FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Yildirim, S Lin, W Hitchins, AD Jaykus, LA Altermann, E Klaenhammer, TR Kathariou, S AF Yildirim, S Lin, W Hitchins, AD Jaykus, LA Altermann, E Klaenhammer, TR Kathariou, S TI Epidemic clone I-specific genetic markers in strains of Listeria monocytogenes serotype 4b from foods (vol 70, pg 4158, 2004) SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Correction C1 N Carolina State Univ, Dept Food Sci, Raleigh, NC 27695 USA. US FDA, Irvine, CA USA. US FDA, Washington, DC 20204 USA. RP Yildirim, S (reprint author), N Carolina State Univ, Dept Food Sci, Raleigh, NC 27695 USA. NR 1 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0099-2240 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD DEC PY 2004 VL 70 IS 12 BP 7581 EP 7581 DI 10.1128/AEM.70.12.7581.2004 PG 1 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 879LM UT WOS:000225719300082 ER PT J AU Onderci, M Sahin, K Sahin, N Gursu, MF Doerge, D Sarkar, FH Kucuk, O AF Onderci, M Sahin, K Sahin, N Gursu, MF Doerge, D Sarkar, FH Kucuk, O TI The effect of genistein supplementation on performance and antioxidant status of Japanese quail under heat stress SO ARCHIVES OF ANIMAL NUTRITION LA English DT Article DE genistein; heat stress; peroxidation; performance; quail ID OXIDATIVE DNA-DAMAGE; LIPID-PEROXIDATION; PROTEIN-TURNOVER; SKELETAL-MUSCLE; SOY ISOFLAVONES; CARCASS TRAITS; VITAMIN-C; GROWTH; TEMPERATURE; CORTICOSTERONE AB Genistein, a phytoestrogen found in soybeans, is a powerful antioxidant. We evaluated the effects of genistein supplementation on performance, carcass characteristics, levels of malondialdehyde (MDA), homocysteine, vitamins C, E, A in Japanese quail (Coturnix coturnix japonica) exposed to high ambient temperature of 34degreesC. Two hundred and forty Japanese quails (10 d old) were randomly assigned to eight treatment groups consisting of 10 replicates of three birds. The birds were kept in an environmental controlled room either for 24 h/d at 22degreesC with (thermoneutral, TN groups) or for 16 h/d at 22degreesC and for 8 h/d (09.00 am to 05.00 pm) at WC (heat stress, HS groups). Birds were fed either a basal (control) diet (TN and HS) or the basal diet supplemented with 200, 400 or 800 mg of genistein per kg of diet. Heat exposure decreased birds' performance when basal diet was fed. Increase in feed intake and body weight, and improvement of feed efficiency and carcass traits were found in genistein-supplemented quails reared under heat stress conditions. Growth rate and feed efficiency improved in quails reared under thermo-neutral conditions as well. Concentration of serum vitamins C, E, and A increased in supplemented birds reared at high temperature, while non-significant changes occurred in TN groups. With genistein supplementation homocysteine levels in serum and MDA levels in serum and liver decreased in all birds of both TN and HS groups. Effects of genistein were relatively greater in heat-stressed quails than in quails kept under thermo-neutral conditions. Results of the present study suggest that supplementation with genistein can be considered to be protective by reducing the negative effects of oxidative stress induced by heat stress in quail. C1 Firat Univ, Fac Vet Sci, Dept Anim Nutr, TR-231119 Elazig, Turkey. Firat Univ, Vet Control & Res Inst, Elazig, Turkey. Firat Univ, Sch Med, Dept Biochem, Elazig, Turkey. US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. RP Sahin, K (reprint author), Firat Univ, Fac Vet Sci, Dept Anim Nutr, TR-231119 Elazig, Turkey. EM nsahinkm@yahoo.com RI Sahin, Kazim/D-5625-2009; Sahin, Nurhan/D-5626-2009; OI Sahin, Nurhan/0000-0001-9487-1154; GURSU, M.Ferit/0000-0003-3552-7315 NR 37 TC 8 Z9 9 U1 2 U2 6 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0003-942X J9 ARCH ANIM NUTR JI Arch. Anim. Nutr. PD DEC PY 2004 VL 58 IS 6 BP 463 EP 471 DI 10.1080/00039420400020017 PG 9 WC Agriculture, Dairy & Animal Science SC Agriculture GA 893WT UT WOS:000226752200004 PM 15732579 ER PT J AU Jia, YP Ramasamy, S Wood, F Alayash, AI Rifkind, JM AF Jia, YP Ramasamy, S Wood, F Alayash, AI Rifkind, JM TI Cross-linking with O-raffinose lowers oxygen affinity and stabilizes haemoglobin in a non-cooperative T-state conformation SO BIOCHEMICAL JOURNAL LA English DT Article DE blood substitute; haemoglobin; modified Hb; oxygen transport; T state ID NITRIC-OXIDE; INOSITOL HEXAPHOSPHATE; FUNCTIONAL-PROPERTIES; QUATERNARY STRUCTURE; SH GROUPS; HEME; COOPERATIVITY; HISTIDINE; BINDING; DEOXYHEMOGLOBIN AB O-R-polyHbA(0) is an intra- and intermolecularly O-raffinose cross-linked derivative of deoxygenated human haemoglobin developed as an oxygen therapeutic. When compared with its native protein (HbA(0)), O-R-polyHbA(0) was found to be locked in the T (tense) quaternary conformation with a lower oxygen affinity, a reduced Bohr effect (50% of HbA(0)) and no measurable cooperativity (h = 1). The kinetics of oxygen and CO binding to the protein indicate lower 'on' rates and faster 'off' rates than HbA(0) and the absence of effects of inositol hexaphosphate (IHP) on the kinetics. Other properties consistent with a T-like conformation are inaccessibility of the betaCys-93 thiol group of O-R-polyHbA(0), the hyperfine splitting from nitrogen in the EPR spectrum of the Fe(II)NO complex of O-R-polyHbA(0) and decreased flexibility in the distal haem pocket, as indicated by low-spin bis-histidine complexes detected by EPR of oxidized chains. A comparison of the properties of O-R-polyHbA(0) with those of HbA(0) with and without IHP, as well as the reaction of nitrite with deoxygenated haemoglobin, provide additional insights into the variations in the conformation of T-state haemoglobin in solution (modifications of the T state produced by adding organic phosphates, like IHP and 2,3-diphosphoglycerate). Although the physiological ramifications of locking HbA0 in the T conformation with the O-raffinose are still unknown, valuable insights into haemoglobin function are provided by these studies of O-R-polyHbA(0). C1 US FDA, Ctr Biol Evaluat & Res, Div Hematol, Lab Biochem & Vasc Biol, Bethesda, MD 20892 USA. NIA, Mol Dynam Sect, NIH, Baltimore, MD 21224 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 48 TC 16 Z9 18 U1 0 U2 1 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON W1N 3AJ, ENGLAND SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD DEC 1 PY 2004 VL 384 BP 367 EP 375 DI 10.1042/BJ20040612 PN 2 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 879DP UT WOS:000225696900017 PM 15303971 ER PT J AU Joo, JN Ahn, HS Delongchamp, RR Nowell, SA Lang, NP AF Joo, JN Ahn, HS Delongchamp, RR Nowell, SA Lang, NP TI A mixture-of-genotypes model for the distribution of thermostable phenol sulfotransferase activity SO BIOMETRICAL JOURNAL LA English DT Article DE bootstrap; density estimation; EM algorithm; genotype; phenotype ID QUANTITATIVE TRAITS AB A statistical method for parametric density estimation based upon a mixture-of-genotypes model is developed for the thermostable phenol sulfotransferase (SULT1A1) activity which has a putative role in modifying risk for colon and prostate cancer/polyps. The EM algorithm for the general mixture model is modified to accommodate the genetic constraints and is used to estimate genotype frequencies from the distribution of the SULT1A1 phenotype. A parametric bootstrap likelihood ratio test is considered as a testing method for the number of mixing components. The size and power of the test is then investigated and compared with the conventional chi-squared test. The relative risk associated with genotypes defined by this model is also investigated through the generalized linear model. This analysis revealed that a genotype with the highest mean value of SULT1A1 activity has greater impact on cancer risk than others. This result suggests that the phenotype with a higher SULT1A1 activity might be important in studying the association between the cancer risk and SULT1A1 activity. C1 SUNY Stony Brook, Dept Appl Math & Stat, Stony Brook, NY 11790 USA. US FDA, Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. Roswell Pk Canc Inst, Buffalo, NY 14263 USA. Univ Arkansas Med Sci, Cent Arkansas Vet Healthcare Syst, Little Rock, AR 72205 USA. Univ Arkansas Med Sci, Coll Med, Dept Surg, Little Rock, AR 72205 USA. RP Ahn, HS (reprint author), SUNY Stony Brook, Dept Appl Math & Stat, Stony Brook, NY 11790 USA. EM hahn@ams.sunysb.edu NR 25 TC 0 Z9 0 U1 0 U2 0 PU AKADEMIE VERLAG GMBH PI BERLIN PA PALISADENSTR 40, D-10243 BERLIN, GERMANY SN 0323-3847 J9 BIOMETRICAL J JI Biom. J. PD DEC PY 2004 VL 46 IS 6 BP 707 EP 719 DI 10.1002/bimj.200310075 PG 13 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 884KJ UT WOS:000226083300008 ER PT J AU Liu, AY Troendle, JF Yu, KF Yuan, VW AF Liu, AY Troendle, JF Yu, KF Yuan, VW TI Conditional maximum likelihood estimation following a group sequential test SO BIOMETRICAL JOURNAL LA English DT Article DE adaptive designs; bias adjustment; conditional bias; interim analysis; secondary endpoints ID CLINICAL-TRIALS; SAMPLE-SIZE; CONFIDENCE-INTERVALS; UNBIASED ESTIMATION; INFERENCE; DESIGN; BIAS AB We consider estimation after a group sequential test. An estimator that is unbiased or has small bias may have substantial conditional bias (Troendle and Yu, 1999, Coburger and Wassmer, 2001). In this paper we derive the conditional maximum likelihood estimators of both the primary parameter and a secondary parameter, and investigate their properties within a conditional inference framework. The method applies to both the usual and adaptive group sequential test designs. C1 NICHHD, Div Epidemiol Stat & Prevent Res, Dept Hlth & Human Serv, Rockville, MD 20852 USA. US FDA, Ctr Biol Evaluat & Res, Off Biostat & Epidemiol Therapeut Evaluat Branch, Rockville, MD 20852 USA. RP Liu, AY (reprint author), NICHHD, Div Epidemiol Stat & Prevent Res, Dept Hlth & Human Serv, 6100 Execut Blvd, Rockville, MD 20852 USA. EM liua@mail.nih.gov OI Liu, Aiyi/0000-0002-6618-5082 NR 31 TC 7 Z9 7 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 DEC PY 2004 VL 46 IS 6 BP 760 EP 768 DI 10.1002/bimj.200410076 PG 9 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 884KJ UT WOS:000226083300012 ER PT J AU Rosenberg, AS Worobec, AS AF Rosenberg, AS Worobec, AS TI Risk-based approach to immunogenicity concerns of therapeutic protein products, part 2 - Considering host specific and product specific factors impacting immunogenicity SO BIOPHARM INTERNATIONAL LA English DT Article ID FIELD-FLOW FRACTIONATION; GLYCOSYLATION SITES; NATURAL ANTIBODIES; TRANSGENIC MICE; CELL TOLERANCE; FORMULATIONS; RESPONSES; ANTIGEN C1 US FDA, Ctr Biol Evaluat & Res, Div Therapeut Prot, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Therapeut Biol Oncol Prod, Bethesda, MD 20892 USA. RP Rosenberg, AS (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Therapeut Prot, Bldg 29A,Room 2D-16,8000 Rockville Pike, Bethesda, MD 20892 USA. EM amy.rosenberg@fda.gov; alexandra.worobec@fda.go NR 42 TC 42 Z9 42 U1 0 U2 3 PU ADVANSTAR COMMUNICATIONS PI DULUTH PA 131 W FIRST ST, DULUTH, MN 55802 USA SN 1542-166X J9 BIOPHARM INT JI Biopharm. Int. PD DEC PY 2004 VL 17 IS 12 BP 34 EP + PG 6 WC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA 884WW UT WOS:000226118400009 ER PT J AU Felix, RJ Jones, KL Johnson, KA McCloskey, CA Chambers, CD AF Felix, RJ Jones, KL Johnson, KA McCloskey, CA Chambers, CD CA Org Teratology Imformation Servi TI Postmarketing surveillance for drug safety in pregnancy: The organization of teratology inforination services project SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Article DE pregnancy exposures; teratogens; drug safety ID 1ST TRIMESTER EXPOSURE; OUTCOMES AB BACKGROUND: Although medications are frequently used during pregnancy, premarketing studies exclude pregnant women, with the result that maternal and fetal risks of medications are largely unknown prior to marketing. METHODS: To demonstrate the feasibility of using Teratology Information Services (TISs) to identify potential subjects who may participate in postmarketing surveillance studies regarding medications taken during pregnancy, maternal characteristics and pregnancy exposure data routinely collected from callers to member agencies of the Organization of Teratology Information Services (OTIS) were pooled for two one-month periods. RESULTS: A total of 3536 calls inquiring about 7746 different agents were received from pregnant women. Of the 40 medications about which pregnant women most frequently asked, the top two were nonprescription acetaminophen and pseudoephedrine, three were prescription drugs with a U.S. Food and Drug Administration pregnancy label category D designation, and five were prescription antidepressants. CONCLUSIONS: TISs are well positioned to prospectively ascertain medication exposures in large numbers of pregnant women and may be an exceptional resource for conducting postmarketing surveillance for the safety of medications taken during pregnancy. Published 2004 Wiley-Liss, Inc(dagger). C1 Univ Calif San Diego, Dept Pediat, Calif Teratogen Informat Serv, San Diego, CA 92103 USA. Univ Calif San Diego, Dept Pediat, Clin Res Program, San Diego, CA 92103 USA. US FDA, Ctr Drug Evaluat & Res, Off Drug Safety, Div Drug Risk Evaluat, Rockville, MD 20857 USA. Univ Calif San Diego, Dept Family & Prevent Med, San Diego, CA 92103 USA. RP Chambers, CD (reprint author), Univ Calif San Diego, Dept Pediat, Calif Teratogen Informat Serv, 200 W Arbor Dr 8446, San Diego, CA 92103 USA. EM chchambers@ucsd.edu NR 15 TC 24 Z9 27 U1 2 U2 2 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 DEC PY 2004 VL 70 IS 12 BP 944 EP 947 DI 10.1002/bdra.20090 PG 4 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 884RF UT WOS:000226102900006 PM 15570610 ER PT J AU Krauthamer, V Smith, TC AF Krauthamer, V Smith, TC TI Acute effects of adrenergic agents on post-defibrillation arrest time in a cultured heart model SO CELLULAR AND MOLECULAR LIFE SCIENCES LA English DT Article DE electroporation; asystole; bigeminy; epinephrine; norepinephrine; isoproterenol; verapamil ID ELECTRICAL SHOCKS; DEFIBRILLATION; ARRHYTHMIAS; ELECTROPORATION; FIBRILLATION; STIMULATION; LIDOCAINE; CELLS AB Possible drug interactions with electrical defibrillation were examined. We tested the hypothesis that adrenergic agents ( epinephrine, norepinephrine, isoproterenol) and a calcium channel blocker ( verapamil), when applied acutely, alter the duration of arrest following a defibrillator shock. A secondary hypothesis ( based on observations) was that the drugs alter the occurrence of changes to normal rhythms following the shock. Dissociated heart cells from 10-day chicken embryos were cultured to form spherical aggregates and plated in petri dishes. In the experiments, the spheres were paced at 0.75 V/cm above contraction threshold, and a biphasic defibrillator shock was applied for 1 ms at 46 V/cm. The arrest time and occurrence of rhythm changes were recorded. The adrenergic agents shortened the duration of arrest following a defibrillator shock, while the calcium channel blocker lengthened the arrest time. Comparisons with the control proportion of double beats showed no significant change with the adrenergic agents and a decrease with verapamil. C1 US FDA, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, Rockville, MD 20852 USA. RP Krauthamer, V (reprint author), US FDA, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, 12725 Twinbrook Pkwy,Mail Stop HFZ-130, Rockville, MD 20852 USA. EM victor.krauthamer@hhs.fda.gov NR 21 TC 1 Z9 1 U1 0 U2 0 PU BIRKHAUSER VERLAG AG PI BASEL PA VIADUKSTRASSE 40-44, PO BOX 133, CH-4010 BASEL, SWITZERLAND SN 1420-682X J9 CELL MOL LIFE SCI JI Cell. Mol. Life Sci. PD DEC PY 2004 VL 61 IS 24 BP 3093 EP 3099 DI 10.1007/s00018-004-4372-9 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 876WK UT WOS:000225529000008 PM 15583870 ER PT J AU Gorlewska-Roberts, KM Teitel, CH Lay, JO Roberts, DW Kadlubar, FF AF Gorlewska-Roberts, KM Teitel, CH Lay, JO Roberts, DW Kadlubar, FF TI Lactoperoxidase-catalyzed activation of carcinogenic aromatic and heterocyclic amines SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID BREAST EPITHELIAL-CELLS; HUMAN-MILK; CANCER; DNA; 2-AMINO-1-METHYL-6-PHENYLIMIDAZO<4,5-B>PYRIDINE; PEROXIDASE; ENZYMES; TISSUE; PHIP; RISK AB Lactoperoxidase, an enzyme secreted from the human mammary gland, plays a host defensive role through antimicrobial activity. It has been implicated in mutagenic and carcinogenic activation in the human mammary gland. The potential role of heterocyclic and aromatic amines in the etiology of breast cancer led us to examination of the lactoperoxidase-catalyzed activation of the most commonly studied arylamine carcinogens: 2-amino-1-methyl-6-phenylimidazo[4,5-b]-pyridine (PhIP), benzidine, 4-aminobiphenyl (ABP), 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx). In vitro activation was performed with lactoperoxidase (partially purified from bovine milk or human milk) in the presence of hydrogen peroxide and calf thymus DNA. Products formed during enzymatic activation were monitored by HPLC with ultraviolet and radiometric detection. Two of these products were characterized as hydrazo and azo derivatives by means of mass spectrometry. The DNA binding level of H-3- and C-14-radiolabeled amines after peroxidase-catalyzed activation was dependent on the hydrogen peroxide concentration, and the highest levels of carcinogen binding to DNA were observed at 100 mu M H2O2. Carcinogen activation and the level of binding to DNA were in the order of benzidine > ABP > IQ > MeIQx > PhIP. One of the ABP adducts was identified, and the level at which it is formed was estimated to be six adducts/105 nucleotides. The susceptibility of aromatic and heterocyclic amines for lactoperoxidase-catalyzed activation and the binding levels of activated products to DNA suggest a potential role of lactoperoxidase-catalyzed activation of carcinogens in the etiology of breast cancer. C1 Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Kadlubar, FF (reprint author), Natl Ctr Toxicol Res, HFT 100,3900 NCTR Rd, Jefferson, AR 72079 USA. EM fkadlubar@nctr.fda.gov RI Lay, Jackson/G-1007-2011 OI Lay, Jackson/0000-0003-3789-2527 NR 27 TC 35 Z9 38 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD DEC PY 2004 VL 17 IS 12 BP 1659 EP 1666 DI 10.1021/tx049787n PG 8 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 881XK UT WOS:000225902600014 PM 15606142 ER PT J AU Turesky, RJ Taylor, J Gehring, T Holland, RD AF Turesky, RJ Taylor, J Gehring, T Holland, RD TI Identification of novel heterocyclic aromatic amines in grilled meats and human urine. SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Meeting Abstract CT 228th National Meeting of the American-Chemical-Society CY AUG 22-26, 2004 CL Philadelphia, PA SP Amer Chem Soc C1 Natl Ctr Toxicol Res, Div Chem, Jefferson, AR 72079 USA. EM Rturesky@nctr.fda.gov NR 0 TC 0 Z9 0 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD DEC PY 2004 VL 17 IS 12 MA 7 BP 1758 EP 1758 PG 1 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 881XK UT WOS:000225902600033 ER PT J AU Powers, JH AF Powers, JH TI Empirical antifungal therapy in febrile neutropenic patients: Caution about composite end points and the perils of P values SO CLINICAL INFECTIOUS DISEASES LA English DT Letter ID CLINICAL-TRIALS C1 US FDA, Off Drug Evaluat 4, Ctr Drug Evaluat & Res, Rockville, MD 20850 USA. RP Powers, JH (reprint author), US FDA, Off Drug Evaluat 4, Ctr Drug Evaluat & Res, HFD-104,9201 Corp Blvd, Rockville, MD 20850 USA. EM powersjoh@cder.fda.gov NR 7 TC 7 Z9 7 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 EI 1537-6591 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD DEC 1 PY 2004 VL 39 IS 11 BP 1738 EP 1739 DI 10.1086/425922 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 904JI UT WOS:000227492100038 PM 15578387 ER PT J AU Winter, HR Trapnell, CB Slattery, JT Jacobson, M Greenspan, DL Hooton, TM Unadkat, JA AF Winter, HR Trapnell, CB Slattery, JT Jacobson, M Greenspan, DL Hooton, TM Unadkat, JA TI The effect of clarithromycin, fluconazole, and rifabutin on dapsone hydroxylamine formation in individuals with human immunodeficiency virus infection (AACTG 283) SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID PNEUMOCYSTIS-CARINII-PNEUMONIA; SULFONAMIDE-REACTIVE METABOLITES; HUMAN LIVER-MICROSOMES; N-HYDROXYLATION; OXIDATIVE STRESS; IN-VITRO; SULFAMETHOXAZOLE; HIV; INHIBITION; PHARMACOKINETICS AB Background: Dapsone hydroxylamine formation is thought to be the cause of the high rates of adverse reactions to dapsone in human immunodeficiency virus (HIV)-infected individuals. Therefore we studied the effect of the commonly coadministered drugs fluconazole, clarithromycin, and rifabutin on hydroxylamine formation in individuals with HIV infection. Methods: HIV-infected subjects (CD4+ greater than or equal to200 cells/mm(3)) were enrolled in a 2-part (A or B) open-label drug interaction study. In part A, subjects (n = 12) received dapsone (100-mg tablet once daily) alone for 2 weeks and then, in a randomly assigned order, received dapsone and either fluconazole (200 mg daily), rifabutin (300 mg daily), or fluconazole plus rifabutin, each for a 2-week period. Part B (n = 11) was identical to part A except that clarithromycin (500 mg twice daily) was substituted for rifabutin. On the last study day of each 2-week period, plasma and urine were collected over ascorbic acid for 24 hours. Results: In part A, fluconazole decreased the area under the plasma concentration-time curve, percent of dose excreted in 24-hour urine, and formation clearance of the hydroxylamine by 49%, 53%, and 55% (n = 12, P < .05), respectively. This inhibition of in vivo hydroxylamine formation was quantitatively consistent with that predicted from human liver microsomal experiments. Rifabutin had no effect on hydroxylamine area under the plasma concentration-time curve or percent excreted in 24-hour urine but increased formation clearance of the hydroxylamine by 92% (n = 12, P < .05). Dapsone clearance was increased by rifabutin or rifabutin plus fluconazole (67% and 38%, respectively) (n = 12, P < .05) but was unaffected by fluconazole or clarithromycin. In part B, hydroxylamine production was unaffected by clarithromycin but was affected by fluconazole in a manner identical to that in part A. Conclusions. On the basis of these data and with the assumption that the exposure to the hydroxylamine is a determinant of dapsone toxicity, we predict that coadministration of fluconazole should decrease the rate of adverse reactions to dapsone in persons with HIV infection but that rifabutin and clarithromycin will have no effect. When dapsone is given in combination with rifabutin, dapsone dosage adjustment may be necessary in light of the increase in dapsone clearance. C1 Univ Washington, Dept Pharmaceut, Seattle, WA 98195 USA. US FDA, Rockville, MD USA. Univ Calif San Francisco, Posit Hlth Program, San Francisco, CA USA. San Francisco Gen Hosp, Med Serv, San Francisco, CA USA. Vanderbilt Univ, Meharry Med Coll, Nashville, TN USA. RP Unadkat, JA (reprint author), Univ Washington, Dept Pharmaceut, H272 Hlth Sci,Box 357610, Seattle, WA 98195 USA. EM jash@u.washington.edu FU NCRR NIH HHS [M01RR00037, M01RR00083]; NIAID NIH HHS [AI27664, AI46339] NR 25 TC 7 Z9 7 U1 1 U2 3 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD DEC PY 2004 VL 76 IS 6 BP 579 EP 587 DI 10.1016/j.clpt.2004.08.016 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 881NE UT WOS:000225873400009 PM 15592329 ER PT J AU Willke, RJ Burke, LB Erickson, P AF Willke, RJ Burke, LB Erickson, P TI Measuring treatment impact: a review of patient-reported outcomes and other efficacy endpoints in approved product labels SO CONTROLLED CLINICAL TRIALS LA English DT Review DE drug development; patient-reported outcomes; health-related quality of life; drug labeling ID QUALITY-OF-LIFE; HEALTH-STATUS MEASURES; TASK-FORCE; INDEX; QUESTIONNAIRE; DERMATOLOGY; MANAGEMENT; ARTHRITIS; THERAPY; DISEASE AB Context: The term "patient-reported outcomes" (PROs) has evolved to include any endpoint derived from patient reports, whether collected in the clinic, in a diary, or by other means. including single-item outcome measures. event logs, symptom reports, formal instruments to measure health-related quality of life (HRQL), health status. adherence, and satisfaction with treatment. This term coincides with the explicit interest from drug development researchers and regulatory authorities in the appropriate utilization and reporting of treatment impact measures. Objective: To determine the level and nature of use of PROs compared to other types of effectiveness endpoints in approved product labeling for new drugs recently approved in the United States. Design and sources: Review and analysis of effectiveness endpoints as reported in clinical study descriptions in approved product labeling of new molecular entities (NMEs) approved in the United States from 1997 through 2002. Main outcome measures: Effectiveness study endpoints reported in approved product labeling that fall into the following categories of measurement: PROs, clinician-reported outcomes (CROs). and laboratory test/device measurement endpoints. Results: PROs were reported in 64 (30%) of the 215 product labels reviewed. Clinician-reported outcomes were reported most frequently (62%) followed by laboratory/device endpoints, (50%). PROs were the only type of endpoint used in the FDA-approved label for 23 products. Formal multiitem PRO scales were cited 22 times. Use of PROs is most common in antiinflammatory, CNS, gastrointestinal, respiratory, allergic conjunctivitis. and urologic therapy areas. The frequency of reported PRO use over this period did not change. Conclusion: PROs, although quite variable as a class of study endpoints, were found to have a significant role in the development and evaluation of new medicines. More formal guidance from the FDA about use of such measures along with continued collaboration by PRO researchers to develop and disseminate standards will enhance the appropriate use of PROs in future drug development and labeling. (C) 2004 Elsevier Inc. All rights reserved. C1 Pfizer Inc, Worldwide Outcomes Res, Bridgewater, NJ 08807 USA. US FDA, Rockville, MD USA. Penn State Univ, Milton Med Sch, Hershey, PA 17033 USA. RP Willke, RJ (reprint author), Pfizer Inc, Worldwide Outcomes Res, 95 Corp Dr,MS 270, Bridgewater, NJ 08807 USA. EM richard.j.willke@pfizer.com NR 52 TC 133 Z9 140 U1 4 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-2456 J9 CONTROL CLIN TRIALS JI Controlled Clin. Trials PD DEC PY 2004 VL 25 IS 6 BP 535 EP 552 DI 10.1016/j.cct.2004.09.003 PG 18 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 881ZI UT WOS:000225907700001 PM 15588741 ER PT J AU Liotta, LA Petricoin, EF Veenstra, TD Conrads, TP AF Liotta, LA Petricoin, EF Veenstra, TD Conrads, TP TI High-resolution serum proteomic patterns for ovarian cancer detection SO ENDOCRINE-RELATED CANCER LA English DT Letter C1 NCI, Biomed Proteom Program, SAIC Frederick Inc, Lab Proteom & Analyt Technol, Frederick, MD 21702 USA. US FDA, Natl Canc Inst, Clin Proteom Program, Ctr Biol & Evaluat Res, Bethesda, MD 20892 USA. Natl Canc Inst, Pathol Lab, Clin Proteom Program, Canc Res Ctr, Bethesda, MD 20892 USA. RP Veenstra, TD (reprint author), NCI, Biomed Proteom Program, SAIC Frederick Inc, Lab Proteom & Analyt Technol, Frederick, MD 21702 USA. EM Veenstra@ncifcrf.gov NR 6 TC 3 Z9 4 U1 0 U2 1 PU SOC ENDOCRINOLOGY PI BRISTOL PA 22 APEX COURT, WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 1351-0088 J9 ENDOCR-RELAT CANCER JI Endocr.-Relat. Cancer PD DEC PY 2004 VL 11 IS 4 BP 585 EP 587 DI 10.1677/erc.1.00873 PG 3 WC Oncology; Endocrinology & Metabolism SC Oncology; Endocrinology & Metabolism GA 890JW UT WOS:000226508500002 ER PT J AU Tylzanowski, P Bossuyt, W Thomas, JT Luyten, FP AF Tylzanowski, P Bossuyt, W Thomas, JT Luyten, FP TI Characterization of Frzb-Cre transgenic mouse SO GENESIS LA English DT Article DE FRZB; Wnt; Cre; LacZ; mouse; embryo ID EXPRESSION; SEQUENCES; PROTEIN; DOMAINS AB The Wnt family of glycoproteins is involved in numerous developmental and disease processes in higher eukaryotes, exerting their action by binding to cell-surface receptors. In the extracellular space, Writs are negatively regulated by secreted antagonists that either bind to the receptors directly (Dkk1) or to Wnt molecules themselves (Sfrp-FRZB family), preventing its subsequent binding to the receptor. Here we report on a transgenic mouse expressing Cre under the control of the mouse Frzb promoter element. Analysis of the Cre expression was carried out at 10.5 and 14.5 dpc using the ROSA26R mouse line. Expression of the transgenic construct was detected in the limbs, the heart, the nasal epithelium, bone, whiskers, and around the orbita of the eye. The mouse could be used for conditional gene modification in those tissues. (C) 2004 Wiley-Liss, Inc. C1 Katholieke Univ Leuven, Dept Rheumatol, Lab Skeletal Dev & Joint Disorders, B-3000 Louvain, Belgium. Katholieke Univ Leuven VIB, Neurogenet Lab, B-3000 Louvain, Belgium. Ctr Biol Evaluat & Res, Food & Drug Admin, Rockville, MD USA. RP Tylzanowski, P (reprint author), Katholieke Univ Leuven, Dept Rheumatol, Lab Skeletal Dev & Joint Disorders, Herestr 49, B-3000 Louvain, Belgium. EM przemko@med.kuleuven.ac.be RI Tylzanowski, Przemko/G-8881-2013 NR 8 TC 6 Z9 6 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1526-954X J9 GENESIS JI Genesis PD DEC PY 2004 VL 40 IS 4 BP 200 EP 204 DI 10.1002/gene.20086 PG 5 WC Developmental Biology; Genetics & Heredity SC Developmental Biology; Genetics & Heredity GA 886KP UT WOS:000226226400002 PM 15593330 ER PT J AU Rodriguez, B Tice, BM Eason, JC Aguel, F Trayanova, N AF Rodriguez, B Tice, BM Eason, JC Aguel, F Trayanova, N TI Cardiac vulnerability to electric shocks during phase 1A of acute global ischemia SO HEART RHYTHM LA English DT Article DE acute ischemia; upper limit of vulnerability; reentry; excitation; conduction failure ID MYOCARDIAL-ISCHEMIA; GUINEA-PIG; IONIC CURRENTS; UPPER LIMIT; K+ CURRENT; DEFIBRILLATION; SIMULATION; ARRHYTHMIAS; MYOCYTES; CHANNELS AB OBJECTIVES The purpose of this study is to characterize the changes in vulnerability to electric shocks during phase lA of global ischemia in the rabbit ventricles and to determine the mechanisms responsible for these changes. BACKGROUND Mechanisms responsible for the changes in cardiac vulnerability over the course of ischemia phase lA remain poorly understood. The lack of understanding results from the rapid ischemic change in cardiac electrophysiologic properties, which renders experimental evaluation of vulnerability difficult. METHODS To examine dynamic changes in vulnerability to electric shocks over the course of acute Global ischemia phase lA this study used a three-dimensional anatomically accurate bidomain model of ischemic rabbit ventricles. Monophasic shocks are applied at various coupling intervals to construct vulnerability grids in normoxia and at various stages of ischemia phase lA. RESULTS Our simulations demonstrate that 2 to 3 minutes after the onset of ischemia, the upper limit of vulnerability remains at its normoxic value (12.75 V/cm); however, arrhythmias are induced at shorter coupling intervals. As ischemia progresses, the upper limit of vulnerability decreases, reaching 6.4 V/cm in the advanced stage of ischemic phase IA, and the vulnerable window shifts towards longer coupling intervals. CONCLUSIONS Changes in the upper limit of vulnerability result from an increase in the spatial extent of the shock-end excitation wavefronts and the slower recovery from shock-induced positive polarization. Shifts in the vulnerable window stem from decreases in local repolarization times and the occurrence of postshock conduction failure caused by prolonged postrepolarization refractoriness. (C) 2004 Heart Rhythm Society. All rights reserved. C1 Tulane Univ, Dept Biomed Engn, New Orleans, LA 70118 USA. Washington & Lee Univ, Lexington, VA 24450 USA. Food & Drug Adm, Rockville, MD USA. RP Rodriguez, B (reprint author), Tulane Univ, Dept Biomed Engn, New Orleans, LA 70118 USA. EM blanca@tulane.edu RI Trayanova, Natalia/A-3386-2010 FU NHLBI NIH HHS [HL063195]; NIBIB NIH HHS [P20EB001432] NR 23 TC 33 Z9 33 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1547-5271 J9 HEART RHYTHM JI Heart Rhythm PD DEC PY 2004 VL 1 IS 6 BP 695 EP 703 DI 10.1016/j.hrthm.2004.08.018 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 894RJ UT WOS:000226809000008 PM 15851241 ER PT J AU Parra, M Pickett, T Delogu, G Dheenadhayalan, V Debrie, AS Locht, C Brennan, MJ AF Parra, M Pickett, T Delogu, G Dheenadhayalan, V Debrie, AS Locht, C Brennan, MJ TI The mycobacterial heparin-binding hemagglutinin is a protective antigen in the mouse aerosol challenge model of tuberculosis SO INFECTION AND IMMUNITY LA English DT Article ID T-CELL; PROTEIN; EXPRESSION; VACCINES; IMMUNITY; HBHA; IMMUNOGENICITY; DISSEMINATION; PERSISTENCE; SMEGMATIS AB The heparin-binding hemagglutinin (HBHA) of Mycobacterium tuberculosis is a surface-expressed adhesin that can affect binding to host cells via a unique, methylated, carboxyl-terminal, lysine-, alanine-, and prolinerich repeat region. It has been implicated in extrapulmonary dissemination of M. tuberculosis from the lung following the initial infection of the host. To assess the vaccine potential of this protein, purified preparations of HBHA were emulsified in a dimethyldioctadecylammonium bromide-monophosphoryl lipid A adjuvant and tested for the ability to reduce M. tuberculosis infection in the mouse aerosol challenge model for tuberculosis. The HBHA-containing vaccine gave a similar to0.7-log reduction in CFU in both mouse lungs and spleens compared to adjuvant controls 28 days following challenge. Although a notable level of serum antibody to HBHA was elicited after three immunizations and the antibodies were able to bind to the surface of M. tuberculosis, passive immunization with monoclonal antibodies directed against HBHA did not protect in the challenge model. Compared to adjuvant controls, an elevated gamma interferon response was generated by splenic and lymph node-derived T cells from immunized mice in the presence of macrophages pulsed with purified HBHA or infected with live M. tuberculosis, suggesting that the effective immunity may be cell mediated. Efforts to construct effective recombinant HBHA vaccines in fast-growing Mycobacterium smegmatis have been unsuccessful so far, which indicates that distinctive posttranslational modifications present in the HBHA protein expressed by M. tuberculosis are critical for generating effective host immune responses. The vaccine studies described here demonstrate that HBHA is a promising new vaccine candidate for tuberculosis. C1 US FDA, Ctr Biol Evaluat & Res, Lab Mycobacterial Dis & Cellular Immunol, Bethesda, MD 20892 USA. Univ Cattolica Sacro Cuore, Inst Microbiol, Rome, Italy. INSERM, U447, Inst Pasteur, Lille, France. RP US FDA, Ctr Biol Evaluat & Res, Lab Mycobacterial Dis & Cellular Immunol, Bldg 29,Rm 503,29 Lincoln Dr,HFM-431, Bethesda, MD 20892 USA. EM Brennan@cber.fda.gov RI Delogu, Giovanni/I-3701-2012 OI Delogu, Giovanni/0000-0003-0182-8267 NR 26 TC 55 Z9 57 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 EI 1098-5522 J9 INFECT IMMUN JI Infect. Immun. PD DEC PY 2004 VL 72 IS 12 BP 6799 EP 6805 DI 10.1128/IAI.72.12.6799-6805.2004 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 875WW UT WOS:000225453900006 PM 15557600 ER PT J AU Yamaguchi, R Momosaki, S Gao, G Hsia, CC Kojiro, M Scudamore, C Tabor, E AF Yamaguchi, R Momosaki, S Gao, G Hsia, CC Kojiro, M Scudamore, C Tabor, E TI Truncated hepatitis C virus core protein encoded in hepatocellular carcinomas SO INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE LA English DT Article DE hepatitis C virus; hepatocellular carcinoma; HCV core gene ID MOLECULAR-CLONING; LIVER-DISEASE; LOCALIZATION; DIVERSITY; GENOTYPES; GENOME AB Studies have suggested that a truncated form of the hepatitis C virus (HCV) core protein can enter hepatocyte nuclei and might play a role in HCV-associated hepatocarcinogenesis. In the present study, the HCV core gene from hepatocellular carcinomas (HCC) and/or adjacent nontumorous liver tissues from eight patients was amplified by nested RT-PCR and sequenced. Mutations in the HCV core gene that would encode a truncated core protein were found in 4 of the 8 patients. Since truncated core proteins have been shown to be capable of entry into the hepatocyte nucleus (unlike HCV itself, which is an exclusively cytoplasmic virus), the detection of mutated sequences encoding them in these four HCC patients suggests that these mutations may have played a role in the development of these HCCs. C1 US FDA, Div Emerging & Transfus Transmitted Dis, Rockville, MD 20852 USA. Kurume Univ, Dept Pathol, Kurume, Fukuoka 830, Japan. Univ British Columbia, Dept Surg, Vancouver, BC V5Z 1M9, Canada. RP Tabor, E (reprint author), US FDA, Ctr Biol Evaluat & Res, HFM-300,1401 Rockville Pike, Rockville, MD 20852 USA. EM tabor@cber.fda.gov NR 17 TC 4 Z9 4 U1 0 U2 0 PU PROFESSOR D A SPANDIDOS PI ATHENS PA 1, S MERKOURI ST, EDITORIAL OFFICE,, ATHENS 116 35, GREECE SN 1107-3756 J9 INT J MOL MED JI Int. J. Mol. Med. PD DEC PY 2004 VL 14 IS 6 BP 1097 EP 1100 PG 4 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 879JF UT WOS:000225712400022 PM 15547681 ER PT J AU Graham, DJ Staffa, JA Shatin, D Andrade, SE Schech, SD La Grenade, L Gurwitz, JH Chan, KA Goodman, MJ Platt, R AF Graham, DJ Staffa, JA Shatin, D Andrade, SE Schech, SD La Grenade, L Gurwitz, JH Chan, KA Goodman, MJ Platt, R TI Incidence of hospitalized rhabdomyolysis in patients treated with lipid-lowering drugs SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID STATIN-ASSOCIATED MYOPATHY; COA REDUCTASE INHIBITORS; PLASMA-CONCENTRATIONS; GEMFIBROZIL; CERIVASTATIN; THERAPY; ACID AB Context Lipid-lowering agents are widely prescribed in the United States. Reliable estimates of rhabdomyolysis risk with various lipid-lowering agents are not available. Objective To estimate the incidence of rhabdomyolysis in patients treated with different statins and fibrates, alone and in combination, in the ambulatory setting. Design, Setting, and Patients Drug-specific inception cohorts of statin and fibrate users were established using claims data from 11 managed care health plans across the United States. Patients with at least 180 days of prior health plan enrollment were entered into the cohorts between January 1, 1998, and June 30, 2001. Person-time was classified as monotherapy or combined statin-fibrate therapy. Main Outcome Measure Incidence rates of rhabdomyolysis per 10000 person-years of treatment, number needed to treat, and relative risk of rhabdomyolysis. Results In 252460 patients treated with lipid-lowering agents, 24 cases of hospitalized rhabdomyolysis occurred during treatment. Average incidence per 10000 person-years for monotherapy with atorvastatin, pravastatin, or simvastatin was 0.44 (95% confidence interval [CI], 0.20-0.84); for cerivastatin, 5.34 (95% Cl, 1.46-13.68); and for fibrate, 2.82 (95% Cl, 0.58-8.24). By comparison,. the incidence during unexposed person-time was 0 (95% Cl, 0-0.48; P=.056). The incidence increased to 5.98 (95% Cl, 0.72-216.0) for combined therapy of atorvastatin, pravastatin, or simvastatin with a fibrate, and to 1035 (95% Cl, 389-2117) for combined cerivastatin-fibrate use. Per year of therapy, the number needed to treat to observe 1 case of rhabdomyolysis was 22 727 for statin monotherapy, 484 for older patients with diabetes mellitus who were treated with both a statin and fibrate, and ranged from 9.7 to 12.7 for patients who were treated with cerivastatin plus fibrate. Conclusions Rhabdomyolysis risk was similar and low for monotherapy with atorvastatin, pravastatin, and simvastatin; combined statin-fibrate use increased risk, especially in older patients with diabetes mellitus. Cerivastatin combined with fibrate conferred a risk of approximately 1 in 10 treated patients per year. C1 US FDA, Off Drug Safety, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. Ctr Hlth Care Policy & Evaluat, Eden Prairie, MN USA. Fallon Fdn, Meyers Primary Care Inst, Worcester, MA USA. Univ Massachusetts, Sch Med, Amherst, MA 01003 USA. Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Harvard Pilgrim Hlth Care, Dept Ambulatory Care & Prevent, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. HealthPartners Res Fdn, Minneapolis, MN USA. RP Graham, DJ (reprint author), US FDA, Off Drug Safety, Ctr Drug Evaluat & Res, 5600 Fishers Ln,HFD-400, Rockville, MD 20857 USA. EM grahamd@cder.fda.gov OI Chan, Kinwei/0000-0001-8161-1986 FU FDA HHS [FD-U-002067, FD-U-002068] NR 30 TC 457 Z9 483 U1 3 U2 21 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD DEC 1 PY 2004 VL 292 IS 21 BP 2585 EP 2590 DI 10.1001/jama.292.21.2585 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 875GU UT WOS:000225409100021 PM 15572716 ER PT J AU Ivshina, AV Vodeiko, GM Kuznetsov, VA Volokhov, D Taffs, R Chizhikov, VI Levandowski, RA Chumakov, KM AF Ivshina, AV Vodeiko, GM Kuznetsov, VA Volokhov, D Taffs, R Chizhikov, VI Levandowski, RA Chumakov, KM TI Mapping of genomic segments of influenza B virus strains by an oligonucleotide microarray method SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID A VIRUS; HYBRIDIZATION; VACCINE; PCR; IDENTIFICATION; REASSORTANTS; EVOLUTION; ARRAYS AB Similar to other segmented RNA viruses, influenza viruses can exchange genome segments and form a wide variety of reassortant strains upon coreplication within a host cell. Therefore, the mapping of genome segments of influenza viruses is essential for understanding their phenotypes. In this work, we have developed an oligonucleotide microarray hybridization method for simultaneous genotyping of all genomic segments of two highly homologous strains of influenza B virus. A few strain-specific oligonucleotide probes matching each of the eight segments of the viral genomes of the B/Beijing/184/93 and B/Shangdong/7/97 strains were hybridized with PCR-amplified fluorescently labeled single-stranded DNA. Even though there were a few mismatches among the genomes of the studied virus strains, microarray hybridization showed highly significant and reproducible discrimination ability and allowed us to determine the origins of individual genomic segments in a series of reassortant strains prepared as vaccine candidates. Additionally, we were able to detect the presence of at least 5% of mixed genotypes in virus stocks even when conventional sequencing methods failed, for example, for the NS segment. Thus, the proposed microarray method can be used for (i) rapid and reliable genome mapping of highly homologous influenza B viruses and (ii) extensive monitoring of influenza B virus reassortants and the mixed genotypes. The array can be expanded by adding new oligoprobes and using more quantitative assays to determine the origin of individual genomic segments in series of reassortant strains prepared as vaccine candidates or in mixed virus populations. C1 US FDA, CBER, Rockville, MD 20852 USA. SRA Int Inc, Bethesda, MD USA. RP Chumakov, KM (reprint author), US FDA, CBER, 1401 Rockville Pike,HFM-470, Rockville, MD 20852 USA. EM chumakov@cber.fda.gov NR 25 TC 18 Z9 23 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD DEC PY 2004 VL 42 IS 12 BP 5793 EP 5801 DI 10.1128/JCM.42.12.5793-5801.2004 PG 9 WC Microbiology SC Microbiology GA 883SK UT WOS:000226035800053 PM 15583314 ER PT J AU Cantilena, LR Katki, AG Klecker, RW Collins, JM AF Cantilena, LR Katki, AG Klecker, RW Collins, JM TI Metabolism by N-acetyltransferase 1 in vitro and in healthy volunteers: A prototype for targeted inhibition SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article DE NATI; p-aminosulicylate; drug metabolism; drug interactions; sulfamethoxazole ID ARYLAMINE N-ACETYLTRANSFERASES; CLINICAL CONSEQUENCES; PHARMACOGENETICS; ACETYLATION; NAT1 AB Inhibition of drug metabolism is generally avoided but can be useful in limited circumstances, such as reducing the formation of toxic metabolites. Acetylation is a major pathway for drug elimination that can also convert substrates into toxic species, including carcinogens. Sulfamethoxazole, a widely used antibiotic, is metabolized via arylamine N-acetyltransferase 1. p-Aminosolicylate, used for antitubercular treatment, is also metabolized by N-acetyltransferase 1 and could potentially inhibit sulfamethoxazole metabolism. Human hepatocytes from 4 donors were incubated in vitro with sulfamethoxazole and p-aminosalicylate at clinically achievable concentrations. p-Aminosalicylate competitively reduced the acetylation of sulfamethoxazole in vitro by 61% to 83% at 200 muM. Four healthy volunteers were studied following doses of 500 mg sulfamethoxazole either alone or during administration of p-aminosalicylate (4 g ter in die). Plasma concentrations of p-aminosalicylate exceeded 100 muM. With each subject as his or her own control, p-aminosalicylate reduced by 5-fold the ratio of plasma concentrations of acetylsulfamethoxazole relative to parent drug (P < .001). Metabolic drug-drug interaction studies in vitro successfully predicted inhibition of acetylation via N-acetyltransferase 1 in vivo, Although no specific toxic species was investigated in this work, the potential was demonstrated for improving the therapeutic index of drugs that have toxic metabolites. C1 Uniformed Serv Univ Hlth Sci, Div Clin Pharmacol & Med Toxicol, Bethesda, MD 20814 USA. US FDA, Lab Clin Pharmacol, Rockville, MD 20857 USA. RP Cantilena, LR (reprint author), Uniformed Serv Univ Hlth Sci, Div Clin Pharmacol & Med Toxicol, Bldg 53,4301 Jones Bridge Rd, Bethesda, MD 20814 USA. NR 17 TC 3 Z9 3 U1 1 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD DEC PY 2004 VL 44 IS 12 BP 1405 EP 1411 DI 10.1177/0091270004270224 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 871YV UT WOS:000225173500009 PM 15545312 ER PT J AU Fifadara, DH Averbukh, A Channin, DS Badano, A AF Fifadara, DH Averbukh, A Channin, DS Badano, A TI Effect of viewing angle on luminance and contrast for a five-million-pixel monochrome display and a nine-million-pixel color liquid crystal display SO JOURNAL OF DIGITAL IMAGING LA English DT Article DE active-matrix liquid crystal display (AMLCD); viewing angle; gray-scale display function (GSDF) ID PERFORMANCE AB Digital imaging systems used in radiology rely on electronic display devices to present images to human observers. Active-matrix liquid crystal displays (AMLCDs) continue to improve and are beginning to be considered for diagnostic image display. In spite of recent progress, AMLCDs are characterized by a change in luminance and contrast response with changes in viewing direction. In this article, we characterize high pixel density AMLCDs (a five-million-pixel monochrome display and a nine-million-pixel color display) in terms of the effect of viewing angle on their luminance and contrast response. We measured angular luminance profiles using a custom-made computer-controlled goniometric instrument and a conoscopic Fourier-optics instrument. We show the angular luminance response as a function of viewing angle, as well as the departure of the measured contrast from the desired response. Our findings indicate small differences between the five-million-pixel (5 MP) and the nine-million-pixel (9 MP) AMLCDs. The 9 MP shows lower variance in contrast with changes in viewing angle, whereas the 5 MP provides a slightly better GSDF compliance for off-normal viewing. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. Northwestern Univ, Sch Med, Dept Radiol, Chicago, IL 60611 USA. RP Badano, A (reprint author), US FDA, Ctr Devices & Radiol Hlth, 12720 Twinbrook Pkwy, Rockville, MD 20857 USA. EM agb@cdrh.fda.gov OI Channin, David/0000-0002-3064-6270; badano, aldo/0000-0003-3712-6670 NR 6 TC 6 Z9 7 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 DEC PY 2004 VL 17 IS 4 BP 264 EP 270 DI 10.1007/s10278-004-1021-7 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 887MU UT WOS:000226311000006 PM 15692870 ER PT J AU Devadas, K Hardegen, NJ Wahl, LM Hewlett, IK Clouse, KA Yamada, KM Dhawan, S AF Devadas, K Hardegen, NJ Wahl, LM Hewlett, IK Clouse, KA Yamada, KM Dhawan, S TI Mechanisms for macrophage-mediated HIV-1 induction SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; TUMOR-NECROSIS-FACTOR; NF-KAPPA-B; ACTIVE ANTIRETROVIRAL THERAPY; INFECTED U1 CELLS; LONG TERMINAL REPEAT; FACTOR-ALPHA; T-CELLS; ENDOTHELIAL-CELLS; TNF-ALPHA AB Viral latency is a long-term pathogenic condition in patients infected with HIV-1. Low but sustained virus replication in chronically infected cells can be activated by stimulation with proinflammatory cytokines such as TNF-alpha, IL-1 beta, or other host factors. However, the precise mechanism by which cellular activation induces. latently infected cells to produce virions has remained unclear. In the present report, we present evidence that activation of HIV-1 replication in latently infected U1 or ACH2 cells by human macrophages is mediated by a rapid nuclear localization of NF-kappaB p50/p65 dimer with concomitant increased expression of proinflammatory cytokines. Multiplexed RT-PCR amplification of mRNA isolated from cocultures of macrophages and U1 and ACH2 cells showed significant induction of IL-1beta, IL-6, IL-8, TNF-alpha, and TGF-beta expression within 3 h of coincubation. Fixation of macrophages, U-1, or ACH2 cells with paraformaldehyde before coculture completely abrogated the induction of NF-kappaB subunits and HIV-1 replication, suggesting that cooperative interaction between the two cell types is an essential process for cellular activation. Pretreatment of macrophage-U1 or macrophage-ACH2 cocultures with neutralizing anti-TNF-alpha Ab down-regulated the replication of HIV-1. In addition, pretreatment of macrophage-U1 or macrophage-ACH2 cocultures with the NF-kappaB inhibitor (E)3-[(4-methylphenyl)sulfonyl]-2-propenenitrile (BAY 11-7082) prevented the induction of cytokine expression, indicating a pivotal role of NF-kappaB-mediated signaling in the reactivation of HIV-1 in latently infected cells by macrophages. These results provide a mechanism by which macrophages induce HIV-1 replication in latently infected cells. C1 US FDA, Immunopatholgenesis Sect, Mol Virol Lab, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. Natl Inst Dent & Craniofacial Res, Cellular Immunol Sect, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. Natl Inst Dent & Craniofacial Res, Dev Mech Sect, Cranofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD 20892 USA. RP Devadas, K (reprint author), US FDA, Immunopatholgenesis Sect, Mol Virol Lab, Ctr Biol Evaluat & Res, 1401 Rockville Pike HFM-315, Rockville, MD 20852 USA. EM devadas@cber.fda.gov; dhawan@cber.fda.gov OI Yamada, Kenneth/0000-0003-1512-6805 NR 66 TC 27 Z9 28 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 1 PY 2004 VL 173 IS 11 BP 6735 EP 6744 PG 10 WC Immunology SC Immunology GA 873UV UT WOS:000225307500030 PM 15557166 ER PT J AU Kim, YH Moody, JD Freeman, JP Brezna, B Engesser, KH Cerniglia, CE AF Kim, YH Moody, JD Freeman, JP Brezna, B Engesser, KH Cerniglia, CE TI Evidence for the existence of PAH-quinone reductase and catechol-O-methyltransferase in Mycobacterium vanhaalenii PYR-1 SO JOURNAL OF INDUSTRIAL MICROBIOLOGY & BIOTECHNOLOGY LA English DT Article DE quinone reductase; catechol-O-methyltransferase; polycyclic aromatic hydrocarbon ID POLYCYCLIC AROMATIC-HYDROCARBONS; SP STRAIN PYR-1; DEGRADING MYCOBACTERIUM; DIHYDRODIOL DEHYDROGENASE; PYRENE DEGRADATION; VANBAALENII PYR-1; METABOLISM; PHENANTHRENE; IDENTIFICATION; FLUORANTHENE AB Polycyclic aromatic hydrocarbon (PAH) quinone reductase (PQR) and catechol-O-methyltransferase (COMT), from the PAH-degrading Mycobacterium vanbaalenii PYR-1, were demonstrated to be constitutive enzymes located in the soluble fraction of cell extracts. PQR activities for the reduction of 9,10-phenanthrenequinone and 4,5-pyrene- quinone were 1.40+/-0.13 and 0.12+/-0.01 mumol min(-1) mg-protein(-1) respectively. The exogenous catechols alizarin, anthrarobin, 2,3-dihydroxynaphthalene and esculetin inhibited PQR activity. Anthrarobin (100 muM) and esculetin (100 muM) inhibited 4,5-pyrenequinone reduction by 64-92%. COMT was involved in the O-methylation of 1,2-dihydroxyphenanthrene to form 1-methoxy-2-hydroxyphenanthrene and 1,2-dimethoxyphenanthrene. Both pyrene and 1-hydroxypyrene were metabolized by M. vanbaalenii PYR-1 to form 1-methoxypyrene, 1-methoxy-2-hydroxypyrene, 1-hydroxy-2-methoxypyrene and 1,2-dimethoxypyrene. Among the catechols tested, anthrarobin showed the highest COMT activity (1.06+/-0.04 nmol/30 min(-1) mg-protein(-1)). These results suggest that the PQR and COMT activities of M. vanbaalenii PYR-1 may play an important role in the detoxification of PAH catechols. C1 US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. US FDA, Natl Ctr Toxicol Res, Dept Chem, Jefferson, AR 72079 USA. Slovak Acad Sci, Inst Mol Biol, Bratislava 84551, Slovakia. Univ Stuttgart, Abt Biol Abluftreinigung, ISWA, D-7000 Stuttgart, Germany. 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 32 TC 33 Z9 35 U1 1 U2 15 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1367-5435 J9 J IND MICROBIOL BIOT JI J. Ind. Microbiol. Biotechnol. PD DEC PY 2004 VL 31 IS 11 BP 507 EP 516 DI 10.1007/s10295-004-0178-x PG 10 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 887BF UT WOS:000226276600004 PM 15549609 ER PT J AU Kawakami, K Kawakami, M Kioi, M Husain, SR Puri, RK AF Kawakami, K Kawakami, M Kioi, M Husain, SR Puri, RK TI Distribution kinetics of targeted cytotoxin in glioma by bolus or convection-enhanced delivery in a murine model SO JOURNAL OF NEUROSURGERY LA English DT Article DE brain tumor; cytotoxin; convection-enhanced delivery; continuous infusion; toxicity; maximum tolerated dose; mouse ID RECEPTOR ALPHA-2 CHAIN; INTERLEUKIN-13 RECEPTOR; BRAIN-TUMORS; PSEUDOMONAS EXOTOXIN; IL-13 RECEPTOR; INFUSION; THERAPY; PROTEIN; CARCINOMA; BINDING AB Object. Interleukin-13 receptor (IL-13R)-targeted cytotoxin (IL-13-PE38) displays a potent antitumor activity against a variety of human tumors including glioblastoma multiforme (GBM) and, thus, this agent is being tested in the clinical trial for the treatment of recurrent GBM. In this study, the authors determined the safety and distribution kinetics of IL-13 cytotoxin when infused intracranially by a bolus injection and by convection-enhanced delivery (CED) in an athymic nude mouse model of GBM. Methods. For the safety studies, athymic nude mice were given intracranial infusions of IL-13 cytotoxin into normal parenchyma by either a bolus injection or a 7-day-long CED. Toxicity was assessed by performing a histological examination of the mouse brains. For the drug distribution studies, nude mice with intracranially implanted U251 GBM tumors were given an intratumor bolus or a CED infusion of IL-13 cytotoxin. Brain tumor samples obtained between 0.25 and 72 hours after the infusion were assessed for drug distribution kinetics by performing immunohistochemical and Western blot analyses. Based on the histological changes in the tumor and brain, the maximum tolerated dose of intracranial IL-13 cytotoxin infusion in nude mice was determined to be 4 mug when delivered by a bolus injection and 10 mug when CED was used. Drug distribution reached the maximum level I hour after the bolus injection and the volume of distribution was determined to be 19.3 +/- 5.8 mm(3). Interleukin-13 cytotoxin was barely detectable 6 hours after the injection. Interestingly, when delivered by bolus injections IL-13 cytotoxin exhibited superior distribution in larger rather than smaller tumors. Convection-enhanced delivery was superior for drug distribution in the U251 tumors because when CED was used the drug remained in the tumors 6 hours after the infusion. Conclusions. These studies provide confirmation of a previous hypothesis that CED of IL-13 cytotoxin is superior to bolus injections not only for the safety of the normal brain but also for maintaining drug levels for a prolonged period in infused brain tumors. These findings are highly relevant and important for the optimal clinical development of IL-13 cytotoxin or any other targeted antitumor agent for GBM therapy, in which multiple routes of delivery of an agent are being contemplated. C1 NIH, Food & Drug Adm, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapy,Lab Mol Tumor Biol, Bethesda, MD 20892 USA. RP Puri, RK (reprint author), NIH, Food & Drug Adm, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapy,Lab Mol Tumor Biol, Bldg 29B,Room 2NN10,29 Lincoln Dr,MSC 4555, Bethesda, MD 20892 USA. EM pufi@cber.fda.gov OI Kioi, Mitomu/0000-0002-7981-3340 NR 32 TC 47 Z9 48 U1 0 U2 2 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD DEC PY 2004 VL 101 IS 6 BP 1004 EP 1011 DI 10.3171/jns.2004.101.6.1004 PG 8 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 879CY UT WOS:000225695200016 PM 15597761 ER PT J AU Aidoo, A Bishop, ME Shelton, S Lyn-Cook, LE Chen, T Manjanatha, MG AF Aidoo, A Bishop, ME Shelton, S Lyn-Cook, LE Chen, T Manjanatha, MG TI The role of dietary daidzein and genistein in 7,12-dimethylbenz[a]anthracene (DMBA)-induced genotoxicity in rat uterus. SO JOURNAL OF NUTRITION LA English DT Meeting Abstract CT International Research Conference on Food, Nutrition, and Cancer CY JUL 15-16, 2004 CL Washington, DC SP Amer Inst Canc Res, World Canc Res Fund Int, BASF Aktiengesellsch, Campbell Soup Co, Cranberry Inst, Danisco USA Inc, DSM Nutr Products Inc, Hills Pet Nutr Inc, Kellogg Co, Natl Fisheries Inst, Solae Co, United Soybean Board C1 US FDA, Jefferson Labs, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD DEC PY 2004 VL 134 IS 12 SU S BP 3539S EP 3539S PG 1 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 880FR UT WOS:000225774900088 ER PT J AU Li, QH Lagakos, SW AF Li, QH Lagakos, SW TI Comparisons of test statistics arising from marginal analyses of multivariate survival data SO LIFETIME DATA ANALYSIS LA English DT Article DE directional tests; marginal model; multivariate survival data; omnibus test; recurring events ID FAILURE TIME DATA; HUMAN-IMMUNODEFICIENCY-VIRUS; REGRESSION-ANALYSIS; ZIDOVUDINE; DIDANOSINE; INFECTION; HAZARDS; MODELS AB We investigate the properties of several statistical tests for comparing treatment groups with respect to multivariate survival data, based on the marginal analysis approach introduced by Wei, Lin and Weissfeld ["Regression Analysis of multivariate incomplete failure time data by modelling marginal distributians," JASA vol. 84 pp. 1065-1073]. We consider two types of directional tests, based on a constrained maximization and on linear combinations of the unconstrained maximizer of the working likelihood function, and the omnibus test arising from the same working likelihood. The directional tests are members of a larger class of tests, from which an asymptotically optimal test can be found. We compare the asymptotic powers of the tests under general contiguous alternatives for a variety of settings, and also consider the choice of the number of survival times to include in the multivariate outcome. We illustrate the results with simulations and with the results from a clinical trial examining recurring opportunistic infections in persons with HIV. C1 US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Li, QH (reprint author), US FDA, Ctr Drug Evaluat & Res, HFD 705, Rockville, MD 20857 USA. EM liq@cder.fda.gov; lagakos@hsph.harvard.edu FU NIAID NIH HHS [AI24643] NR 16 TC 4 Z9 4 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1380-7870 J9 LIFETIME DATA ANAL JI Lifetime Data Anal. PD DEC PY 2004 VL 10 IS 4 BP 389 EP 405 DI 10.1007/s10985-004-4774-x PG 17 WC Mathematics, Interdisciplinary Applications; Statistics & Probability SC Mathematics GA 890OB UT WOS:000226519600006 PM 15690992 ER PT J AU Badano, A Fifadara, DH AF Badano, A Fifadara, DH TI Goniometric and conoscopic measurements of angular display contrast for one-, three-, five-, and nine-million-pixel medical liquid crystal displays SO MEDICAL PHYSICS LA English DT Article DE liquid crystal display; medical display; luminance response; display contrast; viewing angle AB Active-matrix liquid crystal displays (AMLCDs) have become the preferred choice for displaying digital diagnostic images because of their low cost of ownership, high contrast, and small footprint. However, the contrast and luminance of AMLCDs changes significantly with viewing direction. In this paper, we use a goniometric and a conoscopic method to measure angular contrast and luminance in one-, three-, five-, and nine-million-pixel medical AMLCDs. The viewing angle characteristics of the displays are compared by evaluating the compliance with the desired grayscale and recommended tolerance limits. Using the measured contrast responses, we determined the angle along each of the orthogonal and diagonal axes for which the luminance ratio drops to 0.5, 0.2, and 0.1 of the maximum ratio, seen at perpendicular viewing. The results show a reduction as large as 54% in available JND levels between the perpendicular and off-normal viewing directions. All of the display systems proved to have better angular response in the horizontal and vertical direction as compared to the diagonal directions, and none were able to satisfy a 20% contrast tolerance limit for any viewing direction lying in a cone at an angle of 45degrees from the normal. Additionally, we show that the measured contrast can be significantly affected by the measurement method used to record the angular change in luminance. (C) 2004 American Association of Physicists in Medicine. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Badano, A (reprint author), US FDA, Ctr Devices & Radiol Hlth, 12720 Twinbrook Pkwy, Rockville, MD 20857 USA. EM aldo.badano@fda.hhs.gov OI badano, aldo/0000-0003-3712-6670 NR 7 TC 11 Z9 11 U1 0 U2 1 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD DEC PY 2004 VL 31 IS 12 BP 3452 EP 3460 DI 10.1118/1.1824198 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 882FD UT WOS:000225923600031 PM 15651628 ER PT J AU Al-Khaldi, SF Myers, KM Rasooly, A Chizhikov, V AF Al-Khaldi, SF Myers, KM Rasooly, A Chizhikov, V TI Genotyping of Clostridium perfringens toxins using multiple oligonucleotide microarray hybridization SO MOLECULAR AND CELLULAR PROBES LA English DT Article DE DNA microarray; Clostridium perfringens; multiplex PCR ID ESCHERICHIA-COLI; ALPHA-TOXIN; ASSAY; IDENTIFICATION; SEQUENCE; HOMOLOGY AB A microarray-based method for characterization of six Clostridium perfringens toxin genes: iA (iota toxin), cpa (alpha toxin), cpe (enterotoxin E), etxD (epsilon toxin), cpb1 (beta toxin 1),and cpb2 (beta toxin 2) was developed and evaluated using 17 C. perfringens isolates. Three individual oligonucleotide probes (oligoprobes), complementary to the unique sequences of each toxin gene, were designed and immobilized on a surface of aldehyde-coated glass slides. Multiplex PCR was used to simultaneously amplify DNA target regions of all six genes. Single-stranded DNA (ssDNA) samples for microarray analysis were prepared by following a primer extension of amplicons in the presence of one primer. Fluorescent moieties (Cy3) were incorporated into the ssDNA by chemical modification of guanine bases. The presence of toxin genes in C. perfringens was established by hybridization of the fluorescently labeled ssDNA representing different samples to the microarray gene-specific oligoprobes. Results of the study showed sensitivity and specificity of genotyping C. perfringens using multiple microarray-based assays. Published by Elsevier Ltd. C1 US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. RP Al-Khaldi, SF (reprint author), FDA CF SAN, Div Microbiol Studies, HFS-517,5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM sufian.al-khaldi@cfsan.fda.gov NR 17 TC 29 Z9 32 U1 0 U2 3 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0890-8508 J9 MOL CELL PROBE JI Mol. Cell. Probes PD DEC PY 2004 VL 18 IS 6 BP 359 EP 367 DI 10.1016/j.mcp.2004.05.006 PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Cell Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Cell Biology GA 867OO UT WOS:000224852100001 PM 15488374 ER PT J AU Hanna, GM AF Hanna, GM TI Nonequivalence behavior studies for the direct determination of enantiomeric purity and absolute configuration of timolol by NMR SO PHARMAZIE LA English DT Article ID PERFORMANCE LIQUID-CHROMATOGRAPHY; CHIRAL STATIONARY PHASE; BETA-BLOCKERS; ALPHA-1-ACID GLYCOPROTEIN; BLOCKING-AGENTS; HUMAN-PLASMA; RESOLUTION; SEPARATION; COLUMN; DERIVATIVES AB Direct determination of both the enantiomeric purity and absolute configuration of timolol was accomplished utilizing H-1 NMR (400 MHz) spectroscopy with fast diamagnetic chiral solvating agent to dissimilarly perturb the spectra of enantionneric solutes. Nonequivalence behavior was studied for all variables that affect populations and intrinsic spectra of the diastereomeric solvates. Optimization of the experimental conditions in terms of probe temperature, substrate concentration and solvating agent to substrate molar equivalents provided resolved enantionneric signals suitable not only for chiral recognition but also for quantification. Enantiomeric impurity was determined on the basis of relative intensities of the tert-butyl methyl protons resonances; the assignment of enantionneric configuration was based on the relative field positions of these resonances. The analysis of synthetic mixtures of the enantiomers by the proposed NMR method resulted in assay values which agreed closely with the known quantities of each enantiomer in mixtures tested. The mean +/-SD recovery values for the (R)-(+)-enantiomer was 100.0+/-1.6% of added antipode (n = 8). The optically pure enantiomers were used to establish the minimum detection limits of 0.1%. The developed methodology represents a rapid and powerful tool for regulatory analysis. C1 US Dept HHS, US FDA, NE Reg Lab, Jamaica, NY 11435 USA. RP Hanna, GM (reprint author), US Dept HHS, US FDA, NE Reg Lab, 158-15 Liberty Ave, Jamaica, NY 11435 USA. NR 33 TC 3 Z9 3 U1 0 U2 0 PU GOVI-VERLAG PHARMAZEUTISCHER VERLAG GMBH PI ESCHBORN PA PHARMAZEUTISCCARL MANNICH STR 26, D-65760 ESCHBORN, GERMANY SN 0031-7144 J9 PHARMAZIE JI Pharmazie PD DEC PY 2004 VL 59 IS 12 BP 923 EP 928 PG 6 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 879GO UT WOS:000225704600005 PM 15638079 ER PT J AU Stamatas, GN Zmudzka, BZ Kollias, N Beer, JZ AF Stamatas, GN Zmudzka, BZ Kollias, N Beer, JZ TI Non-invasive measurements of skin pigmentation in situ SO PIGMENT CELL RESEARCH LA English DT Review DE melanin; reflectance; spectroscopy; imaging; in vivo ID DIFFUSE-REFLECTANCE SPECTROSCOPY; ULTRAVIOLET-RADIATION; SPECTROPHOTOMETRIC EVALUATION; CONSTITUTIVE PIGMENTATION; TRISTIMULUS COLORIMETRY; OPTICAL-PROPERTIES; EPIDERMAL MELANIN; INDUCED ERYTHEMA; COLOR; INVIVO AB Objective in situ measurements of skin pigmentation are needed for accurate documentation of pigmentation disorders, in studies of constitutive and induced skin pigmentation, for testing of the efficacy of pro-pigmentation or de-pigmentation agents, etc. Non-invasive instrumental measurements of skin pigmentation have been used for many decades. All are based on the ability of melanin to attenuate light. However, hemoglobin in dermal capillaries also attenuates light and needs to be accounted for when pigmentation is assessed. The methods under consideration include: (a) single point measurements, in which light reflected from a defined skin area is collected and a pigment index is calculated representing the average pigmentation over the examined area, and (b) imaging methods that attempt to generate a concentration distribution map of melanin pigment for the skin area being imaged. In this article, we describe the potentials and the limitations of the different approaches to both single point and imaging methods. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. Johnson & Johnson Consumer Prod Inc, Methods & Models Dev, Skillman, NJ 08558 USA. RP Beer, JZ (reprint author), US FDA, Ctr Devices & Radiol Hlth, HFZ-112,9200 Corp Blvd, Rockville, MD 20850 USA. EM janusz.beer@fda.hhs.gov NR 60 TC 96 Z9 102 U1 0 U2 12 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0893-5785 J9 PIGM CELL RES JI Pigm. Cell. Res. PD DEC PY 2004 VL 17 IS 6 BP 618 EP 626 DI 10.1111/j.1600-0749.2004.00204.x PG 9 WC Cell Biology; Dermatology SC Cell Biology; Dermatology GA 874SK UT WOS:000225369900003 PM 15541019 ER PT J AU Jennings, SF Ptitsyn, AA Wilkins, D Bruhn, RE Slikker, W Wren, JD AF Jennings, SF Ptitsyn, AA Wilkins, D Bruhn, RE Slikker, W Wren, JD TI Regional societies: Fostering competitive research through virtual infrastructures SO PLOS BIOLOGY LA English DT Editorial Material C1 Univ Arkansas, Dept Appl Sci, Little Rock, AR 72204 USA. Louisiana State Univ Syst, Pennington Biomed Res Ctr, Baton Rouge, LA USA. Univ Mississippi, Dept Comp & Informat Sci, University, MS 38677 USA. Univ Arkansas, Dept Informat Sci, Little Rock, AR 72204 USA. US FDA, Natl Ctr Toxicol Res, Rockville, MD 20857 USA. Univ Oklahoma, Dept Bot & Microbiol, Adv Ctr Genome Technol, Norman, OK 73019 USA. RP Jennings, SF (reprint author), Univ Arkansas, Dept Appl Sci, Little Rock, AR 72204 USA. EM sfjennings@ualr.edu RI Wren, Jonathan/E-5611-2011; OI Wren, Jonathan/0000-0003-2776-3545; Ptitsyn, Andrey/0000-0003-1196-8757 NR 0 TC 2 Z9 2 U1 0 U2 1 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1544-9173 J9 PLOS BIOL JI PLoS. Biol. PD DEC PY 2004 VL 2 IS 12 BP 2039 EP 2040 AR e372 DI 10.1371/journal.pbio.0020372 PG 2 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 884QA UT WOS:000226099600006 PM 15597114 ER PT J AU Turner, EH AF Turner, EH TI A taxpayer-funded clinical trials registry and results database - It already exists within the US food and drug administration SO PLOS MEDICINE LA English DT Editorial Material ID PAROXETINE C1 US FDA, Rockville, MD 20857 USA. RP Turner, EH (reprint author), Portland VA Med Ctr, Mood Disorders Program, Portland, OR USA. EM turnere@ohsu.edu RI Turner, Erick/A-4848-2008 OI Turner, Erick/0000-0002-3522-3357 NR 16 TC 39 Z9 41 U1 0 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1549-1277 J9 PLOS MED JI PLos Med. PD DEC PY 2004 VL 1 IS 3 BP 180 EP 182 AR e60 DI 10.1371/journal.pmed.0010060.g001 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 902TH UT WOS:000227378900009 PM 15562322 ER PT J AU Kim, SJ Jones, RC Cha, CJ Kweon, O Edmondson, RD Cerniglia, CE AF Kim, SJ Jones, RC Cha, CJ Kweon, O Edmondson, RD Cerniglia, CE TI Identification of proteins induced by polycyclic aromatic hydrocarbon in Mycobacterium vanbaalenii PYR-1 using two-dimensional polyacrylamide gel electrophoresis and de novo sequencing methods SO PROTEOMICS LA English DT Article DE de novo sequencing; Mycobacterium vanbaalenii PYR-1; polycyclic aromatic hydrocarbons; protein identificaion; two-dimensional protein profiles ID SP STRAIN PYR-1; ESCHERICHIA-COLI; ENTEROCOCCUS-FAECALIS; PROTEOME ANALYSIS; DEGRADING MYCOBACTERIUM; MASS-SPECTROMETRY; STRESS-PROTEINS; DEGRADATION; EXPRESSION; BACTERIUM AB Protein profiles of Mycobacterium vanbaalenii PYR-1 grown in the presence of high-molecular-weight polycyclic aromatic hydrocarbons (HMW PAHs) were examined by two-dimensional gel electrophoresis (2-DE). Cultures of M. vanbaalenii PYR-1 were incubated with pyrene, pyrene-4,5-quinone (PQ), phenanthrene, anthracene, and fluoranthene. Soluble cellular protein fractions were analyzed and compared, using immobilized pH gradient (IPG) strips. More than 1000 gel-separated proteins were detected using a 2-DE analysis program within the window of isoelectric point (pI) 4-7 and a molecular mass range of 10100 kDa. We observed variations in the protein composition showing the upregulation of multiple proteins for the five PAH treatments compared with the uninduced control sample. By N-terminal sequencing or mass spectrometry, we further analyzed the proteins separated by 2-DE. Due to the lack of genome sequence information for this species, protein identification provided an analytical challenge. Several PAH-induced proteins were identified including a catalase-peroxidase, a putative monooxygenase, a dioxygenase small subunit, a small subunit of naphthalene-inducible dioxygenase, and aldehyde dehydrogenase. We also identified proteins related to carbohydrate metabolism (enolase, 6-phosphogluconate dehydrogenase, indole-3-glycerol phosphate synthase, and fumarase), DNA translation (probable elongation factor Tsf), heat shock proteins, and energy production (ATP synthase). Many proteins from M. vanbaalenii PYR-1 showed similarity with protein sequences from M. tuberculosis and M. leprae. Some proteins were detected uniquely upon exposure to a specific PAH whereas others were common to more than one PAH, which indicates that induction triggers not only specific responses but a common response in this strain. C1 US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. US FDA, Natl Ctr Toxicol Res, Div Chem, Jefferson, AR 72079 USA. Chungang Univ, Dept Biotechnol, Ansong, South Korea. RP Cerniglia, CE (reprint author), US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. EM ccerniglia@nctr.fda.gov NR 46 TC 45 Z9 47 U1 2 U2 12 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1615-9853 J9 PROTEOMICS JI Proteomics PD DEC PY 2004 VL 4 IS 12 BP 3899 EP 3908 DI 10.1002/pmic.200400872 PG 10 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 880PH UT WOS:000225801200019 PM 15540208 ER PT J AU Stone, HB Moulder, JE Coleman, CN Ang, KK Anscher, MS Barcellos-Hoff, MH Dynan, WS Fike, JR Grdina, DJ Greenberger, JS Hauer-Jensen, M Hill, RP Kolesnick, RN MacVittie, TJ Marks, C McBride, WH Metting, N Pellmar, T Purucker, M Robbins, ME Schiestl, RH Seed, TM Tomaszewski, JE Travis, EL Wallner, PE Wolpert, M Zaharevitz, D AF Stone, HB Moulder, JE Coleman, CN Ang, KK Anscher, MS Barcellos-Hoff, MH Dynan, WS Fike, JR Grdina, DJ Greenberger, JS Hauer-Jensen, M Hill, RP Kolesnick, RN MacVittie, TJ Marks, C McBride, WH Metting, N Pellmar, T Purucker, M Robbins, ME Schiestl, RH Seed, TM Tomaszewski, JE Travis, EL Wallner, PE Wolpert, M Zaharevitz, D TI Models for evaluating agents intended for the prophylaxis, mitigation and treatment of radiation injuries - Report of the NCI workshop, December 3-4, 2003 SO RADIATION RESEARCH LA English DT Article ID ANGIOTENSIN-CONVERTING ENZYME; CENTRAL-NERVOUS-SYSTEM; KERATINOCYTE GROWTH-FACTOR; HEMATOPOIETIC STEM-CELLS; MARROW TRANSPLANT NEPHROPATHY; PROTEASE-ACTIVATED RECEPTOR-1; CHRONIC OXIDATIVE STRESS; TOTAL-BODY IRRADIATION; INDUCED LUNG TOXICITY; NORMAL TISSUE-INJURY AB To develop approaches to prophylaxis/protection, mitigation and treatment of radiation injuries, appropriate models are needed that integrate the complex events that occur in the radiation-exposed organism. While the spectrum of agents in clinical use or preclinical development is limited, new research findings promise improvements in survival after whole-body irradiation and reductions in the risk of adverse effects of radiotherapy. Approaches include agents that act on the initial radiochemical events, agents that prevent or reduce progression of radiation damage, and agents that facilitate recovery from radiation injuries. While the mechanisms of action for most of the agents with known efficacy are yet to be fully determined, many seem to be operating at the tissue, organ or whole animal level as well as the cellular level. Thus research on prophylaxis/protection, mitigation and treatment of radiation injuries will require studies in whole animal models. Discovery, development and delivery of effective radiation modulators will also require collaboration among researchers in diverse fields such as radiation biology, inflammation, physiology, toxicology, immunology, tissue injury, drug development and radiation oncology. Additional investment in training more scientists in radiation biology and in the research portfolio addressing, radiological and nuclear terrorism would benefit the general population in case of a radiological terrorism event or a large-scale accidental event as well as benefit patients treated with radiation. (C) 2004 by Radiation Research Society. C1 NCI, Bethesda, MD USA. Med Coll Wisconsin, Milwaukee, WI USA. MD Anderson Cancer Ctr, Houston, TX USA. Duke Univ, Med Ctr, Durham, NC USA. Lawrence Berkely Natl Lab, Berkeley, CA USA. Med Coll Georgia, Augusta, GA USA. Univ Calif San Francisco, San Francisco, CA USA. Univ Chicago, Chicago, IL USA. Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. Univ Arkansas Med Sci, Little Rock, AR USA. Princess Margaret Hosp, Ontario Canc Inst, Toronto, ON, Canada. Mem Sloan Kettering Canc Ctr, New York, NY USA. Univ Maryland, Baltimore, MD USA. Univ Calif Los Angeles, Los Angeles, CA USA. Dept Energy, Germantown, MD USA. Uniformed Serv Univ Hlth Sci, AFRRI, Bethesda, MD USA. US FDA, Rockville, MD USA. Wake Forest Univ, Sch Med, Winston Salem, NC USA. Catholic Univ Amer, Washington, DC USA. RP Stone, HB (reprint author), EPN 6015A,6130 Executive Blvd,MSC 7440, Bethesda, MD 20892 USA. EM stoneh@mail.nih.gov RI Moulder, John/E-6799-2012 FU NCI NIH HHS [R01 CA098239, R01 CA098239-01A2] NR 197 TC 155 Z9 160 U1 3 U2 10 PU RADIATION RESEARCH SOC PI LAWRENCE PA 810 E TENTH STREET, LAWRENCE, KS 66044 USA SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD DEC PY 2004 VL 162 IS 6 BP 711 EP 728 DI 10.1667/RR3276 PG 18 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA 873ED UT WOS:000225261400014 PM 15548121 ER PT J AU Contrera, JF Matthews, EJ Kruhlak, NL Benz, RD AF Contrera, JF Matthews, EJ Kruhlak, NL Benz, RD TI Estimating the safe starting dose in phase I clinical trials and no observed effect level based on QSAR modeling of the human maximum recommended daily dose SO REGULATORY TOXICOLOGY AND PHARMACOLOGY LA English DT Article DE quantitative structure activity relationship; maximum recommended daily dose; maximum recommended safe starting dose; E-state descriptors; predictive modeling; safety factors; in silico modeling; phase 1 clinical trials; no observed adverse effect level; predictive toxicology ID VARIABLE SELECTION; STATE INDEXES; TOXICITY DATA; PHARMACEUTICALS; SIMILARITY AB Estimating the maximum recommended starting dose (MRSD) of a pharmaceutical for phase I human clinical trials and the no observed effect level (NOEL) for non-pharmaceuticals is currently based exclusively on an extrapolation of the results of animal toxicity studies. This process is inexact and requires the results of toxicity studies in multiple species (rat, dog, and monkey) to identify the no observed adverse effect level (NOAEL) and most sensitive test species. Multiple uncertainty (safety) factors are also necessary to compensate for incompatibility and uncertainty underlying the extrapolation of animal toxicity to humans. The maximum recommended daily dose for pharmaceuticals (MRDD) is empirically derived from human clinical trials. The MRDD is an estimated upper dose limit beyond which a drug's efficacy is not increased and/or undesirable adverse effects begin to outweigh beneficial effects. The MRDD is essentially equivalent to the NOAEL in humans, a dose beyond which adverse (toxicological) or undesirable pharmacological effects are observed. The NOAEL in test animals is currently used to estimate the safe starting dose in human clinical trials. MDL QSAR predictive modeling of the human MRDD may provide a better, simpler and more relevant estimation of the MRSD for pharmaceuticals and the toxic dose threshold of chemicals in humans than current animal extrapolation based risk assessment models and may be a useful addition to current methods. A database of the MRDD for over 1300 pharmaceuticals was compiled and modeled using MDL QSAR software and E-state and connectivity topological descriptors. MDL QSAR MRDD models were found to have good predictive performance with 74-78% of predicted MRDD values for 120 internal and 160 external validation compounds falling within a range of +/-10-fold the actual MRDD value. The predicted MRDD can be used to estimate the MRSD for pharmaceuticals in phase I clinical trials with the addition of a 10-fold safety factor. For non-pharmaceutical chemicals any compound-related effect can be considered an undesirable and adverse toxicological effect and the predicted MRDD can be used to estimate the NOEL with the addition of an appropriate safety factor. Published by Elsevier Inc. C1 ICSAS, Off Pharmaceut Sci Informat & Computat Safety Ana, Ctr Drug Evaluat & Res, US Food & Drug Adm, Rockville, MD 20857 USA. RP Contrera, JF (reprint author), ICSAS, Off Pharmaceut Sci Informat & Computat Safety Ana, Ctr Drug Evaluat & Res, US Food & Drug Adm, 5600 Fishers Lane, Rockville, MD 20857 USA. EM contrerajf@cder.fda.gov NR 19 TC 45 Z9 45 U1 2 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0273-2300 J9 REGUL TOXICOL PHARM JI Regul. Toxicol. Pharmacol. PD DEC PY 2004 VL 40 IS 3 BP 185 EP 206 DI 10.1016/j.yrtph.2004.08.004 PG 22 WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology SC Legal Medicine; Pharmacology & Pharmacy; Toxicology GA 877BC UT WOS:000225541800001 PM 15546675 ER PT J AU Carrington, CD Montwill, B Bolger, PM AF Carrington, CD Montwill, B Bolger, PM TI An intervention analysis for the reduction of exposure to methylmercury from the consumption of seafood by women of child-bearing age SO REGULATORY TOXICOLOGY AND PHARMACOLOGY LA English DT Article DE fish consumption; methylmercury; advisory AB A previously developed exposure model was used [Risk Anal. 22 (2002) 689] to assess the effectiveness of various advisory scenarios on minimizing mercury (Hg) blood levels via the consumption of commercial seafood, both finfish and shellfish. This exposure model was developed to predict levels of Hg in blood in women of child-bearing age in the US based on the frequency of seafood consumption, the amount of seafood consumed per serving, and the types of seafood consumed. Steady-state relationships that employed descriptive statistics to account for toxicokinetic variation were used to predict levels of Hg in blood. The model incorporates an uncertainty dimension that is intended to represent the range of plausible interpretations of the data. The predictability of the model was confirmed via the use of National Health and Nutrition Examination Survey (NHANES) blood Hg data. In the present analysis, the model was used to predict the impact of limitations in the amount or types of seafood consumed on blood Hg levels. Specifically, simulations for various advisory scenarios were developed on the basis of limitations on total consumption of seafood, elimination of the consumption of certain species altogether, and/or a combination of both. In the baseline model, the median (uncertainty) estimates for the 50th, 95th, and 99th per capita population percentiles were 1.25, 8.2, and 16.1 ppb blood Hg, respectively. After restriction of seafood consumption to no more than 12 oz/week, the median (uncertainty) estimates for the 50th, 95th, and 99th per capita population percentiles were 1.22, 6.8, and 10.6ppb blood Hg, respectively. Elimination of MeHg species, with average concentrations above 0.6ppm, resulted in very modest decrements in Hg blood levels, in comparison to either the baseline or the reduced consumption scenarios. These results suggest that strategies to reduce MeHg exposure by reducing the amount of fish consumed (e.g., 12 oz/week) are more effective at eliminating the high end of the exposure distribution than are strategies intended to change the types of fish consumed. Published by Elsevier Inc. C1 US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. RP Carrington, CD (reprint author), US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. EM cdc@cfsan.fda.gov NR 15 TC 36 Z9 38 U1 0 U2 9 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0273-2300 J9 REGUL TOXICOL PHARM JI Regul. Toxicol. Pharmacol. PD DEC PY 2004 VL 40 IS 3 BP 272 EP 280 DI 10.1016/j.yrtph.2004.07.006 PG 9 WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology SC Legal Medicine; Pharmacology & Pharmacy; Toxicology GA 877BC UT WOS:000225541800007 PM 15546681 ER PT J AU Carman, RJ Simon, MA Fernandez, H Miller, MA Bartholomew, MJ AF Carman, RJ Simon, MA Fernandez, H Miller, MA Bartholomew, MJ TI Ciprofloxacin at low levels disrupts colonization resistance of human fecal microflora growing in chemostats SO REGULATORY TOXICOLOGY AND PHARMACOLOGY LA English DT Article DE fluoroquinolone; antimicrobial; antibiotic; residue; nurmi effect; barrier effect; competitive exclusion; intestinal; feces; chemostat ID DIFFICILE-ASSOCIATED DIARRHEA; HEALTHY-VOLUNTEERS; CLOSTRIDIUM-DIFFICILE; ORAL CIPROFLOXACIN; INTESTINAL MICROFLORA; COLONIC MICROFLORA; ETHANOL ELIMINATION; FLORA; IMPACT; PHARMACOKINETICS AB We studied the in vitro effects of a range of ciprofloxacin (CI) concentrations on the human intestinal flora's colonization resistance (CR) to Salmonella kedougou NCTC 12173. Four steady state microbial communities were established in chemostats using inocula from a single pool of human feces. Three chemostats were exposed to CI (0.1, 0.43 and 5 mug/mL, respectively); one served as a no-drug control. The CR of each community was tested by three successive daily challenges of 108 S. kedougou, each delivered in a 1 mL bolus. There was no colonization of the no-drug chemostat. Likewise, after exposure to only 0.1 mug/mL CI there was no loss of CR and S. kedougou did not colonize. Conversely, both the 0.43 and the 5 mug/mL-exposed floras suffered a loss of CR and these chemostats were colonized. S. kedougou overgrew faster and reached higher counts in the presence of 0.43 than it did in the presence of 5 mug/mL. One possible explanation is that CI had a dose-dependent effect on both the challenge strain and CR. Thus, at higher levels, even though CR was disrupted by CI, so too was the growth of the challenge strain. Since exposure to CI elicited a dose-dependent reduction in Escherichia coli counts [Reg. Pharmacol. Toxicol. 33 (2001) 276] our new data suggest that E. coli may contribute to the CR against salmonella. We further conclude that, even at fecal levels below those reached during therapy, CI may impact the human gut flora sufficiently to facilitate colonization by S. kedougou. (C) 2004 Elsevier Inc. All rights reserved. C1 TechLab Inc, Blacksburg, VA 24060 USA. United States Food & Drug Adm, Ctr Vet Med, Rockville, MD 20855 USA. RP Carman, RJ (reprint author), TechLab Inc, 2001 Kraft Dr, Blacksburg, VA 24060 USA. EM rjcarman@techlab.com NR 54 TC 19 Z9 20 U1 2 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0273-2300 J9 REGUL TOXICOL PHARM JI Regul. Toxicol. Pharmacol. PD DEC PY 2004 VL 40 IS 3 BP 319 EP 326 DI 10.1016/j.yrtph.2004.08.005 PG 8 WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology SC Legal Medicine; Pharmacology & Pharmacy; Toxicology GA 877BC UT WOS:000225541800012 PM 15546686 ER PT J AU Williams, RA Thompson, KM AF Williams, RA Thompson, KM TI Integrated analysis: Combining risk and economic assessments while preserving the separation of powers SO RISK ANALYSIS LA English DT Article DE benefit-cost analysis; countervailing risk; economic analysis; risk assessment ID MANAGEMENT AB This article presents a process for an integrated policy analysis that combines risk assessment and benefit-cost analysis. This concept, which explicitly combines the two types of related analyses, seems to contradict the long-accepted risk analysis paradigm of separating risk assessment and risk management since benefit-cost analysis is generally considered to be a part of risk management. Yet that separation has become a problem because benefit-cost analysis uses risk assessment results as a starting point and considerable debate over the last several years focused on the incompatibility of the use of upper bounds or "safe" point estimates in many risk assessments with benefit-cost analysis. The problem with these risk assessments is that they ignore probabilistic information. As advanced probabilistic techniques for risk assessment emerge and economic analysts receive distributions of risks instead of point estimates, the artificial separation between risk analysts and the economic/decision analysts complicates the overall analysis. In addition, recent developments in countervailing risk theory suggest that combining the risk and benefit-cost analyses is required to fully understand the complexity of choices and tradeoffs faced by the decisionmaker. This article also argues that the separation of analysis and management is important, but that benefit-cost analysis has been wrongly classified into the risk management category and that the analytical effort associated with understanding the economic impacts of risk reduction actions need to be part of a broader risk assessment process. C1 Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Thompson, KM (reprint author), Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, 677 Huntington Ave, Boston, MA 02115 USA. EM kimt@hsph.harvard.edu NR 18 TC 10 Z9 11 U1 2 U2 5 PU BLACKWELL PUBLISHERS PI MALDEN PA 350 MAIN STREET, STE 6, MALDEN, MA 02148 USA SN 0272-4332 J9 RISK ANAL JI Risk Anal. PD DEC PY 2004 VL 24 IS 6 BP 1613 EP 1623 DI 10.1111/j.0272-4332.2004.00554.x PG 11 WC Public, Environmental & Occupational Health; Mathematics, Interdisciplinary Applications; Social Sciences, Mathematical Methods SC Public, Environmental & Occupational Health; Mathematics; Mathematical Methods In Social Sciences GA 886NO UT WOS:000226235800018 PM 15660616 ER PT J AU Razzaghi, M Kodell, R AF Razzaghi, M Kodell, R TI Quantitative risk assessment for developmental neurotoxic effects SO RISK ANALYSIS LA English DT Article DE Benchmark dose; developmental neurotoxicity; dose response; likelihood ratio; risk assessment ID DOSE-RESPONSE ASSESSMENT; ADVERSE EFFECT LEVELS; ENVIRONMENTAL CHEMICALS; DEVELOPING RAT; FETAL WEIGHT; TOXICITY; EXPOSURE; MIXTURE; NOAEL; MODEL AB Developmental neurotoxicity concerns the adverse health effects of exogenous agents acting on neurodevelopment. Because human brain development is a delicate process involving many cellular events, the developing fetus is rather susceptible to compounds that can alter the structure and function of the brain. Today, there is clear evidence that early exposure to many neurotoxicants can severely damage the developing nervous system. Although in recent years, there has been much attention given to model development and risk assessment procedures for developmental toxicants, the area of developmental neurotoxicity has been largely ignored. Here, we consider the problem of risk estimation for developmental neurotoxicants from animal bioassay data. Since most responses from developmental neurotoxicity experiments are nonquantal in nature, an adverse health effect will be defined as a response that occurs with very small probability in unexposed animals. Using a two-stage hierarchical normal dose-response model, upper confidence limits on the excess risk due to a given level of added exposure are derived. Equivalently, the model is used to obtain lower confidence limits on dose for a small negligible level of risk. Our method is based on the asymptotic distribution of the likelihood ratio statistic (cf. Crump, 1995). An example is used to provide further illustration. C1 Bloomsburg Univ Penn, Bloomsburg, PA 17815 USA. US FDA, Jefferson Labs, Jefferson, AR USA. RP Razzaghi, M (reprint author), Bloomsburg Univ Penn, Bloomsburg, PA 17815 USA. EM razzaghi@bloomu.edu NR 33 TC 5 Z9 6 U1 0 U2 1 PU BLACKWELL PUBLISHERS PI MALDEN PA 350 MAIN STREET, STE 6, MALDEN, MA 02148 USA SN 0272-4332 J9 RISK ANAL JI Risk Anal. PD DEC PY 2004 VL 24 IS 6 BP 1673 EP 1681 DI 10.1111/j.0272-4332.2004.00558.x PG 9 WC Public, Environmental & Occupational Health; Mathematics, Interdisciplinary Applications; Social Sciences, Mathematical Methods SC Public, Environmental & Occupational Health; Mathematics; Mathematical Methods In Social Sciences GA 886NO UT WOS:000226235800022 PM 15660620 ER PT J AU Gaylor, DW Slikker, W AF Gaylor, DW Slikker, W TI Role of the standard deviation in the estimation of benchmark doses with continuous data SO RISK ANALYSIS LA English DT Article DE analytical measurement variation; benchmark dose; confidence limits; risk assessment; standard deviation among animals ID RISK-ASSESSMENT AB For continuous data, risk is defined here as the proportion of animals with values above a large percentile, e.g., the 99th percentile or below the 1st percentile, for the distribution of values among control animals. It is known that reducing the standard deviation of measurements through improved experimental techniques will result in less stringent (higher) doses for the lower confidence limit on the benchmark dose that is estimated to produce a specified risk of animals with abnormal levels for a biological effect. Thus, a somewhat larger (less stringent) lower confidence limit is obtained that may be used as a point of departure for low-dose risk assessment. It is shown in this article that it is important for the benchmark dose to be based primarily on the standard deviation among animals, s(a), apart from the standard deviation of measurement errors, s(m), within animals. If the benchmark dose is incorrectly based on the overall standard deviation among average values for animals, which includes measurement error variation, the benchmark dose will be overestimated and the risk will be underestimated. The bias increases as s(m), increases relative to s(a). The bias is relatively small if s(m), is less than one-third of s(a), a condition achieved in most experimental designs. C1 US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Gaylor & Assoc LLC, Little Rock, AR USA. RP Slikker, W (reprint author), US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM wslikker@nctr.fda.gov NR 4 TC 10 Z9 10 U1 0 U2 0 PU BLACKWELL PUBLISHERS PI MALDEN PA 350 MAIN STREET, STE 6, MALDEN, MA 02148 USA SN 0272-4332 J9 RISK ANAL JI Risk Anal. PD DEC PY 2004 VL 24 IS 6 BP 1683 EP 1687 DI 10.1111/j.0272-4332.2004.559_1.x PG 5 WC Public, Environmental & Occupational Health; Mathematics, Interdisciplinary Applications; Social Sciences, Mathematical Methods SC Public, Environmental & Occupational Health; Mathematics; Mathematical Methods In Social Sciences GA 886NO UT WOS:000226235800023 PM 15660621 ER PT J AU Scallet, AC Divine, RL Newbold, RR Delclos, KB AF Scallet, AC Divine, RL Newbold, RR Delclos, KB TI Increased volume of the calbindin D28k-labeled sexually dimorphic hypothalamus in genistein and nonylphenol-treated male rats SO TOXICOLOGICAL SCIENCES LA English DT Article DE medial preoptic nucleus; hypothalamus; 3-D reconstruction; endocrine disrupters; estrogens; sex differences; calcium binding proteins ID SPRAGUE-DAWLEY RATS; FINCH SONG SYSTEM; GONADOTROPIN-RELEASING-HORMONE; MEDIAL PREOPTIC AREA; CASTRATED ADULT-RAT; PITUITARY-RESPONSIVENESS; DIETARY EXPOSURE; FEMALE RATS; POSTNATAL-DEVELOPMENT; NEONATAL EXPOSURE AB The adult rat brain develops through an interplay of neuronal proliferation and programmed cell death. Steroid hormones and growth factors may alter the balance between these competing processes. "Endocrine disrupters" (EDs) may also alter brain development, by mimicry or modulation of endogenous hormone systems. Under control conditions, the sexually dimorphic nucleus (SDN) of the medial preoptic hypothalamus becomes larger in adult males than females, but its final volume may also reflect the hormonal conditions prevailing during development. Two EDs that have recently been studied in protocols involving lifespan exposures are the phytoestrogen genistein and the weakly estrogenic compound para-nonylphenol, which is used in the production of many surfactants and plastics. Experimental dietary exposure of adult female rats to genistein or p-nonylphenol began 28 days prior to their mating at concentrations of 5 ppm, 100 ppm, and 500 ppm for genistein or 25 ppm, 200 ppm, and 750 ppm for p-nonylphenol. Exposure of the offspring continued throughout gestation and lactation, as well as in their chow after weaning, until they were sacrificed at 140 days of age for immunohistochemical labeling of the calbindin D28k-labeled subdivision of the SDN: the CALB-SDN. Both genistein and nonylphenol were found to increase the volume of the CALB-SDN in male rats (p's < 0.01), but not in female rats. C1 US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Charles River Labs, Jefferson, AR 72079 USA. NIEHS, Environm Toxicol Program, NIH, Res Triangle Pk, NC 27709 USA. US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Scallet, AC (reprint author), US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, HFT-132,3900 NCTR Dr, Jefferson, AR 72079 USA. EM ascallet@nctr.fda.gov NR 55 TC 22 Z9 24 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD DEC PY 2004 VL 82 IS 2 BP 570 EP 576 DI 10.1093/toxsci/kfh297 PG 7 WC Toxicology SC Toxicology GA 873AY UT WOS:000225252300025 PM 15456915 ER PT J AU Mei, N Chou, MW Fu, PP Heflich, RH Chen, T AF Mei, N Chou, MW Fu, PP Heflich, RH Chen, T TI Differential mutagenicity of riddelliine in liver endothelial and parenchymal cells of transgenic big blue rats SO CANCER LETTERS LA English DT Article DE riddelliine; pyrrolizidine alkaloid; transgenic rat; cII gene; endothelial cell; hemangiosarcomas ID DNA ADDUCT FORMATION; METABOLIC-ACTIVATION; MICE; MUTATIONS; CARCINOGENICITY; MUTAGENESIS; MECHANISMS; EXPOSURE; TOXICITY; GENES AB Riddelliine is a naturally occurring pyrrolizidine alkaloid that induces liver hemangiosarcomas in rats and mice. We previously reported higher levels of DNA adducts in liver endothelial cells than in liver parenchymal cells of riddellime-treated mice and rats [Cancer Lett. 193 (2003) 1191, suggesting that the tumor specificity is due to higher levels of DNA damage in the cells that form hemangosarcomas. In the present study, we evaluated the cell-specificity of riddelliine mutagenicity in rat liver. Female transgenic Big Blue rats were treated by gavage with 0.3 mg riddelliine per kg body weight, 5 days a week for 12 weeks. One day after the last treatment, the rats were sacrificed and liver parenchymal and endothelial cell fractions were isolated and purified. DNA was extracted from the cell fractions and used to assay for mutant frequency (MF) in the cII transgene. While there was no difference in the cII MFs of liver parenchymal cells in control and riddelliine-treated rats, the cII MF of liver endothelial cells from treated rats was significantly greater than the cII MF of endothelial cells from control rats. Molecular analysis of the mutants in liver endothelial cells indicated that G:C --> T:A transversion, a mutation that is characteristically induced by riddelliine, accounted for only 9% of all mutations in control rats, but made up 17% of mutations in treated rats. In contrast, G:C --> A:T transition, the major mutation in control rats where it made up 54% of all mutations, was reduced to 40% of mutations in riddelliine-treated rats. These results suggest that the relatively high mutagenicity of riddelliine in rat liver endothelial cells may be partially responsible for the tumorigenic specificity of this agent. Published by Elsevier Ireland Ltd. C1 US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Mei, N (reprint author), US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. EM nmei@nctr.fda.gov RI mei, nan/E-8915-2011 OI mei, nan/0000-0002-3501-9014 NR 20 TC 20 Z9 20 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD NOV 25 PY 2004 VL 215 IS 2 BP 151 EP 158 DI 10.1016/j.canlet.2004.06.013 PG 8 WC Oncology SC Oncology GA 868QO UT WOS:000224928300003 PM 15488633 ER PT J AU Kibler, KV Miyazato, A Yedavalli, VSRK Dayton, AI Jacobs, BL Dapolito, G Kim, SJ Jeang, KT AF Kibler, KV Miyazato, A Yedavalli, VSRK Dayton, AI Jacobs, BL Dapolito, G Kim, SJ Jeang, KT TI Polyarginine inhibits gp160 processing by furin and suppresses productive human immunodeficiency virus type 1 infection SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CONVERTING ENZYME-INHIBITORS; ENVELOPE GLYCOPROTEIN; PROPROTEIN CONVERTASES; MOLECULAR CLONE; CELLS; HIV-1; ACTIVATION; PROTEIN; PRECURSOR; CLEAVAGE AB Correct endoproteolytic maturation of gp160 is essential for the infectivity of human immunodeficiency virus type 1. This processing of human immunodeficiency virus-1 envelope protein, gp160, into gp120 and gp41 has been attributed to the activity of the cellular subtilisin-like proprotein convertase furin. The prototypic furin recognition cleavage site is Arg-X-Arg/Lys-Arg. Arg-Arg-Arg-Arg- Arg-Arg or longer iterations of polyarginine have been shown to be competitive inhibitors of substrate cleavage by furin. Here, we tested polyarginine for inhibition of productive human immunodeficiency virus-1-infection in T-cell lines, primary peripheral blood mononuclear cells, and macrophages. We found that polyarginine inhibited significantly human immunodeficiency virus-1 replication at concentrations that were benign to cell cultures ex vivo and mice in vivo. Using a fluorogenic assay, we demonstrated that polyarginine potently inhibited substrate-specific proteolytic cleavage by furin. Moreover, we verified that authentic processing of human immunodeficiency virus-1 gp160 synthesized in human cells from an infectious human immunodeficiency virus-1 (HIV-1) molecular clone was effectively blocked by polyarginine. Taken together, our data support that inhibitors of proteolytic processing of gp160 may be useful for combating human immunodeficiency virus-1 and that polyarginine represents a lead example of such inhibitors. C1 NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. Arizona State Univ, Biodesign Inst, Ctr Infect Dis & Vaccinol, Tempe, AZ 85287 USA. NCI, Lab Cell Regulat & Carcinogenesis, NIH, Bethesda, MD 20892 USA. RP Jeang, KT (reprint author), NIAID, Mol Microbiol Lab, NIH, Bldg 4,Rm 306,9000 Rockville Pike, Bethesda, MD 20892 USA. EM kj7e@nih.gov RI Jeang, Kuan-Teh/A-2424-2008 NR 47 TC 28 Z9 29 U1 1 U2 2 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 NOV 19 PY 2004 VL 279 IS 47 BP 49055 EP 49063 DI 10.1074/jbc.M403394200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 870ZP UT WOS:000225098100069 PM 15371436 ER PT J AU Weisz, A Andrzejewski, D Rasooly, RR AF Weisz, A Andrzejewski, D Rasooly, RR TI Determination of 2,4,6-tribromoaniline in the color additives D&C Red Nos. 21 and 22 (Eosin Y) using solid-phase microextraction and gas chromatography-mass spectrometry SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article DE D & C Red No. 21; D & C Red No. 22; eosins; aromatic amine; 2,4,6-tribromoaniline; color additives ID MONOCYCLIC AROMATIC-AMINES; PHLOXINE-B; NOS. 27; QUANTIFICATION; FIBERS AB The present work demonstrates the presence of an impurity, 2,4,6-tribromoaniline (TBA), in the color additives D&C Red Nos. 21 and 21 lake (21L) and describes the determination of TBA in certified lots of D&C Red Nos. 21, 21L and 22 (Eosin Y). A method was developed using solid-phase microextraction with [C-13(6)]TBA as an internal standard followed by gas chromatography-mass spectrometry analysis. Test portions from 23 lots of US-certified color additives D&C Red Nos. 21, 21L and 22 were analyzed for TBA using the new method. These lots represent domestic (four) and foreign (four) manufacturers that requested certification for the color additives during the past 2 years. Of the test portions analyzed, 12 (52.2%) contained TBA in amounts ranging from 19.9 to 638.9 ppm with an average value of similar to278.7 ppm. The remaining 11 (47.2%) test portions contained no detectable TBA or less than 0.01 ppm, which is the limit of quantification of the present method. The wide range of TBA levels found in lots submitted for certification suggest that the contamination with TBA may be avoided or significantly decreased through appropriate changes in the color-manufacturing process. (C) 2004 Elsevier B.V. All rights reserved. C1 US FDA, Ctr Food Safety & Appl Nutr, Off Cosmet & Colors, Chantilly, VA 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, Chantilly, VA USA. EM aweisz@cfsan.fda.gov OI Rasooly, Irit/0000-0002-1368-534X NR 20 TC 4 Z9 4 U1 1 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR A JI J. Chromatogr. A PD NOV 19 PY 2004 VL 1057 IS 1-2 BP 185 EP 191 DI 10.1016/j.chroma.2004.09.065 PG 7 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 871OU UT WOS:000225143900022 PM 15584238 ER PT J AU Goodman, JL AF Goodman, JL TI HIV-1 and HCV infections among antibody-negative blood donors - Reply SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID VIRUS TRANSMISSION C1 US FDA, Bethesda, MD 20892 USA. RP Goodman, JL (reprint author), US FDA, Bethesda, MD 20892 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD NOV 18 PY 2004 VL 351 IS 21 BP 2234 EP 2235 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 871UU UT WOS:000225160600021 ER PT J AU Heller, DN Nochetto, CB AF Heller, DN Nochetto, CB TI Development of multiclass methods for drug residues in eggs: Silica SPE cleanup and LC-MS/MS analysis of ionophore and macrolide residues SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE residues in eggs; ion trap mass spectrometry; ionophore analysis; macrolide analysis; lasalocid; salinomycin; narasin; monensin; novoblocin; erythromycin; tylosin; liquid chromatography-tandem mass spectrometry ID CHROMATOGRAPHY-MASS-SPECTROMETRY; LIQUID-CHROMATOGRAPHY; ANTICOCCIDIAL DRUGS; BOVINE MUSCLE; CONFIRMATION; ANTIBIOTICS; MONENSIN; SALINOMYCIN; NICARBAZIN; NARASIN AB A method was developed that is suitable for screening eggs for a variety of nonpolar residues in a single procedure. Residues are extracted by silica solid-phase extraction (SPE). Analysis is conducted via reverse-phase gradient liquid chromatography, electrospray ionization, and tandem ion trap mass spectrometry. For screening purposes (based on a single precursor-product ion transition) the method can detect ionophore (lasalocid, monensin, salinomycin, narasin) and macrolide (erythromycin, tylosin) residues in egg at similar to1 ng/mL (ppb) and above and novobiocin residues at similar to3 ppb and above. Conditions are described for confirmatory analysis based on multiple ions in the product ion spectrum. The extraction efficiency for ionophores was estimated at 60-85%, depending on drug. Recovery of macrolides and novobiocin was not as good (estimated at 40-55% after a hexane wash of the final extract was included), but the method consistently screened and confirmed these residues at concentrations below the target of 10 ppb. The method was applied to eggs from hens dosed with each drug individually. Lasalocid was found to have the highest probability of detection in eggs based on its high ionization efficiency and higher rate of deposition relative to the other drugs. The method is part of a larger scheme to provide surveillance methods for a wide variety of drug residues in eggs. 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 dheller@cvm.fda.gov NR 23 TC 47 Z9 51 U1 4 U2 16 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0021-8561 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD NOV 17 PY 2004 VL 52 IS 23 BP 6848 EP 6856 DI 10.1021/jf040185j PG 9 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 870TD UT WOS:000225080100002 PM 15537285 ER PT J AU Jacobs, ET Jiang, RY Alberts, DS Greenberg, ER Gunter, EW Karagas, MR Lanza, E Ratnasinghe, L Reid, ME Schatzkin, A Smith-Warner, SA Wallace, K Martinez, ME AF Jacobs, ET Jiang, RY Alberts, DS Greenberg, ER Gunter, EW Karagas, MR Lanza, E Ratnasinghe, L Reid, ME Schatzkin, A Smith-Warner, SA Wallace, K Martinez, ME TI Selenium and colorectal adenoma: Results of a pooled analysis SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID PREDIAGNOSTIC SERUM SELENIUM; NUTRITION EXAMINATION SURVEY; BASE-LINE CHARACTERISTICS; 3RD NATIONAL-HEALTH; CANCER PREVENTION; CLINICAL-TRIAL; RISK; SUPPLEMENTATION; MORTALITY; DESIGN AB Background: Secondary analyses of data from a large randomized clinical trial have suggested that intake of the trace element selenium reduces risk of colorectal neoplasia, but epidemiologic studies have not shown a consistent protective association. Methods: We conducted a combined analysis of data from three randomized trials-the Wheat Bran Fiber Trial, the Polyp Prevention Trial, and the Polyp Prevention Study-which tested the effects of various nutritional interventions for colorectal adenoma prevention among participants who recently had an adenoma removed during colonoscopy. Selenium concentrations were measured from blood specimens from a total of 1763 trial participants, and quartiles of baseline selenium were established from the pooled data. To estimate the association between baseline selenium and colorectal adenoma risk, odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using logistic regression modeling. All statistical tests were two-sided. Results: Individual study results among participants whose blood selenium concentrations were in the highest versus the lowest quartile varied in magnitude (Polyp Prevention Trial: OR = 0.67, 95 % CI = 0.43 to 1.05; P-trend =.21; Wheat Bran Fiber Trial: OR = 0.66,95% CI = 0.40 to 1.10; P-trend =.13, and Polyp Prevention Study: OR = 0.57, 95 % CI = 0.34 to 0.95, P-trend =.04). Analyses of the pooled data showed that individuals whose blood selenium values were in the highest quartile (median = 150 ng/mL) had statistically significantly lower odds of developing a new adenoma compared with those in the lowest quartile (OR = 0.66, 95% CI = 0.50 to 0.87; P-trend =.006). Conclusions: The inverse association between higher blood selenium concentration and adenoma risk supports previous findings indicating that higher selenium status may be related to decreased risk of colorectal cancer. C1 Univ Arizona, Arizona Canc Ctr, Tucson, AZ 85724 USA. Univ Arizona, Enid Zuckerman Arizona Coll Publ Hlth, Tucson, AZ USA. Dartmouth Coll Sch Med, Lebanon, NH USA. Norris Cotton Canc Ctr, Lebanon, NH USA. Ctr Dis Control & Prevent, Atlanta, GA USA. NCI, Bethesda, MD 20892 USA. US FDA, Jefferson, AR USA. Roswell Pk Canc Inst, Buffalo, NY 14263 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Jacobs, ET (reprint author), Univ Arizona, Arizona Canc Ctr, POB 245024, Tucson, AZ 85724 USA. EM jacobse@u.arizona.edu FU NCI NIH HHS [CA-41108, CA-23074, CA-77145, CA95060] NR 33 TC 100 Z9 104 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD NOV 17 PY 2004 VL 96 IS 22 BP 1669 EP 1675 DI 10.1093/jnci/djh310 PG 7 WC Oncology SC Oncology GA 870VA UT WOS:000225085500008 PM 15547179 ER PT J AU Ioannidis, JPA Evans, SJW Gotzsche, PC O'Neill, RT Altman, DG Schulz, K Moher, D AF Ioannidis, JPA Evans, SJW Gotzsche, PC O'Neill, RT Altman, DG Schulz, K Moher, D CA CONSORT Grp TI Better reporting of harms in randomized trials: An extension of the CONSORT statement SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID ADVERSE DRUG-REACTIONS; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; CLINICAL-TRIALS; SAFETY DATA; OUTCOMES; QUALITY; RHEUMATOLOGY; DEFINITIONS; ARTHRITIS; NEED AB In response to overwhelming evidence and the consequences of poor-quality reporting of randomized, controlled trials (RCTs), many medical journals and editorial groups have now endorsed the CONSORT (Consolidated Standards of Reporting Trials) statement, a 22-item checklist and flow diagram. Because CONSORT primarily aimed at improving the quality of reporting of efficacy, only 1 checklist item specifically addressed the reporting of safety. Considerable evidence suggests that reporting of harms-related data from RCTs also needs improvement. Members of the CONSORT Group, including journal editors and scientists, met in Montebello, Quebec, Canada, in May 2003 to address this problem. The result is the following document: the standard CONSORT checklist with 10 new recommendations about reporting harms-related issues, accompanying explanation, and examples to highlight specific aspects of proper reporting. We hope that this document, in conjunction with other CONSORT-related materials (www.consort-statement.org), will help authors improve their reporting of harms-related data from RCTs. Better reporting will help readers critically appraise and interpret trial results. Journals can support this goal by revising Instructions to Authors so that they refer authors to this document. C1 Childrens Hosp Eastern Ontario, Res Inst, Chalmers Res Grp, Ottawa, ON K1H 8L1, Canada. Univ Ioannina, Sch Med, GR-45110 Ioannina, Greece. London Sch Hyg & Trop Med, London WC1, England. Nord Cochrane Ctr, Copenhagen, Denmark. US FDA, Rockville, MD 20857 USA. Canc Res UK, Natl Hlth Serv, Ctr Stat Med, Oxford, England. Family Hlth Int, Res Triangle Pk, NC 27709 USA. Univ Ioannina, Fdn Res & Technol Hellas, Inst Biomed Res, Ioannina, Greece. RP Moher, D (reprint author), Childrens Hosp Eastern Ontario, Res Inst, Chalmers Res Grp, 401 Smyth Rd, Ottawa, ON K1H 8L1, Canada. EM dmoher@uottawa.ca RI Ioannidis, John/G-9836-2011; OI Moher , David /0000-0003-2434-4206 NR 49 TC 553 Z9 566 U1 3 U2 13 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD NOV 16 PY 2004 VL 141 IS 10 BP 781 EP 788 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 872KU UT WOS:000225206900005 PM 15545678 ER PT J AU Holada, K Brouckova, A Simak, J Gahl, WA Vostal, JG AF Holada, K Brouckova, A Simak, J Gahl, WA Vostal, JG TI Platelet cellular prion protein (PRPC) is associated with alpha granules. SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 Charles Univ, Fac Med 1, Inst Microbiol & Immunol, Prague, Czech Republic. US FDA, CBER, Div Hematol, Bethesda, MD 20014 USA. NICHD, Cell Biol & Metab Branch, NIH, Bethesda, MD USA. RI Simak, Jan/C-1153-2011 NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 3882 BP 57B EP 57B PN 2 PG 1 WC Hematology SC Hematology GA 871JO UT WOS:000225127700214 ER PT J AU Cross, A Rapoport, AP Levine, BL Stadtmauer, EA June, CH Mann, D Frasch, C Lynch, C Badros, A Chrisley, L Cotte, J Mair, R Hinkle, J Zhang, L Edelman, R AF Cross, A Rapoport, AP Levine, BL Stadtmauer, EA June, CH Mann, D Frasch, C Lynch, C Badros, A Chrisley, L Cotte, J Mair, R Hinkle, J Zhang, L Edelman, R TI Results of a phase I/II randomized immunotherapy trial testing adoptive transfer of co-stimulated autologous T cells and pneumococcal conjugate vaccine (PCV) immunization after autotransplantation for myeloma (MM). SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 Univ Maryland, Sch Med, Ctr Vaccine Dev, Baltimore, MD 21201 USA. Univ Maryland, Sch Med, Greenebaum Canc Ctr, Baltimore, MD 21201 USA. Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. RI Levine, Bruce/D-1688-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 5088 BP 355B EP 355B PN 2 PG 1 WC Hematology SC Hematology GA 871JO UT WOS:000225127701414 ER PT J AU Chen, BZ Hong, HX Weida, T Ronald, W Bart, B Joshua, E AF Chen, BZ Hong, HX Weida, T Ronald, W Bart, B Joshua, E TI Biomarkers of myeloma-associated lytic bone disease using SELDI-TOF MS. SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 Univ Arkansas, Arkansas Canc Res Ctr, Myeloma Inst Res & Therapy, Little Rock, AR 72204 USA. US FDA, Ctr Toxicol Res, Div Biometry & Risk Assessment, Ctr Toxicoinformat, Jefferson, AR 72079 USA. Univ Arkansas Med Sci, Little Rock, AR 72205 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 2463 BP 676A EP 676A PN 1 PG 1 WC Hematology SC Hematology GA 871JM UT WOS:000225127502463 ER PT J AU Rosenblum, D Hirschfeld, S AF Rosenblum, D Hirschfeld, S TI Threshold of credibility: New approach to licensing acute leukemia therapy SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 US FDA, CBER, Off Cell Tissues & Gene Therapy, Rockville, MD 20857 USA. RI Hirschfeld, Steven/E-2987-2016 OI Hirschfeld, Steven/0000-0003-0627-7249 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 3128 BP 855A EP 855A PN 1 PG 1 WC Hematology SC Hematology GA 871JM UT WOS:000225127503130 ER PT J AU Simak, J Gelderman, MP Yu, H Wright, V Alberts-Grill, N Stranix, JT Baird, AE AF Simak, J Gelderman, MP Yu, H Wright, V Alberts-Grill, N Stranix, JT Baird, AE TI Elevated circulating endothelial microparticles in acute stroke patients: A correlation with brain lesion volume and outcome. SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 US FDA, Ctr Biol Evaluat & Res, Lab Celllular Hematol, Rockville, MD 20857 USA. NINDS, Struct Neurosci Unit, NIH, Bethesda, MD 20892 USA. RI Simak, Jan/C-1153-2011 NR 0 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 NOV 16 PY 2004 VL 104 IS 11 MA 3504 BP 954A EP 954A PN 1 PG 1 WC Hematology SC Hematology GA 871JM UT WOS:000225127503505 ER PT J AU Gelderman, MP Carter, LB Simak, J AF Gelderman, MP Carter, LB Simak, J TI High counts of potentially pathogenic cell membrane microparticles in Apheresis platelets. SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 Ctr Biol Evaluat & Res, Lab Cellular Hematol, Rockville, MD USA. RI Simak, Jan/C-1153-2011 NR 0 TC 2 Z9 2 U1 0 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 3635 BP 988A EP 989A PN 1 PG 2 WC Hematology SC Hematology GA 871JM UT WOS:000225127503636 ER PT J AU Talarico, L Chen, G Pazdur, R AF Talarico, L Chen, G Pazdur, R TI Enrollment of elderly patients in clinical trials for cancer drug registration: A 7-year experience by the US Food and Drug Administration SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 39th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 31-JUN 03, 2003 CL CHICAGO, IL SP Amer Soc Clin Oncol ID BREAST-CANCER; OLDER PATIENTS; ADJUVANT CHEMOTHERAPY; AGE; PARTICIPATION; ONCOLOGISTS; BARRIERS; WOMEN; PATTERNS; THERAPY AB Purpose To analyze the age-related enrollment of cancer patients onto registration trials of new drugs or new indications approved by the US Food and Drug Administration from 1995 to 2002. Patients and Methods This study involved retrospective analyses of demographic data of cancer patients enrolled onto registration trials. The data on 28,766 cancer patients from 55 registration trials were analyzed according to age distributions of greater than or equal to 65, greater than or equal to 70, and greater than or equal to 75 years. The rates of enrollment in each age group for each cancer were compared with the corresponding rates in the US cancer population. The age distributions of the US cancer population were derived from the Surveillance, Epidemiology, and End Results Program of the National Cancer Institute for the period 1995 to 1999 based on the 2000 US Census. Results The proportions of the overall patient populations aged greater than or equal to 65, greater than or equal to 70, and greater than or equal to 75 years were 36%, 20%, and 9% compared with 60%, 46%, and 31%, respectively, in the US cancer population. Statistically significant under-representation of the elderly (P < .001) was noted in registration trials for all cancer treatment except for breast cancer hormonal therapies. Patients aged greater than or equal to 70 years accounted for most of the under-representation. Conclusion Elderly were under-represented in the registration trials of new cancer therapies. Various strategies may be needed to evaluate cancer therapies for the elderly in prospective clinical trials and to improve cancer care in the elderly population. C1 US FDA, Div Oncol Drug Prod, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Talarico, L (reprint author), US FDA, Div Oncol Drug Prod, Ctr Drug Evaluat & Res, 1451 Rockville Pike,HFD 150, Rockville, MD 20857 USA. EM Talarico@cder.fda.gov NR 33 TC 269 Z9 273 U1 1 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD NOV 15 PY 2004 VL 22 IS 22 BP 4626 EP 4631 DI 10.1200/JCO.2004.02.175 PG 6 WC Oncology SC Oncology GA 871ZP UT WOS:000225175600026 PM 15542812 ER PT J AU Gratz, SR Flurer, CL Wolnik, KA AF Gratz, SR Flurer, CL Wolnik, KA TI Analysis of undeclared synthetic phosphodiesterase-5 inhibitors in dietary supplements and herbal matrices by LC-ESI-MS and LC-UV SO JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS LA English DT Article DE dietary supplements; phosphodiesterase-5; sildenafil; vardenafil; tadalafil; electrospray; mass spectrometry; reversed-phase liquid chromatography ID LIQUID-CHROMATOGRAPHY; ERECTILE DYSFUNCTION; SILDENAFIL CITRATE; HUMAN PLASMA; ASSAY AB A liquid chromatography-electrospray ionisation-mass spectrometry (LC-ESI-MS) method was developed to screen for the presence of synthetic phosphodiesterase type 5 (PDE-5) inhibitors including sildenafil, tadalafil and vardenafil. The method was applied to the analysis of dietary supplements and bulk herbal materials. Bulk powders or composites of tablets, capsules or liquids were prepared and an extraction of PDE-5 inhibitors was performed using a mixture of acetonitrile and water with sonication. Identification of sildenafil, vardenafil or tadalafil was accomplished using a single quadrupole mass spectrometer coupled to a liquid chromatograph with an electrospray interface. Positive ion detection in the full scan mode was used while in-source collision induced dissociation (CID) provided several structurally significant fragment ions to aid in the mass spectral identification. Approximately half of the 40 botanical products analyzed were found to contain undeclared synthetic PDE-5 inhibitors. For products found to contain one of these three compounds by LC-MS, HPLC with UV detection was used for quantitation. Published by Elsevier B.V. C1 US FDA, Forens Chem Ctr, Cincinnati, OH 45237 USA. RP Gratz, SR (reprint author), US FDA, Forens Chem Ctr, Cincinnati, OH 45237 USA. EM sgratz@ora.fda.gov NR 14 TC 114 Z9 120 U1 2 U2 12 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0731-7085 J9 J PHARMACEUT BIOMED JI J. Pharm. Biomed. Anal. PD NOV 15 PY 2004 VL 36 IS 3 BP 525 EP 533 DI 10.1016/j.jpba.2004.07.004 PG 9 WC Chemistry, Analytical; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 874MJ UT WOS:000225354200013 PM 15522526 ER PT J AU Kruesi, MJP Casanova, MF Mannheim, G Johnson-Bilder, A AF Kruesi, MJP Casanova, MF Mannheim, G Johnson-Bilder, A TI Reduced temporal lobe volume in early onset conduct disorder SO PSYCHIATRY RESEARCH-NEUROIMAGING LA English DT Article DE frontal lobe; substance abuse; MRI; antisocial personality; attention deficit hyperactivity disorder ID ANTISOCIAL PERSONALITY-DISORDER; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; TEACHER RATING SCALE; BRAIN VOLUME; DEVELOPMENTAL TRAJECTORIES; PSYCHIATRIC-DISORDERS; DISRUPTIVE BEHAVIOR; DISTURBED-CHILDREN; AUTONOMIC MEASURES; CONDITIONED FEAR AB Regional brain volumes derived from magnetic resonance imaging (MRI) scans from 10 youths with early onset conduct disorder and 10 healthy controls matched for age, sex and handedness were compared to determine whether prefrontal or temporal lobe brain volumes differed in the two groups. Right temporal lobe and right temporal gray matter volumes were significantly reduced in subjects with conduct disorder compared with controls. Prefrontal volumes in subjects with conduct disorder were 16% smaller than in controls, but the difference did not reach statistical significance. Early onset conduct disorder without substance abuse comorbidity was also significantly associated with smaller fight temporal gray volumes. Further investigation of both the temporal and frontal localizations of the pathophysiology of early onset conduct disorder is warranted in larger samples. (C) 2004 Elsevier Ireland Ltd. All rights reserved. C1 Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. Univ Louisville, Dept Psychiat, Louisville, KY 40292 USA. US FDA, Rockville, MD 20857 USA. RP Kruesi, MJP (reprint author), Med Univ S Carolina, Dept Psychiat & Behav Sci, 67 President St,POB 250861, Charleston, SC 29425 USA. EM kruesi@musc.edu NR 91 TC 85 Z9 89 U1 14 U2 21 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0925-4927 J9 PSYCHIAT RES-NEUROIM JI Psychiatry Res. Neuroimaging PD NOV 15 PY 2004 VL 132 IS 1 BP 1 EP 11 DI 10.1016/j.psychresns.2004.07.002 PG 11 WC Clinical Neurology; Neuroimaging; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 881WZ UT WOS:000225901400001 PM 15546698 ER PT J AU Horne, AD Clifford, J Goldenthal, KL Kleppinger, C Lachenbruch, PA AF Horne, AD Clifford, J Goldenthal, KL Kleppinger, C Lachenbruch, PA TI Preventive vaccines against bioterrorism: evaluation of efficacy and safety SO VACCINE LA English DT Article DE immunogenicity; non-inferiority; Animal Rule ID COMBINATION VACCINES/; TERRORISM; SMALLPOX; ANTHRAX AB This paper discusses the US Food and Drug Administration's approach to evaluation of vaccines in general, and vaccines against diseases of bioterrorism in particular. We summarize the scientific bases for development and approval of vaccines and then discuss specific issues regarding vaccines against disease organisms that could potentially be used as weapons of bioterrorism. Published by Elsevier Ltd. C1 US FDA, Div Biostat, Off Biostat & Epidemiol, CBER, Rockville, MD 20852 USA. US FDA, Div Vaccines & Related Prod Applicat, Off Vaccine Res & Review, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. NIDA, Ctr Clin Trials Network, NIH, Bethesda, MD 20892 USA. RP Horne, AD (reprint author), US FDA, Div Biostat, Off Biostat & Epidemiol, CBER, HFM-217,1401 Rockville Pike, Rockville, MD 20852 USA. EM horne@cber.fda.gov NR 20 TC 4 Z9 5 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 NOV 15 PY 2004 VL 23 IS 1 BP 84 EP 90 DI 10.1016/j.vaccine.2004.04.037 PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 872IM UT WOS:000225200900012 PM 15519711 ER PT J AU Prikhod'ko, EA Prikhod'ko, GG Siegel, RM Thompson, P Major, ME Cohen, JI AF Prikhod'ko, EA Prikhod'ko, GG Siegel, RM Thompson, P Major, ME Cohen, JI TI The NS3 protein of hepatitis C virus induces caspase-8-mediated apoptosis independent of its protease or helicase activities SO VIROLOGY LA English DT Article DE hepatitis C virus; apoptosis; caspase-8; flavivirus ID ALPHA-MEDIATED APOPTOSIS; NECROSIS-FACTOR RECEPTOR; TNF-INDUCED APOPTOSIS; CORE PROTEIN; VIRAL-HEPATITIS; CELL-DEATH; IN-VITRO; SUBCELLULAR-LOCALIZATION; SERINE PROTEINASE; LANGAT FLAVIVIRUS AB Apoptosis has been implicated in the pathogenesis of hepatitis C virus (HCV)-related disease. Here, we show that expression of HCV NS3, or the NS2/NS3 precursor protein, in mammalian cells results in induction of apoptosis and activation of caspases. HCV NS3-induced apoptosis was blocked by a caspase-8, but not a caspase-9-specific inhibitor. HCV NS3 coimmunoprecipitated with caspase-8, but not with other caspases or with FADD. Coexpression of HCV NS3 and caspase-8 resulted in aggregation of the caspase in punctate structures that colocalized with HCV NS3. Cell lines stably expressing low levels HCV NS3 showed increased sensitivity to Fas-induced cell death. Point mutations of NS3 showed that the pro-apoptotic function of the protein is distinct from its protease and helicase activities. These findings suggest that HCV NS3 promotes caspase-8 induced apoptosis at a pathway site distal to FADD, and that flavivirus NS3 may represent a new class of pro-apoptotic proteins. Published by Elsevier Inc. C1 NIAID, Med Virol Sect, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. Amer Red Cross, Holland Lab, Plasma Derivatives Dept, Rockville, MD 20855 USA. NIAID, Mol Dev Immune Syst Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. US FDA, Lab Hepatitis Res, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Cohen, JI (reprint author), NIAID, Med Virol Sect, Lab Clin Infect Dis, NIH, Bldg 10,Room 11N228m10 Ctr Dr, Bethesda, MD 20892 USA. EM jcohen@niaid.nih.gov RI Siegel, Richard/C-7592-2009 OI Siegel, Richard/0000-0001-5953-9893 NR 74 TC 53 Z9 57 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD NOV 10 PY 2004 VL 329 IS 1 BP 53 EP 67 DI 10.1016/j.virol.2004.08.012 PG 15 WC Virology SC Virology GA 865PQ UT WOS:000224715400006 PM 15476874 ER PT J AU Taha, EI Al-Saidan, S Samy, AM Khan, MA AF Taha, EI Al-Saidan, S Samy, AM Khan, MA TI Preparation and in vitro characterization of self-nanoemulsified drug delivery system (SNEDDS) of all-trans-retinol acetate SO INTERNATIONAL JOURNAL OF PHARMACEUTICS LA English DT Article DE preparation; in vitro characterization; self-nanoemulsified drug delivery system (SNEDDS); all-trans-retinol acetate ID BETA-CAROTENE; HUMAN PLASMA; VITAMIN-A; EMULSIFICATION; FORMULATIONS; ACID AB Purpose: To prepare a self-nanoemulsified drug delivery system (SNEDDS) of all-trans-retinol acetate, with enhanced dissolution and better chance of oral absorption. Method: All-trans-retinol acetate SNEDDS was prepared using different concentrations of soybean oil (solvent) Cremophor EL (surfactant) and Capmul MCM-C8 (co-surfactant). Particle size and turbidity of the SNEDDS were determined after adding water to the oily solution. Dissolution profile of SNEDDS filled in hydroxyl propyl methyl cellulose (HPMC) capsules was determined by using water in USP apparatus 2. Ternary phase diagrams were constructed to identify the self-nanoemulsified region. The SNEDDS were evaluated by the visual observation, turbidity in nephrometric turbidity units (NTU), mean particle size (mum) and Fourier transformed-infrared spectroscopy (FT-IR). SNEDDS were thermally characterized using differential scanning calorimetry (DSC) to ensure the compatibility of the SNEDDS ingredient. Results: From the data obtained in this work, it was clear that surfactant to co-surfactant ratio has the main impact on the physical characteristics of the emulsion formed. The optimum surfactant to co-surfactant ratio was found to be 2:1 (37.5-50% for Cremophor EL, and 18.75-25% for Capmul MCM-C8). With this ratio, the resultant nanoemulsions obtained have a particle size range of 0.103-0.051 mum, turbidity range of 18.12-2.18 NTU and t(30) values (cumulative% all-trans-retinol acetate dissolved in 30 min) of 90.42-99.5. Also the thermograms obtained from DSC experiments showed that there is no incompatibility or interaction between the SNEDDS ingredients (soybean oil, Cremophor EL, and Capmul MCM-C8) and all-trans-retinol acetate. Conclusion: The present study revealed that the self-nanoemulsified drug delivery system of all-trans-retinol acetate increased its dissolution rate and has the potential to enhance its bioavailability without interaction or incompatibility between the ingredients. (C) 2004 Elsevier B.V. All rights reserved. C1 Texas Tech Univ, Hlth Sci Ctr, Dept Pharmaceut Sci, Amarillo, TX 79106 USA. Kuwait Univ, Hlth Sci Ctr, Fac Pharm, Safat, Kuwait. Al Azhar Univ, Fac Pharm, Cairo, Egypt. RP Khan, MA (reprint author), US FDA, CDER, DPQR, LS Bldg 64,HFD-940,5600 Fishers Lane, Rockville, MD 20895 USA. EM Khanm@cder.fda.gov NR 18 TC 59 Z9 60 U1 4 U2 14 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 NOV 5 PY 2004 VL 285 IS 1-2 BP 109 EP 119 DI 10.1016/j.ijpharm.2004.03.034 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 871MA UT WOS:000225136600011 PM 15488684 ER PT J AU Nahum, GG AF Nahum, GG TI Evaluating medical student obstetrics and gynecology clerkship performance: Which assessment tools are most reliable? SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT CREOG/APGO 2004 Annual Meeting CY MAR 03-06, 2004 CL Lake Buena Vista, FL SP CREOG, APGO DE medical student clerkship performance; clinical assessment tools and final grades; National Board of Medical Examiners Subject Test examination; oral examination; clinical performance indicators ID GRADE INFLATION; OSCES AB Objective: This study was undertaken to investigate medical student performance on an obstetrics and gynecology (Ob-Gyn) core clerkship to determine the most discriminating measures of student performance. Study design: Four-hundred twenty-one clinical clerks were assessed with the use of 46 performance indicators in 4 different categories. Final Scores were weighted: (1) Clinical Performance = 60% (2) Formal Presentation = 10%, (3) Oral Examination = 10%, and (4) National Board of Medical Examiners (NBME) Subject Test score = 20%. Results: A total of 17,023 scores were examined. Final Scores were normally distributed. Clinical Performance and Formal Presentation scores were highly skewed, explaining 35% and 5% of the Final Score variance, respectively. Oral Examination scores were slightly skewed, explaining 17% of the variance. The NBME Subject Test score was the only normally distributed performance indicator and, despite comprising only 20% of Final Scores, was the most highly correlated (R = 0.86), explaining 74% of the variance. Conclusion: Despite their minor weighting in our grading system, NBME Subject Test scores were very highly correlated with overall clinical clerkship performance. By combining written Subject Test and Oral Examination scores, 91 % of the variance in Final Scores can be explained. (C) 2004 Elsevier Inc. All rights reserved. C1 Duke Univ, Sch Med, Dept Obstet & Gynecol, Durham, NC USA. RP Nahum, GG (reprint author), US FDA, Ctr Drug Evaluat & Res, US Dept HHS, Off New Drugs, 5600 Fihsers Lane,HFD-020,RKWL 2, Rockville, MD 20857 USA. EM NahumG@CDER.fda.gov NR 14 TC 7 Z9 7 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD NOV PY 2004 VL 191 IS 5 BP 1762 EP 1771 DI 10.1016/j.ajog.2004.07.074 PG 10 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 874FY UT WOS:000225337500045 PM 15547561 ER PT J AU Folb, PI Bernatowska, E Chen, R Clemens, J Dodoo, ANO Ellenberg, SS Farrington, P John, TJ Lambert, PH MacDonald, NE Miller, E Salisbury, D Schmitt, HJ Siegrist, CA Wimalaratne, O AF Folb, PI Bernatowska, E Chen, R Clemens, J Dodoo, ANO Ellenberg, SS Farrington, P John, TJ Lambert, PH MacDonald, NE Miller, E Salisbury, D Schmitt, HJ Siegrist, CA Wimalaratne, O TI A global perspective on vaccine safety and public health: The global advisory committee on vaccine safety SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID INFLAMMATORY-BOWEL-DISEASE; SERIOUS ADVERSE EVENTS; RUBELLA VACCINE; CAUSAL ASSOCIATION; ASEPTIC-MENINGITIS; MASS VACCINATION; MEASLES-VIRUS; MUMPS VACCINE; NO EVIDENCE; FOLLOW-UP AB Established in 1999, the Global Advisory Committee on Vaccine Safety advises the World Health Organization (WHO) on vaccine-related safety issues and enables WHO to respond promptly, efficiently, and with scientific rigor to issues of vaccine safety with potential global importance. The committee also assesses the implications of vaccine safety for practice worldwide and for WHO policies. We describe the principles on which the committee was established-its modus operandi, and the scope of the work undertaken, both present and future. We highlight its recent recommendations on major issues, including the purported link between the measles-mumps-rubella vaccine and autism and the safety of the mumps, influenza, yellow fever, BCG, and smallpox vaccines as well as that of thiomersal-containing vaccines. C1 MRC, ZA-7505 Cape Town, South Africa. Childrens Mem Hlth Inst, Dept Immunol, Warsaw, Poland. Ctr Dis Control & Prevent, Immunizat Safety Branch, Atlanta, GA USA. Int Vaccine Inst, Seoul, South Korea. Univ Ghana, Sch Med, Ctr Trop Clin Pharmacol & Therapeut, Accra, Ghana. US FDA, Off Biostat & Epidemiol, Rockville, MD 20857 USA. Open Univ, Dept Stat, Milton Keynes MK7 6AA, Bucks, England. Kerala State Inst Virol & Infect Dis, Vellore, Tamil Nadu, India. Ctr Med Univ Geneva, Collaborating Ctr Neonatal Vaccinol, WHO, CH-1211 Geneva, Switzerland. Dalhousie Univ, Dept Paediat, Halifax, NS, Canada. Hlth Protect Agcy, Immunisat Dept, London, England. Dept Hlth, Communicable Dis & Immunisat Team, London SE1 6TE, England. Univ Mainz, Ctr Prevent Pediat, D-6500 Mainz, Germany. Med Res Inst, Dept Rabies & Vaccines, Colombo, Sri Lanka. RP Folb, PI (reprint author), MRC, POB 19070, ZA-7505 Cape Town, South Africa. EM pfolb@mrc.ac.za NR 35 TC 31 Z9 36 U1 0 U2 13 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD NOV PY 2004 VL 94 IS 11 BP 1926 EP 1931 DI 10.2105/AJPH.94.11.1926 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 866NS UT WOS:000224780800022 PM 15514229 ER PT J AU Jeske, DR Blessinger, T AF Jeske, DR Blessinger, T TI Tunable approximations for the mean and variance of the maximum of heterogeneous geometrically distributed random variables SO AMERICAN STATISTICIAN LA English DT Article DE expected value; extreme value; negative binomial; system throughput ID ORDER-STATISTICS; REDUNDANT SYSTEMS AB Analysis of the maximum of n independent geometrically distributed random variables arises in a variety of applications in computer science and engineering. Evaluating the mean and variance of the maximum when n is large presents considerable computational challenges. Although approximate formulas have been proposed in the case where each geometric distribution has the same probability of success, the heterogeneous case has not received any attention. We derive an epsilon-accurate approximation for both the mean and the variance in the heterogeneous case. The approximations also apply to the homogeneous case, and offer something new with their ability to tune the approximation to any desired level of accuracy. We illustrate the formulas with a reliability application where the heterogeneous context arose quite naturally. C1 Univ Calif Riverside, Dept Stat, Riverside, CA 92521 USA. Food & Drug Adm, Rockville, MD 20855 USA. RP Jeske, DR (reprint author), Univ Calif Riverside, Dept Stat, Riverside, CA 92521 USA. EM daniel.jeske@ucr.edu NR 11 TC 4 Z9 4 U1 1 U2 1 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 1429 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0003-1305 J9 AM STAT JI Am. Stat. PD NOV PY 2004 VL 58 IS 4 BP 322 EP 327 DI 10.1198/000313004X5509 PG 6 WC Statistics & Probability SC Mathematics GA 866JL UT WOS:000224769700011 ER PT J AU Xing, Y Warnock, JN He, ZM Hilbert, SL Yoganathan, AP AF Xing, Y Warnock, JN He, ZM Hilbert, SL Yoganathan, AP TI Cyclic pressure affects the biological properties of porcine aortic valve leaflets in a magnitude and frequency dependent manner SO ANNALS OF BIOMEDICAL ENGINEERING LA English DT Article DE aortic valve leaflets; collagen synthesis; tissue engineering ID ENDOTHELIAL-CELL PROLIFERATION; INTERSTITIAL-CELLS; HYPERTENSIVE RATS; GENE-EXPRESSION; HEART-VALVES; CHONDROCYTES; STRAIN; TISSUE AB An understanding of how mechanical forces impact cells within valve leaflets would greatly benefit the development of a tissue-engineered heart valve. Previous studies by this group have shown that exposure to constant static pressure leads to enhanced collagen synthesis in porcine aortic valve leaflets. In this study, the effect of cyclic pressure was evaluated using a custom-designed pressure system. Different pressure magnitudes (100, 140, and 170 mmHg) as well as pulse frequencies (0.5, 1.167, and 2 Hz) were studied. Collagen synthesis, cell proliferation, sGAG synthesis, alpha-SMC actin expression, and extracellular matrix (ECM) structure were chosen as markers for valvular biological responses. Results showed that aortic valve leaflets responded to cyclic pressure in a magnitude and frequency-dependent manner. Increases in pressure magnitude (with the frequency fixed at 1.167 Hz) resulted in significant increases in both collagen and sGAG synthesis, while DNA synthesis remained unchanged. Responses to pulse frequency (with the magnitude fixed at 100 mmHg) were more complex. Collagen and sGAG synthesis were increased by 25 and 14% respectively at 0.5 Hz; but were not affected at 1.167 and 2 Hz. In contrast, DNA synthesis increased by 72% at 2 Hz, but not at 0.5 and 1.167 Hz. Under extreme pressure conditions (170 mmHg, 2 Hz), collagen and sGAG synthesis were increased but to a lesser degree than at 170 mmHg, and 1.167 Hz. Cell proliferation was not affected. A notable decline in alpha-SMC actin was observed over the course of the experiments, although no significant difference was observed between the cyclic pressure and control groups. It was concluded that cyclic pressure affected biosynthetic activity of aortic valve leaflets in a magnitude and frequency dependent manner. Collagen and sGAG synthesis were positively correlated and more responsive to pressure magnitude than pulse frequency. DNA synthesis was more responsive to pulse frequency than pressure magnitude. However, when combined, pressure magnitude and pulse frequency appeared to have an attenuating effect on each other. The number of alpha-SMC actin positive cells did not vary with cyclic pressure, regardless of pulse frequency and pressure magnitude. C1 Georgia Inst Technol, Wallace H Coulter Sch Biomed Engn, Atlanta, GA 30322 USA. Georgia Inst Technol, Sch Chem & Biomol Engn, Bioengn Program, Atlanta, GA 30322 USA. Georgia Inst Technol, George W Woodruff Sch Mech Engn, Atlanta, GA 30322 USA. US FDA, Ctr Devices & Radiol Res CDRH, Rockville, MD USA. RP Yoganathan, AP (reprint author), Georgia Inst Technol, Wallace H Coulter Sch Biomed Engn, 313 Ferst Dr, Atlanta, GA 30322 USA. EM ajit.yoganathan@bme.gatech.edu NR 25 TC 50 Z9 50 U1 1 U2 4 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0090-6964 J9 ANN BIOMED ENG JI Ann. Biomed. Eng. PD NOV PY 2004 VL 32 IS 11 BP 1461 EP 1470 DI 10.1114/B:ABME.0000049031.07512.11 PG 10 WC Engineering, Biomedical SC Engineering GA 873RL UT WOS:000225298500001 PM 15636107 ER PT J AU Kirkwood, J Al-Khaldi, SF Mossoba, MM Sedman, J Ismail, AA AF Kirkwood, J Al-Khaldi, SF Mossoba, MM Sedman, J Ismail, AA TI Fourier transform infrared bacteria identification with the use of a focal-plane-array detector and microarray printing SO APPLIED SPECTROSCOPY LA English DT Article DE microarray; bacterial identification; infrared; Fourier transform infrared; FT-IR; food safety; imaging; focal plane array; FPA-FTIR; surface analysis C1 US FDA, Div Microbiol Studies, OPDFB, College Pk, MD 20740 USA. US FDA, Div Gen Sci Support, OSAS, CFSAN, College Pk, MD 20740 USA. McGill Univ, McGill IR Grp, Dept Food Sci & Agr Chem, Montreal, PQ H9X 3V9, Canada. RP Al-Khaldi, SF (reprint author), US FDA, Div Microbiol Studies, OPDFB, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM sufian.al-khaldi@cfsan.fda.gov; ashraf.ismail@mcgill.ca NR 7 TC 15 Z9 15 U1 0 U2 5 PU SOC APPLIED SPECTROSCOPY PI FREDERICK PA 201B BROADWAY ST, FREDERICK, MD 21701 USA SN 0003-7028 J9 APPL SPECTROSC JI Appl. Spectrosc. PD NOV PY 2004 VL 58 IS 11 BP 1364 EP 1368 DI 10.1366/0003702042475376 PG 5 WC Instruments & Instrumentation; Spectroscopy SC Instruments & Instrumentation; Spectroscopy GA 872UG UT WOS:000225233500017 PM 15606943 ER PT J AU Sauder, C Herpfer, I Hassler, C Staeheli, P AF Sauder, C Herpfer, I Hassler, C Staeheli, P TI Susceptibility of Borna disease virus to the antiviral action of gamma-interferon: Evidence for species-specific differences SO ARCHIVES OF VIROLOGY LA English DT Article ID PERSISTENTLY INFECTED-CELLS; CENTRAL-NERVOUS-SYSTEM; VIRAL-INFECTIONS; GENE-EXPRESSION; REPLICATION; ASTROCYTES; SEQUENCE; CULTURES; PROTEIN; TISSUE AB Borna disease virus (BDV) infection in its predominant natural host - horses and sheep - leads to fatal meningoencephalomyelitis. The immune-mediated disease can also be induced experimentally in rats following intra- cerebral BDV infection. Despite a vigorous immune response, BDV persists in the central nervous system (CNS) in surviving rats. However, immunization of rats with BDV-specific T-cells prior to challenge with BDV prevents neurological disease and results in virus clearance from the CNS. To analyze whether interferon gamma (IFNgamma) might contribute to viral clearance in the rat brain, we tested the susceptibility of BDV to the antiviral action of rat IFNgamma using different rat cell lines. Even at high concentrations of IFNgamma, BDV infection of astrocyte and fibroblast cell lines as well as of rat embryo cells could not be inhibited efficiently. Similarly, infection of cultured rat hippocampal slices with BDV was not inhibited by rat IFNgamma. In contrast, de novo BDV infection of monkey kidney cells as well as human oligodendroglial cells was blocked by preincubation with human IFNgamma. Furthermore, IFNgamma reduced the BDV load in persistently BDV-infected human oligodendroglial cells but not in infected rat astrocytes. These data suggest species-specific differences in the susceptibility of BDV to the antiviral action of IFNgamma. C1 Univ Freiburg, Sch Med, Inst Med Microbiol & Hyg, Dept Virol, Freiburg, Germany. Univ Freiburg, Sch Med, Dept Psychiat & Psychotherapy, Freiburg, Germany. RP Sauder, C (reprint author), US FDA, CBER, Bldg 29A,HFM460,Rm 2C20,8800 Rockville Pike, Bethesda, MD 20892 USA. EM sauder@cber.FDA.gov NR 39 TC 2 Z9 3 U1 0 U2 0 PU SPRINGER WIEN PI VIENNA PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 VIENNA, AUSTRIA SN 0304-8608 J9 ARCH VIROL JI Arch. Virol. PD NOV PY 2004 VL 149 IS 11 BP 2171 EP 2186 DI 10.1007/s00705-004-0360-5 PG 16 WC Virology SC Virology GA 866DE UT WOS:000224753200008 PM 15503205 ER PT J AU Rosenberg, AS Worobec, A AF Rosenberg, AS Worobec, A TI A risk-based approach to immunogenicity concerns of therapeutic protein products Part 1 Considering consequences of the immune response to a protein SO BIOPHARM INTERNATIONAL LA English DT Article ID RED-CELL APLASIA; ANTIERYTHROPOIETIN ANTIBODIES; RECOMBINANT ERYTHROPOIETIN; TOLERANCE INDUCTION; REPLACEMENT THERAPY; HEMOPHILIA-A; DISEASE; CYTOKINES; EFFICACY; ALPHA AB For protein therapeutics, immunogenicity testing should be conducted from the earliest stages of product development. C1 CDER, FDA, Div Therapeut Prot, Bethesda, MD 20892 USA. FDA, CDER, Div Therapeut Biol Oncol Prod, Bethesda, MD 20892 USA. RP Rosenberg, AS (reprint author), CDER, FDA, Div Therapeut Prot, Bldg 29A,Room 2D-16,8800 Rockville Pike, Bethesda, MD 20892 USA. EM amy.rosenberg@fda.gov; alexandra.worobec@fda.go NR 29 TC 44 Z9 44 U1 0 U2 8 PU ADVANSTAR COMMUNICATIONS PI DULUTH PA 131 W FIRST ST, DULUTH, MN 55802 USA SN 1542-166X J9 BIOPHARM INT JI Biopharm. Int. PD NOV PY 2004 VL 17 IS 11 BP 22 EP + PG 4 WC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA 883WP UT WOS:000226046700004 ER PT J AU Sergeev, N Distler, M Courtney, S Al-Khaldi, SF Volokhov, D Chizhikov, V Rasooly, A AF Sergeev, N Distler, M Courtney, S Al-Khaldi, SF Volokhov, D Chizhikov, V Rasooly, A TI Multipathogen oligonucleotide microarray for environmental and biodefense applications SO BIOSENSORS & BIOELECTRONICS LA English DT Article DE oligonucleotide microarray; microbial pathogens ID CAMPYLOBACTER-JEJUNI; STAPHYLOCOCCUS-AUREUS; CLOSTRIDIUM-PERFRINGENS; LISTERIA-MONOCYTOGENES; VIRULENCE FACTORS; C-LARI; IDENTIFICATION; UPSALIENSIS; PATHOGENS; ASSAY AB Food-borne pathogens are a major health problem. The large and diverse number of microbial pathogens and their virulence factors has fueled interest in technologies capable of detecting multiple pathogens and multiple virulence factors simultaneously. Some of these pathogens and their toxins have potential use as bioweapons. DNA microarray technology allows the simultaneous analysis of thousands of sequences of DNA in a relatively short time, making it appropriate for biodefense and for public health uses. This paper describes methods for using DNA microarrays to detect and analyze microbial pathogens. The FDA-1 microarray was developed for the simultaneous detection of several food-borne pathogens and their virulence factors including Listeria spp., Campylobacter spp., Staphylococcus aureus enterotoxin genes and Clostridium perfringens toxin genes. Three elements were incorporated to increase confidence in the microarray detection system: redundancy of genes, redundancy of oligonuelcotide probes (oligoprobes) for a specific gene, and quality control oligoprobes to monitor array spotting and target DNA hybridization. These elements enhance the reliability of detection and reduce the chance of erroneous results due to the genetic variability of microbes or technical problems with the microarray. The results presented demonstrate the potential of oligonucteotide microarrays for detection of environmental and biodefense relevant microbial pathogens. (C) 2004 Elsevier B.V. All rights reserved. C1 FDA Ctr Food Safety & Appl Nutr, College Pk, MD USA. Joint Inst Food Safety & Appl Nutr, College Pk, MD USA. FDA Ctr Biol Evaluat & Res, Rockville, MD USA. FDA Ctr Devices & Radiol Hlth, Silver Spring, MD USA. NIH Natl Canc Inst, Rockville, MD 20852 USA. RP Rasooly, A (reprint author), FDA Ctr Food Safety & Appl Nutr, College Pk, MD USA. EM rasoslya@mail.nih.gov NR 23 TC 90 Z9 99 U1 0 U2 8 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 NOV 1 PY 2004 VL 20 IS 4 BP 684 EP 698 DI 10.1016/j.bios.2004.04.030 PG 15 WC Biophysics; Biotechnology & Applied Microbiology; Chemistry, Analytical; Electrochemistry; Nanoscience & Nanotechnology SC Biophysics; Biotechnology & Applied Microbiology; Chemistry; Electrochemistry; Science & Technology - Other Topics GA 875IB UT WOS:000225412600003 PM 15522583 ER PT J AU Wang, RF Chen, HH Paine, DD Cerniglia, CE AF Wang, RF Chen, HH Paine, DD Cerniglia, CE TI Microarray method to monitor 40 intestinal bacterial species in the study of azo dye reduction SO BIOSENSORS & BIOELECTRONICS LA English DT Article DE microarray; human intestinal microflora; azo dye reduction ID ANIMAL FECAL SAMPLES; PCR DETECTION; HUMAN FECES; MICROFLORA; HYBRIDIZATION; METABOLISM; PROBES; FLORA AB Azo dyes are widely used in dye manufacturing, paper printing, textile industries, and as tattoo pigmentation. Since intestinal and skin bacteria can metabolize certain azo dyes to carcinogenic compounds, many researchers have studied the azoreductases of these bacteria. In this study, we used a microarray method to identify the intestinal bacterial species from cultured fecal samples in Brain Heart Infusion (BHI) broth with or without azo dyes that may be involved in azo dye reduction. The microarray was designed to identify 40 bacterial species that are reported in the literature to be predominant in human feces. Results from this study showed 26-30 species are present in the cultured fecal samples. The representative bacteria were then examined for the azo dye reduction activity. Published by Elsevier B.V. C1 Natl Ctr Toxicol Res, Microbiol Div, Jefferson, AR 72079 USA. RP Wang, RF (reprint author), Natl Ctr Toxicol Res, Microbiol Div, Jefferson, AR 72079 USA. EM rwang@nctr.fda.gov NR 28 TC 9 Z9 9 U1 0 U2 4 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 NOV 1 PY 2004 VL 20 IS 4 BP 699 EP 705 DI 10.1016/j.bios.2004.04.011 PG 7 WC Biophysics; Biotechnology & Applied Microbiology; Chemistry, Analytical; Electrochemistry; Nanoscience & Nanotechnology SC Biophysics; Biotechnology & Applied Microbiology; Chemistry; Electrochemistry; Science & Technology - Other Topics GA 875IB UT WOS:000225412600004 PM 15522584 ER PT J AU Lyn-Cook, BD Word, B Goobsy, N Hammons, G Baker, S Baker, S AF Lyn-Cook, BD Word, B Goobsy, N Hammons, G Baker, S Baker, S TI Resveratrol modulates NQO1 expression in pancreatic tumor cells in vitro. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 3rd Annual AACR International Conference CY OCT 16-20, 2004 CL Seattle, WA SP AACR C1 US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Philander Smith Coll, Little Rock, AR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2004 VL 13 IS 11 BP 1847S EP 1847S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 870QO UT WOS:000225073100074 ER PT J AU Sen, G Flora, M Chattopadhyay, G Klinman, DM Lees, A Mond, JJ Snapper, CM AF Sen, G Flora, M Chattopadhyay, G Klinman, DM Lees, A Mond, JJ Snapper, CM TI The critical DNA flanking sequences of a CpG oligodeoxynucleotide, but not the 6 base CpG motif, can be replaced with RNA without quantitative or qualitative changes in Toll-like receptor 9-mediated activity SO CELLULAR IMMUNOLOGY LA English DT Article DE CpG; oligomlcleotides RNA; DNA; adjuvant; humoral immunity ID BACTERIAL-DNA; IMMUNE ACTIVATION; ANTIGEN; RECOGNITION; RESPONSES; CELLS AB Double- and single-stranded oligodeoxynucleotides containing unmethylated cytosine-guanosine (CpG) dinucleotides (CpG-ODN) activate immune cells via TLR9. In this report we synthesized hybrid DNA-RNA molecules (HDR) in order to further explore the structure-immune function relationship of CpG-ODN in TLR9 signaling and the potential immunomodulatory properties of RNA. We demonstrate that replacement of the deoxyadenosine flanking sequences, critical for the immune activating properties of CpG-ODN, with a similar number of adenosines, although not guanosines, cytosines, or uracils, maintains complete immunostimulatory activity of the hybrid oligonucleotide in vitro, whereas a similar RNA replacement of even I base of the required unmethylated 6 base DNA motif (purine-purine-CpG-pyrimidine-pyrimidine) results in a complete loss of activity. Regardless of whether the critical flanking sequence was RNA or DNA there was no significant change in the quantitative or qualitative immune-stimulating activity, or TLR-specificity of the resulting sequences, thus underscoring the relatively permissive functional role of the flanking sequence, and the more specific role of the motif in mediating TLR9 signaling. These data further support a potential role for RNA in immunomodulation. Published by Elsevier Inc. C1 Uniformed Serv Univ Hlth Sci, Inst Vaccine Res, Dept Pathol, Bethesda, MD 20814 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. Biosynexus Inc, Rockville, MD 20850 USA. RP Snapper, CM (reprint author), Uniformed Serv Univ Hlth Sci, Inst Vaccine Res, Dept Pathol, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM csnapper@usuhs.mil FU NIAID NIH HHS [1R01 AI49192] NR 19 TC 22 Z9 22 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 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD NOV-DEC PY 2004 VL 232 IS 1-2 BP 64 EP 74 DI 10.1016/j.cellimm.2005.01.010 PG 11 WC Cell Biology; Immunology SC Cell Biology; Immunology GA 935FF UT WOS:000229764300008 PM 15922717 ER PT J AU da Silva, M Esposito, E Joanna, DMC Canhos, VP Cerniglia, CE AF da Silva, M Esposito, E Joanna, DMC Canhos, VP Cerniglia, CE TI Metabolism of aromatic hydrocarbons by the filamentous fungus Cyclothyrium sp. SO CHEMOSPHERE LA English DT Article DE fungi; pollutants; aromatic hydrocarbons; biotransformation; coelomycetes ID RAT-LIVER MICROSOMES; SP STRAIN PYR-1; CUNNINGHAMELLA-ELEGANS; PLEUROTUS-OSTREATUS; STEREOSELECTIVE METABOLISM; ESTUARINE SEDIMENTS; PHENANTHRENE; PYRENE; OXIDATION; DEGRADATION AB The metabolism of biphenyl, naphthalene, anthracene, phenanthrene, pyrene and benzo[a]pyrene by Cyclothyrium sp. CBS 109850, a coelomycete isolated for the first time in Brazil from industrially polluted estuarine sediment, was studied. The metabolites were extracted and separated by high performance liquid chromatography (HPLC) and characterized by UV spectral analyses and mass, and proton nuclear magnetic resonance (H-1 NMR) spectrometry. Cyclothyrium sp. transformed biphenyl to 4-hydroxybiphenyl and anthracene to anthracene trans-1,2-dihydrodiol. This isolate metabolized 90% of [9-C-14] phenanthrene, producing phenanthrene trans-9,10-dihydrodiol as a major metabolite, phenanthrene trans-3,4-dihydrodiol, 1-hydroxyphenanthrene, 3-hydroxyphenanthrene, 4-hydroxyphenanthrene, and a novel metabolite, 2-hydroxy-7-methoxyphenanthrene. Circular dichroism spectra analyses indicated that the major enantiomers of phenanthrene trans-9, 10-dihydrodiol, phenanthrene trans-3,4-dihydrodiol and pyrene trans-4,5-dihydrodiol, a pyrene metabolite produced previously by Cyclothyrium sp. CBS 109850, were predominantly in the (R,R) configuration, revealing a high stereoselectivity for initial monooxygenation and enzymatic hydration of phenanthrene and pyrene by Cyclothyrium sp. CBS109850. The results also show a high regioselectivity since the K-regions of phenanthrene and pyrene were the major sites of metabolism. (C) 2004 Elsevier Ltd. All rights reserved. C1 Univ Estadual Campinas, Sch Food Engn, Dept Food Sci, BR-13083970 Campinas, SP, Brazil. Univ Mogi Cruzes, Dept Environm Sci, BR-08780911 Mogi Das Cruzes, SP, Brazil. US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. RP da Silva, M (reprint author), INCQS, Dept Microbiol, Fdn Oswaldo Cruz, 4365 Ave Brasil, BR-21045900 Rio De Janeiro, Brazil. EM manuela@incqs.fiocruz.br RI da Silva, Manuela/M-6211-2015 OI da Silva, Manuela/0000-0001-6073-8929 NR 38 TC 21 Z9 21 U1 1 U2 14 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 NOV PY 2004 VL 57 IS 8 BP 943 EP 952 DI 10.1016/j.chemosphere.2004.07.051 PG 10 WC Environmental Sciences SC Environmental Sciences & Ecology GA 867YR UT WOS:000224879400020 PM 15488584 ER PT J AU Baughman, AL Bisgard, KM Edwards, KM Guris, D Decker, MD Holland, K Meade, BD Lynn, F AF Baughman, AL Bisgard, KM Edwards, KM Guris, D Decker, MD Holland, K Meade, BD Lynn, F TI Establishment of diagnostic cutoff points for levels of serum antibodies to pertussis toxin, filamentous hemagglutinin, and fimbriae in adolescents and adults in the United States SO CLINICAL AND DIAGNOSTIC LABORATORY IMMUNOLOGY LA English DT Article ID HIGHLY IMMUNIZED POPULATION; POLYMERASE CHAIN-REACTION; BORDETELLA-PERTUSSIS; CONTROLLED TRIAL; CHANGING EPIDEMIOLOGY; VACCINE EFFECTIVENESS; MIXTURE-MODELS; YOUNG INFANTS; INFECTION; OUTBREAK AB Numerous reports have documented that serologic methods are much more sensitive than culture for the diagnosis of pertussis in adolescents and adults. However, a standardized serologic test for pertussis is not routinely available to most clinicians, and the serologic test levels or cutoff points correlated with diseases have not been determined. The goal of the present study was to examine the distribution of immunoglobulin G (IgG) levels against three Bordetella pertussis antigens (pertussis toxin [PT], filamentous hemagglutinin [FHA], and fimbria types 2 and 3 [FIM]) and to determine population-based antibody levels for the purpose of establishing such diagnostic cutoff points. Enzyme-linked immunosorbent assays (ELISAs) were performed with sera from >6,000 U.S. residents aged 6 to 49 years who participated in the Third National Health and Nutrition Examination Survey. Mixture models were developed to identify hypothesized exposure groups and establish diagnostic cutoffs. Quantifiable (>20 ELISA units/ml [EU]) anti-FHA and anti-FIM IgG antibodies were common (65 and 62% of individuals, respectively), but quantifiable anti-PT IgG antibodies were less frequent (16%). Given the distributions of antibody levels, an anti-PT IgG level of 2:94 EU was proposed as the diagnostic cutoff point. Application of this cutoff point to culture-confirmed illness in a prior study investigating cough illness yielded a high diagnostic sensitivity (80%) and specificity (93%). A standardized ELISA for anti-PT IgG with a single serum sample appears to be useful for the identification of recent B. pertussis infection in adolescents and adults with cough illness. The PT cutoff point will be further evaluated in prospective studies of confirmed B. pertussis infection. C1 Ctr Dis Control & Prevent, Natl Immunizat Program, Atlanta, GA 30333 USA. Vanderbilt Univ, Sch Med, Dept Pediat, Div Infect Dis, Nashville, TN 37212 USA. Vanderbilt Univ, Sch Med, Dept Prevent Med, Nashville, TN 37212 USA. Vanderbilt Univ, Sch Med, Dept Med Infect Dis, Nashville, TN 37212 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 OI Decker, Michael/0000-0003-1008-7472 NR 64 TC 77 Z9 82 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1071-412X J9 CLIN DIAGN LAB IMMUN JI Clin. Diagn. Lab. Immunol. PD NOV PY 2004 VL 11 IS 6 BP 1045 EP 1053 DI 10.1128/CDLI.11.6.1045-1053.2004 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 872YM UT WOS:000225245400010 PM 15539504 ER PT J AU Mikolajczyk, MG Concepcion, NF Wang, T Frazier, D Golding, B Frasch, CE Scott, DE AF Mikolajczyk, MG Concepcion, NF Wang, T Frazier, D Golding, B Frasch, CE Scott, DE TI Characterization of antibodies to capsular polysaccharide antigens of Haemophilus influenzae type b and Streptococcus pneumoniae in human immune globulin intravenous preparations SO CLINICAL AND DIAGNOSTIC LABORATORY IMMUNOLOGY LA English DT Article ID COMMON VARIABLE IMMUNODEFICIENCY; IMMUNOGLOBULIN PREPARATIONS; HEMOPHILUS-INFLUENZAE; IMMUNIZATION; PREVENTION; CHILDREN; DISEASE; ASSAY; HYPOGAMMAGLOBULINEMIA; AGAMMAGLOBULINEMIA AB The most common infections in primary immune deficiency disease (PIDD) patients involve encapsulated bacteria, mainly Haemophilus influenzae type b (Hib) and Streptococcus pneumoniae (pneumococcus). Thus, it is important to know the titers of Hib- and pneumococcus-specific antibodies that are present in immune globulin (Ig) intravenous (IGIV) preparations used to treat PIDD. In this study, seven IGIV preparations were tested by enzyme-linked immunosorbent assay and opsonophagocytic activity for antibody titers to the capsular polysaccharides of Hib and five pneumococcal serotypes. Differences in Hib- and pneumococcus-specific antibody titer were observed among various IGIV preparations, with some products having higher- or lower-than-average titers. Opsonic activity also varied among preparations. As expected, IgG2 was the most active subclass of both binding and opsonic activity except against pneumococcal serotype 6B where IgG3 was the most active. This study determines antibody titers against capsular polysaccharides of Hib and pneumococcus in seven IGIV products that have been shown to be effective in reducing infections in PIDD patients. As donor antibody levels and manufacturing methods continue to change, it may prove useful from a regulatory point of view to reassess IGIV products periodically, to ensure that products maintain antibody levels that are important for the health of IGIV recipients. C1 US FDA, CBER, Off Blood Res & Review, Div Hematol,Lab Plasma Derivat, Rockville, MD 20852 USA. Div Bacterial Parasit & Allergen Prod, Lab Bacterial Polysaccharides, Off Vaccines Res & Review, Bethesda, MD USA. RP Scott, DE (reprint author), US FDA, CBER, Off Blood Res & Review, Div Hematol,Lab Plasma Derivat, 1401 Rockville Pike,HFM-345, Rockville, MD 20852 USA. EM scottd@cber.fda.gov NR 41 TC 29 Z9 29 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1071-412X J9 CLIN DIAGN LAB IMMUN JI Clin. Diagn. Lab. Immunol. PD NOV PY 2004 VL 11 IS 6 BP 1158 EP 1164 DI 10.1128/CDLI.11.6.1158-1164.2004 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 872YM UT WOS:000225245400028 PM 15539522 ER PT J AU Lee, VHL AF Lee, VHL TI Are the elements in place to spark a revolution in drug development? SO CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY LA English DT Meeting Abstract CT 8th World Congress of Clinical Pharmacology and Therapeutics CY AUG 01-06, 2004 CL Brisbane, AUSTRALIA C1 US FDA, Rockville, MD 20857 USA. RI Lee, Vincent/A-9439-2008 OI Lee, Vincent/0000-0001-7708-6269 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING ASIA PI CARLTON PA 54 UNIVERSITY ST, P O BOX 378, CARLTON, VICTORIA 3053, AUSTRALIA SN 0305-1870 J9 CLIN EXP PHARMACOL P JI Clin. Exp. Pharmacol. Physiol. PD NOV PY 2004 VL 31 IS 11 BP A222 EP A222 PG 1 WC Pharmacology & Pharmacy; Physiology SC Pharmacology & Pharmacy; Physiology GA 876IP UT WOS:000225490400038 ER PT J AU Powers, JH AF Powers, JH TI Antimicrobial drug development - the past, the present, and the future SO CLINICAL MICROBIOLOGY AND INFECTION LA English DT Article; Proceedings Paper CT Symposim on Antimicrobial Therapy in the21st Century CY JUN 21, 2003 CL Stockholm, SWEDEN DE antimicrobial resistance; drug development; drug design; clinical trials ID UNITED-STATES; TRENDS AB Antimicrobial resistance has been an issue since the introduction into clinical use of the first agents in the 1940s. Although the discovery and development of new classes of antimicrobials through the 1960s presented an array of treatment options, these options for some serious and life-threatening infectious diseases may now be more limited. This paper examines the history of antimicrobial development, showing how the challenges in discovering new classes of drugs have been with us for the last 40 years. The present state of antimicrobial discovery and development is shaped by these challenges as well as by the economic realities of the pharmaceutical industry. This paper also discusses some of the regulatory considerations in antimicrobial drug development, and presents some potential solutions to the challenges inherent in antimicrobial drug development, including steps taken by the US Food and Drug Administration to streamline the drug review process for antimicrobial agents while maintaining the standards necessary to protect and promote the health of the public. C1 US FDA, Rockville, MD 20850 USA. RP Powers, JH (reprint author), US FDA, 9201 Corp Blvd HFD-104, Rockville, MD 20850 USA. EM POWERSJOH@cder.fda.gov NR 21 TC 62 Z9 68 U1 2 U2 22 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 1198-743X J9 CLIN MICROBIOL INFEC JI Clin. Microbiol. Infect. PD NOV PY 2004 VL 10 SU 4 BP 23 EP 31 DI 10.1111/j.1465-0691.2004.1007.x PG 9 WC Infectious Diseases; Microbiology SC Infectious Diseases; Microbiology GA 875YL UT WOS:000225459000006 PM 15522037 ER PT J AU Tong, WD Xie, W Hong, HX Fang, H Shi, LM Perkins, R Petricoin, EF AF Tong, WD Xie, W Hong, HX Fang, H Shi, LM Perkins, R Petricoin, EF TI Using decision forest to classify prostate cancer samples on the basis of SELDI-TOF MS data: Assessing chance correlation and prediction confidence SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE bioinformatics; chance correlation; class prediction; classification; decision forest; prediction confidence; prostate cancer; proteomics; SELDI-TOF ID GENE-EXPRESSION DATA; ARTIFICIAL NEURAL NETWORKS; PROTEOMIC PATTERNS; TUMOR CLASSIFICATION; MICROARRAY DATA; SERUM; PROFILES AB Class prediction using "omics" data is playing an increasing role in toxicogenomics, diagnosis/prognosis, and risk assessment. These data are usually noisy and represented by relatively few samples and a very large number of predictor variables (e.g., genes of DNA microarray data or m/z peaks of mass spectrometry data). These characteristics manifest the importance of assessing potential random correlation and overfitting of noise for a classification model based on omics data. We present a novel classification method, decision forest (DF), for class prediction using omics data. DF combines the results of multiple heterogeneous but comparable decision tree (DT) models to produce a consensus prediction. The method is less prone to overfitting of noise and chance correlation. A DF model was developed to predict presence of prostate cancer using a proteomic data set generated from surface-enhanced laser deposition/ ionization time-of-flight mass spectrometry (SELDI-TOF MS). The degree of chance correlation and prediction confidence of the model was rigorously assessed by extensive cross-validation and randomization testing. Comparison of model prediction with imposed random correlation demonstrated biologic relevance of the model and the reduction of overfitting in DF. Furthermore, two confidence levels (high and low confidences) were assigned to each prediction, where most misclassifications were associated with the low-confidence region. For the high-confidence prediction, the model achieved 99.2% sensitivity and 98.2% specificity. The model also identified a list of significant peaks that could be useful for biomarker identification. DF should be equally applicable to other omics data such as gene expression data or metabolomic data. The DF algorithm is available upon request. C1 Natl Ctr Toxicol Res, Ctr Toxicoinformat, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. Natl Ctr Toxicol Res, Bioinformat Grp, Jefferson, AR 72079 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. RP Tong, WD (reprint author), Natl Ctr Toxicol Res, Ctr Toxicoinformat, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. EM wtong@nctr.fda.gov NR 30 TC 31 Z9 36 U1 1 U2 8 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD NOV PY 2004 VL 112 IS 16 BP 1622 EP 1627 DI 10.1289/txg.7109 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 878WT UT WOS:000225678800014 PM 15598613 ER PT J AU Pan, YT Edavana, VK Jourdian, WJ Edmondson, R Carroll, JD Pastuszak, I Elbein, AD AF Pan, YT Edavana, VK Jourdian, WJ Edmondson, R Carroll, JD Pastuszak, I Elbein, AD TI Trehalose synthase of Mycobacterium smegmatis - Purification, cloning, expression, and properties of the enzyme SO EUROPEAN JOURNAL OF BIOCHEMISTRY LA English DT Article DE maltose; Mycobacteria; sugar interconversions; trehalose biosynthesis; trehalose metabolism ID YEAST SACCHAROMYCES-CEREVISIAE; OSMOTIC-STRESS; P SYNTHASE; 3 PATHWAYS; BIOSYNTHESIS; METABOLISM; PHOSPHATE; TUBERCULOSIS; FERMENTATION; BIOLOGY AB Trehalose synthase (TreS) catalyzes the reversible interconversion of trehalose (glucosyl-alpha,alpha-1,1-glucose) and maltose (glucosyl-alpha1-4-glucose). TreS was purified from the cytosol of Mycobacterium smegmatis to give a single protein band on SDS gels with a molecular mass of approximate to 68 kDa. However, active enzyme exhibited a molecular mass of approximate to 390 kDa by gel filtration suggesting that TreS is a hexamer of six identical subunits. Based on amino acid compositions of several peptides, the treS gene was identified in the M. smegmatis genome sequence, and was cloned and expressed in active form in Escherichia coli. The recombinant protein was synthesized with a (His)(6) tag at the amino terminus. The interconversion of trehalose and maltose by the purified TreS was studied at various concentrations of maltose or trehalose. At a maltose concentration of 0.5 mM, an equilibrium mixture containing equal amounts of trehalose and maltose (42-45% of each) was reached during an incubation of about 6 h, whereas at 2 mM maltose, it took about 22 h to reach the same equilibrium. However, when trehalose was the substrate at either 0.5 or 2 mM, only about 30% of the trehalose was converted to maltose in greater than or equal to 12 h, indicating that maltose is the preferred substrate. These incubations also produced up to 8-10% free glucose. The K-m for maltose was approximate to 10 mM, whereas for trehalose it was approximate to 90 mM. While beta,beta-trehalose, isomaltose (alpha1,6-glucose disaccharide), kojibiose (alpha1,2) or cellobiose (beta1,4) were not substrates for TreS, nigerose (alpha1,3-glucose disaccharide) and alpha,beta-trehalose were utilized at 20 and 15%, respectively, as compared to maltose. The enzyme has a pH optimum of about 7 and is inhibited in a competitive manner by Tris buffer. [H-3]Trehalose is converted to [H-3]maltose even in the presence of a 100-fold or more excess of unlabeled maltose, and [C-14]maltose produces [C-14]trehalose in excess unlabeled trehalose, suggesting the possibility of separate binding sites for maltose and trehalose. The catalytic mechanism may involve scission of the incoming disaccharide and transfer of a glucose to an enzyme-bound glucose, as [H-3]glucose incubated with TreS and either unlabeled maltose or trehalose results in formation of [H-3]disaccharide. TreS also catalyzes production of a glucosamine disaccharide from maltose and glucosamine, suggesting that this enzyme may be valuable in carbohydrate synthetic chemistry. C1 Univ Arkansas Med Sci, Dept Biochem & Mol Biol, Little Rock, AR 72205 USA. Univ Arkansas Med Sci, Dept Microbiol & Immunol, Little Rock, AR 72205 USA. Univ Michigan, Med Ctr, Dept Biol Chem, Ann Arbor, MI USA. Univ Michigan, Med Ctr, Dept Internal Med, Ann Arbor, MI USA. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Elbein, AD (reprint author), Univ Arkansas Med Sci, Dept Biochem & Mol Biol, Little Rock, AR 72205 USA. EM elbeinaland@uams.edu FU NHLBI NIH HHS [HL-17783]; NIAID NIH HHS [AI-43292] NR 30 TC 50 Z9 63 U1 1 U2 16 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0014-2956 J9 EUR J BIOCHEM JI Eur. J. Biochem. PD NOV PY 2004 VL 271 IS 21 BP 4259 EP 4269 DI 10.1111/j.1432-1033.2004.04365.x PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 866EG UT WOS:000224756000011 PM 15511231 ER PT J AU Wulfkuhle, J Espina, V Liotta, L Petricoin, E AF Wulfkuhle, J Espina, V Liotta, L Petricoin, E TI Genomic and proteomic technologies for individualisation and improvement of cancer treatment SO EUROPEAN JOURNAL OF CANCER LA English DT Review DE molecular profiling; individual targeted therapy; genomics; proteomics; microarrays; protein microarrays; cancer ID GENE-EXPRESSION PROFILES; HUMAN PROSTATE-CANCER; PROTEIN IDENTIFICATION TECHNOLOGY; LASER CAPTURE MICRODISSECTION; KINASE INHIBITOR ZD1839; BREAST-CANCER; MASS-SPECTROMETRY; TARGETED THERAPY; OVARIAN-CANCER; MOLECULAR CLASSIFICATION AB The development of microarray-based technologies for characterising tumours, both at the genomic and proteomic levels, has had a significant impact on the field of oncology. Gene expression profiling of various human tumour tissues has led to the identification of expression patterns related to disease outcome and drug resistance, as well as to the discovery of new therapeutic targets and insights into disease pathogenesis. Protein microarray technologies, such as reverse-phase protein arrays, provide the unique opportunity to profile tissues and assess the activity of signalling pathways within isolated cell populations. This technology can be used to identify patients likely to benefit from specific treatment modalities and also to monitor therapeutic response in samples obtained during and after treatment. Routine application of genomic and proteomic microarray technologies in clinical practice will require significant efforts to standardise the techniques, controls and reference standards, and analytical tools used. Extensive, independent validation using large, statistically-powered datasets will also be necessary. Inclusion of concomitant genomic and proteomic-based molecular profiling techniques into clinical trial protocols will bring us closer to the reality of patient-tailored therapy. Published by Elsevier Ltd. C1 NCI, FDA, Clin Proteom Program, Pathol Lab,Ctr Canc Res, Bethesda, MD 20892 USA. NCI, FDA, Clin Proteomics Program, OffCell & Gene Therapy,Ctr Biol Evaluat & Res,Foo, Bethesda, MD 20892 USA. RP Wulfkuhle, J (reprint author), NCI, FDA, Clin Proteom Program, Pathol Lab,Ctr Canc Res, Bldg 29A-2 B20,HFM 710,8800 Rockville Pike, Bethesda, MD 20892 USA. EM wulfkuhle@cber.fda.gov OI Espina, Virginia/0000-0001-5080-5972 NR 113 TC 62 Z9 65 U1 0 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD NOV PY 2004 VL 40 IS 17 BP 2623 EP 2632 DI 10.1016/j.ejca.2004.05.020 PG 10 WC Oncology SC Oncology GA 881JB UT WOS:000225858900009 PM 15541963 ER PT J AU Shi, LM Tong, WD Goodsaid, F Frueh, FW Fang, H Han, T Fuscoe, JC Casciano, DA AF Shi, LM Tong, WD Goodsaid, F Frueh, FW Fang, H Han, T Fuscoe, JC Casciano, DA TI QA/QC: challenges and pitfalls facing the microarray community and regulatory agencies SO EXPERT REVIEW OF MOLECULAR DIAGNOSTICS LA English DT Editorial Material DE crosslaboratory and crossplatform comparison; meta-analysis; microarray; protocol optimization and standardization; QA/QC; quality metrics and thresholds; regulatory review; reproductibility and accuracy ID GENE-EXPRESSION DATA; DNA MICROARRAYS; OLIGONUCLEOTIDE ARRAYS; CDNA MICROARRAYS; MOLECULAR CLASSIFICATION; EXPERIMENTAL-DESIGN; STATISTICAL DESIGN; PROSTATE-CANCER; DATA QUALITY; RNA AB The scientific community has been enthusiastic about DNA microarray technology for pharmacogenomic and toxicogenomic studies In the hope of advancing personalized medicine and drug development. The US Food and Drug Administration has been proactive In promoting the use of pharmacogenomic data In drug development and has Issued a draft guidance for the pharmaceutical Industry on data submissions. However, many challenges and pitfalls are facing the microarray community and regulatory agencies before microarray data can be reliably applied to support regulatory decision making. Four types of factors (i.e., technical, Instrumental, computational and Interpretative) affect the outcome of a microarray study, and a major concern about microarray studies has been the lack of reproducibility and accuracy. Intralaboratory data consistency Is the foundation of reliable knowledge extraction and meaningful crosslaboratory or crossplatform comparisons; unfortunately, It has not been seriously evaluated and demonstrated In every study. Profound problems In data quality have been observed from analyzing published data sets, and many laboratories have been struggling with technical troubleshooting rather than generating reliable data of scientific significance. The microarray community and regulatory agencies must work together to establish a set of consensus quality assurance and quality control criteria for assessing and ensuring data quality, to Identity critical factors affecting data quality, and to optimize and standardize microarray procedures so that biologic Interpretation and decision-making are not based on unreliable data. These fundamental Issues must be adequately addressed before microarray technology can be transformed from a research tool to clinical practices. C1 US FDA, Natl Ctr Toxicol Res, Ctr Toxicoinformat, Div Syst Toxicol, Jefferson, AR 72079 USA. US FDA, Off Clin Pharmacol & Biopharmaceut, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. US FDA, Natl Ctr Toxicol Res, Z Tech Corp, Jefferson, AR 72079 USA. US FDA, Natl Ctr Toxicol Res, Ctr Funct Genom, Div Syst Toxicol, Jefferson, AR 72079 USA. RP Shi, LM (reprint author), US FDA, Natl Ctr Toxicol Res, Ctr Toxicoinformat, Div Syst Toxicol, HFT-020 3900 NCTR Rd, Jefferson, AR 72079 USA. EM Leming.Shi@fda.hbs.gov NR 117 TC 74 Z9 80 U1 0 U2 3 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 NOV PY 2004 VL 4 IS 6 BP 761 EP 777 DI 10.1586/14737159.4.6.761 PG 17 WC Pathology SC Pathology GA 942QI UT WOS:000230296500002 PM 15525219 ER PT J AU Kim, PI Kang, TH Chung, KJ Kim, IS Chung, KC AF Kim, PI Kang, TH Chung, KJ Kim, IS Chung, KC TI Purification of a constitutive chitosanase produced by Bacillus sp MET 1299 with cloning and expression of the gene SO FEMS MICROBIOLOGY LETTERS LA English DT Article DE chitosanase; Bacillus sp MET 1299; colloidal chitosan; recombinant protein; GST-affinity chromatography ID HEXA-N-ACETYLCHITOHEXAOSE; ACETYL CHITOHEXAOSE; ACTION PATTERN; MICE; STREPTOMYCES; CHITINASE; BACTERIUM; INFECTION; GROWTH; FUNGUS AB A chitosanase produced constitutively by Bacillus sp. MET 1299 was purified by SP-Sephadex column chromatography. The molecular weight was estimated to be 52 kDa by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Optimal enzyme activity was observed at a pH of 5.5 and temperature of 60 degreesC. The purified chitosanase showed high activity on 90% deacetylated colloidal chitosan and beta-glucan, but not on hydrolyzed colloidal chitin, CMC, or their derivatives. The N-terminal amino acid sequence of the enzyme was determined. The cloned full length gene, 1362 bp in size, encoded a single peptide of 453 amino acids and had a conserved amino acid sequence of glycosyl hydrolase family 8. A search of the cDNA sequence with NCBI BLAST showed homology with chitosanase of Bacillus sp. KTCC 0377BP and Bacillus sp. No. 7-M. The recombinant protein was expressed in Escherichia coli, purified using affinity chromatography and characterized. (C) 2004 Federation of European Microbiological Societies. Published by Elsevier B.V. All rights reserved. C1 Chonnam Natl Univ, Sch Biol Sci & Technol, Kwangju 500757, South Korea. Chonnam Natl Univ, Biotechnol Res Inst, Kwangju 500757, South Korea. US FDA, Natl Ctr Toxicol Res, Dept Microbiol, Jefferson, AR 72079 USA. Chonnam Natl Univ, Div Appl Biosci & Biotechnol, Kwangju 500757, South Korea. Chonnam Natl Univ, Inst Agr Sci & Technol, Kwangju 500757, South Korea. RP Chung, KC (reprint author), Chonnam Natl Univ, Sch Biol Sci & Technol, Kwangju 500757, South Korea. EM chungkc@chonnam.ac.kr NR 40 TC 36 Z9 44 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1097 J9 FEMS MICROBIOL LETT JI FEMS Microbiol. Lett. PD NOV 1 PY 2004 VL 240 IS 1 BP 31 EP 39 DI 10.1016/j.femsle.2004.09.006 PG 9 WC Microbiology SC Microbiology GA 867NH UT WOS:000224848800005 PM 15500976 ER PT J AU Etheridge, SM Roesler, CS AF Etheridge, SM Roesler, CS TI Temporal variations in phytoplankton, particulates, and colored dissolved organic material based on optical properties during a Long Island brown tide compared to an adjacent embayment SO HARMFUL ALGAE LA English DT Article DE Aureococcus anophagefferens; brown tide; CDOM; harmful algal blooms; optical properties; pigments ID BOTTOM BOUNDARY-LAYER; AUREOCOCCUS-ANOPHAGEFFERENS; ABSORPTION-COEFFICIENTS; SPECTRAL ABSORPTION; NITROGEN UPTAKE; ATTENUATION; MATTER; WATERS; LIGHT; OCEAN AB Since 1985, the coastal embayments of Long Island, New York, have been plagued with recurrent blooms, aptly called brown tides, of the pelagophyte Aureococcus anophagefferens. The distinct ocean color observed during these blooms suggests that optical methods can be used as a tool to study, detect, and track brown tides. Thus, the goal of our project was to compare the optical properties and pigment composition during bloom and non-bloom conditions and assess temporal variations in the phytoplankton and other constituents in the seawater associated with bloom development. From 17 May to 8 June 2000, we measured a time series of particle size distributions and concentrations as well as size-fractioned algal pigments and optical properties in two Long Island embayments where brown tides are known to occur. During our study, A. anophagefferens represented an insignificant contribution to the algal community in West Neck Bay (WNB), whereas a bloom developed in Quantuck Bay (QB). Initially, temperature and salinity were similar at the two locations; however, bulk optical properties, chlorophyll, and F article concentrations were nearly a factor of 2 greater at QB. Bulk optical properties remained constant at WNB, yet increased exponentially at QB as the bloom developed. The composition of particulates, including phytoplankton, varied little at QB, and the optical properties suggested the dominance of A. anophagefferens (confirmed by microscopy). The largest temporal variations were observed in the colored dissolved organic material (CDOM); the colloidal (0.2-0.7 mum) fraction, exhibiting a strong protein-like signal, increased dramatically at the height of the bloom. At WNB particle sizes and algal composition varied despite the invariant bulk optical properties; CDOM variations were minimal. Overall, the optical properties in the two bays demonstrated that at QB temporal variations were dominated by biomass and colloidal protein changes, whereas shifts in the algal community occurred at WNB. This study demonstrates the utility of in situ optical observations to resolve temporal changes in the ecological conditions associated with algal bloom development. (C) 2004 Elsevier B.V. All rights reserved. C1 Univ Connecticut, Dept Marine Sci, Groton, CT 06340 USA. Bigelow Lab Ocean Sci, W Boothbay Harbor, ME 04575 USA. RP Etheridge, SM (reprint author), US FDA, HFS-426,8301 Muirkirk Rd,Room G-205, Laurel, MD 20708 USA. EM stacey.etheridge@cfsan.fda.gov OI DeGrasse, Stacey/0000-0001-7808-4193 NR 28 TC 13 Z9 19 U1 0 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1568-9883 J9 HARMFUL ALGAE JI Harmful Algae PD NOV PY 2004 VL 3 IS 4 BP 331 EP 342 DI 10.1016/j.hal.2004.06.005 PG 12 WC Marine & Freshwater Biology SC Marine & Freshwater Biology GA 876VE UT WOS:000225525500006 ER PT J AU Pickering, AK Osorio, M Lee, GM Grippe, VK Bray, M Merkel, TJ AF Pickering, AK Osorio, M Lee, GM Grippe, VK Bray, M Merkel, TJ TI Cytokine response to infection with Bacillus anthracis spores SO INFECTION AND IMMUNITY LA English DT Article ID EXPERIMENTAL INHALATION ANTHRAX; LETHAL TOXIN; ALVEOLAR MACROPHAGES; STERNE STRAIN; TNF-ALPHA; MICE; PATHOGENESIS; GERMINATION; RESISTANCE; PATHOLOGY AB Bacillus anthracis, the etiological agent of anthrax, is a gram-positive, spore-forming bacterium. The inhalational form of anthrax is the most severe and is associated with rapid progression of the disease and the outcome is frequently fatal. Transfer from the respiratory epithelium to regional lymph nodes appears to be an essential early step in the establishment of infection. This transfer is believed to occur by means of carriage within alveolar macrophages following phagocytosis. Therefore, the ability of B. anthracis to transit through the host macrophage or dendritic cell appears to be an early and critical step in B. anthracis pathogenesis. In this work we examined the cytokine responses to spore infection in mouse primary peritoneal macrophages, in primary human dendritic cells, and during a spore aerosol infection model utilizing the susceptible A/J mouse strain. We demonstrated that both mouse peritoneal macrophages and human dendritic cells exhibited significant intracellular bactericidal activity during the first hours following uptake, providing the necessary time to mount a cytokine response prior to cell lysis. Strong tumor necrosis factor (TNF-alpha) and interleukin-6 (IL-6) responses were seen in mouse peritoneal macrophages. In addition to TNF-alpha and IL-6, human dendritic cells produced the cytokines IL-1beta, IL-8, and IL-12. A mixture of Th1 and Th2 cytokines were detected in sera obtained from infected animals. In this study, we provide further evidence of an acute cytokine response when cells in culture and mice are infected with B. anthracis spores. C1 US FDA, CBER, DBPAP, Lab Resp & Special Pathogens, Bethesda, MD 20892 USA. US FDA, CBER, DBPAP, Lab Enter & Sexually Transmitted Dis, Bethesda, MD 20892 USA. RP Merkel, TJ (reprint author), US FDA, CBER, DBPAP, Lab Resp & Special Pathogens, Bldg 29,Room 418,29 Lincoln Dr, Bethesda, MD 20892 USA. EM merkel@cber.fda.gov NR 37 TC 70 Z9 75 U1 1 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD NOV PY 2004 VL 72 IS 11 BP 6382 EP 6389 DI 10.1128/IAI.72.11.6382-6389.2004 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 864WS UT WOS:000224664300026 PM 15501768 ER PT J AU Rader, JI Weaver, CM Trucksess, MW AF Rader, JI Weaver, CM Trucksess, MW TI Extension of AOAC Official Method 999.14 (choline in infant formula and milk) to the determination of choline in dietary supplements SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID FOODS; ASSAY AB AOAC Official Method 999.14 is applicable for the determination of choline in milk and infant formulas. To date, its use has not been extended beyond these matrixes. We modified Official Method 999.14 and applied it to the determination of choline in a range of choline-containing dietary supplements. Dietary supplement tablets, capsules, wafers, softgels, liquid products, and drink powders were included. We found that the standard curve could be extended to cover a wider range of choline concentrations and defined a procedure for the use of Norit for samples in which the vitamin C content was high enough to interfere with the analysis. Recoveries of choline added to infant formula powders and to representative dietary supplement tablets, capsules, powdered drink mix, and wafer products were 85-114%. The use of Norit during the procedure did not affect the recovery of choline added to infant formula powders or to dietary supplements. An alkaline digestion was included for use with a product containing lecithin as the sole source of choline. Ten of 11 dietary supplement products analyzed by the modified method contained amounts of choline at or above declarations found on the product labels. The remaining product contained about 40% of the label-declared amount of choline. C1 US FDA, Ctr Food Safety & Appl Nutrit, Div Res & Appl Technol, Off Nutr Prod Labelling & Dietary Supplements, College Pk, MD 20740 USA. RP Rader, JI (reprint author), US FDA, Ctr Food Safety & Appl Nutrit, Div Res & Appl Technol, Off Nutr Prod Labelling & Dietary Supplements, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM Jeanne.Rader@cfsan.fda.gov NR 10 TC 7 Z9 7 U1 0 U2 5 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD NOV-DEC PY 2004 VL 87 IS 6 BP 1297 EP 1304 PG 8 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 878TH UT WOS:000225669200007 PM 15675439 ER PT J AU Chase, CW Ye, L Stoakes, VC Eitenmiller, RR Long, AR AF Chase, CW Ye, L Stoakes, VC Eitenmiller, RR Long, AR TI Interlaboratory verified liquid chromatographic method for analysis of vitamins A and E in soy-based infant formula powder SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID ALPHA-TOCOPHERYL ACETATE; RETINYL PALMITATE AB An interlaboratory verified, liquid chromatographic (LC) method is presented for the analysis of all-rac-alpha-tocopheryl acetate and retinyl palmitate in soy-based infant formula. The extraction procedure uses sample dehydration with magnesium sulfate followed by extraction with isopropanol, hexane-ethyl acetate (85 + 15, v/v). After evaporation and filtration, the sample extract is injected directly onto a normal-phase LC system with fluorescence detection. All-rac-alpha-tocopheryl acetate and retinyl palmitate are quantitated isocratically with a mobile phase of hexane containing 0.50% (v/v) and 0.125% (v/v) isopropanol, respectively. A zero control reference material (ZRM) was spiked at 5 levels, with 5 replicate analyses of 1/2x, x, 2x, 4x, and 16x where "x" is the minimum level of 250 IU/100 kcal (vitamin A) and 0.7 IU/100 kcal (vitamin E) as specified in 21 Code of Federal Regulations 107.100. The following recoveries and RSD values represent an average (n = 25) of the 5 levels for each analyte: all-rac-a-tocopheryl acetate, 100% (RSD = 3.5%); retinyl palmitate, 97.2% (RSD = 2.1%). Two additional laboratories analyzed the fortified ZRM samples. Average recoveries (n = 24) of all-rac-a-tocopheryl acetate and retinyl palmitate at 4 levels were all-rac-a-tocopheryl acetate, 99.0% (RSD = 4.0%), and retinyl palmitate, 96.2% (RSD = 1.4%) at the second laboratory. Average recoveries (n = 24) of all-rac-alpha-tocopheryl acetate and retinyl palmitate at 4 levels were all-rac-alpha-tocopheryl acetate, 102% (RSD = 1.4%) and retinyl palmitate, 95.7% (RSD = 2.0%) at the third laboratory. In addition, 6 replicates of the same commercial soy-based infant formula powder were run by the 3 laboratories. C1 US FDA, Atlanta Ctr Nutrient Anal, Atlanta, GA 30309 USA. Univ Georgia, Dept Food Sci & Technol, Athens, GA 30602 USA. RP Chase, CW (reprint author), US FDA, Pacific Reg Lab NW, 22201 23rd Dr SE, Bothell, WA 98021 USA. EM wchase@ora.fda.gov NR 6 TC 2 Z9 2 U1 0 U2 3 PU AOAC INT PI GAITHERSBURG PA 481 N FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 EI 1944-7922 J9 J AOAC INT JI J. AOAC Int. PD NOV-DEC PY 2004 VL 87 IS 6 BP 1329 EP 1333 PG 5 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 878TH UT WOS:000225669200012 ER PT J AU Williams, KM AF Williams, KM TI Methodological aspects of food allergens SO JOURNAL OF AOAC INTERNATIONAL LA English DT Editorial Material ID PRODUCTS; PEANUT; ELISA C1 US FDA, Ctr Food Safety & Appl Nutr, Immunol Branch, Laurel, MD 20708 USA. RP Williams, KM (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Immunol Branch, 8301 Muirkirk Rd, Laurel, MD 20708 USA. EM kwillia2@cfsan.fda.gov NR 8 TC 1 Z9 1 U1 0 U2 0 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD NOV-DEC PY 2004 VL 87 IS 6 BP 1380 EP 1382 PG 3 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 878TH UT WOS:000225669200017 PM 15675449 ER PT J AU Gendel, SM AF Gendel, SM TI Bioinformatics and food allergens SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID DATABASE; PROTEINS AB Bioinformatics can play an important role in developing improved technology for the detection and characterization of food allergens. However, the full realization of this potential will depend on the development of allergen-specific databases as well as improved methods for data mining within these databases. Examples of existing allergen databases and analysis tools are described, as are the most important issues that need to be addressed in the next stage of database development. C1 US FDA, Natl Ctr Food Safety & Technol, Summit Argo, IL 60501 USA. RP Gendel, SM (reprint author), US FDA, Natl Ctr Food Safety & Technol, 6502 S Archer Rd, Summit Argo, IL 60501 USA. EM sgendel@cfsan.fda.gov NR 10 TC 15 Z9 16 U1 0 U2 1 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD NOV-DEC PY 2004 VL 87 IS 6 BP 1417 EP 1422 PG 6 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 878TH UT WOS:000225669200022 PM 15675454 ER PT J AU Westphal, CD Raybourne, RB AF Westphal, CD Raybourne, RB TI Potential allergenicity of novel proteins in murine models SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID BROWN-NORWAY RAT; FOOD-ALLERGY MODEL; BOVINE BETA-LACTOGLOBULIN; ORAL SENSITIZATION; COWS MILK; ANTIBODY-RESPONSES; IMMUNOGLOBULIN-E; ADVERSE REACTIONS; IMMUNE-RESPONSES; CHOLERA-TOXIN AB Bioengineered crops represent an important advancement for farmers who want to avoid losses caused by insect infestations or adverse environmental conditions. However, the use of modern biotechnology has raised questions regarding the safety of bioengineered foods because of the potential allergenicity of proteins expressed by the newly introduced genes. Standard approaches for safety assessment of these foods are still evolving. Animal models have been suggested as a tool that could help evaluate the potential allergenicity of such compounds. Several investigators are developing animal models to evaluate novel proteins, but none of these have yet been validated. This article reviews the published murine models, rat and mouse in particular, and the different methods used to evaluate parameters related to allergy. It also addresses the factors involved in the development of a model. Finally, it raises some questions that should be considered by the international community so that financial and intellectual efforts can be addressed in a unified manner. C1 US FDA, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. RP Westphal, CD (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 8301 Muirkirk Rd, Laurel, MD 20708 USA. EM carmen.westphal@cfsan.fda.gov NR 70 TC 0 Z9 0 U1 0 U2 0 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD NOV-DEC PY 2004 VL 87 IS 6 BP 1433 EP 1440 PG 8 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 878TH UT WOS:000225669200024 PM 15675456 ER PT J AU Westphal, CD Pereira, MR Raybourne, RB Williams, KM AF Westphal, CD Pereira, MR Raybourne, RB Williams, KM TI Evaluation of extraction buffers using the current approach of detecting multiple allergenic and nonallergenic proteins in food SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID PEANUT AB The detection of food allergens has been a challenge because of the increasing need to ensure the absence of undeclared allergens in foods. The current trend in the detection of some food allergens, like peanuts, is based on the detection of multiple allergenic and nonallergenic proteins, and this is the approach that kit manufacturers have adopted. Because commercial kits differ in their ability to detect allergens, regulatory agencies, the food industry, and kit manufacturers are working together to standardize the detection methods. Three kits for the detection of peanuts have been evaluated for performance by the AOAC Research Institute. For this evaluation, a peanut butter suspension was used as a reference material. Several kit components contribute to between-kit analytical variation, even when the same sample is used. One component of commercial kits, which may be contributing to this variability, is the sample extraction buffer. In this study, differences in extractability of 3 allergenic foods were evaluated by using 4 different extraction buffers. The conclusion is that optimum allergen extractability was buffer-de pendent, and no single buffer is appropriate for use as a universal extraction solution for all allergenic foods. Therefore, a thorough evaluation of sample preparation buffers needs to be performed for every individual allergenic food. In light of the results obtained, the current approach used for detection of peanut allergens based on the detection of multiple allergenic and nonallergenic proteins is being analyzed. C1 US FDA, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. RP Westphal, CD (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 8301 Muirkirk Rd, Laurel, MD 20708 USA. EM carmen.westphal@cfsan.fda.gov NR 10 TC 22 Z9 23 U1 1 U2 1 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD NOV-DEC PY 2004 VL 87 IS 6 BP 1458 EP 1465 PG 8 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 878TH UT WOS:000225669200027 PM 15675459 ER PT J AU Williams, KM Westphal, CD Shriver-Lake, LC AF Williams, KM Westphal, CD Shriver-Lake, LC TI Determination of egg proteins in snack food and noodles SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID LINKED-IMMUNOSORBENT-ASSAY; ENZYME-IMMUNOASSAY; WHITE; PRODUCTS; MILK; ALLERGENS AB Egg is one of the 5 major allergenic foods that are responsible for more than 3/4 of food allergies in children. Food-allergic responses can be controlled by avoidance of the offending foods. The applicability of a commercial enzyme-linked immunosorbent assay (ELISA) kit for the detection of egg in food products such as cookies, crackers, pretzels, salad dressings, and raw and cooked noodles was evaluated. A preliminary evaluation of an antibody-based biosensor was also performed. A National Institute of Standards and Technology (NIST) whole dried egg powder reference material, SRM 8415, was used as a standard. A homogeneous and stable aqueous egg suspension was prepared for the evaluation of the performance of the Veratox for Egg Allergen Test (Neogen Corp., Lansing, MI). This test does not detect egg yolk proteins. Each gram of the aqueous dried egg suspension contained 643 mug whole dried egg, 0.5 mg thimerosal, and 2.5 mg bovine serum albumin. When cookies, crackers, salad dressings, noodles, and ice cream were spiked at a level of 24 mg/kg SRM 8415, recoveries for whole egg averaged about 28%. All foods containing egg as indicated on the ingredient label were found positive by the Veratox test. No false positives occurred in samples that did not contain eggs. Similar results were obtained using the Naval Research Laboratory (NRL) array biosensor, an evanescent wave fluoroimmunosensor. Results for cooked noodles showed that they contained <1% of the egg found in uncooked noodles. A comparison of extracts from cooked and uncooked noodles by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) revealed differences in protein profiles. The boiling of the noodles could have reduced the immunoreactivity of the egg proteins to the antibodies used in the kit or rendered the egg proteins nonextractable. C1 US FDA, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. USN, Res Lab, Ctr Bio Mol Sci & Engn, Washington, DC 20375 USA. RP Williams, KM (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 8301 Muikirk Rd, Laurel, MD 20708 USA. EM kwillia2@cfsan.fda.gov NR 22 TC 17 Z9 21 U1 3 U2 13 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD NOV-DEC PY 2004 VL 87 IS 6 BP 1485 EP 1491 PG 7 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 878TH UT WOS:000225669200031 PM 15675463 ER PT J AU Wang, JH Alvarez, R Roderiquez, G Guan, E Norcross, MA AF Wang, JH Alvarez, R Roderiquez, G Guan, E Norcross, MA TI Constitutive association of cell surface CCR5 and CXCR4 in the presence of CD4 SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE chemokine receptor; chemokine; HIV-1; viral entry ID IMMUNODEFICIENCY-VIRUS TYPE-1; PRINCIPAL HIV-1 CORECEPTOR; PROTEIN-COUPLED RECEPTOR; T-CELLS; CHEMOKINE RECEPTORS; EXPRESSION; INFECTION; ENTRY; MACROPHAGES; HETERODIMERIZATION AB Chemokine receptors CCR5 and CXCR4 are the major coreceptors of HIV-1 infection and also play fundamental roles in leukocyte trafficking, metastasis, angiogenesis, and embyogenesis. Here, we show that transfection of CCR5 into CXCR4 and CD4 expressing 3T3 cells enhances the cell surface level of CXCR4. In CCR5 high expressing cells, cell surface level of CXCR4 was incompletely modulated in the presence of the CXCR4 ligand CXCL12/SDF-1alpha. CCR5 was resistant to ligand-dependent modulation with the CCR5 ligand CCL5/RANTES. Confocal laser microscopy revealed that CCR5 was colocalized with CXCR4 on the cell surface. In CD4 expressing CCR5 and CXCR4 double positive NIH 3T3 cells, immunoprecipitation followed by Western blot analysis revealed that CCR5 was associated with CXCR4 and CD4. CXCR4 and CCR5 were not co-immunoprecipitated in cells expressing CCR5 and CXCR4 but without CD4 expression. Compared to NIH 3T3CD4 cells expressing CXCR4, the entry of an HIV-1 X4 isolate (HCF) into NIH 3T3CD4 expressing both CXCR4 and CCR5 was reduced. Our data indicate that chemokine receptors interact with each other, which may modulate chemokine-chemokine receptor interactions and HIV-1 coreceptor functions. Published 2004 Wiley-Liss, Inc(dagger). C1 US FDA, Ctr Drug Evaluat & Res, Div Therapeut Prot, Lab Immunol,Off Biotechnol Prod, Bethesda, MD 20892 USA. RP Wang, JH (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Therapeut Prot, Lab Immunol,Off Biotechnol Prod, NIH Bldg 29B,Room 4E12,HFM-541,8800 Rockville Pik, Bethesda, MD 20892 USA. EM wangj@cber.fda.gov NR 39 TC 29 Z9 29 U1 0 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD NOV 1 PY 2004 VL 93 IS 4 BP 753 EP 760 DI 10.1002/jcb.20161 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 868SL UT WOS:000224933200013 PM 15660419 ER PT J AU Piperova, LS Moallem, U Teter, BB Sampugna, J Yurawecz, MP Morehouse, KM Luchini, D Erdman, RA AF Piperova, LS Moallem, U Teter, BB Sampugna, J Yurawecz, MP Morehouse, KM Luchini, D Erdman, RA TI Changes in milk fat in response to dietary supplementation with calcium salts of trans-18 : 1 or conjugated linoleic fatty acids in lactating dairy cows SO JOURNAL OF DAIRY SCIENCE LA English DT Article DE lactating cow; trans fatty acids; conjugated linoleic acids ID ABOMASAL INFUSION; HOLSTEIN COWS; OCTADECENOIC ACIDS; DUODENAL FLOW; BLOOD-PLASMA; CLA; ISOMERS; DELTA(9)-DESATURASE; BIOHYDROGENATION; IDENTIFICATION AB Milk fat was investigated in lactating dairy cows fed diets supplemented with Ca salts of trans fatty acids (Ca-tFA) or Ca salts of conjugated linoleic acids (Ca-CLA). Forty-five Holstein cows ( 115 days in milk) were fed a control diet (51% forage; dry matter basis) supplemented with 400 g of EnerG II ( Ca salts of palm oil fatty acids) for 2 wk; subsequently, 5 groups of 9 cows each were assigned for 4 wk to the control diet or diets containing 100 g of Ca-CLA or 100, 200, or 400 g of Ca-tFA in a randomized block design. Treatments had no effect on dry matter intake, milk production, protein, lactose, or somatic cell count. Milk fat percentage was reduced from 3.39% in controls to 3.30, 3.04, and 2.98%, respectively, by the Ca-tFA diets and to 2.54% by the Ca-CLA diet. Milk fat yield (1.24 kg/d in controls) was decreased by 60, 130, and 190 g/d with increasing dose of Ca-tFA and by 290 g/d with the Ca-CLA supplement. Consistent with increased endogenous synthesis of cis-9-containing CLA from precursors provided by the Ca-tFA diets, total CLA were similar in milk of cows fed Ca-CLA or Ca-tFA. Compared with controls, the Ca-CLA diet increased trans-10, cis-12-18: 2 yield in milk, without altering levels of trans-18: 1 isomers. In contrast, yields of most trans-18: 1 isomers were elevated in milk of cows fed Ca-tFA diets, whereas yields of trans-10, cis-12-18: 2 remained similar to control values. We conclude that milk fat depression can occur without an increase in trans-10, cis-12-18: 2 in milk and that other components, perhaps the trans-10-18:1 isomer, may be involved. C1 Univ Maryland, Anim & Avian Sci Dept, College Pk, MD 20742 USA. Univ Maryland, Dept Chem & Biochem, College Pk, MD 20742 USA. US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20742 USA. Bioprod Inc, Fairlawn, OH 44333 USA. RP Erdman, RA (reprint author), Univ Maryland, Anim & Avian Sci Dept, College Pk, MD 20742 USA. EM erdman@umd.edu RI Erdman, Richard/F-6195-2010 OI Erdman, Richard/0000-0001-6954-4282 NR 38 TC 44 Z9 46 U1 1 U2 7 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 NOV PY 2004 VL 87 IS 11 BP 3836 EP 3844 PG 9 WC Agriculture, Dairy & Animal Science; Food Science & Technology SC Agriculture; Food Science & Technology GA 863EU UT WOS:000224544500029 PM 15483168 ER PT J AU Lumsden, JM McCarty, T Petiniot, LK Shen, R Barlow, C Wynn, TA Morse, HC Gearhart, PJ Wynshaw-Boris, A Max, EE Hodes, RJ AF Lumsden, JM McCarty, T Petiniot, LK Shen, R Barlow, C Wynn, TA Morse, HC Gearhart, PJ Wynshaw-Boris, A Max, EE Hodes, RJ TI Immunoglobulin class switch recombination is impaired in Atm-deficient mice SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE ataxia telangiectasia; Ig class switching; B lymphocytes; DNA damage; DNA repair ID DOUBLE-STRAND BREAKS; DNA-DAMAGE-RESPONSE; TELANGIECTASIA MUTATED ATM; CYTIDINE DEAMINASE AID; ATAXIA-TELANGIECTASIA; DEPENDENT PHOSPHORYLATION; B-CELLS; SOMATIC HYPERMUTATION; REGION RECOMBINATION; T-CELLS AB Immunoglobulin class switch recombination (Ig CSR) involves DNA double strand breaks (DSBs) at recombining switch regions and repair of these breaks by nonhomologous end joining. Because the protein kinase ataxia telengiectasia (AT) mutated (ATM) plays a critical role in DSB repair and AT patients show abnormalities of Ig isotype expression, we assessed the role of ATM in CSR by examining ATM-deficient mice. In response to T cell-dependent antigen (Ag), Atm(-/-) mice secreted substantially less Ag-specific IgA, IgG1, IgG2b, and IgG3, and less total IgE than Atm(+/+) controls. To determine whether Atm(-/-) B cells have an intrinsic defect in their ability to undergo CSR, we analyzed in vitro responses of purified B cells. Atm(-/-) cells secreted substantially less IgA, IgG1, IgG2a, IgG3, and IgE than wild-type (WT) controls in response to stimulation with lipopolysaccharide, CD40 ligand, or anti-IgD plus appropriate cytokines. Molecular analysis of in vitro responses indicated that WT and Atm(-/-) B cells produced equivalent amounts of germline IgG1 and IgE transcripts, whereas Atm(-/-) B cells produced markedly reduced productive IgG1 and IgE transcripts. The reduction in isotype switching by Atm(-/-) B cells occurs at the level of genomic DNA recombination as measured by digestion-circularization PCR. Analysis of sequences at CSR sites indicated that there is greater microhomology at the mu-gamma1 switch junctions in ATM B cells than in wild-type B cells, suggesting that ATM function affects the need or preference for sequence homology in the CSR process. These findings suggest a role of ATM in DNA DSB recognition and/or repair during CSR. C1 NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. NIAID, Immunopathol Lab, NIH, Bethesda, MD 20892 USA. NIH, Howard Hughes Med Inst, Res Scholars Program, Bethesda, MD 20892 USA. NIH, Natl Ctr Human Genome Res, Genet Dis Res Branch, Bethesda, MD 20892 USA. NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. NIA, NIH, Bethesda, MD 20892 USA. NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. RP Lumsden, JM (reprint author), NCI, Expt Immunol Branch, NIH, Bldg 10,Room 4B10,10 Ctr Dr, Bethesda, MD 20892 USA. EM lumsdenj@mail.nih.gov RI Wynn, Thomas/C-2797-2011; OI Morse, Herbert/0000-0002-9331-3705 NR 65 TC 92 Z9 94 U1 0 U2 3 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD NOV 1 PY 2004 VL 200 IS 9 BP 1111 EP 1121 DI 10.1084/jem.20041074 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 869CS UT WOS:000224961600004 PM 15504820 ER PT J AU Tollefson, L Kruse, H Wegener, HC AF Tollefson, L Kruse, H Wegener, HC TI "Public health consequences of macrolide use in food animals: A deterministic risk assessment," - A comment on: J. Food Prot 67(5): 980-992 (2004) SO JOURNAL OF FOOD PROTECTION LA English DT Letter ID RESISTANCE C1 US FDA, Ctr Vet Med, Rockville, MD 20857 USA. Natl Vet Inst, Norwegian Zoonosis Ctr, Oslo, Norway. Danish Inst Food & Vet Res, Soborg, Denmark. RP Tollefson, L (reprint author), US FDA, Ctr Vet Med, Rockville, MD 20857 USA. NR 9 TC 1 Z9 1 U1 0 U2 4 PU INT ASSOC FOOD PROTECTION PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD NOV PY 2004 VL 67 IS 11 BP 2368 EP 2369 PG 2 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 868VD UT WOS:000224940200001 PM 15553613 ER PT J AU Kaufman, GE Blackstone, GM Vickery, MCL Bej, AK Bowers, J Bowen, MD Meyer, RF DePaola, A AF Kaufman, GE Blackstone, GM Vickery, MCL Bej, AK Bowers, J Bowen, MD Meyer, RF DePaola, A TI Real-time PCR quantification of Vibrio parahaemolyticus in oysters using an alternative matrix SO JOURNAL OF FOOD PROTECTION LA English DT Article ID GULF-COAST OYSTERS; UNITED-STATES; THERMOLABILE HEMOLYSIN; CRASSOSTREA-VIRGINICA; RAW OYSTERS; VULNIFICUS; TISSUES; GENE; TDH AB This study examined the relationship between levels of total Vibrio parahaernolyticus found in oyster tissues and mantle fluid with the goal of using mantle fluid as a template matrix in a new quantitative real-time PCR assay targeting the thermolabile hemolysin (tlh) gene for the enumeration of total V. parahaemolyticus in oysters. Oysters were collected near Mobile Bay, Ala., in June, July, and September and tested immediately after collection and storage at 26degreesC for 24 h. Initial experiments using DNA colony hybridization targeting tlh demonstrated that natural V. parahaemolyticus levels in the mantle fluid of individual oysters were strongly correlated (r = 0.85 P < 0.05) with the levels found in their tissues. When known quantities of cultured V. parahaemolyticus cells were added to real-time PCR reactions that contained mantle fluid and oyster tissue matrices separately pooled from multiple oysters, a strong linear correlation was observed between the real-time PCR cycle threshold and the log concentration of cells inoculated into each PCR reaction (mantle fluid: r = 0.98, P < 0.05; and oyster: r = 0.99, P < 0.05). However, the mantle fluid exhibited less inhibition of the PCR amplification than the homogenized oyster tissue. Analysis of natural V. parahaemolyticus populations in mantle fluids using both colony hybridization and realtime PCR demonstrated a significant (P < 0.05) but reduced correlation (r = -0.48) between the two methods. Reductions in the efficiency of the real-time PCR that resulted from low population densities of V. parahaemolyticus and PCR inhibitors present in the mantle fluid of some oysters (with significant oyster-to-oyster variation) contributed to the reduction in correlation between the methods that was observed when testing natural V. parahaernolyticus populations. The V. parahaemolyticus-specific real-time PCR assay used for this study could estimate elevated V. parahaeinolyticus levels in oyster mantle fluid within 1 h from sampling time. C1 US FDA, Gulf Coast Seafood Lab, Dauphin Isl, AL 36528 USA. Univ Alabama, Dept Biol, Birmingham, AL 35294 USA. US FDA, Off Math & Stat, College Pk, MD 20740 USA. Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. RP DePaola, A (reprint author), US FDA, Gulf Coast Seafood Lab, POB 158, Dauphin Isl, AL 36528 USA. EM adepaola@cfsan.fda.gov NR 24 TC 34 Z9 42 U1 1 U2 5 PU INT ASSOC FOOD PROTECTION PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD NOV PY 2004 VL 67 IS 11 BP 2424 EP 2429 PG 6 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 868VD UT WOS:000224940200012 PM 15553623 ER PT J AU Yoon, KS Burnette, CN Abou-Zeid, KA Whiting, RC AF Yoon, KS Burnette, CN Abou-Zeid, KA Whiting, RC TI Control of growth and survival of Listeria monocytogenes on smoked salmon by combined potassium lactate and sodium diacetate and freezing stress during refrigeration and frozen storage SO JOURNAL OF FOOD PROTECTION LA English DT Article ID LACTIC-ACID BACTERIA; CLOSTRIDIUM-BOTULINUM; CARNOBACTERIUM SPP.; FISHERY PRODUCTS; COOKED BEEF; INHIBITION; 4-DEGREES-C; TEMPERATURE; BROTH; SCOTT AB In this study, we evaluated the antimicrobial effects of different levels of a potassium lactate (PL) plus sodium diacetate (SDA) mixture against the growth and survival of Listeria monocytogenes Scott A inoculated onto smoked salmon stored at 4, 10, and -20degreesC. The effect of freezing stress on the growth kinetics of L. monocytogenes Scott A on smoked salmon at 4 and 10degreesC was also investigated. The use of PL+SDA at all tested levels (1.5, 3.3, and 5% of a 60% commercial solution of PURASAL P Opti.Form 4) completely inhibited the growth of L. monocytogenes Scott A On smoked salmon stored at 4degreesC during 32 days of storage. It also delayed the growth of L. monocytogenes Scott A on smoked salmon stored at 10degreesC for up to I I days, but a listeriostatic effect was observed only with 5% PURASAL P Opti.Form 4 at 10degreesC after 11 days. Addition of PL+SDA at all tested levels decreased the surviving populations of L. monocytogenes Scott A on smoked salmon during 10 months of frozen storage at -20degreesC. Freezing stress significantly (P < 0.001) extended the lag time and delayed the growth of L. monocytogenes Scott A at both 4 and 10degreesC. However, the effect of freezing stress was more significant at 4degreesC than at 10degreesC, indicating the importance of temperature control of smoked salmon during the retail storage period. C1 Univ Maryland Eastern Shore, Ctr Food Sci & Technol, Princess Anne, MD 21853 USA. US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Yoon, KS (reprint author), Univ Maryland Eastern Shore, Ctr Food Sci & Technol, Princess Anne, MD 21853 USA. EM ksyoon@umes.edu NR 36 TC 45 Z9 46 U1 4 U2 8 PU INT ASSOC FOOD PROTECTION PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD NOV PY 2004 VL 67 IS 11 BP 2465 EP 2471 PG 7 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 868VD UT WOS:000224940200018 PM 15553629 ER PT J AU Rodriguez-Saona, LE Khambaty, FM Fry, FS Dubois, J Calvey, EM AF Rodriguez-Saona, LE Khambaty, FM Fry, FS Dubois, J Calvey, EM TI Detection and identification of bacteria in a juice matrix with Fourier transform-near infrared spectroscopy and multivariate analysis SO JOURNAL OF FOOD PROTECTION LA English DT Article ID ARTIFICIAL NEURAL-NETWORKS; STRAINS; CLASSIFICATION; DISCRIMINATION; SPECTRA AB The use of Fourier transform-near infrared (FT-NIR) spectroscopy combined with multivariate pattern recognition techniques was evaluated to address the need for a fast and sensitive method for the detection of bacterial contamination in liquids. The complex cellular composition of bacteria produces FT-NIR vibrational transitions (overtone and combination bands), forming the basis for identification and subtyping. A database including strains of Escherichia coli, Pseudomonas aeruginosa, Bacillus subtilis, Bacillus cereus, and Bacillus thuringiensis was built, with special-care taken to optimize sample preparation. The bacterial cells were treated with 70% (vol/vol) ethanol to enhance safe handling of pathogenic strains and then concentrated on an aluminum oxide membrane to obtain a thin bacterial film. This simple membrane filtration procedure generated reproducible FT-NIR spectra that allowed for the rapid discrimination among closely related strains. Principal component analysis and soft independent modeling of class analogy of transformed spectra in the region 5,100 to 4,400 cm(-1) were able to discriminate between bacterial species. Spectroscopic analysis of apple juices inoculated with different strains of E. coli at approximately 10(5) CFU/ml showed that FT-NIR spectral features are consistent with bacterial contamination and soft independent modeling of class analogy correctly predicted the identity of the contaminant as strains of E. coli. FT-NIR in conjunction with multivariate techniques can be used for the rapid and accurate evaluation of potential bacterial contamination in liquids with minimal sample manipulation, and hence limited exposure of the laboratory worker to the agents. C1 Ctr Food Safety & Appl Nutr, US FDA, College Pk, MD 20740 USA. Univ Maryland, JIFSAN, College Pk, MD 20742 USA. RP Calvey, EM (reprint author), Ctr Food Safety & Appl Nutr, US FDA, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM elizabeth.calvey@cfsan.fda.gov RI Rodriguez-Saona, Luis/A-8557-2013 NR 26 TC 47 Z9 47 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 NOV PY 2004 VL 67 IS 11 BP 2555 EP 2559 PG 5 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 868VD UT WOS:000224940200030 PM 15553641 ER PT J AU Bey, EA Xu, B Bhattacharjee, A Oldfield, CM Zhao, XX Li, Q Subbulakshmi, V Feldman, GM Wientjes, FB Cathcart, MK AF Bey, EA Xu, B Bhattacharjee, A Oldfield, CM Zhao, XX Li, Q Subbulakshmi, V Feldman, GM Wientjes, FB Cathcart, MK TI Protein kinase C delta is required for P47(phox) phosphorylation and translocation in activated human monocytes SO JOURNAL OF IMMUNOLOGY LA English DT Article ID RESPIRATORY BURST OXIDASE; LOW-DENSITY-LIPOPROTEIN; CYTOSOLIC PHOSPHOLIPASE A(2); SUPEROXIDE ANION PRODUCTION; NADPH-OXIDASE; HUMAN-NEUTROPHILS; COMPONENT P47(PHOX); PLASMA-MEMBRANE; OXIDATION; SITES AB Our laboratory is interested in understanding the regulation of NADPH oxidase activity in human monocyte/macrophages. Protein kinase C (PKC) is reported to be involved in regulating the phosphorylation of NADPH oxidase components in human neutrophils; however, the regulatory roles of specific isoforms of PKC in phosphorylating particular oxidase components have not been determined. In this study calphostin C, an inhibitor for both novel PKC (including PKCdelta, -epsilon, -theta, and -eta) and conventional PKC (including PKCalpha and -beta), inhibited both phosphorylation and translocation of p47(phox), an essential component of the monocyte NADPH oxidase. In contrast, GF109203X, a selective inhibitor of classical PKC and PKCepsilon, did not affect the phosphorylation or translocation of p47(phox), suggesting that PKCdelta, -theta, or -eta is required. Furthermore, rottlerin (at doses that inhibit PKCdelta activity) inhibited the phosphorylation and translocation of p47(phox). Rottlerin also inhibited O(2)(.) production at similar doses. In addition to pharmacological inhibitors, PKCdelta-specific antisense oligodeoxyribonucleotides were used. PKCdelta antisense oligodeoxyribonucleotides inhibited the phosphorylation and translocation of p47(phox) in activated human monocytes. We also show, using the recombinant p47(phox)-GST fusion protein, that p47(phox) can serve as a substrate for PKCdelta in vitro. Furthermore, lysate-derived PKCdelta from activated monocytes phosphorylated p47(phox) in a rottlerin-sensitive manner. Together, these data suggest that PKCdelta plays a pivotal role in stimulating monocyte NADPH oxidase activity through its regulation of the phosphorylation and translocation of p47(phox). C1 Cleveland Clin Fdn, Lerner Res Inst, Dept Cell Biol, Cleveland, OH 44195 USA. Food & Drug Adm, Ctr Biol Evaluat & Res, Off Therapeut & Drug Adm, Div Monoclonal Antibodies, Bethesda, MD 20892 USA. UCL, Dept Med, London, England. RP Cathcart, MK (reprint author), Cleveland Clin Fdn, Lerner Res Inst, Dept Cell Biol, 9500 Euclid Ave, Cleveland, OH 44195 USA. EM cathcam@ccf.org FU NHLBI NIH HHS [HL51068, HL61971] NR 49 TC 130 Z9 133 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 1 PY 2004 VL 173 IS 9 BP 5730 EP 5738 PG 9 WC Immunology SC Immunology GA 864XH UT WOS:000224665900049 PM 15494525 ER PT J AU Liu, K Hirschfeld, S AF Liu, K Hirschfeld, S TI Threshold of credibility: A new approach to product development for metastatic melanoma therapy SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 19th Annual Scientific Meeting of the International-Society-for-Biological-Therapy-of-Cancer CY NOV 04-07, 2004 CL San Francisco, CA SP Int Soc Biol Therapy Canc C1 US FDA, Off Cellular Tissue & Gene Therapy, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. RI Hirschfeld, Steven/E-2987-2016 OI Hirschfeld, Steven/0000-0003-0627-7249 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2004 VL 27 IS 6 BP S55 EP S55 DI 10.1097/00002371-200411000-00196 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 868GT UT WOS:000224902800197 ER PT J AU Chen, B Amos, JA Beck, JC Barton, DE Chan, MM Farkas, DH Lebo, RV O'Connell, CD Richards, CS Roa, BB Silverman, LM Lubin, IM Boone, DJ AF Chen, B Amos, JA Beck, JC Barton, DE Chan, MM Farkas, DH Lebo, RV O'Connell, CD Richards, CS Roa, BB Silverman, LM Lubin, IM Boone, DJ TI Developing a sustainable process to make quality control (QC) materials available in response to the needs of the genetic testing community SO JOURNAL OF MOLECULAR DIAGNOSTICS LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Molecular-Pathology CY NOV 10-13, 2004 CL Los Angeles, CA SP Assoc Mole Pathol C1 Ctr Dis Control & Prevent, Atlanta, GA USA. Specialty Labs, Santa Monica, CA USA. Coriell Inst Med Res, Camden, NJ USA. Our Ladys Hosp Sick Children, CRMGEN Consortium, Dublin 12, Ireland. Our Ladys Hosp Sick Children, Natl Ctr Med Genet, Dublin 12, Ireland. US FDA, Rockville, MD 20857 USA. Baylor Coll Med, Houston, TX 77030 USA. Univ Akron, Childrens Hosp, Med Ctr, Akron, OH 44325 USA. Natl Inst Stand & Technol, Gaithersburg, MD 20899 USA. Oregon Hlth Sci Univ, Portland, OR 97201 USA. Univ Virginia, Charlottesville, VA USA. RI Barton, David/B-9460-2008 NR 0 TC 3 Z9 3 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 1525-1578 J9 J MOL DIAGN JI J. Mol. Diagn. PD NOV PY 2004 VL 6 IS 4 MA G34 BP 412 EP 412 PG 1 WC Pathology SC Pathology GA 885XG UT WOS:000226190000047 ER PT J AU Begier, EM Langford, CA Sneller, MC Wise, RP Ball, R AF Begier, EM Langford, CA Sneller, MC Wise, RP Ball, R CA VAERS Working Grp TI Polyarteritis nodosa reports to the Vaccine Adverse Event Reporting System (VAERS): Implications for assessment of suspected vaccine-provoked vasculitis SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE vasculitis; polyarteritis nodosa; vaccination hepatitis B vaccine ID HEPATITIS-B-VIRUS; RHEUMATIC DISORDERS; HBV INFECTION; PATHOGENESIS; IMMUNIZATION AB Objective. To examine polyarteritis nodosa (PAN) reports to the Vaccine Adverse Event Reporting System (VAERS) as the initial stage in investigating the hypothesis that vaccination can very rarely cause PAN. Methods. We reviewed PAN reports submitted from 1990 through 2001 using a causal inference framework to evaluate the consistency of the reports' clinical details with this hypothesis. We also reviewed published literature relating to the hypothesized association's biological plausibility. Results. VAERS received 25 PAN reports. Ten met our case definition for definite or possible PAN and had no alternative etiology for PAN identified. Nine of these 10 followed hepatitis B vaccine with a modal peak (4 definite cases) in time to symptom onset 2 weeks after vaccination. However, all potential triggering infections were not excluded, and identification of vaccine antigens in clinical specimens was not attempted. Also, 14 of 25 reports were European, with 11 from France. All 9 French reports with a known diagnosis date began during 1994-97, when autoimmune and rheumatologic events following hepatitis B vaccine were a focus of public concern in France. Conclusion. While we identified some supportive evidence, overall, current adverse event reports do not support a causal link between vaccination and PAN. Appropriate prospective evaluation of future post-vaccination PAN cases could add to current knowledge with rigorous confirmation of diagnosis, appropriate testing for possible triggering infections including polymerase chain reaction testing for latent hepatitis B infection, and an attempt to link the vaccine antigen to pathology such as by immunohistochemical staining or immune complex identification. C1 US FDA, CBER, OBE, VSB, Rockville, MD 20852 USA. NIAID, Immunol Dis Sect, Immunoregulat Lab, NIH, Bethesda, MD USA. RP Ball, R (reprint author), US FDA, CBER, OBE, VSB, HFM-222,1401 Rockville Pike, Rockville, MD 20852 USA. EM ballr@cber.fda.gov NR 32 TC 15 Z9 15 U1 2 U2 3 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO, ONTARIO M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD NOV PY 2004 VL 31 IS 11 BP 2181 EP 2188 PG 8 WC Rheumatology SC Rheumatology GA 868GB UT WOS:000224901000016 PM 15517631 ER PT J AU Lim, HW Cyr, WH AF Lim, HW Cyr, WH TI Scientific and regulatory issues related to indoor tanning SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID SUNSCREEN USE; ADOLESCENTS; MELANOMA; CHILDREN; RISK C1 Henry Ford Hosp, Dept Dermatol, Detroit, MI 48202 USA. US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. George Washington Univ, Dept Environm & Occupat Hlth, Washington, DC USA. Dartmouth Hitchcock Med Ctr, Dermatol Sect, Lebanon, NH 03766 USA. Vet Affairs Med Ctr, Dermatoepidemiol Unit, Providence, RI USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. St Lukes Roosevelt Hosp, New York, NY USA. NYU, Sch Med, New York, NY USA. Mt Sinai Hosp, New York, NY 10029 USA. RP Lim, HW (reprint author), Amer Acad Dermatol Inc, POB 4014, Schaumburg, IL 60168 USA. NR 15 TC 10 Z9 10 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD NOV PY 2004 VL 51 IS 5 BP 781 EP 784 DI 10.1016/j.jaad.2004.08.017 PG 4 WC Dermatology SC Dermatology GA 867BB UT WOS:000224816000019 PM 15523359 ER PT J AU Tollefson, L Karp, BE AF Tollefson, L Karp, BE TI Human health impact from antimicrobial use in food animals SO MEDECINE ET MALADIES INFECTIEUSES LA English DT Review DE antimicrobial-resistance; foodborne disease; antibiotics for animals ID SEROTYPE TYPHIMURIUM DT104; DRUG-RESISTANT SALMONELLA; RAW-MILK CHEESE; CAMPYLOBACTER-JEJUNI; MULTIDRUG-RESISTANT; UNITED-STATES; ANTIBIOTIC-RESISTANCE; ESCHERICHIA-COLI; RETAIL MEATS; QUINOLONE RESISTANCE AB There is accumulating evidence that the use of antimicrobials in food-producing animals has adverse human health consequences. The use of antibiotics in food animals selects for resistant pathogens and resistance genes that may be transferred to humans through the consumption or handling of foods of animal origin. Recent studies have demonstrated that antimicrobial-resistance among foodborne bacteria may cause excess cases of illness, prolonged duration of illness, and increased rates of bacteremia, hospitalization, and death. The continued availability of safe and effective antimicrobials for humans and animals depends upon the responsible use of these products. (C) 2004 Elsevier SAS. All rights reserved. C1 US FDA, Ctr Vet Med, Rockville, MD 20855 USA. RP Tollefson, L (reprint author), US FDA, Ctr Vet Med, 7519 Standish Pl, Rockville, MD 20855 USA. EM ltollefs@cvm.fda.gov NR 78 TC 29 Z9 33 U1 3 U2 8 PU EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS PA 23 RUE LINOIS, 75724 PARIS, FRANCE SN 0399-077X J9 MED MALADIES INFECT JI Med. Mal. Infect. PD NOV PY 2004 VL 34 IS 11 BP 514 EP 521 DI 10.1016/j/medmal.2004.07.028 PG 8 WC Infectious Diseases SC Infectious Diseases GA 878MB UT WOS:000225649800004 PM 15620055 ER PT J AU Wagner, RE Beam, CA Beiden, SV AF Wagner, RE Beam, CA Beiden, SV TI Reader variability in mammography and its implications for expected utility over the population of readers and cases SO MEDICAL DECISION MAKING LA English DT Article DE technology assessment; mammography; ROC analysis; multiplereader studies; expected utility analysis ID COMPUTER-AIDED DIAGNOSIS; OF-VARIANCE MODELS; ROC ANALYSIS; BREAST-CANCER; DECISION-MAKING; DESIGN; RADIOLOGISTS; MULTIREADER; COMPONENTS; ACCURACY AB The multiple-reader, multiple-case (MRMC) approach to receiver operating characteristic (ROC) analysis is becoming the dominant assessment paradigm in medical imaging. Its most common version involves having many readers read every patient case in the study, a critical feature since differences among competing imaging modalities are often dominated by differences in reader performance. The present authors hove carried out MPLWC ROC analysis on a uniquely large data set for mammography. The analysis quantifies the great range of observed reader skill in that data set. It also demonstrates that the sample sizes are sufficiently large that the conclusions generalize to the populations sampled here with little uncertainty from the finite sample size. A schematic approach to bracketing the utility matrix is then used to Study trends in the resulting expected utility functions that correspond to the range of observed ROC Curves. This is done for both the screening and the diagnostic context. The results raise 2 hypotheses for further investigation. First, it is possible that the present ambiguity surrounding the effectiveness of mammography is due in part to the observed range of reader skills and corresponding expected utility functions. Second, it is possible that computer-assisted modalities for mammography may lead to improvements in the expected utility function not only for screening but also in the diagnostic context, especially for the lower performing readers. Key words: technology assessment; mammography, ROC analysis; multiplereader studies; expected utility analysis. C1 Univ S Florida, Dept Interdisciplinary Oncol, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. US FDA, Off Sci & Technol, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. RP Wagner, RE (reprint author), US FDA, Off Sci & Technol, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. NR 57 TC 32 Z9 32 U1 1 U2 7 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0272-989X J9 MED DECIS MAKING JI Med. Decis. Mak. PD NOV-DEC PY 2004 VL 24 IS 6 BP 561 EP 572 DI 10.1177/0272989X04271043 PG 12 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA 872KR UT WOS:000225206600001 PM 15534338 ER PT J AU Badano, A Gagne, RM Gallas, BD Jennings, RJ Boswell, JS Myers, KJ AF Badano, A Gagne, RM Gallas, BD Jennings, RJ Boswell, JS Myers, KJ TI Lubberts effect in columnar phosphors SO MEDICAL PHYSICS LA English DT Article DE noise transfer; phosphor blur; modulation transfer function; Monte Carlo simulation; columnar phosphor; Cesium Iodide ID DETECTIVE QUANTUM EFFICIENCY; MODULATION TRANSFER-FUNCTION; RAY FLUORESCENT SCREENS; PHOTOGRAPHIC EMULSIONS; RADIATION DETECTORS; MAMMOGRAPHY; DEVICES; SCINTILLATORS; SYSTEMS; LAYERS AB Noise transfer in granular x-ray imaging phosphor screens is not proportional to the square of the magnitude of the signal transfer when the transfer properties are considered for the entire screen thickness, unless appropriately weighted at each depth of interaction. This property, known as the Lubberts effect, has not yet been studied in columnar structured screens because of a lack of a generalized description of the depth-dependent light transport. In this paper, we investigate the signal and noise transfer characteristics of columnar phosphors used in digital mammography detectors using DETECT-II, an optical Monte Carlo light transport simulation code. We first validate our choice of optical parameters for the description of granular and columnar screens using published normalized modulation transfer (MTF) experimental data. Our calculations of MTF match empirically measured MTFs for a granular film/screen analog system, and for an indirect x-ray digital imaging system with CsI:T1 screen representative of digital mammography systems. Using the depth-dependent spread functions and collection efficiencies, we calculate the signal and noise transfer functions and the Lubberts fraction, which is the ratio of the signal transfer function to the noise transfer function, for different screen thicknesses of granular and columnar phosphors. We find that the Lubberts fraction of a 85 mum granular screen model corresponding to a Gd2O2S:Tb screen is similar to the fraction for a 100 mum columnar CsI:T1 screen. C1 US FDA, Ctr Devices & Radiol Hlth, Lab Assessment Med Imaging Syst, Rockville, MD 20857 USA. Natl Inst Biomed Imaging & Bioengn, NIH, Rockville, MD 20857 USA. RP Badano, A (reprint author), US FDA, Ctr Devices & Radiol Hlth, Lab Assessment Med Imaging Syst, 12720 Twinbrook Pkwy, Rockville, MD 20857 USA. EM aldo.badano@fda.hhs.gov OI Boswell, Jonathan/0000-0003-4552-7490; Gallas, Brandon/0000-0001-7332-1620; badano, aldo/0000-0003-3712-6670 NR 38 TC 39 Z9 39 U1 1 U2 6 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 NOV PY 2004 VL 31 IS 11 BP 3122 EP 3131 DI 10.1118/1.1796151 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 874TI UT WOS:000225372300022 PM 15587665 ER PT J AU Gallas, BD Boswell, JS Badano, A Gagne, RM Myers, KJ AF Gallas, BD Boswell, JS Badano, A Gagne, RM Myers, KJ TI An energy- and depth-dependent model for x-ray imaging SO MEDICAL PHYSICS LA English DT Article DE x-ray spectra; x-ray interactions; point processes; phosphors; optical transport; digital detectors; signal detection; model observers; pixel fill factor; image quality ID DETECTIVE QUANTUM EFFICIENCY; DIGITAL RADIOGRAPHY; OBJECTIVE ASSESSMENT; NOISE-PROPAGATION; PIXEL SIZE; OBSERVER; SYSTEMS; SIGNAL; MAMMOGRAPHY; DETECTABILITY AB In this paper, we model an x-ray imaging system, paying special attention to the energy- and depth-dependent characteristics of the inputs and interactions: x rays are polychromatic, interaction depth and conversion to optical photons is energy-dependent, optical scattering and the collection efficiency depend on the depth of interaction. The model we construct is a random function of the point process that begins with the distribution of x rays incident on the phosphor and ends with optical photons being detected by the active area of detector pixels to form an image. We show how the point-process representation can be used to calculate the characteristic statistics of the model. We then simulate a Gd2O2S:Tb phosphor, estimate its characteristic statistics, and proceed with a signal-detection experiment to investigate the impact of the pixel fill factor on detecting spherical calcifications (the signal). The two extremes possible from this experiment are that SNR2 does not change with fill factor or changes in proportion to fill factor. In our results, the impact of fill factor is between these extremes, and depends on the diameter of the signal. C1 NIBIB, CDRH, Lab Assessment Med Imaging Syst, Rockville, MD 20857 USA. RP Gallas, BD (reprint author), NIBIB, CDRH, Lab Assessment Med Imaging Syst, 12720 Twinbrook Pkwy, Rockville, MD 20857 USA. OI Gallas, Brandon/0000-0001-7332-1620; badano, aldo/0000-0003-3712-6670 NR 67 TC 22 Z9 22 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 NOV PY 2004 VL 31 IS 11 BP 3132 EP 3149 DI 10.1118/1.1806293 PG 18 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 874TI UT WOS:000225372300023 PM 15587666 ER PT J AU Stingley, RL Brezna, B Khan, AA Cerniglia, CE AF Stingley, RL Brezna, B Khan, AA Cerniglia, CE TI Novel organization of genes in a phthalate degradation operon of Mycobacterium vanbaalenii PYR-1 SO MICROBIOLOGY-SGM LA English DT Article ID SP STRAIN PYR-1; POLYCYCLIC AROMATIC-HYDROCARBONS; ESCHERICHIA-COLI; MOLECULAR CHARACTERIZATION; TRANSCRIPTIONAL REGULATOR; PHENANTHRENE DEGRADATION; DEGRADING MYCOBACTERIUM; CATABOLIC PATHWAY; PYRENE; METABOLISM AB Mycobacterium vanbaalenii PYR-1 is capable of degrading polycyclic aromatic hydrocarbons (PAHs) to ring cleavage metabolites. This study identified and characterized a putative phthalate degradation operon in the M. vanbaalenii PYR-1 genome. A putative regulatory protein (phtR) was encoded divergently with five tandem genes: phthalate dioxygenase large subunit (phtAa), small subunit (phtAb), phthalate dihydrodiol dehydrogenase (phtB), phthalate dioxygenase ferredoxin subunit (phtAc) and phthalate dioxygenase ferredoxin reductase (phtAd). A 6(.)7 kb EcoRI fragment containing these genes was cloned into Escherichia coli and converted phthalate to 3,4-dihydroxyphthalate. Homologues to the operon region were detected in a number of PAH-degrading Mycobacterium slop. isolated from various geographical locations. The operon differs from those of other Gram-positive bacteria in both the placement and orientation of the regulatory gene. In addition, the M. vanbaalenii PYR-1 pht operon contains no decarboxylase gene and none was identified within a 37 kb region containing the operon. This study is the first report of a phthalate degradation operon in Mycobacterium spp. C1 US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. Slovak Acad Sci, Inst Mol Biol, Bratislava 84551, Slovakia. RP Khan, AA (reprint author), US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. EM Ashraf@nctr.fda.gov NR 60 TC 35 Z9 40 U1 0 U2 11 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 1350-0872 J9 MICROBIOL-SGM JI Microbiology-(UK) PD NOV PY 2004 VL 150 BP 3749 EP 3761 DI 10.1099/mic.0.27263-0 PN 11 PG 13 WC Microbiology SC Microbiology GA 874TM UT WOS:000225372700022 PM 15528661 ER PT J AU Selvapandiyan, A Debrabant, A Duncan, R Muller, J Salotra, P Gannavaram, S Jeffrey, SL Nakhasi, HL AF Selvapandiyan, A Debrabant, A Duncan, R Muller, J Salotra, P Gannavaram, S Jeffrey, SL Nakhasi, HL TI Centrin deficient Leishmania donovani amastigotes show loss of cytokinesis and growth arrest SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 FDA, CBER, Div Emerging & Transfus Transmitted Dis, Bethesda, MD USA. FDA, CBER, Div Viral Prod, Bethesda, MD USA. Safdarjang Hosp, Inst Pathol, ICMR, New Delhi, India. Mayo Clin, Coll Med, Tumor Biol Program, Rochester, MN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2004 VL 15 SU S MA 786 BP 142A EP 142A PG 1 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648801131 ER PT J AU Hasday, JD Rice, P Martin, E He, J Frank, M DeTolla, L Hester, L O'Neill, T Manka, C Singh, IS AF Hasday, JD Rice, P Martin, E He, J Frank, M DeTolla, L Hester, L O'Neill, T Manka, C Singh, IS TI Febrile-range hyperthermia augments neutrophil accumulation and enhances lung injury in experimental gram-negative bacterial pneumonia SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology CY DEC 04-08, 2004 CL Washington, DC SP Amer Soc Cell Biol C1 Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA. VA Med Ctr, Baltimore, MD USA. US FDA, Div Biotechnol, College Pk, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2004 VL 15 SU S MA 2075 BP 375A EP 376A PG 2 WC Cell Biology SC Cell Biology GA 864QU UT WOS:000224648803145 ER PT J AU Kwon, H Lionberger, RA Yu, LX AF Kwon, Hyojong Lionberger, Robert A. Yu, Lawrence X. TI Impact of P-glycoprotein-mediated intestinal efflux kinetics on oral Bioavailability of P-glycoprotein substrates SO MOLECULAR PHARMACEUTICS LA English DT Article DE transporter; P-glycoprotein; absorption model; bioavailability AB Studies of many P-glycoprotein (Pgp) substrates have demonstrated a significant effect of Pgp-mediated efflux on intestinal drug transport. However, most of these studies were designed to detect whether a particular drug is a Pgp substrate and thus were conducted at very low concentrations. We performed two simulations to evaluate the effect of Pgp-mediated efflux on oral drug absorption at various concentrations. In the first simulation, a steady-state model allowed us to predict whether the contribution of Pgp to oral drug absorption would be significant at clinically relevant concentrations. Our second simulation investigated the role of Pgp-mediated efflux in oral absorption with a dynamic compartmental absorption and transit model linked to a pharmacokinetic model. For high-solubility drugs, Pgp-mediated efflux altered the bioavailability only at drug concentrations corresponding to doses much lower than the usual clinical dose. The ratio of transporter-mediated transport to passive transport determined whether intestinal Pgp transporters would reduce the bioavailability of high-solubility drugs. C1 [Kwon, Hyojong; Lionberger, Robert A.; Yu, Lawrence X.] US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Yu, LX (reprint author), US FDA, Ctr Drug Evaluat & Res, 5600 Fishers Lane, Rockville, MD 20857 USA. EM yul@cder.fda.gov RI Yu, Lawrence/L-6280-2016 NR 29 TC 19 Z9 19 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1543-8384 J9 MOL PHARMACEUT JI Mol. Pharm. PD NOV-DEC PY 2004 VL 1 IS 6 BP 455 EP 465 DI 10.1021/mp049921x PG 11 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA V52IZ UT WOS:000203538500007 PM 16028357 ER PT J AU Moore, M Clements, J Delongchamp, R Thakur, A Myhr, B AF Moore, M Clements, J Delongchamp, R Thakur, A Myhr, B TI Evaluation of statistical methods to analyse mouse lymphoma assay mutation data SO MUTAGENESIS LA English DT Meeting Abstract C1 NCTR, Jefferson, AR USA. Covance, Harrogate, England. Covance, Vienna, VA 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 0267-8357 J9 MUTAGENESIS JI Mutagenesis PD NOV PY 2004 VL 19 IS 6 MA 41 BP 513 EP 513 PG 1 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA 873DA UT WOS:000225258300053 ER PT J AU Chirino, AJ Mire-Sluis, A AF Chirino, AJ Mire-Sluis, A TI Characterizing biological products and assessing comparability following manufacturing changes SO NATURE BIOTECHNOLOGY LA English DT Article ID LASER-INDUCED FLUORESCENCE; RECOMBINANT MONOCLONAL-ANTIBODY; COLONY-STIMULATING FACTOR; SURFACE-PLASMON RESONANCE; HAMSTER OVARY CELLS; CAPILLARY-ELECTROPHORESIS; ANALYTICAL ULTRACENTRIFUGATION; POLYETHYLENE-GLYCOL; FLOW-CYTOMETRY; FACTOR-VIII AB Changes in production methods of a biological product may necessitate an assessment of comparability to ensure that these manufacturing changes have not affected the safety, identity, purity, or efficacy of the product. Depending on the nature of the protein or the change, this assessment consists of a hierarchy of sequential tests in analytical testing, preclinical animal studies and clinical studies. Differences in analytical test results between pre- and post-change products may require functional testing to establish the biological or clinical significance of the observed difference. An underlying principle of comparability is that under certain conditions, protein products may be considered comparable on the basis of analytical testing results alone. However, the ability to compare biological materials is solely dependent on the tests used, since no single analytical method is able to compare every aspect of protein structure or function. The advantages and disadvantages of any given method depends on the protein property being characterized. C1 Xencor Inc, Monrovia, CA 91016 USA. Ctr Drug Evaluat & Res, Off Pharmaceut Sci, Rockville, MD 20852 USA. RP Chirino, AJ (reprint author), Xencor Inc, 111 W Lemon Ave, Monrovia, CA 91016 USA. EM art@xencor.com NR 91 TC 203 Z9 212 U1 1 U2 32 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD NOV PY 2004 VL 22 IS 11 BP 1383 EP 1391 DI 10.1038/nbt1030 PG 9 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 869CL UT WOS:000224960600028 PM 15529163 ER PT J AU Woodcock, J AF Woodcock, J TI Janet Woodcock discusses the role of the FDA in improving pharma productivity SO NATURE REVIEWS DRUG DISCOVERY LA English DT Editorial Material C1 US FDA, HFI 40, Rockville, MD 20857 USA. RP Woodcock, J (reprint author), US FDA, HFI 40, 5600 Fishers Lane, Rockville, MD 20857 USA. NR 0 TC 2 Z9 2 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-1776 J9 NAT REV DRUG DISCOV JI Nat. Rev. Drug Discov. PD NOV PY 2004 VL 3 IS 11 BP 904 EP 904 DI 10.1038/nrd1570 PG 1 WC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA 867HL UT WOS:000224833100008 PM 15558859 ER PT J AU Paule, MG Chelonis, JJ Blake, DJ Dornhoffer, JL AF Paule, MG Chelonis, JJ Blake, DJ Dornhoffer, JL TI Effects of drug countermeasures for space motion sickness on working memory in humans SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Article DE delayed matching-to-sample; short-term memory; meclizine; promethazine; scopolamine; lorazepam ID VERTIGO; MEDICATIONS; COMPENSATION; PERFORMANCE; CHILDREN AB Space motion sickness (SMS) is a problem during the first 72 h of space flight and during transitions from different gravity environments. There currently are no effective drug countermeasures for SMS that also accommodate the retention of optimal cognitive function. This creates a dilemma for astronauts because cognitive skills are particularly important during gravity transitions (e.g., take-off and landing). To quantify the cognitive side effects of potential drug countermeasures, an automated delayed matching-to-sample (DMTS) procedure was used to assess visual working memory before and after drug countermeasures (meclizine 25 mg, scopolamine 0.4 mg, promethazine 25 mg, or lorazepam 1 mg, given orally approximately 45 min prior to testing) and/or the induction of SMS by vestibular stimulation in a rotary chair (spinning). Sixty-seven normal healthy volunteers (mean age, in years, 26.6 +/- 4.8 S.D.; 24 females and 43 males) each participated in two test sessions, one 'off' drug and one 'on' drug. Spinning by itself significantly decreased task accuracy (Acc) and choice response speed, especially at longer recall delays. Meclizine alone had no effect on Acc or speed with or without spinning. Scopolamine alone decreased Acc, and with spinning, slowed speed. Promethazine alone had no adverse effect, but combined with spinning, decreased Acc and speed. Lorazepam alone decreased speed, and with spinning, decreased Acc. The data suggest that, at clinically useful doses, the rank order of the drugs with the best cognitive profiles is meclizine>scopolamine>promethazine>lorazepam. (C) 2004 Elsevier Inc. All rights reserved. C1 US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Behav Toxicol Labs, Jefferson, AR 72079 USA. Univ Arkansas, Off Res & Sponsored Programs, Little Rock, AR 72204 USA. Univ Arkansas Med Sci, Dept Otolaryngol Head & Neck Surg, Little Rock, AR 72204 USA. RP Paule, MG (reprint author), US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Behav Toxicol Labs, HFT-132,3900 NCTR Rd, Jefferson, AR 72079 USA. EM mpaule@nctr.fda.gov FU NCRR NIH HHS [M01RR14288] NR 38 TC 17 Z9 20 U1 2 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0892-0362 J9 NEUROTOXICOL TERATOL JI Neurotoxicol. Teratol. PD NOV-DEC PY 2004 VL 26 IS 6 BP 825 EP 837 DI 10.1016/j.ntt.2004.07.002 PG 13 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA 863GW UT WOS:000224550100014 PM 15451046 ER PT J AU Mackey, EA Anderson, DL Liposky, PJ Lindstrom, RM Chen-Mayer, H Lamaze, GP AF Mackey, EA Anderson, DL Liposky, PJ Lindstrom, RM Chen-Mayer, H Lamaze, GP TI New thermal neutron prompt gamma-ray activation analysis instrument at the National Institute of Standards and Technology Center for Neutron Research SO NUCLEAR INSTRUMENTS & METHODS IN PHYSICS RESEARCH SECTION B-BEAM INTERACTIONS WITH MATERIALS AND ATOMS LA English DT Article DE gamma-ray spectrometry; neutron beam; neutron capture; prompt gamma activation analysis; prompt gamma-rays ID SCATTERING; HYDROGEN; ELEMENTS AB A new thermal neutron prompt gamma-ray activation analysis (PGAA) instrument was designed and built to replace the original PGAA system at the NIST Center for Neutron Research. By placing a sapphire filter in the neutron beam shutter assembly, the fast neutron fluence rate was reduced by a factor of 5 and low-energy (50-200 keV) gamma-ray intensities were reduced by factors of 5-10. The thermal neutron fluence rate was reduced by only a factor of 1.13. A new external beam tube, sample chamber, beam stop, and support structure were built and a new detection system installed. The new beam tube is made of two cylindrical aluminum sections lined with a lithiated polymer. Both sections are kept under vacuum to reduce the number of neutrons scattered by air into the beam tube walls. The sample chamber is also fabricated from aluminum and lined with lithiated polymer, and may be evacuated to minimize the number of neutrons scattered and absorbed by air. The beam tube and sample chamber assembly is suspended from the aluminum support structure. The detection system consists of a 40% efficient (relative) germanium detector (resolution 2.0 at 1332.5 keV) and a bismuth germanate Compton suppressor. The detection system is shielded by lead, surrounded by borated and lithiated polyethylene, and placed on a table attached to the support structure. The new, more compact beam stop is welded to the support structure. Capture gamma-ray photopeaks from H, B, C, N, Na, Al, Fe, Ge, I and Pb in the background spectrum were either of lower intensity or eliminated with the new PGAA instrument. The more efficient detection system, positioned closer to the sample, yielded element sensitivity increases of 5-50%. Limits of detection have been greatly reduced compared with those of the original instrument due to reduced Compton and scattered gamma-ray backgrounds (especially in the low-energy region), increased sensitivities, and reduction of background gamma-ray photopeak intensities. Published by Elsevier B.V. C1 Natl Inst Stand & Technol, Div Analyt Chem, Gaithersburg, MD 20899 USA. US FDA, Elemental Res Branch, College Pk, MD 20740 USA. Natl Inst Stand & Technol, Ctr Neutron Res, Gaithersburg, MD 20899 USA. RP Mackey, EA (reprint author), Natl Inst Stand & Technol, Div Analyt Chem, 100 Bur Dr, Gaithersburg, MD 20899 USA. EM lmackey@nist.gov NR 10 TC 15 Z9 18 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-583X J9 NUCL INSTRUM METH B JI Nucl. Instrum. Methods Phys. Res. Sect. B-Beam Interact. Mater. Atoms PD NOV PY 2004 VL 226 IS 3 BP 426 EP 440 DI 10.1016/j.nimb.2004.05.038 PG 15 WC Instruments & Instrumentation; Nuclear Science & Technology; Physics, Atomic, Molecular & Chemical; Physics, Nuclear SC Instruments & Instrumentation; Nuclear Science & Technology; Physics GA 872MV UT WOS:000225212200020 ER PT J AU Buist, DSM Newton, KM Miglioretti, DL Beverly, K Connelly, MT Andrade, S Hartsfield, CL Wei, FF Chan, KA Kessler, L AF Buist, DSM Newton, KM Miglioretti, DL Beverly, K Connelly, MT Andrade, S Hartsfield, CL Wei, FF Chan, KA Kessler, L TI Hormone therapy prescribing patterns in the United States SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID ESTROGEN PLUS PROGESTIN; RANDOMIZED CONTROLLED-TRIAL; HEALTHY POSTMENOPAUSAL WOMEN; CORONARY-HEART-DISEASE; REPLACEMENT THERAPY; INITIATIVE MEMORY; RISK; CANCER; MULTICENTER; PREVENTION AB OBJECTIVE: We sought to examine prescribing patterns (prevalence and rates of initiation and discontinuation) for estrogen plus progestin (hormone therapy [HT] and estrogen alone [ET]) in the United States in the 2 years before the published results of Women's Health Initiative's (WHI) HT trial's early termination and for 5 months after their release. METHODS: We conducted an observational cohort study of 169,586 women aged 40-80 years who were enrolled in 5 health maintenance organizations in the United States to estimate the prevalence of HT and ET and discontinuation and initiation rates between September 1, 1999, to June 31, 2002 (baseline), and December 31, 2002 (follow-up). We used automated pharmacy data to identify all oral and transdermal estrogen and progestin dispensed during the study period. RESULTS: The prevalence of HT declined 46% from baseline to follow-up (14.6% to 7.9%); ET use declined 28% during the same period (12.6% to 9.1%). ne discontinuation of HT increased almost immediately, from 2.5% at baseline to 13.8% in October 2002. We saw an immediate decrease in HT and ET initiation rates, from 0.4% and 0.3% at baseline, respectively, to 0.2% for W and ET at follow-up. CONCLUSION: ne diffusion of the WHI FIT trial results had an immediate impact on the discontinuation of HT and ET and is likely responsible for the 46% and 28% decline in the initiation of these respective therapies. Further exploration of why women continue to use HT and identification of methods for addressing reasons for continued use are indicated. (C) 2004 by The American College of Obstetricians and Gynecologists. C1 Grp Hlth Cooperat Puget Sound, Ctr Hlth Studies, Seattle, WA 98101 USA. Sch Publ Hlth & Community Med, Seattle, WA 98195 USA. Harvard Univ, Sch Med, Harvard Pilgrim Hlth Care, Dept Ambulatory Care & Prevent, Boston, MA 02115 USA. Harvard Univ, Sch Med, Consultat Serv, Boston, MA 02115 USA. Harvard Vanguard Med Assoc, Boston, MA 02115 USA. Meyers Primary Care Inst, Worcester, MA USA. Kaiser Permanente, Denver, CO USA. Hlth Partners Res Fdn, Minneapolis, MN USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. US FDA, Hlth Maintenance Org, Res Network Ctr Educ & Res Therapeut, Rockville, MD 20857 USA. US FDA, Off Sci & Technol, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Buist, DSM (reprint author), Grp Hlth Cooperat Puget Sound, Ctr Hlth Studies, 1730 Minor Ave,Suite 1600, Seattle, WA 98101 USA. EM buist.d@ghc.org OI Chan, Kinwei/0000-0001-8161-1986 FU AHRQ HHS [U18HS11843-01]; NCI NIH HHS [U19-CA-79689-05] NR 38 TC 140 Z9 141 U1 0 U2 2 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 NOV PY 2004 VL 104 IS 5 BP 1042 EP 1050 DI 10.1097/01.AOG.0000143826.38439.af PN 1 PG 9 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 875JH UT WOS:000225415900027 PM 15516400 ER PT J AU Shahverdi, AR Rafii, F Tavassoli, F Bagheri, M Attar, F Ghahraman, A AF Shahverdi, AR Rafii, F Tavassoli, F Bagheri, M Attar, F Ghahraman, A TI Piperitone from Mentha longifolia var. chorodictya Rech F. reduces the nitrofurantoin resistance of strains of Enterobacteriaceae SO PHYTOTHERAPY RESEARCH LA English DT Article DE Mentha longifolia; nitrofurantoin; piperitone; essential oils; Enterobacteria ID ESSENTIAL OILS; INHIBITION AB The diluted essential oil of Mentha longifolia (L.) var. chlorodictya Rech F. foliage enhanced the bactericidal activity of nitrofurantoin decreasing the minimum inhibitory concentration (MIC) of nitrofurantoin for nitrofurantoin-resistant strains of Enterobacteriaceae. Thin-layer chromatography (TLC) analysis of the essential oil detected a fraction (R(f) = 0.35, UV lambda(MAX) of 232.5), which was the most effective in enhancement of nitrofurantoin activity. Using gas liquid chromatography and known standards, the active fraction was identified as piperitone. 1mul of the piperitone fraction decreased the MIC of nitrofurantoin 3-20 fold for the different strains of Enterobacteriaceae tested. Copyright (C) 2004 John Wiley Sons, Ltd. C1 Univ Tehran, Fac Pharm, Dept Pharmaceut Biotechnol, Tehran 14174, Iran. US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Azarbaijan Med Plants Res Ctr, Ardabil, Iran. Univ Tehran, Cent Herbarium, Fac Sci, Tehran, Iran. RP Shahverdi, AR (reprint author), Univ Tehran, Fac Pharm, Dept Pharmaceut Biotechnol, Tehran 14174, Iran. EM shahverd@sina.tums.ac.ir NR 12 TC 20 Z9 20 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0951-418X J9 PHYTOTHER RES JI Phytother. Res. PD NOV PY 2004 VL 18 IS 11 BP 911 EP 914 DI 10.1002/ptr.1566 PG 4 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 888SK UT WOS:000226394300009 PM 15597306 ER PT J AU Wysowski, DK Nourjah, P AF Wysowski, DK Nourjah, P TI Analyzing prescription drugs as causes of death on death certificates SO PUBLIC HEALTH REPORTS LA English DT Letter C1 US FDA, Off Drug Safety, Rockville, MD 20857 USA. RP Wysowski, DK (reprint author), US FDA, Off Drug Safety, Rockville, MD 20857 USA. NR 2 TC 7 Z9 7 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0033-3549 J9 PUBLIC HEALTH REP JI Public Health Rep. PD NOV-DEC PY 2004 VL 119 IS 6 BP 520 EP 520 DI 10.1016/j.phr.2004.09.001 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 864XB UT WOS:000224665200002 PM 15504443 ER PT J AU Robinson, RA Ilev, IK AF Robinson, RA Ilev, IK TI Design and optimization of a flexible high-peak-power laser-to-fiber coupled illumination system used in digital particle image velocimetry SO REVIEW OF SCIENTIFIC INSTRUMENTS LA English DT Article ID UNCOATED HOLLOW TAPER; DELIVERY-SYSTEM; PULSES AB We present a study on the design and parameter optimization of a flexible high-peak-power fiber-optic laser delivery system using commercially available solid-core silica fibers and an experimental glass hollow waveguide (HW). The fiber-optic delivery system provides a flexible, safe, and easily and precisely positioned laser irradiation for many applications including uniform illumination for digital particle image velocimetry (DPIV). The delivery fibers, when coupled through a line-generating lens, produce a uniform thin laser sheet illumination for accurate and repeatable DPIV two-dimensional velocity measurements. We report experimental results on homogenizing the laser beam profile using various mode-mixing techniques. Furthermore, because a fundamental problem for fiber-optic-based high-peak-power laser delivery systems is the possible damage effects of the fiber material, we determine experimentally the peak power density damage threshold of various delivery fibers designed for the visible spectral range at a typical DPIV laser wavelength of 532 nm. In the case of solid-core silica delivery fibers using conventional lens-based laser-to-fiber coupling, the damage threshold varies from 3.7 GW/cm(2) for a 100-mum-core-diameter high-temperature fiber to 3.9 GW/cm(2) for a 200-mum-core-diameter high-power delivery fiber, with a total output laser energy delivered of at least 3-10 mJ for those respective fibers. Therefore, these fibers are marginally suitable for most macro-DPIV applications. However, to improve the high-power delivery capability for close-up micro-DPIV applications, we propose and validate an experimental fiber link with much higher laser power delivery capability than the solid-core fiber links. We use an uncoated grazing-incidence-based tapered glass funnel coupled to a glass HW with hollow air-core diameter of 700 mum, a low numerical aperture of 0.05, and a thin inside cladding of cyclic olefin polymer coating for optimum transmission at 532 nm. Because of the mode homogenizing effect and lower power density, the taper-waveguide laser delivery technique ensured high damage threshold for the delivery HW, and as a result, no damage occurred at the maximum measured input laser energy of 33 mJ used in this study. (C) 2004 American Institute of Physics. C1 US FDA, CDRH, Rockville, MD 20850 USA. RP Robinson, RA (reprint author), US FDA, CDRH, 9200 Corp Blvd,HFZ-170, Rockville, MD 20850 USA. EM ronald.robinson@fda.hhs.gov NR 14 TC 6 Z9 6 U1 1 U2 1 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 NOV PY 2004 VL 75 IS 11 BP 4856 EP 4862 DI 10.1063/1.1809263] PG 7 WC Instruments & Instrumentation; Physics, Applied SC Instruments & Instrumentation; Physics GA 869DF UT WOS:000224962900076 ER PT J AU Lin, CTJ Lee, JY Yen, ST AF Lin, CTJ Lee, JY Yen, ST TI Do dietary intakes affect search for nutrient information on food labels? SO SOCIAL SCIENCE & MEDICINE LA English DT Article DE information search; food labels; fat; binary choice model; nutrition; USA ID NUTRITION; QUALITY AB Nutrition labels on food packages are designed to promote and protect public health by providing nutrition information so that consumers can make informed dietary choices. High levels of total fat, saturated fat and cholesterol in diets are linked to increased blood cholesterol levels and a greater risk of heart disease. Therefore, an understanding of consumer use of total fat, saturated fat, and cholesterol information on food labels has important implications for public health and nutrition education. This study explores the association between dietary intakes of these three nutrients and psychological or demographic factors and the search for total fat, saturated fat, and cholesterol information on food labels. Psychology literature suggests a negative association between intakes of these nutrients and probability of search for their information on food labels. Health behavior theories also suggest perceived benefits and costs of using labels and perceived capability of using labels are associated with the search behavior. We estimate the relationship between label information search and its predictors using logistic regressions. Our samples came from the 1994-1996 Continuing Survey of Food Intakes by Individuals and Diet and Health Knowledge Survey conducted by the United States Department of Agriculture. Results suggest that search for total fat, saturated fat, and cholesterol information on food labels is less likely among individuals who consume more of the three nutrients, respectively. The search is also related to perceived benefits and costs of using the label, perceived capability of using the label, knowledge of nutrition and fats, perceived efficacy of diets in reducing the risk of illnesses, perceived importance of nutrition in food shopping, perceived importance of a healthy diet, and awareness of linkage between excessive consumption of the nutrients and health problems. These findings suggest encouraging search of food label information among consumers with unhealthy dietary habits would need innovative approaches. Yet, nutrition education can be instrumental in encouraging this search by stimulating motivation and providing technical help. (C) 2004 Elsevier Ltd. All rights reserved. C1 Univ Tennessee, Dept Agr Econ, Knoxville, TN 37996 USA. US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. Univ Florida, Florida Dept Citrus, Gainesville, FL 32601 USA. RP Yen, ST (reprint author), Univ Tennessee, Dept Agr Econ, 308D Morgan Hall, Knoxville, TN 37996 USA. EM syen@utk.edu NR 24 TC 55 Z9 55 U1 1 U2 19 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0277-9536 J9 SOC SCI MED JI Soc. Sci. Med. PD NOV PY 2004 VL 59 IS 9 BP 1955 EP 1967 DI 10.1016/j.socscimed.2004.02.030 PG 13 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 852CZ UT WOS:000223734100016 PM 15312929 ER PT J AU Wang, JY Liu, XL Heflich, RH Chen, T AF Wang, JY Liu, XL Heflich, RH Chen, T TI Time course of cII gene mutant manifestation in the liver, spleen, and bone marrow of N-ethyl-N-nitrosourea-treated big blue transgenic mice SO TOXICOLOGICAL SCIENCES LA English DT Article DE Big Blue transgenic mice; N-ethyl-N-nitrosourea; mutation assay; mutant manifestation ID IN-VIVO; SOMATIC MUTATION; MOLECULAR CHARACTERISTICS; MUTA(TM)MOUSE; INDUCTION; FREQUENCIES; TISSUES; AGENTS; ORGANS; ASSAYS AB The time between treatment and the appearance of mutants (mutant manifestation time) is a critical variable for in vivo transgenic mutation assays. There are, however, limited data describing the optimal sampling time for detecting mutations in various tissues of mutagen-treated animals. In this study, we investigated the time course of cII gene mutant induction in the liver, spleen, and bone marrow of Big Blue transgenic mice treated with N-ethyl-N-nitrosourea (ENU). Six-month-old female mice were treated with a single dose (120 mg/kg) of ENU, and the animals were sacrificed, and the cII mutant frequencies (MFs) were determined at 1, 3, 7, 15, 30, and 120 days after the treatment. The MFs in the liver cII gene of ENU-treated mice increased with time after the treatment, while the MFs for concurrent controls remained constant. The liver cII MFs in ENU-treated mice were significantly increased at day 30 and 120 (p < 0.01), with the largest increase at day 120. The spleen cII MFs in ENU-treated mice were increased significantly at day 7 and later (p < 0.01), and reached a plateau at day 30. In the bone marrow, the cII MFs in ENU-treated mice were increased significantly at all sampling times (p < 0.01), with the maximum MF at day 3. These results confirm that the time after treatment required to reach the maximum MF is tissue specific, with the approximate time for the maximum ENU-induced cII MF response being: bone marrow, 3 days; spleen, 14-30 days; and liver, more than 30 days. C1 US FDA, Div Genet & Reprod Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Univ Arkansas Med Sci, Dept Pharmacol & Toxicol, Little Rock, AR 72205 USA. RP Chen, T (reprint author), US FDA, Div Genet & Reprod Toxicol, Natl Ctr Toxicol Res, HFT-130,3900 NCTR Rd, Jefferson, AR 72079 USA. EM tchen@nctr.fda.gov NR 21 TC 8 Z9 8 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 NOV PY 2004 VL 82 IS 1 BP 124 EP 128 DI 10.1093/toxsci/kfh234 PG 5 WC Toxicology SC Toxicology GA 865LL UT WOS:000224704500014 PM 15282403 ER PT J AU Plakas, SM Wang, ZH El Said, KR Jester, ELE Granade, HR Flewelling, L Scott, P Dickey, RW AF Plakas, SM Wang, ZH El Said, KR Jester, ELE Granade, HR Flewelling, L Scott, P Dickey, RW TI Brevetoxin metabolism and elimination in the Eastern oyster (Crassostrea virginica) after controlled exposures to Karenia brevis SO TOXICON LA English DT Article DE brevetoxin; metabolism; elimination; Eastern oyster; liquid chromatography/mass spectrometry ID NEW-ZEALAND; AUSTROVENUS-STUTCHBURYI; PERNA-CANALICULUS; GREENSHELL MUSSEL; GYMNODINIUM-BREVE; RED TIDE; SHELLFISH; TOXINS; COCKLE; ANALOG AB The metabolism and elimination of brevetoxins were examined in the Eastern oyster (Crassostrea virginica) following controlled exposures to Karenia brevis cultures in the laboratory. After a 2-day exposure period (similar to62 million cells/oyster), elimination of brevetoxins and their metabolites was monitored by using liquid chromatography/mass spectrometry (LC/MS). Composite toxin in oyster extracts was measured by in vitro assay (i.e. cytotoxicity, receptor binding, and ELISA). Of the parent algal toxins, PbTx-1 and PbTx-2 were not detectable by LC/MS in K. brevis-exposed oysters. PbTx-3 and PbTx-9, which are accumulated directly from K. brevis and through metabolic reduction of PbTx-2 in the oyster, were at levels initially (after exposure) of 0.74 and 0.49 mug equiv./g, respectively, and were eliminated largely within 2 weeks after dosing. PbTx-7 and PbTx-10, the reduced forms of PbTx-1, were non-detectable. Conjugative brevetoxin metabolites identified previously in field-exposed oysters were confirmed in the laboratory-exposed oysters. Cysteine conjugates of PbTx-1 and PbTx-2, and their sulfoxides, were in the highest abundance, as apparent in LC/MS ion traces, and were detectable for up to 6 months after dosing. Composite toxin measurements by in vitro assay also reflected persistence (up to 6 months) of brevetoxin residues in the oyster. Levels of cysteine conjugates, as determined by LC/MS, were well correlated with those of composite toxin, as measured by ELISA, throughout depuration. Composite toxin levels by cytotoxicity assay were well correlated with those by receptor binding assay. Cysteine-PbTx conjugates are useful LC/MS determinants of brevetoxin exposure and potential markers for composite toxin in the Eastern oyster. (C) 2004 Elsevier Ltd. All rights reserved. C1 US FDA, Gulf Coast Seafood Lab, Dauphin Isl, AL 36528 USA. Florida Marine Res Inst, Florida Fish & Wildlife Conservat Commiss, St Petersburg, FL 33701 USA. RP Plakas, SM (reprint author), US FDA, Gulf Coast Seafood Lab, POB 158,1 Iberville Dr, Dauphin Isl, AL 36528 USA. EM splakas@cfsan.fda.gov NR 21 TC 55 Z9 56 U1 0 U2 8 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 NOV PY 2004 VL 44 IS 6 BP 677 EP 685 DI 10.1016/j.toxicon.2004.07.027 PG 9 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 869SA UT WOS:000225003200012 PM 15501294 ER PT J AU Muni, NI Pocock, S Berman, MR Yue, LQ AF Muni, NI Pocock, S Berman, MR Yue, LQ TI Use of patient-reported outcomes in evaluation of heart failure device therapy: The regulatory perspective SO VALUE IN HEALTH LA English DT Meeting Abstract C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. Univ London London Sch Hyg & Trop Med, London WC1E 7HT, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 1098-3015 J9 VALUE HEALTH JI Value Health PD NOV-DEC PY 2004 VL 7 IS 6 SU S BP 719 EP 720 DI 10.1016/S1098-3015(10)65896-2 PG 2 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 869YK UT WOS:000225020700264 ER PT J AU Corton, JC Apte, U Anderson, SP Limaye, P Yoon, L Latendresse, J Dunn, C Everitt, JI Voss, KA Swanson, C Kimbrough, C Wong, JS Gill, SS Chandraratna, RAS Kwak, MK Kensler, TW Stulnig, TM Steffensen, KR Gustafsson, JA Mehendale, HM AF Corton, JC Apte, U Anderson, SP Limaye, P Yoon, L Latendresse, J Dunn, C Everitt, JI Voss, KA Swanson, C Kimbrough, C Wong, JS Gill, SS Chandraratna, RAS Kwak, MK Kensler, TW Stulnig, TM Steffensen, KR Gustafsson, JA Mehendale, HM TI Mimetics of caloric restriction include agonists of lipid-activated nuclear receptors SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ALPHA-NULL MICE; PEROXISOME-PROLIFERATOR; GENE-EXPRESSION; ACETAMINOPHEN HEPATOTOXICITY; TISSUE-REPAIR; DIABETIC MICE; MOUSE-LIVER; PPAR-ALPHA; FATTY-ACID; DISEASE AB The obesity epidemic in industrialized countries is associated with increases in cardiovascular disease (CVD) and certain types of cancer. In animal models, caloric restriction (CR) suppresses these diseases as well as chemical-induced tissue damage. These beneficial effects of CR overlap with those altered by agonists of nuclear receptors (NR) under control of the fasting-responsive transcriptional co-activator, peroxisome proliferator-activated co-activator 1alpha (PGC-1alpha). In a screen for compounds that mimic CR effects in the liver, we found statistically significant overlaps between the CR transcript profile in wild-type mice and the profiles altered by agonists of lipid-activated NR, including peroxisome proliferator-activated receptor alpha (PPARalpha), liver X receptor, and their obligate heterodimer partner, retinoid X receptor. The overlapping genes included those involved in CVD (lipid metabolism and inflammation) and cancer (cell fate). Based on this overlap, we hypothesized that some effects of CR are mediated by PPARalpha. As determined by transcript profiling, 19% of all gene expression changes in wild-type mice were dependent on PPARalpha, including Cyp4a10 and Cyp4a14, involved in fatty acid omega-oxidation, acute phase response genes, and epidermal growth factor receptor but not increases in PGC-1alpha. CR protected the livers of wild-type mice from damage induced by thioacetamide, a liver toxicant and hepatocarcinogen. CR protection was lost in PPARalpha-null mice due to inadequate tissue repair. These results demonstrate that PPARalpha mediates some of the effects of CR and indicate that a pharmacological approach to mimicking many of the beneficial effects of CR may be possible. C1 ToxicoGenomics, Chapel Hill, NC 27514 USA. NE Louisiana Univ, Coll Pharm, Dept Toxicol, Monroe, LA 71209 USA. GlaxoSmithKline, Res & Dev, Dept Safety Assessment, Res Triangle Pk, NC 27709 USA. Natl Ctr Toxicol Res, Pathol Associates Int, Jefferson, AR 72079 USA. CIIT Ctr Hlth Res, Res Triangle Pk, NC 27709 USA. ARS, Toxicol & Mycotoxin Res Unit, USDA, Athens, GA 30604 USA. Univ Calif Riverside, Dept Cell Biol & Neurosci, Environm Toxicol Grad Program, Riverside, CA 92521 USA. Allergan Pharmaceut Inc, Dept Biol & Chem, Irvine, CA 92612 USA. Allergan Pharmaceut Inc, Dept Reginoid Res, Irvine, CA 92612 USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Environm Hlth Sci, Baltimore, MD 21205 USA. Karolinska Inst, Novum, Dept Biosci, S-14186 Huddinge, Sweden. Karolinska Inst, Novum, Dept Med Nutr, S-14186 Huddinge, Sweden. RP Corton, JC (reprint author), ToxicoGenomics, 209 Silver Creek Tr, Chapel Hill, NC 27514 USA. EM ccorton@msn.com; mehendale@ulm.edu RI Kensler, Thomas/D-8686-2014; OI Kensler, Thomas/0000-0002-6676-261X; Steffensen, Knut/0000-0001-6093-2801; Stulnig, Thomas/0000-0003-3300-6161; Everitt, Jeffrey/0000-0003-0273-6284 FU NIEHS NIH HHS [ES-09870] NR 65 TC 73 Z9 77 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 29 PY 2004 VL 279 IS 44 BP 46204 EP 46212 DI 10.1074/jbc.M406739200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 865IC UT WOS:000224694900107 PM 15302862 ER PT J AU Guiochon, GA Beaver, LA AF Guiochon, GA Beaver, LA TI Progress and future of instrumental analytical chemistry applied to the environment SO ANALYTICA CHIMICA ACTA LA English DT Article; Proceedings Paper CT 8th International Symposium on Analytical Methodology in the Environmental Fiels/13th Meeting of the Spanish-Society-of-analytical-Chemistry CY OCT 21-24, 2003 CL Univ A Coruna, A Coruna, SPAIN SP Spanish Soc Anal Chem HO Univ A Coruna DE instrumental analytical chemistry; environment; contaminants; biological agents ID SOLID-PHASE EXTRACTION; GAS CHROMATOGRAPHY; WATER EXTRACTION; ONLINE; PESTICIDES; BIOSENSOR; PRODUCE; SAMPLES AB The recent trends in the development of environmental analysis are reviewed with emphasis on the progress of extraction techniques, of methods of analysis of pesticide residues in food, of the search for chemical and biological agents released into the environment, and of analytical instrumentation. A variety of new sorbents have been synthesized for the extraction and concentration of pollutants, including general purpose adsorbents (e.g., porous polystyrene/divinylbenzene resins) and polymers imprinted for specific compounds. New, faster, more selective and sensitive methods have been developed to improve analytical performance, e.g., synthetic fibers in the air pollution, stirbars coated with polymethylsiloxane. Bidimensional gas chromatography has brought a considerable leap in separation power and sensitivity. Finally the combination of open tublar columns and miniaturized quadrupole mass spectrometer allows the rapid identification of viral agents or a wide variety of chemicals. (C) 2004 Elsevier B.V. All rights reserved. C1 Univ Tennessee, Knoxville, TN 37996 USA. US FDA, Rockville, MD 20857 USA. RP Guiochon, GA (reprint author), Univ Tennessee, Knoxville, TN 37996 USA. EM guiochon@utk.edu NR 20 TC 15 Z9 17 U1 1 U2 11 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 OCT 25 PY 2004 VL 524 IS 1-2 BP 1 EP 14 DI 10.1016/j.aca.2004.03.102 PG 14 WC Chemistry, Analytical SC Chemistry GA 858UE UT WOS:000224216700002 ER PT J AU Lord, PG Papoian, T AF Lord, PG Papoian, T TI Genomics and drug toxicity SO SCIENCE LA English DT Editorial Material C1 Johnson & Johnson, Pharmaceut Res & Dev, Raritan, NJ 08869 USA. US FDA, Rockville, MD 20857 USA. RP Johnson & Johnson, Pharmaceut Res & Dev, Raritan, NJ 08869 USA. NR 2 TC 11 Z9 13 U1 0 U2 1 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 EI 1095-9203 J9 SCIENCE JI Science PD OCT 22 PY 2004 VL 306 IS 5696 BP 575 EP 575 DI 10.1126/science.1105854 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 866EN UT WOS:000224756700001 PM 15498974 ER PT J AU Roberts, DW Doerge, DR Churchwell, MI da Costa, GG Marques, MM Tolleson, WH AF Roberts, DW Doerge, DR Churchwell, MI da Costa, GG Marques, MM Tolleson, WH TI Inhibition of extrahepatic human cytochromes P450 1A1 and 1B1 by metabolism of isoflavones found in Trifolium pratense (Red clover) SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE Biochanin A; CYP1A1; CYP1B1; cytochrome P450; demethylation; enzyme inhibition; extrahepatic metabolism; formononetin; hydroxylation; isoflavones; Trifolium pratense ID ESTROGEN-RECEPTOR MODULATORS; SOY ISOFLAVONES; IN-VITRO; HUMAN 17-BETA-HYDROXYSTEROID-DEHYDROGENASE; OXIDATIVE-METABOLISM; SOYBEAN ISOFLAVONES; BIOCHANIN-A; PHYTOESTROGENS; GENISTEIN; CELLS AB Biochanin A and formononetin are the predominant isoflavones in red clover. In a previous study (J. Agric. Food Chem. 2002, 50, 4783-4790), it was demonstrated that human liver microsomes converted biochanin A and formononetin to genistein and daidzein. This paper now shows CYP1B1 catalyzed O-demethylation of biochanin A and formononetin to produce genistein and daidzein, respectively, which inhibit CYP1B1. Recombinant human CYP1A1 or CYP1B1 was incubated with biochanin A or formononetin. CYP1A1 catalyzed isoflavone 4'-O-demethylation and hydroxylations with similar efficiency, whereas CYP1B1 favored 4'-O-ademethylation over hydroxylations. Three of the biochanin A metabolites (5,7,3'-trihydroxy-4'-methoxyisoflavone, 5,7,8-trihydroxy-4'-methoxyisoflavone, and 5,6,7-trihydroxy-4'-methoxyisoflavone) were characterized by H-1 NMR spectroscopy and mass spectrometry. Daidzein (K-i = 3.7 muM) exhibited competitive inhibition of CYP1B1 7-ethoxyresorufin O-deethylase activity, and genistein (K-i = 1.9 muM) exhibited mixed inhibition. Biochanin A and/or formononetin may exert anticarcinogenic effects directly by acting as competitive substrates for CYP1B1 or indirectly through their metabolites daidzein and genistein, which inhibit CYP1B1. C1 Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. Univ Tecn Lisboa, Ctr Quim Estrutural, Inst Super Tecn, P-1049001 Lisbon, Portugal. RP Tolleson, WH (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM wtolleson@nctr.fda.gov RI Marques, M. Matilde/E-2535-2012 OI Marques, M. Matilde/0000-0002-7526-4962 NR 39 TC 35 Z9 37 U1 3 U2 8 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0021-8561 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD OCT 20 PY 2004 VL 52 IS 21 BP 6623 EP 6632 DI 10.1021/jf049418x PG 10 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 862RU UT WOS:000224509400040 PM 15479032 ER PT J AU Dagher, R Johnson, J Williams, G Keegan, P Pazdur, R AF Dagher, R Johnson, J Williams, G Keegan, P Pazdur, R TI Accelerated approval of oncology products: A decade of experience SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Review ID CHRONIC MYELOGENOUS LEUKEMIA; METASTATIC BREAST-CANCER; IMATINIB MESYLATE CAPSULES; CELL LUNG-CANCER; PHASE-III TRIAL; RANDOMIZED-TRIAL; COLORECTAL-CANCER; CONTINUOUS CHEMOTHERAPY; FLUOROURACIL FAILURE; GEFITINIB ZD1839 AB We review the regulatory history of the accelerated approval process and summarize the U.S. Food and Drug Administration experience with accelerated approvals in oncology. The accelerated approval regulations, promulgated in 1992, allow approval of drugs for serious or life-threatening diseases on the basis of a surrogate endpoint that is reasonably likely to predict clinical benefit, such as survival or symptom benefit, pending completion of studies designed to confirm clinical benefit, referred to as phase 4 commitments, which are required to be conducted with due diligence. From 1992 to 2004, 22 applications involving anticancer drugs or biologics were approved. Of these 22 applications, accelerated approval was granted to 15 on the basis of findings from studies without an active comparator (i.e., single-arm studies or studies comparing two dose levels) and to the remaining seven on the basis of one or more randomized studies. Of the 22 approved applications, six (i.e., applications for dexrazoxane, irinotecan, capecitabine, docetaxel, imatinib mesylate, and oxaliplatin) have had one or more indications converted to regular approval. This review reports information that was presented at an Oncologic Drugs Advisory Committee meeting held in March 2003; it also presents a discussion of accelerated approval study designs, the study populations evaluated in the accelerated approval and confirmatory settings, and the integration of accelerated approval into a comprehensive drug development plan. C1 US FDA, Ctr Drug Evaluat & Res, Div Oncol Drug Prod, Rockville, MD 20852 USA. US FDA, Ctr Drug Evaluat & Res, Div Therapeut Biol Oncol Prod, Rockville, MD 20852 USA. RP Dagher, R (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Oncol Drug Prod, 1451 Rockville Pike, Rockville, MD 20852 USA. EM dagherr@cder.fda.gov NR 46 TC 53 Z9 56 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD OCT 20 PY 2004 VL 96 IS 20 BP 1500 EP 1509 DI 10.1093/jnci/djh279 PG 10 WC Oncology SC Oncology GA 863PL UT WOS:000224573900009 PM 15494600 ER PT J AU Lee, HY Moon, H Chun, KH Chang, YS Hassan, K Lin, J Lotan, R Khuri, FR Hong, WK AF Lee, HY Moon, H Chun, KH Chang, YS Hassan, K Lin, J Lotan, R Khuri, FR Hong, WK TI Effects of insulin-like growth factor binding protein-3 and farnesyltransferase inhibitor SCH66336 on Akt expression and apoptosis on non-small-cell lung cancer cells SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID FACTOR RECEPTOR EXPRESSION; IGF-I RECEPTOR; ANTITUMOR-ACTIVITY; PROMOTER METHYLATION; EPITHELIAL-CELLS; TRANSGENIC MICE; RAS MUTATIONS; TRANSFERASE; PATHWAY; KINASE AB Background: Overexpression of insulin-like growth factor binding protein-3 (IGFBP-3) induces apoptosis in non-small-cell lung cancer (NSCLC) cells in vitro and in vivo. However, Ras-mediated signaling pathways could develop resistance to apoptotic activities of IGFBP-3 in NSCLC cells. We thus evaluated the therapeutic potential of the combination of IGFBP-3 and SCH66336, a farnesyltransferase inhibitor that blocks Ras activation, in NSCLC cell lines. Methods: The effects of the combination of adenoviral IGFBP-3 (Ad-IGFBP3) and SCH66336 on proliferation and apoptosis of NSCLC cell lines (H1299, H596, A549, H460, H358, H322, and H226B) were assessed in vitro and in vivo by using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, a How cytometry-based terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick-end labeling assay, western blot analyses, and an NSCLC xenograft tumor model. The specific effects of Ad-IGFBP 3 and SCH66336 on mitogen-activated protein kinase and Akt were assessed by using adenoviral vectors that express constitutively active MEK1 or constitutively active Akt. Synergy was assessed by median effect analysis. Results: The combination of Ad-IGFBP3 and SCH66336 had synergistic anti-proliferative effects in five cell lines (111299, H596, A549, H460, and H322). Antiproliferative effects were accompanied by increased apoptosis in H460 cells in vitro. Overexpression of a constitutively active Akt but not a constitutively active MEK-1 rescued H460 cells from apoptosis induced by single or combined treatment of Ad-IGFBP3 and SCH66336. In H1299 tumor xenografts, Ad-IGFBP3 and SCH66336 was associated with decreased tumor volume, increased apoptosis, and decreased Akt levels. Conclusions: The combination of Ad-IGFBP3 and SCH66336 decreased Akt expression and Simultaneous treatment with IGFBP-3 and SCH66336 may have the potential to be an effective therapeutic strategy in NSCLC. C1 Univ Texas, MD Anderson Canc Ctr, Dept Thorac Head & Neck Med Oncol, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Thorac Surg, Houston, TX 77030 USA. US FDA, Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. Emory Univ, Sch Med, Dept Hematol & Med Oncoll, Winship Canc Ctr, Atlanta, GA USA. RP Lee, HY (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Thorac Head & Neck Med Oncol, 1515 Holcombe Blvd, Houston, TX 77030 USA. EM hlee@mdanderson.org FU NCI NIH HHS [R01 CA100816-01A1] NR 55 TC 50 Z9 52 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD OCT 20 PY 2004 VL 96 IS 20 BP 1536 EP 1548 DI 10.1093/jnci/djh286 PG 13 WC Oncology SC Oncology GA 863PL UT WOS:000224573900013 PM 15494604 ER PT J AU Schwartz, RS Edelman, ER AF Schwartz, RS Edelman, ER CA Consensus Comm TI Preclinical evaluation of drug-eluting stents for peripheral applications - Recommendations from an expert consensus group SO CIRCULATION LA English DT Article DE stents; restenosis; drugs ID PORCINE CORONARY; LOCAL-DELIVERY; COATED STENT; MODEL; RESTENOSIS; ARTERIES; THROMBOSIS; TIME; ERA C1 Minneapolis Heart Inst Fdn, Minnesota Cardiovasc Res Inst, Minneapolis, MN 55407 USA. Harvard MIT Div Hlth Sci & Technol, Cambridge, MA USA. Borgess Med Ctr, Kalamazoo, MI USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. Amer Cardiovasc Res Inst, Atlanta, GA USA. Washington Hosp Ctr, Washington, DC 20010 USA. Columbia Univ, New York, NY USA. Univ Penn Hlth Syst, Philadelphia, PA USA. Armed Forces Inst Pathol, Bethesda, MD USA. US FDA, Rockville, MD 20857 USA. RP Schwartz, RS (reprint author), Minneapolis Heart Inst Fdn, Minnesota Cardiovasc Res Inst, 920 E 28th St, Minneapolis, MN 55407 USA. EM rss@rsschwartz.com NR 35 TC 45 Z9 51 U1 0 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 OCT 19 PY 2004 VL 110 IS 16 BP 2498 EP 2505 DI 10.1161/01.CIR.0000145164.85178.2E PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 863HV UT WOS:000224553000035 PM 15492330 ER PT J AU Peters, JA Kenen, R Giusti, R Loud, J Weissman, N Greene, MH AF Peters, JA Kenen, R Giusti, R Loud, J Weissman, N Greene, MH TI Exploratory study of the feasibility and utility of the colored eco-genetic relationship map (CEGRM) in women at high genetic risk of developing breast cancer SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE genetic counseling; breast cancer genetics; genetic testing; family; friends; relationships; kin; social network; communications; pedigree; genogram; ecomap; psychosocial; psychological; social; familial cancer; hereditary cancer ID FAMILY RELATIONSHIPS; OVARIAN-CANCER; BRCA1; COMMUNICATION; SPIRITUALITY; PERCEPTIONS; DISCLOSURE; RELATIVES; SPOUSES; CONTEXT AB We report here the results of an exploratory feasibility study of the colored eco-genetic relationship map (CEGRM), a novel, recently-developed psychosocial assessment tool, which incorporates features of the genetic pedigree, family systems genogram, and ecomap. The CEGRM presents a simple, concise, visual representation of the social interaction domains of information, services, and emotional support through the application of color-coded symbols to the genetic pedigree. The interactive process of completing the CEGRM was designed to facilitate contemporary genetic counseling goals oh (a) understanding the client in the context of her/his social milieu; (b) bolstering client self-awareness and insight; (c) fostering active client participation and mutuality in the counseling interaction; (d) eliciting illuminating social narratives; and (e) addressing outstanding emotional issues. Twenty women participating in a breast imaging study of women from families with BRCA1/2 mutations completed and evaluated various aspects of the CEGRM. We found that efficient construction of the CEGRM was feasible, and that compliance was excellent. Participants developed insights into their social milieu through observing the visual pattern of relationships illustrated by the CEGRM. The process of co-constructing the CEGRM fostered the participant's active involvement in the session, marked by mutuality and increased empathy. In this clinical research context, the participants felt free to share poignant stories about their friends and families. Further studies are planned to refine the CEGRM and to examine its utility in cancer genetics research. Published 2004 Wiley-Liss, Inc. C1 NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Rockville, MD 20852 USA. New Jersey Med Coll, Dept Sociol & Anthropol, Ewing, NJ USA. US FDA, Rockville, MD 20857 USA. RP Peters, JA (reprint author), NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, NIH,DHHS, 6120 Execut Blvd,EPS 7021, Rockville, MD 20852 USA. EM petersju@mail.nih.gov NR 53 TC 12 Z9 12 U1 2 U2 7 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0148-7299 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD OCT 15 PY 2004 VL 130A IS 3 BP 258 EP 264 DI 10.1002/ajmg.a.30271 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 858HA UT WOS:000224181700007 PM 15378540 ER PT J AU Winthrop, KL Siegel, JN AF Winthrop, KL Siegel, JN TI Tuberculosis cases associated with infliximab and etanercept SO CLINICAL INFECTIOUS DISEASES LA English DT Letter C1 US FDA, Div Therapeut Biol Internal Med Prod, Off Drug Evaluat 6, Ctr Drug Evaluat & Res, Rockville, MD 20852 USA. Ctr Dis Control & Prevent, Div TB Eliminat, Natl Ctr HIV STD & TB Prevent, Atlanta, GA USA. RP Winthrop, KL (reprint author), US FDA, Div Therapeut Biol Internal Med Prod, Off Drug Evaluat 6, Ctr Drug Evaluat & Res, 1401 Rockville Pike,HFM-582, Rockville, MD 20852 USA. NR 6 TC 6 Z9 7 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD OCT 15 PY 2004 VL 39 IS 8 BP 1256 EP 1257 DI 10.1086/424460 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 904JF UT WOS:000227491700031 PM 15486859 ER PT J AU Powers, JH AF Powers, JH TI Considerations in clinical trials of combination antifungal therapy SO CLINICAL INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 2nd John E Bennett Forum on Deep Mycoses Study Design CY FEB, 2003 CL New York, NY ID COMMUNITY-ACQUIRED PNEUMONIA; AMPHOTERICIN-B; INVASIVE ASPERGILLOSIS; LIPOSOMAL AMPHOTERICIN; ANTIBIOTIC-THERAPY; RANDOMIZED-TRIAL; END-POINTS; ENDOCARDITIS; MULTICENTER; FLUCONAZOLE AB The cure rate for serious fungal diseases with currently available agents used as monotherapy is not optimal. The introduction of new classes of antifungal drugs in the last few years naturally leads to the hypothesis that antifungal drugs used in combination may be more effective than the same drugs used alone. The design and interpretation of combination therapy studies raise challenges beyond those encountered when drugs are studied as monotherapy in the treatment of a disease. The definition of combination therapy, the study design, the selection of appropriate patient populations, and the selection of end points, as well as practical considerations, are all important in the design and interpretation of clinical trials of combination therapies. Although combination therapies hold the promise of improved efficacy, it is important to prove this hypothesis, because they also may be associated with increased toxicity and increased drug costs. A careful consideration of study design factors before the initiation of a trial will help obtain the most useful information for patients in this important area. C1 US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20850 USA. NIAID, Dept Infect Dis Attending, NIH, Bethesda, MD USA. RP Powers, JH (reprint author), US FDA, Ctr Drug Evaluat & Res, 9201 Corp Blvd,HFD-104, Rockville, MD 20850 USA. EM powersjoh@cder.fda.gov NR 40 TC 9 Z9 10 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD OCT 15 PY 2004 VL 39 SU 4 BP S228 EP S235 DI 10.1086/421962 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 904UO UT WOS:000227523400012 PM 15546123 ER PT J AU Powers, JH AF Powers, JH TI Issues in clinical trials of prophylaxis of fungal infections SO CLINICAL INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 2nd John E Bennett Forum on Deep Mycoses Study Design CY FEB, 2003 CL New York, NY ID BONE-MARROW TRANSPLANTATION; RANDOMIZED-TRIAL; DOUBLE-BLIND; FLUCONAZOLE; THERAPY; MULTICENTER; RECIPIENTS; CANCER; GUIDELINES AB The validity of the results of a clinical trial is highly dependent upon the design of the trial. The definition of disease, the selection criteria for enrollment in the trial, the selection of the study and control drugs, and the end points all affect whether the information obtained from the trial ultimately is useful in making decisions in clinical practice. These factors all apply to the design of clinical trials of the prophylaxis of infectious diseases. In addition, prophylaxis trials have several important differences from the design of trials of the treatment of those same diseases. The risk-benefit analysis for trials of prophylaxis is different, in that asymptomatic patients are exposed to the drug and more patients will be exposed than will develop the disease under study. Standardization of the design of such clinical trials will allow more efficient development of new drugs and will allow clinicians to compare more accurately the safety and efficacy of prophylactic agents. C1 US FDA, Antimicrobial Drug Dev & Resistance Initiat, Ctr Drug Evaluat & Res, Rockville, MD 20850 USA. NIAID, NIH, Bethesda, MD 20892 USA. RP Powers, JH (reprint author), US FDA, Antimicrobial Drug Dev & Resistance Initiat, Ctr Drug Evaluat & Res, 9201 Corp Blvd,HFD-104, Rockville, MD 20850 USA. EM powersjoh@cder.fda.gov NR 22 TC 8 Z9 8 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD OCT 15 PY 2004 VL 39 SU 4 BP S211 EP S217 DI 10.1086/421959 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 904UO UT WOS:000227523400009 PM 15546120 ER PT J AU Shirota, H Gursel, M Klinman, DM AF Shirota, H Gursel, M Klinman, DM TI Suppressive oligodeoxynucleotides inhibit Th1 differentiation by blocking IFN-gamma- and IL-12-mediated signaling SO JOURNAL OF IMMUNOLOGY LA English DT Article ID T-CELL-CLONE; INDUCED IMMUNE ACTIVATION; STIMULATORY CPG MOTIFS; BACTERIAL-DNA; TYROSINE PHOSPHORYLATION; TRANSCRIPTION FACTOR; INDUCED ARTHRITIS; ANTIGEN; INTERLEUKIN-12; LYMPHOCYTES AB Repetitive TTAGGG motifs present at high frequency in mammalian telomeres can suppress Th1-mediated immune responses. Synthetic oligonucleotides (ODN) containing TTAGGG motifs mimic this activity and have proven effective in the prevention/ treatment of certain Th1-dependent autoimmune diseases. This work explores the mechanism by which suppressive ODN block the induction of Th1 immunity. Findings indicate that these ODN inhibit IFN-gamma-induced STAT1 phosphorylation and IL-12-induced STAT3 and STAT4 phosphorylation. As a result, T-bet expression is reduced as is the maturation of naive CD4(+) cells into Th1 effectors. These changes indirectly support the generation of Th2-dominated immune responses. Suppressive ODN may thus represent a novel approach to influence the Th1:Th2 balance in vivo. C1 US FDA, Ctr Biol Evaluat & Res, Sect Retroviral Immunol, Bethesda, MD 20892 USA. RP Klinman, DM (reprint author), US FDA, Ctr Biol Evaluat & Res, Sect Retroviral Immunol, Bldg 29A Room 3 D10, Bethesda, MD 20892 USA. EM Klinman@cber.fda.gov RI Gursel, Mayda /H-1812-2012 NR 42 TC 52 Z9 60 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 OCT 15 PY 2004 VL 173 IS 8 BP 5002 EP 5007 PG 6 WC Immunology SC Immunology GA 861BX UT WOS:000224392200029 PM 15470043 ER PT J AU Dragunsky, EM Ivanov, AP Wells, VR Ivshina, AV Rezapkin, GV Abe, S Potapova, SG Enterline, JC Hashizume, S Chumakov, KM AF Dragunsky, EM Ivanov, AP Wells, VR Ivshina, AV Rezapkin, GV Abe, S Potapova, SG Enterline, JC Hashizume, S Chumakov, KM TI Evaluation of immunogenicity and protective properties of inactivated poliovirus vaccines: A new surrogate method for predicting vaccine efficacy SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT US-Food-and-Drug-Administration Science Forum CY APR 24-25, 2003 CL Washington, DC SP US FDA ID TRANSGENIC MICE; MOUSE NEUROVIRULENCE; POLIOMYELITIS; RECEPTOR; STRAIN; ERADICATION AB An assay for the evaluation of protective properties of inactivated poliovirus vaccines (IPVs) in transgenic (Tg) mice susceptible to poliovirus has been developed and optimized for type 2 IPV. This method was used to compare the immunogenicity and protective properties of experimental IPV produced from the attenuated Sabin strain (sIPV) with those of conventional IPV (cIPV) produced from the wild-type (wt) poliovirus MEF-1 strain. Modified enzyme-linked immunosorbent assays (ELISAs) were used to measure immune response in serum and saliva samples from test mice. Tg mice were vaccinated and were challenged either with wt poliovirus or virulent poliovirus derived from the vaccine strain. Compared with cIPV, sIPV induced lower levels of antibodies and did not completely protect mice against challenge with wt virus but did protect mice against challenge with the virulent vaccine-derived strain. This may be due to an 18% nucleotide difference between the MEF-1 and Sabin 2 strains, resulting in 72 amino acid substitutions and leading to antigenic dissimilarity. Immunological properties of both strains, revealed by cross-neutralization tests and ELISAs, confirmed that MEF-1 possesses broader immunogenicity than does Sabin 2. This animal model may be used for the assessment of new IPVs and of combination vaccines containing an IPV component. C1 US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. Japan Poliomyelitis Res Inst, Tokyo, Japan. RP Dragunsky, EM (reprint author), HFM-470,NLRC-B-121,1401 Rockville Pike, Rockville, MD 20852 USA. EM dragunsky@cber.fda.gov NR 30 TC 24 Z9 27 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD OCT 15 PY 2004 VL 190 IS 8 BP 1404 EP 1412 DI 10.1086/424524 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 855JF UT WOS:000223968700006 PM 15378432 ER PT J AU Muni, NI Gross, TP AF Muni, NI Gross, TP TI Problems with drug-eluting coronary stents - The FDA perspective SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Muni, NI (reprint author), US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. NR 2 TC 36 Z9 39 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 OCT 14 PY 2004 VL 351 IS 16 BP 1593 EP 1595 DI 10.1056/NEJMp048262 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 861OU UT WOS:000224427300002 PM 15483274 ER PT J AU Costamagna, P Furst, K Tully, K Landis, J Moser, K Quach, L Kwak, J Calvet, H Lindsey, B Flood, J Braun, M Siegel, J Winthrop, K Jereb, J Taylor, Z Iademarco, M Castro, K AF Costamagna, P Furst, K Tully, K Landis, J Moser, K Quach, L Kwak, J Calvet, H Lindsey, B Flood, J Braun, M Siegel, J Winthrop, K Jereb, J Taylor, Z Iademarco, M Castro, K CA CDC TI Tuberculosis associated with blocking agents against tumor necrosis factor-alpha - California, 2002-2003 SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Reprint C1 San Joaquin Cty Publ Hlth Svcs, Stockton, CA 95202 USA. Santa Cruz Cty Hlth Svcs, Santa Cruz, CA 95060 USA. San Diego Cty Dept Hlth, San Diego, CA USA. Cty Orange Hlth Care Agcy, Santa Ana, CA 92702 USA. Long Beach City Dept Hlth & Human Svcs, Long Beach, CA USA. Calif Dept Hlth Svcs, Sacramento, CA 95814 USA. Ctr Biol Evaluat & Res, Washington, DC USA. US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. CDC, Div TB Eliminat, Natl Ctr HIV STD & TB Prevent, Atlanta, GA 30333 USA. Centocor Inc, Malvern, PA USA. Immunex Corp, Thousand Oaks, CA USA. Abbott Labs, Abbott Pk, IL 60064 USA. RP Costamagna, P (reprint author), San Joaquin Cty Publ Hlth Svcs, Stockton, CA 95202 USA. NR 4 TC 1 Z9 1 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD OCT 13 PY 2004 VL 292 IS 14 BP 1676 EP 1678 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 861JS UT WOS:000224413400010 ER PT J AU Wise, RP Iskander, J Pratt, RD Campbell, S Ball, R Pless, RP Braun, MM AF Wise, RP Iskander, J Pratt, RD Campbell, S Ball, R Pless, RP Braun, MM TI Postlicensure safety surveillance for 7-valent pneumococcal conjugate vaccine SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID EVENT-REPORTING-SYSTEM; INFANT-DEATH-SYNDROME; ADVERSE EVENTS; IMMUNIZATION; RISK; PERTUSSIS; VAERS; EPIDEMIOLOGY; EFFICACY; PURPURA AB Context Clinical trials evaluate a vaccine's safety before approval, but some risks may escape detection or adequate characterization until larger population exposures occur after licensure. Objective To summarize reports of events occurring after vaccination with 7-valent pneumococcal conjugate vaccine (PCV), including those that may warrant further investigation to assess possible causation by PCV. Design Descriptive epidemiology of reports submitted to the Vaccine Adverse Event Reporting System (VAERS), a national passive surveillance database. Setting and Patients United States during first 2 years after licensure of PCV (February 2000 through February 2002). Reports studied were for children younger than 18 years and vaccinated with PCV. Main Outcome Measures Numbers and proportional distributions of reports. Results A total of 4154 reports of events following PCV were submitted to VAERS, for a rate of 13.2 reports per 100000 doses distributed. Multiple vaccines were given in 74.3% of reports. The most frequently reported symptoms and signs included fever, injection site reactions, fussiness, rashes, and urticaria. Serious events were described in 14.6% of reports. There were 117 deaths, 23 reports of positive rechallenges, and 34 cases of invasive pneumococcal infections possibly representing vaccine failure. Immune-mediated events occurred in 31.3% of reports. All 14 patients with anaphylactic or anaphylactoid reactions survived. Thrombocytopenia developed in 14 patients and serum sickness in 6 others. Neurologic symptoms occurred in 38% of reports. Seizures described in 393 reports included 94 febrile seizures. Conclusions The majority of reports to VAERS in the first 2 years after licensure of PCV described generally minor adverse events previously identified in clinical trials. The proportion of reports portraying serious events was similar to that for other vaccines. Although there are important limitations in passive surveillance data, and caution in their interpretation is necessary, symptoms experienced by a few children more than once after successive PCV doses, including allergic reactions, prolonged or abnormal crying, fussiness, dyspnea, and gastrointestinal distress, warrant continued surveillance, as do reports of rare but potentially serious events, such as seizures, anaphylactic or anaphylactoid reactions, serum sickness, and thrombocytopenia. C1 US FDA, Ctr Biol Evaluat & Res, Div Epidemiol, Off Biostat & Epidemiol, Rockville, MD 20852 USA. US FDA, Ctr Biol Evaluat & Res, Div Vaccines & Related Prod Applicat, Off Vaccines Res & Review, Rockville, MD 20852 USA. Ctr Dis Control & Prevent, Immunizat Safety Branch, Epidemiol & Surveillance Div, Natl Immunizat Program, Atlanta, GA USA. Ctr Infect Dis Prevent & Control Hlth Canada, Immunizat Safety Unit, Immunizat & Resp Infect Div, Ottawa, ON, Canada. RP Wise, RP (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Epidemiol, Off Biostat & Epidemiol, HFM-225,1401 Rockville Pike, Rockville, MD 20852 USA. EM R.P.Wise@cber.fda.gov NR 33 TC 45 Z9 46 U1 2 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD OCT 13 PY 2004 VL 292 IS 14 BP 1702 EP 1710 DI 10.1001/jama.292.14.1702 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 861JS UT WOS:000224413400029 PM 15479935 ER PT J AU Pena, C Bowsher, K Samuels-Reid, J AF Pena, C Bowsher, K Samuels-Reid, J TI FDA-approved neurologic devices intended for use in infants, children, and adolescents SO NEUROLOGY LA English DT Review ID BRAIN AB The US Food and Drug Administration (FDA) has approved several applications for the marketing of neurologic devices. Nineteen high risk Class III medical devices were approved for the central and peripheral nervous system for marketing between 1994 and 2003, and almost half (n = 8) include indications for use in children as well as adults. On July 24, 2003, the FDA Center for Devices and Radiologic Health released for public comment a draft guidance document entitled "Premarket Assessment of Pediatric Medical Devices," which included in its objectives, the types of information needed to provide reasonable assurance of the safety and effectiveness of medical devices intended for use in children. The draft guidance document is also relevant to the types of information needed to promote the safe and effective development of neurologic devices. We review risk assessment and ways to reduce risk for neurologic devices intended for use in children. We also discuss the deep brain stimulator, the cochlear implant, and the CSF shunt, and considerations for minimizing risks associated with brain development, physical growth, surgery, and human factors. C1 US FDA, CDRH, ODE, Div Gen Restorat & Neurol Devices, Rockville, MD 20850 USA. RP Pena, C (reprint author), US FDA, CDRH, ODE, Div Gen Restorat & Neurol Devices, 9200 Corp Blvd,HFZ-410, Rockville, MD 20850 USA. EM clp@cdrh.fda.gov NR 9 TC 13 Z9 13 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD OCT 12 PY 2004 VL 63 IS 7 BP 1163 EP 1167 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 861HV UT WOS:000224408000006 PM 15477532 ER PT J AU Ang, CYW Hu, LH Heinze, TM Cui, YY Freeman, JP Kozak, K Luo, WH AF Ang, CYW Hu, LH Heinze, TM Cui, YY Freeman, JP Kozak, K Luo, WH TI Instability of St. John's Wort (Hypericum perforatum L.) and degradation of hyperforin in aqueous solutions and functional beverage SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE Hypericum perforaturn L.; St. John's wort; fruit drink; stability; hyperforin degradation ID PERFORMANCE LIQUID-CHROMATOGRAPHY; DIETARY-SUPPLEMENTS; MASS-SPECTROMETRY; ARRAY DETECTION; X RECEPTOR; ANTIDEPRESSANT; STABILITY; EXTRACTS; CONSTITUENTS; COMPONENTS AB Several bioactive botanicals including St. John's wort (SJW; Hypericum perforatum L.) have been used to formulate functional foods and beverages. This study aimed to investigate the stability of SJW components in aqueous solutions and fruit-flavored drinks. Changes of active marker components (hypericin, pseudohypericin, hyperforin, and adhyperforin) as affected by pH and light exposure were determined by HPLC, and the degradation of hyperforin was analyzed by LC-MS/MS and NMR. SJW components were found to be unstable in acidic aqueous solutions. More changes occurred under light exposure, with hyperforin and adhyperforin decreasing the most. Less severe changes were observed in the drink sample as compared to the pH 2.65 solution. Major degradation products of hyperforin in acidic aqueous solutions were identified as furohyperforin, furohyperforin hydroperoxide, and furohyperforin isomer a. The latter was also found in the drink product containing SJW as an ingredient. Biological activities and potential quality and safety implications of these chemical changes are yet to be evaluated. C1 US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Novartis Pharmaceut Corp, E Hanover, NJ 07936 USA. US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Ang, CYW (reprint author), US FDA, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM cang@nctr.fda.gov NR 24 TC 32 Z9 32 U1 1 U2 17 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0021-8561 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD OCT 6 PY 2004 VL 52 IS 20 BP 6156 EP 6164 DI 10.1021/jf0490596 PG 9 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 858SM UT WOS:000224212000017 PM 15453681 ER PT J AU Fraunfelder, FW AF Fraunfelder, FW TI Ocular side effects from herbal medicines and nutritional supplements SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Editorial Material ID NICOTINIC-ACID MACULOPATHY; GINKGO-BILOBA; CANTHAXANTHIN RETINOPATHY; DOUBLE-BLIND; VITAMIN-A; NIACIN MACULOPATHY; CONTROLLED-TRIAL; EPIDEMIC DROPSY; UNITED-STATES; EXTRACT AB PURPOSE: To review the more significant herbal and nutritional agents of clinical importance to ophthalmologists and describe the ocular side effects for each. World Health Organization (WHO) classification and guidelines for clinicians are provided. DESIGN: Retrospective observational case series. METHODS: A retrospective observational case series of reports of ocular side effects or systemic side effects from medications used for the eye from herbal medicines and nutritional supplements. Cases were collected from spontaneous reports submitted to the WHO, the Food and Drug Administration, and the National Registry of Drug, Induced Ocular Side Effects. A review of the world's literature was performed to obtain additional case reports and insight into adverse ocular reactions. Data were collected on age, gender, duration of therapy, concomitant medications, dosage, and dechallenge and rechallenge results. RESULTS: The National Registry of Drug,Induced Ocular Side Effects received 263 spontaneous reports, in addition to 60 case reports from the literature. Canthaxanthine, chamomile, Datura, Echinacea purpurea, Ginkgo biloba, licorice, niacin, and vitamin A are all associated with clinically significant ocular side effects. CONCLUSION: Herbal medicines and nutritional supplements can cause ocular side effects. Clinicians need to recognize these adverse events, because a large segment of the population uses them, many times without the treating physician's knowledge. (C) 2004 by Elsevier Inc. All rights reserved. C1 Oregon Hlth Sci Univ, Casey Eye Inst, Portland, OR 97239 USA. WHO, Ctr Int Drug Monitoring, Uppsala, Sweden. US FDA, Rockville, MD 20857 USA. Casey Eye Inst, Natl Registry Drug Induced Ocular Side Effects, Portland, OR 97239 USA. RP Fraunfelder, FW (reprint author), Oregon Hlth Sci Univ, Casey Eye Inst, 3375 SW Terwilliger Blvd, Portland, OR 97239 USA. EM eyedrug@ohsu.edu NR 73 TC 27 Z9 28 U1 4 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD OCT PY 2004 VL 138 IS 4 BP 639 EP 647 DI 10.1016/j.ajo.2004.04.072 PG 9 WC Ophthalmology SC Ophthalmology GA 864UO UT WOS:000224658600021 PM 15488795 ER PT J AU D'Agnillo, F AF D'Agnillo, F TI Redox active hemoglobin enhances lipopolysaccharide-induced injury to cultured bovine endothelial cells SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE apoptosis; ferryl hemoglobin; hydrogen peroxide; glucose oxidase ID CROSS-LINKED HEMOGLOBIN; BACTERIAL-ENDOTOXIN LIPOPOLYSACCHARIDE; OXIDATIVE STRESS; NITRIC-OXIDE; INFLAMMATORY RESPONSE; BIOLOGICAL-ACTIVITY; TISSUE FACTOR; SEPTIC SHOCK; LUNG INJURY; APOPTOSIS AB The interaction of cell-free hemoglobin with lipopolysaccharide (LPS) is thought to aggravate the pathophysiology of sepsis and/or septic shock. This study examines the possible modulatory role of cell-free hemoglobin on LPS-induced apoptosis of cultured bovine aortic endothelial cells. Experiments were performed with or without fetal bovine serum, a source of LPS-binding protein and soluble CD14. In the absence of serum, LPS alone or coincubated with purified bovine hemoglobin (BvHb), human hemoglobin (Hb), or alpha-cross-linked Hb (alphaHb) did not induce apoptosis. In the presence of serum, LPS induced significant apoptosis. LPS combined with BvHb, Hb, or alphaalphaHb produced the same extent of apoptosis as LPS alone. To examine whether the H2O2-driven redox activity of hemoglobin alters LPS-induced apoptosis, glucose oxidase was added to the system to generate a subtoxic flux of H2O2. The combined treatment of LPS, glucose oxidase, and BvHb, Hb, or alphaalphaHb enhanced apoptosis compared with LPS alone. These findings support a possible mechanism whereby the redox cycling of hemoglobin, and not its direct interaction with LPS, contributes to the hemoglobin-mediated enhancement of LPS-related pathophysiology. C1 US FDA, Ctr Biol Evaluat & Res, Lab Biochem & Vasc Biol, Div Hematol, Bethesda, MD 20892 USA. RP D'Agnillo, F (reprint author), US FDA, Ctr Biol Evaluat & Res, Lab Biochem & Vasc Biol, Div Hematol, 29 Lincoln Dr,Bldg 29,Rm 129, Bethesda, MD 20892 USA. EM dagnillo@cber.fda.gov NR 45 TC 5 Z9 5 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD OCT PY 2004 VL 287 IS 4 BP H1875 EP H1882 DI 10.1152/ajpheart.00164.2004 PG 8 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 854IH UT WOS:000223895800055 PM 15205170 ER PT J AU Hefflin, BJ Gross, TP Schroeder, TJ AF Hefflin, BJ Gross, TP Schroeder, TJ TI Estimates of medical device-associated adverse events from emergency departments SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article AB Background: The true public health burden of adverse events associated with medical devices is unknown. The purpose of this study, therefore, was to produce the first-ever national estimates of medical device-associated adverse events resulting in emergency department (ED) visits. Methods: From July 1999 through June 2000, reports of 10,395 medical device-associated adverse events were accumulated using the National Electronic Injury Surveillance System (NEISS), which collects information on product-related injuries from the ED records of a national stratified probability sample of hospitals. The reports were used to estimate annual total number of medical device-associated adverse events as well as number of adverse events associated with specific devices, injury diagnoses, demographic characteristics, and patient disposition status. Results: The total estimated number of adverse events was 454,383 (95% confidence interval [CI] = 371,156-537,610), involving a broad range of devices from 15 medical specialty groups. Unintentional traumatic events associated with a particular device appeared to be the most common mechanism of injury. The most prevalent types of injuries included contusions/abrasions, punctures, and lacerations; 13% of total estimated cases resulted in patient hospitalization. Adverse events occurred within healthcare facilities, and some were occupationally related, although they occurred at home more frequently than any other location (about 42%). Conclusions: The magnitude of the total estimate, which is over four times greater than the annual number of adverse event reports received by medical device-regulating surveillance systems, emphasizes medical device-associated adverse events as an under-recognized public health problem. Planned collection of more detailed NEISS data will allow for appropriate public health interventions. (C) 2004 American Journal of Preventive Medicine. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. US Consumer Prod Safety Commiss, Bethesda, MD USA. RP Hefflin, BJ (reprint author), US FDA, Ctr Devices & Radiol Hlth, 1350 Piccard Dr,HFZ-541, Rockville, MD 20850 USA. EM bjh@cdrh.fda.gov NR 23 TC 16 Z9 17 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD OCT PY 2004 VL 27 IS 3 BP 246 EP 253 DI 10.1016/j.amepre.2004.04.005 PG 8 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 857IM UT WOS:000224109800009 PM 15450638 ER PT J AU Chu, DMT Sherchand, JB Cross, JH Orlandi, PA AF Chu, DMT Sherchand, JB Cross, JH Orlandi, PA TI Detection of Cyclospora cayetanensis in animal fecal isolates from Nepal using an FTA filter-base polymerase chain reaction method SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID MOLECULAR CHARACTERIZATION; IMPORTED RASPBERRIES; TEMPLATE PREPARATION; COCCIDIAN PARASITES; EIMERIA; INFECTION; OUTBREAK; PCR; IDENTIFICATION; APICOMPLEXA AB Cyclospora cayetanensis is an emerging protozoan parasite capable of causing a protracted diarrheal illness in both immunocompromised and immunocompetent individuals. Ingestion of fresh produce and water sources contaminated with mature sporulated oocysts results in acquisition of cyclosporiasis. Currently, no animal model exists for the study of this pathogenic parasite and the only confirmed reservoir host for C. cayetanensis in nature is humans. Previously, Cyclospora-like oocysts had been detected by microscopy in several animals including non-human primates. However, their phylogenetic relationship to C. cayetanensis remained uncertain due to the limited availability of molecular techniques to differentiate and speciate these isolates. In the present study, we examined a series of fecal isolates obtained from dogs, chickens, and monkeys collected between May and September 2002 from several geographic regions of Nepal. All samples were examined by microscopy and a polymerase chain reaction (PCR) for the presence of C. cayetanensis. Both microscopic and conventional PCR/restriction fragment length polymorphism (RFLP) analysis demonstrated the presence of Cyclospora sp. in the fecal samples of two dogs, one chicken, and one monkey. Application of a species-specific multiplex PCR assay confirmed the presence of both Eimeria sp. and C. cayetanensis in the positive chicken sample and only C. cayetanensis in the dog and monkey samples. However, in the absence of tissue analysis, the assignment of these animals as a natural reservoir host for C. cayetanensis remains to be determined. C1 US FDA, Div Microbiol Studies, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. US FDA, Div Virulence Assessment, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. Tribhuvan Univ, Teaching Hosp, Dept Microbiol Parasitol, Kathmandu, Nepal. Tribhuvan Univ, Teaching Hosp, Infect & Trop Dis Res Ctr, Kathmandu, Nepal. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. RP Chu, DMT (reprint author), US FDA, Div Microbiol Studies, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. EM porlande@cfsan.fda.gov NR 38 TC 23 Z9 36 U1 0 U2 4 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD OCT PY 2004 VL 71 IS 4 BP 373 EP 379 PG 7 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 867CY UT WOS:000224821000001 PM 15516629 ER PT J AU Dubois, J Shaw, RA AF Dubois, J Shaw, RA TI IR spectroscopy - in clinical and diagnostic applications SO ANALYTICAL CHEMISTRY LA English DT Article ID TRANSFORM INFRARED-SPECTROSCOPY; DISEASE PATTERN-RECOGNITION; MIDINFRARED SPECTROSCOPY; BREAST-TUMORS; HUMAN SERUM; SPECTRA; BLOOD; CELLS; ARTHRITIS; SCRAPIE C1 US FDA, Rockville, MD 20857 USA. Univ Maryland, College Pk, MD 20742 USA. Natl Res Council Canada, Ottawa, ON K1A 0R6, Canada. RP US FDA, Rockville, MD 20857 USA. EM shaw@nrc-cnrc.gc.ca NR 44 TC 12 Z9 12 U1 0 U2 2 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 OCT 1 PY 2004 VL 76 IS 19 BP 361A EP 367A PG 7 WC Chemistry, Analytical SC Chemistry GA 858UL UT WOS:000224217400016 ER PT J AU Hayes, JR English, LL Carr, LE Wagner, DD Joseph, SW AF Hayes, JR English, LL Carr, LE Wagner, DD Joseph, SW TI Multiple-antibiotic resistance of Enterococcus spp. isolated from commercial poultry production environments SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID LINCOSAMIDE-STREPTOGRAMIN-B; ANTIMICROBIAL RESISTANCE; QUINUPRISTIN-DALFOPRISTIN; FOOD-ANIMALS; AMINOGLYCOSIDE RESISTANCE; FECAL ENTEROCOCCI; GROWTH PROMOTION; FAECIUM; FAECALIS; DENMARK AB The potential impact of food animals in the production environment on the bacterial population as a result of antimicrobial drug use for growth enhancement continues to be a cause for concern. Enterococci from 82 farms within a poultry production region on the eastern seaboard were isolated to establish a baseline of susceptibility profiles for a number of antimicrobials used in production as well as clinical environments. Of the 541 isolates recovered, Enterococcus faecalis (53%) and E. faecium (31%) were the predominant species, while multiresistant antimicrobial phenotypes were observed among all species. The prevalence of resistance among isolates of E. faecalis was comparatively higher among lincosamide, macrolide, and tetracycline antimicrobials, while isolates of E. faecium were observed to be more frequently resistant to fluoroquinolones and penicillins. Notably, 63% of the E. faecium isolates were resistant to the streptogramin quinupristin-dalfopristin, while high-level gentamicin resistance was observed only among the E. faecalis population, of which 7% of the isolates were resistant. The primary observations are that enterococci can be frequently isolated from the poultry production environment and can be multiresistant to antimicrobials used in human medicine. The high frequency with which resistant enterococci are isolated from this environment suggests that these organisms might be useful as sentinels to monitor the development of resistance resulting from the usage of antimicrobial agents in animal production. C1 Univ Maryland, Dept Mol Genet & Cell Biol, College Pk, MD 20740 USA. Univ Maryland, Dept Biol Resources Engn, College Pk, MD 20740 USA. US FDA, Ctr Vet Med, Laurel, MD USA. RP Joseph, SW (reprint author), Univ Maryland, Dept Mol Genet & Cell Biol, College Pk, MD 20740 USA. EM sj13@umail.umd.edu NR 45 TC 64 Z9 66 U1 0 U2 7 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0099-2240 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD OCT PY 2004 VL 70 IS 10 BP 6005 EP 6011 DI 10.1128/AEM.70.10.6005-6011.2004 PG 7 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 860PT UT WOS:000224356200039 PM 15466544 ER PT J AU Sundaram, AK Pitts, L Muhammad, K Wu, J Betenbaugh, M Woodard, RW Vann, WF AF Sundaram, AK Pitts, L Muhammad, K Wu, J Betenbaugh, M Woodard, RW Vann, WF TI Characterization of N-acetylneuraminic acid synthase isoenzyme 1 from Campylobacter jejuni SO BIOCHEMICAL JOURNAL LA English DT Article DE Campylobacter jejuni; ManNAc analogue; N-acetyl-3-fluoroneuraminic acid; N-acetylneuraminic acid synthase; stereochemical analysis ID 3-DEOXY-D-ARABINO-HEPTULOSONATE 7-PHOSPHATE SYNTHASE; CHORISMATE SYNTHETASE REACTION; ESCHERICHIA-COLI; SIALIC-ACID; ENZYMATIC-SYNTHESIS; NEUB GENES; ANALOGS; STEREOCHEMISTRY; SUBSTRATE; PHOSPHOENOLPYRUVATE AB Escherichia coli NeuNAc (N-acetylneuraminic acid) synthase catalyses the condensation of PEP (phosphoenolpyruvate) and ManNAc (N-acetylmannosamine) to form NeuNAc and is encoded by the neuB gene. Campylobacter jejuni has three neuB genes, one of which is very similar to the E. coli neuB gene. We have characterized the C. jejuni neuraminic acid synthase with respect to acylamino sugar specificity and stereochemistry of the PEP condensation. We determined the specificity of C. jejuni NeuNAc synthase for N-acetylmannosamine, N-butanoylmanno-samine, N-propionoylmannosamine and N-pentanoyimannosamine. We find that, although this enzyme exhibits similar K, values for N-acylmannosamine molecules with different N-acyl groups, the k(cat)/K-m values decreased with increasing chain length. NeuNAc synthase is a member of a PEP-utilizing family of enzymes that form oxo acids from PEP and a monosaccharide. This family includes KDO 8-P (2-keto-3-deoXY-D-mantio-octulosonate 8-phosphate) synthase and DAH 7-P (2-keto-3-deoxy- D-arabino-heptulosonate 7-phosphate) synthase. Both enzymes catalyse the condensation of the re face of the aldehyde group of the monosaccharicle with the si face of the PEP molecule. The C. jejuni NeuNAc synthase catalysed the condensation of Z- and E-[3-(2) H]PEP with ManNAc, yielding (3S)-3-deutero-NeuNAc and (3R)-3-deutero-NeuNAc respectively. The condensation of Z-[3-F]PEP and ManNAc yielded (3S)-3-fluoro-NeuNAc. Results of our studies suggest that the C.jejuni NeuNAc synthase, similar to KDO 8-P synthase and DAH 7-P synthase, catalyses the condensation of the si face of PEP with the aldehyde sugar. The present study is the first stereochernical analysis of the reaction catalysed by a bacteria] NeuNAc synthase. C1 Ctr Biol Evaluat & Res, Lab Bacterial Toxins, Bethesda, MD 20892 USA. Johns Hopkins Univ, Dept Chem Engn, Baltimore, MD 21218 USA. Univ Michigan, Coll Pharm, Dept Med Chem, Ann Arbor, MI 48109 USA. RP Vann, WF (reprint author), Ctr Biol Evaluat & Res, Lab Bacterial Toxins, 8800 Rockville Pike, Bethesda, MD 20892 USA. EM wvann@helix.nih.gov RI Betenbaugh, Michael J./A-3252-2010; OI Betenbaugh, Michael J./0000-0002-6336-4659; Woodard, Ronald/0000-0002-7472-3653 FU NIGMS NIH HHS [GM53069, R01 GM053069] NR 28 TC 21 Z9 21 U1 1 U2 4 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON W1N 3AJ, ENGLAND SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD OCT 1 PY 2004 VL 383 BP 83 EP 89 DI 10.1042/BJ20040218 PN 1 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 863CK UT WOS:000224537800010 PM 15200387 ER PT J AU Lazarus, E AF Lazarus, E TI Implementation of the FDA regulatory approach to cells and tissue: Focus on cord blood SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT 2nd Annual International Umbilical Cord Blood Symposium CY MAY 14-15, 2004 CL Los Angeles, CA C1 US FDA, Div Human Tissues, Off Cellular Tissue & Gene Therapies, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 2004 VL 10 IS 10 MA 22 BP 739 EP 739 DI 10.1016/j.bbmt.2004.06.032 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 860XS UT WOS:000224378100032 ER PT J AU Eiseman, JL Brown-Proctor, C Kinahan, PE Collins, JM Anderson, LW Joseph, E Hamburger, DR Pan, SS Mathis, CA Egorin, MJ Klecker, RW AF Eiseman, JL Brown-Proctor, C Kinahan, PE Collins, JM Anderson, LW Joseph, E Hamburger, DR Pan, SS Mathis, CA Egorin, MJ Klecker, RW TI Distribution of 1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl) uracil in mice bearing colorectal cancer xenografts: Rationale for therapeutic use and as a positron emission tomography probe for thymidylate synthase SO CLINICAL CANCER RESEARCH LA English DT Article ID FLUOROPYRIMIDINE-BASED CHEMOTHERAPY; COLON-CANCER; TUMORS; EFFICACY; AGENTS; FMAU; FAU; PET; DNA AB Purpose: In colorectal, breast, and head and neck cancers, response to 5-fluorouracil is associated with low expression of thymidylate synthase. In contrast, tumors with high expression of thymidylate synthase may be more sensitive to prodrugs such as 1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl) uracil (FAU) that are activated by thymidylate synthase. These studies were designed to evaluate FAU as a potential therapeutic and diagnostic probe. Experimental Design: [F-18]-FAU and [H-3]-FAU were synthesized with >97% radiochemical purity. [H-3]-FAU or [F-18]-FAU was administered intravenously to severe combined immunodeficient mice bearing either HT29 (low thymidylate synthase) or LS174T (high thymidylate synthase) human colon cancer xenografts. Four hours after [H-3]-FAU dosing, tissue distribution of total radioactivity and incorporation of 1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl) 5-methyluracil (FMAU), derived from thymidylate synthase activation of FAU, into tumor DNA was measured. Positron emission tomography (PET) images were obtained for 90 minutes after injection of [F-18]FAU. Thymidylate synthase activity was determined in vitro in tumors from untreated mice by [H-3] release from [H-3]dUMP. Each cell line was incubated in vitro with [H-3]-FAU or [H-3]-FMAU in the absence or presence of 5-fluoro-2'-deoxyuridine (FdUrd) and then was analyzed for incorporation of radiolabel into DNA. Results: Thymidylate synthase enzymatic activity in LS174T xenografts was similar to3.5-fold higher than in HT29 xenografts, and incorporation of radioactivity derived from [H-3]-FAU into LS174T DNA was similar to2-fold higher than into HT29 DNA. At 240 minutes, radioactivity derived from [H-3]-FAU was similar to2-fold higher in tumors than in skeletal muscle. At times up to 90 minutes, PET imaging detected only small differences in uptake of [F-18]-FAU between the tumor types. Fluorine-18 in skeletal muscle was higher than in tumor for the first 90 minutes and plateaued earlier, whereas [F-18] in tumor continued to increase during the 90-minute imaging period. For both cell lines in vitro, FdUrd decreased the rate of incorporation of [H-3]-FAU into DNA, whereas the incorporation of [H-3]-FMAU was increased. Conclusions: These results for FAU incorporation into DNA in vitro and in vivo further support clinical evaluation of FAU as a therapeutic agent in tumors with high concentrations of thymidylate synthase that are less likely to respond to 5-fluorouracil treatment. The high circulating concentrations of thymidine reported in mice may limit their utility in evaluating FAU as a PET probe. C1 Univ Pittsburgh, Inst Canc, Hillman Canc Ctr G27B, Mol Therapeut Drug Discovery Program, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Sch Med, Dept Pharmacol, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Dept Radiol, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Dept Med, Div Hematol Oncol, Pittsburgh, PA USA. US FDA, Lab Clin Pharmacol, Rockville, MD 20857 USA. RP Eiseman, JL (reprint author), Univ Pittsburgh, Inst Canc, Hillman Canc Ctr G27B, Mol Therapeut Drug Discovery Program, UPCI Res Pavil,5117 Ctr Ave, Pittsburgh, PA 15213 USA. EM eisemanj@msx.upmc.edu RI Mathis, Chester/A-8607-2009 FU NCI NIH HHS [2P30CA47904] NR 20 TC 11 Z9 11 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD OCT 1 PY 2004 VL 10 IS 19 BP 6669 EP 6676 DI 10.1158/1078-0432.CCR-03-0686 PG 8 WC Oncology SC Oncology GA 862WF UT WOS:000224521300032 PM 15475457 ER PT J AU Winter, HR Trapnell, CB Slattery, JT Jacobson, M Greenspan, DL Hooton, TM Unadkat, JA AF Winter, HR Trapnell, CB Slattery, JT Jacobson, M Greenspan, DL Hooton, TM Unadkat, JA TI The effect of clarithromycin, fluconazole, and rifabutin on sulfamethoxazole hydroxylamine formation in individuals with human immunodeficiency virus infection (AACTG 283) SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID PNEUMOCYSTIS-CARINII-PNEUMONIA; HUMAN-LIVER-MICROSOMES; SULFONAMIDE-REACTIVE METABOLITES; IN-VITRO; TRIMETHOPRIM-SULFAMETHOXAZOLE; DRUG-INTERACTIONS; ADVERSE REACTIONS; OXIDATIVE STRESS; HIV-INFECTION; TOXICITY AB Background: Sulfamethoxazole hydroxylamine formation, in combination with long-term oxidative stress, is thought to be the cause of high rates of adverse drug reactions to sulfamethoxazole in human immunodeficiency virus (HIV)-infected subjects. Therefore the goal of this study was to determine the effect of fluconazole, clarithromycin, and rifabutin on sulfamethoxazole hydroxylamine formation in individuals with HIV-1 infection. Methods. HIV-1-infected subjects (CD4(+) count greater than or equal to200 cells/mm(3)) were enrolled in a 2-part (A and B), open-label drug interaction study (Adult AIDS Clinical Trial Group [AACTG] 283). In part A (n = 9), subjects received cotrimoxazole (1 tablet of 800 mg sulfamethoxazole/160 mg trimethoprim daily) alone for 2 weeks and then, in a randomly assigned order, cotrimoxazole plus either fluconazole (200 mg daily), rifabutin (300 mg daily), or fluconazole plus rifabutin, each for a 2-week period. Part B (n = 12) was identical to part A except that clarithromycin (500 mg twice daily) was substituted for rifabutin. Results. In part A, fluconazole decreased the area under the plasma concentration-time curve (AUC), percent of dose excreted in 24-hour urine, and formation clearance (CLf) of the hydroxylamine by 37%, 53%, and 61%, respectively (paired t test, P <.05). Rifabutin increased the AUC, percent excreted, and CLf of the hydroxylamine by 55%, 45%, and 53%, respectively (P <.05). Fluconazole plus rifabutin decreased the AUC, percent excreted, and CLf of the hydroxylamine by 21%, 37%, and 46%, respectively (P <.05). In part B the fluconazole data were similar to those of part A. Overall, clarithromycin had no effect on hydroxylamine production. Conclusions. If the exposure (AUC) to sulfamethoxazole hydroxylamine is predictive of sulfamethoxazole toxicity, then rifabutin will increase and clarithromycin plus fluconazole or rifabutin plus fluconazole will decrease the rates of adverse reactions to sulfamethoxazole in HIV-infected subjects. C1 Univ Washington, Dept Pharmaceut, Seattle, WA 98195 USA. US FDA, Rockville, MD 20857 USA. Univ Calif San Francisco, Posit Hlth Program, San Francisco, CA USA. San Francisco Gen Hosp, Med Serv, San Francisco, CA 94110 USA. Meharry Med Coll, Nashville, TN 37208 USA. Vanderbilt Univ, Nashville, TN USA. RP Unadkat, JA (reprint author), Univ Washington, Dept Pharmaceut, H272 Hlth Sci,Box 357610, Seattle, WA 98195 USA. EM jash@u.washington.edu FU NCRR NIH HHS [M01RR00083]; NIAID NIH HHS [AI27664, AI46339]; PHS HHS [M0100095, M01003032] NR 33 TC 9 Z9 9 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD OCT PY 2004 VL 76 IS 4 BP 313 EP 322 DI 10.1016/j.clpt.2004.06.002 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 861MV UT WOS:000224421700004 PM 15470330 ER PT J AU Yamada, H Ishii, KJ Klinman, DM AF Yamada, H Ishii, KJ Klinman, DM TI Suppressive oligodeoxynucleotides inhibit CpG-induced inflammation of the mouse lung SO CRITICAL CARE MEDICINE LA English DT Article DE CpG motif; bacterial DNA; lung; tumor necrosis factor-alpha; macrophage inflammatory protein-2 ID INDUCED IMMUNE ACTIVATION; LOCALIZED BACTERIAL-DNA; NITRIC-OXIDE PRODUCTION; CUTTING EDGE; MOTIFS; MACROPHAGES; SEPSIS; OLIGONUCLEOTIDES; ARTHRITIS; SHOCK AB Objective: To examine the effect of suppressive oligodeoxynucleotides (ODNs) on the pulmonary inflammation induced by immunostimulatory CpG DNA. Design: Prospective, randomized, controlled study. Setting: Research laboratories. Subjects: RAW 264.7 murine macrophage-like cell line and BALB/c mice. Interventions: RAW 264.7 cells were incubated with bacterial DNA or CpG ODN, alone or combined with suppressive ODN. The in vivo effect of suppressive ODN was determined using an acute lung injury model. CpG ODN alone or combined with suppressive ODN was instilled into the mouse lung. Measurements and Main Results: Production of tumor necrosis factor (TNF)-alpha and macrophage inflammatory protein (MIP)-2 by RAW 264.7 cells were measured by enzyme-linked immunosorbent assay (ELISA), whereas their messenger RNA levels were determined by reverse transcriptase-polymerase chain reaction. Synthetic ODN containing CpG motifs (CpG ODN) mimicked the ability of bacterial DNA to stimulate the production of TNF-alpha and MIP-2. Suppressive ODN significantly inhibited the activation of RAW 264.7 cells by both bacterial DNA and CpG ODN. In the lung injury model, production of proinflammatory cytokines (TNF-alpha and IL-6) and chemokines (MIP-2 and KC) in bronchoalveolar lavage (BAL) fluids was measured by ELISA. Neutrophil accumulation in the alveolar spaces was also evaluated. Instillation of CpG ODN into the lungs of normal mice triggered the synthesis of TNF-alpha, IL-6, MIP-2, and KC. Suppressive ODN significantly blocked the production of these proinflammatory cytokines and chemokines and also reduced neutrophil mobilization into the alveolar spaces by CpG DNA. Conclusions. Proinflammatory cytokines and chemokines are up-regulated by CpG motifs in bacterial DNA. Suppressive ODN significantly inhibits the inflammatory response induced by CpG DNA in murine macrophages and the lung. This study supports the use of suppressive ODN to reduce the deleterious inflammatory responses induced by bacterial DNA. C1 Yokohama City Univ, Sch Med, Dept Anesthesiol, Kanazawa Ku, Yokohama, Kanagawa 2360004, Japan. Osaka Univ, Akira Innate Immun Project, ERATO,Res Inst Microbial Dis, Japan Sci & Technol Agcy,Dept Host Def, Osaka, Japan. US FDA, Sect Retroviral Immunol, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. RP Yamada, H (reprint author), Yokohama City Univ, Sch Med, Dept Anesthesiol, Kanazawa Ku, 3-9 Fukuura, Yokohama, Kanagawa 2360004, Japan. EM hyamada@bb.mbn.or.jp RI Ishii, Ken/B-1685-2012 OI Ishii, Ken/0000-0002-6728-3872 NR 30 TC 18 Z9 21 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD OCT PY 2004 VL 32 IS 10 BP 2045 EP 2049 DI 10.1097/01.CCM.0000142397.38134.EF PG 5 WC Critical Care Medicine SC General & Internal Medicine GA 865HH UT WOS:000224692800010 PM 15483413 ER PT J AU Tsai, CA Chen, CH Lee, TC Ho, IC Yang, UC Chen, JJ AF Tsai, CA Chen, CH Lee, TC Ho, IC Yang, UC Chen, JJ TI Gene selection for sample classifications in microarray experiments SO DNA AND CELL BIOLOGY LA English DT Article; Proceedings Paper CT 1st Annual MidSouth-Computational-Biology-and-Bioinformatics-Society Conference (MCBIOS) CY NOV 13-15, 2003 CL Univ Arkansas, Little Rock, AR HO Univ Arkansas ID EXPRESSION DATA; PATTERNS; CANCER; TUMOR; DISCRIMINATION; PROFILES AB DNA microarray technology provides useful tools for profiling global gene expression patterns in different cell/tissue samples. One major challenge is the large number of genes relative to the number of samples. The use of all genes can suppress or reduce the performance of a classification rule due to the noise of nondiscriminatory genes. Selection of an optimal subset from the original gene set becomes an important prestep in sample classification. In this study, we propose a family-wise error (FWE) rate approach to selection of discriminatory genes for two-sample or multiple-sample classification. The FWE approach controls the probability of the number of one or more false positives at a prespecified level. A public colon cancer data set is used to evaluate the performance of the proposed approach for the two classification methods: k nearest neighbors (k-NN) and support vector machine (SVM). The selected gene sets from the proposed procedure appears to perform better than or comparable to several results reported in the literature using the univariate analysis without performing multivariate search. In addition, we apply the FWE approach to a toxicogenomic data set with nine treatments (a control and eight metals, As, Cd, Ni, Cr, Sb, Pb, Cu, and AsV) for a total of 55 samples for a multisample classification. Two gene sets are considered: the gene set Omega(F) formed by the ANOVA F-test, and a gene set Omega(T) formed by the union of one-versus-all t-tests. The predicted accuracies are evaluated using the internal and external crossvalidation. Using the SVM classification, the overall accuracies to predict 55 samples into one of the nine treatments are above 80% for internal crossvalidation. Omega(F) has slightly higher accuracy rates than Omega(T). The overall predicted accuracies are above 70% for the external crossvalidation; the two gene sets Omega(T) and delta(F) performed equally well. C1 Natl Ctr Toxicol Res, FDA, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. Acad Sinica, Inst Stat Sci, Taipei 115, Taiwan. Acad Sinica, Dept Biomed Sci, Taipei 115, Taiwan. Natl Yang Ming Univ, Inst Biopharmaceut Sci, Taipei 112, Taiwan. Natl Yang Ming Univ, Inst Biochem, Taipei 112, Taiwan. RP Chen, JJ (reprint author), Natl Ctr Toxicol Res, FDA, Div Biometry & Risk Assessment, HFT-20, Jefferson, AR 72079 USA. EM jchen@nctr.fda.gov RI Lee, TC/B-3245-2011 NR 21 TC 18 Z9 20 U1 0 U2 1 PU MARY ANN LIEBERT INC PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1044-5498 J9 DNA CELL BIOL JI DNA Cell Biol. PD OCT PY 2004 VL 23 IS 10 BP 607 EP 614 DI 10.1089/1044549042476947 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity GA 870DM UT WOS:000225034200002 PM 15585118 ER PT J AU Delongchamp, RR Velasco, C Razzaghi, M Harris, A Casciano, D AF Delongchamp, RR Velasco, C Razzaghi, M Harris, A Casciano, D TI Median-of-subsets normalization of intensities for cDNA array data SO DNA AND CELL BIOLOGY LA English DT Article; Proceedings Paper CT 1st Annual MidSouth-Computational-Biology-and-Bioinformatics-Society Conference (MCBIOS) CY NOV 13-15, 2003 CL Univ Arkansas, Little Rock, AR HO Univ Arkansas ID MICROARRAY DATA; EXPRESSION DATA; GENE; TOXICOLOGY; VARIANCE AB cDNA arrays allow quantitative measurement of expression levels for thousands of genes simultaneously. The measurements are affected by many sources of variation, and substantial improvements in the precision of estimated effects accompany adjustments for these effects. Two generic nuisance variations, one associated with the magnitude of expression and the other associated with array location, are common in data from filter arrays. Procedures, like normalization using lowess regression, are effective at reducing variation associated with magnitude, and they have been widely adopted. However, variation associated with location has received less attention. Here, a simple, but effective method based on localized median is expounded for dealing with these nuisance effects, and its properties are discussed. The proposed methodology handles location-dependent variation ("splotches") and magnitude-dependent variation (background and/or saturation) effectively. The procedure is related to lowess when implemented to adjust magnitude-dependent variation, and it performs similarly. The proposed methodology is illustrated with data from the National Center for Toxicological Research (NCTR), where treatment differences in levels of mRNA from rat hepatocytes were assessed using P-33-labeled samples hybridized to cDNA spotted arrays. Normalizing intensities by the median-of-subsets removes systematic variation associated with the location of a gene on the array and/or the level of its expression. This procedure is easy to implement using iteratively reweighted least-squares algorithms. Although less sophisticated than lowess, this procedure works nearly as well for normalizing intensities based upon their magnitude. Unlike lowess, it can adjust for location-dependent effects. C1 Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Louisiana State Univ, Hlth Sci Ctr, New Orleans, LA USA. Bloomsburg Univ Penn, Bloomsburg, PA 17815 USA. RP Delongchamp, RR (reprint author), 3900 NCTR Rd, Jefferson, AR 72079 USA. EM rdelongchamp@nctr.fda.gov NR 24 TC 4 Z9 5 U1 0 U2 2 PU MARY ANN LIEBERT INC PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1044-5498 J9 DNA CELL BIOL JI DNA Cell Biol. PD OCT PY 2004 VL 23 IS 10 BP 653 EP 659 DI 10.1089/1044549042476820 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity GA 870DM UT WOS:000225034200007 PM 15585123 ER PT J AU Fang, H Tong, WD Shi, LM Jakab, RL Bowyer, JF AF Fang, H Tong, WD Shi, LM Jakab, RL Bowyer, JF TI Classification of cDNA array genes that have a highly significant discriminative power due to their unique distribution in four brain regions SO DNA AND CELL BIOLOGY LA English DT Article; Proceedings Paper CT 1st Annual MidSouth-Computational-Biology-and-Bioinformatics-Society Conference (MCBIOS) CY NOV 13-15, 2003 CL Univ Arkansas, Little Rock, AR HO Univ Arkansas ID RAT-BRAIN; PARKINSONS-DISEASE; CHOLESTEROL ACYLTRANSFERASE; METHAMPHETAMINE ABUSERS; BASAL GANGLIA; BREAST-CANCER; EXPRESSION; RECEPTOR; NEURONS; MICE AB Novel statistical methods were used to distinguish functionally distinct brain regions using their cDNA array gene expression profiles, and it was found that one of four specific factors is often associated with the most regionally discriminative genes. The gene expression profiles for the substantia nigra (SN), striatum (STR), parietal cortex (PC), and posterolateral cortical amygdaloid nucleus (PLCo) brain regions were determined from each brain region. An F-test identified 339 genes of the 1185 array genes as having a P less than or equal to 0.01 and applied a gene ranking and selection method based on Soft Independent Modeling of Class Analogy (SIMCA) to obtain 59 of the most discriminative genes. Their discriminative power was validated in three steps. The most convincing step showed their ability to correctly predict the brain regional classifications for 18 "test" gene expression sets obtained from the four regions. A two-way Hierarchical Cluster Analysis organized the 59 genes in six clusters according to their expression differences in the brain regions. Expression patterns in the SN and STR regions greatly differed from each other and the PC and PLCo. The closer similarity in the gene expression patterns of the PC and PLCo was probably due to their functional similarity. The important factors in determining differences in the regional gene expression profiles in six clusters were (1) regional myelin/oligodendrocyte levels, (2) resident neuron types, (3) neurotransmitter innervation profiles, and (4) Ca++-dependent signaling and second messenger systems. C1 Natl Ctr Toxicol Res, Div Neurotoxicol, FDA, Jefferson, AR 72079 USA. Natl Ctr Toxicol Res, Ctr Toxicoinformat, Div Biometry & Risk Assessment, FDA, Jefferson, AR 72079 USA. RP Bowyer, JF (reprint author), Natl Ctr Toxicol Res, Div Neurotoxicol, FDA, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM jbowyer@nctr.fda.gov NR 64 TC 4 Z9 4 U1 1 U2 2 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1044-5498 EI 1557-7430 J9 DNA CELL BIOL JI DNA Cell Biol. PD OCT PY 2004 VL 23 IS 10 BP 661 EP 674 DI 10.1089/1044549042476875 PG 14 WC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity GA 870DM UT WOS:000225034200008 PM 15585124 ER PT J AU Hong, HX Tong, WD Perkins, R Fang, H Xie, Q Shi, LM AF Hong, HX Tong, WD Perkins, R Fang, H Xie, Q Shi, LM TI Multiclass decision forest - A novel pattern recognition method for multiclass classification in microarray data analysis SO DNA AND CELL BIOLOGY LA English DT Article; Proceedings Paper CT 1st Annual MidSouth-Computational-Biology-and-Bioinformatics-Society Conference (MCBIOS) CY NOV 13-15, 2003 CL Univ Arkansas, Little Rock, AR HO Univ Arkansas ID GENE-EXPRESSION DATA; BREAST-CANCER CELLS; MICROVESSEL DENSITY; PROSTATE-CANCER; MOLECULAR CLASSIFICATION; TUMOR CLASSIFICATION; CLASS PREDICTION; VEGF EXPRESSION; LNCAP CELLS; APOPTOSIS AB The wealth of knowledge imbedded in gene expression data from DNA microarrays portends rapid advances in both research and clinic. Turning the prodigious and noisy data into knowledge is a challenge to the field of bioinformatics, and development of classifiers using supervised learning techniques is the primary methodological approach for clinical application using gene expression data. In this paper, we present a novel classification method, multiclass Decision Forest (DF), that is the direct extension of the two-class DF previously developed in our lab. Central to DF is the synergistic combining of multiple heterogenic but comparable decision trees to reach a more accurate and robust classification model. The computationally inexpensive multiclass DF algorithm integrates gene selection and model development, and thus eliminates the bias of gene preselection in crossvalidation. Importantly, the method provides several statistical means for assessment of prediction accuracy, prediction confidence, and diagnostic capability. We demonstrate the method by application to gene expression data for 83 small round blue-cell tumors (SRBCTs) samples belonging to one of four different classes. Based on 500 runs of 10-fold crossvalidation, tumor prediction accuracy was -97%, sensitivity was -95%, diagnostic sensitivity was -91%, and diagnostic accuracy was -99.5%. Among 25 genes selected to distinguish tumor class, 12 have functional information in the literature implicating their involvement in cancer. The four types of SRBCTs samples are also distinguishable in a clustering analysis based on the expression profiles of these 25 genes. The results demonstrated that the multiclass DF is an effective classification method for analysis of gene expression data for the purpose of molecular diagnostics. C1 Natl Ctr Toxicol Res, Ctr Toxicoinformat, Div Biometry & Risk Assessment, FDA, Jefferson, AR 72079 USA. Natl Ctr Toxicol Res, Bioinformat Lab, FDA, Jefferson, AR 72079 USA. RP Tong, WD (reprint author), Natl Ctr Toxicol Res, Ctr Toxicoinformat, Div Biometry & Risk Assessment, FDA, Jefferson, AR 72079 USA. EM wtong@nctr.fda.gov NR 56 TC 20 Z9 20 U1 0 U2 0 PU MARY ANN LIEBERT INC PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1044-5498 J9 DNA CELL BIOL JI DNA Cell Biol. PD OCT PY 2004 VL 23 IS 10 BP 685 EP 694 DI 10.1089/1044549042476839 PG 10 WC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity GA 870DM UT WOS:000225034200010 PM 15585126 ER PT J AU Lesko, LJ AF Lesko, LJ TI Translating genomics into good safety science SO EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Meeting Abstract CT 8th European Congress of Pharmaceutical Sciences CY OCT 17-20, 2004 CL Brussels, BELGIUM ID REGULATORY DECISION-MAKING; DRUG DEVELOPMENT; PHARMACOGENOMICS C1 US FDA, Ctr Drug Evaluat & Res, Off Clin Pharmacol & Biopharmaceut, Rockville, MD 20857 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0928-0987 J9 EUR J PHARM SCI JI Eur. J. Pharm. Sci. PD OCT PY 2004 VL 23 SU 1 BP S4 EP S5 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 861OP UT WOS:000224426800008 ER PT J AU Liu, G Zhai, QZ Schaffner, D Popova, T Hayford, A Bailey, C Alibek, K AF Liu, G Zhai, QZ Schaffner, D Popova, T Hayford, A Bailey, C Alibek, K TI Bacillus alcalophilus peptidoglycan induces IFN-alpha-mediated inhibition of vaccinia virus replication SO FEMS IMMUNOLOGY AND MEDICAL MICROBIOLOGY LA English DT Article DE peptidoglycan; lipoteichoic acids; IFN-alpha; NO; macrophages; poxviruses ID MOUSE PERITONEAL-MACROPHAGES; GRAM-POSITIVE BACTERIA; HERPES-SIMPLEX VIRUS; CELL WALL COMPONENTS; NITRIC-OXIDE; INTERFERON-PRODUCTION; INFECTIOUS-DISEASES; MURAMYL PEPTIDES; VIRAL-INFECTION; IMMUNE-RESPONSE AB Bacterial products such as cell walls (CW) and peptidoglycan (PGN) are known to activate macrophages and NK cells during microbial infections. In this report, we demonstrated that whole CW and PGN of four Gram-positive bacteria are capable of enhancing the anti-poxviral activity of murine macrophage RAW 264.7 cells. Among the major Bacillus alcalophilus CW components, PGN contributes the most to antiviral activity and induces remarkably higher levels of IFN-alpha. Anti-IFN-alpha/beta antibody, but not anti-IFN-gamma, anti-IFN-gamma receptor, or anti-IL-12, reversed the PGN-induced inhibition of vaccinia virus replication and reduced nitric oxide (NO) production. Our data thus suggest that PGN induce antiviral activity through IFN-alpha and to a lesser extent, through NO production. (C) 2004 Federation of European Microbiological Societies. Published by Elsevier B.V. All rights reserved. C1 George Mason Univ, Adv Biosys Inc, Manassas, VA 20110 USA. US FDA, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. George Mason Univ, Ctr Biodef, Manassas, VA 20110 USA. RP Liu, G (reprint author), George Mason Univ, Adv Biosys Inc, 10900 Univ Blvd,MSN 1A8, Manassas, VA 20110 USA. EM ge.liu@analex.com NR 49 TC 1 Z9 2 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0928-8244 J9 FEMS IMMUNOL MED MIC JI FEMS Immunol. Med. Microbiol. PD OCT 1 PY 2004 VL 42 IS 2 BP 197 EP 204 DI 10.1016/j.femsim.2004.002 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 859IO UT WOS:000224256800007 PM 15364104 ER PT J AU Delogu, G Bua, A Pusceddu, C Parra, M Fadda, G Brennan, MJ Zanetti, S AF Delogu, G Bua, A Pusceddu, C Parra, M Fadda, G Brennan, MJ Zanetti, S TI Expression and purification of recombinant methylated HBHA in Mycobacterium smegmatis SO FEMS MICROBIOLOGY LETTERS LA English DT Article DE mycobacteria; HBHA; tuberculosis; mycobacterium; vaccine; protein expression; methylation ID HEPARIN-BINDING HEMAGGLUTININ; TUBERCULOSIS; PROTEINS; BIOLOGY; ADHESIN AB The Heparin-Binding Haemagglutinin (HBHA) is a mycobacterial adhesin involved in the dissemination of Mycobacterium tuberculosis from the site of primary infection and a potential candidate for the development of a new vaccine against tuberculosis. Methylation of HBHA is a novel post-translational event that imparts important immunological properties to the protein. Since recombinant HBHA expressed in Escherichia coli is not methylated, we investigated the possibility of producing recombinant methylated HBHA in fast growing mycobacteria for use in immunological and biochemical studies. The complete coding sequence of HBHA was cloned in the plasmid pMV206, under the control of a strong promoter (hsp60) or its own promoter. The constructs generated were electroporated into Mycobacterium smegmatis and the recombinant strains obtained were analyzed for the presence of the HBHA protein using the anti-HBHA monoclonal antibodies D2 and E4. Our results indicate that expression of high amounts of intact protein can be toxic for the mycobacteria, that methylated HBHA can be obtained in M. smegmatis only when using a promoter sequence weaker than hsp60 and that the expression of the complete structural gene is required in order to obtain methylated HBHA. We constructed a recombinant M. smegmatis strain (pMV3-38) that expresses a histidine-tagged methylated HBHA that can be easily purified. The use of fast-growing strains of M. smegmatis to obtain significant amounts of purified HBHA protein within a short timeframe, should be an effective strategy for the evaluation of a new HBHA-based vaccine candidate for tuberculosis. (C) 2004 Federation of European Microbiological Societies. Published by Elsevier B.V. All rights reserved. C1 Univ Sassari, Dept Biomed Sci, I-07100 Sassari, Italy. Catholic Univ, Inst Microbiol, Rome, Italy. US FDA, Lab Mycobacteriol Dis & Cellular Immunol, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. RP Delogu, G (reprint author), Univ Cattolica Sacro Cuore, Ist Microbiol, Lgo F Vito 1, I-00168 Rome, Italy. EM gdelogu@rm.unicatt.it RI Delogu, Giovanni/I-3701-2012; Fadda, Giovanni/K-6224-2012 OI Delogu, Giovanni/0000-0003-0182-8267; NR 24 TC 37 Z9 39 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1097 J9 FEMS MICROBIOL LETT JI FEMS Microbiol. Lett. PD OCT 1 PY 2004 VL 239 IS 1 BP 33 EP 39 DI 10.1016/j.femsle.2004.08.015 PG 7 WC Microbiology SC Microbiology GA 860CS UT WOS:000224317000005 PM 15451098 ER PT J AU de Jager, LS Perfetti, GA Diachenko, GW AF de Jager, LS Perfetti, GA Diachenko, GW TI LC-UV and LGMS analysis of food and drink products containing kava SO FOOD ADDITIVES AND CONTAMINANTS LA English DT Article DE kava; Piper methysticum; kava lactones; LC-MS; food analysis ID PERFORMANCE LIQUID-CHROMATOGRAPHY; PIPER-METHYSTICUM FORST.; KAVALACTONES; LACTONES AB A method for the determination of six kava lactones, methysticin, dihydromethysticin, kawain, dihydrokawain, yangonin and desmethoxyyangonin, in solid foods and beverages has been developed. Solid samples were prepared using methanol extraction, while beverages were extracted using a separate solid phase extraction (SPE) method. After sample preparation, the extracts were analysed using LC-UV or atmospheric pressure photoionization (APPI) LC-MS in the positive mode. Using the method, 10 beverage products, two chocolate products, three unbrewed tea products, three dietary supplements and a drink mix product were analysed. The results obtained using the LC-UV were comparable to those obtained using APPI-LC-MS for most products. Using the SPE method in conjunction with LC-MS, individual kava lactones were detected in drink products at ppb concentrations. Concentrations of total kava lactones ranged between 135-0.035 mg per serving in the food and beverage products tested and between 40-61 mg per serving for the dietary supplement products tested. Results of these analyses as well as extraction efficiency and reproducibility data are reported. C1 US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP de Jager, LS (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM ldejager@cfsan.fda.gov NR 11 TC 6 Z9 6 U1 0 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 OCT PY 2004 VL 21 IS 10 BP 921 EP 934 DI 10.1080/02652030400010454 PG 14 WC Chemistry, Applied; Food Science & Technology; Toxicology SC Chemistry; Food Science & Technology; Toxicology GA 877JI UT WOS:000225564300001 PM 15712517 ER PT J AU Begley, TH Biles, JE Cunningham, C Piringer, O AF Begley, TH Biles, JE Cunningham, C Piringer, O TI Migration of a UV stabilizer from polyethylene terephthalate (PET) into food simulants SO FOOD ADDITIVES AND CONTAMINANTS LA English DT Article DE migration; UV stabilizers; polyethylene terephthalate; diffusion; food simulants; food packaging ID MICROWAVE; PLASTICS; BOTTLES; COOKING; ACID AB The migration characteristics of the UV stabilizer Tinuvin 234 (2-(2H-benzotriazol-2-yl)-4,6-bis (1-methyl-1-phenylethyl)phenol) into food simulants has been measured from polyethylene terephthalate (PET) using HPLC with UV detection. Ethanol/water, isooctane and a fractionated coconut oil simulant (Miglyol(R) were used as food simulating solvents. The migration characteristics were measured at temperatures in the range of 40-70degreesC. Diffusion coefficients were determined to be in the range of 1 X 10(-14) cm(2) s(-1) to 1 x 10(-18) cm(2) s(-1). At 40degreesC, the amount of migration into 95% ethanol after 10 (lays was 2 mug dm(-2). Isooctane is determined to be a good fatty food simulant that provides similar results for PET to those of fatty foods. C1 US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. Fabes GmbH, D-80992 Munich, Germany. RP Begley, TH (reprint author), US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. EM timothy.begley@cfsan.fda.gov NR 12 TC 13 Z9 16 U1 5 U2 26 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0265-203X J9 FOOD ADDIT CONTAM JI Food Addit. Contam. PD OCT PY 2004 VL 21 IS 10 BP 1007 EP 1014 DI 10.1080/02652030400010447 PG 8 WC Chemistry, Applied; Food Science & Technology; Toxicology SC Chemistry; Food Science & Technology; Toxicology GA 877JI UT WOS:000225564300009 PM 15712525 ER PT J AU Kraeling, MEK Yourick, JJ Bronaugh, RL AF Kraeling, MEK Yourick, JJ Bronaugh, RL TI In vitro human skin penetration of diethanolamine SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article DE diethanolamine (DEA); percutaneous absorption; percutaneous penetration; human skin ID INVITRO PERCUTANEOUS-ABSORPTION; METABOLISM AB Concerns about the safety of diethanolamine (DEA) have been raised by the National Toxicology Program (NTP). Therefore, we measured the extent of DEA absorption in human skin relevant to exposures from shampoos, hair dyes and body lotions. Radiolabeled [C-14]-DEA was added to two commercial products from each class and applied to excised viable and non-viable human skin in flow-through diffusion cells. The products remained on the skin for 5, 30 and 24 h for shampoos, hair dyes and body lotions, respectively. After 24 h, most of the absorbed dose was found in skin: 2.8% for shampoos, 2.9% for hair dyes and 10.0% for body lotions. Only small amounts were absorbed into the receptor fluid: 0.08%, 0.09% and 0.9% for shampoos, hair dyes and body lotions respectively. There was no significant difference in the absorption of DEA through viable and non-viable skin or from product application doses of 1, 2 or 3 mg lotion/cm(2). In 72 h daily repeat dose studies with a lotion, DEA appeared to accumulate in the skin (29.2%) with little diffusing out into the receptor fluid. Therefore, skin levels of DEA should not be included in estimates of systemic absorption used in exposure assessments. Published by Elsevier Ltd. C1 US FDA, Off Cosmet & Colors, Laurel, MD 20708 USA. RP Kraeling, MEK (reprint author), US FDA, Off Cosmet & Colors, BRF HFS-128,8301 Muirkirk Rd, Laurel, MD 20708 USA. EM margaret.kraeling@cfsan.fda.gov NR 23 TC 14 Z9 15 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0278-6915 J9 FOOD CHEM TOXICOL JI Food Chem. Toxicol. PD OCT PY 2004 VL 42 IS 10 BP 1553 EP 1561 DI 10.1016/j.fct.2004.047.016 PG 9 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA 850WA UT WOS:000223643900002 PM 15304302 ER PT J AU Wilson, W de Villena, FPM Lyn-Cook, BD Chatterjee, PK Bell, TA Detwiler, DA Gilmore, RC Valladeras, IC Wright, CC Threadgill, DW Grant, DJ AF Wilson, W de Villena, FPM Lyn-Cook, BD Chatterjee, PK Bell, TA Detwiler, DA Gilmore, RC Valladeras, IC Wright, CC Threadgill, DW Grant, DJ TI Characterization of a common deletion polymorphism of the UGT2B17 gene linked to UGT2B15 SO GENOMICS LA English DT Article DE UDP glucuronosyltransferase; gene deletion; polymorphisms (genetics); duplicate genes; genetic variation; genetic diversity ID HUMAN UDP-GLUCURONOSYLTRANSFERASES; PROSTATE-CANCER; 2B15 GENE; RISK; GLUCURONIDATION; ENZYME; CHIMPANZEES; SPECIFICITY; SEQUENCES; HUMANS AB Members of the human UDP-glueuronosyltransferase 213 family are located in a cluster on chromosome 4q13 and code for enzymes whose gene products are responsible for the normal catabolism of steroid hormones. Two members of this family, UGT2B15 and UGT2B17, share over 95% sequence identity. However, UGT2B17 exhibits broader substrate specificity due to a single amino acid difference. Using gene-specific primers to explore the genomic organization of these two genes, it was determined that UGT2B17 is absent in some human DNA samples. The gene-specific primers demonstrated the presence or absence of a 150 kb genomic interval spanning the entire UGT2B17 gene, revealing that UGT2B17 is present in the human genome as a deletion polymorphism linked to UGT2B15. Furthermore, it is shown that the UGT2B17 deletion polymorphism shows Mendelian segregation and allele frequencies that differ between African Americans and Caucasians. (C) 2004 Elsevier Inc. All rights reserved. C1 N Carolina Cent Univ, JLC Biomed Biotechnol Res Inst, Canc Res Program, Durham, NC 27707 USA. Univ N Carolina, Dept Genet, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. Univ N Carolina, Carolina Ctr Genome Sci, Chapel Hill, NC 27599 USA. Natl Ctr Toxicol Res, Div Mol Epidemiol, Jefferson, AR USA. N Carolina Cent Univ, JLC Biomed & Biotechnol Res Inst, Genom Res Program, Durham, NC 27707 USA. RP Grant, DJ (reprint author), N Carolina Cent Univ, JLC Biomed Biotechnol Res Inst, Canc Res Program, 1801 Fayetteville St, Durham, NC 27707 USA. EM dgrant@wpo.nccu.edu RI Threadgill, David/N-4425-2013 OI Threadgill, David/0000-0003-3538-1635 FU NCI NIH HHS [CA992077-02, CA92075-02]; NIGMS NIH HHS [S06 GM008049, S06-GM08049] NR 29 TC 95 Z9 97 U1 0 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD OCT PY 2004 VL 84 IS 4 BP 707 EP 714 DI 10.1016/j.ygeno.2004.06.011 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 857BU UT WOS:000224091200010 PM 15475248 ER PT J AU Favaloro, EJ Lillicrap, D Lazzari, MA Cattaneo, M Mazurier, C Woods, A Meschengieser, S Blanco, A Kempfer, AC Hubbard, A Chang, A AF Favaloro, EJ Lillicrap, D Lazzari, MA Cattaneo, M Mazurier, C Woods, A Meschengieser, S Blanco, A Kempfer, AC Hubbard, A Chang, A TI von Willebrand disease: laboratory aspects of diagnosis and treatment SO HAEMOPHILIA LA English DT Article; Proceedings Paper CT 26th International Congress of the World-Federation-of-Hemophilia CY OCT 17-21, 2004 CL Bangkok, THAILAND SP World Federat Hemophilia DE factor concentrate; diagnosis; treatment; von Willebrand disease; von Willebrand factor ID FACTOR COLLAGEN-BINDING; IN-VITRO; PREVALENCE; TYPE-1 AB von Willebrand disease is the most common inherited bleeding disorder in humans. VWD can be classified into three major types, designated Types 1, 2 and 3; Type 2 can be further separated into subtypes 2A, 2B, 2M and 2N. The diagnosis of VWD requires a personal and family history of bleeding and confirmation by laboratory analysis. Although Types 2 and 3 are relatively straightforward to diagnose, there may be a risk of over-diagnosis of Type 1 because of an overlap within the normal range. We also report on the clinical profile and diagnosis of VWD in a South American cohort of patients and on the in vitro characteristics of some factor concentrates available for treatment of VWD. C1 Queens Univ, Richardson Lab, Dept Pathol & Lab Med, Kingston, ON, Canada. Univ Milan, Osped San Paolo, Hematol Unit, Milan, Italy. US FDA, Ctr Biol Evaluat & Res, Rockville, MD USA. RP Favaloro, EJ (reprint author), Westmead Hosp, ICPMR, Westmead, NSW 2145, Australia. EM emmanuel@icpmr.wsahs.nsw.gov.au RI Hubbard, Anthony/E-2605-2013; OI Cattaneo, Marco/0000-0002-7343-4534; Woods, Adriana/0000-0002-4077-1796 NR 16 TC 23 Z9 24 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 1351-8216 J9 HAEMOPHILIA JI Haemophilia PD OCT PY 2004 VL 10 SU 4 BP 164 EP 168 DI 10.1111/j.1365-2516.2004.00979.x PG 5 WC Hematology SC Hematology GA 885FV UT WOS:000226143400029 PM 15479392 ER PT J AU Manigold, T Piccirillo, CA Shin, EC Mihalik, K Rice, CM Rehermann, B AF Manigold, T Piccirillo, CA Shin, EC Mihalik, K Rice, CM Rehermann, B TI CD4+CD25+T cells regulate hepatitis C virus-specific T cell memory SO HEPATOLOGY LA English DT Meeting Abstract CT 55th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY OCT 29-NOV 02, 2004 CL Boston, MA SP Amer Assoc Study Liver Dis C1 NIDDK, NIH, Bethesda, MD USA. NIAID, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. Rockefeller Univ, New York, NY 10021 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2004 VL 40 IS 4 SU 1 BP 198A EP 198A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 857FR UT WOS:000224102100083 ER PT J AU Fleischer, R Truffa, M AF Fleischer, R Truffa, M TI Permanent hearing loss in patients treated with standard and pegylated forms of interferon: A review of the FDA's Adverse Event Reporting System (AERS). SO HEPATOLOGY LA English DT Meeting Abstract CT 55th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY OCT 29-NOV 02, 2004 CL Boston, MA SP Amer Assoc Study Liver Dis C1 US FDA, Rockville, MD 20857 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 2004 VL 40 IS 4 SU 1 BP 320A EP 320A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 857FR UT WOS:000224102100363 ER PT J AU Galson, S AF Galson, S TI Acetaminophen hepatotoxicity - Reply SO HEPATOLOGY LA English DT Letter C1 US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Galson, S (reprint author), US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. NR 4 TC 1 Z9 1 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2004 VL 40 IS 4 BP 1022 EP 1022 DI 10.1002/hep.20461 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 857AX UT WOS:000224088800032 ER PT J AU He, P Varticovski, L Bowman, ED Fukuoka, J Welsh, JA Miura, K Jen, J Gabrielson, E Brambilla, E Travis, WD Harris, CC AF He, P Varticovski, L Bowman, ED Fukuoka, J Welsh, JA Miura, K Jen, J Gabrielson, E Brambilla, E Travis, WD Harris, CC TI Identification of carboxypeptidase E and gamma-glutamyl hydrolase as biomarkers for pulmonary neuroendocrine tumors by cDNA microarray SO HUMAN PATHOLOGY LA English DT Article DE atypical carcinoid; biomarkers; carboxypeptidase E; gamma-glutamyl hydrolase; gene pulmonary neuroendocrine tumors ID LASER CAPTURE MICRODISSECTION; GENE-EXPRESSION PROFILES; CELL LUNG-CANCER; FOLYLPOLYGLUTAMATE SYNTHETASE; DNA MICROARRAY; CARCINOMAS; PATTERNS; ADENOCARCINOMA; POLYGLUTAMYLATION; CLASSIFICATION AB Pulmonary neuroendocrine tumors vary dramatically in their malignant behavior. Their classification, based on histological examination, is often difficult. In search of molecular and prognostic markers for these tumors, we used cDNA microarray analysis of human transcripts against reference RNA from a well-characterized immortalized bronchial epithelial cell line, BEAS-2B. Tumor cells were isolated by laser-capture microdissection from primary tumors of 17 typical carcinoids, small cell lung cancers, and large cell neuroendocrine carcinomas. An unsupervised, hierarchical clustering algorithm resulted in a precise classification of each tumor subtype according to the proposed histological classification. Selection of genes, using supervised analysis, resulted in the identification of 198 statistically significant genes (P <.004) that also accurately discriminated between 3 predefined tumor subtypes. Two-by-two comparisons of these genes identified classifier genes that distinguished each tumor subtype from the others. Changes in expression of selected differentially expressed genes for each tumor subtype were internally validated by real-time reverse-transcription polymerase chain reaction. Expression of 2 potential classifier gene products, carboxypeptidase E (CPE) and gamma-glutamyl hydrolase (GGH), was validated by immunohistochemistry and cross-validated on additional archival samples of pulmonary neuroendocrine tumors. Kaplan-Meier survival analysis revealed that immunostaining for CPE was a statistically significant predictor of good prognosis, whereas GGH expression correlated with poor prognosis. Thus, cDNA microarray analysis led to the identification of 2 novel biomarkers that should facilitate molecular diagnosis and further study of pulmonary neuroendocrine tumors. (C) 2004 Elsevier Inc. All rights reserved. C1 NCI, Human Carcinogenesis Lab, Natl Inst Hlth, Bethesda, MD 20892 USA. Armed Forces Inst Pathol, Dept Pulm & Mediastinal Pathol, Washington, DC 20306 USA. US FDA, Ctr Biol Evaluat & Res, Div Hematol, Bethesda, MD 20014 USA. Tohoku Univ, Postgrad Med Sch, Dept Surg, Sendai, Miyagi 980, Japan. NCI, Lab Populat Genet, Natl Inst Hlth, Bethesda, MD 20892 USA. Johns Hopkins Univ, Dept Pathol, Baltimore, MD USA. Lab Cellular Pathol, Grenoble, France. RP Harris, CC (reprint author), NCI, Human Carcinogenesis Lab, Natl Inst Hlth, 37 Convent Dr,Bldg 37,Rm 3068, Bethesda, MD 20892 USA. RI Brambilla, Elisabeth/L-8796-2013; OI Miura, Koh/0000-0001-7303-9430 NR 34 TC 46 Z9 49 U1 0 U2 4 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD OCT PY 2004 VL 35 IS 10 BP 1196 EP 1209 DI 10.1016/j.humpath.2004.06.014 PG 14 WC Pathology SC Pathology GA 864AJ UT WOS:000224604700005 PM 15492986 ER PT J AU Benjamin, DK Hirschfeld, S Cunningham, CK McKinney, RE AF Benjamin, DK Hirschfeld, S Cunningham, CK McKinney, RE TI Growth as a part of the composite endpoint in paediatric antiretroviral clinical trials SO JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY LA English DT Article DE height; weight; velocity; children; HIV ID IMMUNODEFICIENCY-VIRUS INFECTION; CHILDREN; ZIDOVUDINE; HIV AB Paediatric HIV is a rapidly emerging disease in many resource-poor countries. Survival into adulthood is possible for HIV-infected children provided that they receive effective antiretroviral therapy (ART). Large trials comparing multiple regimens of ART in children of resource-poor countries have not been completed. Design of those trials will need to incorporate both lessons learned from trials completed in developed countries as well as unique aspects of the developing countries in which they are conducted. Trial design will necessarily include close attention to the endpoint, and in children, special consideration will need to be given to growth as a component of the endpoint-whether or not growth should be a component of the composite endpoint, and if so, how. C1 Duke Univ, Duke Clin Res Inst, Durham, NC 27715 USA. Duke Univ, Dept Pediat, Durham, NC 27706 USA. US FDA, Washington, DC 20204 USA. RP Benjamin, DK (reprint author), Duke Univ, Duke Clin Res Inst, Box 17969, Durham, NC 27715 USA. EM danny.benjamin@duke.edu RI Hirschfeld, Steven/E-2987-2016 OI Hirschfeld, Steven/0000-0003-0627-7249 FU NICHD NIH HHS [1 R03 HD42940-02, HD-03-001] NR 10 TC 3 Z9 3 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-7453 J9 J ANTIMICROB CHEMOTH JI J. Antimicrob. Chemother. PD OCT PY 2004 VL 54 IS 4 BP 701 EP 703 DI 10.1093/jac/dkh410 PG 3 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA 858QP UT WOS:000224207100001 PM 15355940 ER PT J AU Nano, FE Zhang, N Cowley, SC Klose, KE Cheung, KKM Roberts, MJ Ludu, JS Letendre, GW Meierovics, AI Stephens, G Elkins, KL AF Nano, FE Zhang, N Cowley, SC Klose, KE Cheung, KKM Roberts, MJ Ludu, JS Letendre, GW Meierovics, AI Stephens, G Elkins, KL TI A Francisella tularensis pathogenicity island required for intramacrophage growth SO JOURNAL OF BACTERIOLOGY LA English DT Article ID INTRACELLULAR GROWTH; ALLELIC REPLACEMENT; PROTEIN; CELLS; NOVICIDA; STRAIN; IDENTIFICATION; CLONING; MACROPHAGES; TULAREMIA AB Francisella tularensis is a gram-negative, facultative intracellular pathogen that causes the highly infectious zoonotic disease tularemia. We have discovered a ca. 30-kb pathogenicity island of F. tularensis (FPI) that includes four large open reading frames (ORFs) of 2.5 to 3.9 kb and 13 ORFs of 1.5 kb or smaller. Previously, two small genes located near the center of the FPI were shown to be needed for intramacrophage growth. In this work we show that two of the large ORFs, located toward the ends of the FPI, are needed for virulence. Although most genes in the FPI encode proteins with amino acid sequences that are highly conserved between high- and low-virulence strains, one of the FPI genes is present in highly virulent type A F. tularensis, absent in moderately virulent type B F. tularensis, and altered in F. tularensis subsp. novicida, which is highly virulent for mice but avirulent for humans. The G+C content of a 17.7-kb stretch of the FPI is 26.6%, which is 6.6% below the average G+C content of the F. tularensis genome. This extremely low G+C content suggests that the DNA was imported from a microbe with a very low G+C-containing chromosome. C1 Univ Victoria, Dept Biochem & Microbiol, Victoria, BC V8W 3P6, Canada. British Columbia Ctr Dis Control, Vancouver, BC, Canada. Ctr Biol Evaluat & Res Food & Drug Adm, Rockville, MD USA. Univ Texas, Ctr Hlth Sci, Dept Microbiol & Immunol, San Antonio, TX USA. RP Nano, FE (reprint author), Univ Victoria, Dept Biochem & Microbiol, POB 3055 STN CSC, Victoria, BC V8W 3P6, Canada. EM fnano@uvic.ca NR 30 TC 223 Z9 229 U1 1 U2 8 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 OCT PY 2004 VL 186 IS 19 BP 6430 EP 6436 DI 10.1128/JB.186.19.6430-6436.2004 PG 7 WC Microbiology SC Microbiology GA 855QL UT WOS:000223988700011 PM 15375123 ER PT J AU Martinez-Urtaza, J Lozano-Leon, A DePaola, A Ishibashi, M Shimada, K Nishibuchi, M Liebana, E AF Martinez-Urtaza, J Lozano-Leon, A DePaola, A Ishibashi, M Shimada, K Nishibuchi, M Liebana, E TI Characterization of pathogenic Vibrio parahaemolyticus isolates from clinical sources in Spain and comparison with Asian and North American pandemic isolates SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID THERMOSTABLE DIRECT HEMOLYSIN; UNITED-STATES; TRH GENE; STRAINS; O3-K6; SEQUENCE; THAILAND; CLONE; PCR; TDH AB In spite of the potential risk involved with contamination of seafood with Vibrio parahaemolyticus, there is a lack of information on the occurrence of pathogenic V. parahaemolyticus in Europe. This organism was isolated in 1999 from a large outbreak (64 cases admitted to a single hospital) associated with raw oyster consumption in Galicia, Spain, one of the most important regions in shellfish production worldwide. Two V. parahaemolyticus isolates from the 1999 Galicia outbreak, three additional clinical isolates obtained in the same period from hospitals in Spain, two reference strains from clinical sources, and five Spanish environmental isolates were examined. Seventeen isolates belonging to the pandemic clone isolated in Asia and North America were included in the study for comparison. All isolates were characterized by serotyping, PCR for virulence-related genes, pulsed-field gel electrophoresis (PFGE), and plasmid analysis. Four of the five clinical isolates from hospitals in Spain belonged to serotype O4:K11; the remaining isolate was O4:K untypeable (KUT). All five isolates were positive for V. parahaemolyticus toxR and tlh (species-specific genes) and tdh and negative for trh and group-specific PCR (a PCR method for detection of the pandemic clone). PFGE analysis with NotI and Still discriminated the European isolates in two closely related PFGE types included in a homogeneous cluster, clearly differentiated from the Asian and North American isolates. The five environmental isolates belonged to serotypes O2:K28, O2:KUT, O3:K53, O4:KUT, and O8:K22 and were negative for all virulence genes. The five isolates were discriminated into five different PFGE types unrelated to any other isolate included in the study. While the virulence characteristics (tdh positive, trh negative) of the Spanish clinical isolates matched those of the O3:K6 clone from Asia and North America, they were clearly excluded from this clone by group-specific PCR, PFGE, and serotyping. The results of this study suggest that a unique and specific clone could be related to the V. parahaemolyticus infections in Europe. C1 Univ Santiago Compostela, Inst Acuicultura, Santiago De Compostela, Spain. US FDA, Gulf Coast Seafood Lab, Dauphin Isl, AL USA. Osaka Prefectural Inst Publ Hlth, Higashinari Ku, Osaka 537, Japan. Kyoto Univ, Sch Publ Hlth, Sakyo Ku, Kyoto, Japan. Kyoto Univ, Ctr SE Asian Studies, Sakyo Ku, Kyoto, Japan. Vet Labs Agcy, Dept Food & Environm Safety, Addlestone, Surrey, England. RP Martinez-Urtaza, J (reprint author), Univ Santiago Compostela, Inst Acuicultura, Campus Univ Sur, Santiago De Compostela, Spain. EM ucmjmur@usc.es RI Martinez-Urtaza, Jaime/A-5528-2015; Liebana, Ernesto/I-1187-2016 OI Liebana, Ernesto/0000-0003-1979-5731 NR 33 TC 88 Z9 95 U1 0 U2 7 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD OCT PY 2004 VL 42 IS 10 BP 4672 EP 4678 DI 10.1128/JCM.42.10.4672-4678.2004 PG 7 WC Microbiology SC Microbiology GA 862EM UT WOS:000224473000039 PM 15472326 ER PT J AU Gopalakrishnan, M Jadhav, P Gobburu, JVS AF Gopalakrishnan, M Jadhav, P Gobburu, JVS TI A web-based pharmacometrics learning resource SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Meeting Abstract CT 33rd Annual Meeting of the American-College-of-Clinical-Pharmacology CY OCT 03-05, 2004 CL Phoenix, AZ SP Amer Coll Clin Pharmacol C1 US FDA, CDER, OCPB, DPE 1, Rockville, MD 20857 USA. Virginia Commonwealth Univ, Dept Pharmaceut, Richmond, VA 23284 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 OCT PY 2004 VL 44 IS 10 MA 94 BP 1207 EP 1207 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 852JF UT WOS:000223750900092 ER PT J AU Nordstrom, JL Kaysner, CA Blackstone, GM Vickery, MCL Bowers, JC DePaola, A AF Nordstrom, JL Kaysner, CA Blackstone, GM Vickery, MCL Bowers, JC DePaola, A TI Effect of intertidal exposure on Vibrio parahaemolyticus levels in Pacific Northwest oysters SO JOURNAL OF FOOD PROTECTION LA English DT Article ID UNITED-STATES; VULNIFICUS; HEMOLYSIN; GENE AB Interest in Vibrio parahaemolyticus (Vp) increased in the United States following Vp-associated gastroenteritis outbreaks in 1997 and 1998 involving the West Coast and other areas. The present study evaluated multiple aspects of Vp ecology in the Pacific Northwest with three objectives: (i) to determine the effect of low-tide exposure on Vp levels in oysters, (ii) to determine the relationship between total and pathogenic Vp, and (iii) to examine sediments and aquatic fauna as reservoirs for pathogenic Vp. Samples were collected from intertidal reefs along Hood Canal, Wash., in August 2001. Fecal matter from marine mammals and aquatic birds as well as intestinal contents from bottom-dwelling fish were tested. Total and pathogenic Vp levels in all the samples were enumerated with colony hybridization procedures using DNA probes that targeted the thermolabile direct hemolysin (tlh) and thermostable direct hemolysin (tdh) genes, respectively. The mean Vp densities in oysters were four to eight times greater at maximum exposure than at the corresponding first exposure. While tdh-positive Vp counts were generally less than or equal to10 CFU/g at first exposure, counts as high as 160 CFU/g were found at maximum exposure. Vp concentrations in sediments were not significantly different from those in oysters at maximum exposure. Pathogenic (tdh positive) Vp was detected in 9 of 42 (21%) oyster samples at maximum exposure, in 5 of 19 (26%) sediment samples, but in 0 of 9 excreta samples. These results demonstrate that summer conditions permit the multiplication of Vp in oysters exposed by a receding tide. C1 US FDA, Gulf Coast Seafood Lab, Dauphin Isl, AL 36528 USA. US FDA, Seafood Prod Res Ctr, Bothell, WA 98021 USA. US FDA, Div Math, College Pk, MD 20740 USA. RP Nordstrom, JL (reprint author), US FDA, Gulf Coast Seafood Lab, 1 Iberville Dr, Dauphin Isl, AL 36528 USA. EM jessica.nordstrom@cfsan.fda.gov NR 16 TC 13 Z9 14 U1 1 U2 8 PU INT ASSOC FOOD PROTECTION PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD OCT PY 2004 VL 67 IS 10 BP 2178 EP 2182 PG 5 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 861CL UT WOS:000224393600013 PM 15508627 ER PT J AU Keller, SE Chirtel, SJ Merker, RI Taylor, KT Tan, HL Miller, AJ AF Keller, SE Chirtel, SJ Merker, RI Taylor, KT Tan, HL Miller, AJ TI Influence of fruit variety, harvest technique, quality sorting, and storage on the native microflora, of unpasteurized apple cider SO JOURNAL OF FOOD PROTECTION LA English DT Article ID ESCHERICHIA-COLI O157-H7; ACID TOLERANCE; SURVIVAL; OUTBREAK AB Apple variety, harvest, quality sorting, and storage practices were assessed to determine their impact on the microflora of unpasteurized cider. Seven apple varieties were harvested from the tree or the ground. The apples were used fresh or were stored at 0 to 4degreesC for less than or equal to5 months and were pressed with or without quality selection. Cider yield, pH, Brix value, and titratable acidity were measured. Apples, postpressing apple pomace, and cider samples were analyzed for aerobic bacteria, yeasts, and molds. Aerobic bacterial plate counts (APCs) of ciders from fresh ground-picked apples (4.89 log CFU/ml) were higher than those of ciders made from fresh, tree-picked apples (3.45 log CFU/ml). Quality sorting further reduced the average APC to 2.88 log CFU/ml. Differences among all three treatment groups were significant (P < 0.0001). Apple and pomace microbial concentrations revealed harvest and postharvest treatment-dependent differences similar to those found in cider. There were significant differences in APC among apple varieties (P = 0.0001). Lower counts were associated with varieties exhibiting higher Brix values and higher titratable acidity. Differences in APC for stored and fresh apples used for cider production were not significant (P > 0.05). Yeast and mold counts revealed relationships similar to those for APCs. The relationship between initial microbial load found on incoming fruit and final cider microbial population was curvilinear, with the weakest correlations for the lowest apple microflora concentrations. The lack of linearity suggests that processing equipment contributed to cider contamination. Tree-picked quality fruit should be used for unpasteurized cider production, and careful manufacturing practices at cider plants can impact both safety and quality of the final product. C1 US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. US FDA, Natl Ctr Food Safety & Technol, Summit Argo, IL 60501 USA. El Dorado Cty Dept Agr, Placerville, CA 95667 USA. Univ Calif Davis, Dept Food Sci & Technol, Davis, CA 95616 USA. RP Merker, RI (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM robert.merker@cfsan.fda.gov RI Diaz, Belen/B-8946-2012 NR 26 TC 9 Z9 9 U1 0 U2 10 PU INT ASSOC FOOD PROTECTION PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD OCT PY 2004 VL 67 IS 10 BP 2240 EP 2247 PG 8 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 861CL UT WOS:000224393600022 PM 15508636 ER PT J AU Rodriguez, AC Larkin, JW Dunn, J Patazca, E Reddy, NR Alvarez-Medina, M Tetzloff, R Fleischman, GJ AF Rodriguez, AC Larkin, JW Dunn, J Patazca, E Reddy, NR Alvarez-Medina, M Tetzloff, R Fleischman, GJ TI Model of the inactivation of bacterial spores by moist heat and high pressure SO JOURNAL OF FOOD SCIENCE LA English DT Article DE model; spore; high-pressure; inactivation; kinetics; Bacillus stearothermophilus; Clostridium botulinum; sterilization; terminal sterilization; shelf-stable AB Formulae for the prediction of inactivation and accumulated lethality of bacterial spores under moist heat and high pressures were derived on the basis of classic thermodynamic and kinetics principles. The capability of the model to describe the inactivation of bacterial spores was verified using 2 independent data sets corresponding to Clostridium botulinum processed at 60 degreesC to 75 degreesC and Bacillus stearothermophilus processed at 92 degreesC to 110 degreesC. Both sets included pressures between 5 x 10(8) Pa and 7 x 10(8) Pa. The equation fit explained more than 86% of the variation of the rate constant data. The developed equations establish a strong foundation on which to compare high-pressure processing treatments of different systems. This is especially useful because most systems have different transient temperature-pressure conditions. C1 Baxter Healthcare Corp, Round Lake, IL 60073 USA. US FDA, Natl Ctr Food Safety & Technol, Summit Argo, IL USA. IIT, Natl Ctr Food Safety & Technol, Summit Argo, IL USA. RP Rodriguez, AC (reprint author), Baxter Healthcare Corp, RLT-10,Route 120 & Wilson Rd, Round Lake, IL 60073 USA. EM AlfredoRodriguez@baxter.com NR 19 TC 7 Z9 8 U1 0 U2 4 PU INST FOOD TECHNOLOGISTS PI CHICAGO PA 525 WEST VAN BUREN, STE 1000, CHICAGO, IL 60607-3814 USA SN 0022-1147 J9 J FOOD SCI JI J. Food Sci. PD OCT PY 2004 VL 69 IS 8 BP E367 EP E373 PG 7 WC Food Science & Technology SC Food Science & Technology GA 869WW UT WOS:000225016300020 ER PT J AU [Anonymous] AF [Anonymous] TI Quantification of simian foamy virus DNA in macaque PBMCs by real-time taqman PCR assays SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Meeting Abstract RP US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD OCT PY 2004 VL 33 IS 5-6 BP 323 EP 323 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 858GC UT WOS:000224179300130 ER PT J AU Dietz, DM Vogel, MW Rubin, SA Moran, TH Carbone, KM Pletnikov, MV AF Dietz, DM Vogel, MW Rubin, SA Moran, TH Carbone, KM Pletnikov, MV TI Developmental alterations in serotoninergic neurotransmission in Borna disease virus (BDV)-infected rats: A multidisciplinary analysis SO JOURNAL OF NEUROVIROLOGY LA English DT Article DE animal model; Borna; developmental behavioral disorders; serotonin ID NEURODEVELOPMENTAL DAMAGE; BDV INFECTION; CNS DISEASES; AUTISM; BRAIN; PERSISTENT; MECHANISMS; RESPONSES; ABNORMALITIES; ORGANIZATION AB Neonatal Borna disease virus (BDV) infection of the rat brain serves as a valuable model for studying the pathogenesis of neurodevelopmental abnormalities following early brain injury. Previous experiments have demonstrated significant alterations in regional tissue content of serotonin (5-HT) in neonatally BDV-infected Lewis rats. The present study sought to provide more insights into postnatal virus-associated alterations in 5-HT neurotransmission by evaluating the density of 5-HT1a receptors in the hippocampus and 5-HT2a receptors in the cortex, regional 5-HT tissue concentrations, behavioral responses to a 5-HT agonist, quipazine, and numbers of neurons in specific subfields of the hippocampus on days 7, 14, and 30 after neonatal BDV infection in Lewis rats. Neonatal BDV infection was found to be associated with a gradual increase in the density of 5-HT2a and 5-HT1a postsynaptic receptors followed by an elevation of 5-HT contents at both the levels of synaptic terminals (i.e., cortex and hippocampus) and cell bodies (i.e., raphe nuclei). In addition, there was an enhanced behavioral response to quipazine. Virus-associated neurochemical and behavioral changes were accompanied by a decline in the number of neurons in the dentate gyrus and in the CA1 field of the hippocampus. No change in the number of neurons in the CA3/2 field of the hippocampus was observed. The present pattern of BDV-associated alterations in 5-HT brain system along with available data from other laboratories suggest that BDV might compromise axonal transport and/or release of 5-HT, resulting in decreased 5-HT neurotransmission. C1 Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. Univ Maryland, Maryland Psychiat Res Ctr, Baltimore, MD 21201 USA. CBER, US FDA, Bethesda, MD USA. RP Pletnikov, MV (reprint author), Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, 720 Rutland Ave,Ross 618, Baltimore, MD 21205 USA. EM mpletnik@jhmi.edu RI Dietz, David/J-9458-2015; OI Dietz, David/0000-0002-6927-9236; Vogel, Michael/0000-0002-8402-1495 FU NIMH NIH HHS [R01 MH48948] NR 57 TC 7 Z9 8 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PD OCT PY 2004 VL 10 IS 5 BP 267 EP 277 DI 10.1080/13550280490499506 PG 11 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA 854ET UT WOS:000223884600001 PM 15385249 ER PT J AU Rubin, SA Liu, D Pletnikov, M McCullers, JA Ye, ZP Levandowski, RA Johannessen, J Carbone, KM AF Rubin, SA Liu, D Pletnikov, M McCullers, JA Ye, ZP Levandowski, RA Johannessen, J Carbone, KM TI Wild-type and attenuated influenza virus infection of the neonatal rat brain SO JOURNAL OF NEUROVIROLOGY LA English DT Article DE influenza virus; neurotropism; neurovirulence; rat; vaccine ID SYMMETRICAL THALAMIC LESIONS; A VIRUS; ACUTE ENCEPHALOPATHY; INFANT RAT; MENTAL-RETARDATION; NERVOUS-SYSTEM; ENCEPHALITIS; DISORDERS; SCHIZOPHRENIA; EPIDEMICS AB Although influenza virus infection of humans has been associated with a wide spectrum of clinical neurological syndromes, the pathogenesis of influenza virus associated central nervous system (CNS) disease in humans remains controversial. To better study influenza virus neuropathogenesis, an animal model of influenza-associated CNS disease using human virus isolates without adaptation to an animal host was developed. This neonatal rat model of influenza virus CNS infection was developed using low-passage human isolates and shows outcomes in specific brain regions, cell types infected, and neuropathological outcomes that parallel the available literature on cases of human CNS infection. The degree of virus replication and spread in the rat brain correlated with the strains' neurotoxicity potential for humans. In addition, using sensitive neurobehavioral test paradigms, changes in brain function were found to be associated with areas of virus replication in neurons. These data suggest that further evaluation of this pathogenesis model may provide important information regarding influenza virus neuropathogenesis, and that this model may have possible utility as a preclinical assay for evaluating the neurological safety of new live attenuated influenza virus vaccine strains. C1 CBER, DVP, OVRR, US FDA, Bethesda, MD 20892 USA. NIA, Neurosci Lab, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. Johns Hopkins Univ, Dept Psychiat, Baltimore, MD USA. Johns Hopkins Univ, Dept Med, Baltimore, MD USA. St Jude Childrens Res Hosp, Memphis, TN 38105 USA. US FDA, OS, OC, Rockville, MD 20857 USA. CBER, OD, US FDA, Bethesda, MD USA. RP Rubin, SA (reprint author), CBER, DVP, OVRR, US FDA, Bldg 29A,Room 1A-21,8800 Rockville Pike, Bethesda, MD 20892 USA. EM rubins@cber.fda.gov NR 56 TC 7 Z9 9 U1 1 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PD OCT PY 2004 VL 10 IS 5 BP 305 EP 314 DI 10.1080/13550280490499579 PG 10 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA 854ET UT WOS:000223884600005 PM 15385253 ER PT J AU Mohan, N Edwards, ET Cupps, TR Slifman, N Lee, JH Siegel, JN Braun, MM AF Mohan, N Edwards, ET Cupps, TR Slifman, N Lee, JH Siegel, JN Braun, MM TI Leukocytoclastic vasculitis associated with tumor necrosis factor-alpha blocking agents SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE leukocytoclastic vasculitis; tumor necrosis factor-alpha blockers; etanercept; infliximab ID CHIMERIC MONOCLONAL-ANTIBODY; LOW-DOSE METHOTREXATE; RHEUMATOID-ARTHRITIS; CUTANEOUS VASCULITIS; FUSION PROTEIN; CROHNS-DISEASE; ETANERCEPT; INFLIXIMAB; HYPERSENSITIVITY; THERAPY AB Objective. To describe the clinical features of leukocytoclastic vasculitis (LCV) associated with the use of tumor necrosis factor-alpha (TNF-alpha) blockers. Methods. The Adverse Events Reporting System (AERS) of the US Food and Drug Administration (FDA) was queried for reports of patients who developed LCV during or after starting etanercept or infliximab from date of approval of each agent through September 6, 2002. Results. Thirty-five cases of LCV were identified, 20 following etanercept administration and 15 following infliximab administration. Seventeen of the 35 (48.5%) were biopsy-proven cases and the others had skin lesions that were clinically typical for LCV. Twenty-two of 35 (62.8%) patients had complete or marked improvement of skin lesions upon stopping the TNF-alpha blocker. Three patients who had received etanercept had continuing lesions despite discontinuation of the drug; one of these patients improved when switched to infliximab. One patient who received infliximab was reported to have continuing lesions despite discontinuation of the drug and treatment with prednisone and antihistamines. Six patients experienced a positive rechallenge (recurrence of LCV on restarting therapy with a TNF-alpha blocker) and 3 patients a negative rechallenge phenomenon. LCV lesions improved in patients despite continuing use of concomitant medications reportedly associated with LCV. Conclusion. Therapy with TNF-alpha blocking agents may be associated with the development of LCV. Skin lesions improved on discontinuation of anti-TNF-alpha therapy in most patients. Other causes of LCV should be excluded, and evaluation for systemic involvement with appropriate investigations is recommended. C1 Avera Res Inst, Sioux Falls, SD 57105 USA. US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. Georgetown Univ, Med Ctr, Washington, DC USA. RP Mohan, N (reprint author), Avera Res Inst, 2020 S Norton St, Sioux Falls, SD 57105 USA. EM nmohan@pol.net NR 28 TC 109 Z9 115 U1 0 U2 2 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO, ONTARIO M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD OCT PY 2004 VL 31 IS 10 BP 1955 EP 1958 PG 4 WC Rheumatology SC Rheumatology GA 860FC UT WOS:000224326900015 PM 15468359 ER PT J AU Ornstein, DK Rayford, W Fusaro, VA Conrads, TP Ross, SJ Hitt, BA Wiggins, WW Veenstra, TD Liotta, LA Petricoin, EF AF Ornstein, DK Rayford, W Fusaro, VA Conrads, TP Ross, SJ Hitt, BA Wiggins, WW Veenstra, TD Liotta, LA Petricoin, EF TI Serum proteomic profiling can discriminate prostate cancer from benign prostates in men with total prostate specific antigen levels between 2.5 and 15.0 ng/ml SO JOURNAL OF UROLOGY LA English DT Article DE prostate; prostatic neoplasms; prostate-specific antigen; computational biology; spectrum analysis; mass ID MASS-SPECTROMETRY; BREAST-CANCER; SELDI-TOF; PATTERNS; BIOMARKERS; DIAGNOSIS; DISEASE AB Purpose: Artificial intelligence based pattern recognition algorithms have been developed and successfully used to analyze complex serum proteomic data streams generated by surface enhanced, laser desorption ionization time-of-flight mass spectroscopy. In the current study we used a high performance, hybrid quadrupole time-of-flight mass spectrometer to generate discriminatory serum proteomic profiles to determine if this technology could be used to determine the need for prostate biopsy in men with elevated prostate specific antigen (PSA). Materials and Methods: Serum samples were collected from 154 men with serum PSA 2.5 to 15.0 ng/ml and/or abnormal digital rectal examination prior to transrectal ultrasound guided biopsy. Serum samples were applied to WCX2 (weak cation exchange protein chip) Protein Arrays (Ciphergen Biosystems, Fremont, California) by a Biomek 2000 robotic liquid handler (Beckman-Coulter, Chaska, Minnesota) and low molecular weight (less than 20 kDa) protemic patterns were generated with an API QSTAR Pulsar i LC/MS/MS System (Applied Biosystems, Framingham, Massachusetts). High resolution mass spectra were analyzed with a pattern recognition bioinformatics tool, that is Proteome Quest beta version 1.0 (Correlogic Systems, Inc., Bethesda, Maryland), in an attempt to identify and discover key discriminating ion signatures. Serum samples from 63 men (2 or more negative prostate biopsies in 23, 1 negative biopsy in 10 and biopsy detected prostate cancer [CaP] in 30) were used to train the diagnostic algorithm. The remaining 91 samples, including 28 of prostate cancer and 63 of 1 or more negative biopsies, were analyzed in blinded fashion. Results: The most discriminatory model was found using the WCX2 chip. Testing the remaining 91 men with this model yielded 100% sensitivity and 67% specificity. In other words, if the proteomic pattern had been used to determine the need for prostate biopsy in this cohort of men with PSA between 2.5 and 15.0 ng/ml, 67% (42 of 63) with negative biopsies would have avoided unnecessary biopsy, while no cancers would have been missed. Conclusions: Our data demonstrate that high resolution mass spectroscopy can generate serum proteomic patterns that discriminate men with elevated PSA due to benign processes from men with CaP even when PSA is within the diagnostic gray zone. We are currently expanding the testing set to determine the reliability of this new technology to decrease unnecessary prostate biopsies without compromising the detection of curable CaP. C1 Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27515 USA. Louisiana State Univ, Dept Urol, New Orleans, LA USA. NIH, Clin Prote Program, US FDA, Bethesda, MD 20892 USA. Correl Syst, Bethesda, MD USA. RP Ornstein, DK (reprint author), Univ Calif Irvine, Irvine Med Ctr, Dept Urol, 101 City Dr S,Bldg 55,Room 300, Orange, CA 92868 USA. EM dornstei@uci.edu NR 20 TC 82 Z9 90 U1 3 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD OCT PY 2004 VL 172 IS 4 BP 1302 EP 1305 DI 10.1097/01.ju.0000139572.88463.39 PN 1 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 854JN UT WOS:000223899000017 PM 15371828 ER PT J AU Brown, AT Chen, HJ Davis, JA Qureshi, I Cruz, CP Poirier, MA Eidt, JF Moursi, MM AF Brown, AT Chen, HJ Davis, JA Qureshi, I Cruz, CP Poirier, MA Eidt, JF Moursi, MM TI Plasma homocysteine measurements after carotid artery manipulation and clamping in a rat CEA model SO JOURNAL OF VASCULAR SURGERY LA English DT Article; Proceedings Paper CT 8th Biennual Meeting of the International-Society-for-Applied-Cardiovascular-Biology CY FEB 27-MAR 02, 2002 CL ST GALLEN, SWITZERLAND SP Int Soc Appl Cardiovasc Biol ID SMOOTH-MUSCLE-CELLS; INDEPENDENT RISK FACTOR; VASCULAR-DISEASE; METHYLENETETRAHYDROFOLATE REDUCTASE; HYPERHOMOCYSTEINEMIA; HOMOCYST(E)INE; ENDARTERECTOMY; INCREASES; STROKE; ARTERIOSCLEROSIS AB Objective: The effect of a rat carotid endarterectomy (CEA) on homocysteine and the metabolic enzymes methylenetetrahydrofolate reductase (MTHFR) and cystathionine beta-synthase (CBS) was studied. Methods: Rats were placed into 7 groups: (1) no anesthesia (NA), (2) anesthesia only (AO), (3) skin opened and closed (O/C), (4) skin opened with exposure of the carotid artery and closed (O/E/C), (5) carotid isolated and clamped (CO), (6) open CEA, and (7) open femoral endarterectomy (FEA). End points included homocysteine, hepatic MTHFR, and CBS activity. Results: Homocysteine in the NA, AO, O/C, O/E/C, and FEA were low and not different. CEA produced a 6-fold increase in homocysteine when compared with non-CEA groups. Specifically, CEA produced an increase in homocysteine versus the AO group at 2 weeks (11.3 +/- 0.7 vs 2.1 +/- 0.9 mumol/L; P <.001), 4 weeks (8.9 +/- 0.7 vs 3.5 +/- 0.9 mumol/L; P =.004) and 6 weeks (7.7 +/- 0.9 vs 3.1 +/- 1.5 mumol/L; P =.03). The CO group had increased homocysteine versus the O/C, O/E/C, and FEA, but was lower than the CEA group. CEA produced an increase in MTHFR and CBS versus the AO group. Conclusions. CEA resulted in elevated levels of homocysteine; however, when broken down into its component parts, no elevation was observed except for a small increase with the CO procedure. Manipulation of the femoral artery did not raise homocysteine levels. The increase in homocysteine is possibly due to the combination of vessel wall damage and changes in cerebral blood flow dynamics. C1 Univ Arkansas Med Sci, Cent Arkansas Vet HealthCare Syst, Vasc Serv, Little Rock, AR 72205 USA. Natl Ctr Toxicol Res, Div Mol Epidemiol, Jefferson, AR 72079 USA. RP Moursi, MM (reprint author), Univ Arkansas Med Sci, Cent Arkansas Vet HealthCare Syst, Vasc Serv, 112-PV,4300 W 7th St, Little Rock, AR 72205 USA. EM moursimohammedm@exchange.uams.edu NR 37 TC 4 Z9 4 U1 0 U2 0 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 OCT PY 2004 VL 40 IS 4 BP 796 EP 802 DI 10.1016/j.jvs.2004.07.011 PG 7 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 902WZ UT WOS:000227388700032 PM 15472610 ER PT J AU Tollefson, L AF Tollefson, L TI Developing new regulatory approaches to antimicrobial safety SO JOURNAL OF VETERINARY MEDICINE SERIES B-INFECTIOUS DISEASES AND VETERINARY PUBLIC HEALTH LA English DT Article ID RESISTANT SALMONELLA; ANTIBIOTICS AB Resistance to antimicrobial agents is of concern to public health officials worldwide. In industrialized countries, a significant source of antimicrobial-resistant food-borne infections in humans is the acquisition of resistant bacteria originating from animals. The US Food and Drug Administration (FDA) is committed to resolving the public health impact arising from the use of antimicrobial drugs in food-producing animals. The FDAs goal is to ensure that significant human antimicrobial therapies are not compromised or lost while providing for the safe use of antimicrobials in food animals. Recently the FDA published a guidance document titled 'Evaluating the Safety of Antimicrobial New Animal Drugs with Regard to their Microbiological Effects on Bacteria of Human Health Concern' (US Food and Drug Administration, Center for Veterinary Medicine, 2003). This document outlines a pathway drug sponsors can use to address concerns about antimicrobial resistance prior to approval of their drug. The process uses a qualitative risk assessment approach to assess the potential of the intended use of a product to develop resistance in bacteria that may harm humans. The level of risk determines the level of risk management that is required for the drug to be used. The Food and Drug Administration (FDA) always has the option of not approving a drug if the risk of a public health consequence is too high. C1 US FDA, Ctr Vet Med, Rockville, MD 20855 USA. RP Tollefson, L (reprint author), US FDA, Ctr Vet Med, 7519 Standish Pl, Rockville, MD 20855 USA. EM ltollefs@cvm.fda.gov NR 8 TC 4 Z9 6 U1 0 U2 2 PU BLACKWELL VERLAG GMBH PI BERLIN PA KURFURSTENDAMM 58, D-10707 BERLIN, GERMANY SN 0931-1793 J9 J VET MED B JI J. Vet. Med. Ser. B-Infect. Dis. Vet. Public Health PD OCT PY 2004 VL 51 IS 8-9 BP 415 EP 418 DI 10.1111/j.1439-0450.2004.00781.x PG 4 WC Veterinary Sciences SC Veterinary Sciences GA 867TG UT WOS:000224864600013 PM 15525377 ER PT J AU Darnell, MER Subbarao, K Feinstone, SM Taylor, DR AF Darnell, MER Subbarao, K Feinstone, SM Taylor, DR TI Inactivation of the coronavirus that induces severe acute respiratory syndrome, SARS-CoV SO JOURNAL OF VIROLOGICAL METHODS LA English DT Article DE SARS; coronavirus; virus inactivation; tissue culture ID GAMMA-IRRADIATION; VIRUS; GLYCOPROTEIN; VACCINE AB Severe acute respiratory syndrome (SARS) is a life-threatening disease caused by a novel coronavirus termed SARS-CoV. Due to the severity of this disease, the World Health Organization (WHO) recommends that manipulation of active viral cultures of SARS-CoV be performed in containment laboratories at biosafety level 3 (BSL3). The virus was inactivated by ultraviolet light (UV) at 254 nm, heat treatment of 65 degreesC or greater, alkaline (pH > 12) or acidic (pH < 3) conditions, formalin and glutaraldehyde treatments. We describe the kinetics of these efficient viral inactivation methods, which will allow research with SARS-CoV containing materials, that are rendered non-infectious, to be conducted at reduced safety levels. (C) 2004 Elsevier B.V. All rights reserved. C1 US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Taylor, DR (reprint author), US FDA, Ctr Biol Evaluat & Res, 8800 Rockville Pike,HFM448, Bethesda, MD 20892 USA. EM taylord@cber.fda.gov NR 23 TC 27 Z9 29 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 OCT PY 2004 VL 121 IS 1 BP 85 EP 91 DI 10.1016/j.jviromet.2004.06.006 PG 7 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Virology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Virology GA 856JY UT WOS:000224042700012 PM 15350737 ER PT J AU Guest, S Pilipenko, E Sharma, K Chumakov, K Roos, RP AF Guest, S Pilipenko, E Sharma, K Chumakov, K Roos, RP TI Molecular mechanisms of attenuation of the Sabin strain of poliovirus type 3 SO JOURNAL OF VIROLOGY LA English DT Article ID TRACT-BINDING-PROTEIN; INTERNAL RIBOSOMAL ENTRY; 5 NONTRANSLATED REGION; HEPATITIS-C VIRUS; TRANSLATION INITIATION; RNA TRANSLATION; IN-VIVO; UNTRANSLATED REGION; NONCODING REGION; PICORNAVIRUS RNA AB Mutations critical for the central nervous system (CNS) attenuation of the Sabin vaccine strains of poliovirus (PV) are located within the viral internal ribosome entry site (IRES). We examined the interaction of the IRESs of PV type 3 (PV3) and Sabin type 3 (Sabin3) with polypyrimidine tract-binding protein (PTB) and a neural cell-specific homologue, nPTB. PTB and nPTB were found to bind to a site directly adjacent to the attenuating mutation, and binding at this site was less efficient on the Sabin3 IRES than on the PV3 IRES. Translation mediated by the PV3 and Sabin3 IRESs in neurons of the chicken embryo spinal cord demonstrated a translation deficit for the Sabin3 IRES that could be rescued by increasing PTB expression in the CNS. These data suggest that the low levels of PTB available in the CNS, coupled to a reduced binding of PTB on the Sabin3 IRES, leads to its CNS-specific attenuation. This study also demonstrates the use of the chicken embryo to easily investigate translation of RNA within a neuron in the CNS of an intact living organism. C1 Univ Chicago, Dept Neurol, Div Biol Sci, Chicago, IL 60637 USA. Univ Chicago, Div Biol Sci, Dept Neurobiol Pharmacol & Physiol, Chicago, IL 60637 USA. Univ Chicago, Div Biol Sci, Dept Mol Genet & Cell Biol, Chicago, IL 60637 USA. Univ Chicago, Div Biol Sci, Committee Microbiol, Chicago, IL 60637 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. RP Roos, RP (reprint author), Univ Chicago, Dept Neurol, Div Biol Sci, 5841 S Maryland Ave, Chicago, IL 60637 USA. EM rroos@neurology.bsd.uchicago.edu NR 52 TC 53 Z9 55 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD OCT PY 2004 VL 78 IS 20 BP 11097 EP 11107 DI 10.1128/JVI.78.20.1109.11107.2004 PG 11 WC Virology SC Virology GA 858YO UT WOS:000224229000027 PM 15452230 ER PT J AU Maluping, RP Lavilla-Pitogo, CR DePaola, A Janda, JM Krovacek, K AF Maluping, RP Lavilla-Pitogo, CR DePaola, A Janda, JM Krovacek, K TI Occurrence, characterisation and detection of potential virulence determinants of emerging aquatic bacterial pathogens from the Philippines and Thailand SO MICROBIOLOGICA LA English DT Article DE Aeromonas spp.; Vibrio spp.; P shigelloides; Philippines; Thailand; virulence; factors ID AEROMONAS-HYDROPHILA STRAINS; PLESIOMONAS-SHIGELLOIDES; VIBRIO-PARAHAEMOLYTICUS; LOW-TEMPERATURES; TOXIN PRODUCTION; TDH GENE; WATER; SPP.; SOBRIA; GROWTH AB Strains of Aeromonas spp., (1)non-cholera vibrios(1) (NCVs) and Plesiomonas shigelloides isolated from aquatic environments, fish and human diarrhoeal cases in the Philippines and Thailand were characterised for potential virulence markers. Thus, the production of cytotoxin, cell-associated and cell-free haemolysin and their capacity to adhere to human intestinal (Henle 407) cells in vitro was investigated. In addition, the occurrence of tlh and tdh haemolysin genes and urease activity among V. parahaemolyticus strains was investigated. The results showed that strains recovered from clinical sources (human and fish) produced these virulence factors, whereas these are absent in environmental strains. C1 SLU, Fac Med Vet, Dept Biomed Sci & Vet Publ Hlth, Uppsala, Sweden. Univ Philippines, Coll Vet Med, Dept Vet Paraclin Sci, Los Banos, Philippines. SE Asian Fisheries Dev Ctr, Aquaculture Dept, Iloilo, Philippines. US FDA, Gulf Coast Seafood Lab, Dauphin Isl, AL USA. Calif Dept Hlth, Microbial Dis Lab, Richmond, CA USA. RP Maluping, RP (reprint author), SLU, Fac Med Vet, Dept Biomed Sci & Vet Publ Hlth, Uppsala, Sweden. NR 45 TC 0 Z9 0 U1 0 U2 0 PU LUIGI PONZIO E FIGLIO PI PAVIA PA VIA D DA CATALOGNA 1/3, 27100 PAVIA, ITALY SN 1121-7138 J9 MICROBIOLOGICA JI Microbiologica PD OCT PY 2004 VL 27 IS 4 BP 381 EP 389 PG 9 WC Microbiology SC Microbiology GA 883ZG UT WOS:000226053800009 ER PT J AU Hillman, GG Wang, Y Kucuk, O Che, MX Doerge, DR Yudelev, M Joiner, MC Marples, B Forman, JD Sarkar, FH AF Hillman, GG Wang, Y Kucuk, O Che, MX Doerge, DR Yudelev, M Joiner, MC Marples, B Forman, JD Sarkar, FH TI Genistein potentiates inhibition of tumor growth by radiation in a prostate cancer orthotopic model SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID CELL-CYCLE ARREST; RAT PROSTATE; CYTOKINE THERAPY; MAMMARY-CANCER; WISTAR RATS; APOPTOSIS; INDUCTION; CARCINOMA; DIETARY; MICE AB Objective: We have shown previously that pretreatment with genistein potentiated cell killing induced by radiation in human PC-3 prostate carcinoma cell line in vitro. We tested this approach in vivo using an orthotopic prostate carcinoma model of PC-3 cells in nude mice. Methods: Established prostate tumors were pretreated with p.o. genistein at a dose of 5 mg/d for 2 days followed by tumor irradiation with 5 Gy photons. One day after radiation, genistein was resumed and given every other day for 4 weeks. Results: Genistein combined with radiation caused a significantly greater inhibition of primary tumor growth (87%) compared with genistein (30%) or radiation (73%) alone. The number of metastatic lymph nodes was also significantly decreased following genistein and radiation. Paradoxically, genistein alone increased the size of lymph nodes associated with heavy tumor infiltration. Genistein-treated prostate tumors were large with necrosis, apoptotic cells, and giant cells and have a lower proliferation index than in control tumors. Following radiation, areas of tumor destruction replaced by fibrotic tissue and inflammatory cells as well as giant cells were observed, which are typical of radiation effect. After radiation and genistein treatment, an increase in giant cells, apoptosis, inflammatory cells, and fibrosis was observed with decreased tumor cell proliferation consistent with increased tumor cell destruction. Long-term therapy with genistein after prostate tumor irradiation significantly increased survival. Conclusions: Genistein combined with prostate tumor irradiation led to a greater control of the growth of the primary tumor and metastasis to lymph nodes than genistein or radiation alone, resulting in greater survival. C1 Wayne State Univ, Sch Med, Barbara Ann Karmanos Canc Inst, Dept Radiat Oncol, Detroit, MI 48201 USA. Wayne State Univ, Sch Med, Barbara Ann Karmanos Canc Inst, Dept Internal Med, Detroit, MI 48201 USA. Wayne State Univ, Sch Med, Barbara Ann Karmanos Canc Inst, Dept Pathol, Detroit, MI 48201 USA. Harper Univ Hosp, Detroit, MI USA. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Hillman, GG (reprint author), Wayne State Univ, Sch Med, Barbara Ann Karmanos Canc Inst, Dept Radiat Oncol, Hudson Webber Bldg,Room 515,4100 John R Rd, Detroit, MI 48201 USA. EM hillmang@karmanos.org NR 44 TC 84 Z9 87 U1 0 U2 2 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 2004 VL 3 IS 10 BP 1271 EP 1279 PG 9 WC Oncology SC Oncology GA 862KB UT WOS:000224488400011 PM 15486194 ER PT J AU Berhane, B Edmondson, R Zong, N Jones, R Qiao, J Vondriska, TM Ping, PP AF Berhane, Beniam Edmondson, Rick Zong, Nobel Jones, Richard Qiao, Joe Vondriska, Thomas M. Ping, Peipei TI Proteomic analysis of human plasma using a platform involving isoelectric focusing, electrophoresis, MALDI-TOF and LC/MS/MS SO MOLECULAR & CELLULAR PROTEOMICS LA English DT Meeting Abstract C1 [Berhane, Beniam; Zong, Nobel; Qiao, Joe; Vondriska, Thomas M.; Ping, Peipei] Univ Calif Los Angeles, David Geffen Sch Med, Dept Physiol, Los Angeles, CA 90095 USA. [Berhane, Beniam; Zong, Nobel; Qiao, Joe; Vondriska, Thomas M.; Ping, Peipei] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Cardiol, Los Angeles, CA 90095 USA. [Edmondson, Rick; Jones, Richard] Natl Ctr Toxicol Res, Proteom Team, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 1535-9476 J9 MOL CELL PROTEOMICS JI Mol. Cell. Proteomics PD OCT PY 2004 VL 3 IS 10 SU S BP S231 EP S231 PG 1 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA V44IA UT WOS:000202995200558 ER PT J AU Sampson, JH Friedman, AH Reardon, DA Friedman, H Provenzale, JM Bigner, DD Brady, M Raghavan, R Pedain, C Archer, G Lally-Batts, D McGehee, S Tourt-Uhlig, S Grahn, A Dul, JL Croteau, D Sherman, JW Puri, RK AF Sampson, JH Friedman, AH Reardon, DA Friedman, H Provenzale, JM Bigner, DD Brady, M Raghavan, R Pedain, C Archer, G Lally-Batts, D McGehee, S Tourt-Uhlig, S Grahn, A Dul, JL Croteau, D Sherman, JW Puri, RK TI Convection-enhanced delivery of IL13-PE38QQR in malignant glioma: Comparison of observed and predicted drug distribution SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 9th Annual Meeting of the Society-for-Neuro-Oncology CY NOV 18-21, 2004 CL Toronto, CANADA SP Soc Neuro Oncol C1 Duke Univ, Med Ctr, Durham, NC USA. Image Guided Neurol, Baltimore, MD USA. BrainLAB AG, Munich, Germany. NeoPharm Inc, Lake Forest, IL USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. NR 0 TC 0 Z9 0 U1 0 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 2004 VL 6 IS 4 BP 381 EP 382 PG 2 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 860HF UT WOS:000224332400301 ER PT J AU Feinsod, M Chambers, WA AF Feinsod, M Chambers, WA TI Trials and tribulations - A primer on successfully navigating the waters of the food and drug administration SO OPHTHALMOLOGY LA English DT Article AB Conducting clinical trials in a regulated environment constitutes unfamiliar territory for most physicians. There exists no formal training in this subject, so many clinicians lack even a basic understanding of the procedures required by the Federal Food, Drug, and Cosmetic Act and their implications vis-a-vis clinical practice. The authors distill drug regulation to relevant applications and elucidate the rationale and procedures for submitting an Investigational New Drug application by providing a user-friendly road map of the process. (C) 2004 by the American Academy of Ophthalmology. C1 US FDA, Div Anitiinflammatory Analgesic & Opthalm Drug Pr, Rockville, MD 20850 USA. RP Chambers, WA (reprint author), US FDA, Div Anitiinflammatory Analgesic & Opthalm Drug Pr, 9201 Corp Blvd,HFD 550, Rockville, MD 20850 USA. NR 2 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD OCT PY 2004 VL 111 IS 10 BP 1801 EP 1806 DI 10.1016/j.ophtha.2004.05.022 PG 6 WC Ophthalmology SC Ophthalmology GA 858EL UT WOS:000224173000002 PM 15465539 ER PT J AU Biris, AS De, S Mazumder, MK Sims, RA AF Biris, AS De, S Mazumder, MK Sims, RA TI Corona generation and deposition of metal nanoparticles on conductive surfaces and their effects on the substrate surface texture and chemistry SO PARTICULATE SCIENCE AND TECHNOLOGY LA English DT Article DE corona discharge; metal nanoparticles; AFM; SEM/EDX; surface topography; electrochemical behavior ID PARTICLES; GROWTH AB A corona discharge ion bombardment technique was used successfully to generate gold particles of submicron diameters. In a negative corona discharge, the glow region contains electrons. negative ions, and positive ions. Positive ions collided with the negative corona tip electrode, causing it to sputter and emit fine particles of the electrode material. These nanoparticles were deposited on grounded metal substrates or thin mica sheets supported by grounded metal substrates. Scanning electron microscopy (SEM) and atomic force microscopy (A FM) were used to study the size distribution and deposition pattern of the metal nanoparticles. The diameter of these nanoparticles was dependent upon the material of the electrode and ranged from 20 to 450nm for gold and from 15 to 240 nm for tungsten. The nanoparticles were deposited on aluminum, mica, and carbon steel test panels for different amounts of time. The electrochemical response of the carbon steel panels exposed to aerated salt solution was measured by direct current (DC) polarization technique before and after the gold nanoparticles were deposited. This technique was employed to determine the changes in the surface chemistry because of the presence of gold nanoparticles, and it proved to be a sensible method for detecting the presence of fine layers of nanoparticles on the metallic substrate. The presence of the gold nanoparticles increased the electrochemical potential E-corr from -0.640 V to -0.211 V, compared with the value for a noncorrosive surface, like that of pure gold, which is 0 V. C1 Univ Arkansas, Dept Appl Sci, Little Rock, AR 72204 USA. Natl Ctr Toxicol Res, Div Chem, Jefferson, AR 72079 USA. Univ Cent Arkansas, Dept Phys, Conway, AR USA. RP Biris, AS (reprint author), Univ Arkansas, Dept Appl Sci, 2801 S Univ Ave, Little Rock, AR 72204 USA. EM asbiris@ualr.edu RI Biris, Alexandru/A-8507-2010 NR 20 TC 1 Z9 1 U1 0 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0272-6351 J9 PARTICUL SCI TECHNOL JI Part. Sci. Technol. PD OCT-DEC PY 2004 VL 22 IS 4 BP 405 EP 416 DI 10.1080/0276350490516073 PG 12 WC Engineering, Chemical SC Engineering GA 870UT UT WOS:000225084800007 ER PT J AU Powers, JH Zalkikar, J Johann-Liang, R AF Powers, JH Zalkikar, J Johann-Liang, R TI Correlation between bacteriologic eradication and clinical cure in acute otitis media SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Letter ID END-POINTS; TRIALS C1 US FDA, Off Drug Evaluat 4, Rockville, MD 20857 USA. US FDA, Off Biostat, Rockville, MD 20857 USA. US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Powers, JH (reprint author), US FDA, Off Drug Evaluat 4, Rockville, MD 20857 USA. NR 7 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0891-3668 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD OCT PY 2004 VL 23 IS 10 BP 976 EP 976 DI 10.1097/01.inf.0000142629.76912.f2 PG 1 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA 865FH UT WOS:000224687400023 PM 15602210 ER PT J AU Suleiman, OH AF Suleiman, OH TI Radiation doses in pediatric radiology: influence of regulations and standards SO PEDIATRIC RADIOLOGY LA English DT Article DE radiation dose; pediatrics; regulations; standards ID UNITED-STATES AB The benefits of x-ray examinations contribute to the quality of modern medicine; however the risk of using x-rays, a carcinogen, has always been a concern. This concern is heightened for pediatric patients, who have a much greater sensitivity to the carcinogenic effects of radiation than adults. The principle of as low as reasonably achievable, or ALARA, is essential for minimizing the radiation dose patients receive, especially for pediatric patients. In order to keep radiation doses ALARA, one must know the dose patients receive. The determination of radiation dose in a standard way is therefore necessary so that these doses can be compared with practice, and for meaningful comparison against voluntary standards. In extreme situations, where public health needs may require mandatory standards, or regulations, the quantitative measurement and calculation of radiation dose becomes essential. How some radiation dose metrics and standards have evolved, including the value of different metrics such as entrance air kerma, organ dose, and effective dose will be presented. Recent pediatric x-ray studies, whether or not dedicated pediatric equipment is necessary, and recent initiatives by the Food and Drug Administration for pediatric population will be discussed. C1 US FDA, CDER, Rockville, MD 20857 USA. RP Suleiman, OH (reprint author), US FDA, CDER, HFD-103, Rockville, MD 20857 USA. EM SuleimanO@cder.fda.gov NR 5 TC 9 Z9 9 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0301-0449 J9 PEDIATR RADIOL JI Pediatr. Radiol. PD OCT PY 2004 VL 34 SU 3 BP S242 EP S246 DI 10.1007/s00247-004-1276-7 PG 5 WC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging SC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging GA 869RJ UT WOS:000225001400013 PM 15558268 ER PT J AU Hadjiiski, L Chan, HP Sahiner, B Helvie, MA Roubidoux, MA Blane, C Paramagul, C Petrick, N Bailey, J Klein, K Foster, M Patterson, S Adler, D Nees, A Shen, J AF Hadjiiski, L Chan, HP Sahiner, B Helvie, MA Roubidoux, MA Blane, C Paramagul, C Petrick, N Bailey, J Klein, K Foster, M Patterson, S Adler, D Nees, A Shen, J TI Improvement in radiologists' characterization of malignant and benign breast masses on serial mammograms with computer-aided diagnosis: An ROC study SO RADIOLOGY LA English DT Article DE breast neoplasms, diagnosis; computers, diagnostic aid; diagnostic radiology, observer performance ID CANCER DIAGNOSIS; TEXTURE ANALYSIS; NEURAL-NETWORK; CLASSIFICATION; FEATURES; STATISTICS; LESIONS; AREA AB PURPOSE: To evaluate the effects of computer-aided diagnosis (CAD) on radiologists' characterization of masses on serial mammograms. MATERIALS AND METHODS: Two hundred fifty-three temporal image pairs (138 malignant and,115 benign) obtained from 96 patients who had masses on serial mammograms were evaluated. The temporal pairs were formed by matchingmasses of the same view from two different examinations. Eight radiologists, and two breast imaging fellows assessed the temporal pairs with and without computer aid. The classification of accuracy was quantified by using the area under receiver operating characteristic curve (A(z))-. The statistical significance of the difference in A(z) between the different reading conditions was estimated with the Dorfman-Berbaum-Metz method for analysis of multireader multicase data and with the Student paired t test for analysis of observer-specific paired data. RESULTS: The average A(z)for radiologists' estimates of the likelihood of malignancy was 0.79 without CAD and improved to 0.84 with CAD. The improvement was statistically significant (P =.005). The corresponding average partial area index was 0.25 without CAD and improved to 0.37 with CAD. The improvement,was also statistically significant (P =.005). On the basis of Breast Imaging Reporting and Data System assessments, it was estimated that with CAD, each radiologist, on average,, reduced 0.7% (0.8'of 115) ofunnecessary biopsies a nd correctly recommended 5.7% (7.8 of 138) of additional biopsies. CONCLUSION: CAD based on analysis of interval changes can significantly increase radiologists' accuracy in classification of masses and thereby may be useful in improving correct biopsy recommendations. RSNA, 2004. 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 NR 31 TC 60 Z9 62 U1 0 U2 3 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 OCT PY 2004 VL 233 IS 1 BP 255 EP 265 DI 10.1148/radiol.2331030432 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 856WC UT WOS:000224075000033 PM 15317954 ER PT J AU Graf, LL Young, DA Kressin, DC Marlar, RA Jacob, GB Hinderling, PH AF Graf, LL Young, DA Kressin, DC Marlar, RA Jacob, GB Hinderling, PH TI Importance of using controls in in vivo experiments SO RADIOLOGY LA English DT Letter ID VITRO C1 Univ Colorado, Hlth Sci Ctr, Dept Neurol, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Prevent Med & Biometr, Denver, CO 80262 USA. Intel Corp, Capital & Capac Syst Dev, Ocotillio, AZ USA. Univ Oklahoma, Hlth Sci Ctr, Oklahoma City VA Med Ctr, Oklahoma City, OK USA. Berlex Pharmaceut, Dept Diagnost Imaging, Montville, NJ USA. US FDA, Off Clin Pharmacol & Biopharmaceut, Ctr Drug Evaluat & Res, Rockville, MD 20852 USA. RP Hinderling, PH (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Neurol, Denver, CO 80262 USA. EM hinderlingp@cder.fda.gov NR 2 TC 0 Z9 0 U1 0 U2 1 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 OCT PY 2004 VL 233 IS 1 BP 297 EP 298 DI 10.1148/radiol.2331040521 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 856WC UT WOS:000224075000040 PM 15454626 ER PT J AU Moon, H Chen, JJ Gaylor, DW Kodell, RL AF Moon, H Chen, JJ Gaylor, DW Kodell, RL TI A comparison of microbial dose-response models fitted to human data SO REGULATORY TOXICOLOGY AND PHARMACOLOGY LA English DT Article DE model uncertainty; risk assessment; benchmark dose ID RISK-ASSESSMENT; HEALTH RISK; PATHOGENS AB A study of eight mathematical dose-response models for microbial risk assessment was conducted using infectivity and illness data on a variety of microbial pathogens from published studies with human volunteers. The purpose was to evaluate variability among the models for human microbial dose-response data in order to determine whether two-parameter models might suffice for most microbial dose-response data or whether three-parameter models should generally be fitted. Model variability was measured in terms of estimated ED(01)s and ED(10)s, with the view that these effective dose levels correspond to the lower and upper limits of the 1-10% risk range generally recommended for establishing benchmark doses in risk assessment. An investigation of the ranks of the ED01, and ED10 values among the models led to the conclusion that the two-parameter models captured at least as much uncertainty as the three-parameter models for the data examined. A further evaluation of the two-parameter models did not result in the selection of one "best" model, but it did provide some insights into the models' relative behavior. The model uncertainty analysis proposed by Kang et al. [Regulat. Toxicol. Pharmacol. 32 (2000) 68] using four two-parameter models was reinforced. (C) 2004 Elsevier Inc. All rights reserved. C1 Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. Gaylor & Associates LLC, Eureka Springs, AR 72631 USA. RP Kodell, RL (reprint author), Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM rkodell@nctr.fda.gov NR 15 TC 13 Z9 13 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0273-2300 J9 REGUL TOXICOL PHARM JI Regul. Toxicol. Pharmacol. PD OCT PY 2004 VL 40 IS 2 BP 177 EP 184 DI 10.1016/j.yrtph.2004.07.003 PG 8 WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology SC Legal Medicine; Pharmacology & Pharmacy; Toxicology GA 860VR UT WOS:000224372300009 PM 15450720 ER PT J AU Lozier, J AF Lozier, J TI Gene therapy of the hemophilias SO SEMINARS IN HEMATOLOGY LA English DT Article ID HUMAN-FACTOR-VIII; COAGULATION-FACTOR-IX; SUSTAINED PHENOTYPIC CORRECTION; ADENOASSOCIATED VIRAL VECTOR; ADENOVIRUS-MEDIATED EXPRESSION; DEFICIENT MOUSE MODEL; HIGH-LEVEL EXPRESSION; IN-VIVO; B DOGS; IMMUNE TOLERANCE C1 US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Lozier, J (reprint author), US FDA, Ctr Biol Evaluat & Res, 1401 Rockville Pike HFM 340, Rockville, MD 20852 USA. EM lozier@cber.fda.gov NR 73 TC 15 Z9 17 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0037-1963 J9 SEMIN HEMATOL JI Semin. Hematol. PD OCT PY 2004 VL 41 IS 4 BP 287 EP 296 DI 10.1053/j.seminhematol.2004.07.005 PG 10 WC Hematology SC Hematology GA 870JA UT WOS:000225052200005 PM 15508114 ER PT J AU Jacobs, A Jacobson-Kram, D AF Jacobs, A Jacobson-Kram, D TI Human carcinogenic risk evaluation, part III: Assessing cancer hazard and risk in human drug development SO TOXICOLOGICAL SCIENCES LA English DT Editorial Material DE carcinogenicity; risk; drug development ID ASSAYS; MOUSE AB Assessing cancer risk for human pharmaceuticals is important because drugs are taken at pharmacologically active doses and often on a chronic basis. Epidemiologic studies on patient populations have limited value because of the long latency period for most cancers and because these studies lack sensitivity. The Center for Drug Evaluation and Research (CDER) of the U.S. Food and Drug Administration relies on short-term surrogate assays (genetic toxicology studies) to assess risk to patients involved in clinical trials and on rodent carcinogenicity studies to assess cancer risk for drug approval. Unlike some other agencies that typically perform quantitative risk assessments on chemical pollutants or pesticide products, CDER does not perform such quantitative extrapolations. Rather, the evaluation of risk is the result of an integrated assessment of what is known about the drug, and risk is considered in the context of the clinical benefit. Mode of action of carcinogenesis and thresholds for effects are important considerations. The results of carcinogenicity studies of approved products are published in the drug labeling and individual clinicians balance risk and benefit in making prescribing decisions. C1 US FDA, Ctr Drug Evaluat & Res HFD540, Rockville, MD 20857 USA. RP Jacobs, A (reprint author), US FDA, Ctr Drug Evaluat & Res HFD540, Rockville, MD 20857 USA. EM abigail.jacobs@fdahhs.gov NR 8 TC 18 Z9 19 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 OCT PY 2004 VL 81 IS 2 BP 260 EP 262 DI 10.1093/toxsci/kfh167 PG 3 WC Toxicology SC Toxicology GA 855BW UT WOS:000223948900002 PM 15141097 ER PT J AU Scallet, AC Schmued, LC Slikker, W Grunberg, N Faustino, PJ Davis, H Lester, D Pine, PS Sistare, F Hanig, JP AF Scallet, AC Schmued, LC Slikker, W Grunberg, N Faustino, PJ Davis, H Lester, D Pine, PS Sistare, F Hanig, JP TI Developmental neurotoxicity of ketamine: Morphometric confirmation, exposure parameters, and multiple fluorescent labeling of apoptotic neurons SO TOXICOLOGICAL SCIENCES LA English DT Article DE neurodegeneration; apoptosis; blood levels; anesthesia; NMDA; caspase-3 ID PERFORMANCE LIQUID-CHROMATOGRAPHY; DEPARTMENT SAFETY PROFILE; DEVELOPING BRAIN; INTRAMUSCULAR KETAMINE; PEDIATRIC SEDATION; MOUSE-BRAIN; FLUORO-JADE; CELL-DEATH; NEURODEGENERATION; CHILDREN AB Ketamine is a widely used pediatric anesthetic recently reported (C. Ikonomidou et al., 1999, Science 283, 70-74) to enhance neuronal death in neonatal rats. To confirm and extend these results, we treated four groups of PND 7 rats with seven sc doses, one every 90 min, of either saline, 10 mg/kg ketamine, 20 mg/kg ketamine, or a single dose of 20 mg/kg ketamine. The repeated doses of 20 mg/kg ketamine increased the number of silver-positive (degenerating) neurons in the dorsolateral thalamus to a degree comparable to previous results (Ikonomidou et al., 1999, Science 283, 70-74), i.e., 28-fold vs. 31-fold respectively. However, blood levels of ketamine immediately after the repeated 20 mg/kg doses were about 14 mug/ml, about seven-fold greater than anesthetic blood levels in humans (J. M. Malinovsky et al., 1996, Br. J. Anaesth. 77, 203-207; R. A. Mueller and R. Hunt, 1998, Pharmacol. Biochem. Behav. 60, 15-22). Levels of ketamine in blood following exposure to the multiple 10 mg/kg doses of ketamine or to a single 20 mg/kg dose ranged around 2-5 mug/ml; although these blood levels are close to an anesthetic level in humans, they failed to produce neurodegeneration. To investigate the mode of ketamine-induced neuronal death, coronal sections were stained with both Fluoro-Jade B (a green fluorescent stain selective for neurodegeneration) and DAPI (a blue DNA stain), as well as for caspase-3 (using an antisera labeled red with rhodamine). These histochemical results confirmed the developmental neurotoxicity of ketamine, demonstrated that Fluoro-Jade B (FJ-B), like silver methods, successfully stained degenerating neurons in neonatal rats, and indicated that ketamine acts by increasing the rate of neuronal apoptosis. C1 US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. USUHS, Bethesda, MD 20892 USA. US FDA, CDER, Silver Spring, MD 20993 USA. NIDA, NIH, Bethesda, MD 20892 USA. RP Scallet, AC (reprint author), US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, 3900 NCTR Dr, Jefferson, AR 72079 USA. EM AScallet@nctr.fda.gov NR 45 TC 154 Z9 168 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD OCT PY 2004 VL 81 IS 2 BP 364 EP 370 DI 10.1093/toxsci/kfh224 PG 7 WC Toxicology SC Toxicology GA 855BW UT WOS:000223948900014 PM 15254342 ER PT J AU Buehler, PW Alayash, AI AF Buehler, PW Alayash, AI TI Toxicities of hemoglobin solutions: in search of in-vitro and in-vivo model systems SO TRANSFUSION LA English DT Review ID CROSS-LINKED HEMOGLOBIN; CELL-FREE HEMOGLOBIN; SUPEROXIDE DISMUTASE-CATALASE; POLYMERIZED PYRIDOXYLATED HEMOGLOBIN; ISCHEMIA-REPERFUSION INJURY; REGIONAL BLOOD-CIRCULATION; NITRIC-OXIDE SCAVENGER; STROMA-FREE HEMOGLOBIN; POLYOXYETHYLENE CONJUGATE; HEMORRHAGIC-SHOCK AB Several hemoglobin-based oxygen carriers (HBOCs) have been developed with a rationale focused on exploiting one or more physicochemical properties (e.g., oxygen affinity, molecular weight, viscosity, and colloid osmotic pressure) resulting from the chemical or recombinant modification of hemoglobin (Hb). Several chemically modified Hbs have reached late stages of clinical evaluation in the United States and Canada. These Hbs, in general, demonstrated mixed preclinical safety and efficacy, and reasonable safety in Phase I trials. However, as clinical development shifted into later stages, an undesirable safety and efficacy profile became clear in patient populations studied, and as a result some products were withdrawn from further clinical pursuit. Several questions still remain unanswered regarding the safety of Hb products for their proposed clinical indication(s). For example, 1) were preclinical studies predictive of clinical outcome? And, 2) were the most appropriate preclinical studies performed to predict clinical outcome? The primary objectives of this analysis are to explore prelinical safety issues associated with HBOCs and provide an overview of the in-vitro and in-vivo models employed. The methods for obtaining data to serve as a basis for discussion are compiled from a literature-based survey of safety and efficacy derived from biochemical, cellular, and whole animal assessment of HBOCs. Results from this overview of a vast body of published data may provide a means for identifying critical preclinical safety issues, which may ultimately lead to identification of potential limitations in the effective clinical use of certain HBOCs. C1 USDA, ARS, Lab Biochem & Vasc Biol, Div Hematol, Bethesda, MD USA. USDA, ARS, Ctr Biol Evaluat & Res, Bethesda, MD USA. RP Alayash, AI (reprint author), NIH, Bldg 29,Room 112,8800 Rockville Pike, Bethesda, MD 20892 USA. EM alayash@cber.fda.gov NR 154 TC 61 Z9 63 U1 1 U2 7 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD OCT PY 2004 VL 44 IS 10 BP 1516 EP 1530 DI 10.1111/j.1537-2995.2004.04081.x PG 15 WC Hematology SC Hematology GA 858DX UT WOS:000224171600019 PM 15383027 ER PT J AU Babu, U Dalloul, RA Okamura, M Lillehoj, HS Xie, H Raybourne, RB Gaines, D Heckert, RA AF Babu, U Dalloul, RA Okamura, M Lillehoj, HS Xie, H Raybourne, RB Gaines, D Heckert, RA TI Salmonella enteritidis clearance and immune responses in chickens following Salmonella vaccination and challenge SO VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY LA English DT Article DE Salmonella enteritidis; vaccine; chicken; flagella; lymphocyte proliferation ID ENTERICA SEROVAR TYPHIMURIUM; T-CELL RESPONSES; MEDIATED-IMMUNITY; LAYING HENS; WILD-TYPE; INFECTION; VACCINES; MICE; STRAIN; PROTECTION AB Our previous work showed that the cell-mediated immunity (CMI) was enhanced by live Salmonella vaccine (LV). The objective of this study was to evaluate the impact of live and killed Salmonella vaccines on Salmonella enteritidis (SE) clearance and to determine if the clearance was mediated by cell-mediated and/or humoral immunity. Chickens were first immunized at 2 weeks of age followed by a booster dose at 4 weeks, challenged with live SE 2 weeks later (6-week-old) and tested for CMI, antibody response and SE clearance 1-week post SE-challenge (7-week-old). Spleen cell proliferation induced by SE-flagella and Concanavalin A (Con A) were significantly higher and SE shedding was significantly lower in the LV group. The splenic CD3 population was significantly lower and B cells were higher in the control group compared to all the SE-challenged groups (with and without vaccination). Serum antibody to SE-flagella and envelope were significantly higher in the KV group compared to all the other groups. These results suggest that LV protects against SE infection, probably by enhancing the CMI (C) 2004 Elsevier B.V. All rights reserved. C1 US FDA, Ctr Food & Appl Nutr, Laurel, MD 20708 USA. USDA ARS, Anim Parasit Dis Lab, Anim & Nat Resources Inst, Beltsville, MD 20705 USA. Univ Maryland, Virginia Maryland Reg Coll Vet Med, College Pk, MD 20742 USA. RP Babu, U (reprint author), US FDA, Ctr Food & Appl Nutr, HFS 326,8301 Muirkirk Rd, Laurel, MD 20708 USA. EM usb@cfsan.fda.gov OI Dalloul, Rami/0000-0003-4690-9220 NR 34 TC 41 Z9 42 U1 0 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-2427 J9 VET IMMUNOL IMMUNOP JI Vet. Immunol. Immunopathol. PD OCT PY 2004 VL 101 IS 3-4 BP 251 EP 257 DI 10.1016/j.vetimm.2004.05.002 PG 7 WC Immunology; Veterinary Sciences SC Immunology; Veterinary Sciences GA 857XZ UT WOS:000224154600013 PM 15350755 ER PT J AU Trontell, A AF Trontell, A TI Expecting the unexpected - Drug safety, pharmacovigilance, and the prepared mind SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 US FDA, Off Drug Safety, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Trontell, A (reprint author), US FDA, Off Drug Safety, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. NR 1 TC 53 Z9 58 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 SEP 30 PY 2004 VL 351 IS 14 BP 1385 EP 1387 DI 10.1056/NEJMp048187 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 857XT UT WOS:000224153900005 PM 15459298 ER PT J AU Yan, EC Chen, L AF Yan, EC Chen, L TI A cost-related approach for evaluating drug development programs SO STATISTICS IN MEDICINE LA English DT Article DE asymmetric loss; cost and benefit; cost function; posterior distribution ID CONTAMINATED SOILS; RULE AB Most pharmaceutical statisticians make a contribution to drug development at the study level by designing and analysing clinical studies. There is less involvement at the drug project level, especially when it comes to making a strategic decision for a drug development program. Motivated by the assessment of drug safety, this paper presents a new decision rule on whether or not to continue developing a new drug based on a cost function. The cost function takes into account both type I and type 11 errors in a decision making problem. It also incorporates both the cost and benefit from a drug development program. This cost-benefit approach enables company senior management to evaluate a drug program objectively and make decisions in a quantitative and rational manner. The probabilities of making correct decisions are illustrated by using a real data example. Copyright (C) 2004 John Wiley Sons, Ltd. C1 Florida Int Univ, Miami, FL 33199 USA. Pfizer Inc, La Jolla Labs, San Diego, CA 92121 USA. RP Chen, L (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Pharmacoepidemiol & Stat Sci, Off Biostat, HFD-705,12720 Twinbrook Pkwy, Rockville, MD 20857 USA. EM chenli@cder.fda.gov NR 7 TC 2 Z9 2 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD SEP 30 PY 2004 VL 23 IS 18 BP 2863 EP 2873 DI 10.1002/sim.1902 PG 11 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 851FC UT WOS:000223670000006 PM 15344191 ER PT J AU Vodkin, LO Khanna, A Shealy, R Clough, SJ Gonzalez, DO Philip, R Zabala, G Thibaud-Nissen, F Sidarous, M Stromvik, MV Shoop, E Schmidt, C Retzel, E Erpelding, J Shoemaker, RC Rodriguez-Huete, AM Polacco, JC Coryell, V Keim, P Gong, G Liu, L Pardinas, J Schweitzer, P AF Vodkin, LO Khanna, A Shealy, R Clough, SJ Gonzalez, DO Philip, R Zabala, G Thibaud-Nissen, F Sidarous, M Stromvik, MV Shoop, E Schmidt, C Retzel, E Erpelding, J Shoemaker, RC Rodriguez-Huete, AM Polacco, JC Coryell, V Keim, P Gong, G Liu, L Pardinas, J Schweitzer, P TI Microarrays for global expression constructed with a low redundancy set of 27,500 sequenced cDNAs representing an array of developmental stages and physiological conditions of the soybean plant SO BMC GENOMICS LA English DT Article ID GENE-EXPRESSION; UNIFIED CLASSIFICATION; PROTEIN FAMILIES; METAFAM; GENERATION; RESOURCE; GENOMICS; PROGRAM AB Background: Microarrays are an important tool with which to examine coordinated gene expression. Soybean ( Glycine max) is one of the most economically valuable crop species in the world food supply. In order to accelerate both gene discovery as well as hypothesis-driven research in soybean, global expression resources needed to be developed. The applications of microarray for determining patterns of expression in different tissues or during conditional treatments by dual labeling of the mRNAs are unlimited. In addition, discovery of the molecular basis of traits through examination of naturally occurring variation in hundreds of mutant lines could be enhanced by the construction and use of soybean cDNA microarrays. Results: We report the construction and analysis of a low redundancy 'unigene' set of 27,513 clones that represent a variety of soybean cDNA libraries made from a wide array of source tissue and organ systems, developmental stages, and stress or pathogen-challenged plants. The set was assembled from the 5' sequence data of the cDNA clones using cluster analysis programs. The selected clones were then physically reracked and sequenced at the 3' end. In order to increase gene discovery from immature cotyledon libraries that contain abundant mRNAs representing storage protein gene families, we utilized a high density filter normalization approach to preferentially select more weakly expressed cDNAs. All 27,513 cDNA inserts were amplified by polymerase chain reaction. The amplified products, along with some repetitively spotted control or 'choice' clones, were used to produce three 9,728-element microarrays that have been used to examine tissue specific gene expression and global expression in mutant isolines. Conclusions: Global expression studies will be greatly aided by the availability of the sequence-validated and low redundancy cDNA sets described in this report. These cDNAs and ESTs represent a wide array of developmental stages and physiological conditions of the soybean plant. We also demonstrate that the quality of the data from the soybean cDNA microarrays is sufficiently reliable to examine isogenic lines that differ with respect to a mutant phenotype and thereby to define a small list of candidate genes potentially encoding or modulated by the mutant phenotype. C1 Univ Illinois, Dept Crop Sci, Urbana, IL 61801 USA. Univ Minnesota, Ctr Computat Genom & Bioinformat, Minneapolis, MN 55455 USA. Iowa State Univ, USDA ARS, Dept Agron, Ames, IA 50011 USA. Univ Missouri, Dept Biochem, Columbia, MO 65211 USA. No Arizona Univ, Dept Biol, Flagstaff, AZ 86011 USA. Univ Illinois, Keck Ctr Comparat & Funct Genom, Urbana, IL 61801 USA. Epictr, Madison, WI 53713 USA. Univ Illinois, USDA ARS, Natl Soybean Res Lab, Urbana, IL 61801 USA. US FDA, Rockville, MD 20850 USA. Inst Genome Res, Rockville, MD 20850 USA. McGill Univ, Dept Plant Sci, Ste Anne De Bellevue, PQ H9X 3V9, Canada. Macalester Coll, St Paul, MN 55105 USA. Univ Nevada, Sch Med, Dept Microbiol, Reno, NV 89557 USA. Cornell Univ, Biotechnol Resource Ctr, Ithaca, NY 14853 USA. RP Vodkin, LO (reprint author), Univ Illinois, Dept Crop Sci, Urbana, IL 61801 USA. EM l-vodkin@uiuc.edu; anupama.khanna@epicentre.com; l-vodkin@uiuc.edu; sjclough@uiuc.edu; dogonzal@uiuc.edu; philipreena@yahoo.com; g-zabala@uiuc.edu; fthibaud@tigr.org; sidarous@uiuc.edu; martina.stromvik@mcgill.ca; schoop@macalester.edu; shoop@macalesler.edu; ernest@mail.ahc.umn.edu; rcsshoe@iastate.edu; rcsshoe@iastate.edu; PolaccoJ@missouri.edu; PolaccoJ@missouri.edu; Paul.Keim@nau.edu; Paul.Keim@nau.edu; ligong@uiuc.edu; leiliu@uiuc.edu; l-vodkin@uiuc.edu; pas48@cornell.edu RI Clough, Steven/E-6815-2011; Keim, Paul/A-2269-2010 NR 28 TC 54 Z9 64 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2164 J9 BMC GENOMICS JI BMC Genomics PD SEP 29 PY 2004 VL 5 AR 73 DI 10.1186/1471-2164-5-73 PG 18 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 868EG UT WOS:000224896300001 PM 15453914 ER PT J AU Polder, JA Wood, JJ Braun, MM AF Polder, JA Wood, JJ Braun, MM TI Infections associated with musculoskeletal-tissue allografts SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 US FDA, Rockville, MD 20852 USA. RP Polder, JA (reprint author), US FDA, Rockville, MD 20852 USA. EM polder@cber.fda.gov NR 1 TC 0 Z9 0 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 SEP 23 PY 2004 VL 351 IS 13 BP 1359 EP 1359 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 855TP UT WOS:000223997700026 ER PT J AU Brinker, AD Mackey, AC Prizont, R AF Brinker, AD Mackey, AC Prizont, R TI Tegaserod and ischemic colitis SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID SUMATRIPTAN C1 US FDA, Rockville, MD 20857 USA. RP Brinker, AD (reprint author), US FDA, Rockville, MD 20857 USA. EM brinkera@cder.fda.gov NR 5 TC 16 Z9 16 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 SEP 23 PY 2004 VL 351 IS 13 BP 1361 EP 1363 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 855TP UT WOS:000223997700033 PM 15385670 ER PT J AU Leung, AKW White, EL Ross, LJ Reynolds, RC DeVito, JA Borhani, DW AF Leung, AKW White, EL Ross, LJ Reynolds, RC DeVito, JA Borhani, DW TI Structure of Mycobacterium tuberculosis FtsZ reveals unexpected, G protein-like conformational switches SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE FtsZ; crystal structure; tubulin; G-protein; conformational switch ID BACTERIAL-CELL-DIVISION; ELECTRON-DENSITY MAPS; ALPHA-BETA-TUBULIN; CRYSTAL-STRUCTURE; GTP HYDROLYSIS; MOLECULAR REPLACEMENT; Z-RING; ACTIVATION; RESOLUTION; COMPLEX AB We report three crystal structures of the Mycobacterium tuberculosis cell division protein FtsZ, as the citrate, GDP, and GTPgammaS complexes, determined at 1.89, 2.60, and 2.08 Angstrom resolution. MtbFtsZ crystallized as a tight, laterally oriented dimer distinct from the longitudinal polymer observed for alphabeta-tubulin. Mutational data on Escherichia coli FtsZ suggest that this dimer interface is important for proper protofilament and "Z-ring" assembly and function. An alpha-to-beta secondary structure conformational switch at the dimer interface is spatially analogous to, and has many of the hallmarks of, the Switch I conformational changes exhibited by G-proteins upon activation. The presence of a gamma-phosphate in the FtsZ active site modulates the conformation of the "tubulin" loop T3 (spatially analogous to the G-protein Switch II); T3 switching upon gamma-phosphate ligation is directly coupled to the alpha-to-beta switch by steric overlap. The dual conformational switches observed here for the first time in an FtsZ link GTP binding and hydrolysis to FtsZ (and tubulin) lateral assembly and Z-ring contraction, and they are suggestive of an underappreciated functional analogy between FtsZ, tubulin and G-proteins. (C) 2004 Elsevier Ltd. All rights reserved. C1 So Res Inst, Drug Discovery Div, Birmingham, AL 35205 USA. US FDA, Lab Mycobacteria, Bethesda, MD 20892 USA. RP Borhani, DW (reprint author), Abbot Biores Ctr, 100 Res Dr, Worcester, MA 01605 USA. EM david.borhani@alum.mit.edu RI Leung, Adelaine/F-4132-2011; OI Leung, Adelaine/0000-0002-2849-4474; Borhani, David/0000-0002-8486-8792 NR 53 TC 52 Z9 55 U1 0 U2 9 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD SEP 17 PY 2004 VL 342 IS 3 BP 953 EP 970 DI 10.1016/j.jmb.2004.07.061 PG 18 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 853OX UT WOS:000223838000020 PM 15342249 ER PT J AU Rothmann, M AF Rothmann, M TI Design and analysis of non-inferiority mortality trials in oncology - Author's reply SO STATISTICS IN MEDICINE LA English DT Letter C1 US FDA, Rockville, MD 20857 USA. RP Rothmann, M (reprint author), US FDA, HFD-711,5600 Fishers Lane, Rockville, MD 20857 USA. NR 8 TC 1 Z9 1 U1 0 U2 2 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 17 PY 2004 VL 23 IS 17 BP 2774 EP 2778 DI 10.1002/sim.1898 PG 5 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 849GB UT WOS:000223525600011 ER PT J AU Brinker, A Avigan, M AF Brinker, A Avigan, M TI Epidemiology of ischaemic colitis SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS LA English DT Letter ID IRRITABLE-BOWEL-SYNDROME C1 US FDA, Rockville, MD 20857 USA. RP Brinker, A (reprint author), US FDA, Rockville, MD 20857 USA. EM brinkera@cder.fda.gov NR 5 TC 6 Z9 6 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0269-2813 J9 ALIMENT PHARM THERAP JI Aliment. Pharmacol. Ther. PD SEP 15 PY 2004 VL 20 IS 6 BP 697 EP 698 DI 10.1111/j.1365-2036.2004.02117.x PG 2 WC Gastroenterology & Hepatology; Pharmacology & Pharmacy SC Gastroenterology & Hepatology; Pharmacology & Pharmacy GA 851VE UT WOS:000223713300014 PM 15352919 ER PT J AU Krynitsky, AJ Niemann, RA Nortrup, DA AF Krynitsky, AJ Niemann, RA Nortrup, DA TI Determination of perchlorate anion in foods by ion chromatography-tandem mass spectrometry SO ANALYTICAL CHEMISTRY LA English DT Article ID DRINKING-WATER; INHIBITION; EXTRACTION AB A rapid, sensitive, and specific method was developed for determining perchlorate anion in lettuce, cantaloupe, bottled water, and milk. A test portion of chopped crop homogenate was extracted with diluted nitric acid and filtered. Milk proteins were precipitated with acetonitrile, and the supernatant, after centrifugation, was cleaned up on a graphitized carbon solid-phase extraction column. Water samples were analyzed directly. All test solutions were syringe filtered and mixed with an O-18(4)-labeled perchlorate internal standard before ion chromatography-tandem mass spectrometry. A strong anion exchange column eluted with 100 mM ammonium acetate in 50:50 (v/v) acetonittile/water was interfaced via electrospray ionization to a triple stage quadrupole mass spectrometer operated in the negative ion mode. The labeled internal standard corrected for any sample matrix effects on measured signals. Four parent-to-product ion transitions, for loss of oxygen, were monitored for native and O-18(4)-labeled perchlorate anion, respectively: Cl-35-perchlorate, m/z 99 --> 83 and 107 --> 89; 37 Cl-perchlorate, m/z 101 --> 85 and 109 --> 91. The limit of quantitation was 1.0 mug/kg in lettuce, 2.0mug/kg in cantaloupe, 0.50mug/L in bottled water, and 3.0 mug/L in milk. Native perchlorate was recovered from fortified test portions in the range 93-107% for lettuce, 107-114% for cantaloupe, 100-115% for bottled water, and 99-101% for milk. C1 US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Krynitsky, AJ (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM Alex.Krynitsky@cfsan.fda.gov NR 15 TC 78 Z9 89 U1 4 U2 27 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 2004 VL 76 IS 18 BP 5518 EP 5522 DI 10.1021/ac049281+ PG 5 WC Chemistry, Analytical SC Chemistry GA 854UL UT WOS:000223928800037 PM 15362915 ER PT J AU Schwahn, BC Laryea, MD Chen, ZT Melnyk, S Pogribny, I Garrow, T James, SJ Rozen, R AF Schwahn, BC Laryea, MD Chen, ZT Melnyk, S Pogribny, I Garrow, T James, SJ Rozen, R TI Betaine rescue of an animal model with methylenetetrahydrofolate reductase deficiency SO BIOCHEMICAL JOURNAL LA English DT Article DE betaine supplementation; brain development; hyperhomocysteinaemia; methylenetetrahydrofolate reductase (MTHFR); remethylation ID COULOMETRIC ELECTROCHEMICAL DETECTION; FOLIC-ACID DEFICIENCY; HOMOCYSTEINE METHYLTRANSFERASE; METHIONINE METABOLISM; CHOLINE AVAILABILITY; MOUSE-BRAIN; HPLC METHOD; GLOBAL DNA; RAT-BRAIN; LOCALIZATION AB MTHFR (methylenetetrahydrofolate reductase) catalyses the synthesis of 5-methyltetrahydrofolate, the folate derivative utilized in homocysteine remethylation to methionine. A severe deficiency of MTHFR results in hyperhomocysteinaemia and homocystinuria. Betaine supplementation has proven effective in ameliorating the biochemical abnormalities and the clinical course in patients with this deficiency. Mice with a complete knockout of MTHFR serve as a good animal model for homocystinuria; early postnatal death of these mice is common, as with some neonates with low residual MTHFR activity. We attempted to rescue Mthfr-/- mice from postnatal death by betaine supplementation to their mothers throughout pregnancy and lactation. Betaine decreased the mortality of Mthfr-/- mice from 83 % to 26 % and significantly improved somatic development from postnatal day 1, compared with Mthfr-/- mice from unsupplemented dams. Biochemical evaluations demonstrated higher availability of betaine in suckling pups, decreased accumulation of homocysteine, and decreased flux through the trans-sulphuration pathway in liver and brain of Mthfr-/- pups from betaine-supplemented dams. We observed disturbances in proliferation and differentiation in the cerebellum and hippocampus in the knockout mice; these changes were ameliorated by betaine supplementation. The dramatic effects of betaine on survival and growth, and the partial reversibility of the biochemical and developmental anomalies in the brains of MTHFR-deficient mice, emphasize an important role for choline and betaine depletion in the pathogenesis of homocystinuria due to MTHFR deficiency. C1 McGill Univ, Montreal Childrens Hosp, Dept Pediat, Montreal, PQ H3Z 2Z3, Canada. McGill Univ, Montreal Childrens Hosp, Dept Human Genet & Biol, Montreal, PQ H3Z 2Z3, Canada. Univ Dusseldorf, Childrens Hosp, Clin Gen Pediat, D-4000 Dusseldorf, Germany. Univ Arkansas Med Sci, Dept Pediat, Little Rock, AR 72205 USA. Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. Univ Illinois, Dept Food Sci & Human Nutr, Urbana, IL USA. RP Rozen, R (reprint author), McGill Univ, Montreal Childrens Hosp, Dept Pediat, 4060 Ste Catherine W,Room 200, Montreal, PQ H3Z 2Z3, Canada. EM rima.rozen@mcgill.ca NR 40 TC 45 Z9 48 U1 0 U2 3 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON W1N 3AJ, ENGLAND SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD SEP 15 PY 2004 VL 382 BP 831 EP 840 PN 3 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 859AW UT WOS:000224235300007 PM 15217352 ER PT J AU Kioi, M Kawakami, K Puri, RK AF Kioi, M Kawakami, K Puri, RK TI Analysis of antitumor activity of an interleukin-13 (IL-13) receptor-targeted cytotoxin composed of IL-13 antagonist and Pseudomonas exotoxin SO CLINICAL CANCER RESEARCH LA English DT Article ID CELL CARCINOMA-CELLS; HIGH-AFFINITY INTERLEUKIN-4; CHIMERIC PROTEIN; MUTATED FORM; CANCER-CELLS; GLIOMA-CELLS; HUMAN BREAST; TUMOR-CELLS; NECK-CANCER; GROWTH AB We have shown previously that a chimeric fusion protein composed of human interleukin-13 (IL-13) and Pseudomonas exotoxin (PE), termed IL-13 cytotoxin (IL13-PE38), is specifically cytotoxic to various cancer cell lines and primary cell cultures derived from a variety of solid cancers. In addition, we have shown that IL-13 mutant IL-13E13K, in which glutamic acid (E) residue at position 13 of IL-13 molecule was substituted by a lysine (K), is a powerful antagonist of IL-13 and binds to IL-13 receptor with a higher affinity compared with wild-type IL-13. In this study, we have generated an IL-13 cytotoxin IL13E13K-PE38, in which IL-13 antagonist is fused to PE to determine whether this molecule has improved cytotoxicity to tumor cells compared with wild type (wt)IL13-PE38. Highly purified IL13E13K-PE38 was tested in various tumor cell lines including seven glioblastoma multiforme cell lines to compare its binding to the cells, in vitro cytotoxicity, in vivo antitumor activity, and safety in mouse model with wtIL13-PE38. IL13E13K-PE38 bound to U251MG and IL-13Ralpha2 chain-transfected tumor cell lines with 3 to 10 times higher affinity compared with wtIL13-PE38.. However, IL13E13K-PE38 did not show higher cytotoxicity compared with wtIL13PE38 in glioblastoma multiforme or any other cell lines tested. The antitumor activity of IL13E13K-PE38, when administered intraperitoneally to nude mice bearing U251 tumors, was also similar to wtIL13-PE38. Some improvement in antitumor activity was observed when lower doses of IL13E13K-PE38 were injected intratumorally in subcutaneous tumors. These results indicate that in general, IL13E13K-PE38 mediates similar cytotoxicity and antitumor activity to wtIL13-PE38 despite its improved binding affinity to IL-13 receptors. C1 US FDA, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Puri, RK (reprint author), US FDA, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, NIH Bldg 29B,Room 2NN10,29 Lincoln Dr MSC 4555, Bethesda, MD 20892 USA. EM puri@cber.fda.gov OI Kioi, Mitomu/0000-0002-7981-3340 NR 27 TC 30 Z9 30 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD SEP 15 PY 2004 VL 10 IS 18 BP 6231 EP 6238 DI 10.1158/1078-0432.CCR-04-0700 PN 1 PG 8 WC Oncology SC Oncology GA 856XU UT WOS:000224080200034 PM 15448012 ER PT J AU Badano, A Fifadara, DH AF Badano, A Fifadara, DH TI Comparison of conoscopic, telescopic, and goniometric methods for measuring angular emissions from medical liquid-crystal displays SO APPLIED OPTICS LA English DT Article AB Although emissive displays exhibit a quasi-Lambertian emission, the anisotropy of the electro-optic effect that controls light transmission in liquid-crystal displays (LCDs) causes the pixel luminance to vary, sometimes strongly, with the viewing angle. These variations are not identical for all gray levels and can eventually cause gray-scale inversions. We compare methods currently used to measure angular luminance variations in the LCDs: the goniometric method, the telescopic method, and the conoscopic or Fourier-optics method. We show that, although they are the same at the high end of the gray scale, the results of the three methods differ significantly at lower gray levels. In some cases the measured luminance was as much as 38% higher for the conoscopic system, and 26% higher for the telescopic method, than the value obtained with the goniometric approach. This shift in the minimum luminance measurement translates directly into the contrast ratio, affecting the reporting of technical specifications of display systems. (C) 2004 Optical Society of America. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Badano, A (reprint author), US FDA, Ctr Devices & Radiol Hlth, 12720 Twinbrook Pkwy, Rockville, MD 20857 USA. EM agb@cdrh.fda.gov OI badano, aldo/0000-0003-3712-6670 NR 12 TC 6 Z9 6 U1 0 U2 1 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1559-128X EI 2155-3165 J9 APPL OPTICS JI Appl. Optics PD SEP 10 PY 2004 VL 43 IS 26 BP 4999 EP 5005 DI 10.1364/AO.43.004999 PG 7 WC Optics SC Optics GA 853DH UT WOS:000223806100003 PM 15468700 ER PT J AU Stingley, RL Khan, AA Cerniglia, CE AF Stingley, RL Khan, AA Cerniglia, CE TI Molecular characterization of a phenanthrene degradation pathway in Mycobacterium vanbaalenii PYR-1 SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE Mycobacterium vanbaalenii; PAH degradation; phenanthrene degradation ID SP STRAIN PYR-1; POLYCYCLIC AROMATIC-HYDROCARBONS; NUCLEOTIDE-SEQUENCE; FUNCTIONAL-ANALYSIS; GENES; BIODEGRADATION; IDENTIFICATION; CLONING; DIOXYGENASE; EXPRESSION AB Mycobacterium vanbaalenii PYR-1 is capable of degrading a number of polycyclic aromatic hydrocarbons (PAHs) to ring cleavage metabolites via multiple pathways. Genes for the large and small subunits of a pyrene dioxygenase, nidA and nidB, respectively, were previously identified in M. vanbaalenii PYR-1 [Appl. Environ. Microbiol. 67 (2001) 3577]. A library of the M. vanbaalenii PYR-1 genome was constructed in a fosmid vector to identify additional genes involved in PAH degradation. Twelve fosmid clones containing nidA were identified by Southern hybridization. Sequence analysis of one nidA-positive clone, pFOS608, revealed a number of additional genes involved in PAH degradation. At this locus, one putative operon contained genes involved in phthalate degradation, and another contained genes encoding a putative ABC transporter(s). A number of the genes found in this region are homologous to those involved in phenanthrene degradation via the phthalic acid pathway. The majority of phenanthrene degradation genes were located between putative transposase genes. In Escherichia coli, pFOS608 converted phenanthrene into phenanthrene cis-3,4-dihydrodiol, and converted 1-hydroxy-2-naphthoic acid into 2'-carboxybenzalpyruvate, 2-carboxybenzaldehyde, and phthalic acid. A subclone containing nidA and nidB converted phenanthrene into phenanthrene cis-3,4-dihydrodiol, suggesting that the NidAB dioxygenase is responsible for an initial attack on phenanthrene. This study is the first to identify genes responsible for the degradation of phenanthrene via the phthalic acid pathway in Mycobacterium species. Published by Elsevier Inc. C1 US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Khan, AA (reprint author), US FDA, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM ashraf@nctr.fda.gov NR 32 TC 70 Z9 93 U1 1 U2 34 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD SEP 10 PY 2004 VL 322 IS 1 BP 133 EP 146 DI 10.1016/j.bbrc.2004.07.089 PG 14 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 849ZS UT WOS:000223581000020 PM 15313184 ER PT J AU Fan, YX Wong, L Deb, TB Johnson, GR AF Fan, YX Wong, L Deb, TB Johnson, GR TI Ligand regulates epidermal growth factor receptor kinase specificity - Activation increases preference for GAB1 and SHC versus autophosphorylation sites SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-TYROSINE KINASES; HUMAN INSULIN-RECEPTOR; SIGNAL-TRANSDUCTION; CRYSTAL-STRUCTURE; EGF-RECEPTOR; SUBSTRATE PHOSPHORYLATION; CONFORMATIONAL-CHANGE; CATALYTIC SUBUNIT; IN-VITRO; DOMAIN AB The epidermal growth factor receptor (EGFR) kinase catalyzes phosphorylation of tyrosines in its C terminus and in other cellular targets upon epidermal growth factor (EGF) stimulation. Here, by using peptides derived from EGFR autophosphorylation sites and cellular substrates, we tested the hypothesis that ligand may function to regulate EGFR kinase specificity by modulating the binding affinity of peptide sequences to the active site. Measurement of the steady-state kinetic parameters, K-m and k(cat), revealed that EGF did not affect the binding of EGFR peptides but increased the binding affinity for peptides corresponding to the major EGFR-mediated phosphorylation sites of the adaptor proteins Gab1 (Tyr-627) and Shc (Tyr-317), and for peptides containing the previously identified optimal EGFR kinase substrate sequence EEEEYFELV (3-7-fold). Conversely, EGF stimulation increased k(cat) similar to5-fold for all peptides. Thus, ligand changed the relative preference of the EGFR kinase for substrates as evidenced by EGF increases of similar to5-fold in the specificity constants (k(cat)/K-m) for EGFR peptides, whereas similar to 15 - 40-fold increases were observed for other peptides, such as Gab1 Tyr-627. Furthermore, we demonstrate that EGF (i) increased the binding affinity of EGFR to Gab1 Tyr-627 and Shc Tyr-317 sites in purified GST fusion proteins similar to 4-6-fold, and (ii) EGF significantly enhanced the phosphorylation of these sites, relative to EGFR autophosphorylation, in cell lysates containing the full-length Gab1 and Shc proteins. Analysis of peptides containing amino acid substitutions indicated that residues C-terminal to the target tyrosine were critical for EGF-stimulated increases in substrate binding and regulation of kinase specificity. To our knowledge, this represents the first demonstration that ligand can alter specificity of a receptor kinase toward physiologically relevant targets. C1 US FDA, Div Therapeut Prot, Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. RP Fan, YX (reprint author), US FDA, Div Therapeut Prot, Ctr Drug Evaluat & Res, Bldg 29A,Rm 3B-20,8800 Rockville Pike, Bethesda, MD 20892 USA. EM fany@cber.fda.gov; johnsong@cber.fda.gov NR 53 TC 35 Z9 37 U1 0 U2 2 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 10 PY 2004 VL 279 IS 37 BP 38143 EP 38150 DI 10.1074/jbc.M405760200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 851KN UT WOS:000223684100012 PM 15231819 ER PT J AU Young, JF Tong, W Fang, H Xie, Q Pearce, B Hashemi, R Beger, RD Cheeseman, MA Chen, JJ Chang, YCI Kodell, RL AF Young, JF Tong, W Fang, H Xie, Q Pearce, B Hashemi, R Beger, RD Cheeseman, MA Chen, JJ Chang, YCI Kodell, RL TI Building an organ-specific carcinogenic database for sar analyses SO JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A-CURRENT ISSUES LA English DT Article ID POTENCY DATABASE; PREDICTIVE TOXICOLOGY; DATA QUALITY; BIOASSAYS; RECEPTOR; PROGRAM; BINDING AB FDA reviewers need a means to rapidly predict organ-specific carcinogenicity to aid in evaluating new chemicals submitted for approval. This research addressed the building of a database to use in developing a predictive model for such an application based on structure-activity relationships (SAR). The Internet availability of the Carcinogenic Potency Database (CPDB) provided a solid foundation on which to base such a model. The addition of molecular structures to the CPDB provided the extra ingredient necessary for SAR analyses. However, the CPDB had to be compressed from a multirecord to a single record per chemical database; multiple records representing each gender, species, route of administration, and organ-specific toxicity had to be summarized into a single record for each study. Multiple studies on a single chemical had to be further reduced based on a hierarchical scheme. Structural cleanup involved removal of all chemicals that would impede the accurate generation of SAR type descriptors from commercial software programs; that is, inorganic chemicals, mixtures, and organometallics were removed. Counterions such as Na, K, sulfates, hydrates, and salts were also removed for structural consistency. Structural modification sometimes resulted in duplicate records that also had to be reduced to a single record based on the hierarchical scheme. The modified database containing 999 chemicals was evaluated for liver-specific carcinogenicity using a variety of analysis techniques. These preliminary analyses all yielded approximately the same results with an overall predictability of about 63%, which was comprised of a sensitivity of about 30% and a specificity of about 77%. C1 US FDA, Div Biometry & Risk Assessment, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Logicon ROW Sci, Jefferson, AR USA. Armstrong Atlantic State Univ, Dept Comp Sci, Savannah, GA USA. US FDA, Div Chem, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. US FDA, Div Food Contact Notificat, Off Food Addit Safety, Ctr Food Safety & Appl Nutr, College Pk, MD USA. Acad Sinica, Inst Stat Sci, Taipei 11529, Taiwan. RP Young, JF (reprint author), US FDA, Div Biometry & Risk Assessment, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM Jyoung@nctr.fda.gov NR 16 TC 9 Z9 10 U1 0 U2 0 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 SEP 10 PY 2004 VL 67 IS 17 BP 1363 EP 1389 DI 10.1080/15287390490471479 PG 27 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 846IT UT WOS:000223309900004 PM 15371237 ER PT J AU Shinoda, K Xin, KQ Jounai, N Kojima, Y Tamura, Y Okada, E Kawamoto, S Okuda, K Klinman, D Okuda, K AF Shinoda, K Xin, KQ Jounai, N Kojima, Y Tamura, Y Okada, E Kawamoto, S Okuda, K Klinman, D Okuda, K TI Polygene DNA vaccine induces a high level of protective effect against HIV-vaccinia virus challenge in mice SO VACCINE LA English DT Article DE HIV-1; vaccination; multivalent poly epitope vaccine ID CYTOTOXIC T-LYMPHOCYTES; MEDIATED IMMUNE-RESPONSES; PEPTIDE VACCINE; ANTIBODY-RESPONSES; CODON OPTIMIZATION; CELL RESPONSES; RHESUS-MONKEYS; GENE-TRANSFER; PLASMID DNA; IMMUNIZATION AB Single HIV-1 subtype DNA vaccine is unlikely to provide reactive protection across a wide range of HIV strains since the HIV virus changes the antigenic sites, particularly, in env gene. To overcome these issues, we constructed a multivalent poly-epitope DNA vaccine. A polygenic DNA vaccine encoding 20 antigenic epitopes from the HIV-1 Env, Gag, and Pol proteins of several clades was constructed using humanized and optimized codons and it was named here hDNA vaccine. In mice, this hDNA vaccine stimulated the following strong (1) antigen-specific serum antibody (Ab) responses, (2) delayed-type hypersensitivity, (3) the activation of IFN-gamma secretion cells targeting gp120 and synthetic antigenic peptides, in addition (4) a significant level of several peptide specific cytotoxic T lymphocytes (CTL) responses. Challenged with modified vaccinia viruses vPE16 and vP1206 expressing HIV-1 env and gag(.)pol genes, respectively, demonstrated the viral titers in the ovary of the mice vaccinated with hDNA significantly less compared to the unvaccinated mice. Thus, the use of polygene DNA vaccine appears to induce a high level of HIV-specific immune responses and is very effective against challenge with recombinant HIV-vaccinia viruses. (C) 2004 Elsevier Ltd. All rights reserved. C1 Yokohama City Univ, Sch Med, Dept Bacteriol, Kanazawa Ku, Yokohama, Kanagawa 2360004, Japan. Tokyo Dent Coll, Dept Microbiol, Mihama Ku, Chiba 2618502, Japan. US FDA, Ctr Biol Evaluat & Res, Lab Retrovirol & Immunol, Div Viral Prod, Bethesda, MD 20892 USA. RP Okuda, K (reprint author), Yokohama City Univ, Sch Med, Dept Bacteriol, Kanazawa Ku, 3-9 Fukuura, Yokohama, Kanagawa 2360004, Japan. EM kokuda@med.yokohama-cu.ac.jp NR 60 TC 11 Z9 11 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD SEP 9 PY 2004 VL 22 IS 27-28 BP 3676 EP 3690 DI 10.1016/j.vaccine.2004.03.015 PG 15 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 853GL UT WOS:000223815100017 PM 15315847 ER PT J AU Binienda, Z Virmani, A Przybyla-Zawislak, B Schmued, L AF Binienda, Z Virmani, A Przybyla-Zawislak, B Schmued, L TI Neuroprotective effect of L-carnitine in the 3-nitropropionic acid (3-NPA)-evoked neurotoxicity in rats SO NEUROSCIENCE LETTERS LA English DT Article DE 3-nitropropionic acid; L-carnitine; striatum; neuroprotection; fluoro-Jade B; rat ID ACETYL-L-CARNITINE; SUCCINATE-DEHYDROGENASE; BRAIN; DAMAGE; VULNERABILITY; STRIATUM AB A plant and fungal toxin, 3-NPA, acts as an inhibitor of mitochondrial function via irreversible inactivation of the mitochondrial inner membrane enzyme, succinate dehydrogenase (SDH). Inhibition of SDH disturbs electron transport and leads to cellular energy deficits and neuronal injury. We have shown that pretreatment with L-carnitine, while not significantly attenuating SDH inhibition, prevented hypothermia and oxidative stress-associated increased activity of free radical-scavenging enzymes. Here, a neurohistological method was applied to examine the effect of carnitine pretreatment against 3-NPA-induced neurotoxicity. Twenty adult male Sprague-Dawley rats were randomly divided into two groups (n = 10/group). Rats in the first group were injected twice with 3-NPA at 30 mg/kg s.c., 2 days apart, and the second group of animals received L-carnitine pretreatment at 100 mg/kg 30-40 min before 3-NPA administration. Rats in both groups were perfused 7 days later and their brains harvested. Degenerating neurons were identified and localized via the fluorescent marker Fluoro-Jade B. In the three animals that survived 3-NPA dosing, one exhibited no pathology, one exhibited moderate unilateral damage to the striatum, and the third exhibited extensive bilateral neuronal degeneration in multiple forebrain regions. In the seven surviving animals that received L-carnitine prior to 3-NPA insult, six exhibited no lesions, while one exhibited a modest unilateral lesion in the striatum. It appears that L-carnitine is protective against 3-NPA-induced toxicity, as reflected by both reduced mortality and significantly reduced neuronal degeneration. (C) 2004 Elsevier Ireland Ltd. All rights reserved. C1 US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. Sigma Tau Healthsci, Res & Dev, I-00040 Pomezia, Italy. RP Binienda, Z (reprint author), US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. EM zbinienda@nctr.fda.gov NR 20 TC 23 Z9 23 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD SEP 2 PY 2004 VL 367 IS 2 BP 264 EP 267 DI 10.1016/j.neulet.2004.05.031 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 852UW UT WOS:000223783200030 PM 15331167 ER PT J AU Ellenberg, SS Orloff, DG Temple, RJ AF Ellenberg, SS Orloff, DG Temple, RJ TI Homocysteine as a predictive factor for hip fracture in older persons SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 US FDA, Rockville, MD 20852 USA. US FDA, Rockville, MD 20857 USA. RP Ellenberg, SS (reprint author), US FDA, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD SEP 2 PY 2004 VL 351 IS 10 BP 1028 EP 1028 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 850UB UT WOS:000223637400019 ER PT J AU Obuchowski, NA Beiden, SV Berbaum, KS Hillis, SL Ishwaran, H Song, HH Wagner, RF AF Obuchowski, NA Beiden, SV Berbaum, KS Hillis, SL Ishwaran, H Song, HH Wagner, RF TI Multireader, multicase receiver operating characteristic analysis: An empirical comparsion of five methods SO ACADEMIC RADIOLOGY LA English DT Article DE receiver operating characteristic (ROC) curve; ROC analysis; multireader study; multireader multicase (MRMC) study; diagnostic accuracy ID MAXIMUM-LIKELIHOOD ESTIMATION; SIGNAL-DETECTION THEORY; OF-VARIANCE MODELS; ROC ANALYSIS; CHARACTERISTIC CURVES; REGRESSION; COMPONENTS; AREAS; VALIDATION; PARAMETERS AB Rationale and Objectives. Several statistical methods have been developed for analyzing multireader, multicase (MRMC) receiver operating characteristic (ROC) studies. The objective of this article is to increase awareness of these methods and determine if their results are concordant for published datasets. Materials and Methods. Data from three previously published studies were reanalyzed using five MRMC methods. For each method the 95% confidence intervals (CIs) for the mean of the readers' ROC areas for each diagnostic test, the P value for the comparison of the diagnostic tests' mean accuracies, and the 95% CIs for the mean difference in ROC areas of the diagnostic tests were reported. Results. Important differences in P values and CIs were seen when using parametric versus nonparametric estimates of accuracy, and there were the expected differences for random-reader versus fixed-reader models. Controlling for these differences, the Dorfman-Berbaum-Metz (DBM), Obuchowski-Rockette, Beiden-Wagner-Campbell, and Song's multivariate Wilcoxon-Mann-Whitney (WMW) methods gave almost identical results for the fixed-reader model. For the randomreader model, the DBM, Obuchowski-Rockette, and Beiden-Wagner-Campbell methods yielded approximately the same inferences, but the CIs for the Beiden-Wagner-Campbell method tend to be broader. Ishwaran's hierarchical ROC sometimes yielded significance not found with other methods. Song's modification of DBM's jack-knifing algorithm sometimes led to different conclusions than the original DBM algorithm. Conclusion. In choosing and applying MRMC methods, it is important to recognize: (1) the distinction between random reader and fixed-reader models, the uncertainties accounted for by each, and thus the level of generalizeability expected from each; (2) assumptions made by the various MRMC methods; and (3) limitations of a five- or six-reader study when the reader variability is great. C1 Cleveland Clin Fdn, Dept Biostat & Epidemiol, Cleveland, OH 44195 USA. Cleveland Clin Fdn, Dept Radiol, Cleveland, OH USA. US FDA, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, Washington, DC USA. Univ Iowa, Dept Radiol, Iowa City, IA 52242 USA. Iowa City VA Med Ctr, Program Interdisciplinary Res Hlth Care Org, Iowa City, IA USA. Catholic Univ, Coll Med, Dept Biostat, Seoul, South Korea. RP Obuchowski, NA (reprint author), Cleveland Clin Fdn, Dept Biostat & Epidemiol, 9500 Euclid Ave,Desk Wb4, Cleveland, OH 44195 USA. EM nobuchow@bio.ri.ccf.org NR 35 TC 37 Z9 37 U1 0 U2 4 PU ASSOC UNIV RADIOLOGISTS PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523-2251 USA SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD SEP PY 2004 VL 11 IS 9 BP 980 EP 995 DI 10.1016/j.arca.2004.04.014 PG 16 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 854UN UT WOS:000223929000003 PM 15350579 ER PT J AU Bryan, WW AF Bryan, WW TI Regulatory issues in ALS clinical trials SO AMYOTROPHIC LATERAL SCLEROSIS AND OTHER MOTOR NEURON DISORDERS LA English DT Article; Proceedings Paper CT Conference on Amyotrophic Lateral Sclerosis Clinical Trials CY JUN 13-15, 2003 CL Westchester, NY SP Muscular Dystrophy Assoc C1 US FDA, Rockville, MD 20857 USA. RP Bryan, WW (reprint author), US FDA, Rockville, MD 20857 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS AS PI OSLO PA CORT ADELERSGT 17, PO BOX 2562, SOLLI, 0202 OSLO, NORWAY SN 1466-0822 J9 AMYOTROPH LATERAL SC JI Amyotroph. Lateral. Scler. Mot. Neuron Disord. PD SEP PY 2004 VL 5 SU 1 BP 36 EP 41 DI 10.1080/17434470410015964 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 865VG UT WOS:000224731500010 PM 15512868 ER PT J AU Walton, MK AF Walton, MK TI Use of surrogate markers SO AMYOTROPHIC LATERAL SCLEROSIS AND OTHER MOTOR NEURON DISORDERS LA English DT Article; Proceedings Paper CT Conference on Amyotrophic Lateral Sclerosis Clinical Trials CY JUN 13-15, 2003 CL Westchester, NY SP Muscular Dystrophy Assoc C1 US FDA, Div Therapeut Biol Internal Med Prod, Ctr Drug Evaluat & Res, Rockville, MD 20852 USA. RP Walton, MK (reprint author), US FDA, Div Therapeut Biol Internal Med Prod, Ctr Drug Evaluat & Res, 1401 Rockville Pike, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS AS PI OSLO PA CORT ADELERSGT 17, PO BOX 2562, SOLLI, 0202 OSLO, NORWAY SN 1466-0822 J9 AMYOTROPH LATERAL SC JI Amyotroph. Lateral. Scler. Mot. Neuron Disord. PD SEP PY 2004 VL 5 SU 1 BP 103 EP 103 DI 10.1080/17434470410019834 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 865VG UT WOS:000224731500028 PM 15512886 ER PT J AU Ratnasinghe, LD Graubard, BI Kahle, L Tangrea, JA Taylor, PR Hawk, E AF Ratnasinghe, LD Graubard, BI Kahle, L Tangrea, JA Taylor, PR Hawk, E TI Aspirin use and mortality from cancer in a prospective cohort study SO ANTICANCER RESEARCH LA English DT Article DE aspirin; NSAIDs; cancer; cardiovascular disease; NHANES; cohort study ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; COLORECTAL-CANCER; BREAST-CANCER; GASTRIC-CANCER; URINARY-TRACT; NUDE-MICE; RISK; SULINDAC; CHEMOPREVENTION; PREVENTION AB There is evidence that use of aspirin offers several potential health benefits including cancer prevention and cardiovascular disease prevention. The purpose of this study was to assess the association between aspirin use and death from cancer and cardiovascular diseases with a special emphasis on cancer mortality. Materials and Methods: The baseline data for this prospective cohort study were collected in 1971-1975 for the first National Health and Nutrition Examination Study (NHANES I) and 1976-1980 as part of the second NHANES (NHANES II) with mortality follow-up using the National Death Index (NDI) through December 31, 1992. The main analyses were the relative risks of total mortality and cause-specific mortality for persons who used aspirin compared to persons who did not use aspirin adjusted for confounding using Cox proportional hazards. Results: The proportion of aspirin users was lower among cancer cases than non-cases (58% versus 66%) and use of aspirin decreased with age. Consequently, age was a negative confounder attenuating the protective association between aspirin use and cancer and cardiovascular mortality. After adjusting for age, BMI, sex, race, poverty index, education and smoking, we observed a significant association of reduced all cause mortality among all aspirin users (relative risk [RR] = 0.88; 95% confidence interval [CI] 0.85-0.99) and lung cancer mortality among male aspirin users (RR = 0.69; CI 0.49-0.96). However, for women we observed adverse associations between aspirin use and bladder (PR=12.31; CI 2.98-50.80) and brain cancer mortality (RR=3.13; CI 1.09-9.00), although case numbers were small. Conclusion: Aspirin use appears to offer protection from all causes of mortality and lung cancer among men. In women aspirin use is associated with increased risk of bladder and brain cancer. Because of the small number of female bladder (n = 15) and brain (n = 20) cancer cases in this cohort the findings require confirmation. C1 US FDA, Natl Ctr Toxicol Res, Div Mol Epidemiol, Jefferson, AR 72079 USA. UAMS, Arkansas Canc Res Ctr, Little Rock, AR USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD USA. NCI, Div Canc Prevent, GOCRG, Bethesda, MD USA. NCI, Canc Res Ctr, Bethesda, MD USA. Informat Management Serv Inc, Silver Spring, MD USA. RP Ratnasinghe, LD (reprint author), US FDA, Natl Ctr Toxicol Res, Div Mol Epidemiol, 3900 NCTR Dr, Jefferson, AR 72079 USA. EM LRatnasinghe@NCTR.FDA.gov NR 43 TC 85 Z9 86 U1 0 U2 4 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD SEP-OCT PY 2004 VL 24 IS 5B BP 3177 EP 3184 PG 8 WC Oncology SC Oncology GA 864JN UT WOS:000224629900014 PM 15510608 ER PT J AU Goswami, BB Kulka, M Ngo, D Cebula, TA AF Goswami, BB Kulka, M Ngo, D Cebula, TA TI Apoptosis induced by a cytopathic hepatitis A virus is dependent on caspase activation following ribosomal RNA degradation but occurs in the absence of 2 '-5 ' oligoadenylate synthetase SO ANTIVIRAL RESEARCH LA English DT Article DE hepatitis A virus; apoptosis; RNA degradation; caspase ID 5 NONTRANSLATED REGION; FAST-GROWING STRAIN; IN-VITRO; CELL-CULTURE; GENETIC-RECOMBINATION; PERSISTENT INFECTION; INTERNAL INITIATION; PLAQUE-ASSAY; STRANDED-RNA; MRC-5 CELLS AB We have presented previously evidence that the cytopathogenic 18f strain of hepatitis A virus (HAV) induced degradation of ribosomal RNA (rRNA) in infected cells [Arch. Virol. 148 (2003) 1275-1300]. In contrast, the non-cytopathogenic parent virus HM 175 clone 1 had no effect on rRNA integrity. We present here data showing that rRNA degradation is followed by apoptosis accompanied by characteristic DNA laddering in the cytoplasm of 18f infected cells. The DNA laddering coincided with the detection of caspase 3 and PARP-1 cleavage and was dependent upon activation of the caspase pathway, since treatment with Z-VAD-FMK, a pan-caspase inhibitor, inhibited both events. RNase L mRNA was present in both virus-infected and uninfected cells. Messenger RNA for the interferon inducible enzyme 2'-5' oligoadenylate synthetase (2'-5' OAS), which polymerizes ATP into 2'-5' oligo adenylate (2-5A, the activator of RNase L) in the presence of double-stranded RNA, was not detected following virus infection. 2-5' OAS mRNA was induced by treatment of the cells with interferon-beta (IFN-beta). IFN-beta mRNA was marginally induced following infection. However, phosphorylated STAT 1, a key regulator of interferon-stimulated gene transcription was not detected in virus infected cells. STAT 1 phosphorylation in response to IFN treatment was lower in virus-infected cells, compared to uninfected cells treated with interferon, suggesting that l8f virus infection interferes with interferon signaling. The results suggest that l8f infection causes the induction of a 2-5A independent RNase L like activity. Published by Elsevier B.V. C1 US FDA, Div Mol Biol, Off Appl Res & Safety Assessment, OARSA,FDA, Laurel, MD 20708 USA. RP Goswami, BB (reprint author), US FDA, Div Mol Biol, Off Appl Res & Safety Assessment, OARSA,FDA, HFS-025,8301 Muirkirk Rd, Laurel, MD 20708 USA. EM bgoswami@cfsan.fda.gov NR 58 TC 14 Z9 15 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-3542 J9 ANTIVIR RES JI Antiviral Res. PD SEP PY 2004 VL 63 IS 3 BP 153 EP 166 DI 10.1016/j.antiviral.2004.02.004 PG 14 WC Pharmacology & Pharmacy; Virology SC Pharmacology & Pharmacy; Virology GA 862OD UT WOS:000224499600002 PM 15451183 ER PT J AU Campen, DH Graham, D Cheetham, C Shoor, C Levy, G Hui, R Spence, M Ray, WA AF Campen, DH Graham, D Cheetham, C Shoor, C Levy, G Hui, R Spence, M Ray, WA TI Risk of acute cardiac events among patients treated with cyclooyenase-2 selective and non-sSlective-nonsteroidal anti-inflammatory drugs. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the American-College-of-Rheumatology/39th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 16-21, 2004 CL San Antonio, TX SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 US FDA, CDER, Bethesda, MD 20014 USA. Kaiser Permanente, Downey, CA USA. Kaiser Permanente, Santa Clara, CA USA. Kaiser Permanente, Bellflower, CA USA. Vanderbilt Univ, Nashville, TN USA. NR 0 TC 4 Z9 4 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 2004 VL 50 IS 9 SU S BP S657 EP S657 PG 1 WC Rheumatology SC Rheumatology GA 853AS UT WOS:000223799001823 ER PT J AU Stone, JH Rajapakse, VN Hoffman, GS Specks, U Merkel, PA Spiera, R Davis, JC Clair, EWS Veenstra, TD Conrads, TP Liotta, LA Petricoin, EF AF Stone, JH Rajapakse, VN Hoffman, GS Specks, U Merkel, PA Spiera, R Davis, JC Clair, EWS Veenstra, TD Conrads, TP Liotta, LA Petricoin, EF TI A serum proteomic approach to gauging the state of remission in Wegener's granulomatosis SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the American-College-of-Rheumatology/39th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 16-21, 2004 CL San Antonio, TX SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Johns Hopkins Univ, Baltimore, MD USA. NCI, Bethesda, MD 20892 USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Mayo Clin, Rochester, MN USA. Boston Univ, Boston, MA 02215 USA. Beth Israel Med Ctr, New York, NY 10003 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Duke Univ, Durham, NC USA. US FDA, Bethesda, MD 20014 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 JI Arthritis Rheum. PD SEP PY 2004 VL 50 IS 9 SU S BP S118 EP S118 PG 1 WC Rheumatology SC Rheumatology GA 853AS UT WOS:000223799000232 ER PT J AU Pombo, M Berthold, I Gingrich, E Jaramillo, M Leef, M Sirota, L Hsu, H Arciniega, J AF Pombo, M Berthold, I Gingrich, E Jaramillo, M Leef, M Sirota, L Hsu, H Arciniega, J TI Validation of an anti-PA-ELISA for the potency testing of anthrax vaccine in mice SO BIOLOGICALS LA English DT Article ID PROTECTIVE ANTIGEN AB The potency test for the anthrax vaccine currently licensed for human use in the United States (Anthrax Vaccine Adsorbed) involves the protection of actively immunized guinea pigs from a lethal challenge with a virulent strain of Bacillus anthracis. Lethal challenge tests entail the use of specialized containment facilities for the safe and secure handling of the challenge strain. This potential difficulty, plus humane considerations, have prompted us to investigate non-lethal, alternative immunogenicity assays that could be considered as potency tests not only for the current vaccine, but also for vaccines under development. Immunogenicity tests will require suitable measurement of an antibody response to relevant antigens, by methods such as enzyme linked immunosorbent assay (ELISA) or a toxin neutralization assay. Any assay chosen for this purpose should be adequately validated and reproducible by other laboratories. Validation of an analytical procedure requires the demonstration that the assay is suitable for its intended purpose. The objective of this work was to study the performance of an anti-PA-ELISA designed to assess the antibody response to anthrax vaccines in mice. Validation studies were performed according to the guidelines of the International Conference of Harmonization (ICH), and we have established the working range of the assay (37-1159 EU/mL) on the bases of the following parameters: linearity (20-1159 EU/mL; r(2) = 0.99; p-value = 0.21), accuracy (91-118% recovery), precision (less than or equal to20%CV, repeatability; less than or equal to9 and less than or equal to21% CV, intermediate precision per day and per analyst, respectively), detection limit (5 EU/mL), and quantification limit (37 EU/mL). We believe that assay specificity and the above characteristics are adequate to allow this ELISA to be considered for use in a mouse immunogenicity (potency) test of anthrax vaccines, and for the standardization of reagents. Published by Elsevier Ltd on behalf of The International Association for Biologicals. C1 US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. Inst Nacl Higiene Rafael Rangel, Caracas, Venezuela. RP Arciniega, J (reprint author), US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. EM arciniega@cber.fda.gov NR 13 TC 13 Z9 13 U1 0 U2 3 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 2004 VL 32 IS 3 BP 157 EP 163 DI 10.1016/j.biologicals.2004.03.002 PG 7 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA 876FM UT WOS:000225481900006 PM 15536047 ER PT J AU Selvaraj, V Zakroczymski, MA Naaz, A Mukai, M Ju, YH Doerge, DR Katzenellenbogen, JA Helferich, WG Cooke, PS AF Selvaraj, V Zakroczymski, MA Naaz, A Mukai, M Ju, YH Doerge, DR Katzenellenbogen, JA Helferich, WG Cooke, PS TI Estrogenicity of the isoflavone metabolite equol on reproductive and non-reproductive organs in mice SO BIOLOGY OF REPRODUCTION LA English DT Article DE female reproductive tract; steroid hormone receptors; uterus; vagina ID SOY ISOFLAVONES; RECEPTOR-BETA; DIETARY PHYTOESTROGENS; INTERNATIONAL TRENDS; TOPOISOMERASE-II; IMMATURE MOUSE; HABITUAL DIET; IN-VITRO; GENISTEIN; GROWTH AB Equol, a metabolite of the phytoestrogen daidzein, is present at significant levels in some humans who consume soy and in rodents fed soy-based diets. Equol is estrogenic in vitro, but there have been limited studies of its activity in vivo. We evaluated equol effects on reproductive and non-reproductive endpoints in mice. Ovariectomized age-matched (30-day-old) female C57BL/6 mice were fed phytoestrogen-free diets and given a racemic mixture of equol by daily injections (0, 4, 8, 12, or 20 mg [kg body weight](-1) day(-1)) or in the diet (0, 500, or 1000 ppm) for 12 days. Mice were killed, and serum concentrations of total and aglycone equol were measured. Total serum equol concentrations ranged from 1.4 to 7.5 muM with increasing doses of injected equol, but uterine weight increased significantly only at 12 and 20 mg (kg body weight)(-1) day(-1). Dietary equol at 500 or 1000 ppm produced total serum equol concentrations of 5.9 and 8.1 muM, respectively, comparable with those in rodents consuming certain high-soy chows; the proportion of equol present as the free aglycone was much lower with dietary administration than injections, which may be a factor in the greater biological effects induced by injections. Dietary equol did not significantly increase uterine weight. increasing dietary and injected equol doses caused a dose-dependent increase in vaginal epithelial thickness. Uterine epithelial proliferation was increased by equol injections at 8-20 mg (kg body weight)(-1) day(-1) and 1000 ppm dietary equol. Neither dietary nor injected equol decreased thymic or adipose weights. In conclusion, equol is a weak estrogen with modest effects on endpoints regulated by estrogen receptor et when present at serum levels seen in rodents fed soy-based diets, but quantities present in humans may not be sufficient to induce estrogenic effects, although additive effects of equol with other phytoestrogens may occur. C1 Univ Illinois, Dept Vet Biosci, Urbana, IL 61802 USA. Univ Illinois, Dept Food Sci & Human Nutr, Urbana, IL 61802 USA. Univ Illinois, Dept Chem, Urbana, IL 61802 USA. Univ Illinois, Div Nutr Sci, Urbana, IL 61802 USA. US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Cooke, PS (reprint author), Univ Illinois, Dept Vet Biosci, 2001 S Lincoln Ave, Urbana, IL 61802 USA. EM p-cooke@uiuc.edu RI Mukai, Motoko/L-9910-2014 OI Mukai, Motoko/0000-0002-5695-3826 FU NCI NIH HHS [CA77355]; NIEHS NIH HHS [ES011590, T32 ES07326] NR 50 TC 44 Z9 49 U1 0 U2 5 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 2004 VL 71 IS 3 BP 966 EP 972 DI 10.1095/biolreprod.104.029512 PG 7 WC Reproductive Biology SC Reproductive Biology GA 849LX UT WOS:000223541200032 PM 15151933 ER PT J AU Geho, DH Lahar, N Ferrari, M Petricoin, EF Liotta, LA AF Geho, DH Lahar, N Ferrari, M Petricoin, EF Liotta, LA TI Opportunities for nanotechnology-based innovation in tissue proteomics SO BIOMEDICAL MICRODEVICES LA English DT Article DE tissue proteomics; nanotechnology; protein microarrays; mass spectrometry ID CATALYZED REPORTER DEPOSITION; PHASE PROTEIN MICROARRAYS; MASS-SPECTROMETRY; SIGNAL AMPLIFICATION; PROSTATE-CANCER; CLINICAL PROTEOMICS; SILICON SURFACES; OVARIAN-CANCER; SERUM; EXPRESSION AB Within this review we discuss two methodologies used in tissue proteomics, namely mass-spectrometry (MS)-based protein pattern diagnostics and protein microarrays. Further, we describe current goals within the field of tissue proteomics and suggest points of departure for designing nanotechnology-based tools that will enhance the role of molecularly based diagnostics and therapeutics development in clinical medicine. C1 NCI, US FDA, NCI,Clin Proteom Program, Lab Pathol,Ctr Canc Res, Bethesda, MD 20892 USA. US FDA, NCI, Clin Proteom Program, Ctr Biol Evaluat & Res, Bethesda, MD USA. Ohio State Univ, Dept Internal Med, Div Haematol & Oncol, Columbus, OH 43210 USA. Ohio State Univ, Dorothy M Davis Heart & Lung Res Inst, Columbus, OH 43210 USA. RP Geho, DH (reprint author), NCI, US FDA, NCI,Clin Proteom Program, Lab Pathol,Ctr Canc Res, Room 2N212,Bldg 10,10 Ctr Dr, Bethesda, MD 20892 USA. EM gehod@mail.nih.gov NR 59 TC 22 Z9 24 U1 0 U2 2 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1387-2176 J9 BIOMED MICRODEVICES JI Biomed. Microdevices PD SEP PY 2004 VL 6 IS 3 BP 231 EP 239 DI 10.1023/B:BMMD.0000042053.51016.b4 PG 9 WC Engineering, Biomedical; Nanoscience & Nanotechnology SC Engineering; Science & Technology - Other Topics GA 854OX UT WOS:000223914300008 PM 15377833 ER PT J AU Delongchamp, RR Bowyer, JF Chen, JJ Kodell, RL AF Delongchamp, RR Bowyer, JF Chen, JJ Kodell, RL TI Multiple-testing strategy for analyzing cDNA array data on gene expression SO BIOMETRICS LA English DT Article DE decision theory; false discovery rate; false nondiscovery rate; p-value plot; ROC curves; subset selection ID FALSE DISCOVERY RATE; COMPLEX TRAITS; DISSECTION; REGIONS; PLOTS AB An objective of many functional genomics studies is to estimate treatment-induced changes in gene expression. cDNA arrays interrogate each tissue sample for the levels of mRNA for hundreds to tens of thousands of genes, and the use of this technology leads to a multitude of treatment contrasts. By-gene hypotheses tests evaluate the evidence supporting no effect, but selecting a significance level requires dealing with the multitude of comparisons. The p-values from these tests order the genes such that a p-value cutoff divides the genes into two sets. Ideally one set would contain the affected genes and the other would contain the unaffected genes. However, the set of genes selected as affected will have false positives, i.e., genes that are not affected by treatment. Likewise, the other set of genes, selected as unaffected, will contain false negatives, i.e., genes that are affected. A plot of the observed p-values (1 - p) versus their expectation tinder a uniform [0, 1] distribution allows one to estimate the number of true null hypotheses. With this estimate, the false positive rates and false negative rates associated with any p-value cutoff can be estimated. When computed for a range of cutoffs, these rates summarize the ability of the study to resolve effects. In our work, we are more interested in selecting most of the affected genes rather than protecting against a few false positives. An optimum cutoff, i.e., the best set given the data, depends upon the relative cost of falsely classifying a gene as affected versus the cost of falsely classifying a gene as unaffected. We select the cutoff by a decision-theoretic method analogous to methods developed for receiver operating characteristic curves. In addition, we estimate the false discovery rate and the false nondiscovery rate associated with any cutoff value. Two functional genomics studies that were designed to assess a treatment effect are used to illustrate how the methods allowed the investigators to determine a cutoff to suit their research goals. C1 Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. RP Delongchamp, RR (reprint author), Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. EM rdelongchamp@nctr.fda.gov NR 23 TC 41 Z9 41 U1 0 U2 1 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0006-341X J9 BIOMETRICS JI Biometrics PD SEP PY 2004 VL 60 IS 3 BP 774 EP 782 DI 10.1111/j.0006-341X.2004.00228.x PG 9 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 853HP UT WOS:000223818200028 PM 15339301 ER PT J AU Lomander, A Schreuders, P Russek-Cohen, E Ali, L AF Lomander, A Schreuders, P Russek-Cohen, E Ali, L TI Evaluation of chlorines' impact on biofilms on scratched stainless steel surfaces SO BIORESOURCE TECHNOLOGY LA English DT Article DE chlorine; biofilms; surface morphology; 316 stainless steel; image analysis; Escherichia coli ID LISTERIA-MONOCYTOGENES; ESCHERICHIA-COLI; MICROBIAL BIOFILMS; GROWTH; INDUSTRY; GLASS; POLYPROPYLENE; RESISTANCE; ADHERENCE; SURVIVAL AB Biofilms of a wild type Escherichia coli were grown on 316 stainless steel slides in a nutrient starved medium. The stainless steel surfaces were either polished to a smooth finish or scribed. The scribes consisted of lines and crosses. Biofilm samples were taken after 3, 6, 12, 24 and 48 h of growth. After sampling, the slides were soaked in deionized water or 50 or 200 ppm free chlorine prior to vital staining. Images were captured and the areas of viable and total biofilm were estimated. The individual biofilm patches, circularities, total percentage coverage, and viability percentage coverage were analyzed. The biofilms tended to increase in size between 6 and 24 h. A 3-6 h old biofilm on a polished stainless steel surface detached when 200 ppm sodium hypochlorite was applied. When grown in scribes, the circularity decreased up to 24 h, but thereafter increased. As the film grew older, it detached with or without a sodium hypochlorite treatment from the part of the surface that was polished, but remained in the neighborhood of the scribe. Based on the results, we recommend sanitizing at intervals of less than 12 h for this and similar strains of bacteria and protection of stainless steel surfaces to minimize scratching. (C) 2004 Published by Elsevier Ltd. C1 Univ Maryland, Biol Resoures Engn Dept, College Pk, MD 20742 USA. Univ Maryland, Anim & Avian Sci Dept, College Pk, MD 20742 USA. FDA, Div Chem Res & Environm Review, Off Food Addit Safety, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Schreuders, P (reprint author), Univ Maryland, Biol Resoures Engn Dept, College Pk, MD 20742 USA. EM ps129@umail.umd.edu NR 36 TC 30 Z9 33 U1 1 U2 8 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0960-8524 J9 BIORESOURCE TECHNOL JI Bioresour. Technol. PD SEP PY 2004 VL 94 IS 3 BP 275 EP 283 DI 10.1016/j.biotech.2004.01.004 PG 9 WC Agricultural Engineering; Biotechnology & Applied Microbiology; Energy & Fuels SC Agriculture; Biotechnology & Applied Microbiology; Energy & Fuels GA 831LP UT WOS:000222196200007 PM 15182834 ER PT J AU Rosenwald, A Chuang, EY Davis, RE Wiestner, A Alizadeh, AA Arthur, DC Mitchell, JB Marti, GE Fowler, DH Wilson, WH Staudt, LM AF Rosenwald, A Chuang, EY Davis, RE Wiestner, A Alizadeh, AA Arthur, DC Mitchell, JB Marti, GE Fowler, DH Wilson, WH Staudt, LM TI Fludarabine treatment of patients with chronic lymphocytic leukemia induces a p53-dependent gene expression response SO BLOOD LA English DT Article ID PURINE ANALOGS; ZAP-70 EXPRESSION; DRUG-RESISTANCE; CELL-DEATH; P53; MUTATION; CHEMOTHERAPY; SURVIVAL; CYCLOPHOSPHAMIDE; APOPTOSIS AB Fludarabine, the current standard treatment for B-cell chronic lymphocytic leukemia (CLL), can induce apoptosis in CLL cells in vitro, and a number of molecular mechanisms contribute to its cytotoxicity. Using gene expression profiling, we investigated the molecular consequences of fludarabine treatment of patients with CLL in vivo. In 7 patients with CLL, a consistent gene expression signature of in vivo fludarabine exposure was identified. Many of the fludarabine signature genes were known p53 target genes and genes involved in DNA repair. In vitro treatment of CLL cells with fludarabine induced the same set of genes as observed in vivo, and many of these genes were also induced by in vitro exposure of CLL cells to ionizing radiation. Using isogenic p53 wild-type and null lymphoblastoid cell lines, we confirmed that many of the fludarabine signature genes were also p53 target genes. Because in vivo treatment with fludarabine induces a p53-dependent gene expression response, fludarabine treatment has the potential to select p53-mutant CLL cells, which are more drug resistant and associated with an aggressive clinical course. These considerations suggest that fludarabine treatment should be given in strict accordance to the current National Cancer Institute (NCI) guidelines that have established criteria of disease activity that warrant treatment. (C) 2004 by The American Society of Hematology. C1 NCI, Metab Branch, CCR, NIH, Bethesda, MD 20892 USA. NCI, Radiat Biol Branch, CCR, NIH, Bethesda, MD 20892 USA. NCI, Expt Immunol & Transplantat Branch, CCR, NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Gene & Cell Therapy, NIH, Bethesda, MD 20014 USA. Stanford Univ, Dept Biochem, Sch Med, Stanford, CA 94305 USA. RP Staudt, LM (reprint author), NCI, Metab Branch, CCR, NIH, Bldg 10,Rm 4N114, Bethesda, MD 20892 USA. EM lstaudt@mail.nih.gov OI Alizadeh, Arash Ash/0000-0002-5153-5625 NR 34 TC 99 Z9 105 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 SEP 1 PY 2004 VL 104 IS 5 BP 1428 EP 1434 DI 10.1182/blood-2003-09-3236 PG 7 WC Hematology SC Hematology GA 849MX UT WOS:000223544000038 PM 15138159 ER PT J AU Kawakami, M Kawakami, K Takahashi, S Abe, M Puri, RK AF Kawakami, M Kawakami, K Takahashi, S Abe, M Puri, RK TI Analysis of interleukin-13 receptor alpha 2 expression in human pediatric brain tumors SO CANCER LA English DT Article DE interleukin-13 receptor; receptor subunits; pediatric brain tumor; in situ expression ID PLASMINOGEN-ACTIVATOR RECEPTOR; IN-SITU HYBRIDIZATION; HUMAN GLIOMA-CELLS; SIGNAL-TRANSDUCTION; ALPHA-2 CHAIN; PSEUDOMONAS EXOTOXIN; PANCREATIC TUMORS; CHIMERIC PROTEIN; CANCER-THERAPY; IL-4 RECEPTORS AB BACKGROUND. Compared with normal brain tissue cells, human malignant glioma cells express higher levels of interleukin-13 receptor (IL-13R). However, whether this receptor is expressed in situ has not been carefully examined. With IL-13R-targeted cytotoxin (IL13-PE38QQR, comprising IL-13 and a mutated form of Pseudomonas exotoxin [PE]) being tested in three Phase I/II clinical trials for the treatment of adult human glioma, and with pediatric studies being planned, the authors set out to analyze pediatric brain tumor tissue specimens for the expression of IL-13R. METHODS. Using in situ hybridization and immunohistochemical staining, the authors examined 58 pediatric brain tumor specimens for expression of the predominant IL-13 binding and internalizing protein (IL-13Ralpha2) chain at the mRNA and protein levels. RESULTS. overall, approximately 83% of pediatric brain tumor samples expressed IL-13Ralpha2. One hundred percent (11 of 11) high-grade astrocytoma, 79% (26 of 33) low-grade astrocytoma, 67% (4 of 6) medulloblastoma, and 67% (2 of 3) ependymoma samples were positive for IL-13Ralpha2. Among IL-13Ralpha2-positive samples, 88% (42 of 48 samples) had positive expression in greater than or equal to 50% of all tumor fields. The results obtained using both assays were consistent with each other. CONCLUSIONS. The current study established that pediatric brain tumor specimens expressed the IL-13Ralpha2 chain. Because the IL-13Ralpha2 chain is a major binding component of the IL-13R complex, these results suggest that the targeting of IL-13R may represent a useful approach for the treatment of pediatric brain tumors. Published 2004 by the American Cancer Society.* C1 US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Lab Mol Tumor Biol, Bethesda, MD 20892 USA. Nagoya City Univ, Grad Sch Med Sci, Dept Expt Pathol & Tumor Biol, Aichi, Japan. Fujita Hlth Univ, Sch Med, Dept Surg Pathol, Aichi, Japan. RP Puri, RK (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Lab Mol Tumor Biol, NIH Bldg 29B,Room 2NN10,HFM-735, Bethesda, MD 20892 USA. EM puri@cber.fda.gov NR 31 TC 44 Z9 49 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD SEP 1 PY 2004 VL 101 IS 5 BP 1036 EP 1042 DI 10.1002/cncr.20470 PG 7 WC Oncology SC Oncology GA 848HQ UT WOS:000223458600021 PM 15329913 ER PT J AU Allred, CD Allred, KF Ju, YH Goeppinger, TS Doerge, DR Helferich, WG AF Allred, CD Allred, KF Ju, YH Goeppinger, TS Doerge, DR Helferich, WG TI Soy processing influences growth of estrogen-dependent breast cancer tumors SO CARCINOGENESIS LA English DT Article ID SUPPRESSES MAMMARY-CANCER; DIETARY GENISTEIN; IN-VITRO; SOYBEAN ISOFLAVONES; GENE-TRANSCRIPTION; STIMULATE GROWTH; MCF-7 TUMORS; CELLS; RAT; JAPANESE AB Soy-based products consumed in Asian countries are minimally processed whereas in the USA many of the soy foods and soy ingredients are highly processed. Soy foods contain complex mixtures of bioactive compounds, which may interact with one another. The objective of this study was to evaluate the ability of various soy products containing genistin, the glycoside form of genistein, to affect growth of MCF-7 cells transplanted into ovariectomized athymic mice. Products investigated included soy flour, two crude extracts of soy (soy molasses and Novasoy(R)), a mixture of isoflavones and genistin in pure form. Each of the soy flour-processed products was added to the diet to provide equivalent amounts of genistein aglycone equivalents (750 p.p.m.). Tumors in the negative control animals regressed throughout the study while the tumors in the soy flour-fed animals remained basically the same size (neither grew nor regressed). In animals consuming soy molasses, Novasoy(R), mixed isoflavones or genistin alone, tumor growth was stimulated when compared with animals consuming a control diet devoid of soy. These same dietary treatments resulted in increased cellular proliferation. Changes in mRNA expression of gene targets (estrogen responsiveness, cell cycle progression, apoptosis and aromatase activity) in tumors induced by the different diets were evaluated. The relative expression of pS2, progesterone receptor and cyclin D1 was increased in animals consuming the Novasoy(R), mixed isoflavones and genistin. Bcl2 mRNA expression was low in most of the dietary treatment groups compared with positive (estradiol implant) controls. Aromatase expression was not affected in any of the treatment groups. The degree of soy flour processing affects the estrogenicity of products containing a constant amount of genistein. Collectively, these findings suggest that for postmenopausal women with estrogen-dependent breast cancer, the consumption of foods containing soy flour is more advisable than consuming isoflavones in more purified forms. C1 Univ Illinois, Dept Food Sci & Human Nutr, Urbana, IL 61801 USA. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Helferich, WG (reprint author), Univ Illinois, Dept Food Sci & Human Nutr, Urbana, IL 61801 USA. EM helferic@uiuc.edu FU NCI NIH HHS [CA77355]; NIEHS NIH HHS [ES07326] NR 49 TC 98 Z9 106 U1 2 U2 11 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD SEP PY 2004 VL 25 IS 9 BP 1649 EP 1657 DI 10.1093/carcin/bgh178 PG 9 WC Oncology SC Oncology GA 850CM UT WOS:000223588800012 PM 15131010 ER PT J AU Spacek, LA Hurley, BP Acheson, DWK Granok, A Currie, A Doing, K Sears, CL AF Spacek, LA Hurley, BP Acheson, DWK Granok, A Currie, A Doing, K Sears, CL TI Shiga toxin-producing Escherichia coli as a possible etiological agent of chronic diarrhea SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID HEMOLYTIC-UREMIC SYNDROME; ANTIBIOTIC-TREATMENT; O157-H7; RISK; INFECTIONS; DEATH AB We identified Shiga toxin-producing Escherichia coli (STEC) as the likely etiologic pathogen for chronic diarrhea in 2 patients, 1 of whom was immunocompromised with acquired immunodeficiency syndrome, and 1 of whom was immunocompetent. Both were treated with antibiotics, and neither developed systemic complications of the infection. These cases suggest that STEC infection should be considered in the differential diagnosis of chronic diarrhea. C1 Johns Hopkins Med Inst, Baltimore, MD 21205 USA. US FDA, College Pk, MD USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Infect Dis Associates, Nashua, NH USA. Affiliated Labs, Bangor, ME USA. RP Spacek, LA (reprint author), Johns Hopkins Univ, Sch Med, 1830 E Monument St,Rm 401, Baltimore, MD 21205 USA. EM lspacek@jhmi.edu FU NIAID NIH HHS [T32-AI 07291] NR 16 TC 3 Z9 3 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD SEP 1 PY 2004 VL 39 IS 5 BP E46 EP E48 DI 10.1086/422877 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 847CU UT WOS:000223367500030 PM 15356801 ER PT J AU Duncan, RC Salotra, P Goyal, N Akopyants, NS Beverley, SM Nakhasi, HL AF Duncan, RC Salotra, P Goyal, N Akopyants, NS Beverley, SM Nakhasi, HL TI The application of gene expression microarray technology to kinetoplastid research SO CURRENT MOLECULAR MEDICINE LA English DT Review DE microarray; Leishmania; Trypanosoma; stage-specific; fluorescent hybridization; gene discovery; Northern blot; expression profiling ID STAGE-SPECIFIC GENE; TRYPANOSOMA-CRUZI METACYCLOGENESIS; DEVELOPMENTALLY-REGULATED GENES; PROTOZOAN PARASITE LEISHMANIA; CDNA MICROARRAY; DNA-MICROARRAY; 3'-UNTRANSLATED REGION; PLASMODIUM-FALCIPARUM; GENOMIC ORGANIZATION; PROTECTIVE IMMUNITY AB Protozoan parasites in the order Kinetoplastida cause severe disease primarily in tropical and subtropical areas. Vaccines to control these diseases have shown some promise, but none are in active clinical use. Drug treatments are available for all of the acute infections, but the emergence of resistance and an unresponsive chronic phase are current problems. Rapid advances in genomic technology open the possibility of discovering new genes that can contribute to vaccine initiatives or serve as targets for development of new drugs. The DNA microarray is a genomic technology, which is being applied to new gene discovery in kinetoplastid parasites. Both cDNA and genomic microarrays for Leishmania major have identified a number of new genes that are expressed in a stage-specific fashion and preliminary results from a L. donovani genomic microarray also demonstrated new gene discovery. A microarray of Trypanosoma brucei genomic fragments identified new genes whose expression differs between the insect borne stage and the human infectious stage of the parasite. The next few years, building on this foundational work, should witness the most exciting stage as microarrays are applied to questions such as the basis of drug resistance, post kala azar dermal leishmaniasis, the regulation of differentiation to infectious stages, linking coordinately regulated pathways of genes and development of genetically defined parasites that may have potential as live attenuated vaccines. C1 US FDA, CBER, Off Blood Res & Review, Div Emerging & Transfus Transmitted Dis, Bethesda, MD USA. Safdarjang Hosp, Inst Pathol, Indian Council Med Res, New Delhi, India. Cent Drug Res Inst, Div Biochem, Lucknow 226001, Uttar Pradesh, India. Washington Univ, Sch Med, Dept Microbiol, St Louis, MO USA. RP Duncan, RC (reprint author), US FDA, CBER, Off Blood Res & Review, Div Emerging & Transfus Transmitted Dis, Bethesda, MD USA. EM Duncan@CBER.FDA.GOV RI Duncan, Robert/I-8168-2015; OI Duncan, Robert/0000-0001-8409-2501; Beverley, Stephen/0000-0001-5319-0811 NR 86 TC 27 Z9 30 U1 0 U2 2 PU BENTHAM SCIENCE PUBL LTD PI HILVERSUM PA PO BOX 1673, 1200 BR HILVERSUM, NETHERLANDS SN 1566-5240 J9 CURR MOL MED JI Curr. Mol. Med. PD SEP PY 2004 VL 4 IS 6 BP 611 EP 621 DI 10.2174/1566524043360221 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 845CK UT WOS:000223213100007 PM 15357212 ER PT J AU Posadas, EM Davidson, B Kohn, EC AF Posadas, EM Davidson, B Kohn, EC TI Proteomics mind ovarian cancer: Implications for diagnosis and treatment: a critical review of the recent literature SO CURRENT OPINION IN ONCOLOGY LA English DT Review DE ovarian cancer; proteomics; mass spectroscopy; combinatorial signaling therapy; ascites ID CLINICAL PROTEOMICS; SERUM; OSTEOPONTIN; PATTERNS; BIOMARKER AB Purpose of review Epithelial ovarian cancer is the leading cause of death from gynecologic malignancies amongst American women. Emerging proteomic technologies have promise for early diagnosis and in advancing treatment directions. Application of these technologies has produced new biomarkers, diagnostic approaches, and understanding of disease biology. Recent findings Mass spectral blood and tissue analysis has yielded new putative biomarkers that require further validation and assessment of diagnostic specificity and sensitivity. Protein signature patterns derived from mass spectrometry datastreams have been modeled and are moving into validation. Tissue-based protein analysis has led to identification of tumor and stromal protein and signal activation events in ovarian cancer. Clinical trials are now ascertaining tissue samples prior to and during therapy with molecularly targeted agents to evaluate modulation of targeted signaling pathways. Finally, proteomic analysis of tissues and metastases will outline biochemical events underlying the metastatic phenotype of ovarian cancer. Summary Proteomic approaches are experimental technologies applied to ovarian and other cancers. Proper validation and use of findings may advance our understanding of biochemical events that have complicated successful detection and intervention, This knowledge is the first step in fulfilling the promise of personalized molecular medicine. C1 NCI, Pathol Lab, Bethesda, MD 20892 USA. NCI, FDA Clin Prot Program, Bethesda, MD 20892 USA. RP Kohn, EC (reprint author), NCI, Pathol Lab, Bethesda, MD 20892 USA. EM kohne@mail.nih.gov NR 38 TC 33 Z9 34 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-8746 J9 CURR OPIN ONCOL JI Curr. Opin. Oncol. PD SEP PY 2004 VL 16 IS 5 BP 478 EP 484 DI 10.1097/00001622-200409000-00012 PG 7 WC Oncology SC Oncology GA 851UQ UT WOS:000223711600011 PM 15314519 ER PT J AU Brennan, MJ Morris, SL Sizemore, CF AF Brennan, MJ Morris, SL Sizemore, CF TI Tuberculosis vaccine development: research, regulatory and clinical strategies SO EXPERT OPINION ON BIOLOGICAL THERAPY LA English DT Review DE Mycobacterium tuberculosis; tuberculosis vaccines; vaccine regulatory issues; vaccine trials ID BACILLUS-CALMETTE-GUERIN; MYCOBACTERIUM-TUBERCULOSIS; PROTECTIVE EFFICACY; BCG VACCINES; ENHANCED IMMUNOGENICITY; PANTOTHENATE AUXOTROPH; IMMUNE-RESPONSES; RECENT PROGRESS; DNA; MICE AB In the past decade, while the global tuberculosis (TB) epidemic has continued to devastate mankind, considerable progress has nevertheless been made in the development of new and improved vaccines for this ancient disease. Recombinant bacillus Calmette-Guerin strains, DNA-based vaccines, live attenuated Mycobacterium tuberculosis vaccines and subunit vaccines formulated with novel adjuvants have shown promise in preclinical animal challenge models. Three of these vaccines are being evaluated at present in human clinical studies, and several other vaccine preparations are being targeted for clinical trials in the near future. Although the preclinical characterisation and testing of new TB vaccines has clearly led to exciting new findings, complex regulatory and clinical trial design issues remain as a challenge to TB vaccine development. This report reviews some of the exciting advances in TB research that have led to the development of new TB vaccines, and addresses the unique regulatory and clinical issues associated with the testing of novel anti-TB preparations in human populations. C1 US FDA, Ctr Biol Evaluat & Res, Lab Mycobacterial Dis & Cellular Immunol, Bethesda, MD 20892 USA. NIAID, TB & Other Mycobacterial Dis Sect, Resp Dis Branch, Div Microbiol & Infect Dis,NIH, Bethesda, MD 20892 USA. RP Brennan, MJ (reprint author), US FDA, Ctr Biol Evaluat & Res, Lab Mycobacterial Dis & Cellular Immunol, Bldg 29,Rm 503,HFM-431,29 Lincoln Dr, Bethesda, MD 20892 USA. EM brennan@cber.fda.gov; morris@cber.fda.gov NR 69 TC 10 Z9 11 U1 0 U2 0 PU ASHLEY PUBLICATIONS LTD PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1471-2598 J9 EXPERT OPIN BIOL TH JI Expert Opin. Biol. Ther. PD SEP PY 2004 VL 4 IS 9 BP 1493 EP 1504 DI 10.1517/14712598.4.9.1493 PG 12 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 853RQ UT WOS:000223845600012 PM 15335316 ER PT J AU Brown, SL Tavris, DR AF Brown, SL Tavris, DR TI Medical device epidemiology and surveillance: patient safety is the bottom line SO EXPERT REVIEW OF MEDICAL DEVICES LA English DT Editorial Material C1 US FDA, Ctr Devices & Radiol Hlth, Div Postmarket Surveillance, Epidemiol Branch, Rockville, MD 20850 USA. RP Brown, SL (reprint author), US FDA, Ctr Devices & Radiol Hlth, Div Postmarket Surveillance, Epidemiol Branch, 1350 Piccard Dr,HFZ-541, Rockville, MD 20850 USA. EM sbrown@fada.hhs.gov RI Bright, Roselie/D-2240-2016 NR 0 TC 31 Z9 31 U1 0 U2 2 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 SEP PY 2004 VL 1 IS 1 BP 1 EP 2 DI 10.1586/17434440.1.1.1 PG 2 WC Engineering, Biomedical SC Engineering GA 018XC UT WOS:000235797100001 PM 16293003 ER PT J AU Buzatu, DA Biris, AS Biris, AR Lupu, DM Darsey, JA Mazumder, MK AF Buzatu, DA Biris, AS Biris, AR Lupu, DM Darsey, JA Mazumder, MK TI Electronic properties of single-wall carbon nanotubes and their dependence on synthetic methods SO IEEE TRANSACTIONS ON INDUSTRY APPLICATIONS LA English DT Article; Proceedings Paper CT Joint Meeting of the Electrostatistics-Society-of-America/IEEE-Industry-Applications-Society- Electrostatic-Processes-Committee CY JUN 24-27, 2003 CL Little Rock, AK SP Electostatist Soc Amer, IEEE, Ind Applicat Soc Electrstat Processes Comm DE computational; electronic properties; ionization potential; nanotubes; synthesis; work function ID FIELD-EMISSION; EXCHANGE AB Since their discovery in 1991, carbon nanotubes have been intensively studied, and a number of new applications have been identified. Applications range from nanoelectronics to hydrogen absorption for battery electrodes and fuel cells. Because of their high electrical conductivity and strength, high-sensitivity atomic force microscopes already use carbon nanotubes for their tips, and carbon nanostructures are also used as electron beam emitters for medical and, scientific equipment. Electron emission is directly correlated with the work function and the ionization potential of carbon nanotubes. Gaussian 98 software was used to perform theoretical quantum calculations on a limited set of HyperChem 5.01 simulated metallic single-wall carbon nanotubes. These initial sets of calculations show that bandgaps and work functions of these small carbon nanostructures are dependent upon the diameter of the tubes, and to a lesser degree so is the ionization potential. In addition, we demonstrate how the manufacturing methods can directly affect the diameter of the nanotubes produced, and therefore directly influence the electrical properties of the nanotubes. C1 US FDA, Natl Ctr Toxicol Res, Div Chem, Jefferson, AR 72079 USA. Univ Arkansas, Dept Appl Sci, Little Rock, AR 72204 USA. Natl Inst Res & Dev Isotop & Mol Technol, Special Mat Dept, R-3400 Cluj Napoca, Romania. Univ Arkansas, Dept Chem, Little Rock, AR 72204 USA. RP Buzatu, DA (reprint author), US FDA, Natl Ctr Toxicol Res, Div Chem, Jefferson, AR 72079 USA. EM dbuzatu@nctf.fda.gov; asbiris@ualr.edu; mkmazumder@ualr.edu RI Biris, Alexandru/A-8507-2010; Biris, Alexandru /C-4517-2011; Lupu, Dan/C-3346-2009 NR 19 TC 8 Z9 8 U1 0 U2 6 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 0093-9994 J9 IEEE T IND APPL JI IEEE Trans. Ind. Appl. PD SEP-OCT PY 2004 VL 40 IS 5 BP 1215 EP 1219 DI 10.1109/TIA.2004.834051 PG 5 WC Engineering, Multidisciplinary; Engineering, Electrical & Electronic SC Engineering GA 856SZ UT WOS:000224066500006 ER PT J AU Burns, DL Fiddner, S Cheung, AM Verma, A AF Burns, DL Fiddner, S Cheung, AM Verma, A TI Analysis of subassemblies of pertussis toxin subunits in vivo and their interaction with the Ptl transport apparatus SO INFECTION AND IMMUNITY LA English DT Article ID BORDETELLA-PERTUSSIS; MONOCLONAL-ANTIBODIES; S1 SUBUNIT; SECRETION; PROTEINS; GENES; LOCALIZATION; CLONING; SYSTEM; EXPORT AB Pertussis toxin (PT) has an AB(5) structure that is typical of many bacterial protein toxins; however, this toxin is more complex than many toxins since it is composed of five different subunit types, subunits S1 to S5. Little is known about how PT assembles in vivo and how and when it interacts with its secretion apparatus, known as the Ptl transporter. In order to better understand these events, we expressed subsets of the genes encoding the S1, S2, and/or S4 subunits of PT in strains of Bordetella pertussis that either did or did not produce the Ptl proteins. We found evidence to suggest that certain subassemblies of the toxin, including subassemblies consisting of the S1 subunit and incomplete forms of the B oligomer, can form in vivo, at least transiently. These results suggest that the B oligomer of the toxin does not need to completely form before interactions between the S1 subunit and B-oligomer subunits can occur in vivo. All subassemblies localized primarily to the membrane fraction of the cell. Moreover, we found that Ptl-mediated secretion occurs in a strain that produces S1 and an incomplete complement of B-oligomer subunits. These results indicate that subassemblies of the toxin consisting of the S1 subunit and a partial B oligomer can interact with the Ptl system. C1 CBER, US FDA, HFM 434, Lab Resp & Special Pathogens, Bethesda, MD 20892 USA. RP Burns, DL (reprint author), CBER, US FDA, HFM 434, Lab Resp & Special Pathogens, Bldg 29,Room 130,8800 Rockville Pike, Bethesda, MD 20892 USA. EM burns@cber.fda.gov NR 28 TC 4 Z9 13 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD SEP PY 2004 VL 72 IS 9 BP 5365 EP 5372 DI 10.1128/IAI.72.9.5365-5372.2004 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 849ZM UT WOS:000223580400051 PM 15322034 ER PT J AU De Jager, LS Perfetti, GA Diachenko, GW AF De Jager, LS Perfetti, GA Diachenko, GW TI Liquid chromatographic determination of St. John's Wort components in functional foods SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID HYPERICUM-PERFORATUM L.; MASS-SPECTROMETRY; HUMAN PLASMA; HYPERFORIN; EXTRACTS; PSEUDOHYPERICIN; FLUORESCENCE AB A method was developed for determination of St. John's wort marker compounds hypericin, pseudohypericin, hyperforin, and adhyperforin in functional foods. Solid-phase extraction provided analyte extraction and significant sample cleanup prior to analysis using liquid chromatography (LC) with UV and fluorescence detection. In addition to quantification using LC-UV, confirmation was made with electrospray ionization LC mass spectrometry (LC/MS). Several commercially available tea and drink products claiming to contain St. John's wort were tested. Recoveries ranged from 51 to 98% for the liquid samples. Comparison of the concentrations in 4 St. John's wort teas showed a variation in analyte concentration (1044-10 ng/mL marker compounds in brewed tea) and composition. No marker compounds were found in the beverages, indicating possible decomposition of the marker compounds caused by low pH and/or exposure to light. A solvent extraction procedure was developed for analysis of the marker compounds from solid samples. Analytes were detected at low parts per million, with an average recovery of 75%. No St. John's wort components were found in the 2 solid functional food samples analyzed. C1 US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP De Jager, LS (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM Ldejager@cfsan.fda.gov NR 15 TC 2 Z9 2 U1 1 U2 5 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD SEP-OCT PY 2004 VL 87 IS 5 BP 1042 EP 1048 PG 7 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 853YO UT WOS:000223867100004 PM 15493659 ER PT J AU Idowu, OR Kijak, PJ Meinertz, JR Schmidt, LJ AF Idowu, OR Kijak, PJ Meinertz, JR Schmidt, LJ TI Development and validation of a gas chromatography/mass spectrometry procedure for confirmation of para-toluenesulfonamide in edible fish fillet tissue SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article AB Chloramine-T is a disinfectant being developed as a treatment for bacterial gill disease in cultured fish. As part of the drug approval process, a method is required for the confirmation of chloramine-T residues in edible fish tissue. The marker residue that will be used to determine the depletion of chloramine-T residues from the edible tissue of treated fish is para-toluenesulfonamide (p-TSA), a metabolite of chloramine-T. The development and validation of a procedure for the confirmation of p-TSA is described. Homogenized fish tissue is dried by mixing with anhydrous sodium sulfate, and the mixture is extracted with methylene chloride. The extract is passed through a silica gel solid-phase extraction column, from which p-TSA is subsequently eluted with acetonitrile. The acetonitrile extract is evaporated, and the oily residue is dissolved in hexane. The hexane solution is shaken with fresh acetonitrile. The acetonitrile solution is evaporated and the residue is redissolved in dilute potassium hydroxide solution. The aqueous solution is extracted with methylene chloride to further remove more of the fat co-extractive. The aqueous solution is reacted with pentafluorobenzyl bromide in presence of tetrabutylammonium hydrogensulfate. The resulting di-(pentafluorobenzyl) derivative of p-TSA is analyzed by gas chromatography/mass spectrometry. This method permits the confirmation of p-TSA in edible fish tissue at 20 ppb. C1 US FDA, Ctr Vet Med, Laurel, MD 20708 USA. US Geol Survey, Biol Resources Div, La Crosse, WI 54603 USA. RP Idowu, OR (reprint author), US FDA, Ctr Vet Med, 8401 Muirkirk Rd, Laurel, MD 20708 USA. EM oidowu@cvm.fda.gov NR 5 TC 0 Z9 0 U1 0 U2 2 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD SEP-OCT PY 2004 VL 87 IS 5 BP 1098 EP 1108 PG 11 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 853YO UT WOS:000223867100011 PM 15493666 ER PT J AU Jacobson, AP Thunberg, RL Johnson, ML Hammack, TS Andrews, WH AF Jacobson, AP Thunberg, RL Johnson, ML Hammack, TS Andrews, WH TI Alternative anaerobic enrichments to the Bacteriological Analytical Manual culture method for isolation of Shigella sonnei from selected types of fresh produce SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID LISTERIA-MONOCYTOGENES; SALMONELLA-ANATUM; OXYRASE ENZYME; RECOVERY; FOODS; FLEXNERI; GROWTH; REPAIR AB Alternative methods of reducing oxygen during anaerobic enrichment in the Bacteriological Analytical Manual (BAM) Shigella culture method were evaluated and compared to the current and less practical GasPak(R) method. The alternative anaerobic methods included the use of reducing agents in Shigella broth and reducing culture container headspace volume to minimize atmospheric effects on oxygen concentration in Shigella broth during enrichment. The reducing agents evaluated were sodium thioglycollate, L-Cystine, L-cysteine, titanium(III) citrate, and dithiothreitol, each at concentrations of 0.1, 0.05, and 0.01%. The use of Oxyrase for Broth(R) with the enrichment medium (Shigella broth) was evaluated at concentrations of 10, 20 and 30 muL/mL. Recoveries of chill- and freeze-stressed S. sonnei strains 357 and 20143 were determined with each anaerobic method, including the GasPak method, using inoculation levels ranging from 10(0) to 10(3) cells. For each anaerobic method, strain, inoculation level, and stress type, 5 replicate enrichments were evaluated by streaking to MacConkey agar for isolation. The numbers of cultures with each method from which S. sonnei was isolated were used to compare the alternative anaerobic methods to the GasPak method. The alternative anaerobic method with which chill- and freeze-stressed S. sonnei strains 357 and 20143 were isolated most consistently was the use of Oxyrase for Broth in Shigella broth at a concentration of 20 muL/mL. This method was compared to the GasPak anaerobic method in evaluations on the recovery of S. sonnei strains 357 and 20143 from artificially contaminated test portions of parsley, cilantro, green onions, strawberries, carrots, and celery. A third anaerobic method included the use of 0.5 cm mineral oil overlay on cultures containing Oxyrase for Broth at concentrations of 20 muL/mL. Recovery rates of strain 357 were significantly greater (p < 0.05) with the GasPak method than with Oxyrase for Broth, with and without the 0.5 cm mineral oil overlay, for test portions of parsley, cilantro, and celery. When Oxyrase for Broth was used with Shigella broth, strain 357 was isolated at higher rates from all produce types, except cilantro, when 0.5 cm mineral oil overlay was applied to enrichment cultures. The use of mineral oil overlay with Oxyrase for Broth also improved recovery of strain 20143 from test portions of all produce types except green onion and strawberries. These differences were significant (p < 0.05) with parsley, carrots, and cilantro (1 of 2 evaluations). No statistically significant differences (p > 0.05) between the GasPak and Oxyrase for Broth anaerobic methods occurred when mineral oil overlay was used with Oxyrase for Broth. The use of Oxyrase for Broth with a 0.5 cm mineral oil overlay is a practical alternative for anaerobic enrichment with the BAM method in the analysis of some produce types. Differences in recovery among the different produce types and methods occurred between S. sonnei strains 357 and 20143, emphasizing the need for additional S. sonnei strains in future evaluations. C1 US FDA, Div Microbiol Studies, College Pk, MD 20740 USA. RP Jacobson, AP (reprint author), US FDA, Div Microbiol Studies, HFS-516,5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM andrew.jacobson@fda.hhs.gov NR 19 TC 2 Z9 3 U1 2 U2 8 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD SEP-OCT PY 2004 VL 87 IS 5 BP 1115 EP 1122 PG 8 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 853YO UT WOS:000223867100013 PM 15493668 ER PT J AU Chase, GW Ye, L Stoakes, VC Eitenmiller, RR Long, AR AF Chase, GW Ye, L Stoakes, VC Eitenmiller, RR Long, AR TI An interlaboratory-verified method for the determination of vitamins A and E in milk- and soy-based infant formula by liquid chromatography with matrix solid-phase dispersion extraction SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID ACETATE AB An interlaboratory-verified, liquid chromatographic (LC) method is presented for determination of all-racemic alpha-tocopheryl acetate and retinyl palmitate in infant formula. The extraction procedure uses matrix solid-phase dispersion. A sample is mixed with C18, and the mixture is packed into a reservoir and eluted with selective solvents to extract the analytes. After evaporation and filtration, the sample extract is injected directly into a normal-phase LC system with fluorescence detection. All-racemic alpha-tocopheryl acetate and retinyl palmitate are quantitated isocratically with a mobile phase of hexane containing isopropanol at 0.2% (v/v) and 0.125% (v/v), respectively. A nonfortified zero control reference material (ZRM) was spiked at 5 levels, with 5 replicate analyses of 1/2x, x, 2x, 4x, and 16x where "x" represents the minimum levels of 250 IU/100 kcal (vitamin A) and 0.7 IU/100 kcal (vitamin E) as specified in Title 21 of the Code of Federal Regulations, part 107.100. Recoveries of retinyl palmitate ranged from 83.8 to 107%, and those of all-racemic alpha-tocopheryl acetate ranged from 87.7 to 108%. Two additional laboratories analyzed the ZRM samples at 4 spiking levels with 6 replicates. Recoveries of retinyl palmitate and all-racemic alpha-tocopheryl acetate ranged from 92.2 to 104% and from 91.7 to 101%, respectively, in the second laboratory. Recoveries of retinyl palmitate and all-racemic alpha-tocopheryl acetate ranged from 85.3 to 97.0% and from 86.6 to 110%, respectively, in the third laboratory. Relative standard deviations for all 3 laboratories ranged from 0.2 to 7.5% with an average of 2.9%. In addition, each laboratory analyzed a commercial milk- and commercial soy-based infant formula. Excellent agreement in results was obtained between the 3 laboratories for vitamins A and E in all matrixes. C1 US FDA, Atlantic Ctr Nutrient Anal, Athens, GA 30602 USA. Univ Georgia, Dept Food Sci & Technol, Athens, GA 30309 USA. US FDA, Atlanta Ctr Nutrient Anal, Athens, GA 30309 USA. Univ Georgia, Dept Food Sci & Technol, Athens, GA 30602 USA. RP Chase, GW (reprint author), US FDA, Pacific Reg Lab NW, 22201 23rd Dr SE, Bothell, WA 98026 USA. EM William.chase@fda.gov NR 4 TC 4 Z9 4 U1 1 U2 7 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 2004 VL 87 IS 5 BP 1173 EP 1178 PG 6 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 853YO UT WOS:000223867100020 PM 15493675 ER PT J AU Mercer, GE Hurlbut, JA AF Mercer, GE Hurlbut, JA TI A multiresidue pesticide monitoring procedure using gas chromatography/mass spectrometry and selected ion monitoring for the determination of pesticides containing nitrogen, sulfur, and/or oxygen in fruits and vegetables SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID ON-COLUMN INJECTION; EXTRACTION; SPLITLESS; RESIDUES AB A procedure for the analysis of over 100 pesticides that only contain combinations of carbon, hydrogen, nitrogen, sulfur, and oxygen (i.e., no phosphorous or halogen atoms) has been developed. The procedure employs gas chromatography with a mass selective detector (GC/MSD), electron impact ionization, and selected ion monitoring. This GC/MSD procedure provided lower limits of quantitation and increased confirmational data compared to the traditional element-selective GC procedures that are commonly used for the detection of this "class" of pesticides. These analytical improvements were demonstrated by 26 pesticides that were detected at ng/g levels in a variety of fruit and vegetable matrixes using this procedure; these pesticides were missed by the traditional element-selective GC procedures. Validation of the procedure was performed using acetone extraction with solid-phase extraction cleanup. Twenty representative target pesticides were used to demonstrate repeatability and linearity of the chromatographic response and recovery from fruit and vegetable matrixes. C1 US FDA, Pacific Reg Lab NW, Bothell, WA 98021 USA. Western Washington Univ, Dept Chem, Bellingham, WA 98225 USA. RP Mercer, GE (reprint author), US FDA, Pacific Reg Lab NW, 22201 23rd Dr SE, Bothell, WA 98021 USA. EM gmercer@ora.fda.gov NR 19 TC 20 Z9 21 U1 0 U2 0 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD SEP-OCT PY 2004 VL 87 IS 5 BP 1224 EP 1236 PG 13 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 853YO UT WOS:000223867100027 PM 15493682 ER PT J AU Podhorniak, LV Schenck, FJ Krynitsky, A Griffith, F AF Podhorniak, LV Schenck, FJ Krynitsky, A Griffith, F TI Multiresidue method for N-methyl carbamates and metabolite pesticide residues at the parts-per-billion level in selected representative commodities of fruit and vegetable crop groups SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID LIQUID-CHROMATOGRAPHY; ORGANOPHOSPHATE; CLEANUP AB A reversed-phase liquid chromatographic method with both fluorescence and mass spectrometric detection is presented for the determination of 13 parent N-methyl carbamate pesticides and their metabolites, as well as piperonyl butoxide, for a total of 24 compounds in selected fruits and vegetables. The commodities chosen were of special concern to the U.S. Environmental Protection Agency (EPA) because they had the least amount of monitoring data for dietary exposure estimates used in risk assessment. The method is based on a judicious selection of procedures from U.S. Food and Drug Administration sources such as the Pesticide Analytical Manual (Volume I), and Laboratory Information Bulletins, plus additional material from the chemical literature combined in a manner to recover the N-methyl carbamates and their metabolites at the 1 mu/kg or 1 part-per-billion level. The method uses an acetone extraction, followed by an aminopropyl solid-phase extraction cleanup. Determination of residues is by RP-LC, in which the liquid chromatograph is interfaced with either a fluorescence or a mass spectrometric detector. The method is designed so that a set of 6 samples can be prepared in 1 working day for overnight instrumental analysis. Recovery data are presented from analyses of selected commodities in some of EPA's fruit and vegetable crop groupings. A table listing relative retention times is presented for the N-methyl carbamates and their metabolites. C1 US EPA, Off Pesticide Programs, Biol & Econ Anal Div, Analyt Chem Branch,Environm Sci Ctr, Ft George G Meade, MD 20755 USA. US FDA, SE Reg Lab, Atlanta, GA 30309 USA. US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Podhorniak, LV (reprint author), US EPA, Off Pesticide Programs, Biol & Econ Anal Div, Analyt Chem Branch,Environm Sci Ctr, 701 Mapes Rd,Mail Code 7503C,Rm C209, Ft George G Meade, MD 20755 USA. EM Podhomiak.Lynda@epa.gov NR 8 TC 10 Z9 11 U1 1 U2 3 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD SEP-OCT PY 2004 VL 87 IS 5 BP 1237 EP 1251 PG 15 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 853YO UT WOS:000223867100028 PM 15493683 ER PT J AU Cher, ML Li, YW Che, MX Bhagat, S Ellis, KL Kucuk, O Doerge, DR Abrams, J Sarkar, FH AF Cher, ML Li, YW Che, MX Bhagat, S Ellis, KL Kucuk, O Doerge, DR Abrams, J Sarkar, FH TI Regulation of gene expression and inhibition of experimental prostate cancer bone metastasis by dietary genistein SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 4th International Conference on Cancer-Induced Bone Diseases CY DEC 08, 2003 CL San Antonio, TX C1 Wayne State Univ, Detroit, MI USA. Karmanos Canc Inst, Detroit, MI USA. US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2004 VL 19 IS 9 BP 1593 EP 1594 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 850JP UT WOS:000223607500127 ER PT J AU Williams, G AF Williams, G TI Cancer drug development: For populations or for individuals? SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material C1 US FDA, Ctr Drug Evaluat, Div Oncol Drug Prod, Rockville, MD 20857 USA. RP Williams, G (reprint author), US FDA, Ctr Drug Evaluat, Div Oncol Drug Prod, Rockville, MD 20857 USA. NR 4 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 SEP 1 PY 2004 VL 22 IS 17 BP 3441 EP 3442 DI 10.1200/JCO.2004.06.918 PG 2 WC Oncology SC Oncology GA 851UN UT WOS:000223711300003 PM 15277539 ER PT J AU Buchanan, RL Dennis, S Miliotis, M AF Buchanan, RL Dennis, S Miliotis, M TI Initiating and managing risk assessments within a risk analysis framework: FDA/CFSAN'S practical approach SO JOURNAL OF FOOD PROTECTION LA English DT Article; Proceedings Paper CT 1st International Conference on Microbiological Risk Assessment - Foodborne Hazards CY JUL 24-26, 2002 CL Adelphia, MD AB Management of risk analysis involves the integration and coordination of activities associated with risk assessment, risk management, and risk communication. Risk analysis is used to guide regulatory decision making, including trade decisions at national and international levels. The U.S. Food and Drug Administration Center for Food Safety and Applied Nutrition (CFSAN) formed a working group to evaluate and improve the quality and consistency of major risk assessments conducted by the Center. Drawing on risk analysis experiences, CFSAN developed a practical framework for initiating and managing risk assessments, including addressing issues related to (i) commissioning a risk assessment, (ii) interactions between risk managers and risk assessors, and (iii) peer review. C1 US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Buchanan, RL (reprint author), US FDA, Ctr Food Safety & Appl Nutr, HFS-06,5100 Paint Branch Pkwy,2B64, College Pk, MD 20740 USA. EM robert.buchanan@cfsan.fda.gov NR 10 TC 11 Z9 13 U1 1 U2 8 PU INT ASSOC FOOD PROTECTION PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD SEP PY 2004 VL 67 IS 9 BP 2058 EP 2062 PG 5 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 852CF UT WOS:000223732100034 PM 15453602 ER PT J AU Claycamp, HG Hooberman, BH AF Claycamp, HG Hooberman, BH TI Antimicrobial resistance risk assessment in food safety SO JOURNAL OF FOOD PROTECTION LA English DT Article; Proceedings Paper CT 1st International Conference on Microbiological Risk Assessment - Foodborne Hazards CY JUL 24-26, 2002 CL Adelphia, MD ID ANTIBIOTIC-RESISTANCE; UNITED-STATES; INFECTIONS; PATHOGENS; ANIMALS; FRAMEWORK; AGENTS; TOPICS AB Microbiological risk assessments generally focus on estimating adverse human health risks from exposures to human pathogenic microbes. The assessment of potential human health risks posed by pathogens that have acquired resistance to antimicrobial drugs is a new application of risk assessment that is closely related to microbiological risk assessment. Antimicrobial resistance risk assessment is a risk analytical process that focuses on resistance determinants as hazardous agents that might lead to drug-resistant microbial infections in humans exposed to bacteria carrying the determinants. Antimicrobial-resistant infections could occur directly from actively invading or opportunistic pathogens or indirectly from the transfer of resistance genes to other bacteria. Here, we discuss risk assessment models that might be employed to estimate risks from drug-resistant bacteria in the animal food pathway and the types of models and data that may be used for microbiological risk assessments or antimicrobial resistance risk assessments. C1 US FDA, Ctr Vet Med, Off New Anim Drug Evaluat, Rockville, MD 20855 USA. RP Claycamp, HG (reprint author), US FDA, Ctr Vet Med, Off New Anim Drug Evaluat, 7519 Standish Pl,HFV 102, Rockville, MD 20855 USA. EM hclaycam@cvm.fda.gov NR 53 TC 8 Z9 8 U1 0 U2 3 PU INT ASSOC FOOD PROTECTION PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD SEP PY 2004 VL 67 IS 9 BP 2063 EP 2071 PG 9 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 852CF UT WOS:000223732100035 PM 15453603 ER PT J AU Hilbert, SL Yanagida, R Souza, J Wolfinbarger, L Jones, AL Krueger, P Stearns, G Bert, A Hopkins, RA AF Hilbert, SL Yanagida, R Souza, J Wolfinbarger, L Jones, AL Krueger, P Stearns, G Bert, A Hopkins, RA TI Prototype anionic detergent technique used to decellularize allograft valve conduits evaluated in the right ventricular outflow tract in sheep SO JOURNAL OF HEART VALVE DISEASE LA English DT Article; Proceedings Paper CT 6th Annual Hilton Head Workshop CY MAR 06-10, 2002 CL Hilton Head Isl, SC ID ENGINEERED HEART-VALVES; CARDIAC VALVES; IN-VITRO; TISSUE; REPLACEMENT; MYOFIBROBLAST; RESTORATION; EXPERIENCE; HOMOGRAFTS; LEAFLETS AB Background and aim of the study: Biodegradable polymeric materials or extracellular matrix scaffolds are used in tissue-engineered heart valve designs, with the expectation of replicating the anatomic, histological and biomechanical characteristics of semilunar valves. The study aim was to evaluate the extent of in-vivo recellularization and the explant pathology findings of a prototype anionic, non-denaturing detergent and endonuclease technique used to decellularize allograft (homograft) valve conduits implanted in the right ventricular outflow tract (RVOT) of sheep, and to identify possible risks associated with tissue-engineered heart valve conduits based on decellularized allograft semilunar valve scaffolds. Methods: Valve conduits were decellularized using a solution of N-lauroylsarcosinate and endonucleases, rinsed in lactated Ringers solution, and stored in an antibiotic solution at 4degreesC until implanted. Explanted valves and unimplanted controls were examined macroscopically, radiographically (for calcification) and histologically using immunohistochemistry (IHC), routine and special histological stains, transmission electron microscopy (TEM) and polarized light microscopy (evaluation of collagen crimp). Results: Cells and cellular remnants were uniformly absent in the decellularized cusps, but occasional focal sites of arterial wall smooth muscle cells and to a greater extent subvalvular cardiac myocytes were variably retained. The trilaminar histological structure of the cusp was preserved. Valve conduit-related pathology consisted of intracuspal hematoma formation, collagen fraying, thinning of the conduit wall, and inflammatory cells associated with cardiac myocyte remnants. Cuspal calcification was not seen, but elastic fibers in the conduit wall and retained subvalvular cardiac myocyte remnants were liable to calcification. Fibrous sheath formation was present on the luminal. surface of the conduit and extended over the cuspal surfaces to a variable extent. Myofibroblast-like cells repopulated the conduit wall and the basal region of the cusp. Re-endothelialization was variably present on the cuspal surfaces. Conclusion: Explant pathology findings showed that in-vivo recellularization occurred, but was focally limited to regions of the arterial wall and cusp base. Safety concerns related to detergent and endonuclease use were identified. Methods to eliminate the potential for structural deterioration and enhance the rate and extent of recellularization of valve conduit tissue are required. Pathology findings showed implantation of valve conduits in the RVOT of juvenile sheep for 20 weeks to be a reliable animal model for the initial in-vivo assessment of decellularized valves. A 20-week period may be insufficient however to evaluate the long-term safety and effectiveness of a tissue-engineered valve conduit, as these depend on effective and phenotypically appropriate recellularization accompanied by sustained cell viability and function. C1 US FDA, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, Rockville, MD 20857 USA. Rhode Isl Hosp, Collis Cardiac Surg Res Lab, Providence, RI 02903 USA. Brown Med Sch, Div Cardiothorac Surg, Dept Surg, Providence, RI USA. LifeNet, Virginia Beach, VA USA. RP Hopkins, RA (reprint author), Rhoe Isl Hosp, Brown Med Sch, Div Cardiac Surg, 2 Dudley St,500, Providence, RI 02905 USA. EM RAHopkins@lifespan.org RI Liu, Yifei/L-7828-2014 OI Liu, Yifei/0000-0002-1087-9827 NR 36 TC 23 Z9 25 U1 0 U2 3 PU I C R PUBLISHERS PI NORTHWOOD PA CRISPIN HOUSE, 12/A SOUTH APPROACH, MOOR PARK, NORTHWOOD HA6 2ET, ENGLAND SN 0966-8519 J9 J HEART VALVE DIS JI J. Heart Valve Dis. PD SEP PY 2004 VL 13 IS 5 BP 831 EP 840 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 853EG UT WOS:000223808900026 PM 15473487 ER PT J AU Arudchandran, A Bernstein, RM Max, EE AF Arudchandran, A Bernstein, RM Max, EE TI Single-stranded DNA breaks adjacent to cytosines occur during Ig gene class switch recombination SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CYTIDINE DEAMINASE AID; SOMATIC HYPERMUTATION; B-CELLS; S-REGIONS; MU REGION; DEFICIENCY; TRANSCRIPTION; RNA; CLEAVAGE; DELETION AB Class switch recombination (CSR) at the DNA level underlies ability of B lymphocytes to switch from expressing IgM to expressing IgG, IgA, or IgE. The mechanism of CSR is largely unknown, but it is clear that CSR is stimulated by T cell signals and is mediated in part by activation-induced deaminase (AID), an enzyme that is also required for somatic hypermutation of Ig genes. In one current model, AID is proposed to initiate CSR by deaminating cytosines in the unpaired nontemplate, strand of DNA displaced from its complementary strand by the "sterile" RNA transcript across the switch region. We have used LM-PCR to analyze single-strand breaks in CH12F3-2, a murine cell line that switches in vitro to IgA expression. In contrast to the above model, we have detected CSR-associated ssDNA breaks in the template strand of the H chain a switch region, the strand thought to be complexed with RNA. Most breaks are adjacent to cytosines, consistent with mediation by AID, and occur within the novel consensus sequence C*AG, which occurs much more frequently on the template strand than on the putatively displaced nontemplate strand. These results suggest that AID may target the DNA strand bound to RNA, perhaps resembling APOBEC-3G, a cytosine deaminase related to AID that inhibits HIV replication by mutating viral DNA. Furthermore, the absence of detectable breaks in the nontemplate strand within the DNA segment under study suggests that the two DNA strands are handled differently in the generation or processing of strand breaks. C1 US FDA, Ctr Drug Evaluat & Res, Div Therapeut Prot, Off Biotechnol Prod, Bethesda, MD 20892 USA. RP Max, EE (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Therapeut Prot, Off Biotechnol Prod, HFM-541,8800 Rockville Pike, Bethesda, MD 20892 USA. EM max@cber.fda.gov NR 36 TC 16 Z9 16 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 1 PY 2004 VL 173 IS 5 BP 3223 EP 3229 PG 7 WC Immunology SC Immunology GA 849HR UT WOS:000223529800046 PM 15322184 ER PT J AU Lin, FYC Weisman, LE Azimi, PH Philips, JB Clark, P Regan, J Rhoads, GG Frasch, CE Gray, BM Troendle, J Brenner, RA Moyer, P Clemens, JD AF Lin, FYC Weisman, LE Azimi, PH Philips, JB Clark, P Regan, J Rhoads, GG Frasch, CE Gray, BM Troendle, J Brenner, RA Moyer, P Clemens, JD TI Level of maternal IgG anti-group B streptococcus type III antibody correlated with protection of neonates against early-onset disease caused by this pathogen SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID TOXOID CONJUGATE VACCINE; POLYSACCHARIDE VACCINE; PREGNANT-WOMEN; HUMAN-SERA; INFECTION; IMMUNIZATION; IMMUNOGENICITY AB The present study estimates the level of maternal immunoglobulin (Ig) G anti-group B streptococcus (GBS) type III required to protect neonates against early-onset disease (EOD) caused by this pathogen. Levels of maternal serum IgG anti-GBS type III, measured by enzyme-linked immunosorbent assay, in 26 case patients ( neonates with EOD caused by GBS type III) and greater than or equal to43 matched control subjects ( neonates colonized by GBS type III who did not develop EOD) of greater than or equal to 34 weeks gestation were compared. The probability of EOD decreased with increasing levels of maternal IgG anti-GBS type III (P = .01). Neonates whose mothers had greater than or equal to10 mug/mL IgG anti-GBS type III had a 91% lower risk for EOD, compared with those whose mothers had levels of <2 μg/mL. A vaccine that induces IgG anti-GBS type III levels of &GE;10 μg/mL in mothers can be predicted to offer a significant degree of protection against EOD caused by this pathogen. C1 NICHHD, NIH, US Dept HHS, Bethesda, MD 20892 USA. US FDA, Ctr Biol Res & Review, US Dept HHS, Bethesda, MD 20014 USA. Baylor Coll Med, Houston, TX 77030 USA. Childrens Hosp Med Ctr No Calif, Oakland, CA USA. Univ Alabama, Birmingham, AL USA. Univ Florida, Gainesville, FL USA. Columbia Univ Hlth Sci, New York, NY USA. Univ Med & Dent New Jersey, Piscataway, NJ 08854 USA. RP Lin, FYC (reprint author), NICHHD, NIH, US Dept HHS, 6100 Execut Blvd,Rm 7B03,MSC 7510, Bethesda, MD 20892 USA. EM link@exchange.nih.gov FU NICHD NIH HHS [HD-53233, HD-43214, HD-43218, HD-43217, HD-43215, HD-43219, HD-43220] NR 31 TC 59 Z9 61 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD SEP 1 PY 2004 VL 190 IS 5 BP 928 EP 934 DI 10.1086/422756 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 843VL UT WOS:000223114800009 PM 15295698 ER PT J AU Fraunfelder, FW Fraunfelder, FT AF Fraunfelder, FW Fraunfelder, FT TI Evidence for a probable causal relationship between tretinoin, acitretin, and etretinate and intracranial hypertension SO JOURNAL OF NEURO-OPHTHALMOLOGY LA English DT Article ID TRANS-RETINOIC ACID; ACUTE PROMYELOCYTIC LEUKEMIA; PSEUDOTUMOR CEREBRI; ISOTRETINOIN; TETRACYCLINE AB With the recognition that vitamin A and isotretinoin may cause intracranial hypertension, the authors reviewed 331 case reports of ocular side effects associated with the three other marketed retinoids: tretinoin, acitretin, and etretinate. The reports were drawn from the National Registry of Drug-Induced Ocular Side Effects, the World Health Organization (WHO), the Food and Drug Administration, and medical journals between 1979 and 2003. There were 21 cases of intracranial hypertension associated with these three retinoids, leading to an inference that they are probably causally related to intracranial hypertension by WHO criteria. The lack of positive rechallenge data precludes the inference of a definite causal relationship to intracranial hypertension by WHO criteria. The inference of an independent causal role of these retinoids is further cautioned by the fact that six patients were concurrently using tetracycline or minocycline. Even so, the data suggest that all retinoids may, in rare instances, cause intracranial hypertension. C1 Oregon Hlth Sci Univ, Casey Eye Inst, Portland, OR 97201 USA. WHO, Collaborating Ctr Int Drug Monitoring, Uppsala, Sweden. US FDA, Rockville, MD 20857 USA. Casey Eye Inst, Natl Registry Drug Induced Ocular Side Effects, Portland, OR USA. RP Fraunfelder, FW (reprint author), Oregon Hlth Sci Univ, Casey Eye Inst, 3375 SW Terwilliger Blvd, Portland, OR 97201 USA. EM eyedrug@ohsu.edu NR 14 TC 22 Z9 22 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1070-8022 J9 J NEURO-OPHTHALMOL JI J. Neuro-Ophthal. PD SEP PY 2004 VL 24 IS 3 BP 214 EP 216 DI 10.1097/00041327-200409000-00006 PG 3 WC Clinical Neurology; Ophthalmology SC Neurosciences & Neurology; Ophthalmology GA 851TL UT WOS:000223708300006 PM 15348987 ER PT J AU Eller, N Inoue, S Scott, D AF Eller, N Inoue, S Scott, D TI Potential role of interleukin-15 (IL-15) in autoimmunity and impact of IGIV on IL-15 expression SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Meeting Abstract CT 7th International Congress of the International-Society-of-Neuroimmunology CY SEP 28-OCT 02, 2004 CL Venice, ITALY SP Int Soc Neuroimmunol C1 US FDA, Bethesda, MD 20014 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 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD SEP PY 2004 VL 154 IS 1-2 SI SI MA 109 BP 34 EP 34 PG 1 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 855VO UT WOS:000224003200113 ER PT J AU Bavveja, R AF Bavveja, R. TI Appreciating primary clinical efficacy endpoints of neuropharmacological drugs as a guide to directly formulating them into modified release dosage forms SO JOURNAL OF PHARMACY AND PHARMACOLOGY LA English DT Meeting Abstract C1 [Bavveja, R.] US FDA, Rockville, MD 20857 USA. EM BAWEJA@cder.fda.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU PHARMACEUTICAL PRESS-ROYAL PHARMACEUTICAL SOC GREAT BRITIAN PI LONDON PA 1 LAMBETH HIGH ST, LONDON SE1 7JN, ENGLAND SN 0022-3573 J9 J PHARM PHARMACOL JI J. Pharm. Pharmacol. PD SEP PY 2004 VL 56 SU S MA 287 BP S102 EP S102 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA V50KV UT WOS:000203408100287 ER PT J AU Orimo, H Mei, N Boiteux, S Tokura, Y Kasai, H AF Orimo, H Mei, N Boiteux, S Tokura, Y Kasai, H TI Analysis of 8-hydroxyguanine (8-OH-Gua) released from DNA by the formamidopyrimidine DNA glycosylase (Fpg) protein: A reliable method to estimate cellular oxidative stress SO JOURNAL OF RADIATION RESEARCH LA English DT Article ID GAMMA-IRRADIATION; 8-OXOGUANINE; 8-HYDROXYDEOXYGUANOSINE; DAMAGE; HYDROXYLATION; MARKER AB To improve the analyses of a form of oxidative DNA damage, 8-hydroxyguanine (8-OH-Gua), we treated isolated DNA with formamidopyrimidine DNA glycosylase (Fpg) and analyzed the released 8-OH-Gua by using a high-performance liquid chromatography system equipped with an electrochemical detector (HPLC-ECD). The human lung carcinoma cells (A549) and human keratinocyte (HaCaT) were irradiated with gamma-rays. After the isolated DNA was treated with the Fpg protein, we analyzed the released 8-OH-Gua by using an HPLC-ECD. With this method, the background level of 8-OH-Gua in DNA from human lung carcinoma cells was determined to be 3.4 residues per 10(7) guanine (Gua). A similar background level of 8-OH-Gua (3.1 residues per 10(7) Gua) was also detected in human keratinocyte DNA with this method. These background 8-OH-Gua levels in cellular DNA are comparable to that obtained previously by an analysis of 8-OH-dGMP after nuclease P1 digestion of cellular DNA (4.3 residues per 10(7) dCMP). A dose-dependent increase of 8-OH-Gua (0.17/10(7) Gua/Gy) was observed after cells were irradiated with gamma-rays. Twenty hours after gamma-irradiation with 60 Gy, 75% of the 8-OH-Gua produced in keratinocyte DNA was repaired. With our new analysis method, it is possible to detect the small changes in the 8-OH-Gua levels in cellular DNA induced by various environmental factors. C1 Univ Occupat & Environm Hlth, Inst Ind Ecol Sci, Dept Environm Oncol, Kitakyushu, Fukuoka 8078555, Japan. US FDA, Natl Ctr Toxicol Res, Div Geriatr & Reprod Toxicol, Jefferson, AR 72079 USA. CEA, DSV, Dept Radiobiol & Radiopathol, UMR 217,CNRS, F-92265 Fontenay Aux Roses, France. Univ Occupat & Environm Hlth, Dept Dermatol, Kitakyushu, Fukuoka 8078555, Japan. RP Kasai, H (reprint author), Univ Occupat & Environm Hlth, Inst Ind Ecol Sci, Dept Environm Oncol, Kitakyushu, Fukuoka 8078555, Japan. EM h-kasai@med.uoeh-u.ac.jp RI mei, nan/E-8915-2011 OI mei, nan/0000-0002-3501-9014 NR 23 TC 8 Z9 9 U1 0 U2 0 PU JAPAN RADIATION RESEARCH SOC PI CHIBA PA C/O NAT INST RADIOLOGICAL SCI 9-1 ANAGAWA-4-CHOME INAGE-KU, CHIBA, 263, JAPAN SN 0449-3060 J9 J RADIAT RES JI J. Radiat. Res. PD SEP PY 2004 VL 45 IS 3 BP 455 EP 460 DI 10.1269/jrr.45.455 PG 6 WC Biology; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Radiology, Nuclear Medicine & Medical Imaging GA 898TV UT WOS:000227100000013 PM 15613792 ER PT J AU Davis, JA Brown, AT Chen, HJ Wang, YF Poirier, LA Eidt, JF Cruz, CP Moursi, MM AF Davis, JA Brown, AT Chen, HJ Wang, YF Poirier, LA Eidt, JF Cruz, CP Moursi, MM TI Cigarette smoke increases intimal hyperplasia and homocysteine in a rat carotid endarterectomy SO JOURNAL OF SURGICAL RESEARCH LA English DT Article DE homocysteine; CBS; MTHFR; folic acid; cigarette; intimal hyperplasia ID PERCUTANEOUS CORONARY INTERVENTION; PLASMA HOMOCYSTEINE; RISK-FACTOR; FOLIC-ACID; INTERMITTENT CLAUDICATION; CARDIOVASCULAR-DISEASE; LOWERING THERAPY; VASCULAR-DISEASE; HEART-DISEASE; FOLLOW-UP AB Background. Homocysteine and smoking are independent risks for CVD; however their importance in post-CEA intimal hyperplasia is unclear. We performed a CEA in rats exposed to cigarette smoke with the hypothesis that smoking would increase intimal hyperplasia that may be associated with an elevated serum homocysteine. Folic acid (FA) and the homocysteine metabolic enzymes MTHFR and CBS were used to test for the significance of homocysteine elevation. Materials and methods. Rats underwent an open CEA. N = 13 rats received smoke exposure 2 weeks prior, and 2 weeks post-CEA and N = 12 received no smoke. Each group was divided into either control or an FA-added diet resulting in four groups. Rats were sacrificed at 2 weeks post-CEA; liver, urine, blood, and carotid arteries samples were obtained. Results. Smoked rats had increased urinary peak and trough cotinine levels versus non-smoke rats, which decreased with FA. Smoke exposure increased intimal hyperplasia versus non-smoke controls by nearly 120% (57.8 +/- 6.2 versus 26.8 +/- 5.4% luminal stenosis, P = 0.005). Smoke-exposed rats had an increased serum homocysteine versus non-smoke controls (8.3 +/- 0.8 versus 5.7 +/- 0.8 mum, P = 0.014). Smoked rats given FA had decreased serum homocysteine compared to the smoke group. Along with reductions in homocysteine, FA eliminated the increase in intimal hyperplasia seen with smoke exposure (33.5 +/- 6.1 versus 57.8 +/- 6.2% luminal stenosis, P = 0.03). CBS activity decreased in smoked rats by nearly 20% versus non-smoke rats. FA supplementation in smoked rats both (1) increased CBS activity and (2) decreased MTHFR compared to control non-smoke-exposure levels. Conclusion. Smoking increases plasma homocysteine and post-CEA intimal hyperplasia. This suggests homocysteine has an etiological role in the intimal hyperplasia increase observed with smoking, since both were negated with FA. (C) 2004 Elsevier Inc. All rights reserved. C1 Univ Arkansas Med Sci, Cent Arkansas Vet HealthCare Syst, Vasc Serv, Little Rock, AR 72205 USA. Natl Ctr Toxicol Res, Div Mol Epidemiol, Jefferson, AR 72079 USA. RP Moursi, MM (reprint author), Univ Arkansas Med Sci, Cent Arkansas Vet HealthCare Syst, Vasc Serv, 112-PV,43000 W 7th St, Little Rock, AR 72205 USA. EM moursimohammedm@exchange.uams.edu NR 46 TC 7 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 0022-4804 J9 J SURG RES JI J. Surg. Res. PD SEP PY 2004 VL 121 IS 1 BP 69 EP 75 DI 10.1016/j.jss.2004.04.001 PG 7 WC Surgery SC Surgery GA 847ZU UT WOS:000223437500012 PM 15313378 ER PT J AU Brown, SL Woo, EK AF Brown, SL Woo, EK TI Surgical stapler-associated fatalities and adverse events reported to the food and drug administration SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article AB BACKGROUND: Use of stapling devices has become standard practice in many operations, and these devices have many applications, including ligation and division, resection, anastomosis, and fascial closure. The Food and Drug Administration (FDA) regulates surgical staplers as a medical device. Manufacturers and health-care providers report adverse events occurring during the use of surgical staplers to the FDA. STUDY DESIGN: Two FDA adverse event databases, the Manufacturer and User Facility Device Experience database and the Alternative Summary Reporting database were searched for adverse events related to the use of surgical staplers. An FDA recall database, Oracle System Center Automated Retrieval, was searched for surgical stapler recalls and the reason for these recalls. RESULTS: We characterized adverse events from 112 death, 2,180 injury, and 22,804 malfunction reports from FDA adverse event databases. We described 22 recalls for these products that are listed in an FDA database. A majority of these recalls were related to manufacturing or design problems. CONCLUSIONS: The overall incidence of these events remains unknown; because these products are used so frequently, even uncommon adverse events may affect many patients. It is important for health-care providers to report adverse events to manufacturers so that they may work to improve the design of these devices and reduce use errors that contribute to the events. C1 US FDA, Ctr Devices & Radiol Hlth, Off Surveillance & Biometr, Div Postmarket Surveillance,Epidemiol Branch, Rockville, MD 20850 USA. US FDA, Ctr Devices & Radiol Hlth, Off Surveillance & Biometr, Div Postmarket Surveillance,Prod Evaluat Branch, Rockville, MD 20850 USA. RP Brown, SL (reprint author), US FDA, Ctr Devices & Radiol Hlth, Off Surveillance & Biometr, Div Postmarket Surveillance,Epidemiol Branch, 1350 Piccard Dr,HFZ-541, Rockville, MD 20850 USA. NR 13 TC 27 Z9 27 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD SEP PY 2004 VL 199 IS 3 BP 374 EP 381 DI 10.1016/j.jamcollsurg.2004.05.264 PG 8 WC Surgery SC Surgery GA 851LH UT WOS:000223686100004 PM 15325606 ER PT J AU Balter, S Schueler, BA Miller, DL Cole, PE Lu, HT Berenstein, A Albert, R Georgia, JD Noonan, PT Russell, EJ Malisch, TW Vogelzang, RL Geisinger, M Cardella, JF St George, J Miller, GL Anderson, J AF Balter, S Schueler, BA Miller, DL Cole, PE Lu, HT Berenstein, A Albert, R Georgia, JD Noonan, PT Russell, EJ Malisch, TW Vogelzang, RL Geisinger, M Cardella, JF St George, J Miller, GL Anderson, J TI Radiation doses in interventional radiology procedures: The RAD-IR study Part III: Dosimetric performance of the interventional fluoroscopy units SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article AB PURPOSE: To present the physics data supporting the validity of the clinical dose data from the RAD-IR study and to document the performance of dosimetry-components of these systems over time. MATERIALS AND METHODS: Sites at seven academic medical centers in the United States prospectively contributed data for each of 12 fluoroscopic units. All units were compatible with International Electrotechnical Commission (IEC) standard 60601-2-43. Comprehensive evaluations and periodic consistency checks were performed to verify the performance of each unit's dosimeter. Comprehensive evaluations compared system performance against calibrated ionization chambers under nine combinations of operating conditions. Consistency checks provided more frequent dosimetry data, with use of each unit's built-in dosimetry equipment and a standard water phantom. RESULTS: During the 3-year study, data were collected for 48 comprehensive evaluations and 581 consistency checks. For the comprehensive evaluations, the mean (95% confidence interval range) ratio of system to external measurements was 1.03 (1.00-1.05) for fluoroscopy and 0.93 (0.90-0.96) for acquisition. The expected ratio was 0.93 for both. For consistency checks, the values were 1.00 (0.98-1.02) for fluoroscopy and 1.00 (0.98-1.02) for acquisition. Each system was compared across time to its own mean value. Overall uncertainty was estimated by adding the standard deviations of the comprehensive and consistency measurements in quadrature. The authors estimate that the overall error in clinical cumulative dose measurements reported in RAD-IR is 24%. CONCLUSION: Dosimetric accuracy was well within the tolerances established by IEC standard 60601-2-43. The clinical dose data reported in the RAD-IR study are valid. C1 Natl Naval Med Ctr, Dept Radiol, Bethesda, MD 20889 USA. Lenox Hill Hosp, Dept Med, New York, NY 10021 USA. Mayo Clin, Rochester, MN USA. Uniformed Serv Univ Hlth Sci, F Edward Hebert Sch Med, Dept Radiol & Radiol Sci, Bethesda, MD 20814 USA. NCI, Med Oncol Clin Res Unit, Canc Res Ctr, Bethesda, MD 20892 USA. US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. Beth Israel Deaconess Med Ctr, Ctr Endovasc Surg, Hyman Newman Inst Neurol & Neurosurg, New York, NY 10003 USA. NW Mem Hosp, Dept Radiol, Chicago, IL 60611 USA. Northwestern Univ, Feinberg Sch Med, Dept Radiol, Chicago, IL 60611 USA. Cleveland Clin Fdn, Dept Radiol, Cleveland, OH 44195 USA. SUNY Upstate Med Univ, Dept Radiol, Syracuse, NY USA. Univ Texas, SW Med Ctr, Dept Radiol, Dallas, TX 75235 USA. Lahey Clin Fdn, Dept Radiol, Burlington, MA USA. Univ Colorado, Hlth Sci Ctr, Dept Radiol, Denver, CO 80262 USA. RP Miller, DL (reprint author), Natl Naval Med Ctr, Dept Radiol, Bethesda, MD 20889 USA. EM dm72v@nih.gov NR 9 TC 34 Z9 35 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1051-0443 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD SEP PY 2004 VL 15 IS 9 BP 919 EP 926 DI 10.1097/01.RVI.0000130864.68139.08 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA 906XQ UT WOS:000227678600004 PM 15361559 ER PT J AU Forsman, ZH Lednicky, JA Fox, GE Willson, RC White, ZS Halvorson, SJ Wong, C Lewis, AM Butel, JS AF Forsman, ZH Lednicky, JA Fox, GE Willson, RC White, ZS Halvorson, SJ Wong, C Lewis, AM Butel, JS TI Phylogenetic analysis of polyomavirus simian virus 40 from monkeys and humans reveals genetic variation SO JOURNAL OF VIROLOGY LA English DT Article ID PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; VIRAL REGULATORY REGION; NON-HODGKIN-LYMPHOMA; HUMAN-BRAIN-TUMORS; VACUOLATING VIRUS; JC VIRUS; SV40 GENOMES; HUMAN-CELLS; T-ANTIGEN; GROWTH AB A phylogenetic analysis of 14 complete simian virus 40 (SV40) genomes was conducted in order to determine strain relatedness and the extent of genetic variation. This analysis included infectious isolates recovered between 1960 and 1999 from primary cultures of monkey kidney cells, from contaminated poliovaccines and an adenovirus seed stock, from human malignancies, and from transformed human cells. Maximum-parsimony and distance methods revealed distinct SV40 clades. However, no clear patterns of association between genotype and viral source were apparent. One clade (clade A) is derived from strain 776, the reference strain of SV40. Clade B contains isolates from poliovaccines (strains 777 and Baylor), from monkeys (strains N128, Rh911, and K661), and from human tumors (strains SVCPC and SVMEN). Thus, adaptation is not essential for SV40 survival in humans. The C terminus of the T-antigen (T-ag-C) gene contains the highest proportion of variable sites in the SV40 genome. An analysis based on just the T-ag-C region was highly congruent with the whole-genome analysis; hence, sequencing of just this one region is useful in strain identification. Analysis of an additional 16 strains for which only the T-ag-C gene was sequenced indicated that further SV40 genetic diversity is likely, resulting in a provisional clade (clade C) that currently contains strains associated with human tumors and human strain PML-1. Four other polymorphic regions in the genome were also identified. If these regions were analyzed in conjunction with the T-ag-C region, most of the phylogenetic signal could be captured without complete genome sequencing. This report represents the first whole-genome approach to establishing phylogenetic relatedness among different strains of SV40. It will be important in the future to develop a more complete catalog of SV40 variation in its natural monkey host, to determine if SV40 strains from different clades vary in biological or pathogenic properties, and to identify which SV40 strains are transmissible among humans. C1 Baylor Coll Med, Dept Mol Virol & Microbiol, Houston, TX 77030 USA. Univ Houston, Dept Biol & Biochem, Houston, TX 77030 USA. US FDA, Ctr Biol Evaluat & Res, Off Vaccine Res & Review, DNA Virus Lab, Rockville, MD USA. RP Butel, JS (reprint author), Baylor Coll Med, Dept Mol Virol & Microbiol, 1 Baylor Plaza, Houston, TX 77030 USA. EM jbutel@bcm.tmc.edu RI Pepper, John/O-1662-2013 OI Pepper, John/0000-0001-9888-0437 FU NCI NIH HHS [R21 CA096951, CA096951] NR 48 TC 18 Z9 21 U1 1 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD SEP PY 2004 VL 78 IS 17 BP 9306 EP 9316 DI 10.1128/JVI.78.17.9306-9316.2004 PG 11 WC Virology SC Virology GA 847IT UT WOS:000223386600034 PM 15308725 ER PT J AU Liu, T Ye, ZP AF Liu, T Ye, ZP TI Introduction of a temperature-sensitive phenotype into influenza A/WSN/33 virus by altering the basic amino acid domain of influenza virus matrix protein SO JOURNAL OF VIROLOGY LA English DT Article ID M1 PROTEIN; A VIRUS; VIRAL RIBONUCLEOPROTEINS; NUCLEAR TRANSPORT; INFECTED-CELLS; RNA; MEMBRANE; ASSOCIATION; MORPHOLOGY; EXPORT AB Our previous studies with influenza A viruses indicated that the association of M1 with viral RNA and nucleoprotein (NP) is required for the efficient formation of helical ribonucleoprotein (RNP) and for the nuclear export of RNPs. RNA-binding domains of M1 map to the following two independent regions: a zinc finger motif at amino acid positions 148 to 162 and a series of basic amino acids (RKLKR) at amino acid positions 101 to 105. Altering the zinc finger motif of M1 reduces viral growth slightly. A substitution of Ser for Arg at either position 101 or position 105 of the RKLKR domain partially reduces the nuclear export of RNP and viral replication. To further understand the role of the zinc finger motif and the RKLKR domain in viral assembly and replication, we introduced multiple mutations by using reverse genetics to modify these regions of the M gene of influenza virus A/WSN/33. Of multiple mutants analyzed, a double mutant, R101S-R105S, of RKLKR resulted in a temperature-sensitive phenotype. The R101S-RI05S double mutant had a greatly reduced ratio of M1 to NP in viral particles and a weaker binding of M1 to RNPs. These results suggest that mutations can be introduced into the RKLKR domain to control viral replication. C1 CBER FDA, Bethesda, MD 20892 USA. Off Vaccine Res, Div Viral Prod, Lab Pediat & Resp Viral Dis, Bethesda, MD USA. RP Ye, ZP (reprint author), CBER FDA, Bldg 29A,Rm 2B17,8800 Rockville Pk, Bethesda, MD 20892 USA. EM yez@cber.fda.gov NR 42 TC 15 Z9 15 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD SEP PY 2004 VL 78 IS 18 BP 9585 EP 9591 DI 10.1128/JVI.78.18.9585-9591.2004 PG 7 WC Virology SC Virology GA 851QY UT WOS:000223701100001 PM 15331690 ER PT J AU Fernandez, J Taylor, D Morhardt, DR Mihalik, K Puig, M Rice, CM Feinstone, SM Major, ME AF Fernandez, J Taylor, D Morhardt, DR Mihalik, K Puig, M Rice, CM Feinstone, SM Major, ME TI Long-term persistence of infection in chimpanzees inoculated with an infectious hepatitis C virus clone is associated with a decrease in the viral amino acid substitution rate and low levels of heterogeneity SO JOURNAL OF VIROLOGY LA English DT Article ID HYPERVARIABLE REGION 1; CYTOTOXIC T-LYMPHOCYTES; ENVELOPE PROTEIN; SEQUENCE VARIATION; IMMUNE-RESPONSES; REPLICATION; MUTATIONS; EVOLUTION; GENOTYPES; VARIANTS AB Two chimpanzees, 1535 and 1536, became persistently infected following inoculation with RNA transcripts from cDNA clones of hepatitis C virus (HCV). Analysis of the HCV genomes from both animals showed an accumulation of amino acid substitutions over time. The appearance of substitutions in the envelope genes was associated with increased antienvelope antibody titers. However, extensive mutations were not incorporated into hypervariable region 1 (HVR1). A comparison of the nonsynonymous substitution rate/synonymous substitution rate was made at various time points to analyze selective pressure. The highest level of selective pressure occurred during the acute phase and decreased as the infection continued. The nonsynonymous substitution rate was initially higher than the synonymous substitution rate but decreased over time from 3.3 X 10(-3) (chimpanzee 1535) and 3.2 X 10(-3) (chimpanzee 1536) substitutions/site/year at week 26 to 1.4 X 10(-3) (chimpanzee 1535) and 1.7 X 10(-3) (chimpanzee 1536) at week 216, while the synonymous substitution rate remained steady at similar to1 X 10(-3) substitutions/site/year. Analysis of PCR products using single-stranded conformational polymorphism indicated a low level of heterogeneity in the viral genome. The results of these studies confirm that the persistence of infection is not solely due to changes in HVR1 or heterogeneity and that the majority of variants observed in natural infections could not arise simply through mutation during the time period most humans and chimpanzees are observed. These data also indicate that immune pressure and selection continue throughout the chronic phase. C1 US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Lab Hepatitis Viruses, Bethesda, MD 20892 USA. Rockefeller Univ, Ctr Study Hepatitis C, New York, NY USA. RP Major, ME (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Lab Hepatitis Viruses, Bldg 29A,Room 1D10,HVM 448,8800 Rockville Pike, Bethesda, MD 20892 USA. EM major@cber.fda.gov FU NCI NIH HHS [CA85883, R01 CA085883] NR 31 TC 33 Z9 33 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD SEP PY 2004 VL 78 IS 18 BP 9782 EP 9789 DI 10.1128/JVI.78.18.9782-9789.2004 PG 8 WC Virology SC Virology GA 851QY UT WOS:000223701100022 PM 15331711 ER PT J AU Pfefer, TJ Matchette, LS Drezek, R AF Pfefer, TJ Matchette, LS Drezek, R TI Influence of illumination-collection geometry on fluorescence spectroscopy in multilayer tissue SO MEDICAL & BIOLOGICAL ENGINEERING & COMPUTING LA English DT Article DE fibre-optic probe; fluorescence spectroscopy; light-tissue interaction; Monte Carlo modelling; optical diagnostics ID HUMAN COLON TISSUE; TURBID MEDIA; PROBE DESIGN; DEPTH; LIGHT; PROPAGATION; ENDOSCOPY; SPECTRA AB Device-tissue interface geometry influences both the intensity of detected fluorescence and the extent of tissue sampled. Previous modelling studies have often investigated fluorescent light propagation using generalised tissue and illumination-collection geometries. However, the implementation of approaches that incorporate a greater degree of realism may provide more accurate estimates of light propagation. In this study, Monte Carlo modelling was performed to predict how illumination-collection parameters affect signal detection in multilayer tissue. Using the geometry and optical properties of normal and atherosclerotic aortas, results for realistic probe designs and a semi-infinite source-detection scheme were generated and compared. As illumination-collection parameters, including single-fibre probe diameter and fibre separation distance in multifibre probes, were varied, the signal origin deviated significantly from that predicted using the semi-infinite geometry. The semi-infinite case under-predicted the fraction of fluorescence originating from the superficial layer by up to 23% for a 0.2 mm diameter single-fibre probe and over-predicted by 10% for a multifibre probe. These results demonstrate the importance of specifying realistic illumination-collection parameters in theoretical studies and indicate that targeting of specific tissue regions may be achievable through customisation of the illumination-collection interface. The device- and tissue-specific approach presented has the potential to facilitate the optimisation of minimally invasive optical systems for a wide variety of applications. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. Rice Univ, Dept Bioengn, Houston, TX 77251 USA. RP Pfefer, TJ (reprint author), US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. EM tdp@cdrh.fda.gov RI Drezek, Rebekah/A-5101-2012; Pfefer, Josh/I-9055-2012 NR 20 TC 13 Z9 14 U1 0 U2 2 PU PETER PEREGRINUS LTD PI HERTS PA MICHAEL FARADAY HOUSE, SIX HILLS WAY, STEVANAGE, HERTS SG1 2AY, ENGLAND SN 0140-0118 J9 MED BIOL ENG COMPUT JI Med. Biol. Eng. Comput. PD SEP PY 2004 VL 42 IS 5 BP 669 EP 673 DI 10.1007/BF02347549 PG 5 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Mathematical & Computational Biology; Medical Informatics SC Computer Science; Engineering; Mathematical & Computational Biology; Medical Informatics GA 863AC UT WOS:000224531600013 PM 15503968 ER PT J AU Yu, LX Straughn, AB Faustino, PJ Yang, Y Parekh, A Ciavarella, AB Asafu-Adjaye, E Mehta, MU Conner, DP Lesko, LJ Hussain, AS AF Yu, Lawrence X. Straughn, Arthur B. Faustino, Patrick J. Yang, Yongsheng Parekh, Ameeta Ciavarella, Anthony B. Asafu-Adjaye, Ebenezer Mehta, Mehul U. Conner, Dale P. Lesko, Larry J. Hussain, Ajay S. TI The effect of food on the relative bioavailability of rapidly dissolving immediate-release solid oral products containing highly soluble drugs SO MOLECULAR PHARMACEUTICS LA English DT Article DE BCS; food effect; HPLC; metoprolol; propranolol; hydrochlorothiazide AB The purpose of this study is to test the hypothesis that rapidly dissolving immediate-release (IR) solid oral products containing a highly soluble and highly permeable drug [biopharmaceutical classification system (BCS) class I] are bioequivalent under fed conditions. Metoprolol and propranolol (BCS class I) as well as hydrochlorothiazide (BCS class III) were selected as model drugs. The relative bioavailability of two FDA approved (Orange Book AB rating) solid oral dosage forms of metoprolol and propranolol/hydrochlorothiazide (combination tablets) was evaluated in human volunteers under fed conditions using a two-way crossover design. Equal numbers of male and female volunteers were recruited, and racial and/or ethnic minorities were not excluded. The plasma concentrations of metoprolol, propranolol, and hydrochlorothiazide were determined using validated high-performance liquid chromatography (HPLC) methods. Eighteen subjects completed the metoprolol study while 17 subjects completed the propranolol/hydrochlorothiazide combination tablet study. In the metoprolol study, the 90% confidence intervals of C-max and AUC(inf) were 98-118% and 92-115%, respectively. For propranolol, the 90% confidence intervals of C-max and AUC(inf) were 91-121 % and 89-117%, and for hydrochlorothiazide, the 90% confidence intervals for C-max and AUC(inf) were 96-107% and 97-106%, respectively. These study results appear to support the hypothesis that rapidly dissolving IR solid oral products containing a BCS class I drug are likely to be bioequivalent under fed conditions. In addition, BCS class III drugs may have the potential to be bioequivalent under fed conditions. C1 [Yu, Lawrence X.; Faustino, Patrick J.; Yang, Yongsheng; Parekh, Ameeta; Ciavarella, Anthony B.; Asafu-Adjaye, Ebenezer; Mehta, Mehul U.; Conner, Dale P.; Lesko, Larry J.; Hussain, Ajay S.] Food & Drug Adm, Ctr Drug Evaluat & Res, Off Pharmaceut Sci, Rockville, MD 20857 USA. [Straughn, Arthur B.] Univ Tennessee, Coll Pharm, Memphis, TN 38163 USA. RP Yu, LX (reprint author), Food & Drug Adm, Ctr Drug Evaluat & Res, Off Pharmaceut Sci, 5600 Fishers Lane, Rockville, MD 20857 USA. EM yul@cder.fda.gov RI Yu, Lawrence/L-6280-2016 NR 24 TC 22 Z9 22 U1 0 U2 7 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1543-8384 J9 MOL PHARMACEUT JI Mol. Pharm. PD SEP-OCT PY 2004 VL 1 IS 5 BP 357 EP 362 DI 10.1021/mp0499407 PG 6 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA V52IY UT WOS:000203538400004 PM 16026005 ER PT J AU Votano, JR Parham, M Hall, LH Kier, LB Oloff, S Tropsha, A Xie, QA Tong, W AF Votano, JR Parham, M Hall, LH Kier, LB Oloff, S Tropsha, A Xie, QA Tong, W TI Three new consensus QSAR models for the prediction of Ames genotoxicity SO MUTAGENESIS LA English DT Article ID NATIONAL-TOXICOLOGY-PROGRAM; CHEMICAL-STRUCTURE; ELECTROTOPOLOGICAL STATE; MUTAGENICITY; CARCINOGENICITY; SALMONELLA; TOXICITY; SELECTION; CLASSIFICATION; INDEXES AB Three QSAR methods, artificial neural net (ANN), k-nearest neighbors (kNN), and Decision Forest (DF), were applied to 3363 diverse compounds tested for their Ames genotoxicity. The ratio of mutagens to non-mutagens was 60/40 for this dataset. This group of compounds includes >300 therapeutic drugs. All models were developed using the same initial set of 148 topological indices: molecular connectivity chi indices and electrotopological state indices (atom-type, bond-type and group-type E-state), as well as binary indicators. While previous studies have found logP to be a determining factor in genotoxicity, it was not found to be important by any modeling method employed in this study. The three models yielded an average training/test concordance value of 88%, with a low percentage of false positives and false negatives. External validation testing on 400 compounds not used for QSAR model development gave an average concordance of 82%. This value increased to 92% upon removal of less reliable outcomes, as determined by a reliability criterion used within each model. The ANN model showed the best performance in predicting drug compounds, yielding 97% concordance (34/35 drugs) after the removal of less reliable predictions. The appreciable commonality found among the top 10 ranked descriptors from each model is of particular interest because of the diversity in the learning algorithms and descriptor selection techniques employed in this study. Forty percent of the most important descriptors in any one model are found in one or two other models. Fourteen of the most important descriptors relate directly to known toxicophores involved in potent genotoxic responses in Salmonella typhimurium. A comparison of the validation results with those of MULTICASE and DEREK indicated that the new models presented in this work perform substantially better than the former models in predicting genotoxicity of therapeutic drugs. Substantially higher specificity was achieved with these new models as compared with MULTICASE or DEREK with comparable sensitivities among all models. C1 ChemSilico LLC, Tewksbury, MA 01876 USA. Eastern Nazarene Coll, Dept Chem, Quincy, MA 02170 USA. Virginia Commonwealth Univ, Sch Pharm, Dept Med Chem, Richmond, VA 23298 USA. Univ N Carolina, Sch Pharm, Div Med Chem & Nat Prod, Lab Mol Modeling, Chapel Hill, NC 27599 USA. Natl Ctr Toxicol Res, Ctr Toxicoinformat, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. RP Votano, JR (reprint author), ChemSilico LLC, 48 Baldwin St, Tewksbury, MA 01876 USA. EM jvotano@chemsilico.com RI Tropsha, Alexander/G-6245-2014 NR 39 TC 92 Z9 94 U1 2 U2 20 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0267-8357 J9 MUTAGENESIS JI Mutagenesis PD SEP PY 2004 VL 19 IS 5 BP 365 EP 377 DI 10.1093/mutage/geh043 PG 13 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA 856XI UT WOS:000224079000006 PM 15388809 ER PT J AU Temmerman, S Pethe, K Parra, M Alonso, S Rouanet, C Pickett, T Drowart, A Debrie, AS Delogu, G Menozzi, FD Sergheraert, C Brennan, MJ Mascart, F Locht, C AF Temmerman, S Pethe, K Parra, M Alonso, S Rouanet, C Pickett, T Drowart, A Debrie, AS Delogu, G Menozzi, FD Sergheraert, C Brennan, MJ Mascart, F Locht, C TI Methylation-dependent T cell immunity to Mycobacterium tuberculosis heparin-binding hemagglutinin SO NATURE MEDICINE LA English DT Article ID ADHESIN; IMMUNOGENICITY; IDENTIFICATION; VACCINATION; RESPONSES AB Although post-translational modifications of protein antigens may be important componenets of some B cell epitopes, the determinants of T cell immunity are generally nonmodified peptides. Here we show that methylation of the Mycobacterium tuberculosis heparin-binding hemagglutinin ( HBHA) by the bacterium is essential for effective T cell immunity to this antigen in infected healthy humans and in mice. Methylated HBHA provides high levels of protection against M. tuberculosis challenge in mice, whereas nonmethylated HBHA does not. Protective immunity induced by methylated HBHA is comparable to that afforded by vaccination with bacille Calmette et GuErin, the only available anti-tuberculosis vaccine. Thus, post-translational modifications of proteins may be crucial for their ability to induce protective T cell-mediated immunity against infectious diseases such as tuberculosis. C1 Inst Pasteur, INSERM, U629, F-59019 Lille, France. Free Univ Brussels, Hop Erasme, Immunol Lab, B-1070 Brussels, Belgium. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. Brugmann Univ Hosp, Dept Internal Med, B-1020 Brussels, Belgium. Univ Lille 2, Inst Pasteur, CNRS, UMR8525,IBL, F-59019 Lille, France. RP Locht, C (reprint author), Inst Pasteur, INSERM, U629, 1 Rue Prof Calmette, F-59019 Lille, France. EM camille.locht@pasteur-lille.fr RI Pethe, Kevin/D-4505-2011; Delogu, Giovanni/I-3701-2012; Pethe, Kevin/L-1199-2013; Pethe, Kevin/F-9495-2015 OI Delogu, Giovanni/0000-0003-0182-8267; Pethe, Kevin/0000-0003-0297-0150; NR 24 TC 86 Z9 94 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD SEP PY 2004 VL 10 IS 9 BP 935 EP 941 DI 10.1038/nm1090 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 851AZ UT WOS:000223658400030 PM 15300244 ER PT J AU Lesko, LJ Woodcock, J AF Lesko, LJ Woodcock, J TI Translation of pharmacogenomics and pharmacogenetics: a regulatory perspective SO NATURE REVIEWS DRUG DISCOVERY LA English DT Article ID DRUG DEVELOPMENT; DECISION-MAKING; LUNG-CANCER; GEFITINIB; MUTATIONS AB Pharmacogenomics and pharmacogenetics provide methodologies that can lead to DNA-based tests to improve drug selection, identify optimal dosing, maximize drug efficacy or minimize the risk of toxicity. Rapid advances in basic research have identified many opportunities for the development of 'personalized' treatments for individuals and/or subsets of patients defined by genetic and/or genomic tests. However, the integration of these tests into routine clinical practice remains a major multidisciplinary challenge, and even for well-established biomarkers there has been little progress. Here, we consider this challenge from a regulatory perspective, highlighting recent initiatives from the FDA that aim to facilitate the integration of pharmacogenetics and pharmacogenomics into drug development and clinical practice. C1 US FDA, Ctr Drug Evaluat & Res, Off Clin Pharmacol & Biopharmaceut, Rockville, MD 20857 USA. US FDA, Rockville, MD 20857 USA. RP Lesko, LJ (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Clin Pharmacol & Biopharmaceut, Rockville, MD 20857 USA. EM leskol@cder.fda.gov NR 10 TC 126 Z9 137 U1 1 U2 7 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-1776 J9 NAT REV DRUG DISCOV JI Nat. Rev. Drug Discov. PD SEP PY 2004 VL 3 IS 9 BP 763 EP 769 DI 10.1038/nrd1499 PG 7 WC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA 851AD UT WOS:000223654800019 PM 15340386 ER PT J AU Braman, AC Gomez, RG AF Braman, AC Gomez, RG TI Patient personality predicts preference for relationships with doctors SO PERSONALITY AND INDIVIDUAL DIFFERENCES LA English DT Article DE patients; physicians; personality; assertiveness; control; health; demographics; medical care ID DECISION-MAKING; HEALTH LOCUS; INFORMATION; DESIRE; CARE; PARTICIPATION; EFFICACY AB Our study assessed the value of personality variables over and above demographic variables for predicting the type of relationships patients prefer with their doctors-from giving all the decision-making power to the doctors to a more egalitarian, information-seeking relationship. We investigated several personality variables (health locus of control, assertiveness, conservatism, and self-efficacy) in a mailed survey. Hierarchical regression analyses indicated that personality variables explained additional variance in desire for shared decision-making after controlling for demographic variables. Specifically, adults with a greater belief that powerful others (e.g., doctors) controlled their health were less likely to want to seek information or make decisions about their health. Assertive adults were more likely to want comprehensive information. Our findings indicate that personality variables are important in predicting patient preferences regarding their relationships with their doctors. These findings also have important implications for improving patient satisfaction and compliance with medical treatment. (C) 2003 Elsevier Ltd. All rights reserved. C1 Washington Univ, St Louis, MO USA. RP Braman, AC (reprint author), US FDA, Div Drug Mkt Advertising & Commun, Ctr Drug Evaluat & Res, 5600 Fishers Lane,Mailstop HFD-42, Rockville, MD 20857 USA. EM bramana@cder.fda.gov; rggomez@stanford.edu NR 21 TC 27 Z9 29 U1 1 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0191-8869 J9 PERS INDIV DIFFER JI Pers. Individ. Differ. PD SEP PY 2004 VL 37 IS 4 BP 815 EP 826 DI 10.1016/j.paid.2003.10.009 PG 12 WC Psychology, Social SC Psychology GA 849SU UT WOS:000223561800013 ER PT J AU Szarfman, A Tonning, JM Doraiswamy, PM AF Szarfman, A Tonning, JM Doraiswamy, PM TI Pharmacovigilance in the 21st century: New systematic tools for an old problem SO PHARMACOTHERAPY LA English DT Editorial Material DE data mining; adverse events; MGPS; AERS; pancreatitis; valproic acid; antipsychotics ID SPONTANEOUS REPORTING SYSTEM; LARGE FREQUENCY TABLES; FLUOROQUINOLONE ANTIBIOTICS; DIABETES-MELLITUS; TENDON-RUPTURE AB The large number of adverse-event reports generated by marketed drugs and devices argues for the application of validated computerized algorithms to supplement traditional methods of detecting adverse-event signals. Difficulties in accurately estimating patient exposure and background rates for a given event in a specific population hinder risk estimation in spontaneous adverse-event databases. The United States Food and Drug Administration (FDA) is evaluating a Bayesian data mining system called Multi-item Gamma Poisson Shrinker (MGPS) to enhance the FDA's ability to monitor the safety of drugs, biologics, and vaccines after they have been approved for use. The MGPS computes adjusted higher-than-expected reporting relationships between drugs and adverse events across 35 years of data relative to internal background rates. The MGPS can also adjust for random noise by using a model derived from the data, and corrects for temporal trends and confounding related to age, sex, and other variables by stratifying over 900 categories. Signals can then be compared with or used in conjunction with other sources (e.g. clinical trials, general practice databases) to further study the adverse-event risk. The example of pancreatitis risk with atypical antipsychotics, valproic acid, and valproate is used to discuss the strengths and limitations of MGPS versus traditional methods. Validated data mining techniques offer great promise to enhance pharmacovigilance practices. C1 Duke Univ, Med Ctr, Dept Psychiat, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. US FDA, Ctr Drug Evaluat & Res, Off Pharmacoepidemiol & Stat Sci, Immediate Off, Rockville, MD 20857 USA. RP Doraiswamy, PM (reprint author), Duke Univ, Med Ctr, Psychiat Clin Trials, Box 3018, Durham, NC 27710 USA. EM dorai001@mc.duke.edu NR 19 TC 49 Z9 49 U1 0 U2 2 PU PHARMACOTHERAPY PUBLICATIONS INC PI BOSTON PA NEW ENGLAND MEDICAL CENTER, 806, 750 WASHINGTON ST, BOSTON, MA 02111 USA SN 0277-0008 J9 PHARMACOTHERAPY JI Pharmacotherapy PD SEP PY 2004 VL 24 IS 9 BP 1099 EP 1104 DI 10.1592/phco.24.13.1099.38090 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 850FS UT WOS:000223597200001 PM 15460169 ER PT J AU Cui, YY Spann, AP Couch, LH Gopee, NV Evans, FE Churchwell, MI Williams, LD Doerge, DR Howard, PC AF Cui, YY Spann, AP Couch, LH Gopee, NV Evans, FE Churchwell, MI Williams, LD Doerge, DR Howard, PC TI Photodecomposition of Pigment Yellow 74, a pigment used in tattoo inks SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID INDIA INK; RED TATTOO; HEPATITIS-C; GRANULOMATOUS REACTION; MALIGNANT-MELANOMA; INDOCYANINE GREEN; ENDOSCOPIC TATTOO; LASER TREATMENT; SAFETY; RISK AB Tattooing has become a popular recreational practice among younger adults over the past decade. Although some of the pigments used in tattooing have been described, very little is known concerning the toxicology, phototoxicology or photochemistry of these pigments. Seven yellow tattoo inks were obtained from commercial sources and their pigments extracted, identified and quantitatively analyzed. The monoazo compound Pigment Yellow 74 (PY74; CI 11741) was found to be the major pigment in several of the tattoo inks. Solutions of commercial PY74 in tetrahydrofuran (THF) were deoxygenated using argon gas, and the photochemical reaction products were determined after exposure to simulated solar light generated by a filtered 6.5 kW xenon arc lamp. Spectrophotometric and high-pressure liquid chromatography (HPLC) analyses indicated that PY74 photodecomposed to multiple products that were isolated using a combination of silica chromatography and reversed-phase HPLC. Three of the major photodecomposition products were identified by nuclear magnetic resonance and mass spectrometry as N-(2methoxyphenyl)-3-oxobutanamide (o-acetoacetanisidide), 2-(hydroxyimine)-N-(2-methoxyphenyl)-3-oxobutanamide and N,N"-bis(2-methoxyphenyl)urea. These results demonstrate that PY74 is not photostable in THF and that photochemical lysis occurs at several sites in PY74 including the hydrazone and amide groups. The data also suggest that the use of PY74 in tattoo inks could potentially result in the formation of photolysis products, resulting in toxicity at the tattoo site after irradiation with sunlight or more intense light sources. C1 US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. US FDA, Natl Ctr Toxicol Res, Natl Toxicol Program, Ctr Phototoxicol, Jefferson, AR USA. US FDA, Natl Ctr Toxicol Res, Div Chem, Jefferson, AR USA. RP Howard, PC (reprint author), US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, 3900 NCTR Rd,NFT-110, Jefferson, AR 72079 USA. EM phoward@nctr.fda.gov NR 73 TC 44 Z9 45 U1 5 U2 18 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 SEP-OCT PY 2004 VL 80 IS 2 BP 175 EP 184 DI 10.1562/2004-04-06-RA-136.1 PG 10 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 871UE UT WOS:000225158400004 PM 15362942 ER PT J AU Krieg, RC Knuechel, R Schiffmann, E Liotta, LA Petricoin, EF Herrmann, PC AF Krieg, RC Knuechel, R Schiffmann, E Liotta, LA Petricoin, EF Herrmann, PC TI Mitochondrial proteome: Cancer-altered metabolism associated with cytochrome c oxidase subunit level variation SO PROTEOMICS LA English DT Article DE cell lines; cytochrome c oxidase; mitochondria; prostate; protein expression ID PROSTATE-CANCER; GENE-EXPRESSION; CELL CULTURES; CARCINOMA; TISSUE; ASSIGNMENT; GLYCOLYSIS; ULTRASTRUCTURE; RESPIRATION; MICROARRAYS AB Shifts in metabolism associated with tumorigenesis were first noted by Otto Warburg in the 1920s. In the ensuing decades many examples of the phenomenon have been elucidated while the underlying molecular mechanism has remained elusive. As the enzyme complex at the crux of oxidative phosphorylation, cytochrome c oxidase is uniquely positioned to have a very high impact on cellular metabolism. In this study, we test the hypothesis that there is a specific association between altered cytochrome c oxidase subunit levels and altered metabolism by combining the technique of reverse-phase protein microarray with radiolabeled glucose metabolic studies. Such a relationship is observed with five different cell lines, two of which (1542N and 1542T) are a matched set of normal and tumor-based lineages derived from the same prostate gland. By measuring the [C-14]carbon dioxide production of a cell line metabolizing [1-C-14]glucose and comparing those measurements to values obtained for the same cell line metabolizing [6-C-14]glucose, we determined the relative utilization of the hexose monophosphate shunt and glycolysis progressing through the Krebs cycle metabolic pathway in each cell line. In all cases there is an increased utilization of hexose monophosphate shunt relative to glycolysis progressing through the Krebs cycle in tumor derived relative to normal derived cell lines. Additionally, there is an associated increase in the ratio of nuclear encoded cytochrome c oxidase subunits to mitochondrially encoded cytochrome c oxidase subunits in the tumor-derived cell lines. These results demonstrate an alteration in subunit levels of a single enzyme complex (cytochrome c oxidase) commensurate with tumor-altered metabolism. C1 NCI, Lab Pathol, FDA NCI Clin Proteom Program, NIH, Bethesda, MD 20892 USA. UKAachen RWTH, Inst Pathol, Aachen, Germany. CBER, Food & Drug Adm, Div Therapeut Prot, FDA NCI Clin Proteom Program, Bethesda, MD USA. RP Herrmann, PC (reprint author), NCI, Lab Pathol, FDA NCI Clin Proteom Program, NIH, 10 Ctr Dr,Bldg 10,Room 2N212, Bethesda, MD 20892 USA. EM herrmanp@mail.nih.gov NR 40 TC 42 Z9 48 U1 1 U2 3 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1615-9853 J9 PROTEOMICS JI Proteomics PD SEP PY 2004 VL 4 IS 9 BP 2789 EP 2795 DI 10.1002/pmic.200300796 PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 853BN UT WOS:000223801300028 PM 15352252 ER PT J AU May, JC Rey, L Lee, CJ Arciniega, J AF May, JC Rey, L Lee, CJ Arciniega, J TI Evaluation of components of X-ray irradiated 7-valent pneumococcal conjugate vaccine and pneumococcal vaccine polyvalent and X-ray and gamma-ray irradiated acellular pertussis component of DTaP vaccine products SO RADIATION PHYSICS AND CHEMISTRY LA English DT Article; Proceedings Paper CT International Meeting on Radiation Processing CY SEP 07-12, 2003 CL Chicago, IL DE irradiated vaccines; X-ray; Co-60 gamma irradiation; DTaP vaccine; pneumococcal polysaccharide vaccine polyvalent; 7-valent pneumococcal conjugate vaccine ID EFFICACY AB Samples of pneumococcal vaccine polyvalent, 7-valent pneumococcal conjugate vaccine, and two different diphtheria and tetanus toxoids and acellular pertussis vaccines adsorbed were irradiated with X-rays and/or gamma-rays (Co-60). Mouse IgG and IgM antibody responses (ELISA) for types 9V, 14, 18C, and 19F pneumococcal polysaccharides and conjugates indicated that the polysaccharides were more tolerant of the radiation than the conjugates. The mouse antibody response for the detoxified pertussis toxin (PT) antigen, filamentous hemagglutinin antigen (FHA), pertactin (PRN), and fimbriae types 2 and 3 (FIM) antigens for the appropriate vaccine type indicated that the antibody response was not significantly changed in the 25 kGy X-ray irradiated vaccines frozen in liquid nitrogen compared to the control vaccine. (C) 2004 Elsevier Ltd. All rights reserved. C1 US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP May, JC (reprint author), US FDA, Ctr Biol Evaluat & Res, HFM-406,1401 Rockville Pike, Rockville, MD 20852 USA. EM may@cber.fda.gov; louis.rey@bluewin.ch NR 7 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0969-806X J9 RADIAT PHYS CHEM JI Radiat. Phys. Chem. PD SEP-OCT PY 2004 VL 71 IS 1-2 BP 415 EP 418 DI 10.1016/j.radphyschem.2004.03.039 PG 4 WC Chemistry, Physical; Nuclear Science & Technology; Physics, Atomic, Molecular & Chemical SC Chemistry; Nuclear Science & Technology; Physics GA 848ZP UT WOS:000223507200089 ER PT J AU Slikker, W Mei, N Chen, T AF Slikker, W Mei, N Chen, T TI N-ethyl-N-nitrosourea (ENU) increased brain mutations in prenatal and neonatal mice but not in the adults SO TOXICOLOGICAL SCIENCES LA English DT Article DE ethylnitrosourea; mutagenesis; carcinogenesis; development; Big Blue mouse ID LACI TRANSGENIC MICE; IN-VIVO; CANCER INCIDENCE; NERVOUS-SYSTEM; SHORT-TERM; MOUSE; ETHYLNITROSOUREA; RAT; DNA; SPECTRA AB The incidence of childhood cancer is increasing. One of the most common cancers for children under 15 years of age, gliomas for example, has been reported to have increased in incidence over the last 20 years by approximately 40%. The rising trend of childhood cancer in brain may be associated with environmental exposure to genotoxins and susceptibility to mutation in early development. To investigate age-dependent mutagenic sensitivity of brain tissue to genotoxins, the Big Blue mouse model was utilized in this study. Groups of five male mice were treated with a single dose of 120 mg/kg ENU transplacentally at three days before birth (prenatal), eight days (neonate) or eighteen weeks (adult) after birth. The animals were sacrificed six weeks after the treatment. The mutant frequencies and types of mutations in the brain cII gene from ENU-treated and concurrent control mice were determined. A significant increase in mutant frequencies over control was found in the prenatal and neonatal groups whereas there was no significant difference between the adult group and its control. Molecular analysis of the mutants also indicated that the mutational spectra from the ENU-treated mice were age-dependent. The percentage of A:T-->T:A transversion, the typical type of mutation induced by ENU, was inversely related to the treatment age, whereas G:C-->A:T transition was the main type of mutation in the adult group, the same as the control. These results demonstrate a differential mutagenic effect of ENU on the mouse brain depending on the stages of development and suggest an enhanced susceptibility of brain cancer hazard for perinatal exposure to genotoxicants. C1 US FDA, Div Genet & Reprod Toxicol, HFT 130, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Univ Calif Los Angeles, Coll Letters & Sci, Los Angeles, CA 90024 USA. RP Chen, T (reprint author), US FDA, Div Genet & Reprod Toxicol, HFT 130, Natl Ctr Toxicol Res, 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 46 TC 18 Z9 19 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 SEP PY 2004 VL 81 IS 1 BP 112 EP 120 DI 10.1093/toxsci/kfh177 PG 9 WC Toxicology SC Toxicology GA 850CP UT WOS:000223589100014 PM 15159527 ER PT J AU Harris, AJ Shaddock, JG Delongchamp, R Dragan, Y Casciano, DA AF Harris, AJ Shaddock, JG Delongchamp, R Dragan, Y Casciano, DA TI Comparison of basal gene expression in cultured primary rat hepatocytes and freshly isolated rat hepatocytes SO TOXICOLOGY MECHANISMS AND METHODS LA English DT Article DE collagen I; filter array; gene expression; matrigel; primary hepatocytes ID EXTRACELLULAR-MATRIX; BASEMENT-MEMBRANE; ENZYME-ACTIVITIES; CDNA MICROARRAYS; COLLAGEN MATRIX; CELL-CYCLE; LIVER; CYTOCHROME-P-450; GROWTH; LAMININ AB Cultured primary hepatocytes are one of the most suitable in vitro models for hepatic toxicological studies. Unfortunately, there is a temporal loss of liver-specific function in culture that limits their utility for some applications. Plating hepatocytes on a substratum has been shown to stabilize the differentiated phenotype for short-term culture. In order to identify the substratum that best supports in vivo basal hepatocyte gene expression profiles in vitro, the gene expression profiles of primary rat hepatocytes plated on collagen I in hepatocyte maintenance medium (HMM) or hepatocyte culture medium (HCM), or on matrigel in HMM medium for 2 h, 16 h, or 72 h were compared to the expression profiles of freshly isolated rat hepatocytes using the Atlas rat stress array. After 16 h in culture, there were differences in gene expression between cultured primary hepatocytes and freshly isolated hepatocytes, but no apparent substratum effects. At 72 h, the expression of 9 genes was altered in hepatocytes plated on either substratum compared to expression in freshly isolated hepatocytes. However, there were an additional 13 genes with increased expression in hepatocytes plated on collagen I that were expressed at low or non-detectable levels in freshly isolated hepatocytes or primary hepatocytes plated on matrigel. In summary, after 72 h, primary hepatocytes plated on matrigel had basal gene expression patterns more similar to patterns in freshly isolated hepatocytes than did hepatocytes cultured on collagen. In addition, culture on matrigel suppressed the expression of atypical genes in culture. These preliminary studies suggest that culture on matrigel may be preferable for longer-term in vitro toxicological studies. C1 Natl Ctr Toxicol Res, Ctr Hepatotoxic, Jefferson, AR 72079 USA. Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. Natl Ctr Toxicol Res, Off Director, Jefferson, AR 72079 USA. RP Harris, AJ (reprint author), Natl Ctr Toxicol Res, Ctr Hepatotoxic, Jefferson, AR 72079 USA. EM aharris@cteh.com NR 39 TC 3 Z9 3 U1 0 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1537-6524 J9 TOXICOL MECH METHOD JI Toxicol. Mech. Methods PD SEP-OCT PY 2004 VL 14 IS 5 BP 257 EP 270 DI 10.1080/15376520490434629 PG 14 WC Toxicology SC Toxicology GA 850CQ UT WOS:000223589200001 PM 20021105 ER PT J AU Orton, S Stramer, SL Paolillo, J Dodd, RY AF Orton, S Stramer, SL Paolillo, J Dodd, RY TI West Nile Virus interview study in US blood donors SO TRANSFUSION LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Association-of-Blood-Banks CY OCT 23-26, 2004 CL Baltimore, MD SP Amer Assoc Blood Banks C1 US FDA, Rockville, MD 20857 USA. Amer Red Cross, Holland Lab, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 2004 VL 44 IS 9 SU S BP 7A EP 8A PG 2 WC Hematology SC Hematology GA 849XS UT WOS:000223575600024 ER PT J AU Rios, M Zhang, MJ Srinivasan, K Daniel, S Hewlett, IK Dayton, A AF Rios, M Zhang, MJ Srinivasan, K Daniel, S Hewlett, IK Dayton, A TI Long term infection of human primary monocyte/macrophages with WNV produces infectious particles SO TRANSFUSION LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Association-of-Blood-Banks CY OCT 23-26, 2004 CL Baltimore, MD SP Amer Assoc Blood Banks C1 US FDA, DEETD, OBRR, CBER, Bethesda, MD 20014 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 2004 VL 44 IS 9 SU S BP 8A EP 8A PG 1 WC Hematology SC Hematology GA 849XS UT WOS:000223575600025 ER PT J AU Grinev, A Daniel, S Machuca, A Stramer, SL Hewlett, IK Rios, M AF Grinev, A Daniel, S Machuca, A Stramer, SL Hewlett, IK Rios, M TI Genetic variability in West Nile Virus (WNV) isolates from the 2002 epidemic in the US SO TRANSFUSION LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Association-of-Blood-Banks CY OCT 23-26, 2004 CL Baltimore, MD SP Amer Assoc Blood Banks C1 US FDA, DEETD, OBRR, CBER, Bethesda, MD 20014 USA. Amer Red Cross, Gaithersburg, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 2004 VL 44 IS 9 SU S BP 15A EP 15A PG 1 WC Hematology SC Hematology GA 849XS UT WOS:000223575600050 ER PT J AU Hu, J Lee, S Wood, O Taffs, R Akolkar, P Machuca, A Hewlett, IK AF Hu, J Lee, S Wood, O Taffs, R Akolkar, P Machuca, A Hewlett, IK TI Development of an HIV-1 subtype panel for standardization of HIVNAT assays SO TRANSFUSION LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Association-of-Blood-Banks CY OCT 23-26, 2004 CL Baltimore, MD SP Amer Assoc Blood Banks C1 US FDA, CBER, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0041-1132 EI 1537-2995 J9 TRANSFUSION JI Transfusion PD SEP PY 2004 VL 44 IS 9 SU S BP 94A EP 94A PG 1 WC Hematology SC Hematology GA 849XS UT WOS:000223575600322 ER PT J AU Hu, J Lee, S Kerby, S Wood, O Machuca, A Daniel, S Rios, M Bih, A Zekeng, L Hewlett, IK AF Hu, J Lee, S Kerby, S Wood, O Machuca, A Daniel, S Rios, M Bih, A Zekeng, L Hewlett, IK TI Evaluation of multiple NAT and serologic assays for detection of HIV variants in Cameroonian blood samples SO TRANSFUSION LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Association-of-Blood-Banks CY OCT 23-26, 2004 CL Baltimore, MD SP Amer Assoc Blood Banks C1 CBER, Rockville, MD USA. Cameroon Minist Hlth, Yaounde, Cameroon. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0041-1132 EI 1537-2995 J9 TRANSFUSION JI Transfusion PD SEP PY 2004 VL 44 IS 9 SU S BP 94A EP 94A PG 1 WC Hematology SC Hematology GA 849XS UT WOS:000223575600320 ER PT J AU Srinivasan, K Wood, O Lee, S Sylvester, D Kerby, S Francis, K Akolkar, P Taffs, RE Hewlett, IK AF Srinivasan, K Wood, O Lee, S Sylvester, D Kerby, S Francis, K Akolkar, P Taffs, RE Hewlett, IK TI Studies on the potential impact of smallpox vaccination on blood safety and availability SO TRANSFUSION LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Association-of-Blood-Banks CY OCT 23-26, 2004 CL Baltimore, MD SP Amer Assoc Blood Banks C1 US FDA, CBER, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 2004 VL 44 IS 9 SU S BP 96A EP 96A PG 1 WC Hematology SC Hematology GA 849XS UT WOS:000223575600330 ER PT J AU Gao, G Leparc, GF Nemo, G Tabor, E AF Gao, G Leparc, GF Nemo, G Tabor, E TI Absence of Chlamydia pneumoniae DNA in normal blood donors SO TRANSFUSION LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Association-of-Blood-Banks CY OCT 23-26, 2004 CL Baltimore, MD SP Amer Assoc Blood Banks C1 US FDA, CBER, Rockville, MD 20857 USA. Florida Blood Serv, St Petersburg, FL USA. NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 2004 VL 44 IS 9 SU S BP 97A EP 97A PG 1 WC Hematology SC Hematology GA 849XS UT WOS:000223575600334 ER PT J AU Castilho, L Rios, M Pellegrino, J Costa, FF AF Castilho, L Rios, M Pellegrino, J Costa, FF TI High frequency of partial DIIIa and DAR alleles in sickle cell disease patients SO TRANSFUSION LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Association-of-Blood-Banks CY OCT 23-26, 2004 CL Baltimore, MD SP Amer Assoc Blood Banks C1 UNICAMP, Hemoctr, Campinas, SP, Brazil. US FDA, DETTD, CBER, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 2004 VL 44 IS 9 SU S BP 115A EP 115A PG 1 WC Hematology SC Hematology GA 849XS UT WOS:000223575600394 ER PT J AU Virata, ML Yu, MYW AF Virata, ML Yu, MYW TI Anti-D in intravenous immunoglobulins SO TRANSFUSION LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Association-of-Blood-Banks CY OCT 23-26, 2004 CL Baltimore, MD SP Amer Assoc Blood Banks C1 US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 2004 VL 44 IS 9 SU S BP 115A EP 115A PG 1 WC Hematology SC Hematology GA 849XS UT WOS:000223575600395 ER PT J AU McClellan, MB AF McClellan, MB TI Use of outcomes research in assuring patient safety and quality care, second plenary session, ISPOR 8th Annual International Meeting, Arlington, VA, USA SO VALUE IN HEALTH LA English DT Editorial Material C1 US FDA, Rockville, MD 20857 USA. RP McClellan, MB (reprint author), US FDA, Rockville, MD 20857 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 1098-3015 J9 VALUE HEALTH JI Value Health PD SEP-OCT PY 2004 VL 7 IS 5 BP 529 EP 534 DI 10.1111/j.1524-4733.2004.75004.x PG 6 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 852TQ UT WOS:000223779700004 PM 15367248 ER PT J AU Freedberg, DI Venable, RM Rossi, A Bull, TE Pastor, RW AF Freedberg, DI Venable, RM Rossi, A Bull, TE Pastor, RW TI Discriminating the helical forms of peptides by NMR and molecular dynamics simulation SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID ALANINE-BASED PEPTIDES; HYDROGEN-BONDS; PI-HELIX; CIRCULAR-DICHROISM; SCALAR COUPLINGS; ALPHA-HELIX; COIL TRANSITION; PROTEIN; ENERGY; (3H)J(NC') AB The HNCO NMR pulse sequence was applied to three selectively labeled (15)N and (13)C isotopic homologues of the peptide Ac-WAAAH(AAARA)(3)A-NH(2) to probe directly for hydrogen bonds between residues 8 and 11 (characteristic of a 3(10)-helix), 8 and 12 (alpha-helix), and 8 and 13 (pi-helix). The experiments demonstrate conclusively, and in agreement with circular dichroism studies, that the center of the peptide is a-helical; there is no discernible 3(10)- or pi-helix at these specific positions. Molecular dynamics simulations of the preceding peptide and Ac-(AAAAK)(3)A-NH(2) in water using the potential energy parameter set CHARMM22/CMAP correctly yield an a-helix, in contrast to simulations with the set CHARMM22, which result in a pi-helix. 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 pastor@cber.fda.gov NR 57 TC 20 Z9 21 U1 0 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD AUG 25 PY 2004 VL 126 IS 33 BP 10478 EP 10484 DI 10.1021/ja0484146 PG 7 WC Chemistry, Multidisciplinary SC Chemistry GA 847YJ UT WOS:000223433700063 PM 15315464 ER PT J AU Armstrong, DJ AF Armstrong, DJ TI Food as a weapon of terrorism SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 228th National Meeting of the American-Chemical-Society CY AUG 22-26, 2004 CL Philadelphia, PA SP Amer Chem Soc C1 US FDA, Natl Ctr Food Safety & Technol, Summit Argo, IL 60526 USA. EM David.Armstrong@cfsan.fda.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 22 PY 2004 VL 228 MA 115-AGFD BP U68 EP U68 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 851UZ UT WOS:000223712800256 ER PT J AU Buchanan, RL AF Buchanan, RL TI Moving food safety concepts into the 21st century: learning to describe, manage, and even enjoy biological variability SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 228th National Meeting of the American-Chemical-Society CY AUG 22-26, 2004 CL Philadelphia, PA SP Amer Chem Soc C1 US FDA, Ctr Food Safety & Appl Nutr, DHHS, College Pk, MD 20740 USA. EM Robert.Buchanan@cfsan.fda.gov NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 22 PY 2004 VL 228 MA 114-AGFD BP U68 EP U68 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 851UZ UT WOS:000223712800255 ER PT J AU Burnham, J Beru, N AF Burnham, J Beru, N TI FDA's imported and domestic produce survey. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 228th National Meeting of the American-Chemical-Society CY AUG 22-26, 2004 CL Philadelphia, PA SP Amer Chem Soc C1 Ctr Food Safety & Appl Nutr, US FDA, DHHS, College Pk, MD 20740 USA. EM nberu@cfsan.fda.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 22 PY 2004 VL 228 MA 181-AGFD BP U78 EP U78 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 851UZ UT WOS:000223712800321 ER PT J AU Farahani, M Antonucci, JM Guttman, CM AF Farahani, M Antonucci, JM Guttman, CM TI Analysis of the interactions of trialkoxysilanes with dental monomers by MALDI-TOF mass spectrometry. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 228th National Meeting of the American-Chemical-Society CY AUG 22-26, 2004 CL Philadelphia, PA SP Amer Chem Soc C1 US FDA, Off Gener Drugs, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 22 PY 2004 VL 228 MA 38-POLY BP U331 EP U331 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 851VJ UT WOS:000223713801716 ER PT J AU Feng, P AF Feng, P TI Overview of rapid methods for detection of food-borne pathogens and toxins. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 228th National Meeting of the American-Chemical-Society CY AUG 22-26, 2004 CL Philadelphia, PA SP Amer Chem Soc C1 US FDA, Div Microbiol Studies, College Pk, MD 20740 USA. EM pfeng@cfsan.fda.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 22 PY 2004 VL 228 MA 167-AGFD BP U76 EP U76 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 851UZ UT WOS:000223712800307 ER PT J AU Krynitsky, AJ Niemann, RA Nortrup, DA AF Krynitsky, AJ Niemann, RA Nortrup, DA TI Rapid determination of perchlorate anion in foods by ion chromatography-tandem mass spectrometry. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 228th National Meeting of the American-Chemical-Society CY AUG 22-26, 2004 CL Philadelphia, PA SP Amer Chem Soc C1 US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. EM Alex.Krynitsky@cfsan.fda.gov NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 22 PY 2004 VL 228 MA 044-AGRO BP U90 EP U90 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 851UZ UT WOS:000223712800373 ER PT J AU Musser, SM AF Musser, SM TI LC/MS method development for the analysis of dietary supplements. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 228th National Meeting of the American-Chemical-Society CY AUG 22-26, 2004 CL Philadelphia, PA SP Amer Chem Soc C1 US FDA, Instrumentat & Biophys Branch, College Pk, MD 20740 USA. EM Steven.Musser@cfsan.fda.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 22 PY 2004 VL 228 MA 180-ANYL BP U163 EP U163 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 851UZ UT WOS:000223712800666 ER PT J AU Niemann, RA Gay, M AF Niemann, RA Gay, M TI Analysis of dietary supplements for ephedrine alkaloids and synephrine by cation exchange liquid chromatography-ultraviolet/fluorescence detection with confirmation by spectral matching. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 228th National Meeting of the American-Chemical-Society CY AUG 22-26, 2004 CL Philadelphia, PA SP Amer Chem Soc C1 US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. EM rniemann@cfsan.fda.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 22 PY 2004 VL 228 MA 092-ANYL BP U125 EP U125 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 851UZ UT WOS:000223712800578 ER PT J AU Niemann, RA Krynitsky, AJ Nortrup, DA AF Niemann, RA Krynitsky, AJ Nortrup, DA TI Ion chromatographic determination of perchlorate in crops by on-line enrichment and conductivity detection. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 228th National Meeting of the American-Chemical-Society CY AUG 22-26, 2004 CL Philadelphia, PA SP Amer Chem Soc C1 US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. EM rniemann@cfsan.fda.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 22 PY 2004 VL 228 MA 045-AGRO BP U90 EP U90 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 851UZ UT WOS:000223712800374 ER PT J AU Regnault, WF Fitzgerald, RM Antonucci, JM Skrtic, D AF Regnault, WF Fitzgerald, RM Antonucci, JM Skrtic, D TI Effect of fluid environment on ion release from amorphous calcium phosphate filled restorative materials. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 228th National Meeting of the American-Chemical-Society CY AUG 22-26, 2004 CL Philadelphia, PA SP Amer Chem Soc C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. Natl Inst Stand & Technol, Div Polymers, Gaithersburg, MD USA. Amer Dent Assoc Fdn, Paffenbarger Res Ctr, Chicago, IL USA. EM WFR@CDRH.FDA.GOV NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 22 PY 2004 VL 228 MA 264-POLY BP U364 EP U364 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 851VJ UT WOS:000223713801941 ER PT J AU Rossi, LJ Saudarg, DE Varnum, SA Ali, SN AF Rossi, LJ Saudarg, DE Varnum, SA Ali, SN TI Improved HPLC method for the determination of impurities in pyridostigmine bromide tablets. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 228th National Meeting of the American-Chemical-Society CY AUG 22-26, 2004 CL Philadelphia, PA SP Amer Chem Soc C1 US FDA, Philadelphia Dist Off, Sci Branch, Philadelphia, PA 19106 USA. EM lrossi@ora.fda.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 22 PY 2004 VL 228 MA 095-ANYL BP U126 EP U126 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 851UZ UT WOS:000223712800581 ER PT J AU Turesky, RJ Taylor, J Gehring, T Holland, RD AF Turesky, RJ Taylor, J Gehring, T Holland, RD TI Identification of novel heterocyclic aromatic amines in grilled meats and human urine. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 228th National Meeting of the American-Chemical-Society CY AUG 22-26, 2004 CL Philadelphia, PA SP Amer Chem Soc C1 Natl Ctr Toxicol Res, Div Chem, Jefferson, AR 72079 USA. EM Rturesky@nctr.fda.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 22 PY 2004 VL 228 MA 007-TOXI BP U375 EP U375 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 851UZ UT WOS:000223712801594 ER PT J AU Weisz, A Wright, PR Andrzejewski, D Meyers, MB Glaze, K Mazzola, EP AF Weisz, A Wright, PR Andrzejewski, D Meyers, MB Glaze, K Mazzola, EP TI Identification of the decarboxylated analog of tetrabromotetrachloro-fluorescein and its quantification in the color additives D and C red Nos. 27 and 28 (phloxine B) using high-performance liquid chromatography. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 228th National Meeting of the American-Chemical-Society CY AUG 22-26, 2004 CL Philadelphia, PA SP Amer Chem Soc C1 US FDA, Off Cosmet & Colors, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. US FDA, Instrumentat & Biophys Branch, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. EM aweisz@cfsan.fda.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 22 PY 2004 VL 228 MA 096-ANYL BP U126 EP U126 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 851UZ UT WOS:000223712800582 ER PT J AU Simpson, DA Estanislao, LA Evans, SB McArthur, JC Marcus, KD Truffa, MD Lucey, BC Naismith, RE Lonergan, JTF Clifford, DB AF Simpson, DA Estanislao, LA Evans, SB McArthur, JC Marcus, KD Truffa, MD Lucey, BC Naismith, RE Lonergan, JTF Clifford, DB CA HIV Neuromuscular Syndrome Study G TI HIV-associated neuromuscular weakness syndrome (vol 18, pg 1403, 2004) SO AIDS LA English DT Correction C1 Mt Sinai Med Ctr, New York, NY 10029 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Johns Hopkins Univ, Baltimore, MD USA. US FDA, Rockville, MD 20857 USA. Washington Univ, Sch Med, St Louis, MO USA. Univ Calif San Diego, San Diego, CA 92103 USA. Univ Florida, Jacksonville, FL USA. Nassau Cty Med Ctr, Lond Isl, NY USA. BC Ctr Excellence HIV AIDS, Vancouver, BC, Canada. Therapeut Concepts, Houston, TX USA. Northwestern Univ, Chicago, IL 60611 USA. RP Simpson, DA (reprint author), Mt Sinai Med Ctr, New York, NY 10029 USA. NR 1 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD AUG 20 PY 2004 VL 18 IS 12 BP 1751 EP 1751 DI 10.1097/00002030-200408200-00025 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 848NS UT WOS:000223475000025 ER PT J AU Goodman, JL AF Goodman, JL TI The safety and availability of blood and tissues - Progress and challenges SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID COST-EFFECTIVENESS; UNITED-STATES; TRANSMISSION; TRANSFUSION; DONATIONS; VIRUS C1 US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. RP Goodman, JL (reprint author), US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. NR 15 TC 16 Z9 18 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD AUG 19 PY 2004 VL 351 IS 8 BP 819 EP 822 DI 10.1056/NEJMe048146 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 847CY UT WOS:000223367900016 PM 15317896 ER PT J AU Hampshire, VA Doddy, FM Post, LO Koogler, TL Burgess, TM Batten, PO Hudson, R McAdams, DR Brown, MA AF Hampshire, VA Doddy, FM Post, LO Koogler, TL Burgess, TM Batten, PO Hudson, R McAdams, DR Brown, MA TI Adverse drug event reports at the United States Food and Drug Administration Center for Veterinary Medicine SO JAVMA-JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION LA English DT Article ID RETINAL DEGENERATION; CARPROFEN; CATS C1 US FDA, Ctr Vet Med, Rockville, MD 20885 USA. RP Hampshire, VA (reprint author), US FDA, Ctr Vet Med, 7500 Standish Pl, Rockville, MD 20885 USA. NR 15 TC 33 Z9 33 U1 0 U2 1 PU AMER VETERINARY MEDICAL ASSOC PI SCHAUMBURG PA 1931 N MEACHAM RD SUITE 100, SCHAUMBURG, IL 60173-4360 USA SN 0003-1488 J9 JAVMA-J AM VET MED A JI JAVMA-J. Am. Vet. Med. Assoc. PD AUG 15 PY 2004 VL 225 IS 4 BP 533 EP 536 DI 10.2460/javma.2004.225.533 PG 4 WC Veterinary Sciences SC Veterinary Sciences GA 845OF UT WOS:000223253500024 PM 15344359 ER PT J AU Takeshita, F Suzuki, K Sasaki, S Ishii, N Klinman, DM Ishii, KJ AF Takeshita, F Suzuki, K Sasaki, S Ishii, N Klinman, DM Ishii, KJ TI Transcriptional regulation of the human TLR9 gene SO JOURNAL OF IMMUNOLOGY LA English DT Article ID INDUCED IMMUNE ACTIVATION; TOLL-LIKE RECEPTOR-9; NF-KAPPA-B; BACTERIAL-DNA; CPG MOTIFS; MEDIATED REGULATION; CELL-DEVELOPMENT; BINDING PROTEIN; MESSENGER-RNA; C/EBP-ALPHA AB To clarify the molecular basis of human TLR9 (hTLR9) gene expression, the activity of the hTLR9 gene promoter was characterized using the human myeloma cell line RPMI 8226. Reporter gene analysis and EMSA demonstrated that hTLR9 gene transcription was regulated via four cis-acting elements, cAMP response element, 5'-PU box, 3'-PU box, and a C/EBP site, that interacted with the CREBI, Ets2, Elf1, Elk1, and C/EBPalpha transcription factors. Other members of the C/EBP family, such as C/EBPbeta, C/EBPdelta, and C/EBPepsilon, were also important for TLR9 gene transcription. CpG DNA-mediated suppression of TLR9 gene transcription led to decreased binding of the trans-acting factors to their corresponding cis-acting elements. It appeared that suppression was mediated via c-Jun and NF-kappaB p65 and that cooperation among CREB1, Ets2, Elf1, Elk1, and C/EBPalpha culminated in maximal transcription of the TLR9 gene. These findings will help to elucidate the mechanism of TLR9 gene regulation and to provide insight into the process by which TLR9 evolved in the mammalian immune system. C1 US FDA, Ctr Biol Evaluat & Res, Sect Retroviral Immunol, Bethesda, MD 20892 USA. Washington Hosp Ctr, Medstar Res Inst, Mol Endocrinol Lab, Washington, DC 20010 USA. Natl Inst Infect Dis, Dept Bioregulat, Tokyo, Japan. RP Takeshita, F (reprint author), Yokohama City Univ, Sch Med, Dept Mol Biodefense Res, 3-9 Fukuura, Yokohama, Kanagawa 2360004, Japan. EM takesita@yokohama-cu.ac.jp RI Ishii, Ken/B-1685-2012 OI Ishii, Ken/0000-0002-6728-3872 NR 48 TC 65 Z9 68 U1 3 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 AUG 15 PY 2004 VL 173 IS 4 BP 2552 EP 2561 PG 10 WC Immunology SC Immunology GA 845AV UT WOS:000223208900043 PM 15294971 ER PT J AU Price, DL Manatunga, AK AF Price, DL Manatunga, AK TI Modelling relative survival using transformation methods SO STATISTICS IN MEDICINE LA English DT Article DE additive hazards model; relative survival; transformations ID GENERALIZED LINEAR-MODELS AB Patient survival is often assessed as a measure of effectiveness of treatment in cancer clinical trials. The relative survival rate is a measure of patient survival corrected for the effect of other causes of death. We incorporate an additive hazards model for the overall force of mortality focusing attention on the form of the underlying disease process. Transformation models for the cause-specific hazard rate describing the disease process are considered. We demonstrate a method for estimating the transformation parameter providing insight into the appropriate choice of model structure. The models include the additive and multiplicative structures as special cases. We write the models in the generalized linear model framework and demonstrate ease of fitting via existing statistical software. The methodology is applied to a Hodgkin's disease data set to assess the effect of clinical trial results on population survival. Our analysis concludes that the multiplicative structure provides a more appropriate description of the data as compared to the additive structure. Copyright (C) 2004 John Wiley Sons, Ltd. C1 US FDA, Div Biometr 2, Rockville, MD 20857 USA. Emory Univ, Rollins Sch Publ Hlth, Dept Biostat, Atlanta, GA 30322 USA. RP Price, DL (reprint author), US FDA, Div Biometr 2, 5600 Fishers Lane,HFD-715, Rockville, MD 20857 USA. EM priced@cder.fda.gov; amanatu@sph.emory.edu FU NIEHS NIH HHS [R01-ES012458] NR 11 TC 2 Z9 2 U1 3 U2 3 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD AUG 15 PY 2004 VL 23 IS 15 BP 2463 EP 2477 DI 10.1002/sim.1832 PG 15 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 842DM UT WOS:000222983300009 PM 15273959 ER PT J AU Petricoin, EF Liotta, LA AF Petricoin, EF Liotta, LA TI Importance of disclosure of patent applications - Reply SO LANCET LA English DT Letter C1 US FDA, CBER, OCTGT, Bethesda, MD 20892 USA. NCI, NIH, CCR, Pathol Lab, Bethesda, MD USA. RP Petricoin, EF (reprint author), US FDA, CBER, OCTGT, 8800 Rockville Pike, Bethesda, MD 20892 USA. EM petricoin@cber.fda.gov NR 2 TC 0 Z9 0 U1 0 U2 1 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD AUG 14 PY 2004 VL 364 IS 9434 BP 578 EP 579 DI 10.1016/S0140-6736(04)16839-6 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 845WD UT WOS:000223275100019 ER PT J AU Luchtefeld, R Kostoryz, E Smith, RE AF Luchtefeld, R Kostoryz, E Smith, RE TI Determination of ginsenosides Rb-1, R-c, and R-e in different dosage forms of ginseng by negative ion electrospray liquid chromatography-mass spectrometry SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE ginseng; ginsenosides; LC-MS; NMR ID MEYER AB A method based on high-performance liquid chromatography (HPLC) and negative ion electrospray mass spectrometry (LC-MS) has been used to determine ginsenosides R-b1, R-c, and R-e in six different samples of ginseng. These included a liquid extract, capsules, tea bags, and an instant tea. It was found that four of the six samples had detectable levels of at least one of the ginsenosides. The liquid extract, capsules, instant tea, and tea bags labeled ginseng had ginsenosides. The labels on the two samples that did not have ginsenosides indicated that they were a mixture of green tea, licorice, and ginseng. Also, C-13 NMR was used to identify the types of complex carbohydrates present in the samples. One of the samples of tea bags had none of the ginsenosides, but did have complex carbohydrates found in most of the other samples. The instant tea had all three ginsenosides, but had no complex carbohydrates, only sucrose. The amounts of ginsenosides found in standard doses from six different sources of ginseng varied considerably. It was found that steeping a tea bag for a longer time than that recommended on the label produced a larger recovery of ginsenosides and that reusing a tea bag produced even higher recoveries. C1 Univ Missouri, Sch Pharm, Kansas City, MO 64108 USA. US FDA, Kansas Dist Off, Lenexa, KS 66214 USA. RP Smith, RE (reprint author), Univ Missouri, Sch Pharm, 2411 Holmes, Kansas City, MO 64108 USA. EM smithrob@umkc.edu NR 9 TC 12 Z9 13 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0021-8561 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD AUG 11 PY 2004 VL 52 IS 16 BP 4953 EP 4956 DI 10.1021/jf040104j PG 4 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 844DH UT WOS:000223137000003 PM 15291457 ER PT J AU Marchan, V Cieslak, J Livengood, V Beaucage, SL AF Marchan, V Cieslak, J Livengood, V Beaucage, SL TI 2,2,5,5-tetramethylpyrrolidin-3-one-1-sulfinyl group for 5 '-hydroxyl protection of deoxyribonucleoside phosphoramidites in the solid-phase preparation of DNA oligonucleotides SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID MODIFIED PHOSPHOTRIESTER METHOD; GENE-EXPRESSION PATTERNS; LIGHT-DIRECTED SYNTHESIS; SULFUR-TRANSFER REAGENT; A-U-A; OLIGODEOXYRIBONUCLEOTIDE SYNTHESIS; 3H-1,2-BENZODITHIOL-3-ONE 1,1-DIOXIDE; LEVULINIC ACID; ARRAYS; MICROARRAYS AB Several nitrogen-sulfur reagents have been investigated as potential 5'-hydroxyl protecting groups for deoxyribonucleoside phosphoramidites to improve the synthesis of oligonucleotides on glass microarrays. Out of the nitrogen-sulfur-based protecting groups so far investigated, the 2,2,5,5-tetramethylpyrrolidin-3-one-1-sulfinyl group exhibited near optimal properties for 5'-hydroxyl protection by virtue of the mildness of its deprotection conditions. Specifically, the iterative cleavage of a terminal 5'-sulfamidite group in the synthesis of 5'-d(ATCCGTAGCCAAGGTCATGT) on controlled-pore glass is efficiently accomplished by treatment with iodine in the presence of an acidic salt. Hydrolysis of the oligonucleotide to its 2'-deoxyribonucleosides upon exposure to snake venom phosphodiesterase and bacterial alkaline phosphatase did not reveal the formation of any nucleobase adducts or other modifications. These findings indicate that the 2,2,5,5-tetramethylpyrrolidin-3-one-1-sulfinyl group for 5'-hydroxyl protection of phosphoramidites, such as 10a-d, may lead to the production of oligonucleotide microarrays exhibiting enhanced specificity and sensitivity in the detection of nucleic acid targets. C1 US FDA, Ctr Drug Evaluat & Res, Div Therapeut Prot, Bethesda, MD 20892 USA. NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Beaucage, SL (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Therapeut Prot, 8800 Rockville Pike, Bethesda, MD 20892 USA. EM beaucage@cber.fda.gov RI Marchan, Vicente/K-9751-2014 OI Marchan, Vicente/0000-0002-1905-2156 NR 51 TC 4 Z9 4 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD AUG 11 PY 2004 VL 126 IS 31 BP 9601 EP 9610 DI 10.1021/ja0483771 PG 10 WC Chemistry, Multidisciplinary SC Chemistry GA 843TS UT WOS:000223110100053 PM 15291564 ER PT J AU Kaput, J Klein, KG Reyes, EJ Kibbe, WA Cooney, CA Jovanovic, B Visek, WJ Wolff, GL AF Kaput, J Klein, KG Reyes, EJ Kibbe, WA Cooney, CA Jovanovic, B Visek, WJ Wolff, GL TI Identification of genes contributing to the obese yellow A(vy) phenotype: caloric restriction, genotype, diet x genotype interactions SO PHYSIOLOGICAL GENOMICS LA English DT Review DE gene regulation; diabetes; obesity; diabesity; quantitative trait locus; expression ID PANCREATIC BETA-CELLS; INDUCED DIABETES DIABESITY; STEAROYL-COA DESATURASE; FACTOR-KAPPA-B; INSULIN-RECEPTOR; SACCHAROMYCES-CEREVISIAE; SIGNAL-TRANSDUCTION; QUANTITATIVE TRAITS; EXPRESSION PROFILE; INDUCED APOPTOSIS AB The incidence and severity of obesity and type 2 diabetes are increasing in Western societies. The progression of obesity to type 2 diabetes is gradual with overlapping symptoms of insulin resistance, hyperinsulinemia, hyperglycemia, dyslipidemias, ion imbalance, and inflammation; this complex syndrome has been called diabesity. We describe here comparisons of gene expression in livers of A/a (agouti) vs. A(vy)/A (obese yellow) segregants (i.e., littermates) from BALB/cStCrlfC3H/Nctr x VYWffC3Hf/Nctr-A(vy)/a matings in response to 70% and 100% of ad libitum caloric intakes of a reproducible diet. Twenty-eight (28) genes regulated by diet, genotype, or diet x genotype interactions mapped to diabesity quantitative trait loci. A subset of the identified genes is linked to abnormal physiological signs observed in obesity and diabetes. C1 Univ Calif Davis, Davis, CA 95616 USA. Northwestern Univ, Sch Med, Chicago, IL 60611 USA. Univ Arkansas Med Sci, Little Rock, AR 72205 USA. Univ Illinois, Coll Med, Dept Internal Med, Urbana, IL 61821 USA. US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Kaput, J (reprint author), NutraGenomics, Box 32,2201 W Campbell Pk Dr, Chicago, IL 60458 USA. EM jkaput@ucdavis.edu RI Kibbe, Warren/B-2106-2010 OI Cooney, Craig/0000-0003-4279-557X; Kibbe, Warren/0000-0001-5622-7659 FU NIA NIH HHS [P01-AG-20641]; NIMHD NIH HHS [MD-00222] NR 108 TC 22 Z9 22 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1094-8341 J9 PHYSIOL GENOMICS JI Physiol. Genomics PD AUG 11 PY 2004 VL 18 IS 3 BP 316 EP 324 DI 10.1152/physiolgenomics.00065.2003 PG 9 WC Cell Biology; Genetics & Heredity; Physiology SC Cell Biology; Genetics & Heredity; Physiology GA 845JG UT WOS:000223238000010 PM 15306695 ER PT J AU Wang, L Yan, H Wang, SG Cohly, H Fu, PP Hwang, HM Yu, HT AF Wang, L Yan, H Wang, SG Cohly, H Fu, PP Hwang, HM Yu, HT TI Phototoxicity and DNA damage induced by the cosmetic ingredient chemical azulene in human Jurkat T-cells SO MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS LA English DT Article DE azufene; cosmetic ingredient; phototoxicity; comet assay; DNA cleavage ID POLYCYCLIC AROMATIC-HYDROCARBONS; CLEAVAGE; PHOTOMUTAGENICITY; PHOTOGENOTOXICITY; PHOTOCHEMISTRY; OXYGEN; DRUGS AB Previous study showed that the cosmetic ingredient chemical azulene and its derivative gauiazulene exhibited photomutagenicity four- to five-fold higher than spontaneous mutation in Salmonella typhimurium TA102. In this study, phototoxicity including photogenotoxicity of azulene in human Jurkat T-cells is reported. When the cell suspensions are irradiated by light (UVA plus visible light) in the presence of azulene, an azulene dose-dependent cellular DNA damage is observed. At the highest azulene concentration of 50 muM, the average DNA fragmentation is 33 +/- 10%, determined by single cell gel electrophoresis (Comet assay). Cell viability assay using fluorescein diacetate indicates that the cells could endure the damage and remain viable. Further study revealed that the combination of light and azulene can cause single-strand cleavage on pure ThetaX174 plasmid DNA in solution. Studies using scavengers reveal that singlet oxygen and free radicals are involved in causing DNA cleavage. This suggests that the photomutagenicity of azulene in S. typhimurium TA102 could be due to DNA fragmentation caused by the concurrent exposure to azulene and light. (C) 2004 Elsevier B.V. All rights reserved. C1 Jackson State Univ, Dept Chem, Jackson, MS 39217 USA. Univ Mississippi, Med Ctr, Dept Surg, Jackson, MS 39216 USA. Natl Ctr Toxicol Res, Jefferson, AR 72709 USA. Jackson State Univ, Dept Biol, Jackson, MS 39217 USA. RP Yu, HT (reprint author), Jackson State Univ, Dept Chem, 1400 JR Lynch St, Jackson, MS 39217 USA. EM yu@ccaix.jsums.edu FU NIGMS NIH HHS [S06 GM008047, S06 GM008047-290048, S06 GM08047] NR 26 TC 22 Z9 23 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1383-5718 J9 MUTAT RES-GEN TOX EN JI Mutat. Res. Genet. Toxicol. Environ. Mutagen. PD AUG 8 PY 2004 VL 562 IS 1-2 BP 143 EP 150 DI 10.1016/j.mrgentox.2004.06.002 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 848BT UT WOS:000223442800013 PM 15279837 ER PT J AU Pogribny, I Raiche, J Slovack, M Kovalchuk, O AF Pogribny, I Raiche, J Slovack, M Kovalchuk, O TI Dose-dependence, sex- and tissue-specificity, and persistence of radiation-induced genomic DNA methylation changes SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE ionizing radiation; epigenetics; DNA methylation; hypomethylation; DNA repair; genome instability ID ELEVATED MUTATION-RATES; X-RAY-IRRADIATION; IONIZING-RADIATION; IN-VITRO; INSTABILITY; CARCINOGENESIS; MICE; HYPOMETHYLATION; 5-METHYLCYTOSINE; DIFFERENTIATION AB Radiation is a well-known genotoxic agent and human carcinogen that gives rise to a variety of long-term effects. Its detrimental influence on cellular function is actively studied nowadays. One of the most analyzed, yet least understood long-term effects of ionizinsi radiation is transgenerational genomic instability. The inheritance of genomic instability suggests the possible involvement of epigenetic mechanisms. such as changes of the methylation of cytosine residues located within CpG dinucleotides. In the current study we evaluated the dose-dependence of the radiation-induced global genome DNA methylation changes. We also analyzed the effects of acute and chronic high dose (5 Gy) exposure on DNA methylation in liver, spleen, and lung tissues of male and female mice and evaluated the possible persistence of the radiation-induced DNA methylation changes. Here we report that radiation-induced DNA methylation changes were sex- and tissue-specific, dose-dependent, and persistent. In parallel we have Studied the levels of DNA damage in the exposed tissues. Based on the correlation between the levels of DNA methylation and DNA damage we propose that radiation-induced global genome DNA hypomethylation is DNA repair-related. (C) 2004 Elsevier Inc. All rights reserved. C1 Univ Lethbridge, Dept Biol Sci, Lethbridge, AB T1K 3M4, Canada. Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Kovalchuk, O (reprint author), Univ Lethbridge, Dept Biol Sci, 4401 Univ Dr, Lethbridge, AB T1K 3M4, Canada. EM olga.kovalchuk@uleth.ca NR 43 TC 92 Z9 105 U1 3 U2 14 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD AUG 6 PY 2004 VL 320 IS 4 BP 1253 EP 1261 DI 10.1016/j.bbrc.2004.06.081 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 841IL UT WOS:000222923400031 PM 15249225 ER PT J AU Mathews, F Youngman, L Neil, A AF Mathews, F Youngman, L Neil, A TI Proportion of the US population whose intakes of added sugars exceed the suggested maximum in the dietary reference intakes - Reply to LM Bodnar and MC Nelson SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Letter C1 Univ Oxford, Dept Zool, Oxford OX1 3PS, England. US FDA, Ctr Vet Med, Laurel, MD USA. Univ Oxford, Div Publ Hlth & Primary Hlth Care, Inst Hlth Sci, Oxford, England. RP Mathews, F (reprint author), Univ Oxford, Dept Zool, S Parks Rd, Oxford OX1 3PS, England. EM fiona.mathews@zoology.ox.ac.uk NR 4 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD AUG PY 2004 VL 80 IS 2 BP 526 EP 527 PG 2 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 841ET UT WOS:000222912800043 ER PT J AU Beseth, BD Cameron, RB Leland, P You, L Varricchio, F Kreitman, RJ Maki, RA Jablons, DM Husain, SR Puri, RK AF Beseth, BD Cameron, RB Leland, P You, L Varricchio, F Kreitman, RJ Maki, RA Jablons, DM Husain, SR Puri, RK TI Interleukin-4 receptor cytotoxin as therapy for human malignant pleural mesothelioma xenografts SO ANNALS OF THORACIC SURGERY LA English DT Article; Proceedings Paper CT 39th Annual Meeting of the Society-of-Thoracic-Surgeons CY JAN 31-FEB 02, 2003 CL SAN DIEGO, CA SP Soc Thorac Surg ID HIGH-AFFINITY INTERLEUKIN-4; GROWTH-FACTOR; CELL-GROWTH; IN-VITRO; PSEUDOMONAS EXOTOXIN; ANTITUMOR-ACTIVITY; CHIMERIC PROTEIN; KAPOSIS-SARCOMA; CARCINOMA-CELLS; CANCER-THERAPY AB Background. Malignant pleural mesothelioma (MPM) is an uncommon but highly fatal neoplasm for which only limited treatment is available. Methods. Immunohistochemical analysis was used to determine the expression of interleukin-4 receptors (IL-4R) on mesothelioma cell lines and resected mesothelioma tumors. Radioreceptor binding assays were used to show that these IL-4R were high-affinity receptors. Previously, we had shown that a chimeric protein composed of a circularly permuted IL-4 molecule fused to a truncated form of Pseudomonas exotoxin A, IL-4(38-37)PE38KDEL, could be used to kill IL-4R-bearing tumor cells in vitro. The toxicity of this molecule to mesothelioma cell lines was tested using a protein synthesis inhibition assay. A human mesothelioma xenograft model was then developed to assess the efficacy of this molecule in vivo. Results. All MPM cell lines tested were found to express high-affinity cell-surface IL-4R. Immunohistochemical analysis of resected mesothelioma tumor specimens from 13 patients revealed that all tumors expressed moderate-to-high levels of IL-4R. Coculture of malignant mesothelioma cell lines with IL-4(38-37)-PE38KDEL resulted in a dose-dependent inhibition of tumor cell protein synthesis through an interaction with cell-surf ace IL-4R. In a nude mouse xenograft model of human MPM, intratumoral administration of IL-4(38-37)-PE38KDEL mediated a dose-dependent decrease in tumor volume and a dose-dependent increase in survival. Conclusions. The chimeric protein, IL-4(38-37)PE38KDEL, has potent antitumor effects against MPM both in vitro and in vivo. (C) 2004 by The Society of Thoracic Surgeons. C1 Univ Calif Los Angeles, Sch Med, Dept Surg, Sect Gen Thorac Surg, Los Angeles, CA 90095 USA. US FDA, Ctr Biol Evaluat & Res, Lab Mol Tumor Biol, Div Cellular & Gene Therapy, Bethesda, MD 20014 USA. US FDA, Ctr Biol Evaluat & Res, Div Biostat, Bethesda, MD 20014 USA. NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Neurocrine Biosci, San Diego, CA USA. RP Cameron, RB (reprint author), Univ Calif Los Angeles, Sch Med, Dept Surg, Sect Gen Thorac Surg, 10833 Le Conte Ave,Room 62-215 CHS,POB 951741, Los Angeles, CA 90095 USA. EM rcameron@mednet.ucla.edu FU NCI NIH HHS [R01 CA093708, R01 CA093708-01A3] NR 30 TC 7 Z9 7 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 AUG PY 2004 VL 78 IS 2 BP 436 EP 443 DI 10.1016/j.athoracsur.2004.03.010 PG 8 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 842JE UT WOS:000222999300009 PM 15276492 ER PT J AU Gray, JT Hungerford, LL Fedorka-Cray, PJ Headrick, ML AF Gray, JT Hungerford, LL Fedorka-Cray, PJ Headrick, ML TI Extended-spectrum-cephalosporin resistance in Salmonella enterica isolates of animal origin SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID AMPC BETA-LACTAMASE; ENTERITIDIS; CMY-2 AB A total of 112 out of 5,709 Salmonella enterica isolates from domestic animal species exhibited decreased susceptibilities to ceftiofur and ceftriaxone, and each possessed the bla(CMY) gene. Ten Salmonella serotypes were significantly more likely to include resistant isolates. Isolates from turkeys, horses, cats, and dogs were significantly more likely to include resistant isolates. C1 USDA ARS, Antimicrobial Resistance Res Unit, Russell Res Ctr, Athens, GA 30604 USA. US FDA, Antimicrobial Resistance Res Unit, Athens, GA 30604 USA. US FDA, Ctr Vet Med, Rockville, MD 20857 USA. US FDA, Ctr Vet Med, Athens, GA 30605 USA. RP Gray, JT (reprint author), Univ Guelph, Dept Pathobiol, Guelph, ON N1G 2W1, Canada. EM jegray@uoguelph.ca NR 19 TC 28 Z9 30 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD AUG PY 2004 VL 48 IS 8 BP 3179 EP 3181 DI 10.1128/AAC.84.8.3179-3181.2004 PG 3 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 842IV UT WOS:000222998300064 PM 15273145 ER PT J AU Lute, S Aranha, H Tremblay, D Liang, DH Ackermann, HW Chu, B Moineau, S Brorson, K AF Lute, S Aranha, H Tremblay, D Liang, DH Ackermann, HW Chu, B Moineau, S Brorson, K TI Characterization of coliphage PR772 and evaluation of its use for virus filter performance testing SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID INVERTED TERMINAL REPEATS; BACTERIOPHAGE PRD1; MEMBRANE-FILTER; ULTRAFILTRATION MEMBRANES; ELECTRON-MICROSCOPY; PROTEIN-TRANSPORT; INTERNAL MEMBRANE; DNA-REPLICATION; PARTICLES; EVOLUTION AB Virus filtration is a key clearance unit operation in the manufacture of recombinant protein, monoclonal antibody, and plasma-derived biopharmaceuticals. Recently, a consensus has developed among filter manufacturers and end users about the desirability of a common nomenclature and a standardized test for classifying and identifying virus-retentive filters. The Parenteral Drug Association virus filter task force has chosen PR772 as the model bacteriophage to standardize nomenclature for large-pore-size virus-retentive filters (filters designed to retain viruses larger than 50 to 60 nm in size). Previously, the coliphage PR772 (Tectiviridae family) has been used in some filtration studies as a surrogate for mammalian viruses of around 50 to 60 nm. In this report, we describe specific properties of PR772 critical to the support of its use for the standardization of virus filters. The complete genomic sequence of virulent phage PR772 was determined. Its genome contains 14,946 bp with an overall G+C content of 48.3 mol%, and 32 open reading frames of at least 40 codons. Comparison of the PR772 nucleotide sequence with the genome of Tectiviridae family prototype phage PRDI revealed 97.2% identity at the DNA level. By dynamic light- scattering analysis, its hydrodynamic diameter was measured as 82 +/- 6 run, consistent with use in testing large-virus-retentive filters. Finally, dynamic light-scattering analysis of PR772 preparations purified on CsCl gradients showed that the phage preparations are largely monodispersed. In summary, PR772 appears to be an appropriate model bacteriophage for standardization of nomenclature for larger-pore-size virus-retentive filters. C1 US FDA, Ctr Drug Evaluat & Res, Off Biotechnol Prod, Bethesda, MD 20892 USA. Pall Corp, Sci Serv, Port Washington, NY USA. Pall Corp, Lab Serv, Port Washington, NY USA. SUNY Stony Brook, Dept Chem, Stony Brook, NY 11794 USA. SUNY Stony Brook, Dept Mat Sci & Engn, Stony Brook, NY 11794 USA. SUNY Stony Brook, Dept Biomed Engn, Stony Brook, NY 11794 USA. Univ Laval, Fac Med Dent, Felix Reference Ctr Bacterial Viruses, Grp Rech Ecol Buccale, St Foy, PQ G1K 7P4, Canada. Univ Laval, Fac Med, Dept Med Biol, St Foy, PQ G1K 7P4, Canada. Univ Laval, Fac Sci & Genie, Dept Biochim & Microbiol, Quebec City, PQ G1K 7P4, Canada. RP Brorson, K (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Biotechnol Prod, 29 Lincoln Dr, Bethesda, MD 20892 USA. EM brorson@cber.fda.gov RI Moineau, Sylvain/N-3578-2013 NR 35 TC 38 Z9 38 U1 1 U2 9 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0099-2240 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD AUG PY 2004 VL 70 IS 8 BP 4864 EP 4871 DI 10.1128/AEM.70.8.4864-4871.2004 PG 8 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 846BQ UT WOS:000223290100059 PM 15294825 ER PT J AU Schiffenbauer, J Hahn, B Weisman, MH Simon, LS AF Schiffenbauer, J Hahn, B Weisman, MH Simon, LS TI Biomarkers, surrogate markers, and design of clinical trials of new therapies for systemic lupus erythematosus SO ARTHRITIS AND RHEUMATISM LA English DT Article ID INTERFERON-INDUCIBLE GENE; DISEASE-ACTIVITY; INTERLEUKIN-2; INDEX; CELLS; VALIDATION; EXPRESSION; NEPHRITIS; RECEPTOR C1 US FDA, CDER, Rockville, MD 20850 USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA. Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. RP Schiffenbauer, J (reprint author), US FDA, CDER, 9201 Corp Blvd, Rockville, MD 20850 USA. EM schiffenbaue@cder.fda.gov NR 22 TC 27 Z9 27 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 AUG PY 2004 VL 50 IS 8 BP 2415 EP 2422 DI 10.1002/art.20353 PG 8 WC Rheumatology SC Rheumatology GA 844UG UT WOS:000223185500005 PM 15334452 ER PT J AU Hurtt, ME Daston, G Davis-Bruno, K Feuston, M Lima, BS Makris, S McNerney, ME Sandler, JD Whitby, K Weir, P Cappon, GD AF Hurtt, ME Daston, G Davis-Bruno, K Feuston, M Lima, BS Makris, S McNerney, ME Sandler, JD Whitby, K Weir, P Cappon, GD TI Juvenile animal studies: Testing strategies and design SO BIRTH DEFECTS RESEARCH PART B-DEVELOPMENTAL AND REPRODUCTIVE TOXICOLOGY LA English DT Review ID REPRODUCTIVE-SYSTEM C1 Pifzer Global Res & Dev, Groton, CT USA. Procter & Gamble Co, Cincinnati, OH USA. US FDA, Rockville, MD 20857 USA. Sanofi Synthelabo, Malvern, PA USA. Inst Nacl Farm & Medicamento, Lisbon, Portugal. US EPA, Washington, DC 20460 USA. Pfizer Global Res & Dev, Kalamazoo, MI USA. ILSI Hlth & Environm Sci Inst, Washington, DC USA. GlaxoSmithKline, King Of Prussia, PA USA. RP Hurtt, ME (reprint author), Pfizer Global Res & Dev Safety Sci, Eastern Point Rd, Groton, CT 06340 USA. EM mark_e_hurtt@groton.pfizer.com RI iMed.ULisboa, iMed.ULisboa/C-6292-2014; iMed.ULisboa, PharmRegSci /B-5723-2014 OI iMed.ULisboa, PharmRegSci /0000-0003-0910-7245 NR 13 TC 26 Z9 26 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1542-9733 J9 BIRTH DEFECTS RES B JI Birth Defects Res. Part B-Dev. Reprod. Toxicol. PD AUG PY 2004 VL 71 IS 4 BP 281 EP 288 DI 10.1002/bdrb.20017 PG 8 WC Oncology; Genetics & Heredity; Toxicology SC Oncology; Genetics & Heredity; Toxicology GA 852JV UT WOS:000223752500002 PM 15334525 ER PT J AU Dorgan, JF Boakye, NA Fears, TR Schleicher, RL Helsel, W Anderson, C Robinson, J Guin, JD Lessin, S Ratnasinghe, LD Tangrea, JA AF Dorgan, JF Boakye, NA Fears, TR Schleicher, RL Helsel, W Anderson, C Robinson, J Guin, JD Lessin, S Ratnasinghe, LD Tangrea, JA TI Serum carotenoids and alpha-tocopherol and risk of nonmelanoma skin cancer SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID BASAL-CELL CARCINOMA; TRANS-BETA-CAROTENE; UNITED-STATES; VITAMIN-E; PREVENTION TRIAL; DNA PHOTODAMAGE; SUBSEQUENT RISK; CLINICAL-TRIAL; FOLLOW-UP; RETINOL AB Background: Carotenoids and tocopherols have been hypothesized to protect against cancer. Methods: We prospectively evaluated associations of several carotenoids and alpha-tocopherol with risk of nonmelanoma skin cancer using serum collected at baseline from 302 subjects in the Isotretinoin-Basal Cell Carcinoma Prevention Trial. All subjects had at least two BCCs in the 5 years prior to randomization. During 5 years of follow-up, 70 subjects did not develop a nonmelanoma skin cancer, 221 developed a BCC, and 85 developed a squamous cell carcinoma (SCC). Cox proportional hazards models were used to estimate risk ratios. Models were stratified by clinical center and gender and adjusted for age, solar damage, skin type, number of prior BCCs and/or SCCs, treatment group, body mass index, and serum low-density lipoprotein-cholesterol and high-density lipoprotein-cholesterol. Results: Risk of developing a subsequent BCC was not related to serum levels of any of the carotenoids measured or to alpha-tocopherol. Serum levels of alpha-carotene, beta-carotene, lycopene, and alpha-tocopherol also were not independently related to risk of a subsequent SCC. However, serum lutein, zeaxanthin, and beta-cryptoxanthin were positively related to SCC risk; risk ratios for subjects in the highest versus lowest tertiles of these micronutrients were 1.63 [95% confidence interval (95% Cl) 0.88-3.01; P for trend = 0.011, 2.40 (95% Cl 1.30-4.42; P for trend = 0.01), and 2.15 (95% Cl 1.21-3.83; P for trend = 0.09), respectively. Conclusion: Additional research is needed on the relationship of carotenoids to SCC risk in the general population and in subsets of the population who are at increased risk. C1 Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Temple Univ, Sch Med, Philadelphia, PA 19122 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NCI, Canc Res Ctr, Bethesda, MD 20892 USA. Ctr Dis Control & Prevent, Div Sci Lab, Atlanta, GA USA. Informat Management Serv Inc, Silver Spring, MD USA. Loyola Univ, Cardinal Bernardin Canc Ctr, Maywood, IL 60153 USA. Univ Arkansas Med Sci, Little Rock, AR 72205 USA. US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Dorgan, JF (reprint author), Fox Chase Canc Ctr, 333 Cottman Ave, Philadelphia, PA 19111 USA. EM jf_dorgan@fccc.edu NR 47 TC 24 Z9 26 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 2004 VL 13 IS 8 BP 1276 EP 1282 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 844JY UT WOS:000223155500003 PM 15298946 ER PT J AU Holland, RD Taylor, J Schoenbachler, L Jones, RC Freeman, JP Miller, TW Lake, BG Gooderham, NJ Turesky, RJ AF Holland, RD Taylor, J Schoenbachler, L Jones, RC Freeman, JP Miller, TW Lake, BG Gooderham, NJ Turesky, RJ TI Rapid biomonitoring of heterocyclic aromatic amines in human urine by tandem solvent solid phase extraction liquid chromatography electrospray ionization mass spectrometry SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID COLORECTAL-CANCER; COOKED FOODS; 2-AMINO-1-METHYL-6-PHENYLIMIDAZO(4,5-B)PYRIDINE PHIP; CYTOCHROME P4501A2; HYDROLYZED URINE; MODEL SYSTEMS; BREAST-CANCER; METABOLISM; MEAT; RISK AB A rapid and facile tandem solvent solid phase extraction method was established to isolate the heterocyclic aromatic amines (HAAs) 2-amino-3,8-dimethylimidazo[4,5-f] quinoxaline (8-MeIQx), 2-amino-3,4,8-trimethylimidazo[4,5-f] quinoxaline, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine, and 2-amino-9H-pyrido[2,3-b]indole from urine. The HAAs were separated by reversed phase liquid chromatography and quantified by electrospray ionization tandem mass spectrometry (ESI/MS/MS) using selected reaction monitoring. The limits of detection and quantitation of these HAAs approached 1-3 and 2-8 pg/mL, respectively, using only 0.3 mL of urine for analysis. Full product ion spectra were acquired to corroborate analyte identities. The pretreatment of urine from human volunteers that had consumed a grilled beef meal with acid or base at 70 degreesC increased the concentration of HAAs by as much as 6-fold, indicating the presence of phase II conjugates of the parent compounds. HAAs containing an N-methylimidazole moiety undergo facile cleavage of the N-methyl group under collision-induced dissociation conditions, and MS/MS analysis in the constant neutral loss scan mode monitoring the transition [M + H](+) --> [M + H - CH3.](+) revealed the presence of two other HAAs. 2-Amino-3-methylimidazo [4,5-f] quinoxaline (IQx) was identified by coelution of the analyte with synthetic IQx and by acquisition of the product ion spectrum. The second HAA was present in a relatively high abundance in urine. The molecule had the same nominal mass as 8-MeIQx (MH+ at m/z 214), and the product ion spectrum was similar to that of 8-MeIQx. This novel HAA was also found in the grilled meat consumed by the volunteers at a concentration of 8 parts per billion. The accurate mass measurement and product ion spectrum of this molecule by ESI quadrupole time-of-flight mass spectrometry revealed that it was an isomer of 8-MeIQx. This tandem solvent solid phase extraction LC/ESI/MS/MS procedure may be used to rapidly assess the daily exposure to a variety of HAAs in urine. C1 Natl Ctr Toxicol Res, Div Chem, Jefferson, AR 72079 USA. BIBRA Int, Carshalton SM5 4DS, Surrey, England. Univ London Imperial Coll Sci Technol & Med, Div Biomed Sci, London SW7 2AZ, England. RP Turesky, RJ (reprint author), Natl Ctr Toxicol Res, Div Chem, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM Rturesky@nctr.fda.gov NR 58 TC 34 Z9 34 U1 0 U2 13 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD AUG PY 2004 VL 17 IS 8 BP 1121 EP 1136 DI 10.1021/tx049910a PG 16 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 847RG UT WOS:000223412000014 PM 15310244 ER PT J AU Kawakami, K Kawakami, M Puri, RK AF Kawakami, K Kawakami, M Puri, RK TI Nitric oxide accelerates interleukin-13 cytotoxin-mediated regression in head and neck cancer animal model SO CLINICAL CANCER RESEARCH LA English DT Article ID RECEPTOR-TARGETED CYTOTOXIN; PSEUDOMONAS EXOTOXIN; IL-13 RECEPTOR; CELL-LINES; ALPHA-2 CHAIN; GLIOMA-CELLS; IN-VIVO; SIGNAL-TRANSDUCTION; MALIGNANT GLIOMA; FUSION CYTOTOXIN AB Receptors for interleukin-13 (IL-13R) are overexpressed on several types of solid cancers including gliobastoma, renal cell carcinoma, AIDS Kaposi's sarcoma, and head and neck cancer. Recombinant fusion proteins IL-13 cytotoxin (IL13-PE38QQR or IL13-PE38) have been developed to directly target IL-13R-expressing cancer cells. Although it has been found that IL-13 cytotoxin has a direct potent antitumor activity in vivo in nude mice models of human cancers, the involvement of indirect antitumor effecter molecules such as nitric oxide (NO) is unknown. To address this issue, we assessed the effect of NO inhibiter N-omega-monomethyl-L-arginine on IL-13 cytotoxin-mediated cytotoxicity and NO2/NO3 production in HN12 head and neck cancer cells. In addition, antitumor effects and NO levels in HN12 and KCCT873 head and neck tumors xenografted s.c. in nude mice when treated with IL-13 cytotoxin were evaluated by tumor measurement, Western blot, and immunohistochemistry analyses. Pretreatment of animals with N-omega-monomethyl-L-arginine significantly decreased the NO levels and IL-13 cytotoxin-mediated antitumor effects. In addition, depletion of macrophages, known to produce NO, also decreased antitumor activity of IL-13 cytotoxin. Based on these studies, we concluded that NO accelerates antitumor effect of IL-13 cytotoxin on head and neck tumor cells. Because IL-13 cytotoxin is currently being tested in the clinic for the treatment of patients with recurrent glioblastoma maltiforme, our current findings suggest maintaining macrophage and NO-producing cellular function for optimal therapeutic effect of this targeted agent. C1 US FDA, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Puri, RK (reprint author), US FDA, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bldg 10,NIH Bldg 29B,Room 2NN10,HFM-735, Bethesda, MD 20892 USA. EM puri@cber.fda.gov NR 47 TC 9 Z9 9 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD AUG 1 PY 2004 VL 10 IS 15 BP 5264 EP 5270 DI 10.1158/1078-0432.CCR-04-0314 PG 7 WC Oncology SC Oncology GA 845PQ UT WOS:000223257200042 PM 15297430 ER PT J AU Petricoin, EF Liotta, LA AF Petricoin, EF Liotta, LA TI Proteomic pattern complexity reveals a rich and uncharted continent of biomarkers SO CLINICAL CHEMISTRY LA English DT Letter ID OVARIAN-CANCER; SERUM C1 US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. NCI, Ctr Canc Res, Clin Proteom Program, Lab Pathol,FDA, Bethesda, MD USA. RP Petricoin, EF (reprint author), FDA, CBER, Bldg 29A-2D12 8800 Rockville Pike, Bethesda, MD 20892 USA. EM petricoin@cber.fda.gov; liotta1@mail.nih.gov NR 7 TC 3 Z9 3 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD AUG PY 2004 VL 50 IS 8 BP 1476 EP 1477 DI 10.1373/clinchem.2004.035097 PG 2 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 840UN UT WOS:000222885500042 ER PT J AU Mohan, AK Cote, TR Block, JA Manadan, AM Siegel, JN Braun, MM AF Mohan, AK Cote, TR Block, JA Manadan, AM Siegel, JN Braun, MM TI Tuberculosis following the use of etanercept, a tumor necrosis factor inhibitor SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID RHEUMATOID-ARTHRITIS; DEFICIENT MICE; BCG INFECTION; RISK; SURVEILLANCE AB Infliximab, a tumor necrosis factor (TNF) antagonist, is associated with tuberculosis (TB), but it is unknown whether this phenomenon is true of all TNF antagonists. We reviewed 25 cases of TB due to another TNF antagonist, etanercept, that were reported to the US Food and Drug Administration (FDA) between November 1998 and March 2002. Such cases are sometimes incomplete and are subject to underreporting. Fifteen patients received other immunosuppressive medications. The median interval between the receipt of the first dose of etanercept and the diagnosis of TB was 11.5 months. Thirteen patients had extrapulmonary TB at the time of diagnosis. Diagnosis was made on the basis of culture results for 12 patients, biopsy findings for 9, and sputum staining for 4. There were 2 deaths, 1 of which was directly attributed to TB. The estimated number of TB cases reported to the FDA for each person-year of treatment with etanercept (i.e., the "reporting rate") among patients with rheumatoid arthritis (RA) was similar to10 cases/100,000 patient-years of exposure. Clinicians considering etanercept for patients with RA should be alert to the possibility of the occurrence of TB, sometimes with an unusual extrapulmonary presentation. It is unclear whether etanercept therapy increases the risk of TB beyond the elevated TB rates already documented for patients with RA. C1 US FDA, Off Biostat & Epidemiol, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. US FDA, Off Drug Evaluat, Ctr Drugs Evaluat & Res, Rockville, MD 20852 USA. Rush Med Coll, Rheumatol Sect, Chicago, IL 60612 USA. RP Mohan, AK (reprint author), US FDA, Off Biostat & Epidemiol, Ctr Biol Evaluat & Res, 1404 Rockville Pike,Ste 200S, Rockville, MD 20852 USA. EM mohan@cber.fda.gov NR 19 TC 180 Z9 183 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD AUG 1 PY 2004 VL 39 IS 3 BP 295 EP 299 DI 10.1086/421494 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 839VR UT WOS:000222813500001 PM 15306993 ER PT J AU Meyerhoff, A Albrecht, R Meyer, JM Dionne, P Higgins, K Murphy, D AF Meyerhoff, A Albrecht, R Meyer, JM Dionne, P Higgins, K Murphy, D TI US food and drug administration approval of ciprofloxacin hydrochloride for management of postexposure inhalational anthrax SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID CYSTIC-FIBROSIS PATIENTS; BACILLUS-ANTHRACIS; PHARMACOKINETICS; OUTBREAK; THERAPY; SAFETY AB In August 2000, the US Food and Drug Administration (FDA) approved ciprofloxacin hydrochloride ( Cipro; Bayer) for management of postexposure inhalational anthrax. This was the first antimicrobial drug approved by the FDA for use in treating an infection due to a biological agent used intentionally. The terrorist attacks of 2001 involving anthrax underscore the imperative that safe and effective drugs to manage such infections be readily available in the United States. The approval of ciprofloxacin hydrochloride, which was made on the basis of a surrogate human marker of efficacy, made extensive use of data from an animal model of disease. This represents a new direction in the development of efficacy data in support of drug approval and facilitates the availability of those drugs for which there is an urgent need. This article presents the scientific data and regulatory mechanism that supported the approval of ciprofloxacin hydrochloride for management of postexposure of inhalational anthrax. C1 US FDA, Rockville, MD 20857 USA. RP Meyerhoff, A (reprint author), Georgetown Univ, Med Ctr, Div Infect Dis, Kober Cogan 110,3750 Reservoir Rd NW, Washington, DC 20007 USA. EM am282@gunet.georgetown.edu NR 20 TC 17 Z9 19 U1 2 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD AUG 1 PY 2004 VL 39 IS 3 BP 303 EP 308 DI 10.1086/421491 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 839VR UT WOS:000222813500003 PM 15306995 ER PT J AU Boehm, G Racoosin, JA Laughren, TP Katz, R AF Boehm, G Racoosin, JA Laughren, TP Katz, R TI Consensus development conference on antipsychotic drugs and obesity and diabetes - Response SO DIABETES CARE LA English DT Letter C1 US FDA, Ctr Drug Evaluat & Res, Div Neuropharmacol Drug Prod, Rockville, MD 20857 USA. RP Racoosin, JA (reprint author), 5600 Fishers Ln,HFD-120, Rockville, MD 20857 USA. EM racoosinj@cder.fda.gov NR 1 TC 18 Z9 18 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD AUG PY 2004 VL 27 IS 8 BP 2088 EP 2089 DI 10.2337/diacare.27.8.2088-a PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 842TD UT WOS:000223026200045 PM 15277452 ER PT J AU Lesko, LJ AF Lesko, LJ TI Translation of pharmacogenetics into patient benefit SO DRUG METABOLISM REVIEWS LA English DT Meeting Abstract CT 7th European ISSX Meeting CY AUG 29-SEP 02, 2004 CL Vancouver, CANADA C1 US FDA, Off Clin Pharmacol & Biopharmaceut, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. 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 0360-2532 J9 DRUG METAB REV JI Drug Metab. Rev. PD AUG PY 2004 VL 36 SU 1 MA 7 BP 4 EP 4 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 856DF UT WOS:000224023200008 ER PT J AU McDowell, MA Dillon, CF Osterloh, J Bolger, PM Pellizzari, E Fernando, R de Oca, RM Schober, SE Sinks, T Jones, RL Mahaffey, KR AF McDowell, MA Dillon, CF Osterloh, J Bolger, PM Pellizzari, E Fernando, R de Oca, RM Schober, SE Sinks, T Jones, RL Mahaffey, KR TI Hair mercury levels in US children and women of childbearing age: Reference range data from NHANES 1999-2000 SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE blood; child; diet; female; hair; mercury; NHANES; preschool ID METHYLMERCURY EXPOSURE; FISH CONSUMPTION; MATERNAL HAIR; BLOOD; POPULATION; NEUROTOXICITY; INTRAUTERINE; AMERICAN; JAPANESE; EPA AB Exposure to methyl mercury, a risk factor for neurodevelopmental toxicity, was assessed in U.S. children 1-5 years of age (n = 838) and women 16-49 years of age (n = 1,726) using hair mercury analysis during the 1999-2000 National Health and Nutrition Examination Survey (NHANES). The data are nationally representative and are based on analysis of cross-sectional data for the noninstitutionalized, U.S. household population. The survey consisted of interviews conducted in participants' homes and standardized health examinations conducted in mobile examination centers. Distributions of total hair mercury levels expressed as micrograms per gram hair Hg and the association of hair Hg levels with sociodemographic characteristics and fish consumption are reported. Geometric mean (standard error of the geometric mean) hair mercury was 0.12 mug/g (0.01 mug/g) in children, and 0.20 mug/g (0.02 mug/g) in women. Among frequent fish consumers, geometric mean hair mercury levels were 3-fold higher for women (0.38 vs. 0.11 mug/g) and 2-fold higher for children (0.16 vs. 0.08 mug/g) compared with nonconsumers. The NHANES 1999-2000 data provide population-based data on hair mercury concentrations for women and children in the United States. Hair mercury levels were associated with age and fish consumption frequency. C1 Ctr Dis Control & Prevent, Natl Ctr Hlth Stn, Hyattsville, MD 20782 USA. Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Atlanta, GA USA. US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. Res Triangle Inst, Res Triangle Pk, NC USA. Orkand Corp, Falls Church, VA USA. US Environm Protect Agcy, Off Prevent Pesticides & Toxic Subst, Off Sci Coordinat & Policy, Washington, DC USA. RP McDowell, MA (reprint author), Ctr Dis Control & Prevent, Natl Ctr Hlth Stn, 3311 Toledo Rd,Room 4335, Hyattsville, MD 20782 USA. EM MMcDowell@cdc.gov NR 46 TC 186 Z9 191 U1 1 U2 25 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD AUG PY 2004 VL 112 IS 11 BP 1165 EP 1171 DI 10.1289/ehp.7046 PG 7 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 852GN UT WOS:000223743700035 PM 15289161 ER PT J AU Tong, WD Xie, W Hong, HX Shi, LM Fang, H Perkins, R AF Tong, WD Xie, W Hong, HX Shi, LM Fang, H Perkins, R TI Assessment of prediction confidence and domain extrapolation of two structure-activity relationship models for predicting estrogen receptor binding activity SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article ID BETA SUBTYPES; QSAR MODELS; 3D QSAR; CHEMICALS; TOXICOLOGY; AFFINITY; TOXICITY; LIGANDS; ALPHA AB Quantitative structure-activity relationship (QSAR) methods have been widely applied in drug discovery, lead optimization, toxicity prediction, and regulatory decisions. Despite major advances in algorithms and software, QSAR models have inherent limitations associated with a size and chemical-structure diversity of the training set, experimental error, and many characteristics of structure representation and correlation algorithms. Whereas excellent fit to the training data may be readily attainable, often models fail to predict accurately chemicals that are outside their domain of applicability. A QSAR's utility and, in the case of regulatory decisions, justification for usage increasingly depend on the ability to quantify a model's potential for predicting unknown chemicals with some known degree of certainty. It is never possible to predict an unknown chemical with absolute certainty. Here we report on two QSAR models based on different data sets for classification of chemicals according to their ability to bind to the estrogen receptor. The models were developed by using a novel QSAR method, Decision Forest, which combines the results of multiple heterogeneous but comparable Decision Tree models to produce a consensus prediction. We used an extensive cross-validation process to define an applicability domain for model predictions based on two quantitative measures: prediction confidence and domain extrapolation. Together, these measures quantify the accuracy of each prediction within and outside of the training domain. Despite being based on large and diverse training sets, both QSAR models had poor accuracy for chemicals within the domain of low confidence, whereas good accuracy was obtained for those within the domain of high confidence. For prediction in the high confidence domain, accuracy was inversely proportional to the degree of domain extrapolation. The model with a larger training set of 1,092, compared with 232 for the other, was more accurate in predicting chemicals at larger domain extrapolation, and could be particularly useful for rapidly prioritizing potential endocrine disruptors from large chemical universe. C1 Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Ctr Toxicoinformat, Jefferson, AR 72079 USA. Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. RP Tong, WD (reprint author), Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Ctr Toxicoinformat, 3900 NCTR Rd,HFT 020, Jefferson, AR 72079 USA. EM wtong@nctr.fda.gov NR 35 TC 98 Z9 99 U1 1 U2 16 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD AUG PY 2004 VL 112 IS 12 BP 1249 EP 1254 DI 10.1289/txg.7125 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 849GM UT WOS:000223526700018 PM 15345371 ER PT J AU Frueh, FW Huang, SM Lesko, LJ AF Frueh, FW Huang, SM Lesko, LJ TI Regulatory acceptance of toxicogenomics data SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Editorial Material ID PHARMACOGENOMIC DATA SUBMISSIONS; FDA C1 US FDA, Ctr Drug Evaluat & Res, Off Clin Pharmacol & Biopharmaceut, Rockville, MD USA. RP Frueh, FW (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Clin Pharmacol & Biopharmaceut, Rockville, MD USA. EM huangs@cder.fda.gov NR 8 TC 10 Z9 10 U1 0 U2 1 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD AUG PY 2004 VL 112 IS 12 BP A663 EP A664 PG 2 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 849GM UT WOS:000223526700002 PM 15345374 ER PT J AU Lachenbruch, PA AF Lachenbruch, PA TI Healthrelated quality of life, environment, and regulation SO ENVIRONMETRICS LA English DT Article; Proceedings Paper CT International Workshop on Environment and Health Related Quality of Life CY NOV 07-08, 2002 CL Vannes, FRANCE DE environmental events; stratification; stratum by treatment interaction AB This article discusses prevalent and incident environmental events and how they might affect clinical trials. Inclusion of stratification by site and by event time is suggested as a possible method to remove some of the effects in the analysis. Published in 2004 by John Wiley Sons, Ltd. C1 US FDA, CBER, Off Biostat & Epidemiol, Rockville, MD 20852 USA. RP Lachenbruch, PA (reprint author), US FDA, CBER, Off Biostat & Epidemiol, 1401 Rovkville Pike HFM-215, Rockville, MD 20852 USA. EM lachenbruch@cber.fda.gov NR 4 TC 0 Z9 0 U1 0 U2 2 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1180-4009 J9 ENVIRONMETRICS JI Environmetrics PD AUG PY 2004 VL 15 IS 5 BP 409 EP 414 DI 10.1002/env.681 PG 6 WC Environmental Sciences; Mathematics, Interdisciplinary Applications; Statistics & Probability SC Environmental Sciences & Ecology; Mathematics GA 842WK UT WOS:000223035000003 ER PT J AU Nguyen, UD Brown, JS Chang, IA Krycia, J Mirotznik, MS AF Nguyen, UD Brown, JS Chang, IA Krycia, J Mirotznik, MS TI Numerical evaluation of heating of the human head due to magnetic resonance imaging SO IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING LA English DT Article DE finite-difference time domain; magnetic resonance imaging (MRI); specific absorption rate (SAR) ID RF DECOUPLING COIL; TEMPERATURE-CHANGES; ABSORPTION RATES; SAR; FIELDS; MRI; MODEL AB In this paper, we present a numerical model for evaluating tissue heating during magnetic resonance imaging (MRI). Our method, which included a detailed anatomical model of a human head, calculated both the electromagnetic power deposition and the associated temperature elevations during an MRI head examination. Numerical studies were conducted using a realistic birdcage coil excited at frequencies ranging from 63 to 500 MHz. The model was validated both experimentally and analytically. The experimental validation was performed at the MR test facility located at the Food and Drug Administration's Center for Devices and Radiological Health. C1 Catholic Univ Amer, Dept Biomed Engn, Washington, DC 20064 USA. Catholic Univ Amer, Dept Mech Engn, Washington, DC 20064 USA. US FDA, CDRH, Rockville, MD 20852 USA. RP Nguyen, UD (reprint author), Catholic Univ Amer, Dept Biomed Engn, Washington, DC 20064 USA. EM nguyenu@cua.edu; brownjs@cua.edu; iac@cdrh.fda.gov; mirotznik@cua.edu RI Brown, J. Steven/F-9841-2011 OI Brown, J. Steven/0000-0003-4914-7778 NR 27 TC 44 Z9 44 U1 0 U2 4 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 0018-9294 J9 IEEE T BIO-MED ENG JI IEEE Trans. Biomed. Eng. PD AUG PY 2004 VL 51 IS 8 BP 1301 EP 1309 DI 10.1109/TBME.2004.827559 PG 9 WC Engineering, Biomedical SC Engineering GA 838QI UT WOS:000222727600001 PM 15311814 ER PT J AU Williams, KM Bigley, EC AF Williams, KM Bigley, EC TI Identification of an I-E-d-restricted T-cell epitope of Escherichia coli outer membrane protein F (vol 72, pg 3907, 2004) SO INFECTION AND IMMUNITY LA English DT Correction C1 US FDA, Ctr Food Safety & Appl Nutr, Immunobiol Branch, Laurel, MD 20708 USA. RP Williams, KM (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Immunobiol Branch, Laurel, MD 20708 USA. 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 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD AUG PY 2004 VL 72 IS 8 BP 4931 EP 4931 DI 10.1128/IAI.72.8.4931.2004 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 841LW UT WOS:000222932600079 ER PT J AU El-Masri, MM Hammad, TA McLeskey, SW Joshi, M Korniewicz, DM AF El-Masri, MM Hammad, TA McLeskey, SW Joshi, M Korniewicz, DM TI Predictors of nosocomial bloodstream infections among critically ill adult trauma patients SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Article ID INTENSIVE-CARE-UNIT; INJURY SEVERITY SCORE; RISK-FACTORS; ATTRIBUTABLE MORTALITY; MULTIVARIATE-ANALYSIS; BRAIN-INJURY; TRANSFUSION; COMPLICATIONS; ASSOCIATION; PREVENTION AB OBJECTIVE: To identify the independent predictors of nosocomial bloodstream infections (BSIs) among critically ill adult trauma patients. DESIGN: A prospective, cohort design was used to study patients who met predetermined inclusion criteria. Basic descriptive and univariate statistical analyses were performed to identify unadjusted predictors. A forward stepwise multivariate logistic regression analysis was then conducted to identify independent predictors of nosocomial BSI. SETTING: Level I university-affiliated shock trauma center. PATIENTS: Three hundred sixty-one critically ill adult trauma patients, 55 of whom developed nosocomial BSIs (15.2%). RESULTS: Data analysis of 45 variables indicated that only 9 were independent predictors of nosocomial BSI: presence of a chest tube, use of immunosuppressive agents, presence of microbial resistance, length of stay, presence of preexisting infection, percentage change of serum albumin levels, patient disposition, transfusion of 10 or more units of blood, and number of central venous catheters (CVCs) for patients who had 4 or more. The classification index of the final regression model at a cut-off point of 0.5 had a specificity of 97.4%, a sensitivity of 60%, a positive predictive value of 76.7%, a negative predictive value of 93%, and an overall precision of 91%. CONCLUSION: In this study, only 9 variables were independent predictors of nosocomial BSI. Our findings are specific to critically ill adult trauma patients and should be interpreted within the context of this particular population. C1 Univ Windsor, Fac Nursing, Windsor, ON N9B 3P4, Canada. US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. Univ Maryland, Sch Nursing, R Adams Cowley Shock Trauma Ctr, College Pk, MD 20742 USA. Univ Miami, Sch Nursing, Miami, FL 33152 USA. RP El-Masri, MM (reprint author), Univ Windsor, Fac Nursing, 401 Sunset,CHN Room G110, Windsor, ON N9B 3P4, Canada. NR 48 TC 19 Z9 19 U1 2 U2 3 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0899-823X J9 INFECT CONT HOSP EP JI Infect. Control Hosp. Epidemiol. PD AUG PY 2004 VL 25 IS 8 BP 656 EP 663 PG 8 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 846IM UT WOS:000223309200008 PM 15357157 ER PT J AU Meyer, JS Grande, M Johnson, K Ali, SF AF Meyer, JS Grande, M Johnson, K Ali, SF TI Neurotoxic effects of MDMA ("ecstasy") administration to neonatal rats SO INTERNATIONAL JOURNAL OF DEVELOPMENTAL NEUROSCIENCE LA English DT Article DE neurotoxicity; MDMA; neonatal; serotonin; apoptosis; development ID 3,4-METHYLENEDIOXYMETHAMPHETAMINE ECSTASY; LONG-TERM; METHYLENEDIOXYMETHAMPHETAMINE MDMA; SEROTONIN TRANSPORTER; BRAIN; EXPOSURE; DRUG; FOREBRAIN; NEURONS; TERMINALS AB 3,4-Methylenedioxymethamphetamine damages fine serotonergic fibers and nerve terminals in adult organisms. Developing animals seem to be less susceptible to this effect, possibly due to a lack of drug-induced hyperthermia. We tested this hypothesis by producing hyperthermia in neonatal rats for 2 h after each of twice-daily MDMA (10 mg/kg s.c.) or saline injections administered from postnatal days 1-4. Other drug-treated and control litters were maintained at normothermic temperatures following injection. Changes in forebrain serotonergic innervation were assessed at postnatal day 25 (serotonin transporter binding and serotonin levels), postnatal day 60 (serotonin transporter binding), and 9 months of age (serotonin transporter immunohistochemistry). We also determined the influence of MDMA treatment on apoptotic activity by means of immunohistochemistry for cleaved caspase-3 at postnatal day 5. The hippocampus showed significant MDMA-related reductions in serotonergic markers at postnatal day 25 and postnatal day 60. At 9 months, there was no effect of prior MDMA exposure on serotonin transporter-immunoreactive fiber density in the hippocampus; however, significant reductions in fiber density were observed in two neocortical areas and a hyperinnervation was found in the caudate-putamen and nucleus accumbens shell. MDMA treatment also produced a two-fold increase in the number of cleaved caspase-3-immunoreactive cells in the rostral forebrain and hippocampus. All of these effects were completely independent of pup body temperature. These findings demonstrate that neonatal MDMA administration exposure stimulates apoptotic cell death in various forebrain areas and also leads to a long-term reorganization of the forebrain serotonergic innervation. Consequently, offspring of MDMA-using women may be at heightened risk for abnormal neural and behavioral development. (C) 2004 ISDN. Published by Elsevier Ltd. All rights reserved. C1 Univ Massachusetts, Dept Psychol, Neurosci & Behav Program, Amherst, MA 01003 USA. Natl Ctr Toxicol Res, Neurochem Lab, Div Neurotoxicol, Jefferson, AR 72079 USA. RP Meyer, JS (reprint author), Univ Massachusetts, Dept Psychol, Neurosci & Behav Program, Tobin Hall,135 Hicks Way, Amherst, MA 01003 USA. EM jmeyer@psych.umass.edu OI Meyer, Jerrold/0000-0002-8382-7075 FU NCRR NIH HHS [RR 11122]; NIDA NIH HHS [DA 00499] NR 49 TC 39 Z9 40 U1 2 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0736-5748 J9 INT J DEV NEUROSCI JI Int. J. Dev. Neurosci. PD AUG-OCT PY 2004 VL 22 IS 5-6 BP 261 EP 271 DI 10.1016/j.ijdevneu.2004.04.007 PG 11 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA 861XR UT WOS:000224452400003 PM 15380826 ER PT J AU Hoff, PM Saad, ED Pazdur, R Wolff, R Lassere, Y Bogaard, KR Abbruzzese, JL AF Hoff, PM Saad, ED Pazdur, R Wolff, R Lassere, Y Bogaard, KR Abbruzzese, JL TI Phase I trial of combined irinotecan and oxaliplatin given every three weeks to patients with metastatic colorectal cancer SO INVESTIGATIONAL NEW DRUGS LA English DT Article DE colorectal neoplasms; drug therapy; phase I; irinotecan; oxaliplatin ID DNA TOPOISOMERASE-I; THYMIDYLATE SYNTHASE; BIOCHEMICAL MODULATION; 1ST-LINE TREATMENT; PLUS IRINOTECAN; FLUOROURACIL; LEUCOVORIN; CARCINOMA; COMBINATION; TUMORS AB Background: Both irinotecan and oxaliplatin are active agents in the treatment of patients with metastatic colorectal cancer (MCC). There is a strong preclinical rationale for combining these two agents. We sought to determine the dose-limiting toxicity (DLT) and the maximum tolerated dose (MTD) of combined irinotecan and oxaliplatin given every three weeks. Methods: Cohorts of patients with MCC previously treated with 5-fluorouracil received escalating doses of irinotecan (150, 175, and 200 mg/m(2)) and a fixed dose of oxaliplatin (130 mg/m(2)), both given intravenously every 3 weeks. DLT was evaluated within the first course of treatment. Objective responses were evaluated every two courses and were confirmed at least four weeks later. Results: Fourteen patients were treated and evaluated for toxicity. The DLT was neutropenia, with or without fever, and delayed recovery of neutrophil counts was frequent (13 courses in six patients). Other toxic effects (peripheral neuropathy, nausea, vomiting, diarrhea, and fatigue) were mild to moderate. Among 13 patients evaluable for activity, four achieved partial responses and nine had stable disease. Conclusion: The combination of irinotecan and oxaliplatin is safe and apparently active in the treatment of MCC patients. The recommended dose for phase II studies is 175 mg/m(2) irinotecan plus 130 mg/m(2) oxaliplatin, given every 3 weeks. Neutropenia and delayed recovery of neutrophil counts are the predominant early toxicities with this schedule. C1 Univ Texas, MD Anderson Canc Ctr, Dept Gastrointestinal Med Oncol, Unit 426, Houston, TX 77030 USA. Albert Einstein Hosp, Sao Paulo, Brazil. US FDA, Rockville, MD USA. RP Hoff, PM (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Gastrointestinal Med Oncol, Unit 426, 1515 Holcombe Blvd, Houston, TX 77030 USA. EM phoff@mdanderson.org NR 27 TC 2 Z9 3 U1 0 U2 2 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-6997 J9 INVEST NEW DRUG JI Invest. New Drugs PD AUG PY 2004 VL 22 IS 3 BP 307 EP 313 DI 10.1023/B:DRUG.0000026257.31142.41 PG 7 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 816TO UT WOS:000221132400011 PM 15122078 ER PT J AU Yang, HC Chen, S White, DG Zhao, SH McDermott, P Walker, R Meng, JH AF Yang, HC Chen, S White, DG Zhao, SH McDermott, P Walker, R Meng, JH TI Characterization of multiple-antimicrobial-resistant Escherichia coli isolates from diseased chickens and swine in China SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID ANTIBIOTIC-RESISTANCE; VIRULENCE FACTORS; FLUOROQUINOLONE RESISTANCE; EDEMA DISEASE; QUINOLONE RESISTANCE; TOPOISOMERASE-IV; DRUG-RESISTANCE; PARC MUTATIONS; ANIMALS; SALMONELLA AB Escherichia coli isolates from diseased piglets (n = 89) and chickens (n = 71) in China were characterized for O serogroups, virulence genes, antimicrobial susceptibility, class 1 integrons, and mechanisms of fluoroquinolone resistance. 078 was the most common serogroup identified (63%) among the chicken E. coli isolates. Most isolates were PCR positive for the increased serum survival gene (iss; 97%) and the temperature-sensitive hemagglutinin gene (tsh; 93%). The 0 serogroups of swine E. coli were not those typically associated with pathogenic strains, nor did they posses common characteristic virulence factors. Twenty-three serogroups were identified among the swine isolates; however, 38% were 0 nontypeable. Overall, isolates displayed resistance to nalidixic acid (100%), tetracycline (98%), sulfamethoxazole (84%), ampicillin (79%), streptomycin (77%), and trimethoprim-sulfamethoxazole (76%). Among the fluoroquinolones, resistance ranged between 64% to levofloxacin, 79% to ciprofloxacin, and 95% to difloxacin. DNA sequencing of gyrA, gyrB, parC, and parE quinolone resistance-determining regions of 39 nalidixic acid-resistant E. coli isolates revealed that a single gyrA mutation was found in all of the isolates; mutations in parC together with double gyrA mutations conferred high-level resistance to fluoroquinolones (ciprofloxacin MIC, greater than or equal to8 mug/ml). Class 1 integrons were identified in 17 (19%) isolates from swine and 42 (47%) from chickens. The majority of integrons possessed genes conferring resistance to streptomycin and trimethoprim. These findings suggest that multiple-antimicrobial-resistant E. coli isolates, including fluoroquinolone-resistant variants, are commonly present among diseased swine and chickens in China, and they also suggest the need for the introduction of surveillance programs in China to monitor antimicrobial resistance in pathogenic bacteria that can be potentially transmitted to humans from food animals. C1 Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA. China Agr Univ, Beijing, Peoples R China. US FDA, Div Anim & Food Microbiol, Res Off, Ctr Vet Med, Laurel, MD USA. RP Meng, JH (reprint author), Univ Maryland, Dept Nutr & Food Sci, 0122 Skinner Bldg, College Pk, MD 20742 USA. EM jmeng@umd.edu OI Chen, Sheng/0000-0003-3526-7808 NR 40 TC 113 Z9 135 U1 1 U2 23 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD AUG PY 2004 VL 42 IS 8 BP 3483 EP 3489 DI 10.1128/JCM.42.8.3483-3489.2004 PG 7 WC Microbiology SC Microbiology GA 846AH UT WOS:000223286500016 PM 15297487 ER PT J AU Eblen, BS Walderhaug, MO Edelson-Mammel, S Chirtel, SJ De Jesus, A Merker, RI Buchanan, RL Miller, AJ AF Eblen, BS Walderhaug, MO Edelson-Mammel, S Chirtel, SJ De Jesus, A Merker, RI Buchanan, RL Miller, AJ TI Potential for internalization, growth, and survival of Salmonella And Escherichia coli O157 : H7 in oranges SO JOURNAL OF FOOD PROTECTION LA English DT Article ID MICROBIOLOGICAL SAFETY; FRUIT JUICES; APPLE JUICE; TOMATOES; FRESH; ACID; INFILTRATION; SUSPENSIONS; IMMERSION; TISSUE AB Internalization potential, survival, and growth of human pathogens within oranges were investigated in a series of laboratory experiments. Submerging oranges into dye solutions at various temperature differentials was used to assess internalization potential. Conditions in which dye internalization was observed were further studied by applying Escherichia coli 0 157: H7 or Salmonella onto the stem scar, subjecting the oranges to a temperature differential, juicing, and measuring numbers of pathogens in the resulting juice. Pathogens for growth and survival studies were applied to or injected into simulated peel punctures. Oranges with small peel holes of selected sizes were also placed into solutions containing these pathogens. Bacterial survival was also evaluated in orange juice at 4 and 24degreesC. Oranges internalized pathogens at a frequency of 2.5 to 3.0%, which mirrored dye internalization frequency (3.3%). Pathogens were internalized at an uptake level of 0.1 to 0.01% of the challenge applied. Bacteria grew within oranges at 24degreesC, but not at 4degreesC. Thirty-one percent of oranges with 0.91-mm surface holes showed pathogen uptake, whereas 2% of oranges with 0.68-mm holes showed pathogen uptake. Pathogens added to fresh orange juice and incubated at 24degreesC declined 1 log CFU/ml within 3 days. These results suggest that internalization, survival, and growth of human bacterial pathogens can occur within oranges intended for producing unpasteurized juice. C1 US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Eblen, BS (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM beblen@cfsan.fda.gov NR 28 TC 35 Z9 35 U1 1 U2 12 PU INT ASSOC FOOD PROTECTION PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD AUG PY 2004 VL 67 IS 8 BP 1578 EP 1584 PG 7 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 844SD UT WOS:000223179100003 PM 15330518 ER PT J AU Timbo, B Koehler, KM Wolyniak, C Klontz, KC AF Timbo, B Koehler, KM Wolyniak, C Klontz, KC TI Sulfites - A Food and Drug Administration review of recalls and reported adverse events SO JOURNAL OF FOOD PROTECTION LA English DT Article AB Sulfite-sensitive individuals can experience adverse reactions after consuming foods containing sulfiting agents (sulfites), and some of these reactions may be severe. In the 1980s and 1990s, the U.S. Food and Drug Administration (FDA) acted to reduce the likelihood that sulfite-sensitive individuals would unknowingly consume foods containing sulfites. The FDA prohibited the use of sulfites on fruits and vegetables (except potatoes) to be served or presented fresh to the public and required that the presence of detectable levels of sulfites be declared on food labels, even when these sulfites are used as a processing aid or are a component of another ingredient in the food. In the present study, data from FDA recall records and adverse event reports were used to examine the current status of problems of sensitivity to sulfites in foods. From 1996 through 1999, the FDA processed a total of 59 recalls of foods containing undeclared sulfites; these 59 recalls involved 93 different food products. Fifty (55%) of the recalled products were classified as class I, a designation indicating that a consumer reasonably could have ingested greater than or equal to10 mg of undeclared sulfites on a single occasion, a level that could potentially cause a serious adverse reaction in a susceptible person. From 1996 through mid-1999, the FDA received a total of 34 reports of adverse reactions allegedly due to eating foods containing undeclared sulfites. The average of 10 reports per year, although derived from a passive surveillance system, was lower than the average of 111 reports per year that the FDA received from 1980 to 1987, a decrease that may have resulted in part from FDA regulatory action. C1 US FDA, Ctr Food Safty & Appl Nutr, College Pk, MD 20740 USA. RP Timbo, B (reprint author), US FDA, Ctr Food Safty & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM btimbo@cfsan.fda.gov NR 24 TC 20 Z9 25 U1 3 U2 16 PU INT ASSOC FOOD PROTECTION PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD AUG PY 2004 VL 67 IS 8 BP 1806 EP 1811 PG 6 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 844SD UT WOS:000223179100039 PM 15330554 ER PT J AU Donnelly, RP Sheikh, F Kotenko, SV Dickensheets, H AF Donnelly, RP Sheikh, F Kotenko, SV Dickensheets, H TI The expanded family of class II cytokines that share the IL-10 receptor-2 (IL-10R2) chain SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Review DE IFN-lambda; STAT3/STAT1; hepatocytes; 1SGF3; IL-22BP ID T-CELL PROLIFERATION; INDUCIBLE FACTOR; INTERLEUKIN-10 RECEPTOR; CUTTING EDGE; FUNCTIONAL-CHARACTERIZATION; TYROSINE PHOSPHORYLATION; INTERFERON-ALPHA; DENDRITIC CELLS; VIRAL-INFECTION; GENE-EXPRESSION AB Several novel interleukin (IL)-10-related cytokines have recently been discovered. These include IL-22, IL-26, and the interferon-lambda (IFN-lambda) proteins IFN-lambda1 (IL-29), IFN-lambda2 (IL-28A), and IFN-lambda3 (IL-28B). The ligand-binding chains for IL-22, IL-26, and IFN-lambda are distinct from that used by IL-10; however, all of these cytokines use a common second chain, IL-10 receptor-2 (IL-10R2; CRF2-4), to assemble their active receptor complexes. Thus, IL-10R2 is a shared component in at least four distinct class II cytokine-receptor complexes. IL-10 binds to IL-10R1; IL-22 binds to IL-22R1; IL-26 binds to IL-20R1; and IFN-lambda binds to IFN-lambdaR1 (also known as IL-28R). The binding of these ligands to their respective R1 chains induces a conformational change that enables IL-10R2 to interact with the newly formed ligand-receptor complexes. This in turn activates a signal-transduction cascade that results in rapid activation of several transcription factors, particularly signal transducer and activator of transcription (STAT)3 and to a lesser degree, STAT1. Activation by IL-10, IL-22, IL-26, or IFN-lambda can be blocked with neutralizing antibodies to the IL-10R2 chain. Although IL-10R2 is broadly expressed on a wide variety of tissues, only a subset of these tissues expresses the ligand-binding RI chains. The receptors for these cytokines are often present on cell lines derived from various tumors, including liver, colorectal, and pancreatic carcinomas. Consequently, the receptors for these cytokines may provide novel targets for inhibiting the growth of certain types of cancer. C1 US FDA, CDER, Div Therapeut Prot, Rockville, MD 20852 USA. Univ Med & Dent New Jersey, Dept Biochem & Mol Biol, Newark, NJ 07103 USA. RP Donnelly, RP (reprint author), US FDA, CDER, Div Therapeut Prot, HFM-538,1401 Rockville Pike, Rockville, MD 20852 USA. EM donnelly@cber.fda.gov FU NIAID NIH HHS [R01 AI51139, R01 AI051139] NR 51 TC 163 Z9 176 U1 3 U2 11 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 AUG PY 2004 VL 76 IS 2 BP 314 EP 321 DI 10.1189/jlb.0204117 PG 8 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 842CQ UT WOS:000222980900004 PM 15123776 ER PT J AU Eller, N Golding, H Inoue, S Beining, P Inman, J Matthews, N Scott, DE Golding, B AF Eller, N Golding, H Inoue, S Beining, P Inman, J Matthews, N Scott, DE Golding, B TI Systemic and mucosal immunity in rhesus macaques immunized with HIV-1 peptide and gp120 conjugated to Brucella abortus SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Article DE antibodies; CD8(+) T cells; interferon-gamma; tumor necrosis factor; V3-peptide ID T-CELLS; IL-12 EXPRESSION; IFN-GAMMA; V3 LOOP; RESPONSES; STIMULATION; INDUCTION; INFECTION; CD4(+); MICE AB HIV vaccine testing in primates is an important method for determining the possibility of vaccine benefit in humans. Goals of HIV-1 vaccination include establishing neutralizing antibodies and a strong CD8(+) T-cell response. We tested a novel vaccine conjugate for its ability to elicit relevant immune responses to HIV proteins and peptides in rhesus macaques. A neutralizing epitope, V3 loop peptide from HIV-1 envelope, was coupled to heat-inactivated Brucella abortus (V3-HKBA). Rhesus macaques were immunized with this conjugate in the anterior thigh. After two immunizations V3-specific antibodies were found in the sera and at mucosal sites. Neutralizing activity of these antibodies was demonstrated by syncytia inhibition assays. Cellular immune recall responses were demonstrated by antigen-specific induction of interferon-gamma and Regulation on Activation Noraml T Cell Expressed and Secreted (RANTES) secretion in vitro. These results confirm and extend preliminary studies in mice that suggest HKBA is an effective carrier that promotes neutralizing antibody secretion at relevant mucosal sites, as well as cellular immune responses that are correlated with viral protection. C1 Off Blood Res & Review, Div Hematol, Lab Plasma Derivat, Bethesda, MD USA. US FDA, Lab Retrovirus Res, Div Viral Prod, Off Vaccines Res & Review,Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Golding, B (reprint author), DH, HFM-345,1401 Woodmont,Rockville Pike, Rockville, MD 20852 USA. EM golding@cber.fda.gov NR 22 TC 2 Z9 3 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD AUG PY 2004 VL 33 IS 4 BP 167 EP 174 DI 10.1111/j.1600-0684.2004.00068.x PG 8 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 834OZ UT WOS:000222421700001 PM 15271066 ER PT J AU Wang, C Sadovova, N Fu, X Scallet, A Hanig, J Slikker, W AF Wang, C Sadovova, N Fu, X Scallet, A Hanig, J Slikker, W TI The role of NMDA receptors in ketamine-induced apoptosis in rat forebrain culture SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 35th Annual Meeting of the Transactions-of-the-American-Society-for-Neurochemistry CY AUG 14-18, 2004 CL New York, NY SP Transact Amer Soc Neurochem C1 Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Charles River Labs, Jefferson, AR USA. US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD AUG PY 2004 VL 90 SU 1 BP 8 EP 8 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 852NB UT WOS:000223760900028 ER PT J AU Zhu, JP Xu, W Cadet, JL Ali, SF Angulo, JA AF Zhu, JP Xu, W Cadet, JL Ali, SF Angulo, JA TI Influence from the neurokinin-1 receptor in methamphetamine-induced damage of striatal neurons SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 35th Annual Meeting of the Transactions-of-the-American-Society-for-Neurochemistry CY AUG 14-18, 2004 CL New York, NY SP Transact Amer Soc Neurochem C1 CUNY Hunter Coll, Dept Biol Sci, New York, NY 10021 USA. NIDA, Mol Neuropsychiat Sect, NIH, Baltimore, MD USA. US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Neurochem Lab, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD AUG PY 2004 VL 90 SU 1 BP 60 EP 60 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 852NB UT WOS:000223760900213 ER PT J AU Sribnick, EA Chera, B Ali, SF Ray, SK Banik, NL AF Sribnick, EA Chera, B Ali, SF Ray, SK Banik, NL TI Increased calpain expression and neuronal apoptosis in spinal cord of mouse with MPTP induced Parkinson's disease SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 35th Annual Meeting of the Transactions-of-the-American-Society-for-Neurochemistry CY AUG 14-18, 2004 CL New York, NY SP Transact Amer Soc Neurochem C1 Med Univ S Carolina, Dept Neurol, Charleston, SC 29425 USA. US FDA, Neurochem Lab, Div Neurotoxicol, Natl Ctr Toxicol Res, Jefferson, AR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD AUG PY 2004 VL 90 SU 1 BP 95 EP 95 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 852NB UT WOS:000223760900330 ER PT J AU Vogelpoel, H Welink, J Amidon, GL Junginger, HE Midha, KK Moller, H Olling, M Shah, VP Barends, DM AF Vogelpoel, H Welink, J Amidon, GL Junginger, HE Midha, KK Moller, H Olling, M Shah, VP Barends, DM TI Biowaiver monographs for immediate release solid oral dosage forms based on Biopharmaceutics Classification System (BCS) literature data: Verapamil hydrochloride, propranolol hydrochloride, and atenolol SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Editorial Material DE BCS; biowaiver; verapamil; propranolol; atenolol ID HUMAN INTESTINAL PERMEABILITY; APPARENT DRUG PERMEABILITY; EPITHELIAL CACO-2 CELLS; JEJUNAL PERMEABILITY; ABSORPTION; HUMANS; PHARMACOKINETICS; TRANSPORT; BIOAVAILABILITY; MODEL AB Literature data related to the Biopharmaceutics Classification System (BCS) are presented on verapamil hydrochloride, propranolol hydrochloride, and atenolol in the form of BCS-monographs. Data on the qualitative composition of immediate release (IR) tablets containing these active substances with a Marketing Authorization (MA) in the Netherlands (NL) are also provided; in view of these MA's the assumption was made that these tablets were bioequivalent to the innovator product. The development of a database with BCS-related data is announced by the International Pharmaceutical Federation (FIP). (C) 2004 Wiley-Liss, Inc. C1 Natl Inst Publ Hlth & Environm, RIVM, Ctr Qual Chem Pharmaceut Prod, NL-3720 BA Bilthoven, Netherlands. Med Evaluat Board Netherlands, NL-2500 BE The Hague, Netherlands. Univ Michigan, Coll Pharm, Ann Arbor, MI 48109 USA. Leiden Univ, Div Pharmaceut Technol, Leiden Amsterdam Ctr Drug Res, NL-2300 RA Leiden, Netherlands. Univ Saskatchewan, Saskatoon, SK S7N 5C9, Canada. Zent Lab Deutsch Apotheker, D-65760 Eschborn, Germany. US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Barends, DM (reprint author), Natl Inst Publ Hlth & Environm, RIVM, Ctr Qual Chem Pharmaceut Prod, POB 1, NL-3720 BA Bilthoven, Netherlands. EM dirk.barends@rivm.nl NR 58 TC 79 Z9 84 U1 0 U2 6 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0022-3549 J9 J PHARM SCI-US JI J. Pharm. Sci. PD AUG PY 2004 VL 93 IS 8 BP 1945 EP 1956 DI 10.1002/jps.20131 PG 12 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 843HQ UT WOS:000223069700002 PM 15236445 ER PT J AU March, J Kratochvil, C Clarke, G Beardslee, W Derivan, A Emslie, G Green, EP Heiligenstein, J Hinshaw, S Hoagwood, K Jensen, P Lavori, P Leonard, H McNulty, J Michaels, MA Mossholder, A Osher, T Petti, T Prentice, E Vitiello, B Wells, K AF March, J Kratochvil, C Clarke, G Beardslee, W Derivan, A Emslie, G Green, EP Heiligenstein, J Hinshaw, S Hoagwood, K Jensen, P Lavori, P Leonard, H McNulty, J Michaels, MA Mossholder, A Osher, T Petti, T Prentice, E Vitiello, B Wells, K TI AACAP 2002 Research Forum: Placebo and alternatives to placebo in randomized controlled trials in pediatric psychopharmacology SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE placebo; treatment; randomized controlled trial; psychopharmacology; adolescence ID CLINICAL-TRIALS; MENTAL-HEALTH; CHILDREN; FLUOXETINE; DESIGNS; MTA; ADOLESCENTS; STRATEGIES; GUIDELINES; DEPRESSION AB Objective: The use of placebo in the pediatric age group has come under increasing scrutiny. At the 2002 Annual Meeting of the American Academy of Child and Adolescent Psychiatry, the Academy's Workgroup on Research conducted a research forum. The purpose was to identify challenges and their solutions regarding the use of placebo in randomized controlled trials in pediatric psychopharmacology. Method: Workgroups focused on problems and solutions in five areas: ethics and human subjects, research design and statistics, partnering with consumers, U.S. Food and Drug Administration and pharmaceutical industry perspectives, and psychosocial treatments. Results: In many but not all circumstances, inclusion of a placebo control is essential to meet the scientific goals of treatment outcome research. Innovative research designs; involvement of consumers in planning and implementing research; flexibility by industry, academia, the National Institutes of Health, and regulatory agencies acting in partnership; and concomitant use of evidence-based psychosocial services can and should assist in making placebo-controlled trials acceptable. Conclusions: Properly designed placebo-controlled trials remain necessary, ethical, and feasible. C1 Duke Univ, Med Ctr, Durham, NC 27706 USA. Univ Nebraska, Med Ctr, Omaha, NE 68182 USA. Kaiser Permanente Ctr Hlth Res, Portland, OR USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Children & Adults Attent Deficit Disorders, Landover, MD USA. Columbia Univ, New York, NY 10027 USA. Stanford Univ, Stanford, CA 94305 USA. Brown Univ, Providence, RI 02912 USA. Natl Alliance Mentally Ill, Arlington, VA USA. US FDA, Rockville, MD 20857 USA. Federat Families Childrens Mental Hlth, Alexandria, VA USA. Indiana Univ, Med Ctr, Indianapolis, IN 46204 USA. NIMH, Bethesda, MD 20892 USA. RP March, J (reprint author), Duke Univ, Med Ctr, Durham, NC 27706 USA. EM jsmarch@acpub.duke.edu OI Jensen, Peter/0000-0003-2387-0650 NR 36 TC 27 Z9 27 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD AUG PY 2004 VL 43 IS 8 BP 1046 EP 1056 DI 10.1097/01.chi.0000129606.83206.77 PG 11 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 840LX UT WOS:000222861200017 PM 15266201 ER PT J AU Mitchell, AE Bakshi, KS Kimmel, CA Buck, GM Feuston, MH Foster, PMD Friedman, JM Holson, JF Hughes, CL Moore, JA Schwetz, BA Scialli, AR Scott, WJ Vorhees, CV Zirkin, BR AF Mitchell, AE Bakshi, KS Kimmel, CA Buck, GM Feuston, MH Foster, PMD Friedman, JM Holson, JF Hughes, CL Moore, JA Schwetz, BA Scialli, AR Scott, WJ Vorhees, CV Zirkin, BR TI Evaluating chemical and other agent exposures for reproductive and developmental toxicity SO JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A-CURRENT ISSUES LA English DT Reprint ID JP-8 JET FUEL; DOSE-RESPONSE ASSESSMENT; ADVERSE-EFFECT LEVELS; NONCANCER RISK-ASSESSMENT; SPRAGUE-DAWLEY RATS; ORGAN WEIGHT DATA; BORIC-ACID; SAFETY FACTORS; BLOOD-LEVELS; CD-1 MICE C1 CNR, Washington, DC 20418 USA. US EPA, Washington, DC 20460 USA. SUNY Buffalo, Buffalo, NY 14260 USA. Sanofi Pharmaceut, Malvern, PA USA. Chem Ind Inst Toxicol, Res Triangle Pk, NC 27709 USA. Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. WIL Res Lab, Ashland, OH USA. Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. Inst Evaluating Hlth Risks, Washington, DC USA. Natl Ctr Toxicol Res, Rockville, MD USA. Georgetown Univ, Med Ctr, Washington, DC 20007 USA. Univ Cincinnati, Coll Med, Cincinnati, OH USA. Johns Hopkins Univ, Sch Publ Hlth, Baltimore, MD USA. RP Bakshi, KS (reprint author), Natl Acad, Board Environm Studies & Toxicol, Keck Bldg,500 5th St NW, Washington, DC 20001 USA. EM Kbakshi@nas.edu OI Buck Louis, Germaine/0000-0002-1774-4490 NR 267 TC 4 Z9 4 U1 0 U2 0 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 PY 2004 VL 67 IS 15-16 BP 1159 EP 1314 DI 10.1080/15287390490460994 PG 156 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 837LW UT WOS:000222637900001 PM 15205023 ER PT J AU Clavet, CR Margolin, AB Regan, PM AF Clavet, CR Margolin, AB Regan, PM TI Herpes simplex virus type-2 specific glycoprotein G-2 immunomagnetically captured from HEp-2 infected tissue culture extracts SO JOURNAL OF VIROLOGICAL METHODS LA English DT Article DE HSV-2; glycoprotein G-2; type-specific gG-2; immunomagnetic separation ID WESTERN-BLOT IMMUNOBLOT; GENITAL HERPES; HUMAN-SERA; MONOCLONAL-ANTIBODIES; ENZYME IMMUNOASSAYS; COMMON ANTIBODIES; NATURAL-HISTORY; NEONATAL HERPES; WOMEN; IDENTIFICATION AB Monoclonal antibody H1206 anti-HSV-2 gG-2 bound to tosylactivated paramagnetic Dynabeads(R) (Dynal(R)) has been used to isolate HSV-2 type-specific gG-2 from solubilized HEp-2 HSV-2 infected cell extracts. The immunomagnetically captured type-specific glycoprotein reacted strongly with monoclonal antibody H1206 and demonstrated a single band with apparent molecular weight of 100,000 (100 kDa) and a doublet band with an apparent molecular weight of 60,000-64,000 (60-64 kDa). We observed the same exact banding pattern when monoclonal H1206 was immunoblotted with Helix pomatia lectin purified HSV-2 gG-2. The immunomagnetically purified gG-2 was unreactive to monoclonal antibody H1379 anti-HSV-1 gG-1 and four human HSV antibody negative sera. In addition, 20 human HSV antibody positive sera obtained from the Centers for Disease Control (CDC), Atlanta, GA, were used for the evaluation of our methodology. Immunoblotting of the human HSV antibody positive samples were in agreement with the CDC HSV serological designation. Sera characterized by reactivity to the immunomagnetically purified gG-2 in conjunction with Western blot has the potential to be used as a confirmatory serological test or to determine the accuracy of clinical serological immunoassays used to determine HSV-2 seropositivity. (C) 2004 Elsevier B.V. All rights reserved. C1 US FDA, Winchester Engn & Analyt Ctr, Winchester, MA 01890 USA. Univ New Hampshire, Durham, NH 03824 USA. RP Clavet, CR (reprint author), US FDA, Winchester Engn & Analyt Ctr, Winchester, MA 01890 USA. EM cclavet@ora.fda.gov NR 47 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-0934 J9 J VIROL METHODS JI J. Virol. Methods PD AUG PY 2004 VL 119 IS 2 BP 121 EP 128 DI 10.1016/j.jviromet.2004.03.008 PG 8 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Virology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Virology GA 828MX UT WOS:000221978500009 PM 15158593 ER PT J AU Wang, RF Beggs, ML Erickson, BD Cerniglia, CE AF Wang, RF Beggs, ML Erickson, BD Cerniglia, CE TI DNA microarray analysis of predominant human intestinal bacteria in fecal samples SO MOLECULAR AND CELLULAR PROBES LA English DT Article DE microarray; human intestinal bacteria; fecal samples; PCR; 16S rRNA gene amplification ID 16S RIBOSOMAL-RNA; COMB. NOV; HUMAN FECES; GEN. NOV.; FUSOBACTERIUM-PRAUSNITZII; PCR DETECTION; MICROFLORA; IDENTIFICATION; SEQUENCE; PROBES AB A microarray method was developed for the detection of 40 bacterial species reported in the literature to be predominant in the human gastrointestinal tract. The 40 species include seven species each of Bacteroides and Clostridium, six species of Ruminococcus, five species of Bifidobacterium, four species of Eubacterium, two species each of Fusobacterium, Lactobacillus and Enterococcus, and single species each of Collinsella, Eggerthella, Escherichia, Faecalibacterium and Finegoldia. Three 40-mer oligos specific for each bacterial species were designed based on comparison of the 16S rDNA sequences available in the GenBank database, and were used to make the DNA-array on epoxy slides. Using two universal primers, the 16S rRNA gene from bacteria present in fecal samples were amplified and labeled with Cyanine5-dCTP by PCR, and then hybridized to the DNA-array. After resolving some difficulties caused by sequence conflicts in GenBank and inaccurate reference strains, all 40 bacterial reference species gave positive results. The microarray method was used to screen fecal samples obtained from 11 healthy human volunteers for the presence of these intestinal bacteria. The results indicated that 25-37 of the 40 species could be detected in each fecal sample and that 33 of the species were found in a majority of the samples. Published by Elsevier Ltd. C1 US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. Univ Arkansas Med Sci, Dept Geriatr, Microarray Core Facil, Little Rock, AR 72205 USA. RP Wang, RF (reprint author), US FDA, Natl Ctr Toxicol Res, Div Microbiol, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM rwang@nctr.fda.gov NR 50 TC 49 Z9 59 U1 6 U2 9 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 AUG PY 2004 VL 18 IS 4 BP 223 EP 234 DI 10.1016/j.mcp.2004.03.002 PG 12 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Cell Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Cell Biology GA 846JV UT WOS:000223312700003 PM 15271382 ER PT J AU Barmada, S Piccardo, P Yamaguchi, K Ghetti, B Harris, DA AF Barmada, S Piccardo, P Yamaguchi, K Ghetti, B Harris, DA TI GFP-tagged prion protein is correctly localized and functionally active in the brains of transgenic mice SO NEUROBIOLOGY OF DISEASE LA English DT Article DE prion; Golgi apparatus; brain ID GPI-ANCHORED PROTEINS; CLATHRIN-COATED PITS; ULTRASTRUCTURAL-LOCALIZATION; ENDOPLASMIC-RETICULUM; NEUROBLASTOMA-CELLS; AXONAL-TRANSPORT; MESSENGER-RNA; MOUSE-BRAIN; PRP; EXPRESSION AB Prion diseases result from conversion of PrPC, a neuronal membrane glycoprotein of unknown function, into PrPSc, an abnormal conformer that is thought to be infectious. To facilitate analysis of PrP distribution in the brain, we have generated transgenic mice in which a PrP promoter drives expression of PrP-EGFP, a fusion protein consisting of enhanced green fluorescent protein inserted adjacent to the glycolipid attachment site of PrP. We find that PrP-EGFP in the brain is glycosylated and glycolipid-anchored and is localized to the surface membrane and the Golgi apparatus of neurons. Like endogenous PrP, PrP-EGFP is concentrated in synapse-rich regions and along axon tracts. PrP-EGFP is functional in vivo, since it ameliorates the cerebellar neurodegeneration induced by a truncated form of PrP. These observations clarify uncertainties in the cellular localization of PrPC in brain, and they establish PrP-EGFP transgenic mice as useful models for further studies of prion biology. (C) 2004 Elsevier Inc. All rights reserved. C1 Washington Univ, Sch Med, Dept Cell Biol & Physiol, St Louis, MO 63110 USA. Indiana Univ, Sch Med, Div Neuropathol, Indianapolis, IN 46202 USA. US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Harris, DA (reprint author), Washington Univ, Sch Med, Dept Cell Biol & Physiol, 600 S Euclid Ave, St Louis, MO 63110 USA. EM dharris@cellbio.wustl.edu FU NIA NIH HHS [P30 AG10133]; NIGMS NIH HHS [T32GM07200]; NINDS NIH HHS [NS40975] NR 56 TC 42 Z9 43 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 0969-9961 J9 NEUROBIOL DIS JI Neurobiol. Dis. PD AUG PY 2004 VL 16 IS 3 BP 527 EP 537 DI 10.1016/j.nbd.2004.05.005 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 841SF UT WOS:000222951000006 PM 15262264 ER PT J AU Hsia, CC Wu, ZY Li, YS Zhang, F Sun, ZT AF Hsia, CC Wu, ZY Li, YS Zhang, F Sun, ZT TI Nivalenol, a main Fusarium toxin in dietary foods from high-risk areas of cancer of esophagus and gastric cardia in China, induced benign and malignant tumors in mice SO ONCOLOGY REPORTS LA English DT Article DE nivalenol; deoxynivalenol; Fusarium toxins; tricothecenes; esophageal cancer; clastogenic effect; tumorigenic effect; animal studies; chromosome aberration ID HEPATOCELLULAR-CARCINOMA; MYCOTOXINS NIVALENOL; NATURAL OCCURRENCE; SOUTHWEST GERMANY; DEOXYNIVALENOL; ZEARALENONE; TRICHOTHECENES; WHEAT AB This is the first report that a Fusarium toxin nivalenol (NIV) naturally existing at high levels in dietary food in high-risk areas of cancer of esophagus and gastric cardia in China induced benign and malignant tumors in mice. The levels of two Fusarium toxins, nivalenol and deoxynivalenol (DON) were quantitated using high performance liquid chromatography (HPLC) in a total of 97 samples of dietary wheat flour; barley and corn collected from families in two areas with high mortality rate of cancer of esophagus and gastric cardia (132/100,000), Linxian, Henan province and Cixiang, Hepei province, China. The mean level of NIV and DON in three dietary foods was 830 927 mug/kg (range 584-1,780 mug/kg) and 4,281 6,114 mug/kg (range 732-10,980 mug/kg) respectively. The highest mean level of NIV was 1,780 1,705 mug/kg found in barley from Linxian, that of DON was 10,980 10,139 mug/kg found in corn from Cixiang. NIV was undetectable in 2 samples of rice from USA. The mean levels of NIV in three main dietary foods in those two high-risk areas were estimated at 400 to 800-fold higher than that in the USA, where NIV was undetectable in dietary food, and the mortality rate of esophageal cancer is <5/100,000 in white Caucasians in the USA, (odds ratio was estimated at 17-34, p<0.000005). These data suggest that Linxian and Cixiang peasants who consumed a diet with high NIV had significantly higher risk for developing esophageal cancer than the US residents who consumed food without or with negligible amounts of NIV. Three repeated experiments were performed using Balb/C mice with intermittent application of NIV, alternate with 12-Tetradeconoylphorbol-13-acetate (TPA) application on skin. Papillomas and carcinomas developed in a total of 23/49 (47%) mice that survived 11-60 weeks of experiments. Among all the tumors, 4 carcinomas in 3 mice were identified. No tumors were found in the 60 control mice applying either TPA or acetone (solvent) only on skin. C1 US FDA, Ctr Biol Evaluat & Res, Div Emerging & Transfus Transmitted Dis, Lab Hepatitis & Related Emerging Agents, Rockville, MD 20852 USA. Chinese Acad Med Sci, Natl Lab Mol Oncol, Canc Res Inst Hosp, Beijing, Peoples R China. RP Hsia, CC (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Emerging & Transfus Transmitted Dis, Lab Hepatitis & Related Emerging Agents, 1401 Rockville Pike,HFM 310,NIH Campus Bldg 29,Ro, Rockville, MD 20852 USA. EM hsia@cber.fda.gov NR 32 TC 30 Z9 31 U1 0 U2 2 PU PROFESSOR D A SPANDIDOS PI ATHENS PA 1, S MERKOURI ST, EDITORIAL OFFICE,, ATHENS 116 35, GREECE SN 1021-335X J9 ONCOL REP JI Oncol. Rep. PD AUG PY 2004 VL 12 IS 2 BP 449 EP 456 PG 8 WC Oncology SC Oncology GA 838MC UT WOS:000222716400037 PM 15254715 ER PT J AU Hirschfeld, S AF Hirschfeld, S TI The Pediatric Research Equity Act and oncology - Commentary SO PEDIATRIC BLOOD & CANCER LA English DT Editorial Material C1 US FDA, Ctr Biol Evaluat & Res, Off Cellular Tissue & Gene Therapy, Rockville, MD 20852 USA. RP Hirschfeld, S (reprint author), US FDA, Ctr Biol Evaluat & Res, Off Cellular Tissue & Gene Therapy, 1401 Rockville Pike,HFM 755, Rockville, MD 20852 USA. EM hirschfeld@cber.fda.gov RI Hirschfeld, Steven/E-2987-2016 OI Hirschfeld, Steven/0000-0003-0627-7249 NR 0 TC 2 Z9 2 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD AUG PY 2004 VL 43 IS 2 BP 99 EP 102 DI 10.1002/pbc.20085 PG 4 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 835JM UT WOS:000222479000002 PM 15236272 ER PT J AU Byrnes, KR Barna, L Chenault, VM Waynant, RW Ilev, IK Longo, L Miracco, C Johnson, B Anders, JJ AF Byrnes, Kimberly R. Barna, Lauren Chenault, V. Michelle Waynant, Ronald W. Ilev, Ilko K. Longo, Leonardo Miracco, Clelia Johnson, Bryan Anders, Juanita J. TI Photobiomodulation Improves Cutaneous Wound Healing in an Animal Model of Type II Diabetes SO PHOTOMEDICINE AND LASER SURGERY LA English DT Article ID FIBROBLAST-GROWTH-FACTOR; HELIUM-NEON LASER; PERIODONTAL-LIGAMENT CELLS; IN-VITRO; 660 NM; GINGIVAL FIBROBLASTS; ENDOTHELIAL-CELLS; FACTOR EXPRESSION; PSAMMOMYS-OBESUS; LIGHT THERAPY AB Objective: We investigated the effects of photobiomodulation (PBM) on cutaneous wound healing in an animal model of type II diabetes, Psammomys obesus (Sand Rats). Background Data: 632-nm light has been established as the most effective wavelength for treatment of cutaneous wounds; however, the inconsistent efficacy of PBM may be due to inadequate treatment parameter selection. Methods: Using 632-nm light, an initial series of experiments were done to establish optimal treatment parameters for this model. Following creation of bilateral full-thickness skin wounds, non-diabetic Sand Rats were treated with PBM of differing dosages. Wound healing was assessed according to wound closure and histological characteristics of healing. Optimal treatment parameters were then used to treat type II diabetic Sand Rats while a diabetic control group received no irradiation. In order to elucidate the mechanism behind an improvement in wound healing, expression of basic fibroblast growth factor (bFGF) was assessed. Results: Significant improvement in wound healing histology and wound closure were found following treatment with 4 J/cm(2) (16 mW, 250-sec treatments for 4 consecutive days; p < 0.05). The 4 J/cm(2) dosage significantly improved histology and closure of wounds in the diabetic group in comparison to the non-irradiated diabetic group. Quantitative analysis of bFGF expression at 36 h post-injury revealed a threefold increase in the diabetic and non-diabetic Sand Rats after PBM. Conclusions: The results demonstrate that PBM at an energy density of 4 J/cm(2) is effective in improving the healing of cutaneous wounds in an animal model of type II diabetes, suggesting that PBM (632 nm, 4 J/cm(2)) would be effective in treating chronic cutaneous wounds in diabetic patients. C1 [Byrnes, Kimberly R.; Barna, Lauren; Anders, Juanita J.] Uniformed Serv Univ Hlth Sci, Dept Anat Physiol & Genet, Bethesda, MD 20814 USA. [Chenault, V. Michelle] US FDA, Ctr Devices & Radiol Hlth, Off Sci & Technol, Rockville, MD 20857 USA. [Waynant, Ronald W.; Ilev, Ilko K.] US FDA, Ctr Devices & Radiol Hlth, Div Phys, Rockville, MD 20857 USA. [Longo, Leonardo] Univ Siena, Specializat Sch Gen Surg, I-53100 Siena, Italy. [Miracco, Clelia] Univ Siena, Sect Pathol Anat, Dept Human Pathol & Oncol, I-53100 Siena, Italy. [Johnson, Bryan] Uniformed Serv Univ Hlth Sci, F Edward Hebert Sch Med, Bethesda, MD 20814 USA. RP Byrnes, KR (reprint author), Uniformed Serv Univ Hlth Sci, Dept Anat Physiol & Genet, Room B2047,4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM krb27@georgetown.edu OI Byrnes, Kimberly/0000-0002-7501-7734 NR 61 TC 50 Z9 58 U1 0 U2 7 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1549-5418 J9 PHOTOMED LASER SURG JI Photomed. Laser Surg. PD AUG PY 2004 VL 22 IS 4 BP 281 EP U17 PG 12 WC Surgery SC Surgery GA V19DF UT WOS:000208052400002 PM 15345169 ER PT J AU Petricoin, EF Fishman, DA Conrads, TP Veenstra, TD Liotta, LA AF Petricoin, EF Fishman, DA Conrads, TP Veenstra, TD Liotta, LA TI Lessons from Kitty Hawk: From feasibility to routine clinical use for the field of proteomic pattern diagnostics SO PROTEOMICS LA English DT Article DE cancer; diagnostics; mass spectrometry; patterns ID MASS-SPECTROMETRY; OVARIAN-CANCER; SERUM; IDENTIFICATION; MARKERS AB Proteomic pattern diagnostics is a rapidly evolving field of science. Despite the increasingly large number of laboratories reporting exciting success with this concept, recent speculation concerning reproducibility and the nature and identities of the information content of the pattern constituents have served to defocus and polarize the community. These controversies will be rendered obsolete as the field accelerates into a new realm of clinical diagnostics. This new era will see the currently dry biomarker pipeline flooded with new candidate molecules, and the mass spectrometer will continue its maturation into a dominant clinical platform. We reflect on the important lessons gleaned from the Wright brothers' attempts at controlled heavier-than-air flight as a model for perseverance and a view to the very near future for proteomic pattern diagnostics. C1 NCI, FDA, Clin Proteom Program, Off Cell & Gene Therapies,CBER, Bethesda, MD 20892 USA. Northwestern Univ, Natl Ovarian Canc Early Detect Program, Chicago, IL 60611 USA. SAIC Frederick Inc, Lab Proteom & Analyt Technol, NCI, Biomed Proteom Program, Frederick, MD USA. NCI, FDA, Clin Proteom Program, Lab Pathol,Ctr Canc Res,NIH, Bethesda, MD USA. RP Petricoin, EF (reprint author), NCI, FDA, Clin Proteom Program, Off Cell & Gene Therapies,CBER, Bldg 29A,Room 2D12,8800 Rockville Pike, Bethesda, MD 20892 USA. EM petricoin@cber.fda.gov NR 24 TC 26 Z9 27 U1 0 U2 0 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1615-9853 J9 PROTEOMICS JI Proteomics PD AUG PY 2004 VL 4 IS 8 BP 2357 EP 2360 DI 10.1002/pmic.200400865 PG 4 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 844DK UT WOS:000223137300018 PM 15274129 ER PT J AU Reesink, HW Engelfriet, CP AF Reesink, HW Engelfriet, CP TI Are current measures to prevent transfusion-associated protozoal infections sufficient? SO VOX SANGUINIS LA English DT Article C1 Sanquin Blood Bank NW Reg, NL-1066 CX Amsterdam, Netherlands. Sanquin Diagnost Serv, NL-1066 CX Amsterdam, Netherlands. Sanquin Res & Sanquin Diagnost, NL-1066 CX Amsterdam, Netherlands. Hosp Sirio Libanes, Blood Bank, BR-01308050 Sao Paulo, Brazil. Hema Quebec, St Laurent, PQ H4R 2W7, Canada. Shanghai Blood Ctr, Shanghai, Peoples R China. Etab Francais Sang, Ile De France, France. Inst Natl Transfus Sanguine, F-75015 Paris, France. Irish Blood Transfus Serv, Dublin 8, Ireland. Magen David Adom Blood Serv, Tel Aviv, Israel. Osped A Manzoni, Lecce, Italy. Osped Maggiore, IRCCS, Milan, Italy. Tokyo Red Cross Blood Ctr, Shibuya Ku, Tokyo 1500012, Japan. Ctr Transfus & Banc Teixits, Barcelona 08035, Spain. NBTC Tunis, Tunis 1006, Tunisia. Amer Red Cross, Jerome H Holland Lab Biomed Sci, Rockville, MD 20855 USA. Amer Red Cross, Natl Testing & Reference Labs, Gaithersburg, MD 20877 USA. US FDA, OBRR, CBER, Rockville, MD 20852 USA. RP Reesink, HW (reprint author), Sanquin Blood Bank NW Reg, Plesmanlaan 125, NL-1066 CX Amsterdam, Netherlands. EM h.reesink@Sanquin.nl; p.engelfriet@sanquin.nl NR 5 TC 14 Z9 14 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0042-9007 J9 VOX SANG JI Vox Sang. PD AUG PY 2004 VL 87 IS 2 BP 125 EP 138 PG 14 WC Hematology SC Hematology GA 851SQ UT WOS:000223706100011 ER PT J AU Klinman, DA Xie, H Little, SF Currie, D Ivins, BE AF Klinman, DA Xie, H Little, SF Currie, D Ivins, BE TI CpG oligonucleotides improve the protective immune response induced by the anthrax vaccination of rhesus macaques SO VACCINE LA English DT Article DE CpG oligonucleotide; anthrax; vaccine adjuvant ID B SURFACE-ANTIGEN; BACTERIAL-DNA; BACILLUS-ANTHRACIS; SYNTHETIC OLIGODEOXYNUCLEOTIDES; INTERFERON-GAMMA; POTENT ENHANCER; CUTTING EDGE; HUMAN-CELLS; MOTIFS; ADJUVANTS AB Synthetic oligodeoxynucleotides (ODN) containing unmethylated CpG motifs act as immune adjuvants, improving the immune response elicited by co-administered vaccines. Combining CpG ODN with anthrax vaccine adsorbed (AVA, the licensed human vaccine) increased the speed, magnitude and avidity of the resultant anti-anthrax response. The protective activity of these Abs was established by passive transfer to anthrax-challenged mice. The ability of CpG ODN to accelerate and magnify the immune response to AVA suggests this strategy may contribute to the development of prophylactic and therapeutic vaccines against biothreat pathogens. Published by Elsevier Ltd. C1 US FDA, Ctr Biol Evaluat & Res, Sect Retroviral Immunol, Bethesda, MD 20892 USA. USA, Med Res Inst Infect Dis, Bacteriol Div, Frederick, MD USA. RP Klinman, DA (reprint author), US FDA, Ctr Biol Evaluat & Res, Sect Retroviral Immunol, Bldg 29A,Rm 3 D 10, Bethesda, MD 20892 USA. EM klinman@cber.fda.gov NR 41 TC 60 Z9 61 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD JUL 29 PY 2004 VL 22 IS 21-22 BP 2881 EP 2886 DI 10.1016/j.vaccine.2003.12.020 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 842KC UT WOS:000223001900030 PM 15246624 ER PT J AU Summers, RM Bitter, I Petrick, N AF Summers, RM Bitter, I Petrick, N TI Virtual colonoscopy SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter ID COLORECTAL NEOPLASIA C1 NIH, Dept Radiol, Bethesda, MD 20892 USA. US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Summers, RM (reprint author), NIH, Dept Radiol, Bldg 10, Bethesda, MD 20892 USA. EM rms@nih.gov NR 4 TC 4 Z9 4 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUL 28 PY 2004 VL 292 IS 4 BP 432 EP 433 DI 10.1001/jama.292.4.432-b PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 841AA UT WOS:000222900500015 PM 15280337 ER PT J AU Beland, FA Churchwell, MI Hewer, A Phillips, DH da Costa, GG Marques, MM AF Beland, FA Churchwell, MI Hewer, A Phillips, DH da Costa, GG Marques, MM TI Analysis of tamoxifen-DNA adducts in endometrial explants by MS and P-32-postlabeling SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE tamoxifen; P-32-postlabeling; HPLC; electrospray ionization tandem mass spectrometry; DNA adducts; endometrial cancer ID BREAST-CANCER PREVENTION; TRIALS; WOMEN; GENOTOXICITY; CULTURE AB The nonsteroidal antiestrogen tamoxifen increases the risk of endometrial cancer; however, the mechanism for the induction of these tumors is not known. Recently, Sharma et a]. [Biochem. Biophys. Res. Commun. 307 (2003) 157], using high performance liquid chromatography (HPLC) with online postcolumn photochemical activation and fluorescence detection, reported the presence of (E)-alpha-(deoxyguanosin-N-2-yl)tamoxifen in DNA from human endometrial explants incubated with tamoxifen. Inasmuch as the methodology used by these investigators does not allow unambiguous characterization of tamoxifen-DNA adducts, we have used two additional techniques (HPLC coupled with electrospray ionization tandem mass spectrometry and P-32-postlabeling analyses) to assay for the presence of tamoxifen-DNA adducts in the human endometrial explant DNA. Tamoxifen-DNA adducts were not detected by either method. (C) 2004 Elsevier Inc. All rights reserved. C1 Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. Inst Canc Res, Sutton SM2 5NG, Surrey, England. Univ Tecn Lisboa, Ctr Quim Estrutural, Inst Super Tecn, P-104900 Lisbon, Portugal. RP Beland, FA (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. EM fbeland@nctr.fda.gov RI Marques, M. Matilde/E-2535-2012; OI Marques, M. Matilde/0000-0002-7526-4962; Phillips, David/0000-0001-8509-3485 NR 24 TC 14 Z9 15 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUL 23 PY 2004 VL 320 IS 2 BP 297 EP 302 DI 10.1016/j.bbrc.2004.05.168 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 836PJ UT WOS:000222567700003 PM 15219826 ER PT J AU Beland, FA Churchwell, MI Doerge, DR Parkin, DR Malejka-Giganti, D Hewer, A Phillips, DH Carmichael, PL da Costa, GG Marques, MM AF Beland, FA Churchwell, MI Doerge, DR Parkin, DR Malejka-Giganti, D Hewer, A Phillips, DH Carmichael, PL da Costa, GG Marques, MM TI Electrospray ionization-tandem mass spectrometry and P-32-postlabeling analyses of tamoxifen-DNA adducts in humans SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID BREAST-CANCER PREVENTION; HUMAN ENDOMETRIUM; METABOLIC-ACTIVATION; IN-VITRO; IDENTIFICATION; LIVER; TRIALS; WOMEN; QUANTIFICATION; GENOTOXICITY AB Background: Although the nonsteroidal antiestrogen tamoxifen is used as an adjuvant chemotherapeutic agent to treat hormone-dependent breast cancer and as a chemopreventive agent in women with elevated risk of breast cancer, it has also been reported to increase the risk of endometrial cancer. Reports of low levels of tamoxifen-DNA adducts in human endometrial tissue have suggested that tamoxifen induces endometrial cancer by a genotoxic mechanism. However, these findings have been controversial. We used electrospray ionization-tandem mass spectrometry (ES-MS/MS) and (32)p- postlabeling analyses to investigate the presence of tamoxifen-DNA adducts in human endometrial tissue. Methods: Endometrial DNA from eight tamoxifen-treated women and eight untreated women was hydrolyzed to nucleosides and assayed for (E)-alpha-(deoxyguanosin-N-2-yl)-tamoxifen (dG-Tam) and (E)-alpha-(deoxyguanosin-N-2-yl)-N-desmethyltamoxifen (dG-desMeTam), the two major tamoxifen-DNA adducts that have been reported to be present in humans and/or experimental animals treated with tamoxifen, using on-line sample preparation coupled with high-performance liquid chromatography (HPLC) and ES-MS/MS. The same DNA samples were assayed for the presence of dG-Tam and dGdesMeTam by P-32-postlabeling methodology, using two different DNA digestion and labeling protocols, followed by both thin-layer chromatography and HPLC. Results: We did not detect either tamoxifen-DNA adduct by HPLC-ES-MS/MS analyses (limits of detection for dG-Tam and dGdesMeTam were two adducts per 10(9) nucleotides and two adducts per 10(8) nucleotides, respectively) or by P-32- postlabeling analyses (limit of detection for both adducts was one adduct per 109 nucleotides) in any of the endometrial DNA samples. Conclusion: The initiation of endometrial cancer by tamoxifen is probably not due to a genotoxic mechanism involving the formation of dG-Tam or dG-desMeTam. C1 Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. Vet Affairs Med Ctr, Minneapolis, MN USA. Canc Res Inst, Surrey, England. Univ London Imperial Coll Sci Technol & Med, Fac Med, London, England. Inst Super Tecn, Ctr Quim Estrutural, Lisbon, Portugal. RP Beland, FA (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, HFT-110,3900 NCTR Rd, Jefferson, AR 72079 USA. EM fbeland@nctr.fda.gov RI Marques, M. Matilde/E-2535-2012; OI Marques, M. Matilde/0000-0002-7526-4962; Phillips, David/0000-0001-8509-3485 NR 36 TC 35 Z9 36 U1 0 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JUL 21 PY 2004 VL 96 IS 14 BP 1099 EP 1104 DI 10.1093/jnci/djh195 PG 6 WC Oncology SC Oncology GA 839RM UT WOS:000222802600014 PM 15265972 ER PT J AU Bai, R Covell, DG Taylor, GF Kepler, JA Copeland, TD Nguyen, NY Pettit, GR Hamel, E AF Bai, R Covell, DG Taylor, GF Kepler, JA Copeland, TD Nguyen, NY Pettit, GR Hamel, E TI Direct photoaffinity labeling by dolastatin 10 of the amino-terminal peptide of beta-tubulin containing cysteine 12 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BINDING-SITE; ANTINEOPLASTIC AGENTS; VINCA DOMAIN; EXCHANGEABLE SITE; ACID-SEQUENCE; PORCINE BRAIN; CROSS-LINKING; ALPHA-TUBULIN; MICROTUBULE; PROTEIN AB Tubulin with bound [5-H-3] dolastatin 10 was exposed to ultraviolet light, and 8-10% of the bound drug crosslinked to the protein, most of it specifically. The primary cross-link was to the peptide spanning amino acid residues 2-31 of beta-tubulin, but the specific amino acid could not be identified. Indirect studies indicated that cross-link formation occurred between cysteine 12 and the thiazole moiety of dolastatin 10. An equipotent analog of dolastatin 10, lacking the thiazole ring, did not form an ultraviolet light-induced cross-link to beta-tubulin. Preillumination of tubulin with ultraviolet light, known to induce cross-link formation between cysteine 12 and exchangeable site nucleotide, inhibited the binding of [5-H-3] dolastatin 10 and cross-link formation more potently than it inhibited the binding of colchicine or vinblastine to tubulin. Conversely, binding of dolastatin 10 to tubulin inhibited formation of the cross-link between cysteine 12 and the exchangeable site nucleotide. Dithiothreitol inhibited formation of the beta-tubulin/dolastatin 10 cross-link but not the beta-tubulin/exchangeable site nucleotide cross-link. Modeling studies revealed a highly favored binding site for dolastatin 10 at the + end of beta-tubulin in proximity to the exchangeable site GDP. Computational docking of an energy-minimized dolastatin 10 conformation at this site placed the thiazole ring of dolastatin 10 8-9 Angstrom from the sulfur atom of cysteine 12. Dolastatin 15 and cryptophycin 1 could also be docked into positions that overlapped more extensively with the docked dolastatin 10 than with each other. This result was consistent with the observed binding properties of these peptides. C1 NCI, Screening Technol Branch, Dev Therapeut Program, Div Canc Treatment & Diag,NIH, Frederick, MD 21702 USA. Res Triangle Inst, Res Triangle Pk, NC 27709 USA. NCI, Lab Prot Dynam & Signaling, Ctr Canc Res, NIH, Frederick, MD 21702 USA. US FDA, Facil Biotechnol Resources, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. Arizona State Univ, Dept Chem & Biochem, Tempe, AZ 85287 USA. Arizona State Univ, Canc Res Inst, Tempe, AZ 85287 USA. RP Hamel, E (reprint author), NCI, Screening Technol Branch, Dev Therapeut Program, Div Canc Treatment & Diag,NIH, Bldg 469,Rm 104,POB B, Frederick, MD 21702 USA. EM hamele@mail.nih.gov NR 54 TC 20 Z9 21 U1 0 U2 0 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 16 PY 2004 VL 279 IS 29 BP 30731 EP 30740 DI 10.1074/jbc.M402110200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 836CD UT WOS:000222531900104 PM 15123603 ER PT J AU Han, XL Yang, JY Cheng, H Ye, HP Gross, RW AF Han, XL Yang, JY Cheng, H Ye, HP Gross, RW TI Toward fingerprinting cellular lipidomes directly from biological samples by two-dimensional electrospray ionization mass spectrometry SO ANALYTICAL BIOCHEMISTRY LA English DT Article DE electrospray ionization mass spectrometry; lipidome; lipidomics; two-dimensional mass spectrometry ID RAT-LIVER PHOSPHOLIPIDS; QUANTITATIVE-ANALYSIS; INSULIN-RESISTANCE; STRUCTURAL DETERMINATION; CARDIOVASCULAR-DISEASE; HEPATIC STEATOSIS; LITHIATED ADDUCTS; MEMBRANE-LIPIDS; EXTRACTS; PHOSPHATIDYLINOSITOL AB Cellular lipids are composed of linear combinations of aliphatic chains covalently attached to backbones and/or head groups that collectively represent the cellular lipidome. Herein we present a novel two-dimensional electrospray ionization mass spectrometric approach to fingerprint most of the major and many of the minor lipid classes in the hepatic cellular lipidome, which collectively represent > 80% of the total lipid mass, directly from their chloroform extracts. Through lipid class-selective intrasource ionization and subsequent analysis of two-dimensional cross-peak intensities, the chemical identity and mass composition of individual molecular species of most mouse hepatic lipid classes were determined from its chloroform extract. This new integrated platform provides a robust foundation for the automated analysis of multidimensional mass spectra to advance the level of analytical scripting in lipidomics to a new plateau. (C) 2004 Elsevier Inc. All rights reserved. C1 Washington Univ, Sch Med, Div Bioorgan Chem & Mol Pharmacol, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Mol Biol & Pharmacol, St Louis, MO 63110 USA. Washington Univ, Dept Chem, St Louis, MO 63130 USA. US FDA, St Louis, MO 63101 USA. RP Han, XL (reprint author), Washington Univ, Sch Med, Div Bioorgan Chem & Mol Pharmacol, St Louis, MO 63110 USA. EM xianlin@wustl.edu FU NHLBI NIH HHS [R01 HL 41250, P01 HL 57278] NR 36 TC 135 Z9 142 U1 1 U2 15 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 JUL 15 PY 2004 VL 330 IS 2 BP 317 EP 331 DI 10.1016/j.ab.2004.04.004 PG 15 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 834QE UT WOS:000222424800018 PM 15203339 ER PT J AU Wolmark, N Wieand, S Lembersky, B Colangelo, L Smith, R Pazdur, R AF Wolmark, N Wieand, S Lembersky, B Colangelo, L Smith, R Pazdur, R TI A phase III trial comparing oral UFT to FULV in stage II and III carcinoma of the colon: Results of NSABP Protocol C-06. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 NSABP, Pittsburgh, PA USA. FDA, Rockville, MD USA. NR 0 TC 7 Z9 8 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 15 PY 2004 VL 22 IS 14 SU S MA 3508 BP 247S EP 247S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512400976 ER PT J AU Talarico, L Pazdur, R AF Talarico, L Pazdur, R TI Expanded access program (EAP) to investigational drugs. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 US FDA, Rockville, MD 20857 USA. NR 0 TC 1 Z9 1 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 15 PY 2004 VL 22 IS 14 SU S MA 6001 BP 519S EP 519S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512402057 PM 28015072 ER PT J AU Hirschfeld, S AF Hirschfeld, S TI Is participation in oncology clinical trials using gene therapy products safe? SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 US FDA, Rockville, MD 20857 USA. RI Hirschfeld, Steven/E-2987-2016 OI Hirschfeld, Steven/0000-0003-0627-7249 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 15 PY 2004 VL 22 IS 14 SU S MA 6076 BP 538S EP 538S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512402131 PM 28014995 ER PT J AU Bowers, DC McNeil, DE Liu, Y Yasui, Y Stoval, M Gurney, JG Hudson, MM Robison, LL Oeffinger, KC AF Bowers, DC McNeil, DE Liu, Y Yasui, Y Stoval, M Gurney, JG Hudson, MM Robison, LL Oeffinger, KC TI Stroke following therapy for Hodgkin's disease (HO): A report from the childhood cancer survivor study (CCSS). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol C1 Childhood Canc Survivors Study, Dallas, TX USA. Univ Texas, SW Med Ctr, Dallas, TX 75230 USA. US FDA, Rockville, MD 20857 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Minnesota, Minneapolis, MN USA. St Jude Childrens Res Hosp, Memphis, TN 38105 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 15 PY 2004 VL 22 IS 14 SU S MA 8523 BP 804S EP 804S PG 1 WC Oncology SC Oncology GA 849BL UT WOS:000223512403192 PM 28013758 ER PT J AU Mittelstaedt, RA Mei, N Webb, PJ Shaddock, JG Dobrovolsky, VN McGarrity, LJ Morris, SM Chen, T Beland, FA Greenlees, KJ Heflich, RH AF Mittelstaedt, RA Mei, N Webb, PJ Shaddock, JG Dobrovolsky, VN McGarrity, LJ Morris, SM Chen, T Beland, FA Greenlees, KJ Heflich, RH TI Genotoxicity of malachite green and leucomalachite green in female Big Blue B6C3F(1) mice SO MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS LA English DT Article DE mouse micronucleus assay; Hprt mutation assay; cII mutation assay; malachite green; leucomalachite green ID RATS; TOXICITY; CARCINOGENICITY; MUTAGENICITY; METABOLITES; MUTATION; GENE AB Malachite green, a triphenylmethane dye used in aquaculture as an antifungal agent, is rapidly reduced in vivo to leucomalachite green. Previous studies in which female B6C3F(1) mice were fed malachite green produced relatively high levels of liver DNA adducts after 28 days, but no significant induction of liver tumors was detected in a 2-year feeding study. Comparable experiments conducted with leucomalachite green resulted in relatively low levels of liver DNA adducts but a dose-responsive induction of liver tumors. In the present study, we fed transgenic female Big Blue B6C3F(1) mice with 450 ppm malachite green and 204 and 408 ppm leucomalachite green (the high doses used in the tumor bioassays) and evaluated genotoxicity after 4 and 16 weeks of treatment. Neither malachite green nor leucomalachite green increased the peripheral blood micronucleus frequency or Hprt lymphocyte mutant frequency at either time point; however, the 16-week treatment with 408 ppm leucomalachite green did increase the liver cII mutant frequency. Similar increases in liver cII mutant frequency were not seen in the mice treated for 16 weeks with malachite green or in female Big Blue rats treated with a comparable dose of leucomalachite green for 16 weeks in a previous study [Mutat. Res. 547 (2004) 5]. These results indicate that leucomalachite green is an in vivo mutagen in transgenic female mouse liver and that the mutagenicities of malachite green and leucomalachite green correlate with their tumorigenicities in mice and rats. The lack of increased micronucleus frequencies and lymphocyte Hprt mutants in female mice treated with leucomalachite green suggests that its genotoxicity is targeted to the tissue at risk for tumor induction. (C) 2004 Elsevier B.V. All rights reserved. C1 US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. US FDA, Ctr Vet Med, Rockville, MD 20855 USA. RP Mittelstaedt, RA (reprint author), US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM rmittelstaedt@nctr.fda.gov RI mei, nan/E-8915-2011 OI mei, nan/0000-0002-3501-9014 NR 19 TC 41 Z9 46 U1 1 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1383-5718 J9 MUTAT RES-GEN TOX EN JI Mutat. Res. Genet. Toxicol. Environ. Mutagen. PD JUL 11 PY 2004 VL 561 IS 1-2 BP 127 EP 138 DI 10.1016/j.mrgentox.2004.04.003 PG 12 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 840KS UT WOS:000222858100013 PM 15238237 ER PT J AU Hyde, JS Yin, JJ Subczynski, WK Camenisch, TG Ratke, JJ Froncisz, W AF Hyde, JS Yin, JJ Subczynski, WK Camenisch, TG Ratke, JJ Froncisz, W TI Spin-label EPR T-1 values using saturation recovery from 2 to 35 GHz SO JOURNAL OF PHYSICAL CHEMISTRY B LA English DT Article ID LOOP-GAP RESONATOR; LIPID-BILAYERS; CHOLESTEROL; MEMBRANES; PHASE; BACTERIORHODOPSIN; SPECTROSCOPY; SPECTROMETER; OSCILLATOR; NITROXIDES AB EPR saturation-recovery (SR) measurements of the electron spin-lattice relaxation time, T-1, of nitroxide-radical spin probes have been made from 2 to 35 GHz. T-1 values of small water-soluble spin probes increase linearly with microwave frequency throughout the full range of available frequencies. T-1 values of four commonly used hydrophobic probes in lipid bilayers also increase with frequency, but the dependence is weaker and complex. Contributions of dissolved molecular oxygen to relaxation rates were independent of microwave frequency. T-1 values of N-15-containing labels are always somewhat longer than for N-14 labels. Details of the Q-band SR spectrometer, which is based on frequency translation technology, are provided. A new way to suppress free induction decay signals in SR experiments has been found: pump and observing frequencies time-locked and separated by about 1 kHz in frequency. A novel three-loop-two-gap resonator with a sample volume of 30 nl was used for the Q-band measurements. It is concluded that Q-band is a favorable frequency for SR spin-label oximetry studies. C1 Med Coll Wisconsin, Dept Biophys, Milwaukee, WI 53226 USA. US FDA, Instrumentat & Biophys Branch, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. Jagiellonian Univ, Fac Biotechnol, Dept Biophys, Krakow, Poland. RP Hyde, JS (reprint author), Med Coll Wisconsin, Dept Biophys, Milwaukee, WI 53226 USA. EM jshyde@mcw.edu RI Yin, Jun Jie /E-5619-2014 NR 29 TC 34 Z9 35 U1 0 U2 13 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1520-6106 J9 J PHYS CHEM B JI J. Phys. Chem. B PD JUL 8 PY 2004 VL 108 IS 27 BP 9524 EP 9529 DI 10.1021/jp036329z PG 6 WC Chemistry, Physical SC Chemistry GA 835LB UT WOS:000222483500018 ER PT J AU Logvinoff, C Major, ME Oldach, D Heyward, S Talal, A Balfe, P Feinstone, SM Alter, H Rice, CM McKeating, JA AF Logvinoff, C Major, ME Oldach, D Heyward, S Talal, A Balfe, P Feinstone, SM Alter, H Rice, CM McKeating, JA TI Neutralizing antibody response during acute and chronic hepatitis C virus infection SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HYPERVARIABLE REGION 1; FOLLOW-UP; HYPOGAMMAGLOBULINEMIC PATIENTS; VIRAL PERSISTENCE; TYPE-1 INFECTION; IMMUNE-RESPONSE; CHIMPANZEES; PROTEIN; DETERMINANTS; VACCINATION AB Little is known about the role of Abs in determining the outcome of hepatitis C virus (HCV) infection. By using infectious retroviral pseudotypes bearing HCV glycoproteins, we measured neutralizing Ab (nAb) responses during acute and chronic HCV infection. in seven acutely infected health care workers, only two developed a nAb response that failed to associate with viral clearance. In contrast, the majority of chronically infected patients had nAbs. To determine the kinetics of strain-specific and crossreactive nAb emergence, we studied patient H, the source of the prototype genotype 1a H77 HCV strain. An early weak nAb response, specific for the autologous virus, was detected at seroconversion. However, neutralization of heterologous viruses was detected only between 33 and 111 weeks of infection. We also examined the development of nAbs in 10 chimpanzees infected with H77 clonal virus. No nAb responses were detected in three animals that cleared virus, whereas strain-specific nAbs were detected in six of the seven chronically infected animals after approximate to50 weeks of infection. The delayed appearance of high titer crossreactive nAbs in chronically infected patients suggests that selective mechanism(s) may operate to prevent the appearance of these Abs during acute infection. The long-term persistence of these nAbs in chronically infected patients may regulate viral replication. C1 Rockefeller Univ, Ctr Study Hepatitis C, New York, NY 10021 USA. US FDA, Lab Hepatitis Viruses, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. Univ Maryland, Sch Med, Inst Human Virol, Baltimore, MD 21201 USA. Cornell Univ, Weill Med Coll, Dept Med, New York, NY 10021 USA. Cornell Univ, Weill Med Coll, Ctr Study Hepatitis C, New York, NY 10021 USA. Columbia Univ, Div Infect Dis, New York, NY 10032 USA. NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. RP McKeating, JA (reprint author), Rockefeller Univ, Ctr Study Hepatitis C, 1230 York Ave, New York, NY 10021 USA. EM mckeatj@rockefeller.edu OI Oldach, David/0000-0002-8811-2562; McKeating, Jane/0000-0002-7229-5886 FU NCI NIH HHS [R01 CA057973, CA57973, CA85883, R01 CA085883]; NIAID NIH HHS [AI60561, N01AI40034, R01 AI060561] NR 32 TC 243 Z9 260 U1 0 U2 10 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUL 6 PY 2004 VL 101 IS 27 BP 10149 EP 10154 DI 10.1073/pnas.0403519101 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 836CZ UT WOS:000222534200038 PM 15220475 ER PT J AU Fang, GC Chang, CN Wu, YS Fu, PPC Yang, IL Chen, MH AF Fang, GC Chang, CN Wu, YS Fu, PPC Yang, IL Chen, MH TI Characterization, identification of ambient air and road dust polycyclic aromatic hydrocarbons in central Taiwan, Taichung SO SCIENCE OF THE TOTAL ENVIRONMENT LA English DT Article DE ambient air; road dust; gas-phase; particle-phase; source attribute; polycyclic aromatic hydrocarbons; industrial; suburban ID VOLATILE ORGANIC-COMPOUNDS; SUSPENDED PARTICULATE; CARBONYL-COMPOUNDS; METALLIC ELEMENTS; PAH EMISSION; ATMOSPHERE; PARTICLES; PROFILES; MATTER; INDOOR AB The concentrations of ambient air polycyclic aromatic hydrocarbons (PAHs) were measured simultaneously in an industrial area (Taichung Industrial Park, TIP) and suburban area (Tunghai University, THU) in central Taiwan, Taichung. A total of samples were collected simultaneously at the two sites between August 2002 and March 2003. Particle-bound PAHs (p-PAHs) were collected on quartz filters and gas-phase PAHs (g-PAHs) on glass cartridges using polyurethane foam sampler, respectively. Both types of samples were extracted with dichloromethane/n-hexane mixture (50/50, v/v) for 24 h, then the extracts were subjected to gas chromatography/mass spectrometric analysis. Moreover, the roadside dust particle PAHs composition were also collected and analyzed at TIP, THU and traffic road sampling sites. The five main road lines in Taichung City were selected as traffic road sampling sites. Correlation studies between PAHs concentrations and meteorological parameters were revealed that temperature has greater effects (P>0.6) than other meteorological parameters such as wind speed, relative humidity and atmospheric pressure on PAHs and p-PAHs. PAHs sources were resolved by using principal component analysis and diagnostic ratios. The major sources of PAHs were combustion, traffic vehicle exhaust (diesel and gasoline engine), incinerator and industrial stationary sources at both sampling sites in central Taiwan. (C) 2003 Elsevier B.V. All rights reserved. C1 Hungkuang Univ, Air Tox & Environm Anal Lab, Taichung 433, Taiwan. Tunghai Univ, Dept Environm Sci, Taichung 407, Taiwan. Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Fang, GC (reprint author), Hungkuang Univ, Air Tox & Environm Anal Lab, Sha Lu, Taichung 433, Taiwan. EM gcfang@sunrise.hk.edu.tw NR 27 TC 94 Z9 110 U1 4 U2 29 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0048-9697 J9 SCI TOTAL ENVIRON JI Sci. Total Environ. PD JUL 5 PY 2004 VL 327 IS 1-3 BP 135 EP 146 DI 10.1016/j.scitotenv.2003.10.016 PG 12 WC Environmental Sciences SC Environmental Sciences & Ecology GA 830WP UT WOS:000222155200011 PM 15172577 ER PT J AU Simpson, D Estanislao, L Evans, S McArthur, J Marcus, K Truffa, M Lucey, B Naismith, R Lonergan, JT Clifford, D AF Simpson, D Estanislao, L Evans, S McArthur, J Marcus, K Truffa, M Lucey, B Naismith, R Lonergan, JT Clifford, D CA HIV Neuromuscular Syndrome Study G TI HIV-associated neuromuscular weakness syndrome SO AIDS LA English DT Article DE peripheral neuropathy; myopathy; lactic acidosis; ARV toxicity; HIV ID MITOCHONDRIAL-DNA DEPLETION; CRITICAL ILLNESS POLYNEUROPATHY; VIRUS-ASSOCIATED MYOPATHY; LACTIC-ACIDOSIS; PERIPHERAL NEUROPATHY; ANTIRETROVIRAL THERAPY; NUCLEOSIDE ANALOG; INFECTED PATIENTS; CYTOKINE-EXPRESSION; HEPATIC STEATOSIS AB Objective: To investigate progressive, severe neuromuscular weakness associated with lactic acidosis in some HIV-infected patients after exposure to nucleoside reverse transcriptase inhibitors (NRTI). Methods: HIV-associated neuromuscular weakness syndrome (HANWS) was retrospectively identified and classified based on the level of diagnostic certainty: possible (progressive weakness owing to neuromuscular disease), probable (progressive neuromuscular weakness with documented exclusion of confounding causes), or definite (progressive weakness and electrophysiological or pathological evidence of neuromuscular pathology). Results: Of 69 patients identified with HANWS, 27 had definite HANWS, 19 probable, and 23 possible. In 44 patients with documented follow-up, 16 required intubation and nine died. There was a marginal association between death and hyperlactatemia (P = 0.061). At onset of neurological symptoms, 68 were receiving antiretroviral therapy, including stavudine for 61 (89.7%). Serum lactate level was elevated (> 2.2 mmol/l) in 30/37 (81%), with a trend towards an association between hyperlactatemia and stavudine usage (P = 0.087). In 25, neurological symptoms occurred after antiretroviral therapy discontinuation (median, 14 days). Electrophysiological studies (n = 24) indicated sensorimotor neuropathy in 20 patients and myopathy in three. Nerve biopsy (n = 9) revealed axonal degeneration and inflammation in three, mixed axonal and demyelinating lesions in three, and primary axonal neuropathy in three. Of 15 muscle biopsies, three revealed inflammation and four mitochondrial abnormalities. Conclusions: A severe neuromuscular weakness syndrome may occur in HIV-infected individuals. The association with hyperlactatemia and NRTI exposure supports mitochondrial toxicity as a pathogenesis. In some, the onset of neurological symptoms lagged significantly after discontinuation of antiretroviral therapy, suggesting that different etiological mechanisms may underlie these cases. (C) 2004 Lippincott Williams Wilkins. C1 Mt Sinai Med Ctr, New York, NY 10029 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Johns Hopkins Univ, Baltimore, MD USA. Food & Drug Adm, Rockville, MD USA. Washington Univ, Sch Med, St Louis, MO USA. Univ Calif San Diego, Med Ctr, San Diego, CA 92103 USA. RP Simpson, D (reprint author), Mt Sinai Med Ctr, 1 Gustave L Levy Pl,Box 1052, New York, NY 10029 USA. RI Andrade, Hugo/M-6631-2013; OI Andrade, Hugo/0000-0001-6781-6125; Lucey, Brendan/0000-0001-5400-825X NR 40 TC 25 Z9 27 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD JUL 2 PY 2004 VL 18 IS 10 BP 1403 EP 1412 DI 10.1097/01.aids.0000131309.70451.fe PG 10 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 837NF UT WOS:000222641500006 ER PT J AU McNeil, MJ AF McNeil, MJ TI FDA video news show SO AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY LA English DT Letter C1 US FDA, Off Pharmacoepidemiol & Stat Sci, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP McNeil, MJ (reprint author), US FDA, Off Pharmacoepidemiol & Stat Sci, Ctr Drug Evaluat & Res, 5600 Fishers Lane,HFD-030,Room 15B-03, Rockville, MD 20857 USA. EM mcneilm@cder.fda.gov NR 0 TC 0 Z9 0 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 JUL 1 PY 2004 VL 61 IS 13 BP 1340 EP 1340 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 835EK UT WOS:000222463100010 ER PT J AU Brown, P AF Brown, P TI Mad-cow disease in cattle and human beings SO AMERICAN SCIENTIST LA English DT Article ID BOVINE SPONGIFORM ENCEPHALOPATHY; CREUTZFELDT-JAKOB-DISEASE; VARIANT C1 US FDA, TSE Advisory Comm, Rockville, MD 20857 USA. RP Brown, P (reprint author), 7815 Exeter Rd, Bethesda, MD 20814 USA. EM paulwbrown@comcast.net NR 9 TC 5 Z9 5 U1 0 U2 3 PU SIGMA XI-SCI RES SOC PI RES TRIANGLE PK PA PO BOX 13975, RES TRIANGLE PK, NC 27709 USA SN 0003-0996 J9 AM SCI JI Am. Scientist PD JUL-AUG PY 2004 VL 92 IS 4 BP 334 EP 341 DI 10.1511/2004.48.936 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 830AK UT WOS:000222093800012 ER PT J AU Stewart, SFC Lyman, DJ AF Stewart, SFC Lyman, DJ TI Effects of an artery/vascular graft compliance mismatch on protein transport: A numerical study SO ANNALS OF BIOMEDICAL ENGINEERING LA English DT Article DE modeling and simulation in bioengineering/finite-element modeling; artificial internal organs and body structures/; artificial graft; microvascular and macrovascular processes/; arterial compliance; transport processes/convection-diffusion-permeation-reaction processes ID TO-END ANASTOMOSIS; GROWTH-FACTOR PRODUCTION; SHEAR RATE DISTRIBUTION; INTIMAL HYPERPLASIA; ARTERIAL GRAFTS; VASCULAR GRAFTS; DACRON GRAFTS; POLYTETRAFLUOROETHYLENE GRAFT; CAROTID BIFURCATION; ELASTIC PROPERTIES AB Small-diameter vascular graft failure by intimal hyperplasia and thrombosis may result from flow disturbances and disruption of chemical transport in the fluid at the distal anastomosis, because of compliance mismatch between the graft and host artery. In previous studies, lower-than-normal wall shear stress (WSS), particle trapping, and high particle residence times were observed at the distal anastomosis due to a pulsatile tubular expansion effect caused by nonuniform radial deformations. This study was undertaken to examine effects of compliance and radius mismatch on the distribution of a model protein released at the graft-fluid interface. Finite element simulations of end-to-end vascular grafting were performed under pulsatile flow, using fluid-structure coupling to give physiologic wall displacements. Results showed that protein is convected smoothly downstream in a uniform compliant tube. A compliance mismatch disturbed the transport, causing positive and negative gradients in the concentration profile at the distal anastomosis. This was seen when the graft and artery radii were matched at zero pressure and at mean arterial pressure; low WSSs were only observed in the former case. Thus the distal intimal hypertrophy seen in noncompliant grafts may be caused partly by decreased WSS, and partly by concentration gradients of dissolved chemicals affecting chemotaxis of cells. C1 US FDA, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. Univ Utah, Dept Mat Sci & Engn, Salt Lake City, UT 84112 USA. Univ Utah, Dept Bioengn, Salt Lake City, UT 84112 USA. RP Stewart, SFC (reprint author), US FDA, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, 9200 Corp Blvd,HFZ-132, Rockville, MD 20850 USA. EM sxs@cdrh.fda.gov NR 64 TC 21 Z9 21 U1 2 U2 10 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0090-6964 J9 ANN BIOMED ENG JI Ann. Biomed. Eng. PD JUL PY 2004 VL 32 IS 7 BP 991 EP 1006 DI 10.1023/B:ABME.0000032462.56207.65 PG 16 WC Engineering, Biomedical SC Engineering GA 840YV UT WOS:000222897400009 PM 15298437 ER PT J AU Levy, DD Sharma, B Cebula, TA AF Levy, DD Sharma, B Cebula, TA TI Single-nucleotide polymorphism mutation spectra and resistance to quinolones in Salmonella enterica serovar Enteritidis with a mutator phenotype SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID ESCHERICHIA-COLI STRAINS; FLUOROQUINOLONE RESISTANCE; CYSTIC-FIBROSIS; GYRA MUTATIONS; TYPHIMURIUM; ANIMALS; GENE; PATHOGENS; ALLELES; HUMANS AB Resistance to quinolone antibiotics has been associated with single-nucleotide polymorphisms (SNPs) in the quinolone resistance-determining region (QRDR) of gyrA. Mutations in the gyrA gene were compared by using mutant populations derived from wild-type Salmonella enterica serovar Enteritidis and its isogenic mutS::Tn10 mutator counterpart. Spontaneous mutants arising during nonselective growth were isolated by selection with either nalidixic acid, enrofloxacin, or ciprofloxacin. QRDR SNPs were identified in approximately 70% (512 of 695) of the isolates via colony hybridization with radiolabeled oligonucleotide probes. Notably, transition base substitution SNPs in the QRDR were dramatically increased in mutants derived from the mutS strain. Some, but not all, antibiotic-resistant mutants lacking QRDR SNPs were resistant to tetracycline and chloramphenicol, consistent with alterations in nonspecific efflux pumps or other membrane transport mechanisms. Changing the selection conditions shifted the mutation spectrum. Selection with ciprofloxacin was least likely to yield a mutant harboring either a QRDR SNP or chloramphenicol resistance. Selection with enrofloxacin was more likely to yield mutants containing Ser83-->Phe mutations, whereas selection with ciprofloxacin or nalidixic acid favored recovery of Asp87-->Gly mutants. Fluoroquinolone-resistant Salmonella strains isolated from veterinary or clinical settings frequently display a mutational spectrum with a preponderance of transition SNPs in the QRDR, the pattern found in vitro among mutS mutator mutants reported here. Both the preponderance of transition mutations and the varied mutation spectra reported for veterinary and clinical isolates suggest that bacterial mutators defective in methyl-directed mismatch repair may play a role in the emergence of quinolone and fluoroquinolone resistance in feral settings. C1 US FDA, Ctr Food Safety & Appl Nutr, Div Mol Biol, Laurel, MD 20708 USA. RP Cebula, TA (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Div Mol Biol, HFS-025,8301 Muirkirk Rd, Laurel, MD 20708 USA. EM thomas.cebula@cfsan.fda.gov NR 44 TC 35 Z9 40 U1 0 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 JUL PY 2004 VL 48 IS 7 BP 2355 EP 2363 DI 10.1128/AAC.48.7.2355-2363.2004 PG 9 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 834RC UT WOS:000222427200003 PM 15215081 ER PT J AU Yildirim, S Lin, W Hitchins, AD Jaykus, LA Altermann, E Klaenhammer, TR Kathariou, S AF Yildirim, S Lin, W Hitchins, AD Jaykus, LA Altermann, E Klaenhammer, TR Kathariou, S TI Epidemic clone I-specific genetic markers in strains of Listeria monocytogenes serotype 4b from foods SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID MULTILOCUS ENZYME ELECTROPHORESIS; RESTRICTION-MODIFICATION SYSTEM; TEICHOIC-ACID GLYCOSYLATION; SAU3AI RESTRICTION; ESCHERICHIA-COLI; PATHOGENICITY; EXPRESSION; 4B; VIRULENCE; DIFFERENTIATE AB Listeria monocytogenes contamination of ready-to-eat foods has been implicated in numerous outbreaks of food-borne listeriosis. However, the health hazards posed by L. monocytogenes detected in foods may vary, and speculations exist that strains actually implicated in illness may constitute only a fraction of those that contaminate foods. In this study, examination of 34 serogroup 4 (putative or confirmed serotype 4b) isolates of L. monocytogenes obtained from various foods and food-processing environments, without known implication in illness, revealed that many of these strains had methylation of cytosines at GATC sites in the genome, rendering their DNA resistant to digestion by the restriction endonuclease Sau3AI. These strains also harbored a gene cassette with putative restriction-modification system genes as well as other, genomically unlinked genetic markers characteristic of the major epidemic-associated lineage of L. monocytogenes (epidemic clone 1), implicated in numerous outbreaks in Europe and North America. This may reflect a relatively high fitness of strains with these genetic markers in foods and food-related environments relative to other serotype 4b strains and may partially account for the repeated involvement of such strains in human food-borne listeriosis. C1 N Carolina State Univ, Dept Food Sci, Raleigh, NC 27695 USA. US FDA, Washington, DC 20204 USA. US FDA, Irvine, CA USA. RP Kathariou, S (reprint author), N Carolina State Univ, Dept Food Sci, Campus Box 7624, Raleigh, NC 27695 USA. EM skathar@unity.ncsu.edu OI Altermann, Eric/0000-0003-1376-1549 NR 44 TC 43 Z9 47 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0099-2240 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD JUL PY 2004 VL 70 IS 7 BP 4158 EP 4164 DI 10.1128/AEM.70.7.4158-4164.2004 PG 7 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 839BP UT WOS:000222758600049 PM 15240296 ER PT J AU Johnson, J Jinneman, K Stelma, G Smith, BG Lye, D Messer, J Ulaszek, J Evsen, L Gendel, S Bennett, RW Swaminathan, B Pruckler, J Steigerwalt, A Kathariou, S Yidirim, S Volokhov, D Rasooly, A Chizhikov, V Wiedmann, M Fortes, E Duvall, RE Hitchins, AD AF Johnson, J Jinneman, K Stelma, G Smith, BG Lye, D Messer, J Ulaszek, J Evsen, L Gendel, S Bennett, RW Swaminathan, B Pruckler, J Steigerwalt, A Kathariou, S Yidirim, S Volokhov, D Rasooly, A Chizhikov, V Wiedmann, M Fortes, E Duvall, RE Hitchins, AD TI Natural atypical Listeria innocua strains with Listeria monocytogenes pathogenicity island 1 genes SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID BIOCHEMICAL-CHARACTERIZATION; RIBOSOMAL-RNA; SEROTYPE 4B; EVOLUTION; IDENTIFICATION; OPERON; PRFA; P60; 16S AB Identification of bona fide Listeria isolates into the six species of the genus normally requires only a few tests. Aberrant isolates do occur, but even then only one or two extra confirmatory tests are generally needed for identification to species level. We have discovered a hemolytic-positive, rhamnose and xylose fermentation-negative Listeria strain with surprising recalcitrance to identification to the species level due to contradictory results in standard confirmatory tests. The issue had to be resolved by using total DNA-DNA hybridization testing and then confirmed by further specific PCR-based tests including a Listeria microarray assay. The results show that this isolate is indeed a novel one. Its discovery provides the first fully documented instance of a hemolytic Listeria innocua strain. This species, by definition, is typically nonhemolytic. The L. innocua isolate contains all the members of the PrfA-regulated virulence gene cluster (Listeria pathogenicity island 1) of L. monocytogenes. It is avirulent in the mouse pathogenicity test. Avirulence is likely at least partly due to the absence of the L. monocytogenes-specific allele of iap, as well as the absence of inl4, inlB, inlC, and daaA. At least two of the virulence cluster genes, hly and plcA, which encode the L. monocytogenes hemolysin (listeriolysin 0) and inositol-specific phospholipase C, respectively, are phenotypically expressed in this L. innocua strain. The detection by PCR assays of specific L. innocua genes (lin0198, lin0372, lin0419, lin0558, lin1068, lin1073, lin1074, lin2454, and lin2693) and noncoding intergenic regions (lin0454-lin0455 and nadA4-lin2134) in the strain is consistent with its L. innocua DNA-DNA hybridization identity. Additional distinctly different hemolytic L. innocua strains were also studied. C1 US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. US FDA, Bothell, WA 98021 USA. US EPA, Cincinnati, OH 45268 USA. Natl Ctr Food Safety & Technol, Summit Argo, IL 60501 USA. Univ Maryland, College Pk, MD 20742 USA. N Carolina State Univ, Raleigh, NC 27695 USA. US FDA, Ctr Biol, Bethesda, MD 20895 USA. Cornell Univ, Ithaca, NY 14853 USA. RP Hitchins, AD (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM Anthony.Hitchins@cfsan.fda.gov RI Wiedmann, Martin/A-9683-2008 OI Wiedmann, Martin/0000-0002-4168-5662 NR 39 TC 62 Z9 70 U1 0 U2 11 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0099-2240 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD JUL PY 2004 VL 70 IS 7 BP 4256 EP 4266 DI 10.1128/AEM.70.7.4256-4266.2004 PG 11 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 839BP UT WOS:000222758600062 PM 15240309 ER PT J AU Rider, LG Giannini, EH Brunner, HI Ruperto, N James-Newton, L Reed, AM Lachenbruch, PA Miller, FW AF Rider, LG Giannini, EH Brunner, HI Ruperto, N James-Newton, L Reed, AM Lachenbruch, PA Miller, FW CA Int Myositis Assessment Clinical S TI International consensus on preliminary definitions of improvement in adult and juvenile myositis SO ARTHRITIS AND RHEUMATISM LA English DT Article ID COLLEGE-OF-RHEUMATOLOGY; IDIOPATHIC INFLAMMATORY MYOPATHIES; PRELIMINARY CORE SET; DISEASE-ACTIVITY; OUTCOME ASSESSMENT; RESPONSE CRITERIA; ARTHRITIS; DERMATOMYOSITIS; POLYMYOSITIS; THERAPY AB Objective. To use a core set of outcome measures to develop preliminary definitions of improvement for adult and juvenile myositis as composite end points for therapeutic trials. Methods. Twenty-nine experts in the assessment of myositis achieved consensus on 102 adult and 102 juvenile paper patient profiles as clinically improved or not improved. Two hundred twenty-seven candidate definitions of improvement were developed using the experts' consensus ratings as a gold standard and their judgment of clinically meaningful change in the core set of measures. Seventeen additional candidate definitions of improvement were developed from classification and regression tree analysis, a data-mining decision tree tool analysis. Six candidate definitions specifying percentage change or raw change in the core set of measures were developed using logistic regression analysis. Adult and pediatric working groups ranked the 13 top-performing candidate definitions for face validity, clinical sensibility, and ease of use, in which the sensitivity and specificity were greater than or equal to75% in adult, pediatric, and combined data sets. Nominal group technique was used to facilitate consensus formation. Results. The definition of improvement (common to the adult and pediatric working groups) that ranked highest was 3 of any 6 of the core set measures improved by greater than or equal to20%, with no more than 2 worse by greater than or equal to25% (which could not include manual muscle testing to assess strength). Five and 4 additional preliminary definitions of improvement for adult and juvenile myositis, respectively, were also developed, with several definitions common to both groups. Participants also agreed to prospectively test 6 logistic regression definitions of improvement in clinical trials. Conclusion. Consensus preliminary definitions of improvement were developed for adult and juvenile myositis, and these incorporate clinically meaningful change in all myositis core set measures in a composite end point. These definitions require prospective validation, but they are now proposed for use as end points in all myositis trials. C1 NIEHS, Environm Autoimmun Grp, NIH, Bethesda, MD 20892 USA. US FDA, Rockville, MD 20857 USA. Mayo Clin, Rochester, MN USA. IRCCS, Genoa, Italy. Univ Cincinnati, Cincinnati, OH USA. RP Rider, LG (reprint author), NIEHS, Environm Autoimmun Grp, NIH, 9 Mem Dr,Room 1W107,MSC 0958, Bethesda, MD 20892 USA. EM RIDER@niehs.nih.gov RI Song, Yeong Wook/J-2765-2012; OI Harris-Love, Michael/0000-0002-1842-3269; Rider, Lisa/0000-0002-6912-2458; Miller, Frederick/0000-0003-2831-9593 FU NIAMS NIH HHS [AR-48349-01, P60-AR-47784] NR 30 TC 100 Z9 101 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 JUL PY 2004 VL 50 IS 7 BP 2281 EP 2290 DI 10.1002/art.20349 PG 10 WC Rheumatology SC Rheumatology GA 839YG UT WOS:000222820300029 PM 15248228 ER PT J AU McDermott, MK Chen, TH Williams, CM Markley, KM Payne, GF AF McDermott, MK Chen, TH Williams, CM Markley, KM Payne, GF TI Mechanical properties of biomimetic tissue adhesive based on the microbial transglutaminase-catalyzed crosslinking of gelatin SO BIOMACROMOLECULES LA English DT Article ID POLY(ETHYLENE GLYCOL) DIACRYLATE; ENHANCES NEURITE EXTENSION; IN-VIVO EVALUATION; FIBRIN SEALANTS; FACTOR-XIII; PHOTOCROSSLINKABLE CHITOSAN; CONTROLLED-RELEASE; HYDROGELS; MATRICES; MODEL AB Fibrin sealants are a type of soft tissue adhesive that employs biochemical reactions from the late stages of the blood coagulation cascade. Intrinsic to these adhesives are a structural protein and a transglutaminase crosslinking enzyme. We are investigating an alternative biomimetic adhesive based on gelatin and a calcium-independent microbial transglutaminase (mTG). Rheological measurements show that mTG catalyzes the conversion of gelatin solutions into hydrogels, and gel times are on the order of minutes depending on the gelatin type and concentration. Tensile static and dynamic loading of the adhesive hydrogels in bulk form demonstrated that the Young's modulus ranged from 15 to 120 kPa, and these bulk properties were comparable to those reported for hydrogels obtained from fibrin-based sealants. Lap-shear adhesion tests of porcine tissue were performed using a newly published American Society for Testing and Materials (ASTM) standard for tissue adhesives. The gelatin-mTG adhesive bound the opposing tissues together with ultimate adhesive strengths of 12-23 kPa which were significantly higher than the strength observed for fibrin sealants. Even after failure, strands of the gelatin-mTG adhesive remained attached to both of the opposing tissues. These results suggest that gelatin-mTG adhesives may offer the benefits of fibrin sealants without the need for blood products. C1 US FDA, Off Sci & Technol, Div Mech & Mat Sci, Rockville, MD 20850 USA. Texas A&M Univ, Dept Biomed Engn, College Stn, TX 77843 USA. Marquette Univ, Dept Biomed Engn, Milwaukee, WI 53201 USA. Univ Maryland Baltimore Cty, Dept Chem & Biochem Engn, Baltimore, MD 21250 USA. RP Payne, GF (reprint author), Univ Maryland, Inst Biotechnol, Ctr Biosyst Res, 5115 Plant Sci Bldg, College Pk, MD 20742 USA. EM payne@umbi.umd.edu NR 60 TC 85 Z9 86 U1 2 U2 30 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1525-7797 J9 BIOMACROMOLECULES JI Biomacromolecules PD JUL-AUG PY 2004 VL 5 IS 4 BP 1270 EP 1279 DI 10.1021/bm034529a PG 10 WC Biochemistry & Molecular Biology; Chemistry, Organic; Polymer Science SC Biochemistry & Molecular Biology; Chemistry; Polymer Science GA 837VG UT WOS:000222668500017 PM 15244440 ER PT J AU Atreya, CD Mohan, KVK Kulkarni, S AF Atreya, CD Mohan, KVK Kulkarni, S TI Rubella virus and birth defects: Molecular insights into the viral teratogenesis at the cellular level SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Review ID CONGENITAL-RUBELLA; CITRON-KINASE; RETINOBLASTOMA PROTEIN; NONSTRUCTURAL PROTEINS; HUMAN CYTOMEGALOVIRUS; INDUCED APOPTOSIS; INFECTED CELLS; UNITED-STATES; SYNDROME CRS; RHO AB BACKGROUND: In utero rubella virus (RV) infection of a fetus can result in birth defects that are often collectively referred to as congenital rubella syndrome (CRS). In extreme cases, fetal death can occur. In spite of the availability of a safe and effective vaccine against rubella, recent worldwide estimates are that more than 100,000 infants are born with CRS annually. RECENT PROGRESS: Recently, several significant findings in the field of cell biology, as well as in the RV replication and virus-cell interactions, have originated from the authors' laboratory, and other researchers have provided insights into RV teratogenesis. It has been shown that 1) an RV protein induces cell-cycle arrest by generating a subpopulation. of tetraploid nuclei (i.e., 4N DNA) cells, perhaps representative of the tetraploid state following S phase in the cell cycle, due to its interaction with citron-K kinase (CK); 2) RV infection induces apoptosis in cell culture, and 3) CK functional perturbations lead to tetraploidy, followed by apoptosis, in specific cell types. CONCLUSIONS: Based on several similarities between known RV-associated fetal and cellular manifestations and CK deficiency-associated phenotypes, it is reasonable to postulate that P90-CK interaction in RV-infected cells interferes with CK function and induces cell-cycle arrest following S phase in a subpopulation, perhaps representative of tetraploid stage, which could lead to subsequent apoptosis in RV infection. Taking all these observations to the fetal organogenesis level, it is plausible that P90-CK interaction could perhaps be one of the initial steps in RV infection-induced apoptosis-associated fetal birth defects in utero. (C) 2004 Wiley-Liss, Inc. C1 US FDA, Ctr Biol Evaluat & Res, Sect Viral Pathogenesis & Vaccine & Res, Div Viral Prod, Bethesda, MD 20892 USA. RP Atreya, CD (reprint author), US FDA, Ctr Biol Evaluat & Res, Sect Viral Pathogenesis & Vaccine & Res, Div Viral Prod, Bldg 29A,Room 2C-11,HFM-460,8800 Rockville Pike, Bethesda, MD 20892 USA. EM atreya@cber.fda.gov NR 72 TC 23 Z9 26 U1 0 U2 5 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 JUL PY 2004 VL 70 IS 7 BP 431 EP 437 DI 10.1002/bdra.20045 PG 7 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 842EZ UT WOS:000222987400001 PM 15259032 ER PT J AU Schenck, FJ Hobbs, JE AF Schenck, FJ Hobbs, JE TI Evaluation of the Quick, Easy, Cheap, Effective, Rugged, and Safe (QuEChERS) approach to pesticide residue analysis SO BULLETIN OF ENVIRONMENTAL CONTAMINATION AND TOXICOLOGY LA English DT Article ID CLEANUP C1 US FDA, SE Reg Lab, Atlanta, GA 30309 USA. RP Schenck, FJ (reprint author), US FDA, SE Reg Lab, 60 8th St NE, Atlanta, GA 30309 USA. NR 7 TC 78 Z9 95 U1 5 U2 45 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0007-4861 J9 B ENVIRON CONTAM TOX JI Bull. Environ. Contam. Toxicol. PD JUL PY 2004 VL 73 IS 1 BP 24 EP 30 DI 10.1007/s00128-004-0388-y PG 7 WC Environmental Sciences; Toxicology SC Environmental Sciences & Ecology; Toxicology GA 837MA UT WOS:000222638400004 PM 15386067 ER PT J AU Volpe, DA LoRusso, PM Foster, BJ Parchment, RE AF Volpe, DA LoRusso, PM Foster, BJ Parchment, RE TI In vitro and in vivo effects of acetyldinaline on murine megakaryocytopoiesis SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE acetyldinaline; mice; platelets; CFU-meg; in vitro; in vivo ID STEM-CELLS; TOXICITY; CI-994; DRUG; ANTITUMOR; CLONING; MICE AB Purpose. Acetyldinaline (CI-994) has shown preclinical efficacy in vitro and in vivo against solid tumor and leukemia cell lines. Since myelosuppression was the dose-limiting toxicity for acetyldinaline in preclinical and clinical studies, experiments were conducted to examine the in vitro and in vivo effects of acetyldinaline on murine megakaryocytic (CFU-meg) progenitor cells. Methods. Bone marrow and spleen cells from untreated mice were continuously exposed in vitro to acetyldinaline or dinaline in clonal assays. For the in vivo study, BDF1 mice were dosed orally with 50 mg/kg acetyldinaline every day for 14 days. Results. Both acetyldinaline and dinaline induced an in vitro dose-dependent decrease in CFU-meg colonies derived from either the spleen or bone marrow. Splenic CFU-meg were more sensitive in vitro to acetyldinaline and dinaline than their marrow counterparts. In the in vivo experiments, platelet counts decreased throughout the 14-day dosing period and had returned to normal by day 18. Marrow and spleen CFU-meg declined after the first dose but had recovered by days 4 and 7, respectively. Elevated splenic CFU-meg counts were observed through day 20, 6 days after dosing ended. Recovery of platelet counts in treated mice was associated with increases in both marrow and splenic CFU-meg. Conclusions. There was differential in vitro toxicity of acetyldinaline to murine CFU-meg derived from the bone marrow versus spleen. The in vitro assay predicted the more severe effect of acetyldinaline on splenic progenitors than on their marrow counterparts that was observed in the in vivo phase. In addition, megakaryocytopoiesis in the marrow showed evidence of recovery from drug toxicity in the face of continuing daily acetyldinaline treatments. C1 US FDA, CDER, Rockville, MD 20857 USA. Wayne State Univ, Sch Med, Detroit, MI USA. US FDA, Silver Spring, MD 20993 USA. RP Volpe, DA (reprint author), US FDA, CDER, Rockville, MD 20857 USA. EM volpe@cder.fda.gov NR 21 TC 2 Z9 2 U1 0 U2 1 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD JUL PY 2004 VL 54 IS 1 BP 89 EP 94 DI 10.1007/s00280-004-0783-4 PG 6 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 825UD UT WOS:000221783000013 PM 15014898 ER PT J AU Powers, JH Ross, DB Lin, D Soreth, J AF Powers, JH Ross, DB Lin, D Soreth, J TI Linezolid and vancomycin for methicillin-resistant Staphylococcus aureus nosocomial pneumonia - The subtleties of subgroup analyses SO CHEST LA English DT Letter ID CLINICAL-TRIALS; DOUBLE-BLIND; MULTICENTER C1 US FDA, Rockville, MD 20857 USA. RP Powers, JH (reprint author), HFD-104,9201 Corp Blvd, Rockville, MD 20850 USA. EM POWERSJOH@cder.fda.gov NR 8 TC 48 Z9 51 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 JUL PY 2004 VL 126 IS 1 BP 314 EP 315 DI 10.1378/chest.126.1.314 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 841XP UT WOS:000222965900056 PM 15249482 ER PT J AU Okamura, M Lillehoj, HS Raybourne, RB Babu, US Heckert, RA AF Okamura, M Lillehoj, HS Raybourne, RB Babu, US Heckert, RA TI Cell-mediated immune responses to a killed Salmonella enteritidis vaccine: lymphocyte proliferation, T-cell changes and interleukin-6 (IL-6), IL-1, IL-2, and IFN-gamma production SO COMPARATIVE IMMUNOLOGY MICROBIOLOGY AND INFECTIOUS DISEASES LA English DT Article DE chicken; Salmonella enteritidis; killed vaccine; cell proliferation; cytokines ID LINKED-IMMUNOSORBENT-ASSAY; CHICKEN INTERFERON-GAMMA; NEONATAL LEGHORN CHICKS; BLOOD MONONUCLEAR-CELLS; LAYING HENS; ORGAN INVASION; MONOCLONAL-ANTIBODIES; PHAGE TYPE-4; TYPHIMURIUM LIPOPOLYSACCHARIDE; AVIRULENT SALMONELLA AB Two experimental approaches were used to investigate the immunological responses of chickens to a commercial killed Salmonella enteritidis (SE) vaccine. In the first, the effects of host age on antigen-specific proliferative responses and cytokine production were examined. Compared with non-vaccinated controls, 4-wk-old vaccinated chickens showed higher proliferation to SE LPS and flagella. The lymphoproliferation responses to these antigens of 8-mo-old vaccinated chickens were not different compared to the non-vaccinated controls. Increased production of interferon-gamma (IFN-gamma) and interleukin-2 (IL-2) by antigen-stimulated splenocytes following vaccination were, in general, more often observed in 4-wk-old compared with 8-mo-old chickens, whereas serum levels of these cytokines were consistently higher in the vaccinated birds compared with controls regardless of age. The second set of experiments were designed to determine the effects of SE vaccination on mitogen- or antigen-induced splenocyte proliferation and serum nitric oxide (NO) and cytokine levels. Splenocytes from vaccinated chickens stimulated with SE flagella showed significantly increased numbers of TCRgammadelta(+) cells at 7 days post-vaccination compared with non-vaccinated birds. In contrast, no differences were noted with CD4(+), CD8(+), or TCRalphabeta(+) cells at any time points examined. Higher levels of NO production were observed following stimulation with SE flagella at 4, 7, 11, and 14 days after SE vaccination while serum levels of IFN-gamma, IL-1, IL-6, and IL-8 were elevated only at day 7 post-vaccination. In conclusion, younger chickens mounted a more robust antigen-specific immune response to the SE vaccine compared with older birds and vaccination induced not only T-cell-mediated responses but also host innate and pro-inflammatory responses. Published by Elsevier Ltd. C1 USDA, ARS, Anim Parasit Dis Lab, Anim & Nat Resources Inst, Beltsville, MD 20705 USA. US FDA, Immunobiol Branch, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. Univ Maryland, VA MD Reg Coll Vet Med, Dept Avian Dis, College Pk, MD 20742 USA. RP Lillehoj, HS (reprint author), USDA, ARS, Anim Parasit Dis Lab, Anim & Nat Resources Inst, BARC E,Bldg 1043, Beltsville, MD 20705 USA. EM hlilleho@anri.barc.usda.gov NR 70 TC 63 Z9 69 U1 3 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0147-9571 J9 COMP IMMUNOL MICROB JI Comp. Immunol. Microbiol. Infect. Dis. PD JUL PY 2004 VL 27 IS 4 BP 255 EP 272 DI 10.1016/j.cimid.2003.12.001 PG 18 WC Immunology; Microbiology; Veterinary Sciences SC Immunology; Microbiology; Veterinary Sciences GA 832YT UT WOS:000222304300004 PM 15178000 ER PT J AU Tan, YX Shi, LB Tong, WD Hwang, GTG Wang, C AF Tan, YX Shi, LB Tong, WD Hwang, GTG Wang, C TI Multi-class tumor classification by discriminant partial least squares using microarray gene expression data and assessment of classification models SO COMPUTATIONAL BIOLOGY AND CHEMISTRY LA English DT Article DE DPLS; microarray; classification; reliability; leave-half-out cross-validation ID LINEAR-REGRESSION; CANCER; PREDICTION; VALIDATION; DISCOVERY; PROFILES AB High-throughput DNA microarray provides an effective approach to the monitoring of expression levels of thousands of genes in a sample simultaneously. One promising application of this technology is the molecular diagnostics of cancer, e.g. to distinguish normal tissue from tumor or to classify tumors into different types or subtypes. One problem arising from the use of microarray data is how to analyze the high-dimensional gene expression data, typically with thousands of variables (genes) and much fewer observations (samples). There is a need to develop reliable classification methods to make full use of microarray data and to evaluate accurately the predictive ability and reliability of such derived models. In this paper, discriminant partial least squares was used to classify the different types of human tumors using four microarray datasets and showed good prediction performance. Four different cross-validation procedures (leave-one-out versus leave-half-out; incomplete versus full) were used to evaluate the classification model. Our results indicate that discriminant partial least squares using leave-half-out cross-validation provides a more realistic estimate of the predictive ability of a classification model, which may be overestimated by some of the cross-validation procedures, and the information obtained from different cross-validation procedures can be used to evaluate the reliability of the classification model. (C) 2004 Elsevier Ltd. All rights reserved. C1 Univ Calif Los Angeles, Cedars Sinai Med Ctr, David Geffen Sch Med, Burns & Allen Res Inst Microarray Core, Los Angeles, CA 90048 USA. US FDA, Natl Ctr Toxicol Res, Ctr Toxicoinformat, Jefferson, AR 72079 USA. Cornell Univ, Dept Math, Ithaca, NY 14850 USA. RP Wang, C (reprint author), Univ Calif Los Angeles, Cedars Sinai Med Ctr, David Geffen Sch Med, Burns & Allen Res Inst Microarray Core, Los Angeles, CA 90048 USA. EM charles.wang@cshs.org FU NCRR NIH HHS [M01-RR00425] NR 31 TC 47 Z9 49 U1 2 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1476-9271 J9 COMPUT BIOL CHEM JI Comput. Biol. Chem. PD JUL PY 2004 VL 28 IS 3 BP 235 EP 244 DI 10.1016/j.compbiolchem.2004.05.002 PG 10 WC Biology; Computer Science, Interdisciplinary Applications SC Life Sciences & Biomedicine - Other Topics; Computer Science GA 843YB UT WOS:000223122100009 PM 15261154 ER PT J AU Markovic, I Clouse, KA AF Markovic, I Clouse, KA TI Recent advances in understanding the molecular mechanisms of HIV-1 entry and fusion: Revisiting current targets and considering new options for therapeutic intervention SO CURRENT HIV RESEARCH LA English DT Review DE HIV-1 pathogenesis; antiviral therapy; viral entry; membrane fusion; thiol/disulfide exchange; envelope glycoprotein; conformational restructuring; CD4; CCR5; CXCR4 ID HUMAN-IMMUNODEFICIENCY-VIRUS; PROTEIN-DISULFIDE-ISOMERASE; CD4-INDUCED CONFORMATIONAL-CHANGES; SELECTIVE ANTI-HIV-1 ACTIVITY; GP120 ENVELOPE GLYCOPROTEIN; CHEMOKINE RECEPTOR CXCR4; ENV-MEDIATED FUSION; CELL-CELL FUSION; CD4(+) T-CELLS; MONOCLONAL-ANTIBODY AB Recent advances in our understanding of the cellular and molecular mechanisms of HIV-1 entry provide the basis for novel therapeutic strategies that prevent viral penetration of the target cell-membrane, while reducing detrimental virus and treatment effects on cells and prolonging virion exposure to immune defenses. A number of potential sites for therapeutic intervention become accessible during the narrow window between virus attachment and the Subsequent fusion of viral envelope with the cell membrane. Initial approaches considered for prevention of HIV-1 entry included the use of natural ligands, small-molecule inhibitors and/or monoclonal antibodies, which could interfere with gp120-CD4 and/or gp120-CXCR4/CCR5 interaction. Others avenues pursued were the use of agents that interfere with the conformational changes of gp120 or gp41 leading to subsequent fusion of viral and cellular membranes. More recently, strategies have emerged that involve inhibition of thiol/disulfide oxidoreductases (factors which facilitate Env transition from an inactive to a fusion-competent conformation) to block redox exchange, thereby impeding the entry process. This review provides a summary of the cellular and viral factors mediating the HIV-1 entry process, with an emphasis on novel therapeutics targeting Env-receptor/coreceptor interaction, Env conformational change and the membrane fusion process. C1 US FDA, Div Monoclonal Antibodies, Off Biotechnol Prod, Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. RP Markovic, I (reprint author), US FDA, Div Monoclonal Antibodies, Off Biotechnol Prod, Ctr Drug Evaluat & Res, Bldg 29B,Room 3E18,29 Lincoln Dr,HFM-558, Bethesda, MD 20892 USA. EM rnarkovic@cber.fda.gov NR 134 TC 38 Z9 39 U1 2 U2 5 PU BENTHAM SCIENCE PUBL LTD PI HILVERSUM PA PO BOX 1673, 1200 BR HILVERSUM, NETHERLANDS SN 1570-162X J9 CURR HIV RES JI Curr. HIV Res. PD JUL PY 2004 VL 2 IS 3 BP 223 EP 234 DI 10.2174/1570162043351327 PG 12 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 831YH UT WOS:000222232300003 PM 15279586 ER PT J AU Misbin, RI AF Misbin, RI TI The phantom of lactic acidosis due to metformin in patients with diabetes SO DIABETES CARE LA English DT Editorial Material ID CONTRAINDICATIONS; THERAPY; PHENFORMIN; TIME C1 US FDA, Div Endocrinol & Metab, Rockville, MD 20851 USA. RP Misbin, RI (reprint author), US FDA, Div Endocrinol & Metab, 5727 Crawford Dr, Rockville, MD 20851 USA. EM misbinr@cder.fda.gov NR 35 TC 85 Z9 89 U1 0 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD JUL PY 2004 VL 27 IS 7 BP 1791 EP 1793 DI 10.2337/diacare.27.7.1791 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 834FN UT WOS:000222397100046 PM 15220268 ER PT J AU Volokhov, D Pomerantsev, A Kivovich, V Rasooly, A Chizhikov, V AF Volokhov, D Pomerantsev, A Kivovich, V Rasooly, A Chizhikov, V TI Identification of Bacillus anthracis by multiprobe microarray hybridization SO DIAGNOSTIC MICROBIOLOGY AND INFECTIOUS DISEASE LA English DT Article DE multiplex PCR; pXO1; pXO2; virulence factors; anthrax toxins ID POLYMERASE-CHAIN-REACTION; CLOSELY-RELATED BACTERIA; 16S RIBOSOMAL-RNA; DNA-SEQUENCE; GENETIC-RELATIONSHIPS; INFECTIOUS-DISEASES; CHROMOSOMAL MARKER; VIRULENCE FACTORS; GENOME SEQUENCE; MULTIPLEX PCR AB We have developed a rapid assay based on microarray analysis of amplified genetic markers for reliable identification of Bacillus anthracis and its discrimination from other closely related bacterial species of the Bacillus cereus group. By combining polymerase chain reaction (PCR) amplification of six B. anthracis-specific genes (plasmid-associated genes encoding virulence factors (cyaA, pagA, lef, and capA, capB, capC) and one chromosomal marker BA-5449) with analysis of amplicons by microarray hybridization, we were able to unambiguously identify and discriminate B. anthracis among other closely related species. Bacillus identification relied on hybridization with multiple individual microarray oligonucleotide probes (oligoprobes) specific to each target B. anthracis gene. Evaluation of the assay was conducted using several B. anthracis strains (with or without pXO1 and pXO2 plasmids) as well as over 50 other species phylogenetically related to B. anthracis, including B. cereus, B. thuringiensis, B. mycoides, and B. subtilis. The developed microarray analysis of amplified genetic markers protocol provides an efficient method for (i) unambiguous identification and discrimination of B. anthracis from other Bacillus species and (ii) distinguishing between plasmid-containing and plasmid-free Bacillus anthracis strains. (C) 2004 Elsevier Inc. All rights reserved. C1 US FDA, Ctr Biol Evaluat & Res, Kensington, MD 20895 USA. NIAID, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Chizhikov, V (reprint author), US FDA, Ctr Biol Evaluat & Res, Kensington, MD 20895 USA. EM chizhikov@cber.fda.gov NR 55 TC 31 Z9 37 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0732-8893 J9 DIAGN MICR INFEC DIS JI Diagn. Microbiol. Infect. Dis. PD JUL PY 2004 VL 49 IS 3 BP 163 EP 171 DI 10.1016/j.diagmicrobio.2004.03.015 PG 9 WC Infectious Diseases; Microbiology SC Infectious Diseases; Microbiology GA 842EG UT WOS:000222985400003 PM 15246505 ER PT J AU Watson, C AF Watson, C TI Janet Woodcock discusses the FDA and the drug development process SO DRUG DISCOVERY TODAY LA English DT Editorial Material C1 US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Watson, C (reprint author), US FDA, Ctr Drug Evaluat & Res, 5600 Fishers Lane, Rockville, MD 20857 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1359-6446 J9 DRUG DISCOV TODAY JI Drug Discov. Today PD JUL 1 PY 2004 VL 9 IS 13 BP 548 EP 550 AR PII S1359-6446(04)03160-5 DI 10.1016/S1359-6446(04)03160-5 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 832WR UT WOS:000222298900004 ER PT J AU Cheng, CL Yu, LX Lee, HL Yang, CY Lue, CS Chou, CH AF Cheng, CL Yu, LX Lee, HL Yang, CY Lue, CS Chou, CH TI Biowaiver extension potential to BCS Class III high solubility-low permeability drugs: bridging evidence for metformin immediate-release tablet SO EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article DE bioequivalence; biopharmaceutics classification system; biowaiver; interethnic comparison; metformin; pharmacokinetics ID BIOPHARMACEUTICS CLASSIFICATION-SYSTEM; HEALTHY-SUBJECTS; LIQUID-CHROMATOGRAPHY; DIABETES-MELLITUS; CACO-2 CELLS; HUMAN PLASMA; PHARMACOKINETICS; BIOAVAILABILITY; BIOEQUIVALENCE; VOLUNTEERS AB The biopharmaceutics classification system (BCS) allows biowaiver for rapid dissolving immediate-release (IR) products of Class I drugs (high solubility and high permeability). The possibility of extending biowaivers to Class III high solubility and low permeability drugs is currently under scrutiny. In vivo bioequivalence data of different formulations of Class III drugs would support such an extension. The objective of this work was to demonstrate the bioequivalence of two marketed IR tablet products of a Class III drug, metformin hydrochloride, that are rapidly dissolving and have similar in vitro dissolution profiles. The effect of race on the systemic exposure of metformin was also explored. A randomized, open-label, two-period crossover study was conducted in 12 healthy Chinese male volunteers. Each subject received a single-dose of 500 mg of each product after an overnight fasting. The plasma concentrations of metformin were followed for 24 h. No significant formulation effect was found for the bioequivalence metrics: areas under concentration-time curve (AUC(0-1), AUC(0-infinity)) and maximal concentration (C-max). The 90% confidence intervals for the ratio of means were found within the acceptance range of 80-125% for the log-transformed data. Based on these results, it was concluded that the two IR products are bioequivalent. The pharmacokinetic parameters of metformin in Chinese for both products were similar and were in good agreement with those reported for metformin IR tablets in other ethnic populations. This study serves as an example for supporting biowaiver for BCS Class III drugs. (C) 2004 Elsevier B.V. All rights reserved. C1 Natl Cheng Kung Univ, Coll Med, Inst Clin Pharm, Tainan 70101, Taiwan. Chia Nan Univ Pharm & Sci, Dept Pharm, Tainan, Taiwan. US FDA, Ctr Drug Evaluat & Res, Off Pharmaceut Sci, Rockville, MD 20857 USA. Natl Cheng Kung Univ, Coll Med, Dept Publ Hlth, Tainan 70101, Taiwan. Natl Cheng Kung Univ, Coll Med, Dept Orthoped, Tainan 70101, Taiwan. Swiss Pharmaceut Co Ltd, Tainan, Taiwan. RP Chou, CH (reprint author), Natl Cheng Kung Univ, Coll Med, Inst Clin Pharm, 1 Univ Rd, Tainan 70101, Taiwan. EM chenhsi@mail.ncku.edu.tw NR 33 TC 55 Z9 68 U1 1 U2 12 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0928-0987 J9 EUR J PHARM SCI JI Eur. J. Pharm. Sci. PD JUL PY 2004 VL 22 IS 4 BP 297 EP 304 DI 10.1016/j.ejps.2004.03.016 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 834FE UT WOS:000222396200009 PM 15196586 ER PT J AU Williams, KM Bigley, EC AF Williams, KM Bigley, EC TI Identification of an I-E-d-restricted T-cell epitope of Escherichia coli outer membrane protein F SO INFECTION AND IMMUNITY LA English DT Article ID MHC CLASS-II; MAJOR HISTOCOMPATIBILITY COMPLEX; COMPLETE GENOME SEQUENCE; HEN EGG LYSOZYME; SALMONELLA-TYPHIMURIUM PORINS; PEPTIDE BINDING; CRYSTAL-STRUCTURE; 3-DIMENSIONAL STRUCTURE; FLANKING RESIDUES; SHIGELLA-FLEXNERI AB A predominant T-cell epitope of Escherichia coli outer membrane protein F (OmpF) that encompasses amino acids 295 to 314 was identified in H-2(d) mice. BALB/c-derived T-cell hybridomas generated against this region were CD3(+), CD4(+), CD8(-), and T-cell receptor alphabeta and secreted TH-1-associated cytokines (interleukin-2 [IL-2] and gamma interferon), but not a TH-2-associated cytokine (IL-4), when restimulated with peptide 295-314. Class II+ mouse lymphoma (A20) cells, but not class II(-) mouse mastocytoma (P815) cells, supported IL-2 secretion of hybridomas when substituted for syngeneic splenocytes as antigen-presenting cells (APCs). Antibodies specific for I-E-d blocked IL-2 secretion by hybridomas, but I-A(d)-specific antiserum did not. When transfected L cells expressing I-A(d) (AalphaAbeta(d)), I-E-d (EalphaEbeta(d)), or the hybrid molecule I-EalphaAbeta(d) were used as APCs, hybridomas recognized peptide only when presented by the I-E-d-transfected cells. When peptide 295-314 truncated at either the C or the N terminus of the sequence was used, the minimal epitope was determined. Critical residues were determined by using alanine-substituted peptide analogues. T-cell hybridomas were only stimulated by peptides that encompassed amino acids 295 to 303 (9-mer), and the core sequence required a minimum of three additional amino acids at either the amino or the carboxy terminus to induce IL-2 secretion. Critical residues were determined to be phenylalanine at position 295, threonine at position 300, and tyrosines at positions 301 and 302. This study is the first to identify a minimal T-cell epitope and major histocompatibility complex restriction element of the OmpF protein and confirms previous observations that there is considerable degeneracy in the length of peptides that can bind I-E-d and variability in the amino acid composition of the C and N termini of these peptides. C1 US FDA, Ctr Food Safety & Appl Nutr, Immunobiol Branch, Laurel, MD 20708 USA. RP Williams, KM (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Immunobiol Branch, 8301 Muirkirk Rd, Laurel, MD 20708 USA. EM kwillia2@cfsan.fda.gov NR 70 TC 2 Z9 2 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JUL PY 2004 VL 72 IS 7 BP 3907 EP 3913 DI 10.1128/IAI.72.7.3907-3913.2004 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 832QU UT WOS:000222282800026 PM 15213134 ER PT J AU Tollefson, L AF Tollefson, L TI Factual errors in review article SO JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY LA English DT Letter DE antimicrobial resistance; animal agriculture ID INFECTIONS C1 US FDA, Gaithersburg, MD 20878 USA. RP Tollefson, L (reprint author), US FDA, 7519 Standish Pl, Gaithersburg, MD 20878 USA. EM ltollefs@cvm.fda.gov NR 7 TC 4 Z9 4 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-7453 J9 J ANTIMICROB CHEMOTH JI J. Antimicrob. Chemother. PD JUL PY 2004 VL 54 IS 1 BP 271 EP 271 DI 10.1093/jac/dkh267 PG 1 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA 836LV UT WOS:000222558100051 PM 15140865 ER PT J AU Karp, BE Engberg, J AF Karp, BE Engberg, J TI Comment on: Does the use of antibiotics in food animals pose a risk to human health? A critical review of published data SO JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY LA English DT Letter DE antimicrobial resistance; food animals ID CAMPYLOBACTER-JEJUNI; QUINOLONE C1 US FDA, Ctr Vet Med, Rockville, MD 20855 USA. Statens Serum Inst, DK-2300 Copenhagen S, Denmark. RP Karp, BE (reprint author), US FDA, Ctr Vet Med, 7519 Standish Pl, Rockville, MD 20855 USA. EM bkarp@cvm.fda.gov NR 7 TC 5 Z9 7 U1 2 U2 15 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-7453 J9 J ANTIMICROB CHEMOTH JI J. Antimicrob. Chemother. PD JUL PY 2004 VL 54 IS 1 BP 273 EP 274 DI 10.1093/jac/dkh265 PG 2 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA 836LV UT WOS:000222558100053 PM 15140863 ER PT J AU Lang, QY Wai, CM Ang, CYW Cui, YY Heinze, TM Mattia, A Dinovi, M AF Lang, QY Wai, CM Ang, CYW Cui, YY Heinze, TM Mattia, A Dinovi, M TI Sample preparation and determination of Ginkgo terpene trilactones in selected beverage, snack, and dietary supplement products by liquid chromatography with evaporative light-scattering detection SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID PLATELET-ACTIVATING-FACTOR; BILOBA LEAVES; LEAF EXTRACTS; PHYTOPHARMACEUTICALS; SPECTROMETRY; SEPARATION AB Ginkgo biloba leaf extract has been widely used in dietary supplements and more recently in some foods and beverages. Sample preparation procedures for determination of ginkgo terpene trilactones (including bilobalide and ginkgolides A, B, C, and J) in various sample matrixes were developed in this study. Ginkgo leaves and capsules were extracted with 5% KH2PO4 aqueous solution under sonication. Tea bags were extracted with boiling water, whereas drink samples were taken directly from the bottles. After filtration and the addition of NaCl to approximately 30% (w/v), the terpene trilactones in aqueous solutions were quantitatively extracted with ethyl acetate-tetrahydrofuran (4 + 1, v/v). Puff samples (a cereal-based fried snack item) were first defatted by using hexane or by using supercritical fluid extraction and then extracting under sonication with methanol-acetic acid (99. + 1, v/v). After evaporation of the organic phase the terpene trilactones were redissolved in methanol and determined on a C18 reversed-phase column by liquid chromatography (LC) with evaporative light-scattering detection. The method of standard additions and gas chromatography with flame ionization detection were used for method validation. For most samples, the relative standard deviation was <10%. The identities of target compounds in ginkgo leaves and drink samples were confirmed by LC/electrospray ionization-tandem mass spectrometry. C1 US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Univ Idaho, Dept Chem, Moscow, ID 83843 USA. US FDA, Ctr Food Safety & Appl Nutr, Off Food Addit Safety, Div Biotechnol, College Pk, MD 20740 USA. RP Ang, CYW (reprint author), US FDA, Natl Ctr Toxicol Res, 3900 NCTR Rd,HFT-230, Jefferson, AR 72079 USA. EM cang@nctr.fda.gov NR 28 TC 10 Z9 10 U1 1 U2 3 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD JUL-AUG PY 2004 VL 87 IS 4 BP 815 EP 826 PG 12 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 835JO UT WOS:000222479200005 PM 15295874 ER PT J AU Trucksess, MW Whitaker, TB Slate, AB Williams, KM Brewer, VA Whittaker, P Heeres, JT AF Trucksess, MW Whitaker, TB Slate, AB Williams, KM Brewer, VA Whittaker, P Heeres, JT TI Variation of analytical results for peanuts in energy bars and milk chocolate SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article AB Peanuts contain proteins that can cause severe allergic reactions in some sensitized individuals. Studies were conducted to determine the percentage of recovery by an enzyme-linked immunosorbent assay (ELISA) method in the analysis for peanuts in energy bars and milk chocolate and to determine the sampling, subsampling, and analytical variances associated with testing energy bars and milk chocolate for peanuts. Food products containing chocolate were selected because their composition makes sample preparation for subsampling difficult. Peanut-contaminated energy bars, noncontaminated energy bars, incurred milk chocolate containing known levels of peanuts, and peanut-free milk chocolate were used. A commercially available ELISA kit was used for analysis, The sampling, sample preparation, and analytical variances associated with each step of the test procedure to measure peanut protein were determined for energy bars. The sample preparation and analytical variances were determined for milk chocolate. Variances were found to be functions of peanut concentration. Sampling and subsampling variability associated with energy bars accounted for 96.6% of the total testing variability. Subsampling variability associated with powdered milk chocolate accounted for >60% of the total testing variability. The variability among peanut test results can be reduced by increasing sample size, subsample size, and number of analyses. For energy bars the effect of increasing sample size from 1 to 4 bars, subsample size from 5 to 20 g, and number of aliquots quantified from 1 to 2 on reducing the sampling, sample preparation, and analytical variance was demonstrated. For powdered milk chocolate, the effects of increasing subsample size from 5 to 20 g and number of aliquots quantified from 1 to 2 on reducing sample preparation and analytical variances were demonstrated. This study serves as a template for application to other foods, and for extrapolation to different sizes of samples and subsamples as well as numbers of analyses. C1 US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. N Carolina State Univ, USDA ARS, Weaver Lab 124, Raleigh, NC 27695 USA. Univ Maryland, College Pk, MD 20740 USA. RP Trucksess, MW (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM mtruckse@cfsan.fda.gov NR 5 TC 5 Z9 5 U1 0 U2 12 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 2004 VL 87 IS 4 BP 943 EP 949 PG 7 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 835JO UT WOS:000222479200020 PM 15295889 ER PT J AU Whitaker, TB Trucksess, MW Giesbrecht, FG Slate, AB Thomas, FS AF Whitaker, TB Trucksess, MW Giesbrecht, FG Slate, AB Thomas, FS TI Evaluation of sampling plans to detect Cry9C protein in corn flour and meal SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID VARIABILITY; AFLATOXIN AB StarLink is a genetically modified corn that produces an insecticidal protein, Cry9C. Studies were conducted to determine the variability and Cry9C distribution among sample test results when Cry9C protein was estimated in a bulk lot of corn flour and meal. Emphasis was placed on measuring sampling and analytical variances associated with each step of the test procedure used to measure Cry9C in corn flour and meal. Two commercially available enzyme-linked immunosorbent assay kits were used: one for the determination of Cry9C protein concentration and the other for % StarLink seed. The sampling and analytical variances associated with each step of the Cry9C test procedures were determined for flour and meal. Variances were found to be functions of Cry9C concentration, and regression equations were developed to describe the relationships. Because of the larger particle size sampling variability associated with cornmeal was about double that for corn flour. For cornmeal, the sampling variance accounted for 92.6% of the total testing variability. The observed sampling and analytical distributions were compared with the Normal distribution. In almost all comparisons, the null hypothesis that the Cry9C protein values were sampled from a Normal distribution could not be rejected at 95% confidence limits. The Normal distribution and the variance estimates were used to evaluate the performance of several Cry9C protein sampling plans for corn flour and meal. Operating characteristic curves were developed and used to demonstrate the effect of increasing sample size on reducing false positives (seller's risk) and false negatives (buyer's risk). C1 N Carolina State Univ, USDA ARS, Raleigh, NC 27695 USA. US FDA, College Pk, MD 20740 USA. N Carolina State Univ, Dept Stat, Raleigh, NC 27695 USA. RP Whitaker, TB (reprint author), N Carolina State Univ, USDA ARS, Box 7625, Raleigh, NC 27695 USA. EM tom_whitaker@ncsu.edu NR 10 TC 7 Z9 7 U1 1 U2 2 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD JUL-AUG PY 2004 VL 87 IS 4 BP 950 EP 960 PG 11 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 835JO UT WOS:000222479200021 PM 15295890 ER PT J AU Wyckoff, EE Schmitt, M Wilks, A Payne, SM AF Wyckoff, EE Schmitt, M Wilks, A Payne, SM TI HutZ is required for efficient heme utilization in Vibrio cholerae SO JOURNAL OF BACTERIOLOGY LA English DT Article ID COMPLETE GENOME SEQUENCE; GRAM-NEGATIVE BACTERIA; OUTER-MEMBRANE PROTEINS; ESCHERICHIA-COLI; CORYNEBACTERIUM-DIPHTHERIAE; IRON UTILIZATION; YERSINIA-ENTEROCOLITICA; SHIGELLA-DYSENTERIAE; SUICIDE VECTOR; GENES AB Vibrio cholerae, the causative agent of cholera, requires iron for growth. One mechanism by which it acquires iron is the uptake of heme, and several heme utilization genes have been identified in V. cholerae. These include three distinct outer membrane receptors, two TonB systems, and an apparent ABC transporter to transfer heme across the inner membrane. However, little is known about the fate of the heme after it enters the cell. In this report we show that a novel heme utilization protein, HutZ, is required for optimal heme utilization. hutZ (open reading frame [ORF] VCA0907) is encoded with two other genes, hutW (ORF VCA0909) and hutX (ORF VCA0908), in an operon divergently transcribed from the tonB1 operon. A hutZ mutant grew poorly when heme was provided as the sole source of iron, and the poor growth was likely due to the failure to use heme efficiently as a source of iron, rather than to heme toxicity. Heme oxygenase mutants of both Corynebacterium diphtheriae and C. ulcerans fail to use heme as an iron source. When the hutWXZ genes were expressed in the heme oxygenase mutants, growth on heme was restored, and hutZ was required for this effect. Biochemical characterization indicated that HutZ binds heme with high efficiency; however, no heme oxygenase activity was detected for this protein. HutZ may act as a heme storage protein, and it may also function as a shuttle protein that increases the efficiency of heme trafficking from the membrane to heme-containing proteins. C1 Univ Texas, Sect Mol Genet & Microbiol, Austin, TX 78712 USA. Univ Texas, Inst Cellular & Mol Biol, Austin, TX 78712 USA. US FDA, Lab Bacterial Toxins, Div Bacterial Parasit & Allergen Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. Univ Maryland, Sch Pharm, Dept Pharmaceut Sci, Baltimore, MD 21201 USA. RP Wyckoff, EE (reprint author), Univ Texas, Sect Mol Genet & Microbiol, 1 Univ Stn A5000, Austin, TX 78712 USA. EM ewyckoff@mail.utexas.edu FU NIAID NIH HHS [AI48551, AI50669, R01 AI050669, R01 AI048551, R56 AI050669] NR 56 TC 48 Z9 50 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 JUL PY 2004 VL 186 IS 13 BP 4142 EP 4151 DI 10.1128/JB.186.13.4142-4151.2004 PG 10 WC Microbiology SC Microbiology GA 831JA UT WOS:000222189500010 PM 15205415 ER PT J AU Beger, RD Harris, S Xie, Q AF Beger, RD Harris, S Xie, Q TI Models of steroid binding based on the minimum deviation of structurally assigned C-13 NMR spectra analysis (MiDSASA) SO JOURNAL OF CHEMICAL INFORMATION AND COMPUTER SCIENCES LA English DT Article ID AUTOMATED STRUCTURE EVALUATION; RELATIONSHIP QSDAR MODELS; ANALYSIS COSCOSA MODELS; AROMATASE INHIBITORS; BREAST-CANCER; QSAR; REGRESSION; GLOBULIN AB This paper develops a quantitative k-nearest neighbors modeling technique. The technique is used to demonstrate that a compound's biological binding activity to a receptor can be calculated from the minimum of the square root of the sum of squared deviations (SSSD) of a structurally assigned chemical shift on a template between the unknown compound to be predicted and a set of known compounds with known activities. When building models of biological activity, nonlinear relationships are built into the input training data. If a model is developed by selecting only compounds with minimum structurally assigned chemical shift deviations from the unknown compound, some of the nonlinear relationships can be removed. The smaller the total chemical shift deviation between a compound with known activity and another compound with unknown activity, the more likely it will have similar biological, chemical, and physical properties. This means that a model can be produced without rigorous statistics or neural networks. This technique is similar to structure-activity relationship (SAR) modeling, but instead of relying on substructure fragments to produce a model, this new model is based on minimum chemical shift differences on those substructure fragments. We refer to this method as minimum deviation of structurally assigned spectra analysis (MiDSASA) modeling. Modeling by the minimum deviation concept can be applied to other chemoinformatic data analyses such as metabolite concentrations in metabolic pathways for metabolomics research. A MiDSASA template model for 30 steroids binding the corticosterone binding globulin based on the activity factors of the two nearest compounds had a correlation of 0.88. A MiDSASA template model for 50 steroids binding the aromatse enzyme based on the average activity of the four nearest compounds had a correlation of 0.71. C1 US FDA, Natl Ctr Toxicol Res, Div Chem, Jefferson, AR 72079 USA. Northrop Grumman Corp, Jefferson, AR 72079 USA. RP Beger, RD (reprint author), US FDA, Natl Ctr Toxicol Res, Div Chem, Jefferson, AR 72079 USA. EM rbeger@cntr.fda.gov NR 28 TC 5 Z9 5 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0095-2338 J9 J CHEM INF COMP SCI JI J. Chem. Inf. Comput. Sci. PD JUL-AUG PY 2004 VL 44 IS 4 BP 1489 EP 1496 DI 10.1021/ci049925e PG 8 WC Chemistry, Multidisciplinary; Computer Science, Information Systems; Computer Science, Interdisciplinary Applications SC Chemistry; Computer Science GA 841RX UT WOS:000222950200032 PM 15272857 ER PT J AU Glatman-Freedman, A Casadevall, A Dai, ZD Jacobs, WR Li, AP Morris, SL Navoa, JAD Piperdi, S Robbins, JB Schneerson, R Schwebach, JR Shapiro, M AF Glatman-Freedman, A Casadevall, A Dai, ZD Jacobs, WR Li, AP Morris, SL Navoa, JAD Piperdi, S Robbins, JB Schneerson, R Schwebach, JR Shapiro, M TI Antigenic evidence of prevalence and diversity of Mycobacterium tuberculosis arabinomannan SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID TUBERCLE-BACILLI; IN-VITRO; LIPOARABINOMANNAN; ANTIBODIES; VIRULENT; LIPOPOLYSACCHARIDE AB Arabinomannan (AM) is a polysaccharide of the mycobacterial capsule. The capsular polysaccharides of various microorganisms are diverse, and this diversity is important for classification of organisms into serotypes and vaccine development. In the present study we examined the prevalence and diversity of AM among Mycobacterium tuberculosis strains using four AM-binding monoclonal antibodies (MAbs). One of these MAbs, MAb 9d8, is known to bind to AM specifically. By whole-cell enzyme-linked immunosorbent assay (ELISA), the AM recognized by MAb 9d8 was detected on the surfaces of 9 of 11 strains, while 2 strains showed no reactivity with MAb 9d8. However, the AM recognized by MAb 9d8 was found in the culture supernatants of all 11 M. tuberculosis strains tested, as demonstrated by capture ELISA. Other AM-binding MAbs reacted both with the surfaces and with the culture supernatants of all 11 strains. Mice immunized with an experimental AM-recombinant Pseudomonas aeruginosa exoprotein A (rEPA) conjugate vaccine had an increased antibody response to AM and a moderate reduction in the numbers of CFU in their organs 7 days after challenge. Our results indicate that AM was detected in all M. tuberculosis strains tested, with differences in epitope distributions of certain strains. In addition, our results suggest that an experimental AM-rEPA vaccine has a moderate effect on the numbers of CFU in organs early after infection. C1 Yeshiva Univ Albert Einstein Coll Med, Childrens Hosp, Dept Pediat, Bronx, NY 10461 USA. Yeshiva Univ Albert Einstein Coll Med, Dept Med, Bronx, NY 10461 USA. Yeshiva Univ Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10461 USA. Yeshiva Univ Albert Einstein Coll Med, Howard Hughes Med Inst, Bronx, NY 10461 USA. NICHHD, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. RP Glatman-Freedman, A (reprint author), Yeshiva Univ Albert Einstein Coll Med, Childrens Hosp, Dept Pediat, Golding Bldg,Room 702,1300 Morris Pk Ave, Bronx, NY 10461 USA. EM afreedma@aecom.yu.edu FU NHLBI NIH HHS [R01 HL059842, HL059842]; NIAID NIH HHS [AI001691, AI026170, AI033142, AI033774, AI043268, AI052733, AI053192, K08 AI001691, R01 AI026170, R01 AI033142, R01 AI033774, R01 AI043268, R01 AI052733, R03 AI053192, R21 AI043268, R37 AI026170, R37 AI033142] NR 27 TC 25 Z9 27 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 JUL PY 2004 VL 42 IS 7 BP 3225 EP 3231 DI 10.1128/JCM.42.7.3225-3231.2004 PG 7 WC Microbiology SC Microbiology GA 837WN UT WOS:000222672100055 PM 15243086 ER PT J AU McMullen, SE Lansden, JA Schenck, FJ AF McMullen, SE Lansden, JA Schenck, FJ TI Modifications and adaptations of the charm II rapid antibody assay for chloramphenicol in honey SO JOURNAL OF FOOD PROTECTION LA English DT Article AB The Charm 11 screening method for the presence of chloramphenicol in honey has a sensitivity of 0.3 ppb. This screening method is a simple, rapid antibody assay using [H-3]chloramphenicol and a binding reagent. Analysis of different types of honey revealed considerable differences in results. Honey can be liquid, crystallized (creamed), or partially crystallized and is classified by the U.S. Department of Agriculture into seven color categories: water white, extra white, white, extra light amber, light amber, amber, and dark amber. Fortified and nonfortified liquid amber honey tested appropriately with the Charm 11 unit and the negative control provided with the unit after slight modifications were made. However, approximately 70% of creamed honey samples fortified at 0.6 ppb did not test positive for the presence of chloramphenicol using the provided negative control. Matrix quenching effects were evaluated, and these effects were accounted for by establishing different assay conditions for different honey types. C1 US FDA, SE Reg Lab, Atlanta, GA 30309 USA. RP McMullen, SE (reprint author), US FDA, SE Reg Lab, 60 8th St NE, Atlanta, GA 30309 USA. EM smcmulle@ora.fda.gov NR 10 TC 3 Z9 3 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 2004 VL 67 IS 7 BP 1533 EP 1536 PG 4 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 836MK UT WOS:000222559700035 PM 15270516 ER PT J AU Maximova, O Taffs, R Piccardo, P Pomeroy, K McMahon, D Asher, D AF Maximova, O Taffs, R Piccardo, P Pomeroy, K McMahon, D Asher, D TI Quantitative evaluation of abnormal prion protein in scrapie-infected brain by digital morphometric analysis SO JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY LA English DT Meeting Abstract CT 12th International Congress of Histochemistry and Cytochemistry CY JUL 24-29, 2004 CL La Jolla, CA SP Histochem Soc C1 US FDA, CBER, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU HISTOCHEMICAL SOC INC PI SEATTLE PA UNIV WASHINGTON, DEPT BIOSTRUCTURE, BOX 357420, SEATTLE, WA 98195 USA SN 0022-1554 J9 J HISTOCHEM CYTOCHEM JI J. Histochem. Cytochem. PD JUL PY 2004 VL 52 SU 1 BP S25 EP S25 PG 1 WC Cell Biology SC Cell Biology GA 833QI UT WOS:000222352900097 ER PT J AU Espina, V Woodhouse, EC Wulfkuhle, J Asmussen, HD Petricoin, EF Liotta, LA AF Espina, V Woodhouse, EC Wulfkuhle, J Asmussen, HD Petricoin, EF Liotta, LA TI Protein microarray detection strategies: focus on direct detection technologies SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Review DE protein microarray; catalyzed reporter deposition; molecular profiling; fluorescence; chromogens ID CATALYZED REPORTER DEPOSITION; ATOMIC-FORCE MICROSCOPE; ALLERGEN-SPECIFIC IGE; TISSUE MICROARRAYS; SIGNAL AMPLIFICATION; MESSENGER-RNA; CLINICAL PROTEOMICS; CANCER SPECIMENS; CHIP TECHNOLOGY; ARRAYS AB Protein microarrays are being utilized for functional proteomic analysis, providing information not obtainable by gene arrays. Microarray technology is applicable for studying protein-protein, protein-ligand, kinase activity and posuranslational modifications of proteins. A precise and sensitive protein microarray, the direct detection or reverse-phase microarray, has been applied to ongoing clinical trials at the National Cancer Institute for studying phosphorylation events in EGF-receptor-mediated cell signaling pathways. The variety of microarray applications allows for multiple, creative microarray designs and detection strategies. Herein, we discuss detection strategies and challenges for protein microarray technology, focusing on direct detection of protein microarrays. Published by Elsevier B.V. C1 US FDA, NCI, Clin Proteom Program, Pathol Lab,Ctr Canc Res, Bethesda, MD 20892 USA. Univ Colorado, Boulder, CO 80309 USA. US FDA, Ctr Biol Evaluat & Res, NCI, Clin Proteom Program, Bethesda, MD 20892 USA. RP Espina, V (reprint author), US FDA, NCI, Clin Proteom Program, Pathol Lab,Ctr Canc Res, Room B1B53,Bldg 10,9000 Rockville Pike, Bethesda, MD 20892 USA. EM espinav@mail.nih.gov OI Espina, Virginia/0000-0001-5080-5972 NR 84 TC 123 Z9 140 U1 7 U2 32 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-1759 J9 J IMMUNOL METHODS JI J. Immunol. Methods PD JUL PY 2004 VL 290 IS 1-2 BP 121 EP 133 DI 10.1016/j.jim.2004.04.013 PG 13 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA 842QR UT WOS:000223019600009 PM 15261576 ER PT J AU Gans, HA Yasukawa, LL Alderson, A Rinki, M DeHovitz, R Beeler, J Audet, S Maldonado, Y Arvin, AM AF Gans, HA Yasukawa, LL Alderson, A Rinki, M DeHovitz, R Beeler, J Audet, S Maldonado, Y Arvin, AM TI Humoral and cell-mediated immune responses to an early 2-dose measles vaccination regimen in the United States SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 41st Annual Meeting of the Infectious-Diseases-Society-of-America CY OCT 09-12, 2003 CL San Diego, CA SP Infectious Dis Soc Amer ID ADDITIONAL EVIDENCE; MATERNAL ANTIBODY; EXCESS MORTALITY; VIRUS VACCINE; EARLY INFANCY; CHILDREN; AGE; IMMUNIZATION; POPULATION; OUTBREAK AB Background. Shifts in peak measles incidence to children <12 months old and the associated high mortality support the study of an early 2-dose measles vaccine regimen. Methods. Fifty-five infants were vaccinated with measles vaccine at age 6 (n = 32) or 9 (n = 23) months, followed by measles-mumps- rubella (MMR)-II vaccine at age 12 months. A control group received MMR-II only at age 12 months. Measles-specific humoral and cell-mediated immunity were evaluated before, 12 weeks after measles immunization, and 24 weeks after MMR-II. Results. Measles-specific T cell proliferation after both doses of vaccine was equivalent, regardless of age or the presence of passive antibodies. Seroconversion rates, geometric mean titers, and the percentage of infants with antibody titers >120 mIU after the first measles vaccine were lower in infants vaccinated at age 6 months, regardless of the presence of passive antibodies, but measles humoral responses increased after the administration of MMR-II vaccine in children initially vaccinated at age 6 or 9 months. Conclusion. Measles vaccination elicits T cell responses in infants as young as 6 months old, which may prime the humoral response to the second dose. Initiating measles vaccination as an early 2-dose regimen results in an immunologic response that is likely to have clinical benefits in developed and developing countries. C1 Stanford Univ, Sch Med, Dept Pediat, Stanford, CA 94305 USA. Palo Alto Med Fdn, Dept Pediat, Palo Alto, CA USA. US FDA, Div Viral Prod, Bethesda, MD 20014 USA. RP Gans, HA (reprint author), Stanford Univ, Sch Med, Dept Pediat, 300 Pasteur Dr,Rm G312, Stanford, CA 94305 USA. EM hagans@stanford.edu FU NICHD NIH HHS [HD33698, HD01310]; PHS HHS [A137127] NR 48 TC 51 Z9 53 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 JUL 1 PY 2004 VL 190 IS 1 BP 83 EP 90 DI 10.1086/421032 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 828VV UT WOS:000222002700010 PM 15195246 ER PT J AU Zhang, DL Zhang, YT Yin, JJ Zhao, BL AF Zhang, DL Zhang, YT Yin, JJ Zhao, BL TI Oral administration of Crataegus flavonoids protects against ischemia/reperfusion brain damage in gerbils SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE Crataegus flavonoid; ischemia; reperfusion brain damage; natural antioxidant; nitric oxide; reactive oxygen species ID TRANSIENT CEREBRAL-ISCHEMIA; NITRIC-OXIDE SYNTHASE; RAT-BRAIN; TNF-ALPHA; IN-VIVO; REPERFUSION; HAWTHORN; INJURY; EXTRACTS; PEROXYNITRITE AB Stroke is the third leading cause of death as dementia is a main symptom of Alzheimer's disease. One of the important mechanisms in the pathogeny of stroke is free radical production during the reperfusion period, therefore the effects of a type of natural antioxidant, i.e. Crataegus flavonoids (CF), on brain ischemic insults were investigated in Mongolian gerbil stroke model. Results showed that pretreatment of the animals with CF decreased reactive oxygen species (ROS) production, thiobarbituric acid reactive substances content, and nitrite/nitrate concentration in brain homogenate, increased the brain homogenate-associated antioxidant level in a dose-dependent manner. CF pretreatment increased the amount of biologically available NO by scavenging of superoxide anion produced during reperfusion. At same time, in the process of ischemia/reperfusion brain damage, the content of nitrite/nitrate (the end product of NO) increased, and of NO detected by ESR decreased. Oral pretreatment with CF decreased the nitrite/nitrate content in the brain homogenate and increased the biologically available NO concentration in a dose-dependent manner. The increasing effect of antioxidant on NO might be due to its scavenging effect on superoxide anion, which could react with NO into peroxynitrite. iNOS was implied in delayed neuron death after brain ischemic damage and it was found that pretreatment with CF could decrease the protein level of tumor necrosis factor (TNF)-alpha and nuclear factor-kappa B (NF-kappaB), and increase the mRNA level of NOS estimated by western blotting and RT-PCR. More neurons survived and fewer cells suffered apoptosis in the hippocampal CA1 region of CF treated animal brain. These results suggest that oral administration of this antioxidant increases the antioxidant level in the brain and protects the brain against delayed cell death caused by ischemia/reperfusion injury. C1 Acad Sinica, Inst Biophys, Lab Visual Informat Proc, Ctr Brain & Cognit Sci, Beijing 100101, Peoples R China. US FDA, CFSAN, Rockville, MD 20857 USA. RP Zhao, BL (reprint author), Acad Sinica, Inst Biophys, Lab Visual Informat Proc, Ctr Brain & Cognit Sci, 15 Datun Rd, Beijing 100101, Peoples R China. EM zhaobl@sun5.ibp.ac.cn RI Yin, Jun Jie /E-5619-2014; Zhang, Deliang/F-7848-2013; OI Zhang, Deliang/0000-0001-9478-5344 NR 41 TC 62 Z9 73 U1 0 U2 11 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD JUL PY 2004 VL 90 IS 1 BP 211 EP 219 DI 10.1111/j.1471-4159.2004.02480.x PG 9 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 829SY UT WOS:000222071200020 PM 15198680 ER PT J AU Lue, TF Giuliano, F Montorsi, F Rosen, RC Andersson, KE Althof, S Christ, G Hatzichristou, D Hirsch, M Kimoto, Y Lewis, R McKenna, K MacMahon, C Morales, A Mulcahy, J Padma-Nathan, H Pryor, J de Tejada, IS Shabsigh, R Wagner, G AF Lue, Tom F. Giuliano, Francois Montorsi, Francesco Rosen, Raymond C. Andersson, Karl-Erik Althof, Stanley Christ, George Hatzichristou, Dimitrios Hirsch, Mark Kimoto, Yasasuke Lewis, Ronald McKenna, Kevin MacMahon, Chris Morales, Alvaro Mulcahy, John Padma-Nathan, Harin Pryor, John Saenz de Tejada, Inigo Shabsigh, Ridwan Wagner, Gorm TI Summary of the recommendations on sexual dysfunctions in men SO JOURNAL OF SEXUAL MEDICINE LA English DT Article DE guidelines for diagnosis and treatment of men's sexual dysfunctions; management algorithm; erectile dysfunction; premature ejaculation; retrograde ejaculation; priapism; Peryronie's disease AB Introduction. There are few published guidelines for the management of sexual dysfunctions in men and women, despite the prevalence and lack of attention to these problems. Disorders of sexual function in men include erectile dysfunction, orgasm/ejaculation disorders, priapism, and Peyronie's disease. Aim. To provide evidence-based and expert-opinion consensus guidelines for the clinical management of men's sexual dysfunctions. Methods. An International Consultation in collaboration with major urological and sexual medicine societies assembled over 200 multidisciplinary experts from 60 countries into 17 consultation committees. Committee members established the scope and objectives for each chapter. Following intensive review of available data and publications, committees developed evidence-based guidelines in each area. Main Outcome Measure. New algorithms and guidelines for assessment and treatment of men's sexual dysfunction were developed. The Oxford system of evidence-based review was systematically applied. Expert opinion was based on systematic grading of the medical literature, in addition to cultural and ethical considerations. Results. Recommendations and guidelines for men's sexual dysfunction are presented. These guidelines were developed as evidence-based, patient-centered, and multidisciplinary in focus. For the clinical assessment and diagnosis of ED, a basic evaluation was recommended for all patients, with optional and specialized testing reserved for special cases. A new treatment algorithm is proposed. This algorithm provides a clinically relevant guideline for managing ED in the large majority of men. New treatment guidelines and algorithms are provided for men's orgasm and ejaculation disorders, including premature ejaculation, retrograde and delayed ejaculation. Finally, expert opinion-based guidelines for the clinical management of priapism and Peyronie's disease are provided. Conclusions. Additional research is needed to validate and extend these guidelines. Nonetheless, this summary encompasses the recommendations concerning men's sexual dysfunctions presented at the 2nd International Consultation on Sexual Medicine in Paris, France, June 28-July 1, 2003. C1 Univ Calif San Francisco, Dept Urol, San Francisco, CA 94143 USA. Paris S Univ, Le Kremlin Bicetre, France. Univ Vita & Salute San Raffaele, Div Urol, Milan, Italy. Univ Med & Dent New Jersey, Dept Psychiat, New Brunswick, NJ USA. Lund Univ, Dept Clin Pharmacol, Lund, Sweden. Ctr Marital & Sexual Hlth, Beachwood, OH USA. Albert Einstein Coll Med, Bronx, NY 10467 USA. Aristotle Univ Thessaloniki, Dept Urol, GR-54006 Thessaloniki, Greece. US FDA, Rockville, MD 20857 USA. Spinal Injuries Ctr, Dept Urol, Lizuka, Japan. Med Coll Georgia, Dept Urol, Augusta, GA 30912 USA. Northwestern Univ, Dept Physiol, Chicago, IL 60611 USA. Australian Ctr Sexual Hlth, Sydney, NSW, Australia. Queens Univ, Dept Urol, Kingston, ON, Canada. Indiana Univ, Dept Urol, Indianapolis, IN 46204 USA. Male Clin, Beverly Hills, CA USA. Univ London, London, England. Columbia Univ, Dept Urol, New York, NY USA. Univ Copenhagen, Panum Inst, Dept Med Physiol, DK-2200 Copenhagen N, Denmark. RP Lue, TF (reprint author), Univ Calif San Francisco, Dept Urol, San Francisco, CA 94143 USA. EM Tlue@urol.ucsf.edu NR 3 TC 209 Z9 219 U1 2 U2 25 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1743-6095 J9 J SEX MED JI J. Sex. Med. PD JUL PY 2004 VL 1 IS 1 BP 6 EP 23 DI 10.1111/j.1743-6109.2004.10104.x PG 18 WC Urology & Nephrology SC Urology & Nephrology GA V43GV UT WOS:000202924500004 PM 16422979 ER PT J AU Hirsch, M Donatucci, C Glina, S Montague, D Montorsi, F Wyllie, M AF Hirsch, Mark Donatucci, Craig Glina, Sidney Montague, Drogo Montorsi, Francesco Wyllie, Michael TI Standards for clinical trials in male sexual dysfunction: Erectile dysfunction and rapid ejaculation SO JOURNAL OF SEXUAL MEDICINE LA English DT Article DE drug development; clinical pharmacology; clinical drug studies in sexual dysfunction; erectile dysfunction; premature/rapid ejaculation; outcome efficacy assessments; IIEF; daily diaries; per-event questionnaires AB Introduction. The introduction of safe and effective therapies for sexual dysfunctions depend upon appropriate clinical protocol design, study procedures, data collection and analysis. Aim. To provide recommendations/guidelines concerning state-of-the-art knowledge for standards for clinical trials in sexual dysfunction in men, particularly in the areas of erectile dysfunction and rapid ejaculation. Methods. An International Consultation in collaboration with the major urology and sexual medicine associations assembled over 200 multidisciplinary experts from 60 countries into 17 committees. Committee members established specific objectives and scopes for various male and female sexual medicine topics. The recommendations concerning state-of-the-art knowledge in the respective sexual medicine topic represent the opinion of experts from five continents developed in a process over a 2-year period. Concerning the Standards for Clinical Trials in Male Sexual Dysfunction Committee, there were six experts from four countries. Main Outcome Measure. Expert opinion was based on grading of evidence-based medical literature, widespread internal committee discussion, public presentation and debate. Results. Drug development requires a multiphased approach. Phase I studies investigate multiple-dose safety, tolerability and pharmacokinetic issues. Phase 2 programs explore dose ranging (lowest effective, maximally tolerated and toxic doses). Phase 3 trials provide the substantial evidence including drug-drug interaction data and studies in special populations. Clinical studies require validated outcome assessment instruments conducted in defined but representative patient populations. Daily diaries or per-event questionnaires are patient-reported outcomes that assist in retrospective questionnaire interpretation. A qualified biostatistician should calculate the sample power for the trial, type of statistical model and design employed, use of covariate or subgroup analyses, and calculation of effect sizes. Conclusions. More research is needed in developing standards for use in the development of clinical trials and outcomes assessment researching either erectile dysfunction or rapid ejaculation. C1 US FDA, Rockville, MD 20857 USA. Duke Univ, Med Ctr, Durham, NC USA. Albert Einstein Jewish Hosp, Sao Paulo, Brazil. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Univ Vita Salute San Raffaelle, Milan, Italy. Urodoc Ltd, Herne Bay, Kent, England. RP Hirsch, M (reprint author), US FDA, 5600 Fishers Lane, Rockville, MD 20857 USA. EM HIRSCHM@cder.fda.gov NR 4 TC 23 Z9 24 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1743-6095 J9 J SEX MED JI J. Sex. Med. PD JUL PY 2004 VL 1 IS 1 BP 87 EP 91 DI 10.1111/j.1743-6109.2004.10113.x PG 5 WC Urology & Nephrology SC Urology & Nephrology GA V43GV UT WOS:000202924500013 PM 16422988 ER PT J AU Hess, MA AF Hess, MA TI Taking things to heart SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Letter C1 US FDA, Off Execut Programs, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Hess, MA (reprint author), US FDA, Off Execut Programs, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER DIETETIC ASSOC PI CHICAGO PA 216 W JACKSON BLVD #800, CHICAGO, IL 60606-6995 USA SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD JUL PY 2004 VL 104 IS 7 BP 1073 EP 1073 DI 10.1016/j.jada.2004.05.199 PG 1 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 833DB UT WOS:000222315500012 PM 15215760 ER PT J AU Uhl, K Miller, MA Kennedy, DL AF Uhl, K Miller, MA Kennedy, DL TI Complex clinical, legal, and ethical issues of pregnant and postpartum women as subjects in clinical trials SO JOURNAL OF WOMENS HEALTH LA English DT Letter C1 US FDA, Ctr Drug Evaluat & Res, Pregnancy Labeling Team, Rockville, MD 20852 USA. US FDA, Off Womens Hlth, Rockville, MD 20857 USA. RP Uhl, K (reprint author), US FDA, Ctr Drug Evaluat & Res, Pregnancy Labeling Team, 5515 Secur Lane,HFD-020, Rockville, MD 20852 USA. EM uhlk@cder.fda.gov NR 6 TC 2 Z9 2 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1540-9996 J9 J WOMENS HEALTH JI J. Womens Health PD JUL-AUG PY 2004 VL 13 IS 6 BP 743 EP 744 DI 10.1089/jwh.2004.13.743 PG 2 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 849BV UT WOS:000223513700012 PM 15333290 ER PT J AU Westergaard, GC Chavanne, TJ Houser, L Cleveland, A Snoy, PJ Suomi, SJ Higley, JD AF Westergaard, GC Chavanne, TJ Houser, L Cleveland, A Snoy, PJ Suomi, SJ Higley, JD TI Biobehavioural correlates of hand preference in free-ranging female primates SO LATERALITY LA English DT Article ID CEREBROSPINAL-FLUID MONOAMINE; MACAQUES MACACA-MULATTA; MALE RHESUS MACAQUES; LEMUR LEMUR-CATTA; PLASMA-CORTISOL; 5-HYDROXYINDOLEACETIC ACID; AMINE METABOLITES; VIOLENT OFFENDERS; NONHUMAN-PRIMATES; FIRE SETTERS AB In this research we examined biological and behavioural correlates of handedness in a subject cohort of 41 free-ranging young female rhesus macaques (Macaca Mulatta). Specifically, we examined relationships between handedness and cerebrospinal fluid (CSF) concentrations of the monoamine metabolites 5-hydroxymcloleacetic acid (5-HIAA) and homovanillic acid (HVA), plasma concentrations of the hormones cortisol and adrenocorticotropin (ACTH), prolactin, and multiple indices of social behaviour, including proximity to other animals, grooming, submission, and aggression. Handedness was determined through systematic observation of animals reaching for food in their unrestricted home environment. We found a population-level bias for left-hand use in this cohort of young females. The frequency of right versus left hand use was positively correlated with CSF 5-HIAA, plasma cortisol concentrations, the frequency of submissive behaviour, and with the frequency of bouts in which animals received low-level aggression. The positive correlation between right versus left hand use, submissive behaviour, and received aggression found here in females contrasts with the negative correlation among these same variables that we have previously reported in rhesus males. We conclude that these results may be explicable in terms of sex-based differences in rhesus life-history patterns, and that the influence of the serotonergic system on patterns of male aggression, social behaviour, and handedness, and the associations between handedness and social behaviour found previously among males may not be generalised to female rhesus macaques. C1 LABS Virginia Inc, Div Res, Yemassee, SC 29902 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. NICHHD, Poolesville, MD USA. NIAAA, Poolesville, MD USA. RP Westergaard, GC (reprint author), LABS Virginia Inc, Div Res, 95 Castle Hall Rd,POB 557, Yemassee, SC 29902 USA. EM Gwprimate@netscape.net FU NIAAA NIH HHS [N01AA02018, N01AA42002] NR 53 TC 10 Z9 10 U1 2 U2 8 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 1357-650X J9 LATERALITY JI Laterality PD JUL PY 2004 VL 9 IS 3 BP 267 EP 285 DI 10.1080/13576500342000086 PG 19 WC Psychology, Multidisciplinary; Psychology, Experimental SC Psychology GA 839RR UT WOS:000222803100002 PM 15341426 ER PT J AU Zhang, BL Zhang, YQ Shacter, E AF Zhang, BL Zhang, YQ Shacter, E TI Rac1 inhibits apoptosis in human lymphoma cells by stimulating bad phosphorylation on Ser-75 SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID PROTEIN-KINASE PATHWAY; DEATH AGONIST BAD; RHO-GTPASES; SIGNALING PATHWAYS; SURVIVAL SIGNALS; BREAST-CANCER; ACTIVATION; RAS; AKT; MITOCHONDRIA AB The small GTPase Rac1 has emerged as an important regulator of cell survival and apoptosis, but the mechanisms involved are not completely understood. In this report, constitutively active Rac1 is shown to stimulate the phosphorylation of the Bcl-2 family member Bad, thereby suppressing drug-induced caspase activation and apoptosis in human lymphoma cells. Rac1 activation leads to human Bad phosphorylation specifically at serine-75 (corresponding to murine serine-112) both in vivo and in vitro. Inhibition of constitutive and activated Rac1-induced Bad phosphorylation by a cell-permeable competitive peptide inhibitor representing this Bad phosphorylation site sensitizes lymphoma cells to drug-induced apoptosis. The data show further that endogenous protein kinase A is a primary catalyst of cellular Bad phosphorylation in response to Rac activation, while Akt is not involved. These findings define a mechanism by which active Rac1 promotes lymphoma cell survival and inhibits apoptosis in response to cancer chemotherapy drugs. C1 US FDA, Ctr Biol Evaluat & Res, Biochem Lab, Div Therapeut Prot,Off Biotechnol Prod, Bethesda, MD 20892 USA. RP Zhang, BL (reprint author), US FDA, Ctr Biol Evaluat & Res, Biochem Lab, Div Therapeut Prot,Off Biotechnol Prod, 29 Lincoln Dr,Bldg 29A,Rm 2B-24, Bethesda, MD 20892 USA. EM baolin.zhang@fda.gov NR 46 TC 40 Z9 40 U1 1 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JUL PY 2004 VL 24 IS 14 BP 6205 EP 6214 DI 10.1128/MCB.24.14.6205-6214.2004 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 835NQ UT WOS:000222490900009 PM 15226424 ER PT J AU Dragan, YP Sargent, LM Babcock, K Kinunen, N Pitot, HC AF Dragan, YP Sargent, LM Babcock, K Kinunen, N Pitot, HC TI Alterations in specific gene expression and focal neoplastic growth during spontaneous hepatocarcinogenesis in Albumin-SV40 T antigen transgenic rats SO MOLECULAR CARCINOGENESIS LA English DT Article DE albumin-SV40 transgenic rat; insulin growth factor 2; H19 gene expression; hepatomas; c-myc ID FACTOR-II GENE; BECKWITH-WIEDEMANN-SYNDROME; RESISTANT HEPATOCYTE MODEL; IMPRINTED H19 GENE; C-MYC; HEPATOCELLULAR-CARCINOMA; LIVER CARCINOGENESIS; CHEMICAL HEPATOCARCINOGENESIS; BIALLELIC EXPRESSION; BREAST-CANCER AB Transgenic rats containing the mouse albumin promoter and enhancer directing the expression of simian virus (SV40) T antigen (T Ag) exhibited a 100% incidence of hepatic neoplasms by 24-36 wk of age. These transgenic rats exhibited expression of large T Ag and c-myc protein within focal basophilic lesions and nodules, but not in surrounding hepatocytes. At 24 wk of age, female TG+ rats exhibited a significantly greater number of lesions and a much greater percentage of the liver occupied by TG+ focal hepatic lesions than did their male TG+ littermates. Previous studies on these animals [Sargent et al., Cancer Res 1997;57:3451 -3456] demonstrate that at 12 wk of age approximately one-third of metaphases in hepatocytes exhibit a duplication of the 1q3.7-1q4.1 region of rat chromosome 1, with the smallest common region of duplication being that of 1q4.1. Duplication of the 1q3.7-1q4.3 region is also noted in many primary hepatic neoplasms resulting from the multistage model of Initiation-Promotion-Progression (IPP) [Sargent et al., Cancer Res 1996;56:2985-2991]. This region is syntenic with human 11p15.5 and mouse 7qter, which have been implicated in the development of specific neoplasms. Within the syntenic region was a cluster of imprinted genes whose expression we investigated in livers and neoplasms of TG+ rats. H 19 was expressed in almost all of the neoplasms, but not in normal adult liver cells. Igf2 expression was detected in the majority of hepatic neoplasms of female TG+ rats, but in a relatively smaller number of neoplasms of TG+ males. The expression of p57(Kip2) (Kip2), a cyclin-dependent kinase inhibitor that was also in the imprinted region, exhibited some variable increased expression predominantly in hepatic neoplasms from livers of female TG+ rats. Other imprinted genes within the imprinted gene cluster-insulin II (Ins2), Mash2 (which codes for a basic helix-loop-helix transcription factor), and Kvlqt1 (coding for a component of a potassium transport channel)-showed no consistently different expression from that seen in normal hepatocytes. Another gene, also located on the long arm of chromosome 1, that showed changes was the ribonucleotide reductase M1 subunit (Rrm1), in which an increase in its expression was found. This was seen in hepatic neoplasms of TG+ rats of both sexes compared with surrounding normal-appearing liver. Because hepatic neoplasms developing in livers of rats treated with chemical carcinogens commonly exhibit an increased expression of c-myc mRNA, expression of this gene was investigated in focal lesions and livers of TG+ rats, although c-myc was not located on chromosome 1. c-myc mRNA was increased in focal lesions, nodules, and neoplasms in both male and female TG+ rats compared with adult and surrounding liver. Immunostaining for c-myc protein demonstrated detectable levels in isolated single cells as well as focal lesions and neoplasms. Thus, the enhanced c-myc expression, common to all hepatic neoplasms in this system, coupled with enhanced expression of Igf2 in female TG+ rats, may be responsible for the increase in growth rate in hepatic neoplasms of female TG+ rats compared with that in livers of male TG+ rats and may contribute to neoplastic progression in the liver of this transgenic model. Published 2004 Wiley-Liss, Inc.(dagger) C1 Univ Wisconsin, McArdle Lab Canc Res, Sch Med, Madison, WI 53706 USA. NCTR, FDA, Jefferson, AR USA. NIOSH, Morgantown, WV USA. RP Pitot, HC (reprint author), Univ Wisconsin, McArdle Lab Canc Res, Sch Med, 1400 Univ Ave, Madison, WI 53706 USA. NR 79 TC 7 Z9 7 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD JUL PY 2004 VL 40 IS 3 BP 150 EP 159 DI 10.1002/mc.20029 PG 10 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA 836WD UT WOS:000222585800003 PM 15224347 ER PT J AU Clark, LS Harrington-Brock, K Wang, JY Sargent, L Lowry, D Reynolds, SH Moore, MM AF Clark, LS Harrington-Brock, K Wang, JY Sargent, L Lowry, D Reynolds, SH Moore, MM TI Loss of P53 heterozygosity is not responsible for the small colony thymidine kinase mutant phenotype in L5178Y mouse lymphoma cells SO MUTAGENESIS LA English DT Article ID TRIFLUOROTHYMIDINE-RESISTANT; CHROMOSOME ABERRATION; ASSAY SYSTEM; TK; LINE; GENE; MUTAGENESIS; MUTATIONS AB The mouse lymphoma L5178Y Tk(+/-) 3.7.2C assay is a well-characterized in vitro system used for the study of somatic cell mutation. It was determined that this cell line has a heterozygous mutation in exon 5 of Trp53. Based on this assumption that the cell line is heterozygous for the Trp53 gene, it was postulated that the small colony thymidine kinase (Tk) mutant phenotype may be due to a newly induced mutation/deletion in both the Trp53 and Tk1 alleles. The resultant Tk(-/-) mutants would also be Trp53(+/0) or Trp53(+/+) and would lose their ability to grow at normal rates. Subsequently, we published our evaluation of the Trp53 status in L5178Y cells. This analysis included sequencing of Trp53 exon 4 and determined that the mouse lymphoma cell line has a mutation in both of the Trp53 alleles and, therefore, no wild-type Trp53 allele in either Tk(+/-) cells or Tk(-/-) mutants. Because the cells have no wild-type Trp53, it is not possible that the small colony phenotype results from a newly induced loss of both functional Trp53 and Tk. To determine whether small colonies might, however, include the deletion of both Trp53 and Tk we evaluated, using microsatellite marker analysis, a series of small colony mutants. We also utilized in situ hybridization to determine that the Trp53 alleles are, in fact, in their normal chromosome 11 location in Tk(+/-) 3.7.2C mouse lymphoma cells. From all of these analyses we can conclude that the small colony mutant phenotype is not caused by deletion of both Trp53 and Tk1. C1 Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. Univ N Carolina, U N Carolina Curriculum Toxicol, Chapel Hill, NC USA. US EPA, Div Environm Carcinogenesis, Natl Hlth & Environm Effects Res Lab, Res Triangle Pk, NC 27711 USA. NIOSH, Toxicol & Mol Biol Branch, Morgantown, WV 26505 USA. RP Moore, MM (reprint author), Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, HFT 120,3900 NCTR Rd, Jefferson, AR 72079 USA. EM mmmoore@nctr.fda.gov NR 22 TC 5 Z9 5 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0267-8357 J9 MUTAGENESIS JI Mutagenesis PD JUL PY 2004 VL 19 IS 4 BP 263 EP 268 DI 10.1093/mutage/geh024 PG 6 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA 832MS UT WOS:000222272200002 PM 15215324 ER PT J AU Von Tungeln, LS Dobrovolsky, VN Bishop, ME Shaddock, JG Heflich, RH Beland, FA AF Von Tungeln, LS Dobrovolsky, VN Bishop, ME Shaddock, JG Heflich, RH Beland, FA TI Frequency of Tk and Hprt lymphocyte mutants and bone marrow micronuclei in mice treated neonatally with zidovudine and didanosine SO MUTAGENESIS LA English DT Article ID VIRUS REVERSE-TRANSCRIPTASE; ETHYL-N-NITROSOUREA; 3'-AZIDO-3'-DEOXYTHYMIDINE AZT; INTRACELLULAR PHOSPHORYLATION; LYMPHOBLASTOID-CELLS; MOLECULAR ANALYSIS; DNA-POLYMERASES; HIV-INFECTION; CELLULAR DNA; B6C3F1 MICE AB The nucleoside analog zidovudine (3'-azido-3'-deoxythymidine, AZT), by itself or in combination with other anti- retroviral drugs, is used perinatally to prevent mother to child transmission of human immunodeficiency virus type 1. AZT is mutagenic in vitro and mutagenic and carcinogenic when administered to neonatal mice. A previous study indicated that the anti-retroviral agent didanosine (2',3'-dideoxyinosine, ddI) potentiated the mutagenicity of AZT in the thymidine kinase (TK) gene of cultured human TK6 lymphoblastoid cells. We have evaluated whether or not ddI affects the in vivo genotoxicity of AZT by breeding C57Bl/6N/Tk(+/-) female mice with C3H/HeNMTV male mice and treating the offspring daily on postnatal days 1-8 with 200 mg/kg ddI alone or in combination with 200 mg/kg AZT. One day after the last dose, bone marrow polychromatic erythrocytes (PCEs) were obtained to assess the induction of micronuclei; 3 weeks following treatment, the induction of mutants was determined in the hypoxanthine-guanine phosphoribosyltransferase (Hprt) and Tk genes of splenic T lymphocytes from B6C3F(1)/Tk(+/-) mice. The mixture of AZT and ddI, but not ddI alone, caused a significant increase in micronucleated PCEs. When assessed 3 weeks after dosing, ddI did not induce mutations in the Hprt or Tk genes. The mixture of AZT and ddI also did not induce mutations in the Hprt gene, but did induce a significant increase in Tk mutants, similar to that observed previously with AZT alone. The induction of mutations in the Tk gene by the mixture of AZT and ddI was associated with loss of the wild-type Tk(+) allele. These data indicate that, under the conditions of this experiment, ddI is not mutagenic in neonatal B6C3F(1)/Tk(+/-) mice and that it does not potentiate the mutagenicity of AZT. C1 Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. RP Beland, FA (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, HFT-110, Jefferson, AR 72079 USA. EM fbeland@nctr.fda.gov NR 36 TC 10 Z9 10 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0267-8357 J9 MUTAGENESIS JI Mutagenesis PD JUL PY 2004 VL 19 IS 4 BP 307 EP 311 DI 10.1093/mutage/geh033 PG 5 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA 832MS UT WOS:000222272200008 PM 15215330 ER PT J AU Li, YW Che, MX Bhagat, S Ellis, KL Kucuk, O Doerge, DR Abrams, J Cher, ML Sarkar, FH AF Li, YW Che, MX Bhagat, S Ellis, KL Kucuk, O Doerge, DR Abrams, J Cher, ML Sarkar, FH TI Regulation of gene expression and inhibition of experimental prostate cancer bone metastasis by dietary genistein SO NEOPLASIA LA English DT Article DE genistein; prostate cancer; bone metastasis; microarray; gene expression ID KAPPA-B ACTIVATION; MATRIX METALLOPROTEINASES; INDUCED OSTEOCLASTOGENESIS; TUMOR INVASION; CELLS; MICE; OSTEOPROTEGERIN; GROWTH; PROLIFERATION; APOPTOSIS AB Prostate cancer frequently metastasizes to the bone, and the treatment outcome for metastatic prostate cancer has been disappointing so far. Dietary genistein, derived primarily from soy product, has been proposed to be partly responsible for the low rate of prostate cancer in Asians. Our previous studies have shown that genistein elicits pleiotropic effects on prostate cancer cells, but there are no studies documenting comprehensive gene expression profiles and antitumor effects of dietary genistein on human prostate cancer grown in human bone environment. In this study, we investigated the effects of genistein on PC3 prostate cancer cells and experimental PC3 bone tumors created by injecting PC3 cells into human bone fragments previously implanted in severe combined immunodeficient (SCID) mice (SCID human model). We found that genistein significantly inhibited PC3 bone tumor growth using both prevention and intervention strategies. By using microarray and real-time polymerase chain reaction technology, we found that genistein regulated the expression of multiple genes involved in the control of cell growth, apoptosis, and metastasis both in vitro and in vivo. For example, the expression of various metalloproteinases (MMPs) in PC3 bone tumors was inhibited by genistein treatment, whereas osteoprotegerin was upregulated. MMP immunostaining and transfection experiments also demonstrated that MMP-9 expression was inhibited in PC3 cells in vitro and PC3 bone tumors in vivo after genistein treatment. These results, particularly the in vivo results, demonstrate that dietary genistein may inhibit prostate cancer bone metastasis by regulating metastasis-related genes. Genistein may thus be a promising agent for the prevention and/or treatment of prostate cancer. C1 Wayne State Univ, Sch Med, Karmanos Canc Inst, Dept Pathol,Hudson Webber Canc Res Ctr, Detroit, MI 48201 USA. Wayne State Univ, Sch Med, Karmanos Canc Inst, Dept Urol,Hudson Webber Canc Res Ctr, Detroit, MI 48201 USA. Wayne State Univ, Sch Med, Karmanos Canc Inst, Dept Internal Med,Hudson Webber Canc Res Ctr, Detroit, MI 48201 USA. US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AK USA. RP Sarkar, FH (reprint author), Wayne State Univ, Sch Med, Karmanos Canc Inst, Dept Pathol,Hudson Webber Canc Res Ctr, 715,110 E Warren, Detroit, MI 48201 USA. EM fsarkar@med.wayne.edu FU NCI NIH HHS [R01 CA083695, CA-88028, CA83695-01A2, R01 CA088028] NR 45 TC 67 Z9 71 U1 0 U2 1 PU NEOPLASIA PRESS PI ANN ARBOR PA 1150 W MEDICAL CENTER DR, MSRB III, RM 9303, ANN ARBOR, MI 48109-0648 USA SN 1522-8002 J9 NEOPLASIA JI Neoplasia PD JUL-AUG PY 2004 VL 6 IS 4 BP 354 EP 363 DI 10.1593/neo.03478 PG 10 WC Oncology SC Oncology GA 837IZ UT WOS:000222623800007 PM 15256057 ER PT J AU Chang, JT Staffa, JA Parks, M Green, L AF Chang, JT Staffa, JA Parks, M Green, L TI Rhabdomyolysis with HMG-CoA reductase inhibitors and gemfibrozil combination therapy SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Article DE rhabdomyolysis; statins; fibrates; HMG-CoA reductase inhibitors; adverse reactions; renal failure ID AVERAGE CHOLESTEROL LEVELS; CORONARY HEART-DISEASE; SERUM UBIQUINONE; PRAVASTATIN; PREVENTION; LOVASTATIN; EVENTS; TRIAL; DRUGS; MEN AB Context Elevated total cholesterol (total-C) and low-density lipoprotein cholesterol (LDL-C) levels are established risk factors for cardiovascular disease (CVD). HMG-CoA reductase inhibitors (statins) are effective cholesterol-lowering drugs that are commonly prescribed to treat this condition. These drugs are often combined with another class of drugs, fibric acid derivatives, to lower both cholesterol and triglyceride levels. Rhabdomyolysis is a known, rare serious side effect of statin monotherapy and of statin-fibrate combination therapy. Objective To examine Food and Drug Administration's (FDA:s) postmarketing database for cases of rhabdomyolysis in relation to monotherapy and combination use and calculate reporting rates for this event. Design Domestic cases of statin- and statin/gemfibrozil-associated rhabdomyolysis were culled from FDAs database and reviewed. Rhabdomyolysis was defined by CPK greater than or equal to 10 000 IU/L, myopathic signs and symptoms and clinical diagnosis of rhabdomyolysis. Reporting rates, consisting of number of reported cases/number of prescriptions for each drug, were then calculated to determine whether the reporting of rhabdomyolysis cases was commensurate with extent of use of each statin in the population. Setting Cases were obtained from the FDA adverse event reporting system (AERS) database. Patients NA. Main Outcome Measures Number of rhabdomyolysis cases were evaluated, along with outcomes, such as renal failure, dialysis and death. Results Of 866 total reported cases, 482 (56%) were associated with monotherapy and 384 (44%) related to combination therapy. More than 80% of reported cases for each drug resulted in hospitalization for renal failure and dialysis. 80 patients expired from events related directly to rhabdomyolysis. Reporting rates for all statins, except for cerivastatin, were similar and much lower than I per 100000 prescriptions. The cerivastatin-reporting rate was much higher at 4.24/100000 prescriptions. Conclusions Rhabdomyolysis is a rare, serious side effect of statin monotherapy and of statin-fibrate combination therapy. Clinicians need to remain cognizant of this potential adverse event and discuss signs and symptoms of muscle toxicity with patients in order improve the benefits-to-risks of treating dyslipidemia with statins. Published in 2004 by John Wiley Sons, Ltd. C1 US FDA, Div Drug Risk Evaluat, Off Drug Safety, Rockville, MD 20857 USA. US FDA, Div Metab & Endocrine Drug Prod, Rockville, MD 20857 USA. RP Chang, JT (reprint author), US FDA, Div Drug Risk Evaluat, Off Drug Safety, Room 15B-18,HFD-430, Rockville, MD 20857 USA. EM changJ@cder.fda.gov NR 17 TC 95 Z9 99 U1 0 U2 3 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 JUL PY 2004 VL 13 IS 7 BP 417 EP 426 DI 10.1002/pds.977 PG 10 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 836BH UT WOS:000222529300001 PM 15269925 ER PT J AU Leighton, JK DeGeorge, J Jacobson-Kram, D MacGregor, J Mendrick, D Worobec, A AF Leighton, JK DeGeorge, J Jacobson-Kram, D MacGregor, J Mendrick, D Worobec, A TI Pharmacogenomic data submissions to the FDA: non-clinical case studies SO PHARMACOGENOMICS LA English DT Article DE biomarkers; genomic reporting requirements; good laboratory practice study sampling; toxicity signatures; voluntary genomic data submissions; (VGDS) C1 CDER FDA, Div Oncol Drug Prod, Rockville, MD 20850 USA. RP Leighton, JK (reprint author), CDER FDA, Div Oncol Drug Prod, 5600 Fishers Lane, Rockville, MD 20850 USA. EM leightonj@cder.fda.gov NR 4 TC 11 Z9 12 U1 0 U2 0 PU ASHLEY PUBLICATIONS LTD PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1462-2416 J9 PHARMACOGENOMICS JI Pharmacogenomics PD JUL PY 2004 VL 5 IS 5 BP 507 EP 511 DI 10.1517/14622416.5.5.507 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 839LT UT WOS:000222787300011 PM 15212587 ER PT J AU Ruano, G Collins, JM Dorner, AJ Wang, SJ Guerciolini, R Huang, SM AF Ruano, G Collins, JM Dorner, AJ Wang, SJ Guerciolini, R Huang, SM TI Pharmacogenomic data submissions to the FDA: clinical pharmacology case studies SO PHARMACOGENOMICS LA English DT Article DE clinical pharmacology; DNA variants; gene expression; genomic data submission; microarray; pharmacogenetics; pharmacogenomics ID REGULATORY DECISION-MAKING; DRUG DEVELOPMENT C1 Genomas LLC, New Haven, CT USA. George Washington Univ, Dept Biochem & Mol Biol, Washington, DC USA. Ctr Drug Evaluat & Res, Off Clin Pharmacol & Biopharmaceut, Rockville, MD 20850 USA. RP Huang, SM (reprint author), Genomas LLC, New Haven, CT USA. EM huangs@cder.fda.gov NR 4 TC 15 Z9 18 U1 0 U2 0 PU ASHLEY PUBLICATIONS LTD PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1462-2416 J9 PHARMACOGENOMICS JI Pharmacogenomics PD JUL PY 2004 VL 5 IS 5 BP 513 EP 517 DI 10.1517/14622416.5.5.513 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 839LT UT WOS:000222787300012 PM 15212588 ER PT J AU Okosun, IS Chandra, KMD Boev, A Boltri, JM Choi, ST Parish, DC Dever, GEA AF Okosun, IS Chandra, KMD Boev, A Boltri, JM Choi, ST Parish, DC Dever, GEA TI Abdominal adiposity in US adults: prevalence and trends, 1960-2000 SO PREVENTIVE MEDICINE LA English DT Article DE abdominal obesity; race; obesity trends ID INSULIN-RESISTANCE SYNDROME; VISCERAL FAT ACCUMULATION; CORONARY-HEART-DISEASE; UNITED-STATES; CARDIORESPIRATORY FITNESS; CARDIOVASCULAR-DISEASE; NATIONAL-HEALTH; ENERGY-INTAKE; RISK-FACTORS; WEIGHT-LOSS AB Background. There is a large body of epidemiologic evidence linking abdominal obesity to cardiovascular diseases. Abdominal adiposity is an important component of insulin resistance syndrome. Objective. To investigate prevalence and trends in abdominal obesity in U.S. adult population. Design, setting/participants. Nationally representative cross-sectional surveys with an in-person interview and measurement of waist circumference; 23,654 adults aged 20-79 years were examined using data from U.S. National Surveys of 1960-1962 [the first National Health Examination Survey (NHES I)], 1988-1994 [the third National Health and Nutrition Examination Survey (NHANES 111)] and 19992000 [National Health and Nutrition Examination Survey (NHANES 1999-2000)]. Abdominal obesity was defined as waist circumference greater than or equal to102 cm (>40 in.) in men and greater than or equal to88 cm (>35 in.) in women. Results. There was a gradient of increasing waist circumference over the three periods of 1960-1962, 1988-1994 and 1999-2000 in both men and women. In men, the mean waist circumferences were 89,95 and 99 cm for 1960-1962,1988-1994 and 1999-2000, respectively. The corresponding values in women were 77, 92 and 94 cm, respectively. A gradient of increasing prevalence of abdominal obesity from 1960 to 2000 was also observed in men and women. In men, the overall age-adjusted prevalences of abdominal obesity were 12.7%, 29% and 38.3% in 1960-1962, 1988-1994 and 1999-2000, respectively. In women, the analogous values were 19.4%, 38.8% and 59.9%, respectively. Similar trends of increasing waist circumference and abdominal obesity were observed in normal weight, underweight and obese subjects defined using body mass index (BMI). Trends of increasing abdominal obesity with increasing BMI over the three time periods were also observed. Conclusions. The increase in the prevalence of abdominal obesity in the United States between 1960-1962 and 1999-2000 has ominous public health implications across entire population, particularly among normal weight subjects. There is an urgent need to describe a public health strategy for early identification of abdominal obesity. Primary prevention of obesity, including abdominal obesity, should be a major public health priority in the United States. (C) 2004 The Institute For Cancer Prevention and Elsevier Inc. All rights reserved. C1 Mercer Univ, Sch Med, Dept Community Med, Macon, GA 31207 USA. Mercer Univ, Sch Med, Dept Internal Med, Macon, GA 31201 USA. Mercer Univ, Sch Med, Dept Family Med, Macon, GA 31207 USA. US FDA, Ctr Devices & Radiol Hlth, Staff Coll Off Hlth, Gaithersburg, MD 20877 USA. US FDA, Ctr Devices & Radiol Hlth, Ind Program, Gaithersburg, MD 20877 USA. RP Okosun, IS (reprint author), Mercer Univ, Sch Med, Dept Community Med, 1550 Coll St, Macon, GA 31207 USA. EM okosun_i@mercer.edu NR 58 TC 90 Z9 93 U1 0 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-7435 J9 PREV MED JI Prev. Med. PD JUL PY 2004 VL 39 IS 1 BP 197 EP 206 DI 10.1016/j.ypmed.2004.01.023 PG 10 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 834FR UT WOS:000222397500024 PM 15208003 ER PT J AU Spelic, DC Kaczmarek, RV Suleiman, OH AF Spelic, DC Kaczmarek, RV Suleiman, OH TI Nationwide evaluation of X-ray trends survey of abdomen and lumbosacral spine radiography SO RADIOLOGY LA English DT Article DE abdomen, radiography; dosimetry; radiations, exposure to patients and personnel; radiations, measurement; screens and films; special reports; spine, radiograph ID FACILITIES AB Results of the 1995 Nationwide Evaluation of X-ray Trends (NEXT) survey of facilities that perform diagnostic radiographic examinations of the abdomen and lumbosacral spine were compared with those of previous NEXT surveys conducted in 1987 and 1989. A clinically validated radiographic phantom was used in the 1995 survey to capture data about radiation exposure and image quality. Additional data were obtained regarding clinical techniques, facility workloads, x-ray beam quality, film processing quality, and darkroom fog. Mean skin-entrance. air kerma for the abdomen examination dropped from 3.2 mGy (in 1987) to 2.8 mGy at hospitals and from 3.4 mGy (in 1989) to 3.0 mGy at nonhospital facilities. Mean skin-entrance air kerma also decreased for the lumbosacral spine examination from 3.7 mGy (in 1987) to 3.3 mGy at hospitals and from 3.8 mGy (in 1989) to 3.2 mGy at nonhospital facilities. The quality of film processing improved, although 58 (18.3%) of 317 surveyed facilities did not meet the Mammography Quality Standards Act standard for film processing quality, compared with 185 (5.9%) of 3,120 mammography facilities inspected in 1995. Finally, 181 (58.0%) of 312 surveyed facilities had darkroom fog levels greater than the Mammography Quality Standards Act standard, compared with 1,426 (16.6%) of 8,605 mammography facilities inspected in 1995. C1 US FDA, Ctr Devices & Radiol Hlth, Div Mammog Qual, Rockville, MD 20850 USA. US FDA, Radiat Programs, Rockville, MD 20850 USA. RP Spelic, DC (reprint author), US FDA, Ctr Devices & Radiol Hlth, Div Mammog Qual, 1350 Piccard Dr, HFZ-240, Rockville, MD 20850 USA. EM david.spelic@fda.hhs.gov NR 20 TC 8 Z9 8 U1 0 U2 1 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 JUL PY 2004 VL 232 IS 1 BP 115 EP 125 DI 10.1148/radiol.2321020397 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 830YY UT WOS:000222161300015 PM 15220497 ER PT J AU Caporaso, N Marti, GE Goldin, L AF Caporaso, N Marti, GE Goldin, L TI Perspectives on familial chronic lymphocytic leukemia: Genes and the environment SO SEMINARS IN HEMATOLOGY LA English DT Article ID B-CLL; WALDENSTROMS-MACROGLOBULINEMIA; PERIPHERAL-BLOOD; CANCER INCIDENCE; LINKAGE ANALYSIS; ATM MUTATIONS; ANTICIPATION; EXPRESSION; LYMPHOMA; EXPOSURE C1 NCI, Div Canc epidemiol & Genet, Genet Epidemiol Branch, Bethesda, MD 20892 USA. Fed Drug Adm, Div Cell & Gene Therapies, Lab Med & Mol Genet, Flow & Image Cytometry Sect, Bethesda, MD USA. RP Caporaso, N (reprint author), NCI, Div Canc epidemiol & Genet, Genet Epidemiol Branch, EPS 7116,6120 Execut Blvd, Bethesda, MD 20892 USA. NR 62 TC 17 Z9 19 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0037-1963 J9 SEMIN HEMATOL JI Semin. Hematol. PD JUL PY 2004 VL 41 IS 3 BP 201 EP 206 DI 10.1053/j.seminhematol.2004.05.002 PG 6 WC Hematology SC Hematology GA 841BG UT WOS:000222903700004 PM 15269880 ER PT J AU Colman, JR Dechraoui, MYB Dickey, RW Ramsdell, JS AF Colman, JR Dechraoui, MYB Dickey, RW Ramsdell, JS TI Characterization of the developmental toxicity of Caribbean ciguatoxins in finfish embryos SO TOXICON LA English DT Article DE finfish; ciguatoxins; Japanese medaka ID BARRACUDA SPHYRAENA-BARRACUDA; CIGUATERA; FISH; BREVETOXIN; NEUROTOXINS; INHIBITION; GAMBIEROL; SURVIVAL; BIOASSAY; CHANNEL AB Since oviparous fishes mobilize fat stores to produce eggs, we investigated the potential for deposition of gonadal ciguatoxins to the oil laden yolk sacs which nourish developing embryos, and characterized the effects of these toxins on finfish development. Results showed that ciguatoxins are more concentrated in the egg mass (0.18 ng/g) of a toxic fish than in the muscle (< 0.04 ng/g). We used a microinjection technique in a Japanese medaka (Oryzias latipes) developmental fish model to mimic the maternal route of toxin exposure to finfish embryos. We describe the developmental effects of two preparations isolated from Caribbean great barracuda (Sphyraena barracuda): a highly purified toxin (C-CTX-1), and ciguatoxins extracted from the flesh of a toxic fish. C-CTX-1 induced a significant decrease in heart rate after four days, which did not persist with further development. Crude extracts from ciguatoxic fish flesh induced hyperkinetic twitching and severe spinal deformities. These effects were observed in embryos receiving as little as 5 pg/egg, and were consistently found in embryos receiving doses exceeding 10 pg/egg. The occurrence of twitching and spinal deformities increased in both frequency and severity with dose. Larvae suffering from spinal abnormalities were unable to orient themselves, and could not feed, resulting in mortality. The greater distribution of toxin to eggs as compared to flesh suggests that fish with low to moderate (0.5 ppb) flesh toxin levels would maternally transfer detrimental amounts of ciguatoxins to their offspring. Published by Elsevier Ltd. C1 NOAA, Natl Ocean Serv, Marine Biotoxins Program, Ctr Coastal Environm Hlth & Biomol Res, Charleston, SC 29412 USA. Coll Charleston, Grad Program Marine Biol, Charleston, SC 29401 USA. US FDA, Chem Hazards Res Unit, Gulf Coast Seafood Lab, Dauphin Isl, AL USA. RP Ramsdell, JS (reprint author), NOAA, Natl Ocean Serv, Marine Biotoxins Program, Ctr Coastal Environm Hlth & Biomol Res, Charleston, SC 29412 USA. EM john.ramsdell@noaa.gov NR 34 TC 16 Z9 21 U1 3 U2 10 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 2004 VL 44 IS 1 BP 59 EP 66 DI 10.1016/j.toxicon.2004.04.007 PG 8 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 838LI UT WOS:000222714400007 PM 15225563 ER PT J AU Orton, SL Leparc, GF Rossmann, S Lewis, RM AF Orton, SL Leparc, GF Rossmann, S Lewis, RM TI Particulate matter phenomenon: adverse event data and the effect of leukofiltration SO TRANSFUSION LA English DT Article ID RED-BLOOD-CELLS AB BACKGROUND: In February 2002, a multiorganizational task force investigated blood center reports of unusual particulate matter (PM) visible in packed red blood cells (RBC). A cohort study assessed increase in adverse events (AEs) related to this phenomenon, as well as the effect of post-leukofiltration (LF) on PM. METHODS: Two blood centers assessed AEs in patients transfused with RBCs having visible PM (classified as normal by-products of RBC preparation), PM RBCs subsequently LF, or RBCs without visible PM, and the effect of LF on PM removal. RESULTS: There was no difference in AEs in patients transfused with PM RBCs with or without LF compared to patients transfused with RBCs without visible PM. Subsequently filtered PM RBCs had acceptable residual WBC counts and median platelet removal of 92%. CONCLUSION: Transfusion of RBCs with visible PM or RBCs subsequently LF does not appear to increase the risk of an AE. LF use on PM RBCs results in the PM removal without adversely affecting filter performance. The lack of evidence of an increase in AE reports does not mean that there is no effect, and there may be a baseline AE rate attributable to PM which has not been thoroughly researched. C1 US FDA, Div Blood Applicat, CBER, OBRR, Rockville, MD 20857 USA. RP Orton, SL (reprint author), US FDA, Div Blood Applicat, CBER, OBRR, Rockville, MD 20857 USA. EM Orton@cber.fda.gov NR 10 TC 2 Z9 2 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD JUL PY 2004 VL 44 IS 7 BP 973 EP 976 DI 10.1111/j.1537-2995.2004.04004.x PG 4 WC Hematology SC Hematology GA 832YF UT WOS:000222302900005 PM 15225235 ER PT J AU Holness, L Knippen, MA Simmons, L Lachenbruch, PA AF Holness, L Knippen, MA Simmons, L Lachenbruch, PA TI Fatalities caused by TRALI SO TRANSFUSION MEDICINE REVIEWS LA English DT Review ID ACUTE LUNG INJURY; TRANSFUSION; PLASMA AB This article includes a retrospective review of fatalities caused by transfusion-related acute lung injury (TRALI) over a 5-year period (from 1997 to 2002) that were reported to the Center for Biologics Evaluation and Research involving 58 recipient deaths and the corresponding 63 blood component donors. Descriptive statistics are presented. Recipient characteristics include age, sex, and admitting diagnosis. Cardiovascular disease, pulmonary disorders, and cancer were the most frequent diagnoses of transfusion recipients. Reported deaths did not appear to be associated with age, sex, reason for transfusion, or transfusion component. Implicated blood component(s) and clinical symptoms at the time of reaction were recorded. Fresh frozen plasma was implicated in one half of the cases, whereas red blood cells played a role in approximately one third. The clinical characteristics described most often in TRALI reports included shortness of breath, frothy sputum, pulmonary infiltrates, and hypoxia. Donor variables included age, sex, parity, and laboratory tests for antibodies to HLA and/or antigranulocyte antibodies. Laboratory tests showed HLA antibodies and/or antigranulocyte antibodies were positive in the majority of donors tested. More data are needed to better describe the role of antibodies in these reactions. Greater awareness is crucial for the practitioner to be alert for signs and symptoms of TRALI and to be aware of the necessary steps in treatment. (C) 2004 Elsevier Inc. All rights reserved. C1 US FDA, Off Blood Res & Review, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. US FDA, Off Compliance & Biol Qual, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. US FDA, Off Biostat & Epidemiol, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Holness, L (reprint author), US FDA, Off Blood Res & Review, Ctr Biol Evaluat & Res, HFM-375,1401 Rockville Pike, Rockville, MD 20852 USA. EM Holness@cber.fda.gov NR 16 TC 205 Z9 211 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0887-7963 J9 TRANSFUS MED REV JI Transf. Med. Rev. PD JUL PY 2004 VL 18 IS 3 BP 184 EP 188 DI 10.1016/j.tmrv.2004.03.004 PG 5 WC Hematology SC Hematology GA 840NB UT WOS:000222864600004 PM 15248168 ER PT J AU Petricoin, EF Ornstein, DK Liotta, LA AF Petricoin, EF Ornstein, DK Liotta, LA TI Clinical proteomics: applications for prostate cancer biomarker discovery and detection SO UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS LA English DT Article; Proceedings Paper CT Seminar on Chemoprevention of Prostate Cancer CY MAR 05, 2004 CL Reston, VA DE protein microarray; mass spectrometry; diagnostics; biomarkers; proteomics; pattern recognition ID MOLECULAR WEIGHT PROTEINS; MASS-SPECTROMETRY; OVARIAN-CANCER; SERUM; IDENTIFICATION; PATTERNS; ANTIGEN; DISEASE; TRIAL AB The science of proteomics comprises much more than simply generating lists of proteins that change in expression as a cause of or consequence of pathophysiology. The goal of proteomics should be to characterize the information flow through the intercellular protein circuitry that communicates with the extracellular microenvironment and then ultimately to the serum/plasma macroenvironment. Serum proteomic pattern diagnostics is a new type of proteomic concept in which patterns of ion signatures generated from high dimensional mass spectrometry data are used as diagnostic classifiers. This recent approach has exciting potential for clinical utility of diagnostic patterns because low molecular weight metabolites, peptides, and protein fragments may have higher accuracy than traditional biomarkers of cancer detection. Intriguingly, we now have discovered that this diagnostic information exists in a bound state, complexed with circulating highly abundant carrier proteins. These diagnostic fragments may one day be harvested by circulating nanoparticles, designed to absorb, enrich, and amplify the repertoire of diagnostic biomarkers generated-even at the critical, initial stages of carcinogenesis. (C) 2004 Elsevier Inc. All rights reserved. C1 US FDA, Ctr Biol Evaluat & Res, NCI Clin Proteom Program, Off Cell & Gene Therapies, Bethesda, MD 20892 USA. Univ Calif Irvine, Dept Urol, Irvine, CA USA. US FDA, Pathol Lab, Clin Proteom Program, Ctr Canc Res,NCI,NIH, Bethesda, MD 20892 USA. RP Petricoin, EF (reprint author), US FDA, Ctr Biol Evaluat & Res, NCI Clin Proteom Program, Off Cell & Gene Therapies, Bldg 29A,Room 2D12,8800 Rockville Pike, Bethesda, MD 20892 USA. EM petricoin@cber.fda.gov NR 33 TC 48 Z9 56 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1078-1439 J9 UROL ONCOL-SEMIN ORI JI Urol. Oncol.-Semin. Orig. Investig. PD JUL-AUG PY 2004 VL 22 IS 4 BP 322 EP 328 DI 10.1016/j.urolonc.2004.04.011 PG 7 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA 847MB UT WOS:000223395800009 PM 15283891 ER PT J AU Twaddle, NC Churchwell, MI McDaniel, LP Doerge, DR AF Twaddle, NC Churchwell, MI McDaniel, LP Doerge, DR TI Autoclave sterilization produces acrylamide in rodent diets: Implications for toxicity testing SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE acrylamide; glycidamide; DNA adducts; toxicokinetics; mass spectrometry ID HEMOGLOBIN ADDUCTS; HEATED FOODSTUFFS; MAILLARD REACTION; MICE; ACRYLONITRILE; GLYCIDAMIDE; METABOLISM; CARCINOGEN; EXPOSURE; WORKERS AB Acrylamide (AA) is a neurotoxic and carcinogenic contaminant that is formed during the cooking of starchy foods. Assessment of human risks from toxicants is routinely performed using laboratory rodents, and such testing requires careful control of unintended exposures, particularly through the diet. This study describes an analytical method based on liquid chromatography with electrospray tandem mass spectrometry that was used to measure endogenous AA in rodent diets and to survey a number of commercial products for contamination. Method sensitivity permitted accurate quantification of endogenous levels of AA in raw diets below 20 ppb. Autoclaving a standard rodent diet (NIH-31) increased the AA content 14-fold, from 17 to 240 ppb. A nutritionally equivalent diet that was sterilized by irradiation was found to contain similar to10 ppb of AA (NIH-31IR). A toxicokinetic study of AA and its epoxide metabolite, glycidamide, was performed by switching mice from NIH-31IR to the autoclaved diet for a 30 min feeding period (average AA dose administered was 4.5 mug/kg of body weight). The concentrations of AA and glycidamide were measured in serum collected at various times. The elimination half-lives and the areas under the respective concentration-time curves were similar for AA and glycidamide. Mice maintained on autoclaved NIH-31 diet, but otherwise untreated, showed elevated steady state levels of a glycidamide-derived DNA adduct in liver relative to mice maintained on the irradiated diet. This study demonstrates that a heat sterilization procedure used in laboratory animal husbandry (i.e., autoclaving) can lead to the formation of significant levels of AA in basal diets used for toxicity testing. AA in rodent diets is bioavailable, is distributed to tissues, and is metabolically activated to a genotoxic metabolite, which produces quantifiable cumulative DNA damage. Although the contribution of endogenous AA to the incidence of tumors in multiple organs of rodents otherwise untreated in chronic carcinogenicity bioassays (i.e., control groups) is not known, the reduction of endogenous AA through the use of a suitable irradiated diet was deemed to be critical for ongoing studies of AA carcinogenicity and neurotoxicity. C1 US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Doerge, DR (reprint author), US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM ddoerge@nctr.fda.gov NR 17 TC 35 Z9 35 U1 1 U2 9 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0021-8561 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD JUN 30 PY 2004 VL 52 IS 13 BP 4344 EP 4349 DI 10.1021/jf0497657 PG 6 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 832DJ UT WOS:000222247100045 PM 15212490 ER PT J AU Jessouroun, E da Silveira, IFB Larangeira, AP Pereira, S Fernandes, SA Rabinovitch, L Frasch, CE Castro-Faria-Neto, HC Bozza, PT AF Jessouroun, E da Silveira, IFB Larangeira, AP Pereira, S Fernandes, SA Rabinovitch, L Frasch, CE Castro-Faria-Neto, HC Bozza, PT TI Outer membrane vesicles (OMVs) and detoxified lipooligosaccharide (dLOS) obtained from Brazilian prevalent N-meningitidis serogroup B strains protect mice against homologous and heterologous meningococcal infection and septic shock SO VACCINE LA English DT Article DE N. meningitidis vaccines; outer membrane vesicles; cytokines ID NEISSERIA-MENINGITIDIS; IMMUNE-RESPONSE; BACTERICIDAL ANTIBODIES; VACCINE; LIPOPOLYSACCHARIDE; ADJUVANTS; ENDOTOXIN; DISEASE; IMMUNIZATION; EXPRESSION AB Neisseria meningitidis (N. meningitidis) is a serious bacterial pathogen that causes life-threatening invasive bacterial infections especially in children below 2 years of age, teenagers and young adults. We have investigated the protective potential of outer membrane vesicles (OMVs) and detoxified lipooligosaccharide (dLOS) obtained from Brazilian prevalent N. meningitidis serogroup B strains. Swiss mice were immunized with different combinations of OMV and dLOS from N. meningitidis serogroup B strains compared to a reference vaccine (VA-MENGOC-BC(R), Cuba). The OMVs + dLOS from Brazilian prevalent strains induced higher bactericidal antibody titers against homologous and heterologous target strains and stronger inhibition of thrombocytopenia as compared to the reference vaccine. When the challenge was performed with the B strain, all immunogens tested showed similar survival rates (80%) significantly higher than the control group. Bacterial clearance against the group B strain was comparable for animals immunized with the tested immunogen and the reference vaccine. Inclusion of dLOS from the B strain with the OMV, induced a similar clearance of C strain bacteria as compared to VA-MENGOC-BC(R). The immunogens, as well as the reference vaccine drastically inhibited increases in TNF-alpha and IL-6 plasma levels after challenge. In conclusion, the OMV/dLOS formulation obtained from Brazilian prevalent strains of N. meningitidis has a remarkable performance protecting mice against the lethal effects of meningococcal challenge showing a good potential as a vaccine and should be considered for clinical evaluation. (C) 2004 Elsevier Ltd. All rights reserved. C1 Fiocruz MS, Lab Tecnol Bacterianas, Dept Desenvolvimento Tecnol, BR-21045900 Rio De Janeiro, RJ, Brazil. Fiocruz MS, Dept Fisiol & Farmacodinam, Lab Imunofarmacol, BR-21045900 Rio De Janeiro, RJ, Brazil. Fiocruz MS, Inst Oswaldo Cruz, Dept Bacteriol, BR-21045900 Rio De Janeiro, RJ, Brazil. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. RP Jessouroun, E (reprint author), Fiocruz MS, Lab Tecnol Bacterianas, Dept Desenvolvimento Tecnol, BR-21045900 Rio De Janeiro, RJ, Brazil. EM ellen@bio.fiocruz.br RI Rabinovitch, Leon/F-1053-2013; OI Bozza, Patricia/0000-0001-8349-9529 NR 41 TC 9 Z9 9 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD JUN 30 PY 2004 VL 22 IS 20 BP 2617 EP 2625 DI 10.1016/j.vaccine.2003.12.009 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 834LQ UT WOS:000222413000014 PM 15193387 ER PT J AU Kaplan, AV Baim, DS Smith, JJ Feigal, DA Simons, M Jefferys, D Fogarty, TJ Kuntz, RE Leon, MB AF Kaplan, AV Baim, DS Smith, JJ Feigal, DA Simons, M Jefferys, D Fogarty, TJ Kuntz, RE Leon, MB TI Medical device development - From prototype to regulatory approval SO CIRCULATION LA English DT Article; Proceedings Paper CT Dartmouth Drug and Device Development Symposium CY OCT 30-31, 2003 CL Woodstock, VT ID INTERVENTION C1 Dartmouth Hitchcock Med Ctr, Cardiol Sect, Dartmouth Med Sch, Lebanon, NH 03756 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Stanford Univ, Dept Surg, Stanford, CA 94305 USA. Lenox Hill Heart & Vasc Inst, New York, NY USA. US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Kaplan, AV (reprint author), Dartmouth Hitchcock Med Ctr, Cardiol Sect, Dartmouth Med Sch, 1 Med Ctr Dr, Lebanon, NH 03756 USA. EM aaron.v.kaplan@hitchcock.org RI Simons, Michael/G-8553-2014 OI Simons, Michael/0000-0003-0348-7734 NR 5 TC 64 Z9 67 U1 1 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JUN 29 PY 2004 VL 109 IS 25 BP 3068 EP 3072 DI 10.1161/01.CIR.0000134695.65733.64 PG 5 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 833GY UT WOS:000222326300003 PM 15226221 ER PT J AU Mehran, R Leon, MB Feigal, DA Jefferys, D Simons, M Chronos, N Fogarty, TJ Kuntz, RE Baim, DS Kaplan, AV AF Mehran, R Leon, MB Feigal, DA Jefferys, D Simons, M Chronos, N Fogarty, TJ Kuntz, RE Baim, DS Kaplan, AV TI Post-market approval surveillance - A call for a more integrated and comprehensive approach SO CIRCULATION LA English DT Article; Proceedings Paper CT Dartmouth Drug and Device Development Symposium CY OCT 30-31, 2003 CL Woodstock, VT ID REVASCULARIZATION; STENTS C1 Dartmouth Hitchcock Med Ctr, Dartmouth Med Sch, Cardiol Sect, Lebanon, NH 03756 USA. Lenox Hill Heart & Vasc Inst, New York, NY USA. Amer Cardiovasc Res Inst, Atlanta, GA USA. Stanford Univ, Dept Surg, Stanford, CA 94305 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Kaplan, AV (reprint author), Dartmouth Hitchcock Med Ctr, Dartmouth Med Sch, Cardiol Sect, 1 Med Ctr Dr, Lebanon, NH 03756 USA. EM aaron.v.kaplan@hitchcock.org RI Simons, Michael/G-8553-2014 OI Simons, Michael/0000-0003-0348-7734 NR 12 TC 19 Z9 19 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JUN 29 PY 2004 VL 109 IS 25 BP 3073 EP 3077 DI 10.1161/01.CIR.0000134694.78653.B6 PG 5 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 833GY UT WOS:000222326300004 PM 15226222 ER PT J AU Rathbone, MJ Martinez, M AF Rathbone, MJ Martinez, M TI Veterinary drug delivery: Part VI - Preface SO ADVANCED DRUG DELIVERY REVIEWS LA English DT Editorial Material ID BIOPHARMACEUTICS CLASSIFICATION-SYSTEM; CHALLENGES; TABLETS; TASTE C1 InterAg, Hamilton, New Zealand. Food & Drug Adm, Ctr Vet Med, Rockville, MD 20855 USA. RP Rathbone, MJ (reprint author), InterAg, POB 20055,558 Te Rapa Rd, Hamilton, New Zealand. EM mjr@interag.co.nz; marilyn.martinez@fda.hhs.gov NR 16 TC 1 Z9 1 U1 1 U2 3 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 JUN 23 PY 2004 VL 56 IS 10 BP 1339 EP 1344 DI 10.1016/j.addr.2004.04.001 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 832QB UT WOS:000222280900001 PM 15191785 ER PT J AU Yan, SS Gilbert, JM AF Yan, SS Gilbert, JM TI Antimicrobial drug delivery in food animals and microbial food safety concerns: an overview of in vitro and in vivo factors potentially affecting the animal gut microflora SO ADVANCED DRUG DELIVERY REVIEWS LA English DT Review DE antimicrobial agent; activity; in vitro and in vivo; microflora; gastrointestinal tract; food animals; antimicrobial resistance ID ESCHERICHIA-COLI O157-H7; BETA-LACTAM ANTIBIOTICS; PENICILLIN-BINDING PROTEINS; MINIMAL INHIBITORY CONCENTRATIONS; MUTANT PREVENTION CONCENTRATION; INTESTINAL EPITHELIAL-CELLS; BORDER MEMBRANE-VESICLES; GRAM-POSITIVE COCCI; CAMPYLOBACTER-JEJUNI; GASTROINTESTINAL-TRACT AB This review provides an overview of considerations particular to the delivery of antimicrobial agents to food animals. Antimicrobial drugs are used in food animals for a variety of purposes. These drugs may have therapeutic effects against disease agents, or may cause changes in the structure and/or function of systems within the target animal. Routes of administration, quantity, duration, and potency of an antimicrobial drug are all important factors affecting their action(s) and success. Not only might targeted pathogens be affected, but also bacteria residing in (or on) the treated food animals, especially in the intestines (gastrointestinal tract microflora). Resistance to antimicrobial agents can occur through a number of mechanisms. The extent to which resistance develops is greatly affected by the amount of drug [or its metabolite(s)] a bacterium is exposed to, the duration of exposure, and the interaction between an individual antimicrobial agent and a particular bacterium. The impact of antimicrobial agents on the emergence of resistance in vitro and in vivo may not readily correlate. (C) 2004 Elsevier B.V. All rights reserved. C1 US FDA, Ctr Vet Med, Div Human Food Safety, Rockville, MD 20850 USA. RP Gilbert, JM (reprint author), US FDA, Ctr Vet Med, Div Human Food Safety, 7500 Standish Pl,HFV-150, Rockville, MD 20850 USA. EM jgilbert@cvm.fda.gov NR 198 TC 23 Z9 23 U1 0 U2 4 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 JUN 23 PY 2004 VL 56 IS 10 BP 1497 EP 1521 DI 10.1016/j.addr.2004.02.010 PG 25 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 832QB UT WOS:000222280900011 PM 15191795 ER PT J AU Wuilloud, JCA Wuilloud, RG Vonderheide, AP Caruso, JA AF Wuilloud, JCA Wuilloud, RG Vonderheide, AP Caruso, JA TI Gas chromatography/plasma spectrometry - an important analytical tool for elemental speciation studies SO SPECTROCHIMICA ACTA PART B-ATOMIC SPECTROSCOPY LA English DT Review DE review; gas chromatography; plasma spectrometry; ICP; MIP; glow discharge; speciation ID INDUCTIVELY-COUPLED PLASMA; MICROWAVE-INDUCED PLASMA; ATOMIC-EMISSION-SPECTROMETRY; GC-ICP-MS; SOLID-PHASE MICROEXTRACTION; FLIGHT MASS-SPECTROMETRY; ISOTOPE-RATIO MEASUREMENTS; GLOW-DISCHARGE DETECTOR; IN-SITU ETHYLATION; ALKYL DERIVATIZATION METHODS AB In this review, a full discussion and update of the state-of-the-art of gas chromatography (GC) coupled to all known plasma spectrometers is presented. A brief introductive discussion of the advantages and disadvantages of GC-plasma interfaces, as well as types of plasmas and mass spectrometers, is given. The plasma-based techniques covered include inductively coupled plasma mass spectrometry (ICP-MS) microwave-induced plasma optical emission spectrometry (MIP-OES), and inductively coupled plasma optical emission spectrometry (ICP-OES). Also, different variants of plasma sources, such as low power plasmas and glow discharge (GD) sources, are described and compared with respect to their capabilities in elemental speciation. Recent advances and alternative mass analyzers (collision/reaction cell; time-of-flight; double-focusing sector field) are also mentioned. Different aspects of the GC-plasma coupling are discussed with particular attention to the applications of these hyphenated techniques to the analysis of elemental species. Additionally, classical and modem sample preparation methods, including extraction and/or preconcentration and derivatization reactions, are presented and evaluated. (C) 2004 Elsevier B.V. All rights reserved. C1 Univ Cincinnati, Dept Chem, Cincinnati, OH 45221 USA. US FDA, Forens Chem Ctr, Cincinnati, OH 45237 USA. RP Caruso, JA (reprint author), Univ Cincinnati, Dept Chem, POB 0172, Cincinnati, OH 45221 USA. EM joseph.caruso@uc.edu RI Wuilloud, Rodolfo/N-6821-2014 OI Wuilloud, Rodolfo/0000-0002-2962-7718 NR 187 TC 59 Z9 65 U1 2 U2 36 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0584-8547 J9 SPECTROCHIM ACTA B JI Spectroc. Acta Pt. B-Atom. Spectr. PD JUN 18 PY 2004 VL 59 IS 6 BP 755 EP 792 DI 10.1016/j.sab.2004.03.009 PG 38 WC Spectroscopy SC Spectroscopy GA 834TL UT WOS:000222433700001 ER PT J AU Bross, PF Kane, R Farrell, AT Abraham, S Benson, K Brower, ME Bradley, S Gobburu, JV Goheer, A Lee, SL Leighton, J Liang, CY Lostritto, RT McGuinn, WD Morse, DE Rahman, A Rosario, LA Verbois, SL Williams, G Wang, YC Pazdur, R AF Bross, PF Kane, R Farrell, AT Abraham, S Benson, K Brower, ME Bradley, S Gobburu, JV Goheer, A Lee, SL Leighton, J Liang, CY Lostritto, RT McGuinn, WD Morse, DE Rahman, A Rosario, LA Verbois, SL Williams, G Wang, YC Pazdur, R TI Approval summary for bortezomib for injection in the treatment of multiple myeloma SO CLINICAL CANCER RESEARCH LA English DT Article ID SOUTHWEST-ONCOLOGY-GROUP; NF-KAPPA-B; STEM-CELL TRANSPLANTATION; COMBINATION CHEMOTHERAPY; AUTOLOGOUS TRANSPLANTATION; INHIBITOR PS-341; PLUS PREDNISONE; 20S PROTEASOME; THERAPY; DEGRADATION AB Purpose: Multiple myeloma is a malignant plasma cell disorder accounting for about 10% of hematological malignancies. Despite treatment advances, including hematopoietic stem-cell transplantation to facilitate administration of high-dose cytotoxic chemotherapy, the median survival remains approximately 3 years and long-term remissions are rare. Bortezomib (Velcade, formerly known as PS-341; Millennium Pharmaceuticals, Cambridge MA) is a dipeptide boronic acid that inhibits the 20S proteasome involved in the degradation of intracellular proteins, including those affecting cell cycle regulation in mammalian cells. Described herein are the analyses by the United States Food and Drug Administration (FDA) of clinical and nonclinical data submitted in the New Drug Application. Chemistry manufacturing and controls, animal toxicology, and biopharmaceutical data are described. The results of Phase I and Phase II clinical studies in patients with multiple myeloma are summarized. The marketing approval and postmarketing commitments are discussed. Results: Toxicology studies in the rat and monkey identified hematological, lymphoid, cardiac, renal, gastrointestinal, and neurological toxicities of bortezomib. A steep dose-toxicity effect was noted at doses greater than or equal to0.9 mg/m(2). Administration of doses greater than or equal to3.0 mg/m(2) to monkeys resulted in cardiovascular collapse and death 12-14 h postdose. Histopathological evidence of axonal and myelin degeneration of dorsal root ganglia, peripheral nerves, and spinal cord were observed in monkeys and rodents; concurrent clinical observations included tremors and decreased activity. Pharmacokinetic studies in patients with advanced malignancies demonstrated that the mean elimination half-life after the first bortezomib dose varied from 9 to 15 h at doses ranging from 1.45 to 2.00 mg/m(2). The drug is metabolized by cytochrome P450-3A4, -2D6, -2C19, -2C9, and -1A2. Three Phase I studies were performed in a total of 123 patients with advanced malignancies. Dose-limiting toxicity included diarrhea and sensory neurotoxicity. No dose-limiting hematological toxicity was reported. Safety and efficacy were evaluated in an open-label, Phase II study of 202 patients with multiple myeloma who had received at least two prior therapies and had demonstrated disease progression on their most recent therapy. A smaller dose finding study of 54 patients provided additional supportive information. Bortezomib was administered by i.v. bolus on days 1, 4, 8, and 11 in a 21-day cycle for up to eight cycles. The initial dose was 1.3 mg/m(2) except for 28 patients in the dose-finding study who received a 1.0 mg/m(2) dose. The primary study end point in this single-arm trial was response rate, easily measured and thought to correlate with clinical benefit in patients with myeloma. One hundred eighty-eight patients who met the inclusion criteria were included in the FDA efficacy analysis population. Complete responses (CRs) were observed in 5 patients and partial responses (PRs) in 47 patients for an overall response (OR) rate (OR = CR + PR) of 28%. The dose finding study of 54 patients showed a higher response rate for patients given 1.3 mg/m(2) compared with 1.0 mg/m(2) twice weekly for two of the 3-week schedule, but the study was too small for statistical dose-response comparisons. The most commonly reported adverse events were asthenic conditions (including fatigue, malaise, and weakness) in 65%, nausea (64%), diarrhea (51%), appetite decreased (including anorexia; 43%), constipation (43%), thrombocytopenia (43%), peripheral neuropathy (37%, including peripheral sensory neuropathy and peripheral neuropathy aggravated), pyrexia (36%), vomiting (36%), and anemia (32%). Conclusions: The FDA granted marketing approval to Millennium Pharmaceuticals on May 13, 2003 for bortezomib for use as a single agent for the treatment of multiple myeloma in patients who have received at least two prior therapies and have demonstrated disease progression on the last therapy. Accelerated approval was based on a surrogate end point of response rate rather than clinical benefit, such as an improvement in survival. The recommended dose of bortezomib is 1.3 mg/m(2) administered twice weekly for 2 weeks (days 1, 4, 8, and 11) followed by a 10-day rest period (days 12-21). Accelerated approval was based on the results of two Phase II studies in a total of 256 patients and additional Phase I safety information. Mandated Phase IV study commitments to characterize clinical efficacy and safety more precisely are discussed. C1 US FDA, Div Oncol Drug Prod, Ctr Drug Evaluat & Res, Rockville, MD 20852 USA. RP Bross, PF (reprint author), US FDA, Div Oncol Drug Prod, Ctr Drug Evaluat & Res, HFM 755,1401 Rockville Pike, Rockville, MD 20852 USA. EM bross@cber.fda.gov NR 51 TC 206 Z9 216 U1 2 U2 11 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUN 15 PY 2004 VL 10 IS 12 BP 3954 EP 3964 DI 10.1158/1078-0432.CCR-03-0781 PN 1 PG 11 WC Oncology SC Oncology GA 832ED UT WOS:000222249100004 PM 15217925 ER PT J AU Chen, JJ Delongchamp, RR Tsai, CA Hsueh, HM Sistare, F Thompson, KL Desai, VG Fuscoe, JC AF Chen, JJ Delongchamp, RR Tsai, CA Hsueh, HM Sistare, F Thompson, KL Desai, VG Fuscoe, JC TI Analysis of variance components in gene expression data SO BIOINFORMATICS LA English DT Article ID MICROARRAY DATA; DESIGN; VARIABILITY AB Motivation: A microarray experiment is a multi-step process, and each step is a potential source of variation. There are two major sources of variation: biological variation and technical variation. This study presents a variance-components approach to investigating animal-to-animal, between-array, within-array and day-to-day variations for two data sets. The first data set involved estimation of technical variances for pooled control and pooled treated RNA samples. The variance components included between-array, and two nested within-array variances: between-section (the upper- and lower-sections of the array are replicates) and within-section (two adjacent spots of the same gene are printed within each section). The second experiment was conducted on four different weeks. Each week there were reference and test samples with a dye-flip replicate in two hybridization days. The variance components included week-to-week, animal-to-animal and between-array and within-array variances. Results: We applied the linear mixed-effects model to quantify different sources of variation. In the first data set, we found that the between-array variance is greater than the between-section variance, which, in turn, is greater than the within-section variance. In the second data set, for the reference samples, the week-to-week variance is larger than the between-array variance, which, in turn, is slightly larger than the within-array variance. For the test samples, the week-to-week variance has the largest variation. The animal-to-animal variance is slightly larger than the between-array and within-array variances. However, in a gene-by-gene analysis, the animal-to-animal variance is smaller than the between-array variance in four out of five housekeeping genes. In summary, the largest variation observed is the week-to-week effect. Another important source of variability is the animal-to-animal variation. Finally, we describe the use of variance-component estimates to determine optimal numbers of animals, arrays per animal and sections per array in planning microarray experiments. C1 US FDA, Div Biometry & Risk Assessment, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. US FDA, Ctr Funct Genom, Div Genet & Reprod Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Natl Chengchi Univ, Dept Stat, Taipei 11623, Taiwan. US FDA, Div Appl Pharmacol Res, Ctr Drug Evaluat & Res, Laurel, MD 20708 USA. RP Chen, JJ (reprint author), US FDA, Div Biometry & Risk Assessment, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM jchen@nctr.fda.gov OI HSUEH, HUEY-MIIN/0000-0003-0536-9440; Tsai, Chen-An/0000-0002-7490-4331 NR 15 TC 62 Z9 66 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD JUN 12 PY 2004 VL 20 IS 9 BP 1436 EP 1446 DI 10.1093/bioinformatics/bth118 PG 11 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 830MF UT WOS:000222125600011 PM 14962916 ER PT J AU Jia, YP Wood, F Menu, P Faivre, B Caron, A Alayash, AI AF Jia, YP Wood, F Menu, P Faivre, B Caron, A Alayash, AI TI Oxygen binding and oxidation reactions of human hemoglobin conjugated to carboxylate dextran SO BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS LA English DT Article DE hemoglobin; oxygen affinity; redox reaction; blood substitute ID CHEMICALLY-MODIFIED HEMOGLOBINS; POTENTIAL BLOOD SUBSTITUTE; HEME DEGRADATION-PRODUCTS; CELL-FREE HEMOGLOBIN; NITRIC-OXIDE; HYDROGEN-PEROXIDE; CROSS-LINKING; BOVINE HEMOGLOBINS; REDOX PROPERTIES; GUINEA-PIGS AB Human hemoglobin (Hb) conjugated to benzene tetracarboxylate substituted dextran produces a polymeric Hb (Dex-BTC-Hb) with similar oxygen affinity to that of red blood cells (P-50=28-29 mm Hg). Under physiological conditions, the oxygen affinity (P-50) of Dex-BTC-Hb is 26 mm Hg, while that of native purified human HbA(0) is 14 mm Hg, but it exhibits a slight reduction in cooperativity (n(50)), Bohr effect, and lacks sensitivity to inositol hexaphosphate (IHP), when compared to HbA(0). Oxygen-binding kinetics, measured by rapid mixing stopped-flow method showed comparable oxygen dissociation and association rates for both HbA(0) and Dex-BTC-Hb. The rate constant for NO-mediated oxidation of the oxy form of Dex-BTC-Hb, which is governed by NO entry to the heme pocket, was reduced to half of the value obtained for HbA(0). Moreover, Dex-BTC-Hb is only slightly more sensitive to oxidative reactions than HbA(0), as shown by about 2-fold increase in autoxidation, and slightly higher H2O2 reaction and heme degradation rates. Dextran-BTC-based modification of Hb produced an oxygen-carrying compound with increased oxygen release rates, decreased oxygen affinity and reduced nitric oxide scavenging, desirable properties for a viable blood substitute. However, the reduction in the allosteric function of this protein and the lack of apparent quaternary T --> R transition may hinder its physiological role as an oxygen transporter. (C) 2004 Elsevier B.V. All rights reserved. C1 US FDA, Ctr Biol Evaluat & Res, Lab Biochem & Vasc Biol, Bethesda, MD 20892 USA. Univ Henri Poincare Nancy, Sch Pharm, Dept Hematol & Physiol, F-54001 Nancy, France. RP Alayash, AI (reprint author), US FDA, Ctr Biol Evaluat & Res, Lab Biochem & Vasc Biol, 8800 Rockville Pike,NIH Bldg,29,Room 112, Bethesda, MD 20892 USA. EM Alayash@cber.fda.gov RI FAIVRE , Beatrice/B-7535-2012 NR 44 TC 31 Z9 32 U1 1 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-4165 J9 BBA-GEN SUBJECTS JI Biochim. Biophys. Acta-Gen. Subj. PD JUN 11 PY 2004 VL 1672 IS 3 BP 164 EP 173 DI 10.1016/j.bbagen.2004.03.009 PG 10 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 828TW UT WOS:000221997200006 PM 15182936 ER PT J AU Selvapandiyan, A Debrabant, A Duncan, R Muller, J Salotra, P Sreenivas, G Salisbury, JL Nakhasi, HL AF Selvapandiyan, A Debrabant, A Duncan, R Muller, J Salotra, P Sreenivas, G Salisbury, JL Nakhasi, HL TI Centrin gene disruption impairs stage-specific basal body duplication and cell cycle progression in Leishmania SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTOZOAN PARASITE LEISHMANIA; MITOTIC SPINDLE POLES; VIRULENCE FACTOR; DONOVANI; CENTROSOMES; LIPOPHOSPHOGLYCAN; SEGREGATION; DELETION; DEATH; REPLACEMENT AB Centrin is a calcium-binding cytoskeletal protein involved in the duplication of centrosomes in higher eukaryotes. To explore the role of centrin in the protozoan parasite Leishmania, we created Leishmania deficient in the centrin gene (LdCEN). Remarkably, centrin null mutants (LdCEN(-/-)) showed selective growth arrest as axenic amastigotes but not as promastigotes. Flow cytometry analysis confirmed that the mutant axenic amastigotes have a cell cycle arrest at the G(2)/M stage. The axenic amastigotes also showed failure of basal body duplication and failure of cytokinesis resulting in multinucleated "large" cells. Increased terminal deoxy uridine triphosphate nick end labeling positivity was observed in centrin mutant axenic amastigotes compared with wild type cells, suggesting the activation of a programmed cell death pathway. Growth of LdCEN(-/-) amastigotes in infected macrophages in vitro was inhibited and also resulted in large multinucleated parasites. Normal basal body duplication and cell division in the LdCEN knockout promastigote is unique and surprising. Further, this is the first report where disruption of a centrin gene displays stage-specific/celltype-specific failure in cell division in a eukaryote. The centrin null mutant defective in amastigote growth could be useful as a vaccine candidate against leishmaniasis. C1 US FDA, Ctr Biol Evaluat & Res, Off Blood Res & Review, Div Emerging & Transfus Transmitted Dis,Lab Bacter, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Off Vaccines Res & Review, Div Viral Prod,Lab Vector Borne Dis, Bethesda, MD 20892 USA. Safdarjang Hosp, Indian Council Med Res, Inst Pathol, New Delhi 110029, India. Mayo Clin, Coll Med, Tumor Biol Program, Rochester, MN 55905 USA. RP Nakhasi, HL (reprint author), US FDA, Ctr Biol Evaluat & Res, Off Blood Res & Review, Div Emerging & Transfus Transmitted Dis,Lab Bacter, Bldg 29,Rm 222,8800 Rockville Pike, Bethesda, MD 20892 USA. EM nakhasi@cber.fda.gov RI Duncan, Robert/I-8168-2015 OI Duncan, Robert/0000-0001-8409-2501 NR 39 TC 57 Z9 58 U1 2 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 11 PY 2004 VL 279 IS 24 BP 25703 EP 25710 DI 10.1074/jbc.M402794200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 826KL UT WOS:000221827900100 PM 15084606 ER PT J AU Roberts, ES Charboneau, L Espina, V Liotta, LA Petricoin, EF Dreher, KL AF Roberts, ES Charboneau, L Espina, V Liotta, LA Petricoin, EF Dreher, KL TI Application of laser capture microdissection and protein microarray technologies in the molecular analysis of airway injury following pollution particle exposure SO JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A-CURRENT ISSUES LA English DT Article ID KAPPA-B ACTIVATION; ACUTE LUNG INJURY; OIL FLY-ASH; PARTICULATE MATTER; IN-VITRO; GENE-EXPRESSION; METALS; CELLS; PROGRESSION; TISSUE AB Understanding the mechanisms by which various types of air pollution particles (particulate matter, PM) mediate adverse health effects would provide biological plausibility to epidemiological associations of increased rates of morbidity and mortality. The majority of information regarding the means by which PM generates lung injury has been derived from in vitro studies. However, it is unclear as to what extent these mechanisms can be extrapolated to the in vivo situation. Current methods to assess mechanisms of PM-induced lung injury make it difficult to obtain site-specific, sensitive, and comprehensive determinations of cellular and molecular pathology associated with PM-induced injury. In the present study, the ability of laser capture microdissection (LCM) and protein microarray technologies were assessed to examine the effect of residual oil fly ash (ROFA) exposure on airway intracellular signaling pathways and transcription factor activation. Sprague-Dawley rats were intratracheally instilled with 0.5 mg/rat of ROFA. LCM was used to recover airway cells and protein extracts derived from the microdissected airways were analyzed by protein microarray. ROFA exposure increased p-ERK:ERK and p-IkappaB:IkappaB, suggesting changes in cell growth, transformation, and inflammation within the airway. These results are consistent with previously reported in vitro findings, demonstrating for the first time the credibility of applying LCM and protein microarray technologies to assess acute lung injury induced by environmental air pollutants. C1 US EPA, Natl Hlth & Environm Effects Res Lab, Res Triangle Pk, NC 27711 USA. N Carolina State Univ, Coll Vet Med, Dept Mol Biomed Sci, Raleigh, NC 27695 USA. Natl Canc Inst, NIH, Bethesda, MD USA. US FDA, CBER, Rockville, MD USA. RP Dreher, KL (reprint author), US EPA, Natl Hlth & Environm Effects Res Lab, MD-B143-01, Res Triangle Pk, NC 27711 USA. EM DREHER.KEVIN@EPA.GOV OI Espina, Virginia/0000-0001-5080-5972 NR 27 TC 11 Z9 12 U1 0 U2 0 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 JUN 11 PY 2004 VL 67 IS 11 BP 851 EP 861 DI 10.1080/15287390490425768 PG 11 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 820OR UT WOS:000221399700002 PM 15205040 ER PT J AU Munderloh, UG Lynch, MJ Herron, MJ Palmer, AT Kurtti, TJ Nelson, RD Goodman, JL AF Munderloh, UG Lynch, MJ Herron, MJ Palmer, AT Kurtti, TJ Nelson, RD Goodman, JL TI Infection of endothelial cells with Anaplasma marginale and A-phagocytophilum SO VETERINARY MICROBIOLOGY LA English DT Article DE Anaplasma marginale; Anaplasma phagocytophilum; microvascular endothelium; Anaplasma culture ID HUMAN GRANULOCYTIC EHRLICHIOSIS; OUTER-MEMBRANE PROTEINS; MAJOR SURFACE PROTEIN-2; CD4+ T-LYMPHOCYTE; BOVINE ERYTHROCYTES; ADHESION MOLECULES; SELECTIN LIGAND; ETIOLOGIC AGENT; P-SELECTIN; TICK CELLS AB Anaplasma marginale and A. phagocytophilum are obligate intracellular, tick-borne pathogens that target erythrocytes and neutrophil granulocytes, respectively. Because ticks do not directly tap blood vessels, an intermediate tissuemay mediate infection of blood cells. We considered that vascular endothelium interacts with circulating blood cells in vivo, and could be involved in pathogenesis and dissemination of the organisms. We used light and electron microscopy and immune labeling to show that A. phagocytophilum invaded rhesus (RF/6A), human (HMEC-1, MVEC), as well as bovine (BCE C/D-1b) endothelial cell lines, whereas A. marginale infected rhesus and bovine endothelial cells. A. marginale formed large intracellular inclusions that appeared smooth and solid at first, and subsequently coalesced into discrete granules. A. phagocytophilum formed numerous smaller inclusions in each cell. Within 1-3 weeks, the monolayers were destroyed, and lysed cultures were diluted onto fresh monolayers. Electron microscopy demonstrated uneven distribution of A. marginale inside large inclusions, with reticulated forms grouped more tightly than denser cells, whereas in A. phagocytophilum individual organisms appeared more evenly spaced. Specific polyclonal and monoclonal antibodies both labeled A. marginale and A. phagocytophilum in endothelial cells, and oligonucleotide primers complimentary to either A. marginale or A. phagocytophilum amplified their expected target from these cultures. In conclusion, we demonstrate that relevant microvascular endothelium is susceptible to anaplasmas in vitro and may present a link that could explain development of the immune response and persistent infection. (C) 2004 Elsevier B.V. All rights reserved. C1 Univ Minnesota, Dept Entomol, St Paul, MN 55108 USA. Univ Minnesota, Dept Dermatol, Minneapolis, MN 55455 USA. Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Munderloh, UG (reprint author), Univ Minnesota, Dept Entomol, 219 Hodson Hall,1980 Folwell Ave, St Paul, MN 55108 USA. EM munde001@umn.edu FU NIAID NIH HHS [AI42792, AI40952] NR 55 TC 85 Z9 88 U1 1 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1135 J9 VET MICROBIOL JI Vet. Microbiol. PD JUN 10 PY 2004 VL 101 IS 1 BP 53 EP 64 DI 10.1016/j.vetmic.2004.02.011 PG 12 WC Microbiology; Veterinary Sciences SC Microbiology; Veterinary Sciences GA 835HZ UT WOS:000222474700006 PM 15201033 ER PT J AU Tompkins, SM Lo, CY Tumpey, TM Epstein, SL AF Tompkins, SM Lo, CY Tumpey, TM Epstein, SL TI Protection against lethal influenza virus challenge by RNA interference in vivo SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HEPATITIS-B-VIRUS; GENE-EXPRESSION; A VIRUS; HETEROSUBTYPIC IMMUNITY; ADULT MICE; REPLICATION; INHIBITION; INFECTION; SIRNA; DELIVERY AB Influenza virus infection is responsible for hundreds of thousands of deaths annually. Current vaccination strategies and antiviral drugs provide limited protection; therefore, new strategies are needed. RNA interference is an effective means of suppressing virus replication in vitro. Here we demonstrate that treatment with small interfering RNAs (siRNAs) specific for highly conserved regions of the nucleoprotein or acidic polymerase inhibits influenza A virus replication in vivo. Delivery of these siRNAs significantly reduced lung virus titers in infected mice and protected animals from lethal challenge. This protection was specific and not mediated by an antiviral IFN response. Moreover, influenza-specific siRNA treatment was broadly effective and protected animals against lethal challenge with highly pathogenic avian influenza A viruses of the H5 and H7 subtypes. These results indicate that RNA interference is promising for control of influenza virus infection, as well as other viral infections. C1 US FDA, Ctr Biol Evaluat & Res, Lab Immunol & Dev Biol, Div Cell & Gene Therapies, Bethesda, MD 20892 USA. Ctr Dis Control & Prevent, Div Viral & Rickettsial Dis, Influenza Branch, Atlanta, GA 30333 USA. RP Epstein, SL (reprint author), US FDA, Lab Immunol & Dev Biol, Div Cellular & Gene Therapies, Off Cell Tissue & Gene Therapies,Ctr Biol & Evalu, 1401 Rockville Pike,HFM-730, Rockville, MD 20852 USA. EM epsteins@cber.fda.gov RI Tompkins, Stephen/A-3317-2008 OI Tompkins, Stephen/0000-0002-1523-5588 NR 36 TC 272 Z9 305 U1 4 U2 27 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 8 PY 2004 VL 101 IS 23 BP 8682 EP 8686 DI 10.1073/pnas.0402630101 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 829HC UT WOS:000222037000035 PM 15173583 ER PT J AU Kumar, A Vaid, A Syin, C Sharma, P AF Kumar, A Vaid, A Syin, C Sharma, P TI PfPKB, a novel protein kinase B-like enzyme from Plasmodium falciparum - I. Identification, characterization, and possible role in parasite development SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN MALARIA PARASITES; SACCHAROMYCES-CEREVISIAE; INHIBITORS; ACTIVATION; GENOME; HOMOLOG; DIFFERENTIATION; PHOSPHORYLATION; MECHANISM; RESOURCE AB Extracellular signals control various important functions of a eukaryotic cell, which is often achieved by regulating a battery of protein kinases and phosphatases. Protein Kinase B (PKB) is an important member of the phosphatidylinositol 3-kinase-dependent signaling pathways in several eukaryotes, but the role of PKB in protozoan parasites is not known. We have identified a protein kinase B homologue in Plasmodium falciparum (PfPKB) that is expressed mainly in the schizonts and merozoites. Even though PfPKB shares high sequence homology with PKB catalytic domain, it lacks a pleckstrin homology domain typically found at the N terminus of the mammalian enzyme. Biochemical studies performed to understand the mechanism of PfPKB catalytic activation suggested (i) its activation is dependent on autophosphorylation of a serine residue (Ser-271) in its activation loop region and (ii) PfPKB has an unusual N-terminal region that was found to negatively regulate its catalytic activity. We also identified an inhibitor of PfPKB activity that also inhibits P. falciparum growth, suggesting that this enzyme may be important for the development of the parasite. C1 Natl Inst Immunol, Eukaryot Gene Express Lab, New Delhi 110067, India. US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Sharma, P (reprint author), Natl Inst Immunol, Eukaryot Gene Express Lab, New Delhi 110067, India. EM pushkar@nii.res.in OI Kumar, Amit/0000-0003-1732-440X NR 41 TC 33 Z9 34 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 4 PY 2004 VL 279 IS 23 BP 24255 EP 24264 DI 10.1074/jbc.M312855200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 824RA UT WOS:000221702500050 PM 15024016 ER PT J AU Isaacsohn, JL Troendle, AJ Orloff, DG AF Isaacsohn, JL Troendle, AJ Orloff, DG TI Regulatory issues in the approval of new drugs for diabetes mellitus, dyslipidemia, and the metabolic syndrome SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Editorial Material C1 Medpace Inc, Cincinnati, OH 45212 USA. US FDA, Rockville, MD USA. RP Isaacsohn, JL (reprint author), Medpace Inc, 4620 Wesley Ave, Cincinnati, OH 45212 USA. EM j.isoocsohn@medpace.com NR 0 TC 3 Z9 3 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD JUN 3 PY 2004 VL 93 IS 11 SU S BP 49C EP 52C DI 10.1016/j.amjcard.2004.02.007 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 828ER UT WOS:000221957000007 PM 15178516 ER PT J AU Peterson, ED Hirshfeld, JW Ferguson, TB Kramer, JM Califf, RM Kessler, LG AF Peterson, ED Hirshfeld, JW Ferguson, TB Kramer, JM Califf, RM Kessler, LG TI Part II: Sealing holes in the safety net SO AMERICAN HEART JOURNAL LA English DT Article ID DEFIBRILLATOR; PREVENTION; RADIATION; DEVICE; TRIAL C1 Duke Clin Res Inst, CERTs Coordinating Ctr, Durham, NC 27705 USA. Hosp Univ Penn, Philadelphia, PA 19104 USA. Louisiana Hlth Sci Ctr, New Orleans, LA USA. US FDA, Rockville, MD 20857 USA. RP Peterson, ED (reprint author), Duke Clin Res Inst, CERTs Coordinating Ctr, POB 3236, Durham, NC 27705 USA. EM peter016@mc.duke.edu FU AHRQ HHS [U18HS10548] NR 16 TC 6 Z9 6 U1 0 U2 3 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD JUN PY 2004 VL 147 IS 6 BP 985 EP 990 DI 10.1016/j.ahj.2004.03.002 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 832JE UT WOS:000222263000010 PM 15199344 ER PT J AU Jakubzick, C Choi, ES Carpenter, KJ Kunkel, SL Evanoff, H Martinez, FJ Flaherty, KR Toews, GB Colby, TV Travis, WD Joshi, BH Puri, RK Hogaboam, CM AF Jakubzick, C Choi, ES Carpenter, KJ Kunkel, SL Evanoff, H Martinez, FJ Flaherty, KR Toews, GB Colby, TV Travis, WD Joshi, BH Puri, RK Hogaboam, CM TI Human pulmonary fibroblasts exhibit altered interleukin-4 and interleukin-13 receptor subunit expression in idiopathic interstitial pneumonia SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID HUMAN LUNG FIBROBLASTS; HUMAN SYNOVIAL FIBROBLASTS; IL-13 RECEPTOR; SIGNAL-TRANSDUCTION; INTERFERON-GAMMA; TH2 CYTOKINES; PSEUDOMONAS EXOTOXIN; ALVEOLAR MACROPHAGES; SKIN FIBROBLASTS; CARCINOMA-CELLS AB Abnormal proliferation of pulmonary fibroblasts is a prominent feature of chronic pulmonary fibrotic diseases such as idiopathic interstitial pneumonia (IIp), but it is not presently clear how this proliferative response by lung fibroblasts can be therapeutically modulated. In the present study, we examined whether it was possible to selectively target primary human pulmonary fibroblasts grown out of surgical lung biopsies (SLBs) from HP patients based on their expression of interleukin-4 receptor (IL-4R) and IL-13R subunits. Pulmonary fibroblast lines cultured from patients with the severest form of HP, namely usual interstitial pneumonia, exhibited the greatest gene and protein expression of IL-4Ralpha, IL-13Ralpha1, and IL-13Ralpha2 compared with primary pulmonary fibroblast lines grown from other IIP SLBs and normal SLBs. When exposed to increasing concentrations of a chimeric protein comprised of human IL-13 and a truncated version of Pseudomonas exotoxin (IL13-PE), the proliferation of primary usual interstitial pneumonia fibroblasts was inhibited to a much greater extent compared with fibroblast lines from nonspecific interstitial pneumonia and respiratory bronchiolitis/interstitial lung disease patient groups. Fibroblasts from normal patients exhibited minimal susceptibility to the cytotoxic effect of IL13-PE. IL13-PE-mediated targeting of UP fibroblasts was dependent on their expression of IL-4Ralpha and IL-13Ralpha2. Thus, these data suggest that the abnormal proliferative properties of human lung fibroblasts from certain IIP patient groups can be modulated in a manner that is dependent on the IL-4 and IL-13 receptor subunit expression by these cells. C1 Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI 48109 USA. Univ Michigan, Sch Med, Dept Med, Div Pulm & Crit Care Med, Ann Arbor, MI 48109 USA. US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Bethesda, MD USA. Mayo Clin, Scottsdale, AZ USA. Armed Forces Inst Pathol, Washington, DC 20306 USA. RP Hogaboam, CM (reprint author), Univ Michigan, Sch Med, Dept Pathol, Rm 5216B,Med Sci 1,1301 Catherine Rd, Ann Arbor, MI 48109 USA. EM hogaboam@med.umich.edu RI hogaboam, cory /M-3578-2014 FU NHLBI NIH HHS [P50 HL056402, P50 HL56402-04]; NIAID NIH HHS [T32 AI007413] NR 54 TC 28 Z9 30 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD JUN PY 2004 VL 164 IS 6 BP 1989 EP 2001 DI 10.1016/S0002-9440(10)63759-5 PG 13 WC Pathology SC Pathology GA 823HK UT WOS:000221601000013 PM 15161635 ER PT J AU Bernier, R Midthun, K AF Bernier, R Midthun, K TI Getting the science right and doing the right science in vaccine safety SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Editorial Material AB Because of the potential for conflicts of interest, Salmon et al. propose in this issue the creation of an independent vaccine safety board to assume responsibility for, assessing the safety of licensed vaccines. We believe that the current system at the Food and Drug Administration (FDA) and the Centers for Disease Control and Prevention (CDC) facilitates needed interactions between those involved in risk assessment and risk management, provides substantial safeguards against conflicts of interest, and results in sound decisions. The CDC, given its role in promoting immunization, may be perceived to have a greater potential conflict and plans to review its vaccine safety activities. Both agencies recognize the importance of transparency in considering vaccine safety and welcome the opportunity to work with the public and the medical community to improve the quality of scientific information and decisionmaking. C1 Ctr Dis Control & Prevent, Natl Immunizat Program, Atlanta, GA USA. US FDA, Ctr Biol Evaluat & Res, Washington, DC 20204 USA. RP Bernier, R (reprint author), 1600 Clifton Rd,Mailstop E-05, Atlanta, GA 30333 USA. EM rbernier@cdc.gov NR 3 TC 2 Z9 2 U1 0 U2 0 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD JUN PY 2004 VL 94 IS 6 BP 914 EP 917 DI 10.2105/AJPH.94.6.914 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 824WK UT WOS:000221717700010 PM 15249288 ER PT J AU Woo, EJ Ball, R Bostrom, A Shadomy, SV Ball, LK Evans, G Braun, M AF Woo, EJ Ball, R Bostrom, A Shadomy, SV Ball, LK Evans, G Braun, M TI Vaccine risk perception among reporters of autism after vaccination: Vaccine adverse event reporting system 1990-2001 SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID RUBELLA VACCINATION; MEASLES; MUMPS; POPULATION; ASSOCIATION; THIMEROSAL AB Objectives. We investigated vaccine risk perception among reporters of autism to the Vaccine Adverse Event Reporting System (VAERS). Methods. We conducted structured interviews with 124 parents who reported autism and related disorders to VAERS from 1990 to 2001 and compared results with those of a published survey of parents in the general population. Results. Respondents perceived vaccine-preventable diseases as less serious than did other parents. Only 15% of respondents deemed immunization extremely important for children's health; two thirds had withheld vaccines from their children. Conclusions. Views of parents who believe vaccines injured their children differ significantly from those of the general population regarding the benefits of immunization. Understanding the factors that shape this perspective can improve communication among vaccine providers, policymakers, and parents/patients. C1 US FDA, Vaccine Safety Branch, Div Epidemiol, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. Georgia Inst Technol, Sch Publ Policy, Atlanta, GA 30332 USA. Off Publ Hlth & Sci, Dept Hlth & Human Serv, Rockville, MD USA. US Hlth Resources & Serv Adm, Natl Vaccine Injury Compensat Program, Dept Hlth & Human Serv, Rockville, MD 20857 USA. RP Woo, EJ (reprint author), US FDA, Vaccine Safety Branch, Div Epidemiol, Ctr Biol Evaluat & Res, HFM-222,1401 Rockville Pike, Rockville, MD 20852 USA. EM wooj@cber.fda.gov NR 19 TC 25 Z9 25 U1 0 U2 5 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD JUN PY 2004 VL 94 IS 6 BP 990 EP 995 DI 10.2105/AJPH.94.6.990 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 824WK UT WOS:000221717700025 PM 15249304 ER PT J AU Schechtman, LM Stokes, WS AF Schechtman, LM Stokes, WS TI The FDA's regulatory role in the ICCVAM process SO ATLA-ALTERNATIVES TO LABORATORY ANIMALS LA English DT Article; Proceedings Paper CT 4th World Congress on Alternatives and Animal Use in the Life Sciences CY AUG 11-15, 2002 CL New Orleans, LA DE alternative methods; Food and Drug Administration (FDA); Food Drug and Cosmetic Act; ICCVAM Authorization Act; Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM); NTP Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM); regulatory acceptance; validation ID ALTERNATIVE METHODS; ECVAM AB The Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM), a permanent body set forth in the ICCVAM Authorization Act of 2000 (Public Law 106-545), is charged with establishing criteria and processes for the validation and regulatory acceptance of toxicological test methods of interest to Federal agencies, including alternative methods that reduce, refine, or replace the use of animals for research and testing purposes. In response to that mandate, 15 Federal regulatory and research agencies and programmes that would consider utilising such methods or the results derived from them, now participate in cross-agency efforts directed toward the identification, standardisation, validation, acceptance, regulatory implementation and international harmonisation and adoption of such test methods. As an integral member of ICCVAM since its inception, the US Food and Drug Administration (FDA) has established processes for responding to ICCVAM issues and recommendations. The participating FDA units include all FDA research and product-based centres and oversight offices. FDA product centres respond to distinct regulatory mandates and regulate different products. Upon completion of a validation effort, ICCVAM forwards its recommendations to member Government agencies regarding the validity and technical acceptability of a method. The FDA's response consists of the conclusions reached by each of its regulatory components and addresses such factors as their concurrence with ICCVAM's conclusions, the practical applicability of the method to the products they regulate and the feasibility of implementation of an accepted method to supplement or supplant those currently used. Each centre/office independently determines which of the ICCVAM-recommended tests are appropriate for implementation to satisfy its regulatory obligations to ensure product safety and to protect human health. The adoption of a method triggers a notification process to announce the availability and utility of a method, encourage its use, and inform, educate and train end-users and regulatory review staff. C1 FDA Natl Ctr Toxicol Res, Washington Operat, Rockville, MD 20857 USA. Natl Inst Environm Hlth Sci, Environm Toxicol Program, Res Triangle Pk, NC USA. RP Schechtman, LM (reprint author), FDA Natl Ctr Toxicol Res, Washington Operat, HFT-10,5600 Fishers Lane, Rockville, MD 20857 USA. EM lschechtman@nctr.fda.gov NR 16 TC 2 Z9 2 U1 0 U2 1 PU FRAME PI NOTTINGHAM PA RUSSELL & BURCH HOUSE 96-98 NORTH SHERWOOD ST, NOTTINGHAM NG1 4EE, NOTTS, ENGLAND SN 0261-1929 J9 ATLA-ALTERN LAB ANIM JI ATLA-Altern. Lab. Anim. PD JUN PY 2004 VL 32 SU 1B BP 663 EP 668 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 833QA UT WOS:000222352000049 PM 23581155 ER PT J AU Kimmel, G AF Kimmel, G TI Concern over decreased training in embryology and developmental/reproductive toxicology SO BIRTH DEFECTS RESEARCH PART B-DEVELOPMENTAL AND REPRODUCTIVE TOXICOLOGY LA English DT Letter C1 Kimmel & Asociates, Silver Spring, MD 20902 USA. Stephen B Harris Grp, San Diego, CA USA. Pfizer Global Res & Dev, New London, CT USA. Univ Louisville, Sch Dent, Birth Defects Ctr,Syst Anal Lab, Dept Mol Cellular & Craniofacial Biol, Louisville, KY 40292 USA. Bayer CropSci, Res Triangle Pk, NC USA. RTI Int, Sci & Engn Grp, Hlth Sci Unit, Res Triangle Pk, NC USA. Rhodia Inc, Chem Toxicol, Raleigh, NC USA. WIL Res Labs Inc, Ashland, OH USA. US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Kimmel, G (reprint author), Kimmel & Asociates, 607 Somersworth Way, Silver Spring, MD 20902 USA. EM glk4@cdrh.fda.gov 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 1542-9733 J9 BIRTH DEFECTS RES B JI Birth Defects Res. Part B-Dev. Reprod. Toxicol. PD JUN PY 2004 VL 71 IS 3 BP 191 EP 192 DI 10.1002/bdrb.20012 PG 2 WC Oncology; Genetics & Heredity; Toxicology SC Oncology; Genetics & Heredity; Toxicology GA 845AM UT WOS:000223208000009 PM 15282740 ER PT J AU Simak, J Holada, K Risitano, AM Zivny, JH Young, NS Vostal, JG AF Simak, J Holada, K Risitano, AM Zivny, JH Young, NS Vostal, JG TI Elevated circulating endothelial membrane microparticles in paroxysmal nocturnal haemoglobinuria SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE adhesion molecules; endothelial cells; flow cytometry; paroxysmal nocturnal haemoglobinuria; sickle cell disease ID THROMBOTIC THROMBOCYTOPENIC PURPURA; CELL-DERIVED MICROPARTICLES; ACUTE CORONARY SYNDROMES; PLASMINOGEN-ACTIVATOR; DISEASE; PLASMA; APOPTOSIS; RECEPTOR; BLOOD; VESICULATION AB We analysed endothelial cell membrane microparticles (ECMP) in the peripheral blood of patients with paroxysmal nocturnal haemoglobinuria (PNH) (n = 9), aplastic anaemia (AA) (n = 10), sickle cell disease (SCD) (n = 8), and healthy donors (HD) (n = 11). There was no clinically manifested thrombosis in the PNH or AA group, except one cured thrombophlebitis (PNH), while all SCD patients had a history of vaso-occlusive crises. We used three-colour flow cytometry with blood cell-specific antibodies and antibodies to endothelial antigens CD105 and CD144. Phosphatidylserine-positive microparticles were detected using the annexin V-binding (AVB) assay. The population of CD105+AVB+ ECMP was significantly (P < 0.05) higher in SCD (median: 0.568 x 10(9)/l; 25-75th percentile range: 0.351-0.976 x 10(9)/l) and PNH (0.401 x 10(9)/l ; 0.19-0.441 x 10(9)/l) patients when compared with AA (0.122 x 10(9)/l; 0.061-0.172 x 10(9)/l) or HD (0.180 x 10(9)/l; 0.137-0.217 x 10(9)/l) group. Even more pronounced differences were observed in ECMP exhibiting a marker of inflammatory stimulation CD54 (CD105+CD54+). Similarly, ECMP that exhibited endothelial specific and proteolysis-sensitive antigen CD144 were increased in SCD and PNH, but not in AA. Elevated CD54+ ECMP may reflect the inflammatory status of endothelial cells in SCD and PNH, while CD144+ ECMP could indicate continuous endothelial stimulation and/or injury. Analysis of circulating ECMP appears promising to provide useful information on the status of the vascular endothelium in PNH and SCD. C1 US FDA, Lab Cellular Hematol, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. Charles Univ, Sch Med 1, Inst Microbiol & Immunol, Prague, Czech Republic. NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Simak, J (reprint author), US FDA, CBER, 1401 Rockville Pike,HFM-335, Rockville, MD 20852 USA. EM jan.simak@fda.hhs.gov RI Simak, Jan/C-1153-2011 NR 37 TC 75 Z9 77 U1 0 U2 8 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD JUN PY 2004 VL 125 IS 6 BP 804 EP 813 DI 10.1111/j.1365-2141.2004.04974.x PG 10 WC Hematology SC Hematology GA 826YK UT WOS:000221865200014 PM 15180871 ER PT J AU Panguluri, RCK Long, LO Chen, WD Wang, SP Coulibaly, A Ukoli, F Jackson, A Weinrich, S Ahaghotu, C Isaacs, W Kittles, RA AF Panguluri, RCK Long, LO Chen, WD Wang, SP Coulibaly, A Ukoli, F Jackson, A Weinrich, S Ahaghotu, C Isaacs, W Kittles, RA TI COX-2 gene promoter haplotypes and prostate cancer risk SO CARCINOGENESIS LA English DT Article ID SQUAMOUS-CELL CARCINOMA; COLON-CANCER; CYCLOOXYGENASE-2 GENE; DNA-BINDING; EXPRESSION; GROWTH; PROLIFERATION; TRANSCRIPTION; APOPTOSIS; INHIBITOR AB Cyclooxygenase-2 (COX-2) is a key rate-limiting enzyme that converts arachidonic acid into pro-inflamatory prostaglandins. COX-2 expression is strongly correlated with increased tumor microvasculature density and plays an important role in inhibiting apoptosis, stimulating angiogenesis and promoting tumor cell metastasis and invasion. However, little is known about the role that sequence variation of the COX-2 gene contributes to prostate cancer. Thus, we searched for polymorphisms in the promoter region of the COX-2 gene using denaturing high-performance liquid chromatography. Four single nucleotide polymorphisms (SNPs), -1285A/G, -1265G/A, -899G/C and -297C/G, were detected and confirmed by direct sequencing. Three of the SNPs in the promoter region of COX-2 gene create at least three putative transcription factor binding sites and eliminate CCAAT/enhancer binding protein alpha (C/EBPalpha) and NF-kappaB binding sites. A case-control study of the four SNPs in African American (n = 288), Bini Nigerian (n = 264) and European American (n = 184) prostate cancer cases and age-matched controls revealed that SNP -297G was associated with a decreased risk for prostate cancer [odds ratio (OR) = 0.49; CI = 0.2-0.9; P = 0.01]. The effect on risk was observed in both African Americans (OR = 0.51; CI = 0.2-0.9; P = 0.01) and European Americans (OR = 0.33; CI = 0.1-0.9; P = 0.02). In addition, SNPs -1265A and -899C were associated with increased prostate cancer risk in African Americans (OR = 2.72; CI = 1.3-5.8; P = 0.007 and OR = 3.67; CI = 1.4-9.9; P = 0.007, respectively). Haplotype analyses revealed modest effects on susceptibility to prostate cancer across populations. Haplotype GGCC conferred increased risk in the African American and Nigerian populations. Conversely, haplotype AGGG exhibited a negative association with prostate cancer risk in African Americans (OR = 0.4; CI = 0.1-0.9; P = 0.02) and European Americans (OR = 0.2; CI = 0.1-0.9; P = 0.03). These data suggest that variation of the COX-2 promoter may influence the risk and development of prostate cancer. C1 Howard Univ, Natl Human Genome Ctr, Washington, DC 20060 USA. Howard Univ Hosp, Div Urol, Washington, DC 20060 USA. Howard Univ Canc Ctr, Washington, DC 20060 USA. US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Univ Louisville, Sch Nursing, Louisville, KY 40292 USA. Johns Hopkins Med Inst, James Buchanan Brady Urol Inst, Baltimore, MD 21287 USA. RP Kittles, RA (reprint author), Howard Univ, Natl Human Genome Ctr, Washington, DC 20060 USA. EM rkittles@howard.edu FU NCI NIH HHS [1U54CA91431-01]; NCRR NIH HHS [RR03048-13S1] NR 39 TC 84 Z9 91 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JUN PY 2004 VL 25 IS 6 BP 961 EP 966 DI 10.1093/carcin/bgh100 PG 6 WC Oncology SC Oncology GA 825IQ UT WOS:000221750400013 PM 14754878 ER PT J AU Mei, N Heflich, RH Chou, MW Chen, T AF Mei, N Heflich, RH Chou, MW Chen, T TI Mutations induced by the carcinogenic pyrrolizidine alkaloid riddelliine in the liver cII gene of transgenic big blue rats SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID DNA ADDUCT FORMATION; BASE SUBSTITUTIONS; CROSS-LINKS; MICE; MUTAGENICITY; TOXICITY; SPECTRUM; LACI; LUNG AB Riddelliine is a naturally occurring pyrrolizidine alkaloid that forms a number of different mononucleotide and dinucleotide adducts in DNA. It is a rodent carcinogen and a potential human hazard via food contamination. To examine the mutagenicity of riddelliine, groups of six female transgenic Big Blue rats were gavaged with 0.1, 0.3, and 1.0 mg riddelliine per kg body weight. The middle and high doses resulted in liver tumors in a previous carcinogenesis bioassay. The animals were treated 5 days a week for 12 weeks and sacrificed I day after the last treatment. The liver DNA was isolated for analysis of the mutant frequency (MF) in the transgenic cII gene, and the types of mutations were characterized by sequencing the mutants. A significant dose-dependent increase in MF was found, increasing from 30 x 10(-6) in the control animals to 47, 55, and 103 x 10(-6) in the low, middle, and. high dose groups, respectively. Molecular analysis of the mutants indicated that there was a statistically significant difference between the mutational spectra From the riddelliine-treated and the control rats. A G:G T:A transversion (35%) was the major type of mutation in rats treated with riddelliine, whereas a G:C --> A:T transition (55%) was the predominant mutation in the controls. In addition, mutations from the riddelliine-treated rats included an unusually high frequency (8%) of tandem base substitutions of GG --> TT and GG --> AT. These results indicate that riddelliine is a genotoxic carcinogen in rat liver and that the types of mutations induced by riddelliine are consistent with riddelliinie adducts involving G:C base pairs. C1 US FDA, Div Genet & Reprod Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Mei, N (reprint author), US FDA, Div Genet & Reprod Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM nmei@nctr.fda.gov RI mei, nan/E-8915-2011 OI mei, nan/0000-0002-3501-9014 NR 20 TC 29 Z9 30 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD JUN PY 2004 VL 17 IS 6 BP 814 EP 818 DI 10.1021/tx049955b PG 5 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 831YJ UT WOS:000222232500010 PM 15206902 ER PT J AU Linnet, K Kondratovich, MV AF Linnet, K Kondratovich, MV TI Application to HPLC drug assays of a partly nonparametric approach for determination of the limit of detection. SO CLINICAL CHEMISTRY LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Association-for-Clinical-Chemistry CY JUL 25-29, 2004 CL Los Angeles, CA SP Amer Assoc Clin Chem C1 Psychiat Univ Hosp, Risskov, Denmark. US FDA, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUN PY 2004 VL 50 IS 6 SU S BP A40 EP A41 PN 2 PG 2 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 828EC UT WOS:000221955200133 ER PT J AU Bernstein, WB Cox, JH Aronson, NE Tracy, LR Schlienger, K Ratto-Kim, S Garner, R Cotte, J Zheng, ZH Winestone, L Liebig, C Galley, LM Connors, M Birx, DL Carroll, RG Levine, BL AF Bernstein, WB Cox, JH Aronson, NE Tracy, LR Schlienger, K Ratto-Kim, S Garner, R Cotte, J Zheng, ZH Winestone, L Liebig, C Galley, LM Connors, M Birx, DL Carroll, RG Levine, BL TI Immune reconstitution following autologous transfers of CD3/CD28 stimulated CD4(+) T cells to HIV-infected persons SO CLINICAL IMMUNOLOGY LA English DT Article DE HIV; adoptive transfer; immune reconstitution; immunotherapy; ELISpot; TCR V beta; CD28 ID IMMUNODEFICIENCY-VIRUS-INFECTION; ACTIVE ANTIRETROVIRAL THERAPY; CD28 COSTIMULATION; ADOPTIVE TRANSFER; TREATMENT INTERRUPTION; COMBINATION THERAPY; CD8(+); LYMPHOCYTES; REPERTOIRE; RESPONSES AB We have previously shown that adoptive transfer of in vitro CD3/CD28 activated autologous CD4(+) T cells results in increased CD4 counts and CD4/CD8 ratios in HIV+ subjects. In this report, analysis of variable beta (Vbeta) chain T cell receptor (TCR) repertoire showed that CD3/ CD28 stimulation was able to increase polyclonality within skewed spectra types in vitro. In vivo, two of eight subjects showed increase in TCR diversity and importantly, in no subject did a highly skewed in vivo repertoire emerge. Measurement of proliferative response to alloantigen showed increases following infusions. Response to pharmacological stimulus and lectin via Interferon-gamma ELISpot assay showed increases in a subset of subjects following infusions. However, interferon-gamma response to HIV antigens and peptides declined concurrent with stable or diminishing latent infectious viral load in CD4(+) T cells. These data provide further evidence that adoptive transfer of activated autologous CD4(+) T cells can augment the immune system. (C) 2004 Elsevier Inc. All rights reserved. C1 Univ Penn, Ctr Canc, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA. Walter Reed Army Inst Res, Div Retrovirol, Rockville, MD 20850 USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. Natl Naval Med Res Inst, Bethesda, MD 20889 USA. Henry M Jackson Fdn, Rockville, MD 20850 USA. Walter Reed Army Med Ctr, Washington, DC 20307 USA. US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. NIAID, Bethesda, MD 20892 USA. RP Levine, BL (reprint author), Univ Penn, Ctr Canc, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA. EM levinebl@mail.med.upenn.edu RI Levine, Bruce/D-1688-2009; OI Winestone, Lena/0000-0001-9982-1594 NR 51 TC 17 Z9 22 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 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PD JUN PY 2004 VL 111 IS 3 BP 262 EP 274 DI 10.1016/j.clim.2004.03.004 PG 13 WC Immunology SC Immunology GA 830WS UT WOS:000222155500005 PM 15183147 ER PT J AU Bonnel, RA Graham, DJ AF Bonnel, RA Graham, DJ TI Peripheral neuropathy in patients treated with leflunomide SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID RHEUMATOID-ARTHRITIS; MANAGEMENT AB Objective: Our objective was to describe the clinical features, time course, and outcome of new-onset peripheral neuropathy occurring in patients treated with leflunomide. Methods: Case reports of peripheral neuropathy submitted to the US Food and Drug Administration in association with leflunomide use were reviewed. Data on patient demographics, underlying medical conditions and medications, details of leflunomide therapy, and treatment and outcome of the neuropathy event were abstracted. Time to neuropathy onset and time to improvement or recovery were analyzed by survival analysis. Results. Of 80 reported patients, 61% were women. The patients' mean age was 62 years. Symptoms of peripheral neuropathy began after a mean of 6 months of leflunomide use (range, 3 days to 3 years). Electrodiagnostic testing in 37 patients was consistent with a distal axonal, sensory, or sensorimotor polyneuropathy in most patients. Patients who stopped leflunomide use within 30 days of neuropathy symptom onset were more likely to have improvement or recovery than those who continued taking leflunomide for a longer period (P < .001). Conclusion: Leflunomide use is associated with peripheral neuropathy in some patients. This neuropathy is usually axonal in nature, affecting multiple sensory or motor nerves of distal extremities. Patients who stopped leflunomide use within 30 days of symptom onset were more likely to have improvement of symptoms or complete recovery than were patients who continued to use the drug for longer periods of time. C1 US FDA, Off Drug Safety, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Bonnel, RA (reprint author), 5600 Fishers Ln,Room 15B-23,HFD-430, Rockville, MD 20857 USA. EM bonnelr@cder.fda.gov NR 26 TC 28 Z9 30 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD JUN PY 2004 VL 75 IS 6 BP 580 EP 585 DI 10.1016/j.clpt.2004.01.016 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 828AD UT WOS:000221943900011 PM 15179412 ER PT J AU Rudenko, L Matheson, JC Adams, AL Dubbin, ES Greenlees, KJ AF Rudenko, L Matheson, JC Adams, AL Dubbin, ES Greenlees, KJ TI Food consumption clones: What risks associated with animal should be investigated? SO CLONING AND STEM CELLS LA English DT Article; Proceedings Paper CT Workshop on the Assessment of Food Quality from Cloned Animals CY NOV 21-23, 2003 CL Jouy en Josas, FRANCE SP INRA, OECD ID BOVINE SERUM-ALBUMIN; PROTEIN; BEEF AB Somatic Cell Nuclear Transfer (SCNT), or cloning, is likely to be used for the expansion of elite breeding stock of agronomically important livestock used for food. The Center for Veterinary Medicine at the US Food and Drug Administration has been developing a risk assessment to identify hazards and characterize food consumption risks that may result from cloning. The risk assessment is comprised of two prongs. The first evaluates the health of animal clones, and is referred to as the Critical Biological Systems Approach. The second considers the composition of meat and milk from animal clones. Assessing the safety of food products from animal clones and their progeny, at least during these early stages of the development of the technology, is best accomplished by using both approaches: prospectively drawing on our knowledge of biological systems in development and maturation, and in retrograde, from an analysis of food products. Subtle hazards and potential risks that may be posed by animal clones must, however, be considered in the context of other mutations and epigenetic changes that occur in all food animal populations. C1 US FDA, US Dept Hlth & Human Serv, Ctr Vet Med, Rockville, MD 20855 USA. RP Rudenko, L (reprint author), US FDA, US Dept Hlth & Human Serv, Ctr Vet Med, 7500 Standish Pl, Rockville, MD 20855 USA. EM Larisa.Rudenko@fda.hhs.gov NR 14 TC 26 Z9 28 U1 0 U2 6 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1536-2302 J9 CLONING STEM CELLS JI Cloning Stem Cells PD SUM PY 2004 VL 6 IS 2 BP 79 EP 93 DI 10.1089/1536230041372427 PG 15 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Genetics & Heredity SC Cell Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 836CG UT WOS:000222532200005 PM 15268781 ER PT J AU Rao, JY Li, N AF Rao, JY Li, N TI Microfilament actin remodeling as a potential target for cancer drug development SO CURRENT CANCER DRUG TARGETS LA English DT Review DE actin remodeling; small GTPase protein; actin binding protein ID EPIDERMAL GROWTH-FACTOR; HUMAN BLADDER-CANCER; C-RAF KINASE; F-ACTIN; PROSTATE CARCINOMA; CELLULAR-TRANSFORMATION; PHILADELPHIA-CHROMOSOME; MEMBRANE INTERACTIONS; PROGNOSTIC-FACTOR; BINDING PROTEINS AB Actin was first identified in non-muscle cells only about three decades ago, and at about the same time, it was found that actin filaments were disrupted in the malignant transformed cells. The actin network is a rather complex, yet important structural and functional system of all eukaryotic cells. Actin filaments provide the basic infrastructure for maintaining cell morphology and functions such as adhesion, motility, exocytosis, endocytosis, and cell division. Growing evidence from this laboratory and others shows that alterations of actin polymerization, or actin remodeling, plays a pivotal role in regulating the morphologic and phenotypic events of a malignant cell. Actin remodeling is the result of activation of oncogenic actin signaling pathways (e.g., Ras and Src), or inactivation of several important actin-binding proteins that have turner suppressor functions (e.g., gelsolin). Distinctive protein expression patterns of some of these genes in cancer and progressive carcinogenic processes have been observed. It has become evident that actin dynamics are regulated by a complex interplay of the small GTPase proteins of Ras superfamily Rac, Rho, and Cdc42. and efforts to develop specific inhibitors for these small G proteins as anticancer drug are underway. In this review we will discuss how actin remodeling is altered in the malignant transformation process, the functional significance of actin alteration in association with malignant phenotypes, and the approaches of targeting actin remodeling for chemopreventive and chemotherapeutic drug development. Approaches including using nature products directly modulating actin polymerization, using inhibitors of actin pathway small G proteins, and using gene-augmentation for actin binding proteins will be discussed. In addition, the concept of using F/G-actin ratio as a surrogate marker for actin-pathway based therapy will also be introduced. C1 Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA. US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20852 USA. RP Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA. EM jrao@mednet.ucla.edu NR 85 TC 116 Z9 126 U1 4 U2 13 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1568-0096 EI 1873-5576 J9 CURR CANCER DRUG TAR JI Curr. Cancer Drug Targets PD JUN PY 2004 VL 4 IS 4 BP 345 EP 354 DI 10.2174/1568009043332998 PG 10 WC Oncology SC Oncology GA 834YC UT WOS:000222445800004 PM 15180500 ER PT J AU Wade, MM Volokhov, D Peredelchuk, M Chizhikov, V Zhang, Y AF Wade, MM Volokhov, D Peredelchuk, M Chizhikov, V Zhang, Y TI Accurate mapping of mutations of pyrazinamide-resistant Mycobacterium tuberculosis strains with a scanning-frame oligonucleotide microarray SO DIAGNOSTIC MICROBIOLOGY AND INFECTIOUS DISEASE LA English DT Article ID RPOB GENE-MUTATIONS; RIFAMPIN RESISTANCE; DRUG-RESISTANCE; SPECIES IDENTIFICATION; BACTERIAL-POPULATIONS; PNCA MUTATIONS; SUSCEPTIBILITY; HYBRIDIZATION; POLYMORPHISM; ARRAYS AB The increasing emergence of drug-resistant Mycobacterium tuberculosis poses significant threat to the treatment of tuberculosis. Conventional susceptibility testing for the front-line tuberculosis drug pyrazinamide (PZA) is difficult, because of the requirement for acid pH for the drug to show activity. Resistance to PZA in M. tuberculosis is caused by mutations in the pncA gene, and detection of pncA mutations can be an indicator of PZA resistance. In this study, we examined the feasibility of a microarray-based approach exploiting short overlapping oligonucleotides (sliding-frame array) to rapidly detect pncA mutations (substitutions, deletions, and insertions) in multiple strains of PZA-resistant M. tuberculosis. The genetic mapping of these mutations is necessary to link the gene sequence to the protein function defined by mutant phenotype. Microarray analysis was performed in a blind manner using 57 isolates of M. tuberculosis for which the sequence of the pncA gene was previously determined. Our results showed that all mutations could be unambiguously detected, suggesting that microarray can be a routine and valuable toot for rapid identification of drug-resistant M. tuberculosis isolates. We expect that mutation mapping with a sliding-frame microarray will accelerate the molecular analysis of drug-resistant M. tuberculosis bacteria and the microorganism populations. (C) 2004 Elsevier Inc. All rights reserved. C1 Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD 21218 USA. US FDA, Ctr Biol Evaluat & Res, Kensington, MD USA. RP Zhang, Y (reprint author), Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD 21218 USA. EM yzhang@jhsph.edu FU NIAID NIH HHS [R01-AI/HL49485] NR 53 TC 27 Z9 34 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0732-8893 J9 DIAGN MICR INFEC DIS JI Diagn. Microbiol. Infect. Dis. PD JUN PY 2004 VL 49 IS 2 BP 89 EP 97 DI 10.1016/j.diagmicrobio.2004.01.001 PG 9 WC Infectious Diseases; Microbiology SC Infectious Diseases; Microbiology GA 831HR UT WOS:000222186000003 PM 15183857 ER PT J AU Conrads, TP Fusaro, VA Ross, S Johann, D Rajapakse, V Hitt, BA Steinberg, SM Kohn, EC Fishman, DA Whiteley, G Barrett, JC Liotta, LA Petricoin, EF Veenstra, TD AF Conrads, TP Fusaro, VA Ross, S Johann, D Rajapakse, V Hitt, BA Steinberg, SM Kohn, EC Fishman, DA Whiteley, G Barrett, JC Liotta, LA Petricoin, EF Veenstra, TD TI High-resolution serum proteomic features for ovarian cancer detection SO ENDOCRINE-RELATED CANCER LA English DT Review ID PROSTATE-CANCER; PATTERNS AB Serum proteomic pattern diagnostics is an emerging paradigm employing low-resolution mass spectrometry (MS) to generate a set of biomarker classifiers. In the present study, we utilized a well-controlled ovarian cancer serum study set to compare the sensitivity and specificity of serum proteomic diagnostic patterns acquired using a high-resolution versus a low-resolution MS platform. In blinded testing sets the high-resolution mass spectral data contained multiple diagnostic signatures that were superior to the low-resolution spectra in terms of sensitivity and specificity (P < 0.00001) throughout the range of modeling conditions. Four mass spectral feature set patterns acquired from data obtained exclusively with the high-resolution mass spectrometer were 100% specific and sensitive in their diagnosis of serum samples as being acquired from either unaffected patients or those suffering from ovarian cancer. Important to the future of proteomic pattern diagnostics is the ability to recognize inferior spectra statistically, so that those resulting from a specific process error are recognized prior to their potentially incorrect (and damaging) diagnosis. To meet this need, we have developed a series of quality-assurance and in-process control procedures to (a) globally evaluate sources of sample variability, (b) identify outlying mass spectra, and (c) develop quality-control release specifications. From these quality-assurance and control (QA/QC) specifications, we identified 32 mass spectra out of the total 248 that showed statistically significant differences from the norm. Hence, 216 of the initial 248 high-resolution mass spectra were determined to be of high quality and were remodeled by pattern-recognition analysis. Again, we obtained four mass spectral feature set patterns that also exhibited 100% sensitivity and specificity in blinded validation tests (68/68 cancer: including 18/18 stage 1, and 43/43 healthy). We conclude that (a) the use of high-resolution MS yields superior classification patterns as compared with those obtained with lower resolution instrumentation; (b) although the process error that we discovered did not have a deleterious impact on the present results obtained from proteomic pattern analysis, the major source of spectral variability emanated from mass spectral acquisition, and not bias at the clinical collection site; (c) this variability can be reduced and monitored through the use of QA/QC statistical procedures; (d) multiple and distinct proteomic patterns, comprising low molecular weight biomarkers, detected by high-resolution MS achieve accuracies surpassing individual biomarkers, warranting validation in a large clinical study. C1 Natl Canc Inst, SAIC Frederick Inc, Biomed Proteom Program, Lab Proteom & Analyt Technol, Frederick, MD 21702 USA. US FDA, Ctr Biol Evaluat & Res, NCI, Clin Proteom Program, Bethesda, MD 20892 USA. NCI, Pathol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. Correl Syst Inc, Bethesda, MD 20892 USA. NCI, Biostat & Data Management Sect, Ctr Canc Res, Bethesda, MD 20892 USA. Northwestern Univ, Natl Ovarian Canc Early Detect Program, Chicago, IL 60611 USA. NCI, SAIC Frederick Inc, Serum Proteomic Patterns Clin Reference Lab, Frederick, MD 21702 USA. NCI, Ctr Canc Res, Bethesda, MD 20892 USA. RP Veenstra, TD (reprint author), Natl Canc Inst, SAIC Frederick Inc, Biomed Proteom Program, Lab Proteom & Analyt Technol, POB B, Frederick, MD 21702 USA. EM veenstra@ncifcrf.gov FU NCI NIH HHS [N01-CO-12400] NR 16 TC 164 Z9 169 U1 0 U2 7 PU SOC ENDOCRINOLOGY PI BRISTOL PA 22 APEX COURT, WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 1351-0088 J9 ENDOCR-RELAT CANCER JI Endocr.-Relat. Cancer PD JUN PY 2004 VL 11 IS 2 BP 163 EP 178 DI 10.1677/erc.0.0110163 PG 16 WC Oncology; Endocrinology & Metabolism SC Oncology; Endocrinology & Metabolism GA 833RM UT WOS:000222356400002 PM 15163296 ER PT J AU Klinman, DM AF Klinman, DM TI Use of CpG oligodeoxynucleotides as immunoprotective agents SO EXPERT OPINION ON BIOLOGICAL THERAPY LA English DT Review DE CpG oligodeoxynucleotide; host protection; innate immunity ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; INDUCE AUTOIMMUNE-DISEASE; CELL-MEDIATED-IMMUNITY; TOLL-LIKE RECEPTORS; BACTERIAL-DNA; IMMUNOSTIMULATORY DNA; INTERFERON-GAMMA; INNATE IMMUNITY; IN-VIVO; T-CELLS AB Single-stranded oligodeoxynucleotides (ODNs) synthesised to express unmethylated 'CpG motifs' mimic the ability of bacterial DNA to trigger the innate immune system. CpG ODNs stimulate cells that express Toll-like receptor 9, initiating an immunomodulatory cascade resulting in the activation of B and T lymphocytes, natural killer cells, monocytes, macrophages and dendritic cells. CpG ODNs improve the host's ability to resist infection by accelerating and improving the induction of an innate and then adaptive immune response, characterised by the production of Th1 and pro-inflammatory cytokines, chemokines; and polyreactive antibodies. Studies in rodents and non-human primates demonstrate that CpG ODNs can protect the host against bacterial, viral, fungal and parasitic infections. CpG-induced protection develops rapidly but persists for only a few weeks. Preclinical and clinical trials suggest that CpG ODNs can be used safely to activate the human immune system. C1 US FDA, Ctr Biol Evaluat & Res, Sect Retroviral Immunol, Bethesda, MD 20892 USA. RP Klinman, DM (reprint author), US FDA, Ctr Biol Evaluat & Res, Sect Retroviral Immunol, Bldg 29A,Rm 3 D10, Bethesda, MD 20892 USA. EM Klinman@cber.fda.gov NR 97 TC 55 Z9 59 U1 0 U2 5 PU ASHLEY PUBLICATIONS LTD PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1471-2598 J9 EXPERT OPIN BIOL TH JI Expert Opin. Biol. Ther. PD JUN PY 2004 VL 4 IS 6 BP 937 EP 946 DI 10.1517/14712598.4.6.937 PG 10 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 831OO UT WOS:000222204300017 PM 15174975 ER PT J AU Shaikh, B Rummel, N Smith, D AF Shaikh, B Rummel, N Smith, D TI Determination of C-14 residue in eggs of laying hens administered orally with [C-14] sulfaquinoxaline SO FOOD ADDITIVES AND CONTAMINANTS LA English DT Article DE sulfaquinoxaline; total radioactive residue; high-performance liquid chromatography (HPLC) analysis; eggs; oral dose ID METABOLITES; ALBUMIN; YOLK AB Ten layer hens were dosed for 5 consecutive days with 6.2 mg kg(-1) [C-14] sulfaquinoxaline (SQX). Eggs were collected from the hens during the 5-day dosing period and during a 10-day post-dose withdrawal period. Egg yolk and albumen were separated and assayed for total radioactive residues (TRR) using a combustion oxidizer and liquid scintillation counting techniques. Significant amounts of radioactivity were detected on the second day of dosing (greater than 24 h after the initial dose) in both egg yolk and albumen. First eggs were collected about 8 h after dosing; the second-day eggs were collected during 8-h period after the second dose. Radioactive residues reached a maximum on the fifth day of dosing in albumen, whereas on the second day of withdrawal in egg yolk, the peak TRR levels in albumen were about threefold higher than in yolk. Thereafter, the TRR levels declined rapidly in albumen and were detectable up to withdrawal day 6, whereas the TRR levels in egg yolk declined more slowly and were detectable up to withdrawal day 10. High-performance liquid chromatography analysis indicated that the parent drug sulfaquinoxaline was the major component in both the egg albumen and yolk. Additionally, this work suggests that egg yolk is the appropriate matrix for monitoring SQX residues. C1 US FDA, CVM Off Res, Laurel, MD 20708 USA. ARS, USDA, Biosci Res Lab, Fargo, ND 58105 USA. RP Shaikh, B (reprint author), US FDA, CVM Off Res, 8401 Muirkirk Rd, Laurel, MD 20708 USA. EM BSHAIKH@CVM.FDA.GOV NR 10 TC 5 Z9 5 U1 0 U2 0 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 2004 VL 21 IS 6 BP 545 EP 554 DI 10.1080/02652030410001687672 PG 10 WC Chemistry, Applied; Food Science & Technology; Toxicology SC Chemistry; Food Science & Technology; Toxicology GA 826KC UT WOS:000221827000004 PM 15204532 ER PT J AU Sprando, RL Collins, TF Black, TN Oleinik, N Grundel, E Ruggles, DI AF Sprando, RL Collins, TF Black, TN Oleinik, N Grundel, E Ruggles, DI TI Effects of androstenedione on in utero development in rats SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article DE androstenedione; fetus; rats; Estrous ID ANDROGENIC STEROID USE; ANABOLIC-STEROIDS; ESTROUS-CYCLE; PROGESTERONE PRODUCTION; ORAL ANDROSTENEDIONE; SERUM TESTOSTERONE; PREGNANT RATS; YOUNG MEN; ONSET AB This study was conducted to characterize the effect of androstenedione on estrous cyclicity, mating behavior and fetal development. Thirty-day old rats received corn oil alone or androstenedione (in corn oil) at one of four concentrations (0, 1.0, 5.0, 10.0 or 30.0 mg/kg body weight) by gavage for two weeks prior to mating, during the mating period and throughout gestation. Dose related increases in serum androstenedione, estradiol and estrone were observed in all androstenedione treated animals at gestation day 20. A statistically significant increase in serum testosterone concentration was observed in the 30 mg/kg dose group. Feed and fluid consumption were not affected by androstenedione treatment during the pre-mating or gestational periods, however a statistically significant decrease in the number of females with regular estrous cycles was observed in the 10.0 and 30.0 mg/kg dose groups. Exposure to androstenedione did not affect mean body weight gain during pre-mating or gestation. Slight not statistically significant reductions in the number of implants, number of viable fetuses and number of viable male fetuses were observed in the 30.0 mg/kg androstenedione group. Reductions were not observed in the number of corpora lutea. Fetal growth in terms of fetal weight, crown-rump length, anogenital distance and the number of external abnormalities was not affected by androstenedione exposure. At the doses given, androstenedione had no specific effect on the development of individual bones, including sternebrae. Dose related effects of androstenedione were not observed on the development of soft tissues. A statistically significant increase in moderately enlarged ureter at the kidney was observed in both the 1.0 and 5.0 mg/kg dose groups. Organ weights (expressed per gram of body weight or per gram of brain weight) were not affected by androstenedione treatment. Published by Elsevier Ltd. C1 US FDA, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. RP Sprando, RL (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. EM rsprando@cfsan.fda.gov NR 24 TC 9 Z9 9 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0278-6915 J9 FOOD CHEM TOXICOL JI Food Chem. Toxicol. PD JUN PY 2004 VL 42 IS 6 BP 917 EP 924 DI 10.1016/j.fct.2004.01.015 PG 8 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA 821GQ UT WOS:000221448800006 PM 15110100 ER PT J AU Schroeder, CM White, DG Meng, JH AF Schroeder, CM White, DG Meng, JH TI Retail meat and poultry as a reservoir of antimicrobial-resistant Escherichia coli SO FOOD MICROBIOLOGY LA English DT Review DE Escherichia coli; antibiotic resistance; retail meat; poultry; antimicrobial ID HEMOLYTIC-UREMIC SYNDROME; ANTIBIOTIC-RESISTANCE; FOOD ANIMALS; TRIMETHOPRIM-SULFAMETHOXAZOLE; GROUND-BEEF; O157-H7; INFECTIONS; SALMONELLA; EMERGENCE; HUMANS AB The purpose of this review article is to summarize steadily accruing evidence from around the world which indicate retail meat and poultry are a reservoir of antimicrobial-resistant Escherichia coli. The majority of E coli recovered from retail meat and poultry have been found resistant to at least one antimicrobial, and an increasing proportion have been found resistant to clinically important, frontline antimicrobials, including trimethoprim-sulphamethoxazole, fluoroquinolones, and third-generation cephalos-porins. Continued surveillance throughout the food production continuum is needed to detect emerging resistance phenotypes. (C) 2003 Elsevier Ltd. All rights reserved. C1 Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20301 USA. US FDA, Ctr Vet Med, Laurel, MD 20708 USA. RP Schroeder, CM (reprint author), USDA, Food Safety & Inspect Serv, Off Publ Hlth & Sic, Risk Assessment Div,Aerosp Ctr, Mail Drop 334,1400 Independence Ave,SW, Washington, DC 20250 USA. EM carl.schroeder@fsis.usda.gov NR 57 TC 35 Z9 41 U1 0 U2 12 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 2004 VL 21 IS 3 BP 249 EP 255 DI 10.1016/S0740-0020(03)00074-1 PG 7 WC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology SC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology GA 809IE UT WOS:000220629600001 ER PT J AU Olson, SH Carlson, MDA Ostrer, H Harlap, S Stone, A Winters, M Ambrosone, CB AF Olson, SH Carlson, MDA Ostrer, H Harlap, S Stone, A Winters, M Ambrosone, CB TI Genetic variants in SOD2, MPO, and NQO1, and risk of ovarian cancer SO GYNECOLOGIC ONCOLOGY LA English DT Article DE ovarian carcinoma; manganese superoxide dismutase; myeloperoxidase; NAD(P)H : oxidoreductase 1; genetic polymorphisms ID MANGANESE SUPEROXIDE-DISMUTASE; MITOCHONDRIAL TARGETING SEQUENCE; MYELOPEROXIDASE (-463)G->A POLYMORPHISM; DT-DIAPHORASE; CORPUS-LUTEUM; BREAST-CANCER; MNSOD; CARCINOMA; ACID; SUSCEPTIBILITY AB Objective. One way in which parity and use of oral contraceptives may protect against ovarian cancer is by preventing inflammation and oxidative stress associated with ovulation. Since the genes superoxide dismutase (SOD2), myeloperoxidase (MPO), and NAD(P)H:quinone oxidoreductase 1 (NQO1) are involved in inflammation and oxidative stress, we investigated whether variants of these genes are associated with risk of ovarian cancer. Methods. In a hospital-based case-control study, we compared 125 cases and 193 controls with respect to prevalence of (1) the T C (val-->ala) substitution at the -9 position in the signal sequence of SOD2; (2) the G-->A substitution at the -463 position in the promoter region of MPO; and (3) the C-->T (pro-->ser) change in exon 6 of NQO1. Genotyping was done using PCR and gel electrophoresis for MPO and NQO1 and using MALDI-TOF mass spectrometry for SOD2. Results. For SOD2, women with the TC (val/ala) or CC (ala/ala) genotypes were at increased risk [odds ratio (OR) 2.1, 95% confidence interval (CI) 1.1-4.0], Results for MPO and NQO1 were in the hypothesized directions but were not statistically significant. For MPO, there was a small inverse association among women with GA or AA genotypes (OR = 0.72, 95% Cl 0.43 - 1.2). For NQO1, the TT (ser/ser) genotype was associated with somewhat increased risk (OR = 2.3, 95% CI 0.69-7.6). Conclusions. While these results need to be confirmed in other studies, they point to a possible role for genes involved in oxidative stress in the development of ovarian cancer. (C) 2004 Elsevier Inc. All rights reserved. C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NYU, Sch Med, New York, NY 10016 USA. Columbia Univ, Mailman Sch Publ Hlth, New York, NY 10032 USA. Natl Ctr Toxicol Res, Div Mol Epidemiol, Jefferson, AR 72079 USA. Roswell Pk Canc Inst, Buffalo, NY 14263 USA. RP Olson, SH (reprint author), Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA. EM olsons@mskcc.org FU NCI NIH HHS [R01CA61088, R03CA72456] NR 36 TC 61 Z9 64 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 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD JUN PY 2004 VL 93 IS 3 BP 615 EP 620 DI 10.1016/j.ygyno.2004.03.027 PG 6 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 831OS UT WOS:000222204700007 PM 15196853 ER PT J AU Major, ME Dahari, H Mihalik, K Puig, M Rice, CM Neumann, AU Feinstone, SM AF Major, ME Dahari, H Mihalik, K Puig, M Rice, CM Neumann, AU Feinstone, SM TI Hepatitis C virus kinetics and host responses associated with disease and outcome of infection in Chimpanzees SO HEPATOLOGY LA English DT Article ID IMMUNE-RESPONSES; PROTEIN-KINASE; RECOVERED CHIMPANZEES; HYPERVARIABLE REGION; T-LYMPHOCYTES; CLEARANCE; REPLICATION; PKR; RECHALLENGE; PREVENTION AB To study determinants of clinical outcome following HCV infection, viral kinetics, immune events, and intrahepatic cytokine markers were compared in 10 naive chimpanzees. Four of the animals cleared HCV; 6 developed persistent infections. All animals developed similar acute infections with increasing viremia from 1 to 2 weeks, followed by alanine aminotransferase (ALT) elevations and seroconversion. This viremia pattern consisted of a biphasic increase, a rapid slope (mean doubling time [t(2)] = 0.5 days) followed by a slower slope after the second week (t(2) = 7.5 days). This slowing of virus replication correlated in all animals with increased intrahepatic 2'5' oligoadenylate synthetase 1 (2OAS-1) messenger RNA (mRNA) levels and was independent of disease outcome. An effective control of virus replication was observed following increases in intrahepatic interferon gamma (IFN-gamma) mRNA and ALT levels. Although this control was associated in all animals with a 2-log decrease in virus titer, the timing occurred approximately 2 weeks later in, the chronic group (P < .05). Additionally, while cleared infections were characterized by a continual decrease in virus titer, the titers in the persistent infections reached a steady state level of 10(4) to 10(5) RNA copies/mL. This inability of the immune response to sustain viral clearance in the persistent infections was associated with a reduced intrahepatic CD3e and monocyte-induced protein 1alpha (MIP-1alpha) mRNA induction. In conclusion, these data indicate that, regardless of outcome, chimpanzees generate responses that control HCV replication during the early and late acute phase. However, the pathogenesis of HCV may be determined by a more rapid onset of the induced response and the cell population that migrates to the liver. C1 US FDA, DVP, CBER, Lab Hepatitis Viruses, Bethesda, MD 20892 USA. Bar Ilan Univ, Fac Life Sci, Ramat Gan, Israel. Rockefeller Univ, Ctr Study Hepatitis C, New York, NY 10021 USA. RP Major, ME (reprint author), US FDA, DVP, CBER, Lab Hepatitis Viruses, Bldg 29A,Rm 1D10,HFM448,8800 Rockville Pike, Bethesda, MD 20892 USA. EM major@cber.fda.gov FU NCI NIH HHS [CA85883] NR 37 TC 94 Z9 94 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 JUN PY 2004 VL 39 IS 6 BP 1709 EP 1720 DI 10.1002/hep.20239 PG 12 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 826SN UT WOS:000221849000029 PM 15185313 ER PT J AU Yost, LJ Tao, SH Egan, SK Barraj, LM Smith, KM Tsuji, JS Lowney, YW Schoof, RA Rachman, NJ AF Yost, LJ Tao, SH Egan, SK Barraj, LM Smith, KM Tsuji, JS Lowney, YW Schoof, RA Rachman, NJ TI Estimation of dietary intake of inorganic arsenic in US children SO HUMAN AND ECOLOGICAL RISK ASSESSMENT LA English DT Article DE inorganic arsenic; children; diet; exposure ID FDA TOTAL DIET; INTAKE DISTRIBUTIONS; UNITED-STATES; MARKET BASKET; EXPOSURE; FOOD; POPULATION; ELEMENTS; ADULTS; BIAS AB Arsenic is a natural component of the environment and is ubiquitous in soils, water, and the diet. Because dietary intake can be a significant source of background exposure to inorganic arsenic (the most toxicologically significant form), accurate intake estimates are needed to provide a context for risk management of arsenic exposure. Intake of inorganic arsenic by adults is fairly well characterized, but previous estimates of childhood intake were based on inorganic arsenic analyses in a limited number of foods (13 food types). This article estimates dietary intake for U.S. children (1 to 6 years of age) based on reported inorganic arsenic concentrations in 38 foods and in water used in cooking those foods (inorganic arsenic concentration of 0.8 mug/L), and U.S. Department of Agriculture food consumption data. This information is combined using a probabilistic software model to extract food consumption patterns and compute exposure distributions. The mean childhood dietary intake estimate for inorganic arsenic was 3.2 mug/day with a range of 1.6 to 6.2 mug/day for the 10th and 95th percentiles, respectively. For both the mean and 95th percentile inorganic arsenic intake rates, intake was predominantly contributed by grain and grain products, fruits and fruit juices, rice and rice products, and milk. C1 Exponent, Bellevue, WA USA. US FDA, College Pk, MD USA. Exponent, Washington, DC USA. Exponent, Boulder, CO USA. Integral, Bellevue, WA USA. RP Yost, LJ (reprint author), 15375 SE 30th Pl,Suite 250, Bellevue, WA 98007 USA. EM yostl@exponent.com NR 22 TC 51 Z9 51 U1 0 U2 16 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1080-7039 J9 HUM ECOL RISK ASSESS JI Hum. Ecol. Risk Assess. PD JUN PY 2004 VL 10 IS 3 BP 473 EP 483 DI 10.1080/10807030490452151 PG 11 WC Biodiversity Conservation; Environmental Sciences SC Biodiversity & Conservation; Environmental Sciences & Ecology GA 837LS UT WOS:000222637500002 ER PT J AU Klinman, DM Currie, D Gursel, I Verthelyi, D AF Klinman, DM Currie, D Gursel, I Verthelyi, D TI Use of CpG oligodeoxynucleotides as immune adjuvants SO IMMUNOLOGICAL REVIEWS LA English DT Review ID B SURFACE-ANTIGEN; IMMUNOSTIMULATORY DNA-SEQUENCES; TOLL-LIKE RECEPTORS; SYSTEMIC-LUPUS-ERYTHEMATOSUS; PLASMACYTOID DENDRITIC CELLS; INDUCE AUTOIMMUNE-DISEASE; NECROSIS-FACTOR-ALPHA; BACTERIAL-DNA; PLASMID DNA; INNATE IMMUNITY AB Synthetic oligodeoxynucleotides (ODNs) containing unmethylated CpG motifs directly stimulate human B cells and plasmacytoid dendritic cells (pDCs), thereby promoting the production of T helper 1 (Th1) and pro-inflammatory 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 5-500-fold. These effects are optimized by maintaining close physical contact between the CpG DNA and the immunogen. Animal challenge models establish that protective immunity can be accelerated and magnified by coadministering CpG DNA with vaccines. Ongoing clinical studies indicate that CpG ODNs are safe and well tolerated when administered as adjuvants to humans, and in some cases, they increase vaccine-induced immune responses. C1 US FDA, Sect Retroviral Immunol, Div Viral Prod, CBER, Bethesda, MD 20892 USA. US FDA, Div Therapeut Prot, CBER, Bethesda, MD 20014 USA. RP Klinman, DM (reprint author), US FDA, Sect Retroviral Immunol, Div Viral Prod, CBER, Bldg 29A,Room 3D10,8800 Rockville Pike, Bethesda, MD 20892 USA. EM klinman@cber.fda.gov OI Gursel, Ihsan/0000-0003-3761-1166 NR 135 TC 209 Z9 220 U1 1 U2 19 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD JUN PY 2004 VL 199 IS 1 BP 201 EP 216 DI 10.1111/j.0105-2896.2004.00148.x PG 16 WC Immunology SC Immunology GA 818OW UT WOS:000221255400015 PM 15233736 ER PT J AU Garcia-Ojeda, PA Hardy, S Kozlowski, S Stein, KE Feavers, IM AF Garcia-Ojeda, PA Hardy, S Kozlowski, S Stein, KE Feavers, IM TI Surface plasmon resonance analysis of antipolysaccharide antibody specificity: Responses to meningococcal group C conjugate vaccines and bacteria SO INFECTION AND IMMUNITY LA English DT Article ID INFLUENZAE TYPE-B; MURINE IMMUNE-RESPONSE; RANDOMIZED CONTROLLED-TRIAL; A/C POLYSACCHARIDE VACCINE; TETANUS TOXOID CONJUGATE; SEROGROUP-C; GROUP-A; CAPSULAR POLYSACCHARIDE; PROTEIN CONJUGATE; IMMUNOLOGICAL MEMORY AB Antibody (Ab) responses to polysaccharides (PS), such as Neisseria meningitidis group C PS (MCPS), are characterized as being thymus independent and are restricted with regard to clonotype and isotype expression. PS conjugated to proteins, e.g., MCPS coupled with tetanus toxoid or the diphtheria toxin derivative CRM197, elicit thymus-dependent responses. The present study developed a surface plasmon resonance approach to evaluate Ab responses to MCPS conjugate vaccines, including either O-acetylated (OAc+) or de-O-acetylated (OAc-) forms of the PS. The results were generally consistent with those obtained by enzyme-linked immunosorbent assay and showed that sera from mice immunized with conjugate vaccines contain Abs that bind more effectively to OAc+ and OAc- MCPS than sera from mice immunized with fixed bacteria. The data suggest a critical shared or overlapping epitope recognized by all the conjugate vaccine immune sera and strategies for assessing polyclonal Ab avidity. C1 Natl Inst Biol Stand & Controls, Div Bacteriol, Potters Bar EN6 3QG, Herts, England. US FDA, Ctr Drug Evaluat & Res, Div Monoclonal Antibodies, Off Biotechnol Prod, Bethesda, MD 20892 USA. RP Feavers, IM (reprint author), Natl Inst Biol Stand & Controls, Div Bacteriol, Blanche Ln,Potters Bar, Potters Bar EN6 3QG, Herts, England. EM ifeavers@nibsc.ac.uk NR 66 TC 11 Z9 11 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JUN PY 2004 VL 72 IS 6 BP 3451 EP 3460 DI 10.1128/IAI.72.6.3451-3460.2004 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 824CT UT WOS:000221662400044 PM 15155652 ER PT J AU Ito, S Ishii, KJ Shirota, H Klinman, DM AF Ito, S Ishii, KJ Shirota, H Klinman, DM TI CpG oligodeoxynucleotides improve the survival of pregnant and fetal mice following Listeria monocytogenes infection SO INFECTION AND IMMUNITY LA English DT Article ID CELL-MEDIATED-IMMUNITY; BACTERIAL-DNA; INTERFERON-GAMMA; CUTTING EDGE; INTRACELLULAR BACTERIA; DEPENDENT PROTECTION; IFN-GAMMA; MOTIFS; RESPONSES; MURINE AB Listeria infection during pregnancy can cause the death of both mother and fetus. Previous studies established that immunostimulatory CpG oligodeoxynucleotides (ODN) increase the resistance of healthy adult mice to many infectious pathogens, including Listeria monocytogenes. This study examines whether the innate immune response elicited by CpG ODN can reduce the susceptibility of pregnant mice to lethal listeria challenge. The results indicate that CpG ODN treatment significantly improves maternal survival and reduces pathogen transmission to offspring. CpG ODN administered during pregnancy did not induce abortion, birth defects, or reduce the size or health of litters. These findings suggest that CpG ODN may provide a safe and effective means of improving the health of mothers and fetuses during pregnancy. C1 FDA, CBER, Div Viral Prod, Sect Retroviral Immunol, Bethesda, MD 20892 USA. Osaka Univ, Res Inst Microbial Dis, Dept Host Def, Suita, Osaka 5650871, Japan. Japan Sci & Technol Corp, Solut Oriented Res Sci & Technol, Suita, Osaka 5650871, Japan. RP Klinman, DM (reprint author), FDA, CBER, Div Viral Prod, Sect Retroviral Immunol, Bldg 29A,Rm 3D10,8800 Rockville Pike, Bethesda, MD 20892 USA. EM Klinman@cber.fda.gov RI Ishii, Ken/B-1685-2012 OI Ishii, Ken/0000-0002-6728-3872 NR 42 TC 28 Z9 28 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JUN PY 2004 VL 72 IS 6 BP 3543 EP 3548 DI 10.1128/IAI.72.6.3543-3548.2004 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 824CT UT WOS:000221662400055 PM 15155663 ER PT J AU Clark, S Youngman, LD Chukwurah, B Palmer, A Parish, S Peto, R Collins, R AF Clark, S Youngman, LD Chukwurah, B Palmer, A Parish, S Peto, R Collins, R TI Effect of temperature and light on the stability of fat-soluble vitamins in whole blood over several days: implications for epidemiological studies SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY LA English DT Article DE vitamins; blood-based epidemiology; blood collection; stability; temperature; light ID PLASMA; CAROTENOIDS; BIOMARKERS; SEPARATION; RETINOL; SERUM AB Background Biochemical measurement of fat-soluble vitamins would allow direct assessment in epidemiological studies of their association with disease. However, the perceived instability of these compounds and typically high cost of collection and analysis may make their measurement impractical, particularly in large-scale studies. Using a high performance liquid chromatography assay developed in-house, we have investigated the separate effects of temperature and light on the stability of vitamins in whole blood over several days. Methods Multiple blood samples from 10 volunteers were stored at 20degreesC or 4degreesC and in dark or light conditions. Immediately after collection and 1, 2, 3, 4, and 7 days later, samples stored under each condition were centrifuged, and the plasma was aliquoted and stored at -80degreesC. Subsequently, all aliquots from each individual were analysed in one analytical run. Results In whole blood stored under any of the four conditions for up to 7 days, concentrations of alpha-carotene, beta-carotene, lutein, lycopene, retinol, and alpha-tocopherol changed by less than 8%, and cryptoxanthin and gamma-tocopherol by less than 11%. Although significant temperature effects were observed for alpha-carotene, and alpha- and gamma-tocopherol, and a significant effect of light was observed for alpha-carotene, cryptoxanthin, and lycopene, these analytes changed by less than 1% per day under all conditions. Conclusions Concentrations of these fat-soluble vitamins change by only a few per cent in whole blood during storage at room temperature for several days. Hence, delayed separation of blood samples (which may be required for practical reasons in large-scale epidemiological studies) does not preclude reliable measurement of fat-soluble vitamins. C1 Univ Oxford, Radcliffe Infirm, Nuffield Dept Clin Med, CTSU, Oxford OX2 6HE, England. Univ Oxford, Nuffield Dept Clin Med, Epidemiol Studies Unit, Oxford OX2 6HE, England. US FDA, Res Off, Laurel, MD 20708 USA. RP Clark, S (reprint author), Univ Oxford, Radcliffe Infirm, Nuffield Dept Clin Med, CTSU, Harkness Bldg,Woodstock Rd, Oxford OX2 6HE, England. EM sarah.clark@ctsu.ox.ac.uk NR 10 TC 14 Z9 15 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0300-5771 J9 INT J EPIDEMIOL JI Int. J. Epidemiol. PD JUN PY 2004 VL 33 IS 3 BP 518 EP 525 DI 10.1093/ije/dyh064 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 832MR UT WOS:000222272100018 PM 15105406 ER PT J AU De Jesus, AJ Olsen, AR Bryce, JR Whiting, RC AF De Jesus, AJ Olsen, AR Bryce, JR Whiting, RC TI Quantitative contamination and transfer of Escherichia coli from foods by houseflies, Musca domestica L. (Diptera : Muscidae) SO INTERNATIONAL JOURNAL OF FOOD MICROBIOLOGY LA English DT Article DE houseflies; bacterial transfer; food ID REGULATORY ACTION CRITERIA; FLIES; VECTORS; FILTH; FLY AB The housefly, Musca domestica L. (Diptera: Muscidae), is recognized as an important factor in the dissemination of various infectious diseases such as cholera, shigellosis, and salmonellosis. They can also serve as a cross-contamination vector for other foodborne pathogens. However, the potential for bacterial transfer by houseflies has been demonstrated in a qualitative rather than quantitative manner. In this study, the numbers of bacteria a housefly can carry on its body and transfer to a clean surface after exposure to a sugar-milk aqueous solution, steak, and potato salad contaminated with a fluorescent gene Escherichia coli (8 log(10) CFU/ml) were determined. In the first series of experiments to quantify bacterial numbers on the flies, about 40-60 flies were transferred into a sterile cage, exposed to the food for 30 min, the flies immobilized and the attached E. coli on each fly enumerated. Detectable E. coli (>1.7 log(10) CFU/fly) were found on 43% (29/67), 53% (23/43), and 62% (32/52) of the flies in the cages with sugar/milk, steak, and potato salad, respectively. For the positive flies, the geometric mean carriage (log(10) CFU/fly) was 2.93 +/- 1.24 for sugar-milk, 3.77 +/- 1.28 for steak, and 2.25 +/- 0.64 for the potato salad. In the second series of experiments, the transfer of bacteria by individual flies from contaminated food to the inner surface of a sterile jar per each landing was determined. E. coli transferred from the sugar-milk was 3.5 +/- 0.7 log(10) CFU/fly-landing, 3.9 +/- 0.7 for steak and 2.61 +/- 1.16 for the potato salad. From the initial contamination levels of bacteria and the number of transferred bacteria, it can be calculated that flies contaminate clean surfaces with approximately 0.1 mg of food per landing. (C) 2004 Elsevier B.V. All rights reserved. C1 US FDA, Ctr Safety & Appl Nutr, College Pk, MD 20740 USA. RP De Jesus, AJ (reprint author), US FDA, Ctr Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM adejesus@cfsan.fda.gov NR 10 TC 44 Z9 47 U1 0 U2 13 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 JUN 1 PY 2004 VL 93 IS 2 BP 259 EP 262 DI 10.1016/j.ijfoodmicro.2003.12.003 PG 4 WC Food Science & Technology; Microbiology SC Food Science & Technology; Microbiology GA 824YJ UT WOS:000221722800012 PM 15135963 ER PT J AU Bonson, KR AF Bonson, KR TI Review of the evidence for neurotoxic deficits in animals exposed to MDMA SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 24th CINP Congress CY JUN 20-24, 2004 CL Paris, FRANCE SP CINP C1 US FDA, Controlled Subst Staff, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4211 USA SN 1461-1457 J9 INT J NEUROPSYCHOPH JI Int. J. Neuropsychopharmacol. PD JUN PY 2004 VL 7 SU 1 BP S84 EP S84 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 864WF UT WOS:000224663000319 ER PT J AU Williams, AJ Parshikov, IA Moody, JD Heinze, TM Sutherland, JB AF Williams, AJ Parshikov, IA Moody, JD Heinze, TM Sutherland, JB TI Fungal transformation of an antimicrobial fluoroquinolone drug during growth on poultry litter materials SO JOURNAL OF APPLIED POULTRY RESEARCH LA English DT Article DE fluoroquinolone; norfloxacin; poultry litter ID AVIAN ESCHERICHIA-COLI; NORFLOXACIN; RESISTANCE; CIPROFLOXACIN; CHICKENS AB The ability of a nonpathogenic fungus, Pestalotiopsis guepini, to metabolize fluoroquinolone antimicrobial agents during growth on poultry litter materials was investigated. Sterilized rice hulls, ground corncobs, and pine shavings in glass jars covered with foil were moistened with sterile water and inoculated with P. guepini. The litter materials then were dosed with norfloxacin and incubated for 20 d. In rice-hull cultures, P. guepini produced 4 metabolites: 7-amino-1-ethyl-6-fluoro-4-oxo-1,4-dihydroquinolone-3-carboxylic acid, N-formylnorfloxacin, N-acetylnorfloxacin, and desethylene-N-acetylnorfloxacin. In corncob cultures, the fungus produced N-formylnorfloxacin and N-acetylnorfloxacin. In pine-shavings cultures, there was little growth of the fungus and no metabolism of norfloxacin. The results suggest that fungi that grow on poultry litter may degrade residues of antimicrobial drugs. C1 US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Univ Mississippi, Dept Med Chem, University, MS 38677 USA. RP Sutherland, JB (reprint author), US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM jsutherland@nctr.fda.gov OI Parshikov, Igor/0000-0003-1466-1128 NR 28 TC 3 Z9 3 U1 1 U2 4 PU POULTRY SCIENCE ASSOC INC PI SAVOY PA 1111 NORTH DUNLAP AVE, SAVOY, IL 61874-9604 USA SN 1056-6171 J9 J APPL POULTRY RES JI J. Appl. Poult. Res. PD SUM PY 2004 VL 13 IS 2 BP 235 EP 240 PG 6 WC Agriculture, Dairy & Animal Science SC Agriculture GA 968EG UT WOS:000232144100012 ER PT J AU Jang, MS Miao, HX Carlesso, N Shelly, L Zlobin, A Darack, N Qin, JZ Nickoloff, BJ Miele, L AF Jang, MS Miao, HX Carlesso, N Shelly, L Zlobin, A Darack, N Qin, JZ Nickoloff, BJ Miele, L TI Notch-1 regulates cell death independently of differentiation in murine erythroleukemia cells through multiple apoptosis and cell cycle pathways SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Review ID NF-KAPPA-B; ACTIVATED PROTEIN-KINASE; HYBRID POLAR COMPOUNDS; C-JUN; RETINOBLASTOMA PROTEIN; NEOPLASTIC TRANSFORMATION; HEMATOPOIETIC PROGENITORS; SIGNALING PROMOTES; LIGAND JAGGED-1; TRANSGENIC MICE AB Notch signaling is a potential therapeutic target for various solid and hematopoietic malignancies. We have recently shown that downregulation of Notch-1 expression has significant anti-neoplastic activity in pre-clinical models. However, the mechanisms through which Notch modulation may affect cell fate in cancer remain poorly understood. We had previously shown that Notch-1 prevents apoptosis and is necessary for pharmacologically induced differentiation in murine erythroleukemia (MEL) cells. We investigated the mechanisms of these effects using three experimental strategies: (1) MEL cells stably transfected with antisense Notch-1 or constitutively active Notch-1, (2) activation of Notch-1 by a cell-associated ligand, and (d3) activation of Notch-1 by a soluble peptide ligand. We show that: (1) downregulation of Notch-1 sensitizes MEL cells to apoptosis induced by a Ca2+ influx or anti-neoplastic drugs; (2) Notch-1 downregulation induces phosphorylation of c-Jun N-terminal kinase (JNK) while constitutive activation of Notch-1 or prolonged exposure to a soluble Notch ligand abolishes it; (3) Notch-1 has dose-and time-dependent effects on the levels of apoptotic inhibitor Bcl-x(L) and cell cycle regulators p21(cip1)/(waf1), p27(kip1), and Rb; and (4) Notch-1 activation by a cell-associated ligand is accompanied by rapid and transient induction of NF-kappaB DNA-binding activity. The relative effects of Notch-1 signaling on these pathways depend on the levels of Notch-1 expression, the mechanism of activation, and the timing of activation. The relevance of these findings to the role of Notch signaling in differentiation and cancer are discussed. J. Cell. Physiol. 199: 418-433, 2004. (C) 2003 Wiley-Liss, Inc. C1 Univ Illinois, Dept Biopharmaceut Sci, Chicago, IL 60612 USA. Univ Illinois, Ctr Canc, Chicago, IL 60612 USA. Loyola Univ, Cardinal Bernardin Canc Ctr, Maywood, IL USA. Massachusetts Gen Hosp, AIDS Res Ctr Expt Hematol, Boston, MA 02114 USA. Ctr Biol Evaluat & Res, Div Monoclonal Antibodies, Bethesda, MD USA. Loyola Univ, Dept Pathol, Maywood, IL USA. RP Miele, L (reprint author), Univ Illinois, Dept Biopharmaceut Sci, 833 S Wood St,M-C 865, Chicago, IL 60612 USA. EM lmiele@uic.edu FU NCI NIH HHS [1R01 CA84065-01] NR 101 TC 54 Z9 55 U1 2 U2 6 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD JUN PY 2004 VL 199 IS 3 BP 418 EP 433 DI 10.1002/jcp.10467 PG 16 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 817LY UT WOS:000221180200010 PM 15095289 ER PT J AU Huang, SM Lesko, LJ AF Huang, SM Lesko, LJ TI Drug-drug, drug-dietary supplement, and drug-citrus fruit and other food interactions: What have we learned? SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article DE drug-drug interaction; drug-dietary supplement interaction; drug-juice interaction; drug development; exposure-response relationship; labeling; risk management ID ST-JOHNS-WORT; FORTIFIED ORANGE JUICE; INCREASES SERUM CONCENTRATIONS; GRAPEFRUIT JUICE; IN-VITRO; HEALTHY-VOLUNTEERS; P-GLYCOPROTEIN; PHARMACOKINETICS; INHIBITION; BIOAVAILABILITY AB Serious drug-drug interactions hove contributed to recent U.S. market withdrawals and also recent nonapprovals of a few new molecular entities. Many of these interactions involved the inhibition or induction of metabolizing enzymes and efflux transporters, resulting in altered systemic exposure and adverse drug reactions or loss of efficacy. In addition to drug-drug interactions, drug-dietary supplement and drug-citrus fruit interactions, among others, could also cause adverse drug reactions or loss of efficacy and are important issues to consider in the evaluation of new drug candidates. This commentary reviews (1) the Current understanding of the mechanistic basis of these interactions, (2) issues to consider in the interpretation of study results, and (3) recent labeling examples to illustrate the translation of study results to information useful for patients and health care providers. C1 US FDA, Off Clin Pharmacol & Biopharmaceut, CDER, Rockville, MD 20850 USA. RP Huang, SM (reprint author), US FDA, Off Clin Pharmacol & Biopharmaceut, CDER, HFD-850,5600 Fishers Lane,PKLN 6A-19, Rockville, MD 20850 USA. NR 71 TC 90 Z9 94 U1 2 U2 14 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 JUN PY 2004 VL 44 IS 6 BP 559 EP 569 DI 10.1177/0091270004265367 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 822HC UT WOS:000221528800001 PM 15145962 ER PT J AU Ma, JD Nafziger, AN Kashuba, ADM Kim, MF Gaedigk, A Rowland, E Kim, JS Bertino, JS AF Ma, JD Nafziger, AN Kashuba, ADM Kim, MF Gaedigk, A Rowland, E Kim, JS Bertino, JS TI Limited sampling strategy of S-warfarin concentrations, but not warfarin S/R ratios, accurately predicts S-Warfarin AUC during baseline and inhibition in CYP2C9 extensive metabolizers SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article DE CYP2C9; S-warfarin; warfarin S/R ratios; limited sampling strategy; drug metabolism ID CONCENTRATION-TIME CURVE; IN-VITRO; GENETIC POLYMORPHISMS; PLASMA-CONCENTRATION; CYTOCHROME P4502C9; COOPERSTOWN 5+1; AREA; MIDAZOLAM; COCKTAIL; GENOTYPE AB S-warfarin area under the concentration-time curve (AUC(0-infinity)) and clearance are used as measures of cytochrome P450 (CYP) 2C9 activity. In addition, warfarin SIR ratios are used to assess CYP2C9 activity. The determination of S-warfarin AUC(0-infinity) requires multiple blood samples. Limited sampling strategy (LSS) is a validated technique that estimates AUC(0-infinity) using limited blood samples. The objective of this study was to evaluate LSS of S-warfarin concentrations and warfarin S/R ratios to predict S-warfarin AUG(0-infinity) during CYP2C9 baseline activity and inhibition with fluvastatin. Fifty-one healthy subjects, genotyped as CYP2C9 extensive metabolizers, were administered oral warfarin 10 mg. Blood samples were collected over 96 hours. S-warfarin AUC(0-infinity) equations were derived from a training set of 20 subjects using multiple linear regression. Validation of the equations used data from the remaining 31 subjects. All derived equations were within acceptable limits for measures of bias and precision. Single-point and two-point S-warfarin concentrations, but not warfarin SIR ratios, were predictive of S-warfarin AUC(0-infinity) during CYP2C9 baseline activity and inhibition, No correlation was observed between CYP2C9*1/*1 and *1/*2 genotypes and either S-warfarin concentrations or warfarin SIR ratios, The equation using two-point S-warfarin concentrations at 24 and 48 hours was the most accurate predictor of S-warfarin AUG(0-infinity). LSS using S-warfarin concentrations is an efficient and accurate technique to evaluate S-warfarin AUC(0-infinity) when using warfarin as a CYP2C9 probe drug. C1 Bassett Healthcare, Dept Med, Clin Pharmacol Res Ctr, Cooperstown, NY 13326 USA. Bassett Healthcare, Dept Pharm Serv, Cooperstown, NY 13326 USA. Univ N Carolina, Sch Pharm, Chapel Hill, NC USA. US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. Childrens Mercy Hosp & Clin, Div Pediat Clin Pharmacol & Expt Therapeut, Kansas City, MO USA. RP Bertino, JS (reprint author), Bassett Healthcare, Dept Med, Clin Pharmacol Res Ctr, 1 Atwell Rd, Cooperstown, NY 13326 USA. NR 30 TC 10 Z9 12 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 JUN PY 2004 VL 44 IS 6 BP 570 EP 576 DI 10.1177/0091270004265366 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 822HC UT WOS:000221528800002 PM 15145963 ER PT J AU Minor, P Newham, J Jones, N Bergeron, C Gregori, L Asher, D van Engelenburg, F Stroebel, T Vey, M Barnard, G Head, M AF Minor, P Newham, J Jones, N Bergeron, C Gregori, L Asher, D van Engelenburg, F Stroebel, T Vey, M Barnard, G Head, M CA WHO Working Grp Int Reference Mat TI Standards for the assay of Creutzfeldt-Jakob disease specimens SO JOURNAL OF GENERAL VIROLOGY LA English DT Article ID PRION-PROTEIN; MONOCLONAL-ANTIBODY; PRPSC AB Assays for the agent of Creutzfeldt-Jakob disease (CJD) include measurement of infectivity in different animal systems, such as wild-type or transgenic mice, and detection of PrPSc by different methods and formats. The various assays could be best calibrated against each other by use of uniform readily available materials, and samples of four human brains, two from sporadic CJD patients, one from a variant CJD patient and one from a non-CJD patient, have been prepared as 10% homogenates dispensed in 2000 vials each for this purpose. Results of in vitro methods, particularly immunoblot assays, were compared in the first collaborative study described here. While dilution end-points varied, the minimum detectable volume was surprisingly uniform for most assays and differences in technical procedure, other than the sample volume tested, had no detectable systematic effect. The two specimens from sporadic CJD cases contained both type 1 and type 2 prion proteins in approximately equal proportions. The materials have been given the status of reference reagents by the World Health Organization and are available for further study and assessment of other in vitro or in vivo assay procedures. C1 Natl Inst Biol Stand & Controls, Blanche Lane, Potters Bar EN6 3QG, Herts, England. Natl Blood Serv, Natl Transfus Microbiol Reference Lab, London NW9 5BG, England. Univ Toronto, CRND, W Toronto, ON M5S 3H2, Canada. VA Med Ctr, Baltimore, MD 21201 USA. US FDA, CBER, Div Emerging & Transfus Transmitted Dis, OBRR,HFM310, Rockville, MD 20852 USA. Sanquin Res, NL-1066 AD Amsterdam, Netherlands. Med Univ Vienna, Austrian Reference Ctr Human Pr Dis, Inst Neurol, A-1097 Vienna, Austria. Aventis Behring GmbH, D-35002 Marburg, Germany. Univ Cambridge, Dept Clin Vet Med, Cambridge CB3 0EG, England. Western Gen Hosp, Natl Creutzfeldt Jakob Dis Surveillance Unit, Edinburgh EH4 2XU, Midlothian, Scotland. RP Minor, P (reprint author), Natl Inst Biol Stand & Controls, Blanche Lane, Potters Bar EN6 3QG, Herts, England. EM pminor@nibsc.ac.uk OI Head, Mark/0000-0003-2034-8613; Budka, Herbert/0000-0002-1933-1577 NR 13 TC 27 Z9 27 U1 0 U2 0 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 0022-1317 J9 J GEN VIROL JI J. Gen. Virol. PD JUN PY 2004 VL 85 BP 1777 EP 1784 DI 10.1099/vir.0.79959-0 PN 6 PG 8 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA 830IW UT WOS:000222116600048 PM 15166463 ER PT J AU Mire-Sluis, AR Barrett, YC Devanarayan, V Koren, E Liu, H Maia, M Parish, T Scott, G Shankar, G Shores, E Swanson, SJ Taniguchi, G Wierda, D Zuckerman, LA AF Mire-Sluis, AR Barrett, YC Devanarayan, V Koren, E Liu, H Maia, M Parish, T Scott, G Shankar, G Shores, E Swanson, SJ Taniguchi, G Wierda, D Zuckerman, LA TI Recommendations for the design and optimization of immunoassays used in the detection of host antibodies against biotechnology products SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE assays; antibody; immunogenicity AB Most biopharmaceutical therapeutics elicit some level of antibody response against the product. This antibody response can, in some cases, lead to potentially serious side effects and/or loss of efficacy. Therefore, the immunogenicity of therapeutic proteins is a concern for clinicians, manufacturers and regulatory agencies. In order to assess immunogenicity of these molecules, appropriate detection, quantitation and characterization of antibody responses are necessary. Inadequately designed antibody assays have led to the hampering of product development or, during licensure, post-marketing commitments. This document provides scientific recommendations based on the experience of the authors for the development of anti-product antibody immunoassays intended for preclinical or clinical studies. While the main focus of this document is assay design considerations, we provide scientific focus and background to the various assay performance parameters necessary for developing a valid assay. Sections on assay performance parameters, including those that appear in regulatory guidances, are contained in this manuscript. (C) 2004 Elsevier B.V. All rights reserved. C1 US FDA, Ctr Drug Evaluat & Res, Off Biotechnol Prod, Rockville, MD 20852 USA. Bristol Myers Squibb Co, Princeton, NJ 08543 USA. Lilly Corp Ctr, Lilly Res Labs, Global Stat Sci, Indianapolis, IN 46285 USA. Amgen Inc, Clin Immunol, Thousand Oaks, CA 91320 USA. Wyeth Pharmaceut, Pearl River, NY 10965 USA. Proctor & Gamble Pharmaceut, Norwich, NY 13346 USA. MDS Pharma Sci, Ligand Binding Serv, St Laurent, PQ, Canada. Centocor Inc, Dept Clin Pharmacol, Malvern, PA 19355 USA. US FDA, Div Therapeut Prot, CDER, Bethesda, MD 20892 USA. Biomarin Pharmaceut Inc, Clin Lab Operat, Novato, CA 94949 USA. Eli Lilly & Co, Dept Immunotoxicol, Greenfield, IN 46140 USA. ZymoGenet Inc, BioAnalyt Res & Dev, Seattle, WA 98102 USA. RP Mire-Sluis, AR (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Biotechnol Prod, 5515 Secur Lane,HFD-3,Rm 1011, Rockville, MD 20852 USA. EM mire-sluisa@cder.fda.gov NR 6 TC 323 Z9 334 U1 1 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-1759 J9 J IMMUNOL METHODS JI J. Immunol. Methods PD JUN PY 2004 VL 289 IS 1-2 BP 1 EP 16 DI 10.1016/j.jim.2004.06.002 PG 16 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA 842MV UT WOS:000223009400001 PM 15251407 ER PT J AU Tsujimura, H Tamura, T Kong, HJ Nishiyama, A Ishii, KJ Klinman, DM Ozato, K AF Tsujimura, H Tamura, T Kong, HJ Nishiyama, A Ishii, KJ Klinman, DM Ozato, K TI Toll-like receptor 9 signaling activates NF-kappa B through IFN regulatory Factor-8/IFN consensus sequence binding protein in dendritic cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CPG-DNA; GENE-EXPRESSION; BACTERIAL-DNA; KINASE COMPLEX; IKK-ALPHA; PHOSPHORYLATION; MOTIFS; MICE; INTERLEUKIN-12; ICSBP/IRF-8 AB Unmethylated CpG DNA binds to the Toll-like receptor 9 (TLR9) and activates NF-kappaB to induce cytokine genes in dendritic cells (DCs). IFN regulatory factor (IRF)-8/IFN consensus sequence binding protein is a transcription factor important for development and activation of DCs. We found that DCs from IRF-8(-/-) mice were unresponsive to CpG and failed to induce TNF-alpha and IL-6, targets of NF-kappaB. Revealing a signaling defect selective for CpG, these cytokines were robustly induced in IRF-8(-/-) DCs in response to LPS that signals through TLR4. IRF-8(-/-) DCs expressed TLR9, adaptor myeloid differentiation factor 88, and other signaling molecules, but CpG failed to activate NF-kappaB in -/- cells. This was due to the selective inability of -/- DCs to activate I-kappaB kinase alphabeta the kinases required for NF-kappaB in response to CpG. IRF-8 reintroduction fully restored CpG activation of NF-kappaB and cytokine induction in -/- DCs. Together, TLR signals that activate NF-kappaB are diverse among different TLRs, and TLR9 signaling uniquely depends on IRF-8 in DCs. C1 NICHHD, Lab Mol Growth Regulat, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Ozato, K (reprint author), NICHHD, Lab Mol Growth Regulat, NIH, Bldg 6 Room 2A01,6 Ctr Dr, Bethesda, MD 20892 USA. EM ozatok@nih.gov RI Ishii, Ken/B-1685-2012 OI Ishii, Ken/0000-0002-6728-3872 NR 47 TC 92 Z9 96 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 JUN 1 PY 2004 VL 172 IS 11 BP 6820 EP 6827 PG 8 WC Immunology SC Immunology GA 822ZN UT WOS:000221579600039 PM 15153500 ER PT J AU Giles, JA Falconio, J Yuenger, JD Zenilman, JM Dan, M Bash, MC AF Giles, JA Falconio, J Yuenger, JD Zenilman, JM Dan, M Bash, MC TI Quinolone resistance-determining region mutations and por type of Neisseria gonorrhoeae isolates: Resistance surveillance and typing by molecular methodologies SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT International Congress of the International-Society-for-Sexually-Transitted-Disease-Research CY JUL 17-30, 2003 CL Ottawa, CANADA SP Int Soc Sexually Transmitted Dis Res ID LEVEL CIPROFLOXACIN RESISTANCE; MEMBRANE PROTEIN PIB; DECREASED SUSCEPTIBILITY; UNITED-STATES; IN-VITRO; ANTIMICROBIAL RESISTANCE; TOPOISOMERASE-IV; POINT MUTATIONS; HIGH PREVALENCE; DNA GYRASE AB Quinolone resistance is increasing rapidly in Neisseria gonorrhoeae and is a significant public health problem that requires ongoing surveillance. To examine the feasibility of molecular surveillance of quinolone resistance, and to further characterize an outbreak of resistant N. gonorrhoeae in Israel, the quinolone resistance determining region (QRDR) sequences and the por types of 80 N. gonorrhoeae isolates were determined using molecular techniques. QRDRs of gyrA and parC were amplified by polymerase chain reaction and were sequenced directly. The por type was determined by checkerboard hybridizations performed using oligonucleotide probes to regions encoding 5 variable loops of the porin protein. All 42 ciprofloxacin-resistant (CipR) isolates had mutations in QRDRs of both gyrA and parC, and identical mutations were found in 93% of these isolates. One intermediately resistant isolate had 1 mutation in gyrA, and susceptible isolates showed no mutations. Forty isolates had 1 of 2 por types that differed only by an in-frame deletion in variable region 5; all but 1 of these isolates were CipR. QRDR sequencing and por type determination showed that the outbreak of CipR N. gonorrhoeae in Israel was clonal. QRDR mutations were consistent with those previously characterized; this indicates that DNA probes can be developed for rapid detection and surveillance of quinolone-resistant N. gonorrhoeae in settings in which nonculture diagnostic methods are used. C1 Johns Hopkins Univ, Sch Med, Div Allergies & Infect Dis, Baltimore, MD USA. US FDA, Div Bacterial Parasit & Allergen Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. Edith Wolfson Med Ctr, Infect Dis Unit, Tel Aviv, Israel. RP Giles, JA (reprint author), 720 Rutland Ave,1165 Ross, Baltimore, MD 21205 USA. EM jgiles4@jhmi.edu FU NIAID NIH HHS [K24AI01633, R01AI50217, AI38399]; NICHD NIH HHS [R03 HD44396] NR 52 TC 23 Z9 23 U1 1 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JUN 1 PY 2004 VL 189 IS 11 BP 2085 EP 2093 DI 10.1086/386312 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 823ZQ UT WOS:000221653500017 PM 15143477 ER PT J AU Escobedo, MB Gunkel, JH Kennedy, KA Shattuck, KE Sanchez, PJ Seidner, S Hensley, G Cochran, CK Moya, F Morris, B Denson, S Stribley, R Naqvi, M Lasky, RE AF Escobedo, MB Gunkel, JH Kennedy, KA Shattuck, KE Sanchez, PJ Seidner, S Hensley, G Cochran, CK Moya, F Morris, B Denson, S Stribley, R Naqvi, M Lasky, RE CA Texas Neonatal Res Grp TI Early surfactant for neonates with mild to moderate respiratory distress syndrome: A multicenter, randomized trial SO JOURNAL OF PEDIATRICS LA English DT Article AB Objective We studied the efficacy and safety of electively providing surfactant to preterm infants with mild to moderate respiratory distress syndrome (RDS) not requiting mechanical ventilation. Study design A 5-center, randomized clinical trial was performed on 132 infants with RDS, birth weight greater than or equal to1250 grams, gestational age less than or equal to36 weeks, postnatal age 4 to 24 hours, F-IO2 greater than or equal to40% for greater than or equal to1 hour, and no immediate need for intubation. Infants were randomly assigned to intubation, surfactant (Survanta, Ross Laboratories, Columbus, Ohio) administration, and expedited extubation (n = 65) or expectant management (n = 67) with subsequent intubation and surfactant treatment as clinically indicated. The primary outcome was duration of mechanical ventilation. Results infants in the surfactant group had a median duration of mechanical ventilation of 2.2 hours compared with 0.0 hours for control infants, since only 29 of 67 control infants required mechanical ventilation (P = .001). Surfactant-treated infants were less likely to require subsequent mechanical ventilation for worsening respiratory disease (26% vs 43%, relative risk = 0.60; 95% CI, 0.37, 0.99). There were no differences in secondary outcomes (duration of nasal continuous positive airway pressure, oxygen therapy, hospital stay, or adverse outcomes). Conclusions Routine elective intubation for administration of surfactant to preterm infants greater than or equal to1250 grams with mild to moderate RDS is not recommended. C1 Univ Texas, SW Med Ctr, Dallas, TX USA. Univ Texas, Med Branch, Galveston, TX 77550 USA. Univ Texas, Sch Med, Houston, TX USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. Texas Tech Hlth Sci Ctr, Amarillo, TX USA. RP Gunkel, JH (reprint author), FDA, CDER, OCTAP, HFD 960,Div Pediat Drug Dev, 7520 Standish Pl,Ste 229, Rockville, MD 20855 USA. NR 8 TC 35 Z9 39 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD JUN PY 2004 VL 144 IS 6 BP 804 EP 808 DI 10.1016/j.jpeds.2004.03.024 PG 5 WC Pediatrics SC Pediatrics GA 829KT UT WOS:000222047900022 PM 15192630 ER PT J AU Polli, JE Yu, LX Cook, JA Amidon, GL Borchardt, RT Burnside, BA Burton, PS Chen, ML Conner, DP Faustino, PJ Hawi, AA Hussain, AS Joshi, HN Kwei, G Lee, VHL Lesko, LJ Lipper, RA Loper, AE Nerurkar, SG Polli, JW Sanvordeker, DR Taneja, R Uppoor, RS Vattikonda, CS Wilding, I Zhang, G AF Polli, JE Yu, LX Cook, JA Amidon, GL Borchardt, RT Burnside, BA Burton, PS Chen, ML Conner, DP Faustino, PJ Hawi, AA Hussain, AS Joshi, HN Kwei, G Lee, VHL Lesko, LJ Lipper, RA Loper, AE Nerurkar, SG Polli, JW Sanvordeker, DR Taneja, R Uppoor, RS Vattikonda, CS Wilding, I Zhang, G TI Summary workshop report: Biopharmaceutics classification system - implementation challenges and extension opportunities SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Editorial Material DE Biopharmaceutics Classification System (BCS); bioequivalence; oral absorption; regulatory science; solubility; permeability C1 Univ Maryland, Sch Pharm, Baltimore, MD 21201 USA. US FDA, Ctr Drug Evaluat, Rockville, MD 20857 USA. Pfizer Global Res & Dev, Ann Arbor, MI 48105 USA. Univ Michigan, Coll Pharm, Ann Arbor, MI 48109 USA. Univ Kansas, Sch Pharm, Lawrence, KS 66047 USA. Advancis Pharmaceut Corp, Gaithersburg, MD 20878 USA. ADMETRx, Kalamazoo, MI 49007 USA. A Hawi Consulting Ltd, Ridgefield, CT 06877 USA. Barr Labs, Pomona, NY 10970 USA. Merck Res Labs, W Point, PA 19486 USA. ALZA, Mountain View, CA 94039 USA. Bristol Myers Squibb Co, Princeton, NJ 08543 USA. Schering Plough Res Inst, Kenilworth, NJ 07003 USA. Glaxo SmithKline, Res Triangle Pk, NC 27709 USA. Watson Labs, Corona, CA 92880 USA. TAP Pharmaceut, Lake Forest, IL 60045 USA. Pharmaceut Profiles Ltd, Nottingham NG11 6JS, England. Andrx Pharmaceut, Ft Lauderdale, FL 33314 USA. RP Polli, JE (reprint author), Univ Maryland, Sch Pharm, Baltimore, MD 21201 USA. EM jpolli@rx.umaryland.edu RI Lee, Vincent/A-9439-2008 OI Lee, Vincent/0000-0001-7708-6269 NR 1 TC 74 Z9 81 U1 0 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 JUN PY 2004 VL 93 IS 6 BP 1375 EP 1381 DI 10.1002/jps.20064 PG 7 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 826DF UT WOS:000221808700001 PM 15124197 ER PT J AU Myers, MR AF Myers, MR TI Transient temperature rise due to ultrasound absorption at a bone/soft-tissue interface SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID ACOUSTIC RADIATION FORCE; MODELS; BONE AB Thermal effects due to high ultrasound absorption in bone pose an ongoing safety issue. Of considerable concern is the heating of the soft tissue adjacent to the bone surface. Mathematical models can be useful in predicting the transient temperature near the interface during insonation. This paper develops a model that provides the temperature field in terms of simple expressions that convey the functional dependence of the material properties, and are easily incorporated into standards and ultrasound machine software, yet are able to incorporate the material properties of both bone and soft tissue. The model contains an asymptotic theory based upon a "high-attenuation" assumption: the distance diffused by heat over the time of interest is large compared to the ultrasound attenuation length. Model predictions of temperature rise and location of maximum temperature were in close agreement with finite-element calculations, using parameters appropriate for radiation-force imaging and focused-ultrasound surgery. (C) 2004 Acoustical Society of America. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20852 USA. RP Myers, MR (reprint author), US FDA, Ctr Devices & Radiol Hlth, HFZ-132, Rockville, MD 20852 USA. NR 15 TC 18 Z9 20 U1 0 U2 4 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 JUN PY 2004 VL 115 IS 6 BP 2887 EP 2891 DI 10.1121/1.1707091 PG 5 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA 830VZ UT WOS:000222153500020 PM 15237812 ER PT J AU Harris, GR Gammell, PM AF Harris, GR Gammell, PM TI 1-3 piezoelectric composite transducers for swept-frequency calibration of hydrophones from 100 kHz to 2 MHz SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID TIME-DELAY SPECTROMETRY; SENSITIVITY; SURGERY AB Rapid calibration of hydrophones used in biomedical ultrasound is possible with swept frequency techniques such as time delay spectrometry. However, calibrations below 2 MHz largely have been neglected because of insufficient transmitting transducer bandwidth, even though important medical applications operate in this range. To address this deficiency, several transmitting transducer designs were developed and tested, and two 1-3 piezoelectric composite designs were found to have the requisite bandwidth and uniformity of response. In one the element has a plane front face and spherically concave back face (plano-concave), and in the second both faces are concave, but with different radii of curvature (biconcave). The nonuniform thickness disperses the thickness resonance, and the composite structure suppresses radial-mode resonances. Also, the composite's lower acoustic impedance provides a more efficient match to water. The piezoelectric composite transducers were found to have transmitting pressure sensitivities superior to ceramic single-element and segmented designs having similar dimensions, and their responses were significantly more uniform (<25 dB variation from 0.1-2 MHz, with <1 dB fine structure variation), likely due to decreased contributions from radial modes. C1 Food & Drug Adm, Rockville, MD 20850 USA. Gammell Appl Technol LLC, Exmore, VA 23350 USA. RP Harris, GR (reprint author), Food & Drug Adm, 9200 Corp Blvd, Rockville, MD 20850 USA. EM gerald.harris@.fda.hhs.gov NR 19 TC 6 Z9 6 U1 0 U2 4 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 JUN PY 2004 VL 115 IS 6 BP 2914 EP 2918 DI 10.1121/1.1707090 PG 5 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA 830VZ UT WOS:000222153500023 PM 15237815 ER PT J AU Bamford, J Berg, M Bikowski, J Kligman, A Marks, R Plewig, G Sires, B Thiboutot, D Webster, G Yaar, M AF Bamford, J Berg, M Bikowski, J Kligman, A Marks, R Plewig, G Sires, B Thiboutot, D Webster, G Yaar, M TI Standard grading system for Rosacea: Report of the National Rosacea Society Expert Committee on the Classification and Staging of Rosacea SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article C1 US FDA, Div Dermatol & Dental Drug Prod, Rockville, MD 20857 USA. Mayo Clin, Dept Dermatol, Scottsdale, AZ USA. Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA. Mater Misericordiae Hosp, Reg Ctr Dermatol, Dublin 7, Ireland. RP Bamford, J (reprint author), Natl Rosacea Soc, 800 S Northwest Highway,Suite 200, Barrington, IL 60010 USA. NR 9 TC 1 Z9 3 U1 0 U2 4 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD JUN PY 2004 VL 50 IS 6 BP 907 EP 912 DI 10.1016/j.jaad.2004.01.048 PG 6 WC Dermatology SC Dermatology GA 824FJ UT WOS:000221671200014 ER PT J AU LeGault, L Brandt, MB McCabe, N Adler, C Brown, AM Brecher, S AF LeGault, L Brandt, MB McCabe, N Adler, C Brown, AM Brecher, S TI 2000-2001 Food label and package survey: An update on prevalence of nutrition labeling and claims on processed, packaged foods SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Article AB The food label is an important tool for improving the public's understanding of the health benefits of following a nutritious diet. The Center for Food Safety and Applied Nutrition (CFSAN) of the Food and Drug Administration (FDA) has continued to study food labels with its Food Label and Package Survey (FLAPS). Data from the 20002001 FLAPS characterize various aspects of the labeling of processed, packaged foods, including nutrition labeling and various types of label claims. The FDA used a multistage, representative sample of food products from the Information Resources Inc (IRI) 1999 supermarket database as the basis for the FLAPS sample. The final FLAPS database consists of 1,281 foods. An estimated 98.3% of FDA-regulated processed, packaged foods sold annually have nutrition labels, with an additional 1.7% of products exempt from nutrition labeling requirements. Health claims (4.4%), structure/function claims (6.2%), and nutrient content claims (49.7%) were identified on food labels. In addition to the resource this survey provides to CFSAN in assessing health and nutrition information on the food label, registered dietitians and other health professionals can use FLAPS data to assist consumers in choosing a more nutritious diet to improve their health and well-being. C1 US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP LeGault, L (reprint author), US FDA, Ctr Food Safety & Appl Nutr, HFS-840,5100 Paint Branch Parkway, College Pk, MD 20740 USA. EM llegault@cfsan.fda.gov NR 11 TC 44 Z9 44 U1 1 U2 7 PU AMER DIETETIC ASSOC PI CHICAGO PA 216 W JACKSON BLVD #800, CHICAGO, IL 60606-6995 USA SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD JUN PY 2004 VL 104 IS 6 BP 952 EP 958 DI 10.1016/j.jada.2004.03.024 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 826BV UT WOS:000221804800015 PM 15175594 ER PT J AU Xu, L Tsuji, K Mostowski, H Otsu, M Candotti, F Rosenberg, AS AF Xu, L Tsuji, K Mostowski, H Otsu, M Candotti, F Rosenberg, AS TI A convenient method for positive selection of retroviral producing cells generating vectors devoid of selectable markers SO JOURNAL OF VIROLOGICAL METHODS LA English DT Article DE retroviral producing cells; selectable markers; retroviral vectors; gene therapy ID TRANSGENE EXPRESSION; ADENOSINE-DEAMINASE; VIRUS; TITER; LYMPHOCYTES; LEUKEMIA; CLONES; LINE AB Early retroviral vectors containing both a therapeutic gene and a dominant selectable marker gene, offered some distinct advantages with respect to gene therapy, in that they simplified the generation, isolation, and titration of retroviral producer cell clones, as well as the evaluation and selection of successfully targeted cells. However, a number of problems were engendered by this strategy: the promoter driving the selectable marker gene could interfere with transcription of the therapeutic gene, and immune responses could be induced to cells expressing foreign proteins of selection marker origin. Simplified retroviral vectors, which lack a selection marker gene, were constructed to address these problems, but the inability to use a selection marker has made identification and cloning of virus producing transfected cells a heavy burden. To maintain the benefits of simplified retroviral vectors, while providing a facile means to select packaging cells transfected with retroviral DNA. we cloned the bacterial selection marker gene encoding neomycin phosphotransferase (neo) into the plasmid backbone of the vector, but outside of the provirus, resulting in efficient selection of transfected packaging cells and generation of packaged virus which lacks the neo gene. This novel approach generates greater numbers of high infectious titer producing clones, after selection in G418 media, than does a co-transfection approach, due to integration of higher construct copy numbers per cell. No transmission of the selection marker gene to target cells was observed following retroviral transduction. Thus, our strategy eliminates the adverse consequences of a selection-based method, while diminishing the burden of identification of packaging cells transfected with vectors devoid of selectable markers. (C) 2004 Elsevier B.V. All rights reserved. C1 US FDA, CDER, Div Therapeut Prot, Bethesda, MD 20892 USA. US FDA, CDER, Div Cellular & Gene Therapies, Bethesda, MD 20892 USA. NHGRI, GMBB, Disorders Immun Sect, NIH, Bethesda, MD 20892 USA. RP Rosenberg, AS (reprint author), US FDA, CDER, Div Therapeut Prot, Bldg 29A,Room 2B-10,29 Lincoln Dr, Bethesda, MD 20892 USA. EM rosenberg@cber.fda.gov OI Otsu, Makoto/0000-0002-9769-0217 NR 17 TC 2 Z9 2 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 JUN 1 PY 2004 VL 118 IS 1 BP 61 EP 67 DI 10.1016/j.jviromet.2004.01.024 PG 7 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Virology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Virology GA 862ND UT WOS:000224496700008 PM 15158069 ER PT J AU Spann, KA Tran, KC Chi, B Rabin, RL Collins, PL AF Spann, KA Tran, KC Chi, B Rabin, RL Collins, PL TI Suppression of the induction of alpha, beta, and lambda interferons by the NS1 and NS2 proteins of human respiratory syncytial virus in human epithelial cells and macrophages (vol 78, pg 4363, 2004) SO JOURNAL OF VIROLOGY LA English DT Correction C1 NIAID, Infect Dis Lab, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Lab Immunobiochem, Bethesda, MD 20892 USA. RP Spann, KA (reprint author), NIAID, Infect Dis Lab, 9000 Rockville Pike, Bethesda, MD 20892 USA. RI Spann, Kirsten/B-4524-2013 OI Spann, Kirsten/0000-0003-0567-8382 NR 1 TC 9 Z9 9 U1 1 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUN PY 2004 VL 78 IS 12 BP 6705 EP 6705 DI 10.1128/JVI.78.12.6705.2004 PG 1 WC Virology SC Virology GA 825QC UT WOS:000221772000063 ER PT J AU Butler, RN Sprott, R Warner, H Bland, J Feuers, R Forster, M Fillit, H Harman, SM Hewitt, M Hyman, M Johnson, K Kligman, E McClearn, G Nelson, J Richardson, A Sonntag, W Weindruch, R Wolf, N AF Butler, RN Sprott, R Warner, H Bland, J Feuers, R Forster, M Fillit, H Harman, SM Hewitt, M Hyman, M Johnson, K Kligman, E McClearn, G Nelson, J Richardson, A Sonntag, W Weindruch, R Wolf, N TI Biomarkers of aging: From primitive organisms to humans SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID GENE-EXPRESSION PROFILE; VITAMIN-E CONSUMPTION; LIFE-SPAN; CAENORHABDITIS-ELEGANS; CALORIC RESTRICTION; ALZHEIMERS-DISEASE; DWARF MICE; IN-VIVO; LONGEVITY; AGE AB Leading biologists and clinicians interested in aging convened to discuss biomarkers of aging. The goals were to come to a consensus, construct an agenda for future research, and make appropriate recommendations to policy makers and the public-at-large. While there was not total agreement on all issues, they addressed a number of questions, among them whether biomarkers can be identified and used to measure the physiological age of any individual within a population, given emerging information about aging and new technological advances. The hurdles to establishing informative biomarkers include the biological variation between individuals that makes generalizations difficult; the overlapping of aging and disease processes; uncertainty regarding benign versus pathogenic age-related changes; the point at which a process begins to do damage to the organism, and, if so, when does it occur; and when to distinguish critical damage from noncritical damage. Finally, and significantly, it is difficult to obtain funding for this research. C1 Int Longev Ctr USA, New York, NY 10028 USA. Ellison Med Fdn, Bethesda, MD USA. NIA, Biol Aging Program, Bethesda, MD USA. Metagen Inc, Gig Harbor, WA, Australia. Natl Ctr Toxicol Res, Jefferson, AR USA. Tex Coll Osteopath Med, Ft Worth, TX USA. Inst Study Aging, New York, NY USA. Kronos Longev Res Inst, Phoenix, AZ USA. Canyon Ranch Hlth Resort, Tucson, AZ USA. Canyon Ranch Bershires, Lenox, MA USA. Desert Life Med Plaza, Tucson, AZ USA. Penn State Univ, Coll Hlth & Human Dev, University Pk, PA 16802 USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. Wake Forest Univ, Sch Med, Dept Physiol Pharmacol, Winston Salem, NC USA. Univ Wisconsin, Madison, WI USA. Univ Washington, Seattle, WA 98195 USA. RP Butler, RN (reprint author), Int Longev Ctr USA, 60 E 86th St, New York, NY 10028 USA. EM robertb@ilcusa.org NR 56 TC 41 Z9 43 U1 1 U2 5 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD JUN PY 2004 VL 59 IS 6 BP 560 EP 567 PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 834OE UT WOS:000222419600011 ER PT J AU Yang, MH Coles, BF Caporaso, NE Choi, Y Lang, NP Kadlubar, FF AF Yang, MH Coles, BF Caporaso, NE Choi, Y Lang, NP Kadlubar, FF TI Lack of association between Caucasian lung cancer risk and O-6-methylguanine-DNA methyltransferase-codon 178 genetic polymorphism SO LUNG CANCER LA English DT Article DE MGMT; codon 178; genetic polymorphism; lung cancer; RFLP ID O-6-ALKYLGUANINE-DNA ALKYLTRANSFERASE; EXPRESSION; IDENTIFICATION; TUMORIGENESIS; ADDUCTS; MICE AB The formation of DNA adducts is thought to be a critical step for the induction of chemically induced cancer. O-6-Methylguanine-DNA methyltransferase (MGMT) is a ubiquitously expressed enzyme that repairs DNA adducts formed by alkylating carcinogens. Thus, genetic polymorphisms of the MGMT that could result in differences in MGMT activity are potential risk factors for cancer. In the present study, we established a convenient and reliable genotyping method for the MGMT codon 178 polymorphism, a Lys (AAG) to Arg (AGG) substitution, using restriction fragment length polymorphism (RFLP), and studied differences in the distribution of this polymorphism in 92 Caucasian lung cancer patients and 85 controls. Frequencies of the "A" and "G" alleles (MGMT codon 178, AAG and AGG, respectively) were 0.91 and 0.09, respectively. The genetic polymorphism of the MGMT codon 178 was linked with that of the MGMT codon 143 (P < 0.05). The distribution of the MGMT codon 178 genetic polymorphism was not significantly different between lung cancer patients and controls. Thus, our study suggests that the MGMT codon 178 (and possibly 143) polymorphisms do not appear to markedly affect lung cancer risk for this population. In addition, we found an apparent 10 bp-deletion in the intron before exon 5 by DNA sequencing. Because this "deletion" was observed in all sequenced samples (N = 20), the previously reported human (Caucasian) MGMT gene sequence should be revised to exclude this 10 by segment. (C) 2004 Elsevier Ireland Ltd. All rights reserved. C1 Seoul Natl Univ, Coll Med, Inst Canc Res, Dept Prevent Med, Seoul 110799, South Korea. Natl Ctr Toxicol Res, Div Mol Epidemiol, Jefferson, AR 72079 USA. NCI, NIH, Bethesda, MD 20892 USA. Cent Arkansas Vet Hlth Care Syst, Little Rock, AR 72205 USA. RP Yang, MH (reprint author), Seoul Natl Univ, Coll Med, Inst Canc Res, Dept Prevent Med, 28 Yongondong, Seoul 110799, South Korea. EM myang@snu.ac.kr NR 24 TC 26 Z9 28 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0169-5002 J9 LUNG CANCER-J IASLC JI Lung Cancer PD JUN PY 2004 VL 44 IS 3 BP 281 EP 286 DI 10.1016/j.lungcan.2003.12.003 PG 6 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 824MN UT WOS:000221690800002 PM 15140540 ER PT J AU Interewicz, B AF Interewicz, B TI Profiling of normal human leg lymph proteins using the 2-D electrophoreses and SELDI-Tof mass spectrophotometry approach SO LYMPHOLOGY LA English DT Article ID PERIPHERAL LYMPH; NORMAL MEN; COMPLEMENT; TRANSPORT; FLUID AB The parenchymatous cells are supplied by nutrients transported in fluid from blood across the capillary wall. This fluid, called tissue fluid (TF), contains proteins originating from plasma as well as those synthesized and secreted by tissue cells. The protein composition of TF remains largely unknown. The TF which has entered lymphatics is called lymph (L). Harvesting L and measuring its proteins concentrations and identifying them provide an insight into biochemical processes in the TF. Here we describe our initial evaluation of the normal human prenodal L protein profile of m.w. 2.5 to 12.5kDa using the ProteinChip SELDI MS system and compare it with that of plasma (P) protein. This is the first study in the literature providing evidence for the presence of the so far non-identified proteins in L as well as proteins identified in L but absent from P and conversely present in P but not in L. Evident differences between paired L and P samples have been found, along with similarities. Thirteen proteins were detected in P and seven in L in the region of 2.5 to 12.5 kDa. Five identical proteins, although of different relative intensity, were found in L and P. The proteins specific for L but not P had 70 70 and 8619 ion values. P proteins absent from L were of 3890, 3969, 4078, 6863, 7676, 7778, 7847 and 7937 ion values. In addition to detecting some so far unknown proteins in L, these preliminary findings throw a new light on our understanding of the mechanism of transcapillary transport of low m.w. proteins. They challenge the commonly accepted notion of unlimited free diffusion of peptides across the capillary membrane. C1 Polish Acad Sci, Dept Surg Res & Transplantol, Med Res Ctr, PL-02116 Warsaw, Poland. US FDA, CBER, Clin Proteom Program Therapeut Prot, Bethesda, MD 20014 USA. NCI, Pathol Lab, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Interewicz, B (reprint author), Polish Acad Sci, Dept Surg Res & Transplantol, Med Res Ctr, Pawinski Str 5, PL-02116 Warsaw, Poland. EM wlo@cmdik.pan.pl NR 12 TC 14 Z9 15 U1 0 U2 0 PU LYMPHOLOGY PI TUCSON PA C/O C L WITTE MD 1501 N CAMPBELL AVE DEPT SURGERY, TUCSON, AZ 85724 USA SN 0024-7766 J9 LYMPHOLOGY JI Lymphology PD JUN PY 2004 VL 37 IS 2 BP 65 EP 72 PG 8 WC Immunology; Physiology SC Immunology; Physiology GA 839YE UT WOS:000222820100006 PM 15328759 ER PT J AU Murali, B Korrapti, MC Warbritton, A Latendresse, JR Mehendale, HM AF Murali, B Korrapti, MC Warbritton, A Latendresse, JR Mehendale, HM TI Tolerance of aged Fischer 344 rats against chlordecone-amplified carbon tetrachloride toxicity SO MECHANISMS OF AGEING AND DEVELOPMENT LA English DT Article DE aging; chlordecone; carbon tetrachloride; hepatotoxicity; strain difference ID INDUCED POTENTIATION; TISSUE-REPAIR; HEPATOCELLULAR REGENERATION; LIPID-PEROXIDATION; LIVER-INJURY; HEPATOTOXICITY; LETHALITY; GALACTOSAMINE; METABOLISM; DIQUAT AB We have investigated the effects of chlordecone (1)(CD) + CC1(4) combination in adult (3 months), middle aged (14 months), and old aged (24 months) male Fischer 344 (F344) rats. After a non-toxic dietary regimen of CD (10 ppm) or normal powdered diet for 15 days, rats received a single non-toxic dose of CCl4 (100 mul/kg, i.p., 1:4 in corn oil) or corn oi1 (500 mul/kg, i.p.) alone on day 16. Liver injury was assessed by plasma ALT, AST and histopathology during a time course of 0-96 h. Liver tissue repair was measured by [H-3-CH3]-thymidine (H-3-T) incorporation into hepatic nuclear DNA and proliferating cell nuclear antigen (PCNA) immunohistochemistry. Hepatomicrosomal CYP2E1 protein. enzyme activity, and covalent binding of (CCl4)-C-14-derived radiolabel were measured in normal and CD fed rats. Exposure to CCl4 alone caused modest liver injury only in 14- and 24-month-old rats but neither progression of injury nor mortality. The CD + CCl4 combination led to 100% mortality in 3-month-old rats by 72 h, whereas none of the 14- and 24-month-old rats died. Both 3- and 14-month-old rats exposed to CD + CCl4 had identical liver injury up to 36 h indicating that bioactivation-mediated CCl4 injury was the same in the two age groups. Thereafter, liver injury escalated only in 3-month-old while it declined in 14-month-old rats. In 24-month-old rats initial liver injury at 6 h was similar to the 3- and 14-month-old rats and thereafter did not develop to the level of the other two age groups, recovering from injury by 96 h as in the 14-month-old rats. Neither hepatomicrosomal CYP2E1 protein nor the associated p-nitrophenol hydroxylase activity or covalent binding of (CCl4)-C-14-derived radiolabel to liver tissue differed between the age groups or diet regimens 2 h after the administration of (CCl4)-C-14. Compensatory liver tissue repair (3 H-T, PCNA) was prompt and robust soon after CC14 liver injury in the 14- and 24-month-old rats. In stark contrast, in the 3-month-old rats it failed allowing unabated progression of liver injury. These findings suggest that stimulation of early onset and robust liver tissue repair rescue the 14- and 24-month-old F344 rats from the lethal effect of the CD + CCl4 combination. (C) 2004 Elsevier Ireland Ltd. All rights reserved. C1 Univ Louisiana, Coll Hlth Sci, Dept Toxicol, Monroe, LA 71209 USA. Pathol Associates Int, Natl Ctr Toxicol Res, Jefferson, AR 72709 USA. RP Mehendale, HM (reprint author), Univ Louisiana, Coll Hlth Sci, Dept Toxicol, Sugar Hall 306,700 Univ Ave, Monroe, LA 71209 USA. EM mehendale@ulm.edu RI Latendresse, John/A-9215-2009 NR 61 TC 7 Z9 7 U1 0 U2 2 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0047-6374 J9 MECH AGEING DEV JI Mech. Ageing Dev. PD JUN PY 2004 VL 125 IS 6 BP 421 EP 435 DI 10.1016/j.mad.2004.03.005 PG 15 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 831ND UT WOS:000222200200004 PM 15178132 ER PT J AU Kaczmarek, R Spelic, D Moyal, A Hilohi, M AF Kaczmarek, R Spelic, D Moyal, A Hilohi, M TI Preliminary results of the 2003 Nationwide Evaluation of X-Ray Trends (NEXT) survey of upper gastro-intestinal exams SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 25-29, 2004 CL Pittsburgh, PA SP Amer Assoc Physicists Med C1 Ctr Devices & Rad Hlth, Rockville, MD USA. US FDA, Rockville, MD 20857 USA. Sachs Freeman Associates Inc, Rockville, 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 2004 VL 31 IS 6 BP 1725 EP 1725 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 832HW UT WOS:000222259100102 ER PT J AU Shope, T AF Shope, T TI Revision of the federal performance standard for diagnostic X-ray systems - Emphasis on fluoroscopic systems SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 25-29, 2004 CL Pittsburgh, PA SP Amer Assoc Physicists Med C1 US FDA, 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 2004 VL 31 IS 6 BP 1767 EP 1767 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 832HW UT WOS:000222259100273 ER PT J AU Gagne, R Badano, A Boswell, J Gallas, B Jennings, R Myers, K Quinn, P AF Gagne, R Badano, A Boswell, J Gallas, B Jennings, R Myers, K Quinn, P TI Detector considerations, connection of detector based DQE to task based observer performance SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 25-29, 2004 CL Pittsburgh, PA SP Amer Assoc Physicists Med C1 FDA, CDRH, Rockville, MD USA. US FDA, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2004 VL 31 IS 6 BP 1781 EP 1781 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 832HW UT WOS:000222259100335 ER PT J AU Gagne, R Chakrabarti, K Thomas, J Gallas, B Myers, K AF Gagne, R Chakrabarti, K Thomas, J Gallas, B Myers, K TI Toward objective evaluation of imaging phantom scores ACR/MAP SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 25-29, 2004 CL Pittsburgh, PA SP Amer Assoc Physicists Med C1 US FDA, CDRH, Rockville, MD 20857 USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2004 VL 31 IS 6 BP 1786 EP 1786 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 832HW UT WOS:000222259100357 ER PT J AU Wagner, R AF Wagner, R TI Reminiscences from a half-century of image science SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 25-29, 2004 CL Pittsburgh, PA 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 2004 VL 31 IS 6 BP 1806 EP 1806 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 832HW UT WOS:000222259100435 ER PT J AU Badano, A Fifadara, D Gallas, B Myers, K AF Badano, A Fifadara, D Gallas, B Myers, K TI Perspectives on current medical display research SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 25-29, 2004 CL Pittsburgh, PA SP Amer Assoc Physicists Med C1 US FDA, CDRH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2004 VL 31 IS 6 BP 1828 EP 1828 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 832HW UT WOS:000222259100539 ER PT J AU Thomas, J Chakrabarti, K Kaczmarek, R Maslennikov, A Romanyukha, A AF Thomas, J Chakrabarti, K Kaczmarek, R Maslennikov, A Romanyukha, A TI Display performance and object detection variation with viewing angle on CRT and LCD displays SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 25-29, 2004 CL Pittsburgh, PA SP Amer Assoc Physicists Med C1 Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. Ctr Devices & Radiol Hlth, Rockville, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2004 VL 31 IS 6 BP 1829 EP 1829 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 832HW UT WOS:000222259100543 ER PT J AU Thomas, J Chakrabarti, K Kaczmarek, R Maslennikov, A Romanyukha, A AF Thomas, J Chakrabarti, K Kaczmarek, R Maslennikov, A Romanyukha, A TI Intraobserver variability between CRT and flat panel displays SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 25-29, 2004 CL Pittsburgh, PA SP Amer Assoc Physicists Med C1 Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. Ctr Devices & Radiol Hlth, Rockville, MD USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. Ctr Devices & Radiol Hlth, Rockville, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2004 VL 31 IS 6 BP 1829 EP 1829 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 832HW UT WOS:000222259100542 ER PT J AU Suleiman, O Fejka, R Walsh, M AF Suleiman, O Fejka, R Walsh, M TI Human research with radioactive drugs - FDA radiation dose limits SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 25-29, 2004 CL Pittsburgh, PA SP Amer Assoc Physicists Med C1 US FDA, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2004 VL 31 IS 6 BP 1889 EP 1889 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 832HW UT WOS:000222259100826 ER PT J AU Suleiman, O Fejka, R Walsh, M AF Suleiman, O Fejka, R Walsh, M TI The radioactive drug research committee - Microdosing SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 25-29, 2004 CL Pittsburgh, PA SP Amer Assoc Physicists Med C1 US FDA, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2004 VL 31 IS 6 BP 1922 EP 1922 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 832HW UT WOS:000222259100986 ER PT J AU McDermott, PF Bodeis, SM Aarestrup, FM Brown, S Traczewski, M Fedorka-Cray, P Wallace, M Critchley, IA Thornsberry, C Graff, S Flamm, R Beyer, J Shortridge, D Piddock, LJ Ricci, V Johnson, MM Jones, RN Reller, B Mirrett, S Aldrobi, J Rennie, R Brosnikoff, C Turnbull, L Stein, G Schooley, S Hanson, RA Walker, RD AF McDermott, PF Bodeis, SM Aarestrup, FM Brown, S Traczewski, M Fedorka-Cray, P Wallace, M Critchley, IA Thornsberry, C Graff, S Flamm, R Beyer, J Shortridge, D Piddock, LJ Ricci, V Johnson, MM Jones, RN Reller, B Mirrett, S Aldrobi, J Rennie, R Brosnikoff, C Turnbull, L Stein, G Schooley, S Hanson, RA Walker, RD TI Development of a standardized susceptibility test for Campylobacter with quality-control ranges for ciprofloxacin, doxycycline, erythromycin, gentamicin, and meropenem SO MICROBIAL DRUG RESISTANCE-MECHANISMS EPIDEMIOLOGY AND DISEASE LA English DT Article ID RETAIL CHICKEN; AGAR DILUTION; JEJUNI; SALMONELLA; RESISTANCE; POULTRY; PREVALENCE; ETEST; COLI; MEAT AB A standardized agar dilution susceptibility testing method was developed for Campylobacter that consisted of testing on Mueller-Hinton medium supplemented with 5% defibrinated sheep blood in an atmosphere of 10% CO2, 5% O-2, and 85% N-2- Campylobacter jejuni ATCC 33560 was identified as a quality-control (QC) strain. Minimal inhibitory concentration (MIC) QC ranges were determined for two incubation time/temperature combinations: 36degreesC for 48 hr and 42degreesC for 24 hr. Quality-control ranges were determined for ciprofloxacin, doxycycline, erythromycin, gentamicin, and meropenem. For all antimicrobial agents tested at both temperatures, 95-100% of the QC MIC results fell within recommended QC ranges. Twenty-one Campylobacter clinical isolates, encompassing five species of Campylobacter (C. jejuni, C. coli, C. jejuni, subsp. doylei, C. fetus, and C. lari) were tested in conjunction with the C. jejuni QC strain. While C. jejuni and C. coli could be reliably tested under both test conditions, growth of C. jejuni subsp. doylei, C. fetus, and C. lari isolates was inconsistent when incubated at 42degreesC. Therefore, it is recommended that these species only be tested at 36degreesC. C1 US FDA, Ctr Vet Med, Res Off, Laurel, MD 20708 USA. Danish Vet Inst, DK-1790 Copenhagen, Denmark. CMI, Wilsonville, OR 97070 USA. USDA ARS, Russell Res Ctr, Athens, GA 30604 USA. Focus Technol, Herndon, VA USA. Abbott Labs, Abbott Pk, IL 60064 USA. Univ Birmingham, Sch Med, Div Immun & Infect, Birmingham B15 2TT, W Midlands, England. Jones Grp, JMI Labs, N Liberty, IA 52317 USA. Duke Univ, Med Ctr, Clin Microbiol Lab, Durham, NC 27710 USA. Univ Alberta Hosp, Med Microbiol Lab, Edmonton, AB TGG 2J2, Canada. Michigan State Univ, Coll Human Med, E Lansing, MI 48824 USA. Michigan State Univ, Coll Vet Med, E Lansing, MI 48824 USA. RP McDermott, PF (reprint author), US FDA, Ctr Vet Med, Res Off, HFV 530,8401 Muirkirk Rd,Mod 2, Laurel, MD 20708 USA. EM PMcDermo@cvm.fda.gov NR 25 TC 49 Z9 49 U1 0 U2 4 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1076-6294 J9 MICROB DRUG RESIST JI Microb. Drug Resist.-Mechan. Epidemiol. Dis. PD SUM PY 2004 VL 10 IS 2 BP 124 EP 131 DI 10.1089/1076629041310064 PG 8 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA 835NT UT WOS:000222491200007 PM 15256027 ER PT J AU Smith, JS Tian, J Lozier, JN Byrnes, AP AF Smith, JS Tian, J Lozier, JN Byrnes, AP TI Severe pulmonary pathology after intravenous administration of adenovirus vectors in cirrhotic rats SO MOLECULAR THERAPY LA English DT Article DE adenovirus; cirrhosis; lung; pulmonary intravascular macrophage; gene therapy; edema; hemorrhage; coagulopathy ID TUMOR-NECROSIS-FACTOR; DISSEMINATED INTRAVASCULAR COAGULATION; GENE-EXPRESSION INVIVO; ACUTE LUNG INJURY; LIVER-DISEASE; IN-VIVO; NONHUMAN-PRIMATES; INFLAMMATORY RESPONSE; MESSENGER-RNA; TOXICITY AB After an intravascular injection, adenoviral vectors are normally taken up by the reticuloendothelial system in the liver, where they rapidly trigger an innate response. However, we have previously found that the biodistribution of adenoviral vectors is altered in cirrhotic rats due to the presence of pulmonary intravascular macrophages, which cause a shift in vector uptake from the liver to the lungs. We now report that this is correlated with fatal pulmonary hemorrhagic edema in cirrhotic rats. In addition, cirrhotic rats reacted to vector with enormous increases in TNF-alpha and IL-6 and markedly prolonged coagulation times. Although we also saw fatal reactions to high doses of adenoviral vectors in normal rats, the time course and symptoms were very different, and pulmonary hemorrhagic edema was seen only in cirrhotic rats. Because abnormal pulmonary reticuloendothelial uptake is known to occur in humans during cirrhosis and other diseases, there is the potential that intravascular administration of adenoviral vectors might cause lung pathology in such patients. C1 US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Hematol, Bethesda, MD 20892 USA. RP Byrnes, AP (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, HFM-725,29B-2E20,8800 Rockville Pike, Bethesda, MD 20892 USA. EM byrnes@cber.fda.gov RI Byrnes, Andrew/D-2808-2013 OI Byrnes, Andrew/0000-0003-1135-2629 NR 54 TC 28 Z9 30 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 1525-0016 J9 MOL THER JI Mol. Ther. PD JUN PY 2004 VL 9 IS 6 BP 932 EP 941 DI 10.1016/j.ymthe.2004.03.010 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 831NW UT WOS:000222202200022 PM 15194060 ER PT J AU Slikker, W Pogge, A Walker, R Chatziiannou, A Charles, C Ellisman, M AF Slikker, W Pogge, A Walker, R Chatziiannou, A Charles, C Ellisman, M TI Neuroimaging: Strategies to illuminate environment-disease linkages - Session II. Summary and research needs SO NEUROTOXICOLOGY LA English DT Article; Proceedings Paper CT 20th International Neurotoxicology Conference CY NOV 18-21, 2002 CL LITTLE ROCK, AR C1 Natl Ctr Toxicol Res, Div Neurotoxicol, FDA, Jefferson, AR 72079 USA. Univ Arkansas Med Sci, Div PET Res, Little Rock, AR 72205 USA. Univ Calif Los Angeles, Crump Inst Mol Imaging, Los Angeles, CA 90095 USA. Duke Univ, Duke Image Anal Lab, Durham, NC 27708 USA. Univ Calif San Diego, Natl Ctr Microscopy & Imaging Res, La Jolla, CA 92093 USA. RP Pogge, A (reprint author), Natl Ctr Toxicol Res, Div Neurotoxicol, FDA, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM wslikker@nctr.fda.gov RI Charles, Hal/C-7772-2017 OI Charles, Hal/0000-0002-1414-2494 NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0161-813X J9 NEUROTOXICOLOGY JI Neurotoxicology PD JUN PY 2004 VL 25 IS 4 BP 501 EP 502 DI 10.1016/j.neuro.2003.09.011 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA 830KW UT WOS:000222121900002 PM 15183002 ER PT J AU LoPachin, RM Canady, RA AF LoPachin, RM Canady, RA TI Acrylamide toxicities and food safety: Session IV summary and research needs SO NEUROTOXICOLOGY LA English DT Article; Proceedings Paper CT 20th International Neurotoxicology Conference CY NOV 18-21, 2002 CL LITTLE ROCK, AR DE toxic axonopathy; neurotoxicity; acrylamide; neurotransmission; axon degeneration ID NERVE-CELL DAMAGE; SPATIOTEMPORAL CHARACTERISTICS; MORTALITY PATTERNS; MAILLARD REACTION; NEUROPATHY; DEGENERATION; AXONOPATHY; CARCINOGEN; EXPOSURE; RATS C1 Albert Einstein Coll Med, Montefiore Med Ctr, Dept Anesthesiol, Bronx, NY 10467 USA. US FDA, Off Sci & Hlth Coordinat, Rockville, MD 20857 USA. RP LoPachin, RM (reprint author), Albert Einstein Coll Med, Montefiore Med Ctr, Dept Anesthesiol, 111E 210th St, Bronx, NY 10467 USA. EM lopachin@aecom.yu.edu NR 21 TC 5 Z9 8 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0161-813X J9 NEUROTOXICOLOGY JI Neurotoxicology PD JUN PY 2004 VL 25 IS 4 BP 507 EP 509 DI 10.1016/j.neuro.2003.12.002 PG 3 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA 830KW UT WOS:000222121900004 PM 15264346 ER EF