FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Ngundi, MM Kulagina, NV Anderson, GP Taitt, CR AF Ngundi, Miriam M. Kulagina, Nodezhda V. Anderson, George P. Taitt, Chris R. TI Nonantibody-based recognition: alternative molecules for detection of pathogens SO EXPERT REVIEW OF PROTEOMICS LA English DT Review DE alternative recognition; antimicrobial peptide; aptamer; cell-based assays; combinatorial carbohydrate; combinatorial peptide; detection; molecular imprinting; phage display; receptor-based assays ID SURFACE-PLASMON RESONANCE; CELL-BASED BIOSENSOR; CULTURED NEURONAL NETWORKS; PARALYTIC SHELLFISH TOXINS; CHOLERA-TOXIN; IMPRINTED POLYMERS; ESCHERICHIA-COLI; IN-VITRO; ANTIMICROBIAL PEPTIDES; FISH CHROMATOPHORES AB Immunoassays have been well established for many years as the cornerstone of detection technologies. These assays are sensitive, selective and, in general, highly resistant to interference from complex sample matrices when compared with nucleic acid-based tests. However, both antibody- and nucleic acid-based detection systems require a priori knowledge of the target and development of specific reagents; multiplexed assays con become increasingly problematic when attempting to detect a plethora of different targets, the identities of which are unknown. In an effort to circumvent many of the limitations inherent in these conventional assays, other recognition reagents are being explored as alternatives, or indeed as adjuncts, to antibodies for pathogen and toxin detection. This article will review a number of different recognition systems ranging in complexity from small molecules, such as nucleic-acid aptamers, carbohydrates and peptides, to systems as highly complicated as whole cells and organisms. All of these alternative systems have tremendous potential to achieve superior sensitivity, selectivity, and stability, but are also subject to their own limitations, which are also discussed. In short, while in its infancy, this field holds great promise for the development of rapid, fieldable assays that are highly complementary to existing antibody- and nucleic acid-based technologies. C1 USN, Res Lab, Ctr Biomol Sci & Engn, Washington, DC 20375 USA. Covance, Vienna, VA 22182 USA. US FDA, Bethesda, MD 20892 USA. RP Taitt, CR (reprint author), USN, Res Lab, Ctr Biomol Sci & Engn, Code 6900,4555 Overlook Ave SW, Washington, DC 20375 USA. EM crtaitt@cbmse.nrl.navy.mil RI Anderson, George/D-2461-2011 OI Anderson, George/0000-0001-7545-9893 NR 112 TC 43 Z9 45 U1 3 U2 33 PU FUTURE DRUGS LTD PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1478-9450 J9 EXPERT REV PROTEOMIC JI Expert Rev. Proteomics PD OCT PY 2006 VL 3 IS 5 BP 511 EP 524 DI 10.1586/14789450.3.5.511 PG 14 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 136PC UT WOS:000244235600017 PM 17078765 ER PT J AU Sahu, SC Ruggles, DI O'Donnell, MW AF Sahu, Saura C. Ruggles, Dennis I. O'Donnell, Michael W. TI Prooxidant activity and toxicity of nordihydroguaiaretic acid in clone-9 rat hepatocyte cultures SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article DE hepatotoxicity; liver toxicity; hepatocytes; clone-9 cells; NDGA ID RENAL CYSTIC-DISEASE; RAPID COLORIMETRIC ASSAY; LIVER CELL-LINE; LIPID-PEROXIDATION; IN-VITRO; INDUCED HEPATOTOXICITY; PHENOLIC ANTIOXIDANTS; OXIDATIVE STRESS; LUNG-CANCER; END-POINTS AB Nordihydroguaiaretic acid (NDGA) is a polyphenol. It is present at high concentrations in the leaves of the evergreen desert shrub, Larrea tridentate (Creosote bush), which has a long history of medicinal use traditionally by the native Americans and Mexicans. It is generally believed that the antioxidant properties of NDGA are responsible for the medicinal value of this desert shrub. The clone-9 rat hepatocyte cultures were used as an in vitro model to assess the hepatotoxic potential of NDGA and to determine whether it exhibits any prooxidant activity. The hepatocyte cultures were treated with NDGA for 2 h at 37 degrees C at concentrations of 0-100 mu M. After the treatment period the cells, the culture supernatants and cell lysates were assayed for evaluation of prooxidant activity and toxicity of NDGA. Oxidative stress level and oxidative cell injury as measured by the peroxidation of membrane lipids and DNA double-strand breaks were used to index prooxidant activity. Cytotoxicity as measured by the leakage of the liver enzyme lactate dehydrogenase (LDH) into the culture medium, mitochondrial function and extent of cell proliferation were used as the endpoints of toxicity. Significant concentration-dependent differences were observed in these biomarkers over the concentration range examined demonstrating the prooxidant activity and toxicity of NDGA in clone-9 rat hepatocyte cultures. Published by Elsevier Ltd. C1 US FDA, Div Toxicol, Off Appl Res & Safety Assessment, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. US FDA, Div Math, Off Sci Anal & Support, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. RP Sahu, SC (reprint author), US FDA, Div Toxicol, Off Appl Res & Safety Assessment, Ctr Food Safety & Appl Nutr, 8301 Muirkirk Rd, Laurel, MD 20708 USA. EM saura.sahu@fda.hhs.gov NR 79 TC 16 Z9 18 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 OCT PY 2006 VL 44 IS 10 BP 1751 EP 1757 DI 10.1016/j.fct.2006.05.016 PG 7 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA 085XS UT WOS:000240638300016 PM 16839654 ER PT J AU Potter, ME AF Potter, ME CA ICMSF TI Use of epidemiologic data to measure the impact of food safety control programs SO FOOD CONTROL LA English DT Article DE food safety; foodborne disease; epidemiology; evaluation ID SALMONELLA-ENTERITIDIS INFECTIONS; UNITED-STATES; SYNDROMIC SURVEILLANCE; DISEASE; OUTBREAKS; QUALITY; SYSTEM; FORUM; TIME AB The purpose of this ICMSF position paper is to describe epidemiologic data that are useful for evaluating the public health impact of food safety control programs, and to identify how epidemiologic data can be used in the evaluative process. The paper describes how epidemiologic data can be focused on food safety and public health targets by measuring process indicators, physical and/or microbiological outcome indicators and public health outcome indicators. ICMSF believes that integration and application of epidemiologic data from appropriate data systems for the evaluation of food safety strategies will justify and/or lead to proper modification of food safety programs and support efforts to determine equivalency in health protection between alternative food safety strategies. (c) 2005 Elsevier Ltd. All rights reserved. C1 US FDA, Ctr Food Safety & Appl Nutr, Atlanta, GA 30309 USA. RP Potter, ME (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 60 8th St NE, Atlanta, GA 30309 USA. EM mpotter@cfsan.fda.gov NR 36 TC 20 Z9 20 U1 1 U2 1 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 OCT PY 2006 VL 17 IS 10 BP 825 EP 837 DI 10.1016/j.foodcont.2005.05.010 PG 13 WC Food Science & Technology SC Food Science & Technology GA 050SE UT WOS:000238107600011 ER PT J AU Tournas, VH Heeres, J Burgess, L AF Tournas, VH Heeres, J Burgess, L TI Moulds and yeasts in fruit salads and fruit juices SO FOOD MICROBIOLOGY LA English DT Article DE moulds; yeasts; fruit salads; fruit juices ID UNPASTEURIZED ORANGE JUICE; ESCHERICHIA-COLI; APPLE CIDER; OUTBREAK AB Thirty-eight fruit salad samples including cantaloupe, citrus fruits, honeydew, pineapple, cut strawberries and mixed fruit salads, and 65 pasteurized fruit juice samples (apple, carrot, grapefruit, grape and orange juices, apple cider, and soy milk) were purchased from local supermarkets in the Washington, DC area and tested for fungal contamination. The majority of fruit salad samples (97%) were contaminated with yeasts at levels ranging from < 2.0 to 9.72log(10) of colony forming units per gram (cfu/g). Frequently encountered yeasts were Pichia spp., Candida pulcherrima, C lambica, C sake, Rhodotorula spp., and Debaryomyces polymorphus. Low numbers of Penicillium spp. were found in pineapple salads, whereas Cladosporium spp. were present in mixed fruit and cut strawberry salads. Twenty-two per cent of the fruit juice samples tested showed fungal contamination. Yeasts were the predominant contaminants ranging from < 1.0 to 6.83 log(10) efu/ml. Yeasts commonly found in fruit juices were C lambica, C sake, and Rhodotorula rubra. Geotrichum spp. and low numbers of Penicillium and Fusarium spp. (1.70 and 1.60 log(10) efu/ml, respectively) were present in grapefruit juice. (c) 2006 Elsevier Ltd. All rights reserved. C1 Food & Drug Adm, Ctr Food Safety & Appl Nutr HFS 315, College Pk, MD 20740 USA. Univ Maryland, JIFSAN, College Pk, MD 20740 USA. RP Tournas, VH (reprint author), Food & Drug Adm, Ctr Food Safety & Appl Nutr HFS 315, College Pk, MD 20740 USA. EM vtournas@cfsan.fda.gov NR 22 TC 83 Z9 90 U1 4 U2 31 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0740-0020 J9 FOOD MICROBIOL JI Food Microbiol. PD OCT PY 2006 VL 23 IS 7 BP 684 EP 688 DI 10.1016/j.fm.2006.01.003 PG 5 WC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology SC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology GA 053ZS UT WOS:000238345600012 PM 16943069 ER PT J AU Lee, HC Goodman, JL AF Lee, Hin C. Goodman, Jesse L. TI Anaplasma phagocytophilum causes global induction of antiapoptosis in human neutrophils SO GENOMICS LA English DT Article DE Anaplasma phagocytophilum; human granulocytic anaplasmosis; ehrlichiosis; antiapoptosis; microarray analysis; neutrophils ID HUMAN GRANULOCYTIC EHRLICHIOSIS; NF-KAPPA-B; INDUCED APOPTOSIS; CASPASE-3 ACTIVATION; DEATH RECEPTORS; HL-60 CELLS; AGENT; INFECTION; EXPRESSION; SURVIVAL AB Anoplasma phagocytophilum (Ap), the agent of the tick-borne disease human granulocytic anaplasmosis, is an obligate intracellular pathogen unique in its ability to target and replicate within neutrophils. It profoundly inhibits neutrophil apoptosis, prolonging neutrophil survival from hours to days. To determine the basis of antiapoptosis, we compared gene expression in Ap-infected vs mock-infected human neutrophils. Antiapoptosis genes were consistently and significantly up-regulated (2- to 15-fold) within 1-3 h. These genes synergistically inhibit apoptosis through. several interconnected pathways including p38MAPK (MAP2K3), ERK (IER3), PI3K (PRKCD), and NF-kappa B (BCL2A1, NFKB1, NFKBIA, GADD45B). Both extrinsic death receptor (TNFAIP3, CFLAR, SOD2) and intrinsic mitochondrial:(BCL2A1, PIM2, BIRC3) pathways were affected as confirmed by reductions in both caspase 3 and caspase 8 activities. Several important antiapoptotic genes noted to be up-regulated in Ap-infected neutrophils were not up-regulated during Ap infection of HL-60 cells (which is not antiapoptotic). In conclusion, just as apoptosis may be triggered through multiple molecular pathways, effective antiapoptosis of neutrophils is achieved rapidly and redundantly by this intracellular pathogen dependent on cell survival. Published by Elsevier Inc. C1 US FDA, Ctr Biol Evaluat & Res, Off Ctr Director, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Bethesda, MD 20892 USA. RP Goodman, JL (reprint author), US FDA, Ctr Biol Evaluat & Res, Off Ctr Director, NIH Campus,8800 Rockville Pike,Bldg 29B,Suite 5NN, Bethesda, MD 20892 USA. EM jesse.goodman@fda.hhs.gov NR 31 TC 27 Z9 29 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 0888-7543 J9 GENOMICS JI Genomics PD OCT PY 2006 VL 88 IS 4 BP 496 EP 503 DI 10.1016/j.ygeno.2006.06.002 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 093WX UT WOS:000241202100012 PM 16876385 ER PT J AU Shin, EC Mihalik, K Feinstone, SM Rice, CM Rehermann, B AF Shin, Eui-Cheol Mihalik, Kathleen Feinstone, Stephen M. Rice, Charles M. Rehermann, Barbara TI CD8 T cells are recruited to the liver in acute hepatitis C by HCV RNA-induced CXCR3-and CCR5-ligands SO HEPATOLOGY LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 27-31, 2006 CL Boston, MA SP Amer Assoc Study Liver Dis C1 NIDDK, Immunol Sect, LDB, NIH, Bethesda, MD USA. US FDA, Lab Hepatitis Viruses, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. Rockefeller Univ, Ctr Study Hepatitis C, New York, NY 10021 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 2006 VL 44 IS 4 SU 1 MA 27 BP 198A EP 198A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 096FF UT WOS:000241362300028 ER PT J AU Watanabe, H Major, ME AF Watanabe, Hisayoshi Major, Marian E. TI Persistence of hepatitis C virus (HCV) in chimpanzees is associated with a loss of intrahepatic T cell function during the late acute phase SO HEPATOLOGY LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 27-31, 2006 CL Boston, MA SP Amer Assoc Study Liver Dis C1 US FDA, Ctr Biol Evaluat & Res, 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 2006 VL 44 IS 4 SU 1 MA 282 BP 295A EP 295A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 096FF UT WOS:000241362300283 ER PT J AU Soon, GX Laessig, K Fleischer, R AF Soon, Guoxing Laessig, Katherine Fleischer, Russell TI Can ALT and HBV DNA replace liver biopsy for the evaluation of hepatitis B trials? SO HEPATOLOGY LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 27-31, 2006 CL Boston, MA SP Amer Assoc Study Liver Dis C1 FDA, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 2006 VL 44 IS 4 SU 1 MA 980 BP 553A EP 553A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 096FF UT WOS:000241362302074 ER PT J AU Cai, F Adrion, CB Keller, JE AF Cai, Fang Adrion, Carrie B. Keller, James E. TI Comparison of extracellular and intracellular potency of botulinum neurotoxins SO INFECTION AND IMMUNITY LA English DT Article ID SPINAL-CORD CELLS; TETANUS TOXIN; ZINC-BINDING; LIGHT-CHAIN; TYROSINE PHOSPHORYLATION; CLOSTRIDIAL NEUROTOXINS; NEUROMUSCULAR-JUNCTION; ENDOPEPTIDASE ACTIVITY; PROTEOLYTIC ACTIVITY; BIOLOGICAL-ACTIVITY AB Levels of botulinum neurotoxin (BoNT) proteolytic activity were compared using a cell-free assay and living neurons to measure extracellular and intracellular enzymatic activity. Within the cell-free reaction model, BoNT serotypes A and E (BoNT/A and BoNT/E, respectively) were reversibly inhibited by chelating Zn2+ with N,N,N',N'-tetrakis (2-pyridylmethyl) ethylenediamine (TPEN). BoNT/E required relatively long incubation with TPEN to achieve total inhibition, whereas BoNT/A was inhibited immediately upon mixing. When naive Zn2+-containing BoNTs were applied to cultured neurons, the cellular action of each BoNT was rapidly inhibited by subsequent addition of TPEN, which is membrane permeable. Excess Zn2+ added to the culture medium several hours after poisoning fully restored intracellular toxin activity. Unlike TPEN, EDTA irreversibly inhibited both BoNT/A and -E within the cell-free in vitro reaction. Excess Zn2+ did not reactivate the EDTA-treated toxins. However, application of EDTA-treated BoNT/A or -E to cultured neurons demonstrated normal toxin action in terms of both blocking neurotransmission and SNAP-25 proteolysis. Different concentrations of EDTA produced toxin preparations with incrementally reduced in vitro proteolytic activities, which, when applied to living neurons showed undiminished cellular potency. This suggests that EDTA renders the BoNT proteolytic domain conformationally inactive when tested with the cell-free reaction, but this change is corrected during entry into neurons. The effect of EDTA is unrelated to Zn2+ because TPEN could be applied to living cells before or after poisoning to produce rapid and reversible inhibition of both BoNTs. Therefore, bound Zn2+ is not required for toxin entry into neurons, and removal of Zn2+ from cytosolic BoNTs does not irreversibly alter toxin structure or function. We conclude that EDTA directly alters both BoNTs in a manner that is independent of Zn2+. C1 US FDA, Lab Bacterial Toxins, Div Bacterial Parasit & Allergen Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Keller, JE (reprint author), US FDA, Lab Bacterial Toxins, Div Bacterial Parasit & Allergen Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. EM james.keller@fda.hhs.gov FU PHS HHS [Y2-A13744-02] NR 51 TC 5 Z9 5 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD OCT PY 2006 VL 74 IS 10 BP 5617 EP 5624 DI 10.1128/IAI.00552-06 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 090RF UT WOS:000240967900021 PM 16988237 ER PT J AU Choi, E Kioi, M Puri, RK Hogaboam, C AF Choi, E. Kioi, M. Puri, R. K. Hogaboam, C. TI Therapeutic antagonism of IL-13 receptors abrogated chronic fungal asthma SO INFLAMMATION RESEARCH LA English DT Meeting Abstract C1 Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI 48109 USA. US FDA, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. RI hogaboam, cory /M-3578-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIRKHAUSER VERLAG AG PI BASEL PA VIADUKSTRASSE 40-44, PO BOX 133, CH-4010 BASEL, SWITZERLAND SN 1023-3830 J9 INFLAMM RES JI Inflamm. Res. PD OCT PY 2006 VL 55 SU 2 BP S126 EP S126 PG 1 WC Cell Biology; Immunology SC Cell Biology; Immunology GA 100KT UT WOS:000241668700093 ER PT J AU Koturbash, I Baker, M Loree, J Kutanzi, K Hudson, D Pogribny, I Sedelnikova, O Bonner, W Kovalchuk, O AF Koturbash, Igor Baker, Mike Loree, Jonathan Kutanzi, Kristy Hudson, Darryl Pogribny, Igor Sedelnikova, Olga Bonner, William Kovalchuk, Olga TI Epigenetic dysregulation underlies radiation-induced transgenerational genome instability in vivo SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE radiation; transgeneration genome instability; epigenetics; DNA methylation; DNA damage ID METHYLATION PATTERNS; DNA-DAMAGE; EXPRESSION; EXPOSURE; GENE AB Purpose: Although modern cancer radiation therapy has led to increased patient survival rates, the risk of radiation treatment-related complications is becoming a growing problem. Among various complications, radiation also poses a threat to the progeny of exposed parents. It causes transgenerational genome instability that is linked to transgenerational carcinogenesis. Although the occurrence of transgenerational genome instability, which manifests as elevated delayed and nontargeted mutation, has been well documented, the mechanisms by which it arises remain obscure. We hypothesized that epigenetic alterations may play a pivotal role in the molecular etiology of transgenerational genome instability. Methods and Materials: We studied the levels of cytosine DNA methylation in somatic tissues or unexposed offspring upon maternal, paternal, or combined parental exposure. Results: We observed a significant loss of global cytosine DNA methylation in the thymus tissue of the offspring upon combined parental exposure. The loss of DNA methylation was paralleled by a significant decrease in the levels of maintenance (DNMT1) and de novo methyltransferases DNMT3a and 3b and methyl-CpG-binding protein MeCP2. Along with profound changes in DNA methylation, we noted a significant accumulation of DNA strand breaks in thymus, which is a radiation carcinogenesis target organ. Conclusion: The observed changes were indicative of a profound epigenetic dysregulation in the offspring, which in turn could lead to genome destabilization and possibly could serve as precursor for transgenerational carcinogenesis. Future studies are clearly needed to address the cellular and carcinogenic repercussions of those changes. (c) 2006 Elsevier Inc. C1 Univ Lethbridge, Dept Biol Sci, Lethbridge, AB T1K 3M4, Canada. Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 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 15 TC 66 Z9 70 U1 0 U2 2 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 OCT 1 PY 2006 VL 66 IS 2 BP 327 EP 330 DI 10.1016/j.ijrobp.2006.06.012 PG 4 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 086UW UT WOS:000240699500004 PM 16965987 ER PT J AU Loyo-Berrios, NI Orengo, JC Serrano-Rodriguez, RA AF Loyo-Berrios, Nilsa I. Orengo, Juan C. Serrano-Rodriguez, Ruby A. TI Childhood asthma prevalence in Northern Puerto Rico, the Rio Grande, and Loiza experience SO JOURNAL OF ASTHMA LA English DT Article DE prevalence; childhood asthma; wheezing illness; family history; Puerto Rico ID TROPICAL ENVIRONMENT; CHILDREN; RISK; ALPHA-1-ANTITRYPSIN; ALLERGENS; VARIANTS; RHINITIS; EXPOSURE; SMOKING; LIFE AB Objective. Childhood asthma is highly prevalent in some areas of Puerto Rico. The objective of this study was to estimate the prevalence of asthma in two municipalities of Northern Puerto Rico. Methods. Children 6 to 7 and 13 to 14 years of age participated in the school-based cross-sectional study. Results. A total of 1,467 elementary school students and 1,334 junior-high school students were included in the survey. A high prevalence of asthma was observed; 46% in elementary schools and 24% in junior-high schools. In elementary schools, family history of asthma (FHA) was associated with ever wheezed (PR = 2.00, 95% CI 1.59, 2.52), wheeze during last year ( PR = 2.02, 95% CI 1.54, 2.62), and asthma (PR = 2.33, 95% CI 1.86, 2.92). For junior-high schools FHA was associated with ever wheezed (PR = 2.01, 95% CI 1.56, 2.57), wheeze during previous year (PR = 2.00, 95% CI 1.47, 2.73), and asthma (PR = 2.72, 95% CI 2.06, 3.60). Conclusions. This study showed a high prevalence of asthma and related symptoms in Northern Puerto Rico. FHA was strongly associated with asthma and its symptoms. Further research is recommended to look at genetics, sensitivity levels, indoor and outdoor pollution, and gene-environment interactions. C1 US FDA, Ctr Devices & Radiol Hlth, Off Surveillance & Biometr, Div Postmarket Surveillance,Epidemiol Branch, Rockville, MD 20850 USA. Ponce Sch Med, Publ Hlth Program, Ponce, PR USA. Puerto Rico Dept Hlth, Behav Risk Factor Surveillance Syst, San Juan, PR USA. RP Loyo-Berrios, NI (reprint author), US FDA, Ctr Devices & Radiol Hlth, Off Surveillance & Biometr, Div Postmarket Surveillance,Epidemiol Branch, 1350 Piccard Dr, Rockville, MD 20850 USA. EM nilsa.loyo-berrios@fda.hhs.gov NR 32 TC 20 Z9 20 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0277-0903 J9 J ASTHMA JI J. Asthma PD OCT PY 2006 VL 43 IS 8 BP 619 EP 624 DI 10.1080/02770900600878693 PG 6 WC Allergy; Respiratory System SC Allergy; Respiratory System GA 094NZ UT WOS:000241247500010 PM 17050228 ER PT J AU Foley, SL White, DG McDermott, PF Walker, RD Rhodes, B Fedorka-Cray, PJ Simjee, S Zhao, SH AF Foley, Steven L. White, David G. McDermott, Patrick F. Walker, Robert D. Rhodes, Bobbie Fedorka-Cray, Paula J. Simjee, Shabbir Zhao, Shaohua TI Comparison of subtyping methods for differentiating Salmonella enterica serovar Typhimurium isolates obtained from food animal sources SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID FIELD GEL-ELECTROPHORESIS; UNITED-STATES; SEQUENCE; GENES; DNA; EXPRESSION; RESISTANCE; INVASION; STRAINS AB Molecular characterization (e.g., DNA-based typing methods) of Salmonella isolates is frequently employed to compare and distinguish clinical isolates recovered from animals and from patients with food-borne disease and nosocomial infections. In this study, we compared the abilities of different phenotyping and genotyping methods to distinguish isolates of Salmonella enterica serovar Typhimurium from different food animal sources. One hundred twenty-eight S. enterica serovar Typhimurium strains isolated from cattle, pigs, chickens, and turkeys or derived food products were characterized using pulsed-field gel electrophoresis (PFGE), repetitive element PCR (Rep-PCR), multilocus sequence typing (MLST), plasmid profiling, and antimicrobial susceptibility testing. Among the 128 Salmonella isolates tested, we observed 84 Rep-PCR profiles, 86 PFGE patterns, 89 MLST patterns, 36 plasmid profiles, and 38 susceptibility profiles. The molecular typing methods, i.e., PFGE, MLST, and Rep-PCR, demonstrated the best discriminatory power among Salmonella isolates. However, no apparent correlation was evident between the results of one molecular typing method and those of the others, suggesting that a combination of multiple methods is needed to differentiate S. enterica serovar Typhimurium isolates that genetically cluster according to one particular typing method. C1 Marshfield Clin Res Fdn, Natl Farm Med Ctr, Marshfield, WI 54449 USA. US FDA, Ctr Vet Med, Res Off, Div Anim & Food Microbiol, Laurel, MD USA. USDA ARS, Bacterial Epidemiol & Antimicrobial Resistance Re, Athens, Greece. Univ Cent Arkansas, Dept Biol, Conway, AR USA. RP Foley, SL (reprint author), Marshfield Clin Res Fdn, Natl Farm Med Ctr, Marshfield, WI 54449 USA. EM foley.steven@mcrf.mfldclin.edu NR 30 TC 64 Z9 67 U1 0 U2 9 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD OCT PY 2006 VL 44 IS 10 BP 3569 EP 3577 DI 10.1128/JCM.00745-06 PG 9 WC Microbiology SC Microbiology GA 093AF UT WOS:000241138800017 PM 17021084 ER PT J AU Neverov, AA Riddell, MA Moss, WJ Volokhov, DV Rota, PA Lowe, LE Chibo, D Smit, SB Griffin, DE Chumakov, KM Chizhikov, VE AF Neverov, Alexander A. Riddell, Michaela A. Moss, William J. Volokhov, Dmitriy V. Rota, Paul A. Lowe, Luis E. Chibo, Doris Smit, Sheilagh B. Griffin, Diane E. Chumakov, Konstantin M. Chizhikov, Vladimir E. TI Genotyping of measles virus in clinical specimens on the basis of oligonucleotide microarray hybridization patterns SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID MOLECULAR EPIDEMIOLOGY; OUTBREAK INVESTIGATIONS; MUMPS-VIRUS; STRAINS; IDENTIFICATION; ELIMINATION; AUSTRALIA; DNA; CIRCULATION; AFRICA AB An oligonucleotide microarray hybridization method for identification of most known measles virus (MV) genotypes was developed. Like the conventional genotyping method, the microarray relied on detecting sequence differences in the 450-nucleotide region coding for the COOH-terminal 150 amino acids of the nucleoprotein (N). This region was amplified using PCR primers binding to all known MV genotypes. The microarray included 71 pairs of oligonucleotide probes (oligoprobes) immobilized on glass slides. Each pair consisted of a genotype-specific oligoprobe, which matched the sequence of only one target genotype, and a control oligoprobe, which contained mismatches at the nucleotide positions unique to this genotype. A pattern recognition algorithm based on cluster analysis of the ratios of hybridization signals from specific and control oligoprobes was used to identify the specific W genotype. Following the initial validation, the method was used for rapid genotyping of two panels of coded samples. The results of this study showed good sensitivity (90.7%), specificity (100%), and genotype agreement (91.8%) for the new method compared to the results of genotyping conducted using phylogenetic analysis of viral sequences of the C terminus of the N gene. In addition, the microarray demonstrated the ability to identify potential new genotypes of MV based on the similarity of their hybridization patterns with those of known MV genotypes. C1 US FDA, LMD, CBER, Rockville, MD 20852 USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, W Harry Feinstone Dept Mol Microbiol & Immunol, Baltimore, MD USA. WHO, Ctr Dis Control & Prevent, Measles Mumps Rubella & Herpesvirus Branch, Global Measles Ref Lab, Atlanta, GA USA. WHO, Victorian Infect Dis Ref Lab, Western Pacific Reg Measles Ref Lab, Melbourne, Vic, Australia. Natl Inst Communicable Dis, Vaccine Preventable Virus Infect Unit, Johannesburg, South Africa. State Res Ctr Virol & Biotechnol, Inst Mol Biol, Koltsov, Novosibirsk Reg, Russia. RP Neverov, AA (reprint author), US FDA, LMD, CBER, HFM-470,1401 Rockville Pike, Rockville, MD 20852 USA. EM alexander.neverov@fda.hhs.gov OI Chibo, Doris/0000-0002-6950-6910; Riddell, Michaela/0000-0001-8852-0569 NR 38 TC 12 Z9 14 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 OCT PY 2006 VL 44 IS 10 BP 3752 EP 3759 DI 10.1128/JCM.00998-06 PG 8 WC Microbiology SC Microbiology GA 093AF UT WOS:000241138800042 PM 17021105 ER PT J AU Abel, DB Dehdashtian, MM Rodger, ST Smith, AC Smith, LJ Waninger, MS AF Abel, Dorothy B. Dehdashtian, Mark M. Rodger, Stuart T. Smith, Angela C. Smith, Louis J. Waninger, Matthew S. TI Evolution and future of preclinical testing for endovascular grafts SO JOURNAL OF ENDOVASCULAR THERAPY LA English DT Article DE Food and Drug Administration; endovascular graft; stent-graft; preclinical testing; endovascular graft standards; animal studies; sealing; fixation; material fatigue; material durability AB The preclinical testing of endovascular grafts has evolved significantly since the creation and early testing of these devices; however, there are continued limitations in using preclinical testing to predict clinical performance. Early testing was conducted in the absence of standards and guidance specific to endovascular grafts, and references available for vascular grafts and stents did not adequately account for the complexity of endovascular graft systems. Failure of early-generation devices suggested that the testing being conducted was inadequate and that there was a lack of understanding of the in vivo environment. These concerns led to several efforts to improve preclinical testing. The Food and Drug Administration (FDA) sponsored a workshop to discuss the limitations inherent in testing of endovascular grafts, and an ISO standard for endovascular grafts was developed. Publication of the standard in 2003 succeeded in standardizing testing and reporting across device manufacturers; however, several clinical failure modes, such as migration and stent fractures, continued to be unpredicted by current preclinical testing. This, coupled with knowledge gained from additional clinical experience, led the FDA to hold a second workshop to discuss the benefits and limitations of current testing and propose future testing that may better predict device performance. This workshop was successful in accurately describing past testing, determining what has been learned, identifying issues that have not been adequately addressed, proposing modifications to address these limitations, and discussing how the proposed modifications should be implemented. While significant progress has been made in endovascular graft testing, continued collaboration among industry, academia, regulators, and clinicians will provide continued improvement in the predictability of device performance. C1 US FDA, CDRH, ODE, DCD,PVDB, Rockville, MD 20850 USA. Edwards Lifesci, Irvine, CA USA. Vascutek, Inchinnan, Scotland. WL Gore & Assoc Inc, Flagstaff, AZ USA. Cook Inc, Bloomington, IN USA. RP Abel, DB (reprint author), US FDA, CDRH, ODE, DCD,PVDB, 9200 Corp Blvd,HFZ-450, Rockville, MD 20850 USA. EM dorothy.abel@fda.hhs.gov NR 9 TC 16 Z9 16 U1 2 U2 4 PU ALLIANCE COMMUNICATIONS GROUP DIVISION ALLEN PRESS PI LAWRENCE PA 810 EAST 10TH STREET, LAWRENCE, KS 66044 USA SN 1526-6028 J9 J ENDOVASC THER JI J. Endovascular Ther. PD OCT PY 2006 VL 13 IS 5 BP 649 EP 659 DI 10.1583/06-1872.1 PG 11 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 101PO UT WOS:000241752900009 PM 17042666 ER PT J AU Ryabinin, VA Shundrin, LA Kostina, EB Laassri, M Chizhikov, V Shchelkunov, SN Chumakov, K Sinyakov, AN AF Ryabinin, Vladimir A. Shundrin, Leonid A. Kostina, Elena B. Laassri, Majid Chizhikov, Vladimir Shchelkunov, Sergei N. Chumakov, Konstantin Sinyakov, Alexander N. TI Microarray assay for detection and discrimination of Orthopoxvirus species SO JOURNAL OF MEDICAL VIROLOGY LA English DT Article DE smallpox; monkeypox; molecular detection; differentiation; orthopoxviruses; herpesviruses ID GENOMIC ANALYSIS; HUMAN MONKEYPOX; VIRUS; IDENTIFICATION; SEQUENCE; PCR; DIFFERENTIATION; SMALLPOX; PROTEINS; HYBRIDIZATION AB A microarray method was developed for simultaneous detection and identification of six species of Orthopoxvirus (OPV) including Variola, Monkeypox, Cowpox, Camelpox, Vaccinia, and Ectromelia viruses. The method allowed us to discriminate OPV species from varicella-zoster virus (VZV), Herpes Simplex 1 virus (HSV-1), and Herpes Simplex 2 virus (HSV-2) that cause infections with clinical manifestations similar to OPV infections. The nucleotide sequences of the C23L/B29R and the B19R genes identified for 86 and 72 different OPV strains, respectively, were used to design species-specific microarray oligonucleotide probes (oligoprobes). The microarray also contained several oligoprobes selected from the ORF31, US4, and US5 genes of VZV, HSV-1, and HSV-2, respectively. The samples (from HSVs or OPVs) of ssDNAs for analyses were prepared by using asymmetric PCR followed by chemical labeling of ssDNA with Cy3 dye. DNA from 52 samples of various OPV species, two isolates of VZV, two of HSV-1, and three of HSV-2 were tested using the developed microarray assay; all tested viruses were accurately identified. To ensure the robustness of the microarray assay, three additional unrelated variola virus strains with unknown sequences of the C23L/B29R and the B19R genes were tested. In each instance the microarray unambiguously identified them as Variola virus species. The results obtained in this study demonstrated that this new microarray method is a valuable tool for the rapid and accurate detection and differentiation of these important viral pathogens. C1 US FDA, Ctr Biol Evaluat & Res, Lab Method Dev, Rockville, MD 20852 USA. Russian Acad Sci, Inst Chem Biol & Fundamental Med, SB, Novosibirsk, Russia. State Res Ctr Virol & Biotechnol Vector, Koltsov, Russia. RP Laassri, M (reprint author), US FDA, Ctr Biol Evaluat & Res, Lab Method Dev, 1401 Rockville Pike,HFM-470, Rockville, MD 20852 USA. RI Sinyakov, Aleksandr /H-1129-2013 NR 33 TC 22 Z9 25 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0146-6615 J9 J MED VIROL JI J. Med. Virol. PD OCT PY 2006 VL 78 IS 10 BP 1325 EP 1340 DI 10.1002/jmv.20698 PG 16 WC Virology SC Virology GA 081MY UT WOS:000240322900012 PM 16927285 ER PT J AU Kavanaugh, C Seifried, H Ellwood, K Yetley, E Swanson, C Milner, J AF Kavanaugh, Claudine Seifried, Harold Ellwood, Kathleen Yetley, Elizabeth Swanson, Christine Milner, John TI A research agenda for biomarkers as indicators of cancer risk reduction following dietary manipulation SO JOURNAL OF NUTRITION LA English DT Editorial Material C1 NCI, Div Canc Prevent, Rockville, MD 20852 USA. US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. NIH, Off Dietary Supplements, Rockville, MD 20852 USA. RP Seifried, H (reprint author), NCI, Div Canc Prevent, Rockville, MD 20852 USA. EM hs41s@nih.gov NR 1 TC 0 Z9 0 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 OCT PY 2006 VL 136 IS 10 BP 2666S EP 2667S PG 2 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 089OH UT WOS:000240889600034 PM 16988142 ER PT J AU Jadhav, PR Agerso, H Tornoe, CW Gobburu, JVS AF Jadhav, Pravin R. Agerso, Henrik Tornoe, Christoffer W. Gobburu, Jogarao V. S. TI Semi-mechanistic pharmacodynamic modeling for degarelix, a novel gonadotropin releasing hormone (GnRH) blocker SO JOURNAL OF PHARMACOKINETICS AND PHARMACODYNAMICS LA English DT Article DE hpg-axis; testosterone; GnRH; leutinizing hormone; pharmacokinetics; pharmacodynamics; degarelix ID LUTEINIZING-HORMONE; PROSTATE-CANCER; ANTAGONIST; TESTOSTERONE; PHARMACOKINETICS; MEN; LH; SYSTEM; HYPOGONADISM; CETRORELIX AB An integrated semi-mechanistic pharmacodynamic (PD) model describing the relationship between luteinizing hormone (LH) and testosterone (T) after short-term administration of degarelix was developed. Data from three clinical studies involving, intravenous (IV) and subcutaneous (SC) dosing, in healthy male subjects were available. Degarelix pharmacokinetic (PK) data from all studies were modeled simultaneously. One intravenous study was used to develop the PD model and the two other studies (IV and SC dosing) were used to qualify the model. Degarelix PK follows a two-compartment model and exhibits flip-flop kinetics after subcutaneous dosing. Based on physiological mechanism, the gonadotropin releasing hormone (GnRH) time course was described using a pulsatile release model. A precursor-dependent pool model was used to describe the kinetics of LH in the pituitary and plasma compartment. In males, LH regulates T production in leydig cells. Degarelix inhibits the release of LH from the pool compartment to the plasma compartment leading to decreased T production. The plasma half-life of LH (2.6-3.3 hr) and T (2.7 hr) match well with the literature reports. The proposed PD model reasonably described the time course of LH and T including the LH rebound for short-term studies. The model predicted the time course of LH and T for the second IV and SC dosing studies very well. However, the long term simulations from the final model did not match with literature reports. A modification is suggested based on the physiological understanding of the system. The proposed novel modification to precursor models can be of general use for predicting long term responses. C1 Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. Virginia Commonwealth Univ, Dept Pharmaceut, Med Coll Virginia, Richmond, VA 23298 USA. Ferring Pharmaceut AS, Expt Med, Copenhagen, Denmark. RP Gobburu, JVS (reprint author), Ctr Drug Evaluat & Res, 10903 New Hampshire Ave,Bldg 21, Silver Spring, MD 20993 USA. EM jogarao.gobburu@fda.hhs.gov NR 31 TC 8 Z9 9 U1 0 U2 5 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 OCT PY 2006 VL 33 IS 5 BP 609 EP 634 DI 10.1007/s10928-006-9025-1 PG 26 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 083TM UT WOS:000240481100004 PM 16967346 ER PT J AU Burvall, A Barrett, HH Dainty, C Myers, KJ AF Burvall, Anna Barrett, Harrison H. Dainty, Christopher Myers, Kyle J. TI Singular-value decomposition for through-focus imaging systems SO JOURNAL OF THE OPTICAL SOCIETY OF AMERICA A-OPTICS IMAGE SCIENCE AND VISION LA English DT Article ID SPHEROIDAL WAVE-FUNCTIONS; FOURIER-ANALYSIS; FRESNEL ZONE; UNCERTAINTY; RESOLUTION; MODES AB Singular-value decomposition (SVD) of a linear imaging system gives information on the null and measurement components of object and image and provides a method for object reconstruction from image data. We apply SVD to through-focus imaging systems that produce several two-dimensional images of a three-dimensional object. Analytical expressions for the singular functions are derived in the geometrical approximation for a telecentric, laterally shift-invariant system linear in intensity. The modes are evaluated numerically, and their accuracy confirmed. Similarly, the modes are derived and evaluated for a continuous image representing the limit of a large number of image planes. (c) 2006 Optical Society of America. C1 Natl Univ Ireland Univ Coll Galway, Dept Expt Phys, Galway, Ireland. Univ Arizona, Coll Opt Sci, Tucson, AZ 85724 USA. Univ Arizona, Dept Radiol, Tucson, AZ 85724 USA. US FDA, Natl Inst Biomed Imaging & Bioengn, US Nalt Inst Hlth, Ctr Devices & Radiol Hlth,Lab Assessement Med Ima, Rockville, MD 20850 USA. RP Burvall, A (reprint author), Natl Univ Ireland Univ Coll Galway, Dept Expt Phys, Galway, Ireland. EM anna.burvall@nuigalway.ie NR 16 TC 2 Z9 2 U1 1 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 2006 VL 23 IS 10 BP 2440 EP 2448 DI 10.1364/JOSAA.23.002440 PG 9 WC Optics SC Optics GA 089CU UT WOS:000240858500008 PM 16985529 ER PT J AU Badano, A AF Badano, Aldo TI Special section on image quality assessment methods for the design and optimization of display systems - Introduction SO JOURNAL OF THE SOCIETY FOR INFORMATION DISPLAY LA English DT Editorial Material C1 US FDA, Rockville, MD 20857 USA. RP Badano, A (reprint author), US FDA, Rockville, MD 20857 USA. OI badano, aldo/0000-0003-3712-6670 NR 0 TC 0 Z9 0 U1 0 U2 1 PU SOC INFORMATION DISPLAY PI SAN JOSE PA 610 S SECOND STREET, SAN JOSE, CA 95112 USA SN 1071-0922 J9 J SOC INF DISPLAY JI J. Soc. Inf. Disp. PD OCT-DEC PY 2006 VL 14 IS 10-12 BP 829 EP 830 DI 10.1889/1.2372415 PG 2 WC Engineering, Electrical & Electronic; Materials Science, Multidisciplinary; Optics; Physics, Applied SC Engineering; Materials Science; Optics; Physics GA 129LO UT WOS:000243731200001 ER PT J AU Saha, A Liang, H Badano, A AF Saha, Anindita Liang, Hongye Badano, Aldo TI Color measurement methods for medical displays SO JOURNAL OF THE SOCIETY FOR INFORMATION DISPLAY LA English DT Article DE medical display; color measurement; color uniformity; luminance uniformity ID PERFORMANCE AB The effect of different measurement methods on the characterization of display color, maximum color difference, and luminance uniformity of medical liquid-crystal displays are reported. We use a telescopic colorimeter and a custom-designed collimated probe with an internal lens attached to a spectrometer. The maximum color-difference variations were found to be between 0.0047 to 0.0073, in the same range as variations among methods, displays, and screen locations. C1 US FDA, Ctr Devices & Radiol Hlth, Div Imaging & Appl Math,Off Sci & Engn Labs, CDRH NIBIB Lab Assessment Med Imaging Syst, Rockville, MD 20952 USA. RP Badano, A (reprint author), US FDA, Ctr Devices & Radiol Hlth, Div Imaging & Appl Math,Off Sci & Engn Labs, CDRH NIBIB Lab Assessment Med Imaging Syst, 12720 Twinbrook Pkwy, Rockville, MD 20952 USA. EM aldo.badano@fda.hhs.gov OI badano, aldo/0000-0003-3712-6670 NR 10 TC 4 Z9 4 U1 0 U2 2 PU SOC INFORMATION DISPLAY PI SAN JOSE PA 610 S SECOND STREET, SAN JOSE, CA 95112 USA SN 1071-0922 J9 J SOC INF DISPLAY JI J. Soc. Inf. Disp. PD OCT-DEC PY 2006 VL 14 IS 10-12 BP 979 EP 985 DI 10.1889/1.2393035 PG 7 WC Engineering, Electrical & Electronic; Materials Science, Multidisciplinary; Optics; Physics, Applied SC Engineering; Materials Science; Optics; Physics GA 129LO UT WOS:000243731200021 ER PT J AU Mahmood, I Martinez, M Hunter, RP AF Mahmood, I. Martinez, M. Hunter, R. P. TI Interspecies allometric scaling. Part I: prediction of clearance in large animals SO JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS LA English DT Article ID URINARY DETECTION TIME; COMPARATIVE PHARMACOKINETICS; GENTAMICIN PHARMACOKINETICS; CAMELUS-DROMEDARIUS; FLUNIXIN MEGLUMINE; HORSES; DISPOSITION; ANTIPYRINE; ENROFLOXACIN; PLASMA AB Interspecies scaling is a useful tool for the prediction of pharmacokinetic parameters from animals to humans, and it is often used for estimating a first-time in human dose. The knowledge of pharmacokinetics in veterinary species is important for dosage selection, particularly in the treatment of large zoo animal species, such as elephants, giant cats and camels, for which pharmacokinetic data are scant. Therefore, the accuracy in clearance predictions in large animal species, with and without the use of correction factors (rule of exponents), and the impact of species selection in the prediction of clearance in large animal species was examined. Based upon this analysis, it was determined that there is a much larger risk of inaccuracies in the clearance estimates in large animal species when compared with that observed for humans. Unlike in humans, for large animal species, correction factors could not be applied because there was no trend between the exponents of simple allometry and the appropriate correction factor for improving our predictions. Nevertheless, we did see an indication that the exponents of simple allometry may alert us as to when the predicted clearance in the large animal may be underestimated or overpredicted. For example, if a large animal is included in the scaling, the predicted clearance in a large animal should be considered overestimated if the exponent of simple allometry is > 1.3. Despite the potential for extrapolation error, the reality is that allometric scaling is needed across many veterinary practice situations, and therefore will be used. For this reason, it is important to consider mechanisms for reducing the risk of extrapolation errors that can seriously affect target animal safety, therapeutic response, or the accuracy of withdrawal time predictions. C1 US FDA, Ctr Drug Evaluat & Res, Off Drug Evaluat 6,Woodmont Off Ctr 2, Clin Pharmacol & Toxicol Branch HFD 579, Rockville, MD 20852 USA. US FDA, Ctr Vet Med, Off New Anim Drug Evaluat, Div Therapeut Drugs Food Anim HFV 130, Rockville, MD 20852 USA. Elanco Anim Hlth, Vet Safety ADME, Greenfield, IN USA. RP Mahmood, I (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Drug Evaluat 6,Woodmont Off Ctr 2, Clin Pharmacol & Toxicol Branch HFD 579, Rockville, MD 20852 USA. EM mahmoodi@cder.fda.gov RI Hunter, Robert/A-2306-2008 OI Hunter, Robert/0000-0003-1224-2376 NR 49 TC 40 Z9 40 U1 2 U2 8 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0140-7783 J9 J VET PHARMACOL THER JI J. Vet. Pharmacol. Ther. PD OCT PY 2006 VL 29 IS 5 BP 415 EP 423 DI 10.1111/j.1365-2885.2006.00786.x PG 9 WC Pharmacology & Pharmacy; Veterinary Sciences SC Pharmacology & Pharmacy; Veterinary Sciences GA 081BP UT WOS:000240292500012 PM 16958787 ER PT J AU Martinez, M Mahmood, I Hunter, RP AF Martinez, M. Mahmood, I. Hunter, R. P. TI Interspecies allometric scaling: prediction of clearance in large animal species: Part II: mathematical considerations SO JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS LA English DT Article ID COMPARATIVE PHARMACOKINETICS; DRUGS; ENROFLOXACIN; VETERINARY; TIME AB Interspecies scaling is a useful tool for the prediction of pharmacokinetic parameters from animals to humans, and it is often used for estimating a first-time in human dose. However, it is important to appreciate the mathematical underpinnings of this scaling procedure when using it to predict pharmacokinetic parameter values across animal species. When cautiously applied, allometry can be a tool for estimating clearance in veterinary species for the purpose of dosage selection. It is particularly valuable during the selection of dosages in large zoo animal species, such as elephants, large cats and camels, for which pharmacokinetic data are scant. In Part I, allometric predictions of clearance in large animal species were found to pose substantially greater risks of inaccuracies when compared with that observed for humans. In this report, we examine the factors influencing the accuracy of our clearance estimates from the perspective of the relationship between prediction error and such variables as the distribution of body weight values used in the regression analysis, the influence of a particular observation on the clearance estimate, and the 'goodness of fit' (R-2) of the regression line. Ultimately, these considerations are used to generate recommendations regarding the data to be included in the allometric prediction of clearance in large animal species. C1 US FDA, Ctr Vet Med, Off New Anim Drug Evaluat, Div Therapeut Drugs Food Anim HFV 130, Rockville, MD 20855 USA. US FDA, Ctr Drug Evaluat & Res, Off Drug Evaluat 6, Clin Pharmacol & Toxicol Branch HFD 579, Rockville, MD 20855 USA. Elanco Anim Hlth, Greenfield, IN USA. Woodmont Off Ctr II, Rockville, MD USA. RP Martinez, M (reprint author), US FDA, Ctr Vet Med, Off New Anim Drug Evaluat, Div Therapeut Drugs Food Anim HFV 130, 7500 Standish Pl, Rockville, MD 20855 USA. EM mmartin1@cvm.fda.gov RI Hunter, Robert/A-2306-2008 OI Hunter, Robert/0000-0003-1224-2376 NR 15 TC 25 Z9 25 U1 1 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0140-7783 J9 J VET PHARMACOL THER JI J. Vet. Pharmacol. Ther. PD OCT PY 2006 VL 29 IS 5 BP 425 EP 432 DI 10.1111/j.1365-2885.2006.00787.x PG 8 WC Pharmacology & Pharmacy; Veterinary Sciences SC Pharmacology & Pharmacy; Veterinary Sciences GA 081BP UT WOS:000240292500013 PM 16958788 ER PT J AU Wang, JH He, LS Combs, CA Roderiquez, G Norcross, MA AF Wang, Jinhai He, Liusheng Combs, Christian A. Roderiquez, Gregory Norcross, Michael A. TI Dimerization of CXCR4 in living malignant cells: control of cell migration by a synthetic peptide that reduces homologous CXCR4 interactions SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; PROTEIN-COUPLED RECEPTORS; COLONY-STIMULATING FACTOR; HUMAN PRIMARY MONOCYTES; ENERGY-TRANSFER FRET; HIV-1 INFECTION; CHEMOKINE SDF-1-ALPHA; CANCER METASTASIS; TUMOR PROGRESSION; CCR5 AB Chemokine receptor CXCR4 (CD184) may play a role in cancer metastasis and is known to form homodimers. However, it is not clear how transmembrane regions (TM) of CXCR4 and receptor homotypic interactions affect the function of CXCR4 in living cells. Using confocal microscopy and flow cytometric analysis, we showed that high levels of CXCR4 are present in the cytoplasm, accompanied by lower expression on the cell surface in CXCR4 transfectants, tumor cells, and normal peripheral blood lymphocytes. CXCR4 homodimers were detected in tumor cells, both on the cell surface membrane and in the cytoplasm using fluorescence resonance energy transfer and photo-bleaching fluorescence resonance energy transfer to measure energy transfer between CXCR4-CFP and CXCR4-YFP constructs. Disruption of lipid rafts by depletion of cholesterol with methyl-beta-cyclodextrin reduced the interaction between CXCR4 molecules and inhibited malignant cell migration to CXCL12/SDF-1 alpha. A synthetic peptide of TM4 of CXCR4 reduced energy transfer between molecules of CXCR4, inhibited CXCL12-induced actin polymerization, and blocked chemotaxis of malignant cells. TM4 also inhibited migration of normal monocytes toward CXCL12. Reduction of CXCR4 energy transfer by the TM4 peptide and methyl-beta-cyclodextrin indicates that interactions between CXCR4s may play important roles in cell migration and suggests that cell surface and intracellular receptor dimers are appropriate targets for control of tumor cell spread. Targeting chemokine receptor oligomerization and signal transduction for the treatment of cancer, HIV-1 infections, and other CXCR4 mediated inflammatory conditions warrants further investigation. C1 US FDA, Div Therapeut Prot, Off Biotechnol Prod, Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. NHLBI, NIH, Bethesda, MD 20892 USA. NIAMSD, NIH, Bethesda, MD 20892 USA. RP Wang, JH (reprint author), US FDA, Div Therapeut Prot, Off Biotechnol Prod, Ctr Drug Evaluat & Res, Bldg 29B,Room 4E12,8800 Rockville Pike, Bethesda, MD 20892 USA. EM Jinhai.wang@fda.hhs.gov; michael.norcross@fda.hhs.gov NR 41 TC 61 Z9 61 U1 1 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD OCT PY 2006 VL 5 IS 10 BP 2474 EP 2483 DI 10.1158/1535-7163.MCT-05-0261 PG 10 WC Oncology SC Oncology GA 095VE UT WOS:000241335600006 PM 17041091 ER PT J AU Alterman, MA Kornilayev, BA AF Alterman, M. A. Kornilayev, B. A. TI Cytochrome P450 superfamily as a paradigm for targeted proteomics analysis in pharmacoproteomics SO MOLECULAR & CELLULAR PROTEOMICS LA English DT Meeting Abstract C1 US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. Univ Kansas, Lawrence, KS 66045 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 OCT PY 2006 VL 5 IS 10 SU S MA 656 BP S169 EP S169 PG 1 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 098FM UT WOS:000241506400387 ER PT J AU Putt, KS Chen, GW Pearson, JM Sandhorst, JS Hoagland, MS Kwon, JT Hwang, SK Jin, H Churchwell, MI Cho, MH Doerge, DR Helferich, WG Hergenrother, PJ AF Putt, Karson S. Chen, Grace W. Pearson, Jennifer M. Sandhorst, Joseph S. Hoagland, Martin S. Kwon, Jung-Taek Hwang, Soon-Kyung Jin, Hua Churchwell, Mona I. Cho, Myung-Haing Doerge, Daniel R. Helferich, William G. Hergenrother, Paul J. TI Small-molecule activation of procaspase-3 to caspase-3 as a personalized anticancer strategy SO NATURE CHEMICAL BIOLOGY LA English DT Article ID BCL-X-L; CELL-DEATH; APOPTOTIC DEATH; BREAST-CANCER; TUMOR-CELLS; PROTEIN; EXPRESSION; MECHANISM; COMPOUND; PATHWAYS AB Mutation and aberrant expression of apoptotic proteins are hallmarks of cancer. These changes prevent proapoptotic signals from being transmitted to executioner caspases, thereby averting apoptotic death and allowing cellular proliferation. Caspase-3 is the key executioner caspase, and it exists as an inactive zymogen that is activated by upstream signals. Notably, concentrations of procaspase-3 in certain cancerous cells are significantly higher than those in noncancerous controls. Here we report the identification of a small molecule (PAC-1) that directly activates procaspase-3 to caspase-3 in vitro and induces apoptosis in cancerous cells isolated from primary colon tumors in a manner directly proportional to the concentration of procaspase-3 inside these cells. We found that PAC-1 retarded the growth of tumors in three different mouse models of cancer, including two models in which PAC-1 was administered orally. PAC-1 is the first small molecule known to directly activate procaspase-3 to caspase-3, a transformation that allows induction of apoptosis even in cells that have defective apoptotic machinery. The direct activation of executioner caspases is an anticancer strategy that may prove beneficial in treating the many cancers in which procaspase-3 concentrations are elevated. C1 Univ Illinois, Dept Biochem, Urbana, IL 61801 USA. Univ Illinois, Dept Chem, Urbana, IL 61801 USA. Univ Illinois, Dept Food Sci & Human Nutr, Urbana, IL 61801 USA. Seoul Natl Univ, Coll Vet Med, Toxicol Lab, Seoul 151742, South Korea. Seoul Natl Univ, Nano Syst Inst, Natl Core Res Ctr, Seoul 151742, South Korea. US FDA, Natl Ctr Toxicol Res, Jefferson, AR USA. RP Hergenrother, PJ (reprint author), Univ Illinois, Dept Biochem, Urbana, IL 61801 USA. EM hergenro@uiuc.edu RI CHO, Myung-Haing/B-7362-2014 FU NCI NIH HHS [CA77355]; NIA NIH HHS [AG024387]; NIEHS NIH HHS [5T32ES007326-05] NR 35 TC 161 Z9 172 U1 1 U2 18 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1552-4450 J9 NAT CHEM BIOL JI Nat. Chem. Biol. PD OCT PY 2006 VL 2 IS 10 BP 543 EP 550 DI 10.1038/nchembio814 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 095IX UT WOS:000241302500012 PM 16936720 ER PT J AU Vogelbaum, MA Sampson, JH Kunwar, S Chang, SM Lang, FF Shaffrey, M Asher, AL Croteau, D Parker, K Dul, JL Sherman, JW Puri, RK AF Vogelbaum, M. A. Sampson, J. H. Kunwar, S. Chang, S. M. Lang, F. F. Shaffrey, M. Asher, A. L. Croteau, D. Parker, K. Dul, J. L. Sherman, J. W. Puri, R. K. TI Phase I study final safety results: Convection-enhanced delivery of cintredekin besudotox (IL13-PE38QQR) followed by radiation therapy without and with temozolomide in newly diagnosed malignant glioma SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 7th Congress of the European-Association-for-Neuro-Oncology (EANO) CY SEP 14-17, 2006 CL Vienna, AUSTRIA SP European Assoc Neuro Oncol C1 Cleveland Clin Fdn, Cleveland, OH 44195 USA. Duke Univ, Med Ctr, Durham, NC USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Virginia, Charlottesville, VA USA. Carolina Neurosurg & Spine Assoc, Charlotte, NC USA. NeoPharm, Lake Forest, IL USA. US FDA, CBER, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 1 U2 1 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 OCT PY 2006 VL 8 IS 4 BP 453 EP 454 PG 2 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 089JS UT WOS:000240877301240 ER PT J AU Brave, M Dagher, R Farrell, A Abraham, S Ramchandani, R Gobburu, J Booth, B Jiang, XP Sridhara, R Justice, R Pazdur, R AF Brave, Michael Dagher, Ramzi Farrell, Ann Abraham, Sophia Ramchandani, Roshni Gobburu, Jogarao Booth, Brian Jiang, Xiaoping Sridhara, Rajeshwari Justice, Robert Pazdur, Richard TI Topotecan with in combination cisplatin for the treatment of stage IVB, recurrent, or persistent cervical cancer SO ONCOLOGY-NEW YORK LA English DT Article AB Purpose: Topotecan, a camptothecin analog previously approved for the treatment of ovarian cancer and small-cell lung cancer, was granted regular approval by the US Food and Drug Administration (FDA) on June 14, 2006, for use in combination with cisplatin to treat women with stage IVB, recurrent, or persistent carcinoma of the cervix not amenable to curative treatment with surgery and/or radiation therapy. The purpose of this summary is to review the database supporting this approval. Experimental Design: In a randomized multicenter study enrolling 293 eligible patients, topotecan plus cisplatin (TC) was compared with cisplatin monotherapy. The TC regimen consisted of cisplatin 50 mg/m(2) IV over 1 hour on day 1 and topotecan 0.75 mg/m(2) IV over 30 minutes on days 1, 2, and 3 every 21 days. Results: There was a clinically relevant and statistically significant improvement in overall survival in the TC treatment arm. Median overall survival was 9.4 months (95% confidence interval [CI]. 7.9-11.9) in the TC arm, compared to 6.5 months (95% CL 5.8-8.8) with cisplatin alone. The unadjusted hazard ratio for overall survival between treatment arms was 0.76 (95% CI: 0.59-0.98, P = .033)favoring the combination arm. The most common toxicities with TC included myelosuppression, nausea and vomiting, mucositis, rash, and hepatotoxicity. Conclusions: This report describes the FDA's review supporting this first approval of a chemotherapeutic drug for advanced cervical cancer based on demonstration of a survival benefit. C1 US FDA, Ctr Drug Evaluat & Res, Off Oncol Drug Prod, Off New Drugs, Silver Spring, MD 20993 USA. Off Clin Pharmacol, Off Translat Sci, Silver Spring, MD USA. Off Biostat, Silver Spring, MD USA. RP Brave, M (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Oncol Drug Prod, Off New Drugs, 10903 New Hampshire Ave,Bldg 22,Room 2137, Silver Spring, MD 20993 USA. EM michael.brave@17da.hhs.gov NR 23 TC 17 Z9 17 U1 0 U2 2 PU P R R INC PI MELVILLE PA 48 SOUTH SERVICE RD, MELVILLE, NY 11747 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD OCT PY 2006 VL 20 IS 11 BP 1401 EP + PG 5 WC Oncology SC Oncology GA V44BJ UT WOS:000202977900012 PM 17112001 ER PT J AU Schnackenberg, LK AF Schnackenberg, Laura K. TI Metabolomics special focus: an introduction SO PHARMACOGENOMICS LA English DT Editorial Material C1 US FDA, Natl Ctr Toxicol Res, Div Syst Toxicol, Jefferson, AR 72079 USA. RP Schnackenberg, LK (reprint author), US FDA, Natl Ctr Toxicol Res, Div Syst Toxicol, Jefferson, AR 72079 USA. EM laura.schnackenberg@fda.hhs.gov NR 0 TC 1 Z9 1 U1 0 U2 2 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 OCT PY 2006 VL 7 IS 7 BP 1053 EP 1054 DI 10.2217/14622416.7.7.1053 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 099PO UT WOS:000241607800013 PM 17054415 ER PT J AU Schnackenberg, LK Beger, RD AF Schnackenberg, Laura K. Beger, Richard D. TI Monitoring the health to disease continuum with global metabolic profiling and systems biology SO PHARMACOGENOMICS LA English DT Review DE metabolic profiling; metabonomics; metabolomics; systems biology ID NUCLEAR-MAGNETIC-RESONANCE; TANDEM MASS-SPECTROMETRY; MULTIVARIATE STATISTICAL-ANALYSIS; INBORN-ERRORS; GENE-EXPRESSION; H-1-NMR-BASED METABONOMICS; ACETAMINOPHEN TOXICITY; INDUCED HEPATOTOXICITY; NMR-SPECTROSCOPY; DRUG DISCOVERY AB Global metabolic profiling, which includes both metabolomics and metabonomics studies, is the latest 'omics' research platform that is being applied to understand the health and disease continuum. Metabolic profiling analyses have been demonstrated for the investigation of inborn errors of metabolism, organ transplant rejection, drug toxicity, disease diagnosis and prognosis, drug efficacy and nutritional status. Combining information generated from a metabolic profiling platform with that obtained based on genetics, transcriptomics and proteomics research paradigms will pave the way for a better understanding of the mechanisms of disease and toxicity. Metabolomics and nutrition will lay the groundwork for the application of personalized medicine in the 21st century. C1 US FDA, Natl Ctr Toxicol Res, Div Syst Toxicol, Jefferson, AR 72079 USA. RP Schnackenberg, LK (reprint author), US FDA, Natl Ctr Toxicol Res, Div Syst Toxicol, Jefferson, AR 72079 USA. EM laura.schmackenberg@fda.hhs.gov NR 91 TC 42 Z9 56 U1 0 U2 2 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 OCT PY 2006 VL 7 IS 7 BP 1077 EP 1086 DI 10.2217/14622416.7.7.1077 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 099PO UT WOS:000241607800015 PM 17054417 ER PT J AU Philip, BK Anand, SS Palkar, PS Mumtaz, MM Latendresse, JR Mehendale, HM AF Philip, Binu K. Anand, Sathanandam S. Palkar, Prajakta S. Mumtaz, Moiz M. Latendresse, John R. Mehendale, Harihara M. TI Subchronic chloroform priming protects mice from a subsequently administered lethal dose of chloroform SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE autoprotection; chloroform; kidney injury; liver injury; subchronic exposure; Swiss Webster mice; tissue repair ID ACETAMINOPHEN-INDUCED HEPATOTOXICITY; REGENERATIVE CELL-PROLIFERATION; TOXICANT-INDUCED INJURY; TISSUE-REPAIR; CARBON-TETRACHLORIDE; LIVER-INJURY; HEPATOCELLULAR REGENERATION; MEDIATES PROGRESSION; INDUCED CYTOTOXICITY; HEME OXYGENASE-1 AB Protection offered by pre-exposure priming with a small dose of a toxicant against the toxic and lethal effects of a subsequently administered high dose of the same toxicant is autoprotection. Although autoprotection has been extensively studied with diverse toxicants in acute exposure regimen, not much is known about autoprotection after priming with repeated exposure. The objective of this study was to investigate this concept following repeated exposure to a common water contaminant, chloroform. Swiss Webster (SW) mice, exposed continuously to either vehicle (5% Emulphor, unprimed) or chloroform (150 mg/kg/day po, primed) for 30 days, were challenged with a normally lethal dose of chloroform (750 mg chloroform/ kg po) 24 h after the last exposure. As expected, 90% of the unprimed mice died between 48 and 96 h after administration of the lethal dose in contrast to 100% survival of mice primed with chloroform. Time course studies indicated lower hepato- and nephrotoxicity in primed mice as compared to unprimed mice. Hepatic CYP2E1, glutathione levels (GSH), and covalent binding of C-14-chloroform-derived radiolabel did not differ between livers of unprimed and primed mice after lethal dose exposure, indicating that protection in liver is neither due to decreased bioactivation nor increased detoxification. Kidney GSH and glutathione reductase activity were upregulated, with a concomitant reduction in oxidized glutathione in the primed mice following lethal dose challenge, leading to decreased renal covalent binding of C-14-chloroform-derived radiolabel, in the absence of any change in CYP2E1 levels. Buthionine sulfoximine (BSO) intervention led to 70% mortality in primed mice challenged with lethal dose. These data suggest that higher detoxification may play a role in the lower initiation of kidney injury observed in primed mice. Exposure of primed mice to a lethal dose of chloroform led to 40% lower chloroform levels (AUC(15-360 min)) in the systemic circulation. Exhalation of C-14-chlorofonn was unchanged in primed as compared to unprimed mice (AUC(1-6 h)). Urinary excretion of C-14-chloroform was higher in primed mice after administration of the lethal dose. However, neither slightly higher urinary elimination nor unchanged expiration can account for the difference in systemic levels of chloroform. Liver and kidney regeneration was inhibited by the lethal dose in unprimed mice leading to progressive injury, organ failure, and 90% mortality. In contrast, sustained and highly stimulated compensatory hepato- and nephrogenic repair prevented the progression of injury resulting in 100% survival of primed mice challenged with the lethal dose. These findings affirm the critical role of tissue regeneration and favorable detoxification (only in kidney) of the lethal dose of chloroform in subchronic chloroform priming-induced autoprotection. (c) 2006 Elsevier Inc. All rights reserved. C1 Univ Louisiana, Coll Pharm, Dept Toxicol, Monroe, LA 71209 USA. ATSDR, Dept Hlth & Human Serv, Atlanta, GA 30333 USA. Natl Ctr Toxicol Res, Toxicol Pathol Associates, Jefferson, AR 72079 USA. RP Mehendale, HM (reprint author), Univ Louisiana, Coll Pharm, Dept Toxicol, 700 Univ Ave,Sugar Hall 306, Monroe, LA 71209 USA. EM mehendale@ulm.edu RI Latendresse, John/A-9215-2009 FU PHS HHS [U61/ATU681482] NR 54 TC 6 Z9 7 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD OCT 1 PY 2006 VL 216 IS 1 BP 108 EP 121 DI 10.1016/j.taap.2006.04.012 PG 14 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 091CZ UT WOS:000241005100012 PM 16815507 ER PT J AU Darnell, MER Taylor, DR AF Darnell, Miriam E. R. Taylor, Deborah R. TI Evaluation of inactivation methods for severe acute respiratory syndrome coronavirus in noncellular blood products SO TRANSFUSION LA English DT Article ID WAVELENGTH ULTRAVIOLET-LIGHT; SARS-ASSOCIATED CORONAVIRUS; LIPID-ENVELOPED VIRUSES; PLASMA PRODUCTS; INFECTION; MANUFACTURE; PROTEINS; IDENTIFICATION; SENSITIVITY; CONCENTRATE AB Severe acute respiratory syndrome coronavirus (SARS-CoV) has been detected in the blood of infected individuals, which may have the potential to contaminate donated blood and plasma-derived products in the event of a future outbreak. Effective methods for inactivating the SARS-CoV in protein solutions are described in this report. Heat, ultraviolet (UV) irradiation, octanoic acid, and solvent/detergent (S/D) methods were tested individually for their ability to inactivate SARS-CoV in protein solutions appropriately mimicking blood-derived products. Treated samples were tested for inactivation in a tissue culture growth assay. Viral inactivation by heat treatment at 60 degrees C required 15 to 30 minutes to inactivate the SARS-CoV. UVC efficiently inactivated SARS-CoV in 40 minutes, whereas UVA required the addition of psoralen to enhance inactivation of the virus. The presence of bovine serum albumin limited the ability of UVC and UVA to inactivate SARS-CoV and octanoic acid treatment does not reduce the infectivity of SARS-CoV-spiked protein solutions. S/D treatment required 2, 4, and up to 24 hours for Triton X-100, Tween 80, and sodium cholate inactivation, respectively. Heat, UVC irradiation, and S/D treatments effectively inactivate SARS-CoV, whereas octanoic acid treatment is insufficient for inactivation of the virus. C1 US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. RP Taylor, DR (reprint author), 8800 Rockville Pike,HFM310, Bethesda, MD 20892 USA. EM Deborah.Taylor@FDA.HHS.gov NR 28 TC 8 Z9 8 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 OCT PY 2006 VL 46 IS 10 BP 1770 EP 1777 DI 10.1111/j.1537-2995.2006.00976.x PG 8 WC Hematology SC Hematology GA 086NT UT WOS:000240681000016 PM 17002634 ER PT J AU Hsia, CC Purcell, RH Farshid, M Lachenbruch, PA Yu, MYW AF Hsia, Chu Chieh Purcell, Robert H. Farshid, Mahmood Lachenbruch, Peter A. Yu, Mei-ying W. TI Quantification of hepatitis B virus genomes and infectivity in human serum samples SO TRANSFUSION LA English DT Article ID NUCLEIC-ACID AMPLIFICATION; REAL-TIME PCR; HBV-DNA; BLOOD-DONATIONS; DETECTION SYSTEM; COMPETITIVE PCR; HBSAG SUBTYPES; TAQMAN PCR; QUANTITATION; ASSAY AB Hepatitis B virus (HBV) infections are still a major health issue, with approximately 350 million people chronically infected with HBV worldwide. Information about the minimum copy number of HBV genomes required for infection would be useful as a reference for drug and vaccine development; for monitoring HBV patients during treatment; for screening of blood, organ, and tissue donors; and for regulating nucleic acid amplification assays for HBV. Serum samples from chronic carriers (hepatitis B surface antigen-positive and antibody to HBV core antigen-positive) of the three most common subtypes of HBV were studied; their infectivity titers had been evaluated previously in chimpanzees. The genotypes of the HBV samples were determined by DNA sequences and type-specific amino acids of the S gene of HBV. Copy numbers of HBV DNA were quantified by real-time TaqMan polymerase chain reaction (PCR) and by nested PCR applied to limiting dilutions. The copy number determined for each inoculum was compared with previously defined chimpanzee infectivity titers. The genotypes of the HBV adw, ayw, and adr inocula were A, D, and C, respectively. The concentration of HBV DNA was determined to be 5.4 x 10(9), 2.5 x 10(9), and 3.1 x 10(8) genome equivalents (geq) per mL for serum samples containing the adw, ayw, and adr, respectively. The chimpanzee infectivity titers per milliliter of these initial HBV-containing serum samples were previously determined to be 10(7.5) for adw, 10(7.5) for ayw (MS-2 strain), and 10(8) for adr. The minimal copy number of HBV DNA in chronic carriers of HBV that can infect the chimpanzee model was estimated to be from 3 to 169 geq based upon the three well-characterized inocula. C1 US FDA, Div Emerging & Transfus Transmitted Dis, CBER, Bethesda, MD 20014 USA. US FDA, Div Biostat, CBER, Bethesda, MD 20014 USA. US FDA, Div Hematol, CBER, Bethesda, MD 20014 USA. NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Hsia, CC (reprint author), Bldg 29,Room 222,HFM 310,29 Lincoln Dr, Bethesda, MD 20892 USA. EM chuchieh.hsia@fda.hhs.gov NR 46 TC 29 Z9 33 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0041-1132 J9 TRANSFUSION JI Transfusion PD OCT PY 2006 VL 46 IS 10 BP 1829 EP 1835 DI 10.1111/j.1537-2995.2006.00974.x PG 7 WC Hematology SC Hematology GA 086NT UT WOS:000240681000023 PM 17002641 ER PT J AU Srinivasan, K Lee, S Daniel, S Wood, O Akolkar, P Hewlett, I AF Srinivasan, Kumar Lee, Sherwin Daniel, Sylvester Wood, Owen Akolkar, Pradip Hewlett, Indira TI Performance of serological assays used to test blood from recent smallpox vaccinees SO TRANSFUSION LA English DT Letter C1 US FDA, Mol Virol Lab, Div Emerging & Transfus Transmitted Dis, CBER, Rockville, MD 20857 USA. RP Srinivasan, K (reprint author), US FDA, Mol Virol Lab, Div Emerging & Transfus Transmitted Dis, CBER, Rockville, MD 20857 USA. EM Indira.Hewlett@fda.hhs.gov NR 3 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 OCT PY 2006 VL 46 IS 10 BP 1847 EP 1848 DI 10.1111/j.1537-2995.2006.00982.x PG 2 WC Hematology SC Hematology GA 086NT UT WOS:000240681000026 PM 17002644 ER PT J AU Chen, T Guo, L Zhang, L Shi, LM Fang, H Sun, YM Fuscoe, JC Mei, N AF Chen, Tao Guo, Lei Zhang, Lu Shi, Leming Fang, Hong Sun, Yongming Fuscoe, James C. Mei, Nan TI Gene expression profiles distinguish the carcinogenic effects of aristolochic acid in target (kidney) and non-target (liver) tissues in rats SO BMC BIOINFORMATICS LA English DT Article; Proceedings Paper CT 3rd Annual Conference of the MidSouth-Computational-Biology-and-Bioinformatics-Society CY MAR 02-04, 2006 CL Baton Rouge, LA SP MidSouth Computat Biol & Bioinformat Soc ID CHINESE HERBS NEPHROPATHY; APOPTOSIS; IDENTIFICATION; CANCER; CELLS AB Background: Aristolochic acid (AA) is the active component of herbal drugs derived from Aristolochia species that have been used for medicinal purposes since antiquity. AA, however, induced nephropathy and urothelial cancer in people and malignant tumors in the kidney and urinary tract of rodents. Although AA is bioactivated in both kidney and liver, it only induces tumors in kidney. To evaluate whether microarray analysis can be used for distinguishing the tissue-specific carcinogenicity of AA, we examined gene expression profiles in kidney and liver of rats treated with carcinogenic doses of AA. Results: Microarray analysis was performed using the Rat Genome Survey Microarray and data analysis was carried out within ArrayTrack software. Principal components analysis and hierarchical cluster analysis of the expression profiles showed that samples were grouped together according to the tissues and treatments. The gene expression profiles were significantly altered by AA treatment in both kidney and liver (p < 0.01; fold change > 1.5). Functional analysis with Ingenuity Pathways Analysis showed that there were many more significantly altered genes involved in cancer-related pathways in kidney than in liver. Also, analysis with Gene Ontology for Functional Analysis (GOFFA) software indicated that the biological processes related to defense response, apoptosis and immune response were significantly altered by AA exposure in kidney, but not in liver. Conclusion: Our results suggest that microarray analysis is a useful tool for detecting AA exposure; that analysis of the gene expression profiles can define the differential responses to toxicity and carcinogenicity of AA from kidney and liver; and that significant alteration of genes associated with defense response, apoptosis and immune response in kidney, but not in liver, may be responsible for the tissue-specific toxicity and carcinogenicity of AA. C1 US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. US FDA, Natl Ctr Toxicol Res, Div Syst Toxicol, Jefferson, AR 72079 USA. Appl Biosyst Inc, Mol Biol SDS Arrays Grp, Foster City, CA 94404 USA. ZTech Corp, Jefferson, AR 72079 USA. Solexa Inc, Hayward, CA 94545 USA. RP Chen, T (reprint author), US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. EM tao.chen@fda.hhs.gov; lei.guo@fda.hhs.gov; lzhang@solexa.com; leming.shi@fda.hhs.gov; hong.fang@fda.hhs.gov; sunya@appliedbiosystems.com; james.fuscoe@fda.hhs.gov; nan.mei@fda.hhs.gov RI Guo, Lei/E-9232-2011; mei, nan/E-8915-2011 OI mei, nan/0000-0002-3501-9014 NR 34 TC 32 Z9 33 U1 0 U2 2 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 SEP 26 PY 2006 VL 7 SU 2 AR S20 DI 10.1186/1471-2105-7-S2-S20 PG 13 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA 091DY UT WOS:000241007700020 PM 17118142 ER PT J AU Delongchamp, R Lee, T Velasco, C AF Delongchamp, Robert Lee, Taewon Velasco, Cruz TI A method for computing the overall statistical significance of a treatment effect among a group of genes SO BMC BIOINFORMATICS LA English DT Article; Proceedings Paper CT 3rd Annual Conference of the MidSouth-Computational-Biology-and-Bioinformatics-Society CY MAR 02-04, 2006 CL Baton Rouge, LA SP MidSouth Computat Biol & Bioinformat Soc ID P-VALUES; EXPRESSION DATA; TESTS AB Background: In studies that use DNA arrays to assess changes in gene expression, our goal is to evaluate the statistical significance of treatments on sets of genes. Genes can be grouped by a molecular function, a biological process, or a cellular component, e.g., gene ontology (GO) terms. The meaning of an affected GO group is often clearer than interpretations arising from a list of the statistically significant genes. Results: Computer simulations demonstrated that correlations among genes invalidate many statistical methods that are commonly used to assign significance to GO terms. Ignoring these correlations overstates the statistical significance. Meta-analysis methods for combining p-values were modified to adjust for correlation. One of these methods is elaborated in the context of a comparison between two treatments. The form of the correlation adjustment depends upon the alternative hypothesis. Conclusion: Reliable corrections for the effect of correlations among genes on the significance level of a GO term can be constructed for an alternative hypothesis where all transcripts in the GO term increase (decrease) in response to treatment. For general alternatives, which allow some transcripts to increase and others to decrease, the bias of naive significance calculations can be greatly decreased although not eliminated. 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. RP Lee, T (reprint author), Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. EM robert.delongchamp@fda.hhs.gov; taewon.lee@fda.hhs.gov; cvelas@lsuhsc.edu NR 21 TC 20 Z9 20 U1 0 U2 1 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 SEP 26 PY 2006 VL 7 SU 2 AR S11 DI 10.1186/1471-2105-7-S2-S11 PG 9 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA 091DY UT WOS:000241007700011 PM 17118132 ER PT J AU Guo, L Fang, H Collins, J Fan, XH Dial, S Wong, A Mehta, K Blann, E Shi, LM Tong, WD Dragan, YP AF Guo, Lei Fang, Hong Collins, Jim Fan, Xiao-Hui Dial, Stacey Wong, Alex Mehta, Kshama Blann, Ernice Shi, Leming Tong, Weida Dragan, Yvonne P. TI Differential gene expression in mouse primary hepatocytes exposed to the peroxisome proliferator-activated receptor alpha agonists SO BMC BIOINFORMATICS LA English DT Article; Proceedings Paper CT 3rd Annual Conference of the MidSouth-Computational-Biology-and-Bioinformatics-Society CY MAR 02-04, 2006 CL Baton Rouge, LA SP MidSouth Computat Biol & Bioinformat Soc ID ACID-BINDING-PROTEIN; HEPATOCELLULAR-CARCINOMA; RESPONSE ELEMENT; PLASMINOGEN-ACTIVATOR; BETA-OXIDATION; FATTY-ACIDS; PPAR-ALPHA; LIVER; RAT; MICROARRAY AB Background: Fibrates are a unique hypolipidemic drugs that lower plasma triglyceride and cholesterol levels through their action as peroxisome proliferator-activated receptor alpha (PPAR alpha) agonists. The activation of PPAR alpha leads to a cascade of events that result in the pharmacological (hypolipidemic) and adverse (carcinogenic) effects in rodent liver. Results: To understand the molecular mechanisms responsible for the pleiotropic effects of PPAR alpha agonists, we treated mouse primary hepatocytes with three PPAR alpha agonists (bezafibrate, fenofibrate, and WY-14,643) at multiple concentrations (0, 10, 30, and 100 mu M) for 24 hours. When primary hepatocytes were exposed to these agents, transactivation of PPAR alpha was elevated as measured by luciferase assay. Global gene expression profiles in response to PPAR alpha agonists were obtained by microarray analysis. Among differentially expressed genes (DEGs), there were 4, 8, and 21 genes commonly regulated by bezafibrate, fenofibrate, and WY-14,643 treatments across 3 doses, respectively, in a dose-dependent manner. Treatments with 100 mu M of bezafibrate, fenofibrate, and WY-14,643 resulted in 151, 149, and 145 genes altered, respectively. Among them, 121 genes were commonly regulated by at least two drugs. Many genes are involved in fatty acid metabolism including oxidative reaction. Some of the gene changes were associated with production of reactive oxygen species, cell proliferation of peroxisomes, and hepatic disorders. In addition, 11 genes related to the development of liver cancer were observed. Conclusion: Our results suggest that treatment of PPAR alpha agonists results in the production of oxidative stress and increased peroxisome proliferation, thus providing a better understanding of mechanisms underlying PPAR alpha agonist-induced hepatic disorders and hepatocarcinomas. C1 US FDA, Natl Ctr Toxicol Res, Div Syst Toxicol, Jefferson, AR 72079 USA. ZTech Corp, Jefferson, AR 72079 USA. Agilent Technol Inc, Santa Clara, CA 95051 USA. RP Guo, L (reprint author), US FDA, Natl Ctr Toxicol Res, Div Syst Toxicol, Jefferson, AR 72079 USA. EM lei.guo@fda.hhs.gov; hong.fang@fda.hhs.gov; jim_collins@agilent.com; xiaohui.fan@fda.hhs.gov; stacey.dial@fda.hhs.gov; alex_wong@agilent.com; kshama_mehta@agilent.com; ernice.blann@fda.hhs.gov; leming.shi@fda.hhs.gov; weida.tong@fda.hhs.gov; yvonne.dragan@fda.hhs.gov RI Guo, Lei/E-9232-2011 NR 42 TC 33 Z9 35 U1 0 U2 0 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 SEP 26 PY 2006 VL 7 SU 2 AR S18 DI 10.1186/1741-2105-7-S2-S18 PG 12 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA 091DY UT WOS:000241007700018 PM 17118139 ER PT J AU Han, T Wang, JY Tong, WD Moore, MM Fuscoe, JC Chen, T AF Han, Tao Wang, Jianyong Tong, Weida Moore, Martha M. Fuscoe, James C. Chen, Tao TI Microarray analysis distinguishes differential gene expression patterns from large and small colony Thymidine kinase mutants of L5178Y mouse lymphoma cells SO BMC BIOINFORMATICS LA English DT Article; Proceedings Paper CT 3rd Annual Conference of the MidSouth-Computational-Biology-and-Bioinformatics-Society CY MAR 02-04, 2006 CL Baton Rouge, LA SP MidSouth Computat Biol & Bioinformat Soc ID RECOMBINATION ACTIVATING GENES; RESISTANT TFT MUTANTS; TUMOR-SUPPRESSOR GENE; ETHYL-N-NITROSOUREA; CDKN2A; MUTATIONS; FREQUENCY; TK; MUTAGENESIS; PHENOTYPE AB Background: The Thymidine kinase (Tk) mutants generated from the widely used L5178Y mouse lymphoma assay fall into two categories, small colony and large colony. Cells from the large colonies grow at a normal rate while cells from the small colonies grow slower than normal. The relative proportion of large and small colonies after mutagen treatment is associated with a mutagen's ability to induce point mutations and/or chromosomal mutations. The molecular distinction between large and small colony mutants, however, is not clear. Results: To gain insights into the underlying mechanisms responsible for the mutant colony phenotype, microarray gene expression analysis was carried out on 4 small and 4 large colony Tk mutant samples. NCTR-fabricated long-oligonucleotide microarrays of 20,000 mouse genes were used in a two-color reference design experiment. The data were analyzed within ArrayTrack software that was developed at the NCTR. Principal component analysis and hierarchical clustering of the gene expression profiles showed that the samples were clearly separated into two groups based on their colony size phenotypes. The Welch T-test was used for determining significant changes in gene expression between the large and small colony groups and 90 genes whose expression was significantly altered were identified (p < 0.01; fold change > 1.5). Using Ingenuity Pathways Analysis (IPA), 50 out of the 90 significant genes were found in the IPA database and mapped to four networks associated with cell growth. Eleven percent of the 90 significant genes were located on chromosome 11 where the Tk gene resides while only 5.6% of the genes on the microarrays mapped to chromosome II. All of the chromosome 11 significant genes were expressed at a higher level in the small colony mutants compared to the large colony mutants. Also, most of the significant genes located on chromosome 11 were disproportionally concentrated on the distal end of chromosome 11 where the Tk mutations occurred. Conclusion: The results indicate that microarray analysis can define cellular phenotypes and identify genes that are related to the colony size phenotypes. The findings suggest that genes in the DNA segment altered by the Tk mutations were significantly up-regulated in the small colony mutants, but not in the large colony mutants, leading to differential expression of a set of growth regulation genes that are related to cell apoptosis and other cellular functions related to the restriction of cell growth. C1 US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. US FDA, Natl Ctr Toxicol Res, Div Syst Toxicol, Jefferson, AR 72079 USA. RP Chen, T (reprint author), US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. EM tao.han@fda.hhs.gov; jianyong.wang@fda.hhs.gov; weida.tong@fda.hhs.gov; martha.moore@fda.hhs.gov; james.fuscoe@fda.hhs.gov; tao.chen@fda.hhs.gov NR 34 TC 14 Z9 14 U1 0 U2 1 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 SEP 26 PY 2006 VL 7 SU 2 AR S9 DI 10.1186/1471-2105-7-S2-S9 PG 12 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA 091DY UT WOS:000241007700009 PM 17118152 ER PT J AU Han, T Melvin, CD Shi, LM Branham, WS Moland, CL Pine, PS Thompson, KL Fuscoe, JC AF Han, Tao Melvin, Cathy D. Shi, Leming Branham, William S. Moland, Carrie L. Pine, P. Scott Thompson, Karol L. Fuscoe, James C. TI Improvement in the reproducibility and accuracy of DNA microarray quantification by optimizing hybridization conditions SO BMC BIOINFORMATICS LA English DT Article; Proceedings Paper CT 3rd Annual Conference of the MidSouth-Computational-Biology-and-Bioinformatics-Society CY MAR 02-04, 2006 CL Baton Rouge, LA SP MidSouth Computat Biol & Bioinformat Soc ID CROSS-HYBRIDIZATION; GENE; OLIGONUCLEOTIDE; DESIGN; PLATFORMS; ARRAYS; PROBES; SELECTION; SOFTWARE; OLIGOS AB Background: DNA microarrays, which have been increasingly used to monitor mRNA transcripts at a global level, can provide detailed insight into cellular processes involved in response to drugs and toxins. This is leading to new understandings of signaling networks that operate in the cell, and the molecular basis of diseases. Custom printed oligonucleotide arrays have proven to be an effective way to facilitate the applications of DNA microarray technology. A successful microarray experiment, however, involves many steps: well-designed oligonucleotide probes, printing, RNA extraction and labeling, hybridization, and imaging. Optimization is essential to generate reliable microarray data. Results: Hybridization and washing steps are crucial for a successful microarray experiment. By following the hybridization and washing conditions recommended by an oligonucleotide provider, it was found that the expression ratios were compressed greater than expected and data analysis revealed a high degree of non-specific binding. A series of experiments was conducted using rat mixed tissue RNA reference material (MTRRM) and other RNA samples to optimize the hybridization and washing conditions. The optimized hybridization and washing conditions greatly reduced the non-specific binding and improved the accuracy of spot intensity measurements. Conclusion: The results from the optimized hybridization and washing conditions greatly improved the reproducibility and accuracy of expression ratios. These experiments also suggested the importance of probe designs using better bioinformatics approaches and the need for common reference RNA samples for platform performance evaluation in order to fulfill the potential of DNA microarray technology. C1 US FDA, Natl Ctr Toxicol Res, Ctr Funct Genom, Jefferson, AR 72079 USA. US FDA, Natl Ctr Toxicol Res, Div Syst Toxicol, Jefferson, AR 72079 USA. US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Han, T (reprint author), US FDA, Natl Ctr Toxicol Res, Ctr Funct Genom, Jefferson, AR 72079 USA. EM Tao.Han@fda.hhs.gov; Cathy.Melvin@fda.hhs.gov; Leming.Shi@fda.hhs.gov; William.Branham@fda.hhs.gov; Carrie.Moland@fda.hhs.gov; Patrick.Pine@fda.hhs.gov; Karol.Thompson@fda.hhs.gov; James.Fuscoe@fda.hhs.gov NR 37 TC 24 Z9 24 U1 0 U2 2 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 SEP 26 PY 2006 VL 7 SU 2 AR S17 DI 10.1186/1471-2105-7-S2-S17 PG 13 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA 091DY UT WOS:000241007700017 PM 17118138 ER PT J AU Mei, N Guo, L Zhang, L Shi, LM Sun, YMA Fung, C Moland, CL Dial, SL Fuscoe, JC Chen, T AF Mei, Nan Guo, Lei Zhang, Lu Shi, Leming Sun, Yongming Andrew Fung, Chris Moland, Carrie L. Dial, Stacey L. Fuscoe, James C. Chen, Tao TI Analysis of gene expression changes in relation to toxicity and tumorigenesis in the livers of Big Blue transgenic rats fed comfrey (Symphytum officinale) SO BMC BIOINFORMATICS LA English DT Article; Proceedings Paper CT 3rd Annual Conference of the MidSouth-Computational-Biology-and-Bioinformatics-Society CY MAR 02-04, 2006 CL Baton Rouge, LA SP MidSouth Computat Biol & Bioinformat Soc ID HEPATIC VENOOCCLUSIVE DISEASE; SINUSOIDAL OBSTRUCTION SYNDROME; VENO-OCCLUSIVE DISEASE; PYRROLIZIDINE ALKALOIDS; GROWTH-FACTOR; HEPATOCELLULAR-CARCINOMA; HERB TEA; RIDDELLIINE; CIRRHOSIS; CANCER AB Background: Comfrey is consumed by humans as a vegetable and a tea, and has been used as an herbal medicine for more than 2000 years. Comfrey, however, is hepatotoxic in livestock and humans and carcinogenic in experimental animals. Our previous study suggested that comfrey induces liver tumors by a genotoxic mechanism and that the pyrrolizidine alkaloids in the plant are responsible for mutation induction and tumor initiation in rat liver. Results: In this study, we identified comfrey-induced gene expression profile in the livers of rats. Groups of 6 male transgenic Big Blue rats were fed a basal diet and a diet containing 8% comfrey roots, a dose that resulted in liver tumors in a previous carcinogenicity bioassay. The animals were treated for 12 weeks and sacrificed one day after the final treatment. We used a rat microarray containing 26,857 genes to perform genome-wide gene expression studies. Dietary comfrey resulted in marked changes in liver gene expression, as well as in significant decreases in the body weight and increases in liver mutant frequency. When a two-fold cutoff value and a P-value less than 0.01 were selected, 2,726 genes were identified as differentially expressed in comfrey-fed rats compared to control animals. Among these genes, there were 1,617 genes associated by Ingenuity Pathway Analysis with particular functions, and the differentially expressed genes in comfrey-fed rat livers were involved in metabolism, injury of endothelial cells, and liver injury and abnormalities, including liver fibrosis and cancer development. Conclusion: The gene expression profile provides us a better understanding of underlying mechanisms for comfrey-induced hepatic toxicity. Integration of gene expression changes with known pathological changes can be used to formulate a mechanistic scheme for comfrey-induced liver toxicity and tumorigenesis. C1 US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. US FDA, Natl Ctr Toxicol Res, Div Syst Toxicol, Jefferson, AR 72079 USA. Appl Biosyst Inc, Mol Biol SDS Arrays, Foster City, CA 94404 USA. Solexa Inc, Hayward, CA 94545 USA. RP Mei, N (reprint author), US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. EM nan.mei@fda.hhs.gov; lei.guo@fda.hhs.gov; lzhang@solexa.com; leiming.shi@fda.hhs.gov; sunya@appliedbiosystems.com; Chris.Fung@ucsf.edu; carrie.moland@fda.hhs.gov; Stacey.dial@fda.hhs.gov; james.fuscoe@fda.hhs.gov; tao.chen@fda.hhs.gov RI Guo, Lei/E-9232-2011; mei, nan/E-8915-2011 OI mei, nan/0000-0002-3501-9014 NR 58 TC 19 Z9 20 U1 1 U2 7 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 SEP 26 PY 2006 VL 7 SU 2 AR S16 DI 10.1186/1471-2105-7-S2-S16 PG 15 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA 091DY UT WOS:000241007700016 PM 17118137 ER PT J AU Sun, HM Fang, H Chen, T Perkins, R Tong, WD AF Sun, Hongmei Fang, Hong Chen, Tao Perkins, Roger Tong, Weida TI GOFFA: Gene Ontology For Functional Analysis - A FDA Gene Ontology Tool for Analysis of Genomic and Proteomic Data SO BMC BIOINFORMATICS LA English DT Article ID BIOLOGICAL INTERPRETATION; SOFTWARE; GOMINER; SETS AB Background: Gene Ontology (GO) characterizes and categorizes the functions of genes and their products according to biological processes, molecular functions and cellular components, facilitating interpretation of data from high-throughput genomics and proteomics technologies. The most effective use of GO information is achieved when its rich and hierarchical complexity is retained and the information is distilled to the biological functions that are most germane to the phenomenon being investigated. Results: Here we present a FDA GO tool named Gene Ontology for Functional Analysis (GOFFA). GOFFA first ranks GO terms in the order of prevalence for a list of selected genes or proteins, and then it allows the user to interactively select GO terms according to their significance and specific biological complexity within the hierarchical structure. GOFFA provides five interactive functions (Tree view, Terms View, Genes View, GO Path and GO TreePrune) to analyze the GO data. Among the five functions, GO Path and GO TreePrune are unique. The GO Path simultaneously displays the ranks that order GOFFA Tree Paths based on statistical analysis. The GO TreePrune provides a visual display of a reduced GO term set based on a user's statistical cut-offs. Therefore, the GOFFA visual display can provide an intuitive depiction of the most likely relevant biological functions. Conclusion: With GOFFA, the user can dynamically interact with the GO data to interpret gene expression results in the context of biological plausibility, which can lead to new discoveries or identify new hypotheses. C1 [Chen, Tao; Tong, Weida] Natl Ctr Toxicol Res Food & Drug Adm, Jefferson, AR 72079 USA. [Sun, Hongmei; Fang, Hong; Perkins, Roger] Z Tech Corp, Jefferson, AR 72079 USA. RP Tong, WD (reprint author), Natl Ctr Toxicol Res Food & Drug Adm, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM hongmei.sun@fda.hhs.gov; hong.fang@fda.hhs.gov; tao.chen@fda.hhs.gov; roger.perkins@fda.hhs.gov; weida.tong@fda.hhs.gov NR 26 TC 39 Z9 41 U1 0 U2 6 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 SEP 26 PY 2006 VL 7 SU 2 AR S23 DI 10.1186/1471-2105-7-S2-S23 PG 11 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA 091DY UT WOS:000241007700022 PM 17118145 ER PT J AU Salajegheh, M Bryan, WW Dalakas, MC AF Salajegheh, Mohammad Bryan, Wilson W. Dalakas, Marinos C. TI The challenge of diagnosing ALS in patients with prior poliomyelitis SO NEUROLOGY LA English DT Article ID AMYOTROPHIC-LATERAL-SCLEROSIS; POLIO AB Four patients with postpolio syndrome ( PPS) developed ALS. Weakness and atrophy started from previously unaffected extremities but, contrary to PPS, spread to all muscles leading to death within 0.4 to 8 ( mean 3.9) years. Upper motor neuron signs were absent in the atrophic limbs. Abundant spontaneous activity and group atrophy in newly affected muscles were prominent. ALS can rarely occur in the postpolio population starting de novo rather than as evolution of PPS. C1 NINDS, NDS, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Dalakas, MC (reprint author), NINDS, NDS, NIH, Bldg 10,Room 4N248,10 Ctr Dr, Bethesda, MD 20892 USA. EM dalakasm@ninds.nih.gov FU Intramural NIH HHS NR 10 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD SEP 26 PY 2006 VL 67 IS 6 BP 1078 EP 1079 DI 10.1212/01.wnl.0000237342.73436.f6 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 087NU UT WOS:000240749900034 PM 17000983 ER PT J AU Devi, SS Philip, BK Warbritton, A Latendresse, JR Mehendale, HM AF Devi, Sachin S. Philip, Binu K. Warbritton, Alan Latendresse, John R. Mehendale, Harihara M. TI Prior administration of a low dose of thioacetamide protects type 1 diabetic rats from subsequent administration of lethal dose of thioacetamide SO TOXICOLOGY LA English DT Article DE hepatotoxicity; liver; thioacetamide; tissue repair; type 1 diabetes ID LIVER-TISSUE REPAIR; POSTNATALLY DEVELOPING RATS; ACUTE-RENAL-FAILURE; CELL-DIVISION; 2-BUTOXYETHANOL AUTOPROTECTION; HEPATOCELLULAR REGENERATION; INDUCED HEPATOTOXICITY; MODEL HEPATOTOXICANTS; MOLECULAR-MECHANISMS; HEPATIC-FAILURE AB Previously, we reported that an ordinarily non-lethal dose of thioacetamide (TA, 300 mg/kg) causes 90% mortality in type I diabetic rats due to inhibited liver tissue repair, whereas 30 mg TA/kg allows 100% survival due to stimulated although delayed tissue repair. Objective of this investigation was to test whether prior administration of a low dose of TA (30 mg/kg) would lead to sustainable stimulation of liver tissue repair in type I diabetic rats sufficient to protect from a subsequently administered lethal dose of TA. Therefore, in the present study, the hypothesis that preplacement of tissue repair by a low dose of TA (30 mg TA/kg, ip) can reverse the hepatotoxicant sensitivity (autoprotection) in type I diabetic rats was tested. Preliminary studies revealed that a single intraperitoneal (ip) administration of TA causes 90% mortality in diabetic rats with as low as 75 mg/kg. To establish an autoprotection model in diabetic condition, diabetic rats were treated with 30 mg TA/kg (priming dose). Administration of priming dose stimulated tissue repair that peaked at 72 h, at which time these rats were treated with a single ip dose of 75 mg TA/kg. Our results show that tissue repair stimulated by the priming dose enabled diabetic rats to overexpress, calpastatin, endogenous inhibitor of calpain, to inhibit calpain-mediated progression of liver injury induced by the subsequent administration of lethal dose, resulting in 100% survival. Further investigation revealed that protection observed in these rats is not due to decreased bioactivation. These studies underscore the importance of stimulation of tissue repair in the final outcome of liver injury (survival/death) after hepatotoxicant challenge. Furthermore, these results also suggest that it is possible to stimulate tissue repair in diabetics to overcome the enhanced sensitivity of hepatotoxicants. (c) 2006 Elsevier Ireland Ltd. All rights reserved. C1 Univ Louisiana, Dept Toxicol, Coll Pharm, Monroe, LA 71209 USA. Toxicol Pathol Associates, Natl Ctr Toxicol Res, Jefferson, AR USA. RP Mehendale, HM (reprint author), Univ Louisiana, Dept Toxicol, Coll Pharm, 700 Univ Ave, Monroe, LA 71209 USA. EM mehendale@ulm.edu RI Latendresse, John/A-9215-2009 NR 40 TC 5 Z9 5 U1 0 U2 0 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 SEP 21 PY 2006 VL 226 IS 2-3 BP 107 EP 117 DI 10.1016/j.tox.2006.06.007 PG 11 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 089EF UT WOS:000240862400004 PM 16901604 ER PT J AU Malarkey, M Solomon, R Witten, C Bloom, E Wells, M Braun, M Wise, R Zinderman, C Jernigan, DB Kuehnert, MJ Srinivasan, A Wang, S AF Malarkey, M. Solomon, R. Witten, C. Bloom, E. Wells, M. Braun, M. Wise, R. Zinderman, C. Jernigan, D. B. Kuehnert, M. J. Srinivasan, A. Wang, S. TI Brief report: Investigation into recalled human tissue for transplantation - United States, 2005-2006 (Reprinted from MMWR, vol 55, pg 564, 2006) SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Reprint C1 US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. CDC, Div Healthcare Qual Promot, Natl Ctr Preparedness Detect & Control Infect Dis, Atlanta, GA 30333 USA. RP Malarkey, M (reprint author), US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. NR 1 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 SEP 20 PY 2006 VL 296 IS 11 BP 1347 EP 1348 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 085HS UT WOS:000240595800011 ER PT J AU Yin, JJ Kramer, JKG Yurawecz, MP Eynard, AR Mossoba, MM Yu, LL AF Yin, Jun-Jie Kramer, John K. G. Yurawecz, Martin P. Eynard, A. R. Mossoba, Magdi M. Yu, Liangli (Lucy) TI Effects of conjugated linoleic acid (CLA) isomers on oxygen diffusion - Concentration products in liposomes and phospholipid solutions SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE acid; CLA; ESR; free; linoleic; radicals ID PERFORMANCE LIQUID-CHROMATOGRAPHY; RADICAL SCAVENGING PROPERTIES; GAS-CHROMATOGRAPHY; PEROXIDATION; DERIVATIVES; RESONANCE; OXIDATION; MEMBRANES; CELLS AB Conjugated linoleic acids (CLAs) are a group of octadecadienoic acids (18:2) that are naturally present in food products and may have beneficial health effects. Liposomes and ethanol solutions were prepared by mixing synthetic phosphatidylcholines (PCs) with c9, t11-CLA, t10, c12-CLA, and linoleic acid (LA) in the sn-2 position into natural PCs from soybean, egg yolk, rat brain, and rat heart at 5 mol %. The oxygen diffusion-concentration products were measured using electron spin resonance spin-label oximetry methods. Individual synthetic PCs, the phospholipid matrix, and the tested lipid systems all exhibited influence on oxygen diffusion-concentration products during lipid peroxidation. Incorporating 5 mol % PC(c9, t11-CLA) into soy and egg yolk PC increased oxygen consumption in liposome suspensions while it was decreased in rat heart and brain PCs. On the other hand, PC(t10, c12-CLA) increased oxygen consumption in mixtures with egg yolk and rat heart PC but decreased it in soybean and rat brain PC. By comparison, PC(LA) decreased oxygen consumption in every case. In ethanol solutions, all of the synthetic PCs suppressed the capacity to generate peroxide radicals in the order of LA > c9, t11-CLA > t10, c12-CLA. In addition, PCs containing individual CLA isomers and LA differed in their capacities to react with and quench DPPH radicals in both ethanol solution and liposome, suggesting differences between CLA isomers and LA in DPPH radical-fatty acid interactions. Incorporation of CLA isomers and LA into dimyristyl-PC reduced the phase transition temperature from 23.6 to 23.1 and 23.3 degrees C, respectively. The results of this study provide evidence that the behavior of CLA isomers differs in the microenvironment of membranes possibly due to structural differences that affect the permeability of membranes to oxygen and lipid peroxidation. C1 US FDA, CFSAN, Instrumentat & Biophys Branch, College Pk, MD 20740 USA. Agr & Agri Food Canada, Food Res Program, Guelph, ON N1G 5C9, Canada. Inst Biol Celular, RA-5000 Cordoba, Argentina. Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA. RP Yin, JJ (reprint author), US FDA, CFSAN, Instrumentat & Biophys Branch, College Pk, MD 20740 USA. EM jyin@cfsan.fda.gov RI Yin, Jun Jie /E-5619-2014 NR 29 TC 15 Z9 15 U1 0 U2 1 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 20 PY 2006 VL 54 IS 19 BP 7287 EP 7293 DI 10.1021/jf0610918 PG 7 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 083NS UT WOS:000240465000049 PM 16968095 ER PT J AU Jackson, LS Tolleson, WH Chirtel, SJ AF Jackson, Lauren S. Tolleson, William H. Chirtel, Stuart J. TI Thermal inactivation of ricin using infant formula as a food matrix SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE ricin; stability; thermal processing; infant formula; heat; cytotoxicity ID HEAT INACTIVATION; VERONAL BUFFER; CELLS; ENTEROTOXIN; TOXICITY; ABRIN AB Ricin is a potent protein toxin found in the seeds of the castor bean plant, Ricinus communis. Ricin specifically and irreversibly inactivates ribosomes, promoting cell death by inhibiting protein synthesis. It is composed of a ribosome-inactivating enzyme (A-chain) linked to a lectin (B-chain) by a single disulfide bond. Several reports indicate that ricin can be detoxified by thermal treatment; however, the conditions required for inactivation are not well characterized. In addition, little information exists on the thermal stability of ricin added to foods. The objective of this work was to determine the effects of heat treatments on the detection and toxicity of ricin added to milk- and soy-based infant formulas. Reconstituted infant formula powders containing 100 mu g of ricin/mL were heated at 60-90 degrees C for up to 5 h. The heat-treated formulas were analyzed by ELISA to determine levels of ricin. The residual cytotoxicity of ricin-containing infant formula after heat treatments was determined using RAW264.7 mouse macrophage cells. The ELISA and the cytotoxicity assay indicated that ricin detection and toxicity decreased with increasing heating times and temperatures. Minimal losses in detection and toxicity were found for ricin heated at 60 degrees C for 2 h. The half-lives of ricin cytoxic activity in a milk-based infant formula at 60, 70, 75, 80, 85, and 90 degrees C were > 100, 9.8 +/- 0.5, 5.8 +/- 0.9, 5.1 +/- 0.7, 3.1 +/- 0.4, and 1.8 +/- 0.2 min, respectively; the comparable values for a soy-based infant formula were > 100, 16 +/- 1.6, 8.7 +/- 1.2, 6.9 +/- 1.1, 3.0 +/- 0.4, and 2.0 +/- 0.3 min. ELISA detection was a good indicator of the cytotoxicity of heat-treated ricin. The results indicate that ricin is a relatively heat stable protein and may remain toxic under some food processing conditions. C1 US FDA, NCFST, Summit Argo, IL 60501 USA. 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 Jackson, LS (reprint author), US FDA, NCFST, 7502 S Archer Rd, Summit Argo, IL 60501 USA. EM Lauren.Jackson@fda.hhs.gov NR 24 TC 22 Z9 22 U1 0 U2 10 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 20 PY 2006 VL 54 IS 19 BP 7300 EP 7304 DI 10.1021/jf061199n PG 5 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 083NS UT WOS:000240465000051 PM 16968097 ER PT J AU Faris, OP Shein, M AF Faris, Owen P. Shein, Mitchell TI Food and drug administration perspective - Magnetic resonance imaging of pacemaker and implantable cardioverter-defibrillator patients SO CIRCULATION LA English DT Editorial Material DE editorials; defibrillation; imaging; magnetic resonance imaging; pacemakers; pacing ID IN-VITRO; SAFETY; VIVO C1 US FDA, Ctr Devices & Radiol Hlth, Div Cardiovasc Dis, Rockville, MD 20850 USA. RP Shein, M (reprint author), US FDA, Ctr Devices & Radiol Hlth, Div Cardiovasc Dis, 9200 Corp Blvd, Rockville, MD 20850 USA. EM mitchell.shein@fda.hhs.gov NR 8 TC 59 Z9 59 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD SEP 19 PY 2006 VL 114 IS 12 BP 1232 EP 1233 DI 10.1161/CIRCULATIONAHA.106.647800 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 084TG UT WOS:000240556700003 PM 16982951 ER PT J AU Tryndyak, V Kovalchuk, O Pogribny, IP AF Tryndyak, Volodymyr Kovalchuk, Olga Pogribny, Igor P. TI Identification of differentially methylated sites within unmethylated DNA domains in normal and cancer cells SO ANALYTICAL BIOCHEMISTRY LA English DT Article DE DNA methylation; hypermethylation; detection; cancer ID CPG-ISLANDS; PROMOTER HYPERMETHYLATION; BREAST-CANCER; GENOMIC DNA; HYPOMETHYLATION; GENES; AMPLIFICATION; TUMORS; CARCINOGENESIS; EPIGENETICS AB Altered DNA methylation has been linked to neoplastic cell transformation and is a hallmark of cancer progression. Therefore, the screening for differentially methylated sequences as tumor biomarkers has a significant implication in the clinical setting. To determine the cancer-linked alterations in DNA methylation pattern, we have applied an endonuclease, McrBC, to the existing methylation-sensitive arbitrarily primed polymerase chain reaction (msAP-PCR) method and developed McrBC-msAP-PCR. This modified approach allows detection of differentially methylated sites within unmethylated DNA domains enriched by regulatory sequences and CpG islands. In this method, we used digestion of DNA with the McrBC methylation-sensitive endonuclease to selectively exclude the methylated fraction of DNA, which comprises interspersed and tandem-repeated sequences and exons other than first exons, from analysis. The subsequent digestion of unmethylated DNA fragments with SmaI and HpaII methylation-sensitive restriction endonucleases followed by AP-PCR amplification resulted in the detection of unknown unique sequences associated with cancer-linked methylation changes in genomic DNA. Hypermethylation and hypomethylation are visualized by the increase or decrease in the band intensity of DNA fingerprints. By using this technique, we were able to differentiate clearly, identify, and characterize a number of novel unique DNA sequences with differentially methylated sites in normal and breast cancer cell lines and in normal and rat tumor liver tissues. Published by Elsevier Inc. C1 Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. Univ Lethbridge, Dept Biol Sci, Lethbridge, AB T1K 3M4, Canada. RP Pogribny, IP (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. EM ipogribny@nctr.fda.gov NR 40 TC 16 Z9 18 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 SEP 15 PY 2006 VL 356 IS 2 BP 202 EP 207 DI 10.1016/j.ab.2006.05.019 PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 084HJ UT WOS:000240523700005 PM 16824473 ER PT J AU Engel, E Santarelli, F Vasold, R Ulrich, H Maisch, T Konig, B Landthaler, M Gopee, NV Howard, PC Baumler, W AF Engel, Eva Santarelli, Francesco Vasold, Rudolf Ulrich, Heidi Maisch, Tim Koenig, Burkhard Landthaler, Michael Gopee, Neera V. Howard, Paul C. Baeumler, Wolfgang TI Establishment of an extraction method for the recovery of tattoo pigments from human skin using HPLC diode array detector technology SO ANALYTICAL CHEMISTRY LA English DT Article ID QUANTITATIVE EXTRACTION; EXTRAVASATED DYE; EVANS BLUE; LASER; HAIR; SPECTROMETRY; LEATHER; TISSUE; RATS AB Tattooing is a widespread process of puncturing pigments into skin, whereas the resulting concentration inside the skin remains unknown. Many tattoo colorants are organic pigments, such as azo pigments, manufactured for other uses. To remove tattoos from skin, laser pulses at very high intensities are applied to the skin to destroy the tattoo pigments. Recent investigations have shown that several azo compounds are cleaved by laser light leading to potentially toxic or carcinogenic compounds. To assess the risk of tattooing and laser treatment of tattoos, the concentration of the pigments and their decomposition products in the skin must be determined. Therefore, an extraction method was established to determine the concentration of tattoo pigments and decomposition products quantitatively. The extraction of two widely used azo compounds, Pigment Red 22 and Pigment Red 9, and their laser-induced decomposition products, 2-methyl-5-nitroaniline, 4-nitrotoluene, 2,5-dichloraniline, and 1,4-dichlorobenzene, was accomplished using recovery experiments and HPLC-DAD technology. Despite the poor solubility of the pigments, a nearly complete recovery from aqueous suspension (> 92%) or lysed skin (> 94%) was achieved. The decomposition products were extracted from aqueous suspension or skin showing a recovery of up to 100%, except for the very volatile 1,4-DCB. C1 Univ Regensburg, Dept Dermatol, D-8400 Regensburg, Germany. Univ Regensburg, Dept Organ Chem, D-8400 Regensburg, Germany. US FDA, NCTR, Jefferson, AR 72069 USA. RP Baumler, W (reprint author), Univ Regensburg, Dept Dermatol, D-8400 Regensburg, Germany. EM baeumler.wolfgang@klinik.uni-regensburg.de RI Koenig, Burkhard/A-1362-2009 OI Koenig, Burkhard/0000-0002-6131-4850 NR 39 TC 18 Z9 18 U1 4 U2 18 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0003-2700 J9 ANAL CHEM JI Anal. Chem. PD SEP 15 PY 2006 VL 78 IS 18 BP 6440 EP 6447 DI 10.1021/ac0607461 PG 8 WC Chemistry, Analytical SC Chemistry GA 083YO UT WOS:000240495800021 PM 16970319 ER PT J AU Kioi, M Kawakami, M Shimamura, T Husain, SR Puri, RK AF Kioi, Mitomu Kawakami, Mariko Shimamura, Takeshi Husain, Syed R. Puri, Raj K. TI Interleukin-13 receptor alpha 2 chain - A potential biomarker and molecular target for ovarian cancer therapy SO CANCER LA English DT Article DE ovarian cancer; biomarker; interleukin-13; receptor; targeted therapy ID CLEAR-CELL CARCINOMA; ANTITUMOR-ACTIVITY; CYTOTOXIN; IL-13; SERUM; EXPRESSION; XENOGRAFT; SUBUNIT; P53 AB BACKGROUND. Epithelial ovarian cancer demonstrates high mortality due to diagnosis at an advanced stage. In the search for a biomarker for early diagnosis and a target for therapy, the issue of whether interleukin-13 receptor (IL-13R), shown to be expressed on a variety of human cancers, is expressed in ovarian tumor samples was explored. In addition, whether this receptor serves as a biomarker and can be targeted by IL-13 cytotoxin was examined. METHODS. IL-13R expression in 15 normal and 68 ovarian tumor tissue samples was determined by immunohistochemistry. Correlation between clinicopathologic features and IL-13R expression was analyzed. The efficacy of IL-13R-directed cytotoxin was determined in mice with subcutaneous, orthotopic, and peritoneal metastatic ovarian cancer. RESULTS. Immunohistochemical analyses revealed that 83% of ovarian cancer specimens express IL-13R alpha 2, a high-affinity IL-13R subunit chain, whereas normal ovary samples expressed none or very low levels. The majority of clear cell ovarian carcinomas with the worst prognosis showed strong staining for IL-13R alpha 2. IL-13 cytotoxin was highly cytotoxic to the IGROV-1 ovarian cancer cell line in vitro, and it mediated significant antitumor activity against a xenografted tumor model. The antitumor effects were confirmed by treating orthotopically implanted or peritoneal metastatic ovarian tumors, which showed significant extension of survival in immunodeficient mice. IL-13 cytotoxin also prevented cachexia in treated mice. The soluble form of IL-13R alpha 2 was detected in the serum of mice with peritoneal metastasis, and the level decreased to baseline in the treated group. CONCLUSIONS. IL-13R alpha 2 is a promising target for ovarian cancer therapy, and the soluble form of IL-13R may be a possible surrogate marker for disease monitoring. C1 NIH, Tumor Vaccines & Biotechnol Branch, Div Cellular & Gene Therapies, Food & Drug Adm,Ctr Biol Evaluation & Res, Bethesda, MD 20892 USA. RP Puri, RK (reprint author), NIH, Tumor Vaccines & Biotechnol Branch, Div Cellular & Gene Therapies, Food & Drug Adm,Ctr Biol Evaluation & Res, Bldg 29B,Room 2NN20,HFM-710,29 Lincoln Dr, Bethesda, MD 20892 USA. EM raj.puri@fda.hhs.gov OI Kioi, Mitomu/0000-0002-7981-3340 NR 23 TC 41 Z9 44 U1 0 U2 6 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD SEP 15 PY 2006 VL 107 IS 6 BP 1407 EP 1418 DI 10.1002/cncr.22134 PG 12 WC Oncology SC Oncology GA 084MR UT WOS:000240537700026 PM 16902988 ER PT J AU Cohen, MH Johnson, JR Massie, T Sridhara, R McGuinn, WD Abraham, S Booth, BP Goheer, MA Morse, D Chen, XH Chidambaram, N Kenna, L Gobburu, JV Justice, R Pazdur, R AF Cohen, Martin H. Johnson, John R. Massie, Tristan Sridhara, Rajeshwari McGuinn, W. David, Jr. Abraham, Sophia Booth, Brian P. Goheer, M. Anwar Morse, David Chen, Xiao H. Chidambaram, Nallaperumal Kenna, Leslie Gobburu, Jogarao V. Justice, Robert Pazdur, Richard TI Approval summary: Nelarabine for the treatment of T-cell lymphoblastic leukemia/lymphoma SO CLINICAL CANCER RESEARCH LA English DT Article ID REFRACTORY HEMATOLOGIC MALIGNANCIES; CLINICAL-RESPONSE; LEUKEMIA; CHILDREN; ARABINOSYLGUANINE; PHARMACOKINETICS; ARABINOSIDE; 506U78; ADULTS AB Purpose: To describe the clinical studies, chemistry manufacturing and controls, and clinical pharmacology and toxicology that led to Food and Drug Administration approval of nelarabine (Arranon) for the treatment of T-cell acute lymphoblastic leukemia/lymphoblastic lymphoma. Experimental Design: Two phase 2 trials, one conducted in pediatric patients and the other in adult patients, were reviewed. The i.v. dose and schedule of nelarabine in the pediatric and adult studies was 650 mg/m(2)/d daily for 5 days and 1,500 mg/m(2) on days 1, 3, and 5, respectively. Treatments were repeated every 21 days. Study end points were the rates of complete response (CR) and CR with incomplete hematologic or bone marrow recovery (CR*). Results: The pediatric efficacy population consisted of 39 patients who had relapsed or had been refractory to two or more induction regimens. CR to nelarabine treatment was observed in 5 (13%) patients and CR+CR* was observed in 9 (23%) patients. The adult efficacy population consisted of 28 patients. CR to nelarabine treatment was observed in 5 (18%) patients and CR+CR* was observed in 6 (21%) patients. Neurologic toxicity was dose limiting for both pediatric and adult patients. Other severe toxicities included laboratory abnormalities in pediatric patients and gastrointestinal and pulmonary toxicities in adults. Conclusions: On October 28, 2005, the Food and Drug Administration granted accelerated approval for nelarabine for treatment of patients with relapsed or refractory T-cell acute lymphoblastic leukemia/lymphoblastic lymphoma after at least two prior regimens. This use is based on the induction of CRs. The applicant will conduct postmarketing clinical trials to show clinical benefit (e.g., survival prolongation). C1 US FDA, Div Drug Oncol Prod, Off Oncol Drug Prod, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Cohen, MH (reprint author), US FDA, Div Drug Oncol Prod, Off Oncol Drug Prod, Ctr Drug Evaluat & Res, 5600 Fishers Lane, Rockville, MD 20857 USA. EM martin.cohen@fda.hhs.gov NR 11 TC 39 Z9 40 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 SEP 15 PY 2006 VL 12 IS 18 BP 5329 EP 5335 DI 10.1158/1078-0432.CCR-06-0606 PG 7 WC Oncology SC Oncology GA 087AK UT WOS:000240714400014 PM 17000665 ER PT J AU Bertholet, S Goldszmid, R Morrot, A Debrabant, A Afrin, F Collazo-Custodio, C Houde, M Desjardins, M Sher, A Sacks, D AF Bertholet, Sylvie Goldszmid, Romina Morrot, Alexandre Debrabant, Alain Afrin, Farhat Collazo-Custodio, Carmen Houde, Mathieu Desjardins, Michel Sher, Alan Sacks, David TI Leishmania antigens are presented to CD8(+) T cells by a transporter associated with antigen processing-independent pathway in vitro and in vivo SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MHC CLASS-I; DENDRITIC CELLS; CROSS-PRESENTATION; CUTANEOUS LEISHMANIASIS; TOXOPLASMA-GONDII; MYCOBACTERIUM-TUBERCULOSIS; LISTERIA-MONOCYTOGENES; EXOGENOUS ANTIGENS; IMMUNE-RESPONSES; MAJOR INFECTION AB CD8(+) T cells are generated in response to Leishmania major (Lm) or Toxoplasma gondii parasitic infections, indicating that exogenously delivered Ag can be processed for presentation by MHC class I molecules. We show that presentation of Lm nucleotidase (NT)-OVA is TAP independent in vivo and in vitro, and is inhibited by chloroquine, but not by proteasome inhibitors. In contrast, the presentation of T. gondii P30-OVA relies on the TAP/proteasome pathway. Presentation of OVA- or rNT-OVA-coated beads also bypassed TAP requirement above a certain Ag threshold. TAP was also dispensable for the presentation of wild-type Lm Ags to primed CD8(+) T cells in vitro. Finally, in vivo priming of CD8(+) T cells involved in acquired resistance to Lm was not compromised in TAP-deficient mice. Thus, Leishmania Ags, appear to be confined to an intraphagosomal processing pathway that requires higher concentrations of Ags, suggesting that these parasites may have evolved strategies to impair the efficient endoplasmic reticulum-based, TAP-dependent cross-presentation pathway to avoid or delay CD8(+) T cell priming. C1 NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. US FDA, Div Emerging & Transfus Transmitted Dis, Off Blood Res & Review, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. Univ Montreal, Dept Pathol & Biol Cellulaire, Montreal, PQ, Canada. RP Sacks, D (reprint author), NIAID, Parasit Dis Lab, NIH, Bldg 4,Room 126,Ctr Dr MSC 0425, Bethesda, MD 20892 USA. EM dsacks@nih.gov OI Morrot, Alexandre/0000-0001-9432-9701 NR 53 TC 63 Z9 63 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 2006 VL 177 IS 6 BP 3525 EP 3533 PG 9 WC Immunology SC Immunology GA 083RG UT WOS:000240475300004 PM 16951311 ER PT J AU Bhattacharjee, A Xu, B Frank, DA Feldman, GM Cathcart, MK AF Bhattacharjee, Ashish Xu, Bo Frank, David A. Feldman, Gerald M. Cathcart, Martha K. TI Monocyte 15-lipoxygenase expression is regulated by a novel cytosolic signaling complex with protein kinase C delta and tyrosine-phosphorylated Stat3 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID 15-LIPOXYGENASE GENE-EXPRESSION; CENTRIFUGAL ELUTRIATION CCE; MONOCYTE-ENRICHED FRACTIONS; MONONUCLEAR CELL SUBSETS; LOW-DENSITY-LIPOPROTEIN; SERINE PHOSPHORYLATION; TRANSCRIPTIONAL ACTIVATION; ATHEROSCLEROTIC LESIONS; RECEPTOR COMPONENTS; ENDOTHELIAL-CELLS AB Our previous studies demonstrated that the IL-13-induced 15-lipoxygenase expression in primary human monocytes is regulated by the activation of both Stat1 and Stat3 and by protein kinase C (PKC)delta. IL-13 stimulated the phosphorylation of Stat3 on both Tyr(705) and Ser(727). In this study we show that IL-13 induces the association of PKCS with Stat3, not with Stall, and is required for Stat3 Ser 727 phosphorylation. We found a novel IL-13-dependent cytosolic signaling complex of PKCS and tyrosine-phosphorylated Stat3. A tyrosine kinase inhibitor blocked PKC delta association with Stat3 as well as Stat3 Ser 727 phosphorylation. We therefore hypothesized that tyrosine phosphorylation was required for Stat3 interaction with PKC delta and subsequent PKC delta-5-dependent phosphorylation of Stat3 Ser(727). We developed an efficient transfection protocol for human monocytes. Expression of Stat3 containing a mutation in Tyr(705) inhibited the association of PKC5 with Stat3 and blocked Stat3 Ser 727 phosphorylation, whereas transfection with wild-type Stat3 did not. Furthermore, by transfecting monocytes with Stat3 containing mutations in Tyr(705) or Ser(727) or with wild-type Stat3, we demonstrated that both Stat3 tyrosine and serine phosphorylations are required for optimal binding of Stat3 with DNA and maximal expression of 15-lipoxygenase, an important regulator of inflammation and apoptosis. C1 Cleveland Clin Fdn, Dept Cell Biol, Cleveland, OH 44195 USA. Case Western Reserve Univ, Dept Mol Med, Lerner Coll Med, Cleveland Clin, Cleveland, OH 44195 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. US FDA, Div Monoclonal Antibodies, Off Therapeut Res & Review, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Cathcart, MK (reprint author), Cleveland Clin Fdn, Dept Cell Biol, 9500 Euclid Ave, Cleveland, OH 44195 USA. EM cathcam@ccf.org FU NCRR NIH HHS [M01 RR-018390]; NHLBI NIH HHS [HL51068] NR 55 TC 17 Z9 17 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 2006 VL 177 IS 6 BP 3771 EP 3781 PG 11 WC Immunology SC Immunology GA 083RG UT WOS:000240475300031 PM 16951338 ER PT J AU Zhang, P Snyder, S Feng, P Azadi, P Zhang, SS Bulgheresi, S Sanderson, KE He, J Klena, J Chen, T AF Zhang, Pei Snyder, Scott Feng, Peter Azadi, Parastoo Zhang, Shusheng Bulgheresi, Silvia Sanderson, Kenneth E. He, Johnny Klena, John Chen, Tie TI Role of N-acetylglucosamine within core lipopolysaccharide of several species of gram-negative bacteria in targeting the DC-SIGN (CD209) SO JOURNAL OF IMMUNOLOGY LA English DT Article ID ESCHERICHIA-COLI K-12; NEISSERIA-GONORRHOEAE LIPOOLIGOSACCHARIDE; GONOCOCCAL OPACITY PROTEINS; DENDRITIC CELL-FUNCTION; O-ANTIGEN; SALMONELLA-TYPHIMURIUM; SELECTIVE RECOGNITION; CERVICAL EPITHELIA; STRUCTURAL BASIS; CHAIN-LENGTH AB Our recent studies have shown that the dendritic cell-specific ICAM nonintegrin CD209 (DC-SIGN) specifically binds to the core LPS of Escherichia coli K12 (E. coli), promoting bacterial adherence and phagocytosis. In this current study, we attempted to map the sites within the core LPS that are directly involved in LPS-DC-SIGN interaction. We took advantage of four sets of well-defined core LPS mutants, which, are derived from, E. coli, Salmonella enterica serovar Typhimurium, Neisseria gonorrhoeae, and Haemophilus ducreyi and determined interaction of each of these four sets with DC-SIGN. Our results demonstrated that N-acetylglucosamine (GlcNAc) sugar residues within the core LPS in these bacteria play an essential role in targeting the DC-SIGN receptor. Our results also imply that DC-SIGN is an innate immune receptor and the interaction of bacterial core LPS and DC-SIGN may represent a primeval interaction between Gram-negative bacteria and host phagocytic cells. C1 Univ Illinois, Coll Med, Dept Biomed Sci, Rockford, IL 61107 USA. Univ Georgia, Complex Carbohydrate Res Ctr, Athens, GA 30602 USA. US FDA, Div Microbiol Studies, College Pk, MD 20740 USA. Univ Vienna, Dept Marine Biol, Fac Life Sci, Vienna, Austria. Indiana Univ, Sch Med, Dept Microbiol & Immunol, Indianapolis, IN 46202 USA. Univ Canterbury, Sch Biol Sci, Christchurch 1, New Zealand. RP Klena, J (reprint author), Univ Illinois, Coll Med, Dept Biomed Sci, 1601 Parkview Ave, Rockford, IL 61107 USA. EM paua4T@yahoo.com; tiechen@uic.edu RI Bulgheresi, Silvia/B-8972-2009; Bulgheresi, Silvia/C-3128-2013 FU NIAID NIH HHS [R01AI 47736] NR 59 TC 39 Z9 41 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 SEP 15 PY 2006 VL 177 IS 6 BP 4002 EP 4011 PG 10 WC Immunology SC Immunology GA 083RG UT WOS:000240475300056 PM 16951363 ER PT J AU Audet, S Virata-Theimer, ML Beeler, JA Scott, DE Frazier, DJ Mikolajczyk, MG Eller, N Chen, FM Yu, MYW AF Audet, Susette Virata-Theimer, Maria Luisa Beeler, Judy A. Scott, Dorothy E. Frazier, Douglas J. Mikolajczyk, Malgorzata G. Eller, Nancy Chen, Feng-ming Yu, Mei-ying W. TI Measles-virus-neutralizing antibodies in intravenous immunoglobulins SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID HUMAN PLASMA FRACTIONATION; IMMUNE SERUM GLOBULIN; BLOOD-DONORS; UNITED-STATES; PROPHYLAXIS; INFECTION; PROFILES; PRODUCTS; TITERS AB Measles infection induces lifelong immunity; however, wild-type infection stimulates higher levels of measlesvirus-neutralizing antibodies (mnAbs) than does vaccination. Because the proportion of the donor population with vaccine-induced measles immunity is increasing, this study was conducted to determine whether this shift in demographic characteristics affects mnAb levels in contemporary lots of Immune Globulin Intravenous ( Human) ( IGIV). When 166 lots of 7 IGIV products manufactured between 1998 and 2003 were assayed by plaque-reduction neutralization test, there was a progressive decrease in geometric mean titers in lots manufactured between 1999 and 2002. IGIV products manufactured from recovered plasma had significantly higher titers than did those manufactured from Source Plasma, which could reflect a change in donor demographic characteristics, because Source Plasma donors tend to be much younger. A reduction in mnAbs also correlated with the loss of either IgG1 and IgG3, possibly because of certain manufacturing procedures, or bivalent antibodies (i.e., intact IgG and F(ab')2), because of fragmentation. C1 US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Rockville, MD 20852 USA. US FDA, Ctr Biol Evaluat & Res, Div Hematol, Rockville, MD 20852 USA. RP Yu, MYW (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, 1401 Rockville Pike,HFM-345, Rockville, MD 20852 USA. EM mei-ying.yu@fda.hhs.gov NR 26 TC 19 Z9 19 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD SEP 15 PY 2006 VL 194 IS 6 BP 781 EP 789 DI 10.1086/506363 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 081KN UT WOS:000240316600009 PM 16941344 ER PT J AU Dragunsky, EM Ivanov, AP Abe, S Potapova, SG Enterline, JC Hashizume, S Chumakov, KM AF Dragunsky, Eugenia M. Ivanov, Alexander P. Abe, Shinobu Potapova, Svetlana G. Enterline, Joan C. Hashizume, So Chumakov, Konstantin M. TI Further development of a new transgenic mouse test for the evaluation of the immunogenicity and protective properties of inactivated poliovirus vaccine SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID ERADICATION AB Recently, we developed and optimized a new method for the evaluation of the protective properties of serotype 2 inactivated poliovirus vaccines (IPV). The method is based on the immunization and subsequent challenge of transgenic (Tg) mice susceptible to poliovirus. We describe a similar method for the assessment of the protectiveness of serotype 1 IPV and demonstrate that experimental IPV produced from attenuated Sabin strain (sIPV) of serotype 1 poliovirus induced serum neutralizing antibodies, immunoglobulin (Ig) G, IgM, and salivary IgA at titers comparable to those induced by conventional IPV (cIPV) produced from the wild-type Mahoney strain. In contrast to our previous results with serotype 2 sIPV, serotype 1 sIPV provided even better protection of Tg mice than cIPV against challenge with wild-type Mahoney strain. C1 US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. Poliomyelitis Res Inst, Tokyo, Japan. RP Dragunsky, EM (reprint author), HFM-470,NLRC B-121,1401 Rockville Pike, Rockville, MD 20852 USA. EM eugenia.dragunsky@fda.hhs.gov NR 14 TC 4 Z9 4 U1 0 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD SEP 15 PY 2006 VL 194 IS 6 BP 804 EP 807 DI 10.1086/506949 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 081KN UT WOS:000240316600012 PM 16941347 ER PT J AU Baughman, AL Bisgard, KM Lynn, F Meade, BD AF Baughman, Andrew L. Bisgard, Kristine M. Lynn, Freyja Meade, Bruce D. TI Mixture model analysis for establishing a diagnostic cut-off point for pertussis antibody levels SO STATISTICS IN MEDICINE LA English DT Article DE mixture model; diagnostic cut-off point; Third National Health and Nutrition Examination Survey; antibodies; pertussis ID HIGHLY IMMUNIZED POPULATION; BORDETELLA-PERTUSSIS; VACCINE EFFECTIVENESS; UNITED-STATES; ADULTS; ADOLESCENTS; OUTBREAK; PARAPERTUSSIS; TOXIN; IDENTIFICATION AB Previous studies of pertussis (whooping cough) that have derived diagnostic cut-off points for pertussis antibody levels have assumed a single distribution for antibody levels and have used small sample sizes. In a recent study of 5409 serum samples from the Third National Health and Nutrition Examination Survey (NHANES 111), a finite mixture model was developed to examine the distribution of immunoglobulin G (IgG) antibody levels against pertussis toxin (PT), an antigen specific to the Bordetella pertussis bacterium. The mixture model identified three component populations with antibody levels greater than the quantitative assay's lower limit of quantitation (LLQ) and included a point distribution located at or below the LLQ to account for the excess number of antibody values that fell below the LLQ. The mixture model analysis accounted for the NHANES III design. A cut-off point for anti-PT IgG levels was chosen to have a 99 per cent model specificity based on the two overlapping normal distributions assumed for the two component populations with the highest antibody levels. This cut-off point may have a higher diagnostic sensitivity for acute B. pertussis infection than other cut-off points derived by assuming a single distribution for antibody levels. Published in 2005 by John Wiley & Sons, Ltd. C1 Ctr Dis Control & Prevent, Natl Immunizat Program, Atlanta, GA 30333 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. RP Baughman, AL (reprint author), Ctr Dis Control & Prevent, Natl Immunizat Program, 1600 Clifton Rd NE,Mailstop E-61, Atlanta, GA 30333 USA. EM dbaughman@cdc.gov NR 52 TC 14 Z9 15 U1 0 U2 5 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD SEP 15 PY 2006 VL 25 IS 17 BP 2994 EP 3010 DI 10.1002/sim.2442 PG 17 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 077RI UT WOS:000240047100010 PM 16345022 ER PT J AU Benjamin, DK Smith, PB Murphy, MD Roberts, R Mathis, L Avant, D Califf, RM Li, JS AF Benjamin, Daniel K., Jr. Smith, Philip Brian Murphy, M. Dianne Roberts, Rosemary Mathis, Lisa Avant, Debbie Califf, Robert M. Li, Jennifer S. TI Peer-reviewed publication of clinical trials completed for pediatric exclusivity SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; PLASMODIUM-FALCIPARUM MALARIA; JUVENILE RHEUMATOID-ARTHRITIS; DOUBLE-BLIND; OPEN-LABEL; CHILDREN; ADOLESCENTS; EFFICACY; PHARMACOKINETICS; ATOVAQUONE AB Context Much of pediatric drug use is off-label because appropriate pediatric studies have not been conducted and the drugs have not been labeled by the US Food and Drug Administration (FDA) for use in children. In 1997, Congress authorized the FDA to grant extensions of marketing rights known as "pediatric exclusivity" if FDA-requested pediatric trials were conducted. As a result, there have been over 100 product labeling changes. The publication status of studies completed for pediatric exclusivity has not been evaluated. Objective To quantify the dissemination of results of studies conducted for pediatric exclusivity into the peer-review literature. Design Cohort study of all trials conducted for pediatric exclusivity between 1998 and 2004 as determined by MEDLINE and EMBASE searches through 2005, the subsequent labeling changes, and the publication of those studies in peer-reviewed journals. We categorized any labeling changes resulting from the studies as positive or negative for the drug under study. We then evaluated aspects of the studies and product label changes that were associated with subsequent publication in peer-reviewed medical journals. Main Outcome Measures Publication of the trial data in peer-reviewed journals. Results Between 1998 and 2004, 253 studies were submitted to the FDA for pediatric exclusivity: 125 (50%) evaluated efficacy, 51 (20%) were multi-dose pharmacokinetic, 34 (13%) were single-dose pharmacokinetic, and 43 (17%) were safety studies. Labeling changes were positive for 127/253 (50%) of studies; only 113/253 (45%) were published. Efficacy studies and those with a positive labeling change were more likely to be published. Conclusions The pediatric exclusivity program has been successful in encouraging drug studies in children. However, the dissemination of these results in the peer-reviewed literature is limited. Mechanisms to more widely disperse this information through publication warrant further evaluation. C1 Duke Univ, Duke Clin Res Inst, Durham, NC 27705 USA. Duke Univ, Dept Pediat, Durham, NC 27705 USA. Duke Univ, Dept Med, Durham, NC 27705 USA. US FDA, Ctr Drug Evaluat & Res, Off Counter Terrorism & Pediat Drug Dev, Rockville, MD 20857 USA. US FDA, Ctr Drug Evaluat & Res, Off Commissioner, Rockville, MD 20857 USA. US FDA, Ctr Drug Evaluat & Res, Off Pediat Therapeut, Rockville, MD 20857 USA. RP Benjamin, DK (reprint author), Duke Univ, Duke Clin Res Inst, POB 17969, Durham, NC 27705 USA. EM danny.benjamin@duke.edu RI Smith, Phillip/I-5565-2014 FU NICHD NIH HHS [1U10-HD45962-03, U10 HD045962, U10 HD045962-04] NR 37 TC 90 Z9 91 U1 2 U2 6 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 SEP 13 PY 2006 VL 296 IS 10 BP 1266 EP 1273 DI 10.1001/jama.296.10.1266 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 083EA UT WOS:000240437500029 PM 16968851 ER PT J AU Saha, S Takeshita, F Sasaki, S Matsuda, T Tanaka, T Tozuka, M Takase, K Matsumoto, T Okuda, K Ishii, N Yamaguchi, K Klinman, DM Xin, KQ Okuda, K AF Saha, Sukumar Takeshita, Fumihiko Sasaki, Shin Matsuda, Tomoko Tanaka, Toshiyuki Tozuka, Miyuki Takase, Keiko Matsumoto, Tetsuya Okuda, Katsuji Ishii, Norihisa Yamaguchi, Keizo Klinman, Dennis M. Xin, Ke-Qin Okuda, Kenji TI Multivalent DNA vaccine protects mice against pulmonary infection caused by Pseudomonas aeruginosa SO VACCINE LA English DT Article DE Pseudomonas aeruginosa; DNA vaccine; multivalency ID PASSIVE-IMMUNIZATION; ADENOVIRUS VECTOR; IMMUNE-RESPONSES; STRUCTURAL GENE; IMMUNOGENICITY; ELASTASE; IMMUNOTHERAPY; SEPSIS; TUBERCULOSIS; MACROPHAGES AB For efficacious vaccine development against Pseudomonas aeruginosa (P aeruginosa), the immunogenicity of multivalent DNA vaccine was evaluated. Three different plasmids each targeting a fusion of outer membrane proteins (OprF/OprI), a protein regulating type III secretion system (PcrV), or an appendage (PiIA) were prepared and mice were immunized with single (monovalent) or a combination of these plasmids (multivalent) via intramuscular electroporation (imEPT) or gene gun. Immunization with multivalent DNA vaccine via imEPT induced the most potent protection against lethal pneumonia. Although the serum levels of IgG binding to whole bacteria cells were comparable between groups, the strongest immune protection was associated with the serum levels of Th1-dominated multivalent IgG, the bronchoalveolar levels of macrophage inflammatory protein 2 (MIP-2) and IFN-gamma, and the number of neutrophils and macrophages in the bronchoalveolar lavage following intranasal challenge. These results implied the possible clinical application of multivalent DNA vaccine against P. aeruginosa. (c) 2006 Elsevier Ltd. All rights reserved. C1 Yokohama City Univ, Grad Sch Med, Dept Mol Biodef Res, Yokohama, Kanagawa 2360004, Japan. Toho Univ, Sch Med, Dept Microbiol, Tokyo 1430015, Japan. Tokyo Dent Univ, Dept Microbiol, Chiba 2610011, Japan. Natl Inst Infect Dis, Leprosy Res Ctr, Dept Bioregulat, Tokyo 1890002, Japan. US FDA, Ctr Biolog Evaluat & Res, Sect Retroviral Immunol, Bethesda, MD 20892 USA. RP Okuda, K (reprint author), Yokohama City Univ, Grad Sch Med, Dept Mol Biodef Res, Yokohama, Kanagawa 2360004, Japan. EM kokuda@med.yokohama-cu.ac.jp; kokuda@med.yokohama-cu.ac.jp NR 43 TC 24 Z9 25 U1 1 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD SEP 11 PY 2006 VL 24 IS 37-39 BP 6240 EP 6249 DI 10.1016/j.vaccine.2006.05.077 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 086VX UT WOS:000240702200009 PM 16806598 ER PT J AU Sambandamurthy, VK Derrick, SC Hsu, T Chen, B Larsen, MH Jalapathy, KV Chen, M Kim, J Porcelli, SA Chan, J Morris, SL Jacobs, WR AF Sambandamurthy, Vasan K. Derrick, Steven C. Hsu, Tsungda Chen, Bing Larsen, Michelle H. Jalapathy, Kripa V. Chen, Mei Kim, John Porcelli, Steven A. Chan, John Morris, Sheldon L. Jacobs, William R., Jr. TI Mycobacterium tuberculosis Delta RD1 Delta panCD: A safe and limited replicating mutant strain that protects immunocompetent and immunocompromised mice against experimental tuberculosis SO VACCINE LA English DT Article DE tuberculosis; mycobacterial vaccines; BCG; attenuated strains ID BACILLUS-CALMETTE-GUERIN; T-CELL SUBSETS; BOVIS BCG; PANTOTHENATE AUXOTROPH; INTERFERON-GAMMA; IN-VITRO; IMMUNODEFICIENT MICE; IMMUNE-RESPONSE; INFECTION; VACCINES AB The global epidemic of tuberculosis (TB), fueled by the growing HIV pandemic, warrants the development of a safe and effective vaccine against TB. We report the construction and characterization of an unlinked double deletion mutant of Mycobacterium tuberculosis H37Rv that deletes both the primary attenuating mutation of BCG (Delta RD1) and two genes required for the synthesis of pantothenate (Delta panCD). The M. tuberculosis Delta RD1 Delta panCD (mc(2)6030) mutant undergoes limited replication in mice, and yet is both significantly safer than BCG in immunocompromised mice and also safe in guinea pigs. Additionally, the mc(2)6030 strain does not reactivate in a mouse chemo-immunosuppression model. Importantly, long-lived protective immune responses following immunization with the mc(2)6030 strain prolong the survival of wild type mice, and CD4-deficient mice against an aerosol challenge with virulent M. tuberculosis. Given its overall safety and effectiveness, the mc(2)6030 live attenuated strain should be considered as a human vaccine candidate for protecting both healthy and HIV-infected individuals against TB. (c) 2006 Elsevier Ltd. All rights reserved. C1 US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10461 USA. Albert Einstein Coll Med, Dept Med, Bronx, NY 10461 USA. Novartis Inst Trop Dis, Singapore 138670, Singapore. EM jacobsw@hhmi.org FU NIAID NIH HHS [AI 26170, AI-40488, AI-45707] NR 40 TC 102 Z9 104 U1 0 U2 5 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD SEP 11 PY 2006 VL 24 IS 37-39 BP 6309 EP 6320 DI 10.1016/j.vaccine.2006.05.097 PG 12 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 086VX UT WOS:000240702200018 PM 16860907 ER PT J AU Fu, TJ AF Fu, Tong-Jen TI Effect of thermal processing on the detection of food allergens SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Fu, Tong-Jen] US FDA, Natl Ctr Food Safety & Technol, Summit Argo, IL 60501 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 SEP 10 PY 2006 VL 232 MA 234-AGFD BP 140 EP 140 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DB UT WOS:000207781600126 ER PT J AU McDonald, J AF McDonald, Janet TI Allergen labeling requirements in the U.S SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [McDonald, Janet] US FDA, San Francisco Dist Off, Alameda, CA 94502 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 10 PY 2006 VL 232 MA 219-AGFD BP 142 EP 142 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DB UT WOS:000207781600128 ER PT J AU DeVries, JW Trucksess, MW D'Ovidio, KL AF DeVries, Jonathan W., Sr. Trucksess, Mary W. D'Ovidio, Kathleen L. TI Approaches to the removal of fumonisins from corn SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [DeVries, Jonathan W., Sr.] Gen Mills Inc, Medall Labs, Minneapolis, MN 55427 USA. [Trucksess, Mary W.] Ctr Food Safety & Appl Nutr, US FDA, College Pk, MD 20740 USA. [D'Ovidio, Kathleen L.] Univ Maryland, Dept Chem, College Pk, MD 20740 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 SEP 10 PY 2006 VL 232 MA 227-AGFD BP 173 EP 173 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DB UT WOS:000207781600156 ER PT J AU Trucksess, MW Weaver, CM Oles, CJ Rader, JI AF Trucksess, Mary W. Weaver, Carol M. Oles, Carolyn J. Rader, Jeanne I. TI Determination of fumonisin B1 in botanical roots SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Trucksess, Mary W.; Weaver, Carol M.; Oles, Carolyn J.; Rader, Jeanne I.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 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 SEP 10 PY 2006 VL 232 MA 135-AGFD BP 209 EP 209 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DB UT WOS:000207781600192 ER PT J AU Mindak, WR Cheng, J Capar, SG AF Mindak, William R. Cheng, John Capar, Stephen G. TI Methodology for monitoring toxic elements in food by the US Food and Drug Administration SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Mindak, William R.; Cheng, John; Capar, Stephen G.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 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 SEP 10 PY 2006 VL 232 MA 178-AGFD BP 211 EP 211 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DB UT WOS:000207781600194 ER PT J AU Albillos, SM Fu, TJ AF Albillos, Silvia M. Fu, Tong-Jen TI Effect of heat treatment on the structural stability of amandin, the major almond allergen SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Albillos, Silvia M.] Natl Ctr Food Safety & Technol, IIT, Summit Argo, IL 60501 USA. [Fu, Tong-Jen] US FDA, Natl Ctr Food Safety & Technol, Summit Argo, IL 60501 USA. NR 0 TC 0 Z9 0 U1 1 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 SEP 10 PY 2006 VL 232 MA 157-AGFD BP 219 EP 219 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DB UT WOS:000207781600202 ER PT J AU Garber, EAE AF Garber, Eric A. E. TI Food allergens: Methods of detection and the importance of validation SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Garber, Eric A. E.] US FDA, Ctr Food Safety & Appl Nutr, OPDF, College Pk, MD 20740 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 10 PY 2006 VL 232 MA 235-AGFD BP 225 EP 225 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DB UT WOS:000207781600208 ER PT J AU Jackson, LS Al-Taher, F Fu, TJ Gendel, SM AF Jackson, Lauren S. Al-Taher, Fadwa Fu, Tong-Jen Gendel, Steven M. TI Cleaning strategies and validation to prevent allergen cross-contact in food processing operations SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Jackson, Lauren S.; Fu, Tong-Jen; Gendel, Steven M.] US FDA, NCFST, Summit Argo, IL 60501 USA. [Al-Taher, Fadwa] IIT, NCFST, Summit Argo, IL 60501 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 10 PY 2006 VL 232 MA 196-AGFD BP 228 EP 228 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DB UT WOS:000207781600211 ER PT J AU Al-Taher, F Jackson, LS Domanico, M Moorman, MA AF Al-Taher, Fadwa Jackson, Lauren S. Domanico, Mark Moorman, Mark A. TI Transfer of peanut protein from a urethane-faced conveyor belt to a peanut-free cereal SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Al-Taher, Fadwa] IIT, NCFST, Summit Argo, IL 60501 USA. [Jackson, Lauren S.] US FDA, NCFST, Summit Argo, IL 60501 USA. [Domanico, Mark] Kellogg Co, Battle Creek, MI 49014 USA. [Moorman, Mark A.] WK Kellogg Inst Food & Nutr Res, Battle Creek, MI 49017 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 10 PY 2006 VL 232 MA 156-AGFD BP 230 EP 230 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DB UT WOS:000207781600213 ER PT J AU Westphal, CD Shefcheck, KJ AF Westphal, Carmen D. Shefcheck, Kevin J. TI Immunoassays for food allergens: Optimization through proteomic tools SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Westphal, Carmen D.; Shefcheck, Kevin J.] US FDA, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 10 PY 2006 VL 232 MA 192-AGFD BP 232 EP 232 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DB UT WOS:000207781600215 ER PT J AU Musser, SM Shefcheck, KJ Callahan, JH AF Musser, Steven M. Shefcheck, Kevin J. Callahan, John H. TI Confirmation and quantitation of peanut allergens in foods by mass spectrometry SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Musser, Steven M.] US FDA, Off Sci Anal & Support, College Pk, MD 20740 USA. [Shefcheck, Kevin J.; Callahan, John H.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 10 PY 2006 VL 232 MA 247-AGFD BP 294 EP 294 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DB UT WOS:000207781600277 ER PT J AU Trucksess, MW Weaver, CM Oles, CJ Rader, JI AF Trucksess, Mary W. Weaver, Carol M. Oles, Carolyn J. Rader, Jeanne I. TI Determination of mycotoxins in botanical roots and finished products SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Trucksess, Mary W.; Weaver, Carol M.; Oles, Carolyn J.; Rader, Jeanne I.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 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 SEP 10 PY 2006 VL 232 MA 207-AGFD BP 296 EP 296 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DB UT WOS:000207781600279 ER PT J AU Carter, L AF Carter, Lawrence, Jr. TI US FDA mycotoxin program and method of analysis SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Carter, Lawrence, Jr.] US FDA, Chem Branch Mycotoxins 2, Atlanta, GA 30309 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 10 PY 2006 VL 232 MA 181-AGFD BP 298 EP 298 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DB UT WOS:000207781600281 ER PT J AU Niemann, RA Krynitsky, AJ AF Niemann, Richard A. Krynitsky, Alexander J. TI Analytical methods for the determination of perchlorate anion in foods SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Niemann, Richard A.; Krynitsky, Alexander J.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 10 PY 2006 VL 232 MA 180-AGRO BP 553 EP 553 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DB UT WOS:000207781600496 ER PT J AU Shaikh, B Rummel, N Gieseker, C Reimschuessel, R AF Shaikh, Badar Rummel, Nathan Gieseker, Charles Reimschuessel, Renate TI Metabolism and residue depletion of 3H-ivermectin in the muscle tissue of rainbow trout after oral administration SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Shaikh, Badar; Rummel, Nathan; Gieseker, Charles; Reimschuessel, Renate] US FDA, Ctr Vet Med, Res Off, Laurel, MD 20708 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 10 PY 2006 VL 232 MA 22-AGRO BP 632 EP 632 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DB UT WOS:000207781600575 ER PT J AU Beger, R AF Beger, R. TI ANYL 195-Efficacy and toxicity biomarkers of gentamicin dosed rats and the FDA's critical path initiative SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Beger, R.] Natl Ctr Toxicol Res, Div Sytems Toxicol, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 10 PY 2006 VL 232 MA 195-ANYL PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DB UT WOS:000207781601247 ER PT J AU Brorson, K AF Brorson, Kurt TI BIOT 104-Quality by design for biotechnological products SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Brorson, Kurt] Food & Drug Adm, Div Monoclonal Antibodies, Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 10 PY 2006 VL 232 MA 104-BIOT PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DB UT WOS:000207781601791 ER PT J AU Brorson, K Lute, S Bailey, M AF Brorson, Kurt Lute, Scott Bailey, Mark TI BIOT 130-Performance of small virus filters during extensive processing SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Brorson, Kurt; Lute, Scott] US FDA, Div Monoclonal Antibodies, Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. [Bailey, Mark] Eli Lilly & Co, Indianapolis, IN 46285 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 10 PY 2006 VL 232 MA 130-BIOT PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DB UT WOS:000207781601785 ER PT J AU Churchwell, MI Yan, J Xia, QS Fu, PP Beland, FA Doerge, DR AF Churchwell, Mona I. Yan, Jian Xia, Qingsu Fu, Peter P. Beland, Frederick A. Doerge, Daniel R. TI TOXI 52-LC/MS/MS analysis of benzo[a]pyrene DNA adducts derived from diol epoxide and cation radical pathways SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Churchwell, Mona I.; Yan, Jian; Xia, Qingsu; Fu, Peter P.; Beland, Frederick A.; Doerge, Daniel R.] Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 10 PY 2006 VL 232 MA 52-TOXI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DB UT WOS:000207781609671 ER PT J AU Haffner, ME Whitley, J AF Haffner, Marlene E. Whitley, Janet TI MEDI 324-Clinical and regulatory considerations for rare disease therapy SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Haffner, Marlene E.] Off Orphan Prod Dev, Rockville, MD 20857 USA. [Whitley, Janet] Janet Whitley Food & Drug Adm, Alameda, CA 94502 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 10 PY 2006 VL 232 MA 324-MEDI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DB UT WOS:000207781607709 ER PT J AU Hanson, MA Ge, XD Shen, H Brorson, K Rao, G Moreira, AR AF Hanson, Michael A. Ge, Xudong Shen, Hong Brorson, Kurt Rao, Govind Moreira, Antonio R. TI BIOT 210-High-throughput bioreactor validation and use in mammalian cell culture process change studies SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Hanson, Michael A.; Ge, Xudong; Shen, Hong; Rao, Govind; Moreira, Antonio R.] Univ Maryland Baltimore Cty, Dept Chem & Biochem Engn, Baltimore, MD 21250 USA. [Brorson, Kurt] US FDA, Div Monoclonal Antibodies, Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 10 PY 2006 VL 232 MA 210-BIOT PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DB UT WOS:000207781601494 ER PT J AU Junod, S AF Junod, Suzanne TI HIST 28-Celebrating 100 years of food and drug regulation SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Junod, Suzanne] US FDA, PKLN RM HFC 24 1269, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 10 PY 2006 VL 232 MA 28-HIST PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DB UT WOS:000207781603756 ER PT J AU Kozlowski, S AF Kozlowski, Steven TI BIOT 171-Scientific issues in assessing the similarity of follow-on proteins SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Kozlowski, Steven] US FDA, Div Monoclonal Antibodies, Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 10 PY 2006 VL 232 MA 171-BIOT PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DB UT WOS:000207781601788 ER PT J AU Lute, S Norling, L Hanson, M Chen, Q Brorson, K AF Lute, Scott Norling, Lenore Hanson, Michael Chen, Qi Brorson, Kurt TI BIOT 298-Robustness of virus removal by Protein A chromatography is independent of media lifetime and mechanism of degradation SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Lute, Scott; Brorson, Kurt] US FDA, Div Monoclonal Antibodies, Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. [Norling, Lenore; Chen, Qi] Genentech Inc, Late Stage Purificat, San Francisco, CA 94080 USA. [Hanson, Michael] Univ Maryland Baltimore Cty, CDER, US FDA, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 10 PY 2006 VL 232 MA 298-BIOT PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DB UT WOS:000207781601787 ER PT J AU Meyers, BR AF Meyers, Beth R. TI HIST 30-Developments in cosmetics regulation: A historical overview SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Meyers, Beth R.] US FDA, Off Cosmet & Colors, College Pk, MD 20740 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 10 PY 2006 VL 232 MA 30-HIST PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DB UT WOS:000207781603757 ER PT J AU Middendorf, CT AF Middendorf, Christopher T. TI HIST 31-Science and regulation of biological products SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Middendorf, Christopher T.] US FDA, Ctr Biol Evaluat & Res, RKWL HFM 40 RM601, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 10 PY 2006 VL 232 MA 31-HIST PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DB UT WOS:000207781603760 ER PT J AU Morehouse, K McNeal, TP Nyman, PJ Perfetti, GA Diachenko, GW AF Morehouse, Kim McNeal, Timothy P. Nyman, Patricia J. Perfetti, Gracia A. Diachenko, Gregory W. TI ANYL 30-Identification and quantitation of furan in irradiated and heat processed foods by Gas Chromatography/Mass Spectrometry SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Morehouse, Kim; McNeal, Timothy P.; Nyman, Patricia J.; Perfetti, Gracia A.; Diachenko, Gregory W.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 10 PY 2006 VL 232 MA 30-ANYL PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DB UT WOS:000207781601071 ER PT J AU Muthukkumar, S AF Muthukkumar, Subramanian TI BIOT 131-Particulates in biotechnology products SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Muthukkumar, Subramanian] FDA CDER, Div Monoclonal Antibodies, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 10 PY 2006 VL 232 MA 131-BIOT PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DB UT WOS:000207781601789 ER PT J AU Noonan, GO Begley, TH Diachenko, GW Warner, CR AF Noonan, Gregory O. Begley, Timothy H. Diachenko, Gregory W. Warner, Charles R. TI ANYL 33-Semicarbazide formation in bread SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Noonan, Gregory O.; Begley, Timothy H.; Diachenko, Gregory W.; Warner, Charles R.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 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 SEP 10 PY 2006 VL 232 MA 33-ANYL PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DB UT WOS:000207781601058 ER PT J AU Nyman, PJ McNeal, TP Diachenko, GW Perfetti, GA AF Nyman, Patricia J. McNeal, Timothy P. Diachenko, Gregory W. Perfetti, Gracia A. TI ANYL 76-Determination of benzene in beverages by headspace gas-chromatography/mass spectrometry SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Nyman, Patricia J.; McNeal, Timothy P.; Diachenko, Gregory W.; Perfetti, Gracia A.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 10 PY 2006 VL 232 MA 76-ANYL PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DB UT WOS:000207781601072 ER PT J AU Nyman, PJ McNeal, TP Diachenko, GW Perfetti, GA AF Nyman, Patricia J. McNeal, Timothy P. Diachenko, Gregory W. Perfetti, Gracia A. TI ANYL 31-Benzene formation in beverages containing both benzoate salts and ascorbic or erythorbic acids SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Nyman, Patricia J.; McNeal, Timothy P.; Diachenko, Gregory W.; Perfetti, Gracia A.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 10 PY 2006 VL 232 MA 31-ANYL PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DB UT WOS:000207781601070 ER PT J AU Poole, BW Kremzner, ME AF Poole, Barrry W. Kremzner, Mary E. TI HIST 32-History of the drug approval process SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Poole, Barrry W.; Kremzner, Mary E.] US FDA, Ctr Drug Evaluat & Res, Div Drug Informat, HFD 240, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 10 PY 2006 VL 232 MA 32-HIST PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DB UT WOS:000207781603759 ER PT J AU Swann, PG AF Swann, Patrick G. TI BIOT 410-FDA's experience with recent trends and common problems in the development of therapeutic monoclonal antibodies SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Swann, Patrick G.] US FDA, Div Monoclonal Antibodies, Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 10 PY 2006 VL 232 MA 410-BIOT PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DB UT WOS:000207781601786 ER PT J AU Tareke, E Churchwell, MI McDaniel, LP Twaddle, NC Doerge, DR AF Tareke, Eden Churchwell, Mona I. McDaniel, L. Patrice Twaddle, Nathan C. Doerge, Daniel R. TI TOXI 63-Correlation between hemoglobin adducts and DNA adducts following acrylamide and glycidamide exposures in Fischer 344 rats and B6C3F1 mice SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Tareke, Eden; Churchwell, Mona I.; McDaniel, L. Patrice; Twaddle, Nathan C.; Doerge, Daniel R.] NCTR, Div Biochem Toxicol, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 10 PY 2006 VL 232 MA 63-TOXI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DB UT WOS:000207781609760 ER PT J AU Webber, K AF Webber, Keith TI BIOT 124-A regulatory paradigm to encourage innovation SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Webber, Keith] US FDA, CDER OPS, Silver Spring, MD 20903 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 10 PY 2006 VL 232 MA 124-BIOT PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V15DB UT WOS:000207781601764 ER PT J AU Wood, SC Bushar, G Tesfarnariam, B AF Wood, Steven C. Bushar, Grace Tesfarnariam, Belay TI Inhibition of mammalian target of rapamycin modulates expression of adhesion molecules in endothelial cells SO TOXICOLOGY LETTERS LA English DT Article DE rapamycin; cell adhesion molecules; endothelial cells; mTOR signaling ID MONOCYTE CHEMOATTRACTANT PROTEIN-1; MEMBRANE ATTACK COMPLEX; VASCULAR SMOOTH-MUSCLE; RAT CAROTID ARTERIES; P-SELECTIN; NEOINTIMAL FORMATION; INTIMAL HYPERPLASIA; IN-VITRO; TRANSENDOTHELIAL MIGRATION; BALLOON INJURY AB Neointimal hyperplasia often follows angioplasty-induced arterial injury or stenting and results in restenosis. Previous reports have suggested that arterial injury activates complement which amplifies inflammatory responses that may initiate and sustain neointimal hyperplasia. The effects of rapamycin on complement-induced expression of intracellular adhesion molecules (ICAMs) were examined in porcine arterial endothelial cell (PAEC) line that was transformed with large T antigen. Porcine complement was activated by treating sera with zymosan (PO ZYM) to generate C5b-9. C5b-9 binds to PAEC in a concentration- and time-dependent manner. PO ZYM-induced expression of ICAMs was maximally induced by 18 h. Rapamycin reduced the expression of vascular cell adhesion molecule (VCAM) and P-selectin in a concentration-dependent manner. Adhesion of monocytes was reduced by rapamycin and the inhibition was prevented by antibodies to vascular cell adhesion molecule, P-selectin and endothelial-leukocyte adhesion molecule (ELAM). In summary, inhibition of the mammalian target of rapamycin down regulates complement-induced ICAMs expression which may modulate inflammatory responses that follow stent implant-induced restenosis during percutanous coronary interventions. Published by Elsevier Ireland Ltd. C1 US FDA, CDRH, Off Sci & Engn Labs, Silver Spring, MD 20993 USA. Ctr Drug Evaluat & Res, Div Cardiovasc & Renal Prod, Silver Spring, MD USA. RP Wood, SC (reprint author), US FDA, CDRH, Off Sci & Engn Labs, Bldg 64,Rmn 3026,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM steven.wood@fda.hhs.gov NR 36 TC 9 Z9 10 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0378-4274 J9 TOXICOL LETT JI Toxicol. Lett. PD SEP 10 PY 2006 VL 165 IS 3 BP 242 EP 249 DI 10.1016/j.toxlet.2006.04.009 PG 8 WC Toxicology SC Toxicology GA 070BV UT WOS:000239496200005 PM 16797888 ER PT J AU Chen, L Mei, N Yao, L Chen, T AF Chen, Ling Mei, Nan Yao, Lei Chen, Tao TI Mutations induced by carcinogenic doses of aristolochic acid in kidney of Big Blue transgenic rats SO TOXICOLOGY LETTERS LA English DT Article DE aristolochic acid; mutagenicity; kidney; herb; mutational spectrum; carcinogenesis ID CHINESE HERBS NEPHROPATHY; SALMONELLA-TYPHIMURIUM; MUTAGENICITY; DEOXYADENOSINE; INDUCTION; EXPOSURE; ADDUCTS; SPECTRA; CANCER; TUMORS AB Aristolochic acid (AA) is present in at least 65 different kinds of plants, many of which are used as herbal folk remedies. AA is considered one of the most potent plant carcinogens in humans and animals. It has been associated with the development of urothelial cancers in humans, and kidney and forestomach tumors in rats. In the present study, we used the Big Blue transgenic rat model to evaluate the mutagenicity of AA in kidney of rats and to define the mechanism of action for the tumor induction by AA. Groups of six male Big Blue transgenic rats were gavaged with 0, 0. 1, 1.0 and 10.0 mg AA/kg body weight 5 times a week for 12 weeks, a treatment protocol that resulted in tumors in kidneys and other tissues. The animals were sacrificed I day after the final treatment and the kidneys were isolated for assays to determine the mutant frequencies (MFs) and types of mutations induced by AA in the transgenic cII gene. AA treatment resulted in a strong linear relationship between MF inductions and treatment dose (R-2 = 0.998). The cII MFs were 29 +/- 6 x 10(-6), 78 +/- 21 x 10(-6), 242 +/- 104 x 10(-6) and 1319 +/- 360 x 10(-6) in the control, low, medium and high dose treatment groups, respectively (p < 0.001 for all pair wise comparisons among the four treatment groups). These MFs correlated strongly with tumor incidences induced by the different doses of AA (Mengs et al., 1982). Sequence analysis of the W mutants revealed that there was a statistically significant difference between the mutational spectra in the AA-treated and control rats (p < 0.05). A:T -> T:A transversion was the predominant type of mutation in the AA-treated rats whereas G:C -> A:T transition was the main type of mutations in the control rats. These results suggest that AA induces kidney tumors in rats though a mutagenic mechanism of action. Published by Elsevier Ireland. C1 US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. Shanghai Jiao Tong Univ, Coll Life Sci & Technol, Shanghai 200030, Peoples R China. Shanghai Jiao Tong Univ, Coll Agr & Biol, Shanghai 200030, Peoples R China. RP Chen, T (reprint author), 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 30 TC 38 Z9 39 U1 1 U2 4 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0378-4274 J9 TOXICOL LETT JI Toxicol. Lett. PD SEP 10 PY 2006 VL 165 IS 3 BP 250 EP 256 DI 10.1016/j.toxlet.2006.04.008 PG 7 WC Toxicology SC Toxicology GA 070BV UT WOS:000239496200006 PM 16764999 ER PT J AU Thomas, JT Prakash, D Weih, K Moos, M AF Thomas, J. Terrig Prakash, David Weih, Karis Moos, Malcolm, Jr. TI CDMP1/GDF5 has specific processing requirements that restrict its action to joint surfaces SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID IN-SITU HYBRIDIZATION; BONE MORPHOGENETIC PROTEINS; EARLY XENOPUS DEVELOPMENT; TGF-BETA-SUPERFAMILY; BRACHYDACTYLY TYPE-C; PROHORMONE CONVERTASES; EMBRYONIC-DEVELOPMENT; CARTILAGE FORMATION; SPEMANN ORGANIZER; PRO-PROTEIN AB CDMP1/GDF5 has not demonstrated biological activity in Xenopus embryos when overexpressed by mRNA injection. We provide biological and biochemical evidence that to become active, the protein requires cleavage by two distinct proteolytic enzymes. We demonstrate a specific overlap in the expression patterns of CDMP1/GDF5 with the proteases required to release the mature peptide at the location of the future articular surface but not in the future joint space. Taken together, these observations provide a plausible mechanism for local action of CDMP1/GDF5 consistent with requirements imposed by current models of pattern formation in the developing limb. C1 US FDA, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Thomas, JT (reprint author), US FDA, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. EM john.thomas@fda.hhs.gov; malcolm.moos@fda.hhs.gov RI Moos, Malcolm/F-3673-2011 OI Moos, Malcolm/0000-0002-9575-9938 NR 48 TC 14 Z9 15 U1 0 U2 1 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 8 PY 2006 VL 281 IS 36 BP 26725 EP 26733 DI 10.1074/jbc.M603851200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 080LO UT WOS:000240249500090 PM 16829522 ER PT J AU Saylor, DM McDermott, MK Fuller, ER AF Saylor, David M. McDermott, Martin K. Fuller, Edwin R., Jr. TI Analytical model for residual stresses in polymeric containers during cryogenic storage of hematopoietic stem cells SO ACTA BIOMATERIALIA LA English DT Article DE blood bags; hematopoietic stem cells (HSC); cryogenic storage; failure model; residual stresses; thermal expansion mismatch; gas evolution ID BAGS; ICE AB Hematopoietic stem cell (HSC) therapy can significantly lower instances of infection in chemotherapy patients by accelerating the recovery of white blood cells in the body. However, therapy requires that HSCs be stored at cryogenic temperatures to retain the cells' ability to proliferate. Currently, cells are stored in polymeric blood bags that are subject to fracture at the extremely low storage temperatures, which leads to cell contamination, thereby reducing their effectiveness. Therefore, we have developed an analytical model to predict the accumulation of stresses that ultimately lead to crack initiation and bag fracture during cryogenic storage. Our model gives explicit relationships between stress state in the container and thermoelastic properties of the container material, container geometry, and environmental factors that include temperature of the system and pressure induced by excess gas evolving from the stored medium. Predictions based on the model are consistent with experimental observations of bag failures that occurred during cryogenic storage applications. Finally, the model can provide guidance in material selection and bag design to fabricate bags that will be less susceptible to fracture. (C) 2006 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved. C1 US FDA, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, Rockville, MD 20852 USA. NIST, Mat Sci & Engn Labs, Div Ceram, Gaithersburg, MD 20899 USA. RP Saylor, DM (reprint author), US FDA, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, Rockville, MD 20852 USA. EM david.saylor@fda.hhs.gov NR 16 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 1742-7061 J9 ACTA BIOMATER JI Acta Biomater. PD SEP PY 2006 VL 2 IS 5 BP 537 EP 546 DI 10.1016/j.actbio.2006.05.006 PG 10 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 080OO UT WOS:000240257600008 PM 16844438 ER PT J AU Etheridge, S Deeds, J Hall, S White, K Flewelling, L Abbott, J Landsberg, J Conrad, S Bodager, D Jackow, G AF Etheridge, S. Deeds, J. Hall, S. White, K. Flewelling, L. Abbott, J. Landsberg, J. Conrad, S. Bodager, D. Jackow, G. TI Detection methods and their limitations: PSP toxins in the southern puffer fish Sphoeroides nephelus responsible for human poisoning events in Florida in 2004 SO AFRICAN JOURNAL OF MARINE SCIENCE LA English DT Article; Proceedings Paper CT 11th International Conference on Harmful Algae CY NOV 15-19, 2004 CL Cape Town, SOUTH AFRICA DE Florida; HPLC; LCMS; paralytic shellfish poisoning; puffer fish poisoning; saxitoxin ID DINOFLAGELLATE GYMNODINIUM-CATENATUM; GONYAULAX-TAMARENSIS; SAXITOXIN AB High-performance liquid chromatography (HPLC) with post-column derivatisation and fluorescence detection has been commonly used for analysing paralytic shellfish poisoning (PSP) toxins. However, identifying peaks with confidence requires that steps be taken beyond simple chromatographic runs, owing in part to the abundance of substances in natural samples that have intrinsic fluorescence and may co-elute with toxins. The aim of this study was to assess HPLC toxin detection in samples collected from two puffer fish poisoning (PFP) events. Since 2002, PSP toxins have been detected in southern puffer fish Sphoeroides nephelus from the Titusville region of Florida. Despite a current harvesting ban on southern puffer fish in this area, PFP reports continue. Unconsumed puffer fish from two human poisoning events in 2004 were analysed by HPLC for PSP toxins. Saxitoxin was the dominant congener in unconsumed puffers. Decarbamoyl saxitoxin and B1 were also detected. These toxins were confirmed through a series of HPLC steps and subsequently by other methods. This work serves as an example of procedures necessary for HPLC toxin detection, provides a comparison of HPLC with other detection methods, and demonstrates the continued threat of PSP toxicity associated with puffer fish from the Titusville area of Florida. C1 US FDA, Laurel, MD 20708 USA. US FDA, College Pk, MD 20740 USA. Florida Fish & Wildlife Conservat Commiss, Florida Marine Res Inst, St Petersburg, FL 33701 USA. Bur Community Environm Hlth, Florida Dept Hlth, Orlando, FL 32801 USA. Brevard Cty Hlth Dept, Merritt Isl, FL 32953 USA. RP Etheridge, S (reprint author), US FDA, 8301 Muirkirk Rd, Laurel, MD 20708 USA. EM Stacey.Etheridge@fda.hhs.gov OI DeGrasse, Stacey/0000-0001-7808-4193 NR 12 TC 12 Z9 13 U1 1 U2 7 PU NATL INQUIRY SERVICES CENTRE PTY LTD PI GRAHAMSTOWN PA 19 WORCESTER STREET, PO BOX 377, GRAHAMSTOWN 6140, SOUTH AFRICA SN 1814-232X J9 AFR J MAR SCI JI Afr. J. Mar. Sci. PD SEP PY 2006 VL 28 IS 2 BP 383 EP 387 DI 10.2989/18142320609504183 PG 5 WC Marine & Freshwater Biology SC Marine & Freshwater Biology GA 091TA UT WOS:000241050000041 ER PT J AU Deeds, JR Place, AR AF Deeds, J. R. Place, A. R. TI Sterol-specific membrane interactions with the toxins from Karlodinium micrum (Dinophyceae) - a strategy for self-protection? SO AFRICAN JOURNAL OF MARINE SCIENCE LA English DT Article; Proceedings Paper CT 11th International Conference on Harmful Algae CY NOV 15-19, 2004 CL Cape Town, SOUTH AFRICA DE gymnodinosterol; karlotoxin; membrane specificity ID KARENIA-BREVIS; CHOLESTEROL; POLYENE AB The lipophilic toxins from Karlodinium micrum, KmTX, have negative effects on several co-occurring phytoplankton species, yet appear to have no effect on K. micrum itself. One of these compounds, KmTX2, has differing toxicity towards eukaryotic membranes with differing sterol compositions (vertebrate > fungal > dinoflagellate). It is shown that KmTX2 causes lysis in a co-occurring potential grazer Oxyrrhis marina while having no effect on K. micrum itself. K. micrum has a unique membrane sterol profile dominated by (24S)-4 alpha-methyl-5 alpha-ergosta-8(14),22-dien-3 beta-ol (gymnodinosterol), whereas O. marina was shown to possess 5,22-cholestadien-24 beta-methyl-3 beta-ol (brassicasterol) and 5cholesten-3 beta-ol (cholesterol) as its major membrane sterols. In accord with toxicity data from whole cells containing these sterols, free sterols were found to inhibit haemolysis in the order cholesterol > ergosterol > gymnodinosterol. It appears that certain sterols can form stable complexes with the toxin molecule, thereby sequestering it away from erythrocyte membranes. It is concluded that K. micrum protects itself from the membrane-disrupting properties of its own toxins by possessing a membrane sterol that does not interact with these compounds. C1 Univ Maryland, Ctr Marine Biotechnol, Inst Biotechnol, Baltimore, MD 21202 USA. RP Deeds, JR (reprint author), US FDA, Washington Seafood Lab, Laurel, MD 20708 USA. EM jonathan.deeds@fda.hhs.gov RI Place, Allen/F-9267-2013 NR 19 TC 44 Z9 51 U1 0 U2 3 PU NATL INQUIRY SERVICES CENTRE PTY LTD PI GRAHAMSTOWN PA 19 WORCESTER STREET, PO BOX 377, GRAHAMSTOWN 6140, SOUTH AFRICA SN 1814-232X J9 AFR J MAR SCI JI Afr. J. Mar. Sci. PD SEP PY 2006 VL 28 IS 2 BP 421 EP 425 DI 10.2989/18142320609504190 PG 5 WC Marine & Freshwater Biology SC Marine & Freshwater Biology GA 091TA UT WOS:000241050000048 ER PT J AU Oelbermann, M Voroney, RP Thevathasan, NV Gordon, AM Kass, DCL Schlonvoigt, AM AF Oelbermann, Maren Voroney, R. Paul Thevathasan, Naresh V. Gordon, Andrew M. Kass, Donald C. L. Schloenvoigt, Andrea M. TI Soil carbon dynamics and residue stabilization in a Costa Rican and southern Canadian alley cropping system SO AGROFORESTRY SYSTEMS LA English DT Article DE alley cropping; average annual accumulation rate of soil organic carbon; decomposition rate; Erythrina poeppigiana; gross soil organic carbon turnover time; hybrid poplar; residue stabilization ID AGROFORESTRY SYSTEMS; ORGANIC-MATTER; NITROGEN DYNAMICS; SEQUESTRATION; FERTILITY; INPUTS AB Agroforestry systems can play a major role in the sequestration of carbon (C) because of their higher input of organic material to the soil compared to sole crop agroecosystems. This study quantified C input in a 19-year old tropical alley cropping system with E. poeppigiana (Walp.) O.F Cook in Costa Rica and in a 13-year old hybrid poplar (Populus deltoides x nigra DN-177) alley cropping system in southern Canada. Changes in the level of the soil organic carbon (SOC) pool, residue decomposition rate, residue stabilization efficiency, and the annual rate of accumulation of SOC were also quantified in both systems. Carbon input from tree prunings in Costa Rica was 401 g C m(-2) y(-1) compared to 117 g C m(-2) y(-1) from litterfall at the Canadian site. In southern Canada, crop residue input from maize (Zea mays L.) was 212 g C m(-2) y(-1), 83 g C m(-2) y(-1) from soybeans (Glycine max L.) and 125 g C m(-2) y(-1) for wheat (Triticum aestivum L.), and was not significantly different (p < 0.05) from the sole crop. The average yearly C input from crop residues in Costa Rica was significantly greater (p < 0.05) in the alley crop for maize (134 g C m(-2) y(-1)) and Phaseolus vulgaris L. bean crops (35 g C m(-2) y(-1)) compared to the sole crop. The SOC pool was significantly greater (p < 0.05) in the Costa Rican alley crop (9536 g m(-2)) compared to its respective sole crop (6143 g m(-2)) to a 20 cm depth, but no such difference was found for the southern Canadian system. Residue stabilization, defined as the efficiency of the stabilization of added residue (crop residues, tree prunings, litterfall) that is added to the soil C pool, is more efficient in southern Canada (31%) compared to the alley cropping system in Costa Rica (40%). This coincides with a lower organic matter decomposition rate (0.03 y(-1)) to a 20 cm depth in Canada compared to the Costa Rican system (0.06 y(-1)). However, the average annual accumulation rate of SOC is greater in Costa Rica (179 g m(-2) y(-1)) and is likely related to the greater input of organic material derived from tree prunings, compared to that in southern Canada (30 g m(-2) y(-1)) to a 20 cm depth. C1 Univ Waterloo, Dept Environm & Resource Studies, Waterloo, ON N2L 3G1, Canada. Univ Guelph, Dept Land Resource Sci, Guelph, ON N1G 2W1, Canada. Univ Guelph, Dept Environm Biol, Guelph, ON N1G 2W1, Canada. US FDA, NW Reg Lab, US Dept HHS, Jamaica, NY 11433 USA. GFA Terra Syst, Latin Amer Div, D-22359 Hamburg, Germany. RP Oelbermann, M (reprint author), Univ Waterloo, Dept Environm & Resource Studies, Waterloo, ON N2L 3G1, Canada. EM moelberm@fes.uwaterloo.ca OI Oelbermann, Maren/0000-0003-0996-4140 NR 32 TC 35 Z9 39 U1 4 U2 24 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-4366 J9 AGROFOREST SYST JI Agrofor. Syst. PD SEP PY 2006 VL 68 IS 1 BP 27 EP 36 DI 10.1007/s10457-005-5963-7 PG 10 WC Agronomy; Forestry SC Agriculture; Forestry GA 085ON UT WOS:000240613500003 ER PT J AU Schech, SD Brinker, A Shatin, D Burgess, M AF Schech, Stephanie D. Brinker, Allen Shatin, Deborah Burgess, Margaret TI New-onset and idiopathic thrombotic thrombocytopenic purpura: Incidence, diagnostic validity, and potential risk factors SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article DE TTP; automated data; incidence rate; risk factors ID HEMOLYTIC UREMIC SYNDROME; PLASMA-EXCHANGE; CLOPIDOGREL AB Objective: The aim of this study was to determine the incidence rate for new-onset and idiopathic thrombotic thrombocytopenic purpura (TTP) among adults 20-64 years old, the validity of diagnostic criteria, and potential risk factors for TTP. Methods: This retrospective observational study analyzed automated administrative data from 11 geographically dispersed U.S. health plans. Cases of TTP were identified based on the presence of an inpatient hospital claim for TTP (ICD-9-CM 446.6) between 1/11/97 and 12/31/01 and confirmed by medical record review. Pharmacy and medical claims were used to evaluate outpatient drug exposure and comorbidities preceding hospitalization for TTP. Cases and the base population were screened so as to result in an incidence rate for idiopathic TTP. Results: We confirmed new-onset and idiopathic TTP in 9 of 15 presumptive cases for an incidence density of 1.4 per million person-years (95% CI: 0.6-2.6). The rate increased to 1.8 per million person-years after projection and age-standardization. The highest incidence rate of TTP was found in patients 50-64 years old (2.8 per million person-years; 95% CI: 0.8-7.1). These 9 patients had no apparent risk factors for TTP based on claims and medical record data. Conclusions: In a general U.S. population, the incidence rate of confirmed new-onset and idiopathic TTP was lower than previously reported, but appears to be on the rise. Our findings suggest that administrative claims data are useful for identifying outpatient drug exposures and comorbidities potentially associated with TTP. C1 Ctr Hlth Care Policy & Evaluat, Eden Prairie, MN 55344 USA. US FDA, Ctr Drug Evaluat & Res, Off Drug Safety, Rockville, MD 20857 USA. RP Schech, SD (reprint author), Ctr Hlth Care Policy & Evaluat, 12125 Technol Dr, Eden Prairie, MN 55344 USA. EM stephanie_d_schech@uhc.com FU FDA HHS [FD-U-002067-02, FD-U-002067-03] NR 22 TC 5 Z9 5 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD SEP PY 2006 VL 81 IS 9 BP 657 EP 663 DI 10.1002/ajh.20669 PG 7 WC Hematology SC Hematology GA 079ZO UT WOS:000240216600002 PM 16795056 ER PT J AU Ye, HP AF Ye, Hongping TI Simultaneous determination of protein aggregation, degradation, and absolute molecular weight by size exclusion chromatography-multiangle laser light scattering SO ANALYTICAL BIOCHEMISTRY LA English DT Article DE SEC-MALLS; protein aggregation; absolute molecular weight; protein degradation; pharmaceutical proteins; glycoproteins ID PERFORMANCE LIQUID-CHROMATOGRAPHY; GAS-PHASE BINDING; SHORT-TERM; TWEEN 80; STABILITY; ABSORBENCY; DETECTORS; COMPLEXES AB The feasibility of size exclusion chromotography (SEC)-multiangle laser-light scattering as a technique to investigate aggregation and degradation of glycosylated and nonglycosylated proteins, and antibodies under various conditions such as addition of detergent, changes in pH, and variation of protein concentration and heat stress temperature was examined. Separation of proteins and their aggregates was performed using SEC-high-performance liquid chromatography. Detection of analytes was carried out with on-line UV, refractive index, and multiangle laser light-scattering detectors. Quantification and molecular weight determination were performed using commercial software. Aggregation and degradation were examined under various conditions and quantitative results are presented for bovine serum albumin, choriogonadotropin, glyceraldehyde-3-phosphate dehydrogenase, Herceptin, and ReoPro. This method can simultaneously determine both the quantities and the molecular weights of macromolecules from a single injection. The determination of molecular weight is absolute which avoids misleading results caused by molecular shape or interactions with the column matrix. This technique is valuable not only for assessing the extent of aggregation but also for effectively monitoring molecule degradation as evidenced by molecular weight reduction and change in monomer amount. Published by Elsevier Inc. C1 US FDA, Div Pharmaceut Anal, St Louis, MO 63101 USA. RP Ye, HP (reprint author), US FDA, Div Pharmaceut Anal, 1114 Market St,Room 1002, St Louis, MO 63101 USA. EM yeh@cder.fda.gov NR 36 TC 58 Z9 59 U1 5 U2 47 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD SEP 1 PY 2006 VL 356 IS 1 BP 76 EP 85 DI 10.1016/j.ab.2006.05.025 PG 10 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 079JA UT WOS:000240170700010 PM 16839514 ER PT J AU Chen, E Sapirstein, W Ahn, C Swain, J Zuckerman, B AF Chen, Eric Sapirstein, Wolf Ahn, Chul Swain, Julie Zuckerman, Bram TI FDA perspective on clinical trial design for cardiovascular devices SO ANNALS OF THORACIC SURGERY LA English DT Editorial Material C1 US FDA, Ctr Devices & Radiol Hlth, Off Device Evaluat, Rockville, MD 20850 USA. RP Chen, E (reprint author), US FDA, Ctr Devices & Radiol Hlth, Off Device Evaluat, 9200 Corp Blvd,HFX 450, Rockville, MD 20850 USA. EM eric.chen@fda.hhs.gov NR 7 TC 22 Z9 22 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD SEP PY 2006 VL 82 IS 3 BP 773 EP 775 DI 10.1016/j.athoracsur.2006.07.044 PG 3 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 076ZD UT WOS:000239996300001 PM 16928481 ER PT J AU Adjei, MD Heinze, TM Deck, J Freeman, JP Williams, AJ Sutherland, JB AF Adjei, Michael D. Heinze, Thomas M. Deck, Joanna Freeman, James P. Williams, Anna J. Sutherland, John B. TI Transformation of the antibacterial agent norfloxacin by environmental mycobacteria SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID FUNGUS MUCOR-RAMANNIANUS; DEGRADING MYCOBACTERIUM; DEGRADATION; RESISTANCE; PYRENE; METABOLISM; SMEGMATIS; BACTERIA; CIPROFLOXACIN; NITROSATION AB Because fluoroquinolone antimicrobial agents may be released into the environment, the potential for environmental bacteria to biotransform these drugs was investigated. Eight Mycobacterium sp. cultures in a sorbitol-yeast extract medium were dosed with 100 mu g ml(-1) of norfloxacin and incubated for 7 days. The MICs of norfloxacin for these strains, tested by an agar dilution method, were 1.6 to 25 mu g ml(-1). Cultures were extracted with ethyl acetate, and potential metabolites in the extracts were purified by high-performance liquid chromatography. The metabolites were identified using mass spectrometry and nuclear magnetic resonance spectroscopy. N-Acetylnorfloxacin (5 to 50% of the total absorbance at 280 nm) was produced by the eight Mycobacterium strains. N-Nitrosonorfloxacin (5 to 30% of the total absorbance) was also produced by Mycobacterium sp. strain PYR100 and Mycobacterium gilvum PYR-GCK. The MICs of N-nitrosonorfloxacin and N-acetylnorfloxacin were 2- to 38- and 4- to 1,000-fold higher, respectively, than those of norfloxacin for several different bacteria, including the two strains that produced both metabolites. Although N-nitrosonorfloxacin had less antibacterial activity, nitrosamines are potentially carcinogenic. The biotransformation of fluoroquinolones by mycobacteria may serve as a resistance mechanism. C1 US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. US FDA, Div Microbiol, Jefferson, AR 72079 USA. US FDA, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Sutherland, JB (reprint author), US FDA, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM john.sutherland@fda.hhs.gov NR 41 TC 29 Z9 30 U1 4 U2 16 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 2006 VL 72 IS 9 BP 5790 EP 5793 DI 10.1128/AEM.03032-05 PG 4 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 083QT UT WOS:000240474000014 PM 16957195 ER PT J AU Marszal, E Shrake, A AF Marszal, Ewa Shrake, Andrew TI Serpin crystal structure and serpin polymer structure SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Review DE serine protease inhibitor; serpin; serpin polymer; serpin crystal structure; conformational disease ID PLASMINOGEN-ACTIVATOR INHIBITOR-1; ALPHA(1)-ANTITRYPSIN DEFICIENCY; REACTIVE-CENTER; ALPHA-1-PROTEINASE INHIBITOR; CONFORMATIONAL DISEASE; PROTEASE INHIBITOR; ANGSTROM STRUCTURE; NATIVE STRAIN; IN-VIVO; LOOP AB Serpins are a family of structurally homologous proteins having metastable native structures. As a result, a serpin variant destabilized by mutation(s) has a tendency to undergo conformational changes leading to inactive forms, e.g., the latent form and polymer. Serpin polymers are involved in a number of conformational diseases. Although several models for polymer structure have been proposed, the actual structure remains unknown. Here, we provide a comprehensive list of serpins, both free and in complexes, deposited in the Protein Data Bank. Our discussion focuses on structures that potentially can contribute to a better understanding of polymer structure. Published by Elsevier Inc. C1 US FDA, Ctr Biol Evaluat & Res, Div Hematol, Off Blood Res & Review, Bethesda, MD 20892 USA. RP Marszal, E (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Hematol, Off Blood Res & Review, Bethesda, MD 20892 USA. EM ewa.marszal@fda.hhs.gov NR 52 TC 6 Z9 6 U1 0 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD SEP 1 PY 2006 VL 453 IS 1 BP 123 EP 129 DI 10.1016/j.abb.2006.03.006 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 087CT UT WOS:000240720800016 PM 16631102 ER PT J AU Chen, HH Stark, CJ Atreya, CD AF Chen, H. H. Stark, C. J. Atreya, C. D. TI The rubella virus nonstructural protease recognizes itself via an internal sequence present upstream of the cleavage site for trans-activity SO ARCHIVES OF VIROLOGY LA English DT Article ID STRAND RNA VIRUSES; CONSERVED DOMAIN; PROTEINASES; EXPRESSION AB The substrate requirement for rubella virus protease trans-activity is unknown. Here, we analyzed the cleavability of RV P200-derived substrates varying in their N-terminal lengths (72-475 amino acids) from the cleavage site by the RV protease trans-activity. Only substrates with at least 309 amino acid residues N-terminal to the cleavage site were able to undergo cleavage. Further, rubella sequence was found to be necessary in the N-terminal region of the substrate, whereas a heterologous sequence C-terminal to the cleavage site was tolerated. These results demonstrated a requirement for residues located between amino acids 994-1102 of the RV P200 polyprotein, besides its cleavage site for RV protease trans-activity. This region overlaps with the starting site of the essential cis-protease activity of RV P200 polyprotein. This is a novel observation for a viral protease of the family Togaviridae. C1 US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Bethesda, MD 20892 USA. RP Atreya, CD (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, HFM-460,Bldg 29A,2C-11 NIH Campus,8800 Rockville, Bethesda, MD 20892 USA. EM ATREYA@CBER.FDA.GOV NR 18 TC 4 Z9 4 U1 0 U2 0 PU SPRINGER WIEN PI WIEN PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 WIEN, AUSTRIA SN 0304-8608 J9 ARCH VIROL JI Arch. Virol. PD SEP PY 2006 VL 151 IS 9 BP 1841 EP 1851 DI 10.1007/s00705-006-0744-9 PG 11 WC Virology SC Virology GA 073EE UT WOS:000239725000012 PM 16570206 ER PT J AU Curtis, JR Martin, C Saag, KG Kramer, J Patkar, N Shatin, D Burgess, M Xie, A Allison, JJ Braun, MM AF Curtis, Jeffrey R. Martin, Carolyn Saag, Kenneth G. Kramer, Judith Patkar, Nivedita Shatin, Deborah Burgess, Margareth Xie, Aiyuan Allison, Jeroan J. Braun, M. Miles TI Risk of heart failure among younger adults exposed to infliximab and etanercept. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the American-College-of-Rheumatology/41st Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 10-15, 2006 CL Washington, DC SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Univ Alabama, Birmingham, AL USA. Ctr Healthcare Policy & Evaluat, Eden Prairie, MN USA. Duke Univ, Med Ctr, Durham, NC USA. US FDA, Rockville, MD 20857 USA. NR 0 TC 1 Z9 1 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 SEP PY 2006 VL 54 IS 9 SU S BP S372 EP S372 PG 1 WC Rheumatology SC Rheumatology GA 089JR UT WOS:000240877201411 ER PT J AU Lories, RJ Derese, I Tylzanowski, P Thomas, JT Luyten, FP AF Lories, Rik J. Derese, Inge Tylzanowski, Przemko Thomas, J. Terrig Luyten, Frank P. TI Articular chondrocytes express FRZB as a chondroprotective mechanism in a mouse model of inflammation-driven joint destruction. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the American-College-of-Rheumatology/41st Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 10-15, 2006 CL Washington, DC SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Katholieke Univ Leuven, Louvain, Belgium. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. RI Tylzanowski, Przemko/G-8881-2013 NR 0 TC 0 Z9 0 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 SEP PY 2006 VL 54 IS 9 SU S BP S317 EP S317 PG 1 WC Rheumatology SC Rheumatology GA 089JR UT WOS:000240877201267 ER PT J AU Tunyogi-Csapo, M Koreny, T Polgar, A Jacobs, JJ Nyarady, J Glant, TT AF Tunyogi-Csapo, Miklos Koreny, Tamas Polgar, Anna Jacobs, Joshua J. Nyarady, Jozsef Glant, Tibor T. TI Synovial fibroblast as a potential regulator of bone resorption in arthritic joint. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the American-College-of-Rheumatology/41st Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 10-15, 2006 CL Washington, DC SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Katholieke Univ Leuven, Louvain, Belgium. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. NR 0 TC 0 Z9 0 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-US JI Arthritis Rheum. PD SEP PY 2006 VL 54 IS 9 SU S BP S569 EP S569 PG 1 WC Rheumatology SC Rheumatology GA 089JR UT WOS:000240877203099 ER PT J AU Thorpe, SJ Fox, B Heath, A Behr-Gross, ME Virata, ML Yu, MYW AF Thorpe, Susan J. Fox, Bernard Heath, Alan Behr-Gross, Marie-Emmanuelle Virata, Maria L. Yu, Mei-Ying W. TI International collaborative study to assess candidate reference preparations to control the level of anti-D in IVIG for use in Europe and the United States SO BIOLOGICALS LA English DT Article DE anti-Rho; IGIV; haemolysis; haemagglutination; specification; reference preparations AB Regulatory requirements to control the level of anti-D in intravenous immunoglobulin (IVIG) products with European and United States (US) licences are t sigma be introduced. A reference preparation of IVIG containing anti-D at 0.0475 IU/ml and having a nominal titre of 8 using the proposed direct haemagglutination reference method was deemed suitable to define the anti-D limit. This preparation, code 02/228, and a negative control IVIG preparation, code 02/226, were established by the World Health Organization as International Reference Reagents (IRRs). As stocks of the IRRs are limited, new larger fill stocks of positive and negative reference preparations, codes 04/132 and 04/140, respectively, were produced. The results from an international collaborative study involving 16 laboratories showed that preparations 04/132 and 04/140 are indistinguishable from the corresponding IRRs 02/228 and 02/226, respectively, using the proposed direct haemagglutination reference method. Stocks of 041132 and 04/140 have been shared with the European Directorate for the Quality of Medicines (re-coded as 23613 and 23614, respectively) and with the Center for Biologics Evaluation and Research of the United States Food and Drug Administration (re-coded as CBER Lots 1B and 1N-b, respectively) for use as European and US Biological Reference Preparations, respectively. (c) 2005 The International Association for Biologicals. Published by Elsevier Ltd. All rights reserved. C1 Natl Inst Biol Stand & Controls, Potters Bar EN6 3QG, Herts, England. European Directorate Qual Med, Strasbourg, France. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. RP Thorpe, SJ (reprint author), Natl Inst Biol Stand & Controls, Blanche Lane S Mimms, Potters Bar EN6 3QG, Herts, England. EM sthorpe@nibsc.ac.uk RI Thorpe, Susan/E-1808-2013 NR 5 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 1045-1056 J9 BIOLOGICALS JI Biologicals PD SEP PY 2006 VL 34 IS 3 BP 209 EP 212 DI 10.1016/j.biologicals.2006.11.001 PG 4 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA 080FN UT WOS:000240233400006 PM 16492398 ER PT J AU Wood, CE Appt, SE Clarkson, TB Franke, AA Lees, CJ Doerge, DR Cline, JM AF Wood, Charles E. Appt, Susan E. Clarkson, Thomas B. Franke, Adrian A. Lees, Cynthia J. Doerge, Daniel R. Cline, J. Mark TI Effects of high-dose soy lsoflavones and equol on reproductive tissues in female cynomolgus monkeys SO BIOLOGY OF REPRODUCTION LA English DT Article DE estradiol; estrogen receptor; female reproductive tract; mammary glands; uterus ID CONJUGATED EQUINE ESTROGENS; SPRAGUE-DAWLEY RATS; BREAST-CANCER CELLS; POSTMENOPAUSAL WOMEN; PHYSIOLOGICAL CONCENTRATIONS; ENDOMETRIAL CANCER; URINARY-EXCRETION; METABOLITE EQUOL; PROTEIN ISOLATE; RECEPTOR-BETA AB Soy isoflavonoids have well-established estrogenic properties in cell culture and rodent models, raising concerns that high isoflavonoid intake may promote development of uterine and breast cancers. To address this concern we evaluated the effects of high-dose isoflavonoid supplements on reproductive tissues in a postmenopausal primate model. Thirty adult female ovariectomized monkeys (Macaca fascicularis) were randomized to receive a control diet 1) alone, 2) with 509 mg/day of the soy isoflavones genistein and daidzein (IF), or 3) with 1020 mg/day of racemic equol (EQ), an isoflavan, for approximately 1 mo. Doses are expressed in aglycone units as calorically scaled human equivalents. Total serum isoflavonoid levels 4 h postfeeding were < 20 nmol/L, 2570.7 nmol/L, and 6944.8 nmol/L for control, IF, and EQ groups, respectively. Equol was the predominant serum isoflavonoid in both IF (72.5%) and EQ (99.7%) groups. Aglycones represented 0.9% (IF) and 0.5% (EQ) of total serum isoflavonoids. Histologically, uteri and mammary glands were diffusely atrophic in all groups. Uterine weight, endometrial thickness, glandular area, and epithelial proliferation in the uterus were not significantly different among treatment groups (ANOVA P > 0.1 for all). Endometrial progesterone receptor gene expression was significantly increased in the IF group (P = 0.02), while protein expression was not altered (ANOVA P > 0.1). Within the mammary gland, proliferation and indicators of estrogen exposure did not differ among treatment groups (ANOVA P > 0.1 for all). These findings indicate that high doses of dietary soy isoflavonoids have minimal uterotrophic or mammotrophic effects in an established primate model. C1 Wake Forest Univ, Sch Med, Dept Pathol, Sect Comparat Med, Winston Salem, NC 27157 USA. Canc Res Ctr Hawaii, Honolulu, HI 96813 USA. US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Wood, CE (reprint author), Wake Forest Univ, Sch Med, Dept Pathol, Sect Comparat Med, Med Ctr Blvd, Winston Salem, NC 27157 USA. EM chwood@wfubmc.edu FU NCCIH NIH HHS [R01-AT00639]; NCI NIH HHS [P30-CA71789]; NCRR NIH HHS [T32 RR 07009] NR 62 TC 33 Z9 33 U1 2 U2 3 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PD SEP PY 2006 VL 75 IS 3 BP 477 EP 486 DI 10.1095/biolreprod.106.052142 PG 10 WC Reproductive Biology SC Reproductive Biology GA 075VE UT WOS:000239912800020 PM 16723506 ER PT J AU Simmons, J Bernstein, D AF Simmons, John Bernstein, David TI Navigating differences between FDA and EMEA for regulatory compliance during drug development SO BIOPHARM INTERNATIONAL LA English DT Article AB A comparison of regulations and initiatives on both sides of the Atlantic reveals differences that international companies need to understand. C1 Simmons FDA CMC Consulting LLC, Chapin, SC 29036 USA. US FDA, Off New Drug Chem, OPS, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Simmons, J (reprint author), Simmons FDA CMC Consulting LLC, 323 Night Harbor Dr, Chapin, SC 29036 USA. EM Simmonsfdacmc@aol.com; david@bernsteincmc.com NR 11 TC 0 Z9 0 U1 0 U2 0 PU ADVANSTAR COMMUNICATIONS PI DULUTH PA 131 W FIRST ST, DULUTH, MN 55802 USA SN 1542-166X J9 BIOPHARM INT JI Biopharm. Int. PD SEP PY 2006 SU S BP 16 EP + PG 6 WC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA 090NO UT WOS:000240958200002 ER PT J AU Lott, JP Katz, KA AF Lott, J. P. Katz, K. A. TI Pharmaceutical companies' policies and practices regarding prospective registration of dermatology-related clinical trials SO BRITISH JOURNAL OF DERMATOLOGY LA English DT Letter ID MEDICAL-JOURNAL-EDITORS; INTERNATIONAL-COMMITTEE; STATEMENT C1 Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Dermatol, Philadelphia, PA 19104 USA. RP Katz, KA (reprint author), US FDA, CDER, OND, OPE3,DDDP, W022,RM5187,10903 New Hampshire Ave, Silver Spring, MD 20903 USA. EM kenneth.katz@post.harvard.edu NR 10 TC 2 Z9 2 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0007-0963 J9 BRIT J DERMATOL JI Br. J. Dermatol. PD SEP PY 2006 VL 155 IS 3 BP 635 EP 638 DI 10.1111/j.1365-2133.2006.07386.x PG 5 WC Dermatology SC Dermatology GA 072SQ UT WOS:000239693700029 PM 16911301 ER PT J AU Campbell, MJ Esserman, LJ Zhou, Y Shoemaker, M Lobo, M Borman, E Baehner, F Kumar, AS Adduci, K Marx, C Petricoin, EF Liotta, LA Winters, M Benz, S Benz, CC AF Campbell, Michael J. Esserman, Laura J. Zhou, Yamei Shoemaker, Mark Lobo, Margaret Borman, Elizabeth Baehner, Frederick Kumar, Anjali S. Adduci, Kelly Marx, Corina Petricoin, Emanuel F. Liotta, Lance A. Winters, Mary Benz, Stephen Benz, Christopher C. TI Breast cancer growth prevention by statins SO CANCER RESEARCH LA English DT Article ID NF-KAPPA-B; HMG-COA REDUCTASE; RISK; ACTIVATION; INHIBITORS; ISOPRENOIDS; PRAVASTATIN; SIMVASTATIN; EXPRESSION; MUTATIONS AB Statins are cholesterol-lowering drugs with pleiotropic activities including inhibition of isoprenylation reactions and reduction of signals driving cell proliferation and survival responses. The objectives of this study were to examine the effects of statins on breast cancer cells, both in vitro and in vivo, and to begin to determine their mechanism of action. We evaluated the effects of statins on breast cancer cell growth, phosphoprotein signaling intermediates, survival/apoptosis regulators, cell cycle regulators, and activated transcription factors. We also examined the in vivo effect of statin administration in a mouse ErbB(2+) breast cancer model. Only lipophilic statins had direct anticancer activity in vitro. Breast cancer cells with activated Ras or ErbB2 pathways seemed to be more sensitive than those overexpressing estrogen receptor, and this correlated with endogenous levels of activated nuclear factor kappa B (NF-kappa B). Key intermediates regulating cell survival by NF-kappa B activation, as well as cell proliferation by the mitogen activated protein kinase cascade, were among the earliest phosphoproteins influenced by statin treatment. These early effects were followed by declines in activator protein-1 and NF-kappa B activation and concordant changes in other mediators of proliferation and apoptosis. In vivo results showed that oral dosing of statins significantly inhibited the growth of a mouse mammary carcinoma. Lipophilic statins can exert direct anticancer activity in vitro by reducing proliferation and survival signals in susceptible breast cancer phenotypes. Tumor growth inhibition in vivo using a clinically relevant statin dose also seems to be associated with reduced tumor cell proliferation and survival. These findings provide supporting rationale for future statin trials in breast cancer patients. C1 Univ Calif San Francisco, Dept Surg, Mt Zion Med Ctr, Ctr Comprehens Canc, San Francisco, CA 94115 USA. US FDA, Clin Proteom Program, NCI, Bethesda, MD 20014 USA. Buck Inst Age Res, Novato, CA USA. Wheaton Coll, Norton, MA 02766 USA. RP Campbell, MJ (reprint author), Univ Calif San Francisco, Dept Surg, Mt Zion Med Ctr, Ctr Comprehens Canc, Room C342,1600 Divisadero, San Francisco, CA 94115 USA. EM campbellm@surgery.ucsf.edu OI Benz, Stephen/0000-0002-4067-0602 FU NCI NIH HHS [P50-CA58207, R01-CA36773, R01-CA71468]; NIA NIH HHS [R01-AG020521] NR 46 TC 162 Z9 169 U1 2 U2 13 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 1 PY 2006 VL 66 IS 17 BP 8707 EP 8714 DI 10.1158/0008-5472.CAN-05-4061 PG 8 WC Oncology SC Oncology GA 081PL UT WOS:000240329400051 PM 16951186 ER PT J AU Herman, E Zhang, J Knapton, A Lipshultz, SE Rifai, N Sistare, F AF Herman, Eugene Zhang, Jun Knapton, Alan Lipshultz, Steven E. Rifai, Nader Sistare, Frank TI Serum cardiac troponin T as a biomarker for acute myocardial injury induced by low doses of isoproterenol in rats SO CARDIOVASCULAR TOXICOLOGY LA English DT Article AB In rats, high doses of isoproterenol ( Iso) have caused acute myocardial lesions and increased serum levels of cardiac troponin T ( cTnT). We determined whether low doses of Iso also cause cardiac alterations and whether monitoring cTnT levels could detect this injury. Rats received 8 to 500 mu g/kg Iso and were followed for 3 to 48 h. Lesion severity was scored from 0 to 5. Within 3 h, mean cTnT was elevated in all 29 rats receiving 8, 16, 32, or 64 mu g/kg Iso ( 0.20 to 0.28 ng/ mL), but minimal lesions occurred in only two animals. However, by 6 h, cardiac lesions and increases in serum cTnT ( mean = 0.21 to 0.23 ng/ mL) were observed in all 14 rats receiving 32 or 64 mu g/kg Iso. Doses of 125, 250, or 500 mu g/kg Iso caused more significant increases in cTnT levels and marked myocardial lesions that reached a peak 3 to 6 h after dosing. The magnitude of the lesions and cTnT levels declined between 12 and 48 h post treatment. Thus, a range of low Iso doses can cause myocardial lesions, and serum cTnT levels can be monitored to detect the onset and progression of this type of acute cardiac injury in rats; however, careful attention to dosing and sampling times is critical to interpretation. C1 [Herman, Eugene; Zhang, Jun; Knapton, Alan; Sistare, Frank] US FDA, Div Appl Pharmacol Res, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Lipshultz, Steven E.] Univ Miami, Miller Sch Med, Dept Pediat, Miami, FL 33136 USA. [Rifai, Nader] Harvard Univ, Childrens Hosp, Sch Med, Boston, MA 02115 USA. RP Herman, E (reprint author), US FDA, Div Appl Pharmacol Res HFD 910, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM eugene.herman@fda.hhs.gov NR 17 TC 11 Z9 12 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1530-7905 J9 CARDIOVASC TOXICOL JI Cardiovasc. Toxicol. PD SEP PY 2006 VL 6 IS 3-4 BP 211 EP 221 DI 10.1385/CT:6:3:211 PG 11 WC Cardiac & Cardiovascular Systems; Toxicology SC Cardiovascular System & Cardiology; Toxicology GA V44NS UT WOS:000203010000005 PM 17347531 ER PT J AU Seymour, SM Sullivan, EJ Chowdhury, BA Meyer, RJ Davi, RC AF Seymour, Sally M. Sullivan, Eugene J. Chowdhury, Badrul A. Meyer, Robert J. Davi, Ruthanna C. TI Comments on the Salmeterol Multicenter Asthma Research Trial SO CHEST LA English DT Letter C1 US FDA, Silver Spring, MD USA. RP Seymour, SM (reprint author), US FDA, Silver Spring, MD USA. EM sally.seymour@fda.hhs.gov NR 4 TC 1 Z9 1 U1 0 U2 1 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD SEP PY 2006 VL 130 IS 3 BP 930 EP 931 DI 10.1378/chest.130.3.930a PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 085EG UT WOS:000240585600056 PM 16963702 ER PT J AU Evans, JR Short, BL Van Meurs, K Sachs, HC AF Evans, Jacquelyn R. Short, Billie Lou Van Meurs, Krisa Sachs, Hari Cheryl TI Cardiovascular support in preterm infants SO CLINICAL THERAPEUTICS LA English DT Article; Proceedings Paper CT Newborn Drug Development Initiative Workshop CY MAR 29-30, 2004 CL Baltimore, MD SP NICHD, FDA DE infant-newborn; inotrope; hemodynamic instability; hypotension; shock; neonatal intensive care unit ID BIRTH-WEIGHT INFANTS; ARTERIAL-BLOOD-PRESSURE; CHRONIC LUNG-DISEASE; RESPIRATORY-DISTRESS SYNDROME; VENA-CAVA FLOW; INTRAVENTRICULAR HEMORRHAGE; PREMATURE-INFANTS; NEWBORN-INFANTS; MECHANICAL VENTILATION; RANDOMIZED TRIAL AB Background: Despite increasing investigation in the area of cardiovascular instability in preterm infants, huge gaps in knowledge remain. None of the current treatments for hypotension, including the use of inotropic agents, have been well studied in the preterm population, and data regarding safety and efficacy are lacking. Thus, the labeling information regarding the use of inotropes as therapeutic agents in this population is inadequate. Objective: This article reviews the current deficiencies in knowledge with respect to measuring and achieving normal organ perfusion; summarizes the clinical, methodological, and ethical issues to consider when designing trials to evaluate medications for hemodynamic instability in the preterm neonate; and proposes 2 possible trial designs. Unanswered questions and potential obstacles for the systematic study of drugs to treat cardiovascular instability in preterm neonates are discussed. Methods: The neonatal Cardiology Group was established in 2003 by the US Food and Drug Administration (FDA) and the National Institute of Child Health and Human Development (NICHD) as part of the Newborn Drug Development Initiative. The Cardiology Group conducted a number of teleconferences and one meeting to develop a document addressing gaps in knowledge regarding cardiovascular drugs commonly used in low-birth-weight neonates and possible approaches to investigate these drugs. This work was presented at a workshop cosponsored by the NICHD and the FDA held in March 2004 in Baltimore, Maryland. Information for this article was gathered during this initiative. Results: To develop rational, evidence-based guidelines corroborated by robust scientific data for cardiovascular support in newborns, well-designed and adequately powered pharmacologic studies and clinical trials are needed to evaluate the safety and efficacy of inotropic agents and to determine the short- and longterm effects of these drugs. Trials investigating the currently available and novel therapies for cardiovascular instability in neonates will provide information that can be incorporated in I to product labeling and a scientific framework for cardiovascular management in critically ill neonates. The Cardiology Group identified and prioritized 2 conditions for investigation of therapeutic options for the management of neonatal cardiovascular instability (1) cardiovascular instability in preterm neonates; and (2) cardiac dysfunction in neonates after cardiopulmonary bypass surgery. Key research questions in the area of cardiovascular instability in the preterm infant include determining optimal blood pressure (BP) in preterm infants; identifying better measures than BP to determine organ perfusion; optimizing hemodynamic treatments; and clarifying any associations between BP or therapy for low BP and mortality, intraventricular hemorrhage, periventricular leukomalacia, necrotizing enterocolitis, retinopathy of prematurity, and neurodevelopmental outcome. The Cardiology Group concluded that the study of inotropic agents in neonates using outcomes of importance to patients will require a complicated trial design to address the elements discussed. The group proposed 2 clinical trial designs: (1) a placebo-controlled trial with rescue therapy for symptomatic infants; and (2) a targeted BP trial. Conclusion: This summary is intended to stimulate and assist future research in the area of cardiovascular support for preterm infants. (Clin Ther. 2006;28: 1366-1384) Copyright (c) 2006 Excerpta Medica, Inc. C1 Childrens Hosp Philadelphia, Div Neonatol, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Childrens Natl Med Ctr, Div Neonatol, Washington, DC 20010 USA. George Washington Univ, Sch Med, Washington, DC USA. Stanford Univ, Sch Med, Div Neonatal & Dev Med, Palo Alto, CA 94304 USA. US FDA, Off Counter Terrorism & Pediat Drug Dev, Rockville, MD 20857 USA. RP Evans, JR (reprint author), Childrens Hosp Philadelphia, Div Neonatol, Room 2439,Childrens Hosp Philadelphia Main Bldg, Philadelphia, PA 19104 USA. EM evans@email.chop.edu NR 75 TC 21 Z9 25 U1 0 U2 0 PU ELSEVIER PI BRIDGEWATER PA 685 ROUTE 202-206, BRIDGEWATER, NJ 08807 USA SN 0149-2918 J9 CLIN THER JI Clin. Ther. PD SEP PY 2006 VL 28 IS 9 BP 1366 EP 1384 DI 10.1016/j.clinthera.2006.09.006 PG 19 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 100RF UT WOS:000241685600012 PM 17062310 ER PT J AU Ward, RM Benitz, WE Benjamin, DK Blackmon, L Giacoia, GP Hudak, M Lasky, T Rodriguez, W Selen, A AF Ward, Robert M. Benitz, William E. Benjamin, Daniel K., Jr. Blackmon, Lillian Giacoia, George P. Hudak, Mark Lasky, Tamar Rodriguez, William Selen, Arzu TI Criteria supporting the study of drugs in the newborn SO CLINICAL THERAPEUTICS LA English DT Article; Proceedings Paper CT Newborn Drug Development Initiative Workshop CY MAR 29-30, 2004 CL Baltimore, MD SP NICHD, FDA DE newborns; drugs prioritization; neonatal therapeutics; pediatric study ID RESPIRATORY-DISTRESS-SYNDROME; BIRTH-WEIGHT INFANTS; HYPERTROPHIC PYLORIC-STENOSIS; NUTRITION-ASSOCIATED CHOLESTASIS; MECONIUM ASPIRATION SYNDROME; PREMATURE-INFANTS; RANDOMIZED-TRIAL; NEONATAL HYPERBILIRUBINEMIA; SYNTHETIC SURFACTANT; PORACTANT ALPHA AB Background: Profound changes in the development and the maturation of neonates' organs and organ systems over variable periods of time potentially place neonates at increased risk and/or at different risks compared with adults or older children on exposure to pharmaceutical agents. Most studies of drugs in neonates focus on pharmacokinetic and pharmacodynamic end points and include insufficient numbers of patients to permit evaluation of safety. Only one fourth to one third of approved drugs have received adequate pediatric study to permit labeling for treatment of all appropriate pediatric populations. Objective: The initial goal of the Newborn Drug Prioritization Group was to develop a reproducible, objective process for evaluating drugs most in need of study in the neonatal population based on a universally acceptable priority ranking. The criteria would be applicable across therapeutic classes and would identify those drugs for which immediate study was most needed. Methods: Because the therapeutic requirements of the neonate are unique in comparison to older infants and children, the National Institute of Child Health and Human Development and the US Food and Drug Administration (FDA) developed the Newborn Drug Development Initiative to address the limited study of off-patent drugs in newborns. In March 2003, they convened a meeting of pediatric pharmacologists and pediatric specialists from the FDA, the American Academy of Pediatrics, the National Institutes of Health, and academic institutions to discuss how to increase the study of drugs for the newborn. One of the working groups was charged to develop generic criteria for overall prioritization of drugs for study in newborns. Because resources are limited, and not all drugs identified by the 4 clinically focused working groups can receive study at the same time, a process for priority ranking is necessary. Results: The panel identified 4 general categories containing different numbers of criteria as important for ranking drugs for priority investigation: (1) the disease and indication, including elements such as the potential for adverse outcomes, frequency in newborns, and level of evidence for treatment of newborns; (2) drug characteristics, including elements such as duration of dosing, lack of age-appropriate formulation, clinically relevant drug-drug and drug-disease interactions, and drug disposition in newborns; (3) feasibility and methodology for newborn studies, including both analytical considerations and clinical end points; and (4) the ethical basis for study, including elements to address benefit or harm due to exposure to the study drug, study methodology, and benefit of the new treatment relative to established standard therapy. Based on these categories, a list of criteria to warrant study of a drug in newborns was developed. Conclusion: A process for judicious use of limited resources to rectify these deficiencies remains an urgent public health need. (Clin Ther. 2006;28:13851398) Copyright (c) 2006 Excerpta Medica, Inc. C1 Univ Utah, Pediat Pharmacol Program, Salt Lake City, UT 84108 USA. Univ Utah, Dept Pediat, Salt Lake City, UT 84108 USA. Stanford Univ, Sch Med, Dept Pediat, Palo Alto, CA 94304 USA. Lucile Packard Childrens Hosp, Palo Alto, CA USA. Duke Univ, Dept Pediat, Durham, NC 27706 USA. Duke Clin Res Inst, Durham, NC 27706 USA. Univ Maryland, Sch Med, Dept Pediat, Baltimore, MD 21201 USA. NICHHD, Pediat Pharmacol Res Unit Network, NIH, Bethesda, MD 20892 USA. Univ Florida, Dept Pediat, Jacksonville, FL USA. NICHHD, NIH, Bethesda, MD 20892 USA. US FDA, Off New Drugs, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. US FDA, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Ward, RM (reprint author), Univ Utah, Pediat Pharmacol Program, 417 Wakara Way,Suite 3510, Salt Lake City, UT 84108 USA. EM robert.ward@hsc.utah.edu FU NCRR NIH HHS [5 M01 RR000070-43]; NICHD NIH HHS [1U10-HD45962-02, 1 U10 HD45986-01, HD-044799-01, 5 U10 HD027880-15] NR 75 TC 21 Z9 21 U1 0 U2 0 PU ELSEVIER PI BRIDGEWATER PA 685 ROUTE 202-206, BRIDGEWATER, NJ 08807 USA SN 0149-2918 J9 CLIN THER JI Clin. Ther. PD SEP PY 2006 VL 28 IS 9 BP 1385 EP 1398 DI 10.1016/j.clinthera.2006.09.007 PG 14 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 100RF UT WOS:000241685600013 PM 17062311 ER PT J AU Lathers, CM Schraeder, PL AF Lathers, Claire M. Schraeder, Paul L. TI Stress and sudden death SO EPILEPSY & BEHAVIOR LA English DT Review DE sudden death; sudden unexpected death in epilepsy; epilepsy; cardiac disease; psychiatric disorders; stress; depression ID CORONARY-ARTERY-DISEASE; CARDIAC NEURAL DISCHARGE; UNEXPLAINED DEATH; UNEXPECTED DEATH; EPILEPTOGENIC ACTIVITY; MYOCARDIAL-ISCHEMIA; NERVOUS-SYSTEM; MENTAL STRESS; EPILEPSY; DEPRESSION AB Cardiac patients, psychiatric patients, and certain ethnic groups experiencing acute stressful circumstances are at risk for unexpected sudden death. Although stress is associated with changes in autonomic neural function, its role as a potential risk factor for sudden unexpected death in epilepsy (SUDEP) is not known. The association of epilepsy with cardiac abnormalities, such as neurogenic arrhythmias and microscopic perivascular and interstitial fibrosis, and with depression and anxiety indicates that emotional stress should be evaluated as a potential risk factor for SUDEP. The impact of adverse emotional states on the autonomic control of cardiac rhythm is a known important factor leading to cardiac dysrhythmias in humans and other species. The interaction between emotional factors and the arrythmogenic potential of epileptiform discharges and the possibility of benefit from stress management intervention need to be investigated. (C) 2006 Elsevier Inc. All rights reserved. C1 US FDA, Off Director, Ctr Vet Med, Rockville, MD 20855 USA. Drexel Univ, Coll Med, Dept Neurol, Philadelphia, PA 19102 USA. RP Lathers, CM (reprint author), 115 S Manning Blvd, Albany, NY 12203 USA. EM lathers@attglobal.net NR 72 TC 20 Z9 21 U1 1 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1525-5050 J9 EPILEPSY BEHAV JI Epilepsy Behav. PD SEP PY 2006 VL 9 IS 2 BP 236 EP 242 DI 10.1016/j.yebeh.2006.06.001 PG 7 WC Behavioral Sciences; Clinical Neurology; Psychiatry SC Behavioral Sciences; Neurosciences & Neurology; Psychiatry GA 085SO UT WOS:000240624900002 PM 16872908 ER PT J AU Dhawan, S AF Dhawan, Subhash TI Signal amplification systems in immunoassays: implications for clinical diagnostics SO EXPERT REVIEW OF MOLECULAR DIAGNOSTICS LA English DT Review DE diagnostic tests; immunoassays; signal amplification ID CATALYZED REPORTER DEPOSITION; HIGH-SENSITIVITY DETECTION; LYSINE PEPTIDE CHAINS; HORSERADISH-PEROXIDASE; GOLD NANOPARTICLE; QUANTUM DOTS; PROTEIN MICROARRAY; DNA HYBRIDIZATION; PCR; ELISA AB Biomarkers in physiological specimens serve as useful sensors for clinical diagnosis. Accurate detection of specific markers is crucial for the diagnosis of disease, monitoring drug therapy and patient screening. In vitro immunoassays are probably the most common, simple and relatively inexpensive serological tools used in clinical laboratories for the diagnosis and management of disease. Despite continued efforts to improve the performance of immunoassays in the past three decades, there is a need for highly sensitive assays that can detect the lowest levels of disease markers with greater accuracy. This review summarizes recent advances made towards increasing the sensitivity of immunoassays by amplifying detection signals, with implications for the development of highly sensitive diagnostic systems; it also discusses the principles of related methodologies. C1 Ctr Biol Evaluat & Res, Immunopathogenesis Sect, Mol Virol Lab, Div Emerging & Transfus Transmitted Dis, Rockville, MD 20852 USA. RP Dhawan, S (reprint author), Ctr Biol Evaluat & Res, Immunopathogenesis Sect, Mol Virol Lab, Div Emerging & Transfus Transmitted Dis, 1401 Rockville Pike, Rockville, MD 20852 USA. EM subhash.dhawan@fda.hhs.gov NR 65 TC 11 Z9 11 U1 9 U2 26 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1473-7159 J9 EXPERT REV MOL DIAGN JI Expert Rev. Mol. Diagn. PD SEP PY 2006 VL 6 IS 5 BP 749 EP 760 DI 10.1586/14737159.6.5.749 PG 12 WC Pathology SC Pathology GA 093AA UT WOS:000241138300008 PM 17009908 ER PT J AU Holler, T Sivinski, J Jenkins, C Fraser, S AF Holler, Timothy Sivinski, John Jenkins, Came Fraser, Suzanne TI A comparison of yeast hydrolysate and synthetic food attractants for capture of Anastrepha suspensa (Diptera : Tephritidae) SO FLORIDA ENTOMOLOGIST LA English DT Editorial Material ID FRUIT-FLIES DIPTERA; TRAP C1 USDA, APHIS, PPQ, CPHST, Gainesville, FL 32608 USA. Univ Florida, USDA ARS, CMAVE, Gainesville, FL 32608 USA. FDACS, DPI, Caribbean Fruit Fly Certificat Program, Ft Pierce, FL 34982 USA. FDACS, DPI, Biol Control Rearing Facil, Gainesville, FL 32608 USA. RP Holler, T (reprint author), USDA, APHIS, PPQ, CPHST, 1600-1700 SW 23rd Dr, Gainesville, FL 32608 USA. NR 10 TC 7 Z9 8 U1 0 U2 2 PU FLORIDA ENTOMOLOGICAL SOC PI LUTZ PA 16125 E LAKE BURRELL DR, LUTZ, FL 33548 USA SN 0015-4040 J9 FLA ENTOMOL JI Fla. Entomol. PD SEP PY 2006 VL 89 IS 3 BP 419 EP 420 DI 10.1653/0015-4040(2006)89[419:ACOYHA]2.0.CO;2 PG 2 WC Entomology SC Entomology GA 084IP UT WOS:000240526900025 ER PT J AU Collins, TFX Sprando, RL Black, TN Olejnik, N Eppley, RM Alam, HZ Rorie, J Ruggles, DI AF Collins, Thomas F. X. Sprando, Robert L. Black, Thomas N. Olejnik, Nicholas Eppley, Robert M. Alam, Hamida Z. Rorie, James Ruggles, Dennis I. TI Effects of zearalenone on in utero development in rats SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article DE zearalenone; estrogenic mycotoxin; developmental toxicity; rat ID RISK ASSESSMENT; MYCOTOXINS; EXPOSURE; MOUSE; PHYTOESTROGENS; OCHRATOXIN; TOXICITY; BETA AB Zearalenone (ZE), an estrogenic mycotoxin produced by Fusarium graminearum or F. roseum, is one of the most common contaminants of cereal grains world-wide. The objective of this study was to determine the effects of ZE on in utero development of rats. Pregnant female Charles River Sprague-Dawley rats were gavaged once daily with ZE (in corn oil) at doses of 0, 1, 2, 4, or 8 mg/kg body weight on gestation days (GD) 6-19. All females survived to cesarean section on GD 20. At cesarean section, reproductive and developmental parameters were measured and blood was taken for hormone analysis. Dose-related decreases were seen in maternal feed consumption and body weight gain in all treated groups. Delayed fetal development was linked to maternal toxicity. Fetal body weight was significantly decreased in both sexes in all treated groups. ZE retarded skeletal ossification at 4 and 8 mg/kg. Fetal anogenital index (anogenital distance normalized for body weight) was increased in all treated groups, indicating an androgenic effect of ZE during fetal development. Fetal viability was significantly decreased at 8 mg/kg; significant decreases were observed in number of viable fetuses, and number of litters totally resorbed. At 4 and 8 mg/kg, maternal liver-body weight ratios were significantly increased and organ-brain weight ratios for weights of liver, heart, spleen, kidneys, and ovaries were significantly decreased. Gonadotropins (LH, FSH, and prolactin) and sex steroids (progesterone and estradiol) were analyzed from the blood serum obtained at cesarean section. LH in the 0, 1, 2, and 4 mg/kg groups showed minimal variation, and slightly increased at 8 mg/kg. FSH was decreased in the 1, 2, and 4 mg/kg groups, but the level at 8 mg/kg was slightly higher than the control level. Prolactin level was not affected at I mg/kg, slightly increased at 2 and 4 mg/kg, and significantly increased at 8 mg/kg. Progesterone was decreased at 2, 4, and 8 mg/kg and the decreases were significant at 2 and 4 mg/kg. Estradiol level was not affected at I mg/kg, but dose-related decreases were observed at 2, 4, and 8 mg/kg. Only the 8 mg/kg level of estradiol was significantly decreased. In summary, ZE was maternally toxic and fetotoxic but not teratogenic. The increased anogenital distance observed in male and female fetuses was considered a hormonal change rather than a teratologic response. The increased anogenital distance indicated an androgenic effect. Based on the dose-related maternal and fetal toxicity in all treated groups, the NOEL for reproductive and teratogenic effects was less than 1 mg/kg. Published by Elsevier Ltd. C1 US FDA, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. RP Collins, TFX (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. EM tcollins@cfsan.fda.gov NR 42 TC 31 Z9 37 U1 0 U2 6 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 2006 VL 44 IS 9 BP 1455 EP 1465 DI 10.1016/j.fct.2006.04.015 PG 11 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA 080KS UT WOS:000240247100003 PM 16797818 ER PT J AU Guan, D Kniel, K Calci, KR Hicks, DT Pivarnik, LF Hoover, DG AF Guan, D Kniel, K Calci, KR Hicks, DT Pivarnik, LF Hoover, DG TI Response of four types of coliphages to high hydrostatic pressure SO FOOD MICROBIOLOGY LA English DT Article DE high hydrostatic pressure; coliphage ID HEPATITIS-A VIRUS; GREEN ONIONS; INACTIVATION; BACTERIOPHAGES; CALICIVIRUS; RADIATION; OUTBREAK; WATER; FOOD AB Pressure inactivation of four types of coliphages, rho X 174 (ssDNA virus), MS2 (ssRNA virus), lambda imm434 (dsDNA virus) and T4 (dsDNA virus), was studied to evaluate their potential as human enteric viral surrogates for use in validation of commercial pressure processing treatments. Phage rho X 174 demonstrated an unexpected high resistance to pressure with no more than 1-log(10) reduction observed following exposures to 350-600MPa. There was no greater than 1-log(10) reduction below 500MPa for MS2 in modified phosphate-buffered saline, but a 3.3-log(10) reduction was observed for MS2 pressurized at 600 MPa. Coliphages imm434 and T4 were relatively sensitive to pressure in demonstrating inactivation at 350 MPa. At 21 degrees C, lambda imm434 was inactivated in modified phosphate-buffered saline or Dulbecco's Modified Eagle's Medium plus 5% fetal bovine sera by at least 7.5-log(10) when exposed to 400MPa for 5 min. Treatment at 450 MPa for 5 min was necessary to obtain a log(10) reduction of 6-7 for T4. (c) 2005 Elsevier Ltd. All rights reserved. C1 Univ Delaware, Dept Anim & Food Sci, Newark, DE 19716 USA. US FDA, Gulf Coast Seafood Lab, Dauphin Isl, AL 36528 USA. Univ Delaware, Sea Grant Coll Program, Lewes, DE 19958 USA. Univ Rhode Isl, Dept Nutr & Food Sci, Kingston, RI 02881 USA. RP Hoover, DG (reprint author), Univ Delaware, Dept Anim & Food Sci, Newark, DE 19716 USA. EM dgh@udel.edu NR 22 TC 21 Z9 21 U1 0 U2 16 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0740-0020 J9 FOOD MICROBIOL JI Food Microbiol. PD SEP PY 2006 VL 23 IS 6 BP 546 EP 551 DI 10.1016/j.fm.2005.09.003 PG 6 WC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology SC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology GA 043WN UT WOS:000237633700006 PM 16943050 ER PT J AU Puig, M Mihalik, K Tilton, JC Williams, O Merchlinsky, M Connors, M Feinstone, SM Major, ME AF Puig, Montserrat Mihalik, Kathleen Tilton, John C. Williams, Ollie Merchlinsky, Michael Connors, Mark Feinstone, Stephen M. Major, Marian E. TI CD4+ immune escape and subsequent T-cell failure following chimpanzee immunization against hepatitis C virus SO HEPATOLOGY LA English DT Article ID VIRAL CLEARANCE; NONSTRUCTURAL PROTEIN-3; RECOVERED CHIMPANZEES; NEUTRALIZING ANTIBODY; PLUS RIBAVIRIN; INFECTION; RESPONSES; HCV; PERSISTENCE; CD4(+) AB Hepatitis C is a major cause of chronic liver disease, with 170 million individuals infected worldwide and no available vaccine. We analyzed the effects of an induced T-cell response in 3 chimpanzees, targeting nonstructural proteins in the absence of neutralizing antibodies. In all animals the specific T-cell response modified the outcome of infection, producing a 10- to 1,000-fold reduction in peak virus titers. The challenge of 2 immunized animals that had been previously exposed to hepatitis C virus resulted in subclinical infections. Immune responses in the third animal, naive prior to immunization, limited viral replication immediately, evidenced by a 30-fold reduction in virus titer by week 2, declining to a nonquantifiable level by week 6. After 10 weeks of immunological control, we observed a resurgence of virus, followed by progression to a persistent infection. Comparing virus evolution with T-cell recognition, we demonstrated that: (i) resurgence was concomitant with the emergence of new dominant viral populations bearing single amino acid changes in the NS3 and NS5A regions, (ii) these mutations resulted in a loss of CD4+ T-cell recognition, and (iii) subsequent to viral resurgence and immune escape a large fraction of NS3-specific T cells became impaired in their ability to secrete IFN-gamma and proliferate. In contrast, NS3-specific responses were sustained in the recovered/immunized animals presenting with subclinical infections. In conclusion, viral escape from CD4+ T cells can result in the eventual failure of an induced T-cell response that initially controls infection. Vaccines that can induce strong T-cell responses prior to challenge will not necessarily prevent persistent HCV infection. C1 US FDA, Div Viral Prod, Lab Hepatitis Viruses, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. NIAID, Immunoregulat Lab, NIH, Bethesda, MD USA. US FDA, Ctr Biol Evaluat & Res, Viral Dis Lab, Bethesda, MD USA. RP Major, ME (reprint author), US FDA, Div Viral Prod, Lab Hepatitis Viruses, Ctr Biol Evaluat & Res, Bldg 29A-Room 1D10-HFM,8800 Rockville Pike, Bethesda, MD 20892 USA. EM marian.major@fda.hhs.gov FU NCI NIH HHS [CA85883] NR 50 TC 47 Z9 48 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 SEP PY 2006 VL 44 IS 3 BP 736 EP 745 DI 10.1002/hep.21319 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 080IU UT WOS:000240241900025 PM 16941702 ER PT J AU Reddy, NR Tetzloff, RC Solomon, HM Larkin, JW AF Reddy, N. R. Tetzloff, R. C. Solomon, H. M. Larkin, J. W. TI Inactivation of Clostridium botulinum nonproteolytic type B spores by high pressure processing at moderate to elevated high temperatures SO INNOVATIVE FOOD SCIENCE & EMERGING TECHNOLOGIES LA English DT Article DE high pressure processing; inactivation; Clostridium botulinum; spores ID HIGH HYDROSTATIC-PRESSURE; RECIPROCAL PRESSURIZATION; SPOROGENES SPORES; BACTERIAL-SPORES; FOODS; STERILIZATION; PRESERVATION; HEAT AB The effect of high pressure and high temperature treatments at various process times on the inactivation of spores of Clostridium botulinum nonproteolytic type B strains, 2-B, 17-B, KA-P8-B, and KAP9-B, suspended in phosphate buffer (0.067M, pH7.0) and a crabmeat blend was investigated. Spores of KAP8-B were less resistant to high pressure treatment than the spores of 2-B, 17-13, and KAP9-B in both phosphate buffer and crabmeat blend. No survivors of initial counts (> 4.3 logunits) of KAP8-B spores were detected in these menstura after processing at 827MPa and 60 degrees C for 10min. The amount of inactivation of spores of 2-B, 17-B, and KAP9-B in phosphate buffer or crabmeat blend increased with the increase in processing time from 10 to 30min at 827MPa and 75 degrees C. Similar inactivation patterns were observed for these spores in both phosphate buffer and crabmeat blend. A reduction of > 6-logunits of 2-B, 17-B, and KAP9-B spores in phosphate buffer and crabmeat blend was observed at 827MPa and 75 degrees C for a processing time of between 20 and 30min. Crabmeat blend as a suspension menstrum provided no protection against inactivation of spores of 2-B, 17-B, and KAP9-B by high pressure processing. High temperature (> 95 degrees C) and lower pressure (620MPa) treatments for up to 10min were also found to inactivate 17-B spores in phosphate buffer. Spores of nonproteolytic type B strains, 2-B, 17-B, KAP8-B, and KAP9-B in phosphate buffer and crabmeat blend can be inactivated by a combination of high pressure and temperature treatments. (c) 2006 Elsevier Ltd. All rights reserved. C1 US FDA, Natl Ctr Food Safety & Technol, Summit Argo, IL 60501 USA. IIT, Natl Ctr Food Safety & Technol, Summit Argo, IL 60501 USA. US FDA, Div Microbiol Studies, College Pk, MD 20740 USA. RP Reddy, NR (reprint author), US FDA, Natl Ctr Food Safety & Technol, 6502 S Archer Rd, Summit Argo, IL 60501 USA. EM rukma.reddy@fda.hhs.gov NR 36 TC 46 Z9 49 U1 0 U2 18 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1466-8564 J9 INNOV FOOD SCI EMERG JI Innov. Food Sci. Emerg. Technol. PD SEP PY 2006 VL 7 IS 3 BP 169 EP 175 DI 10.1016/j.ifset.2006.03.002 PG 7 WC Food Science & Technology SC Food Science & Technology GA 076CY UT WOS:000239935800002 ER PT J AU Simjee, S Zhang, YF McDermott, PF Donabedian, SM Zervos, MJ Meng, JH AF Simjee, Shabbir Zhang, Yifan McDermott, Patrick F. Donabedian, Susan M. Zervos, Marcus J. Meng, Jianghong TI Heterogeneity of vat(E)-carrying plasmids in Enterococcus faecium recovered from human and animal sources SO INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS LA English DT Article DE E. faecium; plasmids; streptogramin resistance; virginiamycin ID VANCOMYCIN-RESISTANT ENTEROCOCCI; POULTRY PRODUCTION ENVIRONMENT; QUINUPRISTIN-DALFOPRISTIN; GENTAMICIN RESISTANCE; EPIDEMIOLOGY; ANTIBIOTICS; NETHERLANDS; FAECALIS; EUROPE; SATA AB In this study, quinupristin/dalfopristin (Q/D)-resistant Enterococcus faecium isolates (33 from poultry farms and 1 from a human outpatient) with Q/D minimal inhibitory concentrations ranging from 4 mu g/mL to 32 mu g/mL were analysed. Polymerase chain reaction detected the presence of vat(E) in all isolates. Using pulsed-field gel electrophoresis (PFGE), 14 distinct PFGE patterns were identified. The human E. faecium isolate was distinguishable from the 33 farm isolates by PFGE. Southern hybridisation localised the vat(E) gene to an 11 kb plasmid and resulted in five plasmid hybridisation types. The vat(E)-carrying plasmid from the human isolate showed a nearly identical hybridisation pattern to a plasmid from a farm isolate. This study showed that the vat(E) gene, conferring resistance to Q/D, was carried on different plasmids in a heterogeneous group of E. faecium, some of which may be acquired by E. faecium capable of infecting humans. (c) 2006 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved. C1 Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA. US FDA, Dept Anim & Food Microbiol, Res Off, Ctr Vet Med, Laurel, MD USA. Henry Ford Hosp, Detroit, MI 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 26 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-8579 J9 INT J ANTIMICROB AG JI Int. J. Antimicrob. Agents PD SEP PY 2006 VL 28 IS 3 BP 200 EP 205 DI 10.1016/j.ijantimicag.2006.04.004 PG 6 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA 085YH UT WOS:000240639800006 PM 16911866 ER PT J AU Grant, MA Wernberg, JS Van, KT Albert, AM AF Grant, Michael A. Wernberg, Jane S. Van, Khanh T. Albert, Angelina M. TI Two rapid methods for detection of Escherichia coli exceeding 10(4)/g action levels: Precollaborative study SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article AB The current AOAC Method 966.24 for enumeration of Escherichia coli in foods uses a most probable number (MPN) procedure with extensive confirmation steps. Two new methods based on membrane filtration (MF) were compared to the MPN reference method for detection of high levels of E. coli in 5 food types, some of which represent categories for which the U.S. Food and Drug Administration (FDA) mandates additional testing if an action level of 10(4)/g E. coli is exceeded. Ground beef, which is not FDA regulated, was also tested. The 5 food types were all inoculated at 3 levels: 10(2)/g, >= 10(4)/g, and >= 10(5)/g E. coli. An MF protocol using either m-ColiBlue24((R)) (CB) or lauryl sulfate tryptose plus BCIG (LST/BCIG) was an effective potential alternative to the reference method. Sensitivity and specificity for both CB and LST/BCIG were 98 and 100%, respectively. Agreement between MPN and both CB and LST/BCIG was 98%. The 2 proposed methods allow completion of both presumptive and confirmatory steps in 1-3 days, whereas the reference method requires as many as 11 days. Exclusivity testing with 50 non-E. coli strains indicated 100% were correctly ruled out by the proposed protocols. Inclusivity testing was used to determine whether typical results were obtained after incubation of E. coli cultures on CB or LST/BCIG for 24 h. Of 50 E. coli strains tested, 100% yielded typical results after incubation on CB, and 98% yielded typical results after incubation on LST/BCIG. C1 US FDA, Pacific Reg Lab, Bothell, WA 98021 USA. US FDA, Pacific Reg Lab, Irvine, CA 92612 USA. RP Grant, MA (reprint author), US FDA, Pacific Reg Lab, NW, Bothell, WA 98021 USA. EM mike.grant@fda.hhs.gov NR 13 TC 1 Z9 1 U1 0 U2 1 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD SEP-OCT PY 2006 VL 89 IS 5 BP 1317 EP 1326 PG 10 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 089MB UT WOS:000240883600014 PM 17042182 ER PT J AU Nyman, PJ Morehouse, KM McNeal, TP Perfetti, GA Diachenko, GW AF Nyman, Patricia J. Morehouse, Kim M. McNeal, Timothy P. Perfetti, Gracia A. Diachenko, Gregory W. TI Single-laboratory validation of a method for the determination of furan in foods by using static headspace sampling and gas chromatography/mass spectrometry SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article AB A headspace gas chromatography/mass spectrometry method was developed and validated in-house for the determination of furan in foods. The method of standard additions with d(4)-furan as the internal standard was used to quantitate furan. The limit of detection and limit of quantitation (LOQ) values ranged from 0.2 and 0.6 ng/g, respectively, in apple juice to 0.9 and 2.9 ng/g, respectively, in peanut buffer. Recoveries were obtained at 0.5, 1, 2, and 3 times the LOQ. At 1, 2, and 3 times the LOQ, the recoveries ranged from 89.4 to 108%, and the relative standard deviations ranged from 3.3 to 17.3% for all the matrixes. For apple juice, chicken broth, and infant formula, the averaged coefficients of determination from the linear regression analyses were > 0.99 with each food fortified at 0.5, 1, 2, and 3 times the LOQ. The coefficients of determination were > 0.99 for green beans and 0.96 for peanut butter with the foods fortified at 1, 2, and 3 times the LOQ. With in-laboratory precision was determined by comparing the amounts of furan found in 18 samples by 2 analysts on different days with different instruments. For most of the foods, the difference between the amounts found by each analyst was < 18%. The method was used to conduct a survey of > 300 foods. The furan levels found ranged from none detected to 174 ng/g. C1 US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Nyman, PJ (reprint author), US FDA, Ctr Food Safety & Appl Nutr, HFS 245,5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM patricia.nyman@fda.hhs.gov NR 16 TC 29 Z9 31 U1 0 U2 6 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 2006 VL 89 IS 5 BP 1417 EP 1424 PG 8 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 089MB UT WOS:000240883600026 PM 17042194 ER PT J AU Kordzakhia, G Lalley, SP AF Kordzakhia, George Lalley, Steven P. TI Ergodicity and mixing properties of the northeast model SO JOURNAL OF APPLIED PROBABILITY LA English DT Article DE northeast model; facilitated spin-flip system; oriented percolation; exponential mixing ID ISING-MODEL AB The northeast model is a spin system on the two-dimensional integer lattice that evolves according to the following rule: whenever a site's southerly and westerly nearest neighbors have spin 1, it may reset its own spin by tossing a p-coin; at all other times, its spin remains frozen. It is proved that the northeast model has a phase transition at p(c) = 1 - beta(c), where beta(c) is the critical parameter for oriented percolation. For p < p(c), the trivial measure, delta(0), that puts mass one on the configuration with all spins set at 0 is the unique ergodic, translation-invariant, stationary measure. For p ! pc, the product Bernoulli-p measure on configuration space is the unique nontrivial, ergodic, translation-invariant, stationary measure for the system, and it is mixing. For p > (2)/(3), it is shown that there is exponential decay of correlations. C1 Univ Chicago, Dept Stat, Chicago, IL 60637 USA. RP Kordzakhia, G (reprint author), Ctr Drug Evaluat & Res, Div Biometr 1, Bldg 22,Room 4235,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM kordzakh@stat.berkeley.edu; lalley@galton.uchicago.edu NR 7 TC 7 Z9 7 U1 0 U2 0 PU APPLIED PROBABILITY TRUST PI SHEFFIELD PA THE UNIVERSITY, SCHOOL MATHEMATICS STATISTICS, SHEFFIELD S3 7RH, ENGLAND SN 0021-9002 J9 J APPL PROBAB JI J. Appl. Probab. PD SEP PY 2006 VL 43 IS 3 BP 782 EP 792 DI 10.1239/jap/1158784946 PG 11 WC Statistics & Probability SC Mathematics GA 101YQ UT WOS:000241777900014 ER PT J AU Steenbergen, SM Lee, YC Vann, WF Vionnet, J Wright, LF Vimr, ER AF Steenbergen, Susan M. Lee, Young-Choon Vann, Willie F. Vionnet, Justine Wright, Lori F. Vimr, Eric R. TI Separate pathways for O acetylation of polymeric and monomeric sialic acidsand identification of sialyl O-acetyl esterase in Escherichia coli K1 SO JOURNAL OF BACTERIOLOGY LA English DT Article ID MOBILE CONTINGENCY LOCUS; MENINGITIDIS GROUP-B; CAPSULAR POLYSACCHARIDE; GENETIC-ANALYSIS; FORM VARIATION; METABOLISM; SYNTHETASE; MUTATIONS; MECHANISM; DISEASE AB O acetylation at carbon positions 7 or 9 of the sialic acid residues in the polysialic acid capsule of Escherichia coli K1 is catalyzed by a phase-variable contingency locus, neuO, carried by the K1-specific prophage, CUS-3. Here we describe a novel method for analyzing polymeric sialic acid O acetylation that involves the release of surface sialic acids by endo-N-acetyineuraminidase digestion, followed by fluorescent labeling and detection of quinoxalinone derivatives by chromatography. The results indicated that NeuO is responsible for the majority of capsule modification that takes place in vivo. However, a minor neuO-independent O acetylation pathway was detected that is dependent on the bifunctional polypeptide encoded by neuD. This pathway involves O acetylation of monomeric sialic acid and is regulated by another bifunctional enzyme, NeuA, which includes N-terminal synthetase and C-terminal sialyl O-esterase domains. A homologue of the NeuA C-terminal domain (Pm1710) in Pasteurella multocida was also shown to be an esterase, suggesting that it functions in the catabolism of acetylated environmental sialic acids. Our combined results indicate a previously unexpected complexity in the synthesis and catabolism of microbial sialic and polysialic acids. These findings are key to understanding the biological functions of modified sialic acids in E. coli K1 and other species and may provide new targets for drug or vaccine development. C1 Univ Illinois, Dept Pathobiol, Lab Sialobiol, Urbana, IL 61802 USA. Univ Illinois, Dept Pathobiol, Lab Sialobiol & Comparat Metabolom, Urbana, IL 61802 USA. Dong A Univ, Dept Biotechnol, Pusan, South Korea. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. Univ Rochester, Dept Microbiol & Immunol, Rochester, NY 14627 USA. RP Vimr, ER (reprint author), Univ Illinois, Dept Pathobiol, Lab Sialobiol, 2522 VMBSB,2001 S Lincoln Ave, Urbana, IL 61802 USA. EM ervimr@uiuc.edu FU NIAID NIH HHS [R01 AI042015] NR 54 TC 37 Z9 37 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 2006 VL 188 IS 17 BP 6195 EP 6206 DI 10.1128/JB.00466-06 PG 12 WC Microbiology SC Microbiology GA 080LV UT WOS:000240250200018 PM 16923886 ER PT J AU Bian, J Mudano, A Allison, J Briggs, D Cope, J Curtis, J Elkins, M Gross, T Kim, Y McGunagle, D Nair, R Xie, A Saag, KG AF Bian, J. Mudano, A. Allison, J. Briggs, D. Cope, J. Curtis, J. Elkins, M. Gross, T. Kim, Y. McGunagle, D. Nair, R. Xie, A. Saag, K. G. TI Vertebroplasty/kyphoplasty increases the risk of secondary vertebral compression fractures. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 28th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 15-19, 2006 CL Philadelphia, PA SP Amer Soc Bone & Mineral Res C1 UAB, CERTS Musculoskeletal Disorders, 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 1 Z9 1 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2006 VL 21 SU 1 BP S105 EP S105 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 089FS UT WOS:000240866300400 ER PT J AU Donabedian, SM Perri, MB Vager, D Hershberger, E Malani, P Simjee, S Chow, J Vergis, EN Muder, RR Gay, K Angulo, FJ Bartlett, P Zervos, MJ AF Donabedian, S. M. Perri, M. B. Vager, D. Hershberger, E. Malani, P. Simjee, S. Chow, J. Vergis, E. N. Muder, R. R. Gay, K. Angulo, F. J. Bartlett, P. Zervos, M. J. TI Quinupristin-dalfopristin resistance in Enterococcus faecium isolates from humans, farm animals, and grocery store meat in the United States SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID GEL-ELECTROPHORESIS PATTERNS; ANTIMICROBIAL RESISTANCE; FOOD-ANIMALS; STREPTOGRAMIN-A; SATA GENE; QUINUPRISTIN/DALFOPRISTIN; IDENTIFICATION; VIRGINIAMYCIN; INFECTIONS; DENMARK AB Three hundred sixty-one quinupristin-dalfopristin (Q-D) -resistant Enterococcus faecium (QDREF) isolates were isolated from humans, turkeys, chickens, swine, dairy and beef cattle from farms, chicken carcasses, and ground pork from grocery stores in the United States from 1995 to 2003. These isolates were evaluated by pulsed-field gel electrophoresis (PFGE) to determine possible commonality between QDREF isolates from human and animal sources. PCR was performed to detect the streptogramin resistance genes vatD, vatE, and vgbA and the macrolide resistance gene ermB to determine the genetic mechanism of resistance in these isolates. QDREF from humans did not have PFGE patterns similar to those from animal sources. vatE was found in 35%, 26%, and 2% of QDREF isolates from turkeys, chickens, and humans, respectively, and was not found in QDREF isolates from other sources. ermB was commonly found in QDREF isolates from all sources. Known streptogramin resistance genes were absent in the majority of isolates, suggesting the presence of other, as-yet-undetermined, mechanisms of Q-D resistance. C1 Wayne State Univ, Henry Ford Hosp, Sch Med, Detroit, MI 48202 USA. Univ Michigan, Med Ctr, Ann Arbor, MI USA. US FDA, Ctr Vet Med, Rockville, MD 20857 USA. Univ Pittsburgh, Med Ctr, Vet Affairs Med Ctr, Pittsburgh, PA USA. Ctr Dis Control & Prevent, Emerging Infect Program, Atlanta, GA USA. Michigan State Univ, Coll Vet Med, Lansing, MI USA. RP Zervos, MJ (reprint author), Wayne State Univ, Henry Ford Hosp, Sch Med, 2799 W Grand Blvd, Detroit, MI 48202 USA. EM mzervos1@hfhs.org FU DRS NIH HHS [RS1/CCR520614-01]; FDA HHS [FD-U-001577-01] NR 38 TC 21 Z9 23 U1 0 U2 4 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 2006 VL 44 IS 9 BP 3361 EP 3365 DI 10.1128/JCM.02412-05 PG 5 WC Microbiology SC Microbiology GA 086YB UT WOS:000240708000046 PM 16954273 ER PT J AU Amur, SG Burczynski, M Domer, A Goodsaid, F Immermann, F Noory, A Salemo, R Tong, W Frueh, FW AF Amur, Shashi G. Burczynski, Michael Domer, Andrew Goodsaid, Federico Immermann, Fred Noory, Asadollah Salemo, Ronald Tong, Weida Frueh, Felix W. TI Assessment of differential gene expression in peripheral blood mononuclear cells (PBMCS) during drug treatment in cancer patients - A voluntary genomic data submission (VGDS) study SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Meeting Abstract CT 25th Annual Meeting of the American-College-of-Clinical-Pharmacology CY SEP 17-19, 2006 CL Cambridge, MA SP Amer Coll Clin Pharmacol C1 US FDA, Ctr Drug Evaluat & Res, Off Clin Pharmacol, Silver Spring, MD USA. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Wyeth Res, Collegeville, PA 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 2006 VL 46 IS 9 MA 108 BP 1087 EP 1087 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 078HE UT WOS:000240092500117 ER PT J AU Mummaneni, P Amur, SG Goodsaid, F Rudman, A Frueh, FW AF Mummaneni, Padmaja Amur, Shashi G. Goodsaid, Federico Rudman, Allen Frueh, Felix W. TI Genomic biomarkers in FDA-approved drug labels SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Meeting Abstract CT 25th Annual Meeting of the American-College-of-Clinical-Pharmacology CY SEP 17-19, 2006 CL Cambridge, MA SP Amer Coll Clin Pharmacol C1 US FDA, CDER, OCP, Silver Spring, MD USA. NR 0 TC 1 Z9 2 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD SEP PY 2006 VL 46 IS 9 MA 115 BP 1088 EP 1088 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 078HE UT WOS:000240092500121 ER PT J AU Badano, A Schneider, S Samei, E AF Badano, Aldo Schneider, Sarah Samei, Ehsan TI Visual assessment of angular response in medical liquid crystal displays SO JOURNAL OF DIGITAL IMAGING LA English DT Article DE viewing angle; angular contrast; goniometric measurements; AMLCD; medical display; visual threshold ID CONTRAST; LUMINANCE AB In spite of having non-Lambertian emission, displays based on liquid crystal technology are becoming popular for medical diagnostic work stations. For all liquid crystal displays (LCDs), the contrast performance varies with viewing direction. Accurate measurements of the angular distribution of light emission require expensive instrumentation and extensive expertise. We investigated the possibility of using a test pattern to visually assess the angular response performance of LCDs. We found that this procedure offers the end user of displays a simple, fast, and relatively consistent technique to verify that the viewing angle performance of the display device is within certain acceptable limits. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. Duke Univ, Dept Radiol Phys & Biomed Engn, Duke Adv Imaging Labs, Durham, NC 27710 USA. Duke Univ, Med Ctr, Durham, NC 27710 USA. RP Badano, A (reprint author), US FDA, Ctr Devices & Radiol Hlth, 12720 Twinbrook Pkwy, Rockville, MD 20857 USA. EM aldo.badano@fda.hhs.gov OI badano, aldo/0000-0003-3712-6670 NR 9 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0897-1889 J9 J DIGIT IMAGING JI J. Digit. Imaging PD SEP PY 2006 VL 19 IS 3 BP 240 EP 248 DI 10.1007/s10278-006-0633-5 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 082OV UT WOS:000240397100006 PM 16741662 ER PT J AU Guo, CN Doub, WH AF Guo, Changning Doub, William H. TI The influence of actuation parameters on in vitro testing of nasal spray products SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article DE nasal drug delivery; in vitro test; automated actuation; spray pattern; plume geometry; droplet size distribution; laser diffraction; SprayVIEW (TM) ID DEPOSITION; DELIVERY; PUMPS; SIZE AB Nasal spray drug products are normally characterized via measurement of shot weight, spray pattern, plume geometry, and droplet size distribution (DSD). In this project, the actuation parameters, such as stroke length, actuation velocity, and actuation acceleration, were investigated to ascertain how they affect nasal spray characteristics. Pfeiffer nasal spray pump units filled with water were used in the study. Actuation parameters were adjusted using an electronic automated actuation system, SprayVIEW (TM) NSx. Spray pattern and plume geometry measurements were carried out using a high speed optical spray characterization system, SprayVlEW (TM) NSP, and DSD analysis was performed using a Malvern 2600 laser diffraction system. Our results show that different actuation parameters affect the nasal spray characteristics in different ways and to different degrees. Among all the actuation parameters, stroke length and actuation velocity have significant effects on the nasal spray characteristics, while the other actuation parameters have little, if any, effect. Compared to spray pattern, plume geometry and DSD, shot weight provides very little characterization information. The findings from this work suggest that, for in vitro bioavailability (BA) and bioequivalence (BE) studies of nasal spray products, the actuation parameters, stroke length, and velocity must be carefully selected. Spray pattern, plume geometry, and DSD appear to provide critical data for assessment of nasal pump performance. (c) 2006 Wiley-Liss, Inc. C1 US FDA, Div Pharmcaeut Anal, St Louis, MO 63101 USA. RP Guo, CN (reprint author), US FDA, Div Pharmcaeut Anal, 1114 Market St,Room 1002, St Louis, MO 63101 USA. EM changning.guo@fda.hhs.gov NR 11 TC 14 Z9 16 U1 2 U2 4 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 SEP PY 2006 VL 95 IS 9 BP 2029 EP 2040 DI 10.1002/jps.20678 PG 12 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 081NE UT WOS:000240323500014 PM 16865693 ER PT J AU Zmudzka, BZ Hearing, VJ Beer, JZ AF Zmudzka, Barbara Z. Hearing, Vincent J. Beer, Janusz Z. TI Photobiologic role of melanin distribution in the epidermis SO JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY LA English DT Letter ID SKIN C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20852 USA. NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Zmudzka, BZ (reprint author), US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20852 USA. EM barbara.zmudzka@fda.hhs.gov NR 3 TC 5 Z9 6 U1 0 U2 0 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 SEP 1 PY 2006 VL 84 IS 3 BP 231 EP 231 DI 10.1016/j.jphotobiol.2006.05.008 PG 1 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 079YA UT WOS:000240212600010 PM 16857378 ER PT J AU Sergeev, N Rubtcova, E Chizikov, V Schmid, DS Loparev, VN AF Sergeev, Nikolay Rubtcova, Elena Chizikov, Vladimir Schmid, D. Scott Loparev, Vladimir N. TI New mosaic subgenotype of varicella-zoster virus in the USA: VZV detection and genotyping by oligonucleotide-microarray SO JOURNAL OF VIROLOGICAL METHODS LA English DT Article DE varicella-zoster virus; genotyping; microarray; oligonucleotide ID WILD-TYPE STRAINS; SINGLE NUCLEOTIDE POLYMORPHISMS; MOLECULAR EPIDEMIOLOGY; THERMODYNAMIC PARAMETERS; HYBRIDIZATION PROBES; VACCINE STRAIN; DNA; IDENTIFICATION; DIFFERENTIATION; DISCRIMINATION AB A rapid and sensitive microarray-based method was used to distinguish the three major circulating genotypes of varicella-zoster virus (VZV). The method analyzes five variable positions located in a 447-nucleotide variable region I of open reading frame 22 (ORF 22r1); these single nucleotide polymorphisms (SNP) display in stably occurring patterns specific to each of the VZV genotypes established in previously published studies. Pairs of short oligonucleotide probes (oligoprobes) with sequences corresponding to all of the observed SNP were used to detect specific sequences. Fluorescently labeled ssRNA samples for hybridization with a chip were prepared by in vitro T7 polymerase driven transcription of the amplicons of ORF 22r1, followed by chemical labeling with Cy5 into RNA sample. Ratios between fluorescent hybridization signals from each pair of oligoprobes were used to assess the sequence at each SNP. We evaluated six reference VZV strains and 130 VZV clinical specimens to validate the method. The microarray method accurately identified strains isolated in the US in 2001-2002, representing all major genotypes as determined using more extensive sequence analysis, correctly assigning strains to genotypes E (81.5%), J (3%) and M (15.5%). In addition, a new M variant (M3) was identified. Published by Elsevier B.V. C1 Ctr Dis Control & Prevent, Natl Ctr Infect Dis, Div Viral & Rickettsial Dis, Measles & Herpesvirus Team,Natl VZV Lab, Atlanta, GA 30333 USA. US FDA, Ctr Devices & Radiol Hlth, Off Sci & Technol, Div Life Sci, Silver Spring, MD 20993 USA. US FDA, Ctr Biol Evaluat & Res, Off Vaccines Res & Review, Div Viral Prod, Silver Spring, MD 20993 USA. RP Schmid, DS (reprint author), Ctr Dis Control & Prevent, Natl Ctr Infect Dis, Div Viral & Rickettsial Dis, Measles & Herpesvirus Team,Natl VZV Lab, 1600 Clifton Rd,MS G-18, Atlanta, GA 30333 USA. EM dss1@cdc.gov NR 39 TC 28 Z9 31 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-0934 J9 J VIROL METHODS JI J. Virol. Methods PD SEP PY 2006 VL 136 IS 1-2 BP 8 EP 16 DI 10.1016/j.jviromet.2006.03.021 PG 9 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Virology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Virology GA 073IC UT WOS:000239735200002 PM 16675033 ER PT J AU Brown, M Carbone, L Conlee, KM Dawkins, MS Duncan, IJ Fraser, D Griffin, G Hampshire, VA Lambert, LA Mench, JA Morton, D Richmond, J Rollin, BE Rowan, AN Stephens, ML Wurbel, H AF Brown, Marilyn Carbone, Larry Conlee, Kathleen M. Dawkins, Marian S. Duncan, Ian J. Fraser, David Griffin, Gilly Hampshire, Victoria A. Lambert, Lesley A. Mench, Joy A. Morton, David Richmond, Jon Rollin, Bernard E. Rowan, Andrew N. Stephens, Martin L. Wuerbel, Hanno TI Report of the working group on animal distress in the laboratory SO LAB ANIMAL LA English DT Editorial Material ID PSYCHOLOGICAL-RESEARCH; NATIONAL SURVEY; EDUCATION; ATTITUDES AB Finding ways to minimize pain and distress in research animals is a continuing goal in the laboratory animal research field. Pain and distress, however, are not synonymous, and measures that alleviate one may not affect the other. Here, the authors provide a summary of a meeting held in February 2004 that focused on distress in laboratory animals. They discuss the difficulties associated with defining 'distress,' propose methods to aid in recognizing and alleviating distressful conditions, and provide recommendations for animal research conduct and oversight that would minimize distress experienced by laboratory animals. C1 Charles River Labs Fdn, Wilmington, MA 01887 USA. Univ Calif San Francisco, UCSF Lab Anim Res Ctr, San Francisco, CA 94143 USA. Humane Soc United States, Washington, DC 20037 USA. Univ Oxford, Dept Zool, Oxford OX1 3PS, England. Univ Guelph, Dept Anim & Poultry Sci, Guelph, ON N1G 2W1, Canada. Univ British Columbia, Anim Welf Program, Fac Land & Food Syst, Vancouver, BC V6T 1Z4, Canada. Univ British Columbia, W Maurice Young Ctr Appl Eth, Vancouver, BC V6T 1Z4, Canada. Canadian Council Anim Care, Ottawa, ON K1P 5G4, Canada. US FDA, CDRH, ODE, DCD,PVDB, Rockville, MD 20850 USA. Univ Oxford, Linacre Coll, Brighton BN1 3RS, E Sussex, England. Univ Calif Davis, Dept Anim Sci, Davis, CA 95616 USA. Univ Birmingham, Biomed Serv Unit, Birmingham B15 2TT, W Midlands, England. Home Off, London, England. Colorado State Univ, Dept Philosophy, Ft Collins, CO 80523 USA. Univ Giessen, Inst Vet Physiol Anim Welf & Ethol, D-35392 Giessen, Germany. RP Brown, M (reprint author), Charles River Labs Fdn, 251 Ballardvale St, Wilmington, MA 01887 USA. RI Wurbel, Hanno/D-6281-2012 OI Wurbel, Hanno/0000-0002-2934-3010 NR 11 TC 3 Z9 3 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0093-7355 J9 LAB ANIMAL JI Lab Anim. PD SEP PY 2006 VL 35 IS 8 BP 26 EP 30 DI 10.1038/laban0906-26 PG 5 WC Veterinary Sciences SC Veterinary Sciences GA 182QF UT WOS:000247518400007 PM 16943790 ER PT J AU Rothmann, M AF Rothmann, Mark D. TI Inferences on a life distribution by sampling from the ages or the ages at death SO LIFETIME DATA ANALYSIS LA English DT Article DE life distributions; likelihood ratio ordering; nonhomogeneous Poisson processes; weighted distributions ID MODELS AB Consider a system where units having independent and identically distributed lifetimes enter according to a nonhomogeneous Poisson process. After the unit's life in the system, the unit departs the system. For a fixed system time, this paper relates the units' common underlying life distribution with the distribution of the ages of units in the system, the distribution for the system life of units that departed the system and the distribution for the system life of units that have recently departed the system. Results can be used to estimate the underlying life distribution or a truncated version of that distribution based on the ages and/or most recent ages at death in both one sample and two sample situations. Results include a complete characterization of the possible distribution of the ages of those units in the system, how to estimate the underlying life distribution from the most recent ages at death, and how to test for an underlying monotone failure rate function based on independent samples from the ages and most recent ages at death. Two sample inferences that involve a likelihood ratio ordering make use of the results in Dykstra et al. (1995, J Amer Statisc Assoc 90(431):1030-1040), which provides the maximum likelihood estimators and a likelihood ratio test when the two distributions satisfy a likelihood ratio ordering. For the ages of the active units and the ages at death among the departed units, limits for their distributions and strong limiting results for their empirical distributions will be provided. C1 US FDA, Div Biometr 5, Silver Spring, MD 20993 USA. RP Rothmann, M (reprint author), US FDA, Div Biometr 5, 10903 New Hampshire Ave,HFD-711,Mail Stop 1207, Silver Spring, MD 20993 USA. EM mark.rothinann@fda.hhs.gov NR 10 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1380-7870 J9 LIFETIME DATA ANAL JI Lifetime Data Anal. PD SEP PY 2006 VL 12 IS 3 BP 305 EP 323 DI 10.1007/s10985-006-9010-4 PG 19 WC Mathematics, Interdisciplinary Applications; Statistics & Probability SC Mathematics GA 104JE UT WOS:000241953900004 PM 16957988 ER PT J AU Cragan, JD Friedman, JM Holmes, LB Uhl, K Green, NS Riley, L AF Cragan, Janet D. Friedman, J. M. Holmes, Lewis B. Uhl, Kathleen Green, Nancy S. Riley, Laura TI Ensuring the safe and effective use of medications during pregnancy: Planning and prevention through preconception care SO MATERNAL AND CHILD HEALTH JOURNAL LA English DT Article DE preconception care; medications; pregnancy; anticonvulsants; asthma; isotretinoin ID SPINA-BIFIDA; WOMEN; GASTROSCHISIS; MALFORMATIONS; VALPROATE; CHILDREN; ASTHMA; RISK; PHARMACOKINETICS; TERATOGENICITY C1 Ctr Dis Control & Prevent, Natl Ctr Birht DDefects & Dev Disabil, Atlanta, GA 30333 USA. Univ British Columbia, Dept Med Genet, Vancouver, BC V6T 1W5, Canada. MassGen Hosp Children, Genet & Teratol Unit, Boston, MA USA. US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. March Dimes Birth Defects Fsn, White Plains, NY USA. Brigham & Womens Hosp, Dept Obstet & Gynecol, Boston, MA 02115 USA. RP Cragan, JD (reprint author), Ctr Dis Control & Prevent, Natl Ctr Birht DDefects & Dev Disabil, 1600 Clifton Rd NE, Atlanta, GA 30333 USA. EM jcragan@cdc.gov OI Green, Nancy/0000-0002-9877-1561 NR 53 TC 15 Z9 16 U1 0 U2 2 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1092-7875 J9 MATERN CHILD HLTH J JI Matern. Child Health J. PD SEP PY 2006 VL 10 IS 5 SU S BP S129 EP S135 DI 10.1007/s10995-006-0102-2 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 093KM UT WOS:000241167200018 PM 16850277 ER PT J AU Beger, RD Schnackenberg, LK Holland, RD Li, DH Dragan, Y AF Beger, Richard D. Schnackenberg, Laura K. Holland, Ricky D. Li, Donghui Dragan, Yvonne TI Metabonomic models of human pancreatic cancer using 1D proton NMR spectra of lipids in plasma SO METABOLOMICS LA English DT Article DE metabonomics; metabolomics; lipiclomics; NMR; pancreatic cancer ID MAGNETIC-RESONANCE-SPECTROSCOPY; TANDEM MASS-SPECTROMETRY; H-1-NMR-BASED METABONOMICS; QUANTITATIVE-ANALYSIS; CROSS-VALIDATION; LIPIDOMICS; TOXICOLOGY; URINE; PERFORMANCE; METABOLISM AB In this study, we hypothesized that the altered insulin and glucose levels in male pancreatic cancer patients reported in a recent JAMA article would result in an altered lipid profile in the blood of pancreatic cancer patients when compared to controls (Stolzenberg-Solomon et al., 2005). Proton nuclear magnetic resonance (NMR) spectra of human lipophilic plasma extracts were used in order to build partial least squares discriminant function (PLS-DF) models that classified samples as belonging to the pancreatic control group or to the pancreatic cancer group. The sensitivity, specificity, and overall accuracy of the PLS-DF models based on 4 bins were 96%, 88%, and 92%, respectively. The sensitivity, specificity, and overall accuracy of the PLS-DF models based on 5 bins were 98%, 94%, and 96%, respectively. The sensitivity, specificity and overall accuracy of both the 4-bin and 5-bin PLS-DF models dropped only 1-2% during leave-25%-out cross-validation testing. Mass spectrometric profiling of phospholipids in plasma found three phosphatidylinositols that were significantly lower in pancreatic cancer patients than in healthy controls. The cancer models are based upon changes in lipid profiles that may provide a more sensitive and accurate diagnosis of pancreatic cancer than current methods that are based upon a single biomarker. C1 Natl Ctr Toxicol Res, Div Syst Toxicol Food & Drug Adm, Jefferson, AR 72079 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. RP Beger, RD (reprint author), Natl Ctr Toxicol Res, Div Syst Toxicol Food & Drug Adm, Jefferson, AR 72079 USA. EM Richard.Beger@fda.hhs.gov NR 46 TC 48 Z9 50 U1 6 U2 50 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1573-3882 J9 METABOLOMICS JI Metabolomics PD SEP PY 2006 VL 2 IS 3 BP 125 EP 134 DI 10.1007/s11306-006-0026-2 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 151AU UT WOS:000245261500003 ER PT J AU Casciano, DA Woodcock, J AF Casciano, Daniel A. Woodcock, Janet TI Empowering microarrays in the regulatory setting SO NATURE BIOTECHNOLOGY LA English DT Editorial Material C1 Univ Arkansas Med Sci, Little Rock, AR 72223 USA. US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. US FDA, Rockville, MD 20857 USA. RP Casciano, DA (reprint author), Univ Arkansas Med Sci, 47 Marcella Dr, Little Rock, AR 72223 USA. EM dcasciano@sbcglobal.net NR 0 TC 32 Z9 34 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD SEP PY 2006 VL 24 IS 9 BP 1103 EP 1103 DI 10.1038/nbt0906-1103 PG 1 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 083YK UT WOS:000240495200028 PM 16964221 ER PT J AU Frueh, FW AF Frueh, Felix W. TI Impact of microarray data quality on genomic data submissions to the FDA SO NATURE BIOTECHNOLOGY LA English DT Editorial Material C1 US FDA, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Frueh, FW (reprint author), US FDA, Off Clin Pharmacol, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM felix.frueh@fda.hhs.gov NR 4 TC 40 Z9 43 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD SEP PY 2006 VL 24 IS 9 BP 1105 EP 1107 DI 10.1038/nbt0906-1105 PG 3 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 083YK UT WOS:000240495200029 PM 16964222 ER PT J AU Canales, RD Luo, YL Willey, JC Austermiller, B Barbacioru, CC Boysen, C Hunkapiller, K Jensen, RV Knight, CR Lee, KY Ma, YQ Maqsodi, B Papallo, A Peters, EH Poulter, K Ruppel, PL Samaha, RR Shi, LM Yang, W Zhang, L Goodsaid, FM AF Canales, Roger D. Luo, Yuling Willey, James C. Austermiller, Bradley Barbacioru, Catalin C. Boysen, Cecilie Hunkapiller, Kathryn Jensen, Roderick V. Knight, Charles R. Lee, Kathleen Y. Ma, Yunqing Maqsodi, Botoul Papallo, Adam Peters, Elizabeth Herness Poulter, Karen Ruppel, Patricia L. Samaha, Raymond R. Shi, Leming Yang, Wen Zhang, Lu Goodsaid, Federico M. TI Evaluation of DNA microarray results with quantitative gene expression platforms SO NATURE BIOTECHNOLOGY LA English DT Article ID REAL-TIME PCR; RNA 3.0 ASSAY; MULTICENTER EVALUATION; RT-PCR; OLIGONUCLEOTIDE MICROARRAYS; PERFORMANCE AB We have evaluated the performance characteristics of three quantitative gene expression technologies and correlated their expression measurements to those of five commercial microarray platforms, based on the MicroArray Quality Control (MAQC) data set. The limit of detection, assay range, precision, accuracy and fold-change correlations were assessed for 997 TaqMan Gene Expression Assays, 205 Standardized RT (Sta) RT-PCR assays and 244 QuantiGene assays. TaqMan is a registered trademark of Roche Molecular Systems, Inc. We observed high correlation between quantitative gene expression values and microarray platform results and found few discordant measurements among all platforms. The main cause of variability was differences in probe sequence and thus target location. A second source of variability was the limited and variable sensitivity of the different microarray platforms for detecting weakly expressed genes, which affected interplatform and intersite reproducibility of differentially expressed genes. From this analysis, we conclude that the MAQC microarray data set has been validated by alternative quantitative gene expression platforms thus supporting the use of microarray platforms for the quantitative characterization of gene expression. C1 US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. Panomics Inc, Fremont, CA 94555 USA. Univ Toledo, Toledo, OH 43614 USA. ViaLogy Corp, Altadena, CA 91001 USA. Univ Massachusetts, Boston, MA 02125 USA. Gene Express Inc, Toledo, OH 43614 USA. Innovat Anal, Kalamazoo, MI 49009 USA. US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Appl Biosyst Inc, Foster City, CA 94404 USA. RP Goodsaid, FM (reprint author), US FDA, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM Federico.Goodsaid@fda.hhs.gov NR 27 TC 397 Z9 426 U1 4 U2 35 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD SEP PY 2006 VL 24 IS 9 BP 1115 EP 1122 DI 10.1038/nbt1236 PG 8 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 083YK UT WOS:000240495200032 PM 16964225 ER PT J AU Shippy, R Fulmer-Smentek, S Jensen, RV Jones, WD Wolber, PK Johnson, CD Pine, PS Boysen, C Guo, X Chudin, E Sun, YMA Willey, JC Thierry-Mieg, J Thierry-Mieg, D Setterquist, RA Wilson, M Lucas, AB Novoradovskaya, N Papallo, A Turpaz, Y Baker, SC Warrington, JA Shi, LM Herman, D AF Shippy, Richard Fulmer-Smentek, Stephanie Jensen, Roderick V. Jones, Wendell D. Wolber, Paul K. Johnson, Charles D. Pine, P. Scott Boysen, Cecilie Guo, Xu Chudin, Eugene Sun, Yongming Andrew Willey, James C. Thierry-Mieg, Jean Thierry-Mieg, Danielle Setterquist, Robert A. Wilson, Mike Lucas, Anne Bergstrom Novoradovskaya, Natalia Papallo, Adam Turpaz, Yaron Baker, Shawn C. Warrington, Janet A. Shi, Leming Herman, Damir TI Using RNA sample titrations to assess microarray platform performance and normalization techniques SO NATURE BIOTECHNOLOGY LA English DT Article ID GENE-EXPRESSION ANALYSIS; OLIGONUCLEOTIDE ARRAYS; AFFYMETRIX; COMPARABILITY; ACCURACY; PATTERNS; DESIGN; POWER; SIZE AB We have assessed the utility of RNA titration samples for evaluating microarray platform performance and the impact of different normalization methods on the results obtained. As part of the MicroArray Quality Control project, we investigated the performance of five commercial microarray platforms using two independent RNA samples and two titration mixtures of these samples. Focusing on 12,091 genes common across all platforms, we determined the ability of each platform to detect the correct titration response across the samples. Global deviations from the response predicted by the titration ratios were observed. These differences could be explained by variations in relative amounts of messenger RNA as a fraction of total RNA between the two independent samples. Overall, both the qualitative and quantitative correspondence across platforms was high. In summary, titration samples may be regarded as a valuable tool, not only for assessing microarray platform performance and different analysis methods, but also for determining some underlying biological features of the samples. C1 GE Healthcare, Tempe, AZ 85284 USA. Agilent Technol Inc, Santa Clara, CA 95051 USA. Univ Massachusetts, Boston, MA 02125 USA. Express Anal Inc, Durham, NC 27713 USA. Asuragen Inc, Austin, TX 78744 USA. US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. ViaLogy, Altadena, CA 91001 USA. Affymetrix Inc, Santa Clara, CA 95051 USA. Illumina Inc, San Diego, CA 92121 USA. Appl Biosyst Inc, Foster City, CA 94404 USA. Univ Toledo, Toledo, OH 43606 USA. Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. Appl Biosyst Inc, Austin, TX 78744 USA. Stratagene, La Jolla, CA 92037 USA. US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Shippy, R (reprint author), GE Healthcare, 7700 S River Pkwy,Suite 2603, Tempe, AZ 85284 USA. EM richard.shippy@ge.com RI THIERRY-MIEG, Jean/F-1975-2017; OI THIERRY-MIEG, Jean/0000-0002-0396-6789; Johnson, Charles/0000-0003-3892-7082 FU Intramural NIH HHS [Z99 LM999999] NR 31 TC 99 Z9 107 U1 1 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD SEP PY 2006 VL 24 IS 9 BP 1123 EP 1131 DI 10.1038/nbt1241 PG 9 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 083YK UT WOS:000240495200033 PM 16964226 ER PT J AU Tong, WD Lucas, AB Shippy, R Fan, XH Fang, H Hong, HX Orr, MS Chu, TM Guo, X Collins, PJ Sun, YMA Wang, SJ Bao, WJ Wolfinger, RD Shchegrova, S Guo, L Warrington, JA Shi, LM AF Tong, Weida Lucas, Anne Bergstrom Shippy, Richard Fan, Xiaohui Fang, Hong Hong, Huixiao Orr, Michael S. Chu, Tzu-Ming Guo, Xu Collins, Patrick J. Sun, Yongming Andrew Wang, Sue-Jane Bao, Wenjun Wolfinger, Russell D. Shchegrova, Svetlana Guo, Lei Warrington, Janet A. Shi, Leming TI Evaluation of external RNA controls for the assessment of microarray performance SO NATURE BIOTECHNOLOGY LA English DT Article ID CONTROL DATASET; ARRAYS; EXPLORATION AB External RNA controls (ERCs), although important for microarray assay performance assessment, have yet to be fully implemented in the research community. As part of the MicroArray Quality Control (MAQC) study, two types of ERCs were implemented and evaluated; one was added to the total RNA in the samples before amplification and labeling; the other was added to the copyRNAs (cRNAs) before hybridization. ERC concentration-response curves were used across multiple commercial microarray platforms to identify problematic assays and potential sources of variation in the analytical process. In addition, the behavior of different ERC types was investigated, resulting in several important observations, such as the sample-dependent attributes of performance and the potential of using these control RNAs in a combinatorial fashion. This multiplatform investigation of the behavior and utility of ERCs provides a basis for articulating specific recommendations for their future use in evaluating assay performance across multiple platforms. C1 US FDA, Natl Ctr Toxicol Res, Z Tech Corp, Jefferson, AR 72079 USA. Agilent Technol Inc, Santa Clara, CA 95051 USA. GE Healthcare, Tempe, AZ 85284 USA. Zhejiang Univ, Pharmaceut Informat Inst, Hangzhou 310027, Peoples R China. US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. SAS Inst Inc, Cary, NC 27513 USA. Affymetrix Inc, Santa Clara, CA 95051 USA. Appl Biosyst Inc, Foster City, CA 94404 USA. RP Tong, W (reprint author), US FDA, Natl Ctr Toxicol Res, Z Tech Corp, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM weida.tong@fda.hhs.gov RI Guo, Lei/E-9232-2011 NR 19 TC 68 Z9 78 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD SEP PY 2006 VL 24 IS 9 BP 1132 EP 1139 DI 10.1038/nbt1237 PG 8 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 083YK UT WOS:000240495200034 PM 16964227 ER PT J AU Patterson, TA Lobenhofer, EK Fulmer-Smentek, SB Collins, PJ Chu, TM Bao, WJ Fang, H Kawasaki, ES Hager, J Tikhonova, IR Walker, SJ Zhang, LA Hurban, P de Longueville, F Fuscoe, JC Tong, WD Shi, LM Wolfinger, RD AF Patterson, Tucker A. Lobenhofer, Edward K. Fulmer-Smentek, Stephanie B. Collins, Patrick J. Chu, Tzu-Ming Bao, Wenjun Fang, Hong Kawasaki, Ernest S. Hager, Janet Tikhonova, Irina R. Walker, Stephen J. Zhang, Liang Hurban, Patrick de Longueville, Francoise Fuscoe, James C. Tong, Weida Shi, Leming Wolfinger, Russell D. TI Performance comparison of one-color and two-color platforms within the MicroArray Quality Control (MAQC) project SO NATURE BIOTECHNOLOGY LA English DT Article ID GENE-EXPRESSION MEASUREMENTS; OLIGONUCLEOTIDE MICROARRAYS; COMPARABILITY; TECHNOLOGIES; PATTERNS AB Microarray-based expression profiling experiments typically use either a one-color or a two-color design to measure mRNA abundance. The validity of each approach has been amply demonstrated. Here we provide a simultaneous comparison of results from one- and two-color labeling designs, using two independent RNA samples from the MicroArray Quality Control (MAQC) project, tested on each of three different microarray platforms. The data were evaluated in terms of reproducibility, specificity, sensitivity and accuracy to determine if the two approaches provide comparable results. For each of the three microarray platforms tested, the results show good agreement with high correlation coefficients and high concordance of differentially expressed gene lists within each platform. Cumulatively, these comparisons indicate that data quality is essentially equivalent between the one- and two-color approaches and strongly suggest that this variable need not be a primary factor in decisions regarding experimental microarray design. C1 US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Cogenics, Morrisville, NC 27560 USA. Agilent Technol, Integrated Biol Solut, Santa Clara, CA 95052 USA. SAS Inst Inc, Cary, NC 27513 USA. US FDA, Natl Ctr Toxicol Res, ZTech Corp, Jefferson, AR 72079 USA. NCI, Adv Technol Ctr, Bethesda, MD 20892 USA. Yale Univ, WM Keck Biotechnol Resource Lab, New Haven, CT 06511 USA. Wake Forest Univ, Sch Med, Dept Physiol & Pharmacol, Winston Salem, NC 27101 USA. CapitalBio Corp, Beijing 102206, Peoples R China. EAT, Gene Express Chips, B-5000 Namur, Belgium. RP Patterson, TA (reprint author), US FDA, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM tucker.patterson@fda.hhs.gov NR 24 TC 322 Z9 360 U1 3 U2 22 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD SEP PY 2006 VL 24 IS 9 BP 1140 EP 1150 DI 10.1038/nbt1242 PG 11 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 083YK UT WOS:000240495200035 PM 16964228 ER PT J AU Shi, LM Reid, LH Jones, WD Shippy, R Warrington, JA Baker, SC Collins, PJ de Longueville, F Kawasaki, ES Lee, KY Luo, YL Sun, YMA Willey, JC Setterquist, RA Fischer, GM Tong, WD Dragan, YP Dix, DJ Frueh, FW Goodsaid, FM Herman, D Jensen, RV Johnson, CD Lobenhofer, EK Puri, RK Scherf, U Thierry-Mieg, J Wang, C Wilson, M Wolber, PK Zhang, L Amur, S Bao, WJ Barbacioru, CC Lucas, AB Bertholet, V Boysen, C Bromley, B Brown, D Brunner, A Canales, R Cao, XXM Cebula, TA Chen, JJ Cheng, J Chu, TM Chudin, E Corson, J Corton, JC Croner, LJ Davies, C Davison, TS Delenstarr, G Deng, XT Dorris, D Eklund, AC Fan, XH Fang, H Fulmer-Smentek, S Fuscoe, JC Gallagher, K Ge, WG Guo, L Guo, X Hager, J Haje, PK Han, J Han, T Harbottle, HC Harris, SC Hatchwell, E Hauser, CA Hester, S Hong, HX Hurban, P Jackson, SA Ji, HL Knight, CR Kuo, WP LeClerc, JE Levy, S Li, QZ Liu, CM Liu, Y Lombardi, MJ Ma, YQ Magnuson, SR Maqsodi, B McDaniel, T Mei, N Myklebost, O Ning, BT Novoradovskaya, N Orr, MS Osborn, TW Papallo, A Patterson, TA Perkins, RG Peters, EH Peterson, R Philips, KL Pine, PS Pusztai, L Qian, F Ren, HZ Rosen, M Rosenzweig, BA Samaha, RR Schena, M Schroth, GP Shchegrova, S Smith, DD Staedtler, F Su, ZQ Sun, HM Szallasi, Z Tezak, Z Thierry-Mieg, D Thompson, KL Tikhonova, I Turpaz, Y Vallanat, B Van, C Walker, SJ Wang, SJ Wang, YH Wolfinger, R Wong, A Wu, J Xiao, CL Xie, Q Xu, J Yang, W Zhang, L Zhong, S Zong, YP Slikker, W AF Shi, Leming Reid, Laura H. Jones, Wendell D. Shippy, Richard Warrington, Janet A. Baker, Shawn C. Collins, Patrick J. de Longueville, Francoise Kawasaki, Ernest S. Lee, Kathleen Y. Luo, Yuling Sun, Yongming Andrew Willey, James C. Setterquist, Robert A. Fischer, Gavin M. Tong, Weida Dragan, Yvonne P. Dix, David J. Frueh, Felix W. Goodsaid, Federico M. Herman, Damir Jensen, Roderick V. Johnson, Charles D. Lobenhofer, Edward K. Puri, Raj K. Scherf, Uwe Thierry-Mieg, Jean Wang, Charles Wilson, Mike Wolber, Paul K. Zhang, Lu Amur, Shashi Bao, Wenjun Barbacioru, Catalin C. Lucas, Anne Bergstrom Bertholet, Vincent Boysen, Cecilie Bromley, Bud Brown, Donna Brunner, Alan Canales, Roger Cao, Xiaoxi Megan Cebula, Thomas A. Chen, James J. Cheng, Jing Chu, Tzu-Ming Chudin, Eugene Corson, John Corton, J. Christopher Croner, Lisa J. Davies, Christopher Davison, Timothy S. Delenstarr, Glenda Deng, Xutao Dorris, David Eklund, Aron C. Fan, Xiao-hui Fang, Hong Fulmer-Smentek, Stephanie Fuscoe, James C. Gallagher, Kathryn Ge, Weigong Guo, Lei Guo, Xu Hager, Janet Haje, Paul K. Han, Jing Han, Tao Harbottle, Heather C. Harris, Stephen C. Hatchwell, Eli Hauser, Craig A. Hester, Susan Hong, Huixiao Hurban, Patrick Jackson, Scott A. Ji, Hanlee Knight, Charles R. Kuo, Winston P. LeClerc, J. Eugene Levy, Shawn Li, Quan-Zhen Liu, Chunmei Liu, Ying Lombardi, Michael J. Ma, Yunqing Magnuson, Scott R. Maqsodi, Botoul McDaniel, Tim Mei, Nan Myklebost, Ola Ning, Baitang Novoradovskaya, Natalia Orr, Michael S. Osborn, Terry W. Papallo, Adam Patterson, Tucker A. Perkins, Roger G. Peters, Elizabeth H. Peterson, Ron Philips, Kenneth L. Pine, P. Scott Pusztai, Lajos Qian, Feng Ren, Hongzu Rosen, Mitch Rosenzweig, Barry A. Samaha, Raymond R. Schena, Mark Schroth, Gary P. Shchegrova, Svetlana Smith, Dave D. Staedtler, Frank Su, Zhenqiang Sun, Hongmei Szallasi, Zoltan Tezak, Zivana Thierry-Mieg, Danielle Thompson, Karol L. Tikhonova, Irina Turpaz, Yaron Vallanat, Beena Van, Christophe Walker, Stephen J. Wang, Sue Jane Wang, Yonghong Wolfinger, Russ Wong, Alex Wu, Jie Xiao, Chunlin Xie, Qian Xu, Jun Yang, Wen Zhang, Liang Zhong, Sheng Zong, Yaping Slikker, William, Jr. CA MAQC Consortium TI The MicroArray Quality Control (MAQC) project shows inter- and intraplatform reproducibility of gene expression measurements SO NATURE BIOTECHNOLOGY LA English DT Article ID EXTERNAL RNA CONTROLS; PLATFORM CONSISTENCY; PERFORMANCE; CANCER; COMPARABILITY; GENOMICS AB Over the last decade, the introduction of microarray technology has had a profound impact on gene expression research. The publication of studies with dissimilar or altogether contradictory results, obtained using different microarray platforms to analyze identical RNA samples, has raised concerns about the reliability of this technology. The MicroArray Quality Control (MAQC) project was initiated to address these concerns, as well as other performance and data analysis issues. Expression data on four titration pools from two distinct reference RNA samples were generated at multiple test sites using a variety of microarray-based and alternative technology platforms. Here we describe the experimental design and probe mapping efforts behind the MAQC project. We show intraplatform consistency across test sites as well as a high level of interplatform concordance in terms of genes identified as differentially expressed. This study provides a resource that represents an important first step toward establishing a framework for the use of microarrays in clinical and regulatory settings. C1 US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Express Anal Inc, Durham, NC 27713 USA. GE Healthcare, Tempe, AZ 85284 USA. Affymetrix Inc, Santa Clara, CA 95051 USA. Illuminia Inc, San Diego, CA 92121 USA. Agilent Technol, Santa Clara, CA 95051 USA. Eppendorf Array Technol, B-5000 Namur, Belgium. NCI, Ctr Adv Technol, Bethesda, MD 20892 USA. Appl Biosyst Inc, Foster City, CA 94404 USA. Panomics Inc, Fremont, CA 94555 USA. Med Univ Ohio, Toledo, OH 43614 USA. Ambion, Austin, TX 78744 USA. Stratagene Corp, La Jolla, CA 92130 USA. US EPA, Off Res & Dev, Res Triangle Pk, NC 27711 USA. US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. Univ Massachusetts, Boston, MA 02125 USA. Asuragen Inc, Austin, TX 78744 USA. Cogenics, Morrisville, NC 27560 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. Univ Calif Los Angeles, Cedars Sinai Med Ctr, David Geffen Sch Med, Los Angeles, CA 90048 USA. Solexa Inc, Hayward, CA 94545 USA. SAS Inst Inc, Cary, NC 27513 USA. ViaLogy Corp, Altadena, CA 91001 USA. Operon Biotechnol, Huntsville, AL 35805 USA. Z Tech Corp, Jefferson, AR 72079 USA. US FDA, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. CapitalBio Corp, Beijing 102206, Peoples R China. Biogen Idec Inc, San Diego, CA 92122 USA. US EPA, Off Sci Advisor, Washington, DC 20460 USA. Yale Univ, WM Keck Biotechnol Resource Lab, New Haven, CT 06511 USA. TeleChem Arraylt, Sunnyvale, CA 94089 USA. US FDA, Ctr Vet Med, Laurel, MD 20708 USA. Cold Spring Harbor Lab, Woodbury, NY 11797 USA. Burnham Inst, La Jolla, CA 92037 USA. Stanford Univ, Sch Med, Stanford, CA 94305 USA. Gene Express Inc, Toledo, OH 43614 USA. Harvard Univ, Sch Dent Med, Dept Dev Biol, Boston, MA 02115 USA. Vanderbilt Univ, Nashville, TN 37232 USA. Univ Texas, SW Med Ctr, Dallas, TX 75390 USA. Univ Texas, Dept Comp Sci, Richardson, TX 75083 USA. GenUs BioSyst Inc, Northbrook, IL 60062 USA. Natl Hosp Norway, Radium Hosp Hlth Ctr, Norwegian Microarray Consortium, N-0310 Oslo, Norway. Novartis, Cambridge, MA 02139 USA. MD Anderson Canc Ctr, Breast Med Oncol Dept, Unit 1354, Houston, TX 77230 USA. Luminex Corp, Austin, TX 78727 USA. Harvard Univ, Sch Med, Childrens Hosp, Informat Program,Harvard MIT Div Hlth Sci & Tech, Boston, MA 02115 USA. Wake Forest Univ, Sch Med, Dept Physiol & Pharmacol, Winston Salem, NC 27157 USA. Univ Illinois, Dept Bioengn, Urbana, IL 61801 USA. Full Moon Biosyst Inc, Sunnyvale, CA 94085 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 RI Guo, Lei/E-9232-2011; Myklebost, Ola/E-9335-2010; mei, nan/E-8915-2011; Su, Zhenqiang/H-3914-2012; THIERRY-MIEG, Jean/F-1975-2017; OI Myklebost, Ola/0000-0002-2866-3223; mei, nan/0000-0002-3501-9014; THIERRY-MIEG, Jean/0000-0002-0396-6789; Szallasi, Zoltan/0000-0001-5395-7509; Johnson, Charles/0000-0003-3892-7082; Eklund, Aron Charles/0000-0003-0861-1001; Croner, Lisa/0000-0002-3921-1484 FU Intramural NIH HHS [Z99 LM999999] NR 41 TC 1187 Z9 1242 U1 7 U2 84 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD SEP PY 2006 VL 24 IS 9 BP 1151 EP 1161 DI 10.1038/nbt1239 PG 11 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 083YK UT WOS:000240495200036 PM 16964229 ER PT J AU Guo, L Lobenhofer, EK Wang, C Shippy, R Harris, SC Zhang, L Mei, N Chen, T Herman, D Goodsaid, FM Hurban, P Phillips, KL Xu, J Deng, XT Sun, YMA Tong, WD Dragan, YP Shi, LM AF Guo, Lei Lobenhofer, Edward K. Wang, Charles Shippy, Richard Harris, Stephen C. Zhang, Lu Mei, Nan Chen, Tao Herman, Damir Goodsaid, Federico M. Hurban, Patrick Phillips, Kenneth L. Xu, Jun Deng, Xutao Sun, Yongming Andrew Tong, Weida Dragan, Yvonne P. Shi, Leming TI Rat toxicogenomic study reveals analytical consistency across microarray platforms SO NATURE BIOTECHNOLOGY LA English DT Article ID PYRROLIZIDINE SENECIO ALKALOIDS; BIG BLUE RATS; GENE-EXPRESSION; ARISTOLOCHIC ACID; VITAMIN-A; COPPER; METABOLISM; LIVER; MUTAGENICITY; RIDDELLIINE AB To validate and extend the findings of the MicroArray Quality Control (MAQC) project, a biologically relevant toxicogenomics data set was generated using 36 RNA samples from rats treated with three chemicals (aristolochic acid, riddelliine and comfrey) and each sample was hybridized to four microarray platforms. The MAQC project assessed concordance in intersite and cross-platform comparisons and the impact of gene selection methods on the reproducibility of profiling data in terms of differentially expressed genes using distinct reference RNA samples. The real-world toxicogenomic data set reported here showed high concordance in intersite and cross-platform comparisons. Further, gene lists generated by fold-change ranking were more reproducible than those obtained by t-test P value or Significance Analysis of Microarrays. Finally, gene lists generated by fold-change ranking with a nonstringent P-value cutoff showed increased consistency in Gene Ontology terms and pathways, and hence the biological impact of chemical exposure could be reliably deduced from all platforms analyzed. C1 US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Cogenics, Div Clin Data A, Morrisville, NC 27560 USA. Univ Calif Los Angeles, Cedars Sinai Med Ctr, David Geffen Sch Med, Transcript Genom Core, Los Angeles, CA 90048 USA. GE Healthcare, Tempe, AZ 85284 USA. Solexa, Hayward, CA 94545 USA. Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. Appl Biosyst Inc, Foster City, CA 94404 USA. RP Guo, L (reprint author), US FDA, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM lei.guo@fda.hhs.gov; leming.shi@fda.hhs.gov RI Guo, Lei/E-9232-2011; mei, nan/E-8915-2011 OI mei, nan/0000-0002-3501-9014 NR 30 TC 272 Z9 287 U1 1 U2 27 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD SEP PY 2006 VL 24 IS 9 BP 1162 EP 1169 DI 10.1038/nbt1238 PG 8 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 083YK UT WOS:000240495200037 PM 17061323 ER PT J AU Banoo, S Bell, D Bossuyt, P Herring, A Mobey, D Poole, F Smith, PG Sriram, N Wongsrichonalai, C Linke, R O'Brien, R Perkins, M Cunningham, J Matsoso, P Nathanson, CM Olliaro, P Peeling, RW Ramsay, A AF Banoo, Shabir Bell, David Bossuyt, Patrick Herring, Alan Mobey, David Poole, Freddie Smith, Peter G. Sriram, N. Wongsrichonalai, Chansudo Linke, Ralf O'Brien, Rick Perkins, Mark Cunningham, Jane Matsoso, Precious Nathanson, Carl Michael Olliaro, Piero Peeling, Rosanna W. Ramsay, Andy TI Evaluation of diagnostic tests for infectious diseases: general principles SO NATURE REVIEWS MICROBIOLOGY LA English DT Review ID ACCURACY; MEDICINE C1 Med Control Council S Africa, Pretoria, South Africa. WHO, Reg Off Western Pacific, Malaria & Other Vectorborne & Parasit Dis, Manila, Philippines. Univ Amsterdam, Acad Med Ctr, Dept Clin Epidemiol & Biostat, NL-1012 WX Amsterdam, Netherlands. Univ Bristol, Sch Vet, Bristol BS8 1TH, Avon, England. Univ London London Sch Hyg & Trop Med, Clin Res Unit, London WC1E 7HT, England. US FDA, Div Microbiol Devices, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. Univ London London Sch Hyg & Trop Med, Infect Dis Epidemiol Unit, London WC1E 7HT, England. USN, Med Res Unit 2, Jakarta, Indonesia. Fdn Innovat Diagnost FIND, Geneva, Switzerland. WHO, Special Programme Res & Training Trop Dis TDR, UNICEF, UNDP,World Bank, CH-1211 Geneva, Switzerland. RP Banoo, S (reprint author), Med Control Council S Africa, Pretoria, South Africa. EM peelingr@who.int RI Bossuyt, Patrick/B-4557-2016 OI Bossuyt, Patrick/0000-0003-4427-0128 NR 16 TC 5 Z9 7 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1740-1526 J9 NAT REV MICROBIOL JI Nat. Rev. Microbiol. PD SEP PY 2006 SU S BP S21 EP S33 DI 10.1038/nrmico1523 PG 13 WC Microbiology SC Microbiology GA 085RS UT WOS:000240622700004 PM 17034069 ER PT J AU Frueh, FW Rudman, A Simon, K Gutman, S Reed, C Dorner, AJ AF Frueh, F. W. Rudman, A. Simon, K. Gutman, S. Reed, C. Dorner, A. J. TI Experience with voluntary and required genomic data submissions to the FDA: summary report from track 1 of the third FDA-DIA-PWG-PhRMA-BIO pharmacogenomics workshop SO PHARMACOGENOMICS JOURNAL LA English DT Article ID REGULATORY DECISION-MAKING; DRUG DEVELOPMENT C1 US FDA, Off Clin Pharmacol & Biopharmaceut, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. US FDA, Off In Vitro Diagnost Device Evaluat & Safety, Ctr Devices & Radiol Hlth, Rockville, MD USA. Genaissance Pharmacuet, New Haven, CT USA. Wyeth Ayerst Res, Cambridge, MA USA. RP Frueh, FW (reprint author), US FDA, Off Clin Pharmacol & Biopharmaceut, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave,Bldg 21,Room 4512, Silver Spring, MD 20993 USA. EM Felix.Frueh@FDA.gov NR 5 TC 8 Z9 10 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1470-269X J9 PHARMACOGENOMICS J JI Pharmacogenomics J. PD SEP-OCT PY 2006 VL 6 IS 5 BP 296 EP 300 DI 10.1038/sj.tpj.6500380 PG 5 WC Genetics & Heredity; Pharmacology & Pharmacy SC Genetics & Heredity; Pharmacology & Pharmacy GA 096NK UT WOS:000241383900002 PM 16568150 ER PT J AU Pereira, FC Lourenco, ES Borges, F Morgadinho, T Ribeiro, CF Macedo, TR Ali, SF AF Pereira, Frederico Costa Lourenco, Elita Santos Borges, Fernanda Morgadinho, Teresa Ribeiro, Carlos Fontes Macedo, Tice Reis Ali, Syed F. TI Single or multiple injections of methamphetamine increased dopamine turnover but did not decrease tyrosine hydroxylase levels or cleave caspase-3 in caudate-putamen SO SYNAPSE LA English DT Article DE methamphetamine; nigrostriatal pathway; dopamine; Bax; apoptosis ID APOPTOSIS-INDUCING FACTOR; INDUCED NEUROTOXICITY; NEURONAL APOPTOSIS; CELL-DEATH; ENVIRONMENTAL-TEMPERATURE; STRIATAL DOPAMINE; TERMINAL MARKERS; CYTOCHROME-C; RELEASE; MICE AB Methamphetamine (METH), leading to striatal dopamine (DA) nerve terminal toxicity in mammals, is also thought to induce apoptosis of striatal neurons in rodents. We investigated the acute effects induced by multiple injections of METH (4 X 5 mg/kg, i.p.) at 2-h intervals or a single injection of METH (20 mg/kg, i.p.) on terminal dopaminergic toxicity markers, including DA levels, DA turnover, and tyrosine hydroxylase (TH) immunoreactivity in rat caudate-putamen (CPu). We further investigated whether both treatment paradigms would change Bax and activate caspase-3 expression, thus triggering striatal apoptotic mitochondria-dependent biochemical cascades. The first injection of METH (5 mg/kg, i.p.) produced a significant release of DA that peaked 30 min and stayed above control levels up to 1.5 h within CPu. In another set of experiments, rats were killed 1 and 24 h following the last injection, for tissue DA and metabolite content measurement and Western blot analysis (24 h). Multiple doses induced DA depletion and increased turnover at both endpoints. Single-dose METH reproduced these effects at 24 h; however, turnover was significantly higher than that evoked by the multiple doses at 24 h. Although both paradigms evoked similar DA depletion, however, none of the dosing regimens induced changes in TH expression at 24 h. The former paradigm produced an increase in Bax expression in CPu not sufficient to induce cleavage of caspase-3 proenzyme at 24 h. This study suggests that both paradigm induced changes in striatal dopaminergic markers that are independent of terminal degeneration and striatal apoptotic mitochondria-dependent caspase-3 driven cascade within 24 h. C1 US FDA, NCTR, Div Neurotoxicol, Neurochem Lab, Jefferson, AR 72079 USA. Univ Coimbra, Fac Med, Inst Pharmacol & Therapeut, P-3004504 Coimbra, Portugal. Univ Porto, Fac Pharm, Dept Organ Chem, P-405047 Oporto, Portugal. RP Ali, SF (reprint author), US FDA, NCTR, Div Neurotoxicol, Neurochem Lab, HFT-132, Jefferson, AR 72079 USA. EM sali@nctr.fda.gov RI Borges, Fernanda /A-5200-2014; OI Borges, Fernanda /0000-0003-1050-2402; Pereira, Frederico/0000-0002-9381-3320; Fontes Ribeiro, Carlos/0000-0002-9707-4895 NR 46 TC 24 Z9 24 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0887-4476 J9 SYNAPSE JI Synapse PD SEP 1 PY 2006 VL 60 IS 3 BP 185 EP 193 DI 10.1002/syn.20285 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 061SY UT WOS:000238894100001 PM 16739116 ER PT J AU Dnyanmote, AV Sawant, SP Lock, EA Latendresse, JR Warbritton, AA Mehendale, HM AF Dnyanmote, Ankur V. Sawant, Sharmilee P. Lock, Edward A. Latendresse, John R. Warbritton, Alan A. Mehendale, Harihara M. TI Calpastatin overexpression prevents progression of S-1.2-dichlorovinyl-L-cysteine (DCVC)-initiated acute renal injury and renal failure (ARF) in diabetes SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE acute renal failure; calpastatin; calpain; diabetes; progression of injury; tissue repair ID PROXIMAL TUBULAR INJURY; CYSTEINE PROTEASES; CELL INJURY; MEDIATES PROGRESSION; REPERFUSION INJURY; NEUTRAL PROTEASE; CALPAIN ACTIVITY; LIVER-INJURY; CALCIUM; HEPATOCYTES AB Previously we have shown that 90% of streptozotocin (STZ)-induced type-1 diabetic (DB) mice survive from acute renal failure (ARF) and death induced by a normally LD90 dose (75 mg/kg, i.p.) of the nephrotoxicant S-1,2-dichlorovinyl-L-eysteine (DCVC). This remarkable protection is due to a combination of slower progression of DCVC-initiated renal injury and increased compensatory nephrogenic tissue repair in the DB kidneys. BRDU immunohistochemistry revealed that the DB condition led to 4-fold higher number of proximal tubular cells (PTC) entering S-phase of cell cycle. In the present study, we tested the hypothesis that DB-induced augmentation of PTC into S-phase is accompanied by overexpression of the calpain-inhibitor calpastatin, which endogenously prevents the progression of DCVC-initiated renal injury mediated by the calpain escaping out of damaged PTCs. Immumohistochemical detection of renal calpain and its activity in the urine, over a time course after treatment with the LD50 dose of DCVC, indicated progressive increase in leakage of calpain into the extracellular spaces of the injured PTCs of the non-diabetic (NDB) kidneys as compared to the DB kidneys. Calpastatin expression was minimally detected in the NDB kidneys, using immumohistochemistry, over the time course. On the other hand, consistently higher number of tubules in the DB kidney showed calpastatin expression over the time course. The lower leakage of calpain in the DB kidneys was commensurate with constitutively higher expression of calpastatin in the S-phase-laden PTCs of these mice. To test the protective role of newly divided/dividing PTCs, DB mice were given the antimitotic agent colchicine (CLC) (2 mg/kg and 1.5 mg/kg, i.p., on days 8 and 10 after STZ injection) prior to challenge with a LD90 dose of DCVC, which led to 100% mortality by 48 h. Mortality was due to rapid progression of DCVC-initiated renal injury, suggesting that newly divided/ dividing cells are instrumental in mitigating the progression of DCVC-initiated renal injury in DB. The anti-mitotic effect of CLC in DB kidney was associated with lower expression of calpastatin and higher leakage of calpain in the injured tubules. These findings suggest that constitutively higher cell division in the DB kidney is associated with overexpression of calpastatin, which reduces the progression of DCVC-initiated renal injury mediated by calpain on the one hand and accelerates nephrogenic tissue repair on the other, thereby restoring renal structure and function. (c) 2006 Elsevier Inc. All rights reserved. C1 NE Louisiana Univ, Coll Pharm, Dept Toxicol, Monroe, LA 71209 USA. Univ Liverpool, Sch Biomol Sci, Liverpool L3 3AF, Merseyside, England. Natl Ctr Toxicol Res, Toxicol Pathol Assoc, Jefferson, AR 72079 USA. RP Mehendale, HM (reprint author), NE Louisiana Univ, Coll Pharm, Dept Toxicol, 700 Univ Ave, Monroe, LA 71209 USA. EM mehendale@ulm.edu RI Latendresse, John/A-9215-2009 NR 40 TC 3 Z9 3 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD SEP 1 PY 2006 VL 215 IS 2 BP 146 EP 157 DI 10.1016/j.taap.2006.01.018 PG 12 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 080IW UT WOS:000240242100003 PM 16546232 ER PT J AU Chou, MW Fu, PP AF Chou, Ming W. Fu, Peter P. TI Formation of DHP-derived DNA adducts in vivo from dietary supplements and Chinese herbal plant extracts containing carcinogenic pyrrolizidine alkaloids SO TOXICOLOGY AND INDUSTRIAL HEALTH LA English DT Article DE dietary supplement; DNA adduct; pyrrolizidine alkaloid; riddelhine ID METABOLIC-ACTIVATION; TUSSILAGO-FARFARA; RIDDELLIINE; SENKIRKINE; TOXICITY; COMFREY AB We recently determined that the metabolism of a series of tumorigenic pyrrolizidine alkaloids resulted in the formation of a set of 6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine (DHP)derived DNA adducts. These DHP-derived DNA adducts have been proposed as potential biomarkers of pyrrolizidine alkaloid tumorigenicity, as well as pyrrolizidine alkaloid exposure. In this paper, we report that DHP-derived DNA adducts are formed in the liver of female F344 rats, gavaged with three dietary supplements (comfrey root extract, comfrey compound oil, and coltsfoot root extract), or an extract of a Chinese herbal plant, flos farfara (Kuan Tong Hua). C1 Natl Ctr Toxicol Res, Div Biochem Res, Jefferson, AR 72079 USA. RP Chou, MW (reprint author), Natl Ctr Toxicol Res, Div Biochem Res, HFT-140, Jefferson, AR 72079 USA. EM mchou@nctr.fda.gov NR 26 TC 28 Z9 29 U1 0 U2 9 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0748-2337 J9 TOXICOL IND HEALTH JI Toxicol. Ind. Health PD SEP PY 2006 VL 22 IS 8 BP 321 EP 327 DI 10.1177/0748233706071765 PG 7 WC Public, Environmental & Occupational Health; Toxicology SC Public, Environmental & Occupational Health; Toxicology GA 097EX UT WOS:000241430800001 PM 17120530 ER PT J AU McGovern, T Jacobson-Kram, D AF McGovern, Timothy Jacobson-Kram, David TI Regulation of genotoxic and carcinogenic impurities in drug substances and products SO TRAC-TRENDS IN ANALYTICAL CHEMISTRY LA English DT Article DE carcinogenic; genotoxic; impurity; pharmaceutical; regulation ID ACTIVE PHARMACEUTICAL INGREDIENTS; NATIONAL-TOXICOLOGY-PROGRAM; CHEMICAL-STRUCTURE; CLASSIFICATION; MUTAGENICITY; SALMONELLA; LEVEL; MS AB While the use of pharmaceuticals is always a balance of risks and benefits, the same is not true for impurities in pharmaceuticals; impurities carry only risk. A number of international guidelines and regional guidance documents instruct drug developers and regulatory agencies on how to evaluate and to control impurities in drug substances and drug products. These guidelines explicitly identify triggers for reporting, identifying and qualifying impurities. In addition, the guidelines provide direction on the assays that should be used to determine if impurities are genotoxic. However, the guidelines fail to provide direction on how levels of genotoxic impurities should be controlled. This article discusses practical and theoretical methods for controlling levels of genotoxic impurities in drug substances and drug products. Published by Elsevier Ltd. C1 US FDA, Off New Drugs, Silver Spring, MD 20993 USA. US FDA, Div Pulm & Allergy Prod, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Jacobson-Kram, D (reprint author), US FDA, Off New Drugs, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM david.jacobsonkram@fda.hhs.gov NR 19 TC 61 Z9 63 U1 0 U2 4 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 SEP PY 2006 VL 25 IS 8 BP 790 EP 795 DI 10.1016/j.trac.2006.06.004 PG 6 WC Chemistry, Analytical SC Chemistry GA 090OW UT WOS:000240961600015 ER PT J AU Grinev, A Daniel, S Stramer, SL Hewlett, IK Rossmann, SN Caglioti, S Rios, M AF Grinev, A. Daniel, S. Stramer, S. L. Hewlett, I. K. Rossmann, S. N. Caglioti, S. Rios, M. TI Genetic variability of West Nile virus (WNV) in human infection SO TRANSFUSION LA English DT Meeting Abstract CT 59th Annual Meeting of the American-Association-of-Blood-Banks (AABB 2006) CY OCT 21-24, 2006 CL Miami Beach, FL SP Amer Assoc Blood Banks C1 CBER FDA, Bethesda, MD USA. Amer Red Cross, Gaithersburg, MD USA. Gulf Coast Reg Blood Ctr, Houston, TX USA. Blood Syst Labs, Tempe, AZ USA. EM Maria.Rios@fda.hhs.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 2006 VL 46 IS 9 SU S BP 26A EP 26A PG 1 WC Hematology SC Hematology GA 084SG UT WOS:000240554100078 ER PT J AU Rios, M Daniel, S Wood, O Hewlett, IK Caglioti, S Stramer, SL AF Rios, M. Daniel, S. Wood, O. Hewlett, I. K. Caglioti, S. Stramer, S. L. TI Update on investigations of the infectivity of West Nile virus (WNV) in the presence of human specific antibodies to WNV SO TRANSFUSION LA English DT Meeting Abstract CT 59th Annual Meeting of the American-Association-of-Blood-Banks (AABB 2006) CY OCT 21-24, 2006 CL Miami Beach, FL SP Amer Assoc Blood Banks C1 CBER FDA, Bethesda, MD USA. Blood Syst labs, Tempe, AZ USA. Amer Red Cross, Gaithersburg, MD USA. EM Maria.Rios@fda.hhs.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 2006 VL 46 IS 9 SU S BP 26A EP 26A PG 1 WC Hematology SC Hematology GA 084SG UT WOS:000240554100077 ER PT J AU Holness, L Simmons, L Knippen, M AF Holness, L. Simmons, L. Knippen, M. TI Transfusion related fatalities due to mistransfusion SO TRANSFUSION LA English DT Meeting Abstract CT 59th Annual Meeting of the American-Association-of-Blood-Banks (AABB 2006) CY OCT 21-24, 2006 CL Miami Beach, FL SP Amer Assoc Blood Banks C1 US FDA, Off Blood Res & Review Div Blood Applicat, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. US FDA, Off Compliance & Biol Qual, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. EM leslie.holness@fda.hhs.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 2006 VL 46 IS 9 SU S BP 88A EP 89A PG 2 WC Hematology SC Hematology GA 084SG UT WOS:000240554100273 ER PT J AU Golding, H Park, S Nemo, G Todd, DS Busch, MP Khurana, S AF Golding, H. Park, S. Nemo, G. Todd, D. S. Busch, M. P. Khurana, S. TI Evaluation of a new immunoassay for differential diagnosis of HIV infections in the face of vaccine-induced antibodies SO TRANSFUSION LA English DT Meeting Abstract CT 59th Annual Meeting of the American-Association-of-Blood-Banks (AABB 2006) CY OCT 21-24, 2006 CL Miami Beach, FL SP Amer Assoc Blood Banks C1 US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. NHLBI, NIH, Bethesda, MD 20892 USA. Blood Syst & Res Inst, San Francisco, CA USA. EM hana.golding@fda.hhs.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 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 2006 VL 46 IS 9 SU S BP 104A EP 104A PG 1 WC Hematology SC Hematology GA 084SG UT WOS:000240554100321 ER PT J AU Yang, H Anderson, SA AF Yang, H. Anderson, S. A. TI Risk assessment modeling methods for estimation of potential variant Creutzfeldt-Jakob disease (vCJD) risk among US donors SO TRANSFUSION LA English DT Meeting Abstract CT 59th Annual Meeting of the American-Association-of-Blood-Banks (AABB 2006) CY OCT 21-24, 2006 CL Miami Beach, FL SP Amer Assoc Blood Banks C1 US FDA, CBER, Rockville, MD 20857 USA. EM yangh@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 2006 VL 46 IS 9 SU S BP 109A EP 109A PG 1 WC Hematology SC Hematology GA 084SG UT WOS:000240554100336 ER PT J AU Srinivasan, K Akolkar, PN Taffs, RE Hewlett, IK AF Srinivasan, Kumar Akolkar, Pradip N. Taffs, Rolf E. Hewlett, Indira K. TI Absence of detectable viremia in plasma and peripheral blood mononuclear cells from smallpox vaccinees: implications for blood safety SO TRANSFUSION LA English DT Article AB BACKGROUND: Mass smallpox vaccination with live vaccinia virus has been considered as a preventive measure to counter bioterrorism involving smallpox. This has raised concerns about the possibility of vaccinia virus being transmitted from vaccinated blood donors to recipients. The results of this study could be used to define an appropriate deferral period for blood donors (vaccinated against smallpox) to ensure safety of the blood supply. STUDY DESIGN AND METHODS: A procedure was developed to culture vaccinia virus from plasma and peripheral blood mononuclear cells (PBMNCs) of vaccinees enrolled in three smallpox vaccine clinical trials. A total of 665 plasma and PBMNC samples were obtained from 95 vaccinated subjects. RESULTS: Vaccinia viremia was not detected by virus culture from plasma and PBMNC samples of healthy vaccinees 3 to 56 days after vaccination under our assay conditions. Plasma viremia assay had a sensitivity of approximately 66 plaque-forming units per mL with a Vero cell culture assay. CONCLUSION: The results of this study present evidence that in the case of mass vaccination, the risk of transmission of vaccinia virus by blood transfusion would likely be low. C1 DETTD, CBER, FDA, HFM 315,Lab Mol Virol, Rockville, MD 20852 USA. US FDA, Lab Bacterial Parasit & Unconvent Agents, OBRR, CBER, Rockville, MD 20857 USA. RP Srinivasan, K (reprint author), DETTD, CBER, FDA, HFM 315,Lab Mol Virol, 1401 Rockville Pike, Rockville, MD 20852 USA. EM kumar.srinivasan@fda.hhs.gov NR 7 TC 6 Z9 6 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 2006 VL 46 IS 9 BP 1589 EP 1592 DI 10.1111/j.1537-2995.2006.00936.x PG 4 WC Hematology SC Hematology GA 079AD UT WOS:000240147000021 PM 16965588 ER PT J AU Switzer, WM Hewlett, I Aaron, L Wolfe, ND Burke, DS Heneine, W AF Switzer, William M. Hewlett, Indira Aaron, Leslyn Wolfe, Nathan D. Burke, Donald S. Heneine, Walid TI Serologic testing for human T-lymphotropic virus-3 and-4 SO TRANSFUSION LA English DT Letter ID EPIDEMIOLOGY C1 Ctr Dis Control & Prevent, Lab Branch, Div HIV AIDS Prevent, Natl Ctr HIV Hepatitis STD & TB Prevent, Atlanta, GA USA. FDA, Lab Mol Virol, Div Emerging & Transfus Transmitted Dis, OBRR,CBER, Rockville, MD USA. Johns Hopkins Univ, Dept Epidemiol Int Hlth, Bloomberg Sch Publ Hlth, Baltimore, MD USA. RP Switzer, WM (reprint author), Ctr Dis Control & Prevent, Lab Branch, Div HIV AIDS Prevent, Natl Ctr HIV Hepatitis STD & TB Prevent, Atlanta, GA USA. EM bis3@cdc.gov NR 6 TC 12 Z9 13 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 2006 VL 46 IS 9 BP 1647 EP 1648 DI 10.1111/j.1537-2995.2006.00950.x PG 2 WC Hematology SC Hematology GA 079AD UT WOS:000240147000029 PM 16965596 ER PT J AU Dayton, AI AF Dayton, Andrew I. TI Commentary - Beyond open access: open discourse, the next great equalizer SO RETROVIROLOGY LA English DT Editorial Material AB The internet is expanding the realm of scientific publishing to include free and open public debate of published papers. Journals are beginning to support web posting of comments on their published articles and independent organizations are providing centralized web sites for posting comments about any published article. The trend promises to give one and all access to read and contribute to cutting edge scientific criticism and debate. C1 US FDA, Ctr Biol Evaluat & Res, Div Emerging & Transfus Transmitted Dis, Mol Virol Lab, Rockville, MD 20852 USA. RP Dayton, AI (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Emerging & Transfus Transmitted Dis, Mol Virol Lab, HFM 315,1401 Rockville Pike, Rockville, MD 20852 USA. EM dayton@cber.fda.gov NR 1 TC 4 Z9 6 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PD AUG 30 PY 2006 VL 3 AR 55 DI 10.1186/1742-4690-3-55 PG 3 WC Virology SC Virology GA 088NN UT WOS:000240818500001 PM 17007632 ER PT J AU de Jager, LS Perfetti, GA Diachenko, GW AF de Jager, Lowri S. Perfetti, Gracia A. Diachenko, Gregory W. TI Analysis of ginkgolides and bilobalide in food products using LC-APCI-MS SO JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS LA English DT Article DE Ginkgo biloba; Ginkgo; ginkgolide; bilobalide; LC-MS; food analysis ID LIGHT-SCATTERING DETECTION; LIQUID-CHROMATOGRAPHY; TERPENE LACTONES; LEAF EXTRACTS; L. EXTRACT; SPECTROMETRY AB A method was developed for the extraction and quantification of five marker compounds characteristic of Ginkgo biloba. Five ginkgo terpene trilactones: bilobalide and ginkgolides A, B, C, and J, were selected as marker compounds for this study. Initial studies produced a simple methanol extraction method for determination of gingko markers in solid dietary supplements. Five dietary supplements were analyzed and the results were later compared to the concentrations detected in the analysis of beverages. Beverage samples were prepared by extracting the ginkgo terpene trilactones using an optimized solid phase extraction (SPE) method. The extracts were analyzed using LC-atmospheric pressure chemical ionization (APCI)-MS in the negative ionization mode. The limits of detection of the extraction method ranged from 6.8 to 3.2 ng mL(-1). Using the optimized method, 14 drinks and 3 tea products were analyzed. Concentrations of total marker compounds in drinks ranged between 1685 and 21.4 ng mL(-1) with individual ginkgo terpene trilactones being detected at ppb concentrations. Analysis of brewed tea products presented much higher total marker compound concentrations ranging from 8.12 and 16.6 Rg mL(-1). Analytical results reproducibility data, and recovery of the SPE method are presented. (c) Published by Elsevier B.V. C1 US FDA, College Pk, MD USA. RP de Jager, LS (reprint author), US FDA, 5100 Paint Branch Pkwy, College Pk, MD USA. EM ldejager@cfsan.fda.gov NR 14 TC 8 Z9 8 U1 1 U2 10 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 AUG 28 PY 2006 VL 41 IS 5 BP 1552 EP 1559 DI 10.1016/j.jpba.2005.11.023 PG 8 WC Chemistry, Analytical; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 095YI UT WOS:000241343800007 PM 16459046 ER PT J AU Reepmeyer, JC Woodruff, JT AF Reepmeyer, John C. Woodruff, Jeffrey T. TI Use of liquid chromatography-mass spectrometry and a hydrolytic technique for the detection and structure elucidation of a novel synthetic vardenafil designer drug added illegally to a "natural" herbal dietary supplement SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article DE vardenafil; erectile dysfunction; phosphodiesterase-5 inhibitor; dietary supplement; piperidenafil; herbal; designer drug ID ELECTROSPRAY-IONIZATION; PHOSPHODIESTERASE-5 INHIBITORS; ERECTILE DYSFUNCTION; HUMAN PLASMA; SILDENAFIL; IDENTIFICATION; TADALAFIL; PRODUCTS; ANALOGS; SYSTEM AB An herbal dietary supplement, marketed as a natural product for the enhancement of sexual function, was purchased covertly over the internet. The product was analyzed by LC-MS and found to contain a compound related to synthetic phosphodiesterase 5 (PDE-5) inhibitors. Based on LC with photodiode array and mass spectral detection, along with collision-induced dissociation-mass spectral analysis, the structure of the compound was tentatively identified as a designer drug of vardenafil in which the N-ethylpiperazine ring had been replaced by a piperidine ring. This structure was unambiguously confirmed by acid hydrolysis of both the unknown ("piperidenafil") and vardenatil and comparison of their hydrolysis products by LC-MS and GC-MS. The hydrolytic technique proved to be a useful tool for the structure elucidation of piperidenafil and may be a useful technique for the structure elucidation of other erectile dysfunction designer drugs in the future. The dosage level of piperidenafil in the herbal product was 41 mg per capsule when calculated as the free base. (c) 2006 Elsevier B.V. All rights reserved. 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 17 TC 73 Z9 75 U1 2 U2 13 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 25 PY 2006 VL 1125 IS 1 BP 67 EP 75 DI 10.1016/j.chroma.2006.05.018 PG 9 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 072XM UT WOS:000239706400005 PM 16750214 ER PT J AU Sharma, D Agrawal, A Matchette, LS Pfefer, TJ AF Sharma, Divyesh Agrawal, Anant Matchette, L. Stephanie Pfefer, T. Joshua TI Evaluation of a fiberoptic-based system for measurement of optical properties in highly attenuating turbid media SO BIOMEDICAL ENGINEERING ONLINE LA English DT Article ID SOURCE-DETECTOR SEPARATIONS; STATE DIFFUSE-REFLECTANCE; FLUORESCENCE SPECTROSCOPY; CHROMOPHORE CONCENTRATIONS; NONINVASIVE DETERMINATION; ABSORPTION-COEFFICIENTS; MONTE-CARLO; TISSUE; SCATTERING; PROBE AB Background: Accurate measurements of the optical properties of biological tissue in the ultraviolet A and short visible wavelengths are needed to achieve a quantitative understanding of novel optical diagnostic devices. Currently, there is minimal information on optical property measurement approaches that are appropriate for in vivo measurements in highly absorbing and scattering tissues. We describe a novel fiberoptic-based reflectance system for measurement of optical properties in highly attenuating turbid media and provide an extensive in vitro evaluation of its accuracy. The influence of collecting reflectance at the illumination fiber on estimation accuracy is also investigated. Methods: A neural network algorithm and reflectance distributions from Monte Carlo simulations were used to generate predictive models based on the two geometries. Absolute measurements of diffuse reflectance were enabled through calibration of the reflectance system. Spatially-resolved reflectance distributions were measured in tissue phantoms at 405 nm for absorption coefficients (mu(a)) from 1 to 25 cm(-1) and reduced scattering coefficients (mu'(s)) from 5 to 25 cm(-1). These data and predictive models were used to estimate the optical properties of tissue-simulating phantoms. Results: By comparing predicted and known optical properties, the average errors for mu(a) and mu'(s) were found to be 3.0% and 4.6%, respectively, for a linear probe approach. When bifurcated probe data was included and samples with mu(a) values less than 5 cm(-1) were excluded, predictive errors for mu(a) and mu'(s) were further reduced to 1.8% and 3.5%. Conclusion: Improvements in system design have led to significant reductions in optical property estimation error. While the incorporation of a bifurcated illumination fiber shows promise for improving the accuracy of estimates, further study of this approach is needed to elucidate the source of discrepancies between measurements and simulation results at low mu(a) values. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Pfefer, TJ (reprint author), US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. EM divyesh_sharma2001@yahoo.com; anant.agrawal@fda.hhs.gov; stephanie.matchette@fda.hhs.gov; joshua.pfefer@fda.hhs.gov RI Pfefer, Josh/I-9055-2012 NR 34 TC 13 Z9 13 U1 0 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1475-925X J9 BIOMED ENG ONLINE JI Biomed. Eng. Online PD AUG 23 PY 2006 VL 5 AR 49 DI 10.1186/1475-925X-5-49 PG 14 WC Engineering, Biomedical SC Engineering GA 110QS UT WOS:000242394200001 PM 16928274 ER PT J AU Gomes, AV Zong, C Edmondson, RD Li, X Stefani, E Zhang, J Jones, RC Thyparambil, S Wang, GW Qiao, X Bardag-Gorce, F Ping, PP AF Gomes, Aldrin V. Zong, Chenggong Edmondson, Ricky D. Li, Xiaohai Stefani, Enrico Zhang, Jun Jones, Richard C. Thyparambil, Sheeno Wang, Guang-Wu Qiao, Xin Bardag-Gorce, Fawzia Ping, Peipei TI Mapping the murine cardiac 26S proteasome complexes SO CIRCULATION RESEARCH LA English DT Article DE organelle proteomics; 19S and 20S proteasomes; protein degradation; heart ID REGULATORY PARTICLE SUBUNITS; 20S PROTEASOME; MYRISTOYLATED PROTEINS; GAMMA-INTERFERON; PATHWAY; CELLS; PHOSPHORYLATION; REPERFUSION; EXPRESSION; INHIBITORS AB ' The importance of proteasomes in governing the intracellular protein degradation process has been increasingly recognized. Recent investigations indicate that proteasome complexes may exist in a species- and cell-type-specific fashion. To date, despite evidence linking impaired protein degradation to cardiac disease phenotypes, virtually nothing is known regarding the molecular composition, function, or regulation of cardiac proteasomes. We have taken a functional proteomic approach to characterize 26S proteasomes in the murine heart. Multidimensional chromatography was used to obtain highly purified and functionally viable cardiac 20S and 19S proteasome complexes, which were subjected to electrophoresis and tandem mass spectrometry analyses. Our data revealed complex molecular organization of cardiac 26S proteasomes, some of which are similar to what were reported in yeast, whereas others exhibit contrasting features that have not been previously identified in other species or cell types. At least 36 distinct subunits (17 of 20S and 19 of 19S) are coexpressed and assembled as 26S proteasomes in this vital cardiac organelle, whereas the expression of PA200 and 11S subunits were detected with limited participation in the 26S complexes. The 19S subunits included a new alternatively spliced isoform of Rpn10 (Rpn10b) along with its primary isoform (Rpn10a). Immunoblotting and immunocytochemistry verified the expression of key alpha and beta subunits in cardiomyocytes. The expression of 14 constitutive alpha and beta subunits in parallel with their three inducible subunits (beta 1i, beta 2i, and beta 5i) in the normal heart was not expected; these findings represent a distinct level of structural complexity of cardiac proteasomes, significantly different from that of yeast and human erythrocytes. Furthermore, liquid chromatography/ tandem mass spectroscopy characterized 3 distinct types of post-translational modifications including (1) N-terminal acetylation of 19S subunits (Rpn1, Rpn5, Rpn6, Rpt3, and Rpt6) and 20S subunits (alpha 2, alpha 5, alpha 7, beta 3, and beta 4); ( 2) N-terminal myristoylation of a 19S subunit (Rpt2); and (3) phosphorylation of 20S subunits (eg, alpha 7)). Taken together, this report presents the first comprehensive characterization of cardiac 26S proteasomes, providing critical structural and proteomic information fundamental to our future understanding of this essential protein degradation system in the normal and diseased myocardium. C1 Univ Calif Los Angeles, Dept Physiol & Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Cardiac Proteom & Signaling Lab, Los Angeles, CA USA. Univ Calif Los Angeles, Cardiovasc Res Labs, Los Angeles, CA USA. Food & Drug Adm Natl Ctr Toxicol Res, Jefferson, AR USA. Calif State Univ Los Angeles, Div Mol Med, Dept Anesthesiol, Los Angeles, CA 90032 USA. Univ Calif Los Angeles, Harbor Med Ctr, Dept Pathol, Torrance, CA USA. Univ Calif Los Angeles, Harbor Med Ctr, Dept Med, Torrance, CA USA. RP Ping, PP (reprint author), Univ Calif Los Angeles, Dept Physiol & Med, Los Angeles, CA 90024 USA. EM pping@mednet.ucla.edu RI li, xiaohai/B-4249-2010; OI Ping, Peipei/0000-0003-3583-3881 FU NHLBI NIH HHS [HL65431, HL080111, HL63901] NR 42 TC 112 Z9 151 U1 0 U2 4 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 AUG 18 PY 2006 VL 99 IS 4 BP 362 EP 371 DI 10.1161/01.RES.0000237386.98506.f7 PG 10 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 074RL UT WOS:000239829400009 PM 16857966 ER PT J AU Gehring, TA Griffin, B Williams, R Geiseker, C Rushing, LG Siitonen, PH AF Gehring, Theresa A. Griffin, Bill Williams, Rod Geiseker, Charles Rushing, Larry G. Siitonen, Paul H. TI Multiresidue determination of sulfonamides in edible catfish, shrimp and salmon tissues by high-performance liquid chromatography with postcolumn derivatization and fluorescence detection SO JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES LA English DT Article DE sulfonamides; catfish; shrimp; salmon; liquid chromatography ID ICTALURUS-PUNCTATUS; CHANNEL CATFISH; PHARMACOKINETICS AB A liquid chromatographic (LC) method for determining 14 sulfonamide (SA) (sulfanilamide, sulfadiazine (SDZ), sulfathiazole, sulfapyridine, sulfamerazine (SMR), sulfamethazine (SMZ), sulfamethizole, sulfamethoxypyridazine, sulfachloropyridazine (SCP), sulfamonomethoxine, sulfadoxine, sulfamethoxazole, sulfadimethoxine (SDM), and sulfaquinoxaline (SQX)) residues in edible catfish, shrimp and salmon tissues was developed and validated at 5, 10 or 20 ng g(-1). The method was then used to determine residues in tissues of catfish, shrimp and salmon dosed with six selected sulfonamides (sulfadiazine, sulfamerazine, sulfamethazine, sulfachloropyridazine, sulfadimethoxine and sulfaquinoxaline). All assays were within U.S. Food and Drug Administration guidelines for recovery and intra-assay variability. The method was developed to determine possible sulfonamide residues in aquacultured catfish, shrimp and salmon produced for food. (c) 2006 Elsevier B.V. All rights reserved. C1 US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. USDA, Stuttgart Natl Aquaculture Res Ctr, Stuttgart, AR 72160 USA. Univ Arizona, Tucson, AZ 85721 USA. RP Gehring, TA (reprint author), US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. EM Tgehring@nctr.fda.gov NR 9 TC 43 Z9 50 U1 0 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1570-0232 J9 J CHROMATOGR B JI J. Chromatogr. B PD AUG 18 PY 2006 VL 840 IS 2 BP 132 EP 138 DI 10.1016/j.jchromb.2006.04.039 PG 7 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 075KE UT WOS:000239882900008 PM 16750659 ER PT J AU Stultz, BG Lee, HJ Ramon, K Hursh, DA AF Stultz, Brian G. Lee, Heuijung Ramon, Karolyn Hursh, Deborah A. TI Decapentaplegic head capsule mutations disrupt novel peripodial expression controlling the morphogenesis of the Drosophila ventral head SO DEVELOPMENTAL BIOLOGY LA English DT Article DE Drosophila; TGF-beta; Decapentaplegic; dpp; peripodial epithelium; head capsule ID EYE DEVELOPMENT; IMAGINAL DISKS; WING DEVELOPMENT; DPP RECEPTORS; BETA-HOMOLOG; GENE-COMPLEX; COMPOUND EYE; JNK PATHWAY; GERM LAYERS; ADULT HEAD AB Drosophila adult structures derive from imaginal discs, which are sacs with apposed epithelial sheets, the disc proper (DP) and the peripodial epithelium (PE). The Drosophila TGF-beta family member decapentaplegie (dpp) contributes to the development of adult structures through expression in all imaginal discs, driven by enhancers from the 3' cis-regulatory region of the gene. In the eye/antennal disc, there is 3' directed dpp expression in both the DP and PE associated with cell proliferation and eye formation. Here, we analyze a new class of dpp cis-regulatory mutations, which specifically disrupt a previously unknown region of dpp expression, controlled by enhancers in the 5' regulatory region of the gene and limited to the PE of eye/antennal discs. These are the first described Drosophila mutations that act by solely disrupting PE gene expression. The mutants display defects in the ventral adult head and alter peripodial but not DP expression of known dpp targets. However, apoptosis is observed in the underlying DP, suggesting that this peripodial dpp signaling source supports cell survival in the DP. (c) 2006 Elsevier Inc. All rights reserved. C1 US FDA, Ctr Biol Evaluat & Res, Div Cell & Gene Therapy, Cellular & Tissue Therapy Branch, Bethesda, MD 20892 USA. RP Hursh, DA (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Cell & Gene Therapy, Cellular & Tissue Therapy Branch, HFM-740,Bldg 29B,Rm 1E16,8800 Rockville Pike, Bethesda, MD 20892 USA. EM deborah.hursh@fda.hhs.gov NR 57 TC 12 Z9 12 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 0012-1606 J9 DEV BIOL JI Dev. Biol. PD AUG 15 PY 2006 VL 296 IS 2 BP 329 EP 339 DI 10.1016/j.ydbio.2006.05.034 PG 11 WC Developmental Biology SC Developmental Biology GA 076TI UT WOS:000239980200004 PM 16814276 ER PT J AU Heraud, JM Edghill-Smith, Y Ayala, V Kalisz, I Parrino, J Kalyanaraman, VS Manischewitz, J King, LR Hryniewicz, A Trindade, CJ Hassett, M Tsai, WP Venzon, D Nalca, A Vaccari, M Silvera, P Bray, M Graham, BS Golding, H Hooper, JW Franchini, G AF Heraud, Jean-Michel Edghill-Smith, Yvette Ayala, Victor Kalisz, Irene Parrino, Janie Kalyanaraman, Vaniambadi S. Manischewitz, Jody King, Lisa R. Hryniewicz, Anna Trindade, Christopher J. Hassett, Meredith Tsai, Wen-Po Venzon, David Nalca, Aysegul Vaccari, Monica Silvera, Peter Bray, Mike Graham, Barney S. Golding, Hana Hooper, Jay W. Franchini, Genoveffa TI Subunit recombinant vaccine protects against monkeypox SO JOURNAL OF IMMUNOLOGY LA English DT Article ID SMALLPOX VACCINE; VIRUS CHALLENGE; NONHUMAN-PRIMATES; LETHAL MONKEYPOX; MICE; NEUTRALIZATION; INFECTION; IMMUNIZATION; EXPRESSION; ANTIBODIES AB The smallpox vaccine Dryvax, a live vaccinia virus (VACV), protects against smallpox and monkeypox, but is contraindicated in immunocompromised individuals. Because Abs to VACV mediate protection, a live virus vaccine could be substituted by a safe subunit protein-based vaccine able to induce a protective Ab response. We immunized rhesus macaques with plasmid DNA encoding the monkeypox orthologs of the VACV L1R, A27L, A33R, and B5R proteins by the intradermal and i.m. routes, either alone or in combination with the equivalent recombinant proteins produced in Escherichia coli. Animals that received only DNA failed to produce high titer Abs, developed innumerable skin lesions after challenge, and died in a manner similar to placebo controls. By contrast, the animals vaccinated with proteins developed moderate to severe disease (20-155 skin lesions) but survived. Importantly, those immunized with DNA and boosted with proteins had mild disease with 15 or fewer lesions that resolved within days. DNA/protein immunization elicited Th responses and binding Ab titers to all four proteins that correlated negatively with the total lesion number. The sera of the immunized macaques recognized a limited number of linear B cell epitopes that are highly conserved among orthopoxviruses. Their identification may guide future efforts to develop simpler, safer, and more effective vaccines for monkeypox and smallpox. C1 NCI, Anim Models & Retroviral Vaccines Sect, Bethesda, MD 20892 USA. So Res Inst, Frederick, MD 21701 USA. Adv BioSci Labs, Kensington, MD 20895 USA. NIAID, Vaccine Res Ctr, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. Med Univ Bialystok, Dept Gen & Expt Pathol, Bialystok, Poland. NCI, Biostat & Data Management Sect, Bethesda, MD 20892 USA. USA, Med Res Inst Infect Dis, Ft Detrick, MD 21702 USA. NIAID, Biodef Clin Res Branch, Bethesda, MD 20892 USA. RP Franchini, G (reprint author), NCI, Anim Models & Retroviral Vaccines Sect, Bldg 41,Room D-804, Bethesda, MD 20892 USA. EM franchig@mail.nih.gov RI HERAUD, Jean-Michel/O-1464-2013; OI HERAUD, Jean-Michel/0000-0003-1107-0859; Hooper, Jay/0000-0002-4475-0415 FU Intramural NIH HHS; NIAID NIH HHS [N01 AI 15451] NR 35 TC 71 Z9 73 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD AUG 15 PY 2006 VL 177 IS 4 BP 2552 EP 2564 PG 13 WC Immunology SC Immunology GA 073LU UT WOS:000239745300064 PM 16888017 ER PT J AU Young, JF Tsai, CA Chen, JJ Latendresse, JR Kodell, RL AF Young, John F. Tsai, Chen-An Chen, James J. Latendresse, John R. Kodell, Ralph L. TI Database composition can affect the structure-activity relationship prediction SO JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A-CURRENT ISSUES LA English DT Article ID TOXICOLOGY CHALLENGE; DATA-BASES; MUTAGENICITY; SIZE AB The percent active (A) and inactive (I) chemicals in a database can directly affect the sensitivity (% active chemicals predicted correctly) and specificity (% inactive chemicals predicted correctly) of structure-activity relationship (SAR) analyses. Subdividing the National Center for Toxicological Research (NCTR) liver cancer database (NCTRlcdb) into various A/l ratios, which varied from 0.2 to 5.5, resulted in sensitivity/specificity ratios that varied from 0.1 to 6.5. As percent active chemicals increased (increasing A/l ratio), the sensitivity rose, the specificity decreased, and the concordance (% total chemicals predicted correctly) remained fairly constant. The numbers of chemicals in the various data sets ranged from 187 to 999 and appeared to have no affect on any of the 3 predictors of sensitivity, specificity, or concordance. C1 US FDA, Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. Acad Sinica, Inst Stat Sci, Taipei 115, Taiwan. Natl Ctr Toxicol Res, Toxicol Pathol Associates, Jefferson, AR 72079 USA. RP Young, JF (reprint author), US FDA, Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. EM jyoung@nctr.fda.gov RI Latendresse, John/A-9215-2009; OI Tsai, Chen-An/0000-0002-7490-4331 NR 21 TC 2 Z9 2 U1 2 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 AUG 15 PY 2006 VL 69 IS 16 BP 1527 EP 1540 DI 10.1080/15287390500468746 PG 14 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 065HN UT WOS:000239150800002 PM 16854783 ER PT J AU Huang, Y Sadee, W AF Huang, Ying Sadee, Wolfgang TI Membrane transporters and channels in chemoresistance and -sensitivity of tumor cells SO CANCER LETTERS LA English DT Review DE membrane transporter; ABC transporter; SLC transporter; ion channel; chemosensitivity; chemoresistance ID CANCER RESISTANCE PROTEIN; FOLATE CARRIER GENE; CONCENTRATIVE NUCLEOSIDE TRANSPORTER; PERMEABILITY TRANSITION PORE; OVARIAN-CARCINOMA CELLS; MULTIDRUG-RESISTANCE; BREAST-CANCER; P-GLYCOPROTEIN; CELLULAR PHARMACOLOGY; IMATINIB MESYLATE AB Membrane transporters play important roles in mediating chemosensitivity and -resistance of tumor cells. ABC transporters, such as ABCB1/MDR1, ABCC1/MRP1 and ABCG2/BCRP, are frequently associated with decreased cellular accumulation of anticancer drugs and multidrug resistance of tumors. SLC transporters, such as folate, nucleoside, and amino acid transporters, commonly increase chemosensitivity by mediating the cellular uptake of hydrophilic drugs. Ion channels and pumps variably affect sensitivity to anticancer therapy by modulating viability of tumor cells. A pharmacogenomic approach, using correlations between drug potency and transporter gene expression in multiple cancer cell lines, has shown promise for identifying potential drug-transporter relationships and predicting anticancer drug response, in an effort to optimize chemotherapy for individual patients. (c) 2005 Elsevier Ireland Ltd. All rights reserved. C1 US FDA, Natl Ctr Toxicol Res, Div Pharmacogenom & Mol Epidemiol, Jefferson, AR 72079 USA. Ohio State Univ, Program Pharmacogenom, Dept Pharmacol, Ctr Comprehens Canc,Coll Med & Publ Hlth, Columbus, OH 43210 USA. RP Huang, Y (reprint author), US FDA, Natl Ctr Toxicol Res, Div Pharmacogenom & Mol Epidemiol, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM yhuang@nctr.fda.gov FU NIGMS NIH HHS [GM 61390] NR 100 TC 109 Z9 120 U1 1 U2 16 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 2006 VL 239 IS 2 BP 168 EP 182 DI 10.1016/j.canlet.2005.07.032 PG 15 WC Oncology SC Oncology GA 073PF UT WOS:000239754400002 PM 16169662 ER PT J AU Kozlowski, S Swann, P AF Kozlowski, Steven Swann, Patrick TI Current and future issues in the manufacturing and development of monoclonal antibodies SO ADVANCED DRUG DELIVERY REVIEWS LA English DT Review DE monoclonal antibodies; manufacturing; product testing; biological characterization; quality by design ID BIOTECHNOLOGY PRODUCTS; RECOMBINANT; IMMUNOGENICITY; GLYCOSYLATION; OLIGOSACCHARIDES; THERAPEUTICS; RESOLUTION; GALACTOSE; PROTEINS; REMOVAL AB Despite a slow beginning, monoclonal antibodies have had many successes over the past decade. It is important that these successes continue, bringing more products for more indications to market. Although manufacturing is not the most common cause of product failure, product quality issues can delay antibody development. Manufacturing has depended on the triad of process validation, process control and product testing. Applying product knowledge proactively to manufacturing (quality by design) may allow greater flexibility and maintain or improve product quality. An integrated approach to biological characterization is an important aspect of product knowledge. Greater product knowledge also facilitates development in other disciplines. Independent of manufacturing strategy, there are a number of regulatory hurdles in initial and ongoing antibody development. These are described to help prevent unnecessary delays. Published by Elsevier B.V. C1 US FDA, Off Biotechnol Prod, Off Pharmaceut Sci, Ctr Drug Evaluat & Res, Bethesda, MD USA. US FDA, Div Monoclonal Antibodies, Off Pharmaceut Sci, Ctr Drug Evaluat & Res, Bethesda, MD USA. RP Kozlowski, S (reprint author), US FDA, Off Biotechnol Prod, Off Pharmaceut Sci, Ctr Drug Evaluat & Res, Bethesda, MD USA. EM steven.kozlowski@fda.hhs.gov NR 53 TC 85 Z9 90 U1 1 U2 28 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-409X J9 ADV DRUG DELIVER REV JI Adv. Drug Deliv. Rev. PD AUG 7 PY 2006 VL 58 IS 5-6 BP 707 EP 722 DI 10.1016/j.addr.2006.05.002 PG 16 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 084ZO UT WOS:000240573100007 PM 16828921 ER PT J AU Motlekar, N Khan, MA Youan, BBC AF Motlekar, N Khan, MA Youan, BBC TI Preparation and characterization of genistein containing poly(ethylene glycol) microparticles SO JOURNAL OF APPLIED POLYMER SCIENCE LA English DT Article DE amorphous; polyethylene; surfactants; thermal properties; water-soluble polymer ID SOLID DISPERSION-SYSTEMS; SOLVENT EVAPORATION; POLYETHYLENE-GLYCOL; WATER; MICROENCAPSULATION; TOLBUTAMIDE; DISSOLUTION; FORMULATION; SOLUBILITY AB The purpose of this study was to prepare, characterize, and evaluate genistein-containing microparticles with enhanced dissolution profile using poly(ethylene glycol) (PEG) as polymer matrix. Genistein loaded microparticles were prepared by a solvent evaporation process and their surface, thermal, chemical, and dissolution properties were analyzed by microscopy, differential scanning calorimetry, ATR-FTIR spectroscopy, and USP dissolution apparatus II, respectively. The wettability index was also determined. Genistein exhibited an elongated crystal habit. However, the drug containing PEG microparticles were discrete and quasispherical. The ATR-FTIR studies performed on the formulation suggested hydrogen bonding between the drug and the polymer matrix. Thermal analysis indicated a conversion of the crystalline form of the drug to an amorphous form. Genistein, exhibiting low solubility and high permeability, is a Class II drug of the Biopharmaceutical Classification Scheme. However, there was a similar to 9-fold increase in the rate of dissolution of genistein in the case of all formulations as compared to native genistem. This study showed that genistein could be effectively encapsulated into PEG microparticles using an emulsion-solvent evaporation technique, therefore avoiding the potential disadvantages of other solid dispersion techniques. This approach provided a significant enhancement in the drug dissolution profile. (c) 2006 Wiley Periodicals, Inc. C1 Texas Tech Univ, Ctr Hlth Sci, Dept Pharmaceut Sci, Sch Pharm, Amarillo, TX USA. US FDA, Ctr Drug Evaluat & Res, Div Prod Qual Res, Silver Spring, MD USA. RP Youan, BBC (reprint author), Texas Tech Univ, Ctr Hlth Sci, Dept Pharmaceut Sci, Sch Pharm, Amarillo, TX USA. EM bibotti.youan@ttuhsc.edu NR 32 TC 19 Z9 21 U1 1 U2 3 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0021-8995 J9 J APPL POLYM SCI JI J. Appl. Polym. Sci. PD AUG 5 PY 2006 VL 101 IS 3 BP 2070 EP 2078 DI 10.1002/spp.23827 PG 9 WC Polymer Science SC Polymer Science GA 058AU UT WOS:000238637300113 ER PT J AU Okelo, PO Wagner, DD Carr, LE Wheaton, FW Douglass, LW Joseph, SW AF Okelo, P. O. Wagner, D. D. Carr, L. E. Wheaton, F. W. Douglass, L. W. Joseph, S. W. TI Optimization of extrusion conditions for elimination of mesophilic bacteria during thermal processing of animal feed mash SO ANIMAL FEED SCIENCE AND TECHNOLOGY LA English DT Article DE Salmonella typhimurium; Bacillus stearothermophilus; bacteria; feeds; extrusion; mash; thermal processing ID BACILLUS-STEAROTHERMOPHILUS SPORES; RESISTANCE; CONTAMINATION; SALMONELLA AB Salmonella and other pathogenic organisms that infect poultry and other livestock can originate from feed and environmental sources. Thus, measures are taken to control Salmonella infection in animals to improve food safety and reduce production losses. The current study was designed to investigate and optimize extrusion conditions for reducing bacterial counts in a surrogate feed matrix. A single-screw extruder was used to process feed artificially inoculated with Bacillus stearothermophilus 12980 (ATCC, Reston, Virginia). Preliminary experiments demonstrated that Salmonella typhimurium (S. typhimurium NAL(r)) was eliminated from feed under conditions of moderate extrusion stringency (285 g moisture/kg mash feed, 83 degrees C extruder barrel exit temperature, 7 s retention time in the extruder barrel) and, therefore, a more thermotolerant organism was required to conduct the study. Spores of B. stearothermophilus 12980 inoculated into a surrogate feed matrix consisting of 600 g maize meal/kg, 300 g soya bean meal/kg and 100 g animal protein blend/kg, respectively, was used to investigate the effect of three extrusion variables on microbial killing. The three variables were extruder barrel exit temperature (T), mash feed moisture content (M-c), and mean retention time of feed in the extruder barrel (R,). A rotatable central composite statistical design was used with three independent variables and five levels each. The quadratic response surface model fit to spore count data was used to predict extrusion conditions that maximized bacterial killing. The response surface indicated a stationary point within the design region that was a saddle. An estimated ridge of maximum killing indicated that a maximum reduction of 1.03 log cycles would occur under the following extruder settings: T= 110 degrees C, M-c = 245 g/kg and R-t = 11 s. Because the moderate stringency condition (T= 83 degrees C, M-c = 285 g/kg and R, = 7 s) completely eliminated detectable S. typhimurium in the test feed matrix, it would appear that all S. typhimurium cells and all mesophilic organisms of similar thermal tolerance would be eliminated at most extruder conditions within the central composite design region. (c) 2005 Elsevier B.V. All rights reserved. C1 US FDA, Ctr Vet Med, Rockville, MD 20855 USA. US FDA, Coll Vet Med, Laurel, MD 20708 USA. Univ Maryland, Biol Resources Engn Dept, College Pk, MD 20742 USA. Univ Maryland, Anim & Avian Sci Dept, College Pk, MD 20742 USA. Univ Maryland, Dept Mol Genet & Cell Biol, College Pk, MD 20742 USA. RP Okelo, PO (reprint author), US FDA, Ctr Vet Med, Rockville, MD 20855 USA. EM Phares.Okelo@fda.gov NR 21 TC 19 Z9 20 U1 0 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0377-8401 J9 ANIM FEED SCI TECH JI Anim. Feed Sci. Technol. PD AUG 4 PY 2006 VL 129 IS 1-2 BP 116 EP 137 DI 10.1016/j.anifeedsci.2005.12.011 PG 22 WC Agriculture, Dairy & Animal Science SC Agriculture GA 069LQ UT WOS:000239448500008 ER PT J AU Korrapati, MC Chilakapati, J Lock, EA Latendresse, JR Warbritton, A Mehendale, HM AF Korrapati, Midhun C. Chilakapati, Jaya Lock, Edward A. Latendresse, John R. Warbritton, Alan Mehendale, Harihara M. TI Preplaced cell division: a critical mechanism of autoprotection against S-1,2-dichlorovinyl-L-cysteine-induced acute renal failure and death in mice SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE colchicine; phospho; retinoblastoma; tissue repair ID CYCLIN-DEPENDENT KINASES; TISSUE-REPAIR; RETINOBLASTOMA PROTEIN; MOLECULAR-MECHANISMS; PROGNOSTIC-FACTORS; ANTIMITOTIC AGENT; TUBULAR-NECROSIS; INJURY; COLCHICINE; KIDNEY AB Previous studies have shown that renal injury initiated by a lethal dose of S-1,2dichlorovinyl- L-cysteine (DCVC) progresses due to inhibition of cell division and hence renal repair, leading to acute renal failure (ARF) and death in mice. Renal injury initiated by low to moderate doses of DCVC is repaired by timely and adequate stimulation of renal cell division, tubular repair, restoration of renal structure and function leading to survival of mice. Recent studies have established that mice primed with a low dose of DCVC (15 mg/kg ip) 72 h before administration of a normally lethal dose (75 mg/ kg ip) are protected from ARF and death (nephro-autoprotection). We showed that renal cell division and tissue repair stimulated by the low dose are sustained even after the lethal dose administration resulting in survival from ARF and death. If renal cell division induced by the low dose is indeed the critical mechanism of this autoprotection, then its ablation by the antimitotic agent colchicine (1.5 mg CLC/kg ip) should abolish autoprotection. The present interventional experiments were designed to test the hypothesis that DCVC autoprotection is due to stimulated cell division and tissue repair by the priming low dose. CLC intervention at 42 and 66 h after the priming dose resulted in marked progressive elevation of plasma blood urea nitrogen and creatinine resulting in ARF and death of mice. Light microscopic examination of hematoxylin and eosin-stained kidney sections revealed progression of renal necrosis concordant with progressively failing renal function. With CLC intervention, S-phase stimulation (as assessed by BrdU pulse labeling), G1-to-S phase clearance, and cell division were diminished essentially abolishing the promitogenic effect of the priming low dose of DCVC. Phospho-retinoblastoma protein (P-pRB), a crucial protein for S-phase stimulation, and other cellular signaling mechanisms regulating P-pRB were investigated. We report that decreased P-pRB via activation of protein phosphatase-1 by CLC is the critical mechanism of this inhibited S-phase stimulation and ablation of autoprotection with CLC intervention. These findings lend additional support to the notion that stimulated cell division and renal tissue repair by the priming dose of DCVC are the critical mechanisms that allow sustained compensatory tissue repair and survival of mice in nephro-autoprotection. C1 Univ Louisiana Monroe, Coll Pharm, Dept Toxicol, Monroe, LA 71209 USA. Liverpool John Moores Univ, Sch Biomol Sci, Liverpool, Merseyside, England. Pathol Assoc Int, Natl Ctr Toxicol Res, Jefferson, AR USA. RP Mehendale, HM (reprint author), Univ Louisiana Monroe, Coll Pharm, Dept Toxicol, 700 Univ Ave,Sugar Hall 306, Monroe, LA 71209 USA. EM mehendale@ulm.edu RI Latendresse, John/A-9215-2009 FU NIDDK NIH HHS [DK-61650] NR 68 TC 12 Z9 13 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD AUG PY 2006 VL 291 IS 2 BP F439 EP F455 DI 10.1152/ajprenal.00384.2005 PG 17 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 060LD UT WOS:000238802800020 PM 16495211 ER PT J AU Bough, KJ Wetherington, J Hassel, B Pare, JF Gawryluk, JW Greene, JG Shaw, R Smith, Y Geiger, JD Dingledine, RJ AF Bough, Kristopher J. Wetherington, Jonathon Hassel, Bjornar Pare, Jean Francois Gawryluk, Jeremy W. Greene, James G. Shaw, Renee Smith, Yoland Geiger, Jonathan D. Dingledine, Raymond J. TI Mitochondrial biogenesis in the anticonvulsant mechanism of the ketogenic diet SO ANNALS OF NEUROLOGY LA English DT Article ID TEMPORAL-LOBE EPILEPSY; HIGH-FAT DIET; RAT HIPPOCAMPUS; GENE-EXPRESSION; OXIDATIVE-PHOSPHORYLATION; CALORIE RESTRICTION; SKELETAL-MUSCLE; ANIMAL-MODEL; IN-VIVO; BRAIN AB Objective: The full anticonvulsant effect of the ketogenic diet (KD) can require weeks to develop in rats, suggesting that altered gene expression is involved. The KD typically is used in pediatric epilepsies, but is effective also in adolescents and adults. Our goal was to use microarray and complementary technologies in adolescent rats to understand its anticonvulsant effect. Methods: Microarrays were used to define patterns of gene expression in the hippocampus of rats fed a KD or control diet for 3 weeks. Hippocampi from control- and KD-fed rats were also compared for the number of mitochondrial profiles in electron micrographs, the levels of selected energy metabolites and enzyme activities, and the effect of low glucose on synaptic transmission. Results: Most striking was a coordinated upregulation of all (n = 34) differentially regulated transcripts encoding energy metabolism enzymes and 39 of 42 transcripts encoding mitochondrial proteins, which was accompanied by an increased number of mitochondrial profiles, a higher phosphocreatine/creatine ratio, elevated glutamate levels, and decreased glycogen levels. Consistent with increased energy reserves, synaptic transmission in hippocampal slices from KD-fed animals was resistant to low glucose. Interpretation: These data show that a calorie-restricted KD enhances brain metabolism. We propose an anticonvulsant mechanism of the KD involving mitochondrial biogenesis leading to enhanced alternative energy stores. C1 Emory Univ, Dept Pharmacol, Atlanta, GA 30322 USA. Norwegian Def Res Estab, N-2007 Kjeller, Norway. Emory Univ, Yerkes Natl Primate Res Ctr, Atlanta, GA 30322 USA. Univ N Dakota, Dept Pharmacol Physiol & Therapeut, Grand Forks, ND 58201 USA. Emory Univ, Dept Neurol, Atlanta, GA 30322 USA. RP Bough, KJ (reprint author), US FDA, Ctr Drug Evaluat & Res, MPN 1,Room 1345,7520 Standish Pl, Rockville, MD 20855 USA. EM kbough96@yahoo.com RI dingledine, Ray/F-5173-2011 FU NCRR NIH HHS [P20 RR17699]; NIA NIH HHS [AG17628]; NINDS NIH HHS [NS 17701] NR 67 TC 186 Z9 192 U1 0 U2 12 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD AUG PY 2006 VL 60 IS 2 BP 223 EP 235 DI 10.1002/ana.20899 PG 13 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 070PX UT WOS:000239536600011 PM 16807920 ER PT J AU Volokhov, DV George, J Liu, SX Ikonomi, P Anderson, C Chizhikov, V AF Volokhov, Dmitriy V. George, Joseph Liu, Sue X. Ikonomi, Pranvera Anderson, Christine Chizhikov, Vladimir TI Sequencing of the intergenic 16S-23S rRNA spacer (ITS) region of Mollicutes species and their identification using microarray-based assay and DNA sequencing SO APPLIED MICROBIOLOGY AND BIOTECHNOLOGY LA English DT Article ID MYCOPLASMA; STRAINS; GENE; HYBRIDIZATION; PHYLOGENY; CLUSTER; PCR AB We have completed sequencing the 16S-23S rRNA intergenic transcribed spacer (ITS) region of most known Mycoplasma, Acholeplasma, Ureaplasma, Mesoplasma, and Spiroplasma species. Analysis of the sequence data revealed a significant interspecies variability and low intraspecies polymorphism of the ITS region among Mollicutes. This finding enabled the application of a combined polymerase chain reaction-microarray technology for identifying Mollicutes species. The microarray included individual species-specific oligonucleotide probes for characterizing human Mollicutes species and other species known to be common cell line contaminants. Evaluation of the microarray was conducted using multiple, previously characterized, Mollicutes species. The microarray analysis of the samples used demonstrated a highly specific assay, which is capable of rapid and accurate discrimination among Mollicutes species. C1 US FDA, Lab Methods Dev, Div Viral Prod, Off Vaccines Res & Review,Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. ATCC, Manassas, VA 20108 USA. RP Volokhov, DV (reprint author), US FDA, Lab Methods Dev, Div Viral Prod, Off Vaccines Res & Review,Ctr Biol Evaluat & Res, HFM-470,1401 Rockville Pike, Rockville, MD 20852 USA. EM volokhov@cber.fda.gov NR 30 TC 24 Z9 25 U1 1 U2 6 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 AUG PY 2006 VL 71 IS 5 BP 680 EP 698 DI 10.1007/s00253-005-0280-7 PG 19 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 065PI UT WOS:000239171400013 PM 16470366 ER PT J AU Lachenbruch, PA Wittes, J AF Lachenbruch, Peter A. Wittes, Janet TI Some aspects of the application of internal pilot studies SO BIOMETRICAL JOURNAL LA English DT Editorial Material DE clinical trials; internal pilot study; nuisance parameter; sample size recalculation C1 US FDA, Rockville, MD 20857 USA. Stat Collaborat, Washington, DC 20036 USA. RP Lachenbruch, PA (reprint author), US FDA, Rockville, MD 20857 USA. EM lachenbruchpa@aol.com NR 4 TC 0 Z9 0 U1 0 U2 1 PU AKADEMIE VERLAG GMBH PI BERLIN PA PALISADENSTR 40, D-10243 BERLIN, GERMANY SN 0323-3847 J9 BIOMETRICAL J JI Biom. J. PD AUG PY 2006 VL 48 IS 4 BP 556 EP 557 DI 10.1002/bimj.200610243 PG 2 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 080TE UT WOS:000240270500006 PM 16972705 ER PT J AU O'Neill, RT AF O'Neill, R. T. TI FDA's critical path initiative: A perspective on contributions of biostatistics SO BIOMETRICAL JOURNAL LA English DT Article DE adaptive study designs; clinical trial simulation; FDA critical path; guidance development; multiple endpoints; missing data; non-inferiority trials; quantitative risk/safety assessment; regulatory biostatistics AB This article describes the motivation for, description of, and the objectives and plans for the FDA's initiative that was introduced in March of 2004 by way of a report titled 'Innovation or Stagnation? Challenge and Opportunity on the Critical Path to New Medical Products'. The FDA initiative is very much an outreach effort and a wake-up call to many constituencies to contribute and partner to improve the product development process and thereby to contribute to the success rate of new products that will benefit the public. We discuss in general terms where some of the opportunities and challenges exist for the discipline of biostatistics to make contributions to this effort over the next few years. In particular, guidance development in five areas is considered as is the need to devote new energy and efforts to quantitative risk assessment and safety evaluation, an area that has lagged the attention received in the efficacy evaluation area. C1 OTS CDER FDA, Off Biostat, Silver Spring, MD 20993 USA. RP O'Neill, RT (reprint author), OTS CDER FDA, Off Biostat, 10903 New Hampshire Ave,Bldg 22,Room 6012, Silver Spring, MD 20993 USA. EM oneill@cder.fda.gov NR 1 TC 19 Z9 20 U1 3 U2 7 PU AKADEMIE VERLAG GMBH PI BERLIN PA PALISADENSTR 40, D-10243 BERLIN, GERMANY SN 0323-3847 J9 BIOMETRICAL J JI Biom. J. PD AUG PY 2006 VL 48 IS 4 BP 559 EP 564 DI 10.1002/bimj.200510237 PG 6 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 080TE UT WOS:000240270500008 PM 16972706 ER PT J AU Hung, HMJ O'neill, RT Wang, SJ Lawrence, J AF Hung, H. M. James O'neill, Robert T. Wang, Sue-Jane Lawrence, John TI A regulatory view on adaptive/flexible clinical trial design SO BIOMETRICAL JOURNAL LA English DT Article DE statistical information; adaptive information design; superiority; non-inferiority; dropping a treatment arm; statistical efficiency; regulatory evaluation ID GROUP SEQUENTIAL DESIGNS; NON-INFERIORITY HYPOTHESES; ADAPTIVE INTERIM ANALYSES; FLEXIBLE 2-STAGE DESIGNS; SAMPLE-SIZE ADJUSTMENT; CONDITIONAL POWER; SUPERIORITY; INFERENCE; REASSESSMENT; SELECTION AB Recently there is growing interest in use of adaptive or flexible designs for development of pharmaceutical products. Statistical methodology has been greatly advanced in the literature. However, there are still some important issues with the methodology and application. In addition, there are many other challenges with these designs, including efficiency of these designs in the entire development program, trial conduct and logistics, the infrastructure of an adaptive trial, the regulatory evaluation of trial results and trial conduct, etc. Up till now, regulatory experience in these designs is very limited. We share some of the challenges. C1 OB OTS CDER FDA, Div Biometr 1, Rockville, MD 20857 USA. OTS CDER FDA, Off Biostat, Rockville, MD USA. RP Hung, HMJ (reprint author), OB OTS CDER FDA, Div Biometr 1, Rockville, MD 20857 USA. EM hsienming.hung@fda.hhs.gov FU DRS NIH HHS [RSR 04-06, RSR 5-04] NR 38 TC 45 Z9 45 U1 0 U2 2 PU AKADEMIE VERLAG GMBH PI BERLIN PA PALISADENSTR 40, D-10243 BERLIN, GERMANY SN 0323-3847 J9 BIOMETRICAL J JI Biom. J. PD AUG PY 2006 VL 48 IS 4 BP 565 EP 573 DI 10.1002/bimj.200610229 PG 9 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 080TE UT WOS:000240270500009 PM 16972707 ER PT J AU Wittes, J Lachenbruch, PA AF Wittes, Janet Lachenbruch, Peter A. TI Opening the adaptive toolbox SO BIOMETRICAL JOURNAL LA English DT Editorial Material DE adaptive designs; adaptive information design; adaptive study designs; biostatistics; clinical trial simulation; dropping a treatment arm; experimental design; FDA Critical Path; guidance development; multiple endpoints; missing data; non-inferiority; non-inferiority trials; phase III clinical trials; quantitative risk/safety assessment; regulatory biostatistics; regulatory evaluation; statistical efficiency; statistical information; superiority ID CLINICAL-TRIALS; SAMPLE-SIZE; DESIGN AB This is a discussion of the following three papers appearing in this special issue on adaptive designs: 'A regulatory view on adaptive/flexible clinical trial design' by H. M. James Hung, Robert T. O'Neill, Sue-Jane Wang and John Lawrence; 'Confirmatory clinical trials with an adaptive design' by Armin Koch; and 'FDA's critical path initiative: A perspective on contributions of biostatistics' by Robert T. O'Neill. C1 Stat Collaborat, Washington, DC 20036 USA. US FDA, Rockville, MD 20857 USA. RP Wittes, J (reprint author), Stat Collaborat, 1625 Massachusetts Ave NW, Washington, DC 20036 USA. EM janet@stateollab.com NR 15 TC 1 Z9 1 U1 1 U2 4 PU AKADEMIE VERLAG GMBH PI BERLIN PA PALISADENSTR 40, D-10243 BERLIN, GERMANY SN 0323-3847 J9 BIOMETRICAL J JI Biom. J. PD AUG PY 2006 VL 48 IS 4 BP 598 EP 603 DI 10.1002/bimj.200610240 PG 6 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 080TE UT WOS:000240270500013 PM 16972711 ER PT J AU Rozman, KK Bhatia, J Calafat, AM Chambers, C Culty, M Etzel, RA Flaws, JA Hansen, DK Hoyer, PB Jeffery, EH Kesner, JS Marty, S Thomas, JA Umbach, D AF Rozman, Karl K. Bhatia, Jatinder Calafat, Antonia M. Chambers, Christina Culty, Martine Etzel, Ruth A. Flaws, Jodi A. Hansen, Deborah K. Hoyer, Patricia B. Jeffery, Elizabeth H. Kesner, James S. Marty, Sue Thomas, John A. Umbach, David TI NTP-CERHR expert panel report on the reproductive and developmental toxicity of soy formula SO BIRTH DEFECTS RESEARCH PART B-DEVELOPMENTAL AND REPRODUCTIVE TOXICOLOGY LA English DT Review ID HIGH-RISK INFANTS; BIRTH-WEIGHT INFANTS; MILK-BASED FORMULA; NONSPECIFIC MACROMOLECULAR ABSORPTION; CHROMATOGRAPHY-MASS SPECTROMETRY; PREMENOPAUSAL JAPANESE WOMEN; SMALL INTESTINAL BARRIER; PARTIAL WHEY HYDROLYSATE; SPRAGUE-DAWLEY RATS; SEX-HORMONE LEVELS C1 NIEHS, Res Triangle Pk, NC 27709 USA. Indiana Univ, Sch Med, Dept Pharmacol & Toxicol, Indianapolis, IN 46202 USA. Dow Chem Co USA, Toxicol Res Lab, Midland, MI 48674 USA. NIOSH, Cincinnati, OH 45226 USA. Univ Illinois, Dept Food Sci & Human Nutr, Urbana, IL 61801 USA. Univ Arizona, Dept Physiol, Tucson, AZ USA. Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. Univ Maryland, Sch Med, Dept Epidemiol & Prevent Med, Baltimore, MD 21201 USA. George Washington Univ, Sch Publ Hlth & Hlth Serv, Washington, DC USA. Georgetown Univ, Med Ctr, Dept Biochem & Mol Biol, Washington, DC 20007 USA. Univ Calif San Diego, Med Ctr, Dept Pediat, San Diego, CA 92103 USA. Univ Calif San Diego, Med Ctr, Dept Family & Prevent Med, San Diego, CA 92103 USA. Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Atlanta, GA USA. Med Coll Georgia, Dept Pediat, Div Neonatol, Augusta, GA 30912 USA. Univ Kansas, Med Ctr, Dept Pharmacol & Toxicol, Kansas City, KS 66103 USA. RP Rozman, KK (reprint author), NIEHS, POB 12233,EC-32, Res Triangle Pk, NC 27709 USA. FU Intramural NIH HHS [Z99 ES999999] NR 227 TC 23 Z9 26 U1 3 U2 5 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 AUG PY 2006 VL 77 IS 4 BP 280 EP 397 DI 10.1002/bdrb.20086 PG 118 WC Oncology; Genetics & Heredity; Toxicology SC Oncology; Genetics & Heredity; Toxicology GA 086ZF UT WOS:000240711100004 PM 16998908 ER PT J AU Budhu, A Forgues, M Ye, QH Jia, HL He, P Zanetti, KA Kammula, US Chen, YD Qin, LX Tang, ZY Wang, XW AF Budhu, Anuradha Forgues, Marshonna Ye, Qing-Hai Jia, Hu-Liong He, Ping Zanetti, Krista A. Kammula, Udai S. Chen, Yidong Qin, Lun-Xiu Tang, Zhao-You Wang, Xin Wei TI Prediction of venous metastases, recurrence, and prognosis in hepatocellular carcinoma based on a unique immune response signature of the liver microenvironment SO CANCER CELL LA English DT Article ID GENE-EXPRESSION; MOLECULAR SIGNATURE; CANCER; CELLS; MACROPHAGES; PROGRESSION; SURVIVAL; VIRUS; INFLAMMATION; DISEASE AB Hepatocellular carcinoma (HCC) is an aggressive malignancy mainly due to metastases or postsurgical recurrence. We postulate that metastases are influenced by the liver microenvironment. Here, we show that a unique inflammation/immune response-related signature is associated with noncancerous hepatic tissues from metastatic HCC patients. This signature is principally different from that of the tumor. A global Th1/Th2-like cytokine shift in the venous metastasis-associated liver microenvironment coincides with elevated expression of macrophage colony-stimulating factor (CSF1). Moreover, a refined 17 gene signature was validated as a superior predictor of HCC venous metastases in an independent cohort, when compared to other clinical prognostic parameters. We suggest that a predominant humoral cytokine profile occurs in the metastatic liver milieu and that a shift toward anti-inflammatory/immune-suppressive responses may promote HCC metastases. C1 NCI, Liver Carcinogenesis Sect, Human Carcinogenesis Lab, Ctr Canc Res, Bethesda, MD 20892 USA. Fudan Univ, Liver Canc Inst, Shanghai 200032, Peoples R China. Fudan Univ, Zhongshan Hosp, Shanghai 200032, Peoples R China. US FDA, Ctr Biol Evaluat & Res, Div Hematol, Bethesda, MD 20892 USA. NCI, Mol Genet & Carcinogenesis Sect, Human Carcinogenesis Lab, Bethesda, MD 20892 USA. NCI, Canc Prevent Fellowship Program, Div Canc Prevent, Bethesda, MD 20892 USA. Natl Human Genome Res Inst, Canc Genet Lab, Bethesda, MD 20892 USA. NCI, Surg Branch, Bethesda, MD 20892 USA. RP Tang, ZY (reprint author), NCI, Liver Carcinogenesis Sect, Human Carcinogenesis Lab, Ctr Canc Res, Bethesda, MD 20892 USA. EM zytang8@yahoo.com.cn; xw3u@nih.gov RI Wang, Xin/B-6162-2009 FU Intramural NIH HHS NR 40 TC 367 Z9 393 U1 2 U2 39 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD AUG PY 2006 VL 10 IS 2 BP 99 EP 111 DI 10.1016/j.ccr.2006.06.016 PG 13 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 075NH UT WOS:000239891300005 PM 16904609 ER PT J AU Park, J Chen, L Ratnashinge, L Sellers, TA Tanner, JP Lee, JH Dossett, N Lang, N Kadlubar, FF Ambrosone, CB Zachariah, B Heysek, RV Patterson, S Pow-Sang, J AF Park, Jong Chen, Lan Ratnashinge, Luke Sellers, Thomas A. Tanner, Jean-Paul Lee, Ji-Hyun Dossett, Nicole Lang, Nicholas Kadlubar, Fred F. Ambrosone, Christine B. Zachariah, Babu Heysek, Randy V. Patterson, Stephen Pow-Sang, Julio TI Deletion polymorphism of UDP-glucuronosyltransferase 2B17 and risk of prostate cancer in African American and Caucasian men SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID HORMONE LEVELS; SEX-HORMONES; ORAL-CANCER; CYP17 GENE; SERUM TESTOSTERONE; CIGARETTE-SMOKING; N-NITROSAMINES; UNITED-STATES; EXPRESSION; UGT2B15 AB Purpose: UDP-glucuronosyltransferases (UGT) are a family of enzymes that glucuronidate many endogenous chemicals, including androgens. This makes them more hydrophilic, alters biological activity and facilitates their excretion. A deletion polymorphism in the UGT2B17 gene was recently described that was associated with a reduced rate of glucuronidation in vivo. The purpose of this study was to determine if the deletion polymorphism is associated with susceptibility to prostate cancer. Materials and Methods: UGT2B17 expression was determined by reverse transcription-PCR of pathologically normal prostate tissues (n = 5). In a case-control study with 420 patients with incident primary prostate cancer (127 African Americans and 293 Caucasians) and 487 controls (120 African Americans and 367 Caucasians), the frequency of UGT2B17 deletion polymorphism in genomic DNA was compared between cases and controls with PCR analysis. Results: UGT2B17 mRNA was detected only in individuals with at least one UGT2B17 allele. The frequency of the null genotype was present in 0.11 and 0.12 of Caucasian and African American controls, respectively. When all subjects were considered, a significant association was found between the UGT2B17 deletion polymorphism and prostate cancer risk [odds ratio (OR), 1.7; 95% confidence interval (95% CI), 1.2-2.6]. There was an increase in prostate cancer risk among individuals with UGT2B17 deletion polymorphism in Caucasians (OR, 1.9; 95% CI, 1.2-3.0) but not in African Americans (OR, 1.3; 95% CI, 0.6-2.7). Conclusions: These results suggest that the UGT2B17 enzyme may play a role in the metabolism of androgens in prostate tissue and that the UGT2B17 deletion polymorphism is associated with prostate cancer risk. C1 James A Haley Vet Hosp, Div Canc Prevent & Control, H Lee Moffitt Canc Ctr, Tampa, FL 33612 USA. James A Haley Vet Hosp, Genitourinary Div, H Lee Moffitt Canc Ctr, Tampa, FL 33612 USA. James A Haley Vet Hosp, Genitourinary Div, Tampa, FL 33612 USA. Natl Ctr Toxicol Res, Div Pharmacogenom & Mol Epidemiol, Jefferson, AR 72079 USA. Univ Arkansas Med Sci, Arkansas Canc Res Ctr, Little Rock, AR 72205 USA. Univ Arkansas Med Sci, Coll Publ Hlth, Little Rock, AR 72205 USA. Cent Arkansa Vet Hlth Care Syst, Little Rock, AR USA. Roswell Pk Canc Inst, Dept Epidemiol, Buffalo, NY 14263 USA. RP Park, J (reprint author), Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, MRC3047,12902 Magnolia Dr, Tampa, FL 33612 USA. EM Parkj@moffitt.usf.edu FU NIA NIH HHS [1R01AG15722] NR 67 TC 73 Z9 76 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 AUG PY 2006 VL 15 IS 8 BP 1473 EP 1478 DI 10.1158/1055-9965.EPI-06-0141 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 073YT UT WOS:000239779500009 PM 16896035 ER PT J AU Inoue, S Leitner, WW Golding, B Scott, D AF Inoue, Satoshi Leitner, Wolfgang W. Golding, Basil Scott, Dorothy TI Inhibitory effects of B cells on antitumor immunity SO CANCER RESEARCH LA English DT Article ID CD8(+) T-CELLS; CD40 LIGAND; TUMOR IMMUNOSURVEILLANCE; CUTTING EDGE; EXPRESSION; CANCER; MELANOMA; LYMPHOCYTES; ANTIGEN; INTERLEUKIN-10 AB B-cell functions in antitumor immunity are not well understood. In this study, we evaluated the role of B cells in the development of antitumor immunity using Friend murine leukemia virus gag-expressing mouse EL-4 (EL-4 gag), D5 mouse melanoma, or MCA304 mouse sarcoma cells. To screen tumors for susceptibility to B-cell-deficient immune environments, spleen cells from naive C57BL/6 [wild-type (WT)] and B-cell knockout (BKO) mice were cultured with irradiated tumor cells in vitro. When cells were stimulated with EL-4 gag or D5 (but not MCA304 tumors), IFN-gamma production from CD8 T cells and natural killer cells was markedly decreased in WT compared with BKO cultures. IFN-gamma production was correlated with CD40 ligand expression on the tumor and inversely with interleukin-10 (IL-10) production by B cells. Sorted WT B cells produced more IL-10 than CD40 knockout (CD40KO) B cells when cocultured with EL-4 gag or D5 (but not MCA304). IFN-gamma production by BKO cells was reduced by the addition of sorted naive WT B cells (partially by CD40KO B cells) or recombinant mouse IL-10. In vivo tumor progression mirrored in vitro studies in that WT mice were unable to control tumor growth whereas EL-4 gag and D5 tumors (but not MCA304) were eliminated in BKO mice. Robust in vivo antitumor CTLs developed only in BKO tumor-challenged mice. Our studies provide the first mechanistic basis for the concept that B-cell depletion could therapeutically enhance antitumor immune responses to certain tumors by decreasing IL-10 production from B cells. C1 US FDA, Ctr Biol Evaluat & Res, Div Hematol, Rockville, MD 20852 USA. NCI, Dermatol Branch, NIH, Bethesda, MD USA. RP Scott, D (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Hematol, 1401 Rockville Pike,HFM-345, Rockville, MD 20852 USA. EM dorothy.scott@fda.hhs.gov RI Leitner, Wolfgang/F-5741-2011 OI Leitner, Wolfgang/0000-0003-3125-5922 FU Intramural NIH HHS NR 45 TC 121 Z9 130 U1 0 U2 1 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 1 PY 2006 VL 66 IS 15 BP 7741 EP 7747 DI 10.1158/0008-5472.CAN-05-3766 PG 7 WC Oncology SC Oncology GA 069XU UT WOS:000239483500048 PM 16885377 ER PT J AU Schmitt, TC Biris, AS Miller, DW Biris, AR Lupu, D Trigwell, S Rahman, ZU AF Schmitt, T. C. Biris, A. S. Miller, D. W. Biris, A. R. Lupu, D. Trigwell, S. Rahman, Z. U. TI Analysis of effluent gases during the CCVD growth of multi-wall carbon nanotubes from acetylene SO CARBON LA English DT Article DE catalytic chemical vapor deposition; carbon nanotubes; thermodynamic analysis; chromatography ID LARGE-SCALE PRODUCTION; CATALYTIC DECOMPOSITION; HYDROGEN; SUPPORT AB Catalytic chemical vapor deposition was used to grow multi-walled carbon nanotubes on a Fe:Co:CaCO3 catalyst from acetylene. The influent and effluent gases were analyzed by gas chromatography and mass spectrometry at different time intervals during the nanotubes growth process in order to better understand and optimize the overall reaction. A large number of byproducts were identified and it was found that the number and the level for some of the carbon byproducts significantly increased over time. The CaCO3 catalytic support thermally decomposed into CaO and CO2 resulting in a mixture of two catalysts for growing the nanotubes, which were found to have outer diameters belonging to two main groups 8-35 nm and 40-60 nm, respectively. (c) 2006 Elsevier Ltd. All rights reserved. C1 Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Univ Arkansas, Grad Inst Technol, Ctr Nanotechnol, Little Rock, AR 72204 USA. Natl Inst Res & Dev Isotop & Mol Technol, R-400293 Cluj Napoca, Romania. Electrostat & Surface Phys Lab, Kennedy Space Ctr, FL 32899 USA. Univ Cent Florida, Adv Mat Proc & Anal Ctr, Orlando, FL 32826 USA. RP Schmitt, TC (reprint author), Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM tschmitt@nctr.fda.gov RI Biris, Alexandru/A-8507-2010; Lupu, Dan/C-3346-2009; Biris, Alexandru /C-4517-2011 NR 21 TC 30 Z9 31 U1 0 U2 7 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0008-6223 EI 1873-3891 J9 CARBON JI Carbon PD AUG PY 2006 VL 44 IS 10 BP 2032 EP 2038 DI 10.1016/j.carbon.2006.01.008 PG 7 WC Chemistry, Physical; Materials Science, Multidisciplinary SC Chemistry; Materials Science GA 056CX UT WOS:000238499900025 ER PT J AU Tryndyak, VP Muskhelishvili, L Kovalchuk, O Rodriguez-Juarez, R Montgomery, B Churchwell, MI Ross, SA Beland, FA Pogribny, IP AF Tryndyak, Volodymyr P. Muskhelishvili, Levan Kovalchuk, Olga Rodriguez-Juarez, Rocio Montgomery, Beverly Churchwell, Mona I. Ross, Sharon A. Beland, Frederick A. Pogribny, Igor P. TI Effect of long-term tamoxifen exposure on genotoxic and epigenetic changes in rat liver: implications for tamoxifen-induced hepatocarcinogenesis SO CARCINOGENESIS LA English DT Article ID DNA ADDUCT FORMATION; CELL-PROLIFERATION; BREAST-CANCER; GENOMIC HYPOMETHYLATION; HEPATIC DNA; GLOBAL DNA; METHYLATION; HEPATOCYTES; EXPRESSION; INDUCTION AB Tamoxifen is a non-steroidal anti-estrogen used for the treatment of breast cancer and, more recently, as a chemopreventive agent in healthy women at high risk of developing breast cancer. On the other hand, tamoxifen is a potent hepatocarcinogen in rats, with both tumor-initiating and tumor-promoting properties. There is substantial evidence that hepatic tumors in rats are initiated as a result of formation of tamoxifen-DNA adducts; however, events subsequent to DNA adduct formation are not clear. Recently, it has been demonstrated that genotoxic carcinogens, in addition to exerting genotoxic effects, often cause epigenetic alterations. In the current study, we investigated whether or not the mechanism of tamoxifen-induced hepatocarcinogenesis includes both genotoxic and epigenetic components. Female Fisher 344 rats were fed a 420 p.p.m. tamoxifen diet for 6, 12, 18 or 24 weeks. Hepatic tamoxifen-DNA adduct levels, as assessed by high-performance liquid chromatography and electrospray tandem mass spectrometry, were 580 adducts/10(8) nt at 6 weeks, and increased to similar to 1700 adducts/10(8) nt by 18 weeks. Global liver DNA hypomethylation, as determined by an HpaII-based cytosine extension assay, was increased at all time points, with the maximum increase (similar to 200%) occurring at 6 weeks. Protein expressions of maintenance (DNMT1) DNA methyltransferase and de novo DNA methyltransferases DNMT3a and DNMT3b were decreased at all time points. Likewise, trimethylation of histone H4 lysine 20 was significantly decreased at all time points. In contrast, non-target tissues (i.e. mammary gland, pancreas and spleen) did not show any changes in global DNA methylation or DNA methyltransferase activity. These data indicate the importance of genotoxic and epigenetic alterations in the etiology of tamoxifen-induced hepatocarcinogenesis. C1 Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. Univ Lethbridge, Dept Biol Sci, Lethbridge, AB T1K 3M4, Canada. NCI, Div Canc Prevent, Bethesda, MD 20892 USA. Natl Ctr Toxicol Res, Toxicol Pathol Associates, Jefferson, AR 72079 USA. RP Pogribny, IP (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM igor.pogribny@fda.hhs.gov NR 52 TC 54 Z9 57 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD AUG PY 2006 VL 27 IS 8 BP 1713 EP 1720 DI 10.1093/carcin/bgl050 PG 8 WC Oncology SC Oncology GA 074VY UT WOS:000239841100023 PM 16632870 ER PT J AU Lisowska, K Dlugonski, J Freeman, JP Cerniglia, CE AF Lisowska, Katarzyna Dlugonski, Jerzy Freeman, James P. Cerniglia, Carl E. TI The effect of the corticosteroid hormone cortexolone on the metabolites produced during phenanthrene biotransformation in Cunninghamella elegans SO CHEMOSPHERE LA English DT Article DE Cunninghamella elegans; metabolism; phenanthrene; corticosteroids; glucoside conjugates ID POLYCYCLIC AROMATIC-HYDROCARBONS; FUNGUS CUNNINGHAMELLA; DEGRADATION; 11-HYDROXYLATION; PROTOPLASTS; ANTHRACENE AB The metabolism of phenanthrene and the mammalian corticosteroid hormone cortexolone by the fungus Cunninghamella elegans was studied. The amounts of the cortexolone transformation products, cortisol and epicortisol, were affected, by the presence of phenanthrene. Approximately 40% more cortisol was produced by C. elegans in cultures with phenanthrene. In contrast, epicortisol formation decreased. C. elegans transformed phenanthrene to phenanthrene trans-1,2-,3,4-, and 9,10-dihydrodiols, phenols, diphenols (diols) and glucoside conjugates of 1-,2-,3-,4-, and 9-phenanthrols. Almost all of the phenanthrene initially added was metabolized to ethyl acetate extractable metabolites. In the mycelia and culture medium extracts, phenanthrol glucosides represented 80% and 94% of the total metabolites, respectively. The major metabolite was the glucoside conjugate of 1-phenanthrol. The presence of cortexolone affected the biodegradation of phenanthrene by decreasing the amounts of phenanthrene metabolites compared to control cultures. (c) 2006 Elsevier Ltd. All rights reserved. C1 Univ Lodz, Dept Ind Microbiol & Biotechnol, PL-90237 Lodz, Poland. US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. RP Lisowska, K (reprint author), Univ Lodz, Dept Ind Microbiol & Biotechnol, Banacha 12-16, PL-90237 Lodz, Poland. EM katalis@biol.uni.lodz.pl NR 21 TC 11 Z9 13 U1 1 U2 5 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 AUG PY 2006 VL 64 IS 9 BP 1499 EP 1506 DI 10.1016/j.chemosphere.2005.12.066 PG 8 WC Environmental Sciences SC Environmental Sciences & Ecology GA 086CH UT WOS:000240650200009 PM 16504243 ER PT J AU Kawakami, K Terabe, M Kioi, M Berzofsky, JA Puri, RK AF Kawakami, Koji Terabe, Masaki Kioi, Mitornu Berzofsky, Jay A. Puri, Raj K. TI Intratumoral therapy with IL13-PE38 results in effective CTL-mediated suppression of IL-13R alpha 2-expressing contralateral tumors SO CLINICAL CANCER RESEARCH LA English DT Article ID TARGETED CANCER-THERAPY; IL-13 RECEPTOR ALPHA-2; INTERLEUKIN-13 RECEPTOR; PSEUDOMONAS EXOTOXIN; SIGNAL-TRANSDUCTION; CARCINOMA-CELLS; NECK-CANCER; HUMAN HEAD; CYTOTOXIN; PROTEIN AB Purpose: IL13-PE38, a targeted cytotoxin comprised of interleukin 13 (IL-13) and a mutated form of Pseudomonas exotoxin, induces specific killing of tumor cells expressing abundant levels of the IL-13R alpha 2 chain. We hypothesized that tumor cells killed by the cytotoxin may release antigens and/or apoptotic bodies when cells are dying, which then induce adoptive immunity, and that the PE38 portion of IL13-PE38 may act as a stimulant for the induction of a CTL response. Experimental Design: To test this hypothesis, we established D5 melanoma tumors with or without expression of the IL-13R alpha 2 chain in both flanks of C57BL/6 mice, and then IL13-PE38 was injected in the right flank tumors only. Results and Conclusions: When animals with IL-13R alpha 2-expressing D5 tumor (right) were injected with IL13-PE38, right flank tumors expressing the IL-13R alpha 2 chain not only showed dramatic regression but contralateral tumors (left flank) also showed tumor regression. Cell depletion experiments in tumor-bearing animals indicated that both CD8(+) and CD4(+) T cells contribute to the regression of contralateral tumors through CTL activation in the periphery and cellular infiltration into tumors. In addition, intratumoral treatment into s.c. tumors of mice bearing metastatic lung tumors with IL13-PE38 showed not only the reduction of treated s.c. tumor but also the reduction of lung metastasis. Thus, IL13-PE38 mediates an antitumor effect not only directly but also indirectly by inducing a host CD8(+) T cell immune response. Accordingly, targeted cytotoxins may be used to treat local disease even if they cannot be administered systemically, and yet may still induce a reasonable systemic antitumor response. C1 US FDA, Tumor Vaccines & Biotechnol Branch, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. NCI, Vaccine Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Univ Tokyo, Grad Sch Med, Dept Adv Clin Sci & Therapeut, Tokyo, Japan. RP Kawakami, K (reprint author), Kyoto Univ, Grad Sch Med & Publ Hlth, Dept Pharmacoepidemiol, Sakyo Ku, Yoshida Konoecho, Kyoto 6068501, Japan. EM kawakami-k@umin.ac.jp NR 35 TC 14 Z9 16 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 AUG 1 PY 2006 VL 12 IS 15 BP 4678 EP 4686 DI 10.1158/1078-0432.CCR-06-0192 PG 9 WC Oncology SC Oncology GA 073NR UT WOS:000239750400031 PM 16899618 ER PT J AU Case, HS Reed, HL Palinkas, LA Reedy, KR Do, NV Finney, NS Seip, R AF Case, H. Samuel Reed, H. Lester Palinkas, Lawrence A. Reedy, Kathleen R. Do, Nhan Van Finney, Nancy S. Seip, Richard TI Resting and exercise energy use in Antarctica: effect of 50% restriction in temperate climate energy requirements SO CLINICAL ENDOCRINOLOGY LA English DT Article ID THYROID-HORMONE CONCENTRATIONS; PREDICTING BODY DENSITY; LOCAL COLD-ACCLIMATION; LOW-CALORIE DIET; WEIGHT-LOSS; OBESE WOMEN; GENERALIZED EQUATIONS; METABOLIC-RATE; NORMAL MEN; SERUM AB Objective To determine the impact of energy restriction (ER) upon the previously reported increased resting and exercise-related oxygen utilization, reduced body temperature, increased serum TSH, and reduced serum free T3 concentrations found during Antarctic residence (AR). Design Prospective, intervention with both paired controls and a similar reference control group (RG). Patients and measurements Seven subjects were assessed before and after a 50% ER period of 60 h. This ER was carried out within 30 days of arriving in Antarctica in October (OCT) and again after 10 months AR in August (AUG). During the periods of ER, mean energy consumption was 5662 +/- 1344 kJ/day in OCT and 5529 +/- 967 kJ/day in AUG. Resting metabolic rate (RMR), a calculated resting metabolic rate (RMRreg) using a submaximal work regression, serum TSH, FT3 and tympanic temperature (Tty) were measured. These values were compared with a similar RG of 12 subjects reported previously who were studied in California, USA before and then again during AR. Results Weight declined by 1.1 +/- 0.1 kg/day (OCT) and 0.92 +/- 0.2 kg/day (AUG) with ER, resulting in a reduction of body weight by 3.1 +/- 0.4% in OCT (P = 0.0001) and 2.5 +/- 0.4% in AUG (P = 0.0015) during AR. The RMR before ER did not change with AR and it was not significantly different from the RG studied in California. With ER the RMR tended to decline in both OCT (132 +/- 5 to 122 +/- 4 mlO(2)/min/m(2)) and AUG (134 +/- 5 to 126 +/- 5 mlO(2)/min/m(2)), but these were not significant. By contrast, RMRreg obtained before ER was increased with AR by 22.5 +/- 7.8% (P = 0.01) in OCT and by 28.1 +/- 7.0% (P = 0.0008) in AUG over the RG values obtained in California. RMRreg did not decrease with ER in either OCT or AUG. The total energy expenditure derived from these measures of weight loss suggests that 24-h energy requirements are 74.4% [95% confidence interval (CI) 2.6-146.3; P < 0.05] more than those expected in temperate climates. Tty declined by 0.6 +/- 0.2 degrees C (P < 0.01) with AR compared with the RG measured in California, but was not affected by either period of ER. ER had no effect on FT3 but tended to decrease serum TSH in AUG (P = 0.06). Conclusions Exercise-related energy requirements are increased with AR. Moderate ER may reduce resting but not exercise-related energy expenditure and it is associated with a weight loss exceeding expectations for 50% restriction of temperate climate energy predictions. C1 McDaniel Coll, Dept Exercise Sci & Phys Educ, Westminster, MD USA. MultiCare Hlth Syst, Tacoma, WA USA. Univ So Calif, Sch Social Work, Los Angeles, CA 90089 USA. US FDA, Rockville, MD 20857 USA. Madigan Army Med Ctr, Dept Clin Invest, Tacoma, WA 98431 USA. Hartford Hosp, Hartford, CT 06115 USA. RP Case, HS (reprint author), 1201 Pinch Valley Rd, Westminster, MD 21158 USA. EM scase@mcdaniel.edu NR 51 TC 7 Z9 7 U1 1 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0300-0664 J9 CLIN ENDOCRINOL JI Clin. Endocrinol. PD AUG PY 2006 VL 65 IS 2 BP 257 EP 264 DI 10.1111/j.1365-2265.2006.02588.x PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 064RW UT WOS:000239107800020 PM 16886970 ER PT J AU Joner, M Finn, AV Farb, A Ladich, E Kolodgie, FD Skorija, K Gold, HK Virmani, R AF Joner, M. Finn, A. V. Farb, A. Ladich, E. Kolodgie, F. D. Skorija, K. Gold, H. K. Virmani, R. CA CVPATH TI Stent thrombosis in the drug-eluting stents era: Incidence, predictors, mechanisms SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT 28th Congress of the European-Society-of-Cardiology/World Congress of Cardiology CY SEP 02-06, 2006 CL Barcelona, SPAIN SP European Soc Cardiol, World Heart Federat C1 CVPATH, Gaithersburg, MD USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. FDA, Rockville, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD AUG PY 2006 VL 27 SU 1 MA 1011 BP 154 EP 154 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 086JA UT WOS:000240668401079 ER PT J AU Singh, G Graham, D Wang, H Mithal, A Triadafilopoulos, G AF Singh, G. Graham, D. Wang, H. Mithal, A. Triadafilopoulos, G. TI Concomitant aspirin use reduces acute myocardial infarction risk in cyclooxygenase-2 selective and nonselective nonsteroidal anti-inflammatory drug users SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT 28th Congress of the European-Society-of-Cardiology/World Congress of Cardiology CY SEP 02-06, 2006 CL Barcelona, SPAIN SP European Soc Cardiol, World Heart Federat C1 Stanford Univ, Palo Alto, CA 94304 USA. US FDA, Rockville, MD 20857 USA. ICORE, Palo Alto, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD AUG PY 2006 VL 27 SU 1 BP 748 EP 748 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 086JA UT WOS:000240668405270 ER PT J AU Wokovich, AM Prodduturi, S Doub, WH Hussain, AS Buhse, LF AF Wokovich, Anna M. Prodduturi, Suneela Doub, William H. Hussain, Ajaz S. Buhse, Lucinda F. TI Transdermal drug delivery system (TDDS) adhesion as a critical safety, efficacy and quality attribute SO EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS LA English DT Review DE transdermal drug delivery system; transdermal system; drug delivery; patch; adhesion; tack; peel; shear ID PRESSURE-SENSITIVE ADHESIVES; SKIN; PERMEATION; FENTANYL; PATCHES; MATRIX; TOLERABILITY; PERFORMANCE; CONTACT; RELEASE AB Transdermal drug delivery systems (TDDS), also known as "patches," are dosage forms designed to deliver a therapeutically effective amount of drug across a patient's skin. The adhesive of the transdermal drug delivery system is critical to the safety, efficacy and quality of the product. In the Drug Quality Reporting System (DQRS), the United States Food and Drug Administration (FDA) has received numerous reports of "adhesion lacking" for transdermal drug delivery systems. This article provides an overview of types of transdermals, their anatomy, the role of adhesion, the possible adhesion failure modes and how adhesion can be measured. Excerpts from FDA reports on the lack of adhesion of transdermal system products are presented. Pros and cons of in vitro techniques, such as peel adhesion, tack and shear strength, in vivo techniques used to evaluate adhesive properties are discussed. To see a decrease in "adhesion lacking" reports, adhesion needs to become an important design parameter and suitable methods need to be available to assess quality and in vivo performance. This article provides a framework for further discussion and scientific work to improve transdermal adhesive performance. Published by Elsevier B.V. C1 US FDA, Div Pharmaceut Anal, St Louis, MO 63101 USA. Food & Drug Adm, Off Pharmaceut Sci, Silver Spring, MD USA. RP Wokovich, AM (reprint author), US FDA, Div Pharmaceut Anal, 1114 Market St,Room 1002, St Louis, MO 63101 USA. EM anna.wokovich@fda.hhs.gov NR 44 TC 101 Z9 117 U1 5 U2 37 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 AUG PY 2006 VL 64 IS 1 BP 1 EP 8 DI 10.1016/j.ejpb.2006.03.009 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 082FM UT WOS:000240372100001 PM 16797171 ER PT J AU Hastings, KL AF Hastings, Kenneth L. TI The use of hepatotoxic signals to predict the safety of peroxisome proliferator-activated receptor agonists SO EXPERT OPINION ON DRUG METABOLISM & TOXICOLOGY LA English DT Editorial Material DE diseased animal models; Hy's law; PPAR; troglitazone ID PPAR-GAMMA; HYS LAW; ALPHA; TROGLITAZONE; EXPRESSION; LIVER C1 US FDA, Ctr Drug Evaluat & Res, Off New Drugs, Rockville, MD 20857 USA. RP Hastings, KL (reprint author), US FDA, Ctr Drug Evaluat & Res, Off New Drugs, Rockville, MD 20857 USA. EM hastingsk@fda.hhs.gov NR 20 TC 0 Z9 1 U1 0 U2 0 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1742-5255 J9 EXPERT OPIN DRUG MET JI Expert Opin. Drug Metab. Toxicol. PD AUG PY 2006 VL 2 IS 4 BP 489 EP 492 DI 10.1517/17425255.2.4.489 PG 4 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 167VF UT WOS:000246479900001 PM 16859399 ER PT J AU Culp, SJ Mellick, PW Trotter, RW Greenlees, KJ Kodell, RL Beland, FA AF Culp, Sandra J. Mellick, Paul W. Trotter, Ronald W. Greenlees, Kevin J. Kodell, Ralph L. Beland, Frederick A. TI Carcinogenicity of malachite green chloride and leucomalachite green in B6C3F(1) mice and F344 rats SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article DE malachite green; leucomalachite green; carcinogenesis ID NATIONAL-TOXICOLOGY-PROGRAM; BODY-WEIGHT; TRANSGENIC MOUSE; CHANNEL CATFISH; TUMOR-INCIDENCE; DNA ADDUCT; TESTS; METABOLISM; TOXICITY; SURVIVAL AB Malachite green is a triphenylmethane dye used in the fish industry as an anti-fungal agent. Leucomalachite green is formed by the metabolic reduction of malachite green and persists in the tissues of exposed fish. In this study, we examined the carcinogenicity of malachite green chloride and leucomalachite green. Female F344 rats (48 per group) were fed diets containing 0, 100, 300, or 600 ppm malachite green chloride for 104 weeks, at which time the extent of tumorigenesis was assessed. Additional groups of 48 female and 48 male F344 rats were fed diets containing 0, 91, 272, or 543 ppm leucomalachite green for 104 weeks. Groups of 48 female B6C3F(1) mice were fed diets containing 0, 100, 225, or 450 ppm malachite green chloride or 0, 91, 204, or 408 ppm leucomalachite green for 104 weeks. For each of the exposures, food consumption in the treatment groups was similar to the controls. Rats fed malachite green chloride or leucomalachite green had dose-dependent reductions in body weight; in mice, there were no consistent effects upon body weights with either compound. Female rats exposed to malachite green chloride had increased incidences of thyroid gland follicular cell adenoma or carcinoma and hepatocellular adenoma, and a dose-related increasing trend in mammary gland carcinoma. Female rats fed malachite green chloride and female and male rats fed leucomalachite green had a dose-related decreasing trend in the incidence of mononuclear cell leukemia. In male rats fed leucomalachite green there was a decreasing trend in pituitary gland adenoma and an increasing trend in interstitial cell adenoma of the testis. There were no treatment-related neoplasms in female B6C3F(1) mice fed malachite green chloride. Female mice fed leucomalachite green had a dose-related increasing trend in the incidence of hepatocellular adenoma or carcinoma, with the incidence being significant in the highest dose group. (c) 2006 Elsevier Ltd. All rights reserved. C1 Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. Natl Ctr Toxicol Res, Pathol Associates Int, Jefferson, AR 72079 USA. US FDA, Ctr Vet Med, Rockville, MD 20855 USA. Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. RP Beland, FA (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM frederick.beland@fda.hhs.gov NR 43 TC 59 Z9 70 U1 5 U2 32 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 2006 VL 44 IS 8 BP 1204 EP 1212 DI 10.1016/j.fct.2006.01.016 PG 9 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA 076QF UT WOS:000239972100004 PM 16554117 ER PT J AU Reddy, NR Skinner, GE Oh, S AF Reddy, N. Rukma Skinner, Guy E. Oh, Sangsuk TI Clostridium botulinum and its control in low-acid canned foods SO FOOD SCIENCE AND BIOTECHNOLOGY LA English DT Review DE Clostridium botulinum; food-borne botulism; low-acid canned foods ID FOODBORNE BOTULISM; INFANT BOTULISM; UNITED-STATES; TOXIN; OUTBREAK; BUTYRICUM; INACTIVATION; ORGANISM; DEATHS; SUDDEN AB Clostridium botidinum spores are widely distributed in nature. Type A and proteolytic type B bacteria produce heat-resistant spores that are primarily involved in most of the food-borne botulism outbreaks associated with low-acid canned foods. Food-borne botulism results from the consumption of food in which C botulinum has grown and produced neurotoxin. Growth and toxin production of type A and proteolytic type B in canned foods can be prevented by the use of thermal sterilization alone or in combination with salt and nitrite. The hazardousness of C botulinum in low-acid canned foods can also be reduced by preventing post-process contamination and introducing hazard analysis and critical control point (HACCP) practices during production. Effectiveness of non-thermal technologies such C1 US FDA, Natl Ctr Food Safety & Technol, Summit Argo, IL 60501 USA. RP Oh, S (reprint author), US FDA, Natl Ctr Food Safety & Technol, 6502 S Archer Rd, Summit Argo, IL 60501 USA. EM ssoh71@ewha.ac.kr NR 41 TC 1 Z9 1 U1 4 U2 14 PU KOREAN SOC FOOD SCIENCE TECHNOLOGY PI SEOUL PA KOREA SCIENCE TECHNOLOGY CENTER #605, 635-4 YEOGSAM-DONG, KANGNAM-KU, SEOUL 135-703, SOUTH KOREA SN 1226-7708 J9 FOOD SCI BIOTECHNOL JI Food Sci. Biotechnol. PD AUG PY 2006 VL 15 IS 4 BP 499 EP 505 PG 7 WC Food Science & Technology SC Food Science & Technology GA 081MF UT WOS:000240321000003 ER PT J AU Holada, K Glierova, H Simak, J Vostal, JG AF Holada, Karel Glierova, Hana Simak, Jan Vostal, Jaroslav G. TI Expression of cellular prion protein on platelets from patients with gray platelet or Hermansky-Pudlak syndrome and the protein's association with alpha-granules SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Article DE prion protein; PrPc; platelets; alpha granules ID TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHY; CREUTZFELDT-JAKOB-DISEASE; BLOOD-CELLS; INFECTIVITY; COMPONENTS; PRPC; TRANSFUSION; HAMSTER AB The cellular prion protein (PrPc) is a membrane glycoprotein expressed on many human cells including platelets. We investigated the cellular localization of platelet PrPc. In resting platelets most PrPc was localized inside the cells. The correlation of PrPc and P-selectin surface up-regulation after platelet activation suggested its association with alpha-granules. This was confirmed by normal expression of PrPc on Hermansky-Pudlak syndrome platelets, which lack dense granules, and failure of gray platelet syndrome platelets, which lack alpha-granules, to up-regulate PrPc. Our results warrant further studies on the role of platelet PrPc in the transmission of prion diseases by blood transfusion. C1 Charles Univ, Inst Microbiol & Immunol, Fac Med 1, Prague 12820 2, Czech Republic. US FDA, Div Hematol, CBER, Bethesda, MD 20014 USA. RP Holada, K (reprint author), Charles Univ, Inst Microbiol & Immunol, Fac Med 1, Studnickova 7, Prague 12820 2, Czech Republic. EM karel.holada@LF1.cuni.cz RI Simak, Jan/C-1153-2011 NR 18 TC 11 Z9 12 U1 0 U2 3 PU FERRATA STORTI FOUNDATION PI PAVIA PA STRADA NUOVA 134, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD AUG PY 2006 VL 91 IS 8 BP 1126 EP 1129 PG 4 WC Hematology SC Hematology GA 070LI UT WOS:000239523500020 PM 16885055 ER PT J AU Limaye, PB Bhave, VS Palkar, PS Apte, UM Sawant, SP Yu, ST Latendresse, JR Reddy, JK Mehendale, HM AF Limaye, Pallavi B. Bhave, Vishakha S. Palkar, Prajakta S. Apte, Udayan M. Sawant, Sharmilee P. Yu, Songtao Latendresse, John R. Reddy, Janardan K. Mehendale, Harihara M. TI Upregulation of calpastatin in regenerating and developing rat liver: Role in resistance against hepatotoxicity SO HEPATOLOGY LA English DT Article ID CARBON-TETRACHLORIDE HEPATOTOXICITY; ACETAMINOPHEN-INDUCED LETHALITY; ACTIVATED NEUTRAL PROTEASE; TISSUE-REPAIR UNDERLIES; PARTIAL-HEPATECTOMY; CALPAIN INHIBITORS; HEPATOCELLULAR REGENERATION; MEDIATES PROGRESSION; CCL4 HEPATOTOXICITY; HEPATIC-FAILURE AB Acute liver failure induced by hepatotoxic drugs results from rapid progression of injury. Substantial research has shown that timely liver regeneration can prevent progression of injury leading to a favorable prognosis. However, the mechanism by which compensatory regeneration prevents progression of injury is not known. We have recently reported that calpain released from necrotic hepatocytes mediates progression of liver injury even after the hepatotoxic drug is cleared from the body. By examining expression of calpastatin (CAST), an endogenous inhibitor of calpain in three liver cell division models known to be resistant to hepatotoxicity, we tested the hypothesis that increased CAST in the dividing hepatocytes affords resistance against progression of injury. Liver regeneration that follows CCl4-induced liver injury, 70% partial hepatectomy, and postnatal liver development were used. In all three models, CAST was upregulated in the dividing/newly divided hepatocytes and declined to normal levels with the cessation of cell proliferation. To test whether CAST overexpression confers resistance against hepatotoxicity, CAST was overexpressed in the livers of normal SW mice using adenovints before challenging them with acetaminophen (APAP) overdose. These mice exhibited markedly attenuated progression of liver injury and 57% survival. Whereas APAP-bioactivating enzymes and covalent binding of the APAP-derived reactive metabolites remained unaffected, degradation of calpain specific target substrates such as fodrin was significantly reduced in these mice. In conclusion, CAST overexpression could be used as a therapeutic strategy to prevent progression of liver injury where liver regeneration is severely hampered. C1 NE Louisiana Univ, Dept Toxicol, Coll Pharm, Monroe, LA 71209 USA. Northwestern Univ, Feinberg Sch Med, Dept Pathol, Chicago, IL 60611 USA. Natl Ctr Toxicol Res, Toxicol Pathol Associates, Jefferson, AR 72079 USA. RP Mehendale, HM (reprint author), NE Louisiana Univ, Dept Toxicol, Coll Pharm, 700 Univ Ave,Sugar Hall 306 B, Monroe, LA 71209 USA. EM mehendale@ulm.edu RI Latendresse, John/A-9215-2009; OI Bhave, Vishakha/0000-0003-0149-579X NR 49 TC 27 Z9 27 U1 0 U2 4 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD AUG PY 2006 VL 44 IS 2 BP 379 EP 388 DI 10.1002/hep.21250 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 070LF UT WOS:000239523200012 PM 16871587 ER PT J AU Davis, CC Beard, BB Tillman, A Rzasa, J Merideth, E Balzano, Q AF Davis, Christopher C. Beard, Brian B. Tillman, Ahlia Rzasa, John Merideth, Eric Balzano, Quirino TI International intercomparision of specific absorption rates in a flat absorbing phantom in the near-field of dipole antennas SO IEEE TRANSACTIONS ON ELECTROMAGNETIC COMPATIBILITY LA English DT Article DE FCC certification; near-field antenna measurement; specific absorption rate; wireless phones AB This paper reports the results of an international intercomparison of the specific absorption rates (SARs) measured in a flat-bottomed container (flat phantom), filled with human head tissue simulant fluid, placed in the near-field of custom-built dipole antennas operating at 900 and 1800 MHz, respectively. These tests of the reliability of experimental SAR measurements have been conducted as part of a verification of the ways in which wireless phones are tested and certified for compliance with safety standards. The measurements are made using small electric-field probes scanned in the simulant fluid in the phantom to record the spatial SAR distribution. The intercomparison involved a standard fiat phantom, antennas, power meters, and RF components being circulated among 15 different governmental and industrial laboratories. At the conclusion of each laboratory's measurements, the following results were communicated to the coordinators: Spatial SAR scans at 900 and 1800 MHz and 1 and 10 g maximum spatial SAR averages for cubic volumes at 900 and 1800 MHz. The overall results, given as meanstandard deviation, are the following: at 900 MHz. I g average 7.850.76; 10 g average 5.160.45; at 1800 MHz, 1 g average 18.44 +/- 1.65; 10 g average 10.14 +/- 0.85, all measured in units of watt per kilogram, per watt of radiated power. C1 Univ Maryland, Dept Elect & Comp Engn, College Pk, MD 20742 USA. Integrated Def Syst Div, Waltham, MA 02451 USA. US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. RP Davis, CC (reprint author), Univ Maryland, Dept Elect & Comp Engn, College Pk, MD 20742 USA. EM davis@eng.umd.edu OI Beard, Brian/0000-0001-6480-0857 NR 8 TC 8 Z9 8 U1 0 U2 3 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 0018-9375 J9 IEEE T ELECTROMAGN C JI IEEE Trans. Electromagn. Compat. PD AUG PY 2006 VL 48 IS 3 BP 579 EP 588 DI 10.1109/TEMC.2006.877785 PG 10 WC Engineering, Electrical & Electronic; Telecommunications SC Engineering; Telecommunications GA 080JF UT WOS:000240243000017 ER PT J AU Gavrielides, MA Sikudova, E Pitas, I AF Gavrielides, Marios A. Sikudova, Elena Pitas, Ioannis TI Color-based descriptors for image fingerprinting SO IEEE TRANSACTIONS ON MULTIMEDIA LA English DT Article DE color histogram; color quantization; image fingerprinting; image indexing; image representation; retrieval; spatial chromatic histogram ID RETRIEVAL AB Typically, content-based image retrieval (CBIR) systems receive an image or an image description as input and retrieve images from a database that are similar to the query image in regard to properties such as color, texture, shape, or layout. A kind of system that did not receive much attention compared to CBIR systems, is one that searches for images that are not similar but exact copies of the same image that have undergone some transformation. In this paper, we present such a system referred to as an image fingerprinting system, since it aims to extract unique and robust image descriptors (in analogy to human fingerprints). We examine the use of color-based descriptors and provide comparisons for different quantization methods, histograms calculated using color-only and/or spatial-color information with different similarity measures. The system was evaluated with receiver operating characteristic (ROC) analysis on a large database of 919 original images consisting of randomly drawn art images and similar images from specific categories, along with 30 transformed images for each original, totaling 27570 images. The transformed images were produced with attacks that typically occur during digital image distribution, including different degrees of scaling, rotation, cropping, smoothing, additive noise and compression, as well as illumination contrast changes. Results showed a sensitivity of 96% at the small false positive fraction of 4% and a reduced sensitivity of 88% when 13% of all transformations involved changing the illuminance of the images. The overall performance of the system is encouraging for the use of color, and particularly spatial chromatic descriptors for image fingerprinting. C1 Aristotle Univ Thessaloniki, Dept Informat, Artificial Intelligence & Informat Anal Lab, Thessaloniki 54124, Greece. RP Gavrielides, MA (reprint author), US FDA, Div Imaging & Appl Math, Off Sci, Ctr Devices & Radiol Hlth, Rockville, MD 20852 USA. EM marios.gavrielides@fda.hhs.gov; sikudova@fmph.uniba.sk; pitas@zeus.csd.auth.gr NR 17 TC 9 Z9 9 U1 0 U2 2 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 1520-9210 EI 1941-0077 J9 IEEE T MULTIMEDIA JI IEEE Trans. Multimedia PD AUG PY 2006 VL 8 IS 4 BP 740 EP 748 DI 10.1109/TMM.2006.876290 PG 9 WC Computer Science, Information Systems; Computer Science, Software Engineering; Telecommunications SC Computer Science; Telecommunications GA 069BS UT WOS:000239420300009 ER PT J AU Mahajan, B Noiva, R Yadava, A Zheng, H Majam, V Mohan, KVK Moch, JK Haynes, JD Nakhasi, H Kumar, S AF Mahajan, B. Noiva, R. Yadava, A. Zheng, H. Majam, V. Mohan, K. V. Krishna Moch, J. K. Haynes, J. D. Nakhasi, H. Kumar, S. TI Protein disulfide isomerase assisted protein folding in malaria parasites SO INTERNATIONAL JOURNAL FOR PARASITOLOGY LA English DT Article DE Plasmodium falciparum; protein disulfide isomerase; EBA-175; folding ID APICAL MEMBRANE ANTIGEN-1; PROTIST GIARDIA-LAMBLIA; PLASMODIUM-FALCIPARUM; ENDOPLASMIC-RETICULUM; BOND FORMATION; ESCHERICHIA-COLI; MOLECULAR CHAPERONES; VACCINE CANDIDATE; PICHIA-PASTORIS; ACTIVE-SITES AB In eukaryotes, the formation of protein disulfide bonds among cysteine residues is mediated by protein disulfide isomerases and occurs in the highly oxidised environment of the endoplasmic reticulum. This process is poorly understood in malaria parasites. In this paper, we report the gene isolation, sequence and phylogenetic comparisons, protein structure and thioredoxin-domain analyses of nine protein disulfide isomerases-like molecules from five species of malaria parasites including Plasmodium falciparum and Plasmodium vivax (human), Plasmodium knowlesi (simian) and Plasmodium berghei and Plasmodium yoelii (murine). Four of the studied protein disulfide isomerases belong to P. falciparum malaria and have been named PfPDI-8, PtPDI-9, PfPDI-11 and PfPDI-14, based on their chromosomal location. Among these, PfPDI-8 bears the closest similarity to a prototype PDI molecule with two thioredoxin domains (containing CGHC active sites) and a C-terminal Endoplasmic reticulum retrieval signal, SEEL. PfPDI-8 is expressed during all stages of parasite life cycle and is highly conserved (82-96% identity at amino acid level) in the other four Plasmodium species studied. Detailed biochemical analysis of PfPDI-8 revealed that this molecule is a potent oxido-reductase enzyme that facilitated the disulfide-dependent conformational folding of EBA-175, a leading malaria vaccine candidate. These studies open the avenues to understand the process of protein folding and secretory pathway in malaria parasites that in turn might aid in the production of superior recombinant vaccines and provide novel drug targets. Published by Elsevier Ltd on behalf of Australian Society for Parasitology Inc. C1 US FDA, Div Emerging & Transfus Transmitted Dis, Ctr Biol Evaluat & Res, Rockville, MD 20895 USA. Univ S Dakota, Sch Med, Div Basic Biomed Sci, Vermillion, SD 57069 USA. Walter Reed Army Inst Res, Dept Immunol, Silver Spring, MD 20910 USA. RP Kumar, S (reprint author), US FDA, Div Emerging & Transfus Transmitted Dis, Ctr Biol Evaluat & Res, Rockville, MD 20895 USA. EM sanjai.kumar@fda.hhs.gov FU NIGMS NIH HHS [GM073421-01] NR 52 TC 19 Z9 19 U1 1 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0020-7519 J9 INT J PARASITOL JI Int. J. Parasit. PD AUG PY 2006 VL 36 IS 9 BP 1037 EP 1048 DI 10.1016/j.ijpara.2006.04.012 PG 12 WC Parasitology SC Parasitology GA 077RP UT WOS:000240048000007 PM 16806221 ER PT J AU Whiting, RC Rainosek, A Buchanan, RL Miliotis, M LaBarre, D Long, W Ruple, A Schaub, S AF Whiting, R. C. Rainosek, A. Buchanan, R. L. Miliotis, M. LaBarre, D. Long, W. Ruple, A. Schaub, S. TI Determining the microbiological criteria for lot rejection from the performance objective or food safety objective SO INTERNATIONAL JOURNAL OF FOOD MICROBIOLOGY LA English DT Article DE risk analysis; risk assessment; attribute testing AB The Microbiological Criteria (MC) is a set of parameters used to determine whether a specific lot of food is acceptable or not. These parameters are the microbial test protocol and its sensitivity, the confidence level that an unacceptable lot will be detected, the number of samples to be taken and the number of positive samples that are allowed before rejecting the lot. Determining the microbiological criteria begins with knowledge of the distribution of contamination from samples within a lot, particularly within a lot that is just at the unacceptable level of the microbial hazard. The just unacceptable lot can be defined by the Food Safety Objective (FSO) or Performance Objectives (PO), the small fraction of samples that can exceed these values and the standard deviation of the samples from the lot. With this information, a microbial test protocol is chosen to have a sensitivity level that would detect between approximately 15% and 45% of the samples. A confidence level for the MC and the number of positive samples that would be acceptable (c value which is usually zero) are also chosen. With this information the number of samples (n) required can be calculated. A critical factor in setting the microbiological criteria is the sensitivity of the microbiological test (m value). The sample size (weight) and sampling procedure can affect the standard deviation of the samples, particularly foods with non-homogeneous distribution and low numbers of microorganisms. Sampling, sample preparation and analytical procedures that reduce the variation between the samples will affect the choice of m value and maximum lot mean that meets the MC. Published by Elsevier B.V. C1 US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. Univ S Alabama, Dept Math & Stat, Mobile, AL 36688 USA. USDA, Food Safety & Inspect Serv, Washington, DC 20520 USA. Natl Oceanog & Atmospher Adm, Pascagoula, MS 39568 USA. US EPA, Washington, DC 20460 USA. RP Whiting, RC (reprint author), US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. EM chard.whiting@fda.hhs.gov NR 9 TC 24 Z9 26 U1 1 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-1605 J9 INT J FOOD MICROBIOL JI Int. J. Food Microbiol. PD AUG 1 PY 2006 VL 110 IS 3 BP 263 EP 267 DI 10.1016/j.ijfoodmicro.2006.04.038 PG 5 WC Food Science & Technology; Microbiology SC Food Science & Technology; Microbiology GA 076DE UT WOS:000239936400009 PM 16784791 ER PT J AU Jhoo, JW Freeman, JP Ang, CYW Mihalov, JJ AF Jhoo, J. -W. Freeman, J. P. Ang, C. Y. W. Mihalov, J. J. TI Assessment of kavalactones in kava beverage products and aqueous infusions SO JOURNAL OF FOOD SCIENCE LA English DT Article DE aqueous infusion; functional beverages; kava; kavalactones; Piper methysticum ID PERFORMANCE LIQUID-CHROMATOGRAPHY; PIPER-METHYSTICUM; EXTRACTS; LACTONES; PYRONES; ANXIETY AB Kava (Piper methysticum Forst.f.) is traditionally used as a beverage for relaxation in social occasions in South Pacific islands. This study was conducted to develop analytical methods for assessing kavalactone content hi functional beverage products containing kava, as well as beverages prepared from kava roots by a traditional method involving infusion (mild extraction) with water. Samples of fruit-flavored beverages were prepared by solid-phase or liquid-liquid extraction to remove interfering substances and the major kavalactones (methysticin, dihydromethysticin, kavain, dihydrokavain, yangonin, and desmethoxyyangonin) were separated and identified by GC-FID and GC/EI-MS. A difference in kavalactone content was observed between the 2 commercial beverage products (37.03 compared with 0.044 mg per serving in 240 mL). Kava beverages prepared fresh by water infusion contained much, higher levels of kavalactones than the commercial products as determined by a high-performance liquid chromatographic procedure. The results also demonstrated the isomerization of yangonin (Y) to an acidic aqueous solution, with exposure to light, with the presence of cis-Y in a fruit-flavored beverage containing kava. The implications of the isomerization, of Y on quality and safety aspects have yet to be evaluated. The analytical methods developed In this study are potentially applicable to kavalactone analysis in various nonalcoholic, noncarbonated beverages. C1 US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Kangweon Natl Univ, Dept Food Sci & Technol Anim Resources, Chunchon 200701, Kangwon, South Korea. USDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Jhoo, JW (reprint author), US FDA, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM jjhoo@kangwon.ac.kr NR 18 TC 1 Z9 1 U1 2 U2 5 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-1147 J9 J FOOD SCI JI J. Food Sci. PD AUG PY 2006 VL 71 IS 6 BP C345 EP C351 DI 10.1111/j.1750-3841.2006.00102.x PG 7 WC Food Science & Technology SC Food Science & Technology GA 080ZK UT WOS:000240286800006 ER PT J AU Edelson-Mammel, S Porteous, MK Buchanan, RL AF Edelson-Mammel, S. Porteous, M. K. Buchanan, R. L. TI Acid resistance of twelve strains of Enterobacter sakazakii, and the impact of habituating the cells to an acidic environment SO JOURNAL OF FOOD SCIENCE LA English DT Article DE acid tolerance; pH; stationary phase ID ENTEROHEMORRHAGIC ESCHERICHIA-COLI; LISTERIA-MONOCYTOGENES; INFANT FORMULA; NONTHERMAL INACTIVATION; SHIGELLA-FLEXNERI; TYPHIMURIUM DT104; POWDERED MILK; TOLERANCE; PH; SURVIVAL AB The association of powdered infant formula with cases of severe Enterobacter sakazakii infections in immunocompromised and premature neonates jas led to a need to learn about the basic behavior of this emerging pathogen in food systems and the environment. The current study examines the microorganism's stationary-phase acid resistance using 12 strains that had been previously used to characterize its thermal resistance. Acid resistance was determined by initially culturing the isolates for 18 h in brain heart infusion broth (BHI) at 36 degrees C, transferring the cells to tryptic soy broth (TSB) adjusted to pH 3.0 and 3.5, and determining E. sakazakii survival over the course of 5 h incubation at 36 degrees C. At pH 3.5, 10 of the 12 strains showed less than a 1 log cycle decline over the 5-h incubation period, with the most acid sensitive strain showing an approximate 3.5 log cycle decline. At pH 3.0, the decline over the 5-h incubation period ranged from 4.9 to > 6.3 log cycles; however, substantial diversity was evident when the 1-h/pH 3.0 results were compared. The effect of habituating the cells to a moderately acidic environment was determined by growing the strains in TSB with 0% (nonacidogenic) and 1% glucose (acidogenic), transferring the cells to acidified (pH 3.0) BHI, and determining E. sakazakii survival over the course of 5 h of incubation at 36 degrees C. While there was diversity observed among the strains, in general the stationary-phase acid resistances of several of the strains were enhanced, at least transitorily, by growth in the acidogenic medium. No apparent correlation between the stationary-phase relative acid resistances of the strains based on the 1-h/pH 3.0 acid inactivation values and the previously reported thermal D-values was observed. C1 US FDA, DHHS, Ctr Food Safety & Appl Nutr, College Pk, MD USA. Univ Maryland, College Pk, MD 20742 USA. RP Buchanan, RL (reprint author), US FDA, DHHS, Ctr Food Safety & Appl Nutr, College Pk, MD USA. EM robert.buchanan@fda.hhs.gov NR 36 TC 14 Z9 14 U1 0 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-1147 J9 J FOOD SCI JI J. Food Sci. PD AUG PY 2006 VL 71 IS 6 BP M201 EP M207 DI 10.1111/j.1750-3841.2006.00101.x PG 7 WC Food Science & Technology SC Food Science & Technology GA 080ZK UT WOS:000240286800028 ER PT J AU Gursel, M Gursel, I Mostowski, HS Klinman, DM AF Gursel, Mayda Gursel, Ihsan Mostowski, Howard S. Klinman, Dennis M. TI CXCL16 influences the nature and specificity of CpG-Induced immune activation SO JOURNAL OF IMMUNOLOGY LA English DT Article ID PLASMACYTOID DENDRITIC CELLS; NONSPECIFIC CYTOTOXIC-CELLS; TOLL-LIKE RECEPTOR-9; CHEMOKINE LIGAND-16; SCAVENGER RECEPTOR; CELLULAR UPTAKE; CUTTING EDGE; DNA; OLIGODEOXYNUCLEOTIDES; EXPRESSION AB Unmethylated CpG motifs are present at high frequency in bacterial DNA. They provide a danger signal to the mammalian immune system that triggers a protective immune response characterized by the production of Th1 and proinflammatory cytokines and chemokines. Although the recognition of CpG DNA by B cells and plasmacytoid dendritic cells is mediated by TLR 9, these cell types differ in their ability to bind and respond to structurally distinct classes of CpG oligonucleotides. This work establishes that CXCL16, a membrane-bound scavenger receptor, influences the uptake, subcellular localization, and cytokine profile induced by D oligonucleotides. This is the first example of a surface receptor modifying the cellular specificity and nature of the immune response mediated by an intracellular TLR. C1 US FDA, Ctr Biol Evaluat & Res, Sect Retroviral Res, Bethesda, MD 20892 USA. RP Klinman, DM (reprint author), US FDA, Ctr Biol Evaluat & Res, Sect Retroviral Res, Bldg 29A,Room 3D 10, Bethesda, MD 20892 USA. EM klinman@cber.fda.gov RI Gursel, Mayda /H-1812-2012; OI Gursel, Ihsan/0000-0003-3761-1166 NR 39 TC 47 Z9 50 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD AUG 1 PY 2006 VL 177 IS 3 BP 1575 EP 1580 PG 6 WC Immunology SC Immunology GA 065DT UT WOS:000239140300031 PM 16849465 ER PT J AU Haffner, ME Maher, PD AF Haffner, M. E. Maher, P. D. TI Inborn errors of metabolism and the orphan drug act SO JOURNAL OF INHERITED METABOLIC DISEASE LA English DT Meeting Abstract C1 Off Orphan Prod Dev, Food & Drug Adm, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0141-8955 J9 J INHERIT METAB DIS JI J. Inherit. Metab. Dis. PD AUG PY 2006 VL 29 SU 1 BP 82 EP 82 PG 1 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 083OC UT WOS:000240467100300 ER PT J AU Buist, NRM Glenn, B Vugrek, O Wagner, C Stabler, S Allen, RH Pogribny, I Schulze, A Zeisel, SH Baric, I Mudd, SH AF Buist, N. R. M. Glenn, B. Vugrek, O. Wagner, C. Stabler, S. Allen, R. H. Pogribny, I. Schulze, A. Zeisel, S. H. Baric, I. Mudd, S. H. TI S-Adenosylhomocysteine hydrolase deficiency in a 26-year-old man SO JOURNAL OF INHERITED METABOLIC DISEASE LA English DT Article ID N-METHYLTRANSFERASE DEFICIENCY; TOTAL HOMOCYSTEINE; MASS-SPECTROMETRY; FOLATE-DEFICIENCY; INBORN ERROR; SERUM; METABOLISM; METHIONINE; DISORDER; QUANTITATION AB This paper reports the third proven human case of deficient S-adenosylhomocysteine (AdoHcy) hydrolase activity. The patient is similar to the only two previously reported cases with this disorder in having severe myopathy, developmental delay, elevated serum creatine kinase (CK) concentrations, and hypermethioninaemia. Although he has been followed from infancy, the basic enzyme deficiency was established only at age 26 years. The diagnosis was based on markedly elevated plasma concentrations of both AdoHcy and S-adenosylmethionine, some 20% of the mean control activity of AdoHcy hydrolase activity in haemolysates of his red-blood cells, and two missense mutations in his gene encoding AdoHcy hydrolase. He had low values of erythrocyte phosphatidylcholine and plasma free choline and marginally elevated excretion of guanidinoacetate, suggesting that the elevated AdoHcy may have been inhibiting methylation of phosphatidylethanolamine and guanidinoacetate. His leukocyte DNA was globally more methylated than the DNA's of his parents or the mean extent of methylation measured in age-matched control subjects. C1 Oregon Hlth Sci Univ, Dept Pediat, Portland, OR 97225 USA. Oregon Hlth Sci Univ, Dept Med Genet, Portland, OR 97225 USA. Vanderbilt Univ, Dept Biochem, Nashville, TN 37232 USA. Dept Vet Affairs Med Ctr, Nashville, TN 37212 USA. Rudjer Boskovic Inst, Dept Mol Med, Zagreb, Croatia. Univ Colorado, Hlth Sci Ctr, Div Hematol, Denver, CO USA. Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. Univ Childrens Hosp, Heidelberg, Germany. Univ N Carolina, Sch Publ Hlth, Dept Nutr, Chapel Hill, NC 27599 USA. Univ N Carolina, Sch Med, Chapel Hill, NC USA. Univ Hosp Ctr, Dept Pediat, Zagreb, Croatia. Sch Med, Zagreb, Croatia. NIMH, Mol Biol Lab, Bethesda, MD 20892 USA. RP Buist, NRM (reprint author), Oregon Hlth Sci Univ, Dept Pediat, 8510 SW White Pine Lane, Portland, OR 97225 USA. EM Buistnrm@aol.com FU NIA NIH HHS [AG-09834, R01 AG009834]; NIDDK NIH HHS [DK15289, DK55865, P30 DK026657, P30 DK056350-08, R01 DK055865-06A1, R37 DK015289, DK56359, 5P30 DK26657, P30 DK056350, R01 DK015289, R01 DK055865] NR 27 TC 39 Z9 42 U1 0 U2 3 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0141-8955 J9 J INHERIT METAB DIS JI J. Inherit. Metab. Dis. PD AUG PY 2006 VL 29 IS 4 BP 538 EP 545 DI 10.1007/s10545-006-0240-0 PG 8 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 078MH UT WOS:000240107400006 PM 16736098 ER PT J AU Whitney, JB Jiang, SS Mirshahidi, S Goins, LM Ibegbu, C Frankel, F Lieberman, J McClure, HM Raybourne, RB Ruprecht, RM AF Whitney, James B. Jiang, Shisong Mirshahidi, Saied Goins, Lauren M. Ibegbu, Chris Frankel, Fred Lieberman, Judy McClure, Harold M. Raybourne, Richard B. Ruprecht, Ruth M. TI Recombinant Listeria vectors as candidate oral aids vaccines: Primate studies SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Univ Penn, Dept Microbiol, Philadelphia, PA 19104 USA. Ctr Blood Res, Boston, MA 02115 USA. Emory Univ, Yerkes Natl Primate Res Ctr, Atlanta, GA 30329 USA. US FDA, Immunobiol Branch, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 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 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD AUG PY 2006 VL 35 IS 4-5 MA 113 BP 314 EP 315 PG 2 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 063GU UT WOS:000239007300124 ER PT J AU Heraud, JM Golding, H Edghill-Smith, Y Manischewitz, J King, LR Tsai, WP Hryniewicz, A Ayala, V Kalyanaraman, V Silvera, P Bray, M Seder, R Hooper, JW Franchini, G AF Heraud, Jean-Michel Golding, Hana Edghill-Smith, Yvette Manischewitz, Jody King, Lisa R. Tsai, Wen-Po Hryniewicz, Anna Ayala, Victor Kalyanaraman, V. S. Silvera, Peter Bray, Mike Seder, Robert Hooper, Jay W. Franchini, Genoveffa TI Protection from lethal monkeypox challenge afforded by a four-gene-combination DNA vaccine followed by boosting with CpG-adjuvanted monkeypox proteins plus CpG SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. US FDA, Bethesda, MD 20892 USA. Adv Biosci Labs, Bethesda, MD 20895 USA. So Res Inst, Frederick, MD 21701 USA. NIAID, Bethesda, MD 20892 USA. Vaccine Res Ctr, Bethesda, MD 20892 USA. USA, Med Res Inst Infect Dis, Ft Detrick, MD 21702 USA. RI HERAUD, Jean-Michel/O-1464-2013 OI HERAUD, Jean-Michel/0000-0003-1107-0859 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 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD AUG PY 2006 VL 35 IS 4-5 MA 120 BP 317 EP 317 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 063GU UT WOS:000239007300131 ER PT J AU Mahmood, I AF Mahmood, Iftekhar TI Prediction of human drug clearance from animal data: Application of the rule of exponents and 'fu Corrected Intercept Method' (FCIM) SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article DE allometric scaling; preclinical pharmacokinetics; clearance; protein binding; biliary excretion; renal clearance; vertical allometry ID HEPATIC METABOLIC-CLEARANCE; IN-VITRO DATA; INTEGRATION; PARAMETERS AB The objective of this study is to evaluate the predictive performance of the rule of exponents (ROE) and 'fu Corrected Intercept Method'(FCIM) for the human drug clearance. Different classes of drugs such as extensively metabolized, renally excreted, renally secreted, and biliary excreted drugs were used in this analysis. The results of the study indicated that both these methods under given conditions are extremely useful for the prediction of human drug clearance. There are certain situations under which one of these methods is more suited than the other method. Overall, it appears that a rational use of FCIM and the ROE can help a great deal in obtaining a better estimate of the human drug clearance for a wide variety of drugs. The advantages and disadvantages of these two methods are also discussed. (c) 2006 Wiley-Liss, Inc. C1 Woodmont Off Ctr 2, Ctr Drug Evaluat & Res Food & Drug Adm, Clin Pharmacol & Toxicol Branch HFD 579, Rockville, MD 20852 USA. RP Mahmood, I (reprint author), Woodmont Off Ctr 2, Ctr Drug Evaluat & Res Food & Drug Adm, Clin Pharmacol & Toxicol Branch HFD 579, Rockville, MD 20852 USA. EM Mahmoodi@CDER.FDA.GOV NR 19 TC 22 Z9 22 U1 0 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0022-3549 J9 J PHARM SCI-US JI J. Pharm. Sci. PD AUG PY 2006 VL 95 IS 8 BP 1810 EP 1821 DI 10.1002/jps.20650 PG 12 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 069JT UT WOS:000239442900016 PM 16795002 ER PT J AU Moon, H Ahn, H Kodell, RL AF Moon, Hojin Ahn, Hongshik Kodell, Ralph L. TI A computational tool for testing dose-related trend using an age-adjusted bootstrap-based poly-k test SO JOURNAL OF STATISTICAL SOFTWARE LA English DT Article DE bioassay; competing risks; likelihood; sacrifice; survival-adjusted test ID CARCINOGENICITY; BIOASSAYS; DISEASE AB A computational tool for testing for a dose-related trend and/or a pairwise difference in the incidence of an occult tumor via an age-adjusted bootstrap-based poly-k test and the original poly-k test is presented in this paper. The poly-k test ( Bailer and Portier 1988) is a survival-adjusted Cochran-Armitage test, which achieves robustness to effects of differential mortality across dose groups. The original poly-k test is asymptotically standard normal under the null hypothesis. However, the asymptotic normality is not valid if there is a deviation from the tumor onset distribution that is assumed in this test. Our age-adjusted bootstrap-based poly-k test assesses the significance of assumed asymptotic normal tests and investigates an empirical distribution of the original poly-k test statistic using an age-adjusted bootstrap method. A tumor of interest is an occult tumor for which the time to onset is not directly observable. Since most of the animal carcinogenicity studies are designed with a single terminal sacrifice, the present tool is applicable to rodent tumorigenicity assays that have a single terminal sacrifice. The present tool takes input information simply from a user screen and reports testing results back to the screen through a user-interface. The computational tool is implemented in C/C++ and is applied to analyze a real data set as an example. Our tool enables the FDA and the pharmaceutical industry to implement a statistical analysis of tumorigenicity data from animal bioassays via our age-adjusted bootstrap-based poly-k test and the original poly-k test which has been adopted by the National Toxicology Program as its standard statistical test. C1 US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Stony Brook Univ, Stony Brook, NY USA. RP Moon, H (reprint author), US FDA, Natl Ctr Toxicol Res, 3900 NCTR Rd,HFT-20, Jefferson, AR 72079 USA. EM hojin.moon@fda.hhs.gov NR 24 TC 0 Z9 0 U1 0 U2 3 PU JOURNAL OF STATISTICAL SOFTWARE PI LOS ANGELES PA UCLA DEPT STATISTICS, 8130 MATH SCIENCES BLDG, BOX 951554, LOS ANGELES, CA 90095-1554 USA SN 1548-7660 J9 J STAT SOFTW JI J. Stat. Softw. PD AUG PY 2006 VL 16 IS 7 PG 14 WC Computer Science, Interdisciplinary Applications; Statistics & Probability SC Computer Science; Mathematics GA 079VM UT WOS:000240206000001 ER PT J AU Chiesa, OA Von Bredow, J Smith, M Heller, D Condon, R Thomas, MH AF Chiesa, OA Von Bredow, J Smith, M Heller, D Condon, R Thomas, MH TI Bovine kidney tissue/biological fluid correlation for penicillin SO JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS LA English DT Article ID TISSUE; PLASMA; DEPLETION; CALVES; ABUSE; MILK AB Penicillin is one of the most commonly misused drugs in steers and dairy cows. In the US, at slaughter the tolerance is 50 ng/g in kidney and other edible tissues. If the tolerance is exceeded, the carcass may not be used for human food. A preslaughter test for penicillin in an easily accessible biological fluid is needed to predict if the concentration of penicillin is below tolerance in the kidney before the bovine is slaughtered. In this study, 12 steers were injected three times with the approved dose (7000 IU) of penicillin at 12-h intervals. Blood and urine samples were collected at intervals after the final dose of penicillin. At each sampling point, one kidney biopsy sample was collected by laparoscopic surgery in the live animal. Another kidney sample was collected at slaughter. Correlations between plasma and kidney concentrations and between urine and kidney concentrations were determined. These correlations predict with 95% confidence that 99% of the animals will have kidney tissue below penicillin tolerance when the plasma concentration of penicillin is below 0.4 ng/mL and/or the urine penicillin concentration is below 140 ng/mL. C1 US FDA, Div Residue Chem, Res Off, Ctr Vet Med, Laurel, MD 20708 USA. RP Chiesa, OA (reprint author), US FDA, Div Residue Chem, Res Off, Ctr Vet Med, 8401 Muirkirk Rd, Laurel, MD 20708 USA. EM ochiesa@cvm.fda.gov NR 31 TC 16 Z9 16 U1 1 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0140-7783 J9 J VET PHARMACOL THER JI J. Vet. Pharmacol. Ther. PD AUG PY 2006 VL 29 IS 4 BP 299 EP 306 DI 10.1111/j.1365-2885.2006.00747.x PG 8 WC Pharmacology & Pharmacy; Veterinary Sciences SC Pharmacology & Pharmacy; Veterinary Sciences GA 058HH UT WOS:000238655600008 PM 16846467 ER PT J AU Lipshultz, SE Cohen, H Colan, SD Herman, EH AF Lipshultz, Steven E. Cohen, Harvey Colan, Steven D. Herman, Eugene H. TI The relevance of information generated by in vitro experimental models to clinical doxorubicin cardiotoxicity SO LEUKEMIA & LYMPHOMA LA English DT Editorial Material ID ACUTE LYMPHOBLASTIC-LEUKEMIA; CONTINUOUS-INFUSION; CHILDREN; ADRIAMYCIN; CHILDHOOD; THERAPY; DEXRAZOXANE; DRUG C1 Univ Miami, Miller Sch Med, Dept Pediat, Sylvester Comprehens Canc Ctr, Miami, FL 33152 USA. Stanford Univ, Sch Med, Dept Pediat, Palo Alto, CA 94304 USA. Harvard Univ, Sch Med, Childrens Hosp, Dept Cardiol, Boston, MA 02115 USA. US FDA, Div Appl Pharmacol Res, Silver Spring, MD USA. RP Lipshultz, SE (reprint author), Univ Miami, Miller Sch Med, Dept Pediat, Sylvester Comprehens Canc Ctr, Miami, FL 33152 USA. EM SLipshultz@med.miami.edu NR 17 TC 7 Z9 7 U1 0 U2 1 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD AUG PY 2006 VL 47 IS 8 BP 1454 EP 1458 DI 10.1080/10428190600800231 PG 5 WC Oncology; Hematology SC Oncology; Hematology GA 083DH UT WOS:000240435600007 PM 16966253 ER PT J AU Badano, A Kyprianou, IS Sempau, J AF Badano, Aldo Kyprianou, Iacovos S. Sempau, Josep TI Anisotropic imaging performance in indirect x-ray imaging detectors SO MEDICAL PHYSICS LA English DT Article DE Monte Carlo simulation; digital imaging; phosphor screen; cesium iodide; point response function; Swank factor ID MONTE-CARLO-SIMULATION; CESIUM IODIDE SCINTILLATORS; POINT-SPREAD FUNCTION; CODE PENELOPE; FLUORESCENT SCREENS; COLUMNAR PHOSPHORS; ELECTRON; EFFICIENCY; LEKSELL-GAMMA-KNIFE(R); COLLECTION AB We report on the variability in imaging system performance due to oblique x-ray incidence, and the associated transport of quanta (both x rays and optical photons) through the phosphor, in columnar indirect digital detectors. The analysis uses MANTIS, a combined x-ray, electron, and optical Monte Carlo transport code freely available. We describe the main features of the simulation method and provide some validation of the phosphor screen models considered in this work. We report x-ray and electron three-dimensional energy deposition distributions and point-response functions (PRFs), including optical spread in, columnar phosphor screens of thickness 100 and 500 mu m, for 19, 39, 59, and 79 keV monoenergetic x-ray beams incident at 0 degrees, 10 degrees, and 15 degrees. In addition, we present pulse-height spectra for the same phosphor thickness, x-ray energies, and angles of incidence. Our results suggest that the PRF due to the phosphor blur is highly nonsymmetrical, and that the resolution properties of a columnar screen in a tomographic, or tomosynthetic imaging system varies significantly with the angle of x-ray incidence. Moreover, we find that the noise due to the variability in the number of light photons detected per primary x-ray interaction, summarized in the information or Swank factor, is somewhat independent of thickness and incidence angle of the x-ray beam. Our results also suggest that the anisotropy in the PRF is not less in screens with absorptive backings, while. the noise introduced by variations in the gain and optical transport is larger. Predictions from MANTIS, after additional validation, can provide the needed understanding of the extent of such variations, and eventually, lead to the incorporation of the changes in imaging performance with incidence angle into the reconstruction algorithms for volumetric x-ray imaging systems. (C) 2006 American Association of Physicists in Medicine. C1 US FDA, Ctr Devices & Radiol Hlth, NIBIB CDRH Lab Assessment Med Imaging Syst, Div Imaging & Appl Math,Off Sci & Engn Labs, Rockville, MD 20857 USA. Univ Politecn Catalunya, Inst Tecn Energet, E-08028 Barcelona, Spain. RP Badano, A (reprint author), US FDA, Ctr Devices & Radiol Hlth, NIBIB CDRH Lab Assessment Med Imaging Syst, Div Imaging & Appl Math,Off Sci & Engn Labs, 12720 Twinbrook Pkwy, Rockville, MD 20857 USA. EM aldo.badano@fda.hhs.gov RI Sempau, Josep/J-7834-2013; OI Sempau, Josep/0000-0002-2754-7685; badano, aldo/0000-0003-3712-6670 NR 42 TC 35 Z9 35 U1 0 U2 3 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD AUG PY 2006 VL 33 IS 8 BP 2698 EP 2713 DI 10.1118/1.2208925 PG 16 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 074ZZ UT WOS:000239852800004 PM 16967568 ER PT J AU Guo, L Zhang, L Sun, YM Muskhelishvili, L Blann, E Dial, S Shi, LM Schroth, G Dragan, YP AF Guo, Lei Zhang, Lu Sun, Yongming Muskhelishvili, Levan Blann, Ernice Dial, Stacey Shi, Leming Schroth, Gary Dragan, Yvonne P. TI Differences in hepatotoxicity and gene expression profiles by anti-diabetic PPAR gamma agonists on rat primary hepatocytes and human HepG2 cells SO MOLECULAR DIVERSITY LA English DT Article DE apoptosis; ciglitazone; cytotoxicity; cluster analysis; JTT-501; molecular descriptors; peroxisome proliferator-activated receptor gamma; pioglitazone; rat genome microarray; rat primary hepatocytes; rosiglitazone; troglitazone ID NONCYCLIC 1,3-DICARBONYL COMPOUNDS; DIABETES-MELLITUS; LIVER-FAILURE; CANCER CELLS; IN-VITRO; TROGLITAZONE; APOPTOSIS; ROSIGLITAZONE; MICROARRAYS; THIAZOLIDINEDIONES AB Agonists of peroxisome proliferator-activated receptor gamma (PPAR gamma) are a new class of oral drugs designed to treat insulin-resistant diabetes (i.e., type 2 diabetes). However, troglitazone, the first compound in the class approved by the US Food and Drug Administration (FDA). in 1997 was found to be hepatotoxic and was withdrawn from the market after reports of severe liver failure. The mechanism of PPAR gamma agonist-induced hepatotoxicity remains unknown. In this study, we examined the hepatotoxic effects of five PPAR gamma agonists (ciglitazone, pioglitazone, rosiglitazone, troglitazone, and J717-501) on rat primary hepatocytes and human HepG2 cells. We also compared the gene expression profiles of rat primary hepatocytes after exposure to PPAR gamma agonists by using the Rat Genome Survey Microarray system from Applied Biosystems in order to understand the mechanisms of hepatotoxicities induced by PPAR gamma agonists. Consistent with the hepatotoxicity data, our results demonstrate that the gene expression profiles affected by troglitazone and ciglitazone can be clearly distinguished from those by pioglitazone and rosiglitazone. Genes that are differentially expressed between the more toxic troglitazone/ciglitazone group and the less toxic rosiglitazone/pioglitazone group are involved in necrotic, apoptotic, and cell proliferative pathways. The five compounds were also clustered based on a set of molecular descriptors. The clustering based on chemical structural information is in good agreement with the clustering of compounds based on cytotoxicity or gene expression data, indicating a strong relationship between chemical structure and biological endpoints. Our work suggests that microarray analysis together with toxicological observations can be used to rank drugs for hepatotoxicity, and to evaluate the safety of new compounds. C1 US FDA, Natl Ctr Toxicol Res, Div Syst Toxicol, Jefferson, AR 72079 USA. Arrays SDS Res & Dev Grp, Foster City, CA 94404 USA. Appl Biosyst Inc, Bioinformat Grp, Foster City, CA 94404 USA. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Guo, L (reprint author), US FDA, Natl Ctr Toxicol Res, Div Syst Toxicol, Jefferson, AR 72079 USA. EM lei.guo@fda.hhs.gov RI Guo, Lei/E-9232-2011 NR 41 TC 49 Z9 51 U1 0 U2 5 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1381-1991 J9 MOL DIVERS JI Mol. Divers. PD AUG PY 2006 VL 10 IS 3 BP 349 EP 360 DI 10.1007/s11030-006-9038-0 PG 12 WC Biochemistry & Molecular Biology; Chemistry, Applied; Chemistry, Medicinal; Chemistry, Multidisciplinary SC Biochemistry & Molecular Biology; Chemistry; Pharmacology & Pharmacy GA 106YJ UT WOS:000242137600008 PM 17031537 ER PT J AU Venable, RM Skibinsky, A Pastor, RW AF Venable, R. M. Skibinsky, A. Pastor, R. W. TI Constant surface tension molecular dynamics simulations of lipid bilayers with trehalose SO MOLECULAR SIMULATION LA English DT Article DE DPPC; isotherm; equivalence of ensembles; area compressibility modulus; bulk compressibility modulus ID LIQUID/LIQUID INTERFACES; COMPUTER-SIMULATION; ELASTICITY; TRANSITION; MONOLAYERS; MEMBRANES; ALKANES; WATER AB Surface areas and fluctuations evaluated from 50ns molecular dynamics simulations of fully hydrated dipalmitoylphosphatidylcholine (DPPC) bilayers in a 1:2 trehalose:lipid ratio carried out at surface tensions 10, 17 and 25dyn/cm/leaflet are compared with those of pure bilayers under the same conditions. Trehalose increases the surface area, as consistent with the surface tension lowering observed in simulations at constant area. The system bulk elastic modulus K-b = 1.5 +/- 0.3 x 10(10) dyn/cm(2). It is independent of bilayer surface area and trehalose content within statistical error. In contrast, the area elastic modulus K-a shows a strong area dependence. At 64 angstrom(2)/lipid (the experimental surface area), K-a = 138 +/- 26 dyn/cm for a pure DPPC bilayer and 82 +/- 10 dyn/cm for one with trehalose; i.e. trehalose increases fluidity of the bilayer surface at this area per lipid. C1 US FDA, Ctr Biol Evaluat & Res, Biophys Lab, Rockville, MD 20852 USA. RP Pastor, RW (reprint author), US FDA, Ctr Biol Evaluat & Res, Biophys Lab, 1401 Rockville Pike, Rockville, MD 20852 USA. EM richard.pastor@fda.hhs.gov NR 33 TC 14 Z9 14 U1 2 U2 4 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0892-7022 J9 MOL SIMULAT JI Mol. Simul. PD AUG-SEP PY 2006 VL 32 IS 10-11 BP 849 EP 855 DI 10.1080/08927020600615018 PG 7 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 099HY UT WOS:000241585500009 ER PT J AU Gottlieb, S Woodcock, J AF Gottlieb, Scott Woodcock, Janet TI A regulatory perspective on in vitro diagnostics SO NATURE BIOTECHNOLOGY LA English DT Editorial Material ID DRUG DEVELOPMENT; DECISION-MAKING; PHARMACOGENOMICS C1 US FDA, Rockville, MD 20857 USA. RP Gottlieb, S (reprint author), US FDA, Rockville, MD 20857 USA. NR 7 TC 1 Z9 1 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD AUG PY 2006 VL 24 IS 8 BP 927 EP 929 DI 10.1038/nbt0806-927 PG 3 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 072VY UT WOS:000239702300026 PM 16900132 ER PT J AU Trumbo, PR Ellwood, KC AF Trumbo, Paula R. Ellwood, Kathleen C. TI Chromium picolinate intake and risk of type 2 diabetes: An evidence-based review by the United States food and drug administration SO NUTRITION REVIEWS LA English DT Review DE chromium picolinate; diabetes; health claims; type 2 diabetes ID TOTAL PARENTERAL-NUTRITION; IMPAIRED GLUCOSE-TOLERANCE; SUPPLEMENTAL-CHROMIUM; INSULIN SENSITIVITY; DIETARY CHROMIUM; BODY-COMPOSITION; NICOTINIC-ACID; TRIVALENT CHROMIUM; SERUM-CHOLESTEROL; EXERCISE PROGRAM AB The labeling of both health claims that meet significant scientific agreement (SSA) and qualified health claims on conventional foods and dietary supplements requires pre-market approval by the US Food and Drug Administration (FDA). Approval by the FDA involves, in part, a thorough review of the 'Scientific evidence to support an SSA or a qualified health claim. This article discusses FDA's evidence-based review of the scientific evidence on the role of chromium picolinate supplements in reducing the risk of type 2 diabetes. Based on this evidence-based review, FDA issued a letter of enforcement discretion for one qualified health claim on chromium picolinate and risk of insulin resistance, a surrogate endpoint for type 2 diabetes. The agency concluded that the relationship between chromium picolinate intake and insulin resistance is highly uncertain. C1 US FDA, Div Nutr Programs & Labeling, College Pk, MD USA. RP Trumbo, PR (reprint author), HFS-830,5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM Paula.Trumbo@FDA.gov NR 55 TC 23 Z9 25 U1 3 U2 8 PU INT LIFE SCIENCES INST NORTH AMERICA PI WASHINGTON PA ONE THOMAS CIRCLE, N W, 9TH FLOOR, WASHINGTON, DC 20005 USA SN 0029-6643 J9 NUTR REV JI Nutr. Rev. PD AUG PY 2006 VL 64 IS 8 BP 357 EP 363 DI 10.1111/j.1753-4887.2006.tb00220.x PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 076EV UT WOS:000239940700001 PM 16958312 ER PT J AU Cao, XH Gibbs, ST Fang, LY Miller, HA Landowski, CP Shin, HC Lennernas, H Zhong, YQ Amidon, GL Yu, LX Sun, DX AF Cao, Xianhua Gibbs, Seth T. Fang, Lanyan Miller, Heather A. Landowski, Christopher P. Shin, Ho-Chul Lennernas, Hans Zhong, Yanqiang Amidon, Gordon L. Yu, Lawrence X. Sun, Duxin TI Why is it challenging to predict intestinal drug absorption and oral bioavailability in human using rat model SO PHARMACEUTICAL RESEARCH LA English DT Article DE drug transporter; gene expression; inter-species correlation; intestinal permeability; metabolizing enzyme; oral bioavailability ID RESISTANCE-ASSOCIATED PROTEIN-3; HUMAN JEJUNAL PERMEABILITY; IN-VIVO BIOAVAILABILITY; CLINICAL PHARMACOKINETICS; P-GLYCOPROTEIN; GENE-EXPRESSION; N-ACETYLPROCAINAMIDE; 1ST-PASS METABOLISM; TRANSPORT; VERAPAMIL AB Purpose. To study the correlation of intestinal absorption for drugs with various absorption routes between human and rat, and to explore the underlying molecular mechanisms for the similarity in drug intestinal absorption and the differences in oral bioavailability between human and rat. Materials and Methods. The intestinal permeabilities of 14 drugs and three drug-like compounds with different absorption mechanisms in rat and human jejunum were determined by in situ intestinal perfusion. A total of 48 drugs were selected for oral bioavailability comparison. Expression profiles of transporters and metabolizing enzymes in both rat and human intestines (duodenum and colon) were measured using GeneChip analysis. Results. No correlation (r(2) = 0.29) was found in oral drug bioavailability between rat and human, while a correlation (r(2) = 0.8) was observed for drug intestinal permeability with both carrier-mediated absorption and passive diffusion mechanisms between human and rat small intestine. Moderate correlation (with r(2) > 0.56) was also found for the expression levels of transporters in the duodenum of human and rat, which provides the molecular mechanisms for the similarity and correlation of drug absorption between two species. In contrast, no correlation was found for the expressions of metabolizing enzymes between rat and human intestine, which indicates the difference in drug metabolism and oral bioavailability in two species. Detailed analysis indicates that many transporters (such as PepT1, SGLT-1, GLUT5, MRP2, NT2, and high affinity glutamate transporter) share similar expression levels in both human and rat with regional dependent expression patterns, which have high expression in the small intestine and low expression in the colon. However, discrepancy was also observed for several other transporters (such as MDR1, MRP3, GLUT1, and GLUT3) in both the duodenum and colon of human and rat. In addition, the expressions of metabolizing enzymes (CYP3A4/CYP3A9 and UDPG) showed 12 to 193-fold difference between human and rat intestine with distinct regional dependent expression patterns. Conclusions. The data indicate that rat and human show similar drug intestinal absorption profiles and similar transporter expression patterns in the small intestine, while the two species exhibit distinct expression levels and patterns for metabolizing enzymes in the intestine. Therefore, a rat model can be used to predict oral drug absorption in the small intestine of human, but not to predict drug metabolism or oral bioavailability in human. C1 Ohio State Univ, Coll Pharm, Div Pharmaceut, Columbus, OH 43210 USA. Univ Michigan, Coll Pharm, Dept Pharmaceut Sci, Ann Arbor, MI 48109 USA. Uppsala Univ, Dept Pharm, Grp Biopharmaceut, S-75123 Uppsala, Sweden. US FDA, Off Genet Drugs, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Sun, DX (reprint author), Ohio State Univ, Coll Pharm, Div Pharmaceut, 500 W 12Th Ave, Columbus, OH 43210 USA. EM sun.176@osu.edu RI Yu, Lawrence/L-6280-2016; OI Landowski, Christopher/0000-0003-1775-8646; Shin, Ho-chul/0000-0001-5500-3901 NR 83 TC 179 Z9 186 U1 5 U2 54 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 AUG PY 2006 VL 23 IS 8 BP 1675 EP 1686 DI 10.1007/s11095-006-9041-2 PG 12 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 072IC UT WOS:000239666100005 PM 16841194 ER PT J AU Ahmad, SR DalPan, G Raine, JM Hill, R Corsico, CD AF Ahmad, Syed R. DalPan, Gerald Raine, June M. Hill, Richard Corsico, Christopher D. TI What stimulates regulatory action? SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 US FDA, Off Surveillance & Epidemiol, Ctr Drug Evaluat & Res, Silver Spring, MD USA. Med & Healthcare Prod Regulatory Agcy, Post Licensing Div, London, England. Therapuet Goods Adm, Adverse Drug React Unit, Woden, ACT, Australia. Boehringer Ingelheim Pharmaceut Inc, Drug Surveillance & Informat, Ridgefield, CT 06877 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2006 VL 15 SU 1 MA 091 BP S43 EP S43 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 080XG UT WOS:000240281200092 ER PT J AU Burwen, DR La Voie, L Braun, MM Houck, P Hudson, R Ball, R AF Burwen, Dale R. La Voie, Lawrence Braun, M. Miles Houck, Peter Hudson, Rebecca Ball, Robert TI Evaluating adverse events after vaccination in the medicare population SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 US FDA, Rockville, MD 20857 USA. Ctr Medicare & Medicaid Serv, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2006 VL 15 SU 1 MA 168 BP S79 EP S79 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 080XG UT WOS:000240281200169 ER PT J AU Chang, S Farizo, K Braun, MM Ball, R AF Chang, Soju Farizo, Karen Braun, M. Miles Ball, Robert TI Post-licensure safety surveillance of diphtheria, tetanus toxoids, acellular pertussis, hepatitis B and inactivated poliovirus vaccine combined (DTaPHE) from the US vaccine adverse event reporting system (VAERS) SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 US FDA, Off Biostat & Epidemiol, CBER, Rockville, MD 20857 USA. US FDA, Off Vaccines Res & Review, CBER, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2006 VL 15 SU 1 MA 169 BP S79 EP S80 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 080XG UT WOS:000240281200170 ER PT J AU Chang, S Iskander, J Farizo, K Miles Braun, M Ball, R AF Chang, Soju Iskander, John Farizo, Karen Miles Braun, M. Ball, Robert TI Evaluating reports of fever after diphtheria, tetanus toxoids, acellular pertussis, hepatitis b, inactivated poliovirus vaccine combined (DTaPHE) from the US vaccine adverse event reporting system (VAERS) SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 US FDA, Ctr Biol & Evaluat CBER, Off Biostat & Epidemiol, Rockville, MD 20857 USA. Ctr Dis Control & Prevent, Immunizat Safety Off, Off Chief Sci Officer, Atlanta, GA USA. US FDA, CBER, Off Vaccines Res & Review, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2006 VL 15 SU 1 MA 056 BP S26 EP S27 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 080XG UT WOS:000240281200057 ER PT J AU Dobardzic, A Izurieta, HS Iskander, JK Shadomy, S Woo, EJ Rupprecht, C Herrera, G Braun, M Ball, R AF Dobardzic, Azra Izurieta, Hector S. Iskander, John K. Shadomy, Sean Woo, Emily J. Rupprecht, Charles Herrera, Gulliermo Braun, Miles Ball, Robert TI Adverse events associated with purified chick embryo cell culture rabies vaccine in the United States SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 US FDA, OBE, CBER, Rockville, MD 20857 USA. CDC, Atlanta, GA 30333 USA. ORAU, Oak Ridge, TN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2006 VL 15 SU 1 MA 166 BP S78 EP S78 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 080XG UT WOS:000240281200167 ER PT J AU Duggirala, HJ Kandzari, DE Gross, TP AF Duggirala, Hesha J. Kandzari, David E. Gross, Thomas P. TI Postmarket surveillance of drug-eluting stents SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. Duke Univ, Med Ctr, Div Cardiol, Durham, NC 27710 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2006 VL 15 SU 1 MA 458 BP S213 EP S214 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 080XG UT WOS:000240281200459 ER PT J AU Graham, DJ Singh, G Wang, HJ Mithal, A Triadafilopoulos, G AF Graham, David J. Singh, Gurkirpal Wang, Huijian Mithal, Alka Triadafilopoulos, George TI Concomitant aspirin use reduces acute myocardial infarction risk in cyclooxygenase-2 selective and non-selective nonsteroidal anti-inflammatory drug users SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 US FDA, Off Drug Safety, Silver Spring, MD USA. Stanford Univ, Sch Med, Palo Alto, CA 94304 USA. ICORE, Palo Alto, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2006 VL 15 SU 1 MA 129 BP S60 EP S61 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 080XG UT WOS:000240281200130 ER PT J AU Hammad, TA Graham, D Staffa, J Kornegay, C Dal Pan, G AF Hammad, Tarek A. Graham, David Staffa, Judy Kornegay, Cynthia Dal Pan, Gerald TI Association between cyclooxygenase-2 selective non-steroidal anti-inflammatory drugs and acute myocardial infarction in the general practice research database: Preliminary findings SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 US FDA, Off Drug Safety, CDER, Silver Spring, MD USA. RI Research Datalink, Clinical Practice/H-2477-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2006 VL 15 SU 1 MA 125 BP S59 EP S59 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 080XG UT WOS:000240281200126 ER PT J AU Khoie, T O'Connell, KA Pierce, RL Shrake, A Zinderman, CE Wise, RP AF Khoie, Tina O'Connell, Kathryn A. Pierce, Ross L. Shrake, Andrew Zinderman, Craig E. Wise, Robert P. TI Alpha-1 proteinase inhibitor (Human) product postmarketing safety surveillance SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2006 VL 15 SU 1 MA 269 BP S126 EP S127 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 080XG UT WOS:000240281200270 ER PT J AU Zinderman, CE Landow, LL Wise, RP AF Zinderman, Craig E. Landow, Laurence Landow Wise, Robert P. TI Anaphylactoid reactions to dextran 40 and 70: Reports to the US Food and Drug Administration (FDA) SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2006 VL 15 SU 1 MA 246 BP S115 EP S116 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 080XG UT WOS:000240281200247 ER PT J AU Khachik, F AF Khachik, Frederick TI Distribution and metabolism of dietary carotenoids in humans as a criterion for development of nutritional supplements SO PURE AND APPLIED CHEMISTRY LA English DT Article; Proceedings Paper CT 14th International Symposium on Carotenoids CY JUL 17-22, 2005 CL Edinburgh, SCOTLAND DE food carotenoids; human plasma carotenoids; carotenoid metabolism; carotenoid oxidation products; HPLC analysis of carotenoids; multicarotenoid nutritional supplement ID PROSTATE-CANCER RISK; FATTY-ACID ESTERS; LIQUID-CHROMATOGRAPHY; HUMAN PLASMA; STRUCTURAL ELUCIDATION; MACULAR DEGENERATION; GEOMETRICAL-ISOMERS; OXIDATION-PRODUCTS; GREEN VEGETABLES; SQUASH PRODUCTS AB There are approximately 40-50 carotenoids in commonly consumed fruits and vegetables in a typical U.S. diet. These can be divided into carotenoid epoxides, mono- and dihydroxycarotenoids, hydrocarbon carotenoids, and carotenol acyl esters. However, among these, only a selected group of carotenoids are routinely found in human plasma, breast milk, major organs, and ocular tissues. In addition, several carotenoid metabolites have also been isolated and characterized from human plasma, tissues, and ocular tissues. The proposed metabolic transformation of carotenoids in humans will be discussed. Dietary carotenoids and their metabolites have been implicated in the prevention of cancer, cardiovascular disease, and age-related macular degeneration (AMD). An approach for the development of a nutritional supplement that is based on the distribution of carotenoids and their metabolites in humans will be discussed. C1 Univ Maryland, Joint Inst Food Safety & Appl Nutr, Dept Chem & Biochem, College Pk, MD 20742 USA. RP Khachik, F (reprint author), Univ Maryland, Joint Inst Food Safety & Appl Nutr, Dept Chem & Biochem, College Pk, MD 20742 USA. RI Khachik, Frederick/C-5055-2009 NR 40 TC 25 Z9 26 U1 0 U2 7 PU INT UNION PURE APPLIED CHEMISTRY PI RES TRIANGLE PK PA 104 TW ALEXANDER DR, PO BOX 13757, RES TRIANGLE PK, NC 27709-3757 USA SN 0033-4545 J9 PURE APPL CHEM JI Pure Appl. Chem. PD AUG PY 2006 VL 78 IS 8 BP 1551 EP 1557 DI 10.1351/pac200678081551 PG 7 WC Chemistry, Multidisciplinary SC Chemistry GA 068EU UT WOS:000239356100007 ER PT J AU Hadjiiski, L Sahiner, B Helvie, MA Chan, HP Roubidoux, MA Paramagul, C Blane, C Petrick, N Bailey, J Klein, K Foster, M Patterson, SK Adler, D Nees, AV Shen, J AF Hadjiiski, Lubomir Sahiner, Berkman Helvie, Mark A. Chan, Heang-Ping Roubidoux, Marilyn A. Paramagul, Chintana Blane, Caroline Petrick, Nicholas Bailey, Janet Klein, Katherine Foster, Michelle Patterson, Stephanie K. Adler, Dorit Nees, Alexis V. Shen, Joseph TI Breast masses: Computer-aided diagnosis with serial mammograms SO RADIOLOGY LA English DT Article ID RADIOLOGISTS CHARACTERIZATION; CANCER DIAGNOSIS; TEXTURE ANALYSIS; NEURAL-NETWORK; ROC; CLASSIFICATION; IMPROVEMENT; STATISTICS; FEATURES; LESIONS AB Purpose: To retrospectively evaluate effects of computer-aided diagnosis (CAD) involving an interval change classifier (which uses interval change information extracted from prior and current mammograms and estimates a malignancy rating) on radiologists' accuracy in characterizing masses on two-view serial mammograms as malignant or benign. Materials and Methods: The data collection protocol had institutional review board approval. Patient informed consent was waived for this HIPAA-compliant retrospective study. Ninety temporal pairs of two-view serial mammograms (depicting 47 malignant and 43 benign biopsy-proved masses) were obtained from 68 patient files and were digitized. Biopsy was the reference standard. Eight Mammography Quality Standards Act of 1992-accredited radiologists and two breast imaging fellows assessed digitized two-view temporal pairs (in preselected regions of interest only) by estimating likelihood of malignancy and Breast Imaging Reporting and Data System (BI-RADS) category without and with CAD. Observers' rating data were analyzed with Dorfman-Berbaum-Metz (DBM) multireader multicase method. Statistical significance of differences was estimated with the DBM method and Student two-tailed paired t test. Results: Average area under the receiver operating characteristic curve for likelihood of malignancy across the 10 observers was 0.83 (range, 0.74-0.88) without CAD and improved to 0.87 (range, 0.80-0.92) with CAD (P <.05). The average partial area index above a sensitivity of 0.90 for likelihood of malignancy was 0.35 (range, 0.13-0.54) without CAD and 0.49 (range, 0.18-0.73) with CAD-a nonsignificant improvement (P=.11). For BI-RADS assessment, it was estimated that with CAD, six radiologists would correctly recommend additional biopsies for malignant masses (range, 4.3%-10.6%) and five would correctly recommend reduction of biopsy (ie, fewer biopsies) for benign masses (range, 2.3%-9.3%). However, five radiologists would incorrectly recommend additional biopsy for benign masses (range, 2.3%-14.0%), and one would incorrectly recommend reduction of biopsy (4.3%). Conclusion: CAD involving interval change analysis of preselected regions of interest can significantly improve radiologists' accuracy in classifying masses on digitized screen-film mammograms as malignant or benign. (c) RSNA, 2006. C1 Univ Michigan, Med Ctr, Dept Radiol, Ann Arbor, MI 48109 USA. US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Hadjiiski, L (reprint author), Univ Michigan, Med Ctr, Dept Radiol, CGC B2102,1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA. EM lhadjisk@umich.edu FU NCI NIH HHS [R01 CA095153, CA95153] NR 34 TC 20 Z9 22 U1 0 U2 4 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD AUG PY 2006 VL 240 IS 2 BP 343 EP 356 DI 10.1148/radiol.2401042099 PG 14 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 066PO UT WOS:000239242600006 PM 16801362 ER PT J AU Kodell, RL Chen, JJ Delongchamp, RR Young, JF AF Kodell, R. L. Chen, J. J. Delongchamp, R. R. Young, J. F. TI Hierarchical models for probabilistic dose-response assessment SO REGULATORY TOXICOLOGY AND PHARMACOLOGY LA English DT Article DE Bayesian; benchmark dose; binomial; internal dose; Michaelis-Menten; Monte Carlo; PBPK; PK/PD; risk management; two-stage model; uncertainty; Weibull ID RISK-ASSESSMENT; PHARMACOKINETIC MODELS; EXAMPLE; FORMALDEHYDE; CHLORIDE; IMPROVE; HUMANS AB Probabilistic risk assessment is gaining acceptance as the most appropriate way to characterize and communicate uncertainties in estimates of human health risk and/or reference levels of exposure such as benchmark doses. Although probabilistic techniques are well established in the exposure-assessment component of the National Research Council's risk-assessment paradigm, they are less well developed in the dose-response-assessment component. This paper proposes the use of hierarchical statistical models as tools for implementing probabilistic dose-response assessments, in that such models provide a natural connection between the pharmacokinetic (PK) and pharmacodynamic (PD) components of dose-response models. The results show that incorporating internal dose information into dose-response assessments via the coupling of PK and PD models in a hierarchical structure can reduce the uncertainty in the dose-response assessment of risk. However, information on the mean of the internal dose distribution is sufficient; having information on the variance of internal dose does not affect the uncertainty in the resulting estimates of excess risks or benchmark doses. In addition, the complexity of a PK model of internal dose does not affect how the variability in risk is measured via the ultimate endpoint. (c) 2006 Elsevier Inc. All rights reserved. C1 US FDA, Div Biometry & Risk Assessment, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Kodell, RL (reprint author), US FDA, Div Biometry & Risk Assessment, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM rkodell@nctr.fda.gov NR 24 TC 13 Z9 15 U1 1 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 AUG PY 2006 VL 45 IS 3 BP 265 EP 272 DI 10.1016/j.yrtph.2006.05.002 PG 8 WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology SC Legal Medicine; Pharmacology & Pharmacy; Toxicology GA 072OH UT WOS:000239682200005 PM 16769166 ER PT J AU Hussain, SM Javorina, AK Schrand, AM Duhart, HM Ali, SF Schlager, JJ AF Hussain, Saber M. Javorina, Amanda K. Schrand, Amanda M. Duhart, Helen M. Ali, Syed F. Schlager, John J. TI The interaction of manganese nanoparticles with PC-12 cells induces dopamine depletion SO TOXICOLOGICAL SCIENCES LA English DT Article DE nanoparticles; manganese; in vitro toxicity; PC-12 cells; dopamine ID OXIDATIVE STRESS; ULTRAFINE PARTICLES; PC12 CELLS; TOXICITY; BRAIN; NEUROTOXICITY; PREVENTION; MECHANISM; BINDING; ASSAY AB This investigation was designed to determine whether nano-sized manganese oxide (Mn-40nm) particles would induce dopamine (DA) depletion in a cultured neuronal phenotype, PC-12 cells, similar to free ionic manganese (Mn2+). Cells were exposed to Mn-40nm, Mn2+ (acetate), or known cytotoxic silver nanoparticles (Ag-15nm) for 24 h. Phase-contrast microscopy studies show that Mn-40nm or Mn2+ exposure did not greatly change morphology of PC-12 cells. However, Ag-15nm and AgNO3 produce cell shrinkage and irregular membrane borders compared to control cells. Further microscopic studies at higher resolution demonstrated that Mn-40nm nanoparticles and agglomerates were effectively internalized by PC-12 cells. Mitochondrial reduction activity, a sensitive measure of particle and metal cytotoxicity, showed only moderate toxicity for Mn-40nm compared to similar Ag-15nm and Mn2+ doses. Mn-40nm and Mn2+ dose dependently depleted DA and its metabolites, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), while Ag-15nm only significantly reduced DA and DOPAC at concentrations of 50 mu g/ml. Therefore, the DA depletion of Mn-40nm was most similar to Mn2+, which is known to induce concentration-dependent DA depletion. There was a significant increase (> 10-fold) in reactive oxygen species (ROS) with Mn-40nm exposure, suggesting that increased ROS levels may participate in DA depletion. These results clearly demonstrate that nanoscale manganese can deplete DA, DOPAC, and HVA in a dose-dependent manner. Further study is required to evaluate the specific intracellular distribution of Mn-40nm nanoparticles, metal dissolution rates in cells and cellular matrices, if DA depletion is induced in vivo, and the propensity of Mn nanoparticles to cross the blood-brain barrier or be selectively uptaken by nasal epithelium. C1 Air Force Res Lab, Appl Biotechnol Branch, Human Effectiveness Directorate, Wright Patterson AFB, OH 45431 USA. Univ Dayton, Dept Chem & Mat Engn, Dayton, OH 45469 USA. FDA, Natl Ctr Toxicol Res, Neurochem Lab, Div Neurotoxicol, Jefferson, AR 72079 USA. RP Hussain, SM (reprint author), Air Force Res Lab, Appl Biotechnol Branch, Human Effectiveness Directorate, Wright Patterson AFB, OH 45431 USA. EM saber.hussain@wpafb.af.mil NR 27 TC 216 Z9 239 U1 6 U2 55 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD AUG PY 2006 VL 92 IS 2 BP 456 EP 463 DI 10.1093/toxsci/kfl020 PG 8 WC Toxicology SC Toxicology GA 061XN UT WOS:000238907300013 PM 16714391 ER PT J AU Haddad, SA Lichtiger, B Klein, HG AF Haddad, Salim A. Lichtiger, Benjamin Klein, Harvey G. TI In vivo efficacy of shipped HLA-matched platelets SO TRANSFUSION LA English DT Article ID ALLOIMMUNIZED THROMBOCYTOPENIC PATIENTS; REFRACTORY PATIENTS; STORAGE; TRANSFUSION; TEMPERATURE; AGITATION; TRANSPORTATION; SELECTION; VIABILITY; QUALITY AB Background: Platelet (PLT) concentrates are currently stored in an incubator at 20 to 24 degrees C with continuous gentle agitation. PLTs are routinely shipped for transfusion to thrombocytopenic patients, however. There is a concern that PLT concentrates may be adversely affected during the shipping process. Case Report: A 40-year-old woman with severe aplastic anemia and immune refractory to unselected PLT transfusions was transferred to a distant medical center for a hematopoietic peripheral blood progenitor cell transplant where she continued to receive HLA-matched PLTs from her dedicated donors. Sixteen such components were collected and air-shipped in insulated boxes to the transplant center. Thirty-seven platelet-pheresis components from the same dedicated donors had been transfused to the patient before transfer. Corrected count increments (CCIs) at the two sites were compared, with assessment of the role of HLA-match grades. The mean interruption time of controlled agitation during shipment was approximately 10.5 hours. The mean CCI of all distant transfusions was 14,450 +/- 9700 PLTs per mu L(.)m(2) per 10(11) and that of local transfusions was 10730 +/- 4870. The mean donor-paired difference between CCIs at the two sites was 1140 +/- 9940. At the remote location no clinically significant bleeding occurred and one posttransfusion febrile reaction was noted. Conclusion: Despite the study limitations, the effectiveness, in a single patient, of leukoreduced, irradiated apheresis PLTs shipped by lengthy combined surface and airline transport is reported, as measured by posttransfusion CCIs. C1 Warren G Magnuson Clin Ctr, Dept Transfus Med, NIH, Bethesda, MD USA. Univ Texas, MD Anderson Canc Ctr, Dept Lab Med, Houston, TX USA. RP Haddad, SA (reprint author), US FDA, Ctr Biol Evaluat & Res, Off Blood Res & Review, Div Hematol,Lab Cellular Hematol, 1401 Rockville Pike,HFM 335, Rockville, MD 20852 USA. EM salim.haddad@fda.hhs.gov NR 24 TC 4 Z9 6 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 AUG PY 2006 VL 46 IS 8 BP 1306 EP 1310 DI 10.1111/j.1537-2995.2006.00896.x PG 5 WC Hematology SC Hematology GA 066VZ UT WOS:000239259800009 PM 16934064 ER PT J AU Khan, AS Kumar, D AF Khan, Arifa S. Kumar, Dhanya TI Simian foamy virus infection by whole-blood transfer in rhesus macaques: potential for transfusion transmission in humans SO TRANSFUSION LA English DT Article ID IMMUNODEFICIENCY-VIRUS; HUMAN-BEINGS; EPIDEMIOLOGY; TYPE-1; RETROVIRUSES; QUANTITATION; MONKEYS; ASSAY; IDENTIFICATION; ANTIBODIES AB Background: Cross-species infection of humans with simian foamy virus (SFV) has been reported in European and North American nonhuman primate (NHP) handlers, primarily due to wound injuries involving infected animals in research centers and zoos. Additionally, African hunters have been found to be infected with SFV by exposure to body fluids, blood, or tissues of infected NHPs in the wild. The persistence of infectious virus in peripheral blood mononuclear cells (PBMNC) and the recent identification of some infected blood donors has raised safety concerns regarding potential virus transmission by blood transfusion. Study Design and Methods: SFV infection by blood transfusion was evaluated by whole-blood transfer from two naturally-infected rhesus macaques (designated as D1 and D2) to retrovirus-free monkeys. Blood from D1 was transfused to two recipient monkeys R1 and R2 and from D2 to monkeys R3 and R4. Virus transmission was evaluated by immunoassays, polymerase chain reaction assays, and coculture of PBMNC for SFV isolation. Results: SFV infection was seen in R1 and R2 based on development of virus-specific antibodies, identification of SFV sequences in monkey PBMNC, and isolation of infectious virus from PBMNC. Furthermore, both R1 and R2 remained SFV-positive at about 1 year after transfusion, which was the last time tested. No evidence of SFV infection was seen in R3 and R4. Conclusions: SFV transmission in macaques occurred by transfusion of blood from one of two infected donor animals. These results indicate the potential of SFV transfusion transmission in humans, which may depend on virus-specific or donor-related factors. C1 US FDA, Lab Retrovirus Res, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. RP Khan, AS (reprint author), 8800 Rockville Pike,HFM-454,Bldg 29B,Room 4NN10, Bethesda, MD 20892 USA. EM arifa.khan@fda.hhs.gov NR 35 TC 25 Z9 25 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 AUG PY 2006 VL 46 IS 8 BP 1352 EP 1359 DI 10.1111/j.1537-2995.2006.00862.x PG 8 WC Hematology SC Hematology GA 066VZ UT WOS:000239259800016 PM 16934071 ER PT J AU Grinev, A Daniel, S Laassri, M Chizhikov, V Chumakov, K Hewlett, IK Rios, M AF Grinev, A. Daniel, S. Laassri, M. Chizhikov, V. Chumakov, K. Hewlett, I. K. Rios, M. TI Monitoring of genetic variability of West Nile virus in blood donor specimens using a microarray-based assay SO VOX SANGUINIS LA English DT Meeting Abstract C1 US FDA, CBER, Bethesda, MD 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 0042-9007 J9 VOX SANG JI Vox Sang. PD AUG PY 2006 VL 91 SU 3 BP 71 EP 71 PG 1 WC Hematology SC Hematology GA 077AE UT WOS:000239999300167 ER PT J AU Rios, M Daniel, S Stramer, SL Caglioti, S Wood, O Hewlett, IK AF Rios, M. Daniel, S. Stramer, S. L. Caglioti, S. Wood, O. Hewlett, I. K. TI Protective role of natural antibodies in WNV infection: In vitro infectivity of WNVID NAT reactive plasmas containing specific antibodies (IgM and/or IgG) SO VOX SANGUINIS LA English DT Meeting Abstract C1 US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. Amer Red Cross, Gaithersburg, MD USA. Blood Syst Labs, Tempe, AZ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0042-9007 EI 1423-0410 J9 VOX SANG JI Vox Sang. PD AUG PY 2006 VL 91 SU 3 BP 72 EP 72 PG 1 WC Hematology SC Hematology GA 077AE UT WOS:000239999300169 ER PT J AU Castilho, LC Baleotti, W Reid, ME Rios, M Pellegrino, J Fabron, A Costa, F AF Castilho, L. C. Baleotti, W., Jr. Reid, M. E. Rios, M. Pellegrino, J., Jr. Fabron, A., Jr. Costa, F. TI A novel do allele combination namely DOB-WL SO VOX SANGUINIS LA English DT Meeting Abstract C1 Univ Estadual Campinas, Campinas, SP, Brazil. Hemoctr Marilia, Marilia, SP, Brazil. New York Blood Ctr, New York, NY 10021 USA. US FDA, CBER, OBRR, DETTD, Rockville, MD USA. RI Baleotti, Wilson Jr/C-3558-2014 NR 0 TC 1 Z9 1 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0042-9007 J9 VOX SANG JI Vox Sang. PD AUG PY 2006 VL 91 SU 3 BP 106 EP 106 PG 1 WC Hematology SC Hematology GA 077AE UT WOS:000239999300251 ER PT J AU Mahoney, CM Patwardhan, DV McDermott, MK AF Mahoney, Christine M. Patwardhan, Dinesh V. McDermott, M. Ken TI Characterization of drug-eluting stent (DES) materials with cluster secondary ion mass spectrometry (SIMS) SO APPLIED SURFACE SCIENCE LA English DT Article; Proceedings Paper CT 15th International Conference on Secondary Ion Mass Spectrometry (SIMS XV) CY SEP 12-16, 2005 CL Univ Manchester, Manchester, ENGLAND HO Univ Manchester DE depth profile; SIMS; stents; coronary; drug-eluting; DES; Biomaterials; cluster; SIMS; SP5+; polymers; temperature; paclitaxel AB Secondary ion mass spectrometry (SIMS) employing an SF5+ polyatomic primary ion source was utilized to analyze several materials commonly used in drug-eluting stents (DES). Poly(ethylene-co-vinyl acetate) (PEVA), poly(lactic-co-glycolic acid) (PLGA) and various poly(urethanes) were successfully depth profiled using SF5+ bombardment. The resultant molecular depth profiles obtained from these polymeric films showed very little degradation in molecular signal as a function of increasing SF5+ primary ion dose when experiments were performed at low temperatures (signal was maintained for doses up to similar to 5 x 10(15) ions/cm(2)). Temperature was determined to be an important parameter in both the success of the depth profiles and the mass spectral analysis of the polymers. In addition to the pristine polymer films, paclitaxel (drug released in Taxus (TM) stent) containing PLGA films were also characterized, where it was confirmed that both drug and polymer signals could be monitored as a function of depth at lower paclitaxel concentrations (10 wt%). Published by Elsevier B.V. C1 Natl Inst Stand & Technol, Gaithersburg, MD 20899 USA. US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20852 USA. RP Mahoney, CM (reprint author), Natl Inst Stand & Technol, 100 Bur Dr,Mail Stop 8371, Gaithersburg, MD 20899 USA. EM christine.mahoney@nist.gov NR 9 TC 23 Z9 23 U1 1 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-4332 J9 APPL SURF SCI JI Appl. Surf. Sci. PD JUL 30 PY 2006 VL 252 IS 19 SI SI BP 6554 EP 6557 DI 10.1016/j.apsusc.2006.02.107 PG 4 WC Chemistry, Physical; Materials Science, Coatings & Films; Physics, Applied; Physics, Condensed Matter SC Chemistry; Materials Science; Physics GA 085ND UT WOS:000240609900040 ER PT J AU Hoashi, T Muller, J Vieira, WD Rouzaud, F Kikuchi, K Tamaki, K Hearing, VJ AF Hoashi, Toshihiko Muller, Jacqueline Vieira, Wilfred D. Rouzaud, Francois Kikuchi, Kanako Tamaki, Kunihiko Hearing, Vincent J. TI The repeat domain of the melanosomal matrix protein PMEL17/GP100 is required for the formation of organellar fibers SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HERMANSKY-PUDLAK-SYNDROME; MONOCLONAL-ANTIBODY; PLASMINOGEN-ACTIVATOR; MELANOCYTE LINEAGE; SILVER LOCUS; CELLS; IDENTIFICATION; GLYCOPROTEIN; TYROSINASE; GP100 AB Over 125 pigmentation-related genes have been identified to date. Of those, PMEL17/GP100 has been widely studied as a melanoma-specific antigen as well as a protein required for the formation of fibrils in melanosomes. PMEL17 is synthesized, glycosylated, processed, and delivered to melanosomes, allowing them to mature from amorphous round vesicles to elongated fibrillar structures. In contrast to other melanosomal proteins such as TYR and TYRP1, the processing and sorting of PMEL17 is highly complex. Monoclonal antibody HMB45 is commonly used for melanoma detection, but has the added advantage that it specifically reacts with sialylated PMEL17 in the fibrillar matrix in melanosomes. In this study, we generated mutant forms of PMEL17 to clarify the subdomain of PMEL17 required for formation of the fibrillar matrix, a process critical to pigmentation. The internal proline/serine/threonine-rich repeat domain (called the RPT domain) of PMEL17 undergoes variable proteolytic cleavage. Deletion of the RPT domain abolished its recognition by HMB45 and its capacity to form fibrils. Truncation of the C-terminal domain did not significantly affect the processing or trafficking of PMEL17, but, in contrast, deletion of the N-terminal domain abrogated both. We conclude that the RPT domain is essential for its function in generating the fibrillar matrix of melanosomes and that the luminal domain is necessary for its correct processing and trafficking to those organelles. C1 Tokai Univ, Fac Med, Dept Dermatol, Tokyo 1138655, Japan. NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. US FDA, Div Viral Prod, Rockville, MD 20852 USA. RP Hoashi, T (reprint author), Tokai Univ, Fac Med, Dept Dermatol, Tokyo 1138655, Japan. EM thoashi-tky@umin.ac.jp; hearingv@nih.gov FU Intramural NIH HHS NR 52 TC 64 Z9 67 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 JUL 28 PY 2006 VL 281 IS 30 BP 21198 EP 21208 DI 10.1074/jbc.M601643200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 065VF UT WOS:000239187300055 PM 16682408 ER PT J AU Heller, DN Nochetto, CB Rummel, NG Thomas, MH AF Heller, David N. Nochetto, Cristina B. Rummel, Nathan G. Thomas, Michael H. TI Development of multiclass methods for drug residues in eggs: Hydrophilic solid-phase extraction cleanup and liquid chromatography/tandem mass spectrometry analysis of tetracycline, fluoroquinolone, sulfonamide, and beta-lactam residues SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE residues in eggs; ion trap mass spectrometry; sulfonamide analysis; tetracycline analysis; fluoroquinolone analysis; beta-lactam analysis; liquid chromatography/tandem mass spectrometry ID ELECTROSPRAY-IONIZATION; BOVINE-MILK; MULTIRESIDUE DETERMINATION; ONLINE EXTRACTION; LAYING HENS; LC-MS/MS; ANTIBIOTICS; CONFIRMATION; WATER; YOLK AB A method was developed for detection of a variety of polar drug residues in eggs via liquid chromatography/tandem mass spectrometry (LC/MS/MS) with electrospray ionization (ESI). A total of twenty-nine target analytes from four drug classes-sulfonamides, tetracyclines, fluoroquinolones, and, beta-lactams-were extracted from eggs using a hydrophilic-lipophilic balance polymer solid-phase extraction (SPE) cartridge. The extraction technique was developed for use at a target concentration of 100 ng/mL (ppb), and it was applied to eggs containing incurred residues from dosed laying hens. The ESI source was tuned using a single, generic set of tuning parameters, and analytes were separated with a phenyl-bonded silica cartridge column using an LC gradient. In a related study, residues of beta-lactam drugs were not found by LC/MS/MS in eggs from hens dosed orally with, beta-lactam drugs. LC/MS/MS performance was evaluated on two generations of ion trap mass spectrometers, and key operational parameters were identified for each instrument. The ion trap acquisition methods could be set up for screening (a single product ion) or confirmation (multiple product ions). The lower limit of detection for screening purposes was 10-50 ppb (sulfonamides), 10-20 ppb (fluoroquinolones), and 10- 50 ppb (tetracyclines), depending on the drug, instrument, and acquisition method. Development of this method demonstrates the feasibility of generic SPE, LC, and MS conditions for multiclass LC/MS residue screening. C1 US FDA, Ctr Vet Med, Laurel, MD 20708 USA. RP Heller, DN (reprint author), US FDA, Ctr Vet Med, Laurel, MD 20708 USA. EM david.heller@fda.hhs.gov NR 33 TC 71 Z9 77 U1 2 U2 26 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0021-8561 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD JUL 26 PY 2006 VL 54 IS 15 BP 5267 EP 5278 DI 10.1021/jf0605502 PG 12 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 064WH UT WOS:000239120200010 PM 16848505 ER PT J AU Cheng, ZH Su, L Moore, J Zhou, KQ Luther, M Yin, JJ Yu, LL AF Cheng, Zhihong Su, Lan Moore, Jeffrey Zhou, Kequan Luther, Marla Yin, Jun-Jie Yu, Liangli (Lucy) TI Effects of postharvest treatment and heat stress on availability of wheat antioxidants SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE antioxidant activity; wheat; bran; heat stress; reduction of the particle size ID BRAN EXTRACTS; PHENOLIC-ACID; DIFFERENT LOCATIONS; CANCER PREVENTION; FRACTIONS; STABILITY; STORAGE; PHYTOCHEMICALS; TEMPERATURE; VEGETABLES AB This research evaluated the effects of postharvest treatment and heat stress on the availability of wheat antioxidants using Ankor and Trego wheat varieties. The grain, bran, and 40-mesh bran samples of both Ankor and Trego wheat were kept at 25, 60, and 100 degrees C for 9 days. Samples taken at day 0, 1, 2, 3, 5, and 9 were extracted with pure ethanol and examined for antioxidant properties including the scavenging activity against peroxyl ( ORAC), cation ABTS, and 2,2-diphenyl-1-picryhydrazyl (DPPH,) radicals, as well as total phenolic content (TPC) and phenolic acid composition. Both heat stress and postharvest treatment significantly altered the antioxidant properties of wheat grain fractions. The ORAC values of Ankor bran and corresponding 40-mesh bran samples kept at 100 degrees C for 9 days reduced to 61 and 40% of that at day 0 on a per dry weight basis, respectively, while the ORAC values of the grain samples showed no significant change. The overall loss of DPPH, scavenging capacity was 38 and 100% for the bran and 40-mesh Ankor bran samples, respectively, and was 47 and 60% in the bran and 40-mesh Trego bran samples, respectively, whereas no reduction was detected in the grain samples under the same heat stress. Heat stress and postharvest treatment had similar effects on ABTS(center dot+) scavenging capacities and TPC values of grain and fractions of both varieties. These data suggest that whole grain as opposed to its fractions is a preferred form of long-term storage for better preserving natural antioxidants and that the reduction of the particle size may accelerate the loss of natural antioxidants in wheat bran during storage and thermal processing but may enhance the releasable amount of wheat antioxidants from bran. C1 Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA. US FDA, CFSAN, Instrumentat & Biophys Branch, College Pk, MD 20740 USA. RP Yu, LL (reprint author), Univ Maryland, Dept Nutr & Food Sci, 0112 Skiner Bldg, College Pk, MD 20742 USA. EM lyu5@umd.edu RI Yin, Jun Jie /E-5619-2014 NR 28 TC 40 Z9 44 U1 2 U2 21 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0021-8561 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD JUL 26 PY 2006 VL 54 IS 15 BP 5623 EP 5629 DI 10.1021/jf060719b PG 7 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 064WH UT WOS:000239120200060 PM 16848555 ER PT J AU Herrmann, JE Wang, SX Zhang, CY Panchal, RG Bavari, S Lyons, CR Lovchik, JA Golding, B Shiloach, J Lu, S AF Herrmann, John E. Wang, Shixia Zhang, Chuanyou Panchal, Rekha G. Bavari, Sina Lyons, C. Rick Lovchik, Julie A. Golding, Basil Shiloach, Joseph Lu, Shan TI Passive immunotherapy of Bacillus anthracis pulmonary infection in mice with antisera produced by DNA immunization SO VACCINE LA English DT Article DE DNA vaccine; protective antibodies; passive immunity; immunotherapy ID PROTECTIVE ANTIGEN; GENETIC IMMUNIZATION; ANTIBODY FRAGMENTS; BIOLOGICAL WEAPONS; EBOLA-VIRUS; GUINEA-PIGS; IMMUNITY; TOXIN; BIOTERRORISM; COMBINATION AB Because of the high failure rate of antibiotic treatment in patients with anthrax there is a need for additional therapies such as passive immunization with therapeutic antibodies. In this study, we used codon-optimized plasmid DNAs (DNA vaccines) encoding Bacillus anthracis protective antigen (PA) to immunize rabbits for producing anti-anthrax antibodies for use in passive immunotherapy. The antisera generated with these DNA vaccines were of high titer as measured by ELISA. The antisera were also able to protect J774 macrophage cells by neutralizing the cytotoxic effect of exogenously added anthrax lethal toxin, and of the toxin released by B. anthracis (Sterne strain) spores following infection. In addition, the antisera passively protected mice against pulmonary challenge with an approximate 50 LD50 dose of B. anthracis (Sterne strain) spores. The protection in mice was obtained when the antiserum was given 1 h before or 1 h after challenge. We further demonstrated that IgG and F(ab')(2) components purified from anti-PA rabbit hyperimmune sera retained similar levels of neutralizing activities against both exogenously added B. anthracis lethal toxin and toxin produced by B. anthracis (Sterne strain) spores. The high titer antisera we produced will enable an immunization strategy to supplement antibiotic therapy for improving the survival of patients with anthrax. (c) 2006 Elsevier Ltd. All rights reserved. C1 Antibody Sci Inc, Worcester, MA 01603 USA. Univ Massachusetts, Sch Med, Dept Med, Worcester, MA 01655 USA. NCI, SAIC Frederick Inc, Target Struct Based Drug Discovery Grp, Frederick, MD 21702 USA. USA, Med Res Inst Infect Dis, Ft Detrick, MD 21705 USA. Univ New Mexico, Hlth Sci Ctr, Dept Internal Med, Albuquerque, NM 87131 USA. US FDA, Div Hematol, Off Blood Res & Review, Rockville, MD 20852 USA. NIDDK, Biotechnol Unit, NIH, Bethesda, MD 20892 USA. RP Herrmann, JE (reprint author), Antibody Sci Inc, 80 Webster St, Worcester, MA 01603 USA. EM ASI@AbScience.com OI Lu, Shan/0000-0002-8417-7588 FU NCI NIH HHS [N01-CO-12400]; NIAID NIH HHS [U54 AI 057156-01, R43 AI056761] NR 34 TC 15 Z9 15 U1 1 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 JUL 26 PY 2006 VL 24 IS 31-32 BP 5872 EP 5880 DI 10.1016/j.vaccine.2006.04.065 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 069TB UT WOS:000239470000014 PM 16790303 ER PT J AU Salierno, JD Snyder, NS Murphy, AZ Poli, M Hall, S Baden, D Kane, AS AF Salierno, J. D. Snyder, N. S. Murphy, A. Z. Poli, M. Hall, S. Baden, D. Kane, A. S. TI Harmful algal bloom toxins alter c-Fos protein expression in the brain of killifish, Fundulus heteroclitus SO AQUATIC TOXICOLOGY LA English DT Article DE fish; c-fos; brevetoxin; saxitoxin; domoic acid; Fundulus heteroclitus ID CEREBELLAR GRANULE NEURONS; DOMOIC ACID; RAT; ACTIVATION; FOREBRAIN; FISH; IMMUNOREACTIVITY; IDENTIFICATION; TETRODOTOXIN; STIMULATION AB The immediate early gene c-fos, and its protein product c-Fos, are known to be induced in neurons of mammals and fish as a result of neuronal stimulation. The purpose of this study was to quantitatively examine CNS alterations in killifish, Fundulus heteroclitus, in relation to harmful algal bloom (HAB) toxin exposure. c-Fos expression was visualized using immunocytochemistry in the brains of killifish exposed to the excitatory neurotoxins domoic acid (DA) and brevetoxin (PbTx-2), and a paralytic neurotoxin, saxitoxin (STX), released from HABs. In addition, a simulated transport stress experiment was conducted to investigate effects of physical stress on c-Fos induction. Groups of fish were exposed to the different stress agents, brain sections were processed for c-Fos staining, and expression was quantified by brain region. Fish exposed to DA, STX, and transport stress displayed significant alterations in neuronal c-Fos expression when compared to control fish (p < 0.05). DA, PbTx-2, and transport stress increased c-Fos expression in the optic tecta regions of the brain, whereas STX significantly decreased expression. This is the first study to quantify c-Fos protein expression in fish exposed to HAB toxins. General alterations in brain activity, as well as knowledge of specific regions within the brain activated in association with HABs or other stressors, provides valuable insights into the neural control of fish behavior as well as sublethal effects of specific stressors in the CNS. (c) 2006 Elsevier B.V. All rights reserved. C1 Univ Maryland, Sch Med, Dept Epidemiol & Prevent Med, Aquat Pathobiol Ctr, Baltimore, MD 21201 USA. Univ Maryland, Sch Med, Dept Anat & Neurobiol, Baltimore, MD 21201 USA. Georgia State Univ, Dept Biol, Atlanta, GA 30303 USA. USA, Med Res Inst Infect Dis, Integrated Toxicol Div, Ft Detrick, MD 21702 USA. US FDA, Off Seafood, Beltsville Res Facil, Laurel, MD 20708 USA. Univ N Carolina, Marine Sci Res Ctr, Wilmington, NC 28409 USA. Univ Maryland, Virginia Maryland Reg Coll Vet Med, Aquat Pathobiol Ctr, College Pk, MD 20742 USA. RP Kane, AS (reprint author), Univ Maryland, Sch Med, Dept Epidemiol & Prevent Med, Aquat Pathobiol Ctr, Baltimore, MD 21201 USA. EM akane@umaryland.edu FU NIEHS NIH HHS [P01 ES010594, P01 ES010594-07] NR 36 TC 23 Z9 24 U1 4 U2 11 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 20 PY 2006 VL 78 IS 4 BP 350 EP 357 DI 10.1016/j.aquatox.2006.04.010 PG 8 WC Marine & Freshwater Biology; Toxicology SC Marine & Freshwater Biology; Toxicology GA 062HJ UT WOS:000238934900006 PM 16750577 ER PT J AU Rahman, A White, RM AF Rahman, Atiqur White, Robert M. TI Design, conduct, and interpretation of organ impairment studies in oncology patients - In reply SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Letter C1 US FDA, Silver Spring, MD USA. RP Rahman, A (reprint author), US FDA, Silver Spring, MD USA. NR 6 TC 0 Z9 0 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 JUL 20 PY 2006 VL 24 IS 21 BP 3510 EP 3511 DI 10.1200/JCO.2006.06.7199 PG 2 WC Oncology SC Oncology GA 069BC UT WOS:000239418600039 ER PT J AU Koturbash, I Rugo, RE Hendricks, CA Loree, J Thibault, B Kutanzi, K Pogribny, I Yanch, JC Engelward, BP Kovalchuk, O AF Koturbash, I. Rugo, R. E. Hendricks, C. A. Loree, J. Thibault, B. Kutanzi, K. Pogribny, I. Yanch, J. C. Engelward, B. P. Kovalchuk, O. TI Irradiation induces DNA damage and modulates epigenetic effectors in distant bystander tissue in vivo SO ONCOGENE LA English DT Article DE radiation; bystander effect; DNA damage; epigenetics ID INDUCED GENOMIC INSTABILITY; DOUBLE-STRAND BREAKS; HUMAN RAD51 PROTEIN; IONIZING-RADIATION; MAMMALIAN-CELLS; ALPHA-PARTICLES; HOMOLOGOUS RECOMBINATION; HUMAN FIBROBLASTS; HISTONE H2AX; GLOBAL DNA AB Irradiated cells induce chromosomal instability in unirradiated bystander cells in vitro. Although bystander effects are thought to be linked to radiation-induced secondary cancers, almost no studies have evaluated bystander effects in vivo. Furthermore, it has been proposed that epigenetic changes mediate bystander effects, but few studies have evaluated epigenetic factors in bystander tissues in vivo. Here, we describe studies in which mice were unilaterally exposed to X-irradiation and the levels of DNA damage, DNA methylation and protein expression were evaluated in irradiated and bystander cutaneous tissue. The data show that X-ray exposure to one side of the animal body induces DNA strand breaks and causes an increase in the levels of Rad51 in unexposed bystander tissue. In terms of epigenetic changes, unilateral radiation suppresses global methylation in directly irradiated tissue, but not in bystander tissue at given time-points studied. Intriguingly, however, we observed a significant reduction in the levels of the de novo DNA methyltransferases DNMT3a and 3b and a concurrent increase in the levels of the maintenance DNA methyltransferase DNMT1 in bystander tissues. Further more, the levels of two methyl-binding proteins known to be involved in transcriptional silencing, MeCP2 and MBD2, were also increased in bystander tissue. Together, these results show that irradiation induces DNA damage in bystander tissue more than a centimeter away from directly irradiated tissues, and suggests that epigenetic transcriptional regulation may be involved in the etiology of radiation-induced bystander effects. C1 Univ Lethbridge, Dept Biol Sci, Lethbridge, AB T1K 3M4, Canada. MIT, Div Biol Engn, Cambridge, MA 02139 USA. Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. MIT, Dept Nucl Sci & Engn, Cambridge, MA 02139 USA. RP Kovalchuk, O (reprint author), Univ Lethbridge, Dept Biol Sci, 4401 Univ Dr,HH127, Lethbridge, AB T1K 3M4, Canada. EM olga.kovalchuk@uleth.ca FU NCI NIH HHS [P01-CA26731, R01 CA079827, R01CA79827, R21 CA084740]; NIEHS NIH HHS [P30 ES001209-26A1, P30 ES002109, P30-ES02109] NR 68 TC 120 Z9 135 U1 1 U2 17 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD JUL 20 PY 2006 VL 25 IS 31 BP 4267 EP 4275 DI 10.1038/sj.onc.1209467 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 066OU UT WOS:000239240100002 PM 16532033 ER PT J AU Velazquez, L Dallas, S Rose, L Evans, KS Saville, R Wang, J Bradley, SK Bona, JD AF Velazquez, Lydia Dallas, Scott Rose, Lisa Evans, Krista S. Saville, Rebecca Wang, Jialynn Bradley, Sean K. Bona, James D. TI A PHS pharmacist team's response to Hurricane Katrina SO AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY LA English DT Article DE controlled substances; disasters; dispensing; drug distribution; personnel, pharmacy; pharmaceutical care; pharmaceutical services; pharmacists; Public Health Service; volunteers AB Purpose. The challenges and victories that a team of Public Health Service (PHS) pharmacists experienced in establishing pharmacy operations at a federal medical station and conducting outreach missions are described. Summary. The Gulf coast of Mississippi and southeast Louisiana were struck on August 29, 2005, by Hurricane Katrina, which caused widespread infrastructure damage, flooding, and loss of life. A team of 70 officers, which included 8 pharmacists, arrived on September 3 and 4 to establish a 480-bed federal medical station in an aircraft hangar at the naval air station (NAS) in Meridian, Mississippi. Numerous challenges were encountered, including identifying a secure space for a pharmacy, determining how to manage the immediate shortage of medications, devising a dispensing system specific to controlled medications, handling personal medications brought in by patients, and maintaining adequate pharmacy staffing to provide for hospital needs. Two outreach efforts were also undertaken. The first was to assist the NAS pharmacy department, which was overwhelmed with nearly 800 Navy and Coast Guard personnel who were displaced to the Meridian NAS. The second outreach effort was to augment the staff at a local free clinic in Meridian, which needed help to set up their clinic so they could handle the influx of hurricane victims who were arriving daily. Conclusion. A team of PHS pharmacists established a pharmacy, provided pharmaceutical care, and conducted outreach programs to aid victims of Hurricane Katrina. C1 US FDA, Div Pharmaceut Evaluat 1, Off Clin Pharmacol & Biopharmaceut, Silver Spring, MD 20903 USA. US FDA, Div Medicat Errors & Tech Support, Off Drug Safety, Silver Spring, MD 20903 USA. Naytahwaush Clin, Naytahwaush, MN USA. Indian Hlth Serv, White Earth Serv Unit, Dept Pharm, Field Clin, Naytahwaush, MN USA. Indian Hlth Serv, Indian Hlth Ctr, Pine Ridge, SD USA. US FDA, Div Pathogens & Transplant Prod, Silver Spring, MD USA. US FDA, Div Drug Mkt Advertising & Commun, Silver Spring, MD USA. US FDA, Div Oncol Prod, Silver Spring, MD USA. US FDA, Off Orphan Prod Dev, Rockville, MD 20857 USA. RP Velazquez, L (reprint author), US FDA, Div Pharmaceut Evaluat 1, Off Clin Pharmacol & Biopharmaceut, 10903 New Hampshire Ave,White Oak Bldg 221,Room 3, Silver Spring, MD 20903 USA. EM lydia.velazquez@fda.hhs.gov NR 2 TC 5 Z9 6 U1 1 U2 3 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 JUL 15 PY 2006 VL 63 IS 14 BP 1332 EP 1335 DI 10.2146/ajhp060020 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 065KK UT WOS:000239158600005 PM 16809753 ER PT J AU Lozier, J AF Lozier, Jay TI Factor VIII biosynthesis: new inspirations? SO BLOOD LA English DT Editorial Material ID HEMOPHILIA-A; EXPRESSION; SEQUENCE; CDNA AB Many years of study have been devoted to the seemingly simple question of where coagulation factor VIII is made, but the question has never been completely answered. There remains more to know about the origin of coagulation factor VIII in the circulation. Jacquemin and colleagues have shown in this issue of Blood that factor VIII is synthesized in the lung microvascular endothelium. C1 US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. RP Lozier, J (reprint author), US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. NR 7 TC 1 Z9 1 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JUL 15 PY 2006 VL 108 IS 2 BP 414 EP 415 DI 10.1182/blood-2006-05-019414 PG 2 WC Hematology SC Hematology GA 064ZP UT WOS:000239129500009 ER PT J AU Nam, JS Kang, MJ Suchar, AM Shimamura, T Kohn, EA Michalowska, AM Jordan, VC Hirohashi, S Wakefield, LM AF Nam, Jeong-Seok Kang, Mi-Jin Suchar, Adam M. Shimamura, Takeshi Kohn, Ethan A. Michalowska, Aleksandra M. Jordan, V. Craig Hirohashi, Setsuo Wakefield, Lalage M. TI Chemokine (C-C motif) ligand 2 mediates the prometastatic effect of dysadherin in human breast cancer cells SO CANCER RESEARCH LA English DT Article ID MONOCYTE CHEMOATTRACTANT PROTEIN-1; NF-KAPPA-B; LINK NA+/K+-ATPASE; PROGNOSTIC-SIGNIFICANCE; CLINICAL-SIGNIFICANCE; ESTROGEN-RECEPTOR; ADHESION SYSTEM; E-CADHERIN; EXPRESSION; GENE AB Dysadherin, a cancer-associated membrane glycoprotein, down-regulates E-cadherin and promotes cancer metastasis, This study examined the role of dysadherin in breast cancer progression. Expression of dysadherin was found to be highest in breast cancer cell lines and tumors that lacked the estrogen receptor (ER). Knockdown of dysadherin caused increased association of E-cadherin with the actin cytoskeleton in breast cancer cell lines that expressed E-cadherin. However, knockdown of dysadherin could still suppress cell invasiveness in cells that had no functional E-cadherin, suggesting the existence of a novel mechanism of action. Global gene expression analysis identified chemokine (C-C motif) ligand 2 (CCL2) as the transcript most affected by dysadherin knockdown in MDA-MB-231 cells, and dysadherin was shown to regulate CCL2 expression in part through activation of the nuclear factor-kappa B pathway. The ability of dysadherin to promote tumor cell invasion in vitro was dependent on the establishment of a CCL2 autocrine loop, and CCL2 secreted by dysadherin-positive tumor cells also promoted endothelial cell migration in a paracrine fashion. Finally, experimental suppression of CCL2 in MDA-MB-231 cells reduced their ability to metastasize in vivo. This study shows that dysadherin has prometastatic effects that are independent of E-cadherin expression and that CCL2 could play an important role in mediating the prometastatic effect of dysadherin in ER-negative breast cancer. C1 NCI, Lab Cell Regulat & Carcinogenesis, Bethesda, MD 20892 USA. US FDA, Tumor Vaccines & Biotechnol Branch, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Natl Canc Ctr, Res Inst, Div Pathol, Tokyo 104, Japan. RP Wakefield, LM (reprint author), NCI, Lab Cell Regulat & Carcinogenesis, Bldg 41,Room C629,41 Lib Dr,MSC 5055, Bethesda, MD 20892 USA. EM wakefiel@dce41.nci.nih.gov RI Jordan, V. Craig/H-4491-2011 FU Intramural NIH HHS; NCI NIH HHS [Z01 BC005785-11] NR 53 TC 55 Z9 60 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 2006 VL 66 IS 14 BP 7176 EP 7184 DI 10.1158/0008-5472.CAN-06-0825 PG 9 WC Oncology SC Oncology GA 064QE UT WOS:000239103400036 PM 16849564 ER PT J AU Marti, G Orfao, A Goolsby, C AF Marti, Gerald Orfao, Alberto Goolsby, Chuck TI ZAP-70 in CLL: Towards standardization of a biomarker for patient management: History of clinical cytometry special issue SO CYTOMETRY PART B-CLINICAL CYTOMETRY LA English DT Editorial Material DE CLL; ZAP-70; flow cytometry ID CHRONIC LYMPHOCYTIC-LEUKEMIA; EXPRESSION C1 US FDA, Bethesda, MD 20014 USA. Univ Salamanca, Gen Cytometry Serv, Canc Res Ctr, E-37008 Salamanca, Spain. Univ Salamanca, Dept Med, E-37008 Salamanca, Spain. Northwestern Univ, Sch Med, Dept Pathol, Chicago, IL 60611 USA. RP Marti, G (reprint author), NIH, Bldg 29B,room 2NN08,9000 Rockville Pike, Bethesda, MD 20892 USA. EM gemarti@helix.nih.gov NR 24 TC 24 Z9 26 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4949 J9 CYTOM PART B-CLIN CY JI Cytom. Part B-Clin. Cytom. PD JUL 15 PY 2006 VL 70B IS 4 BP 197 EP 200 DI 10.1002/cyto.b.20137 PG 4 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 079ZA UT WOS:000240215200001 PM 16906575 ER PT J AU Roach, M Hanks, G Thames, H Schellhammer, P Shipley, WU Sokol, GH Sandler, H AF Roach, Mack, III Hanks, Gerald Thames, Howard, Jr. Schellhammer, Paul Shipley, William U. Sokol, Gerald H. Sandler, Howard TI Defining biochemical failure following radiotherapy with or without hormonal therapy in men with clinically localized prostate cancer: Recommendations of the RTOG-ASTRO Phoenix Consensus Conference SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE biochemical recurrence; prostate cancer; radiotherapy; PSA failure ID EXTERNAL-BEAM RADIOTHERAPY; ADJUVANT ANDROGEN ABLATION; PHASE-III TRIAL; RADIATION-THERAPY; RADICAL PROSTATECTOMY; SEED IMPLANTATION; ANTIGEN BOUNCE; FREE SURVIVAL; PSA; BRACHYTHERAPY AB In 1996 the American Society for Therapeutic Radiology and Oncology (ASTRO) sponsored a Consensus Conference to establish a definition of biochemical failure after external beam radiotherapy (EBRT). The ASTRO definition defined prostate specific antigen (PSA) failure as occurring after three consecutive PSA rises after a nadir with the date of failure as the point halfway between the nadir date and the first rise or any rise great enough to provoke initiation of therapy. This definition was not linked to clinical progression or survival; it performed poorly in patients undergoing hormonal therapy (HT), and backdating biased the Kaplan-Meier estimates of event-free survival. A second Consensus Conference was sponsored by ASTRO and the Radiation Therapy Oncology Group in Phoenix, Arizona, on January 21, 2005, to revise the ASTRO definition. The panel recommended: (1) a rise by 2 ng/mL or more above the nadir PSA be considered the standard definition for biochemical failure after EBRT with or without HT; (2) the date of failure be determined "at call" (not backdated). They recommended that investigators be allowed to use the ASTRO Consensus Definition after EBRT alone (no hormonal therapy) with strict adherence to guidelines as to "adequate follow-up." To avoid the artifacts resulting from short follow-up, the reported date of control should be listed as 2 years short of the median follow-up. For example, if the median follow-up is 5 years, control rates at 3 years should be cited. Retaining a strict version of the ASTRO definition would allow comparisons with a large existing body of literature. (c) 2006 Elsevier Inc. C1 Univ Calif San Francisco, Dept Radiat Oncol, San Francisco, CA 94143 USA. Fox Chase Canc Ctr, Dept Radiat Oncol, Philadelphia, PA 19111 USA. Univ Texas, MD Anderson Canc Ctr, Dept Biostat & Appl Math, Houston, TX 77030 USA. Eastern Virginia Med Sch, Dept Urol, Norfolk, VA 23501 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02115 USA. US FDA, Rockville, MD 20857 USA. Univ Michigan, Dept Radiat Oncol, Ann Arbor, MI 48109 USA. RP Roach, M (reprint author), Univ Calif San Francisco, Dept Radiat Oncol, 1600 Divisadero St,Suite H1031, San Francisco, CA 94143 USA. EM roach@radonc17.ucsf.edu NR 37 TC 1049 Z9 1063 U1 2 U2 30 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 JUL 15 PY 2006 VL 65 IS 4 BP 965 EP 974 DI 10.1016/j.ijrobp.2006.04.029 PG 10 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 061NH UT WOS:000238878800002 PM 16798415 ER PT J AU Jacobson-Kram, D AF Jacobson-Kram, D. TI Challenges of molecular risk assessment for cancer SO CHEMICO-BIOLOGICAL INTERACTIONS LA English DT Meeting Abstract CT International Conference on Frontiers of Pharmacology and Toxicology CY AUG 28-31, 2006 CL Chicago, IL SP Univ Illinois, Toxicol Res Lab, Dept Pharmacol & Canc Res Ctr, Appl Biosyst, Elsevier, Soc Toxicol, Labcat, Waters Corp, Hilltop Lab Anim, Bristol Myers Squibb, Marshall Farms, Thermo Electron N Amer LLC, AniLytics, EMKA Technologies, PerkinElmer, Life & Analyt Sci C1 US FDA, Ctr Drug Evaluat & Res, Off New Drugs, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0009-2797 J9 CHEM-BIOL INTERACT JI Chem.-Biol. Interact. PD JUL 10 PY 2006 VL 161 IS 3 SI SI BP 177 EP 178 DI 10.1016/j.cbi.2006.05.014 PG 2 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology GA 076UB UT WOS:000239982200003 ER PT J AU Abdy, MJ AF Abdy, M. J. TI Overview of the "Animal Rule" - from a vaccine development perspective SO CHEMICO-BIOLOGICAL INTERACTIONS LA English DT Meeting Abstract CT International Conference on Frontiers of Pharmacology and Toxicology CY AUG 28-31, 2006 CL Chicago, IL SP Univ Illinois, Toxicol Res Lab, Dept Pharmacol & Canc Res Ctr, Appl Biosyst, Elsevier, Soc Toxicol, Labcat, Waters Corp, Hilltop Lab Anim, Bristol Myers Squibb, Marshall Farms, Thermo Electron N Amer LLC, AniLytics, EMKA Technologies, PerkinElmer, Life & Analyt Sci C1 US FDA, CBER, Off Vaccines Res & Review, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0009-2797 J9 CHEM-BIOL INTERACT JI Chem.-Biol. Interact. PD JUL 10 PY 2006 VL 161 IS 3 SI SI BP 182 EP 182 PG 1 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology GA 076UB UT WOS:000239982200011 ER PT J AU MacGill, T Schrager, L Mathis, M Pelsor, F Shapiro, A Cress, L Leissa, B Roberts, R AF MacGill, T. Schrager, L. Mathis, M. Pelsor, F. Shapiro, A. Cress, L. Leissa, B. Roberts, R. TI Development of drug medical countermeasures through the "Animal Rule" SO CHEMICO-BIOLOGICAL INTERACTIONS LA English DT Meeting Abstract CT International Conference on Frontiers of Pharmacology and Toxicology CY AUG 28-31, 2006 CL Chicago, IL SP Univ Illinois, Toxicol Res Lab, Dept Pharmacol & Canc Res Ctr, Appl Biosyst, Elsevier, Soc Toxicol, Labcat, Waters Corp, Hilltop Lab Anim, Bristol Myers Squibb, Marshall Farms, Thermo Electron N Amer LLC, AniLytics, EMKA Technologies, PerkinElmer, Life & Analyt Sci C1 US FDA, Ctr Drug Evaluat & Res, Off Counter Terrorism & Emergency Coordinat, Rockville, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0009-2797 J9 CHEM-BIOL INTERACT JI Chem.-Biol. Interact. PD JUL 10 PY 2006 VL 161 IS 3 SI SI BP 197 EP 197 PG 1 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology GA 076UB UT WOS:000239982200033 ER PT J AU Filipe-Santos, O Bustamante, J Haverkamp, MH Vinolo, E Ku, CL Puel, A Frucht, DM Christel, K von Bernuth, H Jouanguy, E Feinberg, J Durandy, A Senechal, B Chapgier, A Vogt, G de Beaucoudrey, L Fieschi, C Picard, C Garfa, M Chemli, J Bejaoui, M Tsolia, MN Kutukculer, N Plebani, A Notarangelo, L Bodemer, C Geissmann, F Israel, A Veron, M Knackstedt, M Barbouche, R Abel, L Magdorf, K Gendrel, D Agou, F Holland, SM Casanova, JL AF Filipe-Santos, Orchidee Bustamante, Jacinta Haverkamp, Margje H. Vinolo, Emilie Ku, Cheng-Lung Puel, Anne Frucht, David M. Christel, Karin von Bernuth, Horst Jouanguy, Emmanuelle Feinberg, Jacqueline Durandy, Anne Senechal, Brigitte Chapgier, Ariane Vogt, Guillaume de Beaucoudrey, Ludovic Fieschi, Claire Picard, Capucine Garfa, Meriem Chemli, Jalel Bejaoui, Mohamed Tsolia, Maria N. Kutukculer, Necil Plebani, Alessandro Notarangelo, Luigi Bodemer, Christine Geissmann, Frederic Israel, Alain Veron, Michel Knackstedt, Maike Barbouche, Ridha Abel, Laurent Magdorf, Klaus Gendrel, Dominique Agou, Fabrice Holland, Steven M. Casanova, Jean-Laurent TI X-linked susceptibility to mycobacteria is caused by mutations in NEMO impairing CD40-dependent IL-12 production SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID INTERFERON-GAMMA-RECEPTOR; BACILLE CALMETTE-GUERIN; ANHIDROTIC ECTODERMAL DYSPLASIA; AVIUM COMPLEX INFECTION; HYPER-IGM SYNDROME; INCONTINENTIA PIGMENTI; IFN-GAMMA; IKK-GAMMA; GENETIC DISSECTION; CELL-DEVELOPMENT AB Germline mutations in five autosomal genes involved in interleukin (IL)-12-dependent, interferon (IFN)-gamma-mediated immunity cause Mendelian susceptibility to mycobacterial diseases (MSMD). The molecular basis of X-linked recessive (XR)-MSMD remains unknown. We report here mutations in the leucine zipper (LZ) domain of the NF-kappa B essential modulator (NEMO) gene in three unrelated kindreds with XR-MSMD. The mutant proteins were produced in normal amounts in blood and fibroblastic cells. However, the patients' monocytes presented an intrinsic defect in T cell-dependent IL-12 production, resulting in defective IFN-gamma secretion by T cells. IL-12 production was also impaired as the result of a specific defect in NEMO- and NF-kappa B/c-Rel-mediated CD40 signaling after the stimulation of monocytes and dendritic cells by CD40L-expressing T cells and fibroblasts, respectively. However, the CD40-dependent up-regulation of costimulatory molecules of dendritic cells and the proliferation and immunoglobulin class switch of B cells were normal. Moreover, the patients' blood and fibroblastic cells responded to other NF-kappa B activators, such as tumor necrosis factor-alpha, IL-beta, and lipopolysaccharide. These two mutations in the NEMO LZ domain provide the first genetic etiology of XR-MSMD. They also demonstrate the importance of the T cell- and CD40L-triggered, CD40-, and NEMO/NF-kappa B/c-Rel-mediated induction of IL-12 by monocyte-derived cells for protective immunity to mycobacteria in humans. C1 Univ Paris 05, Necker Med Sch, INSERM, U550,Lab Human Genet Infect Dis, F-75015 Paris, France. Inst Pasteur, CNRS, URA 2185, Lab Enzymat Regulat Cellular Act, F-75015 Paris, France. INSERM, U768, Lab Normal & Pathol Dev Immune Syst, F-75015 Paris, France. Hop Necker Enfants Malad, Ctr Study Primary Immunodeficiencies, F-75015 Paris, France. Hop Necker Enfants Malad, Lab Confocal Microscopy, F-75015 Paris, France. Hop Necker Enfants Malad, Dermatol Unit, F-75015 Paris, France. Hop Necker Enfants Malad, Pediat Hematol Immunol Unit, F-75015 Paris, France. Inst Pasteur, CNRS, URA 2582, Lab Mol Signaling & Cellular Activat, F-75015 Paris, France. Necker Enfants Malad Inst, Avenir Team, Lab Mononuclear Phagocyte Biol, INSERM, F-75015 Paris, France. US FDA, Ctr Biol Evaluat & Res, Div Monoclonal Antibodies, Cell Biol Lab, Bethesda, MD 20892 USA. Leiden Univ, Med Ctr, Dept Infect Dis, NL-2300 Leiden, Netherlands. Hop St Louis, Immunol Lab, F-75010 Paris, France. Sahloul Hosp, Dept Pediat, Sousse 4054, Tunisia. Inst Pasteur, Natl Ctr Bone Marrow Transplantat, Tunis 1002, Tunisia. Inst Pasteur, Dept Immunol, Tunis 1002, Tunisia. Univ Athens, P&A Kyriakou Childrens Hosp, Sch Med, Dept Pediat 2, Athens 11527, Greece. Ege Univ, Dept Pediat, TR-35100 Izmir, Turkey. Univ Brescia, Dept Pediat, I-25121 Brescia, Italy. Univ Brescia, Int Mol Med Angello Nocivelli, I-25121 Brescia, Italy. Charite, Dept Pediat Pulm & Immunol, D-13353 Berlin, Germany. Hop St Vincent de Paul, Dept Pediat, F-75014 Paris, France. RP Casanova, JL (reprint author), Univ Paris 05, Necker Med Sch, INSERM, U550,Lab Human Genet Infect Dis, F-75015 Paris, France. EM casanova@necker.fr RI Plebani, Alessandro/C-8593-2011; Vogt, Guillaume/L-6046-2015; KU, Cheng-Lung/L-6073-2015; Notarangelo, Luigi/F-9718-2016 OI Vogt, Guillaume/0000-0001-8192-1247; KU, Cheng-Lung/0000-0002-0643-2256; Notarangelo, Luigi/0000-0002-8335-0262 FU Intramural NIH HHS; Medical Research Council [G0900867] NR 55 TC 131 Z9 138 U1 1 U2 5 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD JUL 10 PY 2006 VL 203 IS 7 BP 1745 EP 1759 DI 10.1084/jem.20050085 PG 15 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 062JN UT WOS:000238940500017 PM 16818673 ER PT J AU O'Connell, KA Wise, RP Lozier, JN Braun, MM AF O'Connell, KA Wise, RP Lozier, JN Braun, MM TI Recombinant factor VIIa and thromboembolic events - In reply SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 US FDA, Div Epidemiol, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. US FDA, Div Hematol, Off Blood Res & Review, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. RP O'Connell, KA (reprint author), US FDA, Div Epidemiol, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. EM kathryn.oconnell@hhs.fda.gov NR 0 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 JUL 5 PY 2006 VL 296 IS 1 BP 44 EP 44 DI 10.1001/jama.296.1.44-a PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 058RU UT WOS:000238683100015 ER PT J AU Joner, M Finn, AV Farb, A Mont, EK Kolodgie, FD Ladich, E Kutys, R Skorija, K Gold, HK Virmani, R AF Joner, M Finn, AV Farb, A Mont, EK Kolodgie, FD Ladich, E Kutys, R Skorija, K Gold, HK Virmani, R TI Pathology of drug-eluting stents in humans - Delayed healing and late thrombotic risk SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Review ID CORONARY-ARTERY; INTRAVASCULAR ULTRASOUND; POOLED ANALYSIS; MODERN-ERA; SIROLIMUS; PACLITAXEL; IMPLANTATION; PREDICTORS; RAPAMYCIN; DELIVERY AB OBJECTIVES This study examined human drug-eluting stents (DES) to determine the long-term effects of these stents on coronary arterial healing and identified mechanisms underlying late stent thrombosis (LST). BACKGROUND Although DES reduce the need for repeat revascularization compared with bare-metal stents (BMS), data suggest the window of thrombotic risk for Cypher (Cordis Corp., Miami Lakes, Florida) and Taxus (Boston Scientific Corp., Natick, Massachusetts) DES extends far beyond that for BMS. METHODS From a registry of 40 autopsies of DES (68 stents), 23 DES cases of > 30 days duration were compared with 25 matched autopsies of BMS implantation. Late stent thrombosis was defined as an acute thrombus within a stent > 30 days old. RESULTS Of 23 patients with DES > 30 days old, 14 had evidence of LST. Cypher and Taxus DES showed greater delayed heating characterized by persistent fibrin deposition (fibrin score 2.3 +/- 1.1 vs. 0.9 +/- 0.8, p = 0.0001) and poorer endothelialization (55.8 +/- 26.5%) compared with BMS (89.8 +/- 20.9, p = 0.0001); Moreover, DES with LST showed more delayed healing compared with patent DES. In 5 of 14 patients suffering LST, antiplatelet therapy had been withdrawn. Additional procedural and pathologic risk factors for LST were: 1) local hypersensitivity reaction; 2) ostial and/or bifurcation stenting; 3) malapposition/incomplete apposition; 4) restenosis; and 5) strut penetration into a necrotic core. CONCLUSIONS The Cypher and Taxus DES result in delayed arterial healing when compared with BMS of similar implant duration. The cause of DES LST is multifactorial with delayed healing in combination with other clinical and procedural risk factors playing a role. C1 Int Registry Pathol, CV Path, Gaithersburg, MD 20878 USA. Massachusetts Gen Hosp, Dept Internal Med, Cardiac Unit, Boston, MA 02114 USA. Miami Dade Cty Med Examiner Dept, Miami, FL USA. US FDA, Int Cardiol Devices Branch, Rockville, MD 20857 USA. RP Virmani, R (reprint author), Int Registry Pathol, CV Path, 19 Firstfield Rd, Gaithersburg, MD 20878 USA. EM rvirmani@cvpath.org NR 39 TC 1513 Z9 1623 U1 18 U2 142 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD JUL 4 PY 2006 VL 48 IS 1 BP 193 EP 202 DI 10.1016/j.jacc.2006.03.042 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 059FH UT WOS:000238718200027 PM 16814667 ER PT J AU Lesko, LJ AF Lesko, Lawrence J. TI Regulatory agencies role in educational program related to drug development and regulatory science SO ACTA PHARMACOLOGICA SINICA LA English DT Meeting Abstract C1 US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 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 1671-4083 J9 ACTA PHARMACOL SIN JI Acta Pharmacol. Sin. PD JUL PY 2006 VL 27 SU 1 BP 31 EP 31 PG 1 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 071HI UT WOS:000239590000179 ER PT J AU Rhee, H Bae, MA Song, BJ AF Rhee, H. Bae, M. A. Song, B. J. TI Pharmacology and toxicology of peroxisome proliferator activated receptor agonists: Differential apoptosis of troglitazone and rosiglitazone SO ACTA PHARMACOLOGICA SINICA LA English DT Meeting Abstract DE troglitazone; hepatotoxicity; rosiglitazone C1 US FDA, Rockville, MD 20857 USA. NIH, Bethesda, MD 20892 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 1671-4083 J9 ACTA PHARMACOL SIN JI Acta Pharmacol. Sin. PD JUL PY 2006 VL 27 SU 1 BP 50 EP 50 PG 1 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 071HI UT WOS:000239590000290 ER PT J AU Virmani, A Gaetani, F Binienda, Z Ali, S AF Virmani, Ashraf Gaetani, Franco Binienda, Zbigniew Ali, Syed TI Coenzyme Q10 and the metabolic approach to neuroprotection SO AGRO FOOD INDUSTRY HI-TECH LA English DT Article ID NEURONAL CELL-DEATH; 3-NITROPROPIONIC ACID; OXIDATIVE STRESS; Q(10); MITOCHONDRIA; TOXICITY; METHAMPHETAMINE; NEUROTOXICITY; DISEASE; ANTIOXIDANT AB A number of metabolically active compounds have been shown to be effective in models of neurodegeneration. These compounds counteract neuronal damage in conditions of ischernia, hypoxia and metabolic compromise. These include Coenzyme Q 10 (CoQ10) which has been shown to have neuroprotective actions in various models. We examined the possible neuroprotective action of CoQ10 and selenium using IMR32 cultured cells subjected to mitochondrial dysfunction by 3-nitropropionic acid (3-NPA) which inhibits succinate dehydrogenase (SDH) at complex of the mitochondrial electron transport chain. The incubation of 3-NPA-treated cells with 20 mu M selenium provided a small protection whereas 5 mu M CoQ10 was more effective protecting significantly the MTT response. However further studies are necessary which would try different combinations of compounds to improve cellular CoQ10 synthesis as well as its action in neurodegenerative disorders. C1 SigmaTau Healthsci SpA, I-00040 Rome, Italy. US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Virmani, A (reprint author), SigmaTau Healthsci SpA, Via Treviso 4, I-00040 Rome, Italy. NR 27 TC 2 Z9 2 U1 1 U2 1 PU TEKNOSCIENZE PUBL PI MILAN PA VIA AURELIO SAFFI 23, 20123 MILAN, ITALY SN 1722-6996 J9 AGRO FOOD IND HI TEC JI Agro Food Ind. Hi-Tech PD JUL-AUG PY 2006 VL 17 IS 4 BP 20 EP 22 PG 3 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 088DB UT WOS:000240790600011 ER PT J AU Barnes, PJ Chowdhury, B Kharitonov, SA Magnussen, H Page, CP Postma, D Saetta, M AF Barnes, Peter J. Chowdhury, Badrul Kharitonov, Sergei A. Magnussen, Helgo Page, Clive P. Postma, Dirkje Saetta, Marina TI Pulmonary biomarkers in chronic obstructive pulmonary disease SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Review DE bronchial biopsy; bronchoalveolar lavage; exhaled breath; condensate; exhaled nitric oxide; induced sputum ID EXHALED BREATH CONDENSATE; BRONCHOALVEOLAR LAVAGE FLUID; RANDOMIZED CONTROLLED-TRIAL; NITRIC-OXIDE MEASUREMENTS; AIR-FLOW OBSTRUCTION; SPUTUM INFLAMMATORY MARKERS; SHORT-TERM RESPONSE; CHRONIC-BRONCHITIS; OXIDATIVE STRESS; SMOKING-CESSATION AB There has been increasing interest in using pulmonary biomarkers to understand and monitor the inflammation in the respiratory tract of patients with chronic obstructive pulmonary disease (COPD). In this Pulmonary Perspective we discuss the merits of the various approaches by reviewing the current literature on pulmonary biomarkers in COPD and underscore the need for more systematic studies in the future. Bronchial biopsies and bronchoalveolar lavage provide valuable information about inflammatory cells and mediators, but are invasive, so that repeated measurements have to be very limited in assessing any interventions. Induced sputum has provided considerable information about the inflammatory process, including mediators and proteinases in COPD, but selectively samples proximal airways and may not closely reflect distal inflammatory processes. Exhaled gases and breath condensate are noninvasive procedures, so repeated measurements are possible, but for some assays the variability is relatively high. There is relatively little information about how any of these biomarkers relate to other clinical outcomes, such as progression of the disease, severity of disease, clinical subtypes, or response to therapy. More information is also needed about the variability in these measurements. In the future, pulmonary biomarkers may be useful in predicting disease progression, indicating disease instability, and in predicting response to current therapies and novel therapies, many of which are now in development. C1 Kings Coll London, Natl Heart & Lung Inst, Imperial Coll London, Guys Kings & St Thomas Sch Biomed Sci, London SW3 6LY, England. US FDA, Rockville, MD 20857 USA. Ctr Pneumol & Thorac Surg, Grosshansdorf, Germany. Univ Groningen Hosp, Groningen, Netherlands. Univ Padua, Dept Cardiothorac & Vasc Sci, Padua, Italy. RP Barnes, PJ (reprint author), Kings Coll London, Natl Heart & Lung Inst, Imperial Coll London, Guys Kings & St Thomas Sch Biomed Sci, Dovehouse St, London SW3 6LY, England. EM p.j.barnes@imperial.ac.uk RI Saetta, Marina/D-1924-2009 NR 144 TC 163 Z9 175 U1 0 U2 19 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD JUL 1 PY 2006 VL 174 IS 1 BP 6 EP 14 DI 10.1164/rccm.200510-1659PP PG 9 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 056DX UT WOS:000238502600004 PM 16556692 ER PT J AU Anderson, KL Lyman, RL Bodeis-Jones, SM White, DG AF Anderson, KL Lyman, RL Bodeis-Jones, SM White, DG TI Genetic diversity and antimicrobial susceptibility profiles among mastitis-causing Staphylococcus aureus isolated from bovine milk samples SO AMERICAN JOURNAL OF VETERINARY RESEARCH LA English DT Article; Proceedings Paper CT 23rd World Buiatrics Congress CY JUL, 2004 CL Quebec City, CANADA ID FIELD GEL-ELECTROPHORESIS; MOLECULAR EPIDEMIOLOGIC ANALYSIS; DAIRY HERDS; CLINICAL MASTITIS; RESISTANT STAPHYLOCOCCUS; MAMMARY-GLANDS; COWS; COUNTRIES; BACTERIA; STRAINS AB Objective-To determine whether particular antimicrobial susceptibility profiles of bovine mastitis-causing Staphylococcus aureus isolates were associated with specific S aureus genotypes. Sample Population-357 S aureus isolates recovered from milk samples submitted for diagnostic bacteriologic testing from 24 dairy herds. Procedures-Antimicrobial susceptibility of S aureus isolates was assessed by determining minimum inhibitory concentrations (MICs) to 14 antimicrobial agents. After digestion of S aureus genomic DNA by Smal, electrophoretic patterns were obtained via pulsed-field gel electrophoresis (PFGE) and used to classify isolates into types. Gels were analyzed, and data were used to prepare dendrograms. Results-308 of 357 (86%) S aureus isolates were susceptible to all antimicrobials evaluated. Forty-nine S aureus isolates were resistant to 1 or more antimicrobials- of these isolates, 37 were resistant only to penicillin: 9 were resistant to penicillin and erythromycin, 2 were resistant to tetracycline, and 1 was resistant to erythfomycin. Isolates were assigned to 7 PFGE types. An association was found between PFGE type and antimicrobial susceptibility profile. Organisms with resistance to at least one of the tested antimicrobial agents were identified in only 4 of the 7 types of S aureus. Conclusions and Clinical Relevance-Antimicrobial resistance was uncommon among the mastitis-causing S aureus isolates identified in the milk samples. A limited number of genotypes were associated with mastitis in these herds. Antimicrobial resistance phenotypes were associated with particular S aureus PFGE types; this association may have implications for future treatment and control of S aureus-associated mastitis in cattle. C1 N Carolina State Univ, Coll Vet Med, Dept Populat Hlth & Pathobiol, Raleigh, NC 27606 USA. US FDA, Ctr Vet Med, Laurel, MD 20708 USA. RP Anderson, KL (reprint author), N Carolina State Univ, Coll Vet Med, Dept Populat Hlth & Pathobiol, Raleigh, NC 27606 USA. NR 46 TC 28 Z9 32 U1 1 U2 6 PU AMER VETERINARY MEDICAL ASSOC PI SCHAUMBURG PA 1931 N MEACHAM RD SUITE 100, SCHAUMBURG, IL 60173-4360 USA SN 0002-9645 J9 AM J VET RES JI Am. J. Vet. Res. PD JUL PY 2006 VL 67 IS 7 BP 1185 EP 1191 DI 10.2460/ajvr.67.7.1185 PG 7 WC Veterinary Sciences SC Veterinary Sciences GA 059EQ UT WOS:000238716500015 PM 16817741 ER PT J AU Buehler, PW Boykins, RA Norris, S Alayash, AI AF Buehler, Paul W. Boykins, Robert A. Norris, Scott Alayash, Abdu I. TI Chemical characterization of diaspirin cross-linked hemoglobin polymerized with poly(ethylene glycol) SO ANALYTICAL CHEMISTRY LA English DT Article ID POLYOXYETHYLENE CONJUGATE; BOVINE HEMOGLOBIN; REDOX PROPERTIES; RESUSCITATION; PEGYLATION; VOLUME; SHOCK AB A lack of specificity associated with chemical modification methods used in the preparation of certain hemoglobin (Hb)-based oxygen carriers (HBOCs) may alter Hb structure and function, as amino acids located in critical regions ( e. g., alpha-beta interfaces and the 2,3-DPG binding pocket) may unintentionally be targeted. Hb protein surface modifications with various poly( ethylene glycol) ( PEG) derivatives have been used as conjugating and polymerizing agents with the intent of improving reaction site specificity/ reproducibility and ultimately reducing the untoward hypertensive response due to nitric oxide scavenging by smaller molecular size tetrameric species (i.e., 64 kDa) in HBOC solutions. Previous experiments performed in our laboratory have evaluated the influence of polymerization of diaspirin alpha- cross-linked Hb (alpha alpha-DBBF-Hb) with a bifunctional modified PEG, bis(maleoylglycylamide) PEG ( BMAA-PEG), in terms of oxygen carrying capacity, redox properties, hypertensive response, and renal clearance in rats. The data presented in this paper specifically evaluate the influence of BMAA-PEG on alpha alpha-DBBF-Hb (Poly-alpha alpha-DBBF-Hb) to identify molecular weight distribution, protein conformation, and site-specific modification, as well as to provide insight into the previously determined in vitro and in vivo functional and vasoactive characteristics of this HBOC. Chemical analysis performed herein reveals nonspecific modifications induced by BMAA-PEG that result in the full modification of alpha alpha-DBBF-Hb leaving no tetrameric crosslinked starting material in solution. These data are inconsistent with the continuing assumption that molecular size (i.e., 64 kDa) has a direct influence on HBOC- mediated vasoactivity and that other protective strategies should be considered to control blood pressure imbalances. C1 US FDA, Ctr Biol Evaluat & Res, Div Hematol, Lab Biochem & Vasc Biol, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Bacterial PArasit & Allergen Prod, Biophys Lab, Bethesda, MD 20892 USA. RP Alayash, AI (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Hematol, Lab Biochem & Vasc Biol, Bethesda, MD 20892 USA. EM alayash@cber.fda.gov NR 30 TC 9 Z9 9 U1 1 U2 11 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0003-2700 EI 1520-6882 J9 ANAL CHEM JI Anal. Chem. PD JUL 1 PY 2006 VL 78 IS 13 BP 4634 EP 4641 DI 10.1021/ac060188q PG 8 WC Chemistry, Analytical SC Chemistry GA 058KZ UT WOS:000238665200054 PM 16808476 ER PT J AU Schultheis, LW Mathis, LL Roca, RA Simone, AF Hertz, SH Rappaport, BA AF Schultheis, LW Mathis, LL Roca, RA Simone, AF Hertz, SH Rappaport, BA TI Pediatric drug development in anesthesiology: an FDA perspective SO ANESTHESIA AND ANALGESIA LA English DT Editorial Material ID ANALGESIA; QUALITY; JOURNALS; TRIALS C1 US FDA, Div Anesthesia Analgesia & Rheumatol Prod, Rockville, MD 20857 USA. US FDA, Div Pediat Drug Dev, Rockville, MD 20857 USA. RP Schultheis, LW (reprint author), US FDA, Div Anesthesia Analgesia & Rheumatol Prod, Rockville, MD 20857 USA. EM schultheisl@cder.fda.gov NR 10 TC 7 Z9 7 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD JUL PY 2006 VL 103 IS 1 BP 49 EP 51 DI 10.1213/01.ANE.0000228302.15293.DE PG 3 WC Anesthesiology SC Anesthesiology GA 058JS UT WOS:000238661900009 PM 16790624 ER PT J AU Donnelly, RP Kotenko, SV AF Donnelly, R. P. Kotenko, S. V. TI Novel IL-10-related cytokines: Potential targets for therapeutic intervention SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Meeting Abstract CT Annual European Congress of Rheumatology (EULAR 2006) CY JUN 21-24, 2006 CL Amsterdam, NETHERLANDS C1 US FDA, Div Therapeut Prot, Ctr Drug Evaluat & Res, Bethesda, MD 20014 USA. Univ Med & Dent New Jersey, Dept Biochem & Mol Biol, Newark, NJ 07103 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD JUL PY 2006 VL 65 SU 2 BP 38 EP 38 PG 1 WC Rheumatology SC Rheumatology GA 209ET UT WOS:000249372500117 ER PT J AU Shoor, SM Cheetham, C Graham, DJ Campen, DH Hui, R Spence, M Levy, G AF Shoor, S. M. Cheetham, C. Graham, D. J. Campen, D. H. Hui, R. Spence, M. Levy, G. TI Risk of myocardial infarction in users of non selective NSAIDS: A nested case control study SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Meeting Abstract CT Annual European Congress of Rheumatology (EULAR 2006) CY JUN 21-24, 2006 CL Amsterdam, NETHERLANDS C1 Kaiser Med Ctr, Santa Clara, CA USA. Kaiser Permanente, Pharm Outcomes Res Grp, Oakland, CA USA. US FDA, CDER, Off Drug Safety, Rockville, MD 20857 USA. Kaiser Permanente, Oakland, CA USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD JUL PY 2006 VL 65 SU 2 BP 61 EP 61 PG 1 WC Rheumatology SC Rheumatology GA 209ET UT WOS:000249372500179 ER PT J AU Singh, G Graham, D Wang, H Mithal, A Triadafilopoulos, G AF Singh, G. Graham, D. Wang, H. Mithal, A. Triadafilopoulos, G. TI Concomitant aspirin use reduces the risk of acute myocardial infarction in users of cyclooxygenase-2 selective and some non-selective nonsteroidal anti-inflammatory drugs SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Meeting Abstract CT Annual European Congress of Rheumatology (EULAR 2006) CY JUN 21-24, 2006 CL Amsterdam, NETHERLANDS C1 Stanford Univ, Sch Med, Palo Alto, CA 94304 USA. Drug Safety Food & Drug Adm, Rockville, MD USA. Stanford Univ, Sch Med, Stanford, CA 94305 USA. ICORE, Palo Alto, CA USA. NR 0 TC 7 Z9 8 U1 1 U2 1 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD JUL PY 2006 VL 65 SU 2 BP 61 EP 61 PG 1 WC Rheumatology SC Rheumatology GA 209ET UT WOS:000249372500178 ER PT J AU Lories, RJU Peeters, J Reekmans, K Tylzanowski, P Thomas, JT Luyten, FP AF Lories, R. J. U. Peeters, J. Reekmans, K. Tylzanowski, P. Thomas, J. T. Luyten, F. P. TI Genetic deletion of FRZB in mice: Evidence for involvement of WNT signaling in an inverse relation between osteoporosis and osteoarthritis SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Meeting Abstract CT Annual European Congress of Rheumatology (EULAR 2006) CY JUN 21-24, 2006 CL Amsterdam, NETHERLANDS C1 US FDA, CBER, Rockville, MD 20857 USA. Katholieke Univ Leuven Hosp, Louvain, Belgium. RI Tylzanowski, Przemko/G-8881-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD JUL PY 2006 VL 65 SU 2 BP 104 EP 104 PG 1 WC Rheumatology SC Rheumatology GA 209ET UT WOS:000249372500308 ER PT J AU Bhagwat, AA Tan, J Sharma, M Kothary, M Low, S Tall, BD Bhagwat, M AF Bhagwat, Arvind A. Tan, Jasmine Sharma, Manan Kothary, Mahendra Low, Sharon Tall, Ben D. Bhagwat, Medha TI Functional heterogeneity of RpoS in stress tolerance of enterohemorrhagic Escherichia coli strains SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID ACID-RESISTANCE SYSTEMS; STATIONARY-PHASE; SHIGELLA-FLEXNERI; ENTERIC BACTERIA; MUTATIONS; GLUTAMATE; O157-H7; SURVIVAL; GENES; EXPRESSION AB The stationary-phase sigma factor (RpoS) regulates many cellular responses to environmental stress conditions such as heat, acid, and alkali shocks. On the other hand, mutations at the rpoS locus have frequently been detected among pathogenic as well as commensal strains of Escherichia coli. The objective of this study was to perform a functional analysis of the RpoS-mediated stress responses of enterohemorrhagic E. coli strains from food-borne outbreaks. E. coli strains belonging to serotypes O157:H7, O111:H11, and O26:H11 exhibited polymorphisms for two phenotypes widely used to monitor rpoS mutations, heat tolerance and glycogen synthesis, as well as for two others, alkali tolerance and adherence to Caco-2 cells. However, these strains synthesized the oxidative acid resistance system through an rpoS-dependent pathway. During the transition from mildly acidic growth conditions (pH 5.5) to alkaline stress (pH 10.2), cell survival was dependent on rpoS functionality. Some strains were able to overcome negative regulation by RpoS and induced higher P-galactosidase activity without compromising their acid resistance. There were no major differences in the DNA sequences in the rpoS coding regions among the tested strains. The heterogeneity of rpoS-dependent phenotypes observed for stress-related phenotypes was also evident in the Caco-2 cell adherence assay. Wild-type O157:H7 strains with native rpoS were less adherent than rpoS-complemented counterpart strains, suggesting that rpoS functionality is needed. These results show that some pathogenic E. coli strains can maintain their acid tolerance capability while compromising other RpoS-dependent stress responses. Such adaptation processes may have significant impact on a pathogen's survival in food processing environments, as well in the host's stomach and intestine. C1 USDA ARS, Prod Qual & Safety Lab, Henry A Wallace Beltsville Agr Res Ctr, Beltsville, MD 20705 USA. USDA ARS, Food Technol & Safety Lab, Henry A Wallace Beltsville Agr Res Ctr, Beltsville, MD 20705 USA. US FDA, Div Virulence Assessment, Laurel, MD 20708 USA. NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. RP Bhagwat, M (reprint author), USDA ARS, Prod Qual & Safety Lab, Henry A Wallace Beltsville Agr Res Ctr, Bldg 002,10300 Baltimore Ave, Beltsville, MD 20705 USA. EM bhagwata@ba.ars.usda.gov OI Tall, Ben/0000-0003-0399-3629 NR 57 TC 36 Z9 40 U1 0 U2 13 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 2006 VL 72 IS 7 BP 4978 EP 4986 DI 10.1128/AEM.02842-05 PG 9 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 062RA UT WOS:000238961000060 PM 16820496 ER PT J AU Brezna, B Kweon, O Stingley, RL Freeman, JP Khan, AA Polek, B Jones, RC Cerniglia, CE AF Brezna, Barbara Kweon, Ohgew Stingley, Robin L. Freeman, James P. Khan, Ashraf A. Polek, Bystrik Jones, Richard C. Cerniglia, Carl E. TI Molecular characterization of cytochrome P450 genes in the polycyclic aromatic hydrocarbon degrading Mycobacterium vanbaalenii PYR-1 SO APPLIED MICROBIOLOGY AND BIOTECHNOLOGY LA English DT Article ID SP STRAIN PYR-1; ENCODING NAPHTHALENE DIOXYGENASE; STEROL 14-ALPHA-DEMETHYLASE; CUNNINGHAMELLA-ELEGANS; NUCLEOTIDE-SEQUENCE; ESCHERICHIA-COLI; DEGRADATION; TUBERCULOSIS; EXPRESSION; OXIDATION AB Mycobacterium vanbaalenii PYR-1 has the ability to degrade low- and high-molecular-weight polycyclic aromatic hydrocarbons (PAHs). In addition to dioxygenases, cytochrome P450 monooxygenases have been implicated in PAH degradation. Three cytochrome P450 genes, cyp151 (pipA), cyp150, and cyp51, were detected and amplified by polymerase chain reaction from M. vanbaalenii PYR-1. The complete sequence of these genes was determined. The translated putative proteins were >= 80% identical to other GenBank-listed mycobacterial CYP151, CYP150, and CYP51. Genes pipA and cyp150 were cloned, and the proteins partially expressed in Escherchia coli as soluble heme-containing cytochrome P450s that exhibited a characteristic peak at 450 nm in reduced carbon monoxide difference spectra. Monooxygenation metabolites of pyrene, dibenzothiophene, and 7-methylbenz[alpha]anthracene were detected in whole cell biotransformations, with E. coli expressing pipA or cyp150 when analyzed by gas chromatography/mass spectrometry. The cytochrome P450 inhibitor metyrapone strongly inhibited the S-oxidation of dibenzothiophene. Thirteen other Mycobacterium strains were screened for the presence of pipA, cyp150, and cyp51 genes, as well as the initial PAH dioxygenase (nidA and nidB). The results indicated that many of the Mycobacterium spp. surveyed contain both monooxygenases and dioxygenases to degrade PAHs. Our results provide further evidence for the diverse enzymatic capability of Mycobacterium spp. to metabolize polycylic aromatic hydrocarbons. C1 US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. Slovak Acad Sci, Inst Mol Biol, Bratislava 84551, Slovakia. Natl Ctr Toxicol Res, Food & Drug Adm, Div Biochem Toxicol, Jefferson, AR 72079 USA. Natl Ctr Toxicol Res, Food & Drug Adm, Div Syst Toxicol, 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 51 TC 24 Z9 24 U1 4 U2 13 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 JUL PY 2006 VL 71 IS 4 BP 522 EP 532 DI 10.1007/s00253-005-0190-8 PG 11 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 063LQ UT WOS:000239020100020 PM 16317545 ER PT J AU Hao, J Vann, WF Hinderlich, S Sundaramoorthy, M AF Hao, J Vann, WF Hinderlich, S Sundaramoorthy, M TI Elimination of 2-keto-3-deoxy-D-glycero-D-galacto-nonulosonic acid 9-phosphate synthase activity from human N-acetylneuraminic acid 9-phosphate synthase by a single mutation SO BIOCHEMICAL JOURNAL LA English DT Article DE bifunctional enzyme; 2-keto-3-deoxy-D-glycero-D-galacto-nonulosonic acid 9-phosphate (KDN-9-P) synthase; N-acetylneuraminic acid 9-phosphate (Neu5Ac-9-P) synthase; saturation mutagenesis; sialic acid; steady-state kinetics ID DEAMINATED NEURAMINIC ACID; SIALIC ACIDS; RAT-LIVER; 3-DEOXY-D-GLYCERO-D-GALACTO-NONULOSONIC ACID; SATURATION MUTAGENESIS; ENZYMATIC-SYNTHESIS; MAMMALIAN-TISSUES; D-MANNOSAMINE; IDENTIFICATION; EXPRESSION AB The most commonly occurring sialic acid Ncu5Ac (N-acetyl-neuraminic acid) and its deaminated form, KDN (2-keto-3-deoxy-D-glycero-D-galacto-nonulosonic acid), participate in many biological functions. The human Neu5Ac-9-P (Neu5Ac 9-phosphate) synthase has the unique ability to catalyse the synthesis of knot only Neu5Ac-9-P but also KDN-9-P (KDN 9-phosphate). Both reactions are catalysed by the mechanism of aldol condensation of PEP (phosphoenolpyruvate) with sugar substrates, ManNAc-6-P (N-acetylmannosamine 6-phosphate) or Man-6-P (mannose 6-phosphate). Mouse and putative rat Neu5Ac-9-P synthases, however, do not show KDN-9-P synthase activity, despite sharing high sequence identity (> 95%) with the human enzyme. Here, we demonstrate that a single mutation, M42T, in human Neu5Ac-9-P synthase can abolish the KDN-9-P synthase activity completely without compromising the Neu5Ac-9-P synthase activity. Saturation mutagenesis of Met(42) of the human Neu5Ac-9-P synthase showed that the substitution with all amino acids except leucine retains only the Neu5Ac-9-P synthase activity at levels comparable with the wild-type enzyme. The M42L mutant, like the wild-type enzyme, showed the additional KDN-9-P synthase activity. In the homology model of human Neu5Ac-9-P synthase, Met(42) is located 22 angstrom (1 angstrom = 0.1 nm) away from the substrate-binding site and the impact of this distant residue on the enzyme functions is discussed. C1 Vanderbilt Univ, Med Ctr, Div Nephrol, Dept Med,Ctr Matrix Biol, Nashville, TN 37232 USA. Vanderbilt Univ, Med Ctr, Dept Biochem, Nashville, TN 37232 USA. US FDA, Lab Bacterial Toxins, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. Charite Univ Med Berlin, Inst Biochem & Mol Biol, D-14195 Berlin, Germany. RP Sundaramoorthy, M (reprint author), Vanderbilt Univ, Med Ctr, Div Nephrol, Dept Med,Ctr Matrix Biol, Nashville, TN 37232 USA. EM m.sundaramoorthy@vanderbilt.edu FU NIDDK NIH HHS [DK62524, R01 DK062524] NR 39 TC 6 Z9 6 U1 0 U2 2 PU PORTLAND PRESS LTD PI LONDON PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD JUL 1 PY 2006 VL 397 BP 195 EP 201 DI 10.1042/BJ20052034 PN 1 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 058XZ UT WOS:000238699200022 PM 16503877 ER PT J AU Kuster, N Torres, VB Nikoloski, N Frauscher, M Kainz, W AF Kuster, Niels Torres, Veronica Berdinas Nikoloski, Neviana Frauscher, Michael Kainz, Wolfgang TI Methodology of detailed dosimetry and treatment of uncertainty and variations for in vivo studies SO BIOELECTROMAGNETICS LA English DT Article DE radiofrequency; electromagnetic fields; specific absorption rate (SAR); SAR variation; SAR uncertainty; risk assessment ID ELECTROMAGNETIC-FIELDS; DIELECTRIC-PROPERTIES; EXPOSURE AB Detailed and accurate dosimetric information is a basic precondition for acquiring adequate interpretations and valuations of in vivo studies testing radiofrequency (RF) electromagnetic fields (EMF). Instantaneous locally induced fields depend on many parameters, for example, orientation of the animal with respect to the incident field, animal size and posture, and tissue distribution. These parameters are often constrained, resulting in significant uncertainties in the dosimetric assessment of the exposure, averaged over all animals and the entire experimental phase, as well as in significant variations of the local exposures during the experiment. A sufficient analysis should therefore include (1) average and peak spatial specific absorption rate (SAR) values for the whole body and specific organs, (2) the uncertainty of each assessed SAR value, and (3) the short term and long term SAR variations between the tissues of individual animals. A methodology to obtain this pertinent information is developed and proposed in this paper. Using this methodology the dosimetry of a rat exposure apparatus operating at the carrier frequency of 1747 MHz, previously developed for a 2-year bioassay study within the European Union project PERFORM, was obtained. We have demonstrated that comprehensive dosimetric data can be obtained with reasonable effort using the proposed method, providing that the exposure setup is soundly formulated. C1 IT IS Fdn, Fdn Res Informat Technol Soc, CH-8004 Zurich, Switzerland. Swiss Fed Inst Technol, Zurich, Switzerland. Austrian Res Ctr Seibersdorf, Seibersdorf, Austria. US FDA, Washington, DC 20204 USA. RP Kuster, N (reprint author), IT IS Fdn, Fdn Res Informat Technol Soc, Zeughausstr 43, CH-8004 Zurich, Switzerland. EM kuster@itis.ethz.ch RI Foundation, IT'IS/B-9559-2008 NR 10 TC 31 Z9 34 U1 0 U2 5 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0197-8462 J9 BIOELECTROMAGNETICS JI Bioelectromagnetics PD JUL PY 2006 VL 27 IS 5 BP 378 EP 391 DI 10.1002/bem.20219 PG 14 WC Biology; Biophysics SC Life Sciences & Biomedicine - Other Topics; Biophysics GA 058VS UT WOS:000238693300006 PM 16615059 ER PT J AU Callaghan, JV Gutman, SI AF Callaghan, JV Gutman, SI TI Counterpoint - Food and Drug Administration guidance for C-reactive protein assays: Matching claims with performance data SO CLINICAL CHEMISTRY LA English DT Editorial Material ID EPIDEMIOLOGIC APPLICATIONS C1 US FDA, Off Vitro Diagnost Device Evaluat & Safety, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. RP Callaghan, JV (reprint author), US FDA, Off Vitro Diagnost Device Evaluat & Safety, Ctr Devices & Radiol Hlth, 2098 Gaither Rd,HFZ-440, Rockville, MD 20850 USA. EM james.callaghan@fda.hhs.gov NR 8 TC 2 Z9 2 U1 0 U2 1 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUL PY 2006 VL 52 IS 7 BP 1256 EP 1257 DI 10.1373/clinchem.2006.072009 PG 2 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 059IF UT WOS:000238725800007 PM 16798965 ER PT J AU Singh, A Goering, RV Simjee, S Foley, SL Zervos, MJ AF Singh, Aparajita Goering, Richard V. Simjee, Shabbir Foley, Steven L. Zervos, Marcus J. TI Application of molecular techniques to the study of hospital infection SO CLINICAL MICROBIOLOGY REVIEWS LA English DT Review ID FIELD GEL-ELECTROPHORESIS; RESISTANT STAPHYLOCOCCUS-AUREUS; FRAGMENT-LENGTH-POLYMORPHISM; POLYMERASE-CHAIN-REACTION; RESTRICTION-ENDONUCLEASE ANALYSIS; INTENSIVE-CARE-UNIT; MULTILOCUS ENZYME ELECTROPHORESIS; ARBITRARILY PRIMED PCR; SEQUENCE-BASED PCR; PROTEIN-A GENE AB Nosocomial infections are an important source of morbidity and mortality in hospital settings, afflicting an estimated 2 million patients in the United States each year. This number represents up to 5% of hospitalized patients and results in an estimated 88, 000 deaths and 4.5 billion dollars in excess health care costs. Increasingly, hospital-acquired infections with multidrug-resistant pathogens represent a major problem in patients. Understanding pathogen relatedness is essential for determining the epidemiology of nosocomial infections and aiding in the design of rational pathogen control methods. The role of pathogen typing is to determine whether epidemiologically related isolates are also genetically related. To determine the molecular relatedness of isolates for epidemiologic investigation, new technologies based on DNA or molecular analysis are methods of choice. These DNA-based molecular methodologies include pulsed-field gel electrophoresis, PCR-based typing methods, and multilocus sequence analysis. Establishing clonality of pathogens can aid in the identification of the source (environmental or personnel) of organisms, distinguish infectious from noninfectious strains, and distinguish relapse from reinfection. The integration of molecular typing with conventional hospital epidemiologic surveillance has been proven to be cost-effective due to the associated reduction in the number of nosocomial infections. Cost-effectiveness is maximized through the collaboration of the laboratory, through epidemiologic typing, and the infection control department during epidemiologic investigations. C1 Henry Ford Hosp, Dept Med, Infect Dis Sect, Detroit, MI 48202 USA. Wayne State Univ, Sch Med, Detroit, MI USA. Creighton Univ, Sch Med, Dept Med Microbiol & Immunol, Omaha, NE USA. US FDA, Div Anim & Food Microbiol, Off Res, Ctr Vet Med, Laurel, MD USA. Marshfield Clin Fdn Med Res & Educ, Marshfield, WI 54449 USA. RP Singh, A (reprint author), Henry Ford Hosp, Dept Med, Infect Dis Sect, W Grand Blvd, Detroit, MI 48202 USA. EM mzervos1@hfhs.org OI Goering, Richard/0000-0001-7502-7185 FU PHS HHS [CCR523452] NR 325 TC 119 Z9 128 U1 0 U2 14 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0893-8512 J9 CLIN MICROBIOL REV JI Clin. Microbiol. Rev. PD JUL PY 2006 VL 19 IS 3 BP 512 EP + DI 10.1128/CMR.00025-05 PG 20 WC Microbiology SC Microbiology GA 069BL UT WOS:000239419600003 PM 16847083 ER PT J AU Hartley, DM Klontz, KC Ryan, P Morris, JG AF Hartley, DM Klontz, KC Ryan, P Morris, JG TI Shigellosis and cryptosporidiosis, Baltimore, Maryland SO EMERGING INFECTIOUS DISEASES LA English DT Letter C1 Univ Maryland, Sch Med, Dept Epidemiol & Prevent Med, Baltimore, MD 21201 USA. George Washington Univ, Sch Publ Hlth & Hlth Serv, Washington, DC USA. US FDA, College Pk, MD USA. Maryland Dept Hlth & Mental Hyg, Baltimore, MD USA. RP Hartley, DM (reprint author), Univ Maryland, Sch Med, Dept Epidemiol & Prevent Med, 660 W Redwood St, Baltimore, MD 21201 USA. EM dhartley@epi.umaryland.edu OI Hartley, David/0000-0001-5202-6278 FU NIAID NIH HHS [K25 AI-58956, K25 AI058956] NR 5 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 JUL PY 2006 VL 12 IS 7 BP 1164 EP 1165 PG 2 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 058BO UT WOS:000238639400026 PM 16845778 ER PT J AU Fuscoe, JC AF Fuscoe, J. C. TI QA/QC issues to aid regulatory acceptance of microarray gene expression data. SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 37th Annual Meeting of the Environmental-Mutagen-Society CY SEP 16-20, 2006 CL Vancouver, CANADA SP Environm Mutagen Soc C1 FDA NCTR, Jefferson, AR USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 JUL PY 2006 VL 47 IS 6 BP 406 EP 406 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 072BP UT WOS:000239647900029 ER PT J AU Koturbash, I Tryndyak, V Boyko, A Rodriguez-Juarez, R Zemp, F Kovalchuk, I Pogribny, I Kovalchuk, O AF Koturbash, I Tryndyak, V Boyko, A. Rodriguez-Juarez, R. Zemp, F. Kovalchuk, I Pogribny, I Kovalchuk, O. TI Epigenetic effectors hold the key to understanding bystander effects: Roles of DNA methylation, histone modifications and MicroRNAs. SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 37th Annual Meeting of the Environmental-Mutagen-Society CY SEP 16-20, 2006 CL Vancouver, CANADA SP Environm Mutagen Soc C1 Univ Lethbridge, Lethbridge, AB T1K 3M4, Canada. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 4 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 JUL PY 2006 VL 47 IS 6 BP 406 EP 406 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 072BP UT WOS:000239647900028 ER PT J AU Goodsaid, FM Fuscoe, JC AF Goodsaid, F. M. Fuscoe, J. C. TI Investigational and regulatory review applications of genomic data at the USFDA. SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 37th Annual Meeting of the Environmental-Mutagen-Society CY SEP 16-20, 2006 CL Vancouver, CANADA SP Environm Mutagen Soc C1 US FDA, OCP, CDER, Silver Spring, MD USA. US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 JUL PY 2006 VL 47 IS 6 BP 407 EP 407 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 072BP UT WOS:000239647900030 ER PT J AU Rosario, L AF Rosario, L. TI The regulatory perspective on pharmacogenomics: Nonclinical and clinical aspects. SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 37th Annual Meeting of the Environmental-Mutagen-Society CY SEP 16-20, 2006 CL Vancouver, CANADA SP Environm Mutagen Soc C1 US FDA, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 JUL PY 2006 VL 47 IS 6 BP 409 EP 409 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 072BP UT WOS:000239647900040 ER PT J AU Janat, F Xu, J Nettleton, D AF Janat, F. Xu, J. Nettleton, D. TI Structural damage in mitochondrial DNA is a sensitive response to oxidative stress in prostate cancer cells. SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 37th Annual Meeting of the Environmental-Mutagen-Society CY SEP 16-20, 2006 CL Vancouver, CANADA SP Environm Mutagen Soc C1 McGill Univ, Ctr Hlth, Montreal, PQ, Canada. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 JUL PY 2006 VL 47 IS 6 BP 431 EP 431 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 072BP UT WOS:000239647900126 ER PT J AU Valentine, CR Dobrovolsky, VN Shaddock, JG Rainey, HF Farrell, JM AF Valentine, C. R. Dobrovolsky, V. N. Shaddock, J. G. Rainey, H. F. Farrell, J. M. TI A direct comparison of the PhiX174 transgenic mutation assay to the lacl assay. SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 37th Annual Meeting of the Environmental-Mutagen-Society CY SEP 16-20, 2006 CL Vancouver, CANADA SP Environm Mutagen Soc ID MICE; GENE C1 US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 2 TC 0 Z9 0 U1 1 U2 2 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 JUL PY 2006 VL 47 IS 6 BP 447 EP 447 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 072BP UT WOS:000239647900184 ER PT J AU Elespuru, RK Spring, S AF Elespuru, R. K. Spring, Silver TI Integrating new technologies into the assessment of heritable genetic effects. SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 37th Annual Meeting of the Environmental-Mutagen-Society CY SEP 16-20, 2006 CL Vancouver, CANADA SP Environm Mutagen Soc C1 US FDA, CDRH, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 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 JUL PY 2006 VL 47 IS 6 BP 452 EP 452 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 072BP UT WOS:000239647900205 ER PT J AU Baker, M Koturbash, I Loree, J Kutanzi, K Pogribny, I Kovalchuk, O AF Baker, M. Koturbash, I Loree, J. Kutanzi, K. Pogribny, I Kovalchuk, O. TI Epigenetic dysregulation underlies the radiation-induced transgeneration genome: Instability In Vivo. SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 37th Annual Meeting of the Environmental-Mutagen-Society CY SEP 16-20, 2006 CL Vancouver, CANADA SP Environm Mutagen Soc C1 Univ Lethbridge, Lethbridge, AB T1K 3M4, Canada. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 JUL PY 2006 VL 47 IS 6 BP 454 EP 454 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 072BP UT WOS:000239647900208 ER PT J AU Parsons, BL Marchant, KE Verkler, TL McKinzie, PB Delongchamp, RR Patterson, TA Broadwater, JR Lamps, LW Kim, LT AF Parsons, B. L. Marchant, K. E. Verkler, T. L. McKinzie, P. B. Delongchamp, R. R. Patterson, T. A. Broadwater, J. R. Lamps, L. W. Kim, L. T. TI Insights into the role of K-RAS mutation in sporadic colon cancer development based upon systematic ACB-PCR measurement of K-RAS mutant fraction. SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 37th Annual Meeting of the Environmental-Mutagen-Society CY SEP 16-20, 2006 CL Vancouver, CANADA SP Environm Mutagen Soc C1 US FDA, Natl Ctr Toxicol Res, Jefferson, AR USA. Cent Arkansas Vet Healthcare Syst, Little Rock, AR USA. Univ Arkansas Med Sci, Little Rock, AR 72205 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 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 JUL PY 2006 VL 47 IS 6 BP 462 EP 462 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 072BP UT WOS:000239647900242 ER PT J AU Morris, SM Akerrnan, GS Melchior, WB Tolleson, WH Churchwell, MI Lin, CY Doerge, DR Beland, FA Chen, JJ AF Morris, S. M. Akerrnan, G. S. Melchior Jr, W. B. Tolleson, W. H. Churchwell, M., I Lin, C. Y. Doerge, D. R. Beland, F. A. Chen, J. J. TI Effect of p53 genotype on MGMT expression and O-6-ethyldeoxyguanosine levels in the livers of ENU-exposed TSGp53 (R) mice. SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 37th Annual Meeting of the Environmental-Mutagen-Society CY SEP 16-20, 2006 CL Vancouver, CANADA SP Environm Mutagen Soc C1 NCTR, Div Genet & Reprod Toxicol, Jefferson, AR USA. NCTR, Div Biochem Toxicol, Jefferson, AR USA. NCTR, Div Biometry & Risk Assessment, Jefferson, AR USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 JUL PY 2006 VL 47 IS 6 BP 466 EP 466 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 072BP UT WOS:000239647900256 ER PT J AU Yamaguchi, Y Takahashi, K Zmudzka, BZ Kornhauser, A Miller, SA Tadokoro, T Berens, W Beer, JZ Hearing, VJ AF Yamaguchi, Yuji Takahashi, Kaoruko Zmudzka, Barbara Z. Kornhauser, Andrija Miller, Sharon A. Tadokoro, Taketsugu Berens, Werner Beer, Janusz Z. Hearing, Vincent J. TI Human skin responses to UV radiation: pigment in the upper epidermis protects against DNA damage in the lower epidermis and facilitates apoptosis SO FASEB JOURNAL LA English DT Article DE pigmentation; melanocyte; melanosome; photoprotection ID REGULATES P53-DEPENDENT APOPTOSIS; SUNBURN CELL-FORMATION; ULTRAVIOLET-RADIATION; IN-VITRO; P53; MELANIN; CANCER; PHOTOPRODUCTS; EXPRESSION; MUTATIONS AB Melanin plays an important role in protecting the skin against UV radiation, and melanomas and basal/squamous cell carcinomas occur more frequently in individuals with fair/light skin. We previously reported that levels of melanin correlate inversely with amounts of DNA damage induced by UV in normal human skin of different racial/ethnic groups. We have now separately examined DNA damage in the upper and lower epidermal layers in various types of skin before and after exposure to UV and have measured subsequent apoptosis and phosphorylation of p53. The results show that two major mechanisms underlie the increased photocarcinogenesis in fair/light skin. First, UV-induced DNA damage in the lower epidermis (including keratinocyte stem cells and melanocytes) is more effectively prevented in darker skin, suggesting that the pigmented epidermis is an efficient UV filter. Second, UV-induced apoptosis is significantly greater in darker skin, which suggests that UV-damaged cells may be removed more efficiently in pigmented epidermis. The combination of decreased DNA damage and more efficient removal of UV-damaged cells may play a critical role in the decreased photocarcinogenesis seen in individuals with darker skin. C1 NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. RP Hearing, VJ (reprint author), NCI, Cell Biol Lab, NIH, Bldg 37,Rm 2132, Bethesda, MD 20892 USA. EM hearingv@nih.gov RI Yamaguchi, Yuji/B-9312-2008 FU Intramural NIH HHS NR 42 TC 95 Z9 97 U1 3 U2 11 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL PY 2006 VL 20 IS 9 BP 1486 EP + DI 10.1096/fj.06-5725fje PG 10 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 080RP UT WOS:000240266000026 PM 16793869 ER PT J AU Limm, W Begley, TH Lickly, T Hentges, SG AF Limm, W Begley, TH Lickly, T Hentges, SG TI Diffusion of limonene in polyethylene SO FOOD ADDITIVES AND CONTAMINANTS LA English DT Article DE migration; diffusion; food-contact materials; packaging ID FOOD SIMULANTS; MIGRATION; PERMEABILITY; TRANSPORT; POLYMERS; PACKAGE; VAPOR; FILMS; MODEL AB Diffusion coefficients of limonene in various linear low-density polyethylene (LLDPE) and low-density polyethylene (LDPE) resins have been determined from sorption data using a thermogravimetric methodology. From these data, one can determine whether polymer synthesis parameters such as the choice of catalytic process or co-monomer result in substantial differences in how much food packaging additives might migrate to food. For example, LLDPE is currently manufactured using either one of two distinct catalytic processes: Ziegler-Natta (ZN) and metallocene, a single-site catalyst. ZN catalysis is a heterogeneous process that has dominated polyolefin synthesis over the last half-century. It involves a transition metal compound containing a metal-carbon bond that can handle repeated insertion of olefin units. In contrast, metallocene catalysis has fewer than 20 years of history, but has generated much interest due to its ability to produce highly stereospecific polymers at a very high yield. In addition to high stereospecificity, metallocene-catalysed polymers are significantly lower in polydispersity than traditional ZN counterparts. Absorption and desorption testing of heat-pressed films made from LLDPE and LDPE resins of varying processing parameters indicates that diffusion coefficients of limonene in these resins do not change substantially. C1 US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. Dow Chem Co USA, Midland, MI 48674 USA. Amer Plast Council, Arlington, VA 22209 USA. RP Limm, W (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy HFS-245, College Pk, MD 20740 USA. EM william.limm@fda.hhs.gov NR 31 TC 7 Z9 7 U1 4 U2 13 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 JUL PY 2006 VL 23 IS 7 BP 738 EP 746 DI 10.1080/02652030600654408 PG 9 WC Chemistry, Applied; Food Science & Technology; Toxicology SC Chemistry; Food Science & Technology; Toxicology GA 051ZU UT WOS:000238201000012 PM 16751151 ER PT J AU Shirota, H Ishii, KJ Takakuwa, H Klinman, DM AF Shirota, H Ishii, KJ Takakuwa, H Klinman, DM TI Contribution of interferon-beta to the immune activation induced by double-stranded DNA SO IMMUNOLOGY LA English DT Article DE type 1 IFNs; Toll-like receptor; DNA; host protection ID DENDRITIC CELL ACTIVATION; TLR9-INDEPENDENT PATHWAYS; MURINE MACROPHAGES; MAMMALIAN DNA; BACTERIAL-DNA; PLASMID DNA; MATURATION; GAMMA; OLIGODEOXYNUCLEOTIDES; CONSEQUENCES AB Introducing double-stranded DNA (dsDNA) into the cytoplasm of macrophages and dendritic cells triggers the activation of these professional antigen-presenting cells (APCs). This process is characterized by the up-regulation of costimulatory molecules and the production of various cytokines, chemokines, and antibacterial/viral factors. Current findings indicate that interferon-beta (IFN-beta) plays a key role in the stimulatory cascade triggered by dsDNA. Both immune and non-immune cells respond to intracytoplasmic dsDNA by up-regulating IFN-beta) expression, a process that reduces host susceptibility to infection. The immune activation induced by dsDNA is independent of MyD88, TRIF and DNA-PKcs, indicating that a Toll-like receptor-independent mechanism underlies the cellular activation mediated by intracytoplasmic dsDNA. C1 US FDA, Ctr Biol Evaluat & Res, Sect Retroviral Immunol, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Lab DNA Viruses, Bethesda, MD 20892 USA. Osaka Univ, Japan Sci & Technol Agcy, ERATO, Res Inst Microbial Dis,Dept Host Def, Osaka, Japan. RP Klinman, DM (reprint author), US FDA, Ctr Biol Evaluat & Res, Sect Retroviral Immunol, Bldg 29A,Rm 3D 10, Bethesda, MD 20892 USA. EM shirota@cber.fda.gov; klinman@cber.fda.gov RI Ishii, Ken/B-1685-2012 OI Ishii, Ken/0000-0002-6728-3872 NR 35 TC 20 Z9 23 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0019-2805 J9 IMMUNOLOGY JI Immunology PD JUL PY 2006 VL 118 IS 3 BP 302 EP 310 DI 10.1111/j.1365-2567.2006.02367.x PG 9 WC Immunology SC Immunology GA 054RR UT WOS:000238396800003 PM 16827891 ER PT J AU Di Pietro, R Fang, H Fields, K Miller, S Flora, M Petricoin, EC Dveksler, G Rana, RA Grimley, PM AF Di Pietro, R. Fang, H. Fields, K. Miller, S. Flora, M. Petricoin, E. C. Dveksler, G. Rana, R. A. Grimley, P. M. TI Peroxiredoxin genes are not induced in myeloid leukemia cells exposed to ionizing radiation SO INTERNATIONAL JOURNAL OF IMMUNOPATHOLOGY AND PHARMACOLOGY LA English DT Article DE oxidative stress; peroxiredoxins; ionizing radiation; myeloid leukemia ID HYDROGEN-PEROXIDE; OXIDATIVE STRESS; C-ABL; MAMMALIAN PEROXIREDOXIN; ANTIOXIDANT PROPERTIES; UP-REGULATION; K562 CELLS; THIOREDOXIN; EXPRESSION; PROTEIN AB Peroxiredoxins (Prx) comprise an extended family of small antioxidant proteins which conserve a thioredoxin-dependent catalytic function that can contribute to cell protection from reactive oxygen species (ROS). ROS generation is one of the deleterious intracellular effects of ionizing radiation, but the role of Prx during radiation treatment has not been extensively explored. Present experiments measure effects of ionizing radiation on expression of human Prx types I (PAGA), II (NKEF-B) and IV (AOE372) in human myeloid leukemia cells (K562). Prx gene transcription was analyzed by amplifying with RT-PCR cDNAs complementary to each Prx-specific coding sequence and by identifying the derived products with Southern blotting procedure. Transcripts of GAPDH were used as the endogenous standard for semi-quantitative comparisons. No consistent increase in Prx gene expression was detected at time intervals up to 72 h after gamma radiation doses that caused cell cycle arrest and nuclear damage (maximum 20 Gy). Immunoblots also were consistent with a prolonged expression or stability of the Prx I/II proteins. Similarly, a cytotoxic concentration of the oxidant hemin, which stimulates rapid hemoglobinization of K562 cells, caused no induction of Prx gene expression. Our results indicate a high Prx stability in human radio-resistant leukemia cells. C1 Univ G DAnnunzio, Dept Biomorphol, I-66013 Chieti, Scalo, Italy. US FDA, Ctr Biol & Drug Evaluat, Bethesda, MD 20014 USA. Uniformed Serv Univ Hlth Sci, Dept Pathol, Bethesda, MD 20814 USA. Uniformed Serv Univ Hlth Sci, Bioinstrumentat Ctr, Bethesda, MD 20814 USA. RP Di Pietro, R (reprint author), Univ G DAnnunzio, Dept Biomorphol, Via Vestini 6, I-66013 Chieti, Scalo, Italy. EM r.dipietro@unich.it OI Di Pietro, Roberta/0000-0002-0709-6901 NR 34 TC 15 Z9 15 U1 0 U2 1 PU BIOLIFE SAS PI SILVA MARINA (TE) PA VIA S STEFANO 39 BIS, 64029 SILVA MARINA (TE), ITALY SN 0394-6320 J9 INT J IMMUNOPATH PH JI Int. J. Immunopathol. Pharmacol. PD JUL-SEP PY 2006 VL 19 IS 3 BP 517 EP 524 PG 8 WC Immunology; Pathology; Pharmacology & Pharmacy SC Immunology; Pathology; Pharmacology & Pharmacy GA 093OC UT WOS:000241176600007 PM 17026836 ER PT J AU Gatson, JW Benz, BF Chandrasekaran, C Satomi, M Venkateswaran, K Hart, ME AF Gatson, Joshua W. Benz, Bruce F. Chandrasekaran, Chitra Satomi, Masataka Venkateswaran, Kasthuri Hart, Mark E. TI Bacillus tequilensis sp nov., isolated from a 2000-year-old Mexican shaft-tomb, is closely related to Bacillus subtilis SO INTERNATIONAL JOURNAL OF SYSTEMATIC AND EVOLUTIONARY MICROBIOLOGY LA English DT Article ID DEPENDENT SUPEROXIDE-DISMUTASE; 16S RIBOSOMAL-RNA; EMENDED DESCRIPTIONS; GENUS PAENIBACILLUS; SOUTHERN SPAIN; SPECIES-LEVEL; IDENTIFICATION; STRAINS; CEREUS; ANTHRACIS AB A Gram-positive, spore-forming bacillus was isolated from a sample taken from an approximately 2000-year-old shaft-tomb located in the Mexican state of Jalisco, near the city of Tequila. Tentative identification using conventional biochemical analysis consistently identified the isolate as Bacillus subtilis. DNA isolated from the tomb isolate, strain 10b(T), and closely related species was used to amplify a Bacillus-specific portion of the highly conserved 16S rRNA gene and an internal region of the superoxide dismutase gene (sodA(int)). Trees derived from maximum-likelihood methods applied to the sodAint sequences yielded non-zero branch lengths between strain 10b(T) and its closest relative, whereas a comparison of a Bacillus-specific 546 bp amplicon of the 16S rRNA gene demonstrated 99% similarity with B. subtilis. Although the 16S rRNA gene sequences of strain 19b T and B. subtilis were 99 % similar, PFGE of Notl-digested DNA of strain 10b(T) revealed a restriction profile that was considerably different from those of B. subtilis and other closely related species. Whereas qualitative differences in whole-cell fatty acids were not observed, significant quantitative differences were found to exist between strain 1 Ob T and each of the other closely related Bacillus species examined. In addition, DNA-DNA hybridization studies demonstrated that strain 10b(T) had a relatedness value of less than 70% with B. subtilis and other closely related species. Evidence from the sodA(int) sequences, whole-cell fatty acid profiles and PFGE analysis, together with results from DNA-DNA hybridization studies, justify the classification of strain 1 Ob T as representing a distinct species, for which the name Bacillus tequilensis sp. nov. is proposed. The type strain is 10b(T) (=ATCC BAA-819(T) = NCTC 13306(T)). C1 Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. CALTECH, Jet Prop Lab, Biotechnol & Planetary Protect Grp, Pasadena, CA 91109 USA. Natl Res Inst Fisheries, Div Food Proc, Yokohama, Kanagawa 2368648, Japan. Texas Wesleyan Univ, Dept Biol, Ft Worth, TX 76105 USA. Univ N Texas, Hlth Sci Ctr, Dept Mol Biol & Immunol, Ft Worth, TX 76107 USA. RP Hart, ME (reprint author), Natl Ctr Toxicol Res, Div Microbiol, HFT-250,3900 NCTR Rd, Jefferson, AR 72079 USA. EM mark.hart@fda.hhs.gov RI Hart, Mark/B-8976-2013 NR 37 TC 27 Z9 39 U1 0 U2 15 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 1466-5026 J9 INT J SYST EVOL MICR JI Int. J. Syst. Evol. Microbiol. PD JUL PY 2006 VL 56 BP 1475 EP 1484 DI 10.1099/ijs.0.63946-0 PN 7 PG 10 WC Microbiology SC Microbiology GA 068IF UT WOS:000239366200002 PM 16825615 ER PT J AU Choudhuri, S Klaassen, CD AF Choudhuri, Supratim Klaassen, Curtis D. TI Structure, function, expression, genomic organization, and single nucleotide polymorphisms of human ABCB1 (MDR1), ABCC (MRP), and ABCG2 (BCRP) efflux transporters SO INTERNATIONAL JOURNAL OF TOXICOLOGY LA English DT Review DE P-glycoprotein; MDR; MRP; BCRP; expression; localization; SNP; function ID ORGANIC ANION-TRANSPORTER; MULTIDRUG-RESISTANCE PROTEIN; DUBIN-JOHNSON-SYNDROME; CONJUGATE EXPORT PUMP; ATP-DEPENDENT TRANSPORT; HUMAN P-GLYCOPROTEIN; CONSTITUTIVE ANDROSTANE RECEPTOR; HEPATOCYTE CANALICULAR ISOFORM; HEALTHY JAPANESE SUBJECTS; KIDNEY PROXIMAL TUBULES AB The ATP-binding cassette (ABC) transporters constitute a large family of membrane proteins, which transport a variety of compounds through the membrane against a concentration gradient at the cost of ATP hydrolysis. Substrates of the ABC transporters include lipids, bile acids, xenobiotics, and peptides for antigen presentation. As they transport exogenous and endogenous compounds, they reduce the body load of potentially harmful substances. One by-product of such protective function is that they also eliminate various useful drugs from the body, causing drug resistance. This review is a brief summary of the structure, function, and expression of the important drug resistance-conferring members belonging to three subfamilies of the human ABC family; these areABCB1(MDR1/P-glycoprotein of subfamily ABCB), subfamily ABCC (MRPs), and ABCG2 (BCRP of subfamily ABCG), which are expressed in various organs. In the text, the transporter symbol that carries the subfamily name (such as ABCB1, ABCC1, etc.) is used interchangeably with the corresponding original names, such as MDR1/P-glycoprotein, MRP1, etc., respectively. Both nomenclatures are maintained in the text because both are still used in the transporter literature. This helps readers relate various names that they encounter in the literature. It now appears that P-glycoprotein, MRP1, MRP2, and BCRP can explain the phenomenon of multidrug resistance in all cell lines analyzed thus far. Also discussed are the gene structure, regulation of expression, and various polymorphisms in these genes. Because genetic polymorphism is thought to underlie interindividual differences, including their response to drugs and other xenobiotics, the importance of polymorphism in these genes is also discussed. C1 USDA, CFSAN, OFAS, DBGNR, College Pk, MD 20740 USA. Univ Kansas, Med Ctr, Dept Pharmacol Toxicol & Therapeut, Kansas City, KS 66103 USA. RP Choudhuri, S (reprint author), USDA, CFSAN, OFAS, DBGNR, 5100 Paint Branch Pkwy,HFS-255, College Pk, MD 20740 USA. EM Supratim.Choudhuri@fda.hhs.gov FU NIEHS NIH HHS [ES009649, ES013714, ES009716] NR 200 TC 201 Z9 216 U1 1 U2 51 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1091-5818 J9 INT J TOXICOL JI Int. J. Toxicol. PD JUL-AUG PY 2006 VL 25 IS 4 BP 231 EP 259 DI 10.1080/10915810600746023 PG 29 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 060FH UT WOS:000238787300001 PM 16815813 ER PT J AU Brzezinski, JL AF Brzezinski, Jennifer L. TI Detection of cashew nut DNA in spiked baked goods using a real-time polymerase chain reaction method SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID ANACARDIUM-OCCIDENTALE L.; FOOD ALLERGENS; BRAZIL-NUT; 2S ALBUMIN; BERTHOLLETIA-EXCELSA; MAJOR ALLERGEN; PEANUT; IDENTIFICATION; EXPRESSION; PROTEINS AB The detection of potentially allergenic foods, such as tree nuts, in food products is a major concern for the food processing industry. A real-time polymerase chain reaction (PCR) method was designed to determine the presence of cashew DNA in food products. The PCR amplifies a 67 bp fragment of the cashew 2S albumin gene, which is detected with a cashew-specific, dual-labeled TaqMan probe. This reaction will not amplify DNA derived from other tree nut species, such as almond, Brazil nut, hazelnut, and walnut, as well as 4 varieties of peanut. This assay was sensitive enough to detect 5 pg purified cashew DNA as well as cashew DNA in a spiked chocolate cookie sample containing 0.01% (100 mg/kg) cashew. C1 US FDA, Forens Chem Ctr, Cincinnati, OH 45237 USA. RP Brzezinski, JL (reprint author), US FDA, Forens Chem Ctr, 6751 Steger Dr, Cincinnati, OH 45237 USA. EM jennifer.brzezinski@fda.gov NR 25 TC 14 Z9 14 U1 4 U2 14 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 2006 VL 89 IS 4 BP 1035 EP 1038 PG 4 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 069TH UT WOS:000239470600018 PM 16915841 ER PT J AU Horwitz, W Albert, R AF Horwitz, William Albert, Richard TI The Horwitz ratio (HorRat): A useful index of method performance with respect to precision SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID IMMUNOAFFINITY COLUMN CLEANUP; QUALITY ASSURANCE; PROFICIENCY TEST; LABORATORIES AB The Horwitz ratio (HorRat) is a normalized performance parameter indicating the acceptability of methods of analysis with respect to among-laboratory precision (reproducibility). It is the ratio of the observed relative standard deviation among laboratories calculated from the actual performance data, RSDR (%), to the corresponding predicted relative standard deviation calculated from the Horwitz equation PRSDR (%) = 2C(-0.15), where C is the concentration found or added, expressed as a mass fraction. It is more or less independent,of analyte, matrix, method, and time of publication (as a surrogate for the state of the art of analytical chemistry). It is now one of the acceptability criteria for many of the recently adopted chemical methods of analysis of AOAC INTERNATIONAL, the European Union, and other European organizations dealing with food analysis (e.g., European Committee for Standardization and Nordic Analytical Committee). The origin and applications of the formula are described. Consistent deviations from the ratio on the low side (values < 0.5) may indicate unreported averaging or excellent training and experience; consistent deviations on the high side (values > 2) may indicate inhomogeneity of the test samples, need for further method optimization or training, operating below the limit of determination, or an unsatisfactory method. C1 US FDA, Rockville, MD 20857 USA. RP Horwitz, W (reprint author), 14800 Pennfield Circle 409, Silver Spring, MD 20906 USA. EM wxhor@aol.com NR 41 TC 187 Z9 193 U1 7 U2 57 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 2006 VL 89 IS 4 BP 1095 EP 1109 PG 15 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 069TH UT WOS:000239470600028 PM 16915851 ER PT J AU Delmonte, P Rader, JI AF Delmonte, Pierluigi Rader, Jeanne I. TI Analysis of isoflavones in foods and dietary supplements SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID PERFORMANCE LIQUID-CHROMATOGRAPHY; MASS-SPECTROMETRIC DETECTION; ELECTROCHEMICAL DETECTION; RED-CLOVER; CAPILLARY-ELECTROPHORESIS; HUMAN URINE; SOY; EXTRACTION; PRODUCTS; QUANTIFICATION AB lsoflavones are phytochernicals found in many plants. Because of their structural similarity to beta-estradiol, health benefits of isoflavones have been evaluated in age-related and hormonedependent diseases. Daidzein, genistein, and glycitein are present as free forms or derivatives in foods containing soy or soy protein extracts. The analysis of isoflavones has become more complex, because preparation's contain isoflavones from multiple sources (e.g., red clover, kudzu). Red clover contains primarily formononetin and biochanin A, while kudzu extracts, which are becoming increasingly common in dietary supplements, contain puerarin and daidzein, among other components. lsoflavones are present in foods and dietary supplements as free compounds, glucoside derivatives, 6"-O-malonyl-7-0-beta-D-glucoside derivatives, and 6"-O-acetyl-7-O-beta-D-glucoside derivatives. High-performance liquid chromatography (HPLC)/tandem mass spectrometry has been applied to the identification of isoflavone derivatives based on the fragmentation pattern of the parent ion, providing high selectivity and sensitivity in the quantitation of isoflavones in complex mixtures. HPLC with ultraviolet detection is often chosen for routine analysis, but a preliminary acid or basic hydrolysis of isoflavone derivatives is often required for the investigation of samples containing extracts from multiple sources. Several internal standards have been used in the analysis of isoflavones from a single botanical source (e.g., soy, red clover), but the identification of a general internal standard remains a challenging process. C1 US FDA, Ctr Food Safety & Appl Nutr, Off Nutr Prod Labeling & Dietary Supplements, College Pk, MD 20740 USA. RP Delmonte, P (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Nutr Prod Labeling & Dietary Supplements, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM pierluigi.delmonte@fda.hhs.gov NR 47 TC 50 Z9 54 U1 2 U2 14 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 2006 VL 89 IS 4 BP 1138 EP 1146 PG 9 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 069TH UT WOS:000239470600034 PM 16915857 ER PT J AU Williams, LD Twaddle, NC Churchwell, MI Doerge, DR AF Williams, Lee D. Twaddle, Nathan C. Churchwell, Mona I. Doerge, Daniel R. TI Quantification of tamoxifen and metabolites and soy isoflavones in human plasma using liquid chromatography with electrospray ionization tandem mass spectrometry SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID BREAST-CANCER RISK; DIETARY GENISTEIN; ADJUVANT BREAST; PREVENTION; ANTIESTROGENS; SERUM AB Tamoxifen is an important estrogen receptor antagonist used successfully for the treatment and prevention of breast cancer. The use of complementary and alternative medicines is an increasingly popular means for patients to participate in their own health care, and soy products, which contain phytoestrogens, have been widely promoted for possible beneficial effects on menopausal symptoms. The possibility that Soy isoflavones could reduce tamoxifen efficacy has been demonstrated in animal models of post-menopausal breast cancer, but the occurrence of such an effect in women has not been explored. This paper describes the development and validation of a sensitive method using solid-phase extraction and isotope dilution liquid chromatography/tandem mass spectrometry with multiple reaction monitoring for the concurrent analysis of the major soy isoflavones (genistein and daidzein), an important metabolite of daidzein (equol), tamoxifen, and its important metabolites (4-hydroxytamoxifen, N-desmethyltamoxifen, and 4-hydroxy-N-desmethyltamoxifen or "endoxifen") in the serum of rats and women. The limits of quantification achieved are sufficient to determine accurately and precisely the concentrations of all of these analytes in women consuming soy foods and/or therapeutic doses of tamoxifen at levels consistent with modulation of estrogen receptor-mediated functions. These procedures enable future investigations of the possible impact of diet on the outcome of breast cancer therapy. C1 US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Doerge, DR (reprint author), US FDA, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM daniel.doerge@fda.hhs.gov FU NIA NIH HHS [P01-AG024387] NR 18 TC 13 Z9 13 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 2006 VL 89 IS 4 BP 1168 EP 1173 PG 6 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 069TH UT WOS:000239470600037 PM 16915860 ER PT J AU Agrawal, A Huang, S Lin, AWH Lee, MH Barton, JK Drezek, RA Pfefer, TJ AF Agrawal, Anant Huang, Stanley Lin, Alex Wei Haw Lee, Min-Ho Barton, Jennifer K. Drezek, Rebekah A. Pfefer, T. Joshua TI Quantitative evaluation of optical coherence tomography signal enhancement with gold nanoshells SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE image enhancement; imaging coherence; optical properties ID MOLECULAR CONTRAST; SOLID TUMOR; PARTICLE-SIZE; GROWTH-FACTOR; AGENTS; CELLS; EXTRAVASATION; SCATTERING; RECEPTORS; LIPOSOMES AB Nanoshell-enhanced optical coherence tomography (OCT) is a novel technique with the potential for molecular imaging and improved disease detection. However, optimization of this approach will require a quantitative understanding of the influence of nanoshell parameters on detected OCT signals. In this study, OCT was performed at 1310 nm in water and turbid tissue-simulating phantoms to which nanoshells were added. The effect of nanoshell concentration, core diameter, and shell thickness on signal enhancement was characterized. Experimental results indicated trends that were consistent with predicted optical properties-a monotonic increase in signal intensity and attenuation with increasing shell and core size. Threshold concentrations for a 2-dB OCT signal intensity gain were determined for several nanoshell geometries. For the most highly backscattering nanoshells tested-291-nm core diameter, 25-nm shell thickness-a concentration of 10(9) nanoshells/ mL was needed to produce this signal increase. Based on these results, we discuss various practical considerations for optimizing nanoshell-enhanced OCT. Quantitative experimental data presented here will facilitate optimization of OCT-based diagnostics and may also be relevant to other reflectance-based approaches as well. (c) 2006 Society of Photo-Optical Instrumentation Engineers. C1 US FDA, Opt Diagnost Lab, Ctr Devices & Radiol Hlth, Rockville, MD 20852 USA. Johns Hopkins Univ, Dept Biomed Engn, Baltimore, MD 21218 USA. Rice Univ, Dept Bioengn, Houston, TX 77251 USA. Univ Arizona, Div Biomed Engn, Tucson, AZ 85721 USA. RP Agrawal, A (reprint author), US FDA, Opt Diagnost Lab, Ctr Devices & Radiol Hlth, 12725 Twinbrook Pkwy,HFZ-130, Rockville, MD 20852 USA. EM anant.agrawal@fda.hhs.gov RI Drezek, Rebekah/A-5101-2012; Pfefer, Josh/I-9055-2012; Huang, Stanley/F-9210-2014 OI Huang, Stanley/0000-0002-8436-1991 FU NCI NIH HHS [R01 CA109385] NR 35 TC 66 Z9 67 U1 2 U2 13 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 2006 VL 11 IS 4 AR 041121 DI 10.1117/1.2339071 PG 8 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 093IM UT WOS:000241162000026 PM 16965149 ER PT J AU Horne, AD AF Horne, A. D. TI Guest editorial - Preventive vaccines SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Editorial Material C1 US FDA, Div Biostat, Off Biostat & Epidemiol, CBER, Rockville, MD 20852 USA. RP Horne, AD (reprint author), US FDA, Div Biostat, Off Biostat & Epidemiol, CBER, 1401 Rockville Pike,HFM-217, Rockville, MD 20852 USA. EM amelia.horne@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1054-3406 J9 J BIOPHARM STAT JI J. Biopharm. Stat. PD JUL-AUG PY 2006 VL 16 IS 4 BP 399 EP 402 DI 10.1080/10543400600719178 PG 4 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 067BR UT WOS:000239276100001 ER PT J AU Harbottle, H White, DG McDermott, PF Walker, RD Zhao, S AF Harbottle, H. White, D. G. McDermott, P. F. Walker, R. D. Zhao, S. TI Comparison of multilocus sequence typing, pulsed-field gel electrophoresis, and antimicrobial susceptibility typing for characterization of Salmonella enterica serotype Newport isolates SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID SEROVAR TYPHIMURIUM; UNITED-STATES; STAPHYLOCOCCUS-AUREUS; BETA-LACTAMASE; DISCRIMINATORY ABILITY; DAIRY FARMS; RESISTANT; DIVERSITY; OUTBREAK; STRAINS AB In the United States, multidrug-resistant phenotypes of Salmonella enterica serotype Newport (commonly referred to as MDR-AmpC) have emerged in animals and humans and have become a major public health problem. Although pulsed-field gel electrophoresis (PFGE) is the current "gold standard" typing method for Salmonella, multilocus sequence typing (MLST) may be more relevant to investigations exploring evolutionary and population biology relationships. In this study. 81 Salmonella enterica serotype Newport isolates from humans, food animals, and retail foods were examined for antimicrobial susceptibility, and characterized using PFGE and MLST of seven genes, aroC, dnaN, hemD, hisD, purE, sucA, and thrA. Forty-nine percent of the isolates were resistant to nine or more of the tested antimicrobials. Salmonella isolates displayed resistance most often to sulfamethoxazole (57%), streptomycin (56%), tetracycline (56%), ampicillin (52%). and ceftiofur (49%) and, to a lesser extent, to kanamycin (19%), trimethoprim-sulfamethoxazole (17%), and gentamicin (11%). A total of 43 PFGE patterns were generated using Xbal, indicating a genetically diverse population. The largest PFGE cluster contained isolates from clinically ill swine, cattle, and humans. MLST resulted in 12 sequence types (STs), with one type encompassing 62% of the strains. Ten new sequence types and one novel allele type were identified. Furthermore, MLST typing showed that strains closely related by PFGE clustered in major STs, whereas more distantly related strains were separated into two clusters by PFGE. The results of this study demonstrated that the MLST scheme employed here clustered S. enterica serovar Newport isolates in distinct molecular populations. and strain discrimination was enhanced by combining PFGE, antimicrobial susceptibility, and MLST results. C1 US FDA, Div Anim & Food Microbiol, Res Off, Ctr Vet Med, Laurel, MD 20708 USA. RP Harbottle, H (reprint author), 8401 Muirkirk Rd, Laurel, MD 20708 USA. EM heather.harbottle@fda.hhs.gov NR 59 TC 92 Z9 99 U1 1 U2 10 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD JUL PY 2006 VL 44 IS 7 BP 2449 EP 2457 DI 10.1128/JCM.00019-06 PG 9 WC Microbiology SC Microbiology GA 065JY UT WOS:000239157400021 PM 16825363 ER PT J AU Akatsuka, T Ishikawa, T Kobayashi, N Duan, H Feinstone, SM Hammock, BD AF Akatsuka, T. Ishikawa, T. Kobayashi, N. Duan, H. Feinstone, S. M. Hammock, B. D. TI Autoantibody response to a drug-metabolizing enzyme, microsomal epoxide hydrolase in hepatitis C and A SO JOURNAL OF CLINICAL VIROLOGY LA English DT Meeting Abstract CT 12th International Symposium on Viral Hepatitis and Liver Disease CY JUL 01-05, 2006 CL Paris, FRANCE SP Pan-Amer Soc Clin Virol, European Soc Clin Virol C1 Saitama Med Sch, Dept Microbiol, Saitama, Japan. Univ Tokyo, Dept Internal Med, Tokyo, Japan. US FDA, Div Viral Prod, Bethesda, MD 20014 USA. Univ Calif Davis, Dept Entomol, Davis, CA 95616 USA. Univ Calif Davis, Canc Res Ctr, Davis, CA 95616 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1386-6532 J9 J CLIN VIROL JI J. Clin. Virol. PD JUL PY 2006 VL 36 SU 2 BP S126 EP S126 DI 10.1016/S1386-6532(06)80389-6 PG 1 WC Virology SC Virology GA 064CR UT WOS:000239067300380 ER PT J AU Perfield, JW Delmonte, P Lock, AL Yurawecz, MP Bauman, DE AF Perfield, JW Delmonte, P Lock, AL Yurawecz, MP Bauman, DE TI Trans-10, trans-12 conjugated linoleic acid does not affect milk fat yield but reduces Delta(9)-desaturase index in dairy cows SO JOURNAL OF DAIRY SCIENCE LA English DT Article DE conjugated linoleic acid; milk fat; lactation; desaturase ID STEAROYL-COA DESATURASE; DIETARY SUPPLEMENTATION; ABOMASAL INFUSION; FISH-OIL; CLA; EXPRESSION; SECRETION; INHIBITION; LACTATION; ISOMERS AB Trans-10, cis-12 conjugated linoleic acid (CLA) is a potent inhibitor of milk fat synthesis, and the magnitude of milk fat depression is often correlated with the fat content of this isomer. However, the trans-10, cis-12CLA content does not always correspond to the extent of milk fat depression, and in some instances, an increase in the milk fat content of trans-10, trans-12 CLA has been observed. We synthesized trans-10, trans-12 CLA (> 90% purity) and investigated its effect on milk fat synthesis and incorporation into plasma lipids. Three rumen-fistulated Holstein cows were randomly assigned in a 3 x 3 Latin square experiment. Treatments were a 4-d abomasal infusion of 1) ethanol (control), 2) a trans-10, cis-12 CLA supplement (positive control), and 3) a trans-10, trans-12 CLA supplement; 5 g/d of the CLA isomer of interest was provided. Milk yield, dry matter intake, and milk protein were unaffected by treatment. Treatment with trans-10, trans-12 CLA had no effect on milk fat yield, whereas treatment with trans-10, cis-12 CLA reduced milk fat yield by 28%. Incorporation of CLA was greatest for the plasma triglyceride fraction, and the milk fat content was subsequently elevated within the respective treatment groups. The milk fatty acid composition indicated that. Delta(9)-desaturase was reduced significantly for both CLA treatments, but the reduction was greater for the treatment with trans-10, trans-12 CLA. Overall, abomasal infusion of trans-10, trans-12 CLA and trans-10, cis-12 CLA altered the desaturase ratios, but only trans-10, cis-12 CLA reduced milk fat synthesis. C1 Cornell Univ, Dept Anim Sci, Ithaca, NY 14853 USA. US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Bauman, DE (reprint author), Cornell Univ, Dept Anim Sci, Ithaca, NY 14853 USA. EM deb6@cornell.edu NR 43 TC 35 Z9 35 U1 0 U2 8 PU AMER DAIRY SCIENCE ASSOC PI SAVOY PA 1111 N DUNLAP AVE, SAVOY, IL 61874 USA SN 0022-0302 J9 J DAIRY SCI JI J. Dairy Sci. PD JUL PY 2006 VL 89 IS 7 BP 2559 EP 2566 PG 8 WC Agriculture, Dairy & Animal Science; Food Science & Technology SC Agriculture; Food Science & Technology GA 053GJ UT WOS:000238293300026 PM 16772575 ER PT J AU Kim, HJ Park, SH Lee, TH Nahm, BH Chung, YH Seo, KH Kim, HY AF Kim, H. J. Park, S. H. Lee, T. H. Nahm, B. H. Chung, Y. H. Seo, K. H. Kim, H. Y. TI Identification of Salmonella enterica serovar Typhimurium using specific PCR primers obtained by comparative genomics in Salmonella serovars SO JOURNAL OF FOOD PROTECTION LA English DT Article ID POLYMERASE-CHAIN-REACTION; REAL-TIME PCR; BACTERIAL PATHOGENS; SEQUENCE; ASSAY; STRAINS; TYPHI; FOOD AB Salmonella enterica serovar Typhimurium is a major foodborne pathogen throughout the world. Until now, the specific target genes for the detection and identification of serovar Typhimurium have not been developed. To determine the specific probes for serovar Typhimurium, the genes of serovar Typhimurium LT2 that were expected to be unique were selected with the BLAST (Basic Local Alignment Search Tool) program within GenBank. The selected genes were compared with 11 genomic sequences of various Salmonella serovars by BLAST Of these selected genes, 10 were expected to be specific to serovar Typhimurium and were not related to virulence factor genes of Salmonella pathogenicity island or to genes of the O and H antigens of Salmonella. Primers for the 10 selected genes were constructed, and PCRs were evaluated with various genomic DNAs of Salmonella and non-Salmonella strains for the specific identification of Salmonella serovar Typhimurium. Among all the primer sets for the 10 genes, STM4497 showed the highest degree of specificity to serovar Typhimurium. In this study, a specific primer set for Salmonella serovar Typhimurium was developed on the basis of the comparison of genomic sequences between Salmonella serovars and was validated with PCR. This method of comparative genomics to select target genes or sequences can be applied to the specific detection of microorganisms. C1 Kyung Hee Univ, Inst Life Sci & Resources, Suwon 449701, South Korea. Kyung Hee Univ, Grad Sch Biotechnol, Suwon 449701, South Korea. Myongji Univ, Green Gene Bio Tech Inc, Yongin 449728, South Korea. Korea Consumer Protect Board, Seoul 137700, South Korea. US FDA, CFSA, OPDFB, College Pk, MD 20740 USA. RP Kim, HY (reprint author), Kyung Hee Univ, Inst Life Sci & Resources, Suwon 449701, South Korea. EM hykim@khu.ac.kr NR 30 TC 23 Z9 25 U1 0 U2 6 PU INT ASSOC FOOD PROTECTION PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD JUL PY 2006 VL 69 IS 7 BP 1653 EP 1661 PG 9 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 064HM UT WOS:000239079800024 PM 16865900 ER PT J AU Pascall, MA Ravishankar, S Ghiron, K Lee, BT Johannessen, JN AF Pascall, Melvin A. Ravishankar, Sadhana Ghiron, Ken Lee, Bowen T. Johannessen, Jan N. TI Evaluation of magnetic resonance for detection of bacterial contamination in low-acid, shelf-stable packaged soymilk SO JOURNAL OF FOOD PROTECTION LA English DT Article ID SURVIVAL AB This study evaluated magnetic resonance (MR) as a nondestructive method for detection of bacterial contamination in shelf-stable soymilk and cheese sauce. To accomplish this, individual 355-ml polymeric trays filled with soymilk and inoculated with Bacillus stearothermophilus and Bacillus subtilis (10(3) CFU) were incubated for up to 28 h at 55 degrees C and 62 h at 37 degrees C, respectively. MR relaxation times (T-2) of these samples were then correlated with the bacterial growth as well as viscosity and pH changes caused by the bacteria in the packaged soymilk. In addition, this study investigated the ability of MR to differentiate between regularly processed cheese sauce and cheese sauce that was modified with alpha-amylase as a spoilage simulation. Results showed increased MR T-2 relaxation times after the bacterial populations reached 10(8) CFU/ml (after 18 h) and 10(7) CFU/ml (after 44 h) for B. stearothermophilus and B. subtilis, respectively. B. subtilis had an undetectable influence on viscosity but a profound influence on pH. B. stearothermophilus, in comparison, significantly lowered the pH and increased the viscosity of the soymilk. MR was able to distinguish between regularly processed 85-g pouches of cheese sauce and other pouches with sauce that were modified with 0.5 ml of 1% alpha-amylase solution. These results showed that MR has the potential to be used for nondestructive detection of physical changes in soymilk and cheese sauce induced by bacterial growth and enzymatic activities, respectively. C1 US Food & Adm, Natl Ctr Food Safety & Technol, Summit Argo, IL 60501 USA. IIT, Natl Ctr Food Safety & Technol, Summit Argo, IL 60501 USA. US FDA, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. RP Pascall, MA (reprint author), Ohio State Univ, Dept Food Sci & Technol, 2015 Fyffe Rd, Columbus, OH 43210 USA. EM pascall.1@osu.edu RI Pascall, Melvin /A-5354-2013 NR 12 TC 6 Z9 6 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 JUL PY 2006 VL 69 IS 7 BP 1668 EP 1674 PG 7 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 064HM UT WOS:000239079800026 PM 16865902 ER PT J AU Jackson, DS Crockett, DF Wolnik, KA AF Jackson, DS Crockett, DF Wolnik, KA TI The indirect detection of bleach (Sodium hypochlorite) in beverages as evidence of product tampering SO JOURNAL OF FORENSIC SCIENCES LA English DT Article DE forensic science; product tampering; adulteration; bleach; sodium hypochlorite; ion chromatography; suppressed conductivity ID CHLOROFORM; CHLORINE AB Bleach (sodium hypochlorite) has been identified as the adulterant in a relatively large number of product tamperings that have been investigated by the Forensic Chemistry Center (FCC) of the U.S. Food and Drug Administration. In this work, household bleach was added to 23 different beverages at each of three levels. The impact of sodium hypochlorite on these beverages over a 13-day study period was evaluated using the following techniques: diphenylamine spot test for oxidizing agents, potassium iodide-starch test paper for oxidizing agents, pH, iodometric titration for quantitating hypochlorite, ion chromatography for chloride and chlorate quantitation, automated headspace sampling with gas chromatography-flame ionization detection (GC-FID) for determination of chloroform, and visual and organoleptic observations. This study has shown that hypochlorite is fragile when added to most common beverages and typically breaks down either partially or completely over time. In cases where a beverage is suspected of being adulterated with bleach but tests for hypochlorite are negative, it is still possible to characterize the product to demonstrate that the results are consistent with the addition of bleach. An adulterated product will give a positive test for oxidizing agents using the diphenylamine spot test. It is likely that the pH of the adulterated product will be higher than a control of that product. Ion chromatographic analysis shows elevated chloride and chlorate as compared with a control. And, chloroform may also be detected by GC-FID especially if the beverage that was adulterated contains citric acid. C1 US FDA, Forens Chem Ctr, Cincinnati, OH 45237 USA. RP Jackson, DS (reprint author), US FDA, Forens Chem Ctr, 6751 Steger Dr, Cincinnati, OH 45237 USA. EM david.jackson@fda.hhs.gov NR 10 TC 7 Z9 7 U1 3 U2 9 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-1198 J9 J FORENSIC SCI JI J. Forensic Sci. PD JUL PY 2006 VL 51 IS 4 BP 827 EP 831 DI 10.1111/j.1556-4029.2006.00160.x PG 5 WC Medicine, Legal SC Legal Medicine GA 060GI UT WOS:000238790200017 PM 16882227 ER PT J AU Li, H AF Li, H TI The covariance structure and likelihood function for multivariate dyadic data SO JOURNAL OF MULTIVARIATE ANALYSIS LA English DT Article DE diallel design; EM algorithm; exchangeability; maximum likelihood; patterned covariance; social relations model ID EM ALGORITHM; MAXIMUM-LIKELIHOOD; QUADRATIC ANALYSES; VARIANCE; MODELS; ECM AB This paper extends the results in Li and Loken [A unified theory of statistical analysis and inference for variance component models for dyadic data, Statist. Sinica 12 (2002) 519-535] on the statistical analysis of measurements taken on dyads to the situations in which more than one attribute are measured on each dyad. Starting from the covariance structure for the univariate case obtained in Li and Loken (2002), the covariance structure for the multivariate case is derived based on the group symmetry induced by the assumed exchangeability in the units. Our primary objective is to document the Gaussian likelihood and the sufficient statistics for multivariate dyadic data in closed form, so that they can be referenced by researchers as they analyze those data. The derivation carried out can also serve as an example of multivariate extension of univariate models based on exchangeability. (c) 2005 Elsevier Inc. All rights reserved. C1 Univ Rochester, Sch Med & Dent, Rochester, NY 14642 USA. RP Li, H (reprint author), US FDA, CDRH HFZ 550, 1350 Piccard Dr, Rockville, MD 20850 USA. EM hx1@cdrh.fda.gov NR 15 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER INC PI SAN DIEGO PA 525 B STREET, STE 1900, SAN DIEGO, CA 92101-4495, UNITED STATES SN 0047-259X J9 J MULTIVARIATE ANAL JI J. Multivar. Anal. PD JUL PY 2006 VL 97 IS 6 BP 1263 EP 1271 DI 10.1016/j.jmva.2005.06.004 PG 9 WC Statistics & Probability SC Mathematics GA 051JY UT WOS:000238158600001 ER PT J AU Suleiman, OH Fejka, R Houn, F Walsh, M AF Suleiman, Orhan H. Fejka, Richard Houn, Florence Walsh, Maria TI The Radioactive Drug Research Committee: Background and retrospective study of reported research data (1975-2004) SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE Food and Drug Administration; Radioactive Drug Research Committee; radiolabeled drugs; drug quality standards; radiation dose limits; basic science research; PET AB In the United States, human research involving radioactive drugs must be conducted under a Food and Drug Administration (FDA) investigational new drug (IND) application, unless specifically exempt from IND requirements, or under the direct oversight of a Radioactive Drug Research Committee (RDRC) as long as certain conditions are met. Research overseen by RDRCs is considered basic science research when its purpose is to advance scientific knowledge and not to determine a radioactive drug's safety and effectiveness as a therapeutic, diagnostic, or preventive medical product in humans. We retrospectively reviewed and analyzed available study data from annual reports submitted to the FDA dating back to 1976. In 1976, there were 18 studies involving 531 subjects compared with 2003, when there were 284 RDRC studies involving 2,797 subjects. In 1976, RDRC subjects were imaged 5% of the time using positron-emitting nuclicles and 77% of the time with conventional gamma-emitting nuclicles. In 2003, this was reversed with 77% using positron emitters and 5% using conventional gamma-emitters. In 1976, pediatric studies comprised 7.3% of all RDRC subjects; today pediatric RDRC studies are rarely conducted. Today the RDRC is used primarily by large medical research institutions. Although the program has a very good safety record, RDRC's 30-y-old regulations need to be revised to be consistent with current scientific knowledge and health policy. C1 US FDA, Off Oncol Drug Prod, Off New Drugs, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. US FDA, Off Drug Evaluat 3, Off New Drugs, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Suleiman, OH (reprint author), US FDA, Off Oncol Drug Prod, Off New Drugs, Ctr Drug Evaluat & Res, Bldg 22,Room 2206,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM Orhan.Suleiman@FDA.HHS.GOV NR 11 TC 4 Z9 4 U1 0 U2 1 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 JUL PY 2006 VL 47 IS 7 BP 1220 EP 1226 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 061NM UT WOS:000238879300027 PM 16818959 ER PT J AU Lyon, RC Taylor, JS Porter, DA Prasanna, HR Hussain, AS AF Lyon, RC Taylor, JS Porter, DA Prasanna, HR Hussain, AS TI Stability profiles of drug products extended beyond labeled expiration dates SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article DE shelf life; drug stability; shelf life extension program; SLEP; expiration date AB The American Medical Association has questioned whether expiration dating markedly underestimates the actual shelf life of drug products. Results from the shelf life extension program (SLEP) have been evaluated to provide extensive data to address this issue. The SLEP has been administered by the Food and Drug Administration for the United States Department of Defense (DOD) for 20 years. This program probably contains the most extensive source of pharmaceutical stability data extant. This report summarizes extended stability profiles for 122 different drug products (3005 different lots). The drug products were categorized into five groups based on incidence of initial extension failures and termination failures (extended lot eventually failed upon re-testing). Based on testing and stability assessment, 88% of the lots were extended at least 1 year beyond their original expiration date for an average extension of 66 months, but the additional stability period was highly variable. The SLEP data supports the assertion that many drug products, if properly stored, can be extended past the expiration date. Due to the lot-to-lot variability, the stability and quality of extended drug products can only be assured by periodic testing and systematic evaluation of each lot. (c) 2006 Wiley-Liss, Inc. and the American Pharmacists Association. C1 US FDA, Div Prod Qual Res, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. US FDA, Div Field Sci, Off Reg Operat, Off Regulatory Affairs, Rockville, MD 20857 USA. Sandoz, Biopharmaceut Dev, Princeton, NJ 08540 USA. RP Lyon, RC (reprint author), US FDA, Div Prod Qual Res, Ctr Drug Evaluat & Res, HFD 941,Life Sci Bldg 64,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM robbe.lyon@fda.hhs.gov NR 9 TC 31 Z9 31 U1 5 U2 18 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 2006 VL 95 IS 7 BP 1549 EP 1560 DI 10.1002/jps.20636 PG 12 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 058IM UT WOS:000238658700015 PM 16721796 ER PT J AU Gao, ZM Moore, TW Doub, WH Westenberger, BJ Buhse, LF AF Gao, ZM Moore, TW Doub, WH Westenberger, BJ Buhse, LF TI Effects of deaeration methods on dissolution testing in aqueous media: A study using a total dissolved gas pressure meter SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article DE dissolution; total dissolved gas pressure meter; dissolved gases; deaeration; degassing ID CALIBRATOR TABLETS; USP; AIR AB Dissolution testing is a critical method for the determination of pharmaceutical product quality and bioequivalence. For some products, dissolved gases in the dissolution medium affect dissolution results thus requiring degassing of the medium prior to use. In this study, we use a total dissolved gas and oxygen meter to measure both oxygen and total gases in dissolution media before and after application of a variety of deaeration methods. Dissolution testing results using a 10 mg Prednisone tablet (NCDA #2) are compared with the percent saturation of oxygen and total gases found in the medium. Reaeration of the medium during different stirring rates was also measured. This study confirms that measurement of total gases and not just oxygen in the medium is necessary to assess adequacy for dissolution testing. For those deaeration techniques that are performed at room temperature, the percent saturation of the total dissolved gases must be well below 100% to prevent outgassing once medium is brought to dissolution test method temperature, typically 37 degrees C. (c) 2006 Wiley-Liss, Inc. and the American Pharmacists Association. C1 US FDA, Ctr Drug Evaluat & Res, Div Pharmaceut Anal, St Louis, MO 63101 USA. RP Gao, ZM (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Pharmaceut Anal, St Louis, MO 63101 USA. EM gaoz@cder.fda.gov NR 14 TC 15 Z9 15 U1 2 U2 4 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 2006 VL 95 IS 7 BP 1606 EP 1613 DI 10.1002/jps.20622 PG 8 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 058IM UT WOS:000238658700020 PM 16732563 ER PT J AU Pal, A Sirota, L Maudru, T Peden, K Lewis, AM AF Pal, A Sirota, L Maudru, T Peden, K Lewis, AM TI Real-time, quantitative PCR assays for the detection of virus-specific DNA in samples with mixed populations of polyornaviruses SO JOURNAL OF VIROLOGICAL METHODS LA English DT Article DE polyomavirus; BKV; JCV; SV40; real-time PCR; TaqMan; Q-PCR ID COMPLETE NUCLEOTIDE-SEQUENCE; HUMAN POLYOMAVIRUS BK; HUMAN BRAIN-TUMORS; JC-VIRUS; SIMIAN-VIRUS-40 INFECTION; NEUTRALIZING ANTIBODIES; RHESUS-MONKEYS; T-ANTIGEN; SV40; CELLS AB Mixtures of polyomaviruses can be present in the central nervous system, the gastrointestinal tract, the genitourinary tract, blood, and urban sewage. We have developed 12 primer/probe sets (four per virus) for real-time, quantitative PCR assays (TaqMan) that can specifically detect BKV, JCV, and SV40 genomes present in mixtures of these viruses. The specificities of these primer/probe sets were determined by evaluating their level of interaction with the DNA from other polyomaviruses and their ability to estimate the number of copies of homologous viral DNA in blinded samples of defined mixtures of three polyomaviral DNAs. Three early region and three late region primer/probe sets determined, within a two-fold range, the number of copies of their respective DNAs. Four sets of SV40 primer/probes also detected 1.1-2.4 copies of SV40 DNA per COS-1 cell, cells estimated to contain a single copy of SV40 DNA. Three JCV primer/probe sets detected 3.7-4.2 copies per cell of JCV DNA in the JCV-transformed cell line M1-HR, cells estimated to contain between 0.5 and I copy of the JCV genome. We suggest that the virus-specific primer/probe sets in this study be considered sufficiently characterized to initiate the quantification of polyomavirus DNA in biological samples. Published by Elsevier B.V. C1 US FDA, CBER, Div Viral Prod, Off Vaccines Res & Review, Bethesda, MD 20892 USA. US FDA, CBER, Div Biostat, Off Biostat & Epidemiol, Bethesda, MD 20892 USA. RP Lewis, AM (reprint author), US FDA, CBER, Div Viral Prod, Off Vaccines Res & Review, Bldg 29A,Room 1BO13,29 Lincoln Dr, Bethesda, MD 20892 USA. EM lewisa@cber.fda.gov NR 60 TC 60 Z9 61 U1 1 U2 5 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 2006 VL 135 IS 1 BP 32 EP 42 DI 10.1016/j.jviromet.2006.01.018 PG 11 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Virology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Virology GA 053KT UT WOS:000238304700005 PM 16527364 ER PT J AU Takeshita, F Tanaka, T Matsuda, T Tozuka, M Kobiyama, K Saha, S Matsui, K Ishii, KJ Coban, C Akira, S Ishii, N Suzuki, K Klinman, DM Okuda, K Sasaki, S AF Takeshita, Fumihiko Tanaka, Toshiyuki Matsuda, Tomoko Tozuka, Miyuki Kobiyama, Kouji Saha, Sukumar Matsui, Kiyohiko Ishii, Ken J. Coban, Cevayir Akira, Shizuo Ishii, Norihisa Suzuki, Koichi Klinman, Dennis M. Okuda, Kenji Sasaki, Shin TI Toll-like receptor adaptor molecules enhance DNA-raised adaptive immune responses against influenza and tumors through activation of innate immunity SO JOURNAL OF VIROLOGY LA English DT Article ID CELL-MEDIATED-IMMUNITY; DENDRITIC CELLS; IN-VIVO; ANTIGEN PRESENTATION; VACCINE ADJUVANTS; GENE-TRANSFER; IMMUNIZATION; EXPRESSION; INDUCTION; CASPASES AB Toll-like receptors (TLRs) recognize microbial components and trigger the signaling cascade that activates the innate and adaptive immunity. TLR adaptor molecules play a central role in this cascade; thus, we hypothesized that overexpression of TLR adaptor molecules could mimic infection without any microbial components. Dual-promoter plasmids that carry an antigen and a TLR adaptor molecule such as the Toll-interleukin-1 receptor domain-containing adaptor-inducing beta interferon (TRIF) or myeloid differentiation factor 88 (MyD88) were constructed and administered to mice to determine if these molecules can act as an adjuvant. A DNA vaccine incorporated with the MyD88 genetic adjuvant enhanced antigen-specific humoral immune responses, whereas that with the TRIF genetic adjuvant enhanced cellular immune responses. Incorporating the TRIF genetic adjuvant in a DNA vaccine targeting the influenza HA antigen or the tumor-associated antigen E7 conferred superior protection. These results indicate that TLR adaptor molecules can bridge innate and adaptive immunity and potentiate the effects of DNA vaccines against virus infection and tumors. C1 Yokohama City Univ, Grad Sch Med, Dept Mol Biodefense Res, Yokohama, Kanagawa 2360004, Japan. ERATO, Akira Innate Immun Program, Japan Sci & Technol Agcy, Osaka, Japan. Natl Inst Infect Dis, Dept Bioregulat, Leprosy Res Ctr, Tokyo 1890002, Japan. Ctr Biol Evaluat & Res, Food & Drug Adm, Sect Retroviral Immunol, Bethesda, MD 20892 USA. RP Takeshita, F (reprint author), Yokohama City Univ, Grad Sch Med, Dept Mol Biodefense Res, 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 35 TC 46 Z9 50 U1 0 U2 7 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 JUL PY 2006 VL 80 IS 13 BP 6218 EP 6224 DI 10.1128/JVI.00121-06 PG 7 WC Virology SC Virology GA 054MJ UT WOS:000238380700003 PM 16775309 ER PT J AU Delogu, G Sanguinetti, M Pusceddu, C Bua, A Brennan, MJ Zanetti, S Fadda, G AF Delogu, Giovanni Sanguinetti, Maurizio Pusceddu, Cinzia Bua, Alessandra Brennan, Michael J. Zanetti, Stefania Fadda, Giovanni TI PE_PGRS proteins are differentially expressed by Mycobacterium tuberculosis in host tissues SO MICROBES AND INFECTION LA English DT Article DE Mycobacterium; tuberculosis; PE_PGRS genes ID GENOME SEQUENCE; INFECTED MICE; BOVIS BCG; GENES; ANTIGENS; VIRULENCE; GROWTH; LUNGS; FTSZ; ATTENUATION AB Characterization of PE-PGRS gene expression will help define the role of this protein family in the biology of Mycobacterium tuberculosis. In this report, quantitative real-time RT-PCR (QRT-PCR) was implemented to assess expression of three PEPGRS genes (rv0746, rv1651c and rv1818c) under different experimental conditions. The three PE-PGRS genes showed a similar expression profile in axenic cultures, with a significant up-regulation occurring at late log and early stationary phases. rv1651c gene expression increased following intracellular growth in bone marrow-derived macrophages but not in type-II human pneumocytes, while rv0746 was induced in both in vitro systems. Following the infection of mice with M. tuberculosis, expression levels of rv1651c and rv0746 normalized to fitsZ and 16S rRNA were highest in the spleen tissue during the chronic stages of murine tuberculosis, with a > 20- and > 30-fold up-regulation, respectively. Levels of expression remained lower in the lung over the same time period. Expression of the rv1818c gene did not change significantly under different experimental conditions tested. The results of this study indicate that M. tuberculosis can differentially regulate expression of PE-PGRS genes and that genes such as rv0746 and rv1651c are significantly induced while M. tuberculosis persists in host cells and tissues. (c) 2006 Elsevier SAS. All rights reserved. C1 Univ Sacred Heart, Inst Microbiol, I-00168 Rome, Italy. Univ Sassari, Dept Biomed Sci, I-07100 Sassari, Italy. US FDA, Ctr Biol Evaluat & Res, Off Vac Res & Review, Bethesda, MD 20892 USA. RP Delogu, G (reprint author), Univ Sacred Heart, Inst Microbiol, Lgo A Gemelli 8, I-00168 Rome, Italy. EM gdelogu@rm.unicatt.it; msanguinetti@rm.unicatt.it; c_pusceddu@hotmail.com; ziaferita@email.it; brennan@cber.fda.gov; zanettis@uniss.it; giovannifadda@rm.unicatt.it RI Sanguinetti, Maurizio/E-8247-2011; Delogu, Giovanni/I-3701-2012; Fadda, Giovanni/K-6224-2012; OI Delogu, Giovanni/0000-0003-0182-8267; Sanguinetti, Maurizio/0000-0002-9780-7059 NR 35 TC 43 Z9 45 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1286-4579 J9 MICROBES INFECT JI Microbes Infect. PD JUL PY 2006 VL 8 IS 8 BP 2061 EP 2067 DI 10.1016/j.micinf.2006.03.015 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 092RN UT WOS:000241115100010 PM 16798044 ER PT J AU Gendel, SM Jenkins, JA AF Gendel, Steven M. Jenkins, John A. TI Allergen sequence databases SO MOLECULAR NUTRITION & FOOD RESEARCH LA English DT Article; Proceedings Paper CT International Workshop on Bioinformatics of Protein Allergenicity CY FEB 22-24, 2005 CL Mallorca, SPAIN SP Hlth & Environm Sci Inst DE allergic; bioinformatics; food allergy; IgE ID IGE-BINDING EPITOPES; G2 GLYCININ ALLERGEN; MOLECULAR CHARACTERIZATION; POTENTIAL ALLERGENICITY; MUTATIONAL ANALYSIS; MAJOR ALLERGEN; PEANUT; PROTEINS AB A number of specialized databases have been developed to facilitate studies of human allergens. These include molecular databases focused on protein sequences and structures, informational databases focused on clinical, biochemical and epidemiological data related to protein allergens, a database on allergen nomenclature, and other knowledge bases or informational websites that are peripherally-related to research on allergens. Examples of each type of databases are listed and described briefly in this review. Database construction and maintenance and their impact on database quality and usefulness are also discussed. C1 US FDA, Natl Ctr Food Safety & Technol, Summit Argo, IL USA. Inst Food Res, Norwich, Norfolk, England. RP Gendel, SM (reprint author), US FDA, Natl Ctr Food Safety & Technol, 6502 S Archer, Summit Argo, IL USA. EM sgendel@cfsan.fda.gov NR 21 TC 16 Z9 17 U1 1 U2 2 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1613-4125 J9 MOL NUTR FOOD RES JI Mol. Nutr. Food Res. PD JUL PY 2006 VL 50 IS 7 BP 633 EP 637 DI 10.1002/mnfr.200500271 PG 5 WC Food Science & Technology SC Food Science & Technology GA 068CA UT WOS:000239348100008 PM 16764016 ER PT J AU Gutman, S Kessler, LG AF Gutman, Steven Kessler, Larry G. TI The US food and drug administration perspective on cancer biomarker development SO NATURE REVIEWS CANCER LA English DT Article ID BREAST-CANCER; BIAS AB Despite the intense interest in biomarker development for cancer management, few biomarker assays for diagnostic uses have been submitted to the US Food and Drug Administration (FDA). What challenges must researchers overcome to bring cancer-detection technologies to the market and, therefore, into clinical use? C1 US FDA, Off In Vitro Diagnost Devices, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. US FDA, Off Sci, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. US FDA, Engn Labs, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Gutman, S (reprint author), US FDA, Off In Vitro Diagnost Devices, Ctr Devices & Radiol Hlth, NFZ-440,2098 Gaither Rd, Rockville, MD 20857 USA. EM steve.gutman@fda.hhs.gov NR 37 TC 120 Z9 128 U1 0 U2 16 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-175X J9 NAT REV CANCER JI Nat. Rev. Cancer PD JUL PY 2006 VL 6 IS 7 BP 565 EP 571 DI 10.1038/nrc1911 PG 8 WC Oncology SC Oncology GA 065ZY UT WOS:000239200200018 PM 16794639 ER PT J AU Goodman, J AF Goodman, Jesse TI US food and drug administration SO ONCOLOGY-NEW YORK LA English DT Letter C1 US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. RP Goodman, J (reprint author), US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU P R R INC PI MELVILLE PA 48 SOUTH SERVICE RD, MELVILLE, NY 11747 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD JUL PY 2006 VL 20 IS 8 BP 946 EP 946 PG 1 WC Oncology SC Oncology GA V44BG UT WOS:000202977600027 ER PT J AU Goodsaid, F Frueh, F AF Goodsaid, Federico Frueh, Felix TI Process map proposal for the validation of genomic biomarkers SO PHARMACOGENOMICS LA English DT Article DE biomarker; clinical; genomic; preclinical; validation ID PROTON PUMP INHIBITORS; GENE COPY NUMBER; THIOPURINE METHYLTRANSFERASE; CLINICAL CONSEQUENCES; FACTOR-RECEPTOR; DIHYDROPYRIMIDINE DEHYDROGENASE; PLASMA-CONCENTRATIONS; WARFARIN SENSITIVITY; COLORECTAL-CANCER; ANTICANCER AGENTS AB How can we encourage the application of novel genomic biomarkers in drug development? A major step in this direction would be a consensus on how to interpret results from measurements of these biomarkers in regulatory submissions. A transparent process for genomic biomarker validation would be of value both for the pharmaceutical industry as well as for regulatory agencies associated with it. A discussion on process map proposals for genomic biomarker validation can help with drafting of guidance documents for this process. C1 US FDA, Genom Grp, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Silver Spring, MD 20903 USA. RP Goodsaid, F (reprint author), US FDA, Genom Grp, Off Clin Pharmacol, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave,Bldg 21,Room 3663, Silver Spring, MD 20903 USA. EM Federico.Goodsaid@fda.hhs.gov NR 57 TC 46 Z9 52 U1 0 U2 2 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 JUL PY 2006 VL 7 IS 5 BP 773 EP 782 DI 10.2217/14622416.7.5.773 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 064EQ UT WOS:000239072400014 PM 16886901 ER PT J AU Sundaresan, PR Slavoff, SA Grundel, E White, KD Mazzola, E Koblenz, D Rader, JI AF Sundaresan, P. Ramnathan Slavoff, Sarah A. Grundel, Erich White, Kevin D. Mazzola, Eugene Koblenz, Daniel Rader, Jeanne I. TI Isolation and characterisation of selected germander diterpenoids from authenticated Teucrium chamaeldrys and T-canadense by HPLC, HPLC-MS and NMR SO PHYTOCHEMICAL ANALYSIS LA English DT Article DE RP-HPLC; HPLC-MS; NMR; diterpenoids; teucrin A; Teucrium chamaedrys; germander ID CHAMAEDRYS L; NEOCLERODANE DITERPENOIDS; HERBAL REMEDIES; HEPATOTOXICITY; HEPATITIS; GLYCOSIDES AB Teucrium species, such as germander, are rich in neo-clerodane diterpenoids and have been used in traditional folk medicine for their stimulant, diuretic, antipyretic and antiseptic properties. However, the furano neo-clerodane diterpenoids present in germander have been implicated in the in vivo hepatotoxicity of this botanical. In this study, authenticated germander (Teucrium chamuedrys L. and Teucrium canadense L.) was used as the source material. Methanol extracts of powdered plant material were prepared and analysed by HPLC using Synergi (R) Max-RP columns with monitoring at 220 nm. Limited amounts of teucrin A and other diterperroid standards were analysed on a Synergi Max-RP column in order to determine their retention times and to generate calibration curves. The same standards were subjected to concurrent mass spectral analysis. Teucrin A and diterpenoids such as dihydroteugin, teuflin, teuflidin and teuevidin were tentatively identified in the plant extracts by HPLC-MS and H-1-NMR experiments. For the isolation of teucrium diterpenoids on a semipreparative scale, a solid-phase extraction method was developed for the first time using styrene divinylbenzene and strata-X sorbents for teucrin A and teuflin, respectively. Semi-preparative HPLC of the methanol extract of the powdered aerial parts of Teucrium plants was carried out on a semipreparative Synergi Max-RP column. with photodiode array detection in order to confirm the identities of some diterpenoids by HPLC-MS and NMR. Copyright (c) 2006 John Wiley & Sons, Ltd. C1 Off Nutr Prod Learning & Dietary Supplements, Div Res & Appl Technol, College Pk, MD 20740 USA. Univ Maryland, Joint Inst Food Safety & Appl Nutr, College Pk, MD 20742 USA. Food & Drug Adm, Ctr Food Safety & Appl Nutr, Off Sci Anal & Support, Div Gen Sci Support, College Pk, MD 20740 USA. RP Sundaresan, PR (reprint author), Off Nutr Prod Learning & Dietary Supplements, Div Res & Appl Technol, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM p.sundaresan@fda.hhs.gov NR 25 TC 19 Z9 19 U1 1 U2 16 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0958-0344 J9 PHYTOCHEM ANALYSIS JI Phytochem. Anal. PD JUL PY 2006 VL 17 IS 4 BP 243 EP 250 DI 10.1002/pca.912 PG 8 WC Biochemical Research Methods; Plant Sciences; Chemistry, Analytical SC Biochemistry & Molecular Biology; Plant Sciences; Chemistry GA 068DP UT WOS:000239352700004 PM 16910040 ER PT J AU Bryant-Genevier, M Sommer, S McMahon, A Ball, R Braun, MM AF Bryant-Genevier, M Sommer, S McMahon, A Ball, R Braun, MM TI Correlates of public health workforce acceptance of smallpox immunization in Virginia SO PUBLIC HEALTH NURSING LA English DT Article DE attitudes; health care personnel; smallpox vaccination ID VACCINATION AB Objective: By October 24, 2003, 38,577 of 500,000 targeted civilians received smallpox vaccine in the Pre-Event Smallpox Vaccination Campaign, Phase I. We investigated reasons for the low vaccination uptake. Design: Cross-sectional survey, conducted in May 2004. Sample: We surveyed 225 health care personnel, potential members of smallpox response teams in Virginia, who were offered vaccination. We assessed respondents' acceptance of vaccination and its association with factors potentially influencing vaccination: perceptions of vaccine safety, contraindications, concerns about bioterrorism, and workplace influences. Results: Among nonvaccinees (n=44), 70% had a contraindication to the vaccine compared with 8% among vaccinees (n=132). The desire to prepare America for potential bioterrorist attack was associated with acceptance of smallpox vaccination (odds ratio [OR]: 17.7, 95% confidence interval [CI]: 3.6-85.9). Among respondents with contraindications, vaccinees reported more often than nonvaccinees having been asked by their supervisors to be vaccinated (OR: 5; 95% CI: 1.1-22.1) and to have been concerned that their vaccination choice would affect positively their job evaluation (OR: 11; 95% CI: 1.6-81.1). Conclusion: Concerns about bioterrorism and willingness to help in the preparedness effort were motivations for vaccination. Continued vigilance to avoid vaccination of those with contraindications is needed. C1 US FDA, Vaccine Safety Branch, CBER, OBE,DE, Rockville, MD 20852 USA. Virginia State Hlth Dept, Div Immunizat, Richmond, VA USA. RP Bryant-Genevier, M (reprint author), US FDA, Vaccine Safety Branch, CBER, OBE,DE, Suite 268 S,HFM-222,1401 Rockville Pike, Rockville, MD 20852 USA. EM marthe.bryant-genevier@fda.hhs.gov NR 9 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0737-1209 J9 PUBLIC HEALTH NURS JI Public Health Nurs. PD JUL-AUG PY 2006 VL 23 IS 4 BP 339 EP 346 DI 10.1111/j.1525-1446.2006.00570.x PG 8 WC Public, Environmental & Occupational Health; Nursing SC Public, Environmental & Occupational Health; Nursing GA 059RH UT WOS:000238749400007 PM 16817805 ER PT J AU Wang, Y Raffoul, JJ Che, MX Doerge, DR Joiner, MC Kucuk, O Sarkar, FH Hillman, GG AF Wang, Y Raffoul, JJ Che, MX Doerge, DR Joiner, MC Kucuk, O Sarkar, FH Hillman, GG TI Prostate cancer treatment is enhanced by genistein in vitro and in vivo in a syngeneic orthotopic tumor model SO RADIATION RESEARCH LA English DT Article ID CARCINOMA-CELLS; DOWN-REGULATION; RAT PROSTATE; MOUSE MODEL; GROWTH; THERAPY; RADIATION; MICE; CARCINOGENESIS; ISOFLAVONES AB Pretreatment with genistein, a bioactive component of soy isoflavones, potentiated cell killing induced by radiation in human PC-3 prostate cancer cells in vitro. Using an orthotopic xenograft in nude mice, we demonstrated that genistein combined with prostate tumor irradiation caused greater inhibition of primary tumor growth and increased control of spontaneous metastasis to para-aortic lymph nodes, increasing mouse survival. Paradoxically, treatment with genistein alone increased metastasis to lymph nodes. This observation is of concern in relation to soy-based clinical trials for cancer patients. To address whether this observation is because nude mice have an impaired immune system, these studies were repeated in orthotopic RM-9 prostate tumors in syngeneic C57BL/6 mice. The combination of genistein with radiation in this model also caused a greater inhibition of primary tumor growth and spontaneous metastasis to regional para-aortic lymph nodes, whereas treatment with genistein alone showed a trend to increased lymph node metastasis. Data from the syngeneic and xenograft models are comparable and indicate that the combination of genistein with radiotherapy is more effective and safer for prostate cancer treatment than genistein alone, which promotes metastatic spread to regional lymph nodes. (c) 2006 by Radiation Research Society. C1 Wayne State Univ, Sch Med, Dept Radiat Oncol, Detroit, MI 48201 USA. Wayne State Univ, Sch Med, Dept Pathol, Detroit, MI 48201 USA. Wayne State Univ, Sch Med, Div Hematol Oncol, Dept Internal Med, Detroit, MI 48201 USA. Wayne State Univ, Sch Med, Barbara Ann Karmanos Canc Inst, Detroit, MI 48201 USA. Harper Univ Hosp, Detroit, MI 48201 USA. US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Hillman, GG (reprint author), Webber Canc Res Ctr, Dept Radiat Oncol, 515 Hudson,4100 John R Rd, Detroit, MI 48201 USA. EM hillmang@karmanos.org NR 27 TC 39 Z9 47 U1 0 U2 0 PU RADIATION RESEARCH SOC PI OAK BROOK PA 820 JORIE BOULEVARD, OAK BROOK, IL 60523 USA SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD JUL PY 2006 VL 166 IS 1 BP 73 EP 80 DI 10.1667/RR3590.1 PN 1 PG 8 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA 057XA UT WOS:000238627300010 PM 16808622 ER PT J AU Olempska-Beer, ZS Merker, RI Ditto, MD DiNovi, MJ AF Olempska-Beer, Zofia S. Merker, Robert I. Ditto, Mary D. DiNovi, Michael J. TI Food-processing enzymes from recombinant microorganisms - a review SO REGULATORY TOXICOLOGY AND PHARMACOLOGY LA English DT Review DE review; food-processing enzymes; recombinant microorganisms; FDA ID COMPLETE GENOME SEQUENCE; ASPERGILLUS-ORYZAE; FUSARIUM-VENENATUM; BACILLUS-SUBTILIS; TRICHODERMA-REESEI; ALPHA-AMYLASE; SAFETY ASSESSMENT; HETEROLOGOUS EXPRESSION; GENE; STRAINS AB Enzymes are commonly used in food processing and in the production of food ingredients. Enzymes traditionally isolated from culturable microorganisms, plants, and mammalian tissues are often not well-adapted to the conditions used in modern food production methods. The use of recombinant DNA technology has made it possible to manufacture novel enzymes suitable for specific food-processing conditions. Such enzymes may be discovered by screening microorganisms sampled from diverse environments or developed by modification of known enzymes using modern methods of protein engineering or molecular evolution. As a result, several important food-processing enzymes such as amylases and lipases with properties tailored to particular food applications have become available. Another important achievement is improvement of microbial production strains. For example, several microbial strains recently developed for enzyme production have been engineered to increase enzyme yield by deleting native genes encoding extracellular proteases. Moreover, certain fungal production strains have been modified to reduce or eliminate their potential for production of toxic secondary metabolites. In this article, we discuss the safety of microorganisms used as hosts for enzyme-encoding genes, the construction of recombinant production strains, and methods of improving enzyme properties. We also briefly describe the manufacture and safety assessment of enzyme preparations and summarize options for submitting information on enzyme preparations to the US Food and Drug Administration. (c) 2006 Elsevier Inc. All rights reserved. C1 US FDA, Ctr Food Safety & Appl Nutr, Off Food Addit Safety, College Pk, MD 20740 USA. RP Olempska-Beer, ZS (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Food Addit Safety, HFS-255,5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM zofia.olempskabeer@fda.hhs.gov NR 84 TC 86 Z9 94 U1 7 U2 86 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 2006 VL 45 IS 2 BP 144 EP 158 DI 10.1016/j.yrtph.2006.05.001 PG 15 WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology SC Legal Medicine; Pharmacology & Pharmacy; Toxicology GA 062PM UT WOS:000238957000004 PM 16769167 ER PT J AU Brahme, A Alvi, MH Saylor, D Fridy, J Rollett, AD AF Brahme, A. Alvi, M. H. Saylor, D. Fridy, J. Rollett, A. D. TI 3D reconstruction of microstructure in a commercial purity aluminum SO SCRIPTA MATERIALIA LA English DT Article DE microstructure reconstructions; three dimensional; aluminum; texture; Voronoi tessellation ID POLYCRYSTALLINE MATERIALS AB The topic of reconstruction of polycrystalline microstructures is briefly reviewed. An example is given of using orientation maps to reconstruct digital microstructures with a representation of a polycrystal structure that includes crystallographic orientation information. The method uses packing of ellipsoids to approximate the grain structure, coupled with Voronoi tessellation. For the example of hot rolled commercial purity aluminum that was chosen, the highly elongated grain shapes required stretching of the tessellation in order to match the observed aspect ratios. (c) 2006 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved. C1 Carnegie Mellon Univ, Pittsburgh, PA 15213 USA. Intel Res, Hillsboro, OR USA. Alcoa Tech Ctr, Alcoa Ctr, PA 15609 USA. US FDA, Rockville, MD 20850 USA. RP Brahme, A (reprint author), Carnegie Mellon Univ, 5000 Forbes Ave, Pittsburgh, PA 15213 USA. EM abrahme@andrew.cmu.edu RI Rollett, Anthony/A-4096-2012; OI Rollett, Anthony/0000-0003-4445-2191; Brahme, Abhijit/0000-0002-2560-7808 NR 13 TC 102 Z9 102 U1 3 U2 24 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6462 J9 SCRIPTA MATER JI Scr. Mater. PD JUL PY 2006 VL 55 IS 1 BP 75 EP 80 DI 10.1016/j.scriptamat.2006.02.017 PG 6 WC Nanoscience & Nanotechnology; Materials Science, Multidisciplinary; Metallurgy & Metallurgical Engineering SC Science & Technology - Other Topics; Materials Science; Metallurgy & Metallurgical Engineering GA 045SL UT WOS:000237762400014 ER PT J AU Abraham, A Plakas, SM Wang, ZH Jester, ELE El Said, KR Granade, HR Henry, MS Blum, PC Pierce, RH Dickey, RW AF Abraham, Ann Plakas, Steven M. Wang, Zhihong Jester, Edward L. E. El Said, Kathleen R. Granade, Hudson R. Henry, Michael S. Blum, Patricia C. Pierce, Richard H. Dickey, Robert W. TI Characterization of polar brevetoxin derivatives isolated from Karenia brevis cultures and natural blooms SO TOXICON LA English DT Article DE brevetoxins; Karenia brevis; Eastern oyster; LC/MS ID OYSTER CRASSOSTREA-VIRGINICA; CONTROLLED EXPOSURES; MARINE AEROSOL; RED TIDE; METABOLISM; TOXINS AB Several novel brevetoxin derivatives were isolated and identified in Karenia brevis cultures and natural blooms by using solid phase extraction (SPE) and LC/MS(MS) techniques. These analogs were more polar compared with previously described brevetoxins, and were poorly extractable by conventional non-polar solvent (chloroform) partitioning. Brevetoxin analogs were structurally confirmed as hydrolyzed (open A-ring) forms of brevetoxins PbTx-1, PbTx-7, PbTx-2, and PbTx-3, and of oxidized PbTx-1 and PbTx-2. Some of these open A-ring derivatives were in greater abundance than their non-hydrolyzed counterparts. All were in much greater abundance in bloom water filtrate compared with cell-rich fractions. Open A-ring compounds were cytotoxic in mouse neuroblastoma (N2a) cell assay. In the K brevis bloom-exposed Eastern oyster, brevetoxin metabolites with opened A rings were identified (e.g., open-ring cysteine-PbTx conjugates), contributing to their overall toxin burden. Published by Elsevier Ltd. C1 US FDA, Gulf Coast Seafood Lab, Dauphin Isl, AL 35628 USA. Mote Marine Lab, Sarasota, FL 34236 USA. RP Abraham, A (reprint author), US FDA, Gulf Coast Seafood Lab, POB 158,1 Iberville Dr, Dauphin Isl, AL 35628 USA. EM ann.abraham@fda.hhs-gov NR 10 TC 35 Z9 38 U1 1 U2 7 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 JUL PY 2006 VL 48 IS 1 BP 104 EP 115 DI 10.1016/j.toxicon.2006.04.015 PG 12 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 074PQ UT WOS:000239824700012 PM 16808941 ER PT J AU Martinez, M McDermott, P Walker, R AF Martinez, M McDermott, P Walker, R TI Pharmacology of the fluoroquinolones: A perspective for the use in domestic animals SO VETERINARY JOURNAL LA English DT Review DE fluoroquinolones; veterinary; pharmacokinetics; pharmacodynamics; resistance ID QUINOLONE RESISTANCE MUTATIONS; MINIMUM INHIBITORY CONCENTRATION; ACRAB EFFLUX PUMP; IN-VITRO MODELS; ESCHERICHIA-COLI; DNA GYRASE; TOPOISOMERASE-IV; STREPTOCOCCUS-PNEUMONIAE; NUCLEOTIDE-SEQUENCE; ELECTROPHORETIC BEHAVIOR AB The fluoroquinolones are a class of compounds that comprise a large and expanding group of synthetic antimicrobial agents. Structurally, all fluoroquinolones contain a fluorine molecule at the 6-position of the basic quinolone nucleus. Despite the basic similarity in the core structure of these molecules, their physicochemical properties, pharmacokinetic characteristics and microbial activities can vary markedly across compounds. The first of the fluoroquinolones approved for use in animals, enrofloxacin, was approved in the late 1980s. Since then, five other fluoroquinolones have been marketed for use in animals in the United States, with others currently under investigation. This review focuses on the use of fluoroquinolones within veterinary medicine, providing an overview of the structure-activity relationship of the various members of the group, the clinical uses of fluoroquinolones in veterinary medicine, their pharmacokinetics and potential interspecies differences, an overview of the current understanding of the pharmacokinetic/pharmacodynamic relationships associated with fluoroquinolones, a summary of toxicities that have been associated with this class of compounds, their use in both in human and veterinary species, mechanisms associated with the development of microbial resistance to the fluoroquinolones, and a discussion of fluoroquinolone dose optimization. Although the review contains a large body of basic research information, it is intended that the contents of this review have relevance to both the research scientist and the veterinary medical practitioner. Published by Elsevier Ltd. C1 US FDA, Ctr Vet Med, Div Anim & Food Microbiol, Res Off, Laurel, MD 20708 USA. US FDA, Ctr Vet Med, Off New Anim Drug Evaluat, Rockville, MD 20855 USA. RP Walker, R (reprint author), US FDA, Ctr Vet Med, Div Anim & Food Microbiol, Res Off, Laurel, MD 20708 USA. EM rwalker@cvm.fda.gov NR 146 TC 160 Z9 165 U1 1 U2 35 PU BAILLIERE TINDALL PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1090-0233 J9 VET J JI Vet. J. PD JUL PY 2006 VL 172 IS 1 BP 10 EP 28 DI 10.1016/j.tvjl.2005.07.010 PG 19 WC Veterinary Sciences SC Veterinary Sciences GA 060DV UT WOS:000238783400005 PM 16154368 ER PT J AU Baleotti, W Rios, M Reid, ME Hashmi, G Fabron, A Pellegrino, J Castilho, L AF Baleotti, W Rios, M Reid, ME Hashmi, G Fabron, A Pellegrino, J Castilho, L TI Dombrock gene analysis in Brazilian people reveals novel alleles SO VOX SANGUINIS LA English DT Article DE Brazilians; Dombrock alleles; genotyping assays; microarray ID BLOOD-GROUP SYSTEM; NULL PHENOTYPE; HY; GLYCOPROTEIN; ANTIBODIES; ANTIGENS; DONORS AB Background and Objectives The Do(a) and Do(b) polymorphisms are associated with three single nucleotide polymorphisms (SNPs) in exon 2 of the DO gene: 378C/T, 624T/C and 793A/G for the DOA and DOB alleles, respectively. The SNPs 350C/T (JO allele) and 323G/T (HY allele) are associated with the Jo(a-) and Hy-negative phenotypes. Recently, two new DO alleles [DOB-SH (378C, 624C, 793G) and DOA-HA (378T, 624T, 793A)] were identified using microarray technology. Although the molecular background of Dombrock alleles is well defined, no studies have been conducted in the Brazilian population. Materials and Methods We employed polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)-based assays and a microarray assay to determine the frequency of the DO alleles (DOA, DOB, HY1, HY2 and JO) in Brazilians. We tested DNA of 288 Brazilians from three different ethnic groups by PCR-RFLP to determine the 793A/G (DOA/DOB), 323G/T (HY), 350C/T (JO) and 898C/G (HY1/HY2) SNPs. We also tested DNA from 162 blood donors by using the HEA Beadchip (TM) assay to determine the 378C/T, 624T/C, 793A/G (DOA/DOB), 350C/T (JO allele) and 323G/T (HY) SNPs. Results Two novel allele combinations were found in our samples: the DOB allele (793G and 323G) associated with 898G (DOB-WL); and an allele carrying the nucleotides 378C, 624C, 793A and 323G (DOA-SH). We also found the DOB-SH and DOA-HA.alleles recently reported. Conclusions Our data demonstrate high heterogeneity of DO alleles in the Brazilian population. Our study also highlights the importance of testing a cohort of different populations to determine DO haplotypes and of establishing reliable genotyping tests for predicting Do(a)/Do(b) status. C1 Univ Estadual Campinas, Hemoctr, BR-13081970 Campinas, SP, Brazil. Hemoctr, Fac Med, Marilia, SP, Brazil. US FDA, DETTD, OBRR, CBER, Rockville, MD 20857 USA. New York Blood Ctr, New York, NY 10021 USA. BioArray Solut, Warren, NJ USA. RP Castilho, L (reprint author), Univ Estadual Campinas, Hemoctr, Rua Carlos Chagas,480,Caixa Postal 6198,Barao Ger, BR-13081970 Campinas, SP, Brazil. EM castilho@unicamp.br RI Castilho, Lilian/F-6123-2012; Baleotti, Wilson Jr/C-3558-2014 OI Castilho, Lilian/0000-0002-3104-647X; NR 19 TC 9 Z9 11 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0042-9007 J9 VOX SANG JI Vox Sang. PD JUL PY 2006 VL 91 IS 1 BP 81 EP 87 DI 10.1111/j.1423-0410.2006.00787.x PG 7 WC Hematology SC Hematology GA 048DY UT WOS:000237929000012 PM 16756606 ER PT J AU Horvath-Arcidiacono, JA Porter, CM Bloom, ET AF Horvath-Arcidiacono, JA Porter, CM Bloom, ET TI Human NK cells can lyse porcine endothelial cells independent of their expression of Gal alpha(1,3)-Gal and killing is enhanced by activation of either effector or target cells SO XENOTRANSPLANTATION LA English DT Article DE human; natural killer cells; pig; tumor necrosis factor-alpha; xenotransplantation ID NATURAL-KILLER-CELLS; CLASS-I MOLECULES; MEDIATED CYTOTOXICITY; XENOGRAFT REJECTION; SKIN XENOGRAFTS; XENOTRANSPLANTATION; PIGS; ANTIBODIES; ADHESION; BABOONS AB Background: Xenotransplantation of pig organs may provide an approach to alleviate the severe shortage of human organs. Natural antibodies against Gal alpha(1,3)-Gal (alpha Gal) epitopes cause hyperacute rejection of pig organs in primates. However, evidence for the role of alpha Gal in the natural killer (NK) cell-mediated xenoresponse has been contradictory. Methods: We investigated the recognition of alpha Gal by human NK cells using endo-beta-galactosidase C, an enzyme that cleaves alpha Gal, and endothelial cells (EC) from alpha 1,3-galactosyltransferase null pigs that do not synthesize alpha Gal. Endo-beta-galactosidase C treatment variably reduced the susceptibility of porcine EC to lysis by fresh human NK cells. Results: Removal of alpha Gal from porcine EC using endo-beta-galactosidase C, produced variable results, i.e. cytotoxicity was decreased in half of the human NK cell donors tested. The two EC strains from alpha Gal-/- pigs were marginally, and not significantly, less susceptible to lysis by naive human NK cells compared with alpha Gal-expressing cells obtained from animals from the same herd, but these differences were not statistically significant (P > 0.10). Treatment of porcine EC with recombinant human tumor necrosis factor (TNF)-alpha, which is known to activate porcine EC, enhanced the susceptibility of all target cells to lysis by fresh human NK cells. Surface expression of MHC or adhesion molecules on alpha Gal-/- cells, compared with wild type cells, showed no consistent difference in either MHC or adhesion molecules CD106 (VCAM-1), CD31 (PECAM) or CD62E (E-selectin), either with or without TNF-alpha stimulation, that could explain the differential susceptibility to lysis. Strikingly, all alpha Gal-/- and wild type EC exhibited similar susceptibility to human NK cells that had been cultured for 5 days with or without interleukin-2. Conclusion: These findings demonstrate that human NK cells can kill porcine targets in the absence of alpha Gal, and donor variability plays a major role in whether alpha Gal has a role in determining susceptibility of porcine EC to lysis. Moreover, susceptibility to lysis of alpha Gal null EC is enhanced to the level of wild type EC by activation of either effector or target cells. Elimination of alpha Gal alone from source pigs will be insufficient to circumvent the NK cell mediated destruction of porcine EC. C1 CBER, DCGT, HFM 725, US FDA,Off Cellular Tissue & Gene Therapies,Gene, Bethesda, MD 20892 USA. RP Bloom, ET (reprint author), CBER, DCGT, HFM 725, US FDA,Off Cellular Tissue & Gene Therapies,Gene, 8800 Rockville Pike,Bldg 29B,Room 2NN04, Bethesda, MD 20892 USA. EM bloom@cber.fda.gov NR 59 TC 15 Z9 16 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD JUL PY 2006 VL 13 IS 4 BP 318 EP 327 DI 10.1111/j.1399-3089.2006.00316.x PG 10 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 052TN UT WOS:000238256900006 PM 16768725 ER PT J AU Andersen, WC Turnipseed, SB Roybal, JE AF Andersen, WC Turnipseed, SB Roybal, JE TI Quantitative and confirmatory analyses of malachite green and leucomalachite green residues in fish and shrimp SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE malachite green; leucomalachite green; LC-VIS; LC-MSn; ND-APCI; fish; shrimp ID PRESSURE CHEMICAL-IONIZATION; TANDEM MASS-SPECTROMETRY; LIQUID-CHROMATOGRAPHY; B6C3F(1) MICE; METABOLITES; SALMON; MUSCLE AB Liquid chromatographic methods are presented for the quantitative and confirmatory determination of malachite green (MG) and leucomalachite green (LMG) for channel catfish, rainbow trout, tilapia, basa, Atlantic salmon, and tiger shrimp. Residues were extracted from tissues with ammonium acetate buffer and acetonitrile and isolated by partitioning into dichloromethane. LMG was quantitatively oxidized to the chromic MG with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone. Extracts were analyzed for total MG by liquid chromatography with both visible detection (LC-VIS) at 618 nm for routine screening and ion trap mass spectrometry (LC-MSn) with no discharge-atmospheric pressure chemical ionization for residue confirmation. The method was validated in each species fortified with LMG at 1, 2, 4, and 10 ng/g (ppb), and average recoveries ranged from 85.9 to 93.9%. Quantitative data were consistent for the two detection methods, with measured method detection limits of 1.0 ng/g for LC-VIS and 0.25 ng/g for LC-MSn. Incurred tissues from catfish, trout, tilapia, and salmon that had been treated with MG were also extracted and analyzed as part of this study. C1 US FDA, Anim Drugs Res Ctr, Denver Fed Ctr, Lakewood, CO 80225 USA. RP Andersen, WC (reprint author), US FDA, Anim Drugs Res Ctr, Denver Fed Ctr, POB 25087, Lakewood, CO 80225 USA. NR 24 TC 64 Z9 65 U1 3 U2 21 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 28 PY 2006 VL 54 IS 13 BP 4517 EP 4523 DI 10.1021/jf0532258 PG 7 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 054ZN UT WOS:000238418100003 PM 16786992 ER PT J AU Tardif, JC Heinonen, T Orloff, D Libby, P AF Tardif, JC Heinonen, T Orloff, D Libby, P TI Vascular biomarkers and surrogates in cardiovascular disease SO CIRCULATION LA English DT Article DE cardiovascular diseases; coronary disease; diagnosis; imaging; prevention ID CORONARY-HEART-DISEASE; RANDOMIZED CONTROLLED-TRIAL; LIPID-LOWERING THERAPY; INTIMA-MEDIA THICKNESS; C-REACTIVE PROTEIN; MYOCARDIAL-INFARCTION; CLINICAL-TRIALS; FAMILIAL HYPERCHOLESTEROLEMIA; POSTMENOPAUSAL WOMEN; ARTERY-DISEASE AB Cardiovascular biomarker research efforts have resulted in the identification of new risk factors and novel drug targets, as well as the establishment of treatment guidelines. Government agencies, academic research institutions, diagnostic industries, and pharmaceutical companies all recognize the importance of biomarkers in advancing therapies to improve public health. In drug development, biomarkers are used to evaluate early signals of efficacy and safety, to select dose, and to identify the target population. The United States Food and Drug Administration has relied on biomarkers to support clinical applications in many therapeutic fields, including cardiovascular disease. The appropriate application of cardiovascular biomarkers requires an understanding of disease natural history, the mechanism of the intervention, and the characteristics and limitations of the biomarker. Channels of communication among researcher, developer, and regulator must remain open to maximize the success of future biomarker efforts. In 2003, 2004, and 2005, an international panel of cardiovascular biomarker experts convened at the "Cardiovascular Biomarker and Surrogate Endpoints Symposia" held in Bethesda, Md, to discuss the use of biomarkers in the development of improved cardiovascular diagnostics and therapeutics. The information presented in the present report summarizes the authors' perspective distilled from these proceedings. C1 Univ Montreal, Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada. Brigham & Womens Hosp, Boston, MA 02115 USA. US FDA, Rockville, MD 20857 USA. RP Tardif, JC (reprint author), Univ Montreal, Montreal Heart Inst, 5000 Belanger St, Montreal, PQ H1T 1C8, Canada. EM jean-claude.tardif@icm-mhi.org NR 44 TC 71 Z9 76 U1 3 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JUN 27 PY 2006 VL 113 IS 25 BP 2936 EP 2942 DI 10.1161/CIRCULATIONAHA.105.598987 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 057CG UT WOS:000238572100013 PM 16801474 ER PT J AU Nam, SH Cheng, J Mindak, WR Capar, SG AF Nam, Sang-Ho Cheng, John Mindak, William R. Capar, Stephen G. TI Preliminary results of extraction, separation and quantitation of arsenic species in food and dietary supplements by HPLC-ICP-MS SO BULLETIN OF THE KOREAN CHEMICAL SOCIETY LA English DT Article DE arsenic speciation; HPLC; ICPMS; food; dietary supplement ID PERFORMANCE LIQUID-CHROMATOGRAPHY; PLASMA-MASS SPECTROMETRY; ATOMIC-ABSORPTION-SPECTROMETRY; MICROWAVE-ASSISTED EXTRACTION; SPECIATION ANALYSIS; DIMETHYLARSINIC ACID; ION CHROMATOGRAPHY; ELECTROSPRAY MS; UNITED-STATES; HUMAN URINE AB Various extraction procedures were investigated using reference materials and samples to evaluate extraction efficiency and effectiveness. Inductively coupled plasma mass spectrometry (ICP-MS) was used to measure total arsenic and to quantitate arsenic species when coupled to an HPLC (high pressure liquid chromatography). Arsenic species were extracted from rice flour (NIST SRM 1568a) with water/methanol mixtures using accelerated solvent extraction (ASE). Total arsenic extraction efficiency ranged from 42 to 64%, for water and various methanol concentrations. From spinach (NIST SRM 1570), freeze-dried apple, and rice flour (NIST SRM 1568a), arsenic species were extracted with trifluoroacetic acid (TFA) at 100 degrees C. Total arsenic extraction efficiency was 90% for spinach, 75% for freeze-dried apple, and 83% for rice flour. Enzymatic extraction with alpha-amylase and sonication resulted in extraction efficiency of 104% for rice flour, 98% for freeze-dried apple, and 7% for spinach. Chromatograms of arsenic species extracted by the optimum extraction methods were obtained, and the species were quantified. Arsenite (As(III)), arsenate (As(V)), dimethylarsinic acid (DMA), and monomethylarsonic acid (MMA) were found in the apple sample, and DMA and As(V) in the rice flour sample. As(V) and MMA were found in three herbal dietary supplement samples. C1 Mokpo Natl Univ, Dept Chem, Choongnam 534729, South Korea. US FDA, Elemental Res Branch, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Nam, SH (reprint author), Mokpo Natl Univ, Dept Chem, Choongnam 534729, South Korea. EM shnam@mokpo.ac.kr NR 38 TC 8 Z9 8 U1 0 U2 15 PU KOREAN CHEMICAL SOC PI SEOUL PA 635-4 YEOGSAM-DONG, KANGNAM-GU, SEOUL 135-703, SOUTH KOREA SN 0253-2964 J9 B KOR CHEM SOC JI Bull. Korean Chem. Soc. PD JUN 20 PY 2006 VL 27 IS 6 BP 903 EP 908 PG 6 WC Chemistry, Multidisciplinary SC Chemistry GA 063WS UT WOS:000239051200018 ER PT J AU Mann, BS Kane, R Brave, M Ryan, Q Hazarika, M Rock, E Senderowicz, A Dagher, R Johnson, J Justice, R Pazdur, R AF Mann, B. S. Kane, R. Brave, M. Ryan, Q. Hazarika, M. Rock, E. Senderowicz, A. Dagher, R. Johnson, J. Justice, R. Pazdur, R. TI An analysis of deficiencies identified during investigational new drug (IND) application reviews by the Division of Drug Oncology Products (DDOP) of the USFDA. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 02-06, 2006 CL Atlanta, GA SP Amer Soc Clin Oncol C1 US FDA, CDER, Silver Spring, MD USA. NR 0 TC 0 Z9 0 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 JUN 20 PY 2006 VL 24 IS 18 SU S MA 6052 BP 313S EP 313S PN 1 PG 1 WC Oncology SC Oncology GA 063HN UT WOS:000239009402124 PM 27954837 ER PT J AU Ross, DB Weiss, KD Keegan, P Justice, R Pazdur, R AF Ross, D. B. Weiss, K. D. Keegan, P. Justice, R. Pazdur, R. TI Temporal trends in oncology product approvals in the United States, 1986-2005. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 02-06, 2006 CL Atlanta, GA SP Amer Soc Clin Oncol C1 US FDA, Silver Spring, MD USA. NR 0 TC 0 Z9 0 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 JUN 20 PY 2006 VL 24 IS 18 SU S BP 333S EP 333S PN 1 PG 1 WC Oncology SC Oncology GA 063HN UT WOS:000239009402203 ER PT J AU Rubinstein, DB Ziv, R Karmely, M Leitner, O Wreschner, D AF Rubinstein, D. B. Ziv, R. Karmely, M. Leitner, O. Wreschner, D. TI Immunization with MUC1/X protein enhances cDNA immunization in generating anti-MUC1 alpha/beta junction antibodies that target cancer cells. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 02-06, 2006 CL Atlanta, GA SP Amer Soc Clin Oncol C1 US FDA, Rockville, MD 20857 USA. Tel Aviv Univ, IL-69978 Tel Aviv, Israel. Weizmann Inst Sci, IL-76100 Rehovot, Israel. NR 0 TC 0 Z9 0 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 JUN 20 PY 2006 VL 24 IS 18 SU S MA 10072 BP 558S EP 558S PN 1 PG 1 WC Oncology SC Oncology GA 063HN UT WOS:000239009403526 PM 27953981 ER PT J AU Sauder, CJ Vandenburgh, KM Iskow, RC Malik, T Carbone, KM Rubin, SA AF Sauder, CJ Vandenburgh, KM Iskow, RC Malik, T Carbone, KM Rubin, SA TI Changes in mumps virus neurovirulence phenotype associated with quasispecies heterogeneity SO VIROLOGY LA English DT Article DE mumps virus; vaccine; Urabe AM9; central nervous system; neurovirulence; neuroattenuation; quasispecies; rat model; genetic heterogeneity ID HEMAGGLUTININ-NEURAMINIDASE GENE; NEWCASTLE-DISEASE-VIRUS; PARAMYXOVIRUS FUSION PROTEIN; MYELITIS FOLLOWING MUMPS; URABE VACCINE STRAIN; NUCLEOTIDE-SEQUENCE; POSITION 1081; AQUEDUCTAL STENOSIS; ENVELOPE PROTEIN; P-GENE AB Mumps vir-us is a highly neurotropic virus with evidence of central nervous system invasion (CNS) in approximately half of all cases of infection. In countries where live attenuated mumps virus vaccines were introduced, the number of mumps cases declined dramatically; however, recently, the safety of some vaccine strains has been questioned. For example, one of the most widely used vaccines, the Urabe AM9 strain, was causally associated with meningitis, leading to the withdrawal of this product from the market in several countries. This highlights the need for a better understanding of the attenuation process and the identification of markers of attenuation. To this end, we further attenuated the Urabe AM9 strain by serial passage in cell culture and compared the complete nucleotide sequences of the parental and passaged viruses. Interestingly, despite a dramatic decrease in virus virulence (as assayed in rats), the only genomic changes were in the form of changes in the level of genetic heterogeneity at specific genome sites, i.e., either selection of one nucleotide variant at positions where the starting material exhibited nucleotide heterogeneity or the evolution of an additional nucleotide to create a heterogenic site. This finding suggests that changes in the level of genetic heterogeneity at specific genome sites can have profound neurovirulence phenotypic consequences and, therefore, caution should be exercised when evaluating genetic markers of virulence or attenuation based only on a consensus sequence. Published by Elsevier C1 US FDA, Ctr Biol Evaluat & Res, DVP, Off Vaccines Res & Review, Bethesda, MD 20892 USA. RP Rubin, SA (reprint author), US FDA, Ctr Biol Evaluat & Res, DVP, Off Vaccines Res & Review, Bldg 29A,Room 1A-21,8800 Rockville Pike, Bethesda, MD 20892 USA. EM rubins@cber.fda.gov NR 52 TC 35 Z9 34 U1 1 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD JUN 20 PY 2006 VL 350 IS 1 BP 48 EP 57 DI 10.1016/j.virol.2006.01.035 PG 10 WC Virology SC Virology GA 056YV UT WOS:000238561900005 PM 16494912 ER PT J AU Drum, B AF Drum, B TI Federal regulation of vision enhancement devices for normal and abnormal vision SO JOURNAL OF MODERN OPTICS LA English DT Article; Proceedings Paper CT Biennial Conference on Development in Vision Enhancement Technology and Their Evaluation CY JUN 03-04, 2005 CL West Virginia Univ, Morgantown, WV SP Natl Sci Fdn, USA Res Off, Natl Aeronaut & Space Adm, West Virginia Univ Eye Inst HO West Virginia Univ AB The Food and Drug Administration (FDA) evaluates the safety and effectiveness of medical devices and biological products as well as food and drugs. The FDA defines a device as a product that is intended, by physical means, to diagnose, treat, or prevent disease, or to affect the structure or function of the body. All vision enhancement devices fulfill this definition because they are intended to affect a function ( vision) of the body. In practice, however, FDA historically has drawn a distinction between devices that are intended to enhance low vision as opposed to normal vision. Most low vision aids are therapeutic devices intended to compensate for visual impairment, and are actively regulated according to their level of risk to the patient. The risk level is usually low (e. g. Class I, exempt from 510(k) submission requirements for magnifiers that do not touch the eye), but can be as high as Class III (requiring a clinical trial and Premarket Approval (PMA) application) for certain implanted and prosthetic devices (e. g. intraocular telescopes and prosthetic retinal implants). In contrast, the FDA usually does not actively enforce its regulations for devices that are intended to enhance normal vision, are low risk, and do not have a medical intended use. However, if an implanted or prosthetic device were developed for enhancing normal vision, the FDA would likely decide to regulate it actively, because its intended use would entail a substantial medical risk to the user. Companies developing such devices should contact the FDA at an early stage to clarify their regulatory status. C1 US FDA, Div Ophthalm & Ear Nose & Throat Devices, Rockville, MD 20850 USA. RP Drum, B (reprint author), US FDA, Div Ophthalm & Ear Nose & Throat Devices, 9200 Corp Blvd, Rockville, MD 20850 USA. EM bruce.drum@fda.hhs.gov NR 1 TC 0 Z9 0 U1 0 U2 1 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0950-0340 J9 J MOD OPTIC JI J. Mod. Opt. PD JUN 15 PY 2006 VL 53 IS 9 BP 1215 EP 1228 DI 10.1080/09800340600618363 PG 14 WC Optics SC Optics GA 048IA UT WOS:000237939600005 ER PT J AU Anand, SS Philip, BK Palkar, PS Mumtaz, MM Latendresse, JR Mehendale, HM AF Anand, SS Philip, BK Palkar, PS Mumtaz, MM Latendresse, JR Mehendale, HM TI Adaptive tolerance in mice upon subchronic exposure to chloroform: Increased exhalation and target tissue regeneration SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE chloroform; exhalation; kidney; liver; tissue repair; tolerance; toxicity ID MALE B6C3F(1) MICE; CELL-PROLIFERATION; PREDICTIVE TOXICOLOGY; INDUCED CYTOTOXICITY; LIVER-REGENERATION; BINARY-MIXTURE; BDF1 MICE; F344 RATS; CORN-OIL; REPAIR AB The aims of the present study were to characterize the subchronic toxicity of chloroform by measuring tissue injury, repair, and distribution of chloroform and to assess the reasons for the development of tolerance to subchronic chloroform toxicity. Male Swiss Webster (SW) mice were given three dose levels of chloroform (150, 225, and 300 mg/kg/day) by gavage in aqueous vehicle for 30 days. Liver and kidney injury were measured by plasma ALT and BUN, respectively, and by histopathology. Tissue regeneration was assessed by 3 H-thymidine incorporation into hepato- and nephro-nuclear DNA and by proliferating cell nuclear antigen staining. In addition, GSH and CYP2E1 in liver and kidney were assessed at selected time points. The levels of chloroform were measured in blood, liver, and kidney during the dosing regimen (1, 7, 14, and 30 days). Kidney injury was evident after I day with all three doses and sustained until 7 days followed by complete recovery. Mild to moderate liver injury was observed from I to 14 days with all three dose levels followed by gradual decrease. Significantly higher regenerative response was evident in liver and kidney at 7 days, but the response was robust in kidney, preventing progression of injury beyond first week of exposure. While the kidney regeneration reached basal levels by 21 days, moderate liver regeneration with two higher doses sustained through the end of the dosing regimen and 3 days after that. Following repeated exposure for 7, 14, and 30 days, the blood and tissue levels of chloroform were substantially lower with all three dose levels compared to the levels observed with single exposure. Increased exhalation of 14 C-chloroform after repeated exposures explains the decreased chloroform levels in circulation and tissues. These results suggest that toxicokinetics and toxicodynamics (tissue regeneration) contribute to the tolerance observed in SW mice to subchronic chloroform toxicity. Neither bioactivation nor detoxification appears to play a decisive role in the development of this tolerance. (c) 2006 Elsevier Inc. All rights reserved. C1 Univ Louisiana Monroe, Coll Pharm, Dept Toxicol, Monroe, LA 71209 USA. ATSDR, Dept Hlth & Human Serv, Atlanta, GA 30333 USA. Natl Ctr Toxicol Res, Toxicol Pathol Associates, Jefferson, AR 72079 USA. RP Mehendale, HM (reprint author), Univ Louisiana Monroe, Coll Pharm, Dept Toxicol, 700 Univ Ave,Sugar Hall 306, Monroe, LA 71209 USA. EM sanand@rx.uga.edu; mehendale@ulm.edu RI Latendresse, John/A-9215-2009 FU PHS HHS [U61/ATU681482] NR 39 TC 9 Z9 9 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD JUN 15 PY 2006 VL 213 IS 3 BP 267 EP 281 DI 10.1016/j.taap.2006.02.007 PG 15 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 054WQ UT WOS:000238409700009 PM 16630638 ER PT J AU Soud, F AF Soud, F CA Food & Drug Adm Arizona State Hlth Dept New Jersey Dept Hlth & Senior Serv New York State Dept Hlth Columbia City Hlth Dept Penn Dept Hlth Natl Ctr Infect Dis TI Update: Guillain-Barre syndrome among recipients of Menactra (R) meningococcal conjugate vaccine - United States, October 2005-February 2006 (Reprinted from MMWR, vol 55, pg 364-366, 2006) SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Reprint C1 US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. Arizona State Hlth Dept, Phoenix, AZ USA. New Jersey Dept Hlth & Senior Serv, Trenton, NJ 08625 USA. New York State Dept Hlth, Albany, NY 12237 USA. Columbus City Hlth Dept, Columbus, OH USA. Penn Dept Hlth, Harrisburg, PA 17108 USA. CDC, Immunizat Safety Off, Natl Immunizat Program, Atlanta, GA 30333 USA. CDC, Natl Ctr Infect Dis, Atlanta, GA 30333 USA. RP Soud, F (reprint author), US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUN 14 PY 2006 VL 295 IS 22 BP 2596 EP 2597 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 052HI UT WOS:000238224000011 ER PT J AU Zhang, P Yu, MYW Venable, R Alter, HJ Shih, JWK AF Zhang, P Yu, MYW Venable, R Alter, HJ Shih, JWK TI Neutralization epitope responsible for the hepatitis B virus subtype-specific protection in chimpanzees SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE hepatitis B surface antigen; neutralizing antibody ID HUMAN MONOCLONAL-ANTIBODIES; SURFACE-ANTIGEN; IMMUNE GLOBULIN; PHYLOGENETIC RELATEDNESS; TUPAIA HEPATOCYTES; ATTACHMENT SITE; PRE-S(2) REGION; INFECTION; GENOTYPES; VACCINE AB Neutralizing monoclonal antibody (BX-182) directed against the d determinant of hepatitis B virus (HBV) surface antigen protected chimpanzees from infection by HBV subtype adw but not by subtype ayw, as demonstrated by intravenously inoculating a mixture of the antibody with the respective subtype of the virus. To elucidate the mechanism underlying the subtype-specific protection, a combinatorial approach of screening random peptide phage libraries, bioinformatics, and structure analysis was used in this study to identify the neutralization epitope responsible for the observed protection. The epitope was mapped at the N terminus of the pre-S1 region of the hepatitis B surface antigen between residues 17 and 21, of which the residues Val-18/Pro-19 were critical for antibody binding. Alignment of amino acid sequences derived from diverse genetic variants of HBV revealed that the epitope was present in ad subtypes and in their corresponding genotypes A, B, C, F, and H. By contrast, this epitope was not found in a majority of ay subtypes or in genotypes D, E, and G, where the antigenic residues Val-18/Pro-19 within the epitope were replaced by Thr/Ser, Thr/Thr, or Ala/Ser, respectively, resulting in a drastic conformational change of the epitope. These data indicate that, by binding discriminately to the subtype "d" epitope in the pre-S1 region, neutralizing antibody BX-182 protects chimpanzees from HBV infection in a subtype-specific manner, suggesting a potential escape mechanism for HBV genetic variants. C1 NIH, Warren Grant Magnuson Clin Ctr, Dept Transfus Med, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Hematol, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Biophys Lab, Bethesda, MD 20892 USA. RP Zhang, P (reprint author), NIH, Warren Grant Magnuson Clin Ctr, Dept Transfus Med, Bethesda, MD 20892 USA. EM pei.zhang@fda.hhs.gov NR 44 TC 12 Z9 12 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 13 PY 2006 VL 103 IS 24 BP 9214 EP 9219 DI 10.1073/pnas.0603316103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 054ID UT WOS:000238369100057 PM 16757558 ER PT J AU Tuo, JS Ning, BT Bojanowski, CM Lin, ZN Ross, RJ Reed, GF Shen, DF Jiao, XD Zhou, M Chew, EY Kadlubar, FF Chan, CC AF Tuo, JS Ning, BT Bojanowski, CM Lin, ZN Ross, RJ Reed, GF Shen, DF Jiao, XD Zhou, M Chew, EY Kadlubar, FF Chan, CC TI Synergic effect of polymorphisms in ERCC6 5 ' flanking region and complement factor H on age-related macular degeneration predisposition SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE Cockayne syndrome; single nucleoticle polymorphism; gene regulation; interaction; DNA repair ID BASE EXCISION-REPAIR; COCKAYNE-SYNDROME; EYE DISEASE; TRANSCRIPTION ELONGATION; FAMILIAL AGGREGATION; OXIDATIVE STRESS; RISK-FACTORS; DNA-REPAIR; MACULOPATHY; OVEREXPRESSION AB This study investigates age-related macular degeneration (AMD) genetic risk factors through identification of a functional single-nucleotide polymorphism (SNP) and its disease association. We chose ERCC6 because of its roles in the aging process, DNA repair, and ocular degeneration from the gene disruption. Bioinformatics indicated a putative binding-element alteration on the sequence containing C-6530 > G SNP in the 5 ' flanking region of ERCC6 from Sp1 on the C allele to SP1, GATA-1, and OCT-1 on the G allele. Electrophoretic mobility shift assays displayed distinctive C and G allele-binding patterns to nuclear proteins. Luciferase expression was higher in the vector construct containing the G allele than that containing the C allele. A cohort of 460 advanced AMD cases and 269 age-matched controls was examined along with pathologically diagnosed 57 AMD and 18 age-matched non-AMD archived cases. ERCC6 C-6530 > G was associated with AMD susceptibility, both independently and through interaction with an SNP (rs380390) in the complement factor H (CFH) intron reported to be highly associated with AMD. A disease odds ratio of 23 was conferred by homozygozity for risk alleles at both ERCC6 and CFH compared with homozygozity for nonrisk alleles. Enhanced ERCC6 expression was observed in lymphocytes from healthy donors bearing ERCC6 C-6530 > G alleles. Intense immunostaining of ERCC6 was also found in AMD eyes from ERCC6 C-6530 > G carriers. The strong AMD predisposition conferred by the ERCC6 and CFH SNPs may result from biological epistasis, because ERCC6 functions in universal transcription as a component of RNA pol I transcription complex. C1 NEI, Immunol Lab, Sect Immunopathol, NIH, Bethesda, MD 20892 USA. NEI, Div Epidemiol & Clin Res, NIH, Bethesda, MD 20892 USA. NEI, Opthtalm Genet & Visual Funct Branch, Sect Ophthalm Mol Genet, Bethesda, MD 20892 USA. Natl Ctr Toxicol Res, Div Phamacogenom & Mol Epidemiol, Jefferson, AR 72079 USA. RP Chan, CC (reprint author), NEI, Immunol Lab, Sect Immunopathol, NIH, 10-10N103,10 Ctr Dr, Bethesda, MD 20892 USA. EM chanc@nei.nih.gov OI Tuo, Jingsheng/0000-0002-1372-7810 FU Intramural NIH HHS [Z99 EY999999] NR 49 TC 71 Z9 75 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 JUN 13 PY 2006 VL 103 IS 24 BP 9256 EP 9261 DI 10.1073/pnas.0603485103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 054ID UT WOS:000238369100064 PM 16754848 ER PT J AU Borrow, R Carlone, GM Rosenstein, N Plikaytis, B Blake, M Feavers, I Martin, D Zollinger, W Robbins, J Aaberge, I Granoff, DM Miller, E van Alphen, L Poolman, J Rappuoli, R Danzig, L Hackell, J Danve, B Caulfield, M Lambert, S Stephens, D AF Borrow, R. Carlone, G. M. Rosenstein, N. Plikaytis, B. Blake, M. Feavers, I. Martin, D. Zollinger, W. Robbins, J. Aaberge, I. Granoff, D. M. Miller, E. van Alphen, L. Poolman, J. Rappuoli, R. Danzig, L. Hackell, J. Danve, B. Caulfield, M. Lambert, S. Stephens, D. TI Neisseria meningitidis group B correlates of protection and assay standardization - International meeting report Emory University, Atlanta, Georgia, United States, 16-17 march 2005 SO VACCINE LA English DT Editorial Material ID INFLUENZAE TYPE-B; MEMBRANE-VESICLE VACCINE; ESCHERICHIA-COLI K1; SERUM BACTERICIDAL ACTIVITY; TOXOID CONJUGATE VACCINE; MENINGOCOCCAL SEROGROUP-B; GROUP-C; CAPSULAR POLYSACCHARIDE; STATISTICAL CONSIDERATIONS; MONOCLONAL-ANTIBODY C1 Manchester Royal Infirm, Vaccine Evaluat Unit, Hlth Protect Agcy, Manchester M13 9WZ, Lancs, England. Ctr Dis Control & Prevent, Atlanta, GA USA. US FDA, Bethesda, MD 20014 USA. Natl Inst Biol Stand & Controls, Potters Bar EN6 3QG, Herts, England. Inst Environm Sci, Porirua, New Zealand. Walter Reed Army Inst Res, Washington, DC USA. NICHHD, NIH, Bethesda, MD 20892 USA. Norwegian Inst Publ Hlth, NO-0403 Oslo, Norway. Childrens Hosp Oakland, Res Inst, Oakland, CA 94660 USA. Hlth Protect Agcy Ctr Infect, London NW9 5EQ, England. Netherlands Vaccine Inst, NL-3720 AL Bilthoven, Netherlands. GlaxoSmithKline Biol, Rixensart, Belgium. Chiron Vaccines, Siena, Italy. Chiron Vaccines, Emeryville, CA 94608 USA. Wyeth Vaccines, Pearl River, NY 10965 USA. Sanofi Pasteur, F-69280 Marcy Letoile, France. Merck & Co Inc, West Point, PA 19486 USA. WHO, CH-1211 Geneva 27, Switzerland. Emory Univ, Dept Med, Atlanta, GA 30322 USA. RP Borrow, R (reprint author), Manchester Med Microbiol Partnership, Meningococcal Reference Unit, Hlth Protect Agcy N W, Manchester Lab,Manchester Royal Infirm, POB 209,Clin Sci Bldg, Manchester M13 9WZ, Lancs, England. EM ray.borrow@hpa.org.uk RI Zollinger, Wendell/B-2887-2011 NR 101 TC 98 Z9 101 U1 0 U2 5 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD JUN 12 PY 2006 VL 24 IS 24 BP 5093 EP 5107 DI 10.1016/j.vaccine.2006.03.091 PG 15 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 058BD UT WOS:000238638200001 PM 16838413 ER PT J AU Laessig, KA Lewis, LL Hammerstrom, TS AF Laessig, KA Lewis, LL Hammerstrom, TS TI Tenofovir DF and emtricitabine vs. zidovudine and lamivudine SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 US FDA, Silver Spring, MD 20993 USA. RP Laessig, KA (reprint author), US FDA, Silver Spring, MD 20993 USA. EM katherine.laessig@fda.hhs.gov NR 3 TC 4 Z9 5 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 8 PY 2006 VL 354 IS 23 BP 2506 EP 2507 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 050PQ UT WOS:000238100800020 PM 16760455 ER PT J AU Nazzal, S Khan, MA AF Nazzal, S Khan, MA TI Controlled release of a self-emulsifying formulation from a tablet dosage form: Stability assessment and optimization of some processing parameters SO INTERNATIONAL JOURNAL OF PHARMACEUTICS LA English DT Article DE self-emulsified drug delivery system; coenzyme Q(10); optimization; controlled release; face-centered cubic design; stability ID DRUG-DELIVERY SYSTEMS; PARTICLE-SIZE; PHYSICOCHEMICAL ASPECTS; MAGNESIUM STEARATE; DIRECT COMPRESSION; CYCLOSPORINE-A; DISSOLUTION; DISPERSION; POWDER; UBIQUINONE AB The objective of this study was to evaluate the effect of some processing parameters on the release of lipid formulation from a tablet dosage form. A 17-run, face-centered cubic design was employed to evaluate the effect of colloidal silicates (XI), magnesium stearate mixing time (X-2), and compression force (X-3) on flow, hardness, and dissolution of Coenzyme Q(10) (CoQ(10)) lipid formulation from a tablet dosage form. The optimized formulation was subsequently subjected to a short-term accelerated stability study. All preparations had a flowability index values ranging from 77 to 90. The cumulative percent of CoQ10 released within 8 It (Y-5) ranged from 40.6% to 90% and was expressed by the following polynomial equation: Y-5 = 49.78 - 16.36X(1) + 2-90X(2) - 3.11X(3) - 0.37X(1)X(2) + 1.06X(1)X(3) - 1.02X(2)X(3) + 11.98X(2)(1) + 10.63 X-2(2) - 7.10X(3)(2). When stored at 4 degrees C, dissolution rates were retained for up to 3 months. Storage at higher temperatures, however, accelerated lipid release and caused leakage, and loss of hardness. Processing parameters have a profound effect on the release of lipid formulations from their solid carriers. While optimized controlled release formulations could be attained, further considerations should be made to prepare "liquisolids" that are physically stable at higher storage temperatures. (c) 2006 Elsevier B.V. All rights reserved. C1 NE Louisiana Univ, Dept Basic Pharmaceut Sci, Coll Pharm, Monroe, LA 71209 USA. Fed Res Ctr, Div Prod Qualit Res Food & Drug Adm, Silver Spring, MD USA. RP Nazzal, S (reprint author), NE Louisiana Univ, Dept Basic Pharmaceut Sci, Coll Pharm, 700 Univ Ave, Monroe, LA 71209 USA. EM nazzal@ulm.edu NR 39 TC 59 Z9 62 U1 4 U2 12 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 JUN 6 PY 2006 VL 315 IS 1-2 BP 110 EP 121 DI 10.1016/j.ijpharm.2006.02.019 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 050RR UT WOS:000238106100013 PM 16563673 ER PT J AU Bright, RA Shen, J AF Bright, R. A. Shen, J. TI Use of a free, publicly-accessible data source to estimate hospitalizations related to adverse medical device events. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 2nd North American Congress of Epidemiology CY JUN 21-24, 2006 CL Seattle, WA C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. RI Bright, Roselie/D-2240-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2006 VL 163 IS 11 SU S BP S188 EP S188 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 051AP UT WOS:000238132901230 ER PT J AU Bright, RA AF Bright, R. A. TI Quantifying the threat to public health posed by adverse medical device events. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 2nd North American Congress of Epidemiology CY JUN 21-24, 2006 CL Seattle, WA C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. RI Bright, Roselie/D-2240-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2006 VL 163 IS 11 SU S BP S171 EP S171 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 051AP UT WOS:000238132901163 ER PT J AU Cope, JU AF Cope, J. U. TI Special considerations of medical device use in children, birth to 21. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 2nd North American Congress of Epidemiology CY JUN 21-24, 2006 CL Seattle, WA C1 US FDA, Rockville, MD 20850 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2006 VL 163 IS 11 SU S BP S171 EP S171 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 051AP UT WOS:000238132901164 ER PT J AU Duggirala, H Kandzari, D Gross, T AF Duggirala, H. Kandzari, D. Gross, T. TI Postmarket surveillance of drug-eluting stents. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 2nd North American Congress of Epidemiology CY JUN 21-24, 2006 CL Seattle, WA C1 US FDA, Rockville, MD 20850 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2006 VL 163 IS 11 SU S BP S172 EP S172 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 051AP UT WOS:000238132901165 ER PT J AU Graham, D AF Graham, D. TI Epidemiology and public policy advocacy-when lives hang in the balance. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 2nd North American Congress of Epidemiology CY JUN 21-24, 2006 CL Seattle, WA C1 US FDA, Rockville, MD 20857 USA. NR 0 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 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2006 VL 163 IS 11 SU S BP S168 EP S168 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 051AP UT WOS:000238132901151 ER PT J AU Hefflin, B Gross, T Schroeder, T AF Hefflin, B. Gross, T. Schroeder, T. TI Estimates of medical device-associated adverse events. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 2nd North American Congress of Epidemiology CY JUN 21-24, 2006 CL Seattle, WA C1 US FDA, Rockville, MD 20850 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2006 VL 163 IS 11 SU S BP S171 EP S171 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 051AP UT WOS:000238132901162 ER PT J AU Kaplan, S Staffa, J D Pan, G AF Kaplan, S. Staffa, J. D Pan, G. TI Adherence to metoclopramide duration of use recommendation: Claims data study. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 2nd North American Congress of Epidemiology CY JUN 21-24, 2006 CL Seattle, WA C1 FDA, Silver Spring, MD 20993 USA. NR 0 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 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2006 VL 163 IS 11 SU S BP S36 EP S36 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 051AP UT WOS:000238132900145 ER PT J AU Ross, M Street, D Ferguson, M Klontz, K Luccioli, S AF Ross, M. Street, D. Ferguson, M. Klontz, K. Luccioli, S. TI Emergency department visits for food allergy reactions from the national electronic injury surveillance system. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 2nd North American Congress of Epidemiology CY JUN 21-24, 2006 CL Seattle, WA C1 Ctr Food Safety & Appl Nutr, FDA, College Pk, MD 20740 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2006 VL 163 IS 11 SU S BP S21 EP S21 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 051AP UT WOS:000238132900085 ER PT J AU Tavris, DR Gallauresi, BA Deyb, S Brindis, R Mitchel, K AF Tavris, D. R. Gallauresi, B. A. Deyb, S. Brindis, R. Mitchel, K. TI Risk of local adverse events by gender following cardiac catheterization. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 2nd North American Congress of Epidemiology CY JUN 21-24, 2006 CL Seattle, WA C1 US FDA, Rockville, MD 20850 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2006 VL 163 IS 11 SU S BP S3 EP S3 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 051AP UT WOS:000238132900012 ER PT J AU Knippen, MA AF Knippen, MA TI Transfusion-related acute lung injury SO AMERICAN JOURNAL OF NURSING LA English DT Article ID TRALI C1 US FDA, Off Compliance & Biol Qual, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. RP Knippen, MA (reprint author), US FDA, Off Compliance & Biol Qual, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. EM maureen.knippen@fda.hhs.gov NR 13 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-936X J9 AM J NURS JI Am. J. Nurs. PD JUN PY 2006 VL 106 IS 6 BP 61 EP 64 PG 4 WC Nursing SC Nursing GA 048YL UT WOS:000237982400044 PM 16728851 ER PT J AU Barr, HJ Ohlhaber, T Finder, C AF Barr, HJ Ohlhaber, T Finder, C TI Focusing in on dose reduction: The FDA perspective SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Editorial Material DE dose reduction; FDA; radiation dose C1 US FDA, Ctr Devices & Radiol Hlth, Div Mammog Qual & Radiat Programs, Rockville, MD 20850 USA. RP Barr, HJ (reprint author), US FDA, Ctr Devices & Radiol Hlth, Div Mammog Qual & Radiat Programs, Piccard Dr, Rockville, MD 20850 USA. EM helen.barr@fda.hhs.gov NR 1 TC 5 Z9 6 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD JUN PY 2006 VL 186 IS 6 BP 1716 EP 1717 DI 10.2214/AJR.06.0425 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 045RI UT WOS:000237759300033 PM 16714664 ER PT J AU Karnaukhova, E Ophir, Y Golding, B AF Karnaukhova, E Ophir, Y Golding, B TI Recombinant human alpha-1 proteinase inhibitor: towards therapeutic use SO AMINO ACIDS LA English DT Review DE alpha-1-proteinase inhibitor; antitrypsin; emphysema; glycosylation; recombinant ID ACTIVE HUMAN ALPHA-1-ANTITRYPSIN; SERPIN-PROTEINASE COMPLEX; HIGH-LEVEL EXPRESSION; REACTIVE CENTER LOOP; HEREDITARY ALPHA(1)-ANTITRYPSIN DEFICIENCY; HUMAN ALPHA-1-PROTEASE INHIBITOR; SERINE-PROTEASE INHIBITORS; YEAST PICHIA-PASTORIS; ESCHERICHIA-COLI; FILAMENTOUS FUNGI AB l Human alpha-1-proteinase inhibitor is a well-characterized protease inhibitor with a wide spectrum of anti-protease activity. Its major physiological role is inhibition of neutrophil elastase in the lungs, and its deficiency is associated with progressive ultimately fatal emphysema. Currently in the US, only plasma-derived human alpha-1-proteinase inhibitor is available for augmentation therapy, which appears to be insufficient to meet the anticipated clinical demand. Moreover, despite effective viral clearance steps in the manufacturing process, the potential risk of contamination with new and unknown pathogens still exists. In response, multiple efforts to develop recombinant versions of human alpha-1-proteinase inhibitor, as an alternative to the plasma-derived protein, have been reported. Over the last two decades, various systems have been used to express the human gene for alpha-1-proteinase inhibitor. This paper reviews the recombinant versions of human alpha-1-proteinase inhibitor produced in various hosts, considers current major safety and efficacy issues regarding recombinant glycoproteins as potential therapeutics, and the factors that are impeding progress in this area(2). C1 US FDA, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Karnaukhova, E (reprint author), US FDA, Div Hematol, Ctr Biol Evaluat & Res, 8800 Rockville Pike,Natl Inst Hlth Bldg 29, Bethesda, MD 20892 USA. EM elena.karnaukhova@fda.hhs.gov NR 195 TC 37 Z9 40 U1 1 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0939-4451 J9 AMINO ACIDS JI Amino Acids PD JUN PY 2006 VL 30 IS 4 BP 317 EP 332 DI 10.1007/s00726-005-0324-4 PG 16 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 053FZ UT WOS:000238292300001 PM 16773239 ER PT J AU Farrell, AT Papadouli, I Hori, A Harczy, M Harrison, B Asakura, W Marty, M Dagher, R Pazdur, R AF Farrell, AT Papadouli, I Hori, A Harczy, M Harrison, B Asakura, W Marty, M Dagher, R Pazdur, R TI The advisory process for anticancer drug regulation: a global perspective SO ANNALS OF ONCOLOGY LA English DT Review DE advisory process; drug regulation; oncology AB Purpose: This paper summarizes the role of external advisors in oncology drug development and regulation from a global perspective. Design: Recently, representatives from the United States Food and Drug Administration, European Medicines Agency, the Japanese Pharmaceuticals and Medical Devices Agency, the Australian Therapeutic Goods Administration and Health Canada held a meeting in conjunction with the American Society of Clinical Oncology meeting. The role of external advisors in oncology drug development and regulation in each of these jurisdictions was presented and discussed. Results: All regulatory bodies described have experience with two forms of outside expertise: advice from individual experts and advice from a group of experts assembled as an advisory group. Regulatory jurisdictions use individual experts variably. In some regions, individual experts provide advice based on knowledge and experience during the drug development phase or in the planning phase for the submission of a drug registration package. In other regions, these individuals serve as external evaluators with the primary responsibility for the review of a clinical trials package submitted for drug registration. Advisory boards have been formalized in all jurisdictions discussed. Advisory boards have a role in discussing specific applications as well as broad policy issues. A common theme is a composition of a core panel of experts with augmentation by additional expertise as needed for consideration of specific scientific questions. In all jurisdictions, advisory board recommendations are not binding on the regulatory body. Conclusions: Global oncology drug development and registration involves the use of experts by regulatory authorities. The types of experts needed, the expert's role and the transparency of the advisory process reflect the individual needs in different regions. C1 US FDA, Ctr Drug Evaluat & Res, Off New Drugs, Off Oncol Drug Prod,Div Drug Oncol Prod, Silver Spring, MD 20993 USA. Hop St Louis, Paris, France. Therapeut Goods Adm, Symonston, Australia. Pharmaceut & Med Devices Agcy, Tokyo, Japan. European Med Agcy, London, England. RP Farrell, AT (reprint author), US FDA, Ctr Drug Evaluat & Res, Off New Drugs, Off Oncol Drug Prod,Div Drug Oncol Prod, 10903 New Hampshire Ave,Bldg 22,Room 2106, Silver Spring, MD 20993 USA. EM farrella@cder.fda.gov NR 5 TC 14 Z9 16 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD JUN PY 2006 VL 17 IS 6 BP 889 EP 896 DI 10.1093/annonc/mdj099 PG 8 WC Oncology SC Oncology GA 044TT UT WOS:000237696000003 PM 16357020 ER PT J AU Brinker, AD Swartz, L AF Brinker, AD Swartz, L TI Growth in clopidogrel-aspirin combination therapy SO ANNALS OF PHARMACOTHERAPY LA English DT Letter C1 US FDA, Off Drug Safety, CDER, Div Drug Risk Evaluat, Silver Spring, MD 20993 USA. RP Brinker, AD (reprint author), US FDA, Off Drug Safety, CDER, Div Drug Risk Evaluat, FDA White Oak Campus,Room 3412,Bldg 22,10903 New, Silver Spring, MD 20993 USA. EM allan.brinker@fda.hhs.gov NR 4 TC 4 Z9 4 U1 0 U2 0 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 JUN PY 2006 VL 40 IS 6 BP 1212 EP 1213 DI 10.1345/aph.1H001 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 054IF UT WOS:000238369300035 PM 16684805 ER PT J AU Schwartz, YS Dushkin, MI Vavilin, VA Melnikova, EV Khoschenko, OM Kozlov, VA Agafonov, AP Alekseev, AY Rassadkin, Y Shestapalov, AM Azaev, MS Saraev, DV Filimonov, PN Kurunov, Y Svistelnik, AV Krasnov, VA Pathak, A Derrick, SC Reynolds, RC Morris, S Blinov, VM AF Schwartz, YS Dushkin, MI Vavilin, VA Melnikova, EV Khoschenko, OM Kozlov, VA Agafonov, AP Alekseev, AY Rassadkin, Y Shestapalov, AM Azaev, MS Saraev, DV Filimonov, PN Kurunov, Y Svistelnik, AV Krasnov, VA Pathak, A Derrick, SC Reynolds, RC Morris, S Blinov, VM TI Novel conjugate of moxifloxacin and carboxymethylated glucan with enhanced activity against Mycobacterium tuberculosis SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID MACROPHAGE SCAVENGER RECEPTORS; MURINE TUBERCULOSIS; INFECTION; ATHEROSCLEROSIS; DEGRADATION; MICE AB Mycobacterium tuberculosis is an intracellular pathogen that persists within macrophages of the human host. one approach to improving the treatment of tuberculosis (TB) is the targeted delivery of antibiotics to macrophages using ligands to macrophage receptors. The moxifloxacin-conjugated dansylated carboxymethylglucan (M-DCMG) conjugate was prepared by chemically linking dansylcadaverine (D) and moxifloxacin (M) to carboxymethylglucan (CMG), a known ligand of macrophage scavenger receptors. The targeted delivery to macrophages and the antituberculosis activity of the conjugate M-DCMG were studied in vitro and in vivo. Using fluorescence microscopy, fluorimetry, and the J774 macrophage cell line, M-DCMG was shown to accumulate in macrophages through scavenger receptors in a dose-dependent (I to 50 mu g/ml) manner. After intravenous administration of M-DCMG into C57BL/6 mice, the fluorescent conjugate was concentrated in the macrophages of the lungs and spleen. Analyses of the pharmacokinetics of the conjugate demonstrated that M-DCMG was more rapidly accumulated and more persistent in tissues than free moxifloxacin. Importantly, therapeutic studies of mycobacterial growth in C57BL/6 mice showed that the M-DCMG conjugate was significantly more potent than free moxifloxacin. C1 US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RAMS, SD, Inst Clin Immunol, Novosibirsk, Russia. Russian Minist Publ Hlth, State Res Ctr Virol & Biotechnol Vector, Koltsov, Novosibirsk, Russia. Russian Minist Publ Hlth, Novosibirsk Inst TB, Novosibirsk, Russia. So Res Inst, Birmingham, AL 35255 USA. RP Morris, S (reprint author), US FDA, Ctr Biol Evaluat & Res, Bldg 29,Room 502,29 Lincoln Dr, Bethesda, MD 20892 USA. EM morris@cber.fda.gov RI Vavilin, Valentin/K-6100-2012; Alekseev, Alexander/C-4998-2011; Kozlov, Vladimir/K-2634-2014; Filimonov, Pavel/N-2431-2014; Krasnov, Vladimir/L-5582-2014; Schwartz, Yakov/G-3006-2014; OI Vavivilin, Valentin/0000-0002-9769-6512; Agafonov, Alexander/0000-0003-2577-0434; Alekseev, Alexander/0000-0003-0015-9305; Kozlov, Vladimir/0000-0002-1756-1782; Filimonov, Pavel/0000-0002-5786-9319; Krasnov, Vladimir/0000-0002-5200-3057; Schwartz, Yakov/0000-0002-3036-9795; Pathak, Ashish/0000-0003-0143-7979 NR 25 TC 8 Z9 15 U1 4 U2 8 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD JUN PY 2006 VL 50 IS 6 BP 1982 EP 1988 DI 10.1128/AAC.00362-05 PG 7 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 048FE UT WOS:000237932200011 PM 16723555 ER PT J AU Ferguson, SA Siitonen, PH Cisneros, FJ Gough, B Young, JF AF Ferguson, SA Siitonen, PH Cisneros, FJ Gough, B Young, JF TI Steady state pharmacokinetics of oral treatment with 13-cis-retinoic acid or all-trans-retinoic acid in male and female adult rats SO BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY LA English DT Article ID ISOTRETINOIN THERAPY; METABOLISM; DEPRESSION; ACNE; PHARMACODYNAMICS; MANAGEMENT; KINETICS; SUICIDE; PROTEIN; PLASMA AB Male and female Sprague-Dawley rats were orally gavaged with 13-cis-retinoic acid (7.5 or 15 mg/kg) or all-trans-retinoic acid (10 or 15 mg/kg) for 7 consecutive days. Blood was collected out to 8 hr after the last gavage on day 7. HPLC serum concentrations of 13-cis-retinoic acid, all-trans-retinoic acid, and 13-cis-4-oxo-retinoic acid were subjected to model independent pharmacokinetic analyses. Peak serum levels of 563 to 1640 ng/ml were observed for rats treated with 13-cis-retinoic acid at 1.5-2 hr after gavage. Peak serum levels of 183 to 267 ng/ml at 1.5 hr after gavage were observed for all-trans-retinoic acids. The elimination half-life of 13-cis-retinoic acid was about 1.5 hr while the elimination half-life of all-trans-retinoic acid was slightly longer. There were no sex differences for any parameter. Serum levels resulting from the 7.5 mg/kg 13-cis-retinoic acid were similar to those of human Accutane((R)) users. C1 US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. US FDA, Div Biometry & Risk Assessment, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Ferguson, SA (reprint author), US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, HFT 132,3900 NCTR Rd, Jefferson, AR 72079 USA. EM sferguson@nctr.fda.gov NR 31 TC 14 Z9 14 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1742-7835 J9 BASIC CLIN PHARMACOL JI Basic Clin. Pharmacol. Toxicol. PD JUN PY 2006 VL 98 IS 6 BP 582 EP 587 DI 10.1111/j.1742-7843.2006.pto_359.x PG 6 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 049AA UT WOS:000237986500009 PM 16700821 ER PT J AU Tang, X Morris, SL Langone, JJ Bockstahler, LE AF Tang, X Morris, SL Langone, JJ Bockstahler, LE TI Simple and effective method for generating single-stranded DNA targets and probes SO BIOTECHNIQUES LA English DT Article ID POLYMERASE CHAIN-REACTION; BASE STACKING HYBRIDIZATION; OLIGONUCLEOTIDE MICROARRAYS; ASYMMETRIC PCR; TRANSCRIPTION; MUTATIONS; GATA-2 AB A simple and efficient PCR method vas developed for generating dye- or radiolabeled single-stranded DNA targets or probes used for hybridization studies. The method involved the use of a pair of long primers with high annealing temperatures and a short, labeled primer with a low annealing temperature in a PCR consisting of two cycles at different temperatures. We used this method to generate dye Ct (TM) 5-labeled and [(32)p]-radiolabeled single-stranded DNA tat-gets and probes. These labeled probes were used successfully for the microarray identification of point mutations in Mycobacterium tuberculosis genes and for the Northern blot detection of expression changes of the GATA-2 gene in Pneumocystis carinii-infected rat lungs. C1 US FDA, Div Biol, Silver Spring, MD 20903 USA. RP Tang, X (reprint author), US FDA, Div Biol, 10903 New Hampshire Ave,Rm 3033, Silver Spring, MD 20903 USA. EM xxt4@cdrh.fda.gov NR 22 TC 5 Z9 5 U1 5 U2 11 PU EATON PUBLISHING CO PI WESTBOROUGH PA ONE RESEARCH DRIVE, SUITE 400A, PO BOX 1070, WESTBOROUGH, MA 01581-6070 USA SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD JUN PY 2006 VL 40 IS 6 BP 759 EP 763 DI 10.2144/000112154 PG 5 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 051RR UT WOS:000238178900017 PM 16774119 ER PT J AU Manigold, T Shin, EC Mizukoshi, E Mihalik, K Murthy, KK Rice, CM Piccirillo, CA Rehermann, B AF Manigold, T Shin, EC Mizukoshi, E Mihalik, K Murthy, KK Rice, CM Piccirillo, CA Rehermann, B TI Foxp3(+)CD4(+)CD25(+) T cells control virus-specific memory T cells in chimpanzees that recovered from hepatitis C SO BLOOD LA English DT Article ID CELLULAR IMMUNE-RESPONSES; IN-VITRO PROLIFERATION; REGULATORY CELLS; VIRAL CLEARANCE; INFECTION; ACTIVATION; ANTIGEN; CD4(+); PERSISTENCE; LYMPHOCYTES AB Hepatitis C virus (HCV) poses a global health problem because it readily establishes persistent infection and a vaccine is not available. CD4(+)CD25(+) T cells have been implicated in HCV persistence because their frequency is increased in the blood of HCV-infected patients and their in vitro depletion results in increased IFN-gamma production by HCV-specific T cells. Studying a well-characterized cohort of 16 chimpanzees, the sole animal model for HCV infection, we here demonstrate that the frequency of Foxp3(+)CD4(+)CD25(+) regulatory T cells (T-Regs) and the extent of suppression was as high in spontaneously HCV-recovered chimpanzees as in persistently HCV-Infected chimpanzees. Foxp3(+)CD4(+)CD25(+) T-Regs, suppressed IFN-gamma production, expansion, and activation-induced cell death of HCV-specific T cells after recovery from HCV infection and in persistent HCV infection. Thus, T-Reg cells control HCV-specific T cells not only in persistent infection but also after recovery, where they may regulate memory T-cell responses by controlling their activation and preventing apoptosis. However, Foxp3+CD4+CD25+ TReg cells of both HCV-recovered and HCV-infected chimpanzees differed from Foxp3(+)CD4(+)CD25(+)TReg cells of HCV-naive chimpanzees in increased IL-2 responsiveness and lower T-cell receptor excision circle content, implying a history of in vivo proliferation. This result suggests that HCV infection alters the population of Foxp3+CD4+CD25+ TReg cells. C1 NIDDK, Immunol Sect, Liver Dis Branch, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Lab Hepatitis Viruses, Bethesda, MD 20014 USA. SW Fdn Biomed Res, Dept Virol & Immunol, San Antonio, TX 78284 USA. Rockefeller Univ, Ctr Study Hepatitis C, New York, NY 10021 USA. NIH, Immunol Lab, Bethesda, MD USA. McGill Univ, Dept Microbiol & Immunol, Montreal, PQ, Canada. RP Rehermann, B (reprint author), NIDDK, Immunol Sect, Liver Dis Branch, NIH, 10 Ctr Dr,Rm 9B16, Bethesda, MD 20892 USA. EM rehermann@nih.gov RI Shin, Eui-Cheol/C-1690-2011 FU Intramural NIH HHS; NCI NIH HHS [CA85883] NR 55 TC 84 Z9 91 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JUN 1 PY 2006 VL 107 IS 11 BP 4424 EP 4432 DI 10.1182/blood-2005-09-3903 PG 9 WC Hematology SC Hematology GA 047KD UT WOS:000237877300038 PM 16478885 ER PT J AU Mohan, J Dement-Brown, J Maier, S Ise, T Kempkes, B Tolnay, M AF Mohan, J Dement-Brown, J Maier, S Ise, T Kempkes, B Tolnay, M TI Epstein-Barr virus nuclear antigen 2 induces FcRH5 expression through CBF1 SO BLOOD LA English DT Article ID HAIRY-CELL LEUKEMIA; FC-RECEPTOR HOMOLOGS; LATENT MEMBRANE-PROTEIN; SIGNAL-BINDING-PROTEIN; MEMORY B-CELLS; J-KAPPA; BURKITTS-LYMPHOMA; GENE-EXPRESSION; UP-REGULATION; IN-VIVO AB Fc-receptor homolog 5 (FcRH5) is a recently identified B-cell membrane protein of unknown function. In Burkitt lymphoma cell lines with chromosome 1q21 abnormalities, FcRH5 expression is deregulated, implicating FcRH5 in lymphomagenesis. Epstein-Barr virus infects and immortalizes B cells, and is implicated in the etiology of several tumors of B-cell origin. Overexpression of genes located on 1q21-25 has been proposed as a surrogate for Epstein-Barr virus in Burkitt lymphoma. We now report that Epstein-Barr virus nuclear antigen 2 (EBNA2) markedly induces the expression of the FcRH5 gene, encoded on chromosome 1q21. Induction occurred in the absence of other viral proteins and did not require de novo protein synthesis. EBNA2 lacks a DNA-binding domain and can target responsive genes through the host DNA binding protein CBF1. We show that induction of FcRH5 by EBNA2 is strictly CBF1 dependent, as it was abolished in CBF1-deficient cells. Accordingly, EBNA2 targeted CBF1 binding sites present in the FcRH5 promoter in vivo, as detected by chromatin immunoprecipitation. These results identify FcRH5 as a novel, direct target of EBNA2 that may contribute to the development of Epstein-Barr virus-associated tumors. C1 US FDA, Ctr Drug Evaluat & Res, Div Monoclonal Antibodies, Rockville, MD 20857 USA. Natl Res Ctr Environm & Hlth, Inst Clin Mol Biol, Munich, Germany. NCI, Mol Biol Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Tolnay, M (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Monoclonal Antibodies, HFD-123,5600 Fishers Lane, Rockville, MD 20857 USA. EM mate.tolnay@fda.hhs.gov RI Kempkes, Bettina/B-3322-2013 NR 59 TC 15 Z9 16 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 JUN 1 PY 2006 VL 107 IS 11 BP 4433 EP 4439 DI 10.1182/blood-2005-09-3815 PG 7 WC Hematology SC Hematology GA 047KD UT WOS:000237877300039 PM 16439682 ER PT J AU Ahn, JY Nowell, S McCann, SE Yu, JH Carter, L Lang, NP Kadlubar, FF Ratnasinghe, LD Ambrosone, CB AF Ahn, Jiyoung Nowell, Susan McCann, Susan E. Yu, Jihnhee Carter, Lisa Lang, Nicholas P. Kadlubar, Fred F. Ratnasinghe, Luke D. Ambrosone, Christine B. TI Associations between catalase phenotype and genotype: Modification by epidemiologic factors SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID PROMOTER REGION; LIPID-PEROXIDATION; PROSTATE-CANCER; BREAST-CANCER; GENE; POLYMORPHISM; SUSCEPTIBILITY; ANTIOXIDANTS; BIOMARKER; OXIDANTS AB Catalase is an endogenous antioxidant enzyme that neutralizes hydrogen peroxide and is induced by oxidative challenge. A -262C -> T polymorphism in the promoter region of the gene (CAT) is associated with risk of several conditions related to oxidative stress. We sought to determine the functional effects of the CAT polymorphism on enzyme activity in erythrocytes and the potential modifying effects of demographic and lifestyle factors on genotype/ phenotype relationships, using specimens and data from controls from breast and prostate cancer studies in Arkansas (n = 420). There was a dose-response reduction in catalase activity by genotype, with geometric means of 115.4 units/mg hemoglobin for those with CC genotypes, 82.1 units/mg for those with CT genotypes, and 73.5 units/mg for those with TT genotypes. Associations were only observed among Caucasians (P < 0.0001), with no effects among African Americans (P = 0.91), and were stronger among women than men, although numbers in stratified analyses were small. Differences in catalase activity by genotype were most pronounced among those in the highest tertiles of consumption of fruits and vegetables (-35%, P = 0.003), with weaker relationships among those who were lower consumers (-21.8%, P = 0.16). Among those with CC genotypes, there was no change in activity by consumption, but there were notable decreases in activity by tertiles of consumption for those with at least one T allele. These data indicate that the CAT -262C -> T polymorphism predicts a portion of catalase phenotype, which may be limited to Caucasians. Associations between genotype and phenotype were modified by dietary factors, illustrating the biochemical complexity of studies of genetic polymorphisms and disease risk. C1 Roswell Pk Canc Inst, Dept Epidemiol, Buffalo, NY 14263 USA. SUNY Buffalo, Dept Biostat, New York, NY USA. Univ Arkansas Med Sci, Little Rock, AR 72205 USA. Cent Arkansas Vet Healthcare Syst, Little Rock, AR 72205 USA. Natl Ctr Toxicol Res, Div Pharmacogenom & Mol Epidemiol, Jefferson, AR 72079 USA. NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NZH, Bethesda, MD USA. RP Ambrosone, CB (reprint author), Roswell Pk Canc Inst, Dept Epidemiol, Elm & Carlton St, Buffalo, NY 14263 USA. EM christine.ambrosone@roswellpark.org FU NCI NIH HHS [R01 CA095222]; NIA NIH HHS [R01 AG15722-03] NR 20 TC 65 Z9 67 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 EI 1538-7755 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JUN PY 2006 VL 15 IS 6 BP 1217 EP 1222 DI 10.1158/1055-9965.EPI-06-0104 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 053IZ UT WOS:000238300100026 PM 16775184 ER PT J AU Zhang, YQ Zhang, BL AF Zhang, YQ Zhang, BL TI D4-GDI, a Rho GTPase regulator, promotes breast cancer cell invasiveness SO CANCER RESEARCH LA English DT Article ID GDP-DISSOCIATION INHIBITOR; DRUG-INDUCED APOPTOSIS; HUMAN LYMPHOMA-CELLS; LY-GDI; BINDING PROTEIN; INVASION; RAC; METASTASIS; INTEGRINS; MOTILITY AB D4-GDI is a Rho GDP dissociation inhibitor that is widely expressed in hematopoietic cells. Its possible expression and function in breast cancer cells has not been described. Here, we found that D4-GDI is expressed in a panel of breast cancer cell lines, but not in benign-derived mammary epithelial cells. Knockdown of D4-GDI expression in MDA-MB-231 cells by RNA interference blocks cell motility and invasion. The cells lacking D4-GDI grown on Matrigel revert to a normal breast epithelial phenotype characterized by the formation of cavitary structures. Silencing D4-GDI expression inhibits PI-integrin expression and cell-matrix adhesion. Reintroduction of D4-GDI fully restored both beta 1-integrin expression and cellular invasion. Knockdown of D4-GDI in BT549 cells results in a similar effect. These results show that D4-GDI modulates breast cancer cell invasive activities. C1 US FDA, Div Therapeut Prot, Off Biotechnol Prod, Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. RP Zhang, BL (reprint author), US FDA, Div Therapeut Prot, Off Biotechnol Prod, Ctr Drug Evaluat & Res, 29 Lincoln Dr,Bldg 29A,Room 2B-24, Bethesda, MD 20892 USA. EM Baolin.zhang@fda.hhs.gov NR 34 TC 67 Z9 74 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 JUN 1 PY 2006 VL 66 IS 11 BP 5592 EP 5598 DI 10.1158/0008-5472.CAN-05-4004 PG 7 WC Oncology SC Oncology GA 049GC UT WOS:000238003100011 PM 16740694 ER PT J AU Pogribny, IP Ross, SA Tryndyak, VP Pogribna, M Poirier, LA Karpinets, TV AF Pogribny, Igor P. Ross, Sharon A. Tryndyak, Volodymyr P. Pogribna, Marta Poirier, Lionel A. Karpinets, Tatiana V. TI Histone H3 lysine 9 and H4 lysine 20 trimethylation and the expression of Suv4-2Oh2 and Suv-39h1 histone methyltransferases in hepatocarcinogenesis induced by methyl deficiency in rats SO CARCINOGENESIS LA English DT Article ID DNA METHYLATION; GENOMIC HYPOMETHYLATION; PRENEOPLASTIC LIVER; GENE-EXPRESSION; HUMAN CANCERS; HUMAN-TUMORS; H19 GENE; HETEROCHROMATIN; EPIGENETICS; REGION AB The field of cancer epigenetics has received much attention in recent years. However, the relationship of cancer epigenetics with cancer etiology is not clear. Recent studies suggest the involvement of altered DNA methylation and histone modifications in the emergence of epigenetically reprogrammed cells with specific tumor-related phenotypes at premalignant stages of tumor development. In this study, we used a methyl-deficient model of rodent hepatocarcinogenesis to examine the roles of DNA, histone H3 lysine 9 and histone H4 lysine 20 methylation, and the level of the expression of Suv39h1 and Suv4-2Oh2 histone methyltransferases in the carcinogenic process. We demonstrated that the development of liver tumors was characterized by progressive demethylation of DNA repeats, decrease in histone H4 lysine 20 trimethylation, and a gradual decrease in the expression of Suv4-2Oh2 histone methyltransferase. A prominent increase in the trimethylation of histone H3 lysine 9 and in the expression of Suv39h1 histone methyltransferase was observed in preneoplastic nodules and liver tumors indicating the promotional role of these epigenetic alterations at later stages of carcinogenesis. The appearance of tumor-specific epigenetic alterations (demethylation of repetitive elements, loss of histone H4 lysine 20 trimethylation, altered expression of Suv4-2Oh2 and Suv39h1 histone methyltransferases) at preneoplastic stages of hepatocarcinogenesis provides experimental support for the epigenetic hypothesis of tumorigenesis that considers stress-induced epigenetic reprogramming of the cell as an important prerequisite to succeeding mutations. C1 NCTR, Jefferson, AR 72078 USA. NCI, Bethesda, MD 20892 USA. Univ Tennessee, Knoxville, TN 37996 USA. RP Pogribny, IP (reprint author), NCTR, Div Biochem Toxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM ipogribny@nctr.fda.gov NR 55 TC 77 Z9 84 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JUN PY 2006 VL 27 IS 6 BP 1180 EP 1186 DI 10.1093/carcin/bgi364 PG 7 WC Oncology SC Oncology GA 060QM UT WOS:000238816700009 PM 16497704 ER PT J AU Zhang, BL AF Zhang, Baolin TI Rho GDP dissociation inhibitors as potential targets for anticancer treatment SO DRUG RESISTANCE UPDATES LA English DT Review DE RhoGDI; D4-GDI; Rho GTPases; cancer; metastasis ID DRUG-INDUCED APOPTOSIS; METASTASIS SUPPRESSOR GENE; GTP-BINDING PROTEINS; HUMAN LYMPHOMA-CELLS; BREAST-CANCER CELLS; PROTEOMIC ANALYSIS; PROGNOSTIC VALUE; BLADDER-CANCER; NADPH OXIDASE; LUNG-CANCER AB The Rho GDP dissociation inhibitors (RhoGDIs) are a major class of regulators of Rho GTPases and play essential roles in normal cell growth and malignant transformation. Although RhoGDIs are known to inhibit Rho activities, recent studies indicate that RhoGDIs can also act as positive regulators through their ability to target Rho GTPases to specific subcellular membranes or to protect the GTPases from degradation by caspases. RhoGDIs are aberrantly expressed in human tumors and this may contribute to Rho-induced cancer progression. This review will discuss the dual roles of RhoGDIs in the regulation of Rho GTPases, highlighting a possible role in regulating tumorigenicity. In addition, the potential for targeting RhoGDIs for anticancer therapy will be discussed. (c) 2006 Elsevier Ltd. All rights reserved. C1 US FDA, Div Therapeut Prot, Off Biotechnol Prod, Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. RP Zhang, BL (reprint author), US FDA, Div Therapeut Prot, Off Biotechnol Prod, Ctr Drug Evaluat & Res, 29 Lincoln Dr,Bldg 29A,Rm 2B-24, Bethesda, MD 20892 USA. EM Baolin.Zhang@FDA.HHS.GOV NR 69 TC 26 Z9 33 U1 0 U2 1 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 1368-7646 J9 DRUG RESIST UPDATE JI Drug Resist. Update PD JUN PY 2006 VL 9 IS 3 BP 134 EP 141 DI 10.1016/j.drup.2006.06.001 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 087FU UT WOS:000240729100004 PM 16807067 ER PT J AU Srinivasan, R Daniels, J Fusaro, V Lundqvist, A Killian, JK Geho, D Quezado, M Kleiner, D Rucker, S Espinac, V Whiteley, G Liotta, L Petricoin, E Pittaluga, S Hitt, B Barrett, AJ Rosenblatt, K Childs, RW AF Srinivasan, R Daniels, J Fusaro, V Lundqvist, A Killian, JK Geho, D Quezado, M Kleiner, D Rucker, S Espinac, V Whiteley, G Liotta, L Petricoin, E Pittaluga, S Hitt, B Barrett, AJ Rosenblatt, K Childs, RW TI Accurate diagnosis of acute graft-versus-host disease using serum proteomic pattern analysis SO EXPERIMENTAL HEMATOLOGY LA English DT Article ID PROSTATE-CANCER; MASS-SPECTROMETRY AB Objective. The rapid diagnosis of acute graft-versus-host disease (GVHD) following allogeneic hematopoietic cell transplantation (HCT) is important for optimizing the management of this life-threatening complication. Current diagnostic techniques are time-consuming and require invasive tissue sampling. We investigated serum protein pattern analysis using surface-enhanced laser desorption ionization time-of-flight (SELDI-TOF) mass spectrometry as a tool to diagnose GVHD. Patients and Methods. Eighty-eight serum samples were obtained from 34 patients undergoing HCT either pretransplant (n = 28 samples) or at various time points posttransplant (n = 60 samples), including 22 samples obtained on the day of onset of acute GVHD symptoms. Serum proteomic spectra generated from a '' training set '' of known samples were used to identify distinct proteomic patterns that best categorized a sample as either pretransplant, posttransplant non-GVHD, or GVHD; these distinct proteomic signatures were subsequently used to classify samples from a masked '' test '' sample set into the appropriate diagnostic category. Results. Proteomic pattern analysis accurately distinguished GVHD samples from both posttransplant non-GVHD samples and pretransplant samples (100% specificity and 100% sensitivity in both cases). Furthermore, distinct serum proteomic signatures were identified that distinguished pretransplant from posttransplant non-GVHD samples (100% specificity and 94% sensitivity). Conclusion. These preliminary data suggest a potential application of SELDI-TOF-based proteomic analysis as a rapid and accurate method to diagnose acute GVHD. (c) 2006 International Society for Experimental Hematology. Published by Elsevier Inc. C1 NHLBI, Hematol Branch, Bethesda, MD 20892 USA. Urol Oncol Branch, Bethesda, MD USA. NCI, Pathol Lab, Bethesda, MD 20892 USA. SAIC Frederick Inc, Bethesda, MD USA. US FDA, Bethesda, MD 20014 USA. Correlog Syst Inc, Bethesda, MD USA. RP Childs, RW (reprint author), NIH, Hematol Branch, 10 Ctr Dr,Bldg 10-CRC,Room 35330, Bethesda, MD 20892 USA. EM childsr@nih.gov OI Kleiner, David/0000-0003-3442-4453; Espina, Virginia/0000-0001-5080-5972; Lundqvist, Andreas/0000-0002-9709-2970 NR 18 TC 45 Z9 46 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD JUN PY 2006 VL 34 IS 6 BP 796 EP 801 DI 10.1016/j.exphem.2006.02.013 PG 6 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 051SG UT WOS:000238180500014 PM 16728285 ER PT J AU Jacobs, A AF Jacobs, Abigail TI Use of nontraditional animals for evaluation of pharmaceutical products SO EXPERT OPINION ON DRUG METABOLISM & TOXICOLOGY LA English DT Review DE Caenorhabditis elegans; ferrets; hamsters; marmosets; minipigs; zebrafish ID DANIO-RERIO; DRUG-METABOLISM; PIG-LIVER; ZEBRAFISH; MODEL; TOXICOLOGY; FERRETS; GENOME; CYP2A AB Although the International Conference on Harmonization Guideline ICH M3 indicates the use of nonrodents for some studies of pharmaceutical products, the specific nonrodent species is not specified. Dogs are used most frequently; however, there may be reasons why dogs are not the best model for a particular drug. Minipigs are being used increasingly for evaluation of toxicity, especially for dermally applied drugs, and for various efficacy models. Hamsters may be used for the evaluation of intraoral drugs and for carcinogenicity studies. Less commonly, pharmaceutical manufacturers may choose on their own to use marmosets, when a nonhuman primate is considered critical to evaluation, or to use ferrets for specific purposes. When nontraditional species are used, there may be less historical information available and unique issues of their care, and differences in physiology and anatomy and susceptibility to infection need to be understood. Nonmammalian test species, such as zebrafish and Caenorhabditis elegans may be used by drug sponsors in screening assays, but are not yet ready for use in pivotal toxicology studies because of the difficulty in extrapolating to mammalian species. Use of nontraditional animal species may be proposed by a drug sponsor to a reviewing division with supporting data and reasons for using a particular species. C1 US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Jacobs, A (reprint author), US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. EM abigail.jacobs@fda.hhs.gov NR 33 TC 26 Z9 30 U1 0 U2 5 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1742-5255 J9 EXPERT OPIN DRUG MET JI Expert Opin. Drug Metab. Toxicol. PD JUN PY 2006 VL 2 IS 3 BP 345 EP 349 DI 10.1517/17425255.2.3.345 PG 5 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 167VE UT WOS:000246479800001 PM 16863438 ER PT J AU Klinman, DM AF Klinman, Dennis M. TI CpG oligonucleotides accelerate and boost the immune response elicited by AVA, the licensed anthrax vaccine SO EXPERT REVIEW OF VACCINES LA English DT Review DE adjuvant; anthrax; CpG oligonucleotide; protection; vaccine ID CO-GLYCOLIDE MICROPARTICLES; HEPATITIS-B-VACCINE; CATIONIC MICROPARTICLES; BACTERIAL-DNA; BACILLUS-ANTHRACIS; PROTECTIVE ANTIGEN; INTERFERON-GAMMA; DELIVERY-SYSTEM; DENDRITIC CELLS; OLIGODEOXYNUCLEOTIDES AB Synthetic oligodeoxynucleotides (ODN) containing unmethylated CpG motifs act as immune adjuvants, improving the immune response elicited by coadministered vaccines. Combining CpG ODN with anthrax vaccine adsorbed (AVA), the licensed human vaccine, can increase the speed, magnitude and avidity of the resultant anti-anthrax response in mice, rhesus macaques and humans. Adsorbing the CpG ODN onto cationic poly(actide-coglycolides) microparticles further boosts immunity to coadministered AVA. The antibody response induced by CpG ODN plus AVA confers protection against systemic anthrax challenge in multiple animal models. These findings suggest that CpG ODN, alone or in combination with other adjuvants and delivery strategies, may support the development of prophylactic and therapeutic vaccines against biothreat pathogens. C1 US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Klinman, DM (reprint author), US FDA, Ctr Biol Evaluat & Res, Bldg 29A,Room 3D 10, Bethesda, MD 20892 USA. EM dennis.klinman@fda.hhs.gov NR 47 TC 18 Z9 19 U1 0 U2 3 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 JUN PY 2006 VL 5 IS 3 BP 365 EP 369 DI 10.1586/14760584.5.3.365 PG 5 WC Immunology SC Immunology GA 089ZZ UT WOS:000240921700014 PM 16827620 ER PT J AU Gursel, M Gursel, I Klinman, DM AF Gursel, M. Gursel, I. Klinman, D. M. TI CXCL16 influences the nature and specificity of CpG DNA-induced immune activation SO FEBS JOURNAL LA English DT Meeting Abstract CT 31st Congress of the Federation-of-European-Biochemical-Societies (FEBS) CY JUN 24-29, 2006 CL Istanbul, TURKEY SP Federat European Biochem Soc C1 US FDA, Sect Retroviral Res, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. EM ihsangursel@yahoo.com 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 1742-464X J9 FEBS J JI FEBS J. PD JUN PY 2006 VL 273 SU 1 BP 67 EP 67 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 061ZR UT WOS:000238914000225 ER PT J AU Gursel, I Gursel, M Klinman, DM AF Gursel, I. Gursel, M. Klinman, D. M. TI Immunotherapeutic applications of CpG ODN SO FEBS JOURNAL LA English DT Meeting Abstract CT 31st Congress of the Federation-of-European-Biochemical-Societies (FEBS) CY JUN 24-29, 2006 CL Istanbul, TURKEY SP Federat European Biochem Soc C1 Bilkent Univ, Dept Mol Biol & Genet, Ankara, Turkey. US FDA, DVP, CBER, Sect Retroviral Res, Bethesda, MD 20014 USA. EM igursel@fen.bilkent.edu.tr RI Gursel, Mayda /H-1812-2012 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 1742-464X J9 FEBS J JI FEBS J. PD JUN PY 2006 VL 273 SU 1 BP 68 EP 68 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 061ZR UT WOS:000238914000229 ER PT J AU Mai, HT Brodie, DL Meyers, MB Baldo, AL Krantz, Z Weisz, A AF Mai, HT Brodie, DL Meyers, MB Baldo, AL Krantz, Z Weisz, A TI Determination of 2,4,6-triiodoresorcinol and other side reaction products and intermediates in the colour additive FD & C Red No. 3 (erythrosine) using high-performance liquid chromatography SO FOOD ADDITIVES AND CONTAMINANTS LA English DT Article DE FD&C Red No. 3; erythrosine; 2,4,6-triiodoresorcinol; 2-(2 ',4 '-dihydroxy-3 ',5 '-diiodobenzoyl) benzoic acid; resorcinol; phthalic acid; sodium iodide; HPLC ID NO-3; RESORCINOL AB An HPLC method was developed for the quantitative determination of 2,4,6-triiodoresorcinol (I3R), 2-(2',4'-dihydroxy-3',5'-diiodobenzoyl) benzoic acid, resorcinol, phthalic acid, and sodium iodide in the colour additive FD&C Red No. 3 (erythrosine) (R3). Due to the fast decomposition of I3R in aqueous solutions, the dye portions analysed were dissolved in methanol and the determinations were performed in the freshly-made solutions. The HPLC method is rapid (50 min total analysis cycle, similar to 16 min to detect I3R and the other intermediates), simple to implement, and generates only small amounts of solvent waste. It was found to be applicable for use in routine batch-certification as shown by the analysis of test portions from 24 lots of R3 submitted for US-certification by domestic and foreign manufacturers during the past three years. C1 US FDA, Off Cosmet & Colours, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Weisz, A (reprint author), US FDA, Off Cosmet & Colours, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. EM aweisz@cfsan.fda.gov NR 9 TC 9 Z9 9 U1 1 U2 4 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 JUN PY 2006 VL 23 IS 6 BP 547 EP 551 DI 10.1080/02652030600550747 PG 5 WC Chemistry, Applied; Food Science & Technology; Toxicology SC Chemistry; Food Science & Technology; Toxicology GA 051ZS UT WOS:000238200800002 PM 16766453 ER PT J AU Collins, TFX Sprando, RL Black, TN Olejnik, N Eppley, RM Hines, FA Rorie, J Ruggles, DI AF Collins, TFX Sprando, RL Black, TN Olejnik, N Eppley, RM Hines, FA Rorie, J Ruggles, DI TI Effects of deoxynivalenol (DON, vomitoxin) on in utero development in rats SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article DE deoxynivalenol; vomitoxin; trichothecene mycotoxin; developmental toxicity; rat ID SPRAGUE-DAWLEY RATS; MATERNAL TOXICITY; B6C3F1 MOUSE; FUSARIUM MYCOTOXINS; FETAL MALFORMATIONS; WHEAT; MICE; 4-DEOXYNIVALENOL; REFUSAL; FOODS AB Deoxynivalenol (DON, vomitoxin), is one of the most common contaminants of cereal grains world-wide. The effects of DON on fetal development were assessed in Charles River Sprague-Dawley rats. Pregnant female rats were gavaged once daily with DON at doses of 0, 0.5, 1, 2.5, or 5 mg/kg body weight on gestation days (GD) 6-19. At cesarean section on GD 20, reproductive and developmental parameters were measured. All females survived to cesarean section. DON caused a dose-related increase in excessive salivation by the pregnant females, a reaction probably linked to the lack of emetic reflex in rats. At 5 mg/kg, feed consumption and mean body weight gain were significantly decreased throughout gestation, mean weight gain (carcass weight), and gravid uterine weight were significantly reduced, 52% of litters (12/23) were totally resorbed, the average number of early and late deaths per litter was significantly increased, average fetal body weight and crown-rump length were significantly decreased, the incidence of runts was significantly increased, and the ossification of fetal sternebrae, centra, dorsal arches, vertebrae, metatarsals, and metacarpals was significantly decreased. At 2.5 mg/kg, DON significantly decreased average fetal body weight, crown-rump length, and vertebral ossification. These effects may be secondary to maternal toxicity and the reduced size of the fetuses. The incidence of misaligned and fused sternebrae was significantly increased at 5.0 mg/kg. No adverse developmental effects were observed at 0.5 and 1.0 mg/kg. Dose-related increases in maternal liver weight-to-body weight ratios were observed in all treated groups (significant at 1, 2.5, and 5 mg/kg). The weight changes were correlated with dose-related cytoplasmic alterations of hepatocytes. The NOEL for maternal toxicity for this study is 0.5 mg/kg based on the dose-related increase in liver-body weight ratio at 1 mg/kg. The NOEL for fetal toxicity is 1 mg/kg based on the general reduction in fetal development at 2.5 and 5 mg/kg. DON is considered a teratogen at 5 mg/kg day in Sprague-Dawley rats based on the anomalous development of the sternebrae. (c) 2005 Elsevier Ltd. All rights reserved. C1 US FDA, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. RP Collins, TFX (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 8301 Muirkirk Rd, Laurel, MD 20708 USA. EM tcollins@cfsan.fda.gov NR 48 TC 18 Z9 23 U1 0 U2 11 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0278-6915 J9 FOOD CHEM TOXICOL JI Food Chem. Toxicol. PD JUN PY 2006 VL 44 IS 6 BP 747 EP 757 DI 10.1016/j.fct.2005.10.007 PG 11 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA 056VG UT WOS:000238552600001 PM 16325976 ER PT J AU Nayak, R Stewart, T Nawaz, M Cerniglia, C AF Nayak, R Stewart, T Nawaz, M Cerniglia, C TI In vitro antimicrobial susceptibility, genetic diversity and prevalence of UDP-glucose 4-epimerase (galE) gene in Campylobacter coli and Campylobacter jejuni from Turkey production facilities SO FOOD MICROBIOLOGY LA English DT Article DE Campylobacter; genotyping; antimicrobial resistance; Turkey; PCR ID GUILLAIN-BARRE-SYNDROME; FIELD GEL-ELECTROPHORESIS; MILLER-FISHER-SYNDROMES; MOLECULAR CHARACTERIZATION; CIPROFLOXACIN RESISTANCE; ANTIBIOTIC-RESISTANCE; BROILER-CHICKENS; EFFLUX PUMP; POULTRY; STRAINS AB This study evaluated the genetic diversity of multi-drug resistant Campylobacter jejuni (n = 44) and C coli (n = 30) isolated from 18 turkey houses. Antimicrobial resistances to amipicillin, ciprofloxacin and nalidixic acid were higher (P<0.05) in C coli than in C jejuni strains. PCR analysis indicated that 82% of total isolates tested, including 91% of C jejuni and 70% of C coli tested positive for a 496-bp UDP-glucose 4-epimerase (galE) gene. The diversity of isolates was mapped by antibiogram, SmaI-PFGE and flaA-RFLP typing methods using the discriminatory index (DI). RFLP was more suitable in discriminating C coli (DI = 0.895) than PFGE (DI = 0.816) or antibiogram profile (DI = 0.552), while either PFGE (DI = 0.941) or RFLP (DI = 0.942) could be used in discriminating C jejuni strains. The combined PFGE and antibiogram dendrogram had the highest DI for both C coli (0.910) and C jejuni (0.968), suggesting that a combination of typing methods is more useful in examining the diverse Campylobacter population on turkey farms. Published by Elsevier Ltd. C1 US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. RP Nayak, R (reprint author), US FDA, Natl Ctr Toxicol Res, Div Microbiol, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM rnayak@nctr.fda.gov NR 56 TC 6 Z9 6 U1 1 U2 3 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0740-0020 J9 FOOD MICROBIOL JI Food Microbiol. PD JUN PY 2006 VL 23 IS 4 BP 379 EP 392 DI 10.1016/j.fm.2005.04.007 PG 14 WC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology SC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology GA 025FI UT WOS:000236250300009 PM 16943028 ER PT J AU Leuschner, RGK Baird, F Donald, B Cox, LJ AF Leuschner, RGK Baird, F Donald, B Cox, LJ TI A medium for the presumptive detection of Enterobacter sakazakii in infant formula (Retraction of vol 21, pg 527, 2004) SO FOOD MICROBIOLOGY LA English DT Correction C1 US FDA, Summit Argo, IL 60501 USA. RP Leuschner, RGK (reprint author), US FDA, 6502 S Archer Rd, Summit Argo, IL 60501 USA. NR 1 TC 1 Z9 1 U1 1 U2 7 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0740-0020 J9 FOOD MICROBIOL JI Food Microbiol. PD JUN PY 2006 VL 23 IS 4 BP 409 EP 409 DI 10.1016/j.fm.2006.01.001 PG 1 WC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology SC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology GA 025FI UT WOS:000236250300012 ER PT J AU Mahmood, I AF Mahmood, I TI Pharmacokinetic simulations and AUC: Center specificity in the limited sampling model - Reply to J. Proost SO INTERNATIONAL JOURNAL OF CLINICAL PHARMACOLOGY AND THERAPEUTICS LA English DT Letter C1 US FDA, Off Therapeut Res & Review, Div Clin Trial Design & Anal,Ctr Biol Evaluat & R, Clin Pharmacol & Toxicol Branch HDF579, Rockville, MD 20852 USA. RP Mahmood, I (reprint author), US FDA, Off Therapeut Res & Review, Div Clin Trial Design & Anal,Ctr Biol Evaluat & R, Clin Pharmacol & Toxicol Branch HDF579, Woodmont Off Ctr 1,Suite 200N,1401 Rockville Pike, Rockville, MD 20852 USA. EM Mahmoodi@cder.fda.gov NR 1 TC 0 Z9 0 U1 0 U2 0 PU DUSTRI-VERLAG DR KARL FEISTLE PI DEISENHOFEN-MUENCHEN PA BAHNHOFSTRASSE 9 POSTFACH 49, D-82032 DEISENHOFEN-MUENCHEN, GERMANY SN 0946-1965 J9 INT J CLIN PHARM TH JI Int. J. Clin. Pharmacol. Ther. PD JUN PY 2006 VL 44 IS 6 BP 293 EP 295 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 059FX UT WOS:000238719800008 ER PT J AU Frisvad, JC Larsen, TO Dalsgaard, PW Seifert, KA Louis-Seize, G Lyhne, EK Jarvis, BB Fettinger, JC Overy, DP AF Frisvad, Jens C. Larsen, Thomas O. Dalsgaard, Petur W. Seifert, Keith A. Louis-Seize, Gerry Lyhne, E. K. Jarvis, Bruce B. Fettinger, James C. Overy, David P. TI Four psychrotolerant species with high chemical diversity consistently producing cycloaspeptide A, Penicillium jamesonlandense sp nov., Penicillium ribium sp nov., Penicillium soppii and Penicillium lanosum SO INTERNATIONAL JOURNAL OF SYSTEMATIC AND EVOLUTIONARY MICROBIOLOGY LA English DT Article ID FUNGI; MYCOTOXINS; CHROMATOGRAPHY; ASPERGILLUS; SOILS; PCR AB Penicillium jamesonlandense is a novel species from Greenland that grows exceptionally slowly at 25 degrees C and has an optimum temperature for growth of 17-18 degrees C. The novel species is more psychrotolerant than any other Penicillium species described to date. Isolates of this novel species produce a range of secondary metabolites with a high chemical diversity, represented by kojic acid, penicillic acid, griseofulvin, pseurotin, chrysogine, tryptoquivalins and cycloaspeptide. Penicillium ribium, another novel psychrotolerant species from the Rocky Mountains, Wyoming, USA, produces asperfuran, kojic acid and cycloaspeptide. Originally reported from an unidentified Aspergillus species isolated from Nepal, cycloaspeptide A is reported here for the first time from the two novel Penicillium species and two known psychrotolerant species with high chemical diversity, Penicillium soppii and Penicillium lanosum. All species, except P. ribium, produce a combination of cycloaspeptide, and griseofulvin. However, P. ribium (3/5 strains) produced the precursor to griseofulvin, norlichexanthone. The type strain of Penicillium jamesonlandense sp. nov. is DACM 234087(T) (= IBT 21984(T)= IBT 24411(T) = CBS 102888(T)) and the type strain of Penicillium ribium sp. nov. is DAOM 234091(T) (= IBT 16537(T) = IBT 24431(T)). C1 Tech Univ Denmark, Ctr Microbial Biotechnol, DK-2800 Lyngby, Denmark. Agr Canada, Natl Programme Environm Sci, Ottawa, ON K1A 0C6, Canada. Univ Maryland, Dept Chem & Biochem, College Pk, MD 20742 USA. Univ Maryland, Joint Inst Food Safety & Appl Nutr, College Pk, MD 20742 USA. Univ Coll Wales Aberystwyth, Inst Biol Sci, Aberystwyth SY23 3DA, Dyfed, Wales. RP Frisvad, JC (reprint author), Tech Univ Denmark, Ctr Microbial Biotechnol, Bldg 221,Soltofts Plads, DK-2800 Lyngby, Denmark. EM jcf@biocentrum.dtu.dk NR 30 TC 21 Z9 23 U1 2 U2 17 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 1466-5026 J9 INT J SYST EVOL MICR JI Int. J. Syst. Evol. Microbiol. PD JUN PY 2006 VL 56 BP 1427 EP 1437 DI 10.1099/ijs.0.64160-0 PG 11 WC Microbiology SC Microbiology GA 055UE UT WOS:000238475200038 PM 16738124 ER PT J AU Deeds, JR Reimschuessel, R Place, AR AF Deeds, Jonathan R. Reimschuessel, Renate Place, Allen R. TI Histopathological effects in fish exposed to the toxins from Karlodinium micrum SO JOURNAL OF AQUATIC ANIMAL HEALTH LA English DT Article ID CHESAPEAKE-BAY; CHLORIDE CELL; RED TIDE; GYRODINIUM-AUREOLUM; GILL EPITHELIA; LSU RDNA; WATER; DINOPHYCEAE; GALATHEANUM; MORPHOLOGY AB Karlodinium micrum (family Dinophyceae) produces toxic compounds (KmTx's) that are associated with fish kills. For zebrafish Danio rerio larvae (24 It old) exposed to either KmTx 1 or KmTx 2, mortality (100% in 24 h) was observed at toxin concentrations of 1 mu g/mL or more, whereas no mortality occurred after 24 h at concentrations of 0.5 mu g/mL or less. Zebrafish and sheepshead minnow Cyprinodon variegatus juveniles (60-90 d old) exposed to KmTx 2 were more sensitive to the toxin's effects than larvae were; mortalities in the juveniles began at 0.1-0.5 pg/mL. In whole, sectioned juvenile zebrafish, gills were the primary site showing injury by light microscopy. Histology of gills in both species treated with 0.5 mu g KmTx 2/mL (100% mortality in 1 h) showed epithelial necrosis and shortening or loss of secondary lamellae. Histology of zebrafish gills treated with 0.05 and 0.1 mu g/mL (0-44% mortality in 4 h) showed clubbing and bridging between secondary lamellae within 4 h of exposure. Sheepshead minnow exposed to 0.1 mu g/mL showed similar gill pathology but no mortality after 6 h. Sheepshead minnow exposed to KmTx 2 at 0.5 mu g/mL or more all died in less than 1 h. Transmission electron microscopy of gills of moribund zebrafish exposed to 0.1 mu g/mL revealed extensive cellular hypertrophy and lysis of epithelial and chloride cells. Because concentrations of KmTx 1 and KmTx 2 range from 0.1 to 0.8 mu g/mL in filtered water samples from K. micrum-associated fish kills, these results suggest that the concentrations of KmTx 1 and KmTx 2 found during fish kills are acutely toxic to fish and that gills are a primary target. C1 Univ Maryland, Ctr Marine Biotechnol, Inst Biotechnol, Baltimore, MD 21202 USA. US FDA, Ctr Food Safety & Appl Nutr, Off Seafood, Laurel, MD 20708 USA. US FDA, Ctr Vet Med, Laurel, MD 20708 USA. RP Deeds, JR (reprint author), Univ Maryland, Ctr Marine Biotechnol, Inst Biotechnol, 701 E Pratt St,Suite 236, Baltimore, MD 21202 USA. EM jdeeds@cfsan.fda.gov RI Place, Allen/F-9267-2013 NR 41 TC 36 Z9 40 U1 1 U2 9 PU AMER FISHERIES SOC PI BETHESDA PA 5410 GROSVENOR LANE SUITE 110, BETHESDA, MD 20814-2199 USA SN 0899-7659 J9 J AQUAT ANIM HEALTH JI J. Aquat. Anim. Health PD JUN PY 2006 VL 18 IS 2 BP 136 EP 148 DI 10.1577/H05-027.1 PG 13 WC Fisheries; Veterinary Sciences SC Fisheries; Veterinary Sciences GA 068YT UT WOS:000239412000007 ER PT J AU Thomas, JA Chakrabarti, K Kaczmarek, RV Maslennikov, A Mitchell, CA Romanyukha, A AF Thomas, JA Chakrabarti, K Kaczmarek, RV Maslennikov, A Mitchell, CA Romanyukha, A TI Optimization of reading conditions for flat panel displays SO JOURNAL OF DIGITAL IMAGING LA English DT Article DE CRT; flat panel; viewing condition; luminance; room illuminance ID RAY-TUBE MONITORS; LIQUID-CRYSTAL; PERFORMANCE; LCD; CRT AB Task Group 18 (TG 18) of the American Association of Physicists in Medicine has developed guidelines for Assessment of Display Performance for Medical Imaging Systems. In this document, a method for determination of the maximum room lighting for displays is suggested. It is based on luminance measurements of a black target displayed on each display device at different room illuminance levels. Linear extrapolation of the above luminance measurements vs. room illuminance allows one to determine diffuse and specular reflection coefficients. TG 18 guidelines have established recommended maximum room lighting. It is based on the characterization of the display by its minimum and maximum luminance and the description of room by diffuse and specular coefficients. We carried out these luminance measurements for three selected displays to determine their optimum viewing conditions: one cathode ray tube and two flat panels. We found some problems with the applicationof the TG 18 guidelines to optimize viewing conditions for IBM T221 flat panels. Introduction of the requirement for minimum room illuminance allows a more accurate determination of the optimal viewing conditions (maximum and minimum room illuminance) for IBM flat panels. It also addresses the possible loss of contrast in medical images on flat panel displays because of the effect of nonlinearity in the dependence of luminance on room illuminance at low room lighting. C1 Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. RP Romanyukha, A (reprint author), 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM aromanyukha@usuhs.mil NR 8 TC 1 Z9 1 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0897-1889 J9 J DIGIT IMAGING JI J. Digit. Imaging PD JUN PY 2006 VL 19 IS 2 BP 181 EP 186 DI 10.1007/s10278-006-9710-z PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 053PQ UT WOS:000238317500013 PM 16437286 ER PT J AU Cole, LE Elkins, KL Michalek, SM Qureshi, N Eaton, LJ Rallabhandi, P Cuesta, N Vogel, SN AF Cole, LE Elkins, KL Michalek, SM Qureshi, N Eaton, LJ Rallabhandi, P Cuesta, N Vogel, SN TI Immunologic consequences of Francisella tularensis live vaccine strain infection: Role of the innate immune response in infection and immunity SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; TOLL-LIKE RECEPTORS; VIRULENT TYPE-A; PROTECTIVE IMMUNITY; LIPID-A; INTRACELLULAR BACTERIUM; GAMMA-INTERFERON; MURINE MACROPHAGES; O-ANTIGEN; ENDOTOXIN TOLERANCE AB Francisella tularensis (Ft), a Gram-negative intracellular bacterium, is the etiologic agent of tularemia. Although attenuated for humans, i.p. infection of mice with < 10 Ft live vaccine strain (LVS) organisms causes lethal infection that resembles human tularemia, whereas the LD50 for an intradermal infection is > 10(6) organisms. To examine the immunological consequences of Ft LVS infection on the innate immune response, the inflammatory responses of mice infected i.p. or intradermally were compared. Mice infected i.p. displayed greater bacterial burden and increased expression of proinflammatory genes, particularly in the liver. In contrast to most LPS, highly purified Ft LVS LPS (10 mu g/ml) was found to be only minimally stimulatory in primary murine macrophages and in HEK293T cells transiently transfected with TLR4/MD-2/CD14, whereas live Ft LVS bacteria were highly stimulatory for macrophages and TLR2-expressing HEK293T cells. Despite the poor stimulatory activity of Ft LVS LPS in vitro, administration of 100 ng of Ft LVS LPS 2 days before Ft LVS challenge severely limited both bacterial burden and cytokine mRNA and protein expression in the absence of detectable Ab at the time of bacterial challenge, yet these mice developed a robust Igm Ab response within 2 days of infection and survived. These data suggest that prior administration of Ft LVS LPS protects the host by diminishing bacterial burden and blunting an otherwise overwhelming inflammatory response, while priming the adaptive immune response for development of a strong Ab response. C1 Univ Maryland, Dept Microbiol & Immunol, Sch Med, Baltimore, MD 21201 USA. US FDA, Ctr Biol Evaluat & Res, Div Bacterial Allergen & Parasit Prod, Lab Mycobacterial Dis & Cellular Immunol, Rockville, MD 20852 USA. Univ Alabama, Dept Microbiol, Birmingham, AL 35294 USA. Univ Missouri, Sch Med, Trauma Res Ctr, Dept Basic Med Sci & Surg Shock, Kansas City, MO 64108 USA. List Biol Labs, Campbell, CA 95008 USA. RP Vogel, SN (reprint author), Univ Maryland, Dept Microbiol & Immunol, Sch Med, 660 W Redwood St,Room 324, Baltimore, MD 21201 USA. EM svogel@som.umaryland.edu RI Cuesta, Natalia/C-1358-2012; Cuesta, Natalia/J-7761-2015 OI Cuesta, Natalia/0000-0003-0809-2934 FU Intramural NIH HHS; NIAID NIH HHS [AI-57168, AI-44936, AI-56460]; NIDCR NIH HHS [DE-09081]; NIGMS NIH HHS [R01 GM050870] NR 71 TC 81 Z9 81 U1 0 U2 7 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUN 1 PY 2006 VL 176 IS 11 BP 6888 EP 6899 PG 12 WC Immunology SC Immunology GA 045PN UT WOS:000237754200056 PM 16709849 ER PT J AU Epstein, SL AF Epstein, SL TI Heterosubtypic immunity to influenza: Right hypothesis, wrong comparison - Reply to Carrat and Lavenu SO JOURNAL OF INFECTIOUS DISEASES LA English DT Letter ID CROSS-PROTECTION; M2 PROTEIN; INFECTION; VACCINATION; CHALLENGE; MICE C1 US FDA, Div Cellular & Gene Therapies, Off Cellular Tissue & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. RP Epstein, SL (reprint author), 1401 Rockville Pike,HFM 730, Rockville, MD 20852 USA. EM suzanne.epstein@fda.hhs.gov NR 10 TC 0 Z9 0 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JUN 1 PY 2006 VL 193 IS 11 BP 1613 EP 1614 DI 10.1086/503782 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 038SS UT WOS:000237246700026 ER PT J AU Zhang, MJ Drenkow, J Lankford, CSR Frucht, DM Rabin, RL Gingeras, TR Venkateshan, C Schwartzkopff, F Clouse, KA Dayton, AI AF Zhang, Mingjie Drenkow, Jorg Lankford, Carla S. R. Frucht, David M. Rabin, Ronald L. Gingeras, Thomas R. Venkateshan, Chettemegre Schwartzkopff, Franziska Clouse, Kathleen A. Dayton, Andrew I. TI HIV regulation of the IL-7R: a viral mechanism for enhancing HIV-1 replication in human macrophages in vitro SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE cytokine receptors; cytokines; Tat; AIDS ID HUMAN-IMMUNODEFICIENCY-VIRUS; MONOCYTE-DERIVED MACROPHAGES; BLOOD MONONUCLEAR-CELLS; TUMOR-NECROSIS-FACTOR; GROWTH-FACTOR; INTERLEUKIN-7 RECEPTOR; T-CELLS; ANTIRETROVIRAL THERAPY; SIGNAL-TRANSDUCTION; CYTOKINE REGULATION AB We report a novel mechanism, involving up-regulation of the interleukin (IL)-7 cytokine receptor, by which human immunodeficiency virus (HIV) enhances its own production in monocyte-derived macrophages (MDM) in vitro. HIV-1 infection or treatment of MDM cultures with exogenous HIV-1 Tat(86) protein up-regulates the IL-7 receptor (IL-7R) et-chain at the levels of steady-state RNA, protein, and functional IL-7R on the cell surface (as measured by ligand-induced receptor signaling). This IL-7R up-regulation is associated with increased amounts of HIV-1 virions in the supernatants of infected MDM cultures treated with exogenous IL-7 cytokine. The overall effect of IL-7 stimulation on HIV replication in MDM culture supernatants is typically in the range of one log and greater. The results are consistent with a model in which HIV infection produces the Tat protein, which in turn up-regulates IL-7R in a paracrine manner. This results in increased IL-7R signaling in response to the IL-7 cytokine, which ultimately promotes early events in HIV replication, including binding/entry and possibly other steps prior to reverse transcription. The results suggest that the effects of IL-7 on HIV replication in MDM should be considered when analyzing and designing clinical trials involving treatment of patients with IL-7 or Tat vaccines. C1 US FDA, Mol Virol Lab, Div Emerging & Transfus Transmitted Dis, Off Blood Res & Review,Ctr Biol Evaluat & Res,CBE, Rockville, MD 20852 USA. US FDA, Lab Immunobiochem, DBPAP, Off Vaccine Res & Review,Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. Affymetrix, Santa Clara, CA USA. Ctr Drug Evaluat & Res, Div Monoclonal Antibodies, Off Biotechnol Prod, Bethesda, MD USA. RP Dayton, AI (reprint author), US FDA, Mol Virol Lab, Div Emerging & Transfus Transmitted Dis, Off Blood Res & Review,Ctr Biol Evaluat & Res,CBE, HFM 315,1401 Rockville Pike, Rockville, MD 20852 USA. EM Dayton@cber.fda.gov OI Gingeras, Thomas/0000-0001-9106-3573 FU Intramural NIH HHS NR 72 TC 11 Z9 11 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD JUN PY 2006 VL 79 IS 6 BP 1328 EP 1338 DI 10.1189/jlb.0704424 PG 11 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 119MC UT WOS:000243015400027 PM 16614257 ER PT J AU Sergeev, N Distler, M Vargas, M Chizhikov, V Herold, KE Rasooly, A AF Sergeev, N Distler, M Vargas, M Chizhikov, V Herold, KE Rasooly, A TI Microarray analysis of Bacillus cereus group virulence factors SO JOURNAL OF MICROBIOLOGICAL METHODS LA English DT Article DE microarray; microbial detection; microbial pathogen ID MULTIPLE SEQUENCE ALIGNMENT; HEMOLYSIN-BL; OLIGONUCLEOTIDE MICROARRAY; ANTHRAX TOXIN; PROTECTIVE ANTIGEN; ENTEROTOXIN GENES; GENOME SEQUENCE; RIBOSOMAL-RNA; STRAINS; PCR AB Bacillus cereus, B. thuringiensis and B. anthracis are closely related medically and economically important bacterial species that belong to the B. cereus group. Members of the B. cereus group carry genes encoding several important virulence factors, including enterotoxins, phospholipases and exotoxins. Since it is difficult to differentiate among B. cereus group members, and because Bacillus virulence factors are very important for pathogenesis, we explored the use of microarray-based detection of virulence factor genes as a tool for strain identification and for determining virulence. Our method requires an initial multiplex PCR amplification step, followed by identification of the PCR amplicons by hybridization to an oligonucleotide microarray containing genes for all three types of Bacillus virulence factors including B. anthracis virulence factors. The DNA chip described here contains 21 identical arrays used for analysis of seven samples in triplicates. Using the arrays, we found that virulence factors are present in several combinations in the strains analyzed. This work also demonstrates the potential of oligonucleotide microarrays for medical, food safety and biodefense analysis of microbial pathogens. Published by Elsevier B.V. C1 NCI, NIH, Rockville, MD 20852 USA. US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. Univ Maryland, College Pk, MD 20742 USA. US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. RP Rasooly, A (reprint author), NCI, NIH, 6130 Execut Blvd,EPN,Room 6035A, Rockville, MD 20852 USA. EM rasoolya@mail.nih.gov NR 62 TC 42 Z9 47 U1 1 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-7012 J9 J MICROBIOL METH JI J. Microbiol. Methods PD JUN PY 2006 VL 65 IS 3 BP 488 EP 502 DI 10.1016/j.mimet.2005.09.013 PG 15 WC Biochemical Research Methods; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 050DU UT WOS:000238068500012 PM 16242802 ER PT J AU Ghoshal, K Li, X Datta, J Bai, SM Pogribny, I Pogribny, M Huang, Y Young, D Jacob, ST AF Ghoshal, K Li, X Datta, J Bai, SM Pogribny, I Pogribny, M Huang, Y Young, D Jacob, ST TI A folate- and methyl-deficient diet alters the expression of DNA methyltransferases and methyl CpG binding proteins involved in epigenetic gene silencing in livers of F344 rats SO JOURNAL OF NUTRITION LA English DT Article DE hepatocarcinogenesis; folate- and methyl-deficient diet; Dnmt1/3a/3b; MBD1-4 ID FOLATE/METHYL DEFICIENCY; NUTRIENT INTERACTIONS; PRENEOPLASTIC LIVER; COLORECTAL-CANCER; TUMOR PROGRESSION; GLYCOSYLASE MBD4; HYPOMETHYLATION; HEPATOCARCINOGENESIS; SUPPRESSION; METABOLISM AB Aberrations in methylation profile of the genome occur in human cancers induced by folate deficiency. To elucidate the underlying mechanism, male F344 rats were fed a diet deficient in L-methionine and devoid of folic acid and choline (FMD diet), which is known to induce hepatocellular carcinomas. We investigated changes in the DNA methylation machinery, namely, de novo DNA methyltransferases (Dnmt3a and 3b), maintenance DNA methyltransferase (Dnmt1), and methyl CpG binding proteins (MBDs), in rat livers during early stages of tumorigenesis. RTPCR and Western blot analyses revealed differential expression of these proteins in the livers of rats fed the FMD diet. Although the hepatic Dnmt1 mRNA level declined with age (P < 0.001), it was elevated (P < 0.001) in deficient rats compared with controls. The changes in hepatic Dnmt1 protein level with the diet correlated with its mRNA levels (r=0.60, P=0.002). Similarly, the Dnmt3a mRNA level was elevated in rats fed the FMD diet (P < 0.001), whereas the Dnmt3b level (mRNA and protein) was not affected by diet or age. Compared with controls, hepatic MBD1-3 RNA levels increased (P < 0.001) and the protein levels of MBD1, 2, and 4 were elevated (P < 0.001) in the deficient rats. In both diet groups, hepatic MBD2 protein decreased (P < 0.001), whereas MeCP2 protein increased (P < 0.001) with age. These results demonstrate that a combined folate and methyl deficiency alters components of the DNA methylation machinery by both transcriptional and posttranscriptional mechanisms during early stages of hepatocarcinogenesis. C1 Ohio State Univ, Dept Mol & Cellular Biochem, Columbus, OH 43210 USA. Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. Ohio State Univ, Dept Internal Med, Columbus, OH 43210 USA. US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Jacob, ST (reprint author), Ohio State Univ, Dept Mol & Cellular Biochem, Columbus, OH 43210 USA. EM ghoshal.1@osu.edu; jacob.42@osu.edu FU NCI NIH HHS [R01 CA086978-01A2, CA 86978, R01 CA086978, R01 CA086978-02, R01 CA086978-03, R01 CA086978-04, R01 CA086978-05, R01 CA086978-06A1] NR 42 TC 113 Z9 126 U1 0 U2 8 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 JUN PY 2006 VL 136 IS 6 BP 1522 EP 1527 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 046SV UT WOS:000237832200014 PM 16702315 ER PT J AU Stein, SE Heller, DN AF Stein, SE Heller, DN TI On the risk of false positive identification using multiple ion monitoring in qualitative mass spectrometry: Large-scale intercomparisons with a comprehensive mass spectral library SO JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY LA English DT Article ID COMPOUND IDENTIFICATION; CONFIRMATION AB Analysts involved in qualitative mass spectrometry have long debated the minimum data requirements for demonstrating that signals from an unknown sample are identical to those from a known compound. Often this process is carried out by comparing a few selected ions acquired by multiple ion monitoring (MIM), with due allowance for expected variability in response. In a few past experiments with electron-ionization mass spectrometry (EI-MS), the number of ions selected and the allowable variability in relative abundance were tested by comparing one spectrum against a library of mass spectra, where library spectra served to represent potential false positive signals in an analysis. We extended these experiments by carrying out large-scale intercomparisons between thousands of spectra and a library of one hundred thousand El mass spectra. The results were analyzed to gain insights into the identification confidence associated with various numbers of selected ions. A new parameter was investigated for the first time, to take into account that a library spectrum with a different base peak than the search spectrum may still cause a false positive identification. The influence of peak correlation among the specific ions in all the library mass spectra was also studied. Our computations showed that (1) false positive identifications can result from similar compounds, or low-abundance peaks in unrelated compounds if the method calls for detection at very low levels; (2) a MIM method's identification confidence improves in a roughly continuous manner as more ions are monitored, about one order of magnitude for each additional ion selected; (3) full scan spectra still represent the best alternative, if instrument sensitivity is adequate. The use of large scale intercomparisons with a comprehensive library is the only way to provide direct evidence in support of these conclusions, which otherwise depend on the judgment and experience of individual analysts. There are implications for residue chemists who would rely on standardized confirmation criteria to assess the validity of a given confirmatory method. For example, standardized confirmation criteria should not be used in the absence of interference testing and rational selection of diagnostic ions. C1 NIST, Mass Spectrometry Data Ctr, Gaithersburg, MD 20899 USA. FDA Ctr Vet Med, Laurel, MD USA. RP Stein, SE (reprint author), NIST, Mass Spectrometry Data Ctr, A111-221, Gaithersburg, MD 20899 USA. EM steve.stein@nist.gov NR 18 TC 26 Z9 27 U1 3 U2 15 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1044-0305 J9 J AM SOC MASS SPECTR JI J. Am. Soc. Mass Spectrom. PD JUN PY 2006 VL 17 IS 6 BP 823 EP 835 DI 10.1016/j.jasms.2006.02.021 PG 13 WC Chemistry, Analytical; Chemistry, Physical; Spectroscopy SC Chemistry; Spectroscopy GA 047YC UT WOS:000237913600009 PM 16603375 ER PT J AU Simak, J Gelderman, MP Yu, H Wright, V Baird, AE AF Simak, J Gelderman, MP Yu, H Wright, V Baird, AE TI Circulating endothelial microparticles in acute ischemic stroke: a link to severity, lesion volume and outcome SO JOURNAL OF THROMBOSIS AND HAEMOSTASIS LA English DT Article DE acute stroke; endoglin; endothelial microparticles; flow cytometry; VE-cadherin ID CELL-DERIVED MICROPARTICLES; MEMBRANE MICROPARTICLES; PROCOAGULANT ACTIVITY; APOPTOSIS; ENDOGLIN; PLASMA; BRAIN; INFILTRATION; GENERATION; MOLECULES AB Background: Endothelial membrane microparticles (EMP) in plasma are elevated in several vascular diseases. Objectives: To test the hypothesis that EMP would be increased in patients with acute ischemic stroke and would correlate with stroke severity, brain lesion volume and outcome. Patients and methods: Forty-one patients were studied and divided into two groups based on the National Institutes of Health Stroke Scale (NIHSS) score: 20 patients with mild stroke (NIHSS score < 5) and 21 patients with moderate-severe stroke (NIHSS score >= 5). Lesion volume was measured using diffusion-weighted magnetic resonance imaging and discharge outcome was based on the discharge Barthel and Rankin scores. Twenty-three age-matched control subjects were also studied. Using flow cytometry, endoglin-positive EMP: CD105(+) CD41a(-)CD45(-) (E+EMP), specific endothelial EMP expressing VE-cadherin and endoglin: CD105(+)CD144(+) (C+EMP), EMP expressing phosphatidylserine: CD105(+)PS(+) CD41a(-) (PS+EMP) and EMP expressing ICAM-1: CD105(+)CD54(+) CD45(-) (I+EMP) were analyzed. Results: Significantly higher PS+EMP counts were observed in the group of acute ischemic stroke patients [median 59 (25th-75th percentile: 28-86) MP mu L-1] relative to the controls [28 (14-36) MP mu L-1] (P = 0.002). All four EMP phenotypes studied were elevated in the subgroup of moderate-severe stroke patients relative to the controls (all P < 0.05). In the patients with acute ischemic stroke three EMP phenotypes (E+EMP, PS+EMP and I+EMP) correlated significantly with brain lesion volume, with I+EMP (P = 0.002) showing the strongest correlation. Admission counts of C+EMP (P = 0.0003) and E+EMP (P = 0.003) correlated significantly with discharge clinical outcome. Conclusions: Certain circulating EMP phenotypes may be associated with severity, lesion volume and outcome of acute ischemic stroke. EMP analysis shows promising contribution to understanding stroke pathophysiology. C1 US FDA, CBER, Lab Cellular Hematol, Rockville, MD 20852 USA. NINDS, Struct Neurosci Unit, NIH, Bethesda, MD 20892 USA. RP Simak, J (reprint author), US FDA, CBER, Lab Cellular Hematol, HFM-335,1401 Rockville Pike, Rockville, MD 20852 USA. EM jan.simak@fda.hhs.gov RI Simak, Jan/C-1153-2011 NR 34 TC 121 Z9 129 U1 0 U2 6 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1538-7933 J9 J THROMB HAEMOST JI J. Thromb. Haemost. PD JUN PY 2006 VL 4 IS 6 BP 1296 EP 1302 DI 10.1111/j.1538-7836.2006.01911.x PG 7 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 043JS UT WOS:000237597900021 PM 16706974 ER PT J AU Vostal, JG AF Vostal, JG TI Efficacy evaluation of current and future platelet transfusion products SO JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE LA English DT Article; Proceedings Paper CT Symposium on Early Massive Trauma Transfusion CY MAY 26-27, 2005 CL USA Inst Surg Res, Ft Sam Houston, TX HO USA Inst Surg Res C1 US FDA, Ctr Biol Evaluat & Res, OBRR, Div Hematol,Lab Cellular Hematol, Rockville, MD 20857 USA. RP Vostal, JG (reprint author), US FDA, Ctr Biol Evaluat & Res, OBRR, Div Hematol,Lab Cellular Hematol, 1401 Rockville Pike, Rockville, MD 20857 USA. EM vostal@cber.fda.gov NR 7 TC 14 Z9 14 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-6061 J9 J TRAUMA JI J. Trauma-Injury Infect. Crit. Care PD JUN PY 2006 VL 60 IS 6 SU S BP S78 EP S79 DI 10.1097/01.ta.0000199921.40502.5d PG 2 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA 055VB UT WOS:000238477600021 PM 16763485 ER PT J AU Portilla, D Li, S Nagothu, KK Megyesi, J Kaissling, B Schnackenberg, L Safirstein, RL Beger, RD AF Portilla, D. Li, S. Nagothu, K. K. Megyesi, J. Kaissling, B. Schnackenberg, L. Safirstein, R. L. Beger, R. D. TI Metabolomic study of cisplatin-induced nephrotoxicity SO KIDNEY INTERNATIONAL LA English DT Article DE peroxisome proliferator activated receptor-alpha; metabolomics; acute renal failure ID ACUTE-RENAL-FAILURE; RABBIT PROXIMAL TUBULES; PPAR-ALPHA; LIPOPROTEIN METABOLISM; GLUCOSE-INTOLERANCE; PHOSPHOLIPASE A(2); HYPOXIC INJURY; RATS; INSULIN; EXPRESSION AB We have shown that cisplatin inhibits fatty acid oxidation, and that fibrate treatment ameliorates renal function by preventing the inhibition of fatty acid oxidation and proximal tubule cell death. Urine samples of mice treated with single injection of cisplatin (20mg/kg body weight) were collected for 3 days and analyzed by H-1-nuclear magnetic resonance (NMR) spectroscopy. In a separate group, urine samples of mice treated with peroxisome proliferator-activated receptor-alpha (PPAR alpha) ligand WY were also analyzed by NMR after 2 days of cisplatin exposure. Biochemical analysis of endogenous metabolites was performed in serum, urine, and kidney tissue. Electron microscopic studies were carried out to examine the effects of PPARa ligand and cisplatin. Principal component analysis demonstrated the presence of glucose, amino acids, and trichloacetic acid cycle metabolites in the urine after 48 h of cisplatin administration. These metabolic alterations precede changes in serum creatinine. Biochemical studies confirmed the presence of glucosuria, but also demonstrated the accumulation of nonesterified fatty acids, and triglycerides in serum, urine, and kidney tissue, in spite of increased levels of plasma insulin. These metabolic alterations were ameliorated by the use of PPARa ligand. Electron microscopic analysis confirmed the protective effect of the fibrate on preventing cisplatin-mediated necrosis of the S3 segment of the proximal tubule. Our study shows that cisplatin-induces a unique NMR metabolic profile in urine of mice that developed acute renal failure, and confirms the protective effect of a fibrate class of PPARa ligands. We propose that the injury-induced metabolic profile may be used as a biomarker of cisplatin-induced nephrotoxicity. C1 Univ Arkansas Med Sci, Dept Internal Med, Div Nephrol, Little Rock, AR 72205 USA. Cent Arkansas Vet Healthcare Syst, Little Rock, AR USA. Univ Zurich, Inst Anat, Div Vegetat Anat, Zurich, Switzerland. US FDA, Div Syst Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Portilla, D (reprint author), Univ Arkansas Med Sci, Dept Med, Div Nephrol, Slot 501,4301 W Markham St, Little Rock, AR 72205 USA. EM portilladidier@uams.edu FU NIDDK NIH HHS [P0-1 DK58324-01A5] NR 43 TC 78 Z9 82 U1 0 U2 22 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD JUN PY 2006 VL 69 IS 12 BP 2194 EP 2204 DI 10.1038/sj.ki.5000433 PG 11 WC Urology & Nephrology SC Urology & Nephrology GA 054LG UT WOS:000238377600018 PM 16672910 ER PT J AU Thomas, J Chakrabarti, K Kaczmarek, R Mitchell, C Romanyukha, A Nemmers, S Loscocc, M AF Thomas, J. Chakrabarti, K. Kaczmarek, R. Mitchell, C. Romanyukha, A. Nemmers, S. Loscocc, M. TI Comparison of the effects of viewing conditions and viewing angle on object dectectability for different AMLCD displays SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 30-AUG 03, 2006 CL Orlando, FL SP Amer Assoc Physicists Med C1 USUHS, Potomac, MD USA. US FDA, ODE, CDRH, Rockville, MD 20857 USA. US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. USUHS, Bethesda, MD USA. Natl Naval Med Res Inst, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2006 VL 33 IS 6 BP 2013 EP 2013 DI 10.1118/1.2240753 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 058TW UT WOS:000238688500173 ER PT J AU Wagner, RF AF Wagner, R. F. TI Bioinformatics, the multiple-biomarker classifier problem, complexity, and uncertainty SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 30-AUG 03, 2006 CL Orlando, FL SP Amer Assoc Physicists Med C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2006 VL 33 IS 6 BP 2231 EP 2232 DI 10.1118/1.2241690 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 058TW UT WOS:000238688502236 ER PT J AU Butaye, P Michael, GB Schwarz, S Barrett, TJ Brisabois, A White, DG AF Butaye, Patrick Michael, Geovana B. Schwarz, Stefan Barrett, Timothy J. Brisabois, Anne White, David G. TI The clonal spread of multidrug-resistant non-typhi Salmonella serotypes SO MICROBES AND INFECTION LA English DT Article DE antibiotic; resistance; Salmonella; epidemiology ID SEROVAR TYPHIMURIUM DT104; MULTIPLE-DRUG RESISTANCE; BACTERIAL PATHOGENS; GENOMIC ISLAND-1; BETA-LACTAMASE; UNITED-STATES; ENTERICA; NEWPORT; CATTLE; INFECTIONS AB Non-typhoid Salmonella are one of the most important organisms causing food-borne diseases worldwide. There have been significant increases in developed countries in recent years in the occurrence of resistance, in particular multidrug resistance phenotypes, in non-typhoid Salmonella spp. Such increases have been observed in many countries, not only within the European community but also the Americas and Southeast Asia. Of particular concern is the increasing detection of Salmonella isolates displaying resistance to key antimicrobials, notably fluoroquinolones and third-generation cephalosporins. An important factor associated with this increase in multidrug resistance among particular Salmonella spp. is the national and international spread of certain clonal genotypes, the most recent being the global epidemic spread of multidrug-resistant S. Typhimurium DT104, since the early 1990s. In this review, we describe examples where particular antimicrobial-resistant Salmonella serotypes emerged, persisted for periods of time, and then quickly decreased in prevalence. (c) 2006 Elsevier SAS. All rights reserved. C1 Vet & Agrochem Res Ctr, CODA, CERVA, VAR, B-1180 Brussels, Belgium. Inst Tierzucht Bundesforschungsanstalt Landwirtsc, D-31535 Neustadt, Germany. Ctr Dis Control & Prevent, Atlanta, GA USA. Agence Francaise Securite Sanitaire Aliments, Unite Caracterisat & Epidemiol Bacterienne, Maisons Alfort, France. US FDA, Off Res, Ctr Vet Med, Laurel, MD 20708 USA. RP Butaye, P (reprint author), Vet & Agrochem Res Ctr, CODA, CERVA, VAR, Groeselenberg 99, B-1180 Brussels, Belgium. EM pabut@var.fgov.be NR 38 TC 63 Z9 67 U1 0 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1286-4579 J9 MICROBES INFECT JI Microbes Infect. PD JUN PY 2006 VL 8 IS 7 BP 1891 EP 1897 DI 10.1016/j.micinf.2005.12.020 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 079CS UT WOS:000240153700028 PM 16714135 ER PT J AU Arlet, G Barrett, TJ Butaye, P Cloeckaert, A Mulvey, MR White, DG AF Arlet, Guillaume Barrett, Timothy J. Butaye, Patrick Cloeckaert, Axel Mulvey, Michael R. White, David G. TI Salmonella resistant to extended-spectrum cephalosporins: prevalence and epidemiology SO MICROBES AND INFECTION LA English DT Article DE Salmonella; extended-spectrum cephalosporins; antibiotic resistance ID AMPC BETA-LACTAMASE; ENTERICA SEROTYPE ENTERITIDIS; MULTIPLE-ANTIBIOTIC-RESISTANCE; FOOD-PRODUCING ANIMALS; ESCHERICHIA-COLI; KLEBSIELLA-PNEUMONIAE; NOSOCOMIAL OUTBREAK; SUBSP ENTERICA; CEFTRIAXONE RESISTANCE; NONTYPHOID SALMONELLA AB Salmonella resistant to extended-spectrum cephalosporins (ESCs) have emerged worldwide since 1988. By 2004, 43 countries had reported this public health problem. Resistance was mediated by classical extended-spectrum beta-lactamases, plasmid-mediated cephalosporinases, and recently a class A carbapenemase. Of these, CMY-2 is the most widely disseminated enzyme. Salmonella enterica serotype Typhimurium and S. enterica serotype Enteritidis are the most common serovars associated with ESC resistance in human infections. Many outbreaks in humans have been reported, most often among children and neonates. ESC-resistant Salmonella is frequently recovered from animals and food, with poultry as primary food source, suggesting that humans are often infected by these routes. (c) 2006 Elsevier SAS. All rights reserved. C1 Fac Med Pierre & Marie Curie, UPRES EA2392, Dept Bacteriol, F-75012 Paris, France. Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. Vet & Agrochem Res Ctr, VAR CODA CERVA, Dept Bacteriol & Immunol, B-1180 Brussels, Belgium. INRA, Unite BioAgresseurs Sante Environm, F-37380 Nouzilly, France. Natl Microbiol Lab, Antimicrobial Resistance & Nosocomial Infect, Winnipeg, MB R3E 3R2, Canada. US FDA, Ctr Vet Med, Div Anim & Food Microbiol, Laurel, MD 20708 USA. RP Arlet, G (reprint author), Fac Med Pierre & Marie Curie, UPRES EA2392, Dept Bacteriol, 27 Rue Chaligny, F-75012 Paris, France. EM guillaume.arlet@tnn.aphp.fr NR 99 TC 85 Z9 88 U1 0 U2 12 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1286-4579 J9 MICROBES INFECT JI Microbes Infect. PD JUN PY 2006 VL 8 IS 7 BP 1945 EP 1954 DI 10.1016/j.micinf.2005.12.029 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 079CS UT WOS:000240153700034 PM 16714134 ER PT J AU Zhang, QJ Sahin, O McDermott, PF Payot, S AF Zhang, Qijing Sahin, Orhan McDermott, Patrick F. Payot, Sophie TI Fitness of antimicrobial-resistant Campylobacter and Salmonella SO MICROBES AND INFECTION LA English DT Article DE antimicrobial resistance; fitness; Campylobacter; Salmonella; adaptation; fluoroquinolone ID ENTERICA SEROVAR TYPHIMURIUM; ANTIBIOTIC-RESISTANCE; BIOLOGICAL COST; IN-VIVO; DRUG-RESISTANCE; COMPENSATORY MUTATIONS; QUINOLONE RESISTANCE; SEROTYPE TYPHIMURIUM; MYCOBACTERIUM-TUBERCULOSIS; FLUOROQUINOLONE RESISTANCE AB Campylobacter and Salmonella are the most commonly reported bacterial causes of human foodborne infections, and increasing proportions of these pathogens become resistant to medically important antimicrobial agents, imposing a burden on public health. Acquisition of resistance to antibiotics affects the adaptation and evolution of Salmonella and Campylobacter in various environments. Many resistance-conferring mutations entail a biological fitness cost, while others (e.g. fluoroquinolone resistance in Campylobacter) have no cost or even enhanced fitness. In Salmonella, the fitness disadvantage due to antimicrobial resistance can be restored by acquired compensatory mutations, which occur both in vitro and in vivo. The compensated or even enhanced fitness associated with antibiotic resistance may facilitate the spread and persistence of antimicrobial-resistant Salmonella and Campylobacter in the absence of selection pressure, creating a significant barrier for controlling antibiotic-resistant foodborne pathogens. (c) 2006 Elsevier SAS. All rights reserved. C1 Iowa State Univ, Dept Vet Microbiol & Prevent Med, Ames, IA 50011 USA. Mustafa Kemal Univ, Fac Vet, Dept Microbiol, TR-31034 Antakya, Turkey. US FDA, Ctr Vet Med, Laurel, MD 20708 USA. INRA, UR086 BioAgresseurs Sante Environm, F-37380 Nouzilly, France. RP Zhang, QJ (reprint author), Iowa State Univ, Dept Vet Microbiol & Prevent Med, Ames, IA 50011 USA. EM zhang123@iastate.edu RI Zhang, Qijing/B-7530-2012; OI Payot, Sophie/0000-0001-7266-3071 FU NIDDK NIH HHS [DK063008] NR 69 TC 48 Z9 50 U1 1 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1286-4579 J9 MICROBES INFECT JI Microbes Infect. PD JUN PY 2006 VL 8 IS 7 BP 1972 EP 1978 DI 10.1016/j.micinf.2005.12.031 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 079CS UT WOS:000240153700037 PM 16714138 ER PT J AU Courtney, S Mossoba, ME Hammack, TS Keys, C Al-Khaldi, SF AF Courtney, S Mossoba, ME Hammack, TS Keys, C Al-Khaldi, SF TI Using PCR amplification to increase the confidence level of Salmonella typhimurium DNA microarray chip hybridization SO MOLECULAR AND CELLULAR PROBES LA English DT Article DE DNA microarray; Salmonella typhimurium; PCR ID OLIGONUCLEOTIDE MICROARRAY; IDENTIFICATION; PATHOGENICITY; PLATFORMS AB In order to design and validate a method to identify virulence genes of Salmonella typhimurium using DNA microarray, a protocol was developed to label the isolated bacterial DNA directly and to use PCR amplification of limited numbers of genes to validate the hybridization signals. Therefore, a DNA microarray chip of 71 virulence genes of S. typhimurium was developed and evaluated using 10 isolates. Each gene was represented by 65 bp oligonucleotide probes (oligoprobes) and immobilized on the surface of chemically modified slides. Whole DNA genomes were digested with Hinf1 and Sau3AI, labeled with a fluorescent tag of Cy3 and then hybridized. The presence of virulence genes in 10 strains of S. typhimurium was established by measuring a fluorescent signal above the background noise of the chip. PCR amplification of 10 genes (orgA, ORF319, ttrB, rmbA, misL, spi4F, spi4H, spi4N, rRNA, and purR) of S. typhimurium was used as a standard to vefify the confidence level of the DNA microarray chip. In conclusion, using PCR amplification to increase the confidence level of the microarray hybridization data was successful. (c) 2006 Elsevier Ltd. All rights reserved. C1 US FDA, Div Microbiol Studies, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Al-Khaldi, SF (reprint author), US FDA, Div Microbiol Studies, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy,HFS-517, College Pk, MD 20740 USA. EM sufian.alkhaldi@fda.hhs.gov NR 22 TC 9 Z9 11 U1 0 U2 0 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-AUG PY 2006 VL 20 IS 3-4 BP 163 EP 171 DI 10.1016/j.mcp.2005.12.001 PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Cell Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Cell Biology GA 050UG UT WOS:000238113600003 PM 16487678 ER PT J AU Myerburg, RJ Feigal, DW Lindsay, BD AF Myerburg, RJ Feigal, DW Lindsay, BD TI Life-threating malfunction of implantable cadiac devices SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 Univ Miami, Miller Sch Med, Miami, FL 33152 USA. NDA Partners, Phoenix, AZ USA. US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. Washington Univ, Sch Med, St Louis, MO 63130 USA. RP Myerburg, RJ (reprint author), Univ Miami, Miller Sch Med, Miami, FL 33152 USA. NR 5 TC 17 Z9 17 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 JUN 1 PY 2006 VL 354 IS 22 BP 2309 EP 2311 DI 10.1056/NEJMp068112 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 047ZZ UT WOS:000237918500001 PM 16702187 ER PT J AU Sansone, SA Rocca-Serra, P Tong, WD Fostel, J Morrison, N Jones, AR AF Sansone, Susanna-Assunta Rocca-Serra, Philippe Tong, Weida Fostel, Jennifer Morrison, Norman Jones, Andrew R. CA RSBI Members TI A strategy capitalizing on synergies: The Reporting Structure for Biological Investigation (RSBI) working group SO OMICS-A JOURNAL OF INTEGRATIVE BIOLOGY LA English DT Article ID TOXICOGENOMICS; STANDARDS; SYSTEMS AB In this article we present the Reporting Structure for Biological Investigation (RSBI), a working group under the Microarray Gene Expression Data (MGED) Society umbrella. RSBI brings together several communities to tackle the challenges associated with integrating data and representing complex biological investigations, employing multiple OMICS technologies. Currently, RSBI includes environmental genomics, nutrigenomics and toxicogenomics communities, where independent activities are underway to develop databases and establish data communication standards within their respective domains. The RSBI working group has been conceived as a "single point of focus" for these communities, conforming to general accepted view that duplication and incompatibility should be avoided where possible. This endeavour has aimed to synergize insular solutions into one common terminology between biologically driven standardisation efforts and has also resulted in strong collaborations and shared understanding between those in the technological domain. Through extensive liaisons with many standards efforts, several threads have been woven with the hope that ultimately technology-centered standards and their specific extensions into biological domains of interest will not only stand alone, but will also be able to function together, as interchangeable modules. This paper is part of the special issue of OMICS on data processing. C1 EBI, EMBL, NuGO, Cambridge CB10 1SD, England. US FDA, Natl Ctr Toxicol Res, Ctr Toxicoinformat, Jefferson, AR 72079 USA. NIEHS, Natl Ctr Toxicogen, Res Triangle Pk, NC 27709 USA. NERC, Bioinformat Ctr, Oxford Ctr Ecol & Hydrol, Oxford OX1 3SR, England. Univ Manchester, Sch Comp Sci, Manchester, Lancs, England. RP Sansone, SA (reprint author), EBI, EMBL, NuGO, Wellcome Trust Gen Campus, Cambridge CB10 1SD, England. EM sansone@ebi.ac.uk OI Sansone, Susanna-Assunta/0000-0001-5306-5690; Jones, Andrew/0000-0001-6118-9327 FU Intramural NIH HHS NR 10 TC 19 Z9 20 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1536-2310 J9 OMICS JI OMICS PD JUN PY 2006 VL 10 IS 2 BP 164 EP 171 DI 10.1089/omi.2006.10.164 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 079XJ UT WOS:000240210900012 PM 16901222 ER PT J AU Hirtz, DG Gilbert, PR Terrill, CM Buckman, SY AF Hirtz, DG Gilbert, PR Terrill, CM Buckman, SY TI Clinical trials in children - How are they implemented? SO PEDIATRIC NEUROLOGY LA English DT Article; Proceedings Paper CT Workshop Towards the Establishment of Clinical Trials in Pediatric and Newborn Stroke CY DEC, 2004 CL New York, NY AB Drug metabolism in children may differ from adults and adverse events may occur that are not predictable from the adult experience. Clinical trials of safety and efficacy are needed both for new treatments and those that may already be in use but have not been tested in infants and children. The role and responsibilities of different participants in a trial are discussed, including the steering committee, the clinical and statistical co-ordinating centers, and the data and safety monitoring board. Advantages of external vs internal pilot studies are reviewed. Information that is available on the websites of the Food and Drug Administration and the National Institute of Neurological Disorders and Stroke may be helpful to those planning clinical trials of interventions in children. (c) 2006 by Elsevier Inc. All rights reserved. C1 NINDS, NIH, Bethesda, MD 20892 USA. Washington Univ, Sch Med, St Louis, MO USA. US FDA, OCTAP, Div Pediat Drug Dev, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Hirtz, DG (reprint author), NINDS, NIH, 6001 Execut Blvd,Room 2212, Bethesda, MD 20892 USA. EM hirtzd@ninds.nih.gov NR 9 TC 3 Z9 3 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0887-8994 J9 PEDIATR NEUROL JI Pediatr. Neurol. PD JUN PY 2006 VL 34 IS 6 BP 436 EP 438 DI 10.1016/j.pediatrneurol.2005.09.011 PG 3 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA 059PU UT WOS:000238745500003 PM 16765820 ER PT J AU Seligman, PJ AF Seligman, Paul J. TI Thinking outside the (black) box: a new research agenda SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Editorial Material C1 US FDA, Ctr Drug Evaluat & Res, Off Pharmacoepidemiol & Stat Sci, Rockville, MD 20857 USA. RP Seligman, PJ (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Pharmacoepidemiol & Stat Sci, Rockville, MD 20857 USA. EM SELIGMANP@cder.fda.gov NR 1 TC 5 Z9 5 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD JUN PY 2006 VL 15 IS 6 BP 387 EP 389 DI 10.1002/pds.1205 PG 3 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 061NY UT WOS:000238880500003 PM 16739245 ER PT J AU Nourjah, P Ahmad, SR Karwoski, C Willy, M AF Nourjah, Parivash Ahmad, Syed Rizwanuddin Karwoski, Claudia Willy, Mary TI Estimates of acetaminophen (paracetamol)-associated overdoses in the United States SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Article DE acetaminophen; drug; overdose; deaths; NHAMCS; NEISS; NHDS ID EXPOSURE SURVEILLANCE SYSTEM; ACUTE LIVER-FAILURE; THERAPEUTIC MISADVENTURE; AMERICAN-ASSOCIATION; HEPATOTOXICITY; TOXICITY; CENTERS; ALCOHOL; RISK AB Objective To estimate the number of acetaminophen-associated overdoses in the United States and identify possible risk factors for intervention. Methods The investigators obtained estimates of acetaminophen-associated overdoses using different national databases. Two emergency room databases, a hospital discharge database, a national mortality file, and a poison surveillance database were used to identify cases. The FDA's spontaneous reporting system was searched to identify possible root causes for overdoses. Results Analysis of national databases show that acetaminophen-associated overdoses account for about 56000 emergency room visits and 26000 hospitalizations yearly. Analysis of national mortality files shows 458 deaths occur each year from acetaminophen-associated overdoses; 100 of these are unintentional. The poison surveillance database showed near-doubling in the number of fatalities associated with acetaminophen from 98 in 1997 to 173 in 2001. AERS data describe a number of possible causes for unintentional acetamillophen-associated overdoses. Conclusions Each year a substantial numbers of Americans experience intentional and unintentional acetaminophen-associated overdoses that, in severe cases, lead to serious illness and possible death. This summary of a series of analyses highlights the need for strategies to reduce this public health burden. Copyright (c) 2005 John Wiley & Sons, Ltd. C1 US FDA, Ctr Drug Evaluat & Res, Div Drug Risk Evaluat, Off Drug Safety, Silver Spring, MD 20993 USA. RP Nourjah, P (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Drug Risk Evaluat, Off Drug Safety, 10903 New Hampshire Ave,3414 Bldg 22, Silver Spring, MD 20993 USA. EM NOURJAHP@CDER.FDA.GOV NR 22 TC 102 Z9 105 U1 0 U2 11 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 JUN PY 2006 VL 15 IS 6 BP 398 EP 405 DI 10.1002/pds.1191 PG 8 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 061NY UT WOS:000238880500007 PM 16294364 ER PT J AU Szarfman, A Tonning, JM Levine, JG Doraiswamy, PM AF Szarfman, A Tonning, JM Levine, JG Doraiswamy, PM TI Atypical antipsychotics and pituitary tumors: A pharmacovigilance study SO PHARMACOTHERAPY LA English DT Article; Proceedings Paper CT 6th International Conference on Bipolar Disorder CY JUN 16-18, 2005 CL Pittsburgh, PA DE antipsychotics; pituitary tumors; hyperprolactinemia; data mining; Multi-item Gamma Poisson Shrinker algorithm; MGPS ID SPONTANEOUS REPORTING SYSTEM; LARGE FREQUENCY TABLES; PROLACTIN LEVELS; SCHIZOPHRENIA; DOPAMINE; HYPERPROLACTINEMIA; RISPERIDONE; DRUGS; PERSPECTIVES; ADOLESCENTS AB Study Objective. To analyze the disproportionality of reporting of hyperprolactinemia, galactorrhea, and pituitary tumors with seven widely used antipsyc otic drugs. Design. Retrospective pharmacovigilance study Data Source. United States Food and Drug Administration's Adverse Event Reporting System (AERS) database. Intervention. We initially identified higher-than-expected postmarketing reports of pituitary tumors associated with risperidone, a potent dopamine D-2-receptor antagonist antipsychotic, by analyzing reporting patterns of these tumors in the AERS database. To further examine this association, we analyzed disproportionate reporting patterns of pituitary tumor reports for seven antipsychotics with different affinities for blocking D-2 receptors: aripiprazole, clozapine, olanzapine, quetiapine, risperidone, ziprasidone, and haloperidol. Measurements and Main Results. To conduct both of these analyses, we used the Multi-item Gamma Poisson Shrinker (MGPS) data mining algorithm applied to the AERS database. The MGPS uses a Bayesian model to calculate adjusted observed: expected ratios of drug-adverse event associations (Empiric Bayes Geometric Mean [EBGM] values) in huge drug safety databases. The higher the adjusted reporting ratio, or EBGM value, the greater the strength of the association between a drug and an adverse event. Risperidone had the highest adjusted reporting ratios for hyperprolactinemia (EBGM 34.9, 90% confidence interval [CI] 32.8-37.1]), galactorrhea (EBGM 19.9, 90% CI 18.6-21.4), and pituitary tumor (EBGM 18.7, 90% CI 14.9-23.3) among the seven antipsychotics, and one of the highest scores for all drugs in the AERS database. Some tumors were associated with visual field defects, hemorrhage, convulsions, surgery, and severe (> 10-fold) prolactin elevations. The EBGM values for risperidone for these adverse events were higher in women, but high EBGM values for these events were also seen in men and children. Moreover, the rank order of the EBGM values for pituitary tumors corresponded to the affinities of these seven drugs for D-2 receptors. Conclusion. Treatment with potent D-2-receptor antagonists, such as risperidone, may be associated with pituitary tumors. These findings are consistent with animal (mice) studies and raise the need for clinical awareness and longitudinal studies. C1 US FDA, Ctr Drug Evaluat & Res, Off Pharmacoepidemiol & Stat Sci, Immediat Off, Silver Spring, MD 20993 USA. Duke Univ, Med Ctr, Dept Psychiat, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. RP Szarfman, A (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Pharmacoepidemiol & Stat Sci, Immediat Off, 10903 New Hampshire Ave,Bldg 22,Room 5464, Silver Spring, MD 20993 USA. NR 31 TC 77 Z9 82 U1 2 U2 9 PU PHARMACOTHERAPY PUBLICATIONS INC PI BOSTON PA NEW ENGLAND MEDICAL CENTER, 806, 750 WASHINGTON ST, BOSTON, MA 02111 USA SN 0277-0008 J9 PHARMACOTHERAPY JI Pharmacotherapy PD JUN PY 2006 VL 26 IS 6 BP 748 EP 758 DI 10.1592/phco.26.6.748 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 049JA UT WOS:000238011100002 PM 16716128 ER PT J AU Adkins, S Webb, SE Achor, D Baker, CA AF Adkins, S. Webb, S. E. Achor, D. Baker, C. A. TI A novel whitelly-transmitted potyvirus isolated from cucurbits in Florida SO PHYTOPATHOLOGY LA English DT Meeting Abstract C1 [Baker, C. A.] FDACS DPI, Gainesville, FL USA. [Adkins, S.] USDA ARS, USHRL, Ft Pierce, FL USA. [Webb, S. E.] Univ Florida, Gainesville, FL USA. [Achor, D.] Univ Florida, Lake Alfred, FL 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 2006 VL 96 IS 6 SU S BP S3 EP S3 PG 1 WC Plant Sciences SC Plant Sciences GA V44GP UT WOS:000202991500016 ER PT J AU Probst, C Njapau, H Cotty, PJ AF Probst, C. Njapau, H. Cotty, P. J. TI Outbreak of acute aflatoxicoses in Kenya, 2004: Etiology of contamination SO PHYTOPATHOLOGY LA English DT Meeting Abstract C1 [Njapau, H.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. [Cotty, P. J.] Univ Arizona, Dept Plant Sci, USDA ARS, Tucson, AZ 85721 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 2006 VL 96 IS 6 SU S BP S94 EP S94 PG 1 WC Plant Sciences SC Plant Sciences GA V44GP UT WOS:000202991500604 ER PT J AU Perrin-Guyomard, A Poul, JM Laurentie, M Sanders, P Fernandez, AH Bartholomew, M AF Perrin-Guyomard, A Poul, JM Laurentie, M Sanders, P Fernandez, AH Bartholomew, M TI Impact of ciprofloxacin in the human-flora-associated (HFA) rat model: Comparison with the HFA mouse model SO REGULATORY TOXICOLOGY AND PHARMACOLOGY LA English DT Article DE human-flora-associated rodent model; intestinal flora; ciprofloxacin; drug residues ID GERM-FREE MICE; COLONIZATION RESISTANCE; INTESTINAL MICROFLORA; FECAL FLORA; CLOSTRIDIUM-DIFFICILE; ESCHERICHIA-COLI; GUT FLORA; TRACT; DIET; COMPETITION AB The ecological impact of different doses of ciprofloxacin was investigated in an experimental germ-free rat model into which human fecal flora was inoculated. Animals received oral doses (gavage) of 0, 0.25, 2.5, and 25 mg/kg body weight (bw) of ciprofloxacin once daily for 5 weeks. All doses of ciprofloxacin significantly reduced aerobic populations. Elimination of Enterobacteriaceae and reduction of bifodibacteria were noticed in the group treated with 25 mg/kg of the antibiotic. The rest of the intestinal flora was not affected. These effects were reversible after the treatment ended. The percentage of resistant enterococci increased in rats treated with 2.5 and 25 mg/kg; however, this increase was not statistically significant. There was a significant (P < 0.05) emergence of ciprofloxacin-resistant Bacteroides fragilis group with 25 mg/kg bw, which is equivalent to a human therapeutic dosage of the antibiotic. The MIC values and the percentage of resistance remained elevated 2 weeks after the end of treatment in this anaerobic population. Although sub-populations of enterococci and Enterobacteriaceae showed decreased susceptibility after ciprofloxacin administration, resistance was not evident. The ability of an exogenous strain of Salmonella to colonize the intestine of animals treated with 25 mg/kg of ciprofloxacin confirmed that the drug disrupted the colonization barrier effect of the indigenous flora at the high dose level tested. No changes in the metabolic parameters occurred during the antibiotic treatment. The results obtained in the HFA rat model were similar to those obtained in our previous study using the HFA mice model where ciprofloxacin at 0.125, 1.25, and 12.5 mg/kg bw induced a decrease of enterococci and Enterobacteriaceae populations. The high dose of ciprofloxacin also induced a decrease in bifidobacteria counts, an increase in levels of resistant B. fragilis group and a significant (P < 0.05) disruption of the colonization resistance of the barrier flora in HFA mice. Published by Elsevier Inc. C1 Agence Francaise Secur Sanit Aliments, Lab Etudes & Rech Medicaments Vet & Desinfectants, F-35302 Fougeres, France. US FDA, Ctr Vet Med, Rockville, MD 20855 USA. RP Perrin-Guyomard, A (reprint author), Agence Francaise Secur Sanit Aliments, Lab Etudes & Rech Medicaments Vet & Desinfectants, BP 90203, F-35302 Fougeres, France. EM a.perrin-guyomard@afssa.fr OI Sanders, Pascal/0000-0003-4019-480X NR 36 TC 11 Z9 13 U1 1 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0273-2300 J9 REGUL TOXICOL PHARM JI Regul. Toxicol. Pharmacol. PD JUN PY 2006 VL 45 IS 1 BP 66 EP 78 DI 10.1016/j.yrtph.2006.02.002 PG 13 WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology SC Legal Medicine; Pharmacology & Pharmacy; Toxicology GA 045VS UT WOS:000237771400007 PM 16563587 ER PT J AU Liang, HY Badano, A AF Liang, HY Badano, A TI Precision of gray level response time measurements of medical liquid crystal display SO REVIEW OF SCIENTIFIC INSTRUMENTS LA English DT Article AB We characterized the instrumentation needed for accurate measurements of temporal response of liquid crystal displays for medical imaging applications. We investigated the effect of display and detector noise on the minimum measurable gray level (or luminance) difference. For a typical display, a gray level difference of 5 at high gray levels and 20 at low gray levels is needed to obtain an accurate measurement. A less noisy light emitting diode light source is employed to study the smallest measurable luminance difference at different luminance levels. We found that luminance differences of the order of 0.5 cd/m(2) can be measured with an uncertainty of 10%. (c) 2006 American Institute of Physics. C1 US FDA, NIBIB, CDRH, Joint Lab Anal Med Images, Rockville, MD 20852 USA. RP Liang, HY (reprint author), US FDA, CDRH, NIBIB,Off Sci & Engn Labs, Lab Assessment Med Imaging Syst,Dept Imaging & Ap, 12720 Twinbrook Pkwy, Rockville, MD 20852 USA. EM aldo.badano@fda.hhs.gov OI badano, aldo/0000-0003-3712-6670 NR 7 TC 7 Z9 7 U1 0 U2 2 PU AMER INST PHYSICS PI MELVILLE PA CIRCULATION & FULFILLMENT DIV, 2 HUNTINGTON QUADRANGLE, STE 1 N O 1, MELVILLE, NY 11747-4501 USA SN 0034-6748 J9 REV SCI INSTRUM JI Rev. Sci. Instrum. PD JUN PY 2006 VL 77 IS 6 AR 065104 DI 10.1063/1.2205151 PG 5 WC Instruments & Instrumentation; Physics, Applied SC Instruments & Instrumentation; Physics GA 059KX UT WOS:000238732800060 ER PT J AU Chen, JJ Tsai, CA Moon, H Ahn, H Young, JJ Chen, CH AF Chen, J. J. Tsai, C. -A. Moon, H. Ahn, H. Young, J. J. Chen, C. -H. TI Decision threshold adjustment in class prediction SO SAR AND QSAR IN ENVIRONMENTAL RESEARCH LA English DT Article DE concordance; cross validation; receiver operating characteristic curve; sensitivity and specificity; weighted k-NN ID CLASSIFICATION; TOXICOLOGY; CANCER; SELECTION; PATTERNS; DATABASE; MODELS AB Standard classification algorithms are generally designed to maximize the number of correct predictions (concordance). The criterion of maximizing the concordance may not be appropriate in certain applications. In practice, some applications may emphasize high sensitivity (e.g., clinical diagnostic tests) and others may emphasize high specificity (e.g., epidemiology screening studies). This paper considers effects of the decision threshold on sensitivity, specificity, and concordance for four classification methods: logistic regression, classification tree, Fisher's linear discriminant analysis, and a weighted k-nearest neighbor. We investigated the use of decision threshold adjustment to improve performance of either sensitivity or specificity of a classifier under specific conditions. We conducted a Monte Carlo simulation showing that as the decision threshold increases, the sensitivity decreases and the specificity increases; but, the concordance values in an interval around the maximum concordance are similar. For specified sensitivity and specificity levels, an optimal decision threshold might be determined in an interval around the maximum concordance that meets the specified requirement. Three example data sets were analyzed for illustrations. C1 Natl Ctr Toxicol Res, Food & Drug Adm, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. Acad Sinica, Inst Stat Sci, Taipei 11529, Taiwan. SUNY Stony Brook, Dept Appl Math & Stat, Stony Brook, NY 11794 USA. RP Chen, JJ (reprint author), Natl Ctr Toxicol Res, Food & Drug Adm, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. EM jchen@nctr.fda.gov OI Tsai, Chen-An/0000-0002-7490-4331 NR 24 TC 14 Z9 14 U1 2 U2 12 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 JUN PY 2006 VL 17 IS 3 BP 337 EP 352 DI 10.1080/10659360600787700 PG 16 WC Chemistry, Multidisciplinary; Computer Science, Interdisciplinary Applications; Environmental Sciences; Mathematical & Computational Biology; Toxicology SC Chemistry; Computer Science; Environmental Sciences & Ecology; Mathematical & Computational Biology; Toxicology GA 070DU UT WOS:000239501300007 PM 16815772 ER PT J AU Li, QH Lagakos, SW AF Li, QH Lagakos, SW TI On the relationship between directional and omnibus statistical tests SO SCANDINAVIAN JOURNAL OF STATISTICS LA English DT Article DE asymptotic equivalence; chi-square partition; constrained tests; directional tests; linear combination tests; omnibus tests ID FAILURE TIME DATA; REGRESSION-ANALYSIS AB A common statistical problem involves the testing of a K-dimensional parameter vector. In both parametric and semiparametric settings, two types of directional tests - linear combination and constrained tests - are frequently used instead of omnibus tests in hopes of achieving greater power for specific alternatives. In this paper, we consider the relationship between these directional tests, as well as their relationship to omnibus tests. Every constrained directional test is shown to be asymptotically equivalent to a specific linear combination test under a sequence of contiguous alternatives and vice versa. Even when the direction of the alternative is known, the constrained test in general will not be optimal unless the objective function used to derive it is efficient. For an arbitrary alternative, insight into the power characteristics of directional tests in comparison to omnibus tests can be gained by a chi-square partition of the omnibus test. C1 US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Cambridge, MA 02138 USA. RP Li, QH (reprint author), US FDA, Ctr Drug Evaluat & Res, HFD-705,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM liq@cder.fda.gov NR 10 TC 4 Z9 4 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0303-6898 J9 SCAND J STAT JI Scand. J. Stat. PD JUN PY 2006 VL 33 IS 2 BP 239 EP 246 DI 10.1111/j.1467-9469.2005.00489.x PG 8 WC Statistics & Probability SC Mathematics GA 037YS UT WOS:000237184600006 ER PT J AU Player, A Wang, YH Bhattacharya, B Rao, M Puri, RK Kawasaki, ES AF Player, Audrey Wang, Yonghong Bhattacharya, Bhaskar Rao, Mahendra Puri, Raj K. Kawasaki, Ernest S. TI Comparisons between transcriptional regulation and RNA expression in human embryonic stem cell lines SO STEM CELLS AND DEVELOPMENT LA English DT Article ID GENE-EXPRESSION; GROWTH ARREST; MOLECULAR SIGNATURE; CANCER; SOX2; DIFFERENTIATION; OCT4; NETWORKS; COMPLEX; BIOLOGY AB Recent studies have focused on transcriptional regulation and gene expression profiling of human embryonic stem cells (hESCs). However, little information is available regarding the relationship between RNA expression and transcriptional regulation, which is critical in the complete understanding of pluripotency and differentiation of hESCs. In the current study, we determined RNA expression of three different hESC lines compared to Human universal reference RNA expression (HuU-RNA) using a full genome expression microarray, and compared our results to target genes previously identified using ChIP-on-chip analysis. The objective was to identify genes common between the two methods, and generate a more reliable list of embryonic signature genes. Even though hESCs were obtained from different sources and maintained under different conditions, a considerable number of genes could be identified as common between RNA expression and transcriptional regulation analyses. As an example, results from ChIP-on-chip studies show that OCT4, SOX2, and NANOG co-occupy SOX2, OCT4, TDGF1, GJA1, SET, and DPPA4 genes. The results are consistent with RNA expression analyses that demonstrate these genes as differently expressed in our hESC lines, further substantiating their role across cell types and confirming their importance as embryonic signatures. In addition, we report the differential expression of growth arrest-specific ( GAS) family of genes in hESC. GAS2L1 and GAS3 members of this family appear to be transcriptionally regulated by OCT4, SOX2, or NANOG, whereas GAS5 and GAS6 are not; all of the -genes are differentially expressed, as determined by microarray and validated via quantitative (Q)-PCR. Collectively, these data provide insight into the relationship between gene expression and transcriptional regulation, resulting in a reliable list of genes associated with hESCs. C1 NCI, Ctr Adv Technol, NIH, Microarray Facil, Bethesda, MD 20892 USA. SAIC Frederick Inc, NCI Frederick, Frederick, MD 21702 USA. US FDA, Ctr Biol & Evaluat & Res, Tumor Vaccines & Biotechnol Branch, Bethesda, MD 20892 USA. NIA, Neurosci Lab, Baltimore, MD 21224 USA. RP Player, A (reprint author), NCI, Ctr Adv Technol, NIH, Microarray Facil, 8717 Grovemont Circle, Bethesda, MD 20892 USA. EM playera@mail.nih.gov FU Intramural NIH HHS; PHS HHS [N01-C)-12400] NR 35 TC 23 Z9 25 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 2006 VL 15 IS 3 BP 315 EP 323 DI 10.1089/scd.2006.15.315 PG 9 WC Cell & Tissue Engineering; Hematology; Medicine, Research & Experimental; Transplantation SC Cell Biology; Hematology; Research & Experimental Medicine; Transplantation GA 064VO UT WOS:000239118100004 PM 16846370 ER PT J AU Kioi, M Husain, SR Croteau, D Kunwar, S Puri, RK AF Kioi, M Husain, SR Croteau, D Kunwar, S Puri, RK TI Convection-enhanced delivery of interleukin-13 receptor-directed cytotoxin for malignant glioma therapy SO TECHNOLOGY IN CANCER RESEARCH & TREATMENT LA English DT Review DE interleukin-13; IL-13 receptor; immunotoxin; cytotoxin; glioblastoma multiforme; convection-enhanced delivery; targeted brain tumor therapy ID PLASMINOGEN-ACTIVATOR RECEPTOR; IL4-PSEUDOMONAS EXOTOXIN NBI-3001; CHIMERIC FUSION PROTEINS; RENAL-CELL CARCINOMA; PSEUDOMONAS EXOTOXIN; IL-13 RECEPTOR; BRAIN-TUMORS; ANTITUMOR-ACTIVITY; GLIOBLASTOMA-MULTIFORME; ALPHA-2 CHAIN AB The treatment of patients with malignant brain tumors, in particular glioblastoma multiforme (GBM) is very challenging because of their diffuse infiltrative nature and the cytological heterogeneity. The median survival of patients with newly diagnosed GBM is only 12-15 months, and only 8-12% of them survive for two years. Novel approaches for brain tumor therapy are needed. Recently, targeted therapies have emerged as promising modality for cancer targeting. We have discovered that high affinity plasma membrane receptor for interleukin-13 (IL-13), an immune regulatory cytokine, is over-expressed in 60-80% of malignant brain tumors. To target these IL-13R, we generated a chimeric fusion protein, composed of human IL-13 and mutated Pseudomonas exotoxin (PE), termed IL-13 cytotoxin (1L-13-PE), and tested its cytotoxicity to IL-13R-expressing GBM cells. IL-13 cytotoxin was highly potent and selective in killing IL-13R-expressing GBM cells. In contrast, normal cells including brain, immune, and endothelial cells were generally not affected by this cytotoxin due to no or low expression of IL-13R. In vivo pre-clinical studies for safety and toxicity were also performed in mice, rats, and monkeys, and IL-13 cytotoxin was found to be well tolerated by both systemic and intracerebral administrations. IL-13 cytotoxin was found to mediate remarkable efficacy in animal models of human brain tumors. Encouraged by these pre-clinical studies, four Phase 1/2 clinical trials in adult patients with recurrent malignant glioma have been completed. These clinical trials involved convection-enhanced delivery (CED) of IL-13 cytotoxin either intratumoral or intraparenchymal after resection of tumor. CED is a novel loco-regional drug delivery method for intracranial tumors that relies on a continuous pressure gradient to distribute drug into interstitial space. This route of IL-13 cytotoxin administration appears to be very well tolerated and have a good risk-benefit profile. Most recently, a randomized controlled Phase 3 clinical trial (PRECISE) with intraparenchymal IL-13 cytotoxin administration was completed and subjects are being monitored for safety and survival. C1 US FDA, Ctr Biol Evaluat & Res, Tumor Vaccines & Biotechnol Branch, Div Cellular & Gene Therapies, Bethesda, MD 20892 USA. NeoPharm Inc, Lake Forest, IL USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Puri, RK (reprint author), US FDA, Ctr Biol Evaluat & Res, Tumor Vaccines & Biotechnol Branch, Div Cellular & Gene Therapies, 29 Lincoln Dr MSC 4555, Bethesda, MD 20892 USA. EM raj.puri@fda.hhs.gov OI Kioi, Mitomu/0000-0002-7981-3340 NR 103 TC 45 Z9 45 U1 1 U2 2 PU ADENINE PRESS PI SCHENECTADY PA 2066 CENTRAL AVE, SCHENECTADY, NY 12304 USA SN 1533-0346 J9 TECHNOL CANCER RES T JI Technol. Cancer Res. Treat. PD JUN PY 2006 VL 5 IS 3 BP 239 EP 250 PG 12 WC Oncology SC Oncology GA 055TN UT WOS:000238473400007 PM 16700620 ER PT J AU Cooper, S Latendresse, JR Doerge, DR Twaddle, NC Fu, X Delclos, KB AF Cooper, S Latendresse, JR Doerge, DR Twaddle, NC Fu, X Delclos, KB TI Dietary modulation of p-nonylphenol-induced polycystic kidneys in male Sprague-Dawley rats SO TOXICOLOGICAL SCIENCES LA English DT Article DE p-nonylphenol; kidney; polycystic kidney; soy; AIN-93G purified diet ID ELECTROSPRAY MASS-SPECTROMETRY; LABORATORY-ANIMAL FEED; SOY PROTEIN; DISEASE PROGRESSION; RODENT DIETS; LIQUID-CHROMATOGRAPHY; REPRODUCTIVE-SYSTEM; ESTROGENIC ACTIVITY; SEXUAL DEVELOPMENT; RENAL INJURY AB We had previously found that p-nonylphenol (NP) at 1000-2000 ppm in a soy- and alfalfa-free diet induced severe polycystic kidney disease (PKD) in both male and female pups exposed from gestation day 7 through postnatal day (PND) 50 and hypothesized that differences in dietary components contributed to the severity of lesions relative to those reported in other studies using similar doses of NP. The present study investigated the dietary modulation of NP-induced PKD using the same exposure regimen with 2000 ppm NP in four different diets: the natural ingredient soy- and alfalfa-free diet that had been used in the earlier study, Purina 5K96; two defined diets AIN-93G, designated AIN-CAS, and a modified AIN-93G with soy protein isolate replacing casein as the protein source (AIN-SPI); and the commonly used natural ingredient diet Purina 5001 (P5001). Serum isoflavone levels were negligible in animals fed the soy-free AIN-CAS and 5K96 diets and were 2- to 18-fold higher in animals fed P5001 than in those fed AIN-SPI. Consumption of P5001 was significantly greater than consumption of the other diets, and those animals fed P5001 were generally significantly heavier than animals receiving the other diets. NP significantly reduced body weight gain in male pups regardless of the diet fed. There was no evidence of NP-induced kidney toxicity in male pups at PND 2, 14, or 21 or in the dams. In PND 50 male pups, serum blood urea nitrogen was significantly elevated by NP in all diet groups. Urine volume and urinary N-acetyl beta-glucuronidase were significantly increased by NP in the soy-free 5K96 and AIN-CAS diet groups. Relative kidney weights were increased by NP in all diet groups except P5001, with the greatest increase in AIN-CAS and 5K96 diet groups. Microscopic evaluation of kidneys from the PND 50 males showed that NP induced PKD in all diet groups but with marked variation in the severity depending on the diet. PKD was severe in 100% of the NP-treated animals in the AIN-CAS and 5K96 groups, moderate in 88% of the AIN-SPI diet group, and mild in only 40% of the P5001 diet group. Thus, diet can significantly modulate the development of PKD induced by dietary NP in rats. Soy components, as well as other complex dietary factors, may account for the level of protection afforded by the P5001 diet. C1 Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. Univ Arkansas Med Sci, Dept Pharmacol & Toxicol, Little Rock, AR 72205 USA. Toxicol Pathol Associates, Jefferson, AR 72079 USA. RP Delclos, KB (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, 3900 NCTR Rd,HFT-110, Jefferson, AR 72079 USA. EM Barry.Delclos@fda.hhs.gov RI Latendresse, John/A-9215-2009 NR 70 TC 6 Z9 8 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD JUN PY 2006 VL 91 IS 2 BP 631 EP 642 DI 10.1093/toxsci/kfj171 PG 12 WC Toxicology SC Toxicology GA 044UG UT WOS:000237697300033 PM 16554316 ER PT J AU Shankar, G Shores, E Wagner, C Mire-Sluis, A AF Shankar, G Shores, E Wagner, C Mire-Sluis, A TI Scientific and regulatory considerations on the immunogenicity of biologics SO TRENDS IN BIOTECHNOLOGY LA English DT Review ID RISK-BASED APPROACH; THERAPEUTIC MONOCLONAL-ANTIBODIES; RED-CELL APLASIA; ANTIERYTHROPOIETIN ANTIBODIES; PROTEIN PRODUCTS; RECOMBINANT; BIOPHARMACEUTICALS; ANIMALS AB Immune responses against non-vaccine biologics can affect their efficacy and safety, resulting in adverse events that could include administration reactions, hypersensitivity, deficiency syndromes and lack of a clinical response in treated patients. With the relatively recent development of numerous biologics, immunogenicity testing has become a key component in the demonstration of clinical safety and efficacy; in fact, it is highly unlikely that regulatory approval would be granted for a biologic without an assessment of its immunogenicity. However, recommendations from regulatory agencies regarding the requirements for when and how to carry out immunogenicity testing are dispersed among numerous guidance documents. To enable the evaluation of the effects of immunogenicity on safety and efficacy, the authors have consolidated recommendations from the regulatory guidelines, and present current approaches and future directions for the assessment of immunogenicity. C1 Centocor Res & Dev Inc, Radnor, PA 19087 USA. CDER, Div Therapeut Prot, FDA, Bethesda, MD 20892 USA. Prod Qual & External Affairs, Newbury Pk, CA 91320 USA. RP Shankar, G (reprint author), Centocor Res & Dev Inc, 145 Kings Prussia Rd, Radnor, PA 19087 USA. EM gshanka3@cntus.jnj.com NR 40 TC 89 Z9 93 U1 0 U2 7 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0167-7799 J9 TRENDS BIOTECHNOL JI Trends Biotechnol. PD JUN PY 2006 VL 24 IS 6 BP 274 EP 280 DI 10.1016/j.tibtech.2005.04.001 PG 7 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 058WO UT WOS:000238695500007 PM 16631266 ER PT J AU Meseda, CA Stout, RR Weir, JP AF Meseda, Clement A. Stout, Richard R. Weir, Jerry P. TI Evaluation of a needle-free delivery platform for prime-boost immunization with DNA and modified vaccinia virus Ankara vectors expressing herpes simplex virus 2 glycoprotein D SO VIRAL IMMUNOLOGY LA English DT Article ID GM-CSF GENE; IMMUNE-RESPONSES; PLASMID DNA; CYTOKINE RESPONSES; VACCINATION; IMMUNOGENICITY; INJECTION; ANTIBODY; MUCOSAL; ROUTE AB A previous report described a prime-boost immunization strategy using plasmid and modified vaccinia virus Ankara (MVA) vectors expressing herpes simplex: virus 2 glycoprotein D (gD). Enhanced humoral and cellular immune responses were elicited by the prime-boost combination compared to plasmid DNA immunization alone. Surprisingly, a more diverse antibody isotype response, and a greater antibody and cellular immune response, was obtained if the gD MVA vector was used as the priming immunization rather than the gD plasmid vector. The present report evaluates the use of a needle-free delivery platform (Biojector) for delivery of plasmid and MVA gD-expressing vectors in a prime-boost immunization strategy. Needle-free delivery of both plasmid and MVA gD expression vectors was efficient, reproducible, and elicited a strong immune response in immunized mice. Biojector delivery of plasmid DNA was able to evoke a broader isotype response and cellular immune response than that obtained by gene gun delivered plasmid DNA. Further, DNA priming by Biojector delivery as part of a prime-boost procedure with MVA-gD2 resulted in a diverse antibody isotype distribution and enhanced cellular immune responses, similar to the responses obtained when MVA-gD2 was used as the priming immunization. Thus, needle-free delivery of plasmid DNA may provide additional flexibility and options for effective prime-boost vaccination. C1 US FDA, Ctr Biol Evaluat & Res, Lab DNA Viruses, Bethesda, MD 20014 USA. Bioject Inc, Tualatin, OR USA. RP Weir, JP (reprint author), Ctr Biol Evaluat & Res, Div Viral Prod, HFM-457,1401 Rockville Pike, Rockville, MD 20852 USA. EM weirj@cber.fda.gov NR 30 TC 12 Z9 13 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0882-8245 J9 VIRAL IMMUNOL JI Viral Immunol. PD SUM PY 2006 VL 19 IS 2 BP 250 EP 259 DI 10.1089/vim.2006.19.250 PG 10 WC Immunology; Virology SC Immunology; Virology GA 061DN UT WOS:000238851500014 PM 16817767 ER PT J AU Roberts, JE Kukielczak, B Chignell, C Sik, B Hu, DN Principato, M AF Roberts, JE Kukielczak, B Chignell, C Sik, B Hu, DN Principato, M TI Simulated microgravity induced damage in human retinal pigment epithelial cells SO MOLECULAR VISION LA English DT Article; Proceedings Paper CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 30-MAY 05, 2005 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol ID WALL VESSEL BIOREACTOR; FACTOR-H POLYMORPHISM; MACULAR DEGENERATION; UVEAL MELANOCYTES; T-LYMPHOCYTES; LIGHT DAMAGE; RAT RETINA; IN-VITRO; ENVIRONMENT; EYE AB Purpose: The goal of this study was to determine the potential damage to the human retina that may occur from weightlessness during space flight using simulated microgravity. Methods: Human retinal pigment epithelial (hRPE) cells were cultured for 24 h in a National Aeronautics and Space Administration-designed rotating wall bioreactor vessel to mimic the microgravity environment of space. Single-stranded breaks in hRPE DNA induced by simulated gravity were measured using the comet assay. In addition, the production of the inflammatory mediator prostaglandin E2 (PGE2) was measured in these cells 48 h after recovery from simulated microgravity exposure. Results: Simulated microgravity induced single-stranded breaks in the hRPE DNA that were not repaired within 48 h. Furthermore, PG E2 production was dramatically increased 48 h after the initial microgravity-induced damage, indicating the induction of an inflammatory response. There was less DNA damage and no PGE2 release in hRPE cells pretreated with the antiinflammatory agent cysteine during their exposure to microgravity. Conclusions: We have demonstrated that the microgravity environment generated by a NASA-designed rotating wall bioreactor vessel induces an inflammatory response in hRPE cells. This system thus constitutes a new model system for the study of inflammation in the retina, a system that does not involve the introduction of an exogenous chemical agent or supplementary irradiation. This in vitro method may also be useful for testing novel therapeutic approaches for suppression of retinal inflammation. Furthermore, we suggest a safe prophylactic treatment for prevention of acute, transitory, or enhanced age-related permanent blindness in astronauts or flight personnel engaged in long-haul flights. C1 Fordham Univ, Dept Nat Sci, New York, NY 10023 USA. Natl Inst Environm Hlth Sci, Lab Chem & Pharmacol, Res Triangle Pk, NC USA. New York Eye & Ear Infirm, Tissue Culture Ctr, New York, NY 10003 USA. New York Eye & Ear Infirm, Dept Pathol & Lab Med, New York, NY 10003 USA. New York Eye & Ear Infirm, Dept Ophthalmol, New York, NY 10003 USA. US FDA, Laurel, MD USA. RP Roberts, JE (reprint author), Fordham Univ, Dept Nat Sci, 113 W 60th St, New York, NY 10023 USA. EM jroberts@fordham.edu FU Intramural NIH HHS NR 46 TC 8 Z9 9 U1 0 U2 4 PU MOLECULAR VISION PI ATLANTA PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E, ATLANTA, GA 30322 USA SN 1090-0535 J9 MOL VIS JI Mol. Vis. PD MAY 30 PY 2006 VL 12 IS 70 BP 633 EP 638 PG 6 WC Biochemistry & Molecular Biology; Ophthalmology SC Biochemistry & Molecular Biology; Ophthalmology GA 050PB UT WOS:000238099300001 PM 16760899 ER PT J AU Williams, FB Sander, LC Wise, SA Girard, J AF Williams, FB Sander, LC Wise, SA Girard, J TI Development and evaluation of methods for determination of naphthodianthrones and flavonoids in St. John's wort SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article DE pressurized fluid extraction; Soxhlet extraction; sonication; St. John's wort; mass spectrometry; liquid chromatography; fluorescence detection; absorbance detection; hypericin; pseudohypericin ID PERFORMANCE LIQUID-CHROMATOGRAPHY; HYPERICUM-PERFORATUM L.; MAGNETIC-RESONANCE-SPECTROSCOPY; MASS-SPECTROMETRY; ACTIVE COMPONENTS; CAPILLARY-ELECTROPHORESIS; ELECTROCHEMICAL DETECTION; EXTRACTION CONDITIONS; DIETARY-SUPPLEMENTS; FUNCTIONAL FOODS AB Several major constituents in St. John's wort were determined for a homogenized plant sample. Three extraction techniques were evaluated: Soxhlet extraction, pressurized-fluid extraction (PFE), and sonication extraction. Levels of nine constituents (chlorogenic acid, rutin, hyperoside, isoquercitrin, quercitrin, quercetin, amentoflavone, pseudohypericin, and hypericin) were measured using liquid chromatography with ultraviolet/visible absorbance, mass spectrometric, and fluorescence detection. Levels of total naphthodianthrones determined by liquid chromatography (LC) with absorbance detection at 590 nm were compared with levels determined by direct spectrophotometry at the same wavelength. Additionally, the methods described in this paper were applied to several brands of St. John's wort finished products. Published by Elsevier B.V. C1 Natl Inst Stand & Technol, Gaithersburg, MD 20899 USA. American Univ, Washington, DC 20016 USA. US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Sander, LC (reprint author), Natl Inst Stand & Technol, Gaithersburg, MD 20899 USA. EM lane.sander@nist.gov NR 49 TC 27 Z9 29 U1 2 U2 13 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 19 PY 2006 VL 1115 IS 1-2 BP 93 EP 102 DI 10.1016/j.chroma.2006.02.078 PG 10 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 041UJ UT WOS:000237481400010 PM 16554056 ER PT J AU Li, H Kijak, PJ Turnipseed, SB Cui, W AF Li, H Kijak, PJ Turnipseed, SB Cui, W TI Analysis of veterinary drug residues in shrimp: A multi-class method by liquid chromatography-quadrupole ion trap mass spectrometry SO JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES LA English DT Article DE shrimp; multi-class; multi-residue; high throughput; veterinary drug; confirmatory; sulfonamide; quinolone; fluoroquinolone; cationic dye; oxytetracycline; toltrazuril sulfone ID ELECTROSPRAY-IONIZATION; BOVINE-MILK; ANTIBIOTICS; CONFIRMATION; IDENTIFICATION; EXTRACTION; PRODUCTS; CHEMICALS; CLEANUP; KIDNEY AB A liquid chromatography-mass spectrometry (LC-MS) method was developed to screen and confirm veterinary drug residues in raw shrimp meat. This method simultaneously monitors 18 drugs of different classes, including oxytetracycline (OTC), sulfonamides, quinolones, cationic dyes, and toltrazuril sulfone (TOLS). The homogenized shrimp meat is extracted with 5% trichloroacetic acid. The extract is further cleaned using polymer-based SPE. A 50 mm phenyl column separates the analytes, prior to analysis with an ion trap mass spectrometer interfaced with an atmospheric pressure chemical ionization source. This method is able to confirm oxytetracycline residues at 200 ng/g, toltrazuril sulfone at 50 ng/g, sulfaquinoxaline at 20 ng/g, and the other 15 drugs at 10 ng/g or lower levels. An estimate of the level of residues can also be made so that only confirmed samples above action levels will be sent for quantitation. The method is validated with both fortified and incurred samples, using multiple shrimp species as well. This multi-class method can provide a means to simultaneously monitor for a wide range of illegal drug residues in shrimp. (c) 2006 Elsevier B.V. All rights reserved. C1 US FDA, Ctr Vet Med, Res Off, Laurel, MD 20708 USA. US FDA, Anim Drug Res Ctr, Denver, CO 80225 USA. RP Kijak, PJ (reprint author), US FDA, Ctr Vet Med, Res Off, Laurel, MD 20708 USA. EM Philip.Kijak@fda.gov NR 26 TC 54 Z9 61 U1 2 U2 14 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 MAY 19 PY 2006 VL 836 IS 1-2 BP 22 EP 38 DI 10.1016/j.jchromb.2006.03.025 PG 17 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 045KJ UT WOS:000237740700003 PM 16597519 ER PT J AU Navarro, VJ Senior, JR AF Navarro, VJ Senior, JR TI Drug-related hepatotoxicity - Reply SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 Thomas Jefferson Univ, Jefferson Med Coll, Philadelphia, PA 19107 USA. US FDA, Silver Spring, MD 20907 USA. RP Navarro, VJ (reprint author), Thomas Jefferson Univ, Jefferson Med Coll, Philadelphia, PA 19107 USA. EM victor.navarro@jefferson.edu NR 5 TC 0 Z9 0 U1 2 U2 3 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 MAY 18 PY 2006 VL 354 IS 20 BP 2192 EP 2193 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 043BX UT WOS:000237575400038 ER PT J AU Hight, SC Cheng, J AF Hight, SC Cheng, J TI Determination of methylmercury and estimation of total mercury in seafood using high performance liquid chromatography (HPLC) and inductively coupled plasma-mass spectrometry (ICP-MS): Method development and validation SO ANALYTICA CHIMICA ACTA LA English DT Article DE methylmercury; total mercury; seafood; inductively coupled plasma-mass spectrometry; high performance liquid chromatography ID ENVIRONMENTAL-SAMPLES; MEDITERRANEAN SEA; CHEMICAL FORM; EDIBLE FISH; CANNED TUNA; ORGANOMERCURY; SPECIATION; SHELLFISH; STORAGE; EXTRACTION AB A method was developed for determination of methylmercury and estimation of total mercury in seafood. Mercury (Hg) compounds were extracted from 0.5 g edible seafood or 0.2 g lyophilized reference material by adding 50 ml aqueous 1 % W/V L-cysteine(.)HCl(.)H(2)O and heating 120 min at 60 degrees C in glass vials. Hg compounds in 50 mu l of filtered extract were separated by reversed-phase high performance liquid chromatography using a C-18 column and aqueous 0.1 % W/V L-cysteine(.)HCl(.)H2O + 0.1 % W/V L-Cysteine mobile phase at room temperature and were detected by inductively coupled plasma-mass spectrometry at mass-to-charge ratio 202. Total Hg was calculated as the mathematical sum of methyl and inorganic Hg determined in extracts. For seafoods containing 0.055-2.78 mg kg(-1) methylmercury and 0.014-0.137 mg kg-1 inorganic Hg, precision of analyses was <= 5% relative standard deviation (R.S.D.) for methylmercury and <= 9% R.S.D. for inorganic Hg. Recovery of added analyte was 94% for methylmercury and 98% for inorganic Hg. Methyl and total Hg results for reference materials agreed with certified values. Limits of quantitation were 0.007 mg kg(-1) methylmercury and 0.005 mg kg(-1) inorganic Hg in edible seafood and 0.617 mg kg(-1) methylmercury and 0.012 mg kg(-1) inorganic Hg in lyophilized reference materials. Evaluation of analyte stability demonstrated that L-cysteine both stabilized and de-alkylated methylmercury, depending on holding time and cysteine concentration. Polypropylene adversely affected methylmercury stability. Total Hg results determined by this method were equivalent to results determined independently by cold vapour-atomic absorption spectrometry. Methylmercury was the predominant form of Hg in finfish. Ratios of methylmercury/total Hg determined by this method were 93-98% for finfish and 38-48% for mollusks. (c) 2006 Elsevier Inc. All rights reserved. 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 44 TC 76 Z9 80 U1 6 U2 51 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0003-2670 J9 ANAL CHIM ACTA JI Anal. Chim. Acta PD MAY 17 PY 2006 VL 567 IS 2 BP 160 EP 172 DI 10.1016/j.aca.2006.03.048 PG 13 WC Chemistry, Analytical SC Chemistry GA 049BM UT WOS:000237990500003 ER PT J AU Geho, D Cheng, MMC Killian, K Lowenthal, M Ross, S Frogale, K Nijdam, J Lahar, N Johann, D Herrmann, P Whiteley, G Ferrari, M Petricoin, E Liotta, L AF Geho, D Cheng, MMC Killian, K Lowenthal, M Ross, S Frogale, K Nijdam, J Lahar, N Johann, D Herrmann, P Whiteley, G Ferrari, M Petricoin, E Liotta, L TI Fractionation of serum components using nanoporous substrates SO BIOCONJUGATE CHEMISTRY LA English DT Article ID PROTEOMIC PATTERNS; MASS-SPECTROMETRY; OVARIAN-CANCER; ADSORPTION; PEPTIDES; PROTEINS; NITROGEN AB Numerous previously uncharacterized molecules resident within the low molecular weight circulatory proteome may provide a picture of the ongoing pathophysiology of an organism. Recently, proteomic signatures composed of low molecular weight molecules have been identified using mass spectrometry combined with bioinformatic algorithms. Attempts to sequence and identify the molecules that underpin the fingerprints are currently underway. The finding that many of these low molecular weight molecules may exist bound to circulating carrier proteins affords a new opportunity for fractionation and separation techniques prior to mass spectrometry-based analysis. In this study we demonstrate a method whereby nanoporous substrates may be used for the facile and reproducible fractionation and selective binding of the serum-based biomarker material, including subcellular proteins found within the serum. Aminopropyl-coated nanoporous silicon, when exposed to serum, can deplete serum of proteins and yield a serum with a distinct, altered MS profile. Additionally, aminopropyl-coated, nanoporous controlled-pore glass beads are able to bind a subset of serum proteins and release them with stringent elution. The eluted proteins have distinct MS profiles, gel electrophoresis profiles, and differential peptide sequence identities, which vary based on the size of the nanopores. These material surfaces could be employed in strategies for the harvesting and preservation of labile and carrier-protein-bound molecules in the blood. C1 NCI, Pathol Lab, US FDA, Clin Proteom Program,NIH, Bethesda, MD 20892 USA. NCI, US FDA, Ctr Biol Evaluat & Res, Clin Proteom Program,Food & Drug Adm, Bethesda, MD 20892 USA. Ohio State Univ, Davis Heart & Lung Res Inst, Columbus, OH 43210 USA. Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43212 USA. SAIC Frederick Inc, Clin Proteom Lab, Gaithersburg, MD 20878 USA. RP Geho, D (reprint author), NCI, Pathol Lab, US FDA, Clin Proteom Program,NIH, Rm 2A33,Bldg 10,10 Ctr Dr, Bethesda, MD 20892 USA. EM herrmanp@mail.nih.gov FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400] NR 23 TC 30 Z9 31 U1 0 U2 9 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 17 PY 2006 VL 17 IS 3 BP 654 EP 661 DI 10.1021/bc0503364 PG 8 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 043CD UT WOS:000237576000012 PM 16704202 ER PT J AU Vugia, D Cronquist, A Hadler, J Tobin-D'Angelo, M Blythe, D Smith, K Thornton, K Morse, D Cieslak, P Jones, T Holt, K Guzewich, J Henao, O Scallan, E Angulo, F Griffin, P Tauxe, R Barzilay, E AF Vugia, D Cronquist, A Hadler, J Tobin-D'Angelo, M Blythe, D Smith, K Thornton, K Morse, D Cieslak, P Jones, T Holt, K Guzewich, J Henao, O Scallan, E Angulo, F Griffin, P Tauxe, R Barzilay, E CA CDC TI Preliminary FoodNet data on the incidence of infection with pathogens transmitted commonly through food - 10 states, United States, 2005 (Reprinted from MMWR, vol 55, pg 392-395, 2006) SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Reprint ID RAW GROUND-BEEF; INSPECTION SERVICE; SAFETY C1 Calif Dept Hlth Serv, Berkeley, CA 94704 USA. Colorado Dept Publ Hlth & Environm, Denver, CO USA. Connecticut Dept Publ Hlth, Hartford, CT USA. Georgia Dept Human Resources, Div Publ Hlth, Atlanta, GA USA. Maryland Dept Hlth & Mental Hyg, Baltimore, MD 21201 USA. Minnesota Dept Hlth, Minneapolis, MN 55414 USA. Univ New Mexico, Hlth Sci Ctr, Inst Publ Hlth, Albuquerque, NM 87131 USA. New York State Dept Hlth, Albany, NY 12237 USA. Oregon State Publ Hlth, Salem, OR USA. Tennessee Dept Hlth, Nashville, TN USA. Food Safety & Inspect Serv, USDA, Washington, DC USA. US FDA, Ctr Food Safety & Appl Nutr, Rockville, MD 20857 USA. CDC, Div Foodborne Bacterial & Mycol Dis, Natl Ctr Zoonot Vector Borne & Enter Dis, Atlanta, GA 30333 USA. RP Vugia, D (reprint author), Calif Dept Hlth Serv, Berkeley, CA 94704 USA. NR 10 TC 6 Z9 6 U1 0 U2 1 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 MAY 17 PY 2006 VL 295 IS 19 BP 2241 EP 2243 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 042UX UT WOS:000237556600010 ER PT J AU Montello, MJ Tarosky, M Pincock, L Montello, N Hess, WA Velazquez, L Patel, A Krzyworzeka, J Hay, E AF Montello, MJ Tarosky, M Pincock, L Montello, N Hess, WA Velazquez, L Patel, A Krzyworzeka, J Hay, E TI Dosing cards for treatment of children exposed to weapons of mass destruction SO AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY LA English DT Article C1 NCI, Protocol & Informat Off, Rockville, MD 20852 USA. US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. Costco Pharm, Southbury, CT USA. Capital Technol Informat Syst, Global Hlth Dev, Rockville, MD USA. Philadelphia Coll Pharm, Philadelphia, PA USA. RP Montello, MJ (reprint author), NCI, Protocol & Informat Off, 6130 Execut Blvd,Suite 6118, Rockville, MD 20852 USA. EM montellom@ctep.nci.nih.gov NR 14 TC 2 Z9 2 U1 0 U2 0 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 MAY 15 PY 2006 VL 63 IS 10 BP 944 EP 949 DI 10.2146/ajhp050372 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 042HB UT WOS:000237517600012 PM 16675651 ER PT J AU Kane, RC Farrell, AT Sridhara, R Pazdur, R AF Kane, RC Farrell, AT Sridhara, R Pazdur, R TI United States Food and Drug Administration approval summary: Bortezomib for the treatment of progressive multiple myeloma after one prior therapy SO CLINICAL CANCER RESEARCH LA English DT Article AB Purpose: On March 25, 2005, bortezomib (Velcade for Injection; Millennium Pharmaceuticals, Inc., Cambridge, MA, and Johnson & Johnson Pharmaceutical Research & Development, L. L.C.) received regular approval from the U.S. Food and Drug Administration (U.S. FDA) for the treatment of multiple myeloma (MM) progressing after at least one prior therapy. This approval was based on bortezomib's efficacy and safety which was shown in a single, large, comparative international open-label phase 3 trial that randomized 669 patients with MM previously treated with at least one systemic regimen to receive single-agent bortezomib or high-dose dexamethasone. The FDA analysis of the trial data and bortezomib's regulatory development are summarized here. Experimental Design and Results: Following a preplanned interim analysis of time to disease progression (the primary end point), an independent data-monitoring committee advised the sponsor to halt the study and offer bortezomib to all dexamethasone-treated study patients. Time to progression was significantly prolonged in the bortezomib treatment arm (median, 6.2 months) compared with the dexamethasone arm (median, 3.5 months; log-rank test, P < 0.0001; hazard ratio, 0.55; 95% confidence interval, 0.44-0.69). Analysis of overall survival done on the interim database (with 20% of events) showed the superiority of bortezomib for patients (log-rank test, P < 0.05; hazard ratio, 0.57; 95% confidence interval, 0.40-0.81). Using criteria from the European Group for Blood and Marrow Transplantation, the response rate (complete plus partial response) with bortezomib was also superior to dexamethasone (38% versus 18%; P < 0.0001). Adverse events on the bortezomib arm were similar to those previously observed in phase 2 studies; some notable adverse events included asthenia, peripheral neuropathy, thrombocytopenia, and neutropenia. Conclusions: The U.S. FDA had earlier (May 2003) granted bortezomib accelerated approval for the treatment of patients with MM progressing after two prior therapies. The results of the phase 3 trial and the FDA analysis of the data, along with the sponsor's completion of other postmarketing commitments, confirm bortezomib's benefit and support regular approval. C1 US FDA, Div Drug Oncol Prod, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Kane, RC (reprint author), US FDA, Div Drug Oncol Prod, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave,Bldg 22,Room 2109, Silver Spring, MD 20993 USA. EM robert.kane@fda.hhs.gov NR 9 TC 183 Z9 193 U1 0 U2 7 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 2006 VL 12 IS 10 BP 2955 EP 2960 DI 10.1158/1078-0432.CCR-06-0170 PG 6 WC Oncology SC Oncology GA 044PX UT WOS:000237685800002 PM 16707588 ER PT J AU Fang, H Xu, LX Chen, TY Cyr, JM Frucht, DM AF Fang, Hui Xu, Lixin Chen, Trina Y. Cyr, Julianne M. Frucht, David M. TI Anthrax lethal toxin has direct and potent inhibitory effects on B cell proliferation and immunoglobulin production SO JOURNAL OF IMMUNOLOGY LA English DT Article ID T-LYMPHOCYTE ACTIVATION; BACILLUS-ANTHRACIS; PROTECTIVE ANTIGEN; IN-VIVO; ADAPTIVE IMMUNITY; DENDRITIC CELLS; GUINEA-PIGS; RECEPTOR 2; MICE; ANTIBODIES AB Protective host immune responses to anthrax infection in humans and animal models are characterized by the development of neutralizing Abs against the receptor-binding anthrax protective Ag (PA), which, together with the lethal factor (LF) protease, composes anthrax lethal toxin (LT). We now report that B cells, in turn, are targets for LT. Anthrax PA directly binds primary B cells, resulting in the LF-dependent cleavage of the MAPK kinases (MAPKKs) and disrupted signaling to downstream MAPK targets. Although not directly lethal to B cells, anthrax LT treatment causes severe B cell dysfunction, greatly reducing proliferative responses to IL-4-, anti-IgM-, and/or anti-CD40 stimulation. Moreover, B cells treated with anthrax LT in vitro or isolated from mice treated with anthrax LT in vivo have a markedly diminished capacity to proliferate and produce IgM in response to TLR-2 and TLR-4 ligands. The suppressive effects of anthrax LT on B cell function occur at picomolar concentrations in vitro and at sublethal doses in vivo. These results indicate that anthrax LT directly inhibits the function of B cells in vitro and in vivo, revealing a potential mechanism through which the pathogen could bypass protective immune responses. C1 US FDA, Div Monoclonal Antibodies, Off Biotechnol Prod, Off Pharmaceut Sci,Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. RP Frucht, DM (reprint author), US FDA, Div Monoclonal Antibodies, Off Biotechnol Prod, Off Pharmaceut Sci,Ctr Drug Evaluat & Res, Bldg 29B,Room 3NN22, Bethesda, MD 20892 USA. EM david.frucht@fda.hhs.gov NR 47 TC 56 Z9 58 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 2006 VL 176 IS 10 BP 6155 EP 6161 PG 7 WC Immunology SC Immunology GA 044WW UT WOS:000237705200054 PM 16670324 ER PT J AU Laassri, M Lottenbach, K Belshe, R Rennels, M Plotkin, S Chumakov, K AF Laassri, M Lottenbach, K Belshe, R Rennels, M Plotkin, S Chumakov, K TI Analysis of reversions in the 5 '-untranslated region of attenuated poliovirus after sequential administration of inactivated and oral poliovirus vaccines SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID POLIOMYELITIS PREVENTION; UNITED-STATES; VACCINATION; STRAINS; IMMUNIZATION; EXCRETION; TYPE-3; VIRUS; RECOMMENDATIONS; POLIOVACCINE AB Replication of Sabin strains used in oral poliovirus vaccine ( OPV) in the intestines of vaccine recipients leads to reversions that increase virus neurovirulence. Previously, a small study reported that prior immunization with inactivated poliovirus vaccine ( IPV) resulted in faster accumulation of revertant virus, thus potentially increasing the risk of vaccine-associated paralytic poliomyelitis. We studied the impact that prior immunization with IPV and OPV has on shedding of revertant virus by healthy infants. By polymerase chain reaction ( PCR), we amplified full-length poliovirus genomes directly from stool specimens from unimmunized infants and from infants previously immunized with IPV or OPV. The amplicons were used to quantify reversions in the 5'-untranslated region, using oligonucleotide microarray hybridization. Nearly all 140 samples that were PCR positive contained varying amounts of revertants of all 3 poliovirus serotypes. Polioviruses of Sabin types 2 and 3 reverted more easily than those of type 1. Prior vaccination with IPV did not increase the proportion of revertants after OPV administration. C1 US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. Univ Maryland, Sch Med, Baltimore, MD 21201 USA. St Louis Univ, St Louis, MO 63103 USA. Univ Penn, Philadelphia, PA 19104 USA. Sanofi Pasteur, Doylestown, PA USA. RP Chumakov, K (reprint author), US FDA, Ctr Biol Evaluat & Res, 1401 Rockville Pike HFM-470, Rockville, MD 20852 USA. EM chumakov@cber.fda.gov FU NIAID NIH HHS [N01-AI-45251, N01-AI-45250] NR 26 TC 11 Z9 12 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD MAY 15 PY 2006 VL 193 IS 10 BP 1344 EP 1349 DI 10.1086/503366 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 036EI UT WOS:000237053400002 PM 16619180 ER PT J AU Giersing, BK Dubovsky, F Saul, A Denamur, F Minor, P Meade, B AF Giersing, Birgitte K. Dubovsky, Filip Saul, Allan Denamur, Francoise Minor, Philip Meade, Bruce TI Potency assay design for adjuvanted recombinant proteins as malaria vaccines SO VACCINE LA English DT Article DE potency; assay; recombinant protein; vaccine ID APICAL MEMBRANE ANTIGEN-1; PLASMODIUM-FALCIPARUM; IMMUNIZATION; INVASION AB Many licensed vaccines are composed of live, attenuated or inactivated whole-cell microorganisms, or they comprise purified components from whole-cell extracts or culture supernatants. For some diseases, pathology is fairly well understood, and there may be known correlates of protection that provide obvious parameters for assessment of vaccine potency. However, this is not always the case, and some effective vaccines are routinely used even though the mechanisms or correlates of protection are unknown. Some more modem vaccine approaches employ purified recombinant proteins, based on molecules that appear on the surface of the pathogen. This is one of the strategies that has been adopted in the quest to develop a malaria vaccine. Use of these parasite antigens as vaccine candidates is supported by substantial epidemiological data, and some have demonstrated the ability to elicit protective responses in animal models of malaria infection. However, there is as yet no immunological correlate of protection and no functional assays or animal models that have demonstrated the ability to predict efficacy in humans. There is little precedence for the most appropriate and practical method for assessing potency of vaccines based on these recombinant molecules for malaria vaccines. This is likely because the majority of malaria vaccine candidates have only recently entered clinical evaluation. The PATH Malaria Vaccine Initiative (MVI) convened a panel with expertise in potency assay design from industry, governmental institutions, and regulatory bodies to discuss and review the rationale, available methods, and best approaches for assessing the potency of recombinant proteins, specifically for their use as malarial vaccines. The aim of this meeting was to produce a discussion document on the practical potency assessment of recombinant protein malaria vaccines, focusing on early phase potency assay development. C1 PATH Malaria Vaccine Inst, Bethesda, MD 20814 USA. NIAID, MVDB, NIH, Rockville, MD 20852 USA. GlaxoSmithKline Biol, B-1330 Rixensart, Belgium. Natl Inst Biol Stand & Controls, Potters Bar EN6 3QG, Herts, England. CBER, OVRR, Lab Methods Dev & Qual Control, Div Bacterial Prod, Rockville, MD 20852 USA. RP Giersing, BK (reprint author), PATH Malaria Vaccine Inst, 7500 Old Georgetown Rd, Bethesda, MD 20814 USA. EM bgiersing@malariavaccine.org RI Saul, Allan/I-6968-2013 OI Saul, Allan/0000-0003-0665-4091 NR 17 TC 14 Z9 14 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X EI 1873-2518 J9 VACCINE JI Vaccine PD MAY 15 PY 2006 VL 24 IS 20 BP 4264 EP 4270 DI 10.1016/j.vaccine.2006.01.005 PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 049LA UT WOS:000238016600003 PM 16767804 ER PT J AU Krynitsky, AJ Niemann, RA Williams, AD Hopper, ML AF Krynitsky, AJ Niemann, RA Williams, AD Hopper, ML TI Streamlined sample preparation procedure for determination of perchlorate anion in foods by ion chromatography-tandem mass spectrometry SO ANALYTICA CHIMICA ACTA LA English DT Article DE perchlorate anion; foods; SPE; IC-MS/MS ID DRINKING-WATER; ELECTROSPRAY AB A rapid, sensitive, and specific method was developed for the determination of perchlorate anion in foods. The foods included high moisture fruits and vegetables, low moisture foods (e.g. wheat flour and corn meal), and infant foods. Improvements to existing procedures were made in sample preparation that reduced sample test portion size from 100 to 5 or 10 g, extraction solvent volume from 150 to 20-40 nil, and replaced blending extraction-vacuum filtration and their associated large glassware with a simple shakeout-centrifugation in a small conical tube. Procedures common to all matrices involved: extraction, centrifugation, graphitized carbon solid phase extraction (SPE) cleanup, and ion chromatography-tandem mass spectrometry (IC-MS/MS) analysis. A Waters IC-Pak Anion HR column (4.6 mm x 75 mm) was eluted with 100 mM ammonium acetate in 50:50 (v/v) acetonitrile/water mobile phase at a rate of 0.35 ml/min. A triple stage quadrupole mass spectrometer, equipped with electrospray ionization (ESI) in the negative ion mode, was used to detect perchlorate anion. An O-18(4)-labeled perchlorate anion internal standard was used to correct for any matrix effects. The method limit of quantitation (LOQ) was: 1.0 mu g/kg in fruits, vegetables, and infant foods; 3.0 mu g/kg in dry products. Fortified test portions gave 80-120% recoveries. Determination of incurred perchlorate anion residues agreed well with results for comparable commodities or products analyzed by published methods. Published by Elsevier B.V. C1 US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. US FDA, SE Reg Lab, Atlanta, GA 30309 USA. US FDA, Total Diet Res Ctr, Lenexa, KS 66214 USA. RP Krynitsky, AJ (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Point Branch Pkwy, College Pk, MD 20740 USA. EM Alex.Krynitsky@fda.hhs.gov NR 19 TC 22 Z9 28 U1 5 U2 20 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0003-2670 J9 ANAL CHIM ACTA JI Anal. Chim. Acta PD MAY 10 PY 2006 VL 567 IS 1 BP 94 EP 99 DI 10.1016/j.aca.2006.01.005 PG 6 WC Chemistry, Analytical SC Chemistry GA 046UO UT WOS:000237836800014 PM 17723384 ER PT J AU Xia, QS Yin, JJ Cherng, SH Wamer, WG Boudreau, M Howard, PC Fu, PP AF Xia, QS Yin, JJ Cherng, SH Wamer, WG Boudreau, M Howard, PC Fu, PP TI UVA photoirradiation of retinyl palmitate - Formation of singlet oxygen and superoxide, and their role in induction of lipid peroxidation SO TOXICOLOGY LETTERS LA English DT Article DE retinyl palmitate; UVA photoirradiation; lipid peroxidation; reactive oxygen species; ESR ID OXIDATIVE STRESS; CANCER-RISK; VITAMIN-A; LIGHT; SKIN; RADICALS; TOXICOLOGY; RETINOIDS; DISEASE; UPDATE AB We have previously reported that photoirradiation of retinyl palmitate (RP) in ethanol with UVA light results in the formation of photodecomposition products, including 5,6-epoxy-RP and anhydroretinol (AR). Photoirradiation in the presence of a lipid, methyl linoleate, induced lipid peroxidation, suggesting that reactive oxygen species (ROS) are formed. In the present study, we employ an electron spin resonance (ESR) spin trap technique to provide direct evidence as to whether or not photoirradiation of RP by UVA light produces ROS. Photoirradiation of RP by UVA in the presence of 2,2,6,6-tetramethylpiperidine (TEMP), a specific probe for singlet oxygen, resulted in the formation of TEMPO, indicating that singlet oxygen was generated. Both 5,5-dimethyl N-oxide pyrroline (DMPO) and 5-tert-butoxycarbonyl 5-methyl-1-pyrroline N-oxide (BMPO) are specific probes for superoxide. When photoirradiation of RP was conducted in the presence of the DMPO or BMPO, ESR signals for DMPO-(OOH)-O-. or BMPO-(OOH)-O-. were obtained. These results unambiguously confirmed the formation of superoxide radical anion. Consistent with a free radical mechanism, there was a near complete and time-dependent photodecomposition of RP and its photodecomposition products. ESR studies on the photoirradiation of 5,6-epoxy-RP and AR indicate that these compounds exhibit similar photosensitizing activities as RP under UVA light. (c) 2005 Published by Elsevier Ireland Ltd. C1 US FDA, Natl Ctr Toxicol Res, Dept Biochem Toxicol, Jefferson, AR 72079 USA. US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Fu, PP (reprint author), US FDA, Natl Ctr Toxicol Res, Dept Biochem Toxicol, HFT-110,3900 NCTR Rd, Jefferson, AR 72079 USA. EM pfu@nctr.fda.gov RI Yin, Jun Jie /E-5619-2014 NR 44 TC 49 Z9 50 U1 1 U2 10 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0378-4274 J9 TOXICOL LETT JI Toxicol. Lett. PD MAY 5 PY 2006 VL 163 IS 1 BP 30 EP 43 DI 10.1016/j.toxlet.2005.09.010 PG 14 WC Toxicology SC Toxicology GA 029BQ UT WOS:000236533300004 PM 16384671 ER PT J AU Chu, PS Lopez, M Serfling, S Gieseker, C Reimschuessel, R AF Chu, PS Lopez, M Serfling, S Gieseker, C Reimschuessel, R TI Determination of 17 alpha-methyltestosterone in muscle tissues of tilapia, rainbow trout, and salmon using liquid chromatography-Tandem mass spectrometry SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE methyltestosterone; tilapia; salmon; trout; LC-MS/MS; method ID METHYLTESTOSTERONE RESIDUES; OREOCHROMIS-NILOTICUS; ANABOLIC-STEROIDS; FISH; ELIMINATION; EXTRACTION; URINE; HAIR AB An analytical method was developed to quantitate and confirm the presence of 17 alpha- methyltestosterone in the muscles of tilapia, rainbow trout, and salmon. The method employed two liquid- liquid partitioning steps and two solid- phase extraction columns for sample cleanup. The final extracts were analyzed on an isocratic reverse-phase liquid chromatography- tandem mass spectrometry system with atmospheric-pressure chemical ionization in the positive ion mode. The method was validated at levels from 0.40 to 1.6 ng/ g, with MT-d(3) used as an internal standard. The accuracy was between 100% and 110%, and coefficients of variation of < 10% were obtained for all three fish species. Muscle tissues from dosed fish were also assayed to demonstrate the effectiveness of the method for recovering the parent drug. 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 19 TC 9 Z9 15 U1 2 U2 13 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 3 PY 2006 VL 54 IS 9 BP 3193 EP 3198 DI 10.1021/jf052701r PG 6 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 042JT UT WOS:000237524900004 PM 16637671 ER PT J AU Schneeman, B Trumbo, P Ellwood, K Satchell, F AF Schneeman, B Trumbo, P Ellwood, K Satchell, F TI The regulatory process to revise nutrient labeling relative to the Dietary Reference intakes SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article; Proceedings Paper CT Symposium on Dietary Reference Intakes for Food Labeling CY APR 04, 2005 CL San Diego, CA SP ASNS, Public Informat Comm, ASCN, Public Informat Comm DE Food and Drug Administration; Dietary Reference Intakes; Recommended Dietary Allowance; 21 CFR; Nutrition Labeling and Education Act AB The Nutrition Labeling and Education Act of 1990-an amendment to the Federal Food, Drug, and Cosmetic Act-paved the way for significant changes in the labeling of foods, nutrient content, and health claims. This article gives an overview of the regulatory process used by the US Food and Drug Administration to revise the food label relative to the Dietary Reference Intakes and in ways that reflect new scientific knowledge and public health issues. C1 US FDA, Ctr Food Safety & Appl Nutr, CFSAN ONPLDS, College Pk, MD USA. RP Schneeman, B (reprint author), US FDA, Ctr Food Safety & Appl Nutr, CFSAN ONPLDS, HFS-800,5100 Paint Branch Pkwy, College Pk, MD USA. EM bschneem@cfsan.fda.gov NR 13 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD MAY PY 2006 VL 83 IS 5 BP 1228S EP 1230S PG 3 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 044MT UT WOS:000237677300034 PM 16685070 ER PT J AU Gallo-Torres, H Brinker, A Avigan, M AF Gallo-Torres, H Brinker, A Avigan, M TI Alosetron: Ischemic colitis and serious complications of constipation SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Editorial Material ID IRRITABLE-BOWEL-SYNDROME; ARTICLE AB Drugs such as alosetron that modulate serotonin effects by stimulating or blocking its receptors may play an important role in the treatment of some patients with irritable bowel system. In the case of alosetron, a 5HT-3 antagonist, an analysis of data from randomized clinical trials and postmarketing experiences have demonstrated a causal relationship between this drug and ischemic colitis and serious complications of constipation. Because the mechanism(s) of drug-induced ischemic colitis and possibly other forms of intestinal ischemia associated with alosetron have not been elucidated, there is need to further assess risk with regard to patient susceptibility and other factors. C1 US FDA, Div Gastroenterol Prod Food & Drug Adm, Off New Durgs, Ctr Drug Evaluat & Res,Off Drug Evaluat 3, Silver Spring, MD 20993 USA. US FDA, Div Drug Risk Evaluat, Off Drug Safety Silver Spring, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Gallo-Torres, H (reprint author), US FDA, Div Gastroenterol Prod Food & Drug Adm, Off New Durgs, Ctr Drug Evaluat & Res,Off Drug Evaluat 3, 10903 New Hampshire Ave,Bldg 22,Room 5106, Silver Spring, MD 20993 USA. NR 20 TC 22 Z9 22 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD MAY PY 2006 VL 101 IS 5 BP 1080 EP 1083 DI 10.1111/j.1572-0241.2006.00650.x PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 041NQ UT WOS:000237463300025 PM 16696787 ER PT J AU Luangtongkum, T Morishita, TY Ison, AJ Huang, SX McDermott, PF Zhang, QJ AF Luangtongkum, T Morishita, TY Ison, AJ Huang, SX McDermott, PF Zhang, QJ TI Effect of conventional and organic production practices on the prevalence and antimicrobial resistance of Campylobacter spp. in poultry SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID ANTIBIOTIC-RESISTANCE; JEJUNI INFECTIONS; BACTERIAL-RESISTANCE; BROILER-CHICKENS; UNITED-STATES; COLI; COLONIZATION; ANIMALS; STRAINS; SUSCEPTIBILITIES AB Intestinal tracts of broilers and turkeys from 10 conventional broiler farms and 10 conventional turkey farms, where antimicrobials were routinely used, and from 5 organic broiler farms and 5 organic turkey farms, where antimicrobials had never been used, were collected and cultured for Campylobacter species. A total of 694 Campylobacter isolates from the conventional and organic poultry operations were tested for antimicrobial resistance to nine antimicrobial agents by the agar dilution method. Although Campylobacter species were highly prevalent in both the conventional and organic poultry operations, the antimicrobial resistance rates were significantly different between the organic operations and the conventional operations. Less than 2% of Campylobacter strains isolated from organically raised poultry were resistant to fluoroquinolones, while 46% and 67% of Campylobacter isolates from conventionally raised broilers and conventionally raised turkeys, respectively, were resistant to these antimicrobials. In addition, a high frequency of resistance to erythromycin (80%), clindamycin (64%), kanamycin (76%), and ampicillin (31%) was observed among Campylobacter isolates from conventionally raised turkeys. None of the Campylobacter isolates obtained in this study was resistant to gentamicin, while a large number of the isolates from both conventional and organic poultry operations were resistant to tetracycline. Multidrug resistance was observed mainly among Campylobacter strains isolated from the conventional turkey operation (81%). Findings from this study clearly indicate the influence of conventional and organic poultry production practices on antimicrobial resistance of Campylobacter on poultry farms. C1 Ohio State Univ, Dept Vet Prevent Med, Columbus, OH 43210 USA. Ohio State Univ, Ohio Agr Res & Dev Ctr, Food Anim Hlth Res Program, Wooster, OH 44691 USA. US FDA, Ctr Vet Med, Div Anim & Food Microbiol, Laurel, MD 20708 USA. RP Morishita, TY (reprint author), Ohio State Univ, Dept Vet Prevent Med, 1920 Coffey Rd, Columbus, OH 43210 USA. EM morishita.1@osu.edu RI Zhang, Qijing/B-7530-2012; OI Huang, Shouxiong/0000-0001-7797-3626 NR 43 TC 102 Z9 109 U1 2 U2 13 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0099-2240 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD MAY PY 2006 VL 72 IS 5 BP 3600 EP 3607 DI 10.1128/AEM.72.5.3600-3607.2006 PG 8 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 041XV UT WOS:000237491200064 PM 16672508 ER PT J AU Shin, ISJ Baer, AN Kwon, HJ Papadopoulos, EJ Siegel, JN AF Shin, ISJ Baer, AN Kwon, HJ Papadopoulos, EJ Siegel, JN TI Guillain-Barre and Miller Fisher syndromes occurring with tumor necrosis factor alpha antagonist therapy SO ARTHRITIS AND RHEUMATISM LA English DT Article; Proceedings Paper CT 57th Annual Meeting of the American-Academy-of-Neurology CY APR 09-19, 2005 CL Miami Beach, FL SP Amer Acad Neurol ID ELEVATED SERUM LEVELS; DEMYELINATION; TNF AB Objective. Diverse neurologic syndromes have been described in association with tumor necrosis factor a (TNF alpha) antagonist therapy for inflammatory arthritides and Crohn's disease. The objective of this study was to review the occurrence and clinical features of Guillain-Barre syndrome and its variant, the Miller Fisher syndrome, during TNFa antagonist therapy. Methods. The postmarketing database of the US Food and Drug Administration (FDA) was searched, following our experience with a patient with rheumatoid arthritis in whom the Miller Fisher syndrome variant of the Guillain-Barre syndrome developed while he was receiving infliximab therapy. Results. Our index patient had a neurologic illness defined initially by ataxia and dysarthria, which fluctuated in relation to each subsequent infliximab infusion and, after 6 months, culminated in areflexic flaccid quadriplegia. In addition, 15 patients in whom Guillain-Barre syndrome developed following TNF alpha antagonist therapy were identified from the FDA database. Guillain-Barr syndrome developed following infliximab therapy in 9 patients, following etanercept therapy in 5 patients, and following adalimumab therapy in 1 patient. Among the 13 patients for whom followup data were available, 1 patient experienced no resolution, 9 patients had partial resolution, and 3 patients had complete resolution of Guillain-Barre syndrome following therapy. Conclusion. An association of Guillain-Barre syndrome with TNF alpha antagonist therapy is supported by the worsening of neurologic symptoms that occurred in our index patient following each infusion of infliximab, and by the temporal association of this syndrome with TNF alpha antagonist therapy in 15 other patients. An acute or subacute demyelinating polyneuropathy should be considered a potential adverse effect of TNF alpha antagonist therapy. C1 SUNY Coll Buffalo, Buffalo, NY 14222 USA. Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Baer, AN (reprint author), Erie Cty Med Ctr & Labs, 462 Grider St, Buffalo, NY 14215 USA. EM alanbaer@buffalo.edu NR 16 TC 91 Z9 97 U1 0 U2 3 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 MAY PY 2006 VL 54 IS 5 BP 1429 EP 1434 DI 10.1002/art.21814 PG 6 WC Rheumatology SC Rheumatology GA 042MV UT WOS:000237533100010 PM 16645971 ER PT J AU Moss, J AF Moss, Julie TI Labeling of trans fatty acid content in food, regulations and limits - The FDA view SO ATHEROSCLEROSIS SUPPLEMENTS LA English DT Article; Proceedings Paper CT 1st International Symposium on Trans Fatty Aids and Health CY SEP 11-13, 2005 CL Rungsted Kyst, DENMARK SP Danish Fitness & Nutr Council DE FDA; labeling; nutrition; trans fatty acids AB With the scientific evidence associating trans fatty acid (TFA) intake with an increased risk of coronary heart disease (CHD), the U.S. Food and Drug Administration (FDA) issued a final rule that requires the declaration of the amount of TFA present in foods, including dietary supplements, on the nutrition label by January 1, 2006. The addition of TFA to the nutrition label will lead to the Prevention of 600 to 1200 cases of CHD and 240-480 deaths each year saving, $900 million to $1.8 billion per year in medical costs, lost productivity, and pain and suffering. For the purpose of nutrition labeling, TFA are defined as the sum of all unsaturated fatty acids that contain one or more isolated (i.e. non-conjugated) double bonds in a trans configuration. There are many, issues that FDA has vet to resolve: (1) defining nutrient content claims for "free" and "reduced" levels of trans fat, (2) placing limits oil the amount of TFA in conjunction with saturated fat limits for nutrient content claims, health claims, and disclosure and disqualifying levels, (3) a daily value, and (4) a possible footnote or disclosure statement to enhance consumer understanding of cholesterol raising lipids. FDA issued all Advanced Notice of Proposed Rulemaking (ANPR) requesting comments on the unresolved issues. FDA will also be conducting consumer research to determine consumer understanding of various TFA labeling possibilities. Comments to the ANPR, results of consumer research and current science will be used by FDA to resolve these issues and to determine future rulemaking for TFA labeling. (c) 2006 Elsevier Ireland Ltd. All rights reserved. C1 US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Moss, J (reprint author), US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. EM Julie.Moss@fda.hhs.gov NR 1 TC 23 Z9 24 U1 2 U2 19 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 1567-5688 J9 ATHEROSCLEROSIS SUPP JI Atheroscler. Suppl. PD MAY PY 2006 VL 7 IS 2 BP 57 EP 59 DI 10.1016/j.atherosclerosissup.2006.04.012 PG 3 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 065AH UT WOS:000239131300015 PM 16713387 ER PT J AU Hess, P Grune, B Anderson, DB Aune, T Botana, LM Caricato, P van Egmond, HP Halder, M Hall, S Lawrence, JF Moffat, C Poletti, R Richmond, J Rossini, GP Seamer, C Vilageliu, JS AF Hess, Philipp Grune, Barbara Anderson, David B. Aune, Tore Botana, Luis M. Caricato, Paolo van Egmond, Hans P. Halder, Marlies Hall, Sherwood Lawrence, James F. Moffat, Colin Poletti, Roberto Richmond, John Rossini, Gian Paolo Seamer, Catherine Vilageliu, Jorge Serratosa TI Three Rs approaches in marine biotoxin testing - The report and recommendations of a joint ECVAM/DG SANCO workshop (ECVAM workshop 55) SO ATLA-ALTERNATIVES TO LABORATORY ANIMALS LA English DT Review ID SHELLFISH POISONING TOXINS; LIQUID-CHROMATOGRAPHIC DETERMINATION; FLUOROMETRIC MICROPLATE ASSAY; SINGLE-LABORATORY VALIDATION; RECEPTOR-BINDING ASSAY; PARALYTIC SHELLFISH; MOUSE BIOASSAY; MASS-SPECTROMETRY; MYTILUS-EDULIS; MIST ALERT(TM) C1 Commiss European Communities, Joint Res Ctr, ECVAM, Inst Hlth & Consumer Protect, I-21020 Ispra, VA, Italy. Inst Marine, Oranmore, Galway, Ireland. Fed Inst Ridk Assessment, Ctr Documentat & Evaluat Alternat Anim Expt, Berlin, Germany. Anim Sci Procedures Inspectorate, Home Off, Dundee, Scotland. Norwegian Sch Vet Sci, Dept Food Safety & Infect Biol, Oslo, Norway. Community Reference Lab Marine Biotoxins, Vigo, Spain. Commiss European Communities, DG SANCO, B-1049 Brussels, Belgium. Rijksinst voor Volksgezondheid Milieu, Lab Fod & Residue Anal, Bilthoven, Netherlands. US FDA, Washington, DC 20204 USA. Fisheries Res Serv Marine Lab, Aberdeen, Scotland. Ctr Ric Marine, Lab Nazl Riferimento, Cesenatico, Italy. Univ Modena, Dipartimento Sci Biomed, I-41100 Modena, Italy. New Zealand Food Safety Author, Wellington, New Zealand. European Food Safety Author, Parma, Italy. RP Hess, P (reprint author), Commiss European Communities, Joint Res Ctr, ECVAM, Inst Hlth & Consumer Protect, I-21020 Ispra, VA, Italy. EM philipp.hess@marine.ie RI Hess, Philipp/G-1761-2010; Rossini, Gian Paolo/E-7281-2015 OI Hess, Philipp/0000-0002-9047-1345; Rossini, Gian Paolo/0000-0002-2326-2893 NR 139 TC 44 Z9 53 U1 0 U2 3 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 MAY PY 2006 VL 34 IS 2 BP 193 EP 224 PG 32 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 044MW UT WOS:000237677600014 PM 16704292 ER PT J AU Martin, PJ Weisdorf, D Przepiorka, D Hirschfeld, S Farrell, A Rizzo, JD Foley, R Socie, G Carter, S Couriel, D Schultz, KR Flowers, MED Filipovich, AH Saliba, R Vogelsang, GB Pavletic, SZ Lee, SJ AF Martin, PJ Weisdorf, D Przepiorka, D Hirschfeld, S Farrell, A Rizzo, JD Foley, R Socie, G Carter, S Couriel, D Schultz, KR Flowers, MED Filipovich, AH Saliba, R Vogelsang, GB Pavletic, SZ Lee, SJ TI National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: VI. Design of clinical trials working group report SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE chronic graft-versus-host disease; allogeneic hematopoietic cell transplantation; consensus; clinical trials; design ID PREDNISONE; THERAPY; CYCLOSPORINE; THALIDOMIDE; DIAGNOSIS AB The complexity of chronic graft-versus-host disease (GVHD) and the lack of established research methods have made it difficult to design, conduct, and analyze clinical trials involving subjects with this disease, even when promising treatment options are available. This consensus document was developed to offer an approach for overcoming these obstacles. Clinical trials in chronic GVHD should adhere to principles of good trial design and practice. Inclusion and exclusion criteria should allow as many subjects to participate as possible without compromising the interpretation of results. Pre-enrollment assessment of chronic GVHD characteristics should be standardized. The protocol should provide clear guidance about administration of study medication and other interventions. Methods of assessing response should be defined and validated in advance. Efficacy endpoints should be selected to reflect clinical benefit. Expert biostatistical support is needed to ensure the validity and reliability of trial results. The use of consistent standards in clinical trial designs to evaluate agents that have activity in pathogenic pathways could facilitate advances in the treatment of chronic GVHD. (C) 2006 American Society for Blood and Marrow Transplantation. C1 Univ Washington, Sch Med, Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. Univ Minnesota, Minneapolis, MN USA. Univ Tennessee, Memphis, TN USA. US FDA, Rockville, MD 20857 USA. Med Coll Wisconsin, Milwaukee, WI 53226 USA. McMaster Univ, Hamilton, ON, Canada. Hop St Louis, Paris, France. EMMES Corp, Rockville, MD USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ British Columbia, British Columbia Childrens Hosp, Vancouver, BC V5Z 1M9, Canada. Univ Cincinnati, Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. NCI, NIH, Bethesda, MD 20892 USA. RP Martin, PJ (reprint author), Univ Washington, Sch Med, Fred Hutchinson Canc Res Ctr, POB 19024,1100 Fairview Ave N,D2-100, Seattle, WA 98109 USA. EM pmartin@fhcrc.org RI Hirschfeld, Steven/E-2987-2016 OI Hirschfeld, Steven/0000-0003-0627-7249 FU Intramural NIH HHS NR 17 TC 104 Z9 112 U1 0 U2 4 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD MAY PY 2006 VL 12 IS 5 BP 491 EP 505 DI 10.1016/j.bbmt.2006.03.004 PG 15 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 039MH UT WOS:000237309500001 PM 16635784 ER PT J AU Tsaneva-Atanasova, K Zimliki, CL Bertram, R Sherman, A AF Tsaneva-Atanasova, K Zimliki, CL Bertram, R Sherman, A TI Diffusion of calcium and metabolites in pancreatic islets: Killing oscillations with a pitchfork SO BIOPHYSICAL JOURNAL LA English DT Article ID CYTOPLASMIC CA2+ OSCILLATIONS; INSULIN-SECRETION; BETA-CELLS; IN-VIVO; OXYGEN-CONSUMPTION; COUPLED BURSTERS; MOUSE ISLETS; SYNCHRONIZATION; MODEL; COMMUNICATION AB Cell coupling is important for the normal function of the beta-cells of the pancreatic islet of Langerhans, which secrete insulin in response to elevated plasma glucose. In the islets, electrical and metabolic communications are mediated by gap junctions. Although electrical coupling is believed to account for synchronization of the islets, the role and significance of diffusion of calcium and metabolites are not clear. To address these questions we analyze two different mathematical models of islet calcium and electrical dynamics. To study diffusion of calcium, we use a modified Morris-Lecar model. Based on our analysis, we conclude that intercellular diffusion of calcium is not necessary for islet synchronization, at most supplementing electrical coupling. Metabolic coupling is investigated with a recent mathematical model incorporating glycolytic oscillations. Bifurcation analysis of the coupled system reveals several modes of behavior, depending on the relative strength of electrical and metabolic coupling. We find that whereas electrical coupling always produces synchrony, metabolic coupling can abolish both oscillations and synchrony, explaining some puzzling experimental observations. We suggest that these modes are generic features of square-wave bursters and relaxation oscillators coupled through either the activation or recovery variable. C1 NIDDK, Lab Biol Modeling, NIH, Bethesda, MD 20892 USA. Fed Dept Agr, Ctr Devices & Radiol Hlth, Rockville, MD USA. Florida State Univ, Dept Math, Tallahassee, FL 32306 USA. Florida State Univ, Inst Mol Biophys, Tallahassee, FL 32306 USA. RP Sherman, A (reprint author), NIDDK, Lab Biol Modeling, NIH, 12 South Dr,Rm 4007, Bethesda, MD 20892 USA. EM asherman@nih.gov RI Tsaneva-Atanasova, Krasimira/A-7153-2011; OI Tsaneva-Atanasova, Krasimira/0000-0002-6294-7051 FU Intramural NIH HHS; NIDDK NIH HHS [Z01 DK013020-16] NR 48 TC 43 Z9 44 U1 0 U2 2 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD MAY PY 2006 VL 90 IS 10 BP 3434 EP 3446 DI 10.1529/biophysj.105.078360 PG 13 WC Biophysics SC Biophysics GA 034CE UT WOS:000236901400010 PM 16500973 ER PT J AU Hughes, A AF Hughes, A TI Risk communication in the face of uncertainty and new findings SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Meeting Abstract C1 US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1542-0752 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD MAY PY 2006 VL 76 IS 5 MA S15 BP 349 EP 349 PG 1 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 048GS UT WOS:000237936200067 ER PT J AU Hansen, DK Wall, KS White, G Pellicore, LS AF Hansen, DK Wall, KS White, G Pellicore, LS TI Teratogenic potential of Citrus aurantium SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Meeting Abstract C1 FDA, NCTR, Jefferson, AR USA. Toxicol Pathol Associates, Jefferson, AR USA. FDA, CFSAN, College Pk, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1542-0752 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD MAY PY 2006 VL 76 IS 5 MA P31 BP 385 EP 385 PG 1 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 048GS UT WOS:000237936200132 ER PT J AU Slikker, W Sadovova, N Zou, X Scallet, AC Patterson, TA Hanig, JP Paule, MG Wang, C AF Slikker, W Sadovova, N Zou, X Scallet, AC Patterson, TA Hanig, JP Paule, MG Wang, C TI Protective effect of midazolam on ketamine-induced neurotoxicity in rat forebrain culture SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Meeting Abstract C1 NCTR, Div Neurotoxicol, FDA, Jefferson, AR USA. Toxicol Pathol Associates, Jefferson, AR USA. FDA, CDER, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1542-0752 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD MAY PY 2006 VL 76 IS 5 MA P53 BP 397 EP 397 PG 1 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 048GS UT WOS:000237936200154 ER PT J AU Mahmood, I AF Mahmood, I TI Prediction of drug clearance in children from adults: a comparison of several allometric methods SO BRITISH JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article DE allometric scaling; children; clearance; exponents; root mean square error ID BODY-MASS; INFANTS; PHARMACOKINETICS; ONTOGENY; PATHWAYS; RISKS; SIZE AB In recent years with the advent of paediatric exclusivity and requirements to conduct clinical studies in children, the current emphasis is to find a safe and efficacious dose of a drug in children. It has been suggested that one can predict the clearance of a drug in children according to the equation: CL in the child = adult CL x (weight of the child/70)(0.75). Considering the controversy surrounding the exponent of 0.75 for the prediction of clearance and lack of any systematic evaluation of the aforementioned proposal, the objectives of the study were as follows: (i) to determine if indeed the exponent 0.75 is the most suitable exponent for the prediction of clearance in children from adult data; (ii) to explore and search for other exponents that are more accurate or as good as 0.75; and (iii) to propose a new approach (if any) based on the findings of the current evaluation. Six methods were used to predict clearance of drugs in children from adult data. Besides evaluating the exponent of 0.75, exponents of 0.80, 0.85 and 1.0 were also evaluated. An empirical approach based on kidney and liver weights was also examined. Based on the results of five methods, a sixth method was introduced. The results of the study indicate that no single method is suitable for all drugs or for all age groups. The exponents 0.75, 0.80, and 0.85 provided the same degree of accuracy or error in the prediction of clearance in children. Since no single method is suitable for all drugs or for all age groups. A combination of approaches is suggested which may help in improving the prediction of clearance in children from adult data. C1 US FDA, Ctr Drug Evaluat & Res, Off Drug Evaluat 6, Clin Pharmacol & Toxicol Branch, Rockville, MD 20852 USA. RP Mahmood, I (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Drug Evaluat 6, Clin Pharmacol & Toxicol Branch, Woodmount Off Ctr 2, Rockville, MD 20852 USA. EM mahmoodi@cder.fda.gov NR 16 TC 65 Z9 70 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0306-5251 J9 BRIT J CLIN PHARMACO JI Br. J. Clin. Pharmacol. PD MAY PY 2006 VL 61 IS 5 BP 545 EP 557 DI 10.1111/j.1365-2125.2006.02622.x PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 036ZI UT WOS:000237116100009 PM 16669848 ER PT J AU Almoosa, KF Ryu, JH Mendez, J Hughes, JT Joung, LR Sullivan, EJ Maurer, J McCormick, FX Sahn, SA AF Almoosa, KF Ryu, JH Mendez, J Hughes, JT Joung, LR Sullivan, EJ Maurer, J McCormick, FX Sahn, SA TI Management of pneumothorax in lymphangioleiomyomatosis - Effects on recurrence and lung transplantation complications SO CHEST LA English DT Article DE lung transplantation; lymphangioleiomyomatosis; pleurodesis; pneumothorax ID PULMONARY LYMPHANGIOLEIOMYOMATOSIS; CYSTIC-FIBROSIS AB Study objectives: Pneumothorax is a common complication of lymphangioleiomyomatosis (LAM) and the optimal approach to its treatment and prevention is unknown. Chemical or surgical pleurodesis are often required to prevent recurrence. However, their efficacy in LAM is unclear, and whether they contribute to perioperative complications during lung transplantation is uncertain. Setting: The LAM Foundation database of registered patients. Design: A questionnaire was sent to all registered patients who had at least one pneumothorax to determine rates and patterns of recurrence and efficacy of interventions. A second questionnaire was sent to registered LAM patients who received a lung transplant. Patients or participants: Of 395 registered patients 260 patients (66%) reported at least one pneumothorax during their lifetime, 193 of whom (74%) completed the questionnaire. Of the 85 lung transplant patients who were sent a separate questionnaire, 80 patients (94%) responded. Interventions: None. Measurements and results: Of the 193 respondents to the pneumothorax questionnaire, data on 676, episodes of pneumothorax were collected. Eighty-two percent (158 of, 193 patients) had their first pneumothorax prior to a diagnosis of LAM. One hundred forty patients (73%) had at least one additional pneumothorax, either an ipilateral recurrence (99 of 146 patients, 71%) or a contralateral pneumothorax (104 of 140 patients, 74%). Recurrence rate's Were 66% after conservative therapy 27% after chemical pleurodesis and 32% after surgery. In patients who had undergone lung transplantation, prior chemical or surgical pleurodesis was performed in 45 of 80 Patients (56%). Fourteen of 80 patients (89%) reported pleural-related postoperative bleeding, M of Whom (93%) had prior pleurodesis. Conclusions: Chemical Pleurodesis or surgery are equally effective and better than conservative therapy in preventing recurrence of pneumothorax in LAM. Due to the high recurrence rate, either procedure should be considered for the initial pneumothorax in these patients. However, both contribute to increased perioperative bleeding following lung transplantation, with no effect on length of hospital stay. C1 Univ Cincinnati, Div Pulm & Crit Care Med, Cincinnati, OH 45267 USA. Mayo Clin Coll Med, Div Pulm & Crit Care Med, Rochester, MN USA. Med Univ S Carolina, Div Pulm & Crit Care Med, Charleston, SC 29425 USA. US FDA, Rockville, MD 20857 USA. Cigna Hlth Care, W Granby, CT USA. RP Almoosa, KF (reprint author), Univ Cincinnati, Div Pulm & Crit Care Med, 231 Albert Sabin Way,6053 MSB, Cincinnati, OH 45267 USA. EM khalid.almoosa@uc.edu OI McCormack, Francis/0000-0001-7168-9464 NR 22 TC 65 Z9 67 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 MAY PY 2006 VL 129 IS 5 BP 1274 EP 1281 DI 10.1378/chest.129.5.1274 PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 043RE UT WOS:000237618400024 PM 16685019 ER PT J AU Beger, RD AF Beger, RD TI Computational modeling of biologically active molecules using NMR spectra SO DRUG DISCOVERY TODAY LA English DT Review ID NUCLEAR-MAGNETIC-RESONANCE; AUTOMATED STRUCTURE EVALUATION; ARYL-HYDROCARBON RECEPTOR; RELATIONSHIP QSDAR MODELS; ANALYSIS COSCOSA MODELS; CHEMICAL-SHIFTS; C-13 NMR; POLYCHLORINATED DIBENZODIOXINS; 3-DIMENSIONAL STRUCTURE; BIPHENYLS BINDING AB The molecular structure and NMR chemical shift information of a compound can be combined to form powerful models of biological activity. NMR spectral data and structure information can be combined on a structural template analogous to 3D-QSAR methodology or orientation independently in spectral space. Surprisingly, quantitative spectrometric data-activity relationship (QSDAR) models built on structure templates are inferior to multi-dimensional QSDAR models built in spectral space. 3D-QSDAR modeling could be useful for estimating chemical toxicity, risk assessment of environmental contaminants and drug lead-compound identifications. C1 US FDA, Div Syst Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72076 USA. RP Beger, RD (reprint author), US FDA, Div Syst Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72076 USA. EM richard.beger@fda.hhs.gov NR 49 TC 8 Z9 8 U1 0 U2 2 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 MAY PY 2006 VL 11 IS 9-10 BP 429 EP 435 DI 10.1016/j.drudis.2006.03.014 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 055JT UT WOS:000238447300010 PM 16635805 ER PT J AU Boam, AB AF Boam, AB TI Regulatory issues facing the development of drug-eluting stents: a USFDA perspective SO EXPERT REVIEW OF MEDICAL DEVICES LA English DT Editorial Material DE coronary; DES; device development; drug eluting stent; PCI; stent ID PERCUTANEOUS CORONARY INTERVENTION; TRIAL; CLOPIDOGREL; RESTENOSIS; THERAPY AB Coronary drug-eluting stents (DES) are a breakthrough technology that has changed the standard of care for many patients undergoing percutaneous intervention for coronary artery disease. Initial trials of two DES demonstrated significant clinical benefit with respect to the need for reintervention when compared with bare metal stents. However, more recent studies of DES involve in-patients with more complex disease, such as bifurcation lesions, chronic total occlusions and multiple-vessel disease. Additionally, DES are now being evaluated in patients previously only considered for surgical intervention. Assessment of DES in these complicated patient populations can lead to challenges in trial design, but the US FDA is willing to consider alternative clinical trial designs and statistical analysis plans. Other complex issues associated with DES include duration of clinical trials to determine safety, and the appropriate dose and duration of concomitant antiplatelet therapy. Finally, the FDA acknowledges that DES are complex products to produce and we believe that through interaction with the FDA during development, difficulties with test methodologies, animal studies and clinical trial designs can be addressed. The future of DES likely involves new stent and carrier materials, including biodegradable materials and new drugs and biologicals. The FDA anticipates continued collaboration with physicians, manufacturers, academic institutions and professional societies. C1 US FDA, Rockville, MD 20850 USA. RP Boam, AB (reprint author), US FDA, 920 Corp Blvd,HFZ-450, Rockville, MD 20850 USA. EM aab@cdrh.fda.gov NR 17 TC 3 Z9 3 U1 0 U2 1 PU FUTURE DRUGS LTD PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1743-4440 J9 EXPERT REV MED DEVIC JI Expert Rev. Med. Devices PD MAY PY 2006 VL 3 IS 3 BP 297 EP 300 DI 10.1586/17434440.3.3.297 PG 4 WC Engineering, Biomedical SC Engineering GA 044PT UT WOS:000237685400011 PM 16681451 ER PT J AU Balague, C Khan, AA Fernandez, L Redolfi, AL Aquili, V Voltattorni, P Hofer, C Ebner, G Duenas, S Cerniglia, CE AF Balague, C Khan, AA Fernandez, L Redolfi, AL Aquili, V Voltattorni, P Hofer, C Ebner, G Duenas, S Cerniglia, CE TI Occurrence of non-O157 Shiga toxin-producing Escherichia coli in ready-to-eat food from supermarkets in Argentina SO FOOD MICROBIOLOGY LA English DT Article DE non-O157 Escherichia coli; Shiga toxin; ready to eat food; pulsed-field gel electrophoresis; multiplex per ID HEMOLYTIC-UREMIC SYNDROME; STRAINS; O157-H7; CATTLE; GENES; BACTERIOPHAGES; IDENTIFICATION; INFECTIONS; SEROTYPES; LOCATION AB Between June 2000 and December 2001, 500 food samples were collected from supermarkets and shops selling ready-to-eat food in Rosario, Argentina, and examined for Escherichia coli. Forty-nine E coli isolates from food samples were further characterized for virulence genes by multiplex polymerase chain reaction (PCR) targeting the stxl, stx2, stx2e, eaeA, CNF1, CNF2, Einv, LTI, STI, and STII genes in four groups. Out of 49 E. coli isolates screened by multiplex PCR, only 10 possessed Shiga toxin genes, stx1 and stx2 genes and none possessed the other genes. The Shiga toxin positive E coli strains (STEC) were isolated from soft, cottage cheeses, chicken with sauce and vegetables mayonase. These E coli isolates were serogrouped and belonged to 018 (two strains), O8, O57w, O79, O44, and O128; three strains were untypeable. Pulsed-field gel electrophoresis (PFGE) with Xbal generated a unique profile for each, having 10 - 15 bands ranging from 50 to 500 kb, except that strain ARG 20 generated small bands and was partly degraded. These strains are potential foodborne pathogens and their presence in ready-to-eat food illustrates the need to keep a careful watch for the source of pathogens and then develop methods to control them. Published by Elsevier Ltd. C1 US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. Univ Nacl Rosario, Fac Biochem & Pharmaceut Sci, Rosario, Argentina. Rosario Food Inst, Rosario, Argentina. RP Khan, AA (reprint author), US FDA, Natl Ctr Toxicol Res, Div Microbiol, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM Ashraf@nctr.fda.gov NR 26 TC 15 Z9 16 U1 1 U2 4 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0740-0020 J9 FOOD MICROBIOL JI Food Microbiol. PD MAY PY 2006 VL 23 IS 3 BP 307 EP 313 DI 10.1016/j.fm.2005.03.005 PG 7 WC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology SC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology GA 979VX UT WOS:000232974200013 PM 16943019 ER PT J AU Waynant, RW AF Waynant, Ronald W. TI Contests and contributions SO IEEE CIRCUITS & DEVICES LA English DT Editorial Material C1 IEEE Circuits & Devices Magazine, FDA CDRH, Rockville, MD 20857 USA. RP Waynant, RW (reprint author), IEEE Circuits & Devices Magazine, FDA CDRH, HFZ-134,12725 Twinbrook Pkwy,Room 267, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 8755-3996 J9 IEEE CIRCUITS DEVICE JI IEEE Circuits Devices PD MAY-JUN PY 2006 VL 22 IS 3 BP 3 EP 3 PG 1 WC Engineering, Electrical & Electronic; Instruments & Instrumentation SC Engineering; Instruments & Instrumentation GA 063QC UT WOS:000239033600001 ER PT J AU Beard, BB Kainz, W Onishi, T Iyama, T Watanabe, S Fujiwara, O Wang, JQ Bit-Babik, G Faraone, A Wiart, J Christ, A Kuster, N Lee, AK Kroeze, H Siegbahn, M Keshvari, J Abrishamkar, H Simon, W Manteuffel, D Nikoloski, N AF Beard, BB Kainz, W Onishi, T Iyama, T Watanabe, S Fujiwara, O Wang, JQ Bit-Babik, G Faraone, A Wiart, J Christ, A Kuster, N Lee, AK Kroeze, H Siegbahn, M Keshvari, J Abrishamkar, H Simon, W Manteuffel, D Nikoloski, N TI Comparisons of computed mobile phone induced SAR in the SAM phantom to that in anatomically correct models of the human head SO IEEE TRANSACTIONS ON ELECTROMAGNETIC COMPATIBILITY LA English DT Article DE FDTD methods; IEEE standards; phantom; simulation; software standards; specific absorption rate (SAR); specific anthropomorphic mannequin (SAM) ID ELECTROMAGNETIC-ENERGY-ABSORPTION; COMMUNICATION DEVICES; CELLULAR TELEPHONES; NEAR-FIELD; 1900 MHZ; EXPOSURE; DIPOLE; CHILDREN; ADULTS; GUIDELINES AB The specific absorption rates (SAR) determined computationally in the specific anthropomorphic mannequin (SAM) and anatomically correct models of the, human head when exposed to a mobile phone model are compared as part of a study organized by IEEE Standards Coordinating Committee 34, Sub-Committee 2, and Working Group 2, and carried out by an international task force comprising 14 government, academic, and industrial research institutions. The detailed study protocol defined the computational head and mobile phone models. The participants used different finite-difference time-domain software and independently positioned,the mobile phone and head models in accordance with the protocol. The results show that when the pinna SAR is calculated separately from the head SAR, SAM produced a higher SAR in the head than the anatomically correct head models. Also the larger (adult) head produced a statistically significant higher peak SAR for both the 1- and 10-g averages than did the smaller (child) head for all conditions of frequency and position. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. NTT DoCoMo Inc, Res & Dev, Wireless Labs, Kanagawa 2398536, Japan. Natl Inst Informat & Commun Technol, Tokyo 1848795, Japan. Nagoya Inst Technol, Grad Sch Engn, Nagoya, Aichi 4668555, Japan. Motorola Florida Res Labs, Corp EME Res Lab, Ft Lauderdale, FL 33322 USA. France Telecom, FTRD, RESA, FACE,IOP, F-92794 Issy Les Moulineaux, France. ITIS, Fdn Res Informat Technol Soc, Zurich, Switzerland. Elect & Telecommun Res Inst, Taejon 305350, South Korea. Univ Utrecht, Dept Radiotherapy, NL-3508 GA Utrecht, Netherlands. Ericsson Radio Syst AB, S-16480 Stockholm, Sweden. Nokia Res Ctr, Radio Technol Lab, Helsinki 00180, Finland. Univ Victoria, Dept Elect & Comp Engn, Victoria, BC V8W 3P6, Canada. IMST GmbH, Antennas & EM Modeling, D-47475 Kamp Lintfort, Germany. RP Beard, BB (reprint author), US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. EM brian.beard@fda.hhs.gov; woIfgang.kainz@fda.hhs.gov; oon-ishite@nttdocomo.co.jp; iyama@nttdocomo.co.jp; wata@nict.go.jp; wara@odin.elcom.nitech.ac.jp; wang@nitech.ac.jp; goga.bit-babik@motorola.com; antonio.faraone@motorola.com; Joe.wiart@francetelecom.com; christ@itis.ethz.ch; kuster@itis.ethz.ch; aklee@etri.re.kr; H.Kroeze@azu.nl; martin.siegbahn@ericsson.com; jafar.keshvari@nokia.com; houman@ece.uvic.ca; simon@imst.de; manteuffel@imst.de RI Foundation, IT'IS/B-9559-2008; OI Beard, Brian/0000-0001-6480-0857 NR 32 TC 78 Z9 81 U1 0 U2 8 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 0018-9375 J9 IEEE T ELECTROMAGN C JI IEEE Trans. Electromagn. Compat. PD MAY PY 2006 VL 48 IS 2 BP 397 EP 407 DI 10.1109/TEMC.2006.873870 PG 11 WC Engineering, Electrical & Electronic; Telecommunications SC Engineering; Telecommunications GA 048OJ UT WOS:000237956100017 ER PT J AU Hu, L Bray, MD Osorio, M Kopecko, DJ AF Hu, L Bray, MD Osorio, M Kopecko, DJ TI Campylobacter jejuni induces maturation and cytokine production in human dendritic SO INFECTION AND IMMUNITY LA English DT Article ID NF-KAPPA-B; SALMONELLA-ENTERICA; BONE-MARROW; T-CELL; ANTIGEN PRESENTATION; HELICOBACTER-PYLORI; IMMUNE-RESPONSES; INFECTION; TYPHIMURIUM; INDUCTION AB Campylobacter jejuni is a leading bacterial cause of human diarrheal disease in both developed and developing nations. Colonic mucosal invasion and the resulting host inflammatory responses are thought to be the key contributing factors to the dysenteric form of this disease. Dendritic cells (DCs) play an important role in both the innate and adaptive immune responses to microbial infection. In this study, the interaction between human monocyte-derived dendritic cells and C. jejuni was studied. We found that C. jejuni was readily internalized by DCs over a 2-h period. However, after a prolonged infection period (24 or 48 h) with C. jejuni, only a few viable bacteria remained intracellularly. Minimal cytotoxicity of C. jejuni to dendritic cells was observed. C. jejuni induced the maturation of dendritic cells over 24 h, as indicated by up-regulation of cell surface marker proteins CD40, CD80, and CD86. In addition, Campylobacter-infected DCs triggered activation of NF-kappa B and significantly stimulated production of interleukin-1 beta (IL-1 beta), IL-6, IL-8, IL-10, IL-12, gamma interferon, and tumor necrosis factor alpha (TNF-alpha) compared to uninfected DCs. Active bacterial invasion of DCs was not necessary for the induction of these cytokines, as heat-killed C. jejuni stimulated similar levels of cytokine production as live bacteria. Purified lipooligosaccharide of C. jejuni appears to be the major stimulant for the increased production of cytokines by DCs. Taken together, these data indicate that during infection, Cantpylobacter triggers an innate inflammatory response through increased production of IL-1 beta, IL-6, IL-8, and TNF-alpha and initiates a Th1-polarized adaptive immune response as predicted from the high level of production of IL-12. C1 US FDA, Lab Enter & Sexually Transmitted Dis, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Kopecko, DJ (reprint author), US FDA, Lab Enter & Sexually Transmitted Dis, Ctr Biol Evaluat & Res, 29 Lincoln Dr,NIH Campus Bldg 29-40,HFM440, Bethesda, MD 20892 USA. EM kopecko@cber.fda.gov NR 56 TC 55 Z9 55 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 MAY PY 2006 VL 74 IS 5 BP 2697 EP 2705 DI 10.1128/IAI.74.5.2697-2705.2006 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 039MX UT WOS:000237311200022 PM 16622206 ER PT J AU Klinman, DM AF Klinman, Dennis M. TI Adjuvant activity of CpG oligodeoxynucleotides SO INTERNATIONAL REVIEWS OF IMMUNOLOGY LA English DT Review DE adjuvant; CpG; innate; oligodeoxynucleotide; Th1 ID B SURFACE-ANTIGEN; IMMUNOSTIMULATORY DNA-SEQUENCES; PLASMACYTOID DENDRITIC CELLS; SYSTEMIC-LUPUS-ERYTHEMATOSUS; INDUCE AUTOIMMUNE-DISEASE; TOLL-LIKE RECEPTORS; BACTERIAL-DNA; IMMUNE-RESPONSES; IN-VIVO; CIRCUMSPOROZOITE PROTEIN AB Synthetic oligodeoxynucleotides (ODNs) containing unmethylated CpG motifs directly stimulate human B cells and plasmacytoid dendritic cells (pDCs), thereby promoting the production of Thl and proinflammatory cytokines and the maturation/activation of professional antigen-presenting cells. These activities enable CpG ODNs to act as immune adjuvants, accelerating and boosting antigen-specific immune responses by 5- to 500-fold. The CpG motifs present in bacterial DNA plasmids may contribute to the immunogenicity of DNA vaccines. Ongoing clinical studies indicate that CpG ODNs are safe and well tolerated when administered as adjuvants to humans and can improve vaccine-induced immune responses. C1 US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. RP Klinman, DM (reprint author), US FDA, Ctr Biol Evaluat & Res, Bldg 29A,Room 3D10, Bethesda, MD USA. EM klinman@cber.fda.gov NR 113 TC 86 Z9 91 U1 0 U2 5 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0883-0185 J9 INT REV IMMUNOL JI Int. Rev. Immunol. PD MAY-AUG PY 2006 VL 25 IS 3-4 BP 135 EP 154 DI 10.1080/08830180600743057 PG 20 WC Immunology SC Immunology GA 063OO UT WOS:000239029400005 PM 16818369 ER PT J AU Chowdhury, BA AF Chowdhury, BA TI Ciclesonide inhalation aerosol for persistent asthma SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Letter C1 US FDA, Div Pulm & Allergy Prod, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Chowdhury, BA (reprint author), US FDA, Div Pulm & Allergy Prod, Ctr Drug Evaluat & Res, Silver Spring, MD USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD MAY PY 2006 VL 117 IS 5 BP 1194 EP 1195 DI 10.1016/j.jaci.2006.02.041 PG 2 WC Allergy; Immunology SC Allergy; Immunology GA 041EM UT WOS:000237436300040 PM 16675356 ER PT J AU Trucksess, M Weaver, C Oles, C D'Ovidio, K Rader, J AF Trucksess, M Weaver, C Oles, C D'Ovidio, K Rader, J TI Determination of aflatoxins and ochratoxin A in ginseng and other botanical roots by immunoaffinity column cleanup and liquid chromatography with fluorescence detection SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID MYCOTOXINS AB Mycotoxins are toxic secondary metabolites produced by certain molds and are common contaminants of many important food crops, such as grains, nuts, and spices. Some mycotoxins are found in fruits, vegetables, and botanical roots. These contaminants have a broad range of toxic effects, including carcinogenicity, immunotoxicity, neurotoxicity, and reproductive and developmental toxicity. The public health concerns related to both acute and chronic effects of mycotoxins in animals have prompted more than 100 countries to establish regulatory limits for some of the well-known mycotoxins, such as the aflatoxins (AFL). Our research focused on method development for 2 of these toxins, AFL and ochratoxin A (OTA), in ginseng and other selected botanical roots. Methods using an immunoaffinity column (IAC) cleanup, liquid chromatographic separation, and fluorescence detection were modified and evaluated. Two types of IAC cleanup were evaluated: IAC for AFL, and IAC for both AFL and OTA. Three derivatization techniques to enhance the fluorescence of the AFL were compared: precolumn trifluoroacetic acid, postcolumn bromination, and postcolumn ultraviolet irradiation. No derivatization was needed for OTA. Results for AFL using the single analyte IAC cleanup and the 3 derivatization techniques were all comparable for ginseng and for other roots such as ginger, licorice, and kava-kava. Recoveries of added AFL for ginseng at levels from 2 to 16 ng/g were about 80%. Using IAC cleanup for both AFL and OTA recoveries of added AFL for ginseng at 4-16 ng/g were about 70%, and for ginger, licorice, and kava-kava were about 60%. Recoveries of added OTA for ginseng, ginger, and echinacea at 4 ng/g were about 55%. C1 US FDA, College Pk, MD USA. Univ Maryland, College Pk, MD 20742 USA. RP Trucksess, M (reprint author), US FDA, 5300 Paint Branch Pkwy, College Pk, MD USA. EM mary.trucksess@fda.hhs.gov FU None [223-01-2464]; PHS HHS [223-01-2464] NR 13 TC 49 Z9 54 U1 2 U2 9 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD MAY-JUN PY 2006 VL 89 IS 3 BP 624 EP 630 PG 7 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 048XP UT WOS:000237980100006 PM 16792061 ER PT J AU McClure, FD Lee, JK AF McClure, FD Lee, JK TI Determining a one-tailed upper limit for future sample relative reproducibility standard deviations SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article AB A formula was developed to determine a one-tailed 100p% upper limit for future sample percent relative reproducibility standard deviations (RSDr,% = 100s(R)/(y) over bar) where SR is the sample reproducibility standard deviation, which is the square root of a linear combination of the sample repeatability variance (s(r)(2)) plus the sample laboratory-to-laboratory variance (s(L)(2)) i.e., s(R) = root s(r)(2) + s(L)(2), and (y) over bar is the sample mean. The future RSDR,% is expected to arise from a population of potential RSDR,% values whose true mean is xi(R),% = 100 sigma(R)/mu, where sigma(R) and mu are the population reproducibility standard deviation and mean, respectively. C1 US FDA, Ctr Food Safety & Appl Nutr, Off Sci Anal & Support, Div Math,US Dept HHS, College Pk, MD 20740 USA. RP McClure, FD (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Sci Anal & Support, Div Math,US Dept HHS, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM foster.mcclure@cfsan.fda.gov NR 10 TC 3 Z9 3 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 MAY-JUN PY 2006 VL 89 IS 3 BP 797 EP 803 PG 7 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 048XP UT WOS:000237980100023 PM 16795922 ER PT J AU Rasooly, A Herold, KE AF Rasooly, A Herold, KE TI Biosensors for the analysis of food- and waterborne pathogens and their toxins SO JOURNAL OF AOAC INTERNATIONAL LA English DT Review ID SURFACE-PLASMON RESONANCE; STAPHYLOCOCCAL-ENTEROTOXIN-B; ESCHERICHIA-COLI O157-H7; OPTIC-BASED BIOSENSOR; BIENZYME ELECTROCHEMICAL BIOSENSOR; QUARTZ-CRYSTAL MICROBALANCE; IN-GROUND BEEF; SALMONELLA-TYPHIMURIUM; RAPID DETECTION; ARRAY BIOSENSOR AB Biosensors are devices which combine a biochemical recognition element with a physical transducer. There are various types of biosensors, including electrochemical, acoustical, and optical sensors. Biosensors are used for medical applications and for environmental testing. Although biosensors are not commonly used for food microbial analysis, they have great potential for the detection of microbial pathogens and their toxins in food. They enable fast or real-time detection, portability, and multipathogen detection for both field and laboratory analysis. Several applications have been developed for microbial analysis of food pathogens, including E. coli O157:H7, Staphylococcus aureus, Salmonella, and Listeria monocytogenes, as well as various microbial toxins such as staphylococcal enterotoxins and mycotoxins. Biosensors have several potential advantages over other methods of analysis, including sensitivity in the range of ng/mL for microbial toxins and < 100 colony-forming units/mL for bacteria. Fast or real-time detection can provide almost immediate interactive information about the sample tested, enabling users to take corrective measures before consumption or further contamination can occur. Miniaturization of biosensors enables biosensor integration into various food production equipment and machinery. Potential uses of biosensors for food microbiology include online process microbial monitoring to provide real-time information in food production and analysis of microbial pathogens and their toxins in finished food. Biosensors can also be integrated into Hazard Analysis and Critical Control Point programs, enabling critical microbial analysis of the entire food manufacturing process. In this review, the main biosensor approaches, technologies, instrumentation, and applications for food microbial analysis are described. C1 NCI, Can Diagnosis Program, NIH, Rockville, MD 20852 USA. US FDA, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, Div Biol Sci, Silver Spring, MD 20903 USA. Univ Maryland, Dept Engn Mech, College Pk, MD 20742 USA. RP Rasooly, A (reprint author), NCI, Can Diagnosis Program, NIH, 6130 Execut Blvd, Rockville, MD 20852 USA. EM rasoolya@mail.nih.gov NR 105 TC 71 Z9 72 U1 2 U2 43 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD MAY-JUN PY 2006 VL 89 IS 3 BP 873 EP 883 PG 11 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 048XP UT WOS:000237980100035 PM 16792089 ER PT J AU Dheenadhayalan, V Delogu, G Sanguinetti, M Fadda, G Brennan, MJ AF Dheenadhayalan, V Delogu, G Sanguinetti, M Fadda, G Brennan, MJ TI Variable expression patterns of Mycobacterium tuberculosis PE(-)PGRS genes: Evidence that PE(-)PGRS16 and PE(-)PGRS26 are inversely regulated in vivo SO JOURNAL OF BACTERIOLOGY LA English DT Article ID COMPLETE GENOME SEQUENCE; PE-PGRS PROTEINS; REAL-TIME PCR; PERSISTENCE; MICROARRAY; VIRULENCE; ANTIGENS; STRAINS; FAMILY; MODEL AB Evaluation of expression of 16 PE-PGRS genes present in Mycobacterium tuberculosis under various growth conditions demonstrated constitutive expression of 7 genes, variable expression of 7 genes, and no expression of 2 genes. An inverse expression profile for genes PE_PGRS16 and PE_PGRS26 was observed to occur in macrophages and in mice infected with M. tuberculosis. Variable expression of PE_PGRS proteins could have implications for their role in the immunopathogenesis of tuberculosis. C1 US FDA, Off Vaccines Res & Review, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. Univ Sacred Heart, Inst Microbiol, Rome, Italy. RP Brennan, MJ (reprint author), US FDA, Off Vaccines Res & Review, Ctr Biol Evaluat & Res, Bldg 29,Rm 503,HFM-431,29 Lincoln Dr, Bethesda, MD 20892 USA. EM michael.brennan@fda.hhs.gov RI Sanguinetti, Maurizio/E-8247-2011; Delogu, Giovanni/I-3701-2012; Fadda, Giovanni/K-6224-2012; OI Delogu, Giovanni/0000-0003-0182-8267; Sanguinetti, Maurizio/0000-0002-9780-7059 NR 25 TC 42 Z9 44 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD MAY PY 2006 VL 188 IS 10 BP 3721 EP 3725 DI 10.1128/JB.188.10.3721-3725.2006 PG 5 WC Microbiology SC Microbiology GA 041ER UT WOS:000237436800032 PM 16672626 ER PT J AU Lyman, DJ Stewart, SFC Murray-Wijelath, J Wijelath, E AF Lyman, DJ Stewart, SFC Murray-Wijelath, J Wijelath, E TI Role of fluid dynamics on the healing of an in vivo tissue engineered vascular graft SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS LA English DT Article DE in vivo tissue engineering; fluid dynamics; fibrin; VEGF; FN; TGF-beta; polyester vascular graft ID POROUS ARTERIAL PROSTHESES; FTIR ANALYSIS; ENDOTHELIAL-CELLS; PULSATILE FLOW; MODEL; DOG; COLLAGEN; FIBRONECTIN; FIBRINOGEN; NEOINTIMA AB A polyester (PET) reinforced fibrin-FN-VEGF-TGF beta vascular graft, formed by a four-step preclotting technique of a porous PET arterial graft, shows the overlapping inflammation, proliferation, and remodeling steps of normal wound healing when implanted in the descending thoracic aorta (DTA) position in the dog, forming a surface layer of endothelial cells. While the DTA grafts readily healed (i.e., endothelialized), similar grafts implanted in the carotid-femoral artery position did not fully heal. Since the initial phases of healing were shown to be dependent upon the transport of blood-borne constituents to the graft surface, the extent of healing appears to be dependent on the fluid dynamics present in the artery-graft-artery construct. The length of the noncompliant graft, the construction of the anastomoses, bends in the construct, graft diameter, and graft compliance can affect the fluid dynamics in the implant, and thus the healing of the graft. This has clinical relevance for the testing and development of new vascular graft materials. (c) 2005 Wiley Periodicals. Inc. C1 Univ Utah, Dept Mat Sci & Engn, Salt Lake City, UT 84112 USA. Univ Utah, Dept Bioengn, Salt Lake City, UT 84112 USA. US FDA, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, Rockville, MD 20850 USA. Univ Washington, Dept Surg, Seattle, WA 98108 USA. VA Med Ctr, PSHCS, Seattle, WA 98108 USA. RP Lyman, DJ (reprint author), POB 5314, Lacey, WA 98509 USA. EM dlypr@comcast.net NR 46 TC 5 Z9 5 U1 2 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4973 J9 J BIOMED MATER RES B JI J. Biomed. Mater. Res. Part B PD MAY PY 2006 VL 77B IS 2 BP 389 EP 400 DI 10.1002/jbm.b.30436 PG 12 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 036UK UT WOS:000237101000022 PM 16278848 ER PT J AU Chen, TH Janjua, R McDermott, MK Bernstein, SL Steidl, SM Payne, GF AF Chen, TH Janjua, R McDermott, MK Bernstein, SL Steidl, SM Payne, GF TI Gelatin-based biomimetic tissue adhesive. Potential for retinal reattachment SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS LA English DT Article DE adhesive; gelatin; lap-shear; retina; transglutaminase ID FIBRIN SEALANTS; CROSS-LINKING; MICROBIAL TRANSGLUTAMINASE; OPHTHALMIC SURGERY; VITREOUS SURGERY; SILICONE OIL; FACTOR-XIII; GLUE; PROTEIN; ABNORMALITIES AB An adhesive that cures under moist/wet conditions could facilitate surgical procedures for retinal reattachment. We are investigating an adhesive that mimics the factor XIIIa-mediated crosslinking of fibrin that occurs in the late stages of the blood coagulation cascade. Specifically, we use gelatin as the structural protein (in place of fibrin), and crosslink gelatin using a calcium-independent microbial transglutaminase (in place of the calcium-dependent transglutaminase factor XIIIa). Injection of gelatin and microbial transglutaminase (mTG) into the vitreous cavity of Sprague Dawley white rats did not elicit structural or cellular damage to the retina as evidenced from histological evaluation 2 weeks post-injection. Qualitative in vitro studies indicate that the gelatin-mTG adhesive binds to bovine retinal tissue under wet conditions. Quantitative lap-shear tests were performed with more robust bovine tissue from the choroid and sclera. The lap-shear strength of the biomimetic gelatin-mTG adhesive was independent of tissue-type and ranged from 15 to 45 kPa, which is comparable to the values reported for other soft-tissue adhesives. These studies suggest that the mTG-crosslinked gelatin may provide a simple, safe, and effective adhesive for ophthalmic applications. (c) 2005 Wiley Periodicals, Inc. C1 Univ Maryland, Biotechnol Inst, Ctr Biosyst Res, College Pk, MD 20742 USA. Univ Maryland, Dept Ophthalmol, Baltimore, MD 21201 USA. US FDA, Off Sci & Technol, Div Mech & Mat Sci, Rockville, MD 20850 USA. Univ Maryland, Dept Chem & Biochem Engn, Baltimore, MD 21250 USA. RP Payne, GF (reprint author), Univ Maryland, Biotechnol Inst, Ctr Biosyst Res, 5115 Plant Sci Bldg, College Pk, MD 20742 USA. EM payne@umbi.umd.edu NR 47 TC 40 Z9 42 U1 2 U2 14 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4973 J9 J BIOMED MATER RES B JI J. Biomed. Mater. Res. Part B PD MAY PY 2006 VL 77B IS 2 BP 416 EP 422 DI 10.1002/jbm.b.30439 PG 7 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 036UK UT WOS:000237101000025 PM 16278851 ER PT J AU Schlesser, JE Gerdes, R Ravishankar, S Madsen, K Mowbray, J Teo, AYL AF Schlesser, JE Gerdes, R Ravishankar, S Madsen, K Mowbray, J Teo, AYL TI Survival of a five-strain cocktail of Escherichia coli O157 : H7 during the 60-day aging period of cheddar cheese made from unpasteurized milk SO JOURNAL OF FOOD PROTECTION LA English DT Article ID HEAT-TREATED MILK; MICROBIOLOGICAL SAFETY; LISTERIA-MONOCYTOGENES; THERMAL INACTIVATION; CAMEMBERT CHEESE; FLUID MILK; MANUFACTURE; BEHAVIOR; FATE AB The U.S. Food and Drug Administration Standard of Identity for Cheddar cheeses requires pasteurization of the milk, or as an alternative treatment, a minimum 60-day aging at >= 2 degrees C for cheeses made from unpasteurized milk, to reduce the number of viable pathogens that may be present to an acceptable risk. The objective of this study was to investigate the adequacy of the 60-day minimum aging to reduce the numbers of viable pathogens and evaluate milk subpasteurization heat treatment as a process to improve the safety of Cheddar cheeses made from unpasteurized milk. Cheddar cheese was made from unpasteurized milk inoculated with 10(1) to 10(5) CFU/ml of a five-strain cocktail of acid-tolerant Escherichia coli O157:H7. Samples were collected during the cheese manufacturing process. After pressing, the cheese blocks were packaged into plastic bags, vacuum sealed, and aged at 7 degrees C. After 1 week, the cheese blocks were cut into smaller-size uniform pieces and then vacuum sealed in clear plastic pouches. Samples were plated and enumerated for E. coli O157:H7. Populations of E. coli O157:H7 increased during the cheese-making operations. Population of E. coli O157:H7 in cheese aged for 60 and 120 days at 7 degrees C decreased less than 1 and 2 log, respectively. These studies confirm previous reports that show 60-day aging is inadequate to eliminate E. coli O157:H7 during cheese ripening. Subpasteurization heat-treatment runs were conducted at 148 degrees F (64.4 degrees C) for 17.5 s on milk inoculated with E. coli O157:H7 at 10(5) CFU/ml. These heat-treatment runs resulted in a 5-log E. coli O157:H7 reduction. C1 Natl Ctr Food Safety & Technol, Summit Argo, IL 60501 USA. US FDA, Summit Argo, IL 60501 USA. IIT, Summit Argo, IL 60501 USA. US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Schlesser, JE (reprint author), Natl Ctr Food Safety & Technol, Moffett Campus, Summit Argo, IL 60501 USA. EM Jschless@cfsan.fda.gov FU FDA HHS [FD-000431] NR 23 TC 36 Z9 36 U1 0 U2 9 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 MAY PY 2006 VL 69 IS 5 BP 990 EP 998 PG 9 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 040HA UT WOS:000237368400002 PM 16715794 ER PT J AU Myers, MR AF Myers, MR TI Tissue deformation induced by radiation force from Gaussian transducers SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID SOFT-TISSUE AB Imaging techniques based upon the tissue mechanical response to an acoustic radiation force are being actively researched. In this paper a model for predicting steady-state tissue displacement induced by a radiation force arising from the absorption of Gaussian ultrasound beams is presented. A simple analytic expression is derived that agrees closely with the numerical quadrature of the displacement convolution integrals. The analytic result reveals the dependence of the steady-state axial displacement upon the operational parameters, e.g.. an inverse proportional relationship to the tissue shear modulus. The derivation requires that the transducer radius be small compared to the focal length, but accurate results were obtained for transducer radii comparable to the focal length. Favorable comparisons with displacement predictions for non-Gaussian transducers indicate that the theory is also useful for a broader range of transducer intensity profiles. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20852 USA. RP Myers, MR (reprint author), US FDA, Ctr Devices & Radiol Hlth, HFZ-170, Rockville, MD 20852 USA. NR 10 TC 6 Z9 6 U1 0 U2 3 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 MAY PY 2006 VL 119 IS 5 BP 3147 EP 3152 DI 10.1121/1.2187087 PN 1 PG 6 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA 041ME UT WOS:000237459500057 PM 16708969 ER PT J AU Hastings, KL AF Hastings, KL TI Risk assessment in drug development: Autoimmunity SO JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A-CURRENT ISSUES LA English DT Article; Proceedings Paper CT Conference on Toxicology and Risk Assessment CY APR 25-28, 2005 CL Fairborn, OH SP Tri-Serv Toxicol, AFRL, Appl Biotechnol Branch, AFRL, Air Force Off Sci Res, AFOIH/Hlth Risk Assessment Branch, Navy, NGRC/Enivironm Hlth Effects Lab, Army, Ctr Hlth Promot & Prevent Med, US Environm Protect Agcy, Natl Ctr Environm Assessment, Agcy Toxic Substances & Dis Regiatry, Div Toxicol, Natl Inst Occupat Safety & Hlth, Natl Res Council/Natl Acad Sci AB Autoimmunity is a physiological condition in which the immune system responds to normal tissues as if they were foreign pathogens. If this reaction produces pathology, it is referred to as autoimmune disease. Many human diseases ( most often chronic in nature) appear to have an autoimmune basis. No model exists that has proven to be sufficiently predictive to screen drugs for potential to induce autoimmunity ( hazard identification); thus, it seems somewhat illogical to consider this as an example of risk assessment. However, given the knowledge currently available, it is at least conceivable that drugs could be identified as having the potential to produce autoimmune reactions, and especially to predict the conditions under which autoimmune disease may be induced. This has proven to be an especially important topic with protein drugs designed to replace endogenous molecules. Immunogenicity, thought to be an important component of protein drug-induced autoimmunity, can be modeled in animals. However, interpretation of results with respect to prediction of ability to induce autoimmune disease remains a serious challenge. C1 US FDA, Off New Drugs, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Hastings, KL (reprint author), US FDA, Off New Drugs, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave,Bldg 22,Rm 6480, Silver Spring, MD 20993 USA. EM hastingsk@cder.fda.gov NR 8 TC 1 Z9 1 U1 1 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 MAY 1 PY 2006 VL 69 IS 9 BP 893 EP 898 DI 10.1080/15287390600591736 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 038SJ UT WOS:000237243600007 ER PT J AU Zinderman, CE Landow, L Wise, RP AF Zinderman, CE Landow, L Wise, RP TI Anaphylactoid reactions to Dextran 40 and 70: Reports to the United States Food and Drug Administration, 1969 to 2004 SO JOURNAL OF VASCULAR SURGERY LA English DT Article ID HAPTEN INHIBITION; SCANDINAVIAN MULTICENTER; ML DEXTRAN-1; PREVENTION; 15-PERCENT; COMPLICATIONS; EXPERIENCE; RISKS AB Background: Clinical dextrans, such as Dextran 40 and Dextran 70, are associated with anaphylactoid reactions caused by dextran-reactive immunoglobulin G antibodies. When infused immediately before clinical dextrans, dextran 1 significantly reduces the incidence of severe anaphylactoid reactions. The objective of the study was to describe the frequency and characteristics of reports submitted to the United States Food and Drug Administration (FDA) for anaphylaxis or anaphylactoid events after clinical dextran administration. Methods: We searched the FDA's Adverse Event Reporting System for reports associated with a clinical dextran and describing anaphylaxis/anaphylactoid reactions. Our case definition for a probable anaphylaxis/anaphylactoid event required signs or symptoms from at least two body systems, with at least one sign or symptom being hypotension, vasodilation, or respiratory difficulty, and onset within 60 minutes. Other reports were considered possible cases if the reporter specifically described the reaction as anaphylaxis or an anaphylactoid reaction. Premier RxMarket Advisor provided estimates of total US hospitalizations with clinical dextran or dextran 1 administration from 2000 to 2004, based on discharge billing data from a sample of US hospitals. The IMS National Sales Perspective provided estimates of total doses of dextrans sold in the United States from 1999 to 2004, based oil volumes of dextrans sold in a sample of retail and nonretail outlets. Results: The FDA received 366 clinical dextran adverse event reports from 1969 to 2004, of which 90 (24.6%) were anaphylaxis/anaphylactoid events. The ratio of hospitalizations where clinical dextran was administered to hospitalizations where dextran 1 was administered was 28.4:1. The expected ratio would be 1:1 if all clinical dextran patients had received dextran 1 pretreatment. The ratio of clinical dextran doses sold to dextran 1 doses sold in the United States was 38.6:1. Conclusions. A high proportion of adverse event reports for clinical dextrans described anaphylaxis or anaphylactoid reactions. Hospital discharge and product sales data suggest that dextran 1 has not been used consistently before clinical dextran administration in recent years. To reduce the risk of anaphylactoid reactions, physicians should consider routine administration of dextran 1 before the infusion of a clinical dextran. C1 US FDA, Ctr Biol Evaluat & Res, Off Biostat & Epidemiol, Rockville, MD 20852 USA. US FDA, Ctr Biol Evaluat & Res, Off Blood Res & Review, Rockville, MD 20852 USA. RP Zinderman, CE (reprint author), US FDA, Ctr Biol Evaluat & Res, Off Biostat & Epidemiol, Suite 200S,HFM-224,1401 Rockville Pike, Rockville, MD 20852 USA. NR 29 TC 37 Z9 39 U1 0 U2 4 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD MAY PY 2006 VL 43 IS 5 BP 1004 EP 1009 DI 10.1016/j.jvs.2006.01.006 PG 6 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 038WY UT WOS:000237261400027 PM 16678697 ER PT J AU Chi, B Dickensheets, HL Spann, KM Alston, MA Luongo, C Dumoutier, L Huang, JY Renauld, JC Kotenko, SV Roederer, M Beeler, JA Donnelly, RP Collins, PL Rabin, RL AF Chi, B Dickensheets, HL Spann, KM Alston, MA Luongo, C Dumoutier, L Huang, JY Renauld, JC Kotenko, SV Roederer, M Beeler, JA Donnelly, RP Collins, PL Rabin, RL TI Alpha and lambda interferon together mediate suppression of CD4 T cells induced by respiratory syncytial virus SO JOURNAL OF VIROLOGY LA English DT Article ID INTERLEUKIN-1 INHIBITOR PRODUCTION; NONSTRUCTURAL PROTEINS NS1; DENDRITIC CELLS; PARAINFLUENZA VIRUS; EPITHELIAL-CELLS; VIRAL-INFECTION; INFLUENZA-VIRUS; PASTEURELLA-HAEMOLYTICA; LYMPHOCYTE-RESPONSES; REGULATORY FACTOR-3 AB The mechanism by which respiratory syncytial virus (RSV) suppresses T-cell proliferation to itself and other antigens is poorly understood. We used monocyte-derived dendritic cells (MDDC) and CD4 T cells and measured [H-3]thymidine incorporation to determine the factors responsible for RSV-induced T-cell suppression. These two cell types were sufficient for RSV-induced suppression of T-cell proliferation in response to cytomegalovirus or Staphylococcus enterotoxin B. Suppressive activity was transferable with supernatants from RSV-infected MDDC and was not due to transfer of live virus or RSV F (fusion) protein. Supernatants from RSV-infected MDDC, but not MDDC exposed to UV-killed RSV or mock conditions, contained alpha interferon (IFN-alpha; median, 43 pg/ml) and IFN-lambda (approximately 1 to 20 ng/ml). Neutralization of IFN-alpha with monoclonal antibody (MAb) against one of its receptor chains, IFNAR2, or of IFN-lambda with MAb against either of its receptor chains, IFN-lambda R1 (interleukin 28R [IL-28R]) or IL-10R2, had a modest effect. In contrast, blocking the two receptors together markedly reduced or completely blocked the RSV-induced suppression of CD4 T-cell proliferation. Defining the mechanism of RSV-induced suppression may guide vaccine design and provide insight into previously uncharacterized human T-cell responses and activities of interferons. C1 US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. US FDA, Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. NIAID, Bethesda, MD 20892 USA. Univ Louvain, Ludwig Inst Canc Res, Brussels Branch, Brussels, Belgium. Univ Louvain, Expt Med Unit, Brussels, Belgium. Univ Med & Dent New Jersey, Dept Biochem & Mol Biol, New Jersey Med Sch, Newark, NJ USA. RP Rabin, RL (reprint author), US FDA, Ctr Biol Evaluat & Res, 29 Lincoln Dr,Room B1, Bethesda, MD 20892 USA. EM rrabin@helix.nih.gov RI Roederer, Mario/G-1887-2011; Spann, Kirsten/B-4524-2013 OI Spann, Kirsten/0000-0003-0567-8382 FU Intramural NIH HHS; NIAID NIH HHS [R01 AI051139, R01 AI51139] NR 62 TC 83 Z9 85 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 MAY PY 2006 VL 80 IS 10 BP 5032 EP 5040 DI 10.1128/JVI.80.10.5032-5040.2006 PG 9 WC Virology SC Virology GA 041LK UT WOS:000237457500038 PM 16641294 ER PT J AU Martina, Y Marcucci, KT Cherqui, S Szabo, A Drysdale, T Srinivisan, U Wilson, CA Patience, C Salomon, DR AF Martina, Y Marcucci, KT Cherqui, S Szabo, A Drysdale, T Srinivisan, U Wilson, CA Patience, C Salomon, DR TI Mice transgenic for a human porcine endogenous retrovirus receptor are susceptible to productive viral infection (vol 80, pg 3135, 2006) SO JOURNAL OF VIROLOGY LA English DT Correction C1 Scripps Res Inst, Dept Mol & Expt Med, La Jolla, CA 92037 USA. US FDA, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. Biogen Inc, Cambridge, MA 02142 USA. RP Martina, Y (reprint author), Scripps Res Inst, Dept Mol & Expt Med, La Jolla, CA 92037 USA. RI Salomon, Daniel/E-9380-2012 NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 2006 VL 80 IS 10 BP 5100 EP 5100 DI 10.1128/JVI.80.10.5100.2006 PG 1 WC Virology SC Virology GA 041LK UT WOS:000237457500049 ER PT J AU Uhl, K Pinnow, E Scott, P Derbis, J Toigo, T AF Uhl, K Pinnow, E Scott, P Derbis, J Toigo, T TI Requirements for contraception use in clinical drug trials submitted to FDA SO JOURNAL OF WOMENS HEALTH LA English DT Meeting Abstract C1 US FDA, OWH, Rockville, MD 20857 USA. US FDA, OSHI, Rockville, MD 20857 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 1540-9996 J9 J WOMENS HEALTH JI J. Womens Health PD MAY PY 2006 VL 15 IS 4 BP 472 EP 472 PG 1 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA 052BO UT WOS:000238205800073 ER PT J AU Phelan, MA Matta, JL Reyes, YM Fernando, R Boykins, RA Blanquet, RS AF Phelan, MA Matta, JL Reyes, YM Fernando, R Boykins, RA Blanquet, RS TI Associations between metals and the blue mesogleal protein of Cassiopea xamachana SO MARINE BIOLOGY LA English DT Article ID SUPEROXIDE-DISMUTASE; DEHYDROGENASE AB The blue mesogleal pigment of the symbiotic jellyfish, Cassiopea xamachana Bigelow, 1882, is composed of two subunits, a larger glycosylated (35 kDa) moiety and a non-glycosylated (30 kDa) variant in lower concentration. In solution, the subunits assemble in large complexes of at least 10(6) kDa. The pigment, known as Cassio Blue, appears to mitigate excessive solar radiation while allowing the passage of the wavelengths optimal for photosynthesis by the numerous algal symbionts in the mesoglea of the jellyfish. The pigment is an abundant protein comprising about 6% of all animal protein in the whole jellyfish and about 33% of all animal protein in the oral appendages. The protein also contains a diverse array of metals, notably Ag, Ca, Cu, Fe, Mg, and Zn, with traces of others. Metal stoichiometry varies among isolates averaging about 1 mol of all metals, taken together, for each mole of the pigment. Given the broad array of metals present, the pigment may also serve another purpose, for example, as a metal reservoir or trap. Few other proteins are associated with such a spectrum of metals. In addition, the amino acid sequences of the pigment tryptic peptides have no reasonable matches in any of the sequence databases. Our findings, taken as a whole, suggest that the Cassio pigment is indeed unusual and is likely a representative of a novel category of proteins, the original member of which is rpulFKz1, a chromoprotein endowed with Frizzled and Kringle domains. C1 US FDA, Div Therapeut Prot, Off Biotechnol Prod, Bethesda, MD 20892 USA. Ponce Sch Med, Dept Pharmacol & Toxicol, Ponce, PR 00732 USA. Univ Puerto Rico, Cayey Univ Coll, Cayey, PR 00736 USA. Res Triangle Inst, Res Triangle Pk, NC 27709 USA. US FDA, Div Bacterial Parasit & Allergen Prod, Off Vaccine Res & Review, Bethesda, MD 20892 USA. Georgetown Univ, Dept Biol, Washington, DC 20057 USA. RP Phelan, MA (reprint author), US FDA, Div Therapeut Prot, Off Biotechnol Prod, Bethesda, MD 20892 USA. EM michael@michaelphelan.us NR 12 TC 1 Z9 1 U1 2 U2 9 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0025-3162 J9 MAR BIOL JI Mar. Biol. PD MAY PY 2006 VL 149 IS 2 BP 307 EP 312 DI 10.1007/s00227-005-0189-9 PG 6 WC Marine & Freshwater Biology SC Marine & Freshwater Biology GA 038AQ UT WOS:000237190200017 ER PT J AU McNichol, BA Rasmussen, SB Meysick, KC O'Brien, AD AF McNichol, BA Rasmussen, SB Meysick, KC O'Brien, AD TI A single amino acid substitution in the enzymatic domain of cytotoxic necrotizing factor type 1 of Escherichia coli alters the tissue culture phenotype to that of the dermonecrotic toxin of Bordetella spp. SO MOLECULAR MICROBIOLOGY LA English DT Article ID ACTIN CYTOSKELETON; BINDING DOMAIN; CELL-BINDING; RHO GTPASES; FACTOR-I; ACTIVATION; CNF1; IDENTIFICATION; DEAMIDATION; PROSTATITIS AB Cytotoxic necrotizing factor type 1 (CNF1) and dermonecrotic toxin (DNT) share homology within their catalytic domains and possess deamidase and transglutaminase activities. Although each toxin has a preferred enzymatic activity (i.e. deamidation for CNF1 and transglutamination for DNT) as well as target substrates, both modify a specific glutamine residue in RhoA, Rac1 and Cdc42, which renders these GTPases constitutively active. Here we show that despite their similar mechanisms of action CNF1 and DNT induced unique phenotypes on HEp-2 and Swiss 3T3 cells. CNF1 induced multinucleation of HEp-2 cells and was cytotoxic for Swiss 3T3 cells (with binucleation of the few surviving cells) while DNT showed no morphological effects on HEp-2 cells but did induce binucleation of Swiss 3T3 cells. To determine if the enzymatic domain of each toxin dictated the induced phenotype, we constructed enzymatically active chimeric toxins and mutant toxins that contained single amino acid substitutions within the catalytic site and tested these molecules in tissue culture and enzymatic assays. Moreover, both site-directed mutant toxins showed reduced time to maximum transglutamination of RhoA compared with the parent toxins. Nevertheless, the substitution of threonine for Lys(1310) in the DNT-based mutant, while affecting transglutamination efficiency of the toxin, did not abrogate that enzymatic activity. C1 Uniformed Serv Univ Hlth Sci, Dept Microbiol & Immunol, Bethesda, MD 20814 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP O'Brien, AD (reprint author), Uniformed Serv Univ Hlth Sci, Dept Microbiol & Immunol, Bethesda, MD 20814 USA. EM aobrien@usuhs.mil OI O'Brien, Alison/0000-0002-1315-3204 FU NIAID NIH HHS [AI38281] NR 42 TC 7 Z9 7 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD MAY PY 2006 VL 60 IS 4 BP 939 EP 950 DI 10.1111/j.1365-2958.2006.05157.x PG 12 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 039HY UT WOS:000237297800012 PM 16677305 ER PT J AU Dambach, MJ Trecki, J Martin, N Markovitz, NS AF Dambach, MJ Trecki, J Martin, N Markovitz, NS TI Oncolytic viruses derived from the gamma 34.5-deleted herpes simplex virus recombinant R3616 encode a truncated UL3 protein SO MOLECULAR THERAPY LA English DT Article DE oncolytic virus; herpes simplex virus-1 ICP34.5 protein; herpes simplex virus-1 UL3 protein; cancer vaccine; gene therapy; nonsense mutation; genotypic characterization; neurotoxicity; DNA mutational analysis; genetic stability ID MALIGNANT GLIOMA; NONHUMAN-PRIMATES; SAFETY EVALUATION; NERVOUS-SYSTEM; BRAIN ADJACENT; MUTANT 1716; TYPE-1; REPLICATION; GENE; NEUROVIRULENCE AB Replication-competent herpes simplex virus (HSV-1) mutants are used in clinical trials in the experimental treatment of cancer. Mutants G207, HSV1716, NV1020, and Oncovex GM-CSF share in common a defect in one or both copies of the gene encoding the neurovirulence factor, ICP34.5, and are thus neuroattenuated. These viruses are acknowledged to differ from one another (a) in the specific types of mutations intentionally introduced during their derivation and (b) in the inherent genetic differences retained from the different parent strains used in their construction. Unintended mutations are expected to emerge at some low frequency during the selection for and passage of mutant viruses. Here we demonstrate that during the construction of the oncolytic virus R3616, a nonsense mutation arose in an untargeted region of the HSV-1 genome that resulted in a substantial truncation of the viral protein known as UL3. This report is the first published documentation that oncolytic herpesviruses developed and used in clinical trials contain adventitious mutations. The implications of these findings for the characterization and development of vectors proposed for use in clinical trials are discussed. C1 US FDA, DCGT, CBER, Rockville, MD 20852 USA. RP Markovitz, NS (reprint author), US FDA, DCGT, CBER, 1401 Rockville Pike,HFM-725, Rockville, MD 20852 USA. EM nancy.markovitz@fda.hhs.gov NR 47 TC 22 Z9 24 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 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2006 VL 13 IS 5 BP 891 EP 898 DI 10.1016/j.ymthe.2006.02.006 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 042JA UT WOS:000237523000011 PM 16574492 ER PT J AU Smith, JS Tian, J Stevenson, SC Byrnes, AP AF Smith, Jeffrey S. Tian, Jie Stevenson, Susan C. Byrnes, Andrew P. TI The Adenoviral Fiber Shaft Is a Major Determinant of Kupffer Cell Necrosis SO MOLECULAR THERAPY LA English DT Meeting Abstract C1 [Smith, Jeffrey S.; Tian, Jie; Byrnes, Andrew P.] US FDA, Div Cell & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. [Stevenson, Susan C.] Novartis Inst Biomed Res Inc, Dept Diabet & Metab, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2006 VL 13 SU 1 MA 381 BP S145 EP S145 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA V32EC UT WOS:000208933501305 ER PT J AU Nahum, GG Uhl, K Kennedy, DL AF Nahum, Gerard G. Uhl, Kathleen Kennedy, Dianne L. TI Antibiotic use in pregnancy and lactation - What is and is not known about teratogenic and toxic risks SO OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 11th Annual FDA Science Forum CY APR 27-28, 2005 CL Washington, DC SP FDA ID PRETERM PREMATURE RUPTURE; ANTITUBERCULOSIS DRUGS; PLACENTAL-TRANSFER; PRELABOR RUPTURE; BREAST-MILK; CLINICAL PHARMACOKINETICS; TRANSPLACENTAL PASSAGE; LABORATORY-ANIMALS; RANDOMIZED-TRIAL; FATTY LIVER AB OBJECTIVE: Over ten million women are either pregnant or lactating in the United States at any time. The risks of medication use for these women are unique. In addition to normal physiologic changes that alter the pharmacokinetics of drugs, there is the concern of possible teratogenic and toxic effects on the developing fetus and newborn. This article reviews the risks and pharmacokinetic considerations for 11 broad-spectrum antibiotics that can be used to treat routine and life-threatening infections during pregnancy and lactation. DATA SOURCES: Information from the U.S. Food and Drug Administration (FDA) product labels, the Teratogen Information Service, REPROTOX, Shepard's Catalog of Teratogenic Agents, Clinical Pharmacology, and the peer-reviewed medical literature was reviewed concerning the use of 11 antibiotics in pregnant and lactating women. The PubMed search engine was used with the search terms "[antibiotic name] and pregnancy," "[antibiotic name] and lactation," and "[antibiotic name] and breastfeeding" from January 1940 to November 2005, as well as standard reference tracing. METHODS OF STUDY SELECTION: One hundred twenty-four references had sufficient information concerning numbers of subjects, methods, and findings to be included. TABULATION, INTEGRATION, AND RESULTS: The teratogenic potential in humans ranged from "none" (penicillin G and VK) to "unlikely" (amoxicillin, chloramphenicol, ciprofloxacin, doxycycline, levofloxacin, and rifampin) to "undetermined" (clindamycin, gentamicin, and vancomycin). Assessments were based on "good data" (penicillin G and VK), "fair data" (amoxicillin, chloramphenicol, ciprofloxacin, doxycycline, levofloxacin, and rifampin), "limited data" (clindamycin and gentamicin), and "very limited data" (vancomycin). Significant pharmacokinetic changes occurred during pregnancy for the penicillins, fluoroquinolones and gentamicin, indicating that dosage adjustments for these drugs may be necessary. With the exception of chloramphenicol, all of these antibiotics are considered compatible with breastfeeding. CONCLUSION: Health care professionals should consider the teratogenic and toxic risk profiles of antibiotics to assist in making prescribing decisions for pregnant and lactating women. These may become especially important if anti-infective countermeasures are required to protect the health, safety, and survival of individuals exposed to pathogenic bacteriologic agents that may occur from bioterrorist acts. C1 Uniformed Serv Univ Hlth Sci, Dept Obstet & Gynecol, Bethesda, MD 20814 USA. US FDA, Off Womens Hlth, Rockville, MD 20857 USA. US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Nahum, GG (reprint author), Box 2184, Rockville, MD 20847 USA. EM GNahum2003@yahoo.com NR 123 TC 64 Z9 73 U1 2 U2 21 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD MAY PY 2006 VL 107 IS 5 BP 1120 EP 1138 DI 10.1097/01.AOG.0000216197.26783.b5 PG 19 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 095GP UT WOS:000241296500022 PM 16648419 ER PT J AU Pazdur, R AF Pazdur, R TI PROs: Defining clinical benefit from the patient's perspective - Draft guidance provides direction in evaluating patient-reported outcomes SO ONCOLOGY-NEW YORK LA English DT Editorial Material C1 US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Pazdur, R (reprint author), US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. NR 1 TC 1 Z9 1 U1 0 U2 0 PU P R R INC PI MELVILLE PA 48 SOUTH SERVICE RD, MELVILLE, NY 11747 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD MAY PY 2006 VL 20 IS 6 BP 660 EP 660 PG 1 WC Oncology SC Oncology GA 052FG UT WOS:000238216400016 PM 16773848 ER PT J AU Lehmann, CU Kim, GR Gujral, R Veltri, MA Clark, JS Miller, MR AF Lehmann, Christoph U. Kim, George R. Gujral, Renmeet Veltri, Michael A. Clark, John S. Miller, Marlene R. TI Decreasing errors in pediatric continuous intravenous infusions SO PEDIATRIC CRITICAL CARE MEDICINE LA English DT Article DE drug therapy; computer-assisted; infusions; medication errors; prevention and control; decision support systems ID MEDICATION ERRORS; PREVENTION; EMERGENCY; PUMPS AB Objective: To evaluate the effect of a Web-based calculator and decision-support system on infusion ordering errors and to estimate error frequency in pharmacy infusion preparation. Design: Data on ordering error frequency and typology were collected before and after implementation of an online infusion ordering system. Data on pharmacy preparation errors of infusions were collected. Setting. A children's hospital at an academic medical center. Patients. None. Data were abstracted from infusion orders. Interventions: Introduction of a voluntary-use Web-based calculator into infusion ordering workflow. Observation only. Main Outcome measures. Number and type of errors in handwritten and calculator-generated orders. Number and type of errors in pharmacy infusion preparation. Results. Before calculator deployment, 129 sequential handwritten infusion orders were collected over 5 weeks. After deployment, of 162 sequential infusion orders, 88% (142) were calculator-generated. Calculator-generated infusion orders contained 83% fewer (p <.001) orders containing one or more errors than handwritten orders. Calculator-generated orders contained no high-risk errors (incorrect decimal, dose, or unit of measure) when compared with handwritten orders and were associated with fewer pharmacy interventions. In 118 sequential pharmacy infusion preparations over 4 wks, there were no errors observed. Conclusion: A Web-based calculator reduced significantly the total number of errors and eliminated all high-risk errors in the prescribing process for continuous pediatric infusions. With no observed errors in pharmacy preparation, this study provides data to support the use of computerized ordering as an independent safe and viable method for ordering continuous pediatric infusions. C1 Johns Hopkins Childrens Med & Surg Ctr, Baltimore, MD 21218 USA. Johns Hopkins Univ, Sch Med, Div Hlth Sci Informat, Baltimore, MD USA. US FDA, Div Psychiat Prod, Columbia, MD USA. Johns Hopkins Univ Hosp, Dept Pharm, Baltimore, MD 21287 USA. Johns Hopkins Childrens Ctr, Baltimore, MD USA. RP Lehmann, CU (reprint author), Johns Hopkins Childrens Med & Surg Ctr, Baltimore, MD 21218 USA. RI Lehmann, Christoph/M-1845-2016; OI Lehmann, Christoph/0000-0001-9559-4646; Veltri, Michael/0000-0003-4013-1956 NR 31 TC 30 Z9 30 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1529-7535 J9 PEDIATR CRIT CARE ME JI Pediatr. Crit. Care Med. PD MAY PY 2006 VL 7 IS 3 BP 225 EP 230 DI 10.1097/01.PCC.0000216415.12120.FF PG 6 WC Critical Care Medicine; Pediatrics SC General & Internal Medicine; Pediatrics GA 087ZL UT WOS:000240781200005 PM 16575355 ER PT J AU Jiang, ZW Dragin, N Jorge-Nebert, LF Martin, MV Guengerich, FP Aklillu, E Ingelman-Sundberg, M Hammons, GJ Lyn-Cook, BD Kadlubar, FF Saldana, SN Sorter, M Vinks, AA Nassr, N von Richter, O Jin, L Nebert, DW AF Jiang, ZW Dragin, N Jorge-Nebert, LF Martin, MV Guengerich, FP Aklillu, E Ingelman-Sundberg, M Hammons, GJ Lyn-Cook, BD Kadlubar, FF Saldana, SN Sorter, M Vinks, AA Nassr, N von Richter, O Jin, L Nebert, DW TI Search for an association between the human CYP1A2 genotype and CYP1A2 metabolic phenotype SO PHARMACOGENETICS AND GENOMICS LA English DT Article DE 4-aminobiphenyl N-hydroxylase; CYP1A2 activity; 7-ethoxyresorufin O-deethylase; genotype-phenotype association study; human CYP1A12 gene; urinary caffeine metabolic ratio ID GENE-EXPRESSION; CYTOCHROME-P450 1A2; CAFFEINE METABOLISM; N-OXIDATION; ENZYMES; CANCER; POLYMORPHISMS; INDUCTION; GENOME; MOUSE AB The genotype responsible for more than 60-fold interindividual differences in human hepatic CYP1A2 constitutive expression is not understood. Resequencing the human CYP1A1_CYP1A2 locus (39.6 kb) in five major geographically isolated subgroups recently led to the identification of 85 single nucleotide polymorphisms (SNPs), 57 of which were double-hit SNPs. Here, we attempted to correlate the CYP1A2 genotype with a metabolic phenotype. We chose 16 SNPs (all having a minor allele frequency >= 0.05 in Caucasians) to genotype 32 DNA samples (26 Caucasians, six Ethiopians) in which CYP1A2 metabolism had previously been determined. From 280 subjects (five locations worldwide) that had been CYP1A2-phenotyped, we genotyped the 10 highest, 14 lowest and eight intermediate DNA samples. Although no SNP was significant (P < 0.05), possibly due to the small sample size, we found a trend for several of the six SNPs across the CYP1A2 linkage disequilibrium block associated with the trait. Five CYP1A2 haplotypes were inferred, two of which had not previously been reported; haplotype 1A2H10 showed the greatest association with CYP1A2 activity. Regulatory sequences responsible for the large interindividual differences in hepatic CYP1A2 gene basal expression might reside, in part, with some of these CYP1A2 SNIPS but, in large part, might be located either cis (in nearby sequences not yet haplotyped) or trans in that they are not linked to the gene. We conclude that no SNP or haplotype in the CYP1A2 gene has yet been identified that can unequivocally be used to predict the metabolic phenotype in any individual patient. Pharmacogenetics and Genomics 16:359-367 (c) 2006 Lippincott Williams & Wilkins. C1 Univ Cincinnati, Med Ctr, Dept Environm Hlth, Cincinnati, OH 45267 USA. Univ Cincinnati, Med Ctr, CEG, Cincinnati, OH 45267 USA. Vanderbilt Univ, Sch Med, Dept Biochem, Nashville, TN 37212 USA. Vanderbilt Univ, Sch Med, Ctr Mol Toxicol, Nashville, TN 37212 USA. Karolinska Univ, Huddinge Hosp, Karolinska Inst, Dept Lab Med,Div Clin Pharmacol, Stockholm, Sweden. Karolinska Inst, IMM, Div Mol Toxicol, Stockholm, Sweden. Natl Ctr Toxicol Res, Div Pharmacogenom & Mol Epidemiol, Jefferson, AR 72079 USA. Cincinnati Childrens Hosp, Med Ctr, Pediat Pharmacol Res Unit, Cincinnati, OH USA. Cincinnati Childrens Hosp, Med Ctr, Div Child & Adolescent Psychiat, Cincinnati, OH USA. ALTANA Pharma AG, Dept Clin Pharmacol, Constance, Germany. ALTANA Pharma AG, Div Drug Metab & Pharmacokinet, Constance, Germany. RP Nebert, DW (reprint author), Univ Cincinnati, Med Ctr, Dept Environm Hlth, POB 670056, Cincinnati, OH 45267 USA. EM dan.nebert@uc.edu RI Jin, Li/C-1468-2009; von Richter, Oliver/O-6412-2016; OI Jin, Li/0000-0002-4546-2415; von Richter, Oliver/0000-0002-5262-9922; Aklillu, Eleni/0000-0002-9788-0790 FU NCI NIH HHS [R01 CA 90426]; NICHD NIH HHS [U10 HD 037249]; NIEHS NIH HHS [P30 ES 00267, P30 ES 06096, R01 ES 08147] NR 48 TC 64 Z9 66 U1 2 U2 14 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 MAY PY 2006 VL 16 IS 5 BP 359 EP 367 DI 10.1097/01.fpc.0000204994.99429.46 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy GA 046ZL UT WOS:000237849500008 PM 16609368 ER PT J AU Mendrick, DL Brazell, C Mansfield, EA Pietrusko, R Barilero, I Hackett, J Sturzebecher, S Jacobson-Kram, D AF Mendrick, DL Brazell, C Mansfield, EA Pietrusko, R Barilero, I Hackett, J Sturzebecher, S Jacobson-Kram, D TI Pharmacogenomics and regulatory decision making: an international perspective SO PHARMACOGENOMICS JOURNAL LA English DT Article C1 Gene Log Inc, Toxicogenom, Gaithersburg, MD 20879 USA. Affymetrix Inc, Regulatory Affairs, Santa Clara, CA USA. Millennium Pharmaceut Inc, Worldwide Regulatory Affairs, Cambridge, MA USA. Johnson & Johnson Pharmaceut, Res & Dev, Global Regulatory Policy & Intelligence, High Wycombe, Bucks, England. CDRH, Off In Vitro Diagnost Device Evaluat & Safety, Rockville, MD USA. Schering AG, Corp Preclin Dev, D-1000 Berlin, Germany. US FDA, CDER, Off New Drugs, Rockville, MD 20857 USA. RP Mendrick, DL (reprint author), Gene Log Inc, Toxicogenom, 610 Profess Dr, Gaithersburg, MD 20879 USA. EM dmendrick@genelogic.com NR 0 TC 2 Z9 3 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1470-269X J9 PHARMACOGENOMICS J JI Pharmacogenomics J. PD MAY PY 2006 VL 6 IS 3 BP 154 EP 157 DI 10.1038/sj.tpj.6500364 PG 4 WC Genetics & Heredity; Pharmacology & Pharmacy SC Genetics & Heredity; Pharmacology & Pharmacy GA 045OM UT WOS:000237751400001 PM 16415918 ER PT J AU Simon, R Wang, SJ AF Simon, R Wang, SJ TI Use of genomic signatures in therapeutics development in oncology and other diseases SO PHARMACOGENOMICS JOURNAL LA English DT Article DE clinical trial; gene expression; genomic signature; oncology; study design; validation ID HLA-B REGION; LUNG-CANCER; GENETIC-VARIATIONS; MICROARRAY DATA; BREAST-CANCER; HYPERSENSITIVITY; ASSOCIATION; ABACAVIR; CLASSIFICATION; CHEMOTHERAPY AB Pharmacogenomics is the science of determining how the benefits and adverse effects of a drug vary among a target population of patients based on genomic features of the patient's germ line and diseased tissue. By identifying those patients who are most likely to respond while eliminating serious adverse effects, the therapeutic index of a drug can be substantially increased. This may facilitate demonstrating the effectiveness of the drug and may avoid subsequent problems due to serious adverse events. Our objective here is to provide clinical trial designs and analysis strategies for the utilization of genomic signatures as classifiers for patient stratification or patient selection in therapeutics development. We review methods for the development of genomic signature classifiers of treatment outcome in high-dimensional settings, where the number of variables available for prediction far exceeds the number of cases. The split-sample and cross-validation methods for obtaining estimates of prediction accuracy in developmental studies are described. We present clinical trial designs for utilizing genomic signature classifiers in therapeutics development. The purpose of the classifier is to facilitate the identification of groups of patients with a high probability of benefiting from it and avoiding serious adverse events. We distinguish exploratory analysis during the development of the genomic classifier from prospective planning and rigorous testing of therapeutic hypotheses in studies that utilize the genomic classifier in therapeutics development. We discuss a variety of clinical trial designs including those utilizing specimen collection and assay prospectively for newly accrued patients and those involving a prospectively planned analysis of archived specimens from a previously conducted clinical trial. Our discussion of the development and use of classifiers of efficacy is mostly focused on applications in oncology using classifiers based on biomarkers measured in tumors. Some of the same considerations apply, however, to development of efficacy and safety classifiers in nononcologic diseases based on single-nucleotide germline polymorphisms. C1 NCI, Biometr Res Branch, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA. US FDA, CDER, Off Biostat, Off Pharmacoepidemiol & Stat Sci, Rockville, MD 20857 USA. RP Simon, R (reprint author), NCI, Biometr Res Branch, Div Canc Treatment & Diag, NIH, MSC 7434,9000 Rockville Pike, Bethesda, MD 20892 USA. EM rsimon@nih.gov NR 25 TC 60 Z9 64 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1470-269X J9 PHARMACOGENOMICS J JI Pharmacogenomics J. PD MAY PY 2006 VL 6 IS 3 BP 166 EP 173 DI 10.1038/sj.tpj.6500349 PG 8 WC Genetics & Heredity; Pharmacology & Pharmacy SC Genetics & Heredity; Pharmacology & Pharmacy GA 045OM UT WOS:000237751400004 PM 16415922 ER PT J AU Coelho, SG Miller, SA Zmudzka, BZ Beer, JZ AF Coelho, SG Miller, SA Zmudzka, BZ Beer, JZ TI Quantification of UV-induced erythema and pigmentation using computer-assisted digital image evaluation SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID SKIN COLOR; VALUES AB Photography has been used in human skin research for some time. With the advent of digital photography in recent years, its use has increased. However, the focus has now turned from documentation to actual analysis and quantification of skin color changes. The advantages of digital photography outweigh any shortcomings as long as consistent, standardized procedures are followed and quality control is implemented. We present a simple procedure to standardize images and discuss a computer-assisted digital image evaluation (CADIE) technique to quantify skin color changes following UV exposure. The CADIE approach is illustrated with examples from two different studies on UV responses in human skin. Using the Commission Internationale de I'Eclairage L*a*b* color coordinate system in combination with a personal computer and image-editing software, we analyzed digital images obtained in these two studies. We demonstrate the feasibility of using digital photography for objective evaluation of UV erythema in different racial/ethnic groups and for measuring pigmentation changes caused by repeated exposures over a period of several weeks. Our results indicate how objective assessment using CADIE can be an adjunct to visual and optical observation in clinical and scientific evaluations. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Coelho, SG (reprint author), US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. EM sergio.coelho@fda.hhs.gov NR 26 TC 25 Z9 25 U1 0 U2 4 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 MAY-JUN PY 2006 VL 82 IS 3 BP 651 EP 655 DI 10.1562/2005-08-02-TSN-635 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 053RS UT WOS:000238323300005 PM 16522135 ER PT J AU Varricchio, F Reed, J AF Varricchio, Frederick Reed, John CA VAERS Working Grp TI Follow-up study of medication errors reported to the vaccine adverse event reporting system (VAERS) SO SOUTHERN MEDICAL JOURNAL LA English DT Article DE vaccine; medication error; surveillance ID INFORMATION; SAFETY AB Background: A study was done to determine if the apparent medication errors found in the Vaccine Adverse Event Reporting System (VAERS) database are true errors, and if true errors are found, to determine what corrective action was taken. Furthermore, if a true error did not occur, we wanted to determine at what point the misinformation was entered into the system. Methods: The VAERS database was searched for reports received between July 1, 2001 and June 30, 2002 which had either been classified as "error" or the word "error" appeared in the text of the report. The database was also searched for reports which indicated that the measles-mumps-rubella (MMR), diphtheria-tetanus-pertussis (DTP), diphtheria-tetanus-acellular pertussis (DTaP) or diphtheria-tetanus-pertussis-haemophilus (DTPH) vaccinations had been administered at an age outside of the usual recommendation. Results: A total of 119 reports of possible errors were found. Follow-up was successful in 102 (86%) cases. Additional information obtained showed that 26 cases were actual medication errors. Seventy-six cases were not actual medication errors; 9 cases were physician decisions, 37 cases were data entry errors and 30 cases were reporter errors. Conclusion: The nature of the actual errors was similar to those reported previously; wrong inoculum, improper interval, wrong route of administration, and overdose. Many errors could have been prevented by more attention to detail. Remedial action usually consisted of retraining. The new requirement that all medications be barcoded, purchasing products from different manufacturers and segregation of vials may help prevent vial confusion. C1 US FDA, Ctr Biol Evaluat & Res, Div Epidemiol, Off Biostat & Epidemiol, Rockville, MD 20857 USA. RP Varricchio, F (reprint author), 6130 Roseland Dr, Rockville, MD 20852 USA. EM Varricchio@comcast.net NR 13 TC 5 Z9 5 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0038-4348 J9 SOUTH MED J JI South.Med.J. PD MAY PY 2006 VL 99 IS 5 BP 486 EP 489 DI 10.1097/01.smj.0000216513.73448.af PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 095NV UT WOS:000241315500011 PM 16711311 ER PT J AU Holsapple, MP Jones, D Kawabata, TT Kimber, I Sarlo, K Selgrade, MK Shah, J Woolhiser, MR AF Holsapple, MP Jones, D Kawabata, TT Kimber, I Sarlo, K Selgrade, MK Shah, J Woolhiser, MR TI Assessing the potential to induce respiratory hypersensitivity SO TOXICOLOGICAL SCIENCES LA English DT Review DE respiratory toxicology-respiratory sensitization; immunotoxicology-chemical allergy; immunotoxicology-protein allergy ID MOLECULAR-WEIGHT CHEMICALS; SERUM-ALBUMIN CONJUGATE; LYMPH-NODE ASSAY; MOUSE IGE TEST; OCCUPATIONAL ASTHMA; FOOD ALLERGY; MICE; ANTIBODIES; IDENTIFICATION; SENSITIZATION AB Acute and repeat dose inhalation studies have been an important part of the safety assessment of drugs, chemicals, and other products throughout the world for many years. It is known that damage to the respiratory tract can be triggered either by nonspecific irritation or by specific immune-mediated pathogenesis, and it is acknowledged that traditional inhalation studies are not designed to address fully the impact of the latter. It is also recognized that different types of immune-mediated responses can be triggered by different classes of compounds and that some immune reactions in the lung are life threatening. As such, it is important to understand as fully as possible the basis for the immune-mediated damage to the lung in order to characterize adequately the risks of individual chemicals or proteins. It is against this background that a review of the methods used to assess the potential for immune-mediated respiratory hypersensitivity was conducted. The primary objectives of this review are to discuss appropriate methods for identifying and characterizing respiratory hypersensitivity hazards and risks; and to identify key data gaps and related research needs with respect to respiratory hypersensitivity testing. The following working definition of respiratory hypersensitivity was formulated: a hypersensitivity response in the respiratory tract precipitated by a specific immune response, mediated by multiple mechanisms, including IgE antibody. Because of the importance played by various classes of compounds, the subsequent sections of this review will consider protein-specific, chemical-specific, and drug-specific aspects of respiratory hypersensitivity. C1 ILSI Hlth & Environm Sci Inst, Washington, DC USA. UK Med & Healthcare Prod Regulatory Agcy, London, England. Pfizer Inc, Groton, CT 06340 USA. Syngenta Cent Toxicol Lab, Macclesfield, Cheshire, England. Procter & Gamble Co, Cincinnati, OH USA. US EPA, Res Triangle Pk, NC 27711 USA. US FDA, Rockville, MD 20857 USA. Dow Chem Co USA, Midland, MI 48674 USA. RP Holsapple, MP (reprint author), 1 Thomas Circle NW 9th Floor, Washington, DC 20005 USA. EM mholsapple@ilsi.org NR 52 TC 37 Z9 37 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAY PY 2006 VL 91 IS 1 BP 4 EP 13 DI 10.1093/toxsci/kfj074 PG 10 WC Toxicology SC Toxicology GA 032WX UT WOS:000236808200002 PM 16339788 ER PT J AU Thomas, T Thomas, K Sadrieh, N Savage, N Adair, P Bronaugh, R AF Thomas, T Thomas, K Sadrieh, N Savage, N Adair, P Bronaugh, R TI Research strategies for safety evaluation of nanomaterials, part VII: Evaluating consumer exposure to nanoscale materials SO TOXICOLOGICAL SCIENCES LA English DT Article DE nanoscale materials; consumer products; regulatory agencies; product safety; exposure assessment AB Considerable media attention has recently been given to novel applications for products that contain nanoscale materials. These products could have utility in several industries that market consumer products, including textiles, sporting equipment, cosmetics, consumer electronics, and household cleaners. Some of the purported benefits of these products include improved performance, convenience, lower cost, as well as other desirable features, when compared to the conventional products that do not contain nanoscale materials. Although there are numerous likely consumer advantages from products containing nanoscale materials, there is very little information available regarding consumer exposure to the nanoscale materials in these products or any associated risks from these exposures. This paper seeks to review a limited subset of products that contain nanoscale materials, assess the available data for evaluating the consumer exposures and potential hazards associated with these products, and discuss the capacity of U.S. regulatory agencies to address the potential risks associated with these products. C1 US Consumer Prod Safety Commiss, Bethesda, MD 20814 USA. ILSI Hlth & Environm Sci Inst, Washington, DC 20005 USA. US FDA, Rockville, MD 20852 USA. US EPA, Washington, DC 20460 USA. US FDA, Laurel, MD 20708 USA. RP Thomas, T (reprint author), US Consumer Prod Safety Commiss, 4330 East West Highway, Bethesda, MD 20814 USA. EM tthomas@cpsc.gov NR 12 TC 52 Z9 56 U1 0 U2 23 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAY PY 2006 VL 91 IS 1 BP 14 EP 19 DI 10.1093/toxsci/kfj129 PG 6 WC Toxicology SC Toxicology GA 032WX UT WOS:000236808200003 PM 16476686 ER PT J AU Wang, C Sadovova, N Hotchkiss, C Fu, X Scallet, AC Patterson, TA Hanig, J Paule, MG Slikker, W AF Wang, C Sadovova, N Hotchkiss, C Fu, X Scallet, AC Patterson, TA Hanig, J Paule, MG Slikker, W TI Blockade of N-methyl-D-aspartate receptors by ketamine produces loss of postnatal day 3 monkey frontal cortical neurons in culture SO TOXICOLOGICAL SCIENCES LA English DT Article DE NMDA receptor; ketamine; antisense oligonucleotide; neurodegeneration; in vitro; neonatal rhesus monkey ID CELL-ADHESION MOLECULE; FACTOR-KAPPA-B; INDUCED APOPTOSIS; UP-REGULATION; RAT HIPPOCAMPUS; NMDA; BRAIN; EXPRESSION; GLUTAMATE; ETHANOL AB Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, is used as a general pediatric anesthetic. Recent data suggest that anesthetic drugs may cause neurodegeneration during development. The purpose of this study was to determine the robustness of ketamine-induced developmental neurotoxicity using rhesus monkey frontal cortical cultures and also to determine if dysregulation of NMDA receptor subunits promotes ketamine-induced cell death. Frontal cortical cells collected from the neonatal monkey were incubated for 24 h with 1, 10, or 20 mu M ketamine alone or with ketamine plus either NR1 antisense oligonucleotides or the nuclear factor kB translocation inhibitor, SN-50. Ketamine caused a marked reduction in the neuronal marker polysialic acid neural cell adhesion molecule and mitochondrial metabolism, as well as an increase in DNA fragmentation and release of lactate dehydrogenase. Ketamine-induced effects were blocked by NR1 antisenses and SN-50. These data suggest that NR1 antisenses and SN-50 offer neuroprotection from the enhanced degeneration induced by ketamine in vitro. C1 US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Toxicol Pathol Associates, Jefferson, AR USA. Bionetics Corp, Jefferson, AR USA. US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Wang, C (reprint author), US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, HFT-132, Jefferson, AR 72079 USA. EM cheng.wang@fda.hhs.gov NR 44 TC 84 Z9 94 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAY PY 2006 VL 91 IS 1 BP 192 EP 201 DI 10.1093/toxsci/kfj144 PG 10 WC Toxicology SC Toxicology GA 032WX UT WOS:000236808200022 PM 16500925 ER PT J AU Marszal, E Shrake, A AF Marszal, E Shrake, A TI Characterization of differences in isoelectric focusing behavior of alpha(1)-proteinase inhibitor products SO TRANSFUSION LA English DT Letter C1 US FDA, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Marszal, E (reprint author), US FDA, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. EM ewa.marszal@fda.hhs.gov NR 7 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 MAY PY 2006 VL 46 IS 5 BP 872 EP 873 DI 10.1111/j.1537-2995.2006.00809.x PG 2 WC Hematology SC Hematology GA 036TK UT WOS:000237098200031 PM 16686863 ER PT J AU Weisz, A Wright, PR Andrzejewski, D Meyers, MB Glaze, K Mazzola, EJ AF Weisz, A Wright, PR Andrzejewski, D Meyers, MB Glaze, K Mazzola, EJ TI Identification of the decarboxylated analog of tetrabromotetrachloro-fluorescein and its quantification in the color additives D&C Red Nos. 27 and 28 (phloxine B) using high-performance liquid chromatography SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article; Proceedings Paper CT 228th National Meeting of the American-Chemical-Society CY AUG 22-26, 2004 CL Philadelphia, PA SP Amer Chem Soc, Amer Chem Soc, Fuel Chem Div, Amer Chem Soc, Petr Chem Div DE D&C Red No. 27; D&C Red No. 28; phloxine B; 2,4,5,7-tetrabromo-6-hydroxy-9-(2,3,4,5-tetrachlorophenyl)-3H-xanthen-3- one (BCPX); color additives; HPLC ID SOLID-PHASE MICROEXTRACTION; COUNTERCURRENT CHROMATOGRAPHY; MASS SPECTROMETRY; SYNTHETIC MIXTURE; COMPONENTS; SEPARATION AB The present work describes (a) the identification and characterization of an impurity, 2,4,5,7-tetrabromo-6-hydroxy-9-(2,3,4,5-tetrachlorophenyl)3H-xanthen-3-one (BCPX), in the color additives D&C Red Nos. 27 and 28 (phloxine B) and (b) the determination of the extent and level of BCPX contamination in certified lots of these colors. For these purposes, BCPX (a compound not previously reported in the literature) was synthetically prepared. Test portions from 42 certified lots of D&C Red Nos. 27, 28 and 27 lakes were analyzed for BCPX using an HPLC method that included gradient elution and UV-vis photodiode array detection. Those lots were submitted for certification by both domestic (six) and foreign (six) manufacturers during the past 4 years. Of the test portions analyzed, 32 (76.2%) contained BCPX in amounts ranging from 0.01 to 3.21%. The remaining 10 test portions (23.8%) contained no detectable BCPX or less than 0.008%, which is the limit of quantification for the present method. The analyses revealed substantial differences in the level of BCPX across different manufacturers. The wide range of BCPX levels found in the analyzed lots suggests that the presence of BCPX in D&C Red Nos. 27 and 28 may be avoided or significantly reduced during the manufacturing process. (c) 2006 Elsevier B.V. All rights reserved. C1 US FDA, Ctr Food Safety & Appl Nutr, Off Cosmet & Colors, College Pk, MD 20740 USA. US FDA, Ctr Food Safety & Appl Nutr, Off Sci Anal & Support, College Pk, MD 20740 USA. RP Weisz, A (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Cosmet & Colors, College Pk, MD 20740 USA. EM aweisz@cfan.fda.gov NR 13 TC 5 Z9 5 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR A JI J. Chromatogr. A PD APR 28 PY 2006 VL 1113 IS 1-2 BP 186 EP 190 DI 10.1016/j.chroma.2006.02.016 PG 5 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 034RF UT WOS:000236947600024 PM 16494889 ER PT J AU Maisel, WH Moynahan, M Zuckerman, BD Gross, TP Tovar, OH Tillman, DB Schultz, DB AF Maisel, WH Moynahan, M Zuckerman, BD Gross, TP Tovar, OH Tillman, DB Schultz, DB TI Pacemaker and ICD generator malfunctions - Analysis of food and drug administration annual reports SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID IMPLANTABLE CARDIOVERTER-DEFIBRILLATOR; SAFETY; DEVICES; THERAPY AB Context Pacemakers and implantable cardioverter-defibrillators (ICDs) are complex medical devices proven to reduce mortality in specific high-risk patient populations. It is not known if increasing device complexity is associated with decreased reliability. Objectives To analyze postapproval annual reports submitted to the US Food and Drug Administration (FDA) by manufacturers of pacemakers and ICDs to determine the reported number and rate of pacemaker and ICD malfunctions and to assess trends in device performance. Design and Setting Pacemaker and ICD annual reports submitted to the FDA for the years 1990-2002 were reviewed. A pacemaker or ICD generator was defined as having malfunctioned if it was explanted due to an observed malfunction, returned to the manufacturer, and confirmed by the manufacturer to be functioning inappropriately. Leads and biventricular devices were not included in the study. Deaths were attributed to device malfunction only if they were witnessed, the malfunction immediately led to the death, and the malfunction was confirmed by the manufacturer. Main Outcome Measures Number of implanted pacemaker and ICD generators; number of reported malfunctions; and annual malfunction replacement rates. Generator malfunction replacement rates were defined as the annual number of replacements due to confirmed malfunction divided by the annual number of implants. Results During the study period, 2.25 million pacemakers and 415780 ICDs were implanted in the United States. Overall, 17 323 devices (8834 pacemakers and 8489 ICDs) were explanted due to confirmed malfunction. Battery/capacitor abnormalities (4085 malfunctions [23.6%]) and electrical issues (4708 malfunctions [27.1%]) accounted for half of the total device failures. The annual pacemaker malfunction replacement rate per 1000 implants decreased significantly during the study, from a peak of 9.0 in 1993 to a low of 1.4 in 2002 (P=.006 for trend). In contrast, the ICD malfunction replacement rate per 1000 implants, after decreasing from 38.6 in 1993 to 7.9 in 1996, increased markedly during the latter half of the study, peaking in 2001 at 36.4 (P=.04 for trend). More than half of the reported ICD malfunctions occurred in the last 3 years of the study. Overall, the annual ICD malfunction replacement rate was significantly higher than the pacemaker malfunction replacement rate (mean [SD], 20.7 [11.6] vs 4.6 [2.2] replacements per 1000 implants; P<.001; rate ratio, 5.9 [95% confidence interval, 2.7-9.1]). Sixty-one deaths (30 pacemaker patients, 31 ICD patients) were attributable to device malfunction. Conclusions This study demonstrates that thousands of patients have been affected by pacemaker and ICD malfunctions, the pacemaker malfunction replacement rate has decreased, the ICD malfunction replacement rate increased during the latter half of the study, and the ICD malfunction replacement rate is significantly higher than that for pacemakers. Although pacemakers and ICDs are important life-sustaining devices that have saved many lives, careful monitoring of device performance is still required. C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Cardiovasc, Boston, MA 02215 USA. US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Maisel, WH (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Cardiovasc, 185 Pilgrim Rd,Baker 4, Boston, MA 02215 USA. EM wmaisel@bidmc.harvard.edu NR 21 TC 176 Z9 177 U1 0 U2 5 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 APR 26 PY 2006 VL 295 IS 16 BP 1901 EP 1906 DI 10.1001/jama.295.16.1901 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 036GI UT WOS:000237059200024 PM 16639048 ER PT J AU Tournas, V Katsoudas, E Miracco, EJ AF Tournas, V Katsoudas, E Miracco, EJ TI Moulds, yeasts and aerobic plate counts in ginseng supplements SO INTERNATIONAL JOURNAL OF FOOD MICROBIOLOGY LA English DT Article DE moulds; yeasts; APCs; ginseng supplements ID EXTRACT AB Forty six ginseng supplement samples including Siberian ginseng root, Chinese ginseng herb and root, and American ginseng root and extract were purchased from retail in the Washington, DC area and from Penn Herb Co. (Philadelphia, PA) and tested for mould and yeast (MY) contamination and the presence of aerobic mesophilic bacteria (APC). Results indicated that 100% of the Siberian ginseng samples were contaminated with fungi and bacteria. MY counts ranged from 8.0 x 10(2) to 1.4 x 10(3) cfu/g whereas the APCs were between 2.3 x 10(4) and 1.0 X 10(6) Cfu/g. Most common fungi encountered in this commodity were Penicillium spp., Eurotium rubrum, E. chevalieri and Rhizopus spp. Seventy-eight percent of the Chinese ginseng herb samples were contaminated with fungi and 89% with bacteria at levels ranging between < 100 and 6.0 x 10(4) and < 100 and 1.2 x 10(6) cfu/g, respectively. Moulds commonly isolated were Alternaria alternata, Aspergillus niger, Aspergillus spp., Cladosporium spp., E. chevalieri, Penicillium spp. and Rhizopus spp. Fifty six percent of the Chinese ginseng root samples tested contained fungi (A. niger, Rhizopus spp. and yeasts), and 100% contained bacteria. Fungal counts ranged between < 100 and 1.4 x 10(3) Cfu/g and APCs were between 3.0 x 10(2) and 6.8 x 10(5) cfu/g. Forty-eight percent of the American ginseng root samples contained moulds and 30% showed bacterial contamination. MY counts were between < 100 and 4.3 x 10(-5) cfu/g whereas APCs were between < 100 and 4.5 x 10(4) cfu/g. A. flavus was isolated from 9% and Penicillium spp. were recovered from 39% of the tested samples. This is the first report of A.flavus contamination in ginseng supplements. No moulds or yeasts were found in ginseng extract, but 50% of these samples contained bacteria at levels ranging between < 100 and 1.0 X 10(3) cfu/g. (c) 2005 Elsevier B.V. All rights reserved. C1 US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. US FDA, N E Reg Lab, Riyadh 11433, Saudi Arabia. Univ Delaware, Newark, DE 19711 USA. RP Tournas, V (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM vtournas@cfsan.fda.gov NR 13 TC 15 Z9 16 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-1605 J9 INT J FOOD MICROBIOL JI Int. J. Food Microbiol. PD APR 25 PY 2006 VL 108 IS 2 BP 178 EP 181 DI 10.1016/j.ijfoodmicro.2005.11.009 PG 4 WC Food Science & Technology; Microbiology SC Food Science & Technology; Microbiology GA 039CD UT WOS:000237276700004 PM 16434118 ER PT J AU Goter-Robinson, C Derrick, SC Yang, AL Jeon, BY Morris, SL AF Goter-Robinson, C Derrick, SC Yang, AL Jeon, BY Morris, SL TI Protection against an aerogenic Mycobacterium tuberculosis infection in BCG-immunized and DNA-vaccinated mice is associated with early type I cytokine responses SO VACCINE LA English DT Article DE tuberculosis; BCG; DNA vaccines; interferon-gamma ID CD8 T-CELLS; PULMONARY TUBERCULOSIS; INTERFERON-GAMMA; OLD MICE; EARLY RESISTANCE; HIV; IMMUNOGENICITY; LYMPHOCYTES; PROTEINS; ANTIGENS AB Although vaccination against tuberculosis (TB) was initiated more than 80 years ago, the correlates of protective immunity against infection by Mycobacterium tuberculosis have still not been well defined. To investigate the vaccine-induced immune responses against TB, we evaluated the early pulmonary cytokine responses elicited by a low dose M. tuberculosis aerogenic challenge in mice that had been immunized with either BCG or a TB DNA vaccine cocktail, two vaccine preparations that induce long-term protection in the mouse model of pulmonary TB. Using three different assays, we showed that specific cytokine responses were elevated in the lungs of vaccinated mice (relative to naive controls) during the second week post-challenge. By measuring cytokine levels in the bronchoalveolar lavage fluid (BAL) and cytokine mRNA concentrations in pulmonary cells, the levels of IFN-gamma, IL-12, and RANTES were shown to be elevated from days 7-14 post-challenge in the lungs. By intracellular cytokine staining (ICS), increased numbers of lung CD4 and CD8 cells expressing IFN-gamma were also seen at days 10 and 14 after the infection. Moreover, increased post-challenge IFN-gamma levels were detected using the ICS and cytokine mRNA assays in aging BCG-immunized mice that had been effectively boosted with a TB DNA vaccine. Taken together, these data suggest that the post-infection induction of early type 1 cytokine responses correlate with the induction of long-term protective immunity in vaccinated mice. (c) 2006 Elsevier Ltd. All rights reserved. C1 US FDA, Lab Mycobacterial Dis & Cellular Immunol, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Derrick, SC (reprint author), US FDA, Lab Mycobacterial Dis & Cellular Immunol, Ctr Biol Evaluat & Res, Bldg 29-Room 509,CBER FDA,29 Lincoln Dr, Bethesda, MD 20892 USA. EM derrick@cber.fda.gov NR 27 TC 20 Z9 22 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 APR 24 PY 2006 VL 24 IS 17 BP 3522 EP 3529 DI 10.1016/j.vaccine.2006.02.005 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 035MM UT WOS:000237005400016 PM 16519971 ER PT J AU Bryant-Genevier, M O'Connell, K Ball, R Braun, MM McMahon, A AF Bryant-Genevier, M O'Connell, K Ball, R Braun, MM McMahon, A TI Passive surveillance for generalized vaccinia in the united states using the vaccine adverse event reporting system (VAERS) SO VACCINE LA English DT Article DE generalized vaccinia; smallpox vaccination; passive surveillance ID SMALLPOX VACCINATION; INTUSSUSCEPTION; COMPLICATIONS AB Background: Generalized vaccinia (GV) is an adverse event specifically associated with smallpox vaccination, but shares clinical features with many common non-vaccine related rashes. We assessed the utility of passive reporting for GV surveillance by reviewing all Vaccine Adverse Event Reporting System (VAERS) reports of any post-smallpox vaccination rash in civilians and military personnel. Methods: We reviewed all reports submitted to VAERS between 12/12/2002 and 3/1 2004 for post-smallpox vaccine (SPV) rashes concerning civilians and military personnel. We evaluated the information contained in the reports independent of VAERS adverse event coding (GV or not GV). We classified the rash reports based on the recently published GV case definition from the Centers for Disease Control and Prevention. Results: Of the 936 rash reports after SPV, 92 were coded as GV. We classified 12 of the 92 as probable GV, and 1 as confirmed GV (14% probable or confirmed). Among the 844 reports not coded as GV, we classified 32 as either probable or confirmed GV (4%). Probable or confirmed reports that were coded as GV were similar to probable or confirmed reports not coded as GV with respect to demographic characteristics of the report subjects, and the location and phenotype (e.g., pustular, vesicular, etc.) of the rashes. Conclusions: A prospective study that applies well-defined clinical, histopathological, and laboratory criteria to smallpox-vaccinated patients with rashes would be necessary to distinguish GV from common alternative diagnoses with which it is easily confused. Published by Elsevier Ltd. C1 CBER, OBE, DE, Food & Drug Adm,Vaccine Safety Branch, Rockville, MD 20852 USA. CBER, OBE, DE, Therapeut & Blood Safety Branch,Food & Drug Adm, Rockville, MD 20852 USA. RP Bryant-Genevier, M (reprint author), CBER, OBE, DE, Food & Drug Adm,Vaccine Safety Branch, Suite 268 S,HFM 222,1401 Rockville Pike, Rockville, MD 20852 USA. EM bryant-genevier@cber.fda.gov NR 10 TC 2 Z9 2 U1 1 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD APR 24 PY 2006 VL 24 IS 17 BP 3632 EP 3635 DI 10.1016/j.vaccine.2006.01.052 PG 4 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 035MM UT WOS:000237005400029 PM 16517033 ER PT J AU Jhoo, JW Freeman, JP Heinze, TM Moody, JD Schnackenberg, LK Beger, RD Dragull, K Tang, CS Ang, CYW AF Jhoo, JW Freeman, JP Heinze, TM Moody, JD Schnackenberg, LK Beger, RD Dragull, K Tang, CS Ang, CYW TI In vitro cytotoxicity of nonpolar constituents from different parts of kava plant (Piper methysticum) SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE kava; Piper methysticum; cytotoxicity; kava toxicity; flavokavain ID KAVALACTONES; EXTRACTS; ANXIETY AB Kava (Piper methysticum), a perennial shrub native to the South Pacific islands, has been used to relieve anxiety. Recently, several cases of severe hepatotoxicity have been reported from the consumption of dietary supplements containing kava. It is unclear whether the kava constituents, kavalactones, are responsible for the associated hepatotoxicity. To investigate the key components responsible for the liver toxicity, bioassay-guided fractionation was carried out in this study. Kava roots, leaves, and stem peelings were extracted with methanol, and the resulting residues were subjected to partition with a different polarity of solvents (hexane, ethyl acetate, n-butanol, and water) for evaluation of their cytotoxicity on HepG2 cells based on the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and lactate dehydrogenase and aspartate aminotransferase enzyme leakage assays. Organic solvent fractions displayed a much stronger cytotoxicity than water fractions for all parts of kava. The hexane fraction of the root exhibited stronger cytotoxic effects than fractions of root extracted with other solvents or extracts from the other parts of kava. Further investigations using bioassay-directed isolation and analysis of the hexane fraction indicated that the compound responsible for the cytotoxicity was flavokavain B. The identity of the compound was confirmed by H-1 and C-13 NMR and MS techniques. C1 US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Kangweon Natl Univ, Dept Food Sci & Technol Anim Resources, Chunchon 200701, South Korea. Univ Hawaii Manoa, Dept Mol Biosci & Bioengn, Honolulu, HI 96822 USA. RP Jhoo, JW (reprint author), US FDA, Natl Ctr Toxicol Res, HFT-230,3900 NCTR Rd, Jefferson, AR 72079 USA. EM jhoo@kangwon.ac.kr NR 14 TC 30 Z9 30 U1 1 U2 3 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 APR 19 PY 2006 VL 54 IS 8 BP 3157 EP 3162 DI 10.1021/jf051853j PG 6 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 036JQ UT WOS:000237067800055 PM 16608246 ER PT J AU Virmani, R Burke, AP Farb, A Kolodgie, FD AF Virmani, R Burke, AP Farb, A Kolodgie, FD TI Pathology of the vulnerable plaque SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID SUDDEN CORONARY DEATH; ACUTE MYOCARDIAL-INFARCTION; UNSTABLE ANGINA-PECTORIS; C-REACTIVE PROTEIN; RISK-FACTORS; THROMBOSIS; LESIONS; ATHEROSCLEROSIS; FREQUENCY; ARTERIES AB The majority of patients with acute coronary syndromes (ACS) present with unstable angina, acute myocardial infarction, and sudden coronary death. The most common cause of coronary thrombosis is plaque rupture followed by plaque erosion, whereas calcified nodule is infrequent. If advances in coronary disease are to occur, it is important to recognize the precursor lesion of ACS. Of the three types of coronary thrombosis, a precursor lesion for acute rupture has been postulated. The non-thrombosed lesion that most resembles the acute plaque rupture is the thin cap fibroatheroma (TCFA), which is characterized by a necrotic core with an overlying fibrous cap measuring < 65 mu m, containing rare smooth muscle cells but numerous macrophages. Thin cap fibroatheromas are most frequently observed in patients dying with acute myocardial infarction and least common in plaque erosion. They are most frequently observed in proximal coronary arteries, followed by mid and distal major coronary arteries. Vessels demonstrating TCFA do not usually show severe narrowing but show positive remodeling. In TCFAs the necrotic core length is approximately 2 to 17 mm (mean 8 mm) and the underlying cross-sectional area narrowing in over 75% of cases is < 75% (diameter stenosis < 50%). The area of the necrotic core in at least 75% of cases is <= 53 mm(2). These lesions have lesser degree of calcification than plaque ruptures. Thin cap fibroatheromas are common in patients with high total cholesterol (TC) and high TC/high-density lipoprotein cholesterol ratio, in women > 50 years, and in those patients with elevated high levels of high sensitivity C-reactive protein. It has only recently been recognized that their identification in living patients might help reduce the incidence of sudden coronary death. C1 CVPath, Int Registry Pathol, Gaithersburg, MD 20878 USA. US FDA, CDRH, ODE, DCD,ICDB, Rockville, MD 20857 USA. RP Virmani, R (reprint author), CVPath, Int Registry Pathol, 19 Firstfield Rd, Gaithersburg, MD 20878 USA. EM rvirmani@cvpath.org NR 19 TC 922 Z9 971 U1 4 U2 63 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD APR 18 PY 2006 VL 47 IS 8 SU C BP C13 EP C18 DI 10.1016/j.jacc.2005.10.065 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 034CZ UT WOS:000236903800004 PM 16631505 ER PT J AU Small, A Ilev, I Chernomordik, V Gandjbakhche, A AF Small, A Ilev, I Chernomordik, V Gandjbakhche, A TI Enhancing diffraction-limited images using properties of the point spread function SO OPTICS EXPRESS LA English DT Article ID DIFFERENTIAL CONFOCAL MICROSCOPY; RESOLUTION; IMPLEMENTATION; ILLUMINATION; CONTRAST AB We propose an algorithm to enhance diffraction-limited images based on pixel-to-pixel correlations introduced by the finite width of the Point Spread Function (PSF). We simulate diffraction-limited images of point sources by convolving the PSF of a diffraction-limited lens with simulated images, and enhance the blurred images with our algorithm. Our algorithm reduces the PSF width, increases the contrast, and reveals structure on a length scale half of that resolvable in the unenhanced image. Our enhanced images compare favorably with images enhanced by conventional Tikhonov regularization. (c) 2006 Optical Society of America. C1 NICHHD, Sect Biomed Stochast Phys, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. US FDA, Off Sci & Engn Labs, Rockville, MD 20851 USA. RP Small, A (reprint author), NICHHD, Sect Biomed Stochast Phys, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. EM smallalex@mail.nih.gov NR 16 TC 4 Z9 4 U1 1 U2 4 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 APR 17 PY 2006 VL 14 IS 8 BP 3193 EP 3203 DI 10.1364/OE.14.003193 PG 11 WC Optics SC Optics GA 037KD UT WOS:000237144700011 PM 19516461 ER PT J AU Moore, MM Chen, T AF Moore, MM Chen, T TI Mutagenicity of bromate: Implications for cancer risk assessment SO TOXICOLOGY LA English DT Article DE potassium bromate; sodium bromate; mutagenicity; genotoxicity; risk assessment ID OXIDATIVE DNA-DAMAGE; POTASSIUM BROMATE; DRINKING-WATER; MICRONUCLEUS TEST; RENAL CARCINOGEN; FOOD-ADDITIVES; F344 RATS; KIDNEY; CELLS; MICE AB Bromate (BrO3-) is a rodent carcinogen that is formed as a drinking water ozone disinfection by-product and also used in some food and consumer products. Therefore, bromate is subject to assessment for its risk to humans. Because the selection of an appropriate model for conducting quantitative cancer risk assessment is based upon an understanding of the chemical's mode-of-action, it is necessary to determine whether the chemical is a mutagenic carcinogen. We present a review of the available information concerning the weight-of-the-evidence that bromate is a mutagenic carcinogen. The evidence indicates that bromate is mutagenic and that this activity is mediated by the formation of oxidative damage to the DNA, thus resulting in chromosomal damage. Not only does bromate induce genetic damage in vitro, it is also demonstrated to induce mutations in the kidney of exposed rats. This is significant because the rat kidney is one of the target tissues for tumor induction. While it is clear that bromate can cause damage in the target tissue, it is not clear whether bromate is a mutagenic carcinogen, that is, whether the observed tumors result from a mutagenic mode-of-action. Further research is needed to clarify bromate's mode-of-action. However, in the absence of additional information, it is reasonable, based on an extensive database, to assume that bromate induces tumors via oxidative damage that causes chromosomal breakage. (c) 2006 Aww Research Foundation. Published by Elsevier Ireland Ltd. All rights reserved. C1 US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. RP Moore, MM (reprint author), US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, HFT-120,3900 NCTR Rd, Jefferson, AR 72079 USA. EM mmmoore@nctr.fda.gov NR 42 TC 46 Z9 47 U1 2 U2 15 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 APR 17 PY 2006 VL 221 IS 2-3 BP 190 EP 196 DI 10.1016/j.tox.2005.12.018 PG 7 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 036BU UT WOS:000237046700010 PM 16460860 ER PT J AU Casanova, MF Giedd, J Rumsey, J Mannheim, G AF Casanova, MF Giedd, J Rumsey, J Mannheim, G TI A negative study on the gyrification index in patients with autism SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 Univ Louisville, Louisville, KY 40292 USA. NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. NIMH, Clin Neurosci Branch, Rockville, MD 20857 USA. US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RI Giedd, Jay/A-3080-2008; Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015 OI Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2006 VL 59 IS 8 SU S MA 359 BP 110S EP 110S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767300355 ER PT J AU Rasooly, A AF Rasooly, A TI Moving biosensors to point-of-care cancer diagnostics SO BIOSENSORS & BIOELECTRONICS LA English DT Editorial Material DE cancer diagnostics; biosensors; point-of-care testing; molecular signatures; ligands; microfluidics; lab-on-a-chip ID SURFACE-PLASMON RESONANCE; IDENTIFICATION C1 NCI, NIH, CDP, Rockville, MD 20852 USA. US FDA, Div Biol Sci, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Rasooly, A (reprint author), NCI, NIH, CDP, 6130 Execut Blvd EPN,Room 6035A, Rockville, MD 20852 USA. EM rasoolya@mail.nih.gov NR 15 TC 17 Z9 17 U1 2 U2 15 PU ELSEVIER ADVANCED TECHNOLOGY PI OXFORD PA OXFORD FULFILLMENT CENTRE THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0956-5663 J9 BIOSENS BIOELECTRON JI Biosens. Bioelectron. PD APR 15 PY 2006 VL 21 IS 10 BP 1847 EP 1850 DI 10.1016/j.bios.2006.02.001 PG 4 WC Biophysics; Biotechnology & Applied Microbiology; Chemistry, Analytical; Electrochemistry; Nanoscience & Nanotechnology SC Biophysics; Biotechnology & Applied Microbiology; Chemistry; Electrochemistry; Science & Technology - Other Topics GA 032EG UT WOS:000236756100001 PM 16556495 ER PT J AU Rasooly, A Jacobson, J AF Rasooly, A Jacobson, J TI Development of biosensors for cancer clinical testing SO BIOSENSORS & BIOELECTRONICS LA English DT Article DE cancer diagnostics; biosensors; point of care testing; molecular signatures; ligands ID PARAFFIN-EMBEDDED TISSUES; POLYMERASE-CHAIN-REACTION; IMMUNOMAGNETIC CELL ENRICHMENT; IMMUNOCYTOCHEMISTRY IN-VITRO; SURFACE-PLASMON RESONANCE; RT-PCR ANALYSIS; BREAST-CANCER; PROMOTER HYPERMETHYLATION; TUMOR-CELLS; BONE-MARROW AB Biosensors are devices that combine a biochemical recognition/binding element (ligand) with a signal conversion unit (transducer). Biosensors are already used for several clinical applications, for example for electrochemical measurement of blood glucose concentrations. Application of biosensors in cancer clinical testing has several potential advantages over other clinical analysis methods including increased assay speed and flexibility, capability for multi-target analyses, automation, reduced costs of diagnostic testing and a potential to bring molecular diagnostic assays to community health care systems and to underserved populations. They have the potential for facilitating Point of Care Testing (POCT), where state-of-the-art molecular analysis is carried out without requiring a state-of-the-art laboratory. However, not many biosensors have been developed for cancer-related testing. One major challenge in harnessing the potential of biosensors is that cancer is a very complex set of diseases. Tumors vary widely in etiology and pathogenesis. Oncologists rely heavily on histological characterization of tumors and a few biomarkers that have demonstrated clinical utility to aid in patient management decisions. New genomic and proteomic molecular tools are being used to profile tumors and produce "molecular signatures." These signatures include genetic and epigenetic signatures, changes in gene expression, protein profiles and post-translational modifications of proteins. These molecular signatures provide new opportunities for utilizing biosensors. Biosensors have enormous potential to deliver the promise of new molecular diagnostic strategies to patients. This article describes some of the basic elements of cancer biology and cancer biomarkers relevant for the development of biosensors for cancer clinical testing, along with the challenges in using this approach. (c) 2006 Elsevier B.V. All rights reserved. C1 NCI, NIH, CDP, Rockville, MD 20852 USA. US FDA, Div Biol Sci, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Rasooly, A (reprint author), NCI, NIH, CDP, 6130 Execut Blvd EPN,6035A, Rockville, MD 20852 USA. EM rasoolya@mail.nih.gov NR 100 TC 99 Z9 101 U1 3 U2 46 PU ELSEVIER ADVANCED TECHNOLOGY PI OXFORD PA OXFORD FULFILLMENT CENTRE THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0956-5663 J9 BIOSENS BIOELECTRON JI Biosens. Bioelectron. PD APR 15 PY 2006 VL 21 IS 10 BP 1851 EP 1858 DI 10.1016/j.bios.2005.01.003 PG 8 WC Biophysics; Biotechnology & Applied Microbiology; Chemistry, Analytical; Electrochemistry; Nanoscience & Nanotechnology SC Biophysics; Biotechnology & Applied Microbiology; Chemistry; Electrochemistry; Science & Technology - Other Topics GA 032EG UT WOS:000236756100002 PM 16458498 ER PT J AU Soper, SA Brown, K Ellington, A Frazier, B Garcia-Manero, G Gau, V Gutman, SI Hayes, DF Korte, B Landers, JL Larson, D Ligler, F Majumdar, A Mascini, M Nolte, D Rosenzweig, Z Wang, J Wilson, D AF Soper, SA Brown, K Ellington, A Frazier, B Garcia-Manero, G Gau, V Gutman, SI Hayes, DF Korte, B Landers, JL Larson, D Ligler, F Majumdar, A Mascini, M Nolte, D Rosenzweig, Z Wang, J Wilson, D TI Point-of-care biosensor systems for cancer diagnostics/prognostics SO BIOSENSORS & BIOELECTRONICS LA English DT Article DE biosensors; cancer; point-of-care ID QUARTZ-CRYSTAL-MICROBALANCE; POLYMERASE-CHAIN-REACTION; LABEL-FREE DETECTION; RESONANCE IMAGING MEASUREMENTS; PHAGE-DISPLAYED LIBRARY; ACOUSTIC-WAVE SENSOR; NANOIMPRINT LITHOGRAPHY; PIEZOELECTRIC BIOSENSOR; MICROFLUIDIC CHIPS; POLY(METHYL METHACRYLATE) AB With the growing number of fatalities resulting from the 100 or so cancer-related diseases, new enabling tools are required to provide extensive molecular profiles of patients to guide the clinician in making viable diagnosis and prognosis. Unfortunately with cancer-related diseases, there is not one molecular marker that can provide sufficient information to assist the clinician in making effective prognoses or even diagnoses. Indeed, large panels of markers must typically be evaluated that cut across several different classes (mutations in certain gene fragments-DNA; over/underexpression of gene activity as monitored by messenger RNAs; the amount of proteins present in serum or circulating tumor cells). The classical biosensor format (dipstick approach for monitoring the presence of a single element) is viewed as a valuable tool in many bioassays, but possesses numerous limitations in cancer due primarily to the single element nature of these sensing platforms. As such, if biosensors are to become valuable tools in the arsenal of the clinician to manage cancer patients, new formats are required. This review seeks to provide an overview of the current thinking on molecular profiling for diagnosis and prognosis of cancers and also, provide insight into the current state-of-the-art in the biosensor field and new strategies that must be considered to bring this important technology into the cancer field. (c) 2006 Elsevier B.V. All rights reserved. C1 Louisiana State Univ, Baton Rouge, LA 70803 USA. Univ Texas, SW Med Ctr, Dallas, TX 75235 USA. Univ Texas, Austin, TX 78712 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. US FDA, Rockville, MD 20857 USA. Univ Michigan, Ann Arbor, MI 48109 USA. NIH, Bethesda, MD 20892 USA. Univ Virginia, Charlottesville, VA 22903 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Univ Calif Berkeley, Berkeley, CA 94720 USA. Univ Florence, Florence, Italy. Purdue Univ, W Lafayette, IN 47907 USA. Univ New Orleans, New Orleans, LA 70148 USA. Arizona State Univ, Tempe, AZ 85287 USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. RP Soper, SA (reprint author), Louisiana State Univ, Baton Rouge, LA 70803 USA. EM chsope@lsu.edu RI Wang, Joseph/C-6175-2011 NR 96 TC 158 Z9 161 U1 10 U2 117 PU ELSEVIER ADVANCED TECHNOLOGY PI OXFORD PA OXFORD FULFILLMENT CENTRE THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0956-5663 J9 BIOSENS BIOELECTRON JI Biosens. Bioelectron. PD APR 15 PY 2006 VL 21 IS 10 BP 1932 EP 1942 DI 10.1016/j.bios.2006.01.006 PG 11 WC Biophysics; Biotechnology & Applied Microbiology; Chemistry, Analytical; Electrochemistry; Nanoscience & Nanotechnology SC Biophysics; Biotechnology & Applied Microbiology; Chemistry; Electrochemistry; Science & Technology - Other Topics GA 032EG UT WOS:000236756100013 PM 16473506 ER PT J AU Belyakov, IM Kuznetsov, VA Kelsall, B Klinman, D Moniuszko, M Lemon, M Markham, PD Pal, R Clements, JD Lewis, MG Strober, W Franchini, GA Berzofsky, JA AF Belyakov, IM Kuznetsov, VA Kelsall, B Klinman, D Moniuszko, M Lemon, M Markham, PD Pal, R Clements, JD Lewis, MG Strober, W Franchini, GA Berzofsky, JA TI Impact of vaccine-induced mucosal high-avidity CD8(+)CTLs in delay of AIDS viral dissemination from mucosa SO BLOOD LA English DT Article ID SIMIAN IMMUNODEFICIENCY VIRUS; CYTOTOXIC T-LYMPHOCYTES; MAJOR HISTOCOMPATIBILITY COMPLEX; I MOLECULE MAMU-A-ASTERISK-01; COLONY-STIMULATING FACTOR; INFECTED RHESUS MACAQUES; CELL RESPONSES; GASTROINTESTINAL-TRACT; PROTECTIVE IMMUNITY; SELECTIVE INDUCTION AB Natural HIV transmission occurs through mucosa, but it is debated whether mucosal cytotoxic T lymphocytes (CTLs) can prevent or reduce dissemination from the initial mucosal site to the systemic circulation. Also, the role of CTL avidity in mucosal AIDS viral transmission is unknown. To address these questions, we used delay in acute-phase peak viremia after intrarectal challenge as an indicator of systemic dissemination. We found that a peptide-prime/poxviral boost vaccine inducing high levels of high-avidity mucosal CTLs can have an impact on dissemination of intrarectally administered pathogenic SHIV-ku2 in macaques and that such protection correlates better with mucosal than with systemic CTLs and particularly with levels of high-avidity mucosal CTLs. C1 NCI, Vaccine Branch, Bethesda, MD 20892 USA. NIAID, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. Gen Inst Singapore, Div Informat & Math Sci, Singapore, Singapore. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. Adv Biosci Labs, Kensington, MD USA. Tulane Univ, Dept Microbiol & Immunol, Sch Med, New Orleans, LA 70118 USA. So Res Inst, Frederick, MD USA. RP Belyakov, IM (reprint author), NCI, Vaccine Branch, Bldg 10,Rm 6B-12, Bethesda, MD 20892 USA. EM belyakov@mail.nih.gov NR 56 TC 105 Z9 107 U1 0 U2 4 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD APR 15 PY 2006 VL 107 IS 8 BP 3258 EP 3264 DI 10.1182/blood-2005-11-4374 PG 7 WC Hematology SC Hematology GA 033FY UT WOS:000236833500044 PM 16373659 ER PT J AU Kawakami, K Terabe, M Kawakami, M Berzofsky, JA Puri, RK AF Kawakami, K Terabe, M Kawakami, M Berzofsky, JA Puri, RK TI Characterization of a novel human tumor antigen interleukin-13 receptor alpha 2 chain SO CANCER RESEARCH LA English DT Article ID REED-STERNBERG CELLS; IL-13 RECEPTOR; PSEUDOMONAS EXOTOXIN; IN-VIVO; FUNCTIONAL-CHARACTERIZATION; SIGNAL-TRANSDUCTION; HODGKIN LYMPHOMA; CANCER VACCINES; DECOY RECEPTOR; BREAST-CANCER AB The interleukin (IL)-13 receptor alpha 2 (IL-13R alpha 2) chain is a primary binding and internalization subunit for a Th2-derived immune regulatory cytokine, IL-13. Although extremely high levels of IL-13R alpha 2 chain are expressed on a variety of human tumor cells and specimens, its precise role in tumor immunology has not been defined. To investigate the role of IL-13R alpha 2 in tumor immunity, we used D5 melanoma cells stably transfected with the human M-13R alpha 2 gene (D5 alpha 2) to assess the effect of an IL-13R alpha 2 DNA vaccine in immunocompetent animals. Prophylactic immunization of mice with the IL-13R alpha 2 DNA vaccine resulted in protection against D5 alpha 2 tumor development. In vivo depletion experiments in C57BL/6 and RAG-2 knockout mice indicated that both T and B cells, but not natural killer cells, were required for the tumor protection. In addition, antibody induced by the IL-13R alpha 2 DNA vaccine showed a modest but significant inhibitory effect on D5 alpha 2 cells in vitro, suggesting that the antibody is biologically functional. The IL-13R alpha 2 DNA vaccine also exhibited antitumor activity against established D5 alpha 2 tumors in mice. Histologic analysis of regressing tumors identified infiltration of CD4(+) and CD8(+) T cells and the expression of CXCL9 chemokine in tumors. Taken together, our results identify the human IL-13R alpha 2 chain as a novel tumor rejection antigen. C1 Univ Tokyo, Grad Sch Med, Dept Adv Clin Sci & Therapeut, Bunkyo Ku, Tokyo 1138655, Japan. US FDA, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. NCI, Vaccine Branch, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Kawakami, K (reprint author), Univ Tokyo, Grad Sch Med, Dept Adv Clin Sci & Therapeut, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1138655, Japan. EM kawakami-k@umin.ac.jp FU Intramural NIH HHS NR 43 TC 20 Z9 22 U1 0 U2 1 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 APR 15 PY 2006 VL 66 IS 8 BP 4434 EP 4442 DI 10.1158/0008-5472.CAN-05-1265 PG 9 WC Oncology SC Oncology GA 033JM UT WOS:000236843200061 PM 16618770 ER PT J AU Lasfar, A Lewis-Antes, A Smirnov, SV Anantha, S Abushahba, W Tian, B Reuhl, K Dickensheets, H Sheikh, F Donnelly, RP Raveche, E Kotenko, SV AF Lasfar, A Lewis-Antes, A Smirnov, SV Anantha, S Abushahba, W Tian, B Reuhl, K Dickensheets, H Sheikh, F Donnelly, RP Raveche, E Kotenko, SV TI Characterization of the mouse IFN-lambda ligand-receptor system: IFN-lambda s exhibit antitumor activity against B16 melanoma SO CANCER RESEARCH LA English DT Article ID INTERFERON-GAMMA RECEPTOR; GENE-THERAPY; TUMOR-CELLS; ALPHA; CYTOKINE; COMPLEX; MICE; CANCER; IL-10; TUMORIGENICITY AB Recently discovered type III IFNs (IFN-lambda) exert their antiviral and immunomodulatory activities through a unique receptor complex composed of IFN-lambda R1 and interleukin-10 receptor 2 To further study type III IFNs, we cloned and characterized mouse IFN-lambda ligand-receptor system. We showed that, similar to their human orthologues, mIFN-lambda 2 and mIFN-lambda 3 signal through the IFN-lambda receptor complex, activate IFN stimulated gene factor 3, and are capable of inducing antiviral protection and MHC class I antigen expression in several cell types including B16 melanoma cells. We then used the murine B16 melanoma model to investigate the potential antitumor activities of IFN-lambda s. We developed B16 cells constitutively expressing murine IFN-lambda 2 (B16.IFN-lambda 2 cells) and evaluated their tumorigenicity in syngeneic C57BL/6 mice. Although constitutive expression of mIFN-lambda 2 in melanoma cells did not affect their proliferation in vitro, the growth of B16.IFN-lambda 2 cells, when injected s.c. into mice, was either retarded or completely prevented. We found that rejection of the modified tumor cells correlated with their level of IFN-lambda 2 expression. We then developed IFN-lambda-resistant B16.IFN-lambda 2 cells (B16.IFN-lambda 2Res cells) and showed that their tumorigenicity was also highly impaired or completely abolished similar to B16.IFN-lambda 2 cells, suggesting that IFN-lambda s engage host mechanisms to inhibit melanoma growth. These in vivo experiments show the antitumor activities of IFN-lambda s and suggest their strong therapeutic potential. C1 Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Biochem & Mol Biol, Newark, NJ 07103 USA. Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Pathol & Lab Med, Newark, NJ 07103 USA. Rutgers State Univ, Dept Pharmacol & Toxicol, Piscataway, NJ 08854 USA. US FDA, Ctr Drug Evaluat & Res, Div Therapeut Prot, Bethesda, MD 20014 USA. RP Kotenko, SV (reprint author), Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Biochem & Mol Biol, Newark, NJ 07103 USA. EM kotenkse@umdnj.edu FU NIAID NIH HHS [AI057468, R01 AI051139, R01 AI057468]; NIEHS NIH HHS [ES05022] NR 45 TC 139 Z9 152 U1 0 U2 11 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 APR 15 PY 2006 VL 66 IS 8 BP 4468 EP 4477 DI 10.1158/0008-5472.CAN-05-3653 PG 10 WC Oncology SC Oncology GA 033JM UT WOS:000236843200065 PM 16618774 ER PT J AU Pedras-Vasconcelos, JA Goucher, D Puig, M Tonelli, LH Wang, V Ito, S Verthelyi, D AF Pedras-Vasconcelos, JA Goucher, D Puig, M Tonelli, LH Wang, V Ito, S Verthelyi, D TI CpG oligodeoxynucleotides protect newborn mice from a lethal challenge with the neurotropic Tacaribe arenavirus SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NITRIC-OXIDE SYNTHASE; LISTERIA-MONOCYTOGENES; VIRUS-INFECTION; CELL RESPONSES; BACTERIAL-DNA; INNATE IMMUNITY; GENITAL HERPES; NEONATAL MICE; LASSA-VIRUS; IFN-GAMMA AB The innate immune system is key to limiting the early spread of most pathogens and directing the development of Ag-specific immunity. Recently, a number of synthetic molecules that activate the innate immune system by stimulating TLRs have been identified. Among them, synthetic oligodeoxynucleotides (ODNs) containing unmethylated CpG motifs (CpG ODNs) were shown to activate TLR9-bearing B cells, macrophages, and dendritic cells to induce a strong proinfiammatory milieu and a type 1-biased immune response that protects mice from a variety of parasitic, bacterial, and viral infections. Although the protective effect of CpG ODN in adult mice was well established, its effectiveness in neonates, which have lower numbers of dendritic, 13, and T cells and tend to favor Th2 responses, was unclear. This study uses the New World arenavirus Tacaribe, a neurotropic pathogen that is lethal in newborn mice, to explore the effectiveness of TLR-mediated innate immune responses. Neonatal BALB/c mice treated with CpG ODN at the time of infection had reduced viral load (p < 0.01) and increased survival (52 %, p < 0.001 i.p.; 36 %, p < 0.05 intranasally). Protection was achieved in mice treated no later than 3 days postchallenge and appears to be mediated by an increase in Ag-specific Abs (IgG and IgM) and. to require inducible NO synthase expression and NO production. To our knowledge, this is the first study assessing the mechanisms by which CpG ODN can protect mice from a neurotropic viral infection. C1 US FDA, Ctr Biol Evaluat & Res, Off Biotechnol Prod, Div Therapeut Prot, Bethesda, MD 20892 USA. NIMH, Sect Neuroendocrine Immunol & Behav, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div viral Prod, Rockville, MD 20852 USA. RP Verthelyi, D (reprint author), Bldg 29A,Room 3B19,8800 Rockville Pike, Bethesda, MD 20892 USA. EM Verthelyi@cber.fda.gov NR 59 TC 36 Z9 40 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 APR 15 PY 2006 VL 176 IS 8 BP 4940 EP 4949 PG 10 WC Immunology SC Immunology GA 059YV UT WOS:000238769000056 PM 16585590 ER PT J AU Ge, XD Hanson, M Shen, H Kostov, Y Brorson, KA Frey, DD Moreira, AR Rao, G AF Ge, XD Hanson, M Shen, H Kostov, Y Brorson, KA Frey, DD Moreira, AR Rao, G TI Validation of an optical sensor-based high-throughput bioreactor system for mammalian cell culture SO JOURNAL OF BIOTECHNOLOGY LA English DT Article DE optical sensor; non-invasive; high-throughput bioreactor; mammalian cell culture; transcriptional profiling ID BIOPROCESS DESIGN; MICROTITER PLATES; SCALE BIOREACTOR; DISSOLVED-OXYGEN; PH SENSOR; MICROBIOREACTOR; FLUORESCENCE AB Cell culture optimization is a labor-intensive process requiring a large number of experiments to be conducted under varying conditions. Here we describe a high-throughput bioreactor system that allows 12 mini stirred-tank bioreactors to be operated simultaneously. All bioreactors are monitored by low-cost minimally invasive optical sensors for pH and dissolved oxygen. The sensors consist of single-use patches affixed inside the bioreactors and monitored optically from the outside. Experimental results show that different sensing patches with the same composition respond consistently. The discrepancy between different pH sensors is less than 0.1 pH units over most of their responsive range. The discrepancy between different dissolved oxygen sensors is less than 10% over the whole range from 0% to 100% dissolved oxygen. The consistency of the sensing system ensures that only an initial one-time calibration is required for the sensing patches. After that, a calibration code is generated and sensing patches of the same composition can be used directly. This greatly reduces the time and cost required for monitored multi-bioreactor operations. We used SP2/0 myeloma/mouse hybridoma cell cultures to demonstrate reactor performance consistency. Transcriptional profiling, HPLC analysis, viable cell count, and viability inspection show that the presence of sensing patches and the use of optical monitoring have no apparent effect on the metabolism of the cells. (c) 2006 Elsevier B.V. All rights reserved. C1 Univ Maryland Baltimore Cty, Ctr Adv Sensor Technol, Dept Chem & Biochem Engn, Baltimore, MD 21250 USA. US FDA, Off Biotechnol Prod, Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. RP Rao, G (reprint author), Univ Maryland Baltimore Cty, Ctr Adv Sensor Technol, Dept Chem & Biochem Engn, 1000 Hilltop Circle, Baltimore, MD 21250 USA. EM grao@umbc.edu NR 28 TC 58 Z9 60 U1 1 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-1656 J9 J BIOTECHNOL JI J. Biotechnol. PD APR 10 PY 2006 VL 122 IS 3 BP 293 EP 306 DI 10.1016/j.biotic.2005.12.009 PG 14 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 027MY UT WOS:000236420900002 PM 16423420 ER PT J AU Nissen, SE AF Nissen, SE TI ADHD drugs and cardiovascular risk SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 Cleveland Clin, Dept Cardiovasc Med, Cleveland, OH 44106 USA. US FDA, Drug Safety & Risk Management Advisory Comm, Rockville, MD 20857 USA. RP Nissen, SE (reprint author), Cleveland Clin, Dept Cardiovasc Med, Cleveland, OH 44106 USA. NR 5 TC 170 Z9 173 U1 0 U2 7 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 APR 6 PY 2006 VL 354 IS 14 BP 1445 EP 1448 DI 10.1056/NEJMp068049 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 029DP UT WOS:000236539000001 PM 16549404 ER PT J AU Roach, JAG Musser, SM Morehouse, K Woo, JYJ AF Roach, JAG Musser, SM Morehouse, K Woo, JYJ TI Determination of usnic acid in lichen toxic to elk by liquid chromatography with ultraviolet and tandem mass spectrometry detection SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE elk deaths; liquid chromatography-tandem mass spectrometry; LC-MS/MS; tumbleweed shield lichen; Usnea barbata; usnic acid; Xanthoparmelia chlorochroa ID IN-VITRO; METABOLITES; EXTRACTION; MS/MS AB Usnic acid is unambiguously confirmed by tandem mass spectrometry (MS/MS) in tumbleweed shield lichen, Xanthoparmelia chlorochroa. The lichen contains 2% usnic acid by liquid chromatography with UV quantification at 282 nm. The UV linear range for usnic acid quantification is from its 4 ng limit of detection to 2 mu g injected. UV signal saturation is recognized by distortion of the usnic acid UV spectrum. Positive ion electrospray-tandem mass spectrometry offers no similar means to recognize quantification data recorded above the linear range of electrospray. Electrospray ionization capacity and matrix effects limit the reliability of tandem mass spectrometry quantification. The combination of UV quantification and MS confirmation provides a reliable analytical method for measuring usnic acid levels in plant material. C1 US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Roach, JAG (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM jroach@cfsan.fda.gov NR 30 TC 14 Z9 14 U1 1 U2 10 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 APR 5 PY 2006 VL 54 IS 7 BP 2484 EP 2490 DI 10.1021/jf052767m PG 7 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 030IR UT WOS:000236628500004 PM 16569032 ER PT J AU Naeger, LK Struble, KA AF Naeger, LK Struble, KA TI Effect of baseline protease genotype and phenotype on HIV response to atazanavir/ritonavir in treatmentexperienced patients SO AIDS LA English DT Article DE HIV protease inhibitor; virologic response; resistance; atazanavir; lopinavir ID BMS-232632; INHIBITOR; RITONAVIR; REGIMENS; SCORE AB Objectives: To assess the virologic response rates of atazanavir/ritonavir and lopinavir/ritonavir based on baseline genotype and phenotype. Methods: Resistance analyses were performed on a Bristol-Myers Squibb-sponsored study comparing the safety and efficacy of atazanavir/ritonavir to lopinavir/ritonavir in treatment-experienced subjects at 48 weeks. Analyses evaluated virologic response based on the presence of baseline primary protease inhibitor mutations and baseline susceptibility. Results: Less than 30% of atazanavir/ritonavir-treated patients were responders if substitutions at positions M46, G73, I84 or L90 were present in their HIV at baseline. In comparison, lopinavir/ritonavir response rates were less than 30% when protease substitutions at M46, I54, or I84 were present at baseline. The response rates were similar between atazanavir/ritonavir and lopinavir/ritonavir-treated subjects with zero to four baseline protease inhibitor mutations, but response rates were reduced if five or more baseline mutations were present: 0% for atazanavir/ritonavir compared with 28% for lopinavir/ritonavir. Baseline phenotype results showed that response rates were similar between atazanavir/ritonavir and lopinavir/ritonavir if shifts in susceptibility were zero to five, but response rates were lower if shifts were greater than five; 11% for atazanavir/ritonavir compared with 27% for lopinavir/ritonavir. Conclusions: Both type and number of baseline protease inhibitor mutations affected virologic response to atazanavir/ritonavir and lopinavir/ritonavir in treatment-experienced subjects. In addition, baseline phenotypic susceptibility could differentiate virologic response rates to the two drugs. These resistance analyses provide information on the likelihood of a virologic response to antiretroviral drugs based on baseline genotypic and phenotypic data, which is valuable to physicians and patients when choosing antiretroviral regimens. (C) 2006 Lippincott Williams & Wilkins. C1 US FDA, Div Antiviral Prod, Ctr New Drug Evaluat, Silver Spring, MD USA. RP Naeger, LK (reprint author), US FDA, CDER, OND, DAVP, 10903 New Hampshire Ave,Bldg 22,Room 6367, Silver Spring, MD 20993 USA. EM lisa.naeger@fda.hhs.gov NR 11 TC 26 Z9 26 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 APR 4 PY 2006 VL 20 IS 6 BP 847 EP 853 DI 10.1097/01.aids.0000218548.77457.76 PG 7 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 031OI UT WOS:000236713500007 PM 16549968 ER PT J AU Rowlands, JC Hoadley, JE AF Rowlands, JC Hoadley, JE TI FDA perspectives on health claims for food labels SO TOXICOLOGY LA English DT Article; Proceedings Paper CT 45th Annual Meeting of the American-College-of-Nutrition CY SEP 30-OCT 03, 2004 CL Long Beach, CA SP Amer Coll Nutr DE Nutrition Labeling Education Act; health claim; nutrition facts panel; nutrient content claim; evidence-based ranking system AB The U.S. Food and Drug Administration's regulatory authority over health claims was clarified in 1990 legislation known as the Nutrition Labeling and Education Act (NLEA). This law established mandatory nutrition labeling for most foods and placed restrictions oil the use of food label claims characterizing the levels or health benefits of nutrients in foods. NLEA set a high threshold for the scientific standard under which the U.S. Food and Drug Administration (FDA) may authorize health claims, this standard is known as the significant scientific agreement (SSA) standard. Subsequent legislation known as the Food and Drug Administration Modernization Act (FDAMA) provided an alternative to FDA review of the health claim where an U.S. government scientific body other that) FDA concluded that there is SSA for a substance/disease relationship. Courts have since extended the scope of health claims to include qualified health claims (QHC) that are health claims not substantiated on evidence that meets the level of SSA standard, but include a qualifying statement intended to convey to the consumer the level of evidence for the claim. FDA has responded by developing an evidence-based ranking system for scientific data to determine the level of evidence substantiating a health claim. The following is in overview of FDA's regulations and evidence-based method for evaluating health claims. (c) 2006 Elsevier Ireland Ltd. All rights reserved. C1 US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Rowlands, JC (reprint author), Dow Chem Co USA, Toxicol & Environm Res & Consulting, 1803 Bldg, Midland, MI 48674 USA. EM JCRowlands@Dow.com NR 6 TC 11 Z9 11 U1 0 U2 9 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 APR 3 PY 2006 VL 221 IS 1 BP 35 EP 43 DI 10.1016/j.tox.2005.10.023 PG 9 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 028YN UT WOS:000236524800006 PM 16480811 ER PT J AU Puig-Basagoiti, F Tilgner, M Forshey, BM Philpott, SM Espina, NG Wentworth, DE Goebel, SJ Masters, PS Falgout, B Ren, P Ferguson, DM Shi, PY AF Puig-Basagoiti, F Tilgner, M Forshey, BM Philpott, SM Espina, NG Wentworth, DE Goebel, SJ Masters, PS Falgout, B Ren, P Ferguson, DM Shi, PY TI Triaryl pyrazoline compound inhibits flavivirus RNA replication SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID WEST-NILE-VIRUS; YELLOW-FEVER ENCEPHALITIS; DENGUE-VIRUS; MONOCLONAL-ANTIBODIES; NONSTRUCTURAL PROTEIN; IN-VITRO; ANTIVIRAL COMPOUNDS; PASSIVE TRANSFER; NS5 PROTEIN; INTERFERON AB Triaryl pyrazoline {[5- (4-chloro-phenyl) -3- thiophen-2 -yl-4,5-dihydro-pyrazol-1-yl}-phenyl-methanone} inhibits flavivirus infection in cell culture. The inhibitor was identified through high-throughput screening of a compound library using a luciferase-expressing West Nile (WN) virus infection assay. The compound inhibited an epidemic strain of WN virus without detectable cytotoxicity (a 50% effective concentration of 28 mu M and a compound concentration of :300 mu M required to reduce 50% cell viability). Besides WN virus, the compound also inhibited other flaviviruses (dengue, yellow fever, and St. Louis encephalitis viruses), an alphavirus (Western equine encephalitis virus), a coronavirus (mouse hepatitis virus), and a rhabdovirus (vesicular stomatitis virus). However, the compound did not suppress an orthomyxovirus (influenza virus) or a retrovirus (human immunodeficiency virus type 1). Mode-of-action analyses in WN virus showed that the compound did. p not inhibit viral entry or virion assembly but specifically suppressed viral RNA synthesis. To examine the mechanism of inhibition of dengue virus, we developed two replicon systems for dengue type 1 virus: (i) a stable cell line that harbored replicons containing a luciferase reporter and a neomycin,Phosphotransferase selection marker and (ii) a luciferase-expressing replicon that could differentiate between viral translation and RNA replication. Analyses of the compound in the dengue type I virus replicon systems showed that it weakly suppressed viral translation but significantly inhibited viral RNA synthesis. Overall, the results demonstrate that triaryl pyrazoline exerts a broad spectrum of antiflavivirus activity through potent inhibition of viral RNA replication. This novel inhibitor could be developed for potential treatment of flavivirus infection. C1 New York State Dept Hlth, Wadsworth Ctr Labs & Res, Albany, NY 12208 USA. SUNY Albany, Dept Biomed Sci, Albany, NY 12208 USA. US FDA, Bethesda, MD 20892 USA. Univ Minnesota, Dept Med Chem, Minneapolis, MN 55455 USA. Univ Minnesota, Ctr Drug Design, Minneapolis, MN 55455 USA. RP Ferguson, DM (reprint author), New York State Dept Hlth, Wadsworth Ctr Labs & Res, 120 New Scotland Ave, Albany, NY 12208 USA. EM ferguson@umn.edu; ship@wadsworth.org OI Wentworth, David/0000-0002-5190-980X FU NIAID NIH HHS [1T32AI05542901A1, AI061193, AI065562, N01-AI25490, N01AI25490, R21 AI065562, U01 AI061193] NR 56 TC 81 Z9 88 U1 1 U2 4 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 APR PY 2006 VL 50 IS 4 BP 1320 EP 1329 DI 10.1128/AAC.50.4.1320-1329.2006 PG 10 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 031EA UT WOS:000236685700029 PM 16569847 ER PT J AU Volokhov, D George, J Anderson, C Duvall, RE Hitchins, AD AF Volokhov, D George, J Anderson, C Duvall, RE Hitchins, AD TI Discovery of natural atypical nonhemolytic Listeria seeligeri isolates SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID SPECIES DEFINITION; MONOCYTOGENES; EVOLUTION; GENE; IDENTIFICATION; LINEAGES; STRAINS; LOCUS AB We found seven Listeria isolates, initially identified as isolates with the Xyl(+) Rha(-) biotype of Listeria welshimeri by phenotypic tests, which exhibited discrepant genotypic properties in a well-validated Listeria species identification oligonucleotide microarray. The microarray gives results of these seven isolates being atypical hly-negative L. seeligeri isolates, not L. welshimeri isolates. The aberrant L. seeligeri isolates were D-xylose fermentation positive, L-rhanmose fermentation negative (Xyl(+) Rha(-)), and nonhemolytic on blood agar and in the CAMP test with both Staphylococcus aureus (S- reaction) and Rhodococcus equi (R- reaction). All genes (if the prfA cluster of L. seeligeri, located in the prs-ldh region, including the orfA2, orfD, prfA, orfE, plcA, hly, orfK, mpl, actA, dplcB, plcB, orfH, orfX, orfl, orfP, orfB, and orfA genes, were checked by PCR and direct sequencing for evidence of their presence in the atypical isolates. The prs-prfA cluster-ldh region of the L. seeligeri isolates was approximately threefold shorter due to the loss of orfD prfA, orfE plcA, hly, orfK, mpl, actA, dplcB, plcB, orfH, orFfX, and orfl The genetic map order of the cluster genes of all the atypical L. seeligeri isolates was prs-orfA2-orfP-orfB-orfA-ldh, which was comparable to the similar region in L. welshimeri, with the exception of the presence of orfA2. DNA sequencing and phylogenetic analysis of 17 housekeeping genes indicated an L. seeligeri genoinic background in all seven of the atypical hly-negative L. seeligeri isolates. Thus, the novel biotype of Xyl(+) Rha(-) Hly(-) L. seeligeri strains can only be distinguished from Xyl(+) Rlia(-) L. welshimeri strains genotypically, not phenotypically. In contrast, the Rha(+) Xyl(+) biotype of L. welshimeri would not present an identification issue. C1 US FDA, Ctr Biol Evaluat & Res, Kensington, MD 20895 USA. US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Volokhov, D (reprint author), US FDA, Ctr Biol Evaluat & Res, Off Vaccine Res & Review, Div Viral Prod,Lab Methods Dev, HFM-470,1401 Rockville Pike, Rockville, MD 20852 USA. EM volokhov@cber.fda.gov NR 37 TC 11 Z9 15 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0099-2240 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD APR PY 2006 VL 72 IS 4 BP 2439 EP 2448 DI 10.1128/AEM.72.4.2439-2448.2006 PG 10 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 032BR UT WOS:000236749400021 PM 16597942 ER PT J AU Monday, SR Keys, C Hanson, P Shen, YL Whittam, TS Feng, P AF Monday, SR Keys, C Hanson, P Shen, YL Whittam, TS Feng, P TI Produce isolates of the Escherichia coli Ont : H52 serotype that carry both Shiga Toxin 1 and stable toxin genes SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID HEMOLYTIC-UREMIC SYNDROME; MULTIPLEX PCR; O157-H7; VIRULENCE AB Produce isolates of the Escherichia coli Ont:H52 serotype carried Shiga toxin I and stable toxin genes but only expressed Stx1. These strains had pulsed-field gel electrophoresis profiles that were 90% homologous to clinical Ont:H52 strains that had identical phenotypes and genotypes. All Ont:H52 strains had identical single nucleotide polymorphism profiles that are suggestive of a unique clonal group. C1 US FDA, Div Microbiol Studies, College Pk, MD 20740 USA. Florida Dept Agr & Consumer Serv, Tallahassee, FL 32339 USA. Michigan State Univ, STEC Ctr, E Lansing, MI 48824 USA. RP Feng, P (reprint author), US FDA, Div Microbiol Studies, HFS-516,5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM pfeng@cfsan.fda.gov NR 18 TC 11 Z9 12 U1 0 U2 0 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 APR PY 2006 VL 72 IS 4 BP 3062 EP 3065 DI 10.1128/AEM.72.4.3062-3065.2006 PG 4 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 032BR UT WOS:000236749400099 PM 16598020 ER EF