ag and growth factor receptors. The activity of PLC gamma is regulated through its controlled membrane translocation and tyrosine (Y) phosphorylation. Four activation-induced tyrosine phosphorylation sites have been previously described (Y472, Y771, Y783, and Y1254), but their specific roles in Ag receptor-induced PLC gamma 1 activation are not fully elucidated. Unexpectedly, we found that the phosphorylation of a PLC gamma 1 construct with all four sites mutated to phenylalanine was comparable with that observed with wild-type PLC gamma 1, suggesting the existence of an unidentified site(s). Sequence alignment with known phosphorylation sites in PLC gamma 2 indicated homology of PLC gamma 1 tyrosine residue 775 (Y775) with PLC gamma 2 Y753, a characterized phosphorylation site. Tyrosine 775 was characterized as a phosphorylation site using phospho-specific anti-Y775 antiserum, and by mutational analysis. Phosphorylation of Y775 did not depend on the other tyrosines, and point mutation of PLC gamma 1 Y775, or the previously described Y783, substantially reduced AgR-induced calcium, NF-AT, and AP-1 activation. Mutation of Y472, Y771, and Y1254 had no effect on overall PLC gamma 1 phosphorylation or activation. Although the concomitant mutation of Y775 and Y783 abolished downstream PLC gamma 1 signaling, these two tyrosines were sufficient to reconstitute the wild-type response in the absence of functional Y472, Y771, and Y1254. These,data establish Y775 as a critical phosphorylation site for PLC gamma 1 activation and confirm the functional importance of Y783. C1 US FDA, Ctr Biol Evaluat & Res, Off Biotechnol Prod, Div Monoclonal Antibodies, Bethesda, MD 20014 USA. RP Rellahan, BL (reprint author), US FDA, Ctr Biol Evaluat & Res, Off Biotechnol Prod, Div Monoclonal Antibodies, Natl Inst Hlsth Campus,Bldg 29B,HFD-123,29 Lincol, Bethesda, MD 20014 USA. EM rellahan@cber.fda.gov NR 25 TC 32 Z9 32 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 MAY 15 PY 2005 VL 174 IS 10 BP 6233 EP 6237 PG 5 WC Immunology SC Immunology GA 924DL UT WOS:000228958900042 PM 15879121 ER PT J AU Buhse, L Kolinski, R Westenberger, B Wokovich, A Spencer, J Chen, CW Turujman, S Gautam-Basak, M Kang, GJ Kibbe, A Heintzelman, B Wolfgang, E AF Buhse, L Kolinski, R Westenberger, B Wokovich, A Spencer, J Chen, CW Turujman, S Gautam-Basak, M Kang, GJ Kibbe, A Heintzelman, B Wolfgang, E TI Topical drug classification SO INTERNATIONAL JOURNAL OF PHARMACEUTICS LA English DT Article DE ointment; cream; gel; lotion; topical drug AB Current definitions of lotions, gels, creams and ointments vary depending on literature source, market history or traditional use. This often leads to confusion when deciding which dosage form to prescribe and/or purchase. The existing classification of topical dosage forms needs to be re-examined to ensure that definitions for different dosage forms are based on consistent scientific principles and that dosage forms can be distinguished from one another. The purpose of this study is to obtain a scientifically based, systematic classification of dosage forms for topical drugs. A variety of prescription and over-the-counter topical products Currently marketed as lotions, gels, creams, and ointments are evaluated using different techniques including rheology (viscosity and shear rate versus shear stress), loss on drying (LOD), specific gravity, surface tension, thermogravimetric analysis (TGA), water absorption, dilution properties, microscopic evaluation, transmittance of visible light, appearance and composition. Rheology is the most discriminating property separating creams and lotions. Water plus volatiles (as measured by LOD) and composition separate ointments and creams. Composition and thermal behavior separate gels from the other dosage forms. Based on these findings, new definitions and a decision tree are presented to assist in the determination of the appropriate nomenclature for a topical dosage form. © 2005 Elsevier B.V. All rights reserved. C1 FDA, Div Pharmaceut Anal, Off Pharmaceut Sci, Ctr Drug Evaluat & Res, St Louis, MO 63101 USA. US FDA, CDER, OPS, Off New Drug Chem, Rockville, MD USA. Wilkes Univ, Wilkes Barre, PA USA. RP Buhse, L (reprint author), FDA, Div Pharmaceut Anal, Off Pharmaceut Sci, Ctr Drug Evaluat & Res, 1114 Market St,Room 1002, St Louis, MO 63101 USA. EM buhsel@cder.fda.gov NR 12 TC 14 Z9 15 U1 3 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5173 J9 INT J PHARM JI Int. J. Pharm. PD MAY 13 PY 2005 VL 295 IS 1-2 BP 101 EP 112 DI 10.1016/j.ijpharm.2005.01.032 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 924BL UT WOS:000228953500011 PM 15847995 ER PT J AU Gonzalez-Moreno, O Calvo, A Joshi, BH Abasolo, I Leland, P Wang, Z Montuenga, L Puri, RK Green, JE AF Gonzalez-Moreno, O Calvo, A Joshi, BH Abasolo, I Leland, P Wang, Z Montuenga, L Puri, RK Green, JE TI Gene expression profiling identifies IL-13 receptor alpha 2 chain as a therapeutic target in prostate tumor cells overexpressing adrenomedullin SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE cDNA microarrays; prostate cancer; adrenomedullin; IL-13R alpha 2; gene expression profiling ID PSEUDOMONAS EXOTOXIN; IN-VIVO; INTERLEUKIN-13 RECEPTOR; SIGNAL-TRANSDUCTION; AUTOCRINE GROWTH; MUTATED FORM; CANCER; LINES; PEPTIDE; CARCINOMA AB Human adrenomedullin (AM) is a 52 amino acid peptide, which shares homology with the calcitonin gene-related peptide. Overexpression of AM in the prostate carcinoma cell line PC-3 results in growth inhibition with a 20% (for human AM) and 35% (for rat AM) increase in doubling time compared to parental or mock-transfected cells. We demonstrate by gene expression profiling that AM overexpression results in the dysregulation of approximately 100 genes. Examples of such genes include many involved in the formation of the cytoskeleton, cell adhesion and the extracellular matrix, as well as regulators of the cell cycle and apoptosis, cytokines and transcription factors. Several genes related to cell growth arrest, such as GADD45, IGF-BP6 and RUNX-3, are upregulated by AM. Interestingly, interleukin-13 receptor alpha 2 (IL-13R alpha 2) transcripts were significantly increased in clones overexpressing AM, which was confirmed by semiquantitative RT-PCR analysis. In addition, PC-3 cells treated with AM showed an overexpression of IL-13R alpha 2, which was abolished when cells were preincubated with an anti-AM blocking antibody. When PC-3 cells overexpressing AM and the IL-13R alpha 2 were treated with the highly specific IL13-PE38 cytotoxin, which binds to this receptor, a concentration-dependent inhibition of protein synthesis was observed. The IC50 (concentration of cytotoxin inhibiting protein synthesis by 50%) ranged from 1 to 4 ng/ml. This cytotoxicity was specific as it was neutralized by the excess of IL-13 and confirmed by clonogenic assays. This study describes a novel AM-induced mechanism of tumor sensitization through the upregulation of functional IL-13R alpha 2 chain, an ideal target for the highly specific recombinant chimeric cytotoxin IL13-PE38. (c) 2004 Wiley-Liss, Inc. C1 NCI, Lab Cell Regulat & Carcinogenesis, NIH, Bethesda, MD 20892 USA. Univ Navarra, Dept Histol & Pathol, E-31080 Pamplona, Spain. Food & Drug Adm, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Lab Mol Tumor Biol, Bethesda, MD USA. Northwestern Univ, Sch Med, Robert H Lurie Comprehens Canc Ctr, Dept Urol, Chicago, IL 60611 USA. RP Green, JE (reprint author), NCI, Lab Cell Regulat & Carcinogenesis, NIH, Bldg 41,Room C629,41 Lib Dr, Bethesda, MD 20892 USA. EM jegreen@nih.gov RI Abasolo, Ibane/H-7741-2012 OI Abasolo, Ibane/0000-0001-5970-6276 NR 43 TC 16 Z9 16 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD MAY 10 PY 2005 VL 114 IS 6 BP 870 EP 878 DI 10.1002/ijc.20789 PG 9 WC Oncology SC Oncology GA 915VF UT WOS:000228338700004 PM 15609296 ER PT J AU Carson, MM Spady, DW Beeler, JA Krezolek, MP Audet, S Pabst, HF AF Carson, MM Spady, DW Beeler, JA Krezolek, MP Audet, S Pabst, HF TI Follow-up of infants given measles vaccine at 6 months of age: antibody and CMI responses to MMRII (R) at 15 months of age and antibody levels at 27 months of age SO VACCINE LA English DT Article DE measles vaccines; vaccination regime; immune response ID IMMUNE-RESPONSES; UNITED-STATES; AIK-C; PROTECTIVE TITERS; EDMONSTON-ZAGREB; IMMUNIZATION; EPIDEMIOLOGY; POPULATIONS; STRAINS; SCHWARZ AB The worldwide elimination of measles is an important target. In developed countries, to control measles outbreaks, immunization from 6 months of age is recommended. In this study, infants (n = 290) who were (1) born to mothers with natural immunity or to vaccinated mothers and (2) previously immunized with Connaught (CLL) or AIK-C measles vaccine at 6 months of age, were evaluated for measles immunity before and after measles-mumps-rubella (MMRII®) at 15 months of age. Eight weeks after MMRII®, 98.9% of infants were seropositive by enzyme immunoassay (EIA) and 70% demonstrated measles specific cellular immunity by blast transformation (BT) of lymphocytes. At 27 months of age, 98.4% of infants had protective antibody levels by plaque reduction neutralization (PRN) test. These results suggest that AIK-C and CLL vaccines elicit durable protective immunity in young infants when used in early immunization programs. Published by Elsevier Ltd. C1 Univ Alberta, Dept Pediat, Edmonton, AB T6G 2R7, Canada. US FDA, Div Viral Prod, Bethesda, MD 20892 USA. RP Carson, MM (reprint author), Capital Hlth, Publ Hlth Div, Suite 1800 Coll Plaza,8215-112 St, Edmonton, AB T6G 2C8, Canada. EM mcarson@cha.ab.ca FU PHS HHS [A133996-03] NR 39 TC 7 Z9 8 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD MAY 9 PY 2005 VL 23 IS 25 BP 3247 EP 3255 DI 10.1016/j.vaccine.2005.01.092 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 924SQ UT WOS:000229001100006 PM 15837229 ER PT J AU Petersen, D Chandramouli, GVR Geoghegan, J Hilburn, J Paarlberg, J Kim, CH Munroe, D Gangi, L Han, J Puri, R Staudt, L Weinstein, J Barrett, JC Green, J Kawasaki, ES AF Petersen, D Chandramouli, GVR Geoghegan, J Hilburn, J Paarlberg, J Kim, CH Munroe, D Gangi, L Han, J Puri, R Staudt, L Weinstein, J Barrett, JC Green, J Kawasaki, ES TI Three microarray platforms: an analysis of their concordance in profiling gene expression SO BMC GENOMICS LA English DT Article ID DENSITY OLIGONUCLEOTIDE ARRAYS; DNA MICROARRAYS; CELL-LINES; MOLECULAR PHARMACOLOGY; PROSTATE-CANCER; CDNA; METAANALYSIS; PATTERNS; CLASSIFICATION; HYBRIDIZATION AB Background: Microarrays for the analysis of gene expression are of three different types: short oligonucleotide (25-30 base), long oligonucleotide (50-80 base), and cDNA ( highly variable in length). The short oligonucleotide and cDNA arrays have been the mainstay of expression analysis to date, but long oligonucleotide platforms are gaining in popularity and will probably replace cDNA arrays. As part of a validation study for the long oligonucleotide arrays, we compared and contrasted expression profiles from the three formats, testing RNA from six different cell lines against a universal reference standard. Results: The three platforms had 6430 genes in common. In general, correlation of gene expression levels across the platforms was good when defined by concordance in the direction of expression difference (upregulation or downregulation), scatter plot analysis, principal component analysis, cell line correlation or quantitative RT-PCR. The overall correlations (r values) between platforms were in the range 0.7 to 0.8, as determined by analysis of scatter plots. When concordance was measured for expression ratios significant at p-values of < 0.05 and at expression threshold levels of 1.5 and 2-fold, the agreement among the platforms was very high, ranging from 93% to 100%. Conclusion: Our results indicate that the long oligonucleotide platform is highly suitable for expression analysis and compares favorably with the cDNA and short oligonucleotide varieties. All three platforms can give similar and reproducible results if the criterion is the direction of change in gene expression and minimal emphasis is placed on the magnitude of change. C1 NCI, Ctr Adv Technol, Canc Res Ctr, Gaithersburg, MD 20877 USA. SAIC Frederick, Lab Mol Technol, Frederick, MD 21701 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. NCI, Canc Res Ctr, Bethesda, MD 20892 USA. RP Kawasaki, ES (reprint author), NCI, Ctr Adv Technol, Canc Res Ctr, Gaithersburg, MD 20877 USA. EM petersed@mail.nih.gov; chandrag@mail.nih.gov; geoghej@mail.nih.gov; hilburnj@mail.nih.gov; paarlbej@mail.nih.gov; kimcha@mail.nih.gov; dmunroe@ncifcrf.gov; gangil@mail.nih.gov; hanj@cber.fda.gov; puri@cber.fda.gov; lstaudt@mail.nih.gov; jw4i@nih.gov; barrett@mail.nih.gov; jegreen@nih.gov; kawasake@mail.nih.gov NR 57 TC 67 Z9 74 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2164 J9 BMC GENOMICS JI BMC Genomics PD MAY 5 PY 2005 VL 6 AR 63 DI 10.1186/1471-2164-6-63 PG 14 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 929XJ UT WOS:000229379600001 PM 15876355 ER PT J AU Whittaker, P Fry, FS Curtis, SK Al-Khaldi, SF Mossoba, MM Yurawecz, MP Dunkel, VC AF Whittaker, P Fry, FS Curtis, SK Al-Khaldi, SF Mossoba, MM Yurawecz, MP Dunkel, VC TI Use of fatty acid profiles to identify food-borne bacterial pathogens and aerobic endospore-forming bacilli SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE gas chromatography; fatty acids; food-borne bacteria; spores ID HEMOLYTIC-UREMIC SYNDROME; CAUSE HEMORRHAGIC COLITIS; ESCHERICHIA-COLI; VIBRIO-VULNIFICUS; YERSINIA-ENTEROCOLITICA; IDENTIFICATION; PURIFICATION; ANTHRACIS; STRAINS; CEREUS AB Capillary gas chromatography (GC) with flame ionization detection was used to determine the cellular fatty acid profiles of various food-borne microbial pathogens and to compare the fatty acid profiles of spores and vegetative cells of the same endospore-forming bacilli. Fifteen bacteria, representing eight genera (Staphylococcus, Listeria, Bacillus, Yersinia, Salmonella, Shigella, Escherichia, and Vibrio) and 11 species were used to compare the extracted fatty acid methyl esters (FAMEs). Endospore-forming bacilli were processed to obtain pure spores and whole cell FAMEs for GC analysis. A data set for each bacterial agent was prepared using fatty acid profiles from five replicates prepared on different days. The results showed that these fatty acid intensity profiles were unique for each of the 11 species and that they could be used as a fingerprint for the organisms. The cellular fatty acid profiles for Bacillus anthracis and Bacillus cereus show that there are two branched chain fatty acids, iso 17:1 omega 10c and 17:1 anteiso, which are unique in these species. Iso 17:1 omega 10c is present in B. cereus vegetative cells and spores but is not observed in B. anthracis. The 17:1 anteiso fatty acid is present in B. anthracis cells but not in B. cereus cells. Fatty acids 16:0 2OH and 17:0 iso 3OH are present in B. anthracis and B. cereus spores but not in the vegetative cells. In summary, analysis of FAMEs from bacteria and spores can provide a sensitive procedure for the identification of food-borne pathogens. C1 Ctr Food Safety & Appl Nutr Food & Drug Adm, College Pk, MD 20740 USA. RP Whittaker, P (reprint author), Ctr Food Safety & Appl Nutr Food & Drug Adm, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM paul.whittaker@fda.hhs.gov NR 34 TC 44 Z9 46 U1 0 U2 7 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0021-8561 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD MAY 4 PY 2005 VL 53 IS 9 BP 3735 EP 3742 DI 10.1021/jf040458a PG 8 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 922BH UT WOS:000228810200071 PM 15853428 ER PT J AU Mei, N Heflich, RH Moore, MM Chen, T AF Mei, N Heflich, RH Moore, MM Chen, T TI Age-dependent sensitivity of Big Blue transgenic mice to the mutagenicity of N-ethyl-N-nitrosourea (ENU) in liver SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article DE ethylnitrosourea; age; neonate; mutagenicity; transgenic mice; sensitivity ID EXPOSED IN-VIVO; HPRT GENE; HEPATOCELLULAR-CARCINOMA; INDUCED MUTATIONS; CHILDRENS HEALTH; MODIFYING ROLE; FEMALE RATS; CANCER; MOUSE; HEPATOCARCINOGENESIS AB The incidence of childhood cancer is increasing and recent evidence suggests an association between childhood cancer and environmental exposure to genotoxins. In the resent study, the Big Blue transgenic mouse model was used to determine whether p specific periods in early life represent windows of vulnerability to mutation induction by genotoxins in mouse liver. Groups of mice were treated with single doses of 120 m N-ethyl-N-nitrosourea (ENU)/kg body weight or the vehicle either transplacentally 9 to the 18-day-old fetus or at postnatal days (PNDs) 1, 8, 15, 42 or 126; the animals were sacrificed 6 weeks after their treatment. The cII mutation assay was performed to determine the mutant frequencies (MFs) in the livers of the mice. Liver cII MFs for both sexes were dependent on the age at which the animals were treated. Perinatal treatment with ENU (either transplacental treatment to the 18-day-old fetus or i.p. injection at PND 1) induced relatively high MFs. However, ENU treatment at PNDs 8 and 15 resulted in the highest mutation induction. The lowest mutation induction occurred in those animals treated as adults (PND 126). For instance, the cII MF for the PND 8 female group was 646 x 10(-6) while the MF for female adults was only 145 x 10(-6), a more than 4-fold difference. Molecular analysis of the mutants found that A:T -> T:A transversions and A:T -> G:C transitions characterized the pattern of mutations induced by ENU in both the neonate and adult mice, while the predominate type of mutation in the controls was G:C -> A:T. The results indicate that mouse liver is most sensitive to ENU-induced mutation during infancy. This period correlates well with the age-dependent sensitivity to carcinogenicity in mouse liver, suggesting that mutation is an important rate-limiting factor for age-related carcinogenesis. (c) 2004 Elsevier B.V. All rights reserved. C1 US FDA, Div Genet & Reprod Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Chen, T (reprint author), US FDA, Div Genet & Reprod Toxicol, Natl Ctr Toxicol Res, HFT-130,3900 NCTR Rd, Jefferson, AR 72079 USA. EM tchen@nctr.fda.gov RI mei, nan/E-8915-2011 OI mei, nan/0000-0002-3501-9014 NR 54 TC 9 Z9 9 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0027-5107 J9 MUTAT RES-FUND MOL M JI Mutat. Res.-Fundam. Mol. Mech. Mutagen. PD MAY 2 PY 2005 VL 572 IS 1-2 BP 14 EP 26 DI 10.1016/j.mrfmmm.2004.11.011 PG 13 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 915ZU UT WOS:000228351500002 PM 15790487 ER PT J AU Dalloul, RA Lillehoj, HS Klinman, DM Ding, XC Min, W Heckert, RA Lillehoj, EP AF Dalloul, RA Lillehoj, HS Klinman, DM Ding, XC Min, W Heckert, RA Lillehoj, EP TI In ovo administration of CpG oligodeoxynucleotides and the recombinant microneme protein MIC2 protects against Eimeria infections SO VACCINE LA English DT Article DE CpG; oligodeoxynucleotide; in ovo vaccination; Eimeria ID BACTERIAL-DNA; NEWCASTLE-DISEASE; BROILER-CHICKENS; MAREKS-DISEASE; MOTIFS; ADJUVANTS; VACCINE; RESISTANCE; IMMUNITY; IMMUNOMODULATION AB We have previously demonstrated that short oligodeoxynucleotides containing unmethylated CpG motifs (CpG ODNs) exert a positive effect on weight loss and oocyst shedding associated with Eimeria infection when injected in vivo. The present work investigated the effects of in ovo vaccination with CpG ODNs and an Eimeria recombinant microneme protein (MIC2), alone or in combination, on susceptibility to coccidiosis. In ovo injection of CpG ODNs alone enhanced resistance to experimental Eimeria acervulina infection as best exemplified by reduced oocyst shedding. Two CpG ODNs reduced the oocyst load, but did not affect weight gain. When co-administered with the recombinant microneme protein, both ODNs reduced oocyst shedding; however, only ODN D 19 plus MIC2 consistently improved weight gain. Vaccinating with ODN 2006 or MIC2 protein curtailed oocyst shedding but did not enhance weight gain in Eimeria tenella-infected birds. Co-administration of CpG ODN and MIC2 did not have an additive effect in reducing the oocyst output; however, it resulted in the highest and lowest Ab response before and after Eimeria tenella infection, respectively. Collectively, CpG ODNs administered in ovo demonstrated immunoenhancing and adjuvant effects following Eimeria infections. Published by Elsevier Ltd. C1 USDA ARS, Anim Parasit Dis Lab, Anim & Nat Resources Inst, Beltsville, MD 20705 USA. US FDA, Ctr Biol Evaluat & Res, Sect Retroviral Immunol, Bethesda, MD 20892 USA. Sunchon Natl Univ, Dept Anim Sci, Choongnam 540742, South Korea. Univ Maryland, Sch Pharm, Dept Pharmaceut Sci, Baltimore, MD 21201 USA. RP Lillehoj, HS (reprint author), USDA ARS, Anim Parasit Dis Lab, Anim & Nat Resources Inst, BARC E,Bldg 1040, Beltsville, MD 20705 USA. EM hlilleho@anri.barc.usda.gov OI Min, Wongi/0000-0003-2437-7366; Dalloul, Rami/0000-0003-4690-9220 NR 34 TC 31 Z9 37 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD MAY 2 PY 2005 VL 23 IS 24 BP 3108 EP 3113 DI 10.1016/j.vaccine.2005.01.073 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 922WP UT WOS:000228870900004 PM 15837209 ER PT J AU Puccioni-Soler, M Yamano, Y Rios, M Goncalves, RR Domingues, RC Carvalho, S Papaiz-Alvarenga, R Jacobson, S AF Puccioni-Soler, M Yamano, Y Rios, M Goncalves, RR Domingues, RC Carvalho, S Papaiz-Alvarenga, R Jacobson, S TI Htlv-i proviral load in Pbmnc and Csf of Ham/Tsp, Htlv-i positive patients with multiple sclerosis-like manifestations, other neurological diseases and asymptomatic carriers SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT 12th International Conference on Human Retrovirology - HTLV and Related Viruses CY JUN 22-25, 2005 CL Montego Bay, JAMAICA SP Int Retrovirol Assoc, Natl Inst Hlth, Univ W Indies, Natl Inst Allergy & Infect Dis, Natl Canc Inst, Natl Inst Neurol Dis & Stroke, BD Biosci, Bristol-Myers Squibb, Ohio State Univ, Ctr Retrovirus Res, Dept Vet Biosci, Genome Sci Lab Ltd, Horai Chem Co Ltd, Natl Inst Drug Abuse, Sci Supplies & Technol, Jamaica Med Fdn, J Wray & Nephew Ltd, Red Stripe, UCSF AIDS & Canc Specimen Resource C1 NIH, Bethesda, MD 20892 USA. Univ Fed Rio de Janeiro, Rio De Janeiro, Brazil. Inst Estadual Hematol Arthur de S Cavalcanti, HEMORIO, Rio De Janeiro, Brazil. MR Muti Imagem, Rio De Janeiro, Brazil. Univ Fed Rio de Janeiro, DMD Clin Pathol, HUCFF UFRJ, Neurolife Lab, Rio De Janeiro, Brazil. US FDA, Bethesda, MD 20014 USA. Kagoshima Univ, Kagoshima 890, Japan. HUGG UNIRIO, HUCFF UFRJ, Rio De Janeiro, Brazil. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD MAY PY 2005 VL 21 IS 5 MA O57 BP 456 EP 457 PG 2 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 936AV UT WOS:000229825700070 ER PT J AU Yao, K Hisada, M Maloney, E Yamano, Y Hanchard, B Wilks, RJ Rios, M Jacobson, S AF Yao, K Hisada, M Maloney, E Yamano, Y Hanchard, B Wilks, RJ Rios, M Jacobson, S TI HTLV-I/II Western blot seroindeterminate status and its association with exposure to prototype HTLV-I. SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT 12th International Conference on Human Retrovirology - HTLV and Related Viruses CY JUN 22-25, 2005 CL Montego Bay, JAMAICA SP Int Retrovirol Assoc, Natl Inst Hlth, Univ W Indies, Natl Inst Allergy & Infect Dis, Natl Canc Inst, Natl Inst Neurol Dis & Stroke, BD Biosci, Bristol-Myers Squibb, Ohio State Univ, Ctr Retrovirus Res, Dept Vet Biosci, Genome Sci Lab Ltd, Horai Chem Co Ltd, Natl Inst Drug Abuse, Sci Supplies & Technol, Jamaica Med Fdn, J Wray & Nephew Ltd, Red Stripe, UCSF AIDS & Canc Specimen Resource C1 NIH, Bethesda, MD 20892 USA. NIH, Viral Epidemiol Branch, Rockville, MD USA. Ctr Dis Control & Prevent, Atlanta, GA USA. Kagoshima Univ, Kagoshima 890, Japan. Univ W Indies, Fac Med Sci, Kingston 7, Jamaica. Ctr Biol Evaluat & Res, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD MAY PY 2005 VL 21 IS 5 MA P74 BP 484 EP 484 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 936AV UT WOS:000229825700155 ER PT J AU Ellenberg, SS Foulkes, MA Midthun, K Goldenthal, KL AF Ellenberg, SS Foulkes, MA Midthun, K Goldenthal, KL TI Evaluating the safety of new vaccines: Summary of a workshop SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID CELL PERTUSSIS-VACCINE; UNITED-STATES; CONJUGATE VACCINE; CONTROLLED TRIAL; CLINICAL-TRIAL; B VACCINATION; INFANTS; DISEASE; HEALTH; RISK AB Public concerns about the safety of vaccines arise on a regular basis. In November 2000, a workshop titled "Evaluation of New Vaccines: How Much Safety Data?" was convened by US Public Health Service agencies, including the Food and Drug Administration, the National Institutes of Health, the Centers for Disease Control and Prevention, and the Health Resources and Services Administration, to discuss appropriate methods for evaluating the safety of new vaccines. Workshop presentations addressed the current standards and approaches for new vaccine evaluation and postlicensure surveillance, as well as public views about vaccine safety and alternative approaches that could be considered. The advantages and disadvantages of conducting large controlled trials before licensure or widespread use of a new vaccine were discussed. We summarize these presentations and discussions. C1 US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. RP Ellenberg, SS (reprint author), Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Div Biostat, Blockley Hall,Room 611,423 Guardian Dr, Philadelphia, PA 19104 USA. EM sellenbe@cceb.upenn.edu NR 36 TC 24 Z9 29 U1 1 U2 1 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD MAY PY 2005 VL 95 IS 5 BP 800 EP 807 DI 10.2105/AJPH.2004.039438 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 922GY UT WOS:000228826000012 PM 15855455 ER PT J AU Jeschke, U Bischof, A Speer, R Briese, V Richter, DU Bergemann, C Mylonas, I Shabani, N Friese, K Karsten, U AF Jeschke, U Bischof, A Speer, R Briese, V Richter, DU Bergemann, C Mylonas, I Shabani, N Friese, K Karsten, U TI Development of monoclonal and polyclonal antibodies and an ELISA for the determination of glycodelin in human serum, amniotic fluid and cystic fluid of benign and malignant ovarian tumors SO ANTICANCER RESEARCH LA English DT Article; Proceedings Paper CT 12th International Hamburg Symposium on Tumor Markers CY NOV 30-DEC 02, 2003 CL Hamburg, GERMANY DE glycodelin; monoclonal antibodies; ELISA; ovarian cancer ID HUMAN PLACENTAL PROTEIN-14; ENDOMETRIAL PROTEIN; STEROID-RECEPTORS; BREAST-CANCER; MESSENGER-RNA; CELLS; EXPRESSION; PP14; GLYCOPROTEIN; STIMULATION AB Objective: The role of glycodelin in human reproduction and gynecological malignancies has been investigated in a large number of studies in recent years. Three dominant functions of this glycoprotein were identified. Glycodelin is immunosuppressive, a morphological marker of differentiation and a contraceptive. Glycodelin is a glycoprotein with a molecular weight of 28 kDa and a carbohydrate content of 17.5%. Unusual LacdiNAc structures were identified on glycodelin A, isolated from amniotic fluid. Because no kit for glycodelin quantification is commercially available, we developed all reagents and a functional ELISA. Materials and Methods: Glycodelin A was purified from amniotic fluid by chromatographic methods. The purity of the isolated protein was checked with SDS-PAGE. Polyclonal antibodies against glycodelin were generated in rabbits. Monoclonal antibodies against glycodelin were generated from immunized BALB/c mice. Positive hybridomas were cloned and cultured. Monoclonal antibodies were isolated by immunoadsorption chromatography from culture supernatants. The glycodelin ELISA was developed in two formats, namely coating with polyclonal antibodies and the use of monoclonal antibodies. Results: The factors of variance for the ELISA were 7% (intra-assay variance) and 15% (inter-assay variance). The glycodelin ELISA was used to determine the glycodelin A concentration in sera of fertile women during the proliferative and secretory phases of the endometrium. The glycodelin A concentration was insignificantly elevated in the secretory phase compared to the proliferative phase. Significantly higher levels of glycodelin A were found in women using oral contraceptives compared to women who were not (p < 0.001). This is probably due to progesterone, which stimulates glycodelin production. We also found significantly increased glycodelin concentrations in the fluids of malignant ovarian cysts compared to benign ovarian tumors (p < 0.001). Furthermore, we tested the monoclonal and polyclonal antibodies successfully in Western blot analysis and immunoadsorption chromatography. Conclusion: We consider the described ELISA for the quantification of glycodelin as a useful tool for the determination of glycodelin in amniotic fluid, serum and cystic fluids. Its most promising application is expected in the diagnosis of ovarian cancer. The antibodies generated are applicable to multiple techniques. C1 Univ Munich, Dept Obstet & Gynecol 1, D-80337 Munich, Germany. Univ Rostock, Dept Obstet & Gynecol, Fac Med, D-18055 Rostock, Germany. NCI FDA, Clin Proteom Program, NIH, Bethesda, MD 20892 USA. Max Delbruck Ctr Mol Med, D-13125 Berlin, Germany. RP Jeschke, U (reprint author), Univ Munich, Dept Obstet & Gynecol 1, Maistr 11, D-80337 Munich, Germany. EM udo.jeschke@med.uni-muenchen.de NR 24 TC 9 Z9 9 U1 0 U2 0 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD MAY-JUN PY 2005 VL 25 IS 3A BP 1581 EP 1589 PG 9 WC Oncology SC Oncology GA 939UF UT WOS:000230097200017 PM 16033064 ER PT J AU Sutherland, JB Cross, EL Heinze, TM Freeman, JP Moody, JD AF Sutherland, JB Cross, EL Heinze, TM Freeman, JP Moody, JD TI Fungal biotransformation of benzo[f]quinoline, benzo[h]quinoline, and phenanthridine SO APPLIED MICROBIOLOGY AND BIOTECHNOLOGY LA English DT Article ID RAT-LIVER HOMOGENATE; MUCOR-RAMANNIANUS; MICROBIAL TRANSFORMATION; CHIRONOMUS-RIPARIUS; AZAARENES; METABOLISM; IDENTIFICATION; BENZOQUINOLINE; ECOTOXICITY; MICROSOMES AB Cultures of Umbelopsis ramanniana (=Mucor ramannianus) were grown in fluid Sabouraud medium for 3 days, dosed with 0.23 mM benzo[f]quinoline, benzo[h]quinoline, or phenanthridine (benzo[c]quinoline), and incubated for another 18 days. Cultures were extracted and metabolites (66-75% of the UV absorbance) were separated by high-performance liquid chromatography. They were identified by mass spectrometry and nuclear magnetic resonance spectroscopy. Benzo[f]quinoline was metabolized to benzo[f]quinoline trans-7,8-dihydrodiol, benzo[f]quinoline N-oxide, and 7-hydroxybenzo[f]quinoline, benzo[h]quinoline was metabolized to benzo[h]quinoline trans-5,6-dihydrodiol, benzo[h]quinoline trans-7,8-dihydrodiol, and 7-hydroxybenzo[h]quinoline, and phenanthridine was metabolized to phenanthridine N-oxide and phenanthridin-6(5H)-one. At least one of the metabolites produced from each compound was mutagenic and could not be considered detoxified. C1 US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Sutherland, JB (reprint author), US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM john.sutherland@fda.hhs.gov NR 28 TC 5 Z9 5 U1 2 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0175-7598 J9 APPL MICROBIOL BIOT JI Appl. Microbiol. Biotechnol. PD MAY PY 2005 VL 67 IS 3 BP 405 EP 411 DI 10.1007/s00253-004-1738-8 PG 7 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 920XH UT WOS:000228728300015 PM 15856220 ER PT J AU Brinker, A Kornegay, C Nourjah, P AF Brinker, A Kornegay, C Nourjah, P TI Trends in adherence to a revised risk management program designed to isotretinoin-exposed decrease or eliminate pregnancies - Evaluation of the Accutane SMART Program SO ARCHIVES OF DERMATOLOGY LA English DT Article; Proceedings Paper CT FDA-Advisory-Committee Meeting CY FEB 26, 2004 CL Gaithersburg, MD SP FDA Advisory Comm ID TELEPHONE INTERVIEWS; NONRESPONSE BIAS AB Objective: To review adherence to selected procedures outlined in the System to Manage Accutane-Related Teratogenicity (SMART) program during the first year of implementation vs; the procedures in effect in the year prior to initiation of the SMART program. Design: Observational. Setting: A novel pharmacy compliance survey and an ongoing, voluntary survey. Patients: Female recipients of isotretinoin. Intervention: In April 2002, Hoffmann-La Roche Inc, Nutley, NJ, manufacturer of Accutane brand isotretinoin and at that time the sole source of isotretinoin, revised earlier guidelines and instituted the SMART risk management program, which included the use of qualification stickers to affix to all prescriptions for Accutane to indicate, among other things, a negative pregnancy test just before the prescription was written. The goal of the SMART program was to decrease or eliminate isotretinoin-exposed pregnancies. Main Outcome Measures: Use and completion of prescription qualification stickers; changes in pretherapy pregnancy testing and birth control use. Results: The results of the pharmacy compliance survey indicated high (> 90%) use of prescription qualification stickers. Results of the patient survey suggested that 9% of prescription qualification stickers within the observed user cohort were issued without a pregnancy test. Furthermore, the pregnancy rate for patients participating in the survey was similar to that reported for cohorts recruited before the SMART program. Conclusions: The usefulness of the results derived from 2 surveys designed to evaluate the SMART program is limited by the lack of reliability and validity of the survey instruments and by questionable generalizability to all female recipients of isotretinoin. The presence of a qualification sticker may not have an impact on pregnancy testing or compliance with effective birth control behaviour as outlined in the SMART program. C1 US FDA, CDER, Off Drug Safety, Rockville, MD 20857 USA. RP Brinker, A (reprint author), 5600 Fishers Ln, Rockville, MD 20857 USA. EM brinkera@cder.fda.gov NR 10 TC 34 Z9 34 U1 1 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD MAY PY 2005 VL 141 IS 5 BP 563 EP 569 DI 10.1001/archderm.141.5.563 PG 7 WC Dermatology SC Dermatology GA 925IC UT WOS:000229045800005 PM 15897377 ER PT J AU Wysowski, DK Swartz, L AF Wysowski, DK Swartz, L TI Relationship between headache and depression in users of isotretinoin SO ARCHIVES OF DERMATOLOGY LA English DT Letter ID FREQUENCY; MIGRAINE C1 US FDA, Div Drug Risk Evaluat, Rockville, MD 20857 USA. RP Wysowski, DK (reprint author), US FDA, Div Drug Risk Evaluat, HFD-430,5600 Fishers Ln,Parklawn Bldg,Room 15B-08, Rockville, MD 20857 USA. EM wysowski@cder.fda.gov NR 5 TC 8 Z9 8 U1 2 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD MAY PY 2005 VL 141 IS 5 BP 640 EP 641 DI 10.1001/archderm.141.5.640 PG 2 WC Dermatology SC Dermatology GA 925IC UT WOS:000229045800022 PM 15897395 ER PT J AU Geho, D Lahar, N Gurnani, P Huebschman, M Herrmann, P Espina, V Shi, A Wulfkuhle, J Garner, H Petricoin, E Liotta, LA Rosenblatt, KP AF Geho, D Lahar, N Gurnani, P Huebschman, M Herrmann, P Espina, V Shi, A Wulfkuhle, J Garner, H Petricoin, E Liotta, LA Rosenblatt, KP TI Pegylated, steptavidin-conjugated quantum dots are effective detection elements for reverse-phase protein microarrays SO BIOCONJUGATE CHEMISTRY LA English DT Article ID BIOLOGICAL DETECTION; ACTIVATION; CANCER; NANOCRYSTALS; SPECIMENS; CELLS AB Protein microarray technologies provide a means of investigating the proteomic content of clinical biopsy specimens in order to determine the relative activity of key nodes within cellular signaling pathways. A particular kind of protein microarray, the reverse-phase microarray, is being evaluated in clinical trials because of its potential to utilize limited amounts of cellular material obtained through biopsy. Using this approach, cellular lysates are arrayed in dilution curves on nitrocellulose substrates for subsequent probing with antibodies. To improve the sensitivity and utility of reverse-phase microarrays, we tested whether a new reporter technology as well as a new detection instrument could enhance microarray performance. We describe the use of an inorganic fluorescent nanoparticle conjugated to streptavidin, Qdot 655 Sav, in a reverse-phase protein microarray format for signal pathway profiling. Moreover, a pegylated form of this bioconjugate, Qdot 655 Sav, is found to have superior detection characteristics in assays performed on cellular protein extracts over the nonpegylated form of the bioconjugate. Hyperspectral imaging of the quantum dot microarray enabled unamplified detection of signaling proteins within defined cellular lysates, which indicates that this approach may be amenable to multiplexed, high-throughput reverse-phase protein microarrays; in which numerous analytes are measured in parallel within a single spot. C1 SW Texas State Univ, Div Translat Pathol, Dept Pathol, Dallas, TX 75390 USA. NCI, Pathol Lab, NIH, FDA Clin Proteom Program, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Off Cellular & Gene Therapy, Bethesda, MD 20892 USA. RP Rosenblatt, KP (reprint author), SW Texas State Univ, Div Translat Pathol, Dept Pathol, Dallas, TX 75390 USA. EM kevin.rosenblatt@utsouthwestern.edu OI Espina, Virginia/0000-0001-5080-5972 NR 26 TC 100 Z9 103 U1 1 U2 7 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1043-1802 J9 BIOCONJUGATE CHEM JI Bioconjugate Chem. PD MAY-JUN PY 2005 VL 16 IS 3 BP 559 EP 566 DI 10.1021/bc0479113 PG 8 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 928MC UT WOS:000229274800012 PM 15898722 ER PT J AU Kawakami, M Kawakami, K Kioi, M Leland, P Puri, RK AF Kawakami, M Kawakami, K Kioi, M Leland, P Puri, RK TI Hodgkin lymphoma therapy with interlepkin-4 receptor-directed cytotoxin in an infiltrating animal model SO BLOOD LA English DT Article ID REED-STERNBERG CELLS; COMBINED IMMUNODEFICIENT MICE; INTERLEUKIN-13 RECEPTOR; CANCER-THERAPY; SCID MICE; IN-VITRO; DISEASE; GROWTH; IMMUNOTOXIN; EXPRESSION AB Hodgkin lymphoma represents unique clinicopathologic features because Hodgkin and Reed-Sternberg (H-RS) cells produce a variety of cytokines, express a variety of cytokine receptors, and are surrounded by numerous nonmalignant immunoreactive cells. We found that receptors for interleukin-4 (IL-4R) are highly expressed in H-RS cells. To target interleukin-4 receptor (IL-4R), we used a recombinant protein fusing circularly permuted human IL-4 and Pseudomonas exotoxin termed IL4(38-37)-PE38KDEL, or IL-4 cytotoxin. The cytotoxic effect of IL-4 cytotoxin on H-RS cell lines was determined to be moderate to high in vitro. We developed an infiltrating model of Hodgkin disease (HD) by injecting an adherent population of HDMyZ cells subcutaneously into the flanks of beige/nude/X-linked immunodeficient mice. The animal model exhibited spontaneous metastasis of H-RS cells to lymph nodes and dissemination to vital organs, including the lungs. Intraperitoneal or intratumoral treatment of these mice with IL-4 cytotoxin resulted in regression of the primary tumor mass and a decrease in the incidence of lymph node metastasis. Mice injected with HD-MyZ cells demonstrated 203% prolonged survival (mean survival, 63 days) compared with control (mean survival, 31 days) when they received systemic IL-4 cytotoxin treatment. Because numerous H-RS cell lines express receptors for IL-4, IL-4 cytotoxin may be a unique agent for the treatment of Hodgkin lymphoma. C1 US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapeut, Lab Mol Tumor Biol, Bethesda, MD 20892 USA. RP Kawakami, K (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapeut, Lab Mol Tumor Biol, Bldg 29B-2E08, Bethesda, MD 20892 USA. EM kawakami-k@umin.ac.jp NR 38 TC 8 Z9 9 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 MAY 1 PY 2005 VL 105 IS 9 BP 3707 EP 3713 DI 10.1182/blood-2004-08-3216 PG 7 WC Hematology SC Hematology GA 921WX UT WOS:000228797400053 PM 15626735 ER PT J AU Stone, A Ratnasinghe, LD Emerson, GL Modali, R Lehman, T Runnells, G Carroll, A Carter, W Barnhart, S Rasheed, AA Greene, G Johnson, DE Ambrosone, CB Kadlubar, FF Lang, NP AF Stone, A Ratnasinghe, LD Emerson, GL Modali, R Lehman, T Runnells, G Carroll, A Carter, W Barnhart, S Rasheed, AA Greene, G Johnson, DE Ambrosone, CB Kadlubar, FF Lang, NP TI CYP3A43 Pro(340)Ala polymorphism and prostate cancer risk in African Americans and Caucasians SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID N-TERMINAL DOMAIN; UNITED-STATES; HUMAN CYTOCHROME-P450; ANDROGEN RECEPTOR; GENETIC VARIANT; TOBACCO USE; WHITE MEN; SMOKING; ASSOCIATION; METABOLISM AB The human cytochrome P450 3A subfamily of enzymes is involved in the metabolism of steroid hormones, carcinogens, and many drugs. A cytosine-to-guanine polymorphism in CYP3A43 results in a proline-to-alanine substitution at codon 340. Although the functional significance of this polymorphism is unknown, we postulate that the substitution of proline, an α-imino acid, with alanine, an amino acid, could be of biochemical significance. In a case-control study with 490 incident prostate cancer cases (124 African Americans and 358 Caucasians) and 494 controls (167 African Americans and 319 Caucasians), we examined the association between CYP3A43 Pro(340)Ala polymorphism and prostate cancer risk. When all subjects were considered, there was a 3-fold increase in risk of prostate cancer among individuals with the CYP3A43-Ala/Ala genotype (odds ratio, 3.0; 95% confidence interval, 1.2-7.2) compared with those with the CYP3A43-Pro/Pro genotype after adjusting for age, race, and smoking. The prevalence of the polymorphism was significantly higher in African Americans than Caucasians (45% versus 13%). In African Americans, there was a 2.6-fold increase in prostate cancer risk among individuals with the CYP3A43-Ala/Ala genotype (odds ratio, 2.6; 95% confidence interval, 1.0-7.0) compared with those with the CYP3A43-Pro/Pro genotype. Among Caucasians, the small number of homozygotes precluded computing risk estimates; there were only three individuals with the CYP3A43-Ala/Ala genotype. Our results suggest that the CYP3A43-Pro(340)Ala polymorphism contributes to prostate cancer risk. C1 Cent Arkansas Vet Hlth Care Syst, Res Serv, Little Rock, AR 72205 USA. Natl Ctr Toxicol Res, Div Mol Epidemiol, Jefferson, AR 72079 USA. Univ Arkansas Med Sci, Arkansas Canc Res Ctr, Little Rock, AR 72205 USA. Univ Arkansas Med Sci, Dept Surg, Coll Med, Little Rock, AR 72205 USA. Roswell Pk Canc Inst, Dept Epidemiol, Buffalo, NY 14263 USA. BioServ Biotechnol Inc, Laurel, MD USA. RP Stone, A (reprint author), Cent Arkansas Vet Hlth Care Syst, Res Serv, Slot 151,4301 W 7th St, Little Rock, AR 72205 USA. EM Stoneannjanette@uams.edu FU NCI NIH HHS [R01CA55751]; NCRR NIH HHS [M01RR14288]; NIA NIH HHS [R01AG15722-02] NR 41 TC 24 Z9 25 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAY PY 2005 VL 14 IS 5 BP 1257 EP 1261 DI 10.1158/1055-9965.EPI-04-0534 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 925DP UT WOS:000229032000034 PM 15894682 ER PT J AU Winters, ME Mehta, AI Petricoin, EF Kohn, EC Liotta, LA AF Winters, ME Mehta, AI Petricoin, EF Kohn, EC Liotta, LA TI Supra-additive growth inhibition by a celecoxib analogue and carboxyamido-triazole is primarily mediated through apoptosis SO CANCER RESEARCH LA English DT Article ID COLON-CANCER CELLS; NF-KAPPA-B; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; FACTOR RECEPTOR TRANSACTIVATION; PROTEIN-KINASE PATHWAY; SMOOTH-MUSCLE-CELLS; EARLY GENE-PRODUCTS; BREAST-CANCER; SIGNALING PATHWAY; CYCLIN D1 AB Combination studies of celecoxib and chemotherapeutic agents suggest that combining cyclooxygenase-2 inhibitors with other agents may have supra-additive or synergistic effects on tumor growth inhibition. Carboxyamido-triazole (CAI), a voltage-independent calcium channel inhibitor, has been shown to induce growth inhibition and apoptosis in cancer cells. We found that continuous exposure to cytostatic doses of CAI and LM-1685, a celecoxib analogue, reduced the proliferation and survival of seven human cancer cell lines by at least one log (P <= 0.001) over either agent alone. To explore the mechanism of action of this combination, we further studied the effects of LM-1685/CAI on CCL-250 colorectal carcinoma cells. We found that the supra-additive antiproliferative effects occurred throughout a range of LM-1685 doses (5-25 mu mol/L) and paralleled a decrease in COX-2 activity as measured by prostaglandin E-2 production. In these cells, treatment with LM-1685/CAI suppressed the extracellular signal-regulated kinase pathway within the first hour but ultimately results in high, sustained activation of ERK over a 9-day period (P = 0.0005). Suppression of cyclin D1 and phospho-AKT, and cleavage of caspase-3 and PARP were concomitant with persistent ERK activation. Addition of PD98059, a MEK-1 inhibitor, suppressed ERK activation and significantly but incompletely reversed these signaling events and apoptosis. Flow cytometry experiments revealed that the CAI/LM-1685 combination induced a 3-fold increase in apoptosis over control (P = 0.005) in 3 days. We show that the combination of CAI and LM-1685 produces a cytotoxic effect by suppressing proliferation and triggering apoptosis. C1 NCI, Pathol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. NCI, US FDA, Clin Proteom Program, Bethesda, MD 20892 USA. Howard Hughes Med Inst, Off Cellular & Gene Therapy, Ctr Biol Evaluat & Res, Food & Drug Adm, Bethesda, MD USA. Howard Hughes Med Inst, Bethesda, MD USA. Tufts Univ, Sch Med, Boston, MA 02111 USA. RP Liotta, LA (reprint author), NCI, Pathol Lab, Ctr Canc Res, 10 Ctr Dr,Bldg 10,Room B1b41, Bethesda, MD 20892 USA. EM liottal@mail.nih.gov NR 68 TC 24 Z9 26 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2005 VL 65 IS 9 BP 3853 EP 3860 DI 10.1158/0008-5472.CAN-04-1989 PG 8 WC Oncology SC Oncology GA 919ZH UT WOS:000228656000048 PM 15867384 ER PT J AU Deschamps, P Kulkarni, PP Gautam-Basak, M Sarkar, B AF Deschamps, P Kulkarni, PP Gautam-Basak, M Sarkar, B TI The saga of copper(II)-L-histidine SO COORDINATION CHEMISTRY REVIEWS LA English DT Review DE copper; copper-histidine; Menkes disease; X-ray structured; copper transport; copper-albumin ID ELECTRON-SPIN-RESONANCE; AMINO-ACID COMPLEXES; HUMAN-SERUM ALBUMIN; COPPER-TRANSPORTING ATPASE; NUCLEAR MAGNETIC-RESONANCE; C-OXIDASE DEFICIENCY; SINGLE-CRYSTAL EPR; KINKY HAIR DISEASE; MENKES-DISEASE; AQUEOUS-SOLUTION AB Copper is an essential trace element required by all living organisms. Since the discovery in 1966 of copper(Il)-(L)-histidine species in human blood, extensive research has been carried out to determine its role in copper transport. A small fraction of copper(II) bound to (L)-histidine maintains an exchangeable pool of copper(II) in equilibrium with albumin in human blood. The exchange of copper(H) between (L)-histidine and albumin modulates the availability of copper to the cell. The role Of L-histidine during its interaction with copper(II)-albumin and in the cellular uptake of copper has generated considerable interest to determine the physico-chemical properties and the structure of physiological copper(II)-(L)-histidine complex. The structure of this complex remained inconclusive for the last four decades despite exhaustive characterization studies in aqueous solution. Recently, the physiological copper(II)-bis((L)-histidinato) complex has been crystallized and the crystal structure has been solved. The structure shows a neutral five coordinate complex with a distorted square planar pyramidal geometry. The unique structural features explain its thermodynamic stability and kinetic reactivity. This review summarizes the overall perspectives encompassing copper(II)-(L)-histidine coordination chemistry and therapeutic applications of the physiological copper(Il)-(L)histidine complex. The copper(II)-(L)-histidine (1:2 complex at physiological pH) has been widely used in the treatment of Menkes disease (a genetic neurodegenerative disorder that leads to early death in the children due to impaired copper metabolism) and more recent use has been reported in the treatment of infantile hypertrophic cardioencephalomyopathy (a condition caused by mutations in SCO2, a cytochrome c oxidase assembly gene). Crown Copyright (c) 2004 Published by Elsevier B.V. All rights reserved. C1 Hosp Sick Children, Dept Struct Biol & Biochem, Toronto, ON M5G 1X8, Canada. US FDA, Ctr Drug Evaluat & Res, Off New Drug Chem, Rockville, MD 20857 USA. Univ Toronto, Dept Biochem, Toronto, ON M5S 1A8, Canada. RP Sarkar, B (reprint author), Hosp Sick Children, Dept Struct Biol & Biochem, 555 Univ Ave, Toronto, ON M5G 1X8, Canada. EM bsarkar@sickkids.ca NR 126 TC 116 Z9 119 U1 5 U2 41 PU ELSEVIER SCIENCE SA PI LAUSANNE PA PO BOX 564, 1001 LAUSANNE, SWITZERLAND SN 0010-8545 J9 COORDIN CHEM REV JI Coord. Chem. Rev. PD MAY PY 2005 VL 249 IS 9-10 BP 895 EP 909 DI 10.1016/j.ccr.2005.09.013 PG 15 WC Chemistry, Inorganic & Nuclear SC Chemistry GA 920GD UT WOS:000228676500003 ER PT J AU Cebula, TA Brown, EW Jackson, SA Mammel, MK Mukherjee, A LeClerc, JE AF Cebula, TA Brown, EW Jackson, SA Mammel, MK Mukherjee, A LeClerc, JE TI Molecular applications for identifying microbial pathogens in the post-9/11 era SO EXPERT REVIEW OF MOLECULAR DIAGNOSTICS LA English DT Review DE bioinformatics; bioterrorism; Eschericha coli; genome; microbial forensics; MLVA; prrosequencing; PCR; SNP ID COMPLETE GENOME SEQUENCE; SINGLE-NUCLEOTIDE POLYMORPHISMS; UROPATHOGENIC ESCHERICHIA-COLI; RPOS INTERGENIC REGION; SALMONELLA-ENTERICA; HORIZONTAL TRANSFER; ALLELE FREQUENCY; MULTIPLEX PCR; GENE-TRANSFER; DNA POOLS AB Rapid advances in molecular and optical technologies over the past 10 years have dramatically impacted the way biologic research is conducted today. Examples include microarrays, capillary sequencing, optical mapping and real-time sequencing (Pyrosequencing). These technologies are capable of rapidly delivering massive amounts of genetic information and are becoming routine mainstays of many laboratories. Fortunately, advances in scientific computing have provided the enormous computing power necessary to analyze these enormous data sets. The application of molecular technologies should prove useful to the burgeoning field of microbial forensics. In the post-9/11 era, when securing America's food supply is a major endeavor, the need for rapid identification of microbes that accidentally or intentionally find their way into foods is apparent. The principle that distinguishes a microbial forensic investigation from a molecular epidemiology study is that a biocrime has been committed. If proper attribution is to be attained, a link must be made between a particular microbe in the food and the perpetrator who placed it there. Therefore, the techniques used must be able to discriminate individual isolates of a particular microbe. A battery of techniques in development for distinguishing individual isolates of particular foodborne pathogens is discussed. C1 US FDA, Ctr Food Safety & Appl Nutr, Off Appl Res & Safety Assessment, Div Mol Biol, Laurel, MD 20708 USA. RP Cebula, TA (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Appl Res & Safety Assessment, Div Mol Biol, HFS-025,8301 Muirkirk Rd, Laurel, MD 20708 USA. EM Thomas.Cebula@fda.hhs.gov; Eric.Brown@fda.hhs.gov; Scott.Jackson@fda.hhs.gov; Mark.Mammel@fda.hhs.gov; Amit.Mukherjee@fda.hhs.gov; Joseph.LeClere@fda.hhs.gov NR 64 TC 14 Z9 15 U1 0 U2 3 PU FUTURE DRUGS LTD PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEYY CENTRAL, LONDON N3 1QB, ENGLAND SN 1473-7159 J9 EXPERT REV MOL DIAGN JI Expert Rev. Mol. Diagn. PD MAY PY 2005 VL 5 IS 3 BP 431 EP 445 DI 10.1586/14737159.5.3.431 PG 15 WC Pathology SC Pathology GA 940SJ UT WOS:000230164100013 PM 15934819 ER PT J AU Kraman, M McCright, B AF Kraman, M McCright, B TI Functional conservation of Notch1 and Notch2 intracellular domains SO FASEB JOURNAL LA English DT Article DE ICD; PEST; CSL ID ANKYRIN REPEATS; CELL FATE; SEL-10; MICE; MUTATION; PROTEOLYSIS; RECEPTORS; PATHWAYS; DEFECTS; PROTEIN AB The Notch receptor is a key component of a highly conserved signaling pathway that regulates cell fate determination during development. In Drosophila, where Notch signaling was first identified and studied, there is only one Notch receptor. In contrast, mammals have four Notch receptor genes, Notch1-4. Notch1 and Notch2 are both required for embryo viability, are widely expressed in mammals, and are structurally conserved. It is presently unknown if these two receptors are functionally redundant or if they have unique capabilities related to differences in their amino acid sequences. In contrast to the rest of the molecule, the amino acid sequences of a large region of the Notch intracellular domain are not highly conserved and thus may be able to interact with distinct transcription factors and mediate the expression of different sets of genes. To determine if the function of this region is conserved, the last 426 amino acids of the Notch2 receptor have been replaced with the corresponding region of Notch1 in mice by using gene targeting. We have determined that even though the amino acid sequences of this region are only 37% identical (137/426), the C-terminal region of the Notch1 intracellular domain can functionally replace that of Notch2 in vivo. C1 US FDA, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP McCright, B (reprint author), US FDA, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. EM mccright@cber.fda.gov NR 32 TC 19 Z9 19 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAY PY 2005 VL 19 IS 7 BP 1311 EP + DI 10.1096/fj.04-3407fje PG 16 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 933CU UT WOS:000229602600012 PM 15897231 ER PT J AU Fu, X Latendresse, JR Muskhelishvili, L Blaydes, BS Delclos, KB AF Fu, X Latendresse, JR Muskhelishvili, L Blaydes, BS Delclos, KB TI Dietary modulation of 7,12-dimethylbenz[a]anthracene (DMBA)-induced adrenal toxicity in female Sprague-Dawley rats SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article DE apoptosis; DMBA; adrenal toxicity; soy; diet ID POLYCYSTIC KIDNEY-DISEASE; SUPPRESSES MAMMARY-CANCER; ESTROGEN-RECEPTORS ALPHA; NECROSIS-FACTOR-ALPHA; 7,12-DIMETHYLBENZANTHRACENE DMBA; COLON CARCINOGENESIS; FATTY-ACIDS; CELL-DEATH; GENISTEIN; APOPTOSIS AB In this study, dietary modulation of 7,12-dimethylbenz[a]anthracene-(DMBA)-induced adrenal toxicity in rats was investigated. Beginning at postnatal day (PND) 21, female Sprague-Dawley rats were fed either soy-containing NIH-31 diet or soy- and alfalfa-free 5K96 diet. On the first day of diestrus when the animals were PND 50 5, rats received either an oral dose of 80 mg/kg DMBA or sesame oil, the vehicle, and were sacrificed at 24, 36, or 48 h after treatment. Apoptosis was manifested at 24 and 36 h after DMBA treatment in the zona reticularis (ZR) and the zona fasciculata (ZF) of the adrenal cortex; this was followed by severe hemorrhagic necrosis at 48 h. DMBA-induced apoptosis, evaluated by the TUNEL assay, immunohistochemical analysis of activated caspase 3, and the ratio of expression of pro-apoptotic Bax to anti-apoptotic Bcl2, was greater in rats fed NIH-31 diet relative to rats fed 5K96 diet at 24 h after treatment. Four of six DMBA-treated rats fed 5K96 diet had severe adrenal necrosis by 48 h, whereas this lesion was present in only two of six DMBA-treated rats fed NIH-31 diet. DMBA also caused a significant decrease of serum corticosterone relative to controls at 48 h in rats fed 5K96 diet. The present study indicated that diet modulates DMBA-induced adrenal toxicity in female rats, with increased apoptosis early and reduced necrosis later in rats fed a soy-containing diet. (c) 2005 Elsevier Ltd. All rights reserved. C1 US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. Chalk River Labs, Pathol Serv, Jefferson, AR 72079 USA. RP Fu, X (reprint author), US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM xfu@nctr.fda.gov; bdelclos@nctr.fda.gov RI Latendresse, John/A-9215-2009 NR 40 TC 10 Z9 10 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 MAY PY 2005 VL 43 IS 5 BP 765 EP 774 DI 10.1016/j.fct.2005.01.017 PG 10 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA 912ZX UT WOS:000228120400016 PM 15778017 ER PT J AU Tanaka, T Nakamura, H Yodoi, J Bloom, ET AF Tanaka, T Nakamura, H Yodoi, J Bloom, ET TI Redox regulation of the signaling pathways leading to eNOS phosphorylation SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE nitric oxide synthase; thiols; Akt; endothelial cells; signal transduction; xenotransplantation; free radicals ID NITRIC-OXIDE SYNTHASE; AKT-DEPENDENT PHOSPHORYLATION; NECROSIS-FACTOR-ALPHA; T-CELL PROLIFERATION; HUMAN NK CELLS; ENDOTHELIAL-CELLS; HYDROGEN-PEROXIDE; OXIDATIVE STRESS; THIOL LEVELS; IFN-GAMMA AB Oxidative stress rnediates positive and negative effects on physiological processes. Recent reports show that H2O2 induces phosphorylation and activation of endothelial nitric oxide synthase (eNOS) through an Akt-pliospliorylatioii-depeiideiit pathway. In this study, we assessed activation of eNOS and Akt by determining their phosphorylation status. Whereas moderate levels of H2O2 (100 mu M) activated the Akt/eNOS pathway higher levels (500 mu M) did not, suggesting differential effects by differing levels of oxidative stress. We then found that two pro-oxidants with activity on sulfydryl groups, 1-chloro-2,4-dinitrobenzene (CDNB) and diethyl maleate (DEM), blocked the phosphorlation events induced by 100 mu M H2O2. GSH was not a target thiol in this system because blithionine sulfoximine did not inhibit this phosphorylation. However, down-regulation of cell membrane Surface and intracellular free thiols was associated with the inhibition of phosphorylation, Suggesting that oxidation of non-GSH thiols inhibits the H2O2-induced phosphorylation of eNOS and Akt. DTT reversed the inhibitory effects of CDNB and DEM on Akt phosphorylation and concomitantly restored cell surface thiol levels more efficiently than it restored intracellular thiols. suggesting a more prominent rote for the former. Similarly, DEM and CDNB inhibited TNF-alpha-induced Akt and eNOS phosphorylation, suggesting that thiol modification is involved in eNOS inductive pathways. Our findings suggest that eNOS activation is exquisitely sensitive to regulation by redox and that cell surface thiols, other than glutathione, regulate signal transduction leading to phosphorylation of Akt and eNOS. Published bv Elsevier Inc. C1 Food & Drug Adm, Ctr Biol Evaluat & Res, Lab Immunol & Virol, Div Cellular & Gene Therapies, Bethesda, MD 20892 USA. Kyoto Univ Hosp, Dept Expt Therapeut, Translat Res Ctr, Kyoto 606, Japan. Kyoto Univ, Inst Virus Res, Dept Biol Responses, Kyoto 606, Japan. RP Bloom, ET (reprint author), Food & Drug Adm, Ctr Biol Evaluat & Res, Lab Immunol & Virol, Div Cellular & Gene Therapies, 880 Rockville Pike, Bethesda, MD 20892 USA. EM bloom@cber.fda.gov NR 50 TC 37 Z9 38 U1 1 U2 8 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 MAY 1 PY 2005 VL 38 IS 9 BP 1231 EP 1242 DI 10.1016/j.freeradbiomed.2005.01.002 PG 12 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 917AW UT WOS:000228429200012 PM 15808421 ER PT J AU Wang, JH Cawley, NX Voutetakis, A Rodriguez, YM Goldsmith, CM Nieman, LK Hoque, ATMS Frank, SJ Snell, CR Loh, YP Baum, BJ AF Wang, JH Cawley, NX Voutetakis, A Rodriguez, YM Goldsmith, CM Nieman, LK Hoque, ATMS Frank, SJ Snell, CR Loh, YP Baum, BJ TI Partial redirection of transgenic human growth hormone secretion from rat salivary glands SO HUMAN GENE THERAPY LA English DT Article ID PERIPHERAL MEMBRANE-PROTEIN; PATHWAY-SORTING RECEPTOR; GRANULE CONTENT PROTEINS; MEDIATED GENE-TRANSFER; CARBOXYPEPTIDASE-E; ENDOCRINE SECRETION; NEUROENDOCRINE CELLS; SUBMANDIBULAR-GLANDS; HUMAN PROINSULIN; EXOCRINE GLANDS AB Regulated secretory pathway proteins, when delivered as transgenes to salivary glands, are secreted predominantly into saliva. This is not useful for those proteins whose therapeutic function is required systemically, for example, human growth hormone (hGH). One strategy to improve the efficiency of hGH secretion into the bloodstream involves manipulation of existing sorting signals. The C terminus of hGH is highly conserved and contains a domain similar to the regulated pathway sorting domain of pro-opiomelanocortin ( POMC). We hypothesized that, similar to POMC, mutation of this domain would divert hGH secretion from the regulated to the constitutive pathway, which in salivary glands leads to the bloodstream. Several mutations were made in the C terminus of the hGH cDNA and tested in vitro. One biologically active mutant containing E174A and E186A substitutions, and with an included C-terminal extension, was studied in greater detail. Compared with wild-type hGH, we found that this mutant hGH accumulated in the Golgi/trans-Golgi network and showed increased basal secretion in AtT20 cells, a model endocrine cell line. Importantly, in vivo, the mutant hGH displayed a relative increase in the proportion of constitutive pathway secretion seen from rat salivary glands, with a significantly lower saliva-versus-serum secretion ratio (p = 0.03). Although this mutant is unlikely to be therapeutically beneficial, these results suggest that the final destination of a transgenic secretory protein may be controlled by reengineering its sorting determinants. C1 Natl Inst Dent & Craniofacial Res, Gene Therapy & Therapeut Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NICHHD, Dev Neurobiol Lab, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NICHHD, Pediat & Reprod Endocrinol Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. US FDA, Div Hematol, Off Blood Res & Review, Ctr Biol Evaluat & Res,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Univ Alabama, Dept Med, Div Endocrinol Diabet & Metab, Birmingham, AL 35294 USA. Medivir UK, Cambridge CB1 9PT, England. RP Baum, BJ (reprint author), Natl Inst Dent & Craniofacial Res, Gene Therapy & Therapeut Branch, NIH, Dept Hlth & Human Serv, Bldg 10,Room 1N113,MSC-1190, Bethesda, MD 20892 USA. EM lohp@mail.nih.gov; bbaum@dir.nidcr.nih.gov FU NIDDK NIH HHS [DK46395] NR 47 TC 17 Z9 18 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD MAY PY 2005 VL 16 IS 5 BP 571 EP 583 DI 10.1089/hum.2005.16.571 PG 13 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 931RR UT WOS:000229503300004 PM 15916482 ER PT J AU Ivanov, AP Dragunsky, EM Ivanova, OE Rezapkin, GV Potapova, SG Chumakov, KM AF Ivanov, A. P. Dragunsky, E. M. Ivanova, O. E. Rezapkin, G. V. Potapova, S. G. Chumakov, K. M. TI Poliovirus-Binding Inhibition ELISA for Evaluation of Immune Response to Oral Poliovirus Vaccine A Possible Alternative to the Neutralization Test SO HUMAN VACCINES LA English DT Article DE Poliovirus; OPV; IPV; ELISA; binding inhibition AB This study describes an ELISA variant (Binding Inhibition ELISA, BI ELISA) for the quantitative determination of neutralization-relevant antibodies to polioviruses. The test differs from previously described analogs by utilizing polyclonal immune reagents: capture antibodies and biotin-labeled detecting antibodies. The BI ELISA was compared with the conventional neutralization test (NT) by testing live Sabin and wild-type poliovirus strains. The comparison of 68 serum samples taken from Oral Poliovirus Vaccine (OPV) recipients showed 100% specificity and sensitivity for Sabin 1 and Sabin 2, and 100% sensitivity and 97% specificity for Sabin 3. Good correlations (r = 0.7, 0.77, 0.65 for Sabin 1, 2, 3, respectively) were demonstrated between the NT and BI ELISA results. These results indicate that the BI ELISA can be used as a reliable alternative to the NT for determination of neutralization-relevant antibodies to polioviruses in vaccinees and in large-scale sero-epidemiological studies. C1 [Ivanov, A. P.; Dragunsky, E. M.; Rezapkin, G. V.; Potapova, S. G.; Chumakov, K. M.] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. [Ivanova, O. E.] MP Chumakov Inst Poliomyelitis & Viral Encephalit, Moscow, Russia. RP Ivanov, AP (reprint author), US FDA, Ctr Biol Evaluat & Res, I HFM 470,NLRC B-121, Rockville, MD 20852 USA. EM ivanov@cber.fda.gov OI Ivanova, O.E./0000-0003-1784-4827 FU US Department of Health; Human Services National Vaccine Program Office FX This work was supported by grants from the US Department of Health and Human Services National Vaccine Program Office. We greatly acknowledge Dr. Olga Utnitskaya, State Center of Sanitary-Epidemiological Surveillance, Ekaterinburg, Russian Federation, for collecting serum samples. NR 11 TC 0 Z9 1 U1 0 U2 1 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1554-8600 J9 HUM VACCINES JI Hum. Vaccines PD MAY-JUN PY 2005 VL 1 IS 3 BP 102 EP 105 DI 10.4161/hv.1.3.1719 PG 4 WC Biotechnology & Applied Microbiology; Immunology SC Biotechnology & Applied Microbiology; Immunology GA V19ZT UT WOS:000208111000003 PM 17012865 ER PT J AU Harris, GR AF Harris, GR TI Progress in medical ultrasound exposimetry SO IEEE TRANSACTIONS ON ULTRASONICS FERROELECTRICS AND FREQUENCY CONTROL LA English DT Review ID SPATIAL-AVERAGING CORRECTIONS; TIME-DELAY SPECTROMETRY; IN-SITU EXPOSURE; RELEASE ELLIPSOIDAL REFLECTORS; INTENSITY FOCUSED ULTRASOUND; PULSED RADIATION PRESSURE; PVDF MEMBRANE HYDROPHONE; LOW-FREQUENCY RESPONSE; FIBER-TIP SENSOR; DIAGNOSTIC ULTRASOUND AB Biomedical applications of ultrasound have experienced tremendous growth over the past 50 years. Early work in thermal therapy and surgery soon was followed by diagnostic imaging and Doppler. Because patient safety was an important issue from the beginning, the study of methods for measuring exposure levels, and their relationship to possible biological effects, paralleled the growth of the various therapeutic and diagnostic techniques. The diverse conditions of use have presented a range of exposure measurement challenges, and the sensors and techniques used to evaluate ultrasound fields have had to evolve as new or expanded clinical applications have emerged. In this paper some of the more notable of these developments are presented and discussed. Topics covered include devices and techniques, methods of calibration, progress in standardization, and current problem areas, including the effects of nonlinear propagation. Some early methods are described, but emphasis is given to more recent work applicable to present and future uses of ultrasound in medicine and biology. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. RP US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. EM grh@cdrh.fda.gov NR 209 TC 30 Z9 31 U1 1 U2 12 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0885-3010 EI 1525-8955 J9 IEEE T ULTRASON FERR JI IEEE Trans. Ultrason. Ferroelectr. Freq. Control PD MAY PY 2005 VL 52 IS 5 BP 717 EP 736 DI 10.1109/TUFFC.2005.1503960 PG 20 WC Acoustics; Engineering, Electrical & Electronic SC Acoustics; Engineering GA 936MO UT WOS:000229860300005 PM 16048175 ER PT J AU Jacobson-Kram, D Jacobs, A AF Jacobson-Kram, D Jacobs, A TI Use of genotoxicity data to positive genetox findings on or impurity .... Now what? SO INTERNATIONAL JOURNAL OF TOXICOLOGY LA English DT Article; Proceedings Paper CT 25th Annual Conference of the American-College-of-Toxicology CY NOV 07-10, 2004 CL Palm Springs, CA SP Amer Coll Toxicol DE barcinogenicity; clinical trials; genotoxic impurities; genotoxicity; pharmaceutical safety; weight-of-evidence ID ABERRATIONS IN-VITRO; CHROMOSOME-ABERRATIONS; CYTOTOXICITY; CHEMICALS; ASSAY AB Results from carcinogenicity studies are generally not available for drugs until the time of approval. Many people, including healthy volunteers are often exposed to pharmacologically active doses of the drug before carcinogenicity results are available. The Food and Drug Administration (FDA) Center for Drug Evaluation and Research uses results of genetic toxicology studies as a surrogate for carcinogenicity during the drug development phase (clinical trials). A number of issues are considered in deciding whether drugs that give positive results in genetic toxicology studies can be given to subjects in clinical trials. These relate to the drug indication, the target population, duration of treatment, and importance of the drug. In general, single-dose clinical studies are permitted regardless of the genetox results. In situations where a genetic toxicology assay showed a positive result, some review divisions have asked sponsors to perform a Syrian hamster embryo (SHE) cell transformation assay or a p53 carcinogenicity study prior to allowing repeat-dose clinical trials to proceed. This paper discusses alternatives to SHE cell and p53 assays when faced with a positive result in a genetic toxicology assay. In addition, this paper discusses factors to consider when setting limits for genotoxic impurities in drug substances and products. C1 US FDA, Ctr Drug Evaluat & Res, Off New Drugs, Rockville, MD 20852 USA. RP Jacobson-Kram, D (reprint author), US FDA, Ctr Drug Evaluat & Res, Off New Drugs, HFD-024,5515 Secur Lane, Rockville, MD 20852 USA. EM jacobsonkram@cder.fda.gov NR 21 TC 20 Z9 20 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1091-5818 J9 INT J TOXICOL JI Int. J. Toxicol. PD MAY-JUN PY 2005 VL 24 IS 3 BP 129 EP 133 DI 10.1080/10915810590952933 PG 5 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 946UV UT WOS:000230599700001 PM 16040563 ER PT J AU Leighton, JK AF Leighton, JK TI Application of emerging technologies in toxicology and safety assessment: regulatory perspectives SO INTERNATIONAL JOURNAL OF TOXICOLOGY LA English DT Article; Proceedings Paper CT 23rd Annual Meeting of the American-College-of-Toxicology CY NOV 10-13, 2002 CL HERSHEY, PA SP Amer Coll Toxicol DE biomarkers; carcinogenicity assessment; critical path; toxicogenomics; transgenic animals AB Emerging technologies applied in the regulatory field encompass a group of technologies that are used in addition to or in replacement of the standard toxicology studies conducted to support an Investigational New Drug Application (IND) or New Drug Application (NDA). The standard package includes general toxicology studies of various duration, safety pharmacology studies, genetic toxicology studies, and reproductive toxicology studies. New and emerging technologies applied to the regulation of new drugs include the use of novel biomarkers, transfected cells and transgenic animals, and the "omics" technologies (toxicogenomics, proteomics, and metabonomics). These technologies are at various stages of regulatory development and acceptance. For example, the use of transgenic animals have gained acceptance by regulatory authorities to replace a 2-year carcinogenicity assay. Alternatively, the "omics" technologies are not sufficiently advanced to achieve regulatory acceptance as replacements, although these assays have a role early in drug development and they may prove useful as supplements to standard studies. Data from these assays have been used to address specific mechanistic questions in combination with standard toxicology assays. C1 US FDA, CDER, Div Oncol Drug Prod, Rockville, MD 20852 USA. RP Leighton, JK (reprint author), US FDA, CDER, Div Oncol Drug Prod, 1451 Rockville Pike, Rockville, MD 20852 USA. EM LEIGHTONJ@cder.fda.gov NR 6 TC 17 Z9 18 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1091-5818 J9 INT J TOXICOL JI Int. J. Toxicol. PD MAY-JUN PY 2005 VL 24 IS 3 BP 153 EP 155 DI 10.1080/10915810590948352 PG 3 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 946UV UT WOS:000230599700005 PM 16040567 ER EF