FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Klauda, JB Kucerka, N Brooks, BR Pastor, RW Nagle, JF AF Klauda, JB Kucerka, N Brooks, BR Pastor, RW Nagle, JF TI Simulation-based methods for interpreting X-ray data from lipid bilayers SO BIOPHYSICAL JOURNAL LA English DT Article ID MOLECULAR-DYNAMICS SIMULATIONS; COMPUTER-SIMULATION; SURFACE-TENSION; LIQUID/LIQUID INTERFACES; COMPONENT VOLUMES; PHASE DMPC; GEL PHASE; WATER; AREA; UNDULATIONS AB The fully hydrated liquid crystalline phase of the dimyristoylphosphatidycholine lipid bilayer at 30 degrees C was simulated using molecular dynamics with the CHARMM potential for five surface areas per lipid ( A) in the range 55-65 angstrom(2) that brackets the previously determined experimental area 60.6 angstrom(2). The results of these simulations are used to develop a new hybrid zero-baseline structural model, denoted H2, for the electron density profile, p(z), for the purpose of interpreting x-ray diffraction data. H2 and also the older hybrid baseline model were tested by fitting to partial information from the simulation and various constraints, both of which correspond to those available experimentally. The A, p(z), and F(q) obtained from the models agree with those calculated directly from simulation at each of the five areas, thereby validating this use of the models. The new H2 was then applied to experimental dimyristoylphosphatidycholine data; it yields A 60.6 +/- 0.5 angstrom(2), in agreement with the earlier estimate obtained using the hybrid baseline model. The electron density profiles also compare well, despite considerable differences in the functional forms of the two models. Overall, the simulated p( z) at A 60.7 angstrom(2) agrees well with experiment, demonstrating the accuracy of the CHARMM lipid force field; small discrepancies indicate targets for improvements. Lastly, a simulation-based model-free approach for obtaining A is proposed. It is based on interpolating the area that minimizes the difference between the experimental F( q) and simulated F( q) evaluated for a range of surface areas. This approach is independent of structural models and could be used to determine structural properties of bilayers with different lipids, cholesterol, and peptides. C1 NIH, Lab Computat Biol, Bethesda, MD 20892 USA. Carnegie Mellon Univ, Dept Phys, Pittsburgh, PA 15213 USA. Carnegie Mellon Univ, Dept Biol Sci, Pittsburgh, PA 15213 USA. US FDA, Ctr Biol Evaluat & Res, Biophys Lab, Rockville, MD 20852 USA. RP Klauda, JB (reprint author), NIH, Lab Computat Biol, Bldg 10, Bethesda, MD 20892 USA. EM klauda@helix.nih.gov RI Klauda, Jeffery/A-4345-2008; Nagle, John/B-1917-2015 OI Nagle, John/0000-0002-9844-5934 FU Intramural NIH HHS; NIGMS NIH HHS [GM44976, R01 GM044976, R01 GM044976-15A1] NR 42 TC 139 Z9 140 U1 1 U2 25 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD APR PY 2006 VL 90 IS 8 BP 2796 EP 2807 DI 10.1529/biophysj.105.075697 PG 12 WC Biophysics SC Biophysics GA 024WK UT WOS:000236226900015 PM 16443652 ER PT J AU Luderer, U Collins, TFX Daston, GP Fischer, LJ Gray, RH Mirer, FE Olshan, AF Setzer, RW Treinen, KA Vermeulen, R AF Luderer, U Collins, TFX Daston, GP Fischer, LJ Gray, RH Mirer, FE Olshan, AF Setzer, RW Treinen, KA Vermeulen, R TI NTP-CERHR Expert Panel Report on the Reproductive and Developmental Toxicity of Styrene SO BIRTH DEFECTS RESEARCH PART B-DEVELOPMENTAL AND REPRODUCTIVE TOXICOLOGY LA English DT Review ID REINFORCED-PLASTICS INDUSTRY; DRUG-METABOLIZING-ENZYMES; SPERM CHROMATIN-STRUCTURE; CRL-CD RATS; ORGANIC-SOLVENTS; SPONTANEOUS-ABORTIONS; EXPOSED WORKERS; INHALED STYRENE; CHRONIC TOXICITY/ONCOGENICITY; CONGENITAL-MALFORMATIONS C1 NIEHS, Res Triangle Pk, NC 27709 USA. Univ Calif Irvine, Irvine, CA USA. US FDA, Laurel, MD USA. Procter & Gamble Co, Cincinnati, OH USA. Michigan State Univ, E Lansing, MI USA. Johns Hopkins Univ, Baltimore, MD USA. United Auto Workers Union, Int Union, Detroit, MI USA. Univ N Carolina, Chapel Hill, NC USA. US Environm Protect Agcy, Res Triangle Pk, NC USA. Schering Plough Res Inst, Lafayette, NJ USA. NCI, Bethesda, MD USA. RP Luderer, U (reprint author), NIEHS, EC-32,POB 12233, Res Triangle Pk, NC 27709 USA. RI Vermeulen, Roel/F-8037-2011 OI Vermeulen, Roel/0000-0003-4082-8163 NR 132 TC 2 Z9 2 U1 0 U2 4 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 APR PY 2006 VL 77 IS 2 BP 110 EP 193 DI 10.1002/bdrb.20061 PG 84 WC Oncology; Genetics & Heredity; Toxicology SC Oncology; Genetics & Heredity; Toxicology GA 036CN UT WOS:000237048600004 PM 16345075 ER PT J AU Ng, D Marti, GE Fontaine, L Toro, JR Caporaso, N Goldin, LR AF Ng, D Marti, GE Fontaine, L Toro, JR Caporaso, N Goldin, LR TI High-density mapping and follow-up studies on chromosomal regions 1, 3, 6, 12, 13 and 17 in 28 families with chronic lymphocytic leukaemia SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE chronic lymphocytic leukaemia; family studies; linkage analysis ID LINKAGE ANALYSIS; GENOME; SCAN AB A subset of chronic lymphocytic leukaemia (CLL) shows familial aggregation. Studies show an increased risk for CLL and other lymphoproliferative disease among first-degree relatives of affected individuals. A genome-wide scan of 18 CLL families in 2003 detected LOD or non-parametric linkage scores >= 1.0 on chromosomes 1, 3, 6, 12, 13 and 17. Follow-up study with 28 families showed no evidence of linkage at 1p22.1-p21.2, 3q22.1, 3q26.2, 6q22.31-q23.2, 12q24.23, 14q32.13, 17p13.3. Chromosome 13q21.33 remains a region of interest with a P-value of 0.013 (marker D13S1291) and warrants additional molecular investigation as a susceptibility region for CLL. C1 NCI, Genet Epidemiol Branch, DCEG, DHHS, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Flow & Image Cytometry Sect, Lab Stem Cell Biol,Off Cellular Tissues & Gene Th, Bethesda, MD 20014 USA. Westat Res Inc, Rockville, MD USA. RP Ng, D (reprint author), NCI, Genet Epidemiol Branch, DCEG, DHHS, 6120 Execut Blvd,Room 7005,MSC 7236, Bethesda, MD 20892 USA. EM davidng@mail.nih.gov FU Intramural NIH HHS NR 12 TC 13 Z9 14 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD APR PY 2006 VL 133 IS 1 BP 59 EP 61 DI 10.1111/j.1365-2141.2006.05972.x PG 3 WC Hematology SC Hematology GA 017YY UT WOS:000235730600006 PM 16512829 ER PT J AU Chiesa, OA Cullison, R Anderson, DE Moulton, K Galuppo, LD von Bredow, J AF Chiesa, OA Cullison, R Anderson, DE Moulton, K Galuppo, LD von Bredow, J TI Development of a technique for serial bilateral renal biopsy in steers SO CANADIAN JOURNAL OF VETERINARY RESEARCH-REVUE CANADIENNE DE RECHERCHE VETERINAIRE LA English DT Article ID LAPAROSCOPIC OVARIECTOMY; STANDING HORSES; GENTAMICIN; ABDOMEN; ANATOMY; SAMPLES; KIDNEY; COWS AB A biopsy procedure was developed to provide serial kidney samples from standing steers. Ten clinically normal steers were given intramuscular injections of gentamicin sulfate, 4 mg/kg body weight. Renal biopsy was performed at 5 separate times. After feed was withheld for 24 h, laparoscopic surgery was performed in standing stocks. Acepromazine, xylazine, and butorphanol were used for sedation and analgesia, and 2% lidocaine was used for local anesthesia. Two incisions approximately 2 cm long were made in the paralumbar fossa to allow for trocar introduction. The abdomen was insufflated with CO2 and, with endoscopic guidance, a biopsy forceps used to remove a kidney sample 2 to 3 mm in diameter, by either a left or a right abdominal approach. Each operation was recorded on videotape, and images were also captured with a digital medical device system. Respiration, heart rate, temperature, appetite, attitude, and postural positions were evaluated at 12, 24, 48, and 72 h after surgery. The 51. laparoscopic procedures provided 48 renal samples (approximately 100 mg each). The 1st and 2nd samples were from the right kidney, and the 3rd sample was from either the left or the right kidney; the 4th and 5th samples were from the left kidney. Adhesions made an approach from the right side difficult for the 3rd sample. No clinical changes were observed in 9 steers after the procedure. One steer died after the 3rd procedure owing to hemorrhage. C1 US FDA, Div Residue Chem, Ctr Vet Med, Res Off, Laurel, MD 20708 USA. Univ Calif Davis, Vet Teaching Hosp, Davis, CA 95616 USA. Ohio State Univ, Coll Vet Med, Columbus, OH 43210 USA. RP Chiesa, OA (reprint author), US FDA, Div Residue Chem, Ctr Vet Med, Res Off, 8401 Muirkirk Rd, Laurel, MD 20708 USA. EM ochiesa@cvm.fda.gov OI Anderson, David/0000-0003-0745-7591 NR 22 TC 5 Z9 6 U1 0 U2 2 PU CANADIAN VET MED ASSOC PI OTTAWA PA 339 BOOTH ST ATTN: KIMBERLY ALLEN-MCGILL, OTTAWA, ONTARIO K1R 7K1, CANADA SN 0830-9000 J9 CAN J VET RES JI Can. J. Vet. Res.-Rev. Can. Rech. Vet. PD APR PY 2006 VL 70 IS 2 BP 87 EP 93 PG 7 WC Veterinary Sciences SC Veterinary Sciences GA 033JV UT WOS:000236844200002 PM 16639940 ER PT J AU Hirsch, DS Shen, Y Wu, WJ AF Hirsch, DS Shen, Y Wu, WJ TI Growth and motility inhibition of breast cancer cells by epidermal growth factor receptor degradation is correlated with inactivation of Cdc42 SO CANCER RESEARCH LA English DT Article ID ACTIN STRESS FIBERS; RHO-GTPASES; RAS TRANSFORMATION; HUMAN TUMORS; C-CBL; TYROSINE KINASES; PROTEIN; EXPRESSION; ADHESION; C-CBL/SLI-1 AB Overexpression of epidermal growth factor receptor (EGFR) contributes to increased cell proliferation and migration in breast cancer. However, mechanisms of EGFR overexpression remain elusive and often cannot be attributed to gene amplification. In NIH3T3 fibroblasts, active Cdc42 inhibits c-CIA-regulated EGFR degradation to induce cellular transformation. Here, we use two EGFR-overexpressing breast cancer cell lines, MDA-MB-231 and BT20, its models to test the hypothesis that up-regulated Cdc42 activity impairs c-Cbl-mediated EGFR degradation and contributes to EGFR overexpression. We show that silencing Cdc42 significantly reduces protein levels of EGFR, leading to a marked reduction in cell proliferation and migration, and c-Cbl knockdown increases the levels of EGFR. Expression of c-Cbl-N480, a c-Cbl mutant that is not regulated by Cdc42 and blocks Cdc42-induced transformation but still binds and ubiquitinates EGFR, enhances the rate of EGFR degradation and subsequently inhibits cell proliferation. Moreover, down-regulated EGFR signaling induced by c-Cbl-N480 decreased activity of Cdc42 and Rac1, resulting in inhibition of cell migration. These findings indicate that Cdc42 and c-Cbl are critical components involved in the regulation of EGFR protein levels anti that restoration of proper EGFR degradation by disrupting Cdc42 regulation of c-Cbl can reduce cell proliferation and migration in MDA-MB-231 and BT20 cells. C1 US FDA, Div Monoclonal Antibodies, Off Biotechnol Prod, Off Pharmaceut Sci,Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. RP Wu, WJ (reprint author), US FDA, Div Monoclonal Antibodies, Off Biotechnol Prod, Off Pharmaceut Sci,Ctr Drug Evaluat & Res, Room 3NN-15,Bldg 29B,29 Lincoln Dr, Bethesda, MD 20892 USA. EM wen.wu@fda.hhs.gov NR 36 TC 59 Z9 68 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD APR 1 PY 2006 VL 66 IS 7 BP 3523 EP 3530 DI 10.1158/0008-5472.CAN-05-1547 PG 8 WC Oncology SC Oncology GA 030TO UT WOS:000236657800029 PM 16585176 ER PT J AU Ju, YH Fultz, J Allred, KF Doerge, DR Helferich, WG AF Ju, YH Fultz, J Allred, KF Doerge, DR Helferich, WG TI Effects of dietary daidzein and its metabolite, equol, at physiological concentrations on the growth of estrogen-dependent human breast cancer (MCF-7) tumors implanted in ovariectomized athymic mice SO CARCINOGENESIS LA English DT Article ID SPRAGUE-DAWLEY RATS; CELLS IN-VITRO; RECEPTOR-BETA; PHYTO-ESTROGENS; SOY ISOFLAVONES; S-EQUOL; POSTMENOPAUSAL WOMEN; SOYBEAN ISOFLAVONES; INTESTINAL BACTERIA; STIMULATE GROWTH AB Genistein and daidzein are the main isoflavones in legumes. Equol is an intestinal bacterial metabolite of daidzein. In this study, we evaluated the estrogenic potential of daidzein and synthetic (+/-)-equol to stimulate growth of estrogen-dependent breast cancer (MCF-7) in vitro and in vivo. We hypothesize that estrogenic effects of daidzein and (+/-)-equol could modulate the growth of MCF-7 cells both in vitro and also once implanted into ovariectomized athymic mice. At concentrations between 0.001 and 50 mu M, daidzein and (+/-)-equol stimulated the growth of MCF-7 cells with maximal stimulation at 1 mu M in vitro. To evaluate their effects on the growth of MCF-7 cells implanted in ovariectomized athymic mice, two dietary dose-response studies [daidzein (125, 250, 500 and 1000 p.p.m.) and (+/-)-equol (250, 500 and 1000 p.p.m.)] were conducted. Tumor size and body weight were monitored weekly during the study. At completion of the study, we analyzed cellular proliferation of tumors using immunohistochemical staining (ki-67), pS2 expression in tumors using a real time quantitative reverse transcription-polymerase chain reaction (qRT-PCR), and total daidzein and (+/-)-equol levels in plasma using liquid chromatography-electrospray tandem mass spectrometry (LC-ES/MS/MS). Dietary daidzein had a slight but significant stimulatory effect on MCF-7 tumor growth in mice. No significant induction of pS2 mRNA (an estrogen-responsive marker) in tumors by dietary daidzein was observed. Total plasma daidzein concentrations in plasma were between 0.25 and 1.52 mu M. Dietary equol treatment (for 37 weeks) did not stimulate MCF-7 tumor growth. There were no statistical differences in tumor size, proliferation and pS2 expression among any treatment groups. Total equol concentrations in plasma were 2.10-3.21 mu M. In conclusion, daidzein and (+/-)-equol have proliferative effects on MCF-7 cell growth in vitro within the concentration range tested. Dietary daidzein had a slight but significant stimulatory effect on tumor growth, whereas (+/-)-equol did not stimulate the growth of estrogen-dependent breast tumor growth in athymic mice, increase the cell proliferation in tumors, or induce an estrogen-responsive pS2 expression. Total daidzein or (+/-)-equol plasma levels in mice fed the isoflavones were in the range that stimulated MCF-7 cell growth in vitro. These results suggest that pharmacokinetic and/or metabolic factors attenuate the estrogenic effects of daidzein and equol in vivo. 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, 905 S Goodwin,Room 580 Bevier Hall, Urbana, IL 61801 USA. EM helferic@uiuc.edu FU NIA NIH HHS [P01-AG024387]; NIEHS NIH HHS [T32 ES07326] NR 69 TC 89 Z9 102 U1 0 U2 8 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD APR PY 2006 VL 27 IS 4 BP 856 EP 863 DI 10.1093/carcin/bgi320 PG 8 WC Oncology SC Oncology GA 025GF UT WOS:000236252600022 PM 16399773 ER PT J AU Dobrovolskaia, E Gam, A Slater, JE AF Dobrovolskaia, E Gam, A Slater, JE TI Competition enzyme-linked immunosorbant assay (ELISA) can be a sensitive method for the specific detection of small quantities of allergen in a complex mixture SO CLINICAL AND EXPERIMENTAL ALLERGY LA English DT Article DE allergen; cockroach; ELISA; potency; standardization ID MOLECULAR-CLONING; COCKROACH; STABILITY; VACCINES; EXTRACTS; IGE AB Rationale The competition ELISA assay is used to determine the potency of US standardized allergen extracts. We have been concerned that the competition ELISA is not sensitive to changes in individual allergen levels. This study was designed to determine the sensitivity of the competition ELISA to detect the specific loss of Bla g 1 and Bla g 2 in cockroach extracts. Methods German cockroach extract E3Cg was made from defatted German cockroaches. New Zealand White rabbits were immunized with rBla g 1 or rBla g 2. Optimal dilutions of anti-Bla g 1 and anti-Bla g 2 sera were established by ELISA. E3Cg was selectively depleted of Bla g 1 or Bla g 2 by immunoabsorption with anti-Bla g 1 or anti-Bla g 2 attached to Protein G agarose beads. Competition ELISA using pooled human sera, or mixed anti-Bla g 1 and anti-Bla g 2 serum, was performed on the depleted extracts, and on depleted extracts reconstituted with rBla g 1 or rBla g 2. Results Unlike pooled human-allergic IgE sera, anti-Bla g 1 and anti-Bla g 2 IgG - in dilutions as low as 10(-6), could be used in the competition ELISA to measure the loss of allergen in depleted E3Cg. As little as 0.001 mu g/mL of added rBla g 1 and 0.1 mu g/mL of added rBla g 2, could be detected. Conclusion The competition ELISA can be highly sensitive to compositional differences in complex allergen mixtures, even when the specific detecting antibody is present in relatively small amounts. C1 US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. RP Slater, JE (reprint author), US FDA, CBER, HFM-422,1401 Rockville Pike, Rockville, MD 20852 USA. EM slaterj@cber.fda.gov NR 12 TC 12 Z9 12 U1 2 U2 5 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0954-7894 J9 CLIN EXP ALLERGY JI Clin. Exp. Allergy PD APR PY 2006 VL 36 IS 4 BP 525 EP 530 DI 10.1111/j.1365-2222.2006.02466.x PG 6 WC Allergy; Immunology SC Allergy; Immunology GA 025CC UT WOS:000236241900016 PM 16630159 ER PT J AU Goldman, JM Jackson, JL Whitehead, SF Rausch, TL Weininger, S AF Goldman, JM Jackson, JL Whitehead, SF Rausch, TL Weininger, S TI The Medical Device "Plug-and-Play" (MD PnP) Interoperability Program SO COMPUTER LA English DT Article C1 Massachusetts Gen Hosp, Med Device Plug Play Interoperabil Program, Dept Anesthesia, Boston, MA 02114 USA. Massachusetts Gen Hosp, Med Device Plug Play Interoperabil Program, Dept Biomed Engn, Boston, MA 02114 USA. Ctr Integrat Med & Innovat Technol, Cambridge, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Kaiser Permanente Mid Atlantic States, Rockville, MD USA. FDA Ctr Devices & Radiol Hlth, OSEL, DESE, Rockville, MD USA. RP Goldman, JM (reprint author), Massachusetts Gen Hosp, Med Device Plug Play Interoperabil Program, Dept Anesthesia, Boston, MA 02114 USA. EM jmgoldman@partners.org; jljackson@partners.org; swhitehead@partners.org; tracy.rausch@kp.org; sandy.weininger@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU IEEE COMPUTER SOC PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1314 USA SN 0018-9162 J9 COMPUTER JI Computer PD APR PY 2006 VL 39 IS 4 BP 30 EP 31 PG 2 WC Computer Science, Hardware & Architecture; Computer Science, Software Engineering SC Computer Science GA 030DD UT WOS:000236612600007 ER PT J AU Jetley, R Iyer, SP Jones, PL AF Jetley, R Iyer, SP Jones, PL TI A formal methods approach to medical device review SO COMPUTER LA English DT Article ID COMPREHENSION AB Agencies such as the US Food and Drug Administration need effective means for assuring that medical software is safe and reliable. The FDA has been striving for a more rigorous engineering-based review strategy to provide this assurance. Although regulatory processes work reasonably well for device production processes, they're insufficient for assessing software. To address this problem, researchers at the FDA's Center for Devices and Radiological Health/Office of Science and Engineering Laboratories (CDRH/OSEL) have been collaborating with university researchers to explore ways to use formal modeling methods and static analysis techniques to improve the review process. These techniques include developing usage models to aid premarket review and using abstraction-driven slicing techniques to facilitate postmarket forensic analysis. C1 N Carolina State Univ, Dept Comp Sci, Raleigh, NC 27695 USA. US FDA, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, Rockville, MD 20857 USA. RP Jetley, R (reprint author), N Carolina State Univ, Dept Comp Sci, Raleigh, NC 27695 USA. EM rpjetley@alumni.ncsu.edu; purush@csc.ncsu.edu; PaulL.Jones@fda.hhs.gov NR 13 TC 21 Z9 21 U1 0 U2 4 PU IEEE COMPUTER SOC PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1314 USA SN 0018-9162 J9 COMPUTER JI Computer PD APR PY 2006 VL 39 IS 4 BP 61 EP + DI 10.1109/MC.2006.113 PG 8 WC Computer Science, Hardware & Architecture; Computer Science, Software Engineering SC Computer Science GA 030DD UT WOS:000236612600012 ER PT J AU Chen, HZ AF Chen, HZ TI Recent advances in azo dye degrading enzyme research SO CURRENT PROTEIN & PEPTIDE SCIENCE LA English DT Review DE azo dyes; azoreductase; commensal bacteria; environmental microorganisms; biodegradation; aromatic amines; carcinogenicity ID HUMAN INTESTINAL MICROFLORA; PHANEROCHAETE-CHRYSOSPORIUM; MICROBIAL DECOLORIZATION; TRIPHENYLMETHANE DYES; MOLECULAR-CLONING; AROMATIC-AMINES; SUDAN-I; AZOREDUCTASE ACTIVITY; AEROBIC AZOREDUCTASE; FUNGAL DEGRADATION AB Azo dyes, which are characterized by one or more azo bonds, are a predominant class of colorants used in tattooing, cosmetics, foods, and consumer products. These dyes are mainly metabolized by bacteria to colorless aromatic amines, some of which are carcinogenic, by azoreductases that catalyze a NAD(P)H-dependent reduction. The resulting amines are further degraded aerobically by bacteria. Some bacteria have the ability to degrade azo dyes both aerobically and anaerobically. Plant-degrading white rot fungi can break down azo dyes by utilizing a number of oxidases and peroxidases its well. In yeast, it ferric reductase system participates in the extracellular reduction of azo dyes. Recently, two types of azoreductases have been discovered in bacteria. The First class of azoreductases is monomeric flavin-free enzymes containing a putative NAD(P)H binding motif at their N-termini the second class is polymeric flavin dependent enzymes which are Studied more extensively. Azoreductases from bacteria represent novel families of enzymes with little similarity to other reductases. Dissociation and reconstitution of the flavin dependent azoreductases demonstrate that the non-covalent bound flavin prosthetic group is required for the enzymatic functions. In this review, Structures and carcinogenicity of azo colorants, protein structure, enzymatic function, and substrate specificity, as well as application of the azo dyes and azoreductases will be discussed. C1 US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. RP Chen, HZ (reprint author), US FDA, Natl Ctr Toxicol Res, Div Microbiol, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM hchen@nctr.fda.gov NR 113 TC 82 Z9 89 U1 4 U2 27 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1389-2037 J9 CURR PROTEIN PEPT SC JI Curr. Protein Pept. Sci. PD APR PY 2006 VL 7 IS 2 BP 101 EP 111 DI 10.2174/138920306776359786 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 026LD UT WOS:000236339500001 PM 16611136 ER PT J AU Jaffe, BD Evans, TA Howell, S Westergaard, GC Snoy, PJ Higley, JD AF Jaffe, BD Evans, TA Howell, S Westergaard, GC Snoy, PJ Higley, JD TI Left versus right nipple preference in free-ranging infant rhesus macaques (Macaca mulatta) SO DEVELOPMENTAL PSYCHOBIOLOGY LA English DT Article DE nipple preference; nursing; laterality; infancy; development; macaque; Macaca mulatta ID JAPANESE MACAQUES; NONHUMAN-PRIMATES; LATERALITY; MONKEYS; HANDEDNESS; BEHAVIOR; MOTHER; FIELD; HAND AB The examination of nonhuman primate (NHP) lateralized behaviors may provide insight into the evolution of hemispheric specialization. This study examined nipple preference in 64 infant macaques in order to consider the ontogeny of lateralized behavior We used a focal animal sampling method to record nipple contact during 15, 30-min observation sessions collected across each infant's first year of lift. Using a lateralized behavior index (LBI) we calculated individual and population preferences (LBI = (R-L)I(R + L); "R" = mean right nipple contact, "L" = mean left nipple contact). Strength of preference was calculated as the absolute value of this score. Infants exhibited no population preference for a particular nipple, but showed a significant strength of preference that developed after 48 hr Interestingly, successive siblings preferred the nipple not used by the previous infant. These findings suggest that nipple preference is guided by external stimuli, and that nipple preference during infancy may not be a behavioral representation of hemispheric specialization. (c) 2006 Wiley Periodicals, Inc. C1 Alpha Genesis Inc, Yemassee, SC 29945 USA. US FDA, Div Vet Serv, Poolesville, MD USA. NIAAA, NIH, Poolesville, MD USA. RP Howell, S (reprint author), Alpha Genesis Inc, 95 Castle Hall Rd,POB 557, Yemassee, SC 29945 USA. EM suehowell@alphagenesisinc.com FU NIAAA NIH HHS [N01AA02018]; PHS HHS [223-01-1101] NR 25 TC 7 Z9 9 U1 0 U2 4 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0012-1630 J9 DEV PSYCHOBIOL JI Dev. Psychobiol. PD APR PY 2006 VL 48 IS 3 BP 266 EP 272 DI 10.1002/dev.20128 PG 7 WC Developmental Biology; Psychology SC Developmental Biology; Psychology GA 031UN UT WOS:000236729800007 PM 16568413 ER PT J AU Leighton, JX Brown, P Ellis, A Harlow, P Harrouk, W Pine, PS Robison, T Rosario, L Thompson, K AF Leighton, JX Brown, P Ellis, A Harlow, P Harrouk, W Pine, PS Robison, T Rosario, L Thompson, K TI Workgroup report: Review of genomics data based on experience with mock submissions - View of the CDER pharmacology toxicology Nonclinical Pharmacogenomics Subcommittee SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE data visualization; electronic data files; MIAME/MINTox; mock submission content; quality control metrics; toxicogenomics ID MICROARRAYS AB Over the past few years, both the U.S. Food and Drug Administration (FDA) and the pharmaceutical industry have recognized the potential importance of pharmacogenomics and toxicogenomics to drug development. To resolve the uncertainties surrounding the use of microarray technology and the presentation of genomics data for regulatory purposes, several pharmaceutical companies and genomics technology providers have provided the FDA with reports of genomics studies that included supporting toxicology data (e.g., serum chemistry, histopathology). These Studies were not associated with any active drug application and were exploratory or hypothesis generating in nature. For training purposes, these reports were reviewed by the Nonclinical Pharmacogenomics Subcommittee consisting of the Center for Drug Evaluation and Research pharmacology and toxicology researchers and reviewers. In this article, we describe some of these Submissions and report on our assessment of data content, format, and quality control metrics that were useful for evaluating these nonclinical genomics submissions, specifically, in relation to the proposed MIAME/MINTox (minimum information about a microarray experiment/minimum information needed for a toxicology experiment) recommendations. These genomics submissions allowed both researchers and regulators to gain experience in the process of reviewing and analyzing toxicogenomics data. The experience will allow development of recommendations for the submission and review of these data as the state of the science evolves. C1 US FDA, Off Oncol Drug Prod, Silver Spring, MD 20993 USA. US FDA, Off New Drugs, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. US FDA, Off Pharmaceut Sci, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Leighton, JX (reprint author), US FDA, Off Oncol Drug Prod, Bldg 22,Room 2118,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM leightonj@fda.hhs.gov NR 19 TC 18 Z9 20 U1 0 U2 0 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD APR PY 2006 VL 114 IS 4 BP 573 EP 578 DI 10.1289/ehp.8318 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 030QX UT WOS:000236650500043 PM 16581548 ER PT J AU Sahin, N Sahin, K Onderci, M Sarkar, FH Doerge, D Prasad, A Kucuk, O AF Sahin, N Sahin, K Onderci, M Sarkar, FH Doerge, D Prasad, A Kucuk, O TI Effects of dietary genistein on nutrient use and mineral status in heat-stressed quails SO EXPERIMENTAL ANIMALS LA English DT Article DE bone; digestibility; genistein; quail; stress ID TYROSINE KINASE INHIBITORS; SOY ISOFLAVONES; BONE LOSS; OVARIECTOMIZED RATS; JAPANESE-QUAIL; TEMPERATURE; PERFORMANCE; SUPPLEMENTATION; PHYTOESTROGENS; OSTEOCLASTS AB Genistein is a powerful antioxidant and plays a role in calcium and bone metabolism. We evaluated the efficacy of dietary supplementation with genistein on the nutrient use and mineral concentrations in tibia and serum of quails reared at high environmental temperature (34 degrees C). Two hundred and forty Japanese quails (10 days old) were randomly assigned to 8 treatment groups consisting of 10 replicates of 3 birds. The birds were kept in a temperature-controlled room at 22 degrees C (Thermoneutral, TN groups) or 34 degrees C (for 8 h/d; 09.00 am-05.00 pm; Heat stress, HS groups). Birds were fed either a basal diet (TN and HS) or the basal diet supplemented with 200, 400 or 800 mg of genistein/kg of diet. Heat exposure decreased apparent nutrient digestibility and bone mineralization when the basal diet was fed (P < 0.001). Apparent digestibility of dry matter (DM) (P < 0.05), crude protein (CP) (P < 0.05) and ash (P < 0.01) was significantly improved by genistein supplementation. However, this improvement was not in direct proportion to increased doses of supplement since there was no difference when diets included either 400 or 800 mg genistein/kg of diet (P < 0.05) in birds reared under heat stress. The amounts of Ca, P, Mg, Mn, Zn, Fe and Cu in the excreta decreased (P < 0.01), while Ca, P, Mg, Mn, Zn and Cu concentrations in tibia ash increased in quails reared under heat stress conditions (P < 0.01) with genistein supplementation. Ca and P concentrations in tibia ash were also increased in birds kept under thermoneutral conditions with genistein supplementation. Increased serum alkaline phosphatase activity (P < 0.01) was associated with increasing dietary genistein in all groups. In conclusion, genistein supplementation to the basal diet improved digestibility of CP, DM and ash and levels of Ca and P and bone mineralization in quails reared under heat stress conditions. C1 Firat Univ, Fac Vet Sci, Dept Anim Nutr, TR-231119 Elazig, Turkey. Vet Control & Res Inst, Elazig, Turkey. Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Sahin, N (reprint author), Firat Univ, Fac Vet Sci, Dept Anim Nutr, TR-231119 Elazig, Turkey. RI Sahin, Nurhan/D-5626-2009; Sahin, Kazim/D-5625-2009; OI Sahin, Nurhan/0000-0001-9487-1154 NR 40 TC 8 Z9 10 U1 0 U2 4 PU INT PRESS EDITING CENTRE INC PI TOKYO PA 1-2-3 SUGAMO, TOSHIMA-KU, TOKYO, 170 0002, JAPAN SN 1341-1357 J9 EXP ANIM TOKYO JI Exp. Anim. PD APR PY 2006 VL 55 IS 2 BP 75 EP 82 DI 10.1538/expanim.55.75 PG 8 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 036CG UT WOS:000237047900001 PM 16651689 ER PT J AU Wiesenfeld, PW Sapienza, PP Flynn, TJ Ford, CE Ross, IA Sahu, S Kim, CS O'Donnell, MW Collins, TFX Sprando, RL AF Wiesenfeld, PW Sapienza, PP Flynn, TJ Ford, CE Ross, IA Sahu, S Kim, CS O'Donnell, MW Collins, TFX Sprando, RL TI Effects of oral androstenedione on phospholipid fatty acids, ATP, caspase-3, prostaglandin E-2 and C-reactive protein in serum and livers of pregnant and non-pregnant female rats SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article DE androstenedione; pregnant; rats; liver; fatty acids; C-reactive protein; prostaglandin E-2 ID ANDROGENIC-ANABOLIC STEROIDS; PROHORMONE SUPPLEMENTATION; CELL-DEATH; APOPTOSIS; CHOLESTEROL; INFLAMMATION; LIPOPROTEIN; HEPATOTOXICITY; BODYBUILDERS; MACROPHAGES AB Androstenedione, a steroidal dietary supplement taken to enhance athletic performance, could affect serum and liver lipid metabolism, induce liver toxicity or alter inflammatory response depending on dose and duration of exposure. Pregnancy could further exaggerate these effects. To examine this, mature female rats were gavaged with 0, 5, 30 or 60 mg/kg/day androstenedione beginning two weeks prior to mating and continuing through gestation day 19. Non-pregnant female rats were gavaged over the same time frame with 0 or 60 mg/kg/day androstenedione. Serum was collected and livers were removed from dams on gestation day 20 and from non-pregnant rats after 5 weeks of treatment. Androstenedione had no effect on serum total cholesterol, triglycerides or HDL-cholesterol, but significantly decreased C-reactive protein in pregnant rats and prostaglandin E-2 in serum of both pregnant and non-pregnant rats. There were treatment related decreases in liver ATP and, to a lesser degree, caspase-3 and no change in alkaline phosphatase of pregnant female rats. Androstenedione decreased docosahexaenoic acid in both serum and liver phospholipids of pregnant female rats. In conclusion, oral androstenedione did not result in overt hepatotoxicity in pregnant female rats, but produced modest changes in lipid metabolism and may impair regeneration of injured hepatic cells or tissue. Published by Elsevier Ltd. C1 US FDA, Ctr Food Safety & Appl Nutr, Off Appl Res & Safety Assessment, Laurel, MD 20708 USA. US FDA, Ctr Food Safety & Appl Nutr, Off Sci Anal & Support, Laurel, MD 20708 USA. RP Wiesenfeld, PW (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Appl Res & Safety Assessment, 8301 Muirkirk Rd, Laurel, MD 20708 USA. EM pwiesenf@cfsan.fda.gov OI Flynn, Thomas/0000-0002-7248-0643 NR 54 TC 4 Z9 4 U1 0 U2 5 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 APR PY 2006 VL 44 IS 4 BP 579 EP 587 DI 10.1016/j.fct.2005.09.005 PG 9 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA 032VJ UT WOS:000236803700017 PM 16289525 ER PT J AU Zhou, KQ Yin, JJ Yu, LL AF Zhou, KQ Yin, JJ Yu, LL TI ESR determination of the reactions between selected phenolic acids and free radicals or transition metals SO FOOD CHEMISTRY LA English DT Article DE wheat; phenolic acid; radical; chelating; antioxidant; ESR; ferulic acid; 4-coumaric acid; syringic acid; vanillic acid; 4-hydroxy benzoic acid ID WHOLE-GRAIN CONSUMPTION; ANTIOXIDANT ACTIVITY; FERULIC ACID; WHEAT EXTRACTS; HEART-DISEASE; IN-VITRO; RISK; ASSAY; BRAN; MECHANISMS AB Five phenolic acids commonly present in wheat grain and fractions were examined and compared for their radical-scavenging properties and chelating capacities. The free radical-scavenging properties were evaluated against 2,2-diphenyl-1-picryhydrazyl radical (DPPHcenter dot), radical cation (ABTS(center dot+)), peroxide radical anion (O-2(center dot-)) and hydroxyl radical (HOcenter dot),whereas the chelating properties were evaluated against Fe (II) and Cu (II) using spectrophotometric and electron spin resonance measurements. These phenolic acids differed in their abilities to react with and quench HOcenter dot,O-2(center dot-), ABTS(center dot+)and DPPHcenter dot, as well as their capacities to form chelating complexes with transition metals. 4-Hydroxybenzoic acid had neither free radical-scavenging nor chelating activity under the experimental conditions. Strong structure-activity relationships were observed in the present study. Both substituents on the phenyl ring and the conjugated carbon skeleton may influence the antioxidant properties of phenolic acids. The presence of an additional methoxyl group in the ortho position of the hydroxyl group showed a strong influence on the chelating property of phenolic acids and their radical-scavenging capacity against O-2(center dot), ABTS(center dot+) and DPPHcenter dot, but not on their HOcenter dot-scavenging activity. (c) 2005 Elsevier Ltd. All rights reserved. C1 Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA. US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Yu, LL (reprint author), Univ Maryland, Dept Nutr & Food Sci, 0112 Skinner Bldg, College Pk, MD 20742 USA. EM LY46@umail.umd.edu RI Yin, Jun Jie /E-5619-2014 NR 39 TC 45 Z9 47 U1 2 U2 10 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0308-8146 J9 FOOD CHEM JI Food Chem. PD APR PY 2006 VL 95 IS 3 BP 446 EP 457 DI 10.1016/j.foodchem.2005.01.026 PG 12 WC Chemistry, Applied; Food Science & Technology; Nutrition & Dietetics SC Chemistry; Food Science & Technology; Nutrition & Dietetics GA 977TE UT WOS:000232825300010 ER PT J AU Han, J Farnsworth, RL Tiwani, JL Tian, J Lee, H Ikonomi, P Byrnes, AP Goodman, JL Puri, RK AF Han, J Farnsworth, RL Tiwani, JL Tian, J Lee, H Ikonomi, P Byrnes, AP Goodman, JL Puri, RK TI Quality prediction of cell substrate using gene expression profiling SO GENOMICS LA English DT Article DE 293 cells; cell confluence; DNA microarray; gene expression profile; class prediction; real-time PCR ID CDNA MICROARRAY ANALYSIS; OXIDATIVE-PHOSPHORYLATION; RNA; CANCER; CYCLE AB Changes in cell culture conditions influence the metabolism of cells, which consequently affects the quality of the products that they produce, such as viral vectors, recombinant proteins, or vaccines. Currently there is no effective technique available to monitor global quality of cells in cell culture. Here we describe a new method using gene expression profiling by microarray to predict the quality of cell substrates. human embryonic kidney 293 cells are a commonly used cell substrate in the production of biological products. We demonstrate that the yield of adenoviral vectors was lower in over-confluent 293 cells, compared to 40 or 90% confluent cells. Total RNA derived from these cells of different confluence states was reverse transcribed, labeled, and used to hybridize I OK cDNA arrays to determine biomarkers for confluence states. Phenotype scatter-plot analysis and cluster analysis were used for class discovery. Based on this approach, we identified genes that were either up-regulated or down-modulated in response to different cell confluence states. By multivariate predictive models we identified a set of 37 genes that were either down-regulated or up-regulated compared to 90% confluent cells as a predictor of cell confluence and quality of 293 cell cultures. The predictive accuracy of these models was assessed by the leave-one-out cross-validation method. The expression of selected gene predictors was validated by quantitative PCR analysis. Our results demonstrate that gene expression profiling can assess the quality of cell substrates prior to large-scale production of a biological product. Published by Elsevier Inc. C1 US FDA, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. Amer Type Culture Collect, Manassas, VA 20110 USA. US FDA, Div Biostat, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. US FDA, Lab Immunol & Virol, 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 29B,Room 2NN20,29 Lincoln Dr, Bethesda, MD 20892 USA. EM puri@cber.fda.gov RI Byrnes, Andrew/D-2808-2013 OI Byrnes, Andrew/0000-0003-1135-2629 NR 27 TC 8 Z9 8 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 0888-7543 J9 GENOMICS JI Genomics PD APR PY 2006 VL 87 IS 4 BP 552 EP 559 DI 10.1016/j.ygeno.2005.11.017 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 031CJ UT WOS:000236681400014 PM 16413166 ER PT J AU Qiang, R Wu, DG Chen, J Wang, SM Wilton, D Kainz, W AF Qiang, R Wu, DG Chen, J Wang, SM Wilton, D Kainz, W TI An efficient two-dimensional FDTD method for bio-electromagnetic applications SO IEEE TRANSACTIONS ON MAGNETICS LA English DT Article; Proceedings Paper CT 15th Biennial Conference on Computation of Electromagnetic Fields CY JUN 26-30, 2005 CL Shenyang, PEOPLES R CHINA DE algebraic multi-grid method; bio-electromagnetics; FDTD method; unconditionally stable algorithm ID ALGORITHM; MODEL AB We propose an efficient algorithm for the simulation of densely sampled biological objects. This technique is based on an algebraic multi-grid (AMG) accelerated Crank-Nicholson (CN) finite-difference time-domain (FDTD) method. Using this scheme, simulation time step sizes are no longer limited by the Courant-Friedrich-Levy (CFL) number. A practical guideline on how to choose appropriate time-step sizes for accurate bioelectromagnetic applications is also presented. Numerical examples are used to demonstrate the effectiveness of this technique. C1 Univ Houston, Dept Elect & Comp Engn, Houston, TX 77204 USA. NIH, Bethesda, MD 20892 USA. US FDA, CDRH, Rockville, MD 20852 USA. RP Qiang, R (reprint author), Univ Houston, Dept Elect & Comp Engn, Houston, TX 77204 USA. EM jchen18@uh.edu NR 17 TC 4 Z9 4 U1 1 U2 4 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 0018-9464 J9 IEEE T MAGN JI IEEE Trans. Magn. PD APR PY 2006 VL 42 IS 4 BP 1391 EP 1394 DI 10.1109/TMAG.2006.871947 PG 4 WC Engineering, Electrical & Electronic; Physics, Applied SC Engineering; Physics GA 030ZZ UT WOS:000236675200223 ER PT J AU Pagan-Ramos, E Master, SS Pritchett, CL Reimschuessel, R Trucksis, M Timmins, GS Deretic, V AF Pagan-Ramos, E Master, SS Pritchett, CL Reimschuessel, R Trucksis, M Timmins, GS Deretic, V TI Molecular and physiological effects of mycobacterial oxyR inactivation SO JOURNAL OF BACTERIOLOGY LA English DT Article ID OXIDATIVE STRESS-RESPONSE; GENE-EXPRESSION; PATHOGENIC MYCOBACTERIA; ISONIAZID ACTIVATION; TRANSCRIPTION FACTOR; CATALASE-PEROXIDASE; PROMOTER REGION; NITRIC-OXIDE; TUBERCULOSIS; MARINUM AB The majority of slow-growing mycobacteria have a functional oxyl?, the central regulator of the bacterial oxidative stress response. In contrast, this gene has been inactivated during the evolution of Mycobacterium tuberculosis. Here we inactivated the oxyR gene in Mycobacterium marinum, an organism used to model M. tuberculosis pathogenesis. Inactivation of oxyl? abrogated induction of ahpC, a gene encoding alkylhydroperoxide reductase, normally activated upon peroxide challenge. The absence of oxyR also resulted in increased sensitivity to the front-line antituberculosis drug isoniazid. Inactivation of oxyR in M. marinum did not affect either virulence in a fish infection model or survival in human macrophages. Our findings demonstrate, at the genetic and molecular levels, a direct role for OxyR in ahpC regulation in response to oxidative stress. Our study also indicates that oxyR is not critical for virulence in M. marinum. However, oxyR inactivation confers increased sensitivity to isonicotinic acid hydrazide, suggesting that the natural loss of oxyR in the tubercle bacillus contributes to the unusually high sensitivity of M. tuberculosis to isoniazid. C1 Univ Michigan, Sch Med, Dept Microbiol, Ann Arbor, MI 48105 USA. Univ New Mexico, Hlth Sci Ctr, Dept Mol Genet & Microbiol, Albuquerque, NM 87131 USA. Univ New Mexico, Hlth Sci Ctr, Sch Pharm, Albuquerque, NM 87131 USA. Univ New Mexico, Hlth Sci Ctr, Dept Cell Biol & Physiol, Albuquerque, NM 87131 USA. Univ Maryland, Sch Med, Dept Microbiol & Immunol, Baltimore, MD 21201 USA. US FDA, Coll Vet Med, Rockville, MD 20857 USA. Univ Massachusetts, Sch Med, Dept Med, Worcester, MA 01605 USA. RP Timmins, GS (reprint author), Univ New Mexico, Hlth Sci Ctr, Coll Pharm, 915 Camino Salud NE, Albuquerque, NM 87131 USA. EM gtimmins@salud.unm.edu RI Master, Sharon/B-1035-2009; OI timmins, graham/0000-0002-4971-718X; Deretic, Vojo/0000-0002-3624-5208 FU NIAID NIH HHS [R01 AI042999, AI42999, AI063486, R21 AI063486] NR 44 TC 22 Z9 24 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 APR PY 2006 VL 188 IS 7 BP 2674 EP 2680 DI 10.1128/JB.188.7.2674-2680.2006 PG 7 WC Microbiology SC Microbiology GA 027GP UT WOS:000236403300041 PM 16547055 ER PT J AU Lin, FYC Whiting, A Adderson, E Takahashi, S Dunn, DM Weiss, R Azimi, PH Philips, JB Weisman, LE Regan, J Clark, P Rhoads, GG Frasch, CE Troendle, J Moyer, P Bohnsack, JF AF Lin, FYC Whiting, A Adderson, E Takahashi, S Dunn, DM Weiss, R Azimi, PH Philips, JB Weisman, LE Regan, J Clark, P Rhoads, GG Frasch, CE Troendle, J Moyer, P Bohnsack, JF TI Phylogenetic lineages of invasive and colonizing strains of serotype III group B streptococci from neonates: A multicenter prospective study SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID AGALACTIAE STRAINS; DISEASE; VIRULENCE; IDENTIFICATION; INFECTIONS; PATTERNS; CLONE; DNA AB This study compares the phylogenetic lineages of invasive serotype III group B streptococci (GBS) to those of colonizing strains in order to determine lineages associated with invasive disease. Isolates from 29 infants with early-onset disease (EOD) and from 196 colonized infants, collected in a prospective, multicenter study, were assigned a sequence type (ST) by multilocus sequence typing. Overall, 54.5% of the isolates were in the ST-19 complex, and 40.4% were in the ST-17 complex. Invasive strains were more likely to be in the ST-17 complex than were colonizing strains (59% versus 38%, P = 0.03). After we adjusted for potential confounders, the ST-17 complex was more likely to be associated with EOD than were other lineages (odds ratio = 2.51, 95% confidence interval = 1.02 to 6.20). These data support the hypothesis that ST-17 complex GBS are more virulent than other serotype III GBS. C1 NICHHD, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Res & Review, Bethesda, MD 20014 USA. Dept Hlth & Human Serv, Bethesda, MD 20014 USA. Univ Utah, Hlth Sci Ctr, Dept Pediat, Salt Lake City, UT USA. Univ Utah, Hlth Sci Ctr, Genome Ctr, Salt Lake City, UT USA. St Jude Childrens Hosp, Dept Infect Dis, Memphis, TN 38105 USA. Joshi Eiyoh Univ, Div Microbiol, Saitama, Saitama, Japan. Childrens Hosp, Med Ctr No Calif, Oakland, CA USA. Univ Alabama, Birmingham, AL USA. Baylor Coll Med, Houston, TX 77030 USA. Columbia Univ, New York, NY USA. Univ Florida, Gainesville, FL USA. Univ Med & Dent New Jersey, Piscataway, NJ 08854 USA. RP Lin, FYC (reprint author), 6100 Execut Blvd,Rm 7B03,MSC 7510, Bethesda, MD 20892 USA. EM Link@exchange.nih.gov FU Intramural NIH HHS NR 21 TC 40 Z9 40 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 APR PY 2006 VL 44 IS 4 BP 1257 EP 1261 DI 10.1128/JCM.44.4.1257-1261.2006 PG 5 WC Microbiology SC Microbiology GA 032XS UT WOS:000236810500009 PM 16597848 ER PT J AU Loud, JT Weissman, NE Peters, JA Giusti, RM Wilfond, BS Burke, W Greene, MH AF Loud, JT Weissman, NE Peters, JA Giusti, RM Wilfond, BS Burke, W Greene, MH TI Deliberate deceit of family members: A challenge to providers of clinical genetics services SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID BRCA2 MUTATION CARRIERS; OVARIAN-CANCER RISK; BREAST-CANCER; ORAL-CONTRACEPTIVES; DISCLOSURE; SUSCEPTIBILITY; WOMEN; PREDISPOSITION; COMMUNICATION; MAMMOGRAPHY C1 NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Rockville, MD 20853 USA. US FDA, Rockville, MD USA. NHGRI, Dept Clin Bioeth, Ctr Clin, NIH, Bethesda, MD 20892 USA. NHGRI, Social Behav Res Branch, NIH, Bethesda, MD 20892 USA. Univ Washington, Dept Med Hist & Eth, Seattle, WA 98195 USA. RP Loud, JT (reprint author), NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, NIH,DHHS, 6120 Execut Blvd,EPS 7028, Rockville, MD 20853 USA. EM LoudJ@mail.nih.gov NR 31 TC 9 Z9 9 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 APR 1 PY 2006 VL 24 IS 10 BP 1643 EP 1646 DI 10.1200/JCO.2005.02.6203 PG 4 WC Oncology SC Oncology GA 030UK UT WOS:000236660200024 PM 16575016 ER PT J AU Hammad, TA Laughren, TP Racoosin, JA AF Hammad, TA Laughren, TP Racoosin, JA TI Suicide rates in short-term randomized controlled trials of newer antidepressants SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Article ID SEROTONIN REUPTAKE INHIBITORS; RECORD-LINKAGE; RISK; DEPRESSION; PLACEBO; METAANALYSIS; FLUOXETINE; MORTALITY AB Concerns have been raised about the appropriateness of placebo controls in clinical trials for major depressive disorder (MDD), given that there are approved treatments for this illness. Critics have argued that patients with untreated depression Would be exposed to an unnecessary risk of suicide. There is also a competing concern that antidepressant drug treatment itself may induce suicidal behavior and thinking (suicidality). To examine this question, we have evaluated the rate of suicide in placebo- and active drug-treated groups of patients with MDD and various anxiety disorders participating in short-term randomized controlled trials (RCTs). We examined data from all manufacturer-sponsored short-term RCTs of 9 commonly used antidepressants in patients with MDD and various anxiety disorders. All short-term RCTs of antidepressants in patients with MDD and various anxiety disorders were included. Individual patients' data were available for all trials. Data were available for the 207 trials conducted in patients with MDD, including a total of 40,028 patients. There were 21 cases of suicide in these patients. Forty-four trials were conducted in patients with various anxiety disorders, including a total of 10,972 patients. There were 2 cases of suicide in these patients. Overall, at least 1 case of suicide occurred in 21 of the 251 trials. Sixteen of the suicides in MDD trials Occurred in trials that had only an active control comparison group, and most of these (14 cases) were observed in the non-North American trials. In the placebo-controlled MDD trials, the rate ratios of suicide in the combined drug groups compared with placebo were 1.07 (0.1 -63.4) and 0.5 (0.0-36.7) for the non-North American and North American trials, respectively. In the anxiety disorder studies, the overall rate ratio of suicide for the selective serotonin reuptake inhibitors compared with placebo was 0.9 (0.0-71.4). Neither use of placebo nor of antidepressants in short-term RCTs was associated with an increased risk of completed suicide among patients with MDD or various anxiety disorders. Nonetheless, because of the small numbers of suicides in these trials and the subsequent lack of statistical power, ail increased risk of completed suicide in association with either drug or placebo treatment cannot be definitively excluded. C1 US FDA, Ctr Drug Evaluat & Res, Div Neuropharmacol Drug Prod, Silver Spring, MD 20993 USA. RP Hammad, TA (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Neuropharmacol Drug Prod, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM hammadt@cder.fda.gov NR 12 TC 74 Z9 74 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-0749 J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD APR PY 2006 VL 26 IS 2 BP 203 EP 207 DI 10.1097/01.jcp.0000203198.11453.95 PG 5 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 029JW UT WOS:000236559600017 PM 16633153 ER PT J AU Zheng, J Meng, JH Zhao, SH Singh, R Song, WX AF Zheng, J Meng, JH Zhao, SH Singh, R Song, WX TI Adherence to and invasion of human intestinal epithelial cells by Campylobacter jejuni and Campylobacter coli isolates from retail meat products SO JOURNAL OF FOOD PROTECTION LA English DT Article ID DISTENDING TOXIN PRODUCTION; CULTURED-MAMMALIAN-CELLS; HEP-2 CELLS; ESCHERICHIA-COLI; CACO-2 CELLS; 7 VIRULENCE; GENES; PCR; COLONIZATION; INFECTION AB The abilities of 34 Campylobacter jejuni and 9 Campylobacter coli isolates recovered from retail meats to adhere to and invade human intestinal epithelial T84 cells were examined and compared with those of a well-characterized human clinical strain, C jejuni 81-176, to better assess the pathogenic potential of these meat isolates. The meat isolates exhibited a wide range of adherence and invasion abilities; a few of the isolates adhered to and invaded T84 cells almost as well as did C jejuni 81-176. There was a significant correlation between the adherence ability and the invasion ability of the Campylobacter isolates. The presence of eight putative virulence genes in these Campylobacter isolates that are potentially responsible for adherence and invasion or that encode cytolethal distending toxin was determined using PCR. All Campylobacter isolates possessed flaA, cadF, pldA, cdtA, cdtB, and cdtC, and most (91%) also contained the ciaB gene. However, the virBII gene, carried by virulence plasmid pVir, was absent in almost all the Campylobacter isolates. Our findings indicated that C jejuni and C. coli present in retail meat were diverse in their ability to adhere to and invade human intestinal epithelial cells and that the putative virulence genes were widespread among the Campylobacter isolates. Thus, despite of the presence of the putative virulence genes, only some but not all Campylobacter strains isolated from retail meat can effectively invade human intestinal epithelial cells in vitro. C1 Univ Maryland, Dept Cell Biol & Mol Genet, College Pk, MD 20742 USA. Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA. US FDA, Ctr Vet Med, Res Off, Laurel, MD 20708 USA. RP Song, WX (reprint author), Univ Maryland, Dept Cell Biol & Mol Genet, College Pk, MD 20742 USA. EM wenxsong@umd.edu NR 52 TC 31 Z9 31 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 MAR PY 2006 VL 69 IS 4 BP 768 EP 774 PG 7 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 034JS UT WOS:000236925900009 PM 16629018 ER PT J AU Devadas, K Dhawan, S AF Devadas, Krishnakumar Dhawan, Subhash TI Hemin activation ameliorates HIV-1 infection via heme oxygenase-1 induction SO JOURNAL OF IMMUNOLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; REVERSE-TRANSCRIPTASE; PROTEASE INHIBITORS; DISEASE PROGRESSION; CORECEPTOR USAGE; MECHANISMS; RESISTANCE; REPLICATION; MACROPHAGES; ZIDOVUDINE AB Hemin, a critical component of hemoglobin, is an active ingredient of a biologic therapeutic approved by the Food and Drug Administration for the treatment of acute porphyries. This report describes a biological function of this molecule in inducing host defense against HIV-1 infection via heme oxygenase-1 (HO-1) induction. Treatment of monocytes with hemin substantially inhibited HIV replication, as evident by nearly undetectable viral RNA and cell-free HIV-1 p24 protein in a dose-dependent manner. Hemin exposure of these cells before infection, at the time of infection, or after infection caused > 90% reduction of HIV DNA with substantially low levels of HIV-1 p24 and HIV-associated cytopathic effects. In addition, hemin treatment significantly suppressed infection of both monocytes and T cells inoculated with R5, X4, R5X4 tropic strains, and reverse transcriptase-resistant, azidothymidine-resistant, ddC/ddI-resistant, nivirapine-resistant, and other clinical HIV isolates. Intraperitoneal administration of hemin 4 days after HIV infection reduced viral load in the serum of human PBMC-reconstituted nonobese diabetic SCID mice by > 6-fold. Suppression of HIV replication in hemin-activated cells correlated with the induction of HO-1 and was attenuated by tin protoporphyrin (SnPP) IX, an inhibitor of HO-1 activity, suggesting a pivotal role of this endogenous enzyme in the regulation of HIV infection. Hemin-induced HO-1 induction in the CCR-5, CXCR-4, and CD4 coexpressing GHOST(3) cells was consistent with the inhibition of Tat-dependent activation of long terminal repeat promoter leading to reduced GFP expression. These findings suggest an important role of hemin-induced HO-1 activity as a host defense mechanism against HIV-1 infection. C1 US FDA, Ctr Biol Evaluat & Res, Div Emerging & Transfus Transmitted Dis, Immunopathogenesis Sect,Lab Mol Virol, Rockville, MD 20852 USA. RP Dhawan, S (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Emerging & Transfus Transmitted Dis, Immunopathogenesis Sect,Lab Mol Virol, 1401 Rockville Pike HFM-315, Rockville, MD 20852 USA. EM dhawan@cber.fda.gov NR 38 TC 65 Z9 67 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 APR 1 PY 2006 VL 176 IS 7 BP 4252 EP 4257 PG 6 WC Immunology SC Immunology GA 059YY UT WOS:000238769300051 PM 16547262 ER PT J AU Arora, K Hill, CM Reischl, IG Chen, T Kozlowski, S AF Arora, Kamalpreet Hill, Chris M. Reischl, Ilona G. Chen, Trina Kozlowski, Steven TI Statins, inhibitors of HMG CoA reductase, directly affect morphology and migration of activated CD4 T lymphocytes. SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 US FDA, CDER, DivMonoclonal Antibodies, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S39 EP S39 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837100180 ER PT J AU Max, EE Arudchandran, A Bernstein, RM AF Max, Edward E. Arudchandran, Arulvathani Bernstein, Ralph M. TI Single-strand DNA breaks associated with class switch recombination SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 US FDA, CDER, OBP, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S235 EP S235 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837102088 ER PT J AU Shin, EC Seifert, U Rice, CM Feinstone, SM Kloetzel, PM Rehermann, B AF Shin, Eui-Cheol Seifert, Ulrike Rice, Charles M. Feinstone, Stephen M. Kloetzel, Peter-M. Rehermann, Barbara TI Double-stranded RNA-induced type IIFN induces immunoproteasomes during viral infection SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 NIDDK, Immunol Sect, LDB, NIH, Bethesda, MD 20892 USA. Humboldt Univ, Charite, D-10117 Berlin, Germany. Rockefeller Univ, New York, NY 10021 USA. US FDA, CBER, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S54 EP S54 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837100251 ER PT J AU Sloane, E Langer, S Milligan, E Jekich, B Mahoney, J Huberty, G Hughes, T Coats, B Klinman, D Poole, S Maier, S Johnson, K Leinwand, L Chavez, R Watkins, L AF Sloane, Evan Langer, Steve Milligan, Erin Jekich, Brian Mahoney, John Huberty, Garth Hughes, Travis Coats, Benjamin Klinman, Dennis Poole, Steve Maier, Steve Johnson, Kirk Leinwand, Leslie Chavez, Ray Watkins, Linda TI A novel anti-inflammatory cytokine based non-viral gene therapy: Controlling neuropathic pain and beyond SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 Univ Colorado, Boulder, CO 80309 USA. US FDA, Rockville, MD 20857 USA. Natl Inst Biol Stand & Controls, Potters Bar EN6 3QG, Herts, England. Avigen Inc, Alameda, CA 94502 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S34 EP S34 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837100155 ER PT J AU King, KE Ponnamperuma, RM Weinberg, WC AF King, K. E. Ponnamperuma, R. M. Weinberg, W. C. TI Differential activation of NF kappa B subunits in keratinocytes overexpressing triangle Np63 isoforms SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 03-06, 2006 CL Philadelphia, PA SP Soc Investigat Dermatol C1 US FDA, Immunobiol Lab, Off Biotechnol Prod, CDER, Bethesda, MD 20014 USA. RI Weinberg, Wendy/A-8920-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2006 VL 126 SU 1 MA 115 BP 20 EP 20 PG 1 WC Dermatology SC Dermatology GA 117RU UT WOS:000242891500116 ER PT J AU Altiner, A Tock, CL Turner, LR Terunuma, A Miller, S Beer, J Yee, CL Udey, MC Vogel, JC AF Altiner, A. Tock, C. L. Turner, L. R. Terunuma, A. Miller, S. Beer, J. Yee, C. L. Udey, M. C. Vogel, J. C. TI Identifying biosensor genes that quantify human epidermal response to UV radiation SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 03-06, 2006 CL Philadelphia, PA SP Soc Investigat Dermatol C1 NIH, Dermatol Branch, Bethesda, MD 20892 USA. Howard Hughes Med Inst, Bethesda, MD 20817 USA. US FDA, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2006 VL 126 SU 1 MA 857 BP 143 EP 143 PG 1 WC Dermatology SC Dermatology GA 117RU UT WOS:000242891500850 ER PT J AU Beer, JZ Cyr, W Coelho, SG Zmudzka, BZ Miller, SA AF Beer, J. Z. Cyr, W. Coelho, S. G. Zmudzka, B. Z. Miller, S. A. TI What is FDA doing about indoor tanning? SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 03-06, 2006 CL Philadelphia, PA SP Soc Investigat Dermatol C1 US FDA, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2006 VL 126 SU 1 MA 900 BP 150 EP 150 PG 1 WC Dermatology SC Dermatology GA 117RU UT WOS:000242891500895 ER PT J AU Miller, SA Zmudzka, BZ Coelho, SG Beer, JZ AF Miller, S. A. Zmudzka, B. Z. Coelho, S. G. Beer, J. Z. TI UV exposure regimens for indoor tanning - an update SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 03-06, 2006 CL Philadelphia, PA SP Soc Investigat Dermatol C1 US FDA, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2006 VL 126 SU 1 MA 921 BP 154 EP 154 PG 1 WC Dermatology SC Dermatology GA 117RU UT WOS:000242891500915 ER PT J AU Whiting, SJ Calvo, MS AF Whiting, SJ Calvo, MS TI Overview of the Proceedings from Experimental Biology 2005 Symposium: Optimizing vitamin D intake for populations with special needs: Barriers to effective food fortification and supplementation SO JOURNAL OF NUTRITION LA English DT Article; Proceedings Paper CT Symposium on Optimizing Vitamin D Intake for Populations with Special Needs CY APR 04, 2005 CL San Diego, CA SP Amer Soc Nutr ID CALCIUM; PREVENTION C1 Univ Saskatchewan, Coll Pharm & Nutr, Saskatoon, SK S7N 5C9, Canada. Ctr Food Safety & Appl Nutr, Off Appl Res & Safety Assessment, US FDA, Laurel, MD 20708 USA. RP Calvo, MS (reprint author), Univ Saskatchewan, Coll Pharm & Nutr, Saskatoon, SK S7N 5C9, Canada. EM susan.whiting@usask.ca NR 20 TC 17 Z9 18 U1 0 U2 2 PU AMER SOCIETY NUTRITIONAL SCIENCE PI BETHESDA PA 9650 ROCKVILLE PIKE, RM L-2407A, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD APR PY 2006 VL 136 IS 4 BP 1114 EP 1116 PG 3 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 028AE UT WOS:000236456900048 PM 16549490 ER PT J AU Calvo, MS Whiting, SJ AF Calvo, MS Whiting, SJ TI Public health strategies to overcome barriers to optimal vitamin D status in populations with special needs SO JOURNAL OF NUTRITION LA English DT Article; Proceedings Paper CT Symposium on Optimizing Vitamin D Intake for Populations with Special Needs CY APR 04, 2005 CL San Diego, CA SP Amer Soc Nutr DE vitamin D; fortification; supplementation ID D INSUFFICIENCY; EDIBLE MUSHROOMS; AFRICAN-AMERICAN; UNITED-STATES; WOMEN; HYPERPARATHYROIDISM; SUPPLEMENTATION; BIOAVAILABILITY; FORTIFICATION; SUFFICIENCY AB In North America, there is increasing public health awareness of the importance of adequate vitamin D intake to the maintenance of optimal vitamin D status and overall health. Experts now define this as circulating levels of 25-hydroxyvitamin D of 75-80 nmol/L. This serum level and high levels of dietary intake have been associated with significantly reduced risk of chronic diseases, such as osteoporosis, cardiovascular disease, diabetes, and some cancers. All of these diseases are more prevalent in the elderly of all races, and some are more prevalent and of greater severity among blacks than whites. Our objective is to review recent actions to increase public awareness of the health importance of maintaining optimal circulating 25(OH)D and potential strategies to increase vitamin D intake. Clinicians and educators are encouraged to promote improved vitamin D intake and status, particularly among the elderly and blacks. This will largely depend on combined efforts to judiciously fortify our food supply and to develop individual supplementation protocols for supplements or controlled use of UV light exposure to maintain optimal serum 25(OH)D, especially in high-risk groups. Growing evidence supports a low risk of toxicity with vitamin D use in fortification or supplementation, despite its past reputation of potential toxicity in excess. The cost to fortify food or supplements with vitamin D is relatively inexpensive compared with developing drugs used to treat or prevent chronic diseases; moreover, there is significant potential for broad health benefits in the reduced risk and prevention of multiple chronic diseases. C1 US FDA, Ctr Food Safety & Appl Nutr, Laurel, MD USA. Univ Saskatchewan, Coll Pharm & Nutr, Saskatoon, SK, Canada. RP Calvo, MS (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Laurel, MD USA. EM mona.calvo@cfsan.fda.gov NR 32 TC 45 Z9 45 U1 1 U2 4 PU AMER SOCIETY NUTRITIONAL SCIENCE PI BETHESDA PA 9650 ROCKVILLE PIKE, RM L-2407A, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD APR PY 2006 VL 136 IS 4 BP 1135 EP 1139 PG 5 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 028AE UT WOS:000236456900053 PM 16549495 ER PT J AU Gulmann, C Sheehan, KM Kay, EW Liotta, LA Petricoin, EF AF Gulmann, C Sheehan, KM Kay, EW Liotta, LA Petricoin, EF TI Array-based proteomics: mapping of protein circuitries for diagnostics, prognostics, and therapy guidance in cancer SO JOURNAL OF PATHOLOGY LA English DT Review DE proteomics; protein microarrays; biomarker discovery; bioinformatics; cancer ID ROLLING-CIRCLE AMPLIFICATION; TISSUE MICROARRAYS; ANTIBODY MICROARRAYS; GENE-EXPRESSION; SIGNALING NETWORK; BREAST-CANCER; CARCINOMA; PATHOLOGY; TUMORS; IMMUNOHISTOCHEMISTRY AB The human proteome, due to the enormity of post-translational permutations that result in large numbers of isoforms, is much more complex than the genome and alterations in cancer can occur in ways that are not predictable by translational analysis alone. Proteomic analysis therefore represents a more direct way of investigating disease at the individual patient level. Furthermore, since most novel therapeutic targets are proteins, proteomic analysis potentially has a central role in patient care. At the same time, it is becoming clear that mapping entire networks rather than individual markers may be necessary for robust diagnostics as well as tailoring of therapy. Consequently, there is a need for high-throughput multiplexed proteomic techniques, with the capability of scanning multiple cases and analysing large numbers of endpoints. New types of protein arrays combined with advanced bioinformatics are currently being used to identify molecular signatures of individual tumours based on protein pathways and signalling cascades. It is envisaged that analysing the cellular 'circuitry' of ongoing molecular networks will become a powerful clinical tool in patient management. Copyright (c) 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. C1 Beaumont Hosp, Dept Pathol, Dublin 9, Ireland. Royal Coll Surgeons Ireland, Dublin 2, Ireland. NCI, FDA, Clin Prote Program, Pathol Lab, Bethesda, MD 20892 USA. George Mason Univ, Ctr Appl Prote & Mol Med, Manassas, VA USA. RP Gulmann, C (reprint author), Beaumont Hosp, Dept Pathol, Beaumont Rd, Dublin 9, Ireland. EM cgulmann@rcsi.ie NR 65 TC 74 Z9 78 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0022-3417 J9 J PATHOL JI J. Pathol. PD APR PY 2006 VL 208 IS 5 BP 595 EP 606 DI 10.1002/path.1958 PG 12 WC Oncology; Pathology SC Oncology; Pathology GA 028HT UT WOS:000236478500001 PM 16518808 ER PT J AU Chiesa, OA Von Bredow, J Heller, D Nochetto, C Smith, M Moulton, K Thomas, M AF Chiesa, OA Von Bredow, J Heller, D Nochetto, C Smith, M Moulton, K Thomas, M TI Use of tissue-fluid correlations to estimate gentamicin residues in kidney tissue of Holstein steers SO JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS LA English DT Article ID DRUG RESIDUE; COMPARATIVE PHARMACOKINETICS; SERIAL BIOPSY; URINE; ANIMALS; SAMPLES; PLASMA; ABUSE; SHEEP; MILK AB Gentamicin continues to be one of the most effective antibiotics for the treatment of gram-negative infections. Greater than 90% of the drug is rapidly eliminated from the body in < 2 days, however, a small residue remains bound to the kidney cortex tissue for many months. In beef steers, the gentamicin residue is unacceptable and its presence is monitored by the FAST (Fast Antimicrobial Screen Test) applied to the kidney at the time of slaughter. The sensitivity of the FAST to gentamicin in the kidney cortex is reported to be 100 ng/g, therefore, this level of gentamicin defines the acceptable limit of gentamicin drug residue in the bovine kidney. In the present study, three doses of 4 mg/kg gentamicin was administered intramuscularly to eight steers. Gentamicin was allowed to deplete from the kidneys for a range of times from 7 to 10 months. At slaughter the level of gentamicin in the kidney cortex varied from 91 to 193 ng/g, but a total of 160 FAST tests performed on the kidneys were negative. Blood and urine samples were collected at varying times following the last dose of gentamicin. Kidney tissue samples were collected by laparoscopic surgery in the live steers as well as the final sample obtained at slaughter. Plasma levels of gentamicin declined rapidly to nondetectable within 3 days, while measurable urine persisted for 75 days before the concentration of gentamicin declined to levels too low to quantitate by the available liquid chromatography tandem mass spectrometry (LC/MS/MS) technique. An estimated correlation between an extrapolation of urine gentamicin concentration to the corresponding kidney tissue sample suggests a urine to kidney tissue relationship of 1:100. A test system sufficiently sensitive to a urine gentamicin concentration of 1 ng/mL will correlate with the estimated 100 ng/g gentamicin limit of the FAST applied to the fresh kidney of the recently slaughtered bovine. C1 US FDA, Ctr Vet Med, Res Off, Div Residue Chem, Laurel, MD 20708 USA. RP Chiesa, OA (reprint author), US FDA, Ctr Vet Med, Res Off, Div Residue Chem, 8401 Muirkirk Rd, Laurel, MD 20708 USA. EM ochiesa@cvm.fda.gov NR 38 TC 20 Z9 22 U1 0 U2 5 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0140-7783 J9 J VET PHARMACOL THER JI J. Vet. Pharmacol. Ther. PD APR PY 2006 VL 29 IS 2 BP 99 EP 106 DI 10.1111/j.1365-2885.2006.00720.x PG 8 WC Pharmacology & Pharmacy; Veterinary Sciences SC Pharmacology & Pharmacy; Veterinary Sciences GA 017ZD UT WOS:000235731200004 PM 16515663 ER PT J AU Martina, Y Marcucci, KT Cherqui, S Szabo, A Drysdale, T Srinivisan, U Wilson, CA Patience, C Salomon, DR AF Martina, Y Marcucci, KT Cherqui, S Szabo, A Drysdale, T Srinivisan, U Wilson, CA Patience, C Salomon, DR TI Mice transgenic for a human porcine endogenous retrovirus receptor are susceptible to productive viral infection SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN-CELLS; IN-VIVO; REPLICATION-COMPETENT; ENDOTHELIAL-CELLS; MINIATURE SWINE; NO EVIDENCE; LEUKEMIA-VIRUS; HOST-RANGE; NUDE-MICE; PIG AB Porcine endogenous retrovirus (PERV) is considered one of the major risks in xenotransplantation. No valid animal model has been established to evaluate the risks associated with PERV transmission to human patients by pig tissue xenotransplantation or to study the potential pathogenesis associated with PERV infection. In previous work we isolated two genes encoding functional human PERV receptors and proved that introduction of these into mouse fibroblasts allowed the normally nonpermissive mouse cells to become productively infected (T. A. Ericsson, Y. Takeuchi, C. Templin, G. Quinn, S. F. Farhadian, J.C. Wood, B. A. Oldmixon, K. M. Suling, J.K. Ishii, Y. Kitagawa, T. Miyazawa, D. R. Salomon, R. A. Weiss, and C. Patience, Proc. Nail. Acad. Sci. USA 100:6759-6764, 2003). In the present study we created mice transgenic for human PERV-A receptor 2 (HuPAR-2). After inoculation of transgenic animals with infectious PERV supernatants, viral DNA and RNA were detected at multiple time points, indicating productive replication. This establishes the role of HuPAR-2 in PERV infection in vivo; in addition, these transgenic mice represent a new model for determining the risk of PERV transmission and potential pathogenesis. These mice also create a unique opportunity to study the immune response to PERV infection and test potential therapeutic or preventative modalities. C1 Scripps Res Inst, Dept Mol & Expt Med, La Jolla, CA 92037 USA. US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. Biogen Inc, Cambridge, MA 02142 USA. RP Salomon, DR (reprint author), Scripps Res Inst, Dept Mol & Expt Med, MEM-241,10550 N Torrey Pines Rd, La Jolla, CA 92037 USA. EM dsalomon@scripps.edu RI Salomon, Daniel/E-9380-2012; OI Cherqui, Stephanie/0000-0003-1240-5219 FU NIAID NIH HHS [AI52349, R01 AI052349, R56 AI052349]; NIDDK NIH HHS [5T32DK007022/25, T32 DK007022] NR 66 TC 32 Z9 33 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD APR PY 2006 VL 80 IS 7 BP 3135 EP 3146 DI 10.1128/JVI.80.7.3135-3146.2006 PG 12 WC Virology SC Virology GA 025ZB UT WOS:000236305200002 PM 16537582 ER PT J AU Bassen, H Kainz, W Mendoza, G Kellom, T AF Bassen, H Kainz, W Mendoza, G Kellom, T TI MRI-induced heating of selected thin wire metallic implants - laboratory and computational studies - findings and new questions raised SO MINIMALLY INVASIVE THERAPY & ALLIED TECHNOLOGIES LA English DT Review DE MRI; magnetic resonance imaging; medical implant; heating; safety; RF; radio frequency ID INTERVENTIONAL MRI; SAFETY AB We performed experiments and computer modeling of heating of a cardiovascular stent and a straight, thin wire by RF fields in a 1.5 T MRI birdcage coil at 64 MHz. We used ASTM F2182-02a standard and normalized results to 4 W/kg whole body average. We used a rectangular saline-gel filled phantom and a coiled, double stent ( Intracoil by ev3 Inc) 11 cm long. The stent had thin electrical insulation except for bare ends ( simulating drug eluting coating). The stent and phantom were placed close to the wall of the RF Coil and had approximately 0.5 degrees C initial temperature rise at the ends ( local SAR=320 W/kg). We exposed a wire ( 24.1 cm, 0.5 mm diameter) with 0.5 mm insulation and saw an 8.6 degrees C temperature rise ( local SAR=5680 W/kg) at the bare ends. All heating was within 1 mm(3) of the ends, so the position of our fiber optic temperature probe was critical for repeatability. Our computational study used finite difference time domain software with a thermodynamics solver. We modeled a coiled bare-wire stent as a spiral with a rectangular cross section and found a maximum increase of 0.05 degrees C induced at the tips for plane wave exposures. A maximum local SAR of up to 200 W/kg occurred in a volume of only 8 x 10(-3) mm. We developed improved computational exposure sources - optimized birdcage coils and quasi-MRI fields that may eliminate the need to model an RF coil. We learned that local ( point) SAR ( initial linear temperature rise) is the most reliable indicator of the maximum heating of an implant. Local SAR depends greatly on implant length, insulation and shape, and position in the MRI coil. Accurate heating must be measured with sensors or software having millimeter resolution. Many commercially available fiber optic temperature probes do meet this requirement. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20852 USA. RP Bassen, H (reprint author), US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20852 USA. EM howard.bassen@fda.hhs.gov NR 12 TC 31 Z9 31 U1 0 U2 9 PU TAYLOR & FRANCIS AS PI OSLO PA PO BOX 12 POSTHUSET, NO-0051 OSLO, NORWAY SN 1364-5706 J9 MINIM INVASIV THER JI Minim. Invasive Ther. Allied Technol. PD APR PY 2006 VL 15 IS 2 BP 76 EP 84 DI 10.1080/13645700600640931 PG 9 WC Surgery SC Surgery GA 044BH UT WOS:000237646600005 PM 16754190 ER PT J AU Myers, KM Gaba, J Al-Khaldi, SF AF Myers, KM Gaba, J Al-Khaldi, SF TI Molecular identification of Yersinia enterocolitica isolated from pasteurized whole milk using DNA microarray chip hybridization SO MOLECULAR AND CELLULAR PROBES LA English DT Article DE DNA microarray; Yersinia enterocolitica; multiplex PCR; DNA microarray; whole milk ID OLIGONUCLEOTIDE MICROARRAY; NUCLEOTIDE-SEQUENCE; BETA-LACTAMASES; VIRULENCE; GENE; ENTEROTOXIN; PREVALENCE; CHROMOSOME; EXPRESSION; STRAINS AB A DNA microarray chip of four virulence genes and 16S ribosomal DNA gene conserved region among all Gram negative species, including Yersinia, as a positive control was developed and evaluated using 22 Yersinia enterocolitica isolates. Eight different oligonucleotide probes (oligoprobes) with an average size of 22 bp, complementary to the unique sequences of each gene, were designed and immobilized on the surface of chemically modified slides. Multiplex PCR was used to simultaneously amplify DNA target regions of all five genes, and single stranded DNA (ssDNA) samples for microarray analysis were prepared by using a primer extension of amplicons in the presence of one printer of all genes. The presence of genes in Y. enterocolitica was established by hybridization of the fluorescently labeled ssDNA representing different samples of the microarray gene-specific oligoprobes and confirmed by PCR. Results of the study showed specificity of genotyping Y. enterocolitica using multiple microarray-based assays. Final validation of the chip's ability to identify Y. enterocolitica genes from adulterated pasteurized whole milk was confirmed and successful. The limit of chip detection of virulence genes in pasteurized whole milk was found to be 1000 CFU per hybridization. (c) 2005 Elsevier Ltd. All rights reserved. C1 US FDA, Div Microbiol Studies, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Al-Khaldi, SF (reprint author), US FDA, Div Microbiol Studies, Ctr Food Safety & Appl Nutr, HFS-517,5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM sufian.al-khaldi@cfsan.fda.gov NR 29 TC 31 Z9 33 U1 1 U2 6 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 APR PY 2006 VL 20 IS 2 BP 71 EP 80 DI 10.1016/j.mcp.2005.09.006 PG 10 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Cell Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Cell Biology GA 028RH UT WOS:000236505500001 PM 16330182 ER PT J AU Guerry, P Ewing, CP Schirm, M Lorenzo, M Kelly, J Pattarini, D Majam, G Thibault, P Logan, S AF Guerry, P Ewing, CP Schirm, M Lorenzo, M Kelly, J Pattarini, D Majam, G Thibault, P Logan, S TI Changes in flagellin glycosylation affect Campylobacter autoagglutination and virulence SO MOLECULAR MICROBIOLOGY LA English DT Article ID ENTEROPATHOGENIC ESCHERICHIA-COLI; PSEUDAMINIC ACID; POSTTRANSLATIONAL MODIFICATION; PROTEIN GLYCOSYLATION; VIBRIO-CHOLERAE; JEJUNI 81-176; IN-VITRO; GENE; IDENTIFICATION; ADHERENCE AB Analysis of the complete flagellin glycosylation locus of Campylobacter jejuni strain 81-176 revealed a less complex genomic organization than the corresponding region in the genome strain, C. jejuni NCTC 11168. Twenty-four of the 45 genes found between Cj1293 and Cj1337 in NCTC 11168 are missing in 81-176. Mutation of six new genes, in addition to three previously reported, resulted in a non-motile phenotype, consistent with a role in synthesis of pseudaminic acid (PseAc) or transfer of PseAc to flagellin. Mutation of Cj1316c or pseA had been shown to result in loss of the acetamidino form of pseudaminic acid (PseAm). Mutation of a second gene also resulted in loss of PseAm, as well as a minor modification that appears to be PseAm extended with N-acetyl-glutamic acid. Previously described mutants in C. jejuni 81-176 and Campylobacter coli VC167 that produced flagella lacking PseAm or PseAc failed to autoagglutinate. This suggests that interactions between modifications on adjacent flagella filaments are required for autoagglutination. Mutants (81-176) defective in autoagglutination showed a modest reduction in adherence and invasion of INT407 cells. However, there was a qualitative difference in binding patterns to INT407 cells using GFP-labelled 81-176 and mutants lacking PseAm. A mutant lacking PseAm was attenuated in the ferret diarrhoeal disease model. C1 USN, Med Res Ctr, Enter Dis Dept, Silver Spring, MD USA. Univ Montreal, Inst Res Immunol & Canc, Montreal, PQ, Canada. Food & Drug Adm MOD1, Beltsville, MD USA. Natl Res Council Canada, Ottawa, ON, Canada. RP Guerry, P (reprint author), USN, Med Res Ctr, Enter Dis Dept, 503 Robert Grant Ave, Silver Spring, MD USA. EM guerryp@nmrc.navy.mil RI Guerry, Patricia/A-8024-2011 FU NIAID NIH HHS [R01 AI043559, R01 AI43559] NR 54 TC 136 Z9 139 U1 2 U2 14 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD APR PY 2006 VL 60 IS 2 BP 299 EP 311 DI 10.1111/j.1365-2958.2006.05100.x PG 13 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 026GZ UT WOS:000236328700006 PM 16573682 ER PT J AU Gambus, A Jones, RC Sanchez-Diaz, A Kanemaki, M van Deursen, F Edmondson, RD Labib, K AF Gambus, A Jones, RC Sanchez-Diaz, A Kanemaki, M van Deursen, F Edmondson, RD Labib, K TI GINS maintains association of Cdc45 with MCM in replisome progression complexes at eukaryotic DNA replication forks SO NATURE CELL BIOLOGY LA English DT Article ID CELL-FREE-EXTRACTS; YEAST SACCHAROMYCES-CEREVISIAE; SISTER-CHROMATID COHESION; POLYMERASE-ALPHA; S-PHASE; BUDDING YEAST; MULTIPROTEIN COMPLEX; FISSION YEAST; IN-VITRO; PROTEINS AB The components of the replisome that preserve genomic stability by controlling the progression of eukaryotic DNA replication forks are poorly understood. Here, we show that the GINS ( go ichi ni san) complex allows the MCM ( minichromosome maintenance) helicase to interact with key regulatory proteins in large replisome progression complexes (RPCs) that are assembled during initiation and disassembled at the end of S phase. RPC components include the essential initiation and elongation factor, Cdc45, the checkpoint mediator Mrc1, the Tof1 - Csm3 complex that allows replication forks to pause at protein - DNA barriers, the histone chaperone FACT ( facilitates chromatin transcription) and Ctf4, which helps to establish sister chromatid cohesion. RPCs also interact with Mcm10 and topoisomerase I. During initiation, GINS is essential for a specific subset of RPC proteins to interact with MCM. GINS is also important for the normal progression of DNA replication forks, and we show that it is required after initiation to maintain the association between MCM and Cdc45 within RPCs. C1 Univ Manchester, Paterson Inst Canc Res, Canc Res UK, Manchester M20 4BX, Lancs, England. US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Labib, K (reprint author), Univ Manchester, Paterson Inst Canc Res, Canc Res UK, Wilmslow Rd, Manchester M20 4BX, Lancs, England. EM klabib@picr.man.ac.uk RI Sanchez-Diaz, Alberto/L-2320-2014 NR 60 TC 406 Z9 412 U1 3 U2 14 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 J9 NAT CELL BIOL JI Nat. Cell Biol. PD APR PY 2006 VL 8 IS 4 BP 358 EP U41 DI 10.1038/ncb1382 PG 34 WC Cell Biology SC Cell Biology GA 029KA UT WOS:000236560000014 PM 16531994 ER PT J AU Shone, C Ferreira, J Boyer, A Cirino, N Egan, C Evans, E Kools, J Sharma, S AF Shone, C Ferreira, J Boyer, A Cirino, N Egan, C Evans, E Kools, J Sharma, S TI The 5th International Conference on Basic and Therapeutic Aspects of Botulinum and Tetanus Neurotoxins. Workshop review: Assay's and detection SO NEUROTOXICITY RESEARCH LA English DT Article; Proceedings Paper CT 5th International Conference on Basic and Therapeutic Aspects of Botulinum and Tetanus Toxins CY JUN 23-25, 2005 CL Denver, CO SP Allergan Inc DE botulinum; neurotoxin; assay; detection; endopeptidase; PCR ID LINKED-IMMUNOSORBENT-ASSAY; CLOSTRIDIUM-BOTULINUM; MASS-SPECTROMETRY; GENE CLUSTERS; B NEUROTOXIN; TOXIN; MOUSE; PCR; DIFFERENTIATION; IDENTIFICATION AB The development of diagnostic tests for the botulinum neurotoxins is complicated by their extremely high potencies and the considerable diversity observed within the neurotoxin family. Current approaches for the detection of the toxins and the organism include amplified immunoassays and PCR techniques. Assays which exploit the biological activities within the botulinum toxins are also in development. These are based on both antibody and mass spectrometric techniques which measure the endopeptidase activities of the neurotoxins. This overview of the Assays and Detection Workshop of the 5th International Conference on Basic and Therapeutic Aspects of Botulinum and Tetanus Neurotoxins discusses recent progress in the development of these assay systems and the issues that need to be overcome prior to their implementation. C1 Hlth Protect Agcy, Ctr Emergency Preparedness & Response, Salisbury SP4 0JG, Wilts, England. Ctr Dis Control & Prevent, Botulism Publ Hlth Res & Preparedness Lab, Natl Botulism Surveillance & Reference Unit, Atlanta, GA 30333 USA. Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Atlanta, GA 30341 USA. New York State Dept Hlth, Wadsworth Ctr, Albany, NY 12208 USA. US FDA, CFSAN, College Pk, MD 20740 USA. RP Shone, C (reprint author), Hlth Protect Agcy, Ctr Emergency Preparedness & Response, Salisbury SP4 0JG, Wilts, England. EM Cliff.Shone@hpa.org.uk FU NIAID NIH HHS [R01 AI055578] NR 28 TC 13 Z9 16 U1 0 U2 0 PU F P GRAHAM PUBLISHING CO PI MOUNTAIN HOME PA PO BOX 370, MOUNTAIN HOME, TN 37684 USA SN 1029-8428 J9 NEUROTOX RES JI Neurotox. Res. PD APR PY 2006 VL 9 IS 2-3 BP 205 EP 216 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 056QV UT WOS:000238541100018 PM 16785119 ER PT J AU Gierhart, BS AF Gierhart, Brenda S. TI When does a "less than perfect" sex life become female sexual dysfunction? SO OBSTETRICS AND GYNECOLOGY LA English DT Editorial Material C1 US FDA, Ctr Drug Evaluat & Res, Div Metab & Endocrinol Prod, Silver Spring, MD USA. RP Gierhart, BS (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Metab & Endocrinol Prod, Silver Spring, MD USA. EM GIERHARTB@cder.fda.gov NR 4 TC 7 Z9 7 U1 0 U2 1 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 APR PY 2006 VL 107 IS 4 BP 750 EP 751 DI 10.1097/01.AOG.0000204866.43734.22 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 095GM UT WOS:000241296200001 PM 16582107 ER PT J AU Ricci, MS Zong, WX AF Ricci, M. Stacey Zong, Wei-Xing TI Chemotherapeutic approaches for targeting cell death pathways SO ONCOLOGIST LA English DT Review DE chemotherapy; apoptosis; necrosis; autophagy; senescence; mitotic catastrophe ID TUMOR-NECROSIS-FACTOR; APOPTOSIS-INDUCING LIGAND; MITOCHONDRIAL PERMEABILITY TRANSITION; CYTOCHROME-C RELEASE; GROWTH IN-VIVO; CA-2&-INDUCED MEMBRANE TRANSITION; ADENINE-NUCLEOTIDE TRANSLOCATOR; SMALL-MOLECULE ANTAGONISTS; TRAIL-INDUCED APOPTOSIS; MYELOID-LEUKEMIA CELLS AB For several decades, apoptosis has taken center stage as the principal mechanism of programmed cell death in mammalian tissues. It also has been increasingly noted that conventional chemotherapeutic agents not only elicit apoptosis but other forms of nonapoptotic death such as necrosis, autophagy, mitotic catastrophe, and senescence. This review presents background on the signaling pathways involved in the different cell death outcomes. A re-examination of what we know about chemotherapy-induced death is vitally important in light of new understanding of nonapoptotic cell death signaling pathways. If we can precisely activate or inhibit molecules that mediate the diversity of cell death outcomes, perhaps we can succeed in more effective and less toxic chemotherapeutic regimens. C1 SUNY Stony Brook, Dept Mol Genet & Microbiol, Stony Brook, NY 11794 USA. NCI, Bethesda, MD 20892 USA. Food & Drug Adm Interagcy Oncol Task Force, Bethesda, MD USA. RP Zong, WX (reprint author), SUNY Stony Brook, Dept Mol Genet & Microbiol, 128 Life Sci Bldg, Stony Brook, NY 11794 USA. EM wzong@notes.cc.sunysb.edu FU NCI NIH HHS [K01 CA098092, K01 CA098092-01A2, K01 CA098092-02, K01 CA098092-03, K01 CA098092-04, K01 CA098092-05, K01 CA098092-06] NR 184 TC 189 Z9 204 U1 1 U2 7 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PD APR PY 2006 VL 11 IS 4 BP 342 EP 357 DI 10.1634/theoncologist.11-4-342 PG 16 WC Oncology SC Oncology GA 085TK UT WOS:000240627100004 PM 16614230 ER PT J AU Rader, JI Schneeman, BO AF Rader, JI Schneeman, BO TI Prevalence of neural tube defects, folate status, and folate fortification of enriched cereal-grain products in the United States SO PEDIATRICS LA English DT Article DE public health; public policy ID FOLIC-ACID INTAKE; FOOD FORTIFICATION; HOMOCYSTEINE; RESTENOSIS; PREVENTION AB IN THEIR RECENT report, Williams et al(1) examined data from 21 population-based birth defect surveillance systems for trends in prevalence of spina bifida and anencephaly for specific racial/ethnic groups from 1995 to 2002. Data were stratified into pre-, optional, and mandatory fortification intervals, coincident with the authorization of folate fortification of enriched cereal-grain products by the Food and Drug Administration (FDA) in 1996. Williams et al1 found prevalence values per 10 000 births for spina bifida for Hispanic, non-Hispanic white, and non-Hispanic black women of 4.18, 3.37, and 2.90, respectively, for the mandatory fortification interval versus corresponding values for the same groups of 6.49, 5.13, and 3.57, respectively, for the prefortification interval. These results suggested that folate fortification was associated with significant decreases in the prevalence of spina bifida among non-Hispanic white and Hispanic births (34% and 36% decreases, respectively). The 19% decline in the prevalence of spina bifida among non-Hispanic black births was borderline statistically significant. 1 This failure to find a statistically significant decline among non-Hispanic black births may have been attributable to smaller samples examined ( total cases were 515 for non-Hispanic black births, 2672 for non-Hispanic white births, and 1281 for Hispanic births). In their editorial on the article by Williams et al,(1) Brent and Oakley(2) argued that folic acid fortification levels in the United States are too low. They have inappropriately generalized the data of Williams et al1 into a broad criticism of the current folic acid fortification program and a call for increased fortification. This warrants our response. Consideration of whether increases in fortification are warranted depends a number of complex issues. For example, are the residual neural tube defects (NTDs) in all racial/ethnic groups folate sensitive? If so, then would increasing the levels of folic acid in enriched cereal-grain products be effective in reducing the remaining NTDs? Can increased fortification, if appropriate, be achieved without unduly increasing risk for people in the nontarget population? These issues are considered next. C1 US FDA, Div Res & Appl Technol, Off Nutr Prod Labeling & Dietary Supplements, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Rader, JI (reprint author), US FDA, Div Res & Appl Technol, Off Nutr Prod Labeling & Dietary Supplements, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM Jeanne.Rader@cfsan.fda.gov NR 18 TC 22 Z9 25 U1 0 U2 8 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD APR PY 2006 VL 117 IS 4 BP 1394 EP 1399 DI 10.1542/peds.2005-2745 PG 6 WC Pediatrics SC Pediatrics GA 029EA UT WOS:000236540500074 PM 16585338 ER PT J AU Devadas, K Boykins, RA Hardegen, NJ Philp, D Kleinman, HK Osa, EO Wang, J Clouse, KA Wahl, LM Hewlett, IK Rappaport, J Yamada, KM Dhawan, S AF Devadas, K Boykins, RA Hardegen, NJ Philp, D Kleinman, HK Osa, EO Wang, J Clouse, KA Wahl, LM Hewlett, IK Rappaport, J Yamada, KM Dhawan, S TI Selective side-chain modification of cysteine and arginine residues blocks pathogenic activity of HIV-1-Tat functional peptides SO PEPTIDES LA English DT Article DE HIV-Tat; peptides; AIDS; vaccination ID IMMUNODEFICIENCY-VIRUS TYPE-1; TAT-NEUTRALIZING ANTIBODIES; VASCULAR ENDOTHELIAL-CELLS; FIBROBLAST-GROWTH-FACTOR; NF-KAPPA-B; KAPOSIS-SARCOMA; T-CELLS; FLK-1/KDR RECEPTOR; IMMUNE-RESPONSES; RHESUS MACAQUES AB Extracellular Tat protein of HIV-1 activates virus replication in HIV-infected cells and induces a variety of host factors in the uninfected cells, some of which play a critical role in the progression of HIV infection. The cysteine-rich and arginine-rich basic domains represent key components of the HIV-Tat protein for pathogenic effects of the full-length Tat protein and, therefore, could be ideal candidates for the development of a therapeutic AIDS vaccine. The present study describes selective modifications of the side-chain functional groups of cysteine and arginine amino acids of these HIV-Tat peptides to minimize the pathogenic effects of these peptides while maintaining natural peptide linkages. Modification of cysteine by introducing either a methyl or t-butyl group in the free sulfhydryl group and replacing the guanidine group with a urea linkage in the side chain of arginine in the cysteine-rich and arginine-rich Tat peptide sequences completely blocked the ability of these peptides to induce HIV replication, chemokine receptor CCR-5 expression, and NF-kappa B activity in monocytes. Such modifications also inhibited angiogenesis and migration of Kaposi's sarcoma cells normally induced by Tat peptides. Such chemical modifications of the cysteine-rich and arginine-rich peptides did not affect their reactivity with antibodies against the full-length Tat protein. With an estimated 40 million HIV-positive individuals worldwide and approximately 4 million new infections emerging every year, a synthetic subunit HIV-Tat vaccine comprised of functionally inactive Tat domains could provide a safe, effective, and economical therapeutic vaccine to reduce the progression of HIV disease. Published by Elsevier Inc. C1 US FDA, Ctr Biol Evaluat & Res, Mol Virol Lab, Immunopathogenesis Sect, Rockville, MD 20852 USA. US FDA, Ctr Biol Evaluat & Res, Biophys Lab, Rockville, MD 20852 USA. Natl Inst Dent & Craniofacial Res, Oral Infect & Immun Branch, Cellular Immunol Sect, NIH, Bethesda, MD 20892 USA. Natl Inst Dent & Craniofacial Res, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Drug Evaluat & Res, Cell Biol Lab, Bethesda, MD 20892 USA. Natl Inst Dent & Craniofacial Res, Immunopathol Sect, NIH, Bethesda, MD 20892 USA. Temple Univ, Ctr Neurovirol & Canc Biol, Philadelphia, PA 19122 USA. RP Dhawan, S (reprint author), US FDA, Ctr Biol Evaluat & Res, Mol Virol Lab, Immunopathogenesis Sect, 1401 Rockville Pike HFM-315, Rockville, MD 20852 USA. EM dhawan@cber.fda.gov OI Yamada, Kenneth/0000-0003-1512-6805 NR 56 TC 2 Z9 2 U1 1 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-9781 J9 PEPTIDES JI Peptides PD APR PY 2006 VL 27 IS 4 BP 611 EP 621 DI 10.1016/j.peptides.2005.09.013 PG 11 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA 036BX UT WOS:000237047000002 PM 16256245 ER PT J AU Wang, SJ Hung, HMJ O'Neill, RT AF Wang, SJ Hung, HMJ O'Neill, RT TI Adapting the sample size planning of a phase III trial hased on phase II data SO PHARMACEUTICAL STATISTICS LA English DT Article DE adaptation; clinical endpoint; effect size threshold; launching probability; phase II; phase III; surrogate endpoint; uncertainty ID CLINICAL-TRIALS; END-POINTS; RATES AB Traditionally, in clinical development plan, phase II trials are relatively small and can be expected to result in a large degree of uncertainty in the estimates based on which Phase III trials are planned. Phase II trials are also to explore appropriate primary efficacy endpoint(s) or patient populations. When the biology of the disease and pathogenesis of disease progression are well understood, the phase II and phase III studies may be performed in the same patient population with the same primary endpoint, e.g. efficacy measured by HbA1c in non-insulin dependent diabetes mellitus trials with treatment duration of at least three months. In the disease areas that molecular pathways are not well established or the clinical outcome endpoint may not be observed in a short-term study, e.g. mortality in cancer or AIDS trials, the treatment effect may be postulated through use of intermediate surrogate endpoint in phase II trials. However, in many cases, we generally explore the appropriate clinical endpoint in the phase II trials. An important question is how much of the effect observed in the surrogate endpoint in the phase II study can be translated into the clinical effect in the phase III trial. Another question is how much of the uncertainty remains in phase III trials. In this work, we study the utility of adaptation by design (not by statistical test) in the sense of adapting the phase II information for planning the phase III trials. That is, we investigate the impact of using various phase II effect size estimates on the sample size planning for phase III trials. In general, if the point estimate of the phase II trial is used for planning, it is advisable to size the phase III trial by choosing a smaller alpha level or a higher power level. The adaptation via using the lower limit of the one standard deviation confidence interval from the phase II trial appears to be a reasonable choice since it balances well between the empirical power of the launched trials and the proportion of trials not launched if a threshold lower than the true effect size of phase III trial can be chosen for determining whether the phase III trial is to be launched. Published in 2006 by John Wiley & Sons, Ltd. C1 US FDA, Off Biostat, OPaSS, CDER, Silver Spring, MD 20993 USA. US FDA, Div Biometr 1, Off Biostat, Off Pharmacoepidemiol & Stat Sci,Ctr Drug Evaluat, Rockville, MD 20857 USA. RP Wang, SJ (reprint author), US FDA, Off Biostat, OPaSS, CDER, HFD-700,WO 22,Room 6216,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM suejane.wang@cder.fda.gov FU DRS NIH HHS [RSR 04-06, RSR 05-12] NR 15 TC 23 Z9 23 U1 1 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1539-1604 J9 PHARM STAT JI Pharm. Stat. PD APR-JUN PY 2006 VL 5 IS 2 BP 85 EP 97 DI 10.1002/pst.217 PG 13 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 054HF UT WOS:000238366700003 PM 17080765 ER PT J AU Hung, HMJ Wang, SJ O'Neill, RT AF Hung, HMJ Wang, SJ O'Neill, RT TI Methodological issues with adaptation of clinical trial design SO PHARMACEUTICAL STATISTICS LA English DT Article DE sample size re-estimation; interim change of endpoint; dropping a treatment arm; adaptive test ID GROUP-SEQUENTIAL DESIGNS; ADAPTIVE INTERIM ANALYSES; SAMPLE-SIZE REESTIMATION; FLEXIBLE 2-STAGE DESIGNS; PROGNOSTIC FACTORS; TREATMENT SELECTION; CONDITIONAL POWER; INFERENCE; TESTS; SUPERIORITY AB Adaptation of clinical trial design generates many issues that have not been resolved for practical applications, though statistical methodology has advanced greatly. This paper focuses on some methodological issues. In one type of adaptation such as sample size re-estimation, only the postulated value of a parameter for planning the trial size may be altered. In another type, the originally intended hypothesis for testing may be modified using the internal data accumulated at an interim time of the trial, such as changing the primary endpoint and dropping a treatment arm. For sample size re-estimation, we make a contrast between an adaptive test weighting the two-stage test statistics with the statistical information given by the original design and the original sample mean test with a properly corrected critical value. We point out the difficulty in planning a confirmatory trial based on the crude information generated by exploratory trials. In regards to selecting a primary endpoint, we argue that the selection process that allows switching from one endpoint to the other with the internal data of the trial is not very likely to gain a power advantage over the simple process of selecting one from the two endpoints by testing them with an equal split of alpha (Bonferroni adjustment). For dropping a treatment arm, distributing the remaining sample size of the discontinued arm to other treatment arms can substantially improve the statistical power of identifying a superior treatment arm in the design. A common difficult methodological issue is that of how to select an adaptation rule in the trial planning stage. Pre-specification of the adaptation rule is important for the practicality consideration. Changing the originally intended hypothesis for testing with the internal data generates great concerns to clinical trial researchers. Copyright (C) 2006 John Wiley & Sons, Ltd. C1 US FDA, Div Biometr 1, OB, CDER, Silver Spring, MD 20993 USA. US FDA, Off Biostat, CDER, Silver Spring, MD USA. RP Hung, HMJ (reprint author), US FDA, Div Biometr 1, OB, CDER, 10903 New Hampshire Ave,Bldg 22 Rm 4238,HFD-710,M, Silver Spring, MD 20993 USA. EM hsienming.hung@fda.hhs.gov FU DRS NIH HHS [RSR #99/00-08] NR 49 TC 16 Z9 16 U1 0 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1539-1604 J9 PHARM STAT JI Pharm. Stat. PD APR-JUN PY 2006 VL 5 IS 2 BP 99 EP 107 DI 10.1002/pst.219 PG 9 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 054HF UT WOS:000238366700004 PM 17080766 ER PT J AU Senior, JR AF Senior, JR TI How can 'Hy's Law' help the clinician? SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Editorial Material ID INDUCED LIVER-INJURY; CAUSALITY ASSESSMENT; ADVERSE REACTIONS; FAILURE; DRUGS; TRANSPLANTATION; TRIALS C1 US FDA, Off Pharmacoepidemiol & Stat Sci, Ctr Drug Evaluat & Res, HFD 030, Silver Spring, MD 20993 USA. RP Senior, JR (reprint author), US FDA, Off Pharmacoepidemiol & Stat Sci, Ctr Drug Evaluat & Res, HFD 030, 10903 New Hampshire Ave,White Oak Bldg 22,Room 54, Silver Spring, MD 20993 USA. EM seniorj@cder.fda.gov NR 26 TC 22 Z9 22 U1 1 U2 2 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD APR PY 2006 VL 15 IS 4 BP 235 EP 239 DI 10.1002/pds.1210 PG 5 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 035IT UT WOS:000236995000004 PM 16552792 ER PT J AU Temple, R AF Temple, R TI Hy's Law: predicting serious hepatotoxicity SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Editorial Material C1 US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Temple, R (reprint author), US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. EM robert.temple@hhs.fda.gov NR 4 TC 114 Z9 120 U1 2 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 APR PY 2006 VL 15 IS 4 BP 241 EP 243 DI 10.1002/pds.1211 PG 3 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 035IT UT WOS:000236995000005 PM 16552790 ER PT J AU Fang, H Xie, Q Boneva, R Fostel, J Perkins, R Tong, WD AF Fang, H Xie, Q Boneva, R Fostel, J Perkins, R Tong, WD TI Gene expression profile exploration of a large dataset on chronic fatigue syndrome SO PHARMACOGENOMICS LA English DT Article DE ArrayTrack; bioinformatics; chronic fatigue syndrome (CFS); correspondence analysis; DNA microarray; gene expression patterns; multidimensional fatigue inventory (MFI); pathway analysis; Wichita CFS Surveillance Study; Zung self-rating depression scale ID RATING DEPRESSION SCALE; BREAST-CANCER; IDENTIFICATION; CLASSIFICATION; DEFINITION; PREVALENCE; DISCOVERY; INFECTION; SEQUENCES; SYMPTOMS AB Objective: To gain understanding of the molecular basis of chronic fatigue syndrome (CFS) through gene expression analysis using a large microarray data set in conjunction with clinically administrated questionnaires. Method: Data from the Wichita (KS, USA) CFS Surveillance Study was used, comprising 167 participants with two self-report questionnaires (multidimensional fatigue inventory [MFI] and Zung depression scale [Zung]), microarray data, empiric classification, and others. Microarray data was analyzed using bioinformatics tools from ArrayTrack. Results: Correspondence analysis was applied to the MFI questionnaire to select the 23 samples having either the most or the least fatigue, and to the Zung questionnaire to select the 26 samples having either the most or least depression; ten samples were common, resulting in a total of 39 samples. The MFI and Zung-based CFS/non-CFS (NF) classifications on the 39 samples were consistent with the empiric classification. Two differentially-expressed gene lists were determined, 188 fatigue-related genes and 164 depression-related genes, which shared 24 common genes and involved 11 common pathways. Principal component analysis based on 24 genes clearly separates 39 samples with respect to their likelihood to be CFS. Most of the 24 genes are not previously reported for CFS, yet their functions are consistent with the prevailing model of CFS, such as immune response, apoptosis, ion channel activity, signal transduction, cell-cell signaling, regulation of cell growth and neuronal activity. Hierarchical cluster analysis was performed based on 24 genes to classify 128 (=167-39) unassigned samples. Several of the 11 identified common pathways are supported by earlier findings for CFS, such as cytokine-cytokine receptor interaction and neuroactive ligand-receptor interaction. Importantly, most of the 11 common pathways are interrelated, suggesting complex biological mechanisms associated with CFS. Conclusion: Bioinformatics is critical in this study to select definitive sample groups, analyze gene expression data and gain insight into biological mechanisms. The 24 identified common genes and 11 common pathways could be important in future studies of CFS at the molecular level. C1 US FDA, Natl Ctr Toxicol Res, Ctr Toxicoinformat, Jefferson, AR 72079 USA. Natl Ctr Toxicol Res, Z Tech Corp, Div Bioinformat, Jefferson, AR 72079 USA. Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. Alpha Gamma Technol Inc, Raleigh, NC 27609 USA. RP Tong, WD (reprint author), US FDA, Natl Ctr Toxicol Res, Ctr Toxicoinformat, HFT-020,3900 NCTR Rd, Jefferson, AR 72079 USA. EM wtong@nctr.fda.gov NR 63 TC 35 Z9 36 U1 1 U2 3 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1462-2416 J9 PHARMACOGENOMICS JI Pharmacogenomics PD APR PY 2006 VL 7 IS 3 BP 429 EP 440 DI 10.2217/14622416.7.3.429 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 036LF UT WOS:000237071900019 PM 16610953 ER PT J AU Miller, SA Coelho, SG Zmudzka, BZ Beer, JZ AF Miller, SA Coelho, SG Zmudzka, BZ Beer, JZ TI Reduction of the UV burden to indoor tanners through new exposure schedules: a pilot study SO PHOTODERMATOLOGY PHOTOIMMUNOLOGY & PHOTOMEDICINE LA English DT Article DE indoor tanning; pigmentation; sunlamps; UV ID ULTRAVIOLET-RADIATION; HUMAN-SKIN; TANNING FACILITIES; PIGMENTATION; ERYTHEMA; MELANIN; COLOR AB Background: The development of new pigmentation (tan) in human skin after UV exposure requires several days. Once it is developed, the tan can last for weeks. Current recommendations for tanning exposure schedules in the USA (FDA Letter to Manufacturers: Policy on maximum timer interval and exposure schedule for sunlamps, August 21, 1986) allow exposures three times per week for the development of a tan, and one to two times per week for maintenance exposures. However, this policy is often interpreted in the indoor tanning industry as allowing three exposures per week on a continuous basis. We believe that the reduction of the recommended cumulative dose to indoor tanners should be explored. Two approaches for achieving this are (1) decreasing the number of exposures and (2) increasing the time interval between exposures. To explore such changes, we conducted a pilot study. Methods: The pilot study involved three exposure schedules (evaluated on each of six subjects) that evolved throughout the course of the study. Digital photography, visual assessment and diffuse reflectance spectrometry were used to assess skin color changes. The six pilot subjects were studied for 8-18 weeks. The changes in skin color obtained through the use of the different exposure schedules were compared with changes reported by Caswell (Caswell M, The kinetics of the tanning response to tanning bed exposures, Photodermatol Photoimmunol Photomed 2000: 16: 10-14) who used schedules based on current recommendations. Results: Two out of the three experimental schedules produced tans comparable with those reported by Caswell. In these two schedules, cumulative doses were a factor of 2-3 below doses from current schedules. Conclusion: The UV burden to indoor tanners can be substantially reduced without compromising the cosmetic effect. These results need to be confirmed in a larger study. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. RP Miller, SA (reprint author), US FDA, Ctr Devices & Radiol Hlth, 12725 Twinbrook Pkwy HFZ-130, Rockville, MD 20850 USA. NR 24 TC 10 Z9 10 U1 0 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0905-4383 J9 PHOTODERMATOL PHOTO JI Photodermatol. Photoimmunol. Photomed. PD APR PY 2006 VL 22 IS 2 BP 59 EP 66 DI 10.1111/j.1600-0781.2006.00206.x PG 8 WC Dermatology SC Dermatology GA 022AE UT WOS:000236026200002 PM 16606410 ER PT J AU Doerge, DR Twaddle, NC Churchwell, MI Newbold, RR Delclos, KB AF Doerge, DR Twaddle, NC Churchwell, MI Newbold, RR Delclos, KB TI Lactational transfer of the soy isoflavone, genistein, in Sprague-Dawley rats consuming dietary genistein SO REPRODUCTIVE TOXICOLOGY LA English DT Article DE genistein; soy; lactation; neonatal; mass spectrometry ID NEONATAL EXPOSURE; FEMALE RATS; PHYTOESTROGEN GENISTEIN; F-1 GENERATIONS; BIOAVAILABILITY; HYPOTHALAMUS; NONYLPHENOL; EXPRESSION; VOLUME AB Exposures of Sprague-Dawley rats to the soy isoflavone, genistein, throughout the entire lifespan have produced a number of effects on reproductive tissues, immune function, neuroendocrine function and behavior. Our previous studies investigated pharmacokinetics and disposition of genistein during adult and fetal periods and this study describes the internal exposures of post-natal day 10 (PND10) rat pups due to lactational transfer of genistein. Conjugated and aglycone forms of genistein were measured by using LC/MS/MS in serum (PND10) and milk (PND7) from lactating dams consuming a genistein-fortified soy-free diet, and in serum from their pups at a time when milk was the only food source (PND10). This study shows that limited lactational transfer of genistein to rat pups occurs and that internal exposures to the active aglycone form of genistein are generally lower than those measured previously in the fetal period. These results suggest that developmental effects attributable to genistein exposure in our chronic and multi-generation studies are more likely to result from fetal exposures because of the higher levels of the active estrogenic aglycone form of genistein in utero, although the possibility of neonatal responses cannot be excluded. (c) 2005 Elsevier Inc. All rights reserved. C1 US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. NIEHS, Dev Endocrinol & Endorcine Disrupter Sect, Mol Toxicol Lab, NIH DHHS, Res Triangle Pk, NC 27709 USA. RP Doerge, DR (reprint author), US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. EM ddoerge@nctr.fda.gov FU PHS HHS [224-93-0001] NR 32 TC 43 Z9 43 U1 0 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0890-6238 J9 REPROD TOXICOL JI Reprod. Toxicol. PD APR PY 2006 VL 21 IS 3 BP 307 EP 312 DI 10.1016/j.reprotox.2005.09.007 PG 6 WC Reproductive Biology; Toxicology SC Reproductive Biology; Toxicology GA 023VG UT WOS:000236153700014 PM 16257506 ER PT J AU Laughren, T Levin, R AF Laughren, T Levin, R TI Food and drug administration perspective on negative symptoms in schizophrenia as a target for a drug treatment claim SO SCHIZOPHRENIA BULLETIN LA English DT Article DE schizophrenia; negative symptoms; drug development AB Negative symptoms of schizophrenia are not adequately addressed by available treatments for schizophrenia. Thus, it is reasonable to consider them as a target for a drug claim. This article describes the thought process that the Food and Drug Administration (FDA) will undertake in considering negative symptoms of schizophrenia as a novel and distinct drug target. Beyond this basic question, this article identifies a number of design issues that the FDA needs to consider regarding how best to conduct studies to support claims for this target. These design issues include (1) what population to study, (2) what phase of illness to target, (3) whether to focus on the negative symptom domain overall or on some specific aspect of negative symptoms, (4) the role of functional measures in negative symptom trials, and (5) optimal designs for targeting drugs for add-on therapy or broad-spectrum agents. C1 US FDA, DNDP, Rockville, MD 20853 USA. RP Laughren, T (reprint author), US FDA, DNDP, 5600 Fishers Lane,HFD-120, Rockville, MD 20853 USA. EM laughren@cder.fda.gov NR 6 TC 48 Z9 49 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD APR PY 2006 VL 32 IS 2 BP 220 EP 222 DI 10.1093/schbul/sbi039 PG 3 WC Psychiatry SC Psychiatry GA 023DV UT WOS:000236106600007 PM 16079389 ER PT J AU King, JW Hopper, ML Snyder, JM AF King, JW Hopper, ML Snyder, JM TI Extraction and enrichment of pesticides for analysis using binary supercritical fluid mixtures SO SEPARATION SCIENCE AND TECHNOLOGY LA English DT Article DE analysis; extraction; enrichment; pesticides; supercritical fluids ID CARBON-DIOXIDE; HELIUM; SOLVATION; MATRICES; DENSITY AB To improve the extraction selectivity in analytical supercritical fluid extraction (SFE), binary mixtures of supercritical fluids have been used to selectively produce lipid-free extracts of trace pesticide residues for chromatographic analysis. Mixtures of nitrogen and HC-134a have been used in conjunction with carbon dioxide to selectively extract both fortified and incurred residues from a variety of fatty foods using both experimental and commercially-available extraction instrumentation. Extraction of fortified pesticides in butter fat showed high recoveries for both organo-chlorine and -phosphorus pesticides with recoveries declining for specific pesticide moieties at the 1 ppb spiking level for CO2/N-2 mixtures. For CO2 and HC-134a mixtures, there was poor and little improvement in analyte recovery relative to using neat SC-CO2 for fortified organochlorine pesticides in butter fat at the 0.5-5.0 ppm level. However using a CO2/HC-134a mixture for organophosphorus pesticides in butter fat improved recoveries (> 90%) of the analytes at the 1-3.5 ppm level relative to using neat SC-CO2 . Excellent recoveries were obtained for incurred organochlorine and -phosphorus pesticides from a variety of food products at ppb levels using either CO2/N-2 or CO2/HC-134 mixtures. Results from these and additional experiments suggest that binary fluid mixtures can significantly reduce the need for additional sample cleanup prior to chromatographic analysis, allowing in some cases, direct injection of the extract after dilution into the gas chromatograph. C1 Univ Arkansas, Dept Chem Engn, Bell Engn Ctr 3202, Fayetteville, AR 72701 USA. US FDA, Total Diet & Pesticide Res Ctr, Lenexa, KS USA. USDA, ARS, Natl Ctr Agr Utilizat Res, Peoria, IL USA. RP King, JW (reprint author), Univ Arkansas, Dept Chem Engn, Bell Engn Ctr 3202, Fayetteville, AR 72701 USA. EM jwking1@uark.edu NR 18 TC 4 Z9 4 U1 1 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0149-6395 J9 SEPAR SCI TECHNOL JI Sep. Sci. Technol. PD APR PY 2006 VL 41 IS 5 BP 861 EP 875 DI 10.1080/01496390600600070 PG 15 WC Chemistry, Multidisciplinary; Engineering, Chemical SC Chemistry; Engineering GA 031YQ UT WOS:000236741500005 ER PT J AU Miura, M Miura, Y Padilla-Nash, HM Molinolo, AA Fu, BJ Patel, V Seo, BM Sonoyama, W Zheng, JJ Baker, CC Chen, WJ Ried, T Shi, ST AF Miura, Masako Miura, Yasuo Padilla-Nash, Hesed M. Molinolo, Alfredo A. Fu, Baojin Patel, Vyomesh Seo, Byoung-Moo Sonoyama, Wataru Zheng, Jenny J. Baker, Carl C. Chen, Wanjun Ried, Thomas Shi, Songtao TI Accumulated chromosomal instability in murine bone marrow mesenchymal stem cells leads to malignant transformation SO STEM CELLS LA English DT Article DE bone marrow-derived mesenchymal stem cell; malignant transformation chromosomal instability; fibrosarcoma ID ACUTE MYELOID-LEUKEMIA; TELOMERASE EXPRESSION; STROMAL CELLS; IN-VIVO; CANCER; IDENTIFICATION; MOUSE; DIFFERENTIATION; TRANSPLANTATION; SENESCENCE AB Despite recent emerging evidence suggesting that cancer stem cells subsist in a variety of tumors, it is not yet fully elucidated whether postnatal stem cells are directly involved in tumorigenesis. We used murine bone marrow-derived mesenchymal stem cells (BMMSCs) as a model to test a hypothesis that tumorigenesis may originate from spontaneous mutation of stem cells. In this study, we demonstrated that murine BMMSCs, after numerous passages, obtained unlimited population doublings and proceeded to a malignant transformation state, resulting in fibrosarcoma formation in vivo. Transformed BMMSCs colonized to multiple organs when delivered systemically through the tail vein. Fibrosarcoma cells formed by transformed BMMSCs contained cancer progenitors, which were capable of generating colony clusters in vitro and fibrosarcoma in vivo by the second administration. The mechanism by which BMMSCs transformed to malignant cells was associated with accumulated chromosomal abnormalities, gradual elevation in telomerase activity, and increased c-myc expression. Moreover, BMMSCs and their transformed counterpart, fibrosarcoma-forming cells, demonstrated different sensitivity to anti-cancer drugs. BMMSCs/fibrosarcoma transformation system may provide an ideal system to elucidate the mechanism of how stem cells become cancer cells and to screen anti-sarcoma drugs. C1 Natl Inst Dent & Craniofacial Res, Dent Biol Unit, NIH, Bethesda, MD 20892 USA. Natl Canc Inst, Genet Branch, Canc Res Ctr, NIH, Bethesda, MD USA. Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD USA. NCI, Cellular Oncol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Drug Evaluat & Res, Off Clin Pharmacol & Biopharmaceut, Food & Drug Adm, Rockville, MD 20857 USA. Natl Inst Dent & Craniofacial Res, Oral Infect & Immun Branch, Bethesda, MD USA. RP Shi, ST (reprint author), Natl Inst Dent & Craniofacial Res, Dent Biol Unit, NIH, Bldg 30,Room 131,30 Convent Dr MSC4320, Bethesda, MD 20892 USA. EM sshi@mail.nih.gov FU Intramural NIH HHS NR 30 TC 334 Z9 367 U1 1 U2 11 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1066-5099 J9 STEM CELLS JI Stem Cells PD APR PY 2006 VL 24 IS 4 BP 1095 EP 1103 DI 10.1634/stemcells.2005-0403 PG 9 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA 085WY UT WOS:000240636300032 PM 16282438 ER PT J AU Yan, J Xia, QS Webb, P Warbritton, AR Wamer, WG Howard, PC Boudreau, M Fu, PP AF Yan, J Xia, QS Webb, P Warbritton, AR Wamer, WG Howard, PC Boudreau, M Fu, PP TI Levels of retinyl palmitate and retinol in stratum corneum, epidermis and dermis of SKH-1 mice SO TOXICOLOGY AND INDUSTRIAL HEALTH LA English DT Article DE retinyl palmitate; retinol; skin ID LIQUID-CHROMATOGRAPHIC DETERMINATION; HAIRLESS MOUSE SKIN; VITAMIN-A; IN-VIVO; ACID; TOCOPHEROLS; CAROTENOIDS; IRRADIATION; RADIATION; ACETATE AB Vitamin A ( retinol) regulates many biological functions, including epidermal cell growth. Retinyl palmitate ( RP) is the major esterified form of retinol and the predominant component of retinoids in the skin; however, how endogenous levels of RP and retinol in the skin are affected by the age of the animal remains unknown. Furthermore, the levels of retinol and RP in the various skin layers - the stratum corneum, epidermis and dermis of skin - have not been reported. In this paper, we report the development of a convenient method for separation of the skin from SKH-1 female mice into the stratum corneum, epidermis, and dermis and the determination of the levels of RP and retinol in the three fractions by HPLC analysis. The total quantities of RP and retinol from the stratum corneum, epidermis, and dermis are comparable to those extracted from the same amount of intact skin from the same mouse. There was an age-related effect on the levels of RP and retinol in the skin and liver of female mice. An age-related effect was also observed in the stratum corneum, epidermis, and dermis. The levels of RP and retinol were highest in the epidermis of 20-week-old mice, and decreased when the age increased to 60- and 68-weeks. The total amount of RP at 20 weeks of age was found to be 1.52 ng/mg skin, and decreased about 4-fold at 60- and 68-weeks of age. A similar trend was found for the effects of age on the levels of retinol. C1 US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Toxicol Pathol Associates, Jefferson, AR 72079 USA. US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Fu, PP (reprint author), US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM pfu@nctr.fda.gov NR 32 TC 9 Z9 9 U1 0 U2 2 PU HODDER ARNOLD, HODDER HEADLINE PLC PI LONDON PA 338 EUSTON ROAD, LONDON NW1 3BH, ENGLAND SN 0748-2337 J9 TOXICOL IND HEALTH JI Toxicol. Ind. Health PD APR PY 2006 VL 22 IS 3 BP 103 EP 112 DI 10.1191/0748233706th252oa PG 10 WC Public, Environmental & Occupational Health; Toxicology SC Public, Environmental & Occupational Health; Toxicology GA 032HI UT WOS:000236765000001 PM 16716039 ER PT J AU Rios, M Zhang, MJ Grinev, A Srinivasan, K Daniel, S Wood, O Hewlett, IK Dayton, AI AF Rios, M Zhang, MJ Grinev, A Srinivasan, K Daniel, S Wood, O Hewlett, IK Dayton, AI TI Monocytes-macrophages are a potential target in human infection with West Nile virus through blood transfusion SO TRANSFUSION LA English DT Article ID COLONY-STIMULATING FACTOR; DENDRITIC CELLS; ENCEPHALITIS-VIRUS; IMMUNE-RESPONSES; UNITED-STATES; EXPRESSION; GENERATION AB BACKGROUND: West Nile virus (WNV) transmission by transfusion was documented in 2002. Approximately 80 percent of WNV infections are asymptomatic and 1 percent develop severe neurological illness. In animals, Langerhans-dendritic cells support initial viral replication, followed by replication in lymphoid tissues and dissemination to organs and possibly to the CNS. The cellular tropism of WNV infection after transfusion and the particular human blood cells that sustain viral replication remain largely unknown. Whether primary monocyte-derived macrophages (MDMs) support WNV infection-replication and produce infectious virions, with an in vitro system, was investigated. STUDY DESIGN AND METHODS: Elutriated monocytes (CD33+/CD14+) from suitable blood donors were cultured in the presence of macrophage-colony-stimulating factor, infected with WNV-NY99 at different time points, washed, and cultivated for up to 47 days. Supernatants were tested for WNV replication by TaqMan reverse transcription-polymerase chain reaction (RT-PCR), with primers for the envelope and/or 3'NC regions, and by cDNA-PCR to detect WNV minus-strand RNA and for the presence of functional virions by infectivity assays in Vero cells. RESULTS: RT-PCR TaqMan of supernatants demonstrated productive infection of MDMs. Viral load reached 2 to 5 log above baseline in 3 to 6 days and then declined, with detectable viral replication persisting for up to 47 days. WNV minus-strand RNA was detected in Day 4 cultures, indicating active viral replication. Infected MDM cultures showed no cytopathic changes. Supernatants that were TaqMan-positive for the presence of WNV-infected Vero cells and produced cytopathic effects within 3 to 5 days of culture. CONCLUSION: The susceptibility of monocytes-macrophages to productive infection in vitro is compatible with a potential role in initial WNV replication and propagation after transmission by transfusion. C1 US FDA, LMV, DETTD, OBRR,CBER, Bethesda, MD 20892 USA. RP Rios, M (reprint author), US FDA, LMV, DETTD, OBRR,CBER, 8800 Rockville Pike, Bethesda, MD 20892 USA. EM maria.rios@fda.hhs.gov NR 26 TC 39 Z9 44 U1 1 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0041-1132 J9 TRANSFUSION JI Transfusion PD APR PY 2006 VL 46 IS 4 BP 659 EP 667 DI 10.1111/j.1537-2995.2006.00769.x PG 9 WC Hematology SC Hematology GA 026HD UT WOS:000236329100025 PM 16584445 ER PT J AU Niu, MT Knippen, M Simmons, L Holness, LG AF Niu, MT Knippen, M Simmons, L Holness, LG TI Transfusion-transmitted Klebsiella pneumoniae fatalities, 1995 to 2004 SO TRANSFUSION MEDICINE REVIEWS LA English DT Review ID BLOOD-STREAM INFECTIONS; NEONATAL INTENSIVE-CARE; BACTERIAL-CONTAMINATION; UNITED-STATES; YERSINIA-ENTEROCOLITICA; SEPSIS; BACTEREMIA; EPIDEMIOLOGY; NURSERY; COLONIZATION AB Transfusion-transmitted bacterial sepsis is the third most common cause of transfusion-related fatalities reported to the Food and Drug Administration. Between October 1, 1995, and September 30, 2004, there were 665 reported transfusion fatalities. Eighty-five (13%) deaths were due to transfusion-transmitted bacterial infections, of which 58 (68%) were due to gram-negative organisms. The most common gram-negative organism associated with transfusion-transmitted deaths after receipt of platelets was Klebsiella pneumoniae. This article summarizes retrospectively the case series of deaths due to transfusion-transmitted K pneumoniae infection, reported to the Food and Drug Administration, 1995 to 2004. There were 12 deaths due to transfusion-transmitted K pneumoniae infection with 7 (58%) of the 12 cases occurring in 2002. Eleven deaths were caused by the transfusion of contaminated platelets and 1 death attributed to contaminated red blood cells. Extensive review of the seven 2002 fatality reports did not identify a common (shared) lot for items used during collection or processing of the blood product. In conclusion, in cases of suspected transfusion-transmititted septicemia, broad spectrum antibiotic coverage including coverage of gram-negative organisms should be considered. Strict adherence to infection control measures while collecting, processing, and handling all blood and blood components in both the clinical settings and in the laboratory should be followed. Further development of simple and effective test procedures for detecting bacteria in the blood is needed. (c) 2006 Elsevier Inc. All rights reserved. C1 US FDA, Ctr Biol Evaluat & Res, Off Blood Res & Review, Div Blood Applicat, Rockville, MD 20852 USA. US FDA, Off Compliance & Biol Qual, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Niu, MT (reprint author), US FDA, Ctr Biol Evaluat & Res, Off Blood Res & Review, Div Blood Applicat, 1401 Rockville Pike,HFM 370, Rockville, MD 20852 USA. EM niu@cber.fda.gov NR 58 TC 22 Z9 25 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC 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 APR PY 2006 VL 20 IS 2 BP 149 EP 157 DI 10.1016/j.tmrv.2005.11.007 PG 9 WC Hematology SC Hematology GA 032DN UT WOS:000236754200004 PM 16565027 ER PT J AU Engelfriet, CP Reesink, HW Henn, G Mayr, WR Olyntho, S Wendel, S Robillard, P Turek, P Krusius, T Koskinen, S Taaning, E Jorgensen, J Rebibo, D Hauser, L Zorzi, P Legras, JF Slimani, A Vo-Mai, M Trouvin, JH Andreu, G Kretschmer, V Keller-Stanislawski, B Mentzer, D Politis, C Lawlor, E Laspina, S Grazzini, G Hassan, HJ Aprili, G Okazaki, H Faber, JC Benson, S Solheim, BG Letowska, M Selivanov, E Danilova, T Snopek, I Nel, T Martin, MP Senn, M Stainsby, D Cohen, H Jones, H Blumberg, N Braun, MM Malarkey, MA Epstein, JS Menitove, JE Lipton, KS AF Engelfriet, CP Reesink, HW Henn, G Mayr, WR Olyntho, S Wendel, S Robillard, P Turek, P Krusius, T Koskinen, S Taaning, E Jorgensen, J Rebibo, D Hauser, L Zorzi, P Legras, JF Slimani, A Vo-Mai, M Trouvin, JH Andreu, G Kretschmer, V Keller-Stanislawski, B Mentzer, D Politis, C Lawlor, E Laspina, S Grazzini, G Hassan, HJ Aprili, G Okazaki, H Faber, JC Benson, S Solheim, BG Letowska, M Selivanov, E Danilova, T Snopek, I Nel, T Martin, MP Senn, M Stainsby, D Cohen, H Jones, H Blumberg, N Braun, MM Malarkey, MA Epstein, JS Menitove, JE Lipton, KS TI Haemovigilance SO VOX SANGUINIS LA English DT Article ID RESIDUAL RISK; TRANSFUSION; INFECTIONS C1 Sanquin Res & Sanquin Diagnost Serv, NL-1006 AD Amsterdam, Netherlands. Sanquin Blood Bank NW, NL-1006 AC Amsterdam, Netherlands. Sanquin Diagnost Serv, NL-1006 AC Amsterdam, Netherlands. Austrian Red Cross, Blood Donat Ctr Wien Niederosterreich & Burgenlan, A-1040 Vienna, Austria. Hosp Sirio Libanes, Blood Bank, BR-01308050 Sao Paulo, Brazil. Inst Natl Sante Publ Quebec, Montreal, PQ H2J 3G8, Canada. Gen Fac Hosp, Prague 12800, Czech Republic. Univ Copenhagen, Herlev Hosp, Dept Clin Immunol, DK-2730 Herlev, Denmark. Blood Bank, DK-2730 Herlev, Denmark. Aarhus Univ Hosp, Skejby Sygehus, Dept Clin Immunol, Reg Blood Transfus Ctr, DK-8200 Aarhus N, Denmark. Univ Hosp, Inst Transfus Med & Haemostaseol, D-35033 Marburg, Germany. Paul Ehrlich Inst, Dept Safety Med & In Vitro Diagnost, D-63225 Langen, Germany. Athens Gen Hosp George Gennimatas, Reg Blood Transfus Ctr 3, GR-11527 Athens, Greece. Natl Blood Ctr, Irish Blood Transfus Serv, Natl Haemovigilance Off, Dublin 8, Ireland. CRCC, Dipartimento Diritto Salute Reg Toscana, I-50139 Florence, Italy. Ist Super Sanita, Dipartimento Ematol Oncol & Med Mol, I-00161 Rome, Italy. Azienda Osped Verona, Dipartimento Immunoematol & Med Trasfus, I-37126 Verona, Italy. Japanese Red Cross Soc Blood Serv Headquarters, Cent Blood Inst, Dept Res & Dev, Minato Ku, Tokyo 1050011, Japan. Luxembourg Red Cross Blood Serv, Luxembourg, Luxembourg. New Zealand Blood Serv, EPSOM, Auckland, New Zealand. Rikshosp Univ Hosp, Inst Immunol, NO-0027 Oslo, Norway. Inst Hematol & Blood Transfus, PL-00957 Warsaw, Poland. Russian Res Inst Haematol & Transfusiol, St Petersburg, Russia. Dept Transfusiol Hosp, Topolcany 95501, Slovakia. S African Haemovigilance Programme, ZA-9310 Danhof, South Africa. Minst Sanidad & Consumo, Programa Estatal Hemovigliancia, Madrid 28015, Spain. Swiss Agcy Therapeut Prod, Swissmed, CH-3000 Bern, Switzerland. Manchester Blood Ctr, Manchester M13 9LL, Lancs, England. Univ Rochester, Med Ctr, Labs & Transfus Med, Blood Bank, Rochester, NY 14642 USA. US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. Community Blood Ctr Greater Kansas City, Kansas City, MO 64111 USA. AABB, Bethesda, MD 20814 USA. RP Engelfriet, CP (reprint author), Sanquin Res & Sanquin Diagnost Serv, POB 9190, NL-1006 AD Amsterdam, Netherlands. EM p.engelfriet@sanquin.nl; h.reesink@sanquin.nl; gabriela.henn@roteskreuz.at; olynthos@ihsl.com.br; snwendel@uninet.com.br; pierre.robillard@inspq.qc.ca; turek.petr@vfn.cz; tom.krusius@bts.redcross.fi; sinikka.koskinen@bts.redcross.fi; elta@herlevhosp.dk; janjorgensen@dadlnet.dk; danielle.rebibo@efs.sante.fr; lisette.hauser@efs.sante.fr; Pierrette.ZORZI@afssaps.sante.fr; Jean-Francois.LEGRAS@afssaps.sante.fr; ahmed.slimani@efs.sante.fr; Maiphuong.VOMAI@afssaps.sante.fr; Jean-Hugues.TROUVIN@afssaps.sante.fr; georges.andreu@efs.sante.fr; kretschv@mailer.uni-marburg.de; kelbr@PEI.de; cpolitis@hol.gr; emer.lawlor@ibts.ie; stefan.laspina@ibts.ie; giuliano.grazzini@simti.it; j.hassan@iss.it; giuseppe.aprili@simti.it; okazaki@bs.jrc.or.jp; transfusion@croix-rouge.lu; simon.benson@nzblood.co.nz; bjarte.solheim@rikshospitalet.no; letowska@ihit.waw.pl; haematology@atlant.ru; ivan.snopek@hospitalto.sk; teresa.nel@pathcare.co.za; mpmartin@msc.es; Marianne.senn@swissmedic.ch; dorothy.stainsby@nbs.nhs.uk; neil_blumberg@urmc.rochester.edu; epsteinj@cber.fda.gov; jem@cbckc.org; karen@aabb.org RI Grazzini, Giuliano/I-5550-2015 NR 8 TC 24 Z9 24 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0042-9007 J9 VOX SANG JI Vox Sang. PD APR PY 2006 VL 90 IS 3 BP 207 EP 241 DI 10.1111/j.1423-0410.2006.00742.x PG 35 WC Hematology SC Hematology GA 017MP UT WOS:000235698000012 ER PT J AU Gieseker, CM Serfling, SG Reimschuessel, R AF Gieseker, CM Serfling, SG Reimschuessel, R TI Formalin treatment to reduce mortality associated with Saprolegnia parasitica in rainbow trout, Oncorhynchus mykiss SO AQUACULTURE LA English DT Article DE Saprolegnia; formalin; control ID CHANNEL CATFISH; WINTER SAPROLEGNIOSIS; BROWN TROUT; SUSCEPTIBILITY; FISH AB Formalin has been used to treat fish egg fungal infections, but its ability to reduce mortality in fish with fungal infections has not been clearly demonstrated. An experimental infection was induced with abrasion, exposure, and temperature stress to evaluate the ability of formalin to reduce mortalities in rainbow trout (Oncorhynchus mykiss) infected with Saprolegnia parasitica (ATCC 22284). The trout were anesthetized and abraded with a controlled abrasion technique. Temperature stress was performed concurrently with the fungal exposure by moving the trout from an acclimation temperature (15 +/- 2 degrees C) to a higher exposure temperature (22 +/- 2 degrees C) as they were immersed in an exposure tank inoculated with S. parasitica for 4 h. After the exposure, the fish were randomly distributed into 16 experimental tanks (3 fish/tank). Four treatment doses (0, 50, 100, and 150 ppm formalin solution) were evaluated. Fish were given three treatments of 1 h duration: on day 1, 1 h after the fungal exposure, and then the morning of days 3 and 5. The infection rate was 100% for all of the four trials in the study. The average percent mortality from the four trials was 67 (0 ppm), 35 (50 ppm), 29 (100 ppm), and 40 (150 ppm). Statistical analysis of the percent mortality at days 5 and 19 showed that the 50-, 100-, and 150-ppm doses were all significantly different from the 0-ppm dose on both days. Published by Elsevier B.V. C1 US FDA, Ctr Vet Med, Res Off, Laurel, MD 20708 USA. RP Gieseker, CM (reprint author), US FDA, Ctr Vet Med, Res Off, 8401 Muirkirk Rd, Laurel, MD 20708 USA. EM charles.gieseker@fda.hhs.gov NR 21 TC 33 Z9 37 U1 0 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0044-8486 J9 AQUACULTURE JI Aquaculture PD MAR 31 PY 2006 VL 253 IS 1-4 BP 120 EP 129 DI 10.1016/j.aquaculture.2005.07.039 PG 10 WC Fisheries; Marine & Freshwater Biology SC Fisheries; Marine & Freshwater Biology GA 034BF UT WOS:000236898700015 ER PT J AU Khan, IA AF Khan, IA TI Issues related to botanicals SO LIFE SCIENCES LA English DT Article; Proceedings Paper CT Workshop on Natureceuticals, Nutraceuticals, Herbal Botanicals, and Psychoactives - Drug Discovery and Drug-Drug Interactions CY NOV 05-07, 2004 CL Baltimore, MD SP Natl Inst Drug Abuse, Amer Assoc Pharmaceut Sci DE botanicals; quality; safety and efficacy ID PERFORMANCE LIQUID-CHROMATOGRAPHY; LIGHT-SCATTERING DETECTION; DIETARY-SUPPLEMENTS; HYPERICUM-PERFORATUM; MEDICINAL-PLANTS; IDENTIFICATION; SEPARATION; PRODUCTS; LACTONES; SAPONINS AB Herbal product studies cannot be considered scientifically valid if the product tested was not authenticated and characterized in order to ensure reproducibility in the manufacturing of the product in question. Many studies refer to the use of standardized material, but in reality they are referring to chemical standardization. While chemical standardization is important, its utility is limited when the starting material is not well characterized botanically. Although the resulting studies are sound with respect to the actual product tested, adequate authentication of the product cannot be compared to other products on the market. Also, a comparison of one study to another cannot be made due to inconsistencies in the identity of the botanical matrix. The tools needed for authentication of the field plant material also depend on the plant and process involved. This could be as straightforward as botanical/morphological identification or as elaborate as genetic or chemical profiling. Authenticated raw material is the basic starting point for the development of a botanical product. However, harvesting, storing, processing and formulating methods may dramatically affect the quality and consistency of the final product by altering the desired marker components or by increasing the possibility of unwanted contaminants. Thus, validated methods to ensure quality control in manufacturing and storage are required tools for optimal efficacy and safety of the products. These controls are also critical for the evaluation of pharmacological, toxicological and clinical studies of the botanical supplements. (c) 2006 Elsevier Inc. All fights reserved. C1 Univ Mississippi, Sch Pharm, Dept Pharmacognosy, FDA Program,Natl Ctr Nat Prod Res, University, MS 38677 USA. Univ Mississippi, Sch Pharm, Dept Pharmacognosy, FDA Program,Res Inst Pharmaceut Sci, University, MS 38677 USA. RP Khan, IA (reprint author), Univ Mississippi, Sch Pharm, Dept Pharmacognosy, FDA Program,Natl Ctr Nat Prod Res, University, MS 38677 USA. EM ikhan@olemiss.edu NR 62 TC 32 Z9 33 U1 3 U2 7 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0024-3205 J9 LIFE SCI JI Life Sci. PD MAR 27 PY 2006 VL 78 IS 18 BP 2033 EP 2038 DI 10.1016/j.lfs.2005.12.019 PG 6 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 027XC UT WOS:000236448400003 PM 16487545 ER PT J AU Antonucci, J Icenogle, TB Regnault, WF Liu, DW O'Donnell, JNR Skrtic, D AF Antonucci, J. Icenogle, Tonya B. Regnault, William F. Liu, Da-Wei O'Donnell, Justin N. R. Skrtic, Drago TI Polymerization shrinkage and stress development in bioactive urethane acrylic resin composites SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 231st National Meeting of the American-Chemical-Society CY MAR 26-30, 2006 CL Atlanta, GA SP Amer Chem Soc C1 Natl Inst Stand & Technol, Div Polymer, Gaithersburg, MD 20899 USA. US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. EM joseph.antonucci@nist.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 MAR 26 PY 2006 VL 231 MA 339-POLY PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 050YE UT WOS:000238125909849 ER PT J AU Freedberg, DI Norris, SE AF Freedberg, Daron I. Norris, Scott E. TI Pucker determination in five-membered rings from residual dipolar couplings SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 231st National Meeting of the American-Chemical-Society CY MAR 26-30, 2006 CL Atlanta, GA SP Amer Chem Soc C1 US FDA, Off Vaccines Res & Review, CBER, Bethesda, MD 20892 USA. EM daron_freedberg@nih.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 MAR 26 PY 2006 VL 231 MA 2-CARB PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 050YE UT WOS:000238125900556 ER PT J AU Furness, MS AF Furness, M. Scott TI The role of chemists in the FDA drug approval process SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 231st National Meeting of the American-Chemical-Society CY MAR 26-30, 2006 CL Atlanta, GA SP Amer Chem Soc C1 US FDA, Off Gener Drugs, Rockville, MD 20855 USA. EM furnesss@cder.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 MAR 26 PY 2006 VL 231 MA 14-CINF PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 050YE UT WOS:000238125902716 ER PT J AU Lague, P Marchand, PCE Roux, B Pastor, RW AF Lague, Patrick Marchand, Pavillon C. E. Roux, Benoit Pastor, Richard W. TI Impact of the influenza hemagglutinin fusion peptide on membrane structure from molecular dynamics simulations SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 231st National Meeting of the American-Chemical-Society CY MAR 26-30, 2006 CL Atlanta, GA SP Amer Chem Soc C1 Univ Laval, Dept Biochem, Quebec City, PQ G1K 7P4, Canada. Cornell Univ, Weill Med Coll, Dept Physiol & Biophys, Ithaca, NY 14853 USA. US FDA, Biophys Lab, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. EM Patrick.Lague@rsvs.ulaval.ca NR 0 TC 0 Z9 0 U1 0 U2 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 MAR 26 PY 2006 VL 231 MA 143-PHYS PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 050YE UT WOS:000238125908258 ER PT J AU MacCuspie, RI Banerjee, IA Gummalla, S Mostowski, H Krause, P Matsui, H AF MacCuspie, Robert I. Banerjee, Ipsita A. Gummalla, Sanjay Mostowski, Howard Krause, Phil Matsui, Hiroshi TI Multiplexed peptide nanotube pathogen assays SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 231st National Meeting of the American-Chemical-Society CY MAR 26-30, 2006 CL Atlanta, GA SP Amer Chem Soc C1 CUNY Hunter Coll, Dept Chem, New York, NY 10021 USA. Fordham Univ, Dept Chem, Bronx, NY 10458 USA. CUNY Hunter Coll, Ctr Biol Evaluat & Res, Off Vaccines Res & Review, Div Viral Prod,Food & Drug Adm, New York, NY 10021 USA. CUNY Hunter Coll, Dept Chem, New York, NY 10021 USA. EM nano_rob@yahoo.com 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 MAR 26 PY 2006 VL 231 MA 5-IEC PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 050YE UT WOS:000238125904591 ER PT J AU Rogers, L Murray, D Venable, R Pastor, RW AF Rogers, Laura Murray, Diana Venable, Rick Pastor, Richard W. TI Phosphoinositide lipid models SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 231st National Meeting of the American-Chemical-Society CY MAR 26-30, 2006 CL Atlanta, GA SP Amer Chem Soc C1 Cornell Univ, Weill Med Coll, Dept Microbiol & Immunol, New York, NY 10021 USA. US FDA, Ctr Biol Evaluat & Res, Biophys Lab, Rockville, MD 20857 USA. EM lar2012@med.cornell.edu 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 MAR 26 PY 2006 VL 231 MA 411-PHYS PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 050YE UT WOS:000238125908528 ER PT J AU Rubin, S Mauldin, J Chumakov, K Vanderzanden, J Iskow, R Carbone, K AF Rubin, S Mauldin, J Chumakov, K Vanderzanden, J Iskow, R Carbone, K TI Serological and phylogenetic evidence of monotypic immune responses to different mumps virus strains SO VACCINE LA English DT Article DE mumps virus; antibody; neutralization; vaccine; efficacy; protection ID HIGHLY VACCINATED POPULATION; HYDROPHOBIC PROTEIN GENE; FIELD EVALUATION; HN PROTEIN; OUTBREAK; GENOTYPES; ANTIBODIES; FAILURE; IDENTIFICATION; SWITZERLAND AB The recent resurgence of mumps epidemics in many countries with ongoing vaccination programs along with evidence of antigenic diversity among mumps virus strains have recently challenged the assumption that mumps virus is serologically monotypic. To address this controversy, we sought to identify two mumps virus strains that would best represent different serotypes, should multiple serotypes exist, and assess the ability of human sera to neutralize both strains. The virus strains, Enders and Lo1, were selected based upon a phylogenetic analysis of the major target of neutralizing antibody, the viral hemagglutinin-neuraminidase (HN) protein, along with data reported by others indicating that (1) these viruses are antigenically distinct and (2) genotypically similar strains have been implicated in cases of reinfection. Our results show that of sera capable of neutralizing one of the virus strains, 90% could neutralize the other, although significant differences in neutralization titers were noted. Though the latter confirms the existence of inter-strain antigenic variability, the fact that few sera were unable to neutralize both virus strains argues against the presence of multiple serotypes. Of those sera incapable of co-neutralization, all but one had low neutralization titers (1:8), suggesting that individuals possessing low levels of neutralizing antibody may be at risk for breakthrough infections, thereby providing an explanation for cases of infection in previously infected or vaccinated individuals. Published by Elsevier Ltd. C1 US FDA, CBER, OVRR, DVP, Bethesda, MD 20892 USA. RP Rubin, S (reprint author), US FDA, CBER, OVRR, DVP, Bldg 29A,Room 1A-21,8800 Rockville Pike, Bethesda, MD 20892 USA. EM rubins@cber.fda.gov NR 49 TC 33 Z9 36 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 MAR 24 PY 2006 VL 24 IS 14 BP 2662 EP 2668 DI 10.1016/j.vaccine.2005.10.050 PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 025IU UT WOS:000236259900025 PM 16309801 ER PT J AU Woo, EJ Miller, NB Ball, R AF Woo, EJ Miller, NB Ball, R CA VAERS Working Grp TI Adverse events after hepatitis A B combination vaccine SO VACCINE LA English DT Article DE Twinrix((R)); hepatitis A; hepatitis B; adverse event ID REPORTING-SYSTEM VAERS; SAFETY; SURVEILLANCE AB In May 2001, the U.S. Food and Drug Administration (FDA) approved Hepatitis A Inactivated and Hepatitis B Recombinant Vaccine (HEPAB) for immunization of adults. From May 2001 to September 2003, the Vaccine Adverse Event Reporting System (VAERS) received 305 reports of adverse events after HEPAB. Many events were similar to those reported after the monovalent hepatitis A and B vaccines. Non-serious events included constitutional symptoms and local reactions. Serious events included neurologic, hepatobiliary, and dermatologic conditions, and detailed medical and epidemiological review did not suggest a clear pattern of evidence supporting a causal relationship with the vaccine, except for injection site reactions and some allergic reactions. Published by Elsevier Ltd. C1 US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Woo, EJ (reprint author), US FDA, Ctr Biol Evaluat & Res, 1401 Rockville Pike, Rockville, MD 20852 USA. EM wooj@cber.fda.gov NR 25 TC 10 Z9 10 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD MAR 24 PY 2006 VL 24 IS 14 BP 2685 EP 2691 DI 10.1016/j.vaccine.2005.10.049 PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 025IU UT WOS:000236259900028 PM 16310295 ER PT J AU Badano, A Sempau, J AF Badano, A Sempau, J TI MANTIS: combined x-ray, electron and optical Monte Carlo simulations of indirect radiation imaging systems SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID POINT-SPREAD FUNCTION; CODE PENELOPE; COLUMNAR PHOSPHORS; LEKSELL-GAMMA-KNIFE(R); SCINTILLATORS; COLLECTION; EFFICIENCY; TRANSPORT; SCREENS; BEAMS AB We describe MANTIS (Monte carlo x-rAy electroN opTical Imaging Simulation), a tool for simulating imaging systems that tracks x-rays, electrons and optical photons in arbitrary materials and complex geometries. The x-ray and electron transport and involved physics models are from the PENELOPE package, and the optical transport and corresponding physics models are from DETECT-II and include Fresnel refraction and reflection at material boundaries, bulk absorption and scattering. Complex geometries can be handled with the aid of the geometry routines included in PENELOPE. When x-rays or electrons interact and deposit energy in the scintillator, the code generates a number of optical quanta according to a user-selected model for the conversion process. The optical photons are then tracked until they reach an absorption event, which in some cases contributes to the output signal, or escape from the geometry. We demonstrate the capabilities of this new tool with respect to the statistics of the optical signal detected and to the three-dimensional point-response functions corresponding to columnar phosphor screens. C1 NIBIB, CDRH, Lab Assessment Med Imaging Syst, Rockville, MD 20857 USA. Univ Politecn Catalunya, Inst Tecn Energet, E-08028 Barcelona, Spain. RP Badano, A (reprint author), NIBIB, CDRH, Lab Assessment Med Imaging Syst, 12720 Twinbrook Pkwy,HFZ-142, Rockville, MD 20857 USA. EM aldo.badano@fda.hhs.gov; josep.sempau@upc.es RI Sempau, Josep/J-7834-2013; OI Sempau, Josep/0000-0002-2754-7685; badano, aldo/0000-0003-3712-6670 NR 37 TC 51 Z9 51 U1 0 U2 9 PU IOP PUBLISHING LTD PI BRISTOL PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD MAR 21 PY 2006 VL 51 IS 6 BP 1545 EP 1561 DI 10.1088/0031-9155/51/6/013 PG 17 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 034QA UT WOS:000236944500013 PM 16510962 ER PT J AU Shaddock, JG Dobrovolsky, VN Mittelstaedt, RA Heflich, RH Parsons, BL AF Shaddock, JG Dobrovolsky, VN Mittelstaedt, RA Heflich, RH Parsons, BL TI Frequency and types of spontaneous Hprt lymphocyte mutations in Pms2-deficient mice SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article DE Pms2; mismatch repair; mutation; Hprt ID DNA MISMATCH REPAIR; TRANSGENIC REPORTER GENE; MSH2 DEFICIENT MICE; MUTANT FREQUENCIES; T-LYMPHOCYTES; CELLS; SPECTRUM; MLH1; TRANSITIONS; INSTABILITY AB Deficiencies in DNA mismatch repair (MMR) result in predisposition to neoplasia in both rodents and humans. Pms2 is one of the several proteins involved in the eukaryotic MMR system. In order to determine the effect of Pms2-deficiency on mutation, we measured mutant frequencies in the endogenous Hprt gene of lymphocytes from male Pms2(-/-), Pms2(+/-), and Pms2(+/+) mice. Spleens were removed from mice of various ages and lymphocytes isolated from spleens were cultured to determine the frequency of 6-thioguanine-resistant mutants. Mean mutant frequencies in Pms2(-/-) mice at 6, 10, 18, and 34 weeks of age [42.6 x 10(-6) (n = 6), 38.5 x 10(-6) (n = 6), 58.2 x 10(-6) (n = 9), and 49.1 x 10(-6) (n = 5), respectively] were significantly higher than those of comparably aged Pms2(+/+) and Pms2(+/-) mice (all less than 3 x 10(-6)). Mutant clones from the mice were expanded, RNA extracted, and Hprt cDNA amplified by RT-PCR. DNA sequencing analysis of 221 mutant cDNAs from the three different Pms2 genotypes identified 182 clones with independent mutations, including five clones that contained multiple mutations. When compared to the mutational spectrum observed in Pms2(+/+) and Pms2(+/-) mice, the mutational spectrum for Pms2(-/-) mice was significantly different. The Pms2(-/-) mutational analysis indicated that loss of the Pms2 protein causes increases in the frequencies of strand-slippage-type frameshift mutations and of A:T -> G:C transitions in the Hprt gene. The absolute frequencies of A:T -> G:C transitions in MMR-deficient mice suggest increases in this mutation may be a common feature of MMR-deficient mice, not just of Pms2-deficient mice, and may be related to the cancer predisposition that results from loss of MMR function. Published by Elsevier B.V. C1 US FDA, Div Genet & Reprod Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Parsons, BL (reprint author), US FDA, Div Genet & Reprod Toxicol, Natl Ctr Toxicol Res, HFT-120,3900 NCTR Rd, Jefferson, AR 72079 USA. EM bparsons@nctr.fda.gov NR 31 TC 7 Z9 7 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0027-5107 J9 MUTAT RES-FUND MOL M JI Mutat. Res.-Fundam. Mol. Mech. Mutagen. PD MAR 20 PY 2006 VL 595 IS 1-2 BP 69 EP 79 DI 10.1016/j.mrfmmm.2005.10.007 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 022IQ UT WOS:000236049300010 PM 16336979 ER PT J AU Callahan, JH Shefcheck, KJ Williams, TL Musser, SM AF Callahan, JH Shefcheck, KJ Williams, TL Musser, SM TI Detection, confirmation, and quantification of staphylococcal enterotoxin B in food matrixes using liquid chromatography-mass spectrometry SO ANALYTICAL CHEMISTRY LA English DT Article ID LINKED IMMUNOSORBENT-ASSAY; LASER-DESORPTION IONIZATION; ELECTROSPRAY IONIZATION; COMPARATIVE PROTEOMICS; ENZYME-IMMUNOASSAY; BIOSENSOR; PROTEINS; IDENTIFICATION; TOXINS; IMMUNOSENSOR AB Although immunoassay-based methods are sensitive and widely used for measuring protein toxins in food matrixes, there is a need for methods that can directly confirm the molecular identity of the toxin in situations where immunoassay tests yield a positive result. A method has been developed that uses mass spectrometry to identify a protein toxin, staphylococcal enterotoxin B (SEB), in a model food matrix, apple juice. The approach employs ultrafiltration to remove low molecular weight components from the sample, after which the remaining high molecular weight fraction, containing the protein, is digested with trypsin. The tryptic fragments are separated from residual biopolymers and analyzed by liquid chromatography-electrospray mass spectrometry. The background is still sufficiently complex that tandem mass spectrometry (MS/MS) is used to confirm the identity of target peptides. limits of detection are 80 ng of SEB for MS and 100 ng for full scan MS/MS, using a tryptic fragment as the analytical tar-get. Lower detection limits can be obtained using selected ion monitoring and multiple reaction monitoring. The presence of SEB can be confirmed at concentrations as low as 5 parts-per-billion by increasing the size of the sample to 10 mL. The method is applicable to the detection of SEB in other water-soluble food matrixes. C1 US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Callahan, JH (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM john.callahan@cfsan.fda.gov NR 53 TC 36 Z9 37 U1 0 U2 9 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 MAR 15 PY 2006 VL 78 IS 6 BP 1789 EP 1800 DI 10.1021/ac051292v PG 12 WC Chemistry, Analytical SC Chemistry GA 025ZY UT WOS:000236307700010 PM 16536413 ER PT J AU LaPorte, T Gonidi, G Heisey-Grove, D Gadam, P Soliva, S Neves, P DeMaria, A Fico, N Trujillo, S Njapau, H Warner, CR Canas, BJ Eppley, RM Garber, EAE Stack, ME Tournas, VH Park, DL Rogers, HS Patel, M Osterloh, J Calafat, AM Fry, A Bowen, A DuBois, A AF LaPorte, T Gonidi, G Heisey-Grove, D Gadam, P Soliva, S Neves, P DeMaria, A Fico, N Trujillo, S Njapau, H Warner, CR Canas, BJ Eppley, RM Garber, EAE Stack, ME Tournas, VH Park, DL Rogers, HS Patel, M Osterloh, J Calafat, AM Fry, A Bowen, A DuBois, A TI Multiple outbreaks of gastrointestinal illness among school children associated with consumption of flour tortillas - Massachusetts, 2003-2004 (Reprinted from MMWR, vol 55, pg 8-11, 2006) SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Reprint C1 Massachusetts Dept Publ Hlth, Boston, MA 02111 USA. Joint Inst Food Safety & Appl Nutr, College Pk, MD USA. CDC, Natl Ctr Environm Hlth, Atlanta, GA 30333 USA. CDC, Natl Ctr Infect Dis, Atlanta, GA 30333 USA. RP LaPorte, T (reprint author), Massachusetts Dept Publ Hlth, Boston, MA 02111 USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAR 15 PY 2006 VL 295 IS 11 BP 1244 EP 1246 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 021GV UT WOS:000235972600009 ER PT J AU Reddy, RN Latendresse, JR Mehendale, HM AF Reddy, RN Latendresse, JR Mehendale, HM TI Colchicine antimitosis causes progression of S-(1,2-dichlorovinyl)-L-cysteine-induced injury leading to acute renal failure and death in mice SO TOXICOLOGY LA English DT Article DE blood urea nitrogen; colchicine; S-(1,2-dichlorovinyl)-L-cysteine; nephrogenic tissue repair ID REGENERATING RAT-LIVER; CELL-DEATH; HEPATOCELLULAR REGENERATION; MEDIATES PROGRESSION; CCL4 AUTOPROTECTION; CYSTEINE PROTEASES; CALPAIN INHIBITORS; PUBLIC-HEALTH; HEPATOTOXICITY; TOXICITY AB Objective of the present study was to test the importance of tissue repair in the final outcome of S-(1,2-dichlorovinyl)-L-Cysteine (DCVC)-induced nephrotoxicity using colchicine (CLC) intervention. Male Swiss Webster (SW) mice were administered a normally nonlethal dose of DCVC (30 mg/kg, i.p.) on day 0 and CLC (2 mg/kg, i.p.) at 42 and 66 h after administration of DCVC. The mice were observed for mortality and various renal injury and repair parameters were studied during a time course of 0-14 days. Administration of 30 mg DCVC/kg led to loss of renal architecture by day 1, which sustained until day 5, and regressed thereafter to reach normal architecture by day 10 resulting in 100% survival. Renal dysfunction as assessed by increases in plasma BUN and creatinine levels was concordant during this time course. Urinary volume increased significantly between days 10 and 14 with significant increases in urinary glucose concentrations on days 1-4. Calpain leakage increased from day 1 and remained so until day 5 before declining at later time points. In contrast, CLC intervention led to marked inhibition of S-phase DNA synthesis and 100% mortality by 120 It. H&E sections of kidneys revealed loss of renal architecture on day 1 which progressively worsened from day 2 to 4. Polyuria and glycosuria were evident during the first 2 and 3 days, respectively. Calpain immunohistochemistry revealed progressive leakage of calpain in the extracellular space during 2-4 days which lead to increased renal injury as evident from significant increases in calpain specific breakdown products (CSBPs) of alpha-fodrin during the same period of time. The group of mice receiving 2 mg CLC/kg alone showed a significant increase in urinary creatinine concentration on day 5. Neither the expression nor localization of aquaporin 1 was altered in any of the treatment groups. These results show that antimitotic intervention after DCVC-initiated renal injury leads to expansion and progression of that injury, which appears to be due to proteolytic destruction of neighboring cells mediated by calpain leaking out of necrosed renal tubular epithelial cells. (c) 2006 Elsevier Ireland Ltd. All rights reserved. C1 Univ Louisiana Monroe, Coll Pharm, Dept Toxicol, Monroe, LA 71209 USA. Natl Ctr Toxicol Res, Toxicol Pathol Associates, Jefferson, AR 72079 USA. RP Mehendale, HM (reprint author), Univ Louisiana Monroe, Coll Pharm, Dept Toxicol, 700 Univ Ave,Sugar Hall, Monroe, LA 71209 USA. EM mehendale@ulm.edu RI Latendresse, John/A-9215-2009 FU NIDDK NIH HHS [DK-61650] NR 44 TC 7 Z9 7 U1 0 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0300-483X J9 TOXICOLOGY JI Toxicology PD MAR 15 PY 2006 VL 220 IS 2-3 BP 147 EP 159 DI 10.1016/j.tox.2005.12.012 PG 13 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 024KA UT WOS:000236192700007 PM 16457931 ER PT J AU Sawant, SP Dnyanmote, AV Warbritton, A Latendresse, JR Mehendale, HM AF Sawant, SP Dnyanmote, AV Warbritton, A Latendresse, JR Mehendale, HM TI Type 2 diabetic rats are sensitive to thioacetamide hepatotoxicity SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE CCl4; liver injury; thioacetamide; tissue repair; type 2 diabetes ID LIVER-TISSUE REPAIR; CARBON-TETRACHLORIDE; MODEL HEPATOTOXICANTS; MEDIATES PROGRESSION; HEPATIC-FAILURE; PROTEIN-KINASE; DNA-SYNTHESIS; HIGH GLUCOSE; CELL-CYCLE; S-OXIDE AB Previously, we reported high hepatotoxic sensitivity of type 2 diabetic (DB) rats to three dissimilar hepatotoxicants. Additional work revealed that a normally nonlethal close of CCl4 was lethal in DB rats due to inhibited compensatory tissue repair. The present study was conducted to investigate the importance of compensatory tissue repair in determining the final outcome of hepatotoxicity in diabetes, using another structurally and mechanistically dissimilar hepatotoxicant, thioacetamide (TA), to initiate liver injury. A normally nonlethal dose of TA (300 mg/kg, ip), caused 100% mortality in DB rats. Time Course studies (0 to 96 11) showed that in the non-DB rats, liver injury initiated by TA as assessed by plasma alanine or aspartate aminotransferase and hepatic necrosis progressed up to 48 h and regressed to normal at 96 h resulting in 100% survival. In the DB rats, liver injury rapidly progressed resulting in progressively deteriorating liver due to rapidly expanding injury, hepatic failure, and 100% mortality between 24 and 48 h post-TA treatment. Covalent binding of C-14-TA-derived radiolabel to liver tissue did not differ from that observed in the non-DB rats, indicating similar bioactivation-based initiation of hepatotoxicity. S-phase DNA synthesis measured by [H-3]-thymidine incorporation, and advancement of cells through the cell division cycle measured by PCNA immunohistochemistry, were substantially inhibited in the DB rats compared to the non-DB rats challenged with TA. Thus, inhibited cell division and compromised tissue repair in the DB rats resulted in progressive expansion of liver injury culminating in mortality. In conclusion, it appears that similar to type I diabetes, type 2 diabetes also increases sensitivity to dissimilar hepatotoxicants due to inhibited compensatory tissue repair, suggesting that sensitivity to hepatotoxicity in diabetes occurs in the absence as well as presence of insulin. (c) 2005 Elsevier Inc. All rights reserved. C1 NE Louisiana Univ, Coll Pharm, Dept Toxicol, Monroe, LA 71209 USA. Natl Ctr Toxicol Res, Toxicol Pathol Associates, Jefferson, AR 72079 USA. RP Mehendale, HM (reprint author), NE Louisiana Univ, Coll Pharm, Dept Toxicol, 700 Univ Ave,Sugar Hall 306, Monroe, LA 71209 USA. EM mehendale@ulm.edu RI Latendresse, John/A-9215-2009 NR 61 TC 12 Z9 14 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD MAR 15 PY 2006 VL 211 IS 3 BP 221 EP 232 DI 10.1016/j.taap.2005.07.019 PG 12 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 029BM UT WOS:000236532900005 PM 16153671 ER PT J AU Donthamsetty, S Bhave, VS Mitra, M Mehendale, H Latendresse, J AF Donthamsetty, S Bhave, VS Mitra, M Mehendale, H Latendresse, J TI Nonalcoholic steatohepatitis (NASH): Mechanism of hepatotoxic sensitivity SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 Univ Louisiana, Coll Pharm, Monroe, LA 71209 USA. NCTR, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2006 VL 20 IS 5 BP A1380 EP A1380 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 026GA UT WOS:000236326205073 ER PT J AU Donthamsetty, S Bhave, VS Mitra, M Mehendale, H Latendresse, J AF Donthamsetty, S Bhave, VS Mitra, M Mehendale, H Latendresse, J TI Nonalcoholic steatohepatitis (NASH): Mechanism of hepatotoxic sensitivity SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 Louisiana Univ, Coll Pharm, Monroe, LA 71209 USA. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2006 VL 20 IS 5 BP A1136 EP A1136 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 026GA UT WOS:000236326202439 ER PT J AU Satchithanandam, S Markus, G Grundel, E White, KD Rader, JI AF Satchithanandam, S Markus, G Grundel, E White, KD Rader, JI TI Concentrations of the alkaloids magnoflorine, N-methylcystine and baptifoline in samples of blue cohosh SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Annual Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Expt Therapeut C1 US FDA, College Pk, MD 20740 USA. Univ Innsbruck, A-6020 Innsbruck, Austria. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2006 VL 20 IS 5 BP A1020 EP A1020 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 026GA UT WOS:000236326201438 ER PT J AU Sundaresan, PR Grundel, E White, KD Mazzola, E Rader, JI AF Sundaresan, PR Grundel, E White, KD Mazzola, E Rader, JI TI Evidence for the presence of selected diterpenoids from the methanol extracts of authenticated T. chamaedrys and T. canadense by LC/MS and NMR SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 CFSAN, FDA, Div Res Appl Tech, ONPLDS, College Pk, MD 20740 USA. CFSAN, FDA, Div Gen Serv Supp, OSAS, College Pk, MD 20740 USA. Univ Maryland, Dept Chem & Biochem, College Pk, MD 20742 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2006 VL 20 IS 5 BP A1020 EP A1020 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 026GA UT WOS:000236326201439 ER PT J AU Whittaker, P Day, JB Curtis, SK Fry, FS AF Whittaker, P Day, JB Curtis, SK Fry, FS TI Rapid identification of Francisella tularensis using fatty acid profiles SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2006 VL 20 IS 5 BP A1299 EP A1299 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 026GA UT WOS:000236326204199 ER PT J AU Lindenbach, BD Meuleman, P Ploss, A Vanwolleghem, T Syder, AJ McKeating, JA Lanford, RE Feinstone, SM Major, ME Leroux-Roels, G Rice, CM AF Lindenbach, BD Meuleman, P Ploss, A Vanwolleghem, T Syder, AJ McKeating, JA Lanford, RE Feinstone, SM Major, ME Leroux-Roels, G Rice, CM TI Cell culture-grown hepatitis C virus is infectious in vivo and can be recultured in vitro SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE animal model; pathogenesis; reverse genetics; viral hepatitis ID EFFICIENT REPLICATION; CDNA-CLONE; CHIMPANZEES; DENSITY; GENOME; RNA; ENHANCEMENT; LIPOPROTEIN; RESPONSES; DISEASE AB Hepatitis C virus (HCV) is a major cause of chronic liver disease, frequently progressing to cirrhosis and increased risk of hepatocellular carcinoma. Current therapies are inadequate and progress in the field has been hampered by the lack of efficient HCV culture systems. By using a recently described HCV genotype 2a infectious clone that replicates and produces infectious virus in cell culture (HCVcc), we report here that HCVcc strain FL-J6/JFH can establish long-term infections in chimpanzees and in mice containing human liver grafts. Importantly, virus recovered from these animals was highly infectious in cell culture, demonstrating efficient ex vivo culture of HCV. The improved infectivity of animal-derived HCV correlated with virions of a lower average buoyant density than HCVcc, suggesting that physical association with low-density factors influences viral infectivity. These results greatly extend the utility of the HCVcc genetic system to allow the complete in vitro and in vivo dissection of the HCV life cycle. C1 Rockefeller Univ, Ctr Study Hepatitis C, Lab Virol & Infect Dis, New York, NY 10021 USA. Univ Ghent, Ctr Vaccinol, B-9000 Ghent, Belgium. Ghent Hosp, B-9000 Ghent, Belgium. Univ Birmingham, Sch Med, Biomed Res Inst, Div Immun & Infect, Birmingham B15 2TT, W Midlands, England. SW Natl Primate Res Ctr, Dept Virol & Immunol, San Antonio, TX 78245 USA. SW Fdn Biomed Res, San Antonio, TX 78245 USA. US FDA, Lab Hepatitis Viruses, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Rice, CM (reprint author), Rockefeller Univ, Ctr Study Hepatitis C, Lab Virol & Infect Dis, 1230 York Ave, New York, NY 10021 USA. EM ricec@mail.rockefeller.edu RI Meuleman, Philip/H-2899-2013; OI Meuleman, Philip/0000-0001-6821-234X; McKeating, Jane/0000-0002-7229-5886 FU Medical Research Council [G0400802, G0801976]; NCI NIH HHS [CA10702, CA57973, CA85883, R01 CA057973, R01 CA085883]; NCRR NIH HHS [P51 RR013986, RR13986]; NIAID NIH HHS [N01AI40034, N01AI40035]; NIDDK NIH HHS [DK70497, F32 DK070497] NR 27 TC 299 Z9 308 U1 0 U2 16 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 MAR 7 PY 2006 VL 103 IS 10 BP 3805 EP 3809 DI 10.1073/pnas.0511218103 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 024VU UT WOS:000236225300055 PM 16484368 ER PT J AU Andrews, KW Schweitzer, A Zhao, C Holden, J Roseland, J Brandt, M Spease, C Woo, J Dwyer, J Picciano, M Saldanha, LG Fisher, K Betz, JM Yetley, E AF Andrews, KW Schweitzer, A Zhao, C Holden, J Roseland, J Brandt, M Spease, C Woo, J Dwyer, J Picciano, M Saldanha, LG Fisher, K Betz, JM Yetley, E TI Caffeine, theobromine and theophylline content of commonly purchased weight loss and sports performance enhancing dietary supplements SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 USDA, Nutrient Data Lab, Beltsville, MD 20705 USA. FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 6 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 6 PY 2006 VL 20 IS 4 BP A180 EP A180 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 024OW UT WOS:000236206501291 ER PT J AU Axume, J Smith, S Pogribny, I Moriarty, D Caudill, MA AF Axume, J Smith, S Pogribny, I Moriarty, D Caudill, MA TI The methylenetetrahydrofolate reductase (MTHFR) 677 C > T polymorphism and folate interact to influence global leukocyte DNA methylation in young Mexican American women. SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 Calif State Polytech Univ Pomona, Pomona, CA 91768 USA. City Hope Natl Med Ctr, Duarte, CA 91010 USA. Beckman Res Inst, Duarte, CA 91010 USA. Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 6 PY 2006 VL 20 IS 4 BP A601 EP A601 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 024OW UT WOS:000236206505065 ER PT J AU Bhattacharjee, A Xu, B Frank, D Feldman, G Cathcart, M AF Bhattacharjee, A Xu, B Frank, D Feldman, G Cathcart, M TI Monocyte 15-lipoxygenase expression is regulated by a novel cytosolic signaling complex with PKC delta and tyrosine phosphorylated Stat3 SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 Cleveland Clin Fdn, Lerner Res Inst, Cleveland, OH 44195 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. US FDA, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 6 PY 2006 VL 20 IS 4 BP A635 EP A635 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 024OW UT WOS:000236206505218 ER PT J AU Herman, E Knapton, A Miller, TJ Espandiari, P Anderson, R Moore, S Hanig, J AF Herman, E Knapton, A Miller, TJ Espandiari, P Anderson, R Moore, S Hanig, J TI Examination of the female Sprague-Dawley rat as a model of rosiglitazone (RSG)-induced toxicity. SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 US FDA, DAPR, Silver Spring, MD 20993 USA. Ciphergen Biosyst Inc, Fremont, CA 94555 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 6 PY 2006 VL 20 IS 4 BP A234 EP A234 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 024OW UT WOS:000236206502025 ER PT J AU Mitra, MS Shashikiran, D Latendresse, J Mehendale, HM AF Mitra, MS Shashikiran, D Latendresse, J Mehendale, HM TI Upregulated cardioprotective mechanisms protect diet restricted rats against doxorubicin-induced cardiotoxicity SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 NE Louisiana Univ, Monroe, LA 71209 USA. NCTR, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 6 PY 2006 VL 20 IS 4 BP A232 EP A232 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 024OW UT WOS:000236206502017 ER PT J AU Murgai, M Mayda, M Rios, M Hammamieh, R Jett, M AF Murgai, M Mayda, M Rios, M Hammamieh, R Jett, M TI Gene expression analysis of the West Nile virus and the dengue serotypes SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 Walter Reed Army Inst Res, Silver Spring, MD 20910 USA. US FDA, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 6 PY 2006 VL 20 IS 4 BP A62 EP A62 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 024OW UT WOS:000236206500297 ER PT J AU Atrasheuskaya, AV Neverov, AA Rubin, S Ignatyev, GM AF Atrasheuskaya, AV Neverov, AA Rubin, S Ignatyev, GM TI Horizontal transmission of the Leningrad-3 live attenuated mumps vaccine virus SO VACCINE LA English DT Article DE mumps vaccine virus transmission ID SECONDARY IMMUNE-RESPONSES; MEASLES-VIRUS; ASEPTIC-MENINGITIS; OUTBREAK; CHILDREN; EPIDEMIC; FAILURE; RUBELLA; THROAT AB Here we describe symptomatic transmission of the Leningrad-3 mumps vaccine virus from healthy vaccinees to previously vaccinated contacts. Throat swab and serum samples were taken from six symptomatic mumps cases and from 13 family contacts. Assessment of serum IgG and IgM anti-mumps virus antibodies and IgG avidity testing was performed using commercial test kits. Sera neutralizing antibodies were measured by plaque reduction neutralization assay using the L-3 vaccine mumps virus as the target. All six of the symptomatic mumps cases and three contact subjects tested positive for mumps by RT-PCR. The genomic sequences tested (F, SH and HN genes) of all nine of these samples were identical to the L-3 mumps vaccine strain. All 13 contacts were asymptomatic; however clear serological evidence of mumps infection was found in some of them. The likely epidemiological source of the transmitted L-3 mumps virus was children who were recently vaccinated at the schools attended by the six symptomatic mumps patients described here. The L-3 mumps vaccine virus can be shed and transmitted horizontally, even to subjects previously vaccinated with the same virus. (c) 2005 Elsevier Ltd. All rights reserved. C1 State Res Ctr Virol & Biotechnol Vector, Inst Mol Biol, Lab Immunol Safety, Koltsov 630559, Novosibirsk, Russia. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. RP Atrasheuskaya, AV (reprint author), State Res Ctr Virol & Biotechnol Vector, Inst Mol Biol, Lab Immunol Safety, Koltsov 630559, Novosibirsk, Russia. EM ignat@vector.nsc.ru NR 33 TC 17 Z9 23 U1 1 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD MAR 6 PY 2006 VL 24 IS 10 BP 1530 EP 1536 DI 10.1016/j.vaccine.2005.10.009 PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 025IQ UT WOS:000236259500006 PM 16266774 ER PT J AU Stone, M Racoosin, JA Laughren, T AF Stone, M Racoosin, JA Laughren, T TI Conventional vs. atypical antipsychotic medications SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 US FDA, Silver Spring, MD 20993 USA. RP Stone, M (reprint author), US FDA, Silver Spring, MD 20993 USA. NR 0 TC 1 Z9 1 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 MAR 2 PY 2006 VL 354 IS 9 BP 973 EP 973 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 017FN UT WOS:000235679600016 ER PT J AU Gallas, BD AF Gallas, BD TI One-shot estimate of MRMC variance: AUC SO ACADEMIC RADIOLOGY LA English DT Article DE MRMC; ROC; AUC; variance; reader variability; case variability; jackknife; ANOVA; bootstrap ID OPERATING CHARACTERISTIC CURVES; MAXIMUM-LIKELIHOOD ESTIMATION; SIGNAL-DETECTION THEORY; DORFMAN-BERBAUM-METZ; NONPARAMETRIC APPROACH; ROC ANALYSIS; MULTIREADER; AREA; VARIABILITY; VALIDATION AB Rationale and Objectives. One Popular study design for estimating the area under the receiver operating characteristic curve (AUC) is the one in which a set of readers reads a set of cases: a fully crossed design in which every reader reads every case. The variability of the subsequent reader-averaged AUC has two sources: the multiple readers and the multiple cases (MRMC). In this article, we present a nonparametric estimate for the variance of the reader-averaged AUC that is unbiased and does not use resampling tools. Materials and Methods. The one-shot estimate is based on the MRMC variance derived by the mechanistic approach of Barrett et al. (2005), as well as the nonparametric variance of a single-reader AUC derived in the literature on U statistics. We investigate the bias and variance properties of the one-shot estimate through a set of Monte Carlo simulations with simulated model observers and images. The different simulation configurations vary numbers of readers and cases, amounts of image noise and internal noise, as well as how the readers are constructed. We compare the one-shot estimate to a method that uses the jackknife resampling technique with an analysis of variance model at its foundation (Dorfman et al. 1992). The name one-shot highlights that resampling is not used. Results. The one-shot and jackknife estimators behave similarly, with the one-shot being marginally more efficient when the number of cases is small. Conclusions. We have derived a one-shot estimate of the MRMC variance of AUC that is based on a probabilistic foundation with limited assumptions, is unbiased, and compares favorably to an established estimate. C1 US FDA, CDRH, NIBIB CDRH Lab Assessment Med Imaging Syst, Rockville, MD 20852 USA. RP Gallas, BD (reprint author), US FDA, CDRH, NIBIB CDRH Lab Assessment Med Imaging Syst, Bldg 1,HFZ-140,12720 Twinbrook Pkwy,Rm 158, Rockville, MD 20852 USA. EM brandon.gallas@fda.hhs.gov OI Gallas, Brandon/0000-0001-7332-1620 NR 34 TC 68 Z9 68 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 MAR PY 2006 VL 13 IS 3 BP 353 EP 362 DI 10.1016/j.acra.2005.11.030 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 020QO UT WOS:000235925100011 PM 16488848 ER PT J AU Gao, LF Wen, LJ Yu, H Zhang, L Meng, Y Shao, YT Xu, DQ Zhao, XJ AF Gao, LF Wen, LJ Yu, H Zhang, L Meng, Y Shao, YT Xu, DQ Zhao, XJ TI Knockdown of Stat3 expression using RNAi in hibits growth of laryngeal tumors in vivo SO ACTA PHARMACOLOGICA SINICA LA English DT Article DE RNA interference; Stat3 protein; laryngeal neoplasms; nude mice ID PROSTATE-CANCER CELLS; SIGNALING INDUCES APOPTOSIS; BREAST-CARCINOMA CELLS; CONSTITUTIVE ACTIVATION; SUPPRESSES GROWTH; NECK-CANCER; INHIBITION; LEUKEMIA; PATHWAY; HEAD AB Aim: To study the effect of pSilencer 1.0-U6-siRNA-stat3 on the growth of human laryngeal tumors in nude mice. Methods: Hep2 cells were transplanted into nude mice, then at the time of tumor formation, growth rates were observed. After the tumor formed, pSilencer 1.0-U6-siRNA-stat3 was injected. Tumor volumes were calculated, and growth curves were plotted. Representative histological sections were taken from mice bearing transplantation tumors in both treated and control groups, and stat3, pTyr- stat3, Bcl-2, cyclin D1, and survivin expression were detected by Western blotting. survivin mRNA levels were detected by Northern blotting, hematoxylin and eosin staining and terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick end-labeling (TUNEL) assay to confirm the apoptosis of tumors. Results: In nude mice, pSilencer 1.0-U6-siRNA-stat3 significantly suppressed the growth of tumors compared with controls (P < 0.01). In suppressed stat3 expression, and downregulated BcL2, cyclin D1, and survivin expression within the tumor. This significantly induced apoptosis of the tumors. Conclusion: pSilencer 1.0-U6-siRNA-stat3 was able to inhibit the growth of transplanted human laryngeal tumors in nude mice and induce apoptosis. C1 Jilin Univ, Basic Sch Med, Dept Pathophysiol, Changchun 130021, Peoples R China. Jilin Univ, Hosp 2, Dept ENT, Changchun 130012, Peoples R China. Food & Drug Adm, Ctr Biol Evaluat & Res, Lab Enter & Sexually Transmitted Dis, Bethesda, MD USA. RP Zhao, XJ (reprint author), Jilin Univ, Basic Sch Med, Dept Pathophysiol, Changchun 130021, Peoples R China. EM pro_2@jlu.edu.cn NR 31 TC 27 Z9 33 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1671-4083 J9 ACTA PHARMACOL SIN JI Acta Pharmacol. Sin. PD MAR PY 2006 VL 27 IS 3 BP 347 EP 352 DI 10.1111/j.1745-7254.2006.00277.x PG 6 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 015YK UT WOS:000235587300013 PM 16490172 ER PT J AU Wysowski, DK Nourjah, P AF Wysowski, DK Nourjah, P TI Deaths attributed to X-ray contrast media on US death certificates SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE anaphylaxis; contrast media; death certificate; drug reactions; imaging report; mortality; renal failure ID ANGIOGRAPHY; AGENTS AB OBJECTIVE. The objectives of our study were to determine the number, rate, and types of deaths attributed to specific X-ray contrast media on the basis of U.S. death certificates and to attempt to assess the comparative safety of commonly used diagnostic X-ray contrast agents using death certificate information. CONCLUSION. From 1999 through 2001, deaths attributed to the International Classification of Diseases (ICD) code for contrast media occurred at the rate of 1.1-1.2 per million contrast media packages distributed. An analysis of 1999 death certificates indicated that most deaths attributed to contrast media predictably were associated with renal failure or nephropathy and anaphylaxis or allergic reactions. Risk assessment of the comparative safety of classes or agents was limited by lack of specific contrast media names. Names of administered contrast agents should be recorded in patients' medical records and communicated to primary care physicians and certifiers of death in the event of serious sequelae after an identified recent radiologic procedure. C1 US FDA, Div Drug Risk Evaluat, Silver Spring, MD 20993 USA. RP Wysowski, DK (reprint author), US FDA, Div Drug Risk Evaluat, HFD-433,White Oak,Bldg 22,Room 3424,10903 New Ham, Silver Spring, MD 20993 USA. NR 12 TC 16 Z9 19 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAR PY 2006 VL 186 IS 3 BP 613 EP 615 DI 10.2214/AJR.04.1790 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 016JN UT WOS:000235616600004 PM 16498085 ER PT J AU Hammad, TA Laughren, T Racoosin, J AF Hammad, TA Laughren, T Racoosin, J TI Suicidality in pediatric patients treated with antidepressant drugs SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID FLUOXETINE TREATMENT; DEPRESSION; CHILDREN; RISK; ADOLESCENTS; EMERGENCE; PLACEBO; TRIALS AB Context: There has been concern that widely used antidepressant agents might be associated with an increased risk of suicidal ideation and behavior (suicidality) in pediatric patients. Objective: To investigate the relationship between antidepressant drugs and suicidality in pediatric patients participating in randomized, placebo-controlled trials. Data Sources: Data were derived from 23 trials conducted in 9 drug company-supported programs evaluating the effectiveness of antidepressants in pediatric patients and 1 multicenter trial (the Treatment for Adolescents With Depression Study) that evaluated fluoxetine hydrochloride. Study Selection: All placebo-controlled trials submitted to the Food and Drug Administration were eligible for inclusion. Evaluable data were derived from 4582 patients in 24 trials. Sixteen trials studied patients with major depressive disorder, and the remaining 8 studied obsessive-compulsive disorder (n=4), generalized anxiety disorder (n=2), attention-deficit/hyperactivity disorder (n=1), and social anxiety disorder (n=1). Only 20 trials were included in the risk ratio analysis of suicidality because 4 trials had no events in the drug or placebo groups. Data Extraction: Individual patient data were available for all the trials. Data Synthesis: A meta-analysis was conducted to obtain overall suicidality risk estimates for each drug individually, for selective serotonin reuptake inhibitors in depression trials as a group, and for all evaluable trials combined. There were no completed suicides in any of these trials. The multicenter trial was the only individual trial to show a statistically significant risk ratio (4.62; 95% confidence interval [CI], 1.02-20.92). The overall risk ratio for selective serotonin reuptake inhibitors in depression trials was 1.66 (95% CI, 1.02-2.68) and for all drugs across all indications was 1.95 (95% CI, 1.28-2.98). The overall risk difference for all drugs across all indications was 0.02 (95% CI, 0.01-0.03). Conclusion: Use of antidepressant drugs in pediatric patients is associated with a modestly increased risk of suicidality. C1 US FDA, Ctr Drug Evaluat & Res, Div Neuropharmacol Drug Prod, Rockville, MD 20857 USA. RP Laughren, T (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Neuropharmacol Drug Prod, HFD-120,5600 Fishers Lane, Rockville, MD 20857 USA. EM laughren@cder.fda.gov NR 18 TC 496 Z9 502 U1 8 U2 51 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD MAR PY 2006 VL 63 IS 3 BP 332 EP 339 DI 10.1001/archpsyc.63.3.332 PG 8 WC Psychiatry SC Psychiatry GA 021GH UT WOS:000235971200013 PM 16520440 ER PT J AU Pavletic, SZ Martin, P Lee, SJ Mitchell, S Jacobsohn, D Cowen, EW Turner, ML Akpek, G Gilman, A McDonald, G Schubert, M Berger, A Bross, P Chien, JW Couriel, D Dunn, JP Fall-Dickson, J Farrell, A Flowers, MED Greinix, H Hirschfeld, S Gerber, L Kim, S Knobler, RT Lachenbruch, PA Miller, FW Mittleman, B Papadopoulos, E Parsons, SK Przepiorka, D Robinson, M Ward, M Reeve, B Rider, LG Shulman, H Schultz, KR Weisdorf, D Vogelsang, GB AF Pavletic, SZ Martin, P Lee, SJ Mitchell, S Jacobsohn, D Cowen, EW Turner, ML Akpek, G Gilman, A McDonald, G Schubert, M Berger, A Bross, P Chien, JW Couriel, D Dunn, JP Fall-Dickson, J Farrell, A Flowers, MED Greinix, H Hirschfeld, S Gerber, L Kim, S Knobler, RT Lachenbruch, PA Miller, FW Mittleman, B Papadopoulos, E Parsons, SK Przepiorka, D Robinson, M Ward, M Reeve, B Rider, LG Shulman, H Schultz, KR Weisdorf, D Vogelsang, GB TI Measuring therapeutic response in chronic graft-versus-host disease: National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: IV. Response Criteria Working Group report SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Review DE chronic graft-versus-host disease; allogencic cell transplantation; response criteria; consensus ID BONE-MARROW-TRANSPLANTATION; STEM-CELL TRANSPLANTATION; SLEEP QUALITY INDEX; CANCER-PATIENTS; PINCH STRENGTH; PSYCHOMETRIC EVALUATION; RHEUMATOID-ARTHRITIS; SYMPTOM-INVENTORY; RANDOMIZED-TRIAL; ACTIVITIES SCALE AB The lack of standardized criteria for quantitative measurement of therapeutic response in clinical trials poses a major obstacle for the development of new agents in chronic g-raft-versus-host disease (GVHD). This consensus document was developed to address several objectives for response criteria to be used in chronic GVHD-related clinical trials. The proposed measures should be practical for use both by transplantation and nontransplantation medical providers, adaptable for use in adults and in children, and focused on the most important chronic GVHD manifestations. The measures should also give preference to quantitative, rather than semiquantitative, measures; capture information regarding signs, symptoms, and function separately from each other; and use validated scales whenever possible to demonstrate improved patient outcomes and meet requirements for regulatory approval of novel agents. Based on these criteria, we propose a set of measures to be considered for use in clinical trials, and forms for data collection are provided (http://www.asbmt.org/ GvHDForms). Measures should be made at 3-month intervals and whenever major changes are made in treatment. Provisional definitions of complete response, partial response, and progression are proposed for each organ and for overall outcomes. The proposed response criteria are based on current expert consensus opinion and are intended to improve consistency in the conduct and reporting of chronic GVHD trials, but their use remains to be demonstrated in practice. (C) 2006 American Society for Blood and Marrow Transplantation. C1 NCI, Graft Versus Host & Autoimmun Unit, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA. Univ Washington, Sch Med, Fred Hutchinson Canc Res Ctr, Seattle, WA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Northwestern Univ, Childrens Mem Hosp, Sch Med, Chicago, IL 60614 USA. Univ Maryland, Sch Med, Baltimore, MD 21201 USA. Univ N Carolina, Sch Med, Chapel Hill, NC USA. NIH, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. US FDA, Rockville, MD 20857 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Natl Inst Nursing Res, NIH, Bethesda, MD USA. Med Univ Vienna, Vienna, Austria. NIEHS, NIH, Bethesda, MD USA. NIAMSD, Bethesda, MD 20892 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Tufts New England Med Ctr, Boston, MA USA. Univ Tennessee, Memphis, TN USA. NEI, NIH, Bethesda, MD 20892 USA. Univ British Columbia, British Columbia Childrens Hosp, Vancouver, BC V5Z 1M9, Canada. Univ Minnesota, Minneapolis, MN USA. RP Pavletic, SZ (reprint author), NCI, Graft Versus Host & Autoimmun Unit, Expt Transplantat & Immunol Branch, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM pavletis@mail.nih.gov RI Hirschfeld, Steven/E-2987-2016; OI Hirschfeld, Steven/0000-0003-0627-7249; Rider, Lisa/0000-0002-6912-2458; Miller, Frederick/0000-0003-2831-9593 FU Intramural NIH HHS; NCI NIH HHS [R01 CA118953] NR 66 TC 233 Z9 245 U1 2 U2 5 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 MAR PY 2006 VL 12 IS 3 BP 252 EP 266 DI 10.1016/j.bbmt.2006.01.008 PG 15 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 024JF UT WOS:000236190600002 PM 16503494 ER PT J AU Shrake, A Frazier, D Schwarz, FP AF Shrake, A Frazier, D Schwarz, FP TI Thermal stabilization of human albumin by medium- and short-chain n-alkyl fatty acid anions SO BIOPOLYMERS LA English DT Article DE albumin; human albumin; differential scanning calorimetry; albumin thermal stability; albumin unfolding; albumin denaturation ID HUMAN-SERUM-ALBUMIN; HUMAN PLASMA ALBUMIN; PROTEIN DENATURATION; PHYSICAL CHEMISTRY; BINDING; LIGAND; RELAXATION; STABILITY; CONSTANTS; LENGTH AB A comprehensive study of the thermal stabilization of defatted human albumin monomer by n-alkyl fatty acid anions (FAAs), formate through n-decanoate, was carried out by differential scanning calorimetry (DSC). The concentration of each ligand affording maximum thermal stabilization was determined; n-nonanoate provides the greatest stabilization but is only marginally better than n-octanoate and n-decanoate. The use of reversible thermodynamics and a two-state denaturation model for albumin has been validated. Standard free energies of binding, calculated from increases in free energy of denaturation, for n-butanoate and longer FAAs, are linear with n-alkyl chain length whereas those for formate, acetate, and n-propionate deviate from linearity; those for acetate and n-propionate are even greater than that of n-butanoate, thereby suggesting, in addition to the common class of sites available to all such ligands, the presence of an additional class of lower affinity binding sites available only to these shortest ligands. Competition experiments involving acetate and n-octanoate and involving n-pentanoate and n-octanoate confirmed the binding of acetate to lower affinity sites unavailable to n-octanoate and n-pentanoate. Furthermore, an equation is provided, allowing computation of the transition temperature as a function of the free energy for any reversible process causing a change in thermal stability of a protein undergoing reversible, two-state denaturation. With this equation, modeling the competition experiments by using the binding parameters determined by DSC provides additional support for the class of lower affinity sites, which play a significant role in thermal stabilization of albumin at higher concentrations of these shortest FAAs. (c) 2005 Wiley Periodicals, Inc. C1 US FDA, Div Hematol, Off Blood Res & Review, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. NIST, Ctr Adv Res Biotechnol, Rockville, MD 20850 USA. RP Shrake, A (reprint author), US FDA, Div Hematol, Off Blood Res & Review, Ctr Biol Evaluat & Res, 29 Lincoln Dr, Bethesda, MD 20892 USA. EM strake@cber.fda.gov NR 37 TC 14 Z9 14 U1 4 U2 10 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0006-3525 J9 BIOPOLYMERS JI Biopolymers PD MAR PY 2006 VL 81 IS 4 BP 235 EP 248 DI 10.1002/bip.20406 PG 14 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 046IH UT WOS:000237804400001 PM 16273515 ER PT J AU Sun, HH Collins, JM Mangner, TJ Muzik, O Shields, AF AF Sun, HH Collins, JM Mangner, TJ Muzik, O Shields, AF TI Imaging the pharmacokinetics of [F-18]FAU in patients with tumors: PET studies SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE FAU; PET; thymidine kinase; proliferation ID POSITRON-EMISSION-TOMOGRAPHY; THYMIDYLATE SYNTHASE INHIBITORS; CANCER CELL-LINES; DIHYDROPYRIMIDINE DEHYDROGENASE; PROTEIN EXPRESSION; LIVER METASTASES; CARCINOMA; 5-FLUOROURACIL; MICE; XENOGRAFTS AB Purpose: FAU (1-(2'-deoxy-2'-fluoro-beta- D- arabinofuranosyl) uracil) can be phosphorylated by thymidine kinase, methylated by thymidylate synthase, followed by DNA incorporation and thus functions as a DNA synthesis inhibitor. This first-in-human study of [F-18] FAU was conducted in cancer patients to determine its suitability for imaging and also to understand its pharmacokinetics as a potential antineoplastic agent. Methods: Six patients with colorectal (n=3) or breast cancer (n= 3) were imaged with [F-18] FAU. Serial blood and urine samples were analyzed using HPLC to determine the clearance and metabolites. Results: Imaging showed that [F-18] FAU was concentrated in breast tumors and a lymph node metastasis (tumor-to-normal breast tissue ratio 3.7-4.7). FAU retention in breast tumors was significantly higher than in normal breast tissues at 60 min and retained in tumor over 2.5 h postinjection. FAU was not retained above background in colorectal tumors. Increased activity was seen in the kidney and urinary bladder due to excretion. Decreased activity was seen in the bone marrow with a mean SUV 0.6. Over 95% of activity in the blood and urine was present as intact [F-18] FAU at the end of the study. Conclusions: Increased [F-18] FAU retention was shown in the breast tumors but not in colorectal tumors. The increased retention of FAU in the breast compared to bone marrow indicates that FAU may be useful as an unlabeled antineoplastic agent. The low retention in the marrow indicates that unlabeled FAU might lead to little marrow toxicity; however, the images were not of high contrast to consider FAU for diagnostic clinical imaging. C1 Wayne State Univ, Karmanos Canc Inst, Detroit, MI 48201 USA. Wayne State Univ, Dept Med, Detroit, MI 48202 USA. Wayne State Univ, Dept Pediat, Detroit, MI 48202 USA. Wayne State Univ, Dept Radiol, Detroit, MI USA. US FDA, Rockville, MD 20857 USA. RP Shields, AF (reprint author), Wayne State Univ, Karmanos Canc Inst, 4100 John R St,4HWCRC, Detroit, MI 48201 USA. EM shieldsA@karmanos.org FU NCI NIH HHS [CA 39566, CA 82645] NR 29 TC 11 Z9 11 U1 0 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD MAR PY 2006 VL 57 IS 3 BP 343 EP 348 DI 10.1007/s00280-005-0037-0 PG 6 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 996US UT WOS:000234201200010 PM 16001172 ER PT J AU Lyn-Cook, BD Yan-Sanders, Y Moore, S Taylor, S Word, B Hammons, GJ AF Lyn-Cook, BD Yan-Sanders, Y Moore, S Taylor, S Word, B Hammons, GJ TI Increased levels of NAD(P)H: quinone oxidoreductase 1 (NQO1) in pancreatic tissues from smokers and pancreatic adenocarcinomas: A potential biomarker of early damage in the pancreas SO CELL BIOLOGY AND TOXICOLOGY LA English DT Article DE NQO1; pancreatic; pancreatitis; smoking; polymorphism ID DT-DIAPHORASE ACTIVITY; NAD(P)H-QUINONE OXIDOREDUCTASE; CIGARETTE-SMOKING; MITOMYCIN-C; LUNG-CANCER; RISK-FACTOR; POLYMORPHISM; EXPRESSION; ASSOCIATION; ACTIVATION AB NAD(P)H:quinone oxidoreductase 1 (NQO1) is elevated in several human tumors. This study was conducted to determine whether increased levels of NQO1 expression also occur in human pancreatic tumor tissue, and to compare expression levels in nontumorous tissue from smokers with those in nonsmokers. The expression of NQO1 was examined in pancreatic tissue samples from 82 human donors. These samples included normal (n = 20), smokers (n = 25), pancreatitis (n = 7), and adenocarcinomas of the pancreas (n = 30). Genotyping for the C609T polymorphism in NQO1 by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis was also performed. Polymorphic variants were confirmed by automatic sequencing. Higher levels of NQO1 expression were demonstrated in pancreatic adenocarcinomas (0.831 +/- 0.021) compared to those in nontumorous tissues from nonsmokers (0.139 +/- 0.024). These high levels were also found in smokers (0.729 +/- 0.167) and in pancreatitis tissues (0.923 +/- 0.184). NQO1 activity was also higher in smokers (2.43 +/- 0.61 nmol/min per mg protein) compared to nonsmokers (0.44 +/- 0.05 nmol/min per mg protein; p < 0.05). No differences were found in genotype distribution and frequencies of the variant alleles between normal and cancer tissues in this relatively small sample pool. Seventy-five percent of the normal pancreatic tissues showed 609(C/C) and 25% 609(C/T). In pancreatic adenocarcinomas the frequency distribution was 65% C/C, 30% C/T and 5% T/T. The increased expression in noncancer pancreatic tissue from smokers and the fact that smoking is a moderate risk factor for pancreatic cancer suggest that NQO1 expression may be a good candidate as a biomarker for pancreatic cancer, especially in risk groups such as smokers. C1 Natl Ctr Toxicol Res, Div Mol Epidemiol, Jefferson, AZ USA. RP Lyn-Cook, BD (reprint author), Natl Ctr Toxicol Res, Div Mol Epidemiol, Jefferson, AZ USA. EM blyncook@nctr.fda.gov NR 37 TC 25 Z9 27 U1 0 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0742-2091 J9 CELL BIOL TOXICOL JI Cell Biol. Toxicol. PD MAR PY 2006 VL 22 IS 2 BP 73 EP 80 DI 10.1007/s10565-006-0156-3 PG 8 WC Cell Biology; Toxicology SC Cell Biology; Toxicology GA 020RO UT WOS:000235928200001 PM 16532285 ER PT J AU Cysyk, RL Parker, RJ Barchi, JJ Steeg, PS Hartman, NR Strong, JA AF Cysyk, RL Parker, RJ Barchi, JJ Steeg, PS Hartman, NR Strong, JA TI Reaction of geldanamycin and C17-substituted analogues with glutathione: Product identifications and pharmacological implications SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID HEAT-SHOCK-PROTEIN; HERBIMYCIN-A; FISCHER-344 RATS; ANTITUMOR AGENT; KINASE-ACTIVITY; V-SRC; METABOLISM; INHIBITION; HSP90; DERIVATIVES AB 17-Dimethylaminoethylamino-17-demethoxygeldanamycin (DMAG) and 17-allylamino-17-demethoxy-geldanamycin (17-AAG) are two derivatives of geldanamycin (GA) that are currently undergoing clinical evaluation as anticancer agents. These agents bind to heat shock protein 90 (hsp90), resulting in the destabilization of client proteins and inhibition of tumor growth. In a search for the mechanism of hepatotoxicity, which is a dose-limiting toxicity for these agents, we found that GA and its derivatives, 17-AAG and 17-DMAG, react chemically (i.e., nonenzymatically) with glutathione (GSH). A combination of liquid chromatography/electrospray ionization/mass spectrometry and nuclear magnetic resonance analyses were used to identify the product of this reaction as a GSH adduct in which the thiol group of GSH is substituted in the 19-position of the benzoquinone ring. The reaction proceeds rapidly with GA and 17-DMAG (half-lives of approximately 1.5 and 36 min, respectively) and less rapidly with 17-AAG and its major metabolite, 17-AG (half-lives of approximately 9.8 and 16.7 h). The reaction occurs at pH 7.0, 37 degrees C, and a physiological concentration of GSH, indicating that cellular GSH could play a role in modulating the cellular toxicity of these agents and therefore be a factor in their mechanism of differential toxicity. Moreover, reactions with thiol groups of critical cellular proteins could be important to the mechanism of toxicity with this class of anticancer agents. C1 US FDA, Ctr Drug Evaluat & Res, Lab Clin Pharmacol, Silver Spring, MD 20993 USA. NCI, Mol Therapeut Program, NIH, Bethesda, MD 20892 USA. NCI, Med Chem Lab, NIH, Ft Detrick, MD 21702 USA. RP Strong, JA (reprint author), US FDA, Ctr Drug Evaluat & Res, Lab Clin Pharmacol, White Oak Bldg 64,Room 2026,10903 New Hampshire A, Silver Spring, MD 20993 USA. EM strongj@cder.fda.gov RI Barchi Jr., Joseph/N-3784-2014 NR 28 TC 71 Z9 73 U1 1 U2 5 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 MAR PY 2006 VL 19 IS 3 BP 376 EP 381 DI 10.1021/tx050237e PG 6 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 028BE UT WOS:000236459700005 PM 16544941 ER PT J AU Mwengee, W Butler, T Mgema, S Mhina, G Almasi, Y Bradley, C Formanik, JB Rochester, CG AF Mwengee, W Butler, T Mgema, S Mhina, G Almasi, Y Bradley, C Formanik, JB Rochester, CG TI Treatment of plague with gentamicin or doxycycline in a randomized clinical trial in Tanzania SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID YERSINIA-PESTIS INFECTION; PNEUMONIC PLAGUE; TRANSFERABLE PLASMID; BUBONIC PLAGUE; ANTIBIOTICS; SUSCEPTIBILITIES; AMINOGLYCOSIDES; RESISTANCE; OUTBREAK; VIETNAM AB Background. Over the past 50 years, antibiotics of choice for treatment of plague, including streptomycin, chloramphenicol, and tetracycline, have mostly become outdated or unavailable. To test gentamicin in the treatment of naturally occurring plague and the implications of its use in the treatment of bioterrorist plague, a randomized, comparative, open-label, clinical trial comparing monotherapy with gentamicin or doxycycline was conducted in Tanzania. Methods. Sixty-five adults and children with symptoms of bubonic, septicemic, or pneumonic plague of similar to 3 days duration were enrolled in the study. Bubo aspirates and blood were cultured for Yersinia pestis. Acute-phase and convalescent-phase serum samples were tested for antibody against fraction 1 antigen of Y. pestis. Thirty-five patients were randomized to receive gentamicin ( 2.5mg/ kg intramuscularly every 12 h for 7 days), and 30 patients were randomized to receive doxycycline ( 100 mg [ adults] and 2.2 mg/ kg [ children] orally every 12 h for 7 days). Serum creatinine concentrations were measured before and after treatment, and peak and trough concentrations of antibiotics were measured. Results. Three patients, 2 of whom were treated with gentamicin and 1 of whom was treated with doxycycline, died on the first or second day of treatment, and these deaths were attributed to advanced disease and complications including pneumonia, septicemia, hemorrhage, and renal failure at the start of therapy. All other patients experienced cure or an improved condition after receiving therapy, resulting in favorable response rates of 94% for gentamicin (95% CI, 81.1%-99.0%) and 97% for doxycycline ( 95% CI, 83.4%-99.8%). Y. pestis isolates obtained from 30 patients belonged to biotype antigua and were susceptible to gentamicin and doxycycline, which had MICs of 0.13 mg/ L and 0.25-0.5 mg/ L, respectively. Serum concentrations of antibiotics were within therapeutic ranges, and adverse events were infrequent. Patients treated with gentamicin demonstrated a modest increase in the mean serum creatinine concentration after treatment (P <.05 by paired t test). Conclusions. Both gentamicin and doxycycline were effective therapies for adult and pediatric plague, with high rates of favorable responses and low rates of adverse events. C1 Texas Tech Univ, Hlth Sci Ctr, Dept Internal Med, Lubbock, TX 79409 USA. Texas Tech Univ, Hlth Sci Ctr, Dept Pathol, Lubbock, TX 79409 USA. Reg Med Off, Tanga, Tanzania. Lushoto Dist Hosp, Lushoto, Tanzania. Ricerca Biosci, Concord, OH USA. US FDA, Ctr Drug Evaluat & Res, Div Biometr 3, Rockville, MD 20857 USA. RP Butler, T (reprint author), Care of Greenough III William B, Johns Hopkins Univ, Dept Geriatr Med, 5505 Hopkins Bayview Circle, Baltimore, MD 21224 USA. EM trigsby@jhmi.edu NR 43 TC 34 Z9 37 U1 0 U2 7 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 MAR 1 PY 2006 VL 42 IS 5 BP 614 EP 621 DI 10.1086/500137 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 008SE UT WOS:000235060200006 PM 16447105 ER PT J AU Mahmood, I AF Mahmood, I TI Comments on "A mathematical description of the functionality of correction factors used in allometry for predicting human drug clearance" SO DRUG METABOLISM AND DISPOSITION LA English DT Editorial Material AB In a recent paper, Tang and Mayersohn [(2005) Drug Metab Dispos 33: 1294-1296] mathematically described the functionality of the correction factors (CFs), maximum life-span potential (MLP), and brain weight (BrW) used in allometric scaling for the prediction of human drug clearance. They found that there is an intrinsic defect in using correction factors because different combinations of species will produce different prediction results. Analysis with real examples reveals that different predicted clearance values observed with different combinations of animal species, with or without CFs, are not due to the intrinsic defect of the correction factors; rather, it is the effect of the species, observed clearance values in the species, and the range of the body weights. Even if one does not use the CF, the predicted clearance by the simple allometry will still vary by severalfold, depending on the species used in the scaling. C1 US FDA, Ctr Drug Evaluat & Res, Off Drug Evaluat 6, Clin Pharmacol & Toxicol Branch,Woodmont Off Ctr, Rockville, MD 20857 USA. RP Mahmood, I (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Drug Evaluat 6, Clin Pharmacol & Toxicol Branch,Woodmont Off Ctr, Rockville, MD 20857 USA. EM Mahmoodi@CDER.FDA.GOV NR 6 TC 5 Z9 5 U1 0 U2 1 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0090-9556 J9 DRUG METAB DISPOS JI Drug Metab. Dispos. PD MAR PY 2006 VL 34 IS 3 BP 507 EP 509 DI 10.1124/dmd.105.007187 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 014SU UT WOS:000235501100026 PM 16495384 ER PT J AU Sawyer, JRR Binz, RL Wang, JY Moore, MM AF Sawyer, JRR Binz, RL Wang, JY Moore, MM TI Multicolor spectral karyotyping of the L5178Y Tk(+/-)-3.7.2C mouse lymphoma cell line SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article DE multicolor spectral koryotyping; L5178Y/Tk(+/-)-3.7.2C mouse lymphoma cell line; mouse lymphoma mutation assay; mutagenesis ID CYTOGENETIC CHARACTERIZATION; ASSAY SYSTEM; CHROMOSOMES; HETEROZYGOSITY; ABERRATIONS AB The L5178Y/Tk(+/-)-3.7.2C mouse lymphoma cell line is characterized, at the cytogenetic level, by a karyotype involving both numerical and complex structural aberrations. While the karyotype is remarkably normal for a transformed cell line that has been in culture for almost half a century, there are a number of chromosomal alterations that because of their complexity cannot be fully characterized by routine or even high-resolution G-banding studies. Multicolor spectral karyotyping (SKY) was performed on the cell line in anticipation of identifying the previously unresolved chromosome aberrations and confirming interpretations previously identified by banding studies. New chromosome aberrations detected by SKY include numerical aberrations of chromosome 15, duplications of regions of chromosomes 4, 5, 12, and 18, and deletion of chromosome 14. Complex unbalanced translocations involved segments of chromosomes 6, 14, and 15. In total, the SKY technique was able to provide new refined designations on segments of eight different chromosome pairs (4, 5, 6, 9, 12, 14, 15, 18) and identified all three previously unidentified marker chromosomes. This analysis provides an updated standard reference for the karyotype of the L5178Y/Tk(+/-)-1-3.7.2C cell line used in the in vitro mouse lymphoma mutation assay. C1 Natl Ctr Toxicol Res, Div Genet & Reprod Teoxicol, Jefferson, AR 72079 USA. Univ Arkansas Med Sci, Dept Pharmacol & Toxicol, Little Rock, AR 72205 USA. Univ Arkansas Med Sci, Dept Pathol, Cytogenet Lab, Little Rock, AR 72205 USA. RP Moore, MM (reprint author), Natl Ctr Toxicol Res, Div Genet & Reprod Teoxicol, HFT 120,3900 NCTR Rd, Jefferson, AR 72079 USA. EM mmoore@nctr.fda.gov NR 24 TC 7 Z9 7 U1 1 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD MAR PY 2006 VL 47 IS 2 BP 127 EP 131 DI 10.1002/em.20175 PG 5 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 012OL UT WOS:000235348400006 PM 16247762 ER PT J AU Corvi, R Ahr, HJ Albertini, S Blakey, DH Clerici, L Coecke, S Douglas, GR Gribaldo, L Groten, JP Haase, B Hamernik, K Hartung, T Inoue, T Indans, I Maurici, D Orphanides, G Rembges, D Sansone, SA Snape, JR Toda, E Tong, WD van Delft, JH Weis, B Schechtman, LM AF Corvi, R Ahr, HJ Albertini, S Blakey, DH Clerici, L Coecke, S Douglas, GR Gribaldo, L Groten, JP Haase, B Hamernik, K Hartung, T Inoue, T Indans, I Maurici, D Orphanides, G Rembges, D Sansone, SA Snape, JR Toda, E Tong, WD van Delft, JH Weis, B Schechtman, LM TI Meeting report: Validation of toxicogenomics-based test systems: ECVAM-ICCVAM/NICEATM considerations for regulatory use SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE acceptance; alternatives; biomarker; predictive test; regulatory use; standardization; toxicogenomics; toxicology; validation ID GENE-EXPRESSION DATABASE; MICROARRAY DATA; STANDARDS; CANCER; INFORMATION; REPOSITORY; TOXICOLOGY; PLATFORMS; PROFILES AB This is the report of the first workshop "Validation of Toxicogenomics-Based Test Systems" held 11-12 December 2003 in Ispra, Italy. The workshop was hosted by the European Centre for the Validation of Alternative Methods (ECVAM) and organized jointly by ECVAM, the U.S. Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM), and the National Toxicology Program (NTP) Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM). The primary aim of the workshop was for participants to discuss and define principles applicable to the validation of toxicogenomics platforms as well as validation of specific toxicologic test methods that incorporate toxicogenomics technologies. The workshop was viewed as an opportunity for initiating a dialogue between technologic experts, regulators, and the principal validation bodies and for identifying those factors to which the validation process would be applicable. It was felt that to do so now, as the technology is evolving and associated challenges are identified, would be a basis for the future validation of the technology when it reaches the appropriate stage. Because of the complexity of the issue, different aspects of the validation of toxicogenomics-based test methods were covered. The three focus areas include a) biologic validation of toxicogenomics-based test methods for regulatory decision making, b) technical and bioinformatics aspects related to validation, and c) validation issues as they relate to regulatory acceptance and use of toxicogenomics-based test methods. In this report we summarize the discussions and describe in detail the recommendations for future direction and priorities. C1 Joint Res Ctr European Commiss, European Ctr Validat Alternat Methods, IHCP, I-21120 Ispra, Italy. Bayer HealthCare AG, Wuppertal, Germany. Hoffmann La Roche AG, Basel, Switzerland. Hlth Canada, Environm Hlth Canada, Ottawa, ON K1A 0L2, Canada. JRC, IHCP, Ispra, Italy. TNO, Utrecht, Netherlands. QIAGEN, Hilden, Germany. US EPA, Washington, DC 20460 USA. Natl Inst Hlth Sci, Tokyo 158, Japan. Hlth Safety Execut, London, England. Syngenta, Macclesfield, Cheshire, England. European Bioinformat Inst, European Mol Biol Lab, Cambridge, England. AstraZeneca, Brixham, England. Org Econ Cooperat & Dev, Paris, France. US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Univ Maastricht, Maastricht, Netherlands. NIEHS, NIH, US Dept HHS, Res Triangle Pk, NC 27709 USA. US Interagcy Coordinating Comm Validat Alternat M, Res Triangle Pk, NC USA. US FDA, Natl Ctr Toxicol Res, Rockville, MD 20857 USA. RP Corvi, R (reprint author), Joint Res Ctr European Commiss, European Ctr Validat Alternat Methods, IHCP, Via E Fermi 1, I-21120 Ispra, Italy. EM raffaella.corvi@jrc.it OI Sansone, Susanna-Assunta/0000-0001-5306-5690 NR 49 TC 52 Z9 57 U1 0 U2 6 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 MAR PY 2006 VL 114 IS 3 BP 420 EP 429 DI 10.1289/ehp.8247 PG 10 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 018NK UT WOS:000235771000040 PM 16507466 ER PT J AU Guo, TL Chi, RP Zhang, XL Musgrove, DL Weis, C Germolec, DR White, KL AF Guo, TL Chi, RP Zhang, XL Musgrove, DL Weis, C Germolec, DR White, KL TI Modulation of immune response following dietary genistein exposure in F-0 and F-1 generations of C57BL/6 mice: Evidence of thymic regulation SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article DE genistein; natural killer cell activity; anti-CD3 mediated proliferation and phenotypic markers ID SPRAGUE-DAWLEY RATS; ESTROGEN-RECEPTOR-ALPHA; NATURAL-KILLER-CELLS; PHYTOESTROGEN GENISTEIN; PHYTO-ESTROGENS; BREAST-CANCER; MOUSE THYMUS; EXPRESSION; IMMUNOSUPPRESSION; 17-BETA-ESTRADIOL AB To further determine whether genistein (GEN) modulation of the immune responses was related to its endocrine-disrupting properties and time of exposure, pregnant C57BL/6 mice were exposed to GEN at 0-1250 ppm in feed starting on day 14 of gestation. The C57BL/6 offspring were exposed to GEN in utero and lactationally, and through feed after weaning until postnatal day 42. In dams, exposure to GEN increased the terminal body weight (250 and 1250 ppm), the number of splenic T cells and NK cells (250 ppm), and the activity of NK cells (250 ppm). In F-1 males, GEN increased the terminal body and spleen weights (25 and 250 ppm), the number of CD4(+)CD8(+) and CD4(-)CD8(+) thymocytes (25 ppm), and the number of splenic T cell subsets and NK cells (25 and 250 ppm). Moreover, splenic NK cell activity and atiti-CD3-mediated splenocyte proliferation were increased in all treatment groups. In F-1 females, the percentages of CD4-CD8+ and CD4(-)CD8(-) thymocytes (25 and 250 ppm), and CD4(+)CD8(-) and CD4(+)CD8(+) splenocytes (25 and 250 ppm) were increased. In contrast, the percentage and number of CD4+CD8+ thymocytes were decreased (250 ppm). Exposure to GEN decreased the percentages of splenic NK cells in all treatment groups, and decreased the activity of splenic NK cells at the 25 ppm concentration. Additionally, evaluation of CD25(+) and CD44(+) expression by thymocytes indicated that the decrease in the percentage of CD44(+)CD25(+) thymocytes was at least partially responsible for the decrease in the percentage of CD4-CD8- thymocytes in F-1 male mice. Overall, the results demonstrate that GEN can modulate the immune system in both adult and developing C57BL/6 mice in a dose-specific manner. The gender-specific effects of GEN on the immune responses in F-1 mice suggest that GEN may modulate the immune system by functioning as either an estrogen agonist or antagonist. The differential effects of GEN on thymocytes in F-1 male and female mice indicate that GEN immunomodulation might be related to its effect on thymus. (c) 2005 Elsevier Ltd. All rights reserved. C1 Virginia Commonwealth Univ, Dept Pharmacol & Toxicol, Richmond, VA 23298 USA. US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. NIEHS, Mol Toxicol Lab, Res Triangle Pk, NC 27709 USA. RP Guo, TL (reprint author), Virginia Commonwealth Univ, Dept Pharmacol & Toxicol, POB 980613, Richmond, VA 23298 USA. EM tlguo@hsc.vcu.edu FU NIEHS NIH HHS [R21ES 012286, N01-ES-05454, R21 ES012286-02, R21 ES012286-01, R21 ES012286-03] NR 45 TC 14 Z9 15 U1 1 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0278-6915 J9 FOOD CHEM TOXICOL JI Food Chem. Toxicol. PD MAR PY 2006 VL 44 IS 3 BP 316 EP 325 DI 10.1016/j.fct.2005.08.001 PG 10 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA 026DU UT WOS:000236317800002 PM 16162389 ER PT J AU Yu, HN Yin, JJ Shen, SR AF Yu, HN Yin, JJ Shen, SR TI Effects of epi-gallocatechin gallate on PC-3 cell cytoplasmic membrane in the presence Of Cu2+ SO FOOD CHEMISTRY LA English DT Article DE epigallocatechin gallate; Cu2+; rearrangement; cytoplasm membrane; free radicals; prostate cancer cells ID CANCER; TEA; CATECHINS AB Catechins, which exist in green tea, are excellent antioxidants and metals enhance their pro-oxidative character. In this study, we investigated damage to the cell cytoplasmic membrane of the androgen-insensitive prostate cancer cell PC-3 from rearrangement of EGCG (epigallocatechin gallate), the main bioactive component of catechins. In a cell culture system containing Cu2+ the generation of free radicals from EGCG rearrangement was measured. Electron microscopy, flow cytometry, gel electrophoresis, and ESR measurements showed that the cytoplasmic membrane of PC-3 cells was disrupted in this culture system and that the death of most cells followed within a few minutes. Hydroxyl radicals, detected in the ESR experiment using the spin trapping method, may cause damage to the cytoplasmic membrane. Analysis of F-12 medium after 6 h, by HPLC, showed small amounts of EGCG when PC-3 cells were absent, and no detectable levels when PC-3 cells were present. In addition to the concentration and order in which EGCG and Cu2+ are added to the culture medium, oxides, polymers, or some compounds integrated with the cytoplasmic membrane of the PC-3 cells themselves may have a key role in damage to the PC-3 cell cytoplasmic membrane. (c) 2005 Elsevier Ltd. All rights reserved. C1 Zhejiang Univ, Dept Tea Sci, Hangzhou 310029, Peoples R China. US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Shen, SR (reprint author), Zhejiang Univ, Dept Tea Sci, Hangzhou 310029, Peoples R China. EM shrshen@zju.edu.cn RI Yin, Jun Jie /E-5619-2014 NR 28 TC 13 Z9 18 U1 0 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0308-8146 J9 FOOD CHEM JI Food Chem. PD MAR PY 2006 VL 95 IS 1 BP 108 EP 115 DI 10.1016/j.foodchem.2004.12.023 PG 8 WC Chemistry, Applied; Food Science & Technology; Nutrition & Dietetics SC Chemistry; Food Science & Technology; Nutrition & Dietetics GA 976VQ UT WOS:000232762000015 ER PT J AU Zhao, S McDermott, PF Friedman, S Abbott, J Ayers, S Glenn, A Hall-Robinson, E Hubert, SK Harbottle, H Walker, RD Chiller, TM White, DG AF Zhao, S McDermott, PF Friedman, S Abbott, J Ayers, S Glenn, A Hall-Robinson, E Hubert, SK Harbottle, H Walker, RD Chiller, TM White, DG TI Antimicrobial resistance and genetic relatedness among Salmonella from retail foods of animal origin: NARMS retail meat surveillance SO FOODBORNE PATHOGENS AND DISEASE LA English DT Article ID MONITORING PROGRAMS; HEALTH CONSEQUENCES; UNITED-STATES; SOUTH-AFRICA; BACTERIA; ENTERICA; HUMANS; SUSCEPTIBILITY; INFECTIONS; PULSENET AB Salmonella isolates were recovered from a monthly sampling of chicken breasts, ground turkey, ground beef, and pork chops purchased from selected grocery stores in six participating FoodNet sites (Connecticut, Georgia, Maryland, Minnesota, Oregon, and Tennessee) in 2002 and an additional two sites in 2003 (California and New York). In 2002 and 2003, a total of 6,046 retail meats were examined, including 1,513 chicken breasts, 1,499 ground turkey samples, 1,522 ground beef samples, and 1,502 pork chops. Retail meat samples tested increased to 3,533 in 2003 as compared to 2,513 in 2002. Overall, six percent of 6,046 retail meat samples (n = 365) were contaminated with Salmonella, the bulk recovered from either ground turkey (52%) or chicken breast (39%). Salmonella isolates were serotyped and susceptibility tested using a panel of 16 antimicrobial agents. S. Heidelberg was the predominant serotype identified (23%), followed by S. Saintpaul (12%), S. Typhimurium (11%), and S. Kentucky (10%). Overall, resistance was most often observed to tetracycline (40%), streptomycin (37%), ampicillin (26%), and sulfamethoxazole (25%). Twelve percent of isolates were resistant to cefoxitin and ceftiofur, though only one isolate was resistant to ceftriaxone. All isolates were susceptible to amikacin and ciprofloxacin; however, 3% of isolates were resistant to nalidixic acid and were almost exclusive to ground turkey samples (n = 11/12). All Salmonella isolates were analyzed for genetic relatedness using pulsed-field gel electrophoresis (PFGE) patterns generated by digestion with Xba1 or Xba1 plus Bln1. PFGE fingerprinting profiles showed that Salmonella, in general, were genetically diverse with a total of 175 Xba1 PFGE profiles generated from the 365 isolates. PFGE profiles showed good correlation with serotypes and in some instances, antimicrobial resistance profiles. Results demonstrated a varied spectrum of antimicrobial resistance and PFGE patterns, including several multidrug resistant clonal groups among Salmonella isolates, and signify the importance of sustained surveillance of foodborne pathogens in retail meats. C1 US FDA, Div Anim & Food Microbiol, Res Off, CVM, Laurel, MD 20708 USA. Ctr Dis Control & Prevent, Atlanta, GA USA. RP White, DG (reprint author), US FDA, Div Anim & Food Microbiol, Res Off, CVM, 8401 Muirkirk Rd, Laurel, MD 20708 USA. EM dwhite@cvm.fda.gov NR 39 TC 59 Z9 61 U1 1 U2 10 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1535-3141 J9 FOODBORNE PATHOG DIS JI Foodborne Pathog. Dis. PD SPR PY 2006 VL 3 IS 1 BP 106 EP 117 DI 10.1089/fpd.2006.3.106 PG 12 WC Food Science & Technology SC Food Science & Technology GA 052RV UT WOS:000238252200015 PM 16602986 ER PT J AU Jeschke, U Kuhn, C Mylonas, I Schulze, S Friese, K Mayr, D Speer, R Briese, V Richter, DU Haase, M Karsten, U AF Jeschke, U Kuhn, C Mylonas, I Schulze, S Friese, K Mayr, D Speer, R Briese, V Richter, DU Haase, M Karsten, U TI Development and characterization of monoclonal antibodies for the immunohistochemical detection of glycodelin A in decidual, endometrial and gynaecological tumour tissues SO HISTOPATHOLOGY LA English DT Article DE decidua; endometrium; glycodelin; gynaecological cancer; monoclonal antibodies ID AMNIOTIC-FLUID TRANSFERRIN; HUMAN PLACENTAL PROTEIN-14; BREAST-CANCER; STEROID-RECEPTORS; EARLY-PREGNANCY; OVARIAN-TUMORS; MESSENGER-RNA; CELLS; EXPRESSION; PP14 AB Aims: Glycodelin is a glycoprotein with a molecular weight of 28 kDa. Unusual LacdiNAc structures have been identified on glycodelin A, isolated from amniotic fluid. Three major functions of this glycoprotein have been identified. Glycodelin is an immunosuppressive molecule, a marker of morphological differentiation, and a contraceptive. Because no monoclonal antibodies for glycodelin A are commercially available, our aim was to develop and characterize three monoclonal antibodies against this glycoprotein. Methods and results: Glycodelin A was purified from amniotic fluid by three chromatographic steps and its purity was checked by SDS-PAGE. Antibodies were generated from immunized BALB/c mice. Three IgG1 monoclonal antibodies detecting glycodelin A were cloned. All three antibodies recognized carbohydrate structures of glycodelin A and did not cross-react with glycodelin S. They are applicable to immunohistochemistry (frozen and paraffin sections), ELISA and Western blots. Conclusion: The new antibodies can be used for the detection of glycodelin A in frozen and paraffin-embedded decidual and endometrial tissue. One antibody (A87-B/D2) can be used for the detection of glycodelin in endometrial and ovarian tumour tissues. Because glycodelin A is a major secretory endometrial product during the luteal phase, in early pregnancy and in gynaecological tumours, the new antibodies are, potentially, valuable tools for the study of endometrial development and tumour progression. C1 Univ Munich, Dept Obstet & Gynaecol 1, D-80337 Munich, Germany. Univ Munich, Inst Pathol, D-80337 Munich, Germany. NIH, NCI FDA Clin Proteom Program, Bethesda, MD USA. Univ Rostock, Dept Obstet & Gynaecol, Fac Med, Rostock, Germany. Glycotope GmbH, Berlin, Germany. RP Jeschke, U (reprint author), Univ Munich, Dept Obstet & Gynaecol 1, Maistr 11, D-80337 Munich, Germany. EM udo.jeschke@med.uni-muenchen.de NR 36 TC 13 Z9 13 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0309-0167 J9 HISTOPATHOLOGY JI Histopathology PD MAR PY 2006 VL 48 IS 4 BP 394 EP 406 DI 10.1111/j.1365-2559.2006.02351.x PG 13 WC Cell Biology; Pathology SC Cell Biology; Pathology GA 013OY UT WOS:000235419900007 PM 16487361 ER PT J AU Selvapandiyan, A Duncan, R Debrabant, A Lee, N Sreenivas, G Salotra, P Nakhasi, HL AF Selvapandiyan, A Duncan, R Debrabant, A Lee, N Sreenivas, G Salotra, P Nakhasi, HL TI Genetically modified live attenuated parasites as vaccines for leishmaniasis SO INDIAN JOURNAL OF MEDICAL RESEARCH LA English DT Review DE animal model; Leishmania; leishmaniasis; live attenuated parasite ID PROTEINASE-DEFICIENT MUTANTS; TARGETED GENE DELETION; TYPE-1 IMMUNE-RESPONSE; CUTANEOUS LEISHMANIASIS; VISCERAL LEISHMANIASIS; MAJOR INFECTION; CPG OLIGODEOXYNUCLEOTIDES; LIPOPHOSPHOGLYCAN LPG; LEISHMANOLYSIN GP63; SUSCEPTIBLE MICE AB Leishmaniasis causes significant morbidity and mortality worldwide and is an important public health problem. Even though it is endemic in developing countries in tropical regions of the world, in recent years economic globalization and increased travel has extended its reach to people in developed countries. Leishmania is usually spread by the bite of the female sandfly. In addition, nave populations can be exposed to Leishmania infection through transfusion of blood and blood products from infected asymptomatic individuals. There are several clinical forms of leishmaniasis caused by different species of the parasite. In some cases, the only possible cure for this disease is drug treatment. However, prolonged use of such drugs has led to parasite drug resistance. At present there are no effective vaccines against Leishmania. Many vaccine strategies have been pursued, including the use of whole cell lysate, killed, avirulent or irradiated parasites. Additionally, DNA vaccines and purified or recombinant parasite antigens have also been tested. Most of these strategies have shown some degree of effectiveness in animal models but little or no protection in humans. There is now a general consensus among Leishmania vaccine researchers that parasite persistence may be important for effective protective response and could be achieved by live attenuated parasite immunization. In this article we reviewed the efforts in developing genetically defined live attenuated Leishmania parasites as vaccine candidates with the goal of achieving a low level of parasite persistence without being virulent in the host and inducing protective immunity. C1 US FDA, DETTD, OBRR, CBER, Bethesda, MD 20892 USA. Inst Pathol, New Delhi, India. RP Nakhasi, HL (reprint author), US FDA, DETTD, OBRR, CBER, Bldg 29,Room 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 83 TC 22 Z9 23 U1 1 U2 8 PU INDIAN COUNCIL MEDICAL RES PI NEW DELHI PA PO BOX 4911 ANSARI NAGAR, NEW DELHI 110029, INDIA SN 0971-5916 J9 INDIAN J MED RES JI Indian J. Med. Res. PD MAR PY 2006 VL 123 IS 3 BP 455 EP 466 PG 12 WC Immunology; Medicine, General & Internal; Medicine, Research & Experimental SC Immunology; General & Internal Medicine; Research & Experimental Medicine GA 052OR UT WOS:000238243500022 PM 16778323 ER PT J AU Janes, BK Stibitz, S AF Janes, BK Stibitz, S TI Routine markerless gene replacement in Bacillus anthracis SO INFECTION AND IMMUNITY LA English DT Article ID HOMOLOGOUS RECOMBINATION; STREPTOCOCCUS-MUTANS; BORDETELLA-PERTUSSIS; ESCHERICHIA-COLI; REGULATOR; CHROMOSOME; CLONING; TRANSFORMATION; EXPRESSION; HYDROLASE AB An improved genetic tool suitable for routine markerless allelic exchange in Bacillus anthracis has been constructed. Its utility was demonstrated by the introduction of insertions, deletions, and missense mutations on the chromosome and plasmid pXO1 of the Sterne strain of B. anthracis. C1 US FDA, Div Bacterial Parasit & Allergen Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Stibitz, S (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Bacterial Prod, 8800 Rockville Pike, Bethesda, MD 20892 USA. EM stibitz@helix.nih.gov NR 27 TC 107 Z9 110 U1 1 U2 9 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 MAR PY 2006 VL 74 IS 3 BP 1949 EP 1953 DI 10.1128/IAI.74.3.1949-1953.2006 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 019ED UT WOS:000235817500059 PM 16495572 ER PT J AU Zhang, JS Alston, MA Huang, H Rabin, RL AF Zhang, JS Alston, MA Huang, H Rabin, RL TI Human T cell cytokine responses are dependent on multidrug resistance protein-1 SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE T cells; cytokines; Multidrug Resistance Protein-1 (MRP1); peroxisome proliferator-activated receptor-c (PPARc) ID MULTIDRUG-RESISTANCE PROTEIN-1; ACTIVATED RECEPTOR-GAMMA; PERIPHERAL-BLOOD; PPAR-GAMMA; MESSENGER-RNA; KAPPA-B; LEUKOTRIENE C-4; DENDRITIC CELLS; FLOW-CYTOMETRY; NUCLEAR FACTOR AB Multidrug resistance protein-1 (MRP1) belongs to subfamily C of the ATP-binding cassette transporters, and exports leukotriene C-4 and organic anions including the fluorescent calcium indicator indo-1. The observation that leukocytes from patients with an autoimmune disease exported indo-1 at a higher rate than controls prompted the hypothesis that MRP1 contributes to the function of activated cells. To test this, we defined the expression of MRP1 on resting and activated human T cells, and determined whether T cell activation is dependent upon MRP1 function. MRP1 is expressed on resting memory but not on naive CD4 and CD8 T cells. After activation through the TCR, cord blood CD4 T cells express high levels of MRP1. Blockade of MRP1 with the specific inhibitor MK-571 abrogated superantigen-induced expression of IFN-gamma, tumor necrosis factor-alpha, IL-10, IL-2, IL-4 and CD69 by T cells without affecting their viability, and was reversible upon removal of MK-571 from the culture media. Electrophoretic mobility shift assays demonstrate that MRP1 blockade with MK-571 induces activation of the transcriptional repressor peroxisome proliferator-activated receptor-gamma in CD4 T cells, thus providing insight into the potential mechanism by which their responses are abrogated. C1 US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Rabin, RL (reprint author), US FDA, Ctr Biol Evaluat & Res, 29 Lincoln Dr,MSC-4555,Bldg 29,Room B1, Bethesda, MD 20892 USA. EM rrabin@helix.nih.gov RI ZHANG, JINSONG/E-1656-2011 OI ZHANG, JINSONG/0000-0002-2195-2997 NR 50 TC 17 Z9 19 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD MAR PY 2006 VL 18 IS 3 BP 485 EP 493 DI 10.1093/intimm/dxh389 PG 9 WC Immunology SC Immunology GA 018NT UT WOS:000235771900010 PM 16481346 ER PT J AU Casanova, JA Gross, LK McMullen, SE Schenck, FJ AF Casanova, JA Gross, LK McMullen, SE Schenck, FJ TI Use of Griess reagent containing vanadium(III) for post-column derivatization and simultaneous determination of nitrite and nitrate in baby food SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID SIMULTANEOUS SPECTROPHOTOMETRIC DETERMINATION; COLUMN PRECONCENTRATION; WATER SAMPLES; METHEMOGLOBINEMIA AB An ion chromatographic method with post-column derivatization and spectrophotometric detection is presented for the determination of nitrate and nitrite (NOx) in baby food. NOx residues found naturally or added as preservatives were extracted from baby foods and determined by using ion chromatography with post-column derivatization and spectrophotometric detection. Nitrate was reduced to nitrite online by post-column reduction using vanadium(III) chloride and heat. Nitrite reacted with Griess reagent to produce a dye that was detected at 525 nm. The use of V(III) and heat to promote the reduction of nitrate to nitrite online is a novel feature of this detection system. The determination of incurred NOx residues in samples by using AOAC Method 993.03 yielded results comparable to those obtained by ion chromatography with spectrophotometric detection. The toxic and carcinogenic metal cadmium used in the AOAC Method to reduce the nitrate to nitrite was avoided. The proposed method provides simultaneous determination of nitrate and nitrite. Average recoveries of nitrate and nitrite residues ranged from 82 to 107% for fortification levels of 25-400 ppm. 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. EM fschenck@ora.fda.gov NR 28 TC 7 Z9 7 U1 0 U2 4 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD MAR-APR PY 2006 VL 89 IS 2 BP 447 EP 451 PG 5 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 029UX UT WOS:000236591000016 PM 16640292 ER PT J AU Carson, M Reeves, V AF Carson, M Reeves, V TI Veterinary drug residues SO JOURNAL OF AOAC INTERNATIONAL LA English DT Editorial Material C1 US FDA, Laurel, MD USA. US FDA, Rockville, MD 20857 USA. RP Carson, M (reprint author), US FDA, Laurel, MD USA. NR 0 TC 0 Z9 0 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 MAR-APR PY 2006 VL 89 IS 2 BP 566 EP 566 PG 1 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 029UX UT WOS:000236591000033 ER PT J AU Quon, DG Carson, MC Nochetto, C Heller, DN Butterworth, F AF Quon, DG Carson, MC Nochetto, C Heller, DN Butterworth, F TI Peer validation of a method to confirm chloramphenicol in honey by liquid chromatography-tandem mass spectrometry SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article; Proceedings Paper CT Symposium on Veterinary Drug Residues CY 2003 CL Atlanta, GA SP AOAC ID SOLID-PHASE EXTRACTION; FOOD-PRODUCING ANIMALS; SULFATHIAZOLE RESIDUES; OXYTETRACYCLINE RESIDUES; GAS-CHROMATOGRAPHY; CHEMICAL-ANALYSIS; DRUG RESIDUES; SHRIMP TISSUE; MILK; ANTIBIOTICS AB Chloramphenicol (CAP) is extracted from an aqueous dilution of honey using ethyl acetate. The extracts are evaporated and redissolved in water. CAP is then extracted from the aqueous solutions using reversed-phase solid-phase extraction cartridges. CAP is eluted from the reversed-phase cartridges with acetonitrile-water and re-extracted into ethyl acetate. The ethyl acetate is evaporated, and the residue is reconstituted in an aqueous solution. Extracts are chromatographed using a reversed-phase column and analyzed by electrospray negative mode tandem mass spectrometry. Four product ions of precursors m/z 321 or 323 are monitored. The method meets confirmation criteria recommended by the U.S. Food and Drug Administration and 4-point identification criteria established by the European Union. With slight modifications to accommodate different equipment, the method was validated in 2 laboratories. C1 US FDA, Ctr Vet Med, Res Off, Laurel, MD 20708 USA. Canadian Food Inspect Agcy, Addit & Chem Contaminants Unit, Calgary Lab, Calgary, AB T2L 2L1, Canada. RP Carson, MC (reprint author), US FDA, Ctr Vet Med, Res Off, 8401 Muirkirk Rd, Laurel, MD 20708 USA. EM mary.carson@fda.gov NR 45 TC 9 Z9 9 U1 0 U2 4 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD MAR-APR PY 2006 VL 89 IS 2 BP 586 EP 593 PG 8 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 029UX UT WOS:000236591000036 PM 16640310 ER PT J AU Andreishcheva, EN Vann, WF AF Andreishcheva, EN Vann, WF TI Gene products required for de novo synthesis of polysialic acid in Escherichia coli K1 SO JOURNAL OF BACTERIOLOGY LA English DT Article ID CAPSULAR POLYSACCHARIDES; NEISSERIA-MENINGITIDIS; SIALIC-ACID; MOLECULAR-CLONING; COLOMINIC ACID; K5; CLUSTER; K92; BIOSYNTHESIS; PURIFICATION AB Escherichia coli K1 is responsible for 80% of E. coli neonatal meningitis and is a common pathogen in urinary tract infections. Bacteria of this serotype are encapsulated with the alpha(2-8)-polysialic acid NeuNAc(alpha 2-8), common to several bacterial pathogens. The gene cluster encoding the pathway for synthesis of this polymer is organized into three regions: (i) kpsSCUDEF, (ii) neuDBACES, and (iii) kpsMT. The K1 polysialyltransferase, NeuS, cannot synthesize polysialic acid de novo without other products of the gene cluster. Membranes isolated from strains having the entire K1 gene cluster can synthesize polysialic acid de novo. We designed a series of plasmid constructs containing fragments of regions 1 and 2 in two compatible vectors to determine the minimum number of gene products required for de novo synthesis of the pollysialic acid from CMP-NeuNAc in K1 E. coli. We measured the ability of the various combinations of region 1 and 2 fragments to restore polysialyltransferase activity in vitro in the absence of exogenously added pollysaccharide acceptor. The products of region 2 genes neuDBACES alone were not sufficient to support de novo synthesis of polysialic acid in vitro. Only membrane fractions harboring NeuES and KpsCS could form sialic polymer in the absence of exogenous acceptor at the concentrations formed by wild-type E. coli K1 membranes. Membrane fractions harboring NeuES and KpsC together could form small quantities of the sialic polymer de novo. C1 US FDA, Lab Bacterial Toxins, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Vann, WF (reprint author), US FDA, Lab Bacterial Toxins, Ctr Biol Evaluat & Res, Bldg 29,Room 103,8800 Rockville Pike, Bethesda, MD 20892 USA. EM wvann@helix.nih.gov NR 38 TC 32 Z9 32 U1 1 U2 5 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 MAR PY 2006 VL 188 IS 5 BP 1786 EP 1797 DI 10.1128/JB.188.5.1786-1797.2006 PG 12 WC Microbiology SC Microbiology GA 019EU UT WOS:000235819200012 PM 16484189 ER PT J AU Yang, PL Fleming, TR AF Yang, PL Fleming, TR TI Simultaneous use of weighted logrank and standardized Kaplan-Meier statistics SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Article DE censored data; clinical trials; joint distribution; rank-based statistics ID CENSORED SURVIVAL-DATA; TESTS; RANK AB Rank-based test procedures in censored survival data differ considerably in their sensitivity to various alternatives to the hypothesis of equality of underlying distributions. Procedures based on the simultaneous use of multiple statistics provide an appealing approach to obtaining more global sensitivity while maintaining the sensitivity to alternatives of interest. In this article, the joint distribution of weighted logrank statistics (to assess overall differences in time-to-event distributions) and a standardized difference in Kaplan-Meier estimates (to assess differences at a specific prespecified time post randomization) is obtained and this result is used to formulate statistical test procedures based on the simultaneous use of these two types of statistics. Simulations are used to assess small sample properties of this approach and its usefulness is illustrated in important recent oncology clinical trials. C1 Univ Washington, Dept Biostat, Seattle, WA 98195 USA. US FDA, Silver Spring, MD USA. RP Fleming, TR (reprint author), Univ Washington, Dept Biostat, Box 357232, Seattle, WA 98195 USA. EM tfleming@u.washington.edu NR 19 TC 0 Z9 0 U1 0 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1054-3406 J9 J BIOPHARM STAT JI J. Biopharm. Stat. PD MAR-APR PY 2006 VL 16 IS 2 BP 241 EP 252 DI 10.1080/10543400500508952 PG 12 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 024YX UT WOS:000236233600008 PM 16584070 ER PT J AU Wood, JJ Malek, MA Frassica, FJ Power, JA Mohan, AK Bloom, ET Braun, MM Cote, TR AF Wood, JJ Malek, MA Frassica, FJ Power, JA Mohan, AK Bloom, ET Braun, MM Cote, TR TI Autologous cultured chondrocytes: Adverse events reported to the united states food and drug administration SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID ARTICULAR-CARTILAGE DEFECTS; REPAIR; KNEE; TRANSPLANTATION; IMPLANTATION; TRIAL; CELLS AB Background: Carticel is an autologous cultured chondrocyte product that has been approved by the United States Food and Drug Administration for the repair of symptomatic cartilaginous defects of the femoral condyle that are caused by acute or repetitive trauma in patients who have been previously managed with arthroscopy or other surgical procedures. The present report describes the adverse events following Carticel implantation as reported to the Food and Drug Administration from 1996 to 2003. Methods: We reviewed adverse event reports that had been submitted to the Food and Drug Administration's Med-Watch system for information on demographic characteristics, adverse events, and surgical revisions. Adverse events were categorized into sixteen non-mutually exclusive groups. Five categories were used to classify reoperations. Food and Drug Administration regulations require manufacturers to report adverse events; however, reporting by clinicians and others is voluntary. Therefore, adverse event reporting is likely to underestimate the number of event occurrences. Adverse events may be either causally or coincidentally related to the product. Results: A total of 497 adverse events among 294 patients receiving Carticel were reported. The median interval from Carticel implantation to the diagnosis of an adverse event was 240 days (range, one to 2105 days). The median age of the patients was thirty-eight years, and 63% of the patients were male. Of the 270 events for which the anatomic site was noted, 258 (96%) involved the femoral condyles. More than one adverse event was reported for 135 patients (46%). The most commonly reported events were graft failure (seventy-three patients; 25%), delamination (sixty-five patients; 22%), and tissue hypertrophy (fifty-two patients; 18%). In addition, eighteen surgical site infections were reported, including eleven joint and seven soft-tissue infections. Surgical revision subsequent to Carticel implantation was mentioned in the records for 273 patients (93%). The reasons for the 389 revision procedures included graft-related problems (187 procedures; 48.1%), periarticular soft-tissue problems (ninety-seven procedures; 24.9%), and intra-articular problems (sixty-three procedures; 16.2%). Eight patients had a total knee replacement. Based on the manufacturer's reported distribution of 7500 Carticel lots between 1995 and 2002, 285 patients (3.8%) had an adverse event that was reported to the Food and Drug Administration. Conclusions: The most common adverse events reported in association with the Carticel technique involved graft failure, delamination, and tissue hypertrophy. C1 Ctr Dis Control, Atlanta, GA 30329 USA. US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. Johns Hopkins Univ, Baltimore, MD 21287 USA. RP Wood, JJ (reprint author), 11631 SW 2nd St, Pembroke Pines, FL 33025 USA. EM braunm@cber.fda.gov NR 25 TC 111 Z9 119 U1 2 U2 10 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD MAR PY 2006 VL 88A IS 3 BP 503 EP 507 DI 10.2106/JBJS.E.00103 PG 5 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 021IU UT WOS:000235977700006 PM 16510814 ER PT J AU Hubinger, JC Havery, DC AF Hubinger, JC Havery, DC TI Analysis of consumer cosmetic products for phthalate esters SO JOURNAL OF COSMETIC SCIENCE LA English DT Article ID CHROMATOGRAPHY-MASS-SPECTROMETRY; SOLID-PHASE MICROEXTRACTION; N-BUTYL PHTHALATE; PERFORMANCE LIQUID-CHROMATOGRAPHY; HUMAN REFERENCE POPULATION; EXPERT PANEL REPORT; GAS-CHROMATOGRAPHY; WATER SAMPLES; DEVELOPMENTAL TOXICITY; LATE PREGNANCY AB A rapid and sensitive reverse-phase HPLC method with UV detection was developed for the quantitation of dimethyl phthalate (DMP), diethyl phthalate (DEP), butyl benzyl phthalate (BBP), dibutyl phthalate (DBP). and di(2-ethylhexyl) phthalate (DEHP) in cosmetic preparations. Average recoveries of the phthalate esters were better than 90%. In a survey of 48 consumer cosmetic products, including hair care products, deodorants, lotions and creams, nail products, fragrances, and body washes, most products were found to contain at least one phthalate ester. DEP was detected most frequently at concentrations up to 38,663 ppm. DBP was found in fewer products, but at levels up to 59,815 ppm. Based on the available exposure and toxicity data, the FDA has concluded that there is insufficient data to conclude that a human health hazard exists from exposure to phthalate esters from cosmetic products. C1 US FDA, College Pk, MD 20740 USA. RP Hubinger, JC (reprint author), US FDA, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. NR 68 TC 45 Z9 47 U1 6 U2 26 PU SOC COSMETIC CHEMISTS PI NEW YORK PA 120 WALL STREET, SUITE 2400, NEW YORK, NY 10005-4088 USA SN 1525-7886 J9 J COSMET SCI JI J. Cosmet. Sci. PD MAR-APR PY 2006 VL 57 IS 2 BP 127 EP 137 PG 11 WC Chemistry, Applied; Dermatology SC Chemistry; Dermatology GA 045SK UT WOS:000237762300003 PM 16688376 ER PT J AU Chun, J Martin, JA Chen, LW Lee, J Ye, L Eitenmiller, RR AF Chun, J Martin, JA Chen, LW Lee, J Ye, L Eitenmiller, RR TI A differential assay of folic acid and total folate in foods containing enriched cereal-grain products to calculate mu g dietary folate equivalents (mu g DFE) SO JOURNAL OF FOOD COMPOSITION AND ANALYSIS LA English DT Article DE analysis; folic acid; total folate; mu g DFE; food folate ID TRI-ENZYME EXTRACTION; MICROBIOLOGICAL ASSAY; TRIENZYME EXTRACTION; BIOAVAILABILITY; FORTIFICATION AB A method was developed to differentiate folic acid from total folate in enriched cereal products. By elimination of the protease and conjugase digestion steps from the trienzyme digestion used to measure total folate, folic acid can be directly quantified by the microbiological assay using Lactobacillus casei (ssp. rhamnosus) ATCC 7469. Determination of total folate by the trienzyme digestion together with assay of folic acid by the procedure reported here allows calculation of food folate and mu g dietary folate equivalents (mu g DFE). Recovery studies conducted at five concentration levels in a non-fortified wheat flour gave a mean recovery of 95.5 (RSD% 9.7) for folic acid and 98.5 (RSD% 5.0) for total folate. Recoveries from a variety of enriched cereal foods ranged from 88% to 99% for the folic acid extraction and 90% to 96% for the trienzyme digestion. Analysis of SRM 1846 Infant Formula (n = 11) gave means +/- S.D. Of 123.5 +/- 6.9 mu g/100 g of folic acid and 136.6 +/- 6.7 mu g/100g of total folate (reference concentration value = 129 +/- 28 mu g/100 g). Intermediate precision determined as intra-laboratory reproducibility(r) gave RSDr % values of 4.32 for the folic acid assay and 3.15 for the total folate assay. Microgram DFE values were determined for several enriched cereals by calculating food folate as the difference between total folate and folic acid and the formula mu g DFE = mu g food folate + (1.7 x mu g folic acid). The differential assay of folic acid and total folate is a simple and accurate procedure to determine mu g DFE in enriched cereal-grains or foods containing enriched flour. (c) 2005 Elsevier Inc. All rights reserved. C1 Univ Georgia, Dept Food Sci & Technol, Athens, GA 30602 USA. US FDA, Atlanta Ctr Nutrient Anal, SE Reg Lab, Atlanta, GA 30309 USA. Chungbuk Natl Univ, Dept Food Sci & Technol, Cheongju 361763, Chungbuk, South Korea. RP Eitenmiller, RR (reprint author), Univ Georgia, Dept Food Sci & Technol, Athens, GA 30602 USA. EM eiten@uga.edu NR 25 TC 8 Z9 8 U1 1 U2 8 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0889-1575 J9 J FOOD COMPOS ANAL JI J. Food Compos. Anal. PD MAR-MAY PY 2006 VL 19 IS 2-3 BP 182 EP 187 DI 10.1016/j.jfca.2005.07.001 PG 6 WC Chemistry, Applied; Food Science & Technology SC Chemistry; Food Science & Technology GA 998FI UT WOS:000234303600011 ER PT J AU Zhao, S McDermott, PF Friedman, S Qaiyumi, S Abbott, J Kiessling, C Ayers, S Singh, R Hubert, S Sofos, J White, DG AF Zhao, S McDermott, PF Friedman, S Qaiyumi, S Abbott, J Kiessling, C Ayers, S Singh, R Hubert, S Sofos, J White, DG TI Characterization of antimicrobial-resistant Salmonella isolated from imported foods SO JOURNAL OF FOOD PROTECTION LA English DT Article ID ENTERICA SEROTYPE TYPHIMURIUM; CLASS-I INTEGRONS; ANTIBIOTIC-RESISTANCE; QUINOLONE RESISTANCE; MOLECULAR CHARACTERIZATION; MULTIDRUG-RESISTANT; GYRA MUTATIONS; UNITED-STATES; ANIMALS; INFECTIONS AB Two-hundred eight Salmonella isolates recovered from over 5,000 imported foods entering the United States in 2001 were tested for antimicrobial susceptibilities and further characterized for quinolone resistance mechanisms, integron carriage, and genetic relatedness. Salmonella Weltevreden (20%), Salmonella Newport (6%), Salmonella Lexington (5%), and Salmonella Thompson (4%) were the four most common serotypes recovered. Twenty-three (11%) isolates were resistant to at least one antimicrobial, and seven (3.4%) to three or more antimicrobials. Resistance was most often observed to tetracycline (9%), followed by sulfamethoxazole (5%), streptomycin (4%), nalidixic acid (3%), and trimethoprinVsulfamethoxazole (2%). One Salmonella Schwarzengrund isolate recovered from squid imported from Taiwan exhibited resistance to eight antimicrobials, including ampicillin, chloramphenicol, gentamicin, kanamycin, nalidixic acid, sulfamethoxazole, tetracycline, and trimethoprim/sulfamethoxazole. Six isolates (Salmonella Bareilly, Salmonella Derby, Salmonella Ohio and three Salmonella Schwarzengrund) contained class 1 integrons, which carried several resistance genes including dhfrI/dhfrXII, aadA, pse-1, and sat], conferring resistance to trimethoprim/sulfamethoxazole, streptomycin, ampicillin, and streptothricin, respectively. Five of six nalidixic acid-resistant isolates possessed DNA point mutations at either Ser83 or Asp87 in DNA gyrase. One ciprofloxacinresistant isolate possessed double mutations in DNA gyrase at positions Ser83 and Asp87 as well as a single mutation at Ser80 in parC. The top three serotypes identified, Salmonella Weltevreden (n = 41), Salmonella Newport (n = 13), and Salmonella Lexington (n = 11), were further characterized for genetic relatedness by pulsed-field gel electrophoresis. Fiftyfive distinct pulsed-field gel electrophoresis patterns were observed among the 65 isolates, indicating extensive genetic diversity among these Salmonella serotypes contaminating imported foods. C1 US FDA, CVM, Res Off, Div Anim & Food Microbiol, Laurel, MD 20708 USA. US FDA, Denver Dist Lab, Denver, CO 80225 USA. Colorado State Univ, Dept Anim Sci, Ft Collins, CO 80523 USA. RP White, DG (reprint author), US FDA, CVM, Res Off, Div Anim & Food Microbiol, 8401 Muirkirk Rd, Laurel, MD 20708 USA. EM dwhite@cvm.fda.gov NR 45 TC 37 Z9 38 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 MAR PY 2006 VL 69 IS 3 BP 500 EP 507 PG 8 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 019YA UT WOS:000235873300005 PM 16541678 ER PT J AU Thammasuvimol, G Seo, KH Song, KY Holt, PS Brackett, RE AF Thammasuvimol, G Seo, KH Song, KY Holt, PS Brackett, RE TI Optimization of ferrioxamine E concentration as effective supplementation for selective isolation of Salmonella enteritidis in egg white SO JOURNAL OF FOOD PROTECTION LA English DT Article ID SHELL EGGS; HENS EGG; ENRICHMENT MEDIA; GROWTH; IRON; PREENRICHMENT; INFECTION; ENTERICA; ALBUMIN AB Utilization of ferrioxamine E (FE) as a sole source of iron distinguishes Salmonella from a number of related species, including Escherichia coli. FE is not able to serve as a source of iron for E. coli or the Proteus-Providencia-Morganella group. This confers a selective advantage on Salmonella Enteritidis in egg white supplemented with FE. The optimum concentration of FE that promoted a selective advantage for Salmonella in egg white was determined. Four supplementation concentrations were evaluated (25, 50, 200, and 500 mu g/ml) in egg white artificially inoculated with proportionally mixed cultures of a rifampin-resistant strain of Salmonella Enteritidis (0.1 ml of 10(2) CFU/ml) and E. coli K-12 (0.1 ml of 10(1) through 10(8) CFU/ml). After a 24-h incubation at 37 degrees C, Salmonella and E. coli populations were enumerated. At higher concentrations of FE (> 50 mu g/ml), both Salmonella and E. coli were able to use the iron supplement (1 to 8.5 log CFU/ml and 1.8 to 8 log CFU/ml, respectively); however, lower FE concentrations (<= 50 mu g/ml) exclusively promoted Salmonella growth. Salmonella was unrecoverable without supplementation. This study indicates that optimum levels of FE supplementation in egg can improve the selective detection for Salmonella Enteritidis among other competitive organisms. C1 US FDA, Ctr Food Safety & Appl Nutr, Off Plant & Dairy Foods, College Pk, MD 20740 USA. USDA ARS, SE Poultry Res Lab, Athens, GA 30605 USA. RP Seo, KH (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Plant & Dairy Foods, 5100 Paint Branch Pkway, College Pk, MD 20740 USA. EM kseo@cfsan.fda.gov NR 18 TC 6 Z9 7 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 MAR PY 2006 VL 69 IS 3 BP 634 EP 638 PG 5 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 019YA UT WOS:000235873300023 PM 16541696 ER PT J AU Seo, KH Valentin-Bon, IE Brackett, RE AF Seo, KH Valentin-Bon, IE Brackett, RE TI Detection and enumeration of Salmonella Enteritidis in homemade ice cream associated with an outbreak: Comparison of conventional and real-time PCR methods SO JOURNAL OF FOOD PROTECTION LA English DT Article ID POLYMERASE-CHAIN-REACTION; RISK-ASSESSMENT; UNITED-STATES; SHELL EGGS; QUANTIFICATION; GENE; INFECTIONS; BACTERIA AB Salmonellosis caused by Salmonella Enteritidis (SE) is a significant cause of foodborne illnesses in the United States. Consumption of undercooked eggs and egg-containing products has been the primary risk factor for the disease. The importance of the bacterial enumeration technique has been enormously stressed because of the quantitative risk analysis of SE in shell eggs. Traditional enumeration methods mainly depend on slow and tedious most-probable-number (MPN) methods. Therefore, specific, sensitive, and rapid methods for SE quantitation are needed to collect sufficient data for risk assessment and food safety policy development. We previously developed a real-time quantitative PCR assay for the direct detection and enumeration of SE and, in this study, applied it to naturally contaminated ice cream samples with and without enrichment. The detection limit of the real-time PCR assay was determined with artificially inoculated ice cream. When applied to the direct detection and quantification of SE in ice cream, the real-time PCR assay was as sensitive as the conventional plate count method in frequency of detection. However, populations of SE derived from real-time quantitative PCR were approximately I log higher than provided by MPN and CFU values obtained by conventional culture methods. The detection and enumeration of SE in naturally contaminated ice cream can be completed in 3 h by this real-time PCR method, whereas the cultural enrichment method requires 5 to 7 days. A commercial immunoassay for the specific detection of SE was also included in the study. The real-time PCR assay proved to be a valuable tool that may be useful to the food industry in monitoring its processes to improve product quality and safety. C1 US FDA, Ctr Food Safety & Appl Nutr, Off Plant & Dairy Foods, College Pk, MD 20740 USA. RP Seo, KH (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Plant & Dairy Foods, 5100 Paint Branch Pkway, College Pk, MD 20740 USA. EM kseo@cfsan.fda.gov NR 23 TC 25 Z9 29 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 MAR PY 2006 VL 69 IS 3 BP 639 EP 643 PG 5 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 019YA UT WOS:000235873300024 PM 16541697 ER PT J AU DeFrancesco, JV Witkowski, MR Ciolino, LA AF DeFrancesco, JV Witkowski, MR Ciolino, LA TI GHB free acid: I. Solution formation studies and spectroscopic characterization by (HNMR)-H-1 and FT-IR SO JOURNAL OF FORENSIC SCIENCES LA English DT Article; Proceedings Paper CT 55th Annual Meeting of the American-Academy-of-Forensic-Sciences CY FEB 17-22, 2003 CL CHICAGO, IL SP Amer Acad Forens Sci DE forensic science; GHB free acid; gamma-hydroxybutyric acid; GHB; gamma-hydroxybutyrate; solution spectroscopic analysis; FT-IR; NMR; (HNMR)-H-1; GBL; interconversion; sodium oxybate ID GAMMA-HYDROXYBUTYRATE GHB; MASS-SPECTROMETRY; URINE; IDENTIFICATION; CHROMATOGRAPHY; GBL AB In forensic evidence, gamma-hydroxybutyric acid (GHB) has frequently been encountered in one of its salt forms (gamma-hydroxybutyrate), but has also been encountered in its free acid form (GHB). Owing to the physical properties, encounters of the free acid have been largely restricted to forensic exhibits comprising aqueous solutions, such as acidic beverages that have been "spiked" or formulated with GHB salts or gamma-butyrolactone (GBL). The analysis of GHB free acid presents particular difficulties including the potential for altering the original proportions of GHB free acid, GHB carboxylate, and GBL in the course of analysis, and discrimination between GHB free acid and carboxylate forms. In this work, the formation of GHB free acid in aqueous solutions (water and/or D2O) was studied as a function of solution pH. Proton nuclear magnetic resonance ((HNMR)-H-1) and Fourier-transform infrared spectrometry (FT-IR) measurements were obtained on freshly prepared mixtures of NaGHB and HCl stock solutions representing a series of points along the GHB titration curve. Both (HNMR)-H-1 and FT-IR were shown to track the changing proportions of GHB free acid and carboxylate forms as a function of pH, while simultaneously monitoring for the formation of the lactone (GBL). The results were consistent with acid-base conversion behavior for a carboxylic acid. (HNMR)-H-1 was shown to provide an ideal means for analysis of aqueous-based GHB/GBL forensic exhibits based on simple dilution of the neat liquid exhibit, without altering the original proportions of GHB free acid, carboxylate, and GBL in the samples. C1 US FDA, Forens Chem Ctr, Cincinnati, OH 45267 USA. US Drug Enforcement Adm, N Cent Reg Lab, Chicago, IL 60606 USA. RP Witkowski, MR (reprint author), US FDA, Forens Chem Ctr, 6751 Steger Dr, Cincinnati, OH 45267 USA. EM mwitkows@ora.fda.gov NR 28 TC 8 Z9 8 U1 1 U2 9 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-1198 J9 J FORENSIC SCI JI J. Forensic Sci. PD MAR PY 2006 VL 51 IS 2 BP 321 EP 329 DI 10.1111/j.1556-4029.2006.00073.x PG 9 WC Medicine, Legal SC Legal Medicine GA 019MV UT WOS:000235841900013 PM 16566765 ER PT J AU Witkowski, MR Ciolino, LA DeFrancesco, JV AF Witkowski, MR Ciolino, LA DeFrancesco, JV TI GHB free acid: II. Isolation and spectroscopic characterization for forensic analysis SO JOURNAL OF FORENSIC SCIENCES LA English DT Article; Proceedings Paper CT 55th Annual Meeting of the American-Academy-of-Forensic-Sciences CY FEB 17-22, 2003 CL CHICAGO, IL SP Amer Acad Forens Sci DE forensic science; GHB free acid; gamma-hydroxybutyric acid; GHB; gamma-hydroxybutyrate; spectroscopic analysis; isolation; FTIR; NMR; (HNMR)-H-1; GBL; interconversion; sodium oxybate ID GBL; INTERCONVERSION AB A reference standard for gamma-hydroxybutyric acid (GHB) free acid is not commercially available, making its analysis in forensic exhibits more difficult. GHB free acid is typically encountered in aqueous solution and in the presence of the lactone, gamma-butyrolactone (GBL), presenting difficulty in Fourier transform infrared (FT-IR) analysis. The strong infrared (IR) absorptivity of the GBL carbonyl band, the shifting of the GBL carbonyl band in aqueous solutions, and the position of the O-H bend for water can mask the main carbonyl band for GHB free acid. Model solutions of beta-hydroxybutyric acid (BHB) and GBL were studied in order to further understand the masking of the GHB free acid carbonyl band in FT-IR analysis. The use of second derivative FT-IR spectroscopy was shown to provide resolution of the free acid carbonyl band, and a presumptive test for GHB free acid was developed and applied. An extension of this work included preparing, for use as a standard reference material, small amounts (<= 10 mg) of GHB free acid. Preparation was based on the instantaneous reaction of GHB's sodium salt with a stoichiometric amount of hydrochloric acid in aqueous solution, and subsequent isolation of the free acid in neat liquid form. Both FT-IR and proton nuclear magnetic resonance spectra of the neat reference material were obtained and used to verify its identity. The isolation of GHB free acid from actual forensic exhibits is also presented, with identity confirmation using FT-IR. C1 US FDA, Forens Chem Ctr, Cincinnati, OH 45237 USA. US Drug Enforcement Adm, N Cent Reg Lab, Chicago, IL 60606 USA. RP Witkowski, MR (reprint author), US FDA, Forens Chem Ctr, 6751 Steger Dr, Cincinnati, OH 45237 USA. EM mwitkows@ora.fda.gov NR 18 TC 5 Z9 5 U1 0 U2 6 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-1198 J9 J FORENSIC SCI JI J. Forensic Sci. PD MAR PY 2006 VL 51 IS 2 BP 330 EP 339 DI 10.1111/j.1556-4029.2006.00074.x PG 10 WC Medicine, Legal SC Legal Medicine GA 019MV UT WOS:000235841900014 PM 16566766 ER PT J AU Hsia, CC Purcell, RH Farshid, M Lachenbruch, PA Yu, MYW AF Hsia, Chu Chieh Purcell, Robert H. Farshid, Mahmood Lachenbruch, Peter A. Yu, Mei-Ying W. TI Infectious dose of HBV in terms of copy number of DNA in human sera SO JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY LA English DT Meeting Abstract C1 Ctr Biol Evaluat & Res, Bethesda, MD USA. NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0815-9319 J9 J GASTROEN HEPATOL JI J. Gastroenterol. Hepatol. PD MAR PY 2006 VL 21 SU 2 BP A102 EP A102 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 179WG UT WOS:000247320400093 ER PT J AU Sheehan, KM Gulmann, C Barrett, HL Eichler, GS Kay, EW Liotta, LA Petricoin, EF AF Sheehan, KM Gulmann, C Barrett, HL Eichler, GS Kay, EW Liotta, LA Petricoin, EF TI Proteomic profiling of the epithelial and stromal components of matched normal and colonic carcinomas using protein microarrays SO JOURNAL OF PATHOLOGY LA English DT Meeting Abstract CT 189th Meeting of the Pathological-Society-of-Great-Britain-and-Ireland CY JAN 04-06, 2006 CL Robinson Coll, Cambridge, ENGLAND SP Patholog Soc Great Britain Ireland HO Robinson Coll C1 NCI, Pathol Lab, NCI FDA Clin Proteom Program, Bethesda, MD 20892 USA. RCSI & Beaumont Hosp, Dept Pathol, Dublin, Ireland. NCI, Mol Pharmacol Lab, Bethesda, MD 20892 USA. George Mason Univ, Ctr Appl Proteom & Mol Med, Manassas, VA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0022-3417 J9 J PATHOL JI J. Pathol. PD MAR PY 2006 VL 208 SU S BP 14A EP 14A PG 1 WC Oncology; Pathology SC Oncology; Pathology GA 019OU UT WOS:000235847400056 ER PT J AU Katchman, AN Koerner, J Tosaka, T Woosley, RL Ebert, SN AF Katchman, AN Koerner, J Tosaka, T Woosley, RL Ebert, SN TI Comparative evaluation of HERG currents and QT intervals following challenge with suspected torsadogenic and nontorsadogenic drugs SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID TORSADES-DE-POINTES; PNEUMOCYSTIS-CARINII PNEUMONIA; ISOLATED RABBIT HEART; ARSENIC TRIOXIDE; VENTRICULAR-TACHYCARDIA; CARDIAC REPOLARIZATION; PENTAMIDINE THERAPY; POTASSIUM CURRENTS; FEMALE GENDER; K+ CHANNELS AB The purpose of the present study was to comparatively evaluate human HERG currents and QT intervals following challenge with suspected torsadogenic and nontorsadogenic drugs. Various concentrations of 14 different drugs were initially evaluated in terms of their relative potency to block I HERG in stably transfected human embryonic kidney cells. Four general categories of drugs were identified: high-potency blockers ( IC50 < 0.1 mu M) included lidoflazine, terfenadine, and haloperidol; moderate-potency blockers ( 0.1 mu M < IC50 < 1 mu M) included sertindole, thioridazine, and prenylamine; low-potency blockers ( IC50 > 1 mu M) included propafenone, loratadine, pyrilamine, lovastatin, and chlorpheniramine; and ineffective blockers ( IC50 > 300 mu M) included cimetidine, pentamidine, and arsenic trioxide. All measurements were performed using similar conditions and tested acute drug effects only ( < 30 min of drug exposure per measurement). Since two of the drugs that were ineffective I HERG blockers, arsenic trioxide and pentamidine, have been associated with cardiac repolarization delays ( QT interval lengthening) and torsades de pointes ventricular arrhythmias in patients, we chose to evaluate them further using the isolated perfused rabbit heart model. Neither arsenic trioxide nor pentamidine had any significant effect on QT intervals in this model, even at relatively high ( micromolar) concentrations. Similar results were obtained for loratadine in this model. When the hearts were challenged with a known torsadogenic drug such as cisapride, significant QT lengthening was rapidly induced. These results demonstrate that arsenic trioxide and pentamidine are essentially devoid of direct acute effects on cardiac repolarization or inhibition of I-HERG. C1 Univ Cent Florida, Biomol Sci Ctr, Orlando, FL 32816 USA. Georgetown Univ, Med Ctr, Dept Pharmacol, Washington, DC 20007 USA. US FDA, Rockville, MD 20857 USA. C Path Inst, Tucson, AZ USA. RP Ebert, SN (reprint author), Univ Cent Florida, Biomol Sci Ctr, 4000 Cent Florida Blvd,Bldg 20 BMS, Orlando, FL 32816 USA. EM ebert@mail.ucf.edu OI Woosley, Raymond L./0000-0002-2588-328X FU AHRQ HHS [U18 HS010385]; NHLBI NIH HHS [HL58743] NR 39 TC 81 Z9 83 U1 1 U2 5 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD MAR PY 2006 VL 316 IS 3 BP 1098 EP 1106 DI 10.1124/jpet.105.093393 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 014JM UT WOS:000235476000016 PM 16278312 ER PT J AU DeVeaugh-Geiss, J March, J Shapiro, M Andreason, PJ Emslie, G Ford, LM Greenhill, L Murphy, D Prentice, E Roberts, R Silva, S Swanson, JM Van Zwieten-Boot, B Vitiello, B Wagner, KD Mangum, B AF DeVeaugh-Geiss, J March, J Shapiro, M Andreason, PJ Emslie, G Ford, LM Greenhill, L Murphy, D Prentice, E Roberts, R Silva, S Swanson, JM Van Zwieten-Boot, B Vitiello, B Wagner, KD Mangum, B TI Child and adolescent psychopharmacology in the new millennium: A workshop for academia, industry, and government SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE pediatric psychopharmacology; pediatric depression; psychopharmacology trials; pediatric research equity act; best pharmaceuticals for children act ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; PEDIATRIC PSYCHOPHARMACOLOGY; PSYCHOTROPIC MEDICATIONS; INDIVIDUAL SUBJECTS; CONTROLLED-TRIAL; CLINICAL-TRIALS; PATTERNS; PLACEBO; SAFETY; METHYLPHENIDATE AB Objective: To give academic researchers, government officials, and industry scientists an opportunity to assess the state of pediatric psychopharmacology and identify challenges facing professionals in the field. Method: Increased federal spending and the introduction of pediatric exclusivity led to large increases in pediatric psychopharmacology research in the 1990s. Despite the increase in research, concerns exist about methods and incentives for making new medications available for use in pediatric psychiatric disorders. In recognition of these concerns, the Duke Clinical Research Institute held a roundtable in September 2004. Participants from the National Institutes of Health, regulatory agencies, academia, and the pharmaceutical industry spoke about the effects of government regulations such as the U.S. Food and Drug Administration Modernization Act and the Pediatric Research Equity Act on pediatric research from academic, clinical, and industry perspectives, and bioethical considerations of such research. Conclusions: To ensure development of new drugs for treating psychiatric disorders in children and adolescents, we must address the challenges posed by the regulatory environment governing pediatric psychopharmacology research. Strategies were identified for improving the evidence base for psychopharmacologic interventions in youth before widespread use and for more effectively defining a research agenda for the future. C1 Duke Clin Res Inst, Durham, NC 27715 USA. US FDA, Rockville, MD 20857 USA. Univ Texas, SW Med Ctr, Dallas, TX 75230 USA. Johnson & Johnson Consumer Prod Inc, Titusville, NJ USA. New York State Psychiat Inst & Hosp, New York, NY 10032 USA. Univ Nebraska Med Ctr, Omaha, NE 68198 USA. Univ Calif Irvine, Irvine, CA USA. Committee Med Prod Human Use Med Evaluat Board, The Hague, Netherlands. NIMH, Bethesda, MD 20892 USA. Univ Texas, Med Branch, Galveston, TX 77550 USA. RP DeVeaugh-Geiss, J (reprint author), Duke Clin Res Inst, POB 17969, Durham, NC 27715 USA. EM BRAINSTORMCNS@aol.com NR 38 TC 21 Z9 21 U1 3 U2 5 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 MAR PY 2006 VL 45 IS 3 BP 261 EP 270 DI 10.1097/01.chi.0000194568.70912.ee PG 10 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 017VZ UT WOS:000235722700001 PM 16540810 ER PT J AU Khurana, S Needham, J Mathieson, B Rodriguez-Chavez, IR Catanzaro, AT Bailer, RT Kim, J Polonis, V Cooper, DA Guerin, J Peterson, ML Gurwith, M Nguyen, N Graham, BS Golding, H AF Khurana, S Needham, J Mathieson, B Rodriguez-Chavez, IR Catanzaro, AT Bailer, RT Kim, J Polonis, V Cooper, DA Guerin, J Peterson, ML Gurwith, M Nguyen, N Graham, BS Golding, H CA HIV Vaccine Trial Network TI Human immunodeficiency virus (HIV) vaccine trials: a novel assay for differential diagnosis of HIV infections in the face of vaccine-generated antibodies SO JOURNAL OF VIROLOGY LA English DT Article ID EFFICACY TRIALS; CLINICAL-TRIALS; LESSONS; DISCRIMINATION; VOLUNTEERS; RESPONSES AB All current human immunodeficiency virus (HfV) vaccine candidates contain multiple viral components and elicit antibodies that react positively in licensed HIV diagnostic tests, which contain similar viral products. Thus, vaccine trial participants could be falsely diagnosed as infected with HIV. Additionally, uninfected, seropositive vaccinees may encounter long-term social and economic harms. Moreover, this also interferes with early detection of true HIV infections during preventive HIV vaccine trials. An HIV-seropositive test result among uninfected vaccine trial participants is a major public health concern for volunteers who want to participate in future HIV vaccine trials. Based on the increased number of HIV vaccines being tested globally, it is essential to differentiate vaccine- from virus-induced antibodies. Using a whole-HIV-genome phage display library, we identified conserved sequences in Env-gp41 and Gag-p6 which are recognized soon after infection, do not contain protective epitopes, and are not part of most current HIV vaccines. We established a new HIV serodetection assay based on these peptides. To date, this assay, termed HIV-SELECTEST, demonstrates > 99% specificity and sensitivity. Importantly, in testing of plasma samples from multiple HIV vaccine trials, uninfected trial participants scored negative, while all intercurrent infections were detected within I to 3 months of HIV infection. The new HIV-SELECTEST is a simple but robust diagnostic tool for easy implementation in HIV vaccine trials and blood banks worldwide. C1 Ctr Biol Evaluat & Res, Div Viral Prod, FDA, Bethesda, MD 20892 USA. Ctr Biol Evaluat & Res, Core Facil, FDA, Bethesda, MD 20892 USA. NIH, Off AIDS Res, Bethesda, MD 20892 USA. NIAID, Vaccine Clin Res Branch, Div AIDS, NIH, Bethesda, MD 20892 USA. NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. USAMC, Armed Forces Res Inst Med Sci, APO, AP 96546 USA. US Mil HIV Res Program, Rockville, MD 20850 USA. Univ New S Wales, Natl Ctr HIV Epidemiol & Clin Res, Sydney, NSW 2010, Australia. VaxGen Inc, Brisbane, CA 94005 USA. RP Golding, H (reprint author), Ctr Biol Evaluat & Res, Div Viral Prod, FDA, Bethesda, MD 20892 USA. EM goldingh@cber.FDA.gov NR 13 TC 21 Z9 25 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAR PY 2006 VL 80 IS 5 BP 2092 EP 2099 DI 10.1128/JVI.80.5.2092-2099.2006 PG 8 WC Virology SC Virology GA 013CY UT WOS:000235388400003 PM 16474117 ER PT J AU Yakovenko, ML Cherkasova, EA Rezapkin, GV Ivanova, OE Ivanov, AP Eremeeva, TP Baykova, OY Chumakov, KM Agol, VI AF Yakovenko, ML Cherkasova, EA Rezapkin, GV Ivanova, OE Ivanov, AP Eremeeva, TP Baykova, OY Chumakov, KM Agol, VI TI Antigenic evolution of vaccine-derived polioviruses: Changes in individual epitopes and relative stability of the overall immunological properties SO JOURNAL OF VIROLOGY LA English DT Article ID IMMUNODEFICIENT PATIENT; TYPE-3 POLIOVIRUS; SABIN STRAIN; GENETIC STABILITY; RECEPTOR; NEUTRALIZATION; CIRCULATION; SENSITIVITY; NUCLEOTIDE; EXCRETION AB The Sabin oral poliovirus vaccine (OPV) readily undergoes changes in antigenic sites upon replication in humans. Here, a set of antigenically altered descendants of the three OPV serotypes (76 isolates) was characterized to determine the driving forces behind these changes and their biological implications. The amino acid residues of OPV derivatives that lie within or close to the known antigenic sites exhibited a marked tendency to be replaced by residues characteristic of homotypic wild polioviruses, and these changes may occur very early in OPV evolution. The specific amino acid alterations nicely correlated with serotype-specific changes in the reactivity of certain individual antigenic sites, as revealed by the recently devised monoclonal antibody-based enzyme-linked immunosorbent assay. In comparison to the original vaccine, small changes, if any, in the neutralizing capacity of human or rabbit sera were observed in highly diverged vaccine polioviruses of three serotypes, in spite of strong alterations of certain epitopes. We propose that the common antigenic alterations in evolving OPV strains largely reflect attempts to eliminate fitness-decreasing mutations acquired either during the original selection of the vaccine or already present in the parental strains. Variability of individual epitopes does not appear to be primarily caused by, or lead to, a significant immune evasion, enhancing only slightly, if at all, the capacity of OPV derivatives to overcome immunity in human populations. This study reveals some important patterns of poliovirus evolution and has obvious implications for the rational design of live viral vaccines. C1 US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. Moscow MV Lomonosov State Univ, AN Belozersky Inst Phys Chem Biol, Moscow 119899, Russia. Russian Acad Med Sci, MP Chumakov Inst Poliomyelitis & Viral Encephalit, Moscow 142782, Russia. RP Chumakov, KM (reprint author), US FDA, Ctr Biol Evaluat & Res, 1401 Rockville Pike,HFM-470, Rockville, MD 20852 USA. EM chumakov@cber.fda; agol@belozersky.msu.ru RI Agol, Vadim/E-1941-2013; OI Ivanova, O.E./0000-0003-1784-4827 NR 71 TC 30 Z9 31 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 MAR PY 2006 VL 80 IS 6 BP 2641 EP 2653 DI 10.1128/JVI.80.6.2641-2653.2006 PG 13 WC Virology SC Virology GA 023MS UT WOS:000236131400006 PM 16501074 ER PT J AU Hampshire, V AF Hampshire, Victoria TI Veterinarian turns relief worker SO LAB ANIMAL LA English DT Editorial Material C1 US FDA, Rockville, MD 20857 USA. RP Hampshire, V (reprint author), US FDA, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0093-7355 J9 LAB ANIMAL JI Lab Anim. PD MAR PY 2006 VL 35 IS 3 BP 43 EP 43 PG 1 WC Veterinary Sciences SC Veterinary Sciences GA 070TB UT WOS:000239545900010 PM 16505826 ER PT J AU O'Hanlon, TP Carrick, DM Targoff, IN Arnett, FC Reveille, JD Carrington, M Gao, AJ Oddis, CV Morel, PA Malley, JD Malley, K Shamim, EA Rider, LG Chanock, SJ Foster, CB Bunch, T Blackshear, PJ Plotz, PH Love, LA Miller, FW AF O'Hanlon, TP Carrick, DM Targoff, IN Arnett, FC Reveille, JD Carrington, M Gao, AJ Oddis, CV Morel, PA Malley, JD Malley, K Shamim, EA Rider, LG Chanock, SJ Foster, CB Bunch, T Blackshear, PJ Plotz, PH Love, LA Miller, FW TI Immunogenetic risk and protective factors for the idiopathic inflammatory myopathies - Distinct HLA-A -B, -Cw,-DRB1, and-DQA1 allelic profiles distinguish European American patients with different myositis autoantibodies SO MEDICINE LA English DT Article ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; TRANSFER RNA-SYNTHETASES; INCLUSION-BODY MYOSITIS; GENE-EXPRESSION DATA; CLASS-II ALLELES; AUTOIMMUNE-DISEASES; RHEUMATOID-ARTHRITIS; ANTI-JO-1 ANTIBODIES; CLASSIFICATION; ASSOCIATION AB The idiopathic inflammatory myopathies (IIM) are systemic connective tissue diseases defined by chronic muscle inflammation and weakness associated with autoimmunity. We have performed low to high resolution Molecular typing to assess the genetic variability of major histocompatibility complex loci (HLA-A. -B, -Cw, -DRB1, and -DQA1) in a large population of European American patients with IIM (n = 571) representing the major myositis autoantibody groups. We established that alleles of the 8.1 ancestral haplotype (8.1 AH) are important risk factors for the development of IIM in patients producing anti-synthetase/anti-Jo-1, -La, -PM/Scl, and -Ro autoantibodies. Moreover, a random forests classification analysis suggested that 8.1 AH-associated alleles B*0801 and DRB1*0301 are the principal HLA risk markers. In addition, we have identified several novel HLA susceptibility factors associated distinctively with particular myositis-specific (MSA) and myositis-associated autoantibody (MAA) groups of the IIM. IIM patients with anti-PL-7 (anti-threonyl-tRNA synthetase) autoantibodies have a unique HLA Class 1 risk allele, Cw*0304 (pcorr = 0.046), and lack the 8.1 AH markers associated with other anti-synthetase autoantibodies (for example, anti-Jo-1 and anti-PL-12). In addition, HLA-B*5001 and DQA1*0104 are novel potential risk factors among anti-signal recognition particle autoantibody-positive IIM patients (pcorr = 0.024 and p 0.010, respectively). Among those patients with MAA, HLA DRB1*11 and DQA1*06 alleles were identified as risk factors for myositis patients with anti-Ku (pcorr = 0.041) and anti-La (pcorr = 0.023) autoantibodies, respectively. Amino acid sequence analysis of the FILA DRB1 third hypervariable region identified a consensus motif, D-70 (hydrophilic)/R-71 (basic)/(14)A (hydrophobic), conferring protection among patients producing ailti-synthetase/anti-Jo-1 and -PM/Scl autoantibodies. Together, these data demonstrate that HLA signatures, comprising both risk and protective alleles or motifs, distinguish IIM patients with different myositis autoantibodies and may have diagnostic and pathogenic implications. Variations in associated polymorphisims for these immune response genes may reflect divergent pathogenic mechanisms and/or responses to unique environmental triggers in different groups of subjects resulting in the heterogeneous syndromes of the IIM. C1 Natl Inst Environm Hlth Sci, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NIH, Dept Hlth & Human Serv, Ctr Informat Technol, Bethesda, MD 20892 USA. NCI, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. Natl Inst Arthritis & Musculoskeletal Dis, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. Univ Oklahoma, Hlth Sci Ctr, Vet Affairs Med Ctr, Norman, OK 73019 USA. Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USA. Univ Texas, Hlth Sci Ctr, Houston, TX USA. SAIC Frederick Natl Canc Inst, Basic Res Program, Frederick, MD USA. Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. Malley Res Programming Inc, Rockville, MD USA. Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21205 USA. Mayo Clin, Rochester, MN USA. US FDA, Rockville, MD 20857 USA. RP O'Hanlon, TP (reprint author), Natl Inst Environm Hlth Sci, NIH, Dept Hlth & Human Serv, 9 Mem Dr,Room 1W101,MSC 0958, Bethesda, MD 20892 USA. EM ohanlont@niehs.nih.gov OI Rider, Lisa/0000-0002-6912-2458; Miller, Frederick/0000-0003-2831-9593; Morel, Penelope/0000-0002-1743-3676 FU Intramural NIH HHS NR 55 TC 73 Z9 73 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7974 J9 MEDICINE JI Medicine (Baltimore) PD MAR PY 2006 VL 85 IS 2 BP 111 EP 127 DI 10.1097/01.md.0000217525.82287.eb PG 17 WC Medicine, General & Internal SC General & Internal Medicine GA 032XG UT WOS:000236809100006 PM 16609350 ER PT J AU Salotra, P Duncan, RC Singh, R Raju, BVS Sreenivas, G Nakhasi, HL AF Salotra, P Duncan, RC Singh, R Raju, BVS Sreenivas, G Nakhasi, HL TI Upregulation of surface proteins in Leishmania donovani isolated from patients of post kala-azar dermal leishmaniasis SO MICROBES AND INFECTION LA English DT Article DE PKDL; visceral leishmaniasis; Leishmania donovani; genomic microarray ID PREDICT SUBSEQUENT DEVELOPMENT; DNA MICROARRAY ANALYSIS; GENE-EXPRESSION; VISCERAL LEISHMANIASIS; PERIPHERAL-BLOOD; PROTEASE MSP; LIFE-CYCLE; CELLS; CHAGASI; FAMILY AB Five to fifteen percent of visceral leishmaniasis (VL) patients in India develop post kala-azar dermal leishmaniasis (PKDL), usually 1-2 years after apparent clinical cure. There is evidence pointing to a role played by the host immune responses in the disease pathogenesis, however, the contribution of changes in parasite gene expression has not been explored. Highly sensitive gene expression microarray technology was employed to identify genes that are differentially expressed in Leishmania parasites isolated from PKDL patients in comparison with those from VL. Hybridization on Leishmania donovani genomic microarray comprised of unique clones allowed us to identify 46/2268 (2%) clones that showed statistically significant (P < 0.05) changes in expression (1.5-3.5-fold) in parasites of PKDL origin compared to those of VL origin. Sequence analysis of six genomic clones, consistently showing approximately 2-fold higher expression in PKDL parasites, revealed significant homology with gp63, gp46, putative amastin, a putative reductase and a possible calpain-like protein. The gene products showing upregulated expression in PKDL isolates may be candidates playing a role in the altered clinical manifestation in PKDL. Such differentially expressed genes hold the key to understanding the parasite genetic factors that contribute to the persistence after clinical cure of VL. (c) 2005 Elsevier SAS. All rights reserved. C1 ICMR, Inst Pathol, Mol Biol Lab, New Delhi, India. US FDA, Ctr Biol Evaluat & Res, Div Emerging & Transfus Transmitted Dis, Bethesda, MD 20014 USA. RP Salotra, P (reprint author), ICMR, Inst Pathol, Mol Biol Lab, Safdarjung Hosp Campus, New Delhi, India. EM salotra@vsnl.com OI Singh, Ruchi/0000-0001-8094-4703 NR 35 TC 30 Z9 33 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1286-4579 J9 MICROBES INFECT JI Microbes Infect. PD MAR PY 2006 VL 8 IS 3 BP 637 EP 644 DI 10.1016/j.micinf.2005.08.018 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 045PL UT WOS:000237754000007 PM 16469521 ER PT J AU Collazo, CM Sher, A Meierovics, AI Elkins, KL AF Collazo, CM Sher, A Meierovics, AI Elkins, KL TI Myeloid differentiation factor-88 (MyD88) is essential for control of primary in vivo Francisella tularensis LVS infection, but not for control of intramacrophage bacterial replication SO MICROBES AND INFECTION LA English DT Article DE Francisella tularensis; immunology; bacterial infections; toll-like receptors ID TOLL-LIKE RECEPTORS; CELL-MEDIATED-IMMUNITY; LIVE VACCINE STRAIN; INTERFERON-GAMMA; LISTERIA-MONOCYTOGENES; CUTTING EDGE; PROTECTIVE IMMUNITY; INTRACELLULAR BACTERIA; STAPHYLOCOCCUS-AUREUS; MYD88-DEFICIENT MICE AB The means by which Francisella turlarensis, the causative agent of tularemia, are recognized by mammalian immune systems are poorly understood. Here we wished to explore the contribution of the MyD88/Toll-like receptor signaling pathway in initiating murine responses to F. tularensis Live Vaccine Strain (LVS). MyD88 knockout (KO) mice, but not TLR2-, TLR4- or TLR9-deficient mice, rapidly succumbed following in vivo bacterial infection via the intradermal route even with a very low dose of LVS (5 x 10) that was 100,000-fold less than the LD50 of normal wild-type (WT) mice. By day 5 after LVS infection, bacterial organ burdens were 5-6 logs higher in MyD88 knockout mice; further, unlike infected WT mice, levels of interferon-y in the sera of LVS-infected MyD88 KO were undetectable. An in vitro culture system was used to assess the ability of bone marrow macrophages derived from either KO or WT mice to support bacterial growth, or to control intracellular bacterial replication when co-cultured with immune lymphocytes. In this assay, bacterial replication was similar in macrophages derived from either WT or any of the TLR KO mice. Bacterial growth was controlled in co-cultures containing macrophages from MyD88 KO mice or TLR KO mice as well as in co-cultures containing immune WT splenic lymphocytes and WT macrophages. Further, MyD88-deficient LVS-immune splenocytes controlled intracellular growth comparably to those from normal mice. Thus MyD88 is essential for innate host resistance to LVS infection, but is not required for macrophage control of intracellular bacterial growth. Published by Elsevier SAS. C1 US FDA, Ctr Biol Evaluat & Res, Div Bacterial Parasit & Allergen Prod, Lab Mycobacterial Dis & Cellular Immunol, Rockville, MD 20852 USA. NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Elkins, KL (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Bacterial Parasit & Allergen Prod, Lab Mycobacterial Dis & Cellular Immunol, 1401 Rockville Pike,HFM 431, Rockville, MD 20852 USA. EM karen.elkins@fda.hhs.gov NR 55 TC 50 Z9 51 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1286-4579 J9 MICROBES INFECT JI Microbes Infect. PD MAR PY 2006 VL 8 IS 3 BP 779 EP 790 DI 10.1016/j.micinf.2005.09.014 PG 12 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 045PL UT WOS:000237754000023 PM 16513388 ER PT J AU Hu, L McDaniel, JP Kopecko, DJ AF Hu, L McDaniel, JP Kopecko, DJ TI Signal transduction events involved in human epithelial cell invasion by Campylobacter jejuni 81-176 SO MICROBIAL PATHOGENESIS LA English DT Article DE signal transduction; invasion; Campylobacter jejuni; epithelial cells; phosphorylation; G protein ID HUMAN INTESTINAL-CELLS; CAMPYLOBACTER-JEJUNI; CYTOKINE PRODUCTION; INT-407 CELLS; SALMONELLA-TYPHIMURIUM; LISTERIA-MONOCYTOGENES; ADENYLATE-CYCLASE; PERTUSSIS TOXIN; PROTEIN; KINASE AB Analyses of invasive enteric bacteria (e.g. Shigella, Salmonella, Listeria, and Campylobacter) have shown that these pathogens initiate orchestrated signal transduction cascades in host cells leading to host cytoskeletal rearrangements that result in bacterial uptake. This current study was specifically aimed at examining the involvement of host membrane caveolae and certain protein kinases in epithelial cell invasion by C jejuni strain 81-176, for which we have previously characterized the kinetics of entry and a unique microtubule-dependent mechanism of internalization. Utilizing in vitro cultured cell invasion assays with a gentamicin-kill step, disruption of membrane caveolae, by pretreatment of INT407 cell monolayers with filipin III reduced C jejuni 81-176 entry by >95%. Strain 81-176 uptake into INT407 cells was markedly inhibited by monolayer pretreatment with the protein kinase inhibitors genistein and staurosporine, or specific inhibitors of PI 3-kinase, wortmannin and LY294002. Western blot analysis using monoclonal anti-protein tyrosine phosphorylation antibody revealed distinctive changes during invasion in phosphorylation of at least nine proteins. Further inhibitor studies indicated that heterotrimeric G proteins, plus ERK and p38 MAP kinase activation are also involved in C jejuni 81-176 invasion. These results suggest that C. jejuni 81-176 interact at host cell surface membrane caveolae with G protein-coupled receptors, which presumably trigger G-proteins and kinases to activate host proteins including PI 3-kinase and MAP kinases, that appear to be intimately involved in the events controlling 81-176 internalization. C1 US FDA, Lab Enter & Sexually Transmitted Dis, Ctr Biol Evaluat & Res, NIH, Bethesda, MD 20892 USA. RP Kopecko, DJ (reprint author), US FDA, Lab Enter & Sexually Transmitted Dis, Ctr Biol Evaluat & Res, NIH, Campus Bldg 29-420,29 Lincoln Dr, Bethesda, MD 20892 USA. EM kopecko@cber.fda.gov NR 37 TC 44 Z9 46 U1 2 U2 5 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0882-4010 J9 MICROB PATHOGENESIS JI Microb. Pathog. PD MAR PY 2006 VL 40 IS 3 BP 91 EP 100 DI 10.1016/j.micpath.2005.11.004 PG 10 WC Immunology; Microbiology SC Immunology; Microbiology GA 019FL UT WOS:000235820900001 PM 16426812 ER PT J AU Patsner, B AF Patsner, Bruce TI Expert witnesses: Perpetuating a flawed system and ethical issues related to medical expert testimony SO OBSTETRICS AND GYNECOLOGY LA English DT Letter C1 US FDA, CDER, DRUP, Silver Spring, MD USA. RP Patsner, B (reprint author), US FDA, CDER, DRUP, Silver Spring, MD USA. NR 2 TC 0 Z9 0 U1 0 U2 0 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 MAR PY 2006 VL 107 IS 3 BP 739 EP 739 DI 10.1097/01.AOG.0000203433.20622.86 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 095GJ UT WOS:000241295900032 PM 16507950 ER PT J AU Schnackenberg, LK Jones, RC Thyparambil, S Taylor, JT Han, T Tong, WD Hansen, DK Fuscoe, JC Edmondson, RD Beger, RD Dragan, YP AF Schnackenberg, LK Jones, RC Thyparambil, S Taylor, JT Han, T Tong, WD Hansen, DK Fuscoe, JC Edmondson, RD Beger, RD Dragan, YP TI An integrated study of acute effects of valproic acid in the liver using metabonomics, proteomics, and transcriptomics platforms SO OMICS-A JOURNAL OF INTEGRATIVE BIOLOGY LA English DT Article ID TANDEM MASS-SPECTROMETRY; SYSTEMS BIOLOGY; SHOTGUN PROTEOMICS; METABOLISM; MICROARRAY; IDENTIFICATION; MITOCHONDRIA; TECHNOLOGY; EXCRETION; DISCOVERY AB An integrated omics approach was undertaken in order to elucidate a systems biology level understanding of the acute hepatotoxcity of valproic acid (VPA). Metabonomics, proteomics and gene expression microarray platforms were employed in this systems biology study. CD-1 female pregnant mice were injected subcutaneously with 600 mg/kg VPA or vehicle control. Urine, serum, and liver tissue were collected at 6, 12, and 24 h after dosing. Principal component analysis (PCA) of the metabonomics data showed clustering of the dosed groups away from the controls for the urine samples. Looser clustering was seen in the other sample sets investigated. However, VPA administration resulted in altered glucose concentrations in urine samples at 12 and 24 h and in aqueous liver tissue extracts at 12 h after VPA administration. Proteomics studies identified two proteins, glycogen phosphorylase and amylo-1,6-glucosidase, which were increased in dosed animals relative to control. Both of these proteins are involved in converting glycogen to glucose. Examination of the expression of 20,000 liver genes did not reveal significantly altered expression at 6, 12, or 24 h after VPA exposure. The combined studies indicated a perturbation in the glycogenolysis pathway following administration of VPA. C1 US FDA, Natl Ctr Toxicol Res, Div Syst Toxicol, Jefferson, AR 72079 USA. US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. Univ Arkansas Med Sci, Dept Biochem & Mol Biol, Little Rock, AR 72205 USA. RP Beger, RD (reprint author), US FDA, Natl Ctr Toxicol Res, Div Syst Toxicol, Jefferson, AR 72079 USA. EM Richard.Beger@fda.hhs.gov NR 40 TC 35 Z9 38 U1 1 U2 13 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1536-2310 J9 OMICS JI OMICS PD MAR PY 2006 VL 10 IS 1 BP 1 EP 14 DI 10.1089/omi.2006.10.1 PG 14 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 055UK UT WOS:000238475800001 PM 16584314 ER PT J AU Anand, KJS Aranda, JV Berde, CB Buckman, S Capparelli, EV Carlo, W Hummel, P Johnston, CC Lantos, J Tutag-Lehr, V Lynn, AM Maxwell, LG Oberlander, TF Raju, TNK Soriano, SG Taddio, A Walco, GA AF Anand, KJS Aranda, JV Berde, CB Buckman, S Capparelli, EV Carlo, W Hummel, P Johnston, CC Lantos, J Tutag-Lehr, V Lynn, AM Maxwell, LG Oberlander, TF Raju, TNK Soriano, SG Taddio, A Walco, GA TI Summary proceedings from the neonatal pain-control group SO PEDIATRICS LA English DT Article; Proceedings Paper CT Newborn Drug Development Initiative Workshop CY MAR 29-30, 2004 CL Baltimore, MD SP NICHD, FDA DE pain; neonate; Newborn Drug Development Initiative; analgesia; anesthesia ID LOW-BIRTH-WEIGHT; SYSTEMIC CLEARANCE PATHWAYS; RANDOMIZED CONTROLLED-TRIAL; INTENSIVE-CARE-UNIT; BLOOD-FLOW VELOCITY; POSTOPERATIVE PAIN; NEWBORN-INFANTS; PRETERM INFANTS; PREMATURE-INFANTS; PROCEDURAL PAIN AB Recent advances in neurobiology and clinical medicine have established that the fetus and newborn may experience acute, established, and chronic pain. They respond to such noxious stimuli by a series of complex biochemical, physiologic, and behavioral alterations. Studies have concluded that controlling pain experience is beneficial with respect to short-term and perhaps long-term outcomes. Yet, pain-control measures are adopted infrequently because of unresolved scientific issues and lack of appreciation for the need for control of pain and its long-term sequelae during the critical phases of neurologic maturation in the preterm and term newborn. The neonatal pain-control group, as part of the Newborn Drug Development Initiative (NDDI) Workshop I, addressed these concerns. The specific issues addressed were (1) management of pain associated with invasive procedures, (2) provision of sedation and analgesia during mechanical ventilation, and (3) mitigation of pain and stress responses during and after surgery in the newborn infant. The cross-cutting themes addressed within each category included (1) clinical-trial designs, (2) drug prioritization, (3) ethical constraints, (4) gaps in our knowledge, and (5) future research needs. This article provides a summary of the discussions and deliberations. Full-length articles on procedural pain, sedation and analgesia for ventilated infants, perioperative pain, and study designs for neonatal pain research were published in Clinical Therapeutics (June 2005). C1 Univ Arkansas Med Sci, Dept Pediat, Little Rock, AR 72205 USA. Univ Arkansas Med Sci, Dept Anesthesiol, Little Rock, AR 72205 USA. Univ Arkansas Med Sci, Dept Neurobiol, Little Rock, AR 72205 USA. Univ Arkansas Med Sci, Dept Pharmacol, Little Rock, AR 72205 USA. Wayne State Univ, Childrens Hosp Michigan, Dept Pediat Pharmacol & Pharmaceut Sci, Detroit, MI USA. Wayne State Univ, Childrens Hosp Michigan, Eugene Applebaum Sch Pharm & Hlth Sci, Dept Pharmaceut, Detroit, MI USA. Harvard Univ, Sch Med, Dept Anaesthesia, Div Pain Med, Boston, MA USA. Harvard Univ, Sch Med, Dept Pediat, Div Pain Med, Boston, MA USA. Harvard Univ, Sch Med, Childrens Hosp Boston, Dept Anesthesiol, Boston, MA USA. US FDA, Ctr Drug Evaluat & Res, Off Counter Terrorism & Pediat Drug Dev, Rockville, MD 20857 USA. Univ Calif San Diego, Dept Pediat, Pediat Pharmacol Res Unit, La Jolla, CA 92093 USA. Univ Alabama, Dept Pediat, Birmingham, AL USA. Loyola Univ, Med Ctr, Dev Follow Up Program, Maywood, IL 60153 USA. McGill Univ, Sch Nursing, Montreal, PQ, Canada. Univ Chicago, Dept Pediat, MacLean Ctr Clin Med Eth, Robert Wood Johnson Clin Scholars Program, Chicago, IL 60637 USA. Univ Chicago, Dept Med, MacLean Ctr Clin Med Eth, Robert Wood Johnson Clin Scholars Program, Chicago, IL 60637 USA. Univ Washington, Sch Med, Childrens Hosp & Reg Med Ctr, Dept Anesthesiol & Pediat, Seattle, WA USA. Univ Penn, Childrens Hosp Philadelphia, Dept Anesthesiol, Philadelphia, PA 19104 USA. Univ British Columbia, BC Childrens Hosp, Div Dev Pediat, Vancouver, BC V5Z 1M9, Canada. NICHHD, Pregnancy & Perinatol Branch, Ctr Dev Biol & Perinatal Med, Rockville, MD USA. Hosp Sick Children, Dept Pharm, Toronto, ON M5G 1X8, Canada. Hosp Sick Children, Populat Hlth Sci Res Inst, Toronto, ON M5G 1X8, Canada. Univ Med & Dent New Jersey, Hackensack Univ Med Ctr, Dept Pediat, Newark, NJ USA. RP Anand, KJS (reprint author), Arkansas Childrens Hosp, Slot 900,800 Marshall St, Little Rock, AR 72202 USA. EM anandsunny@uams.edu OI Anand, Kanwaljeet/0000-0001-6498-1483 FU NICHD NIH HHS [R01 HD36484] NR 169 TC 104 Z9 112 U1 2 U2 9 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD MAR PY 2006 VL 117 IS 3 SU S BP S9 EP S22 DI 10.1542/peds.2005-0620C PG 14 WC Pediatrics SC Pediatrics GA 017XT UT WOS:000235727300002 PM 16777824 ER PT J AU Giacoia, GP Birenbaum, DL Sachs, HC Mattison, DR AF Giacoia, GP Birenbaum, DL Sachs, HC Mattison, DR TI The Newborn Drug Development Initiative - Introduction SO PEDIATRICS LA English DT Editorial Material DE clinical research/trials; neonatology; clinical-trial design ID NEONATAL INTENSIVE-CARE; METABOLIZING-ENZYMES; PRETERM INFANTS; ANESTHETIC AGENTS; RENAL-FUNCTION; DELIVERY; PHARMACOKINETICS; ONTOGENY; BRAIN; SERUM AB The Best Pharmaceuticals for Children Act (BPCA; Pub L 107-109) was enacted in January 2002 and will sunset in October 2007. The BPCA established processes for studying off-patent and on-patent drugs that are used in pediatric population. Although some drugs have been successfully developed for the neonate (eg, surfactant, nitric oxide), drug development for the youngest, least mature, and most vulnerable pediatric patients is generally lacking. Most drugs are empirically administered to newborns once efficacy has been demonstrated in adults and usefulness is suspected or demonstrated in the older pediatric population. Unfortunately, this process undermines the ability to perform the appropriate studies necessary to demonstrate a drug's short- and long-term safety and efficacy and establish appropriate dosing in neonates. The Newborn Drug Development Initiative Workshop I (held March 29-30, 2004) specifically addressed scientific, clinical, and ethical concerns in the development of trials of pediatric therapeutic agents for neonates. Implementation of the BPCA for all pediatric populations will foster collaboration among federal agencies and academic institutions on scientific investigation, clinical-study design, and consideration of the weight of evidence and address ethical issues related to the performance of drug studies. C1 NICHHD, Obstet & Pediat Pharmacol Branch, Ctr Res Mothers & Children, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. US FDA, Dept Hlth & Human Serv, Ctr Drug Evaluat & Res, Div Pediat Drug Dev,Off Counter Terrorism & Pedia, Silver Spring, MD USA. RP Giacoia, GP (reprint author), NICHHD, Obstet & Pediat Pharmacol Branch, Ctr Res Mothers & Children, NIH,Dept Hlth & Human Serv, 6100 Execut Blvd,MSC 7510, Bethesda, MD 20892 USA. EM gg65m@nih.gov RI Mattison, Donald/C-2015-2009; Mattison, Donald/L-4661-2013 OI Mattison, Donald/0000-0001-5623-0874 NR 39 TC 19 Z9 19 U1 0 U2 0 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD MAR PY 2006 VL 117 IS 3 SU S BP S1 EP S8 DI 10.1542/peds.2005-0620B PG 8 WC Pediatrics SC Pediatrics GA 017XT UT WOS:000235727300001 PM 16777817 ER PT J AU Salerno, RA Lesko, LJ AF Salerno, RA Lesko, LJ TI Three years of promise, proposals, and progress on optimizing the benefit/risk of medicines: a commentary on the 3rd FDA-DIA-PWG-PhRMA-BIO pharmacogenomics workshop SO PHARMACOGENOMICS JOURNAL LA English DT Editorial Material ID REGULATORY DECISION-MAKING; DRUG DEVELOPMENT C1 Wyeth Ayerst Res, Worldwide Regulatory Affairs, Pharma & Translat Med, Collegeville, PA 19454 USA. US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Salerno, RA (reprint author), Wyeth Ayerst Res, Worldwide Regulatory Affairs, Pharma & Translat Med, 500 Arcola Rd, Collegeville, PA 19454 USA. EM salernr@wyeth.com; leskol@cder.fda.gov NR 5 TC 8 Z9 11 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1470-269X J9 PHARMACOGENOMICS J JI Pharmacogenomics J. PD MAR-APR PY 2006 VL 6 IS 2 BP 78 EP 81 DI 10.1038/sj.tpj.6500345 PG 4 WC Genetics & Heredity; Pharmacology & Pharmacy SC Genetics & Heredity; Pharmacology & Pharmacy GA 033XV UT WOS:000236889200001 PM 16402087 ER PT J AU Wang, SJ Cohen, N Katz, DA Ruano, G Shaw, PM Spear, B AF Wang, SJ Cohen, N Katz, DA Ruano, G Shaw, PM Spear, B TI Retrospective validation of genomic biomarkers - what are the questions, challenges and strategies for developing useful relationships to clinical outcomes - workshop summary SO PHARMACOGENOMICS JOURNAL LA English DT Editorial Material ID PHARMACOGENOMIC DATA SUBMISSIONS; FDA C1 US FDA, Off Biostat, OPaSS, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. Johnson & Johnson Consumer Prod Inc, Pharmaceut R&D, Raritan, NJ USA. Abbott Labs, Abbott Pk, IL 60064 USA. Merck & Co Inc, Blue Bell, PA USA. Genomas Inc, Hartford, CT USA. RP Wang, SJ (reprint author), US FDA, Off Biostat, OPaSS, Ctr Drug Evaluat & Res, HFD-400,WO 22,Room 6216,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM wangs@cder.fda.gov NR 6 TC 22 Z9 22 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1470-269X J9 PHARMACOGENOMICS J JI Pharmacogenomics J. PD MAR-APR PY 2006 VL 6 IS 2 BP 82 EP 88 DI 10.1038/sj.tpj.6500363 PG 7 WC Genetics & Heredity; Pharmacology & Pharmacy SC Genetics & Heredity; Pharmacology & Pharmacy GA 033XV UT WOS:000236889200002 PM 16402078 ER PT J AU Trepicchio, WL Essayan, D Hall, ST Schechter, G Tezak, Z Wang, SJ Weinreich, D Simon, R AF Trepicchio, WL Essayan, D Hall, ST Schechter, G Tezak, Z Wang, SJ Weinreich, D Simon, R TI Designing prospective clinical pharmacogenomic (PG) trials: meeting report on drug development strategies to enhance therapeutic decision making SO PHARMACOGENOMICS JOURNAL LA English DT Editorial Material ID MICROARRAY DATA; LUNG-CANCER; MUTATIONS; GEFITINIB; FDA C1 Millennium Pharmaceut Inc, Div Mol Med, Cambridge, MA 02139 USA. NCI, Biometr Res Branch, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. GeneLog Inc, Gaithersburg, MD USA. US FDA, Off Biostat, Off Pharmacoepidemiol & Stat Sci, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. US FDA, Ctr Devices & Radiol Hlth, OIVD, Rockville, MD 20857 USA. US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. GlaxoSmithKline Inc, Us Regulatory Affairs, Res Triangle Pk, NC USA. Amgen Inc, Regulatory Affairs, Thousand Oaks, CA USA. RP Trepicchio, WL (reprint author), Millennium Pharmaceut Inc, Div Mol Med, 40 Landsdowne St, Cambridge, MA 02139 USA. EM wtrepicchio@mpi.com NR 11 TC 4 Z9 7 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1470-269X J9 PHARMACOGENOMICS J JI Pharmacogenomics J. PD MAR-APR PY 2006 VL 6 IS 2 BP 89 EP 94 DI 10.1038/sj.tpj.6500344 PG 6 WC Genetics & Heredity; Pharmacology & Pharmacy SC Genetics & Heredity; Pharmacology & Pharmacy GA 033XV UT WOS:000236889200003 PM 16402088 ER PT J AU Shepherd, KR Lee, ESY Schmued, L Jiao, Y Ali, SF Oriaku, ET Lamango, NS Soliman, KFA Charlton, CG AF Shepherd, KR Lee, ESY Schmued, L Jiao, Y Ali, SF Oriaku, ET Lamango, NS Soliman, KFA Charlton, CG TI The potentiating effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on paraquat-induced neurochemical and behavioral changes in mice SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE Parkinson's disease; paraquat; dopamine; methylation; MPTP ID ADENOSYL-L-METHIONINE; ENVIRONMENTAL RISK-FACTORS; PARKINSONS-DISEASE; RAT-BRAIN; SUBSTANTIA-NIGRA; S-ADENOSYLMETHIONINE; DOPAMINERGIC-NEURONS; N-METHYLTRANSFERASE; MOVEMENT-DISORDERS; CELL LOSS AB Although the etiology of Parkinson's disease (PD) is not fully understood, there are numerous studies that have linked the increased risk for developing PD to pesticides exposure including paraquat (PQ). Moreover, the exposure to a combination of compounds or chemical mixtures has been suggested to further increase this risk. In the current study, the effects of PQ on the nigrostriatal dopaminergic system in male C57BL6 mice exposed to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) were examined to assess the impact of toxic substance mixtures exposure on neurochemical and behavioral changes. In this study, a low non-toxic dose of MPTP (10mg/kg) was injected once a day for 5 days and was followed by PQ (7mg/kg) once a day for 6 days (subacute protocol) or once a week for 10 weeks (chronic protocol). The results from the subacute protocol showed that PQ reduced the turnover of dopamine (DA) as indicated by a 21% and a 22.3% decrease in dihydroxyphenyl acetic acid (DOPAC), homovanillic acid and increased S-adenosyl methionine/S-adenosyl homocysteine index (SAM/SAH) by 100%. However, the administration of PQ to MPTP primed mice resulted in the decrease of DOPAC, HVA, DA, by 35.8%, 35.2% and 22.1%, respectively. In addition, PQ decreased the total number of movements (TM) by 28% but MPTP plus PQ decreased TM by 41%. The SAM/SAH index showed that MPTP increased methylation by 33.3%, but MPTP plus PQ increased methylation by 81%. In the chronic protocol, the data showed that MPTP administration did not affect DA, DOPAC, and HVA levels. The administration of PQ led to significant decrease in DOPAC, HVA, and TD by 31.6%, 19.9%, and 21.2% respectively with no effect on DA levels. The MPTP plus PQ group showed reduced DA, DOPAC, HVA, and total distance traveled by 58.4%, 82.8%, 55.8%, and 83.9%, respectively. Meanwhile, PQ administration caused a reduction in tyrosine hydroxylase immunoreactivity in the substantia nigra, and this effect was more pronounced in MPTP pretreated mice. It was concluded from this study that prior treatment with MPTP potentiated the effects of PQ in reducing DA, DOPAC, HVA, TH immunoreactivity, locomotor activity, and increasing the methylation index. The enhanced effects of PQ following MPTP administration further support the role of toxic substance mixtures in causing Parkinson's disease. (c) 2006 Elsevier Inc. All rights reserved. C1 Florida A&M Univ, Coll Pharm & Pharmaceut Sci, Tallahassee, FL 32307 USA. Meharry Med Coll, Dept Pharmacol, Nashville, TN 37208 USA. US FDA, NCTR, Div Neurotoxicol, Neurochem Lab, Jefferson, AR 72079 USA. St Jude Childrens Hosp, Memphis, TN 38105 USA. RP Shepherd, KR (reprint author), Florida A&M Univ, Coll Pharm & Pharmaceut Sci, Tallahassee, FL 32307 USA. EM krsheph@emory.edu FU NCRR NIH HHS [RR 03020]; NIGMS NIH HHS [GM 08111]; PHS HHS [R01 28432] NR 74 TC 25 Z9 27 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD MAR PY 2006 VL 83 IS 3 BP 349 EP 359 DI 10.1016/j.pbb.2006.02.013 PG 11 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA 053IM UT WOS:000238298800001 PM 16580056 ER PT J AU Hanna, GM AF Hanna, GM TI NMR regulatory analysis: enantiomeric purity determination for (R)-(-)-desoxyephedrine and antipode methamphetamine SO PHARMAZIE LA English DT Article ID PERFORMANCE LIQUID-CHROMATOGRAPHY; SPECTROMETRIC DETERMINATION; PRECOLUMN DERIVATIZATION; MASS-SPECTROMETRY; STATIONARY PHASES; CHIRAL REAGENT; AMPHETAMINE; URINE; RESOLUTION; DRUG AB Regulatory enantiomeric purity direct determination for (S)-(+)-methamphetamine, the widely abused DEA schedule II controlled substance, and (R)-(-)-desoxyephedrine, over-the-counter nasal inhaler decongestant were developed using 400 MHz H-1 NMR spectroscopy. The efficient enantiomeric differentiation was obtained using a diamagnetic chiral solvating agent to dissimilarly perturb the NMR spectra of the enantiomeric solutes. Nonequivalence behavior was studied in terms of all variables that affect population and intrinsic spectra of the fast diastereomeric solvates. Assignment of enantiomer configuration was based on the relative field position of the resolved enantiomeric signals. Optimization of experimental conditions provided significant resolved enantiomeric signals suitable for quantification. Utilizing the relative intensities of the corresponding enantiomeric signals of the N-CH3 assigned to (S)-(+)-methamphetamine and (R)-(-)-desoxyephedrine, the analysis of synthetic enantiomeric mixtures by the proposed methods demonstrated excellent agreements with the known values of the enantiomers present. The mean +/- SD recovery values for the (R)-(-)-enantiomer was 99.9 +/- 0.4% of added antipode (n = 7). The optically pure enantiomer was used to establish the minimum amount detected by the proposed NMR spectroscopic method. C1 US FDA, NE Reg Lab, US Dept HHS, Jamaica, NY 11435 USA. RP Hanna, GM (reprint author), US FDA, NE Reg Lab, US Dept HHS, 158-15 Liberty Ave, Jamaica, NY 11435 USA. NR 37 TC 4 Z9 4 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 MAR PY 2006 VL 61 IS 3 BP 188 EP 193 PG 6 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 036LJ UT WOS:000237072300005 PM 16599257 ER PT J AU Lobato, MN Wang, YC Becerra, JE Simone, PM Castro, KG AF Lobato, MN Wang, YC Becerra, JE Simone, PM Castro, KG TI Improved program activities are associated with decreasing tuberculosis incidence in the United States SO PUBLIC HEALTH REPORTS LA English DT Article ID DIRECTLY OBSERVED THERAPY; NEW-YORK-CITY; TRANSMISSION; CONTACTS; TRENDS AB Objective. This study was conducted to determine whether improvements in tuberculosis (TB) program activities correlate with incident TB cases. Methods. National TB surveillance data and program data from patients with pulmonary and laryngeal TB and their contacts were collected. These data were analyzed using regression models to assess the association between changes in incident TB cases and indicators of program performance (a time series of percent changes in program indices). Results. A total of 1,361,113 contacts exposed to 150,668 TB patients were identified through contact investigations. From 1987 to 1992 (the period of TB resurgence and antedating increased funding), there was a decline in several measures used by TB programs for outcomes of contact investigations. From 1993 to 1998 (the period after increases in TB funds), there was an observable improvement in the program indices. Four program indices for contacts and two for TB cases (directly observed therapy and completion of therapy) were statistically associated (p <= 0.01) with the decline in TB incident cases. Conclusions. These analyses suggest that expanded TB program activities resulted in the reduction in national TB cases and underscore the importance of treatment completion for TB disease and latent TB infection. Based on these results, we propose that further improvements in these activities will accelerate the decline of TB in the United States. C1 Ctr Dis Control & Prevent, Natl Ctr HIV STD & TB Prevent, Div TB Eliminat, Atlanta, GA USA. US FDA, Off Biostat, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. Ctr Dis Control & Prevent, Natl Ctr Infect Dis, Div Global Migrat & Quarantine, Atlanta, GA USA. RP Lobato, MN (reprint author), CDC, 1600 Clifton Rd,Mailstop E-10, Atlanta, GA 30333 USA. EM mn10@cdc.gov RI Becerra, Jose/C-4071-2014 NR 28 TC 8 Z9 8 U1 0 U2 2 PU ASSOC SCHOOLS PUBLIC HEALTH PI WASHINGTON PA 1101 15TH ST NW, STE 910, WASHINGTON, DC 20005 USA SN 0033-3549 J9 PUBLIC HEALTH REP JI Public Health Rep. PD MAR-APR PY 2006 VL 121 IS 2 BP 108 EP 115 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 020IA UT WOS:000235900900002 PM 16528941 ER PT J AU Wilding, P Joos, T Kricka, LJ Shi, L AF Wilding, P Joos, T Kricka, LJ Shi, L TI Guidelines for terminology for microtechnology in clinical laboratories SO PURE AND APPLIED CHEMISTRY LA English DT Article DE microtechnology; microfabricated devices; microfabrication; nomenclature; nanotechnology; IUPAC Chemistry and Human Health Division AB There is no formal terminology used to describe the scope and use of microtechnology in the clinical laboratory. For many laboratory scientists, the word "microchip" is synonymous with high-density microarrays used primarily for investigating gene expression. The document proposes a system of "categories" and "descriptors" that facilitates the classification of a device in a way that communicates details of its function and analytical role, and describes the analytical principle involved and the methods and materials used for its manufacture. Adoption of this system would enable scientists to employ four descriptors that clearly delineate the function, analytical role, and chemical or physical principle involved in the device. Examples of existing commercial devices are given to illustrate the utility of the system. C1 Univ Penn, Med Ctr, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. Univ Tubingen, NMI Naturwissensch & Med Inst, D-72770 Reutlingen, Germany. US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Wilding, P (reprint author), Univ Penn, Med Ctr, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. EM pwilding@mail.med.upenn.edu NR 13 TC 1 Z9 1 U1 0 U2 0 PU INT UNION PURE APPLIED CHEMISTRY PI RES TRIANGLE PK PA 104 TW ALEXANDER DR, PO BOX 13757, RES TRIANGLE PK, NC 27709-3757 USA SN 0033-4545 J9 PURE APPL CHEM JI Pure Appl. Chem. PD MAR PY 2006 VL 78 IS 3 BP 677 EP 684 DI 10.1351/pac200678030677 PG 8 WC Chemistry, Multidisciplinary SC Chemistry GA 025FH UT WOS:000236250200006 ER PT J AU Matthews, EJ Kruhlak, NL Cimino, MC Benz, RD Contrera, JF AF Matthews, EJ Kruhlak, NL Cimino, MC Benz, RD Contrera, JF TI An analysis of genetic toxicity, reproductive and developmental toxicity, and carcinogenicity data: I. Identification of carcinogens using surrogate endpoints SO REGULATORY TOXICOLOGY AND PHARMACOLOGY LA English DT Article DE genetic toxicity; genetox; reproductive and developmental toxicity; reprotox; rodent carcinogenicity bioassay; surrogate; database ID NATIONAL-TOXICOLOGY-PROGRAM; PREDICTING RODENT CARCINOGENICITY; SISTER-CHROMATID EXCHANGE; CHEMICAL-STRUCTURE; BALB/C-3T3 CELLS; TOX PROGRAM; PHASE-III; MUTAGENICITY; SALMONELLA; ASSAY AB A retrospective analysis of standard genetic toxicity (genetox) tests, reproductive and developmental toxicity (reprotox) studies, and rodent carcinogenicity bioassays (rcbioassay) was performed to identify the genetox and reprotox endpoints whose results best correlate with rcbioassay observations. A database of 7205 chemicals with genetox (n = 4961), reprotox (n = 2173), and rcbioassay (n = 1442) toxicity data was constructed; 1112 of the chemicals have both genetox and rcbioassay data and 721 chemicals have both reprotox and rcbioassay data. This study differed from previous studies by using conservative weight of evidence criteria to classify chemical carcinogens, data from 63 genetox and reprotox toxicological endpoints, and a new statistical parameter of correlation indicator (Cl, the average of specificity and positive predictivity) to identify good surrogate endpoints for predicting carcinogenicity. Among 63 endpoints, results revealed that carcinogenicity was well correlated with certain tests for gene mutation (n = 8), in vivo clastogenicity (n = 2), unscheduled DNA synthesis assay (n = 1), and reprotox (n = 3). The current FDA regulatory battery of four genetox tests used to predict carcinogenicity includes two tests with good correlation (gene mutation in Salmonella and in vivo micronucleus) and two tests with poor correlation (mouse lymphoma gene mutation and in vitro chromosome aberrations) by our criteria. Published by Elsevier Inc. C1 US FDA, Ctr Drug Evaluat & Res, Off Pharmaceut Sci Informat & Compuatat Safety An, Silver Spring, MD 20993 USA. US EPA 7403M, Washington, DC 20460 USA. RP Matthews, EJ (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Pharmaceut Sci Informat & Compuatat Safety An, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM matthewse@cder.fda.gov NR 43 TC 74 Z9 74 U1 0 U2 6 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0273-2300 J9 REGUL TOXICOL PHARM JI Regul. Toxicol. Pharmacol. PD MAR PY 2006 VL 44 IS 2 BP 83 EP 96 DI 10.1016/j.yrtph.2005.11.003 PG 14 WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology SC Legal Medicine; Pharmacology & Pharmacy; Toxicology GA 018VU UT WOS:000235793700002 PM 16386343 ER PT J AU Matthews, EJ Kruhlak, NL Cimino, MC Benz, RD Contrera, JF AF Matthews, EJ Kruhlak, NL Cimino, MC Benz, RD Contrera, JF TI An analysis of genetic toxicity, reproductive and developmental toxicity, and carcinogenicity data: II. Identification of genotoxicants, reprotoxicants, and carcinogens using in silico methods SO REGULATORY TOXICOLOGY AND PHARMACOLOGY LA English DT Article DE MC4PC; computational toxicology; quantitative structure-activity relationships; predictive modeling; genetic toxicity; genetox; reproductive and developmental toxicity; reprotox; carcinogenicity; rodent carcinogenicity bioassay; surrogate ID SISTER CHROMATID EXCHANGES; HAMSTER OVARY CELLS; SALMONELLA MUTAGENICITY; CHROMOSOMAL-ABERRATIONS; RODENT CARCINOGENS; CHEMICAL-STRUCTURE; STRUCTURAL BASIS; MOUSE LYMPHOMA; TOX PROGRAM; PREDICTION AB This study examined a novel method to identify carcinogens that employed expanded data sets composed of in silico data pooled with actual experimental genetic toxicity (genetox) and reproductive and developmental toxicity (reprotox) data. We constructed 21 modules using the MC4PC program including 13 of 14 (11 genetox and 3 reprotox) tests that we found correlated with results of rodent carcinogenicity bioassays (rcbioassays) [Matthews, E.J., Kruhlak, N.L., Cimino, M.C., Benz, R.D., Contrera, J.F., 2005b. An analysis of genetic toxicity, reproductive and developmental toxicity, and carcinogenicity data: I. Identification of carcinogens using surrogate endpoints. Regul. Toxicol. Pharmacol.]. Each of the 21 modules was evaluated by cross-validation experiments and those with high specificity (SP) and positive predictivity (PPV) were used to predict activities of the 1442 chemicals tested for carcinogenicity for which actual genetox or reprotox data were missing. The expanded data sets had similar to 70% in silico data pooled with similar to 30% experimental data. Based upon SP and PPV, the expanded data sets showed good correlation with carcinogenicity testing results and had correlation indicator (CI, the average of SP and PPV) values of 75.5-88.7%. Conversely, expanded data sets for 9 non-correlated test endpoints were shown not to correlate with carcinogenicity results (CI values < 75%). Results also showed that when Salmonella mutagenic carcinogens were removed from the 12 correlated, expanded data sets, only 7 endpoints showed added value by detecting significantly more additional carcinogens than noncarcinogens. Published by Elsevier Inc. C1 US FDA, Ctr Drug Evaluat & Res, Off Pharmaceut Sci Informat & Computat Safety Ana, Silver Spring, MD 20993 USA. US EPA 7403M, Washington, DC 20460 USA. RP Matthews, EJ (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Pharmaceut Sci Informat & Computat Safety Ana, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM matthewse@cder.fda.gov NR 30 TC 61 Z9 61 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 0273-2300 J9 REGUL TOXICOL PHARM JI Regul. Toxicol. Pharmacol. PD MAR PY 2006 VL 44 IS 2 BP 97 EP 110 DI 10.1016/j.yrtph.2005.10.004 PG 14 WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology SC Legal Medicine; Pharmacology & Pharmacy; Toxicology GA 018VU UT WOS:000235793700003 PM 16352383 ER PT J AU Bailey, AB Chanderbhan, R Collazo-Braier, N Cheeseman, MA Twaroski, ML AF Bailey, AB Chanderbhan, R Collazo-Braier, N Cheeseman, MA Twaroski, ML TI The use of structure-activity relationship analysis in the food contact notification program (vol 42, pg 225, 2005) SO REGULATORY TOXICOLOGY AND PHARMACOLOGY LA English DT Correction C1 US FDA, Div Food Contact Notificat, Off Food Addit Safety, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Twaroski, ML (reprint author), US FDA, Div Food Contact Notificat, Off Food Addit Safety, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy,HFS 275, College Pk, MD 20740 USA. EM Michelle.Twaroski@cfsan.fda.gov NR 1 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0273-2300 J9 REGUL TOXICOL PHARM JI Regul. Toxicol. Pharmacol. PD MAR PY 2006 VL 44 IS 2 BP 190 EP 190 DI 10.1016/j.yrtph.2005.11.004 PG 1 WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology SC Legal Medicine; Pharmacology & Pharmacy; Toxicology GA 018VU UT WOS:000235793700012 ER PT J AU Dnyanmote, AV Sawant, SP Lock, EA Latendresse, JR Warbritton, AA Mehendale, HM AF Dnyanmote, AV Sawant, SP Lock, EA Latendresse, JR Warbritton, AA Mehendale, HM TI Diabetic mice are protected from normally lethal nephrotoxicity of S-1, 2-dichlorovinyl-L-cysteine (DCVC): Role of nephrogenic tissue repair SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE kidney; regeneration; type-1 diabetes; streptozotocin ID ACUTE-RENAL-FAILURE; ACUTE TUBULAR-NECROSIS; GENTAMICIN-NEPHROTOXICITY; CISPLATIN NEPHROTOXICITY; MEDIATES PROGRESSION; LIVER-INJURY; RISK-FACTORS; RAT; METABOLISM; TOXICITY AB Streptozotocin (STZ)-induced diabetic (DB) rats are protected from nephrotoxicity of gentamicin, cisplatin and mercuric chloride, although the mechanisms remain unclear. Ninety percent of DB mice receiving a LD90 dose (75 mg/kg, ip) of S-1,2-dichlorovinyl-L-cysteine (DCVC) survived in contrast to only 10% of the nondiabetic (NDB) mice surviving the same dose. We tested the hypothesis that the mechanism of protection is upregulated tissue repair. In the NDB mice, DCVC produced steep temporal increases in blood urea nitrogen (BUN) and plasma creatinine, which were associated with proximal tubular cell (PTC) necrosis, acute renal failure (ARF), and death within 48 It. In contrast, in the DB mice, BUN and creatinine increased less steeply, declining after 36 It to completely resolve by 96 It. HPLC analysis of plasma and urine revealed that DB did not alter the toxicokinetics of DCVC. Furthermore, activity of renal cysteine conjugate lyase, the enzyme that bioactivates DCVC, was unaltered in DB mice, undermining the possibility of lower bioactivation of DCVC leading to lower injury. [3H]-thymidine pulse labeling and PCNA analysis indicated an early onset and sustained nephrogenic tissue repair in DCVC-treated DB mice. BRDU immunohistochemistry revealed a fourfold increase in the number of cells in S-phase in the DB kidneys even without exposure to DCVC. Blocking the entry of cells into S-phase by antimitotic intervention using colchicine abolished stimulated nephrogenic tissue repair and nephroprotection. These findings suggest that preplacement of S-phase cells in the kidney due to diabetes is critical in mitigating the progression of DCVC-initiated renal injury by upregulation of tissue repair, leading to survival of the DB mice by avoiding acute renal failure. (c) 2005 Elsevier Inc. All rights reserved. C1 NE Louisiana Univ, Coll Pharm, Dept Toxicol, Monroe, LA 71209 USA. Med Univ S Carolina, Dept Pharmaceut Sci, Charleston, SC 29425 USA. Natl Ctr Toxicol Res, Toxicol Pathol Associates, Jefferson, AR 72079 USA. RP Mehendale, HM (reprint author), NE Louisiana Univ, Coll Pharm, Dept Toxicol, 700 Univ Ave, Monroe, LA 71209 USA. EM mehendale@ulm.edu RI Latendresse, John/A-9215-2009 NR 53 TC 8 Z9 8 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD MAR 1 PY 2006 VL 211 IS 2 BP 133 EP 147 DI 10.1016/j.taap.2005.07.015 PG 15 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 018LR UT WOS:000235766300006 PM 16125744 ER PT J AU Gemeniano, M Mpanju, O Salomon, DR Elden, MV Wilson, CA AF Gemeniano, M Mpanju, O Salomon, DR Elden, MV Wilson, CA TI The infectivity and host range of the ecotropic porcine endogenous retrovirus, PERV-C, is modulated by residues in the C-terminal region of its surface envelope protein SO VIROLOGY LA English DT Article DE porcine endogenous retrovirus; receptor binding domain; envelope; virus entry ID MURINE LEUKEMIA-VIRUS; RECEPTOR-BINDING DOMAIN; MINIATURE SWINE; SUBGROUP-B; IDENTIFICATION; CELLS; GLYCOPROTEIN; ACTIVATION; ENTRY; DETERMINANTS AB Endogenous retroviral genetic material serves as a reservoir for the generation of retroviral pathogens by recombination between activated endogenous or exogenous infectious agents. Some porcine tissues actively express infectious porcine endogenous retroviruses (PERVs). Of the three classes of PERV characterized to date, two, PERV-A and B, are capable of infecting human cells in vitro, whereas PERV-C cannot. Here, we demonstrate that the PERV-C envelope Surface protein (SU) when disassociated from its C-terminus binds human cells. Further, we show that PERV-C binding to human cells is not inhibited in 293 cells productively infected with PERV-A, confirming that the molecule PERV-C interacts with on human cells is distinct from that used by PERV-A. Moreover, we demonstrate that the envelope region encompassing the proline-rich region is required for binding to cells in addition to the putative variable region A (VRA) and B (VRB). The region in the C-terminus of the SU that alters the binding and infectivity properties of PERV-C differs by only nine residues from the analogous region of PERV-A. Caution may be warranted even when a xenotransplantation product is from source pigs that do not express human-tropic viruses, as minimal mutations within PERV-C combined with selection in a human recipient Could render PERV-C infectious in humans. Published by Elsevier Inc. C1 US FDA, Ctr Biol Evaluat & Res, Lab Immunol & Virol, Div Cellular & Gene Therapies, Bethesda, MD 20892 USA. Scripps Res Inst, Dept Mol & Expt Med, La Jolla, CA 92037 USA. NIMH, Lab Cellular & Mol Regulat, NIH, Bethesda, MD 20892 USA. RP Wilson, CA (reprint author), US FDA, Ctr Biol Evaluat & Res, Lab Immunol & Virol, Div Cellular & Gene Therapies, 8000 Rockville Pike,HFM-725,Bldg 29B,Room 2NN12, Bethesda, MD 20892 USA. EM wilsonc@cber.fda.gov RI Salomon, Daniel/E-9380-2012 FU NIAID NIH HHS [R0A AI52349] NR 32 TC 34 Z9 36 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD MAR 1 PY 2006 VL 346 IS 1 BP 108 EP 117 DI 10.1016/j.virol.2005.10.021 PG 10 WC Virology SC Virology GA 020SJ UT WOS:000235930400011 PM 16309725 ER PT J AU Xie, JT Shao, ZH Hoek, TLV Chang, WT Li, J Mehendale, S Wang, CZ Hsu, CW Becker, LB Yin, JJ Yuan, CS AF Xie, JT Shao, ZH Hoek, TLV Chang, WT Li, J Mehendale, S Wang, CZ Hsu, CW Becker, LB Yin, JJ Yuan, CS TI Antioxidant effects of ginsenoside Re in cardiomyocytes SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE antioxidant effect; ginsenoside Re; ESR spectroscopy; cardiomyocyte; ischemia and reperfusion damage; antimycin A; H2O2 ID ATTENUATES OXIDANT STRESS; PANAX-GINSENG; SUPEROXIDE ANION; BERRY EXTRACT; CELLS; LEAVES; DIFFERENTIATION; REPERFUSION; MODULATION; PRODUCTS AB We have previously demonstrated that American ginseng berry extract exhibited significant protection against oxidant-mediated injury in cardiomyocytes. To extend this work, we sought to investigate the antioxidant effects of Re, a protopanaxatriols-type and single chemical integrant present in American ginseng berry extract, using the same chick cardiomyocyte model of oxidant injury as well as ESR spectroscopy in a cell-free chemical system. In cells exposed to 2 h of H2O2 (0.5 mM), pretreatment with Re (0.05, 0.1, or 0.5 mg/ml for 2 h) significantly attenuated 2,7'-dichlorofluorescein (DCF) fluorescence by 51% (from 1345 +/- 67 to 658 46 a.u., P < 0.001), and remarkably reduced cell death (from 51.5 +/- 3.0% to 11.8 +/- 1.5%, P < 0.001, compared to the control). Similar results were also observed in cells exposed to antimycin A (100 mu M), a mitochondrial electron transport chain site III inhibitor which increases endogenous oxidative stress. In the ESR study, however, Re failed to reduce the formation of the superoxide/DMPO adduct and DPPH radicals. These results suggest that ginsenoside Re functions as an antioxidant, protecting cardiomyocytes from oxidant injury induced by both exogenous and endogenous oxidants, and that its protective effects may be mostly attributed to scavenging H2O2 and hydroxyl radicals. (c) 2006 Elsevier B.V. All rights reserved. C1 Univ Chicago, Pritzker Sch Med, Dept Anesthesia & Crit Care, Sch Med, Chicago, IL 60637 USA. Univ Chicago, Pritzker Sch Med, Tang Ctr Herbal Med Res, Chicago, IL 60637 USA. Univ Chicago, Pritzker Sch Med, Sect Emergency Med, Chicago, IL 60637 USA. Univ Chicago, Pritzker Sch Med, Dept Med, Gastroenterol Sect, Chicago, IL 60637 USA. Univ Chicago, Pritzker Sch Med, Comm Clin Pharmacol & Pharmacogenom, Chicago, IL 60637 USA. US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Yuan, CS (reprint author), Univ Chicago, Pritzker Sch Med, Dept Anesthesia & Crit Care, Sch Med, 5841 S Maryland Ave,MC 4028, Chicago, IL 60637 USA. EM cyuan@midway.uchicago.edu RI Yin, Jun Jie /E-5619-2014 FU NCCIH NIH HHS [AT002445, AT002176] NR 53 TC 83 Z9 97 U1 2 U2 20 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD FEB 27 PY 2006 VL 532 IS 3 BP 201 EP 207 DI 10.1016/j.ejphar.2005.01.001 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 022SZ UT WOS:000236077400001 PM 16497296 ER PT J AU Delmonte, P Perry, J Rader, JI AF Delmonte, P Perry, J Rader, JI TI Determination of isoflavones in dietary supplements containing soy, Red Clover and kudzu: Extraction followed by basic or acid hydrolysis SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article DE isoflavones; dietary supplements; soy isoflavones; Red Clover extract; kudzu extract ID PERFORMANCE LIQUID-CHROMATOGRAPHY; MASS-SPECTROMETRY; TRIFOLIUM-PRATENSE; FOODS; QUANTIFICATION; PRODUCTS AB Isoflavones are phytochemicals found in many plants. Because of their structural similarity to P-estradiol, health benefits of isoflavones have been evaluated in age-related and hormone-dependent diseases. Dietary supplement preparations contain extracts from soy, Red Clover and kudzu. Soy products contain primarily genistein, daidzein, and glycitein, while Red Clover products contain primarily formononetin and biochanin A Kudzu extracts contain puerarin and daidzein among other components. Previous methods of analysis focused on the determination of isoflavones from a single botanical source, while dietary supplements are often a blend of extracts from different plants. We developed a method for the analysis of isoflavones in dietary supplements regardless of their botanical composition, using HPLC-PDA because of its applicability to routine analysis. Isoflavones are found as free compounds, glucoside derivatives, 6"-O-malonyl-beta-(D)-glucoside and 6"-O-acetyl-beta-(D)-glucoside derivatives. In this study, the samples were extracted at room temperature with 50:50 (v/v) MeCN/water, and then analyzed before and after hydrolyzing the isoflavones by acid or basic digestion. 2'-Methoxy-flavone and 6-methoxy-flavone were used as internal standards and were added together to every sample. Daidzein, glycitein, genistein, puerarin, calycosin, pratensein, pseudobaptigenin, formononetin, biochanin A and prunetin were among the isoflavones determined. Published by Elsevier B.V. C1 US FDA, Off Nutr Prod Labeling & Dietary Supplements, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Delmonte, P (reprint author), US FDA, Off Nutr Prod Labeling & Dietary Supplements, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM pierluigi.delmonte@cfsan.fda.gov NR 22 TC 78 Z9 81 U1 2 U2 15 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 FEB 24 PY 2006 VL 1107 IS 1-2 BP 59 EP 69 DI 10.1016/j.chroma.2005.11.060 PG 11 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 014UF UT WOS:000235505100008 PM 16413562 ER PT J AU Nunnery, J Angulo, FJ Tollefson, L AF Nunnery, J Angulo, FJ Tollefson, L TI Public health and policy SO PREVENTIVE VETERINARY MEDICINE LA English DT Article DE antimicrobial agents; monitoring; surveillance; public health AB Antimicrobial agent usage data are essential for focusing efforts to reduce misuse and overuse of antimicrobial agents in food producing animals because these practices may select for resistance in bacteria of animals. Transfer of resistant bacteria from animals to humans can lead to human infection caused by resistant pathogens. Resistant infections can lead to treatment failures, resulting in prolonged or more severe illness. Multiple World Health Organization (WHO) reports have concluded that both antimicrobial resistance and antimicrobial usage should be monitored on the national level. The system for collecting antimicrobial usage data should be clear and transparent to facilitate trend analysis and comparison within and among countries. Therapeutic, prophylactic and growth promotion use should be recorded, along with route of administration and animal species and/ or production class treated. The usage data should be compared to resistance data, and the comparison should be made available in a timely manner. In the United States, surveillance of antimicrobial resistance in foodborne bacteria is performed by the National Antimicrobial Resistance Monitoring System (NARMS) for enteric bacteria, however, the United States still lacks a mechanism for collecting antimicrobial usage data. Combined with antimicrobial resistance information from NARMS, antimicrobial usage data will help to direct education efforts and policy decisions, minimizing the risk that people will develop antimicrobial resistant infections as a result of eating food of animal origin. Ultimately mitigation strategies guided by usage data will be more effective in maintaining antimicrobial drugs for appropriate veterinary use and in protecting human health. (C) 2005 Elsevier B.V. All rights reserved. C1 Ctr Dis Control & Prevent, Foodborne & Diarrheal Dis Branch, Div Bacterial & Mycot Dis, Atlanta, GA 30333 USA. US FDA, Ctr Vet Med, Rockville, MD 20855 USA. RP Angulo, FJ (reprint author), Ctr Dis Control & Prevent, Foodborne & Diarrheal Dis Branch, Div Bacterial & Mycot Dis, 1600 Clifton Rd, Atlanta, GA 30333 USA. EM fja0@cdc.gov NR 7 TC 6 Z9 7 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-5877 J9 PREV VET MED JI Prev. Vet. Med. PD FEB 24 PY 2006 VL 73 IS 2-3 BP 191 EP 195 DI 10.1016/j.prevetmed.2005.09.014 PG 5 WC Veterinary Sciences SC Veterinary Sciences GA 022FE UT WOS:000236039700009 PM 16269192 ER PT J AU Bowyer, JF Schmued, LC AF Bowyer, JF Schmued, LC TI Fluoro-Ruby labeling prior to an amphetamine neurotoxic insult shows a definitive massive loss of dopaminergic terminals and axons in the caudate-putamen SO BRAIN RESEARCH LA English DT Article DE amphetamine; dopamine; caudate putamen; neurodegeneration; Fluoro-Ruby ID METHAMPHETAMINE NEUROTOXICITY; HYPERTHERMIA; TRANSPORT; GLUTAMATE; RELEASE; RATS AB Fluoro-Ruby (FR) was injected into the substantia nigra (SNc) to label dopaminergic axons and terminals in the caudate putamen (CPu) of rats 7 days prior to a neurotoxic D-amphetamine (AMPH) exposure. Three days after AMPH exposure, a massive loss in the TH immunoreactive (TH+) axons and terminals was seen in the CPu. The FR-labeled (FR+) axons and terminals in the CPu were greatly diminished with those remaining being enlarged or swollen after AMPH. Fluoro-Jade C (FJ-C) labeling was used to verify AMPH-induced axonal and terminal degeneration. This study demonstrates that fluorescent anterograde tract tracers can be used to show the subsequent axonal and terminal degeneration after systemic exposures to toxins and provides direct evidence that CPu axons and terminals from SNc dopaminergic neurons can be destroyed after neurotoxic exposure to AMPH. Published by Elsevier B.V. C1 Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. RP Bowyer, JF (reprint author), Natl Ctr Toxicol Res, Div Neurotoxicol, HFT-132, Jefferson, AR 72079 USA. EM jbowyer@nctr.fda.gov NR 18 TC 16 Z9 16 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD FEB 23 PY 2006 VL 1075 BP 236 EP 239 DI 10.1016/j.brainres.2005.12.062 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 029LS UT WOS:000236564700026 PM 16458862 ER PT J AU Niemann, RA Krynitsky, AJ Nortrup, DA AF Niemann, RA Krynitsky, AJ Nortrup, DA TI Ion chromatographic determination of perchlorate in foods by on-line enrichment and suppressed conductivity detection SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article; Proceedings Paper CT 230th National Meeting of the American-Chemical-Society CY AUG 28-SEP 01, 2005 CL Washington, DC DE perchlorate; ion chromatography; suppressed conductivity; anion exchange; determination; food ID TANDEM MASS-SPECTROMETRY; LIQUID-CHROMATOGRAPHY; ACCUMULATION; MATRICES; SAMPLES; IODIDE; PLANTS; RIVER; MILK AB Systemic uptake of perchlorate anion, a rocket fuel component and potential thyroid function disruptor, by leafy vegetables and other crops grown in contaminated waters is a public health concern. A column-switching anion-exchange chromatographic method with suppressed conductivity detection, described in this paper, achieved a 3-6 mu g/kg method limit of quantitation in analysis of the wet weight edible portion of cantaloupe, carrots, lettuce, and spinach samples with field-incurred perchlorate. A test portion was blended with dilute nitric acid, and the extract was filtered under vacuum. A portion of the measured filtrate was acidified to pH similar to 2 by addition of cation-exchange resin, 4 mL was passed through a graphitized carbon cleanup column, and an aliquot of a collected fraction was pushed through a short precolumn for anion extraction, enrichment, and injection onto the analytical column. Statistical comparison with determination by tandem mass spectrometry-ion chromatography analysis of untreated filtrate revealed that the difference between means was not significant at the 95% confidence level (P value >= 0.12) for crops tested. In addition, the method was applied to cooked vegetables processed as baby food. C1 US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Niemann, RA (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM richard.niemann@fda.hhs.gov NR 29 TC 6 Z9 6 U1 0 U2 6 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 FEB 22 PY 2006 VL 54 IS 4 BP 1137 EP 1143 DI 10.1021/jf058125g PG 7 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 016NV UT WOS:000235627800022 PM 16478228 ER PT J AU Navarro, VJ Senior, JR AF Navarro, VJ Senior, JR TI Current concepts - Drug-related hepatotoxicity SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Review ID INDUCED LIVER-INJURY; CAUSALITY ASSESSMENT; INDUCED HEPATITIS; ADVERSE REACTIONS; MEDICAL PROGRESS; UNITED-STATES; DISEASE; TROGLITAZONE; FAILURE; RISK C1 Thomas Jefferson Univ, Jefferson Med Coll, Dept Med, Div Gastroenterol & Hepatol, Philadelphia, PA 19107 USA. US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Navarro, VJ (reprint author), 132 S 10th St,Suite 480 Main, Philadelphia, PA 19107 USA. EM victor.navarro@jefferson.edu NR 62 TC 411 Z9 448 U1 2 U2 27 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 FEB 16 PY 2006 VL 354 IS 7 BP 731 EP 739 DI 10.1056/NEJMra052270 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 012CP UT WOS:000235316100009 PM 16481640 ER PT J AU Flowers, CM Racoosin, JA Kortepeter, C AF Flowers, CM Racoosin, JA Kortepeter, C TI Seizure activity and off-label use of tiagabine SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 US FDA, Rockville, MD 20852 USA. RP Flowers, CM (reprint author), US FDA, Rockville, MD 20852 USA. EM flowersc@cder.fda.gov NR 3 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 FEB 16 PY 2006 VL 354 IS 7 BP 773 EP 774 DI 10.1056/NEJMc055301 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 012CP UT WOS:000235316100038 PM 16481654 ER PT J AU Ochiai, H Campbell, SA Archer, GE Chewning, TA Dragunsky, E Ivanov, A Gromeier, M Sampson, JH AF Ochiai, H Campbell, SA Archer, GE Chewning, TA Dragunsky, E Ivanov, A Gromeier, M Sampson, JH TI Targeted therapy for glioblastoma multiforme neoplastic meningitis with intrathecal delivery of an oncolytic recombinant poliovirus SO CLINICAL CANCER RESEARCH LA English DT Article ID MALIGNANT GLIOMA; GROWTH-FACTOR; VIRUS MUTANT; RECEPTOR; EXPRESSION; PATHWAY; MEDULLOBLASTOMA; NEUROVIRULENCE; TRANSLATION; METASTASES AB Purpose: The toxicity and antitumor activity of regional intrathecal delivery of an oncolytic recombinant poliovirus, PVS-RIPO, was evaluated in rodent models of glioblastoma multiforme neoplastic meningitis. Experimental Design: To evaluate for toxicity, PVS-RIPO was administered into the spinal cord of transgenic mice that express the human poliovirus receptor, CD155, and into the intrathecal space of athymic rats without tumor. To evaluate efficacy, two different doses of PVS-RIPO were administered intrathecally 3 days after athymic rats were inoculated intrathecally with an aggressive human glioblastoma multiforme xenograft. Results: No clinical or histologic evidence of toxicity was found. In efficacy studies, median survival was increased by 174.47% from 8.5 days in the group treated with UV light-inactivated virus to 15 days in the rats treated with 1.0 x 10(7) plaque-forming units (pfu) of PVS-RIPO (P < 0.0001). A similar increase in median survival was seen in the group receiving 1.0 x 109 pfu PVS-RIPO (P < 0.0001); however, there was no statistically significant dose-response relationship (P = 0.345). In addition, 1 of 10 rats in lower-dose PVS-RIPO-treated group and 3 of 10 rats in higher-dose PVS-RIPO -treated group survived >60 days after tumor cell inoculation and had no evidence of residual tumor at autopsy. Conclusion: These results suggest that intrathecal treatment with PVS-RIPO may be useful for treatment of neoplastic meningitis in patients with glioblastoma multiforme and provides a rationale for clinical trials in this area. C1 Duke Univ, Med Ctr, Div Neurosurg, Dept Surg, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Mol Genet & Microbiol, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA. US FDA, Ctr Biol Evaluat & Res, Rockville, MD USA. RP Sampson, JH (reprint author), Duke Univ, Med Ctr, Div Neurosurg, Dept Surg, Box 3050, Durham, NC 27710 USA. EM john.sampson@duke.edu FU NINDS NIH HHS [2P50 NS 20023-21, P50 NS020023] NR 41 TC 23 Z9 27 U1 1 U2 9 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 FEB 15 PY 2006 VL 12 IS 4 BP 1349 EP 1354 DI 10.1158/1078-0432.CCR-05-1595 PG 6 WC Oncology SC Oncology GA 016AD UT WOS:000235592000036 PM 16489093 ER PT J AU Waibel, KH Golding, H Manischewitz, J King, LR Tuchscherer, M Topolski, RL Walsh, DS AF Waibel, KH Golding, H Manischewitz, J King, LR Tuchscherer, M Topolski, RL Walsh, DS TI Clinical and immunological comparison of smallpox vaccine administered to the outer versus the inner upper arms of vaccinia-naive adults SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID RESPONSES; VIRUS; PROTECTION; ANTIBODIES AB Background. Current recommendations direct health care providers to administer smallpox vaccine to the upper outer arm. However, concerns about cosmetically bothersome scarring, accidental contact transmission, interference by body tattoos, and even malignant transformation suggest evaluation of alternate vaccination sites is warranted. Methods. We randomized 20 vaccinia-naive adults to undergo smallpox vaccination on the outer (n=10) or inner (n=10) upper arm. Evaluations included major reaction ("take") rates and vaccination site cultures on postvaccination day 7, determination of serum vaccinia-specific neutralizing antibody titers on days 0 (prevaccination) and 21, and determination of adverse events. Results. On postvaccination day 7, a total of 18 participants ( 9 per group) had major reactions, 17 of whom had culture evidence of viable vaccinia. The inner and outer arm groups had similar major reaction mean sizes (P=.17), but the amount of erythema ( in square centimeters) was smaller in the inner arm group (P=.05). At day 21, all participants had higher titers of vaccinia-specific neutralizing antibodies, compared with at day 0, and the geometric mean titer values of the 2 vaccine groups were similar (P=.45). Adverse event rates were similar. Conclusion. The comparable clinical, immunological, and tolerability outcomes between smallpox vaccine applied to the conventional upper outer arm site versus the upper inner arm, coupled with modestly less vaccine-site erythema on the inner arm, indicate that the inner arm may be a suitable alternate vaccination site. C1 Dwight D Eisenhower Army Med Ctr, Dept Med, Allergy & Immunol Serv, Ft Gordon, GA 30905 USA. Dwight D Eisenhower Army Med Ctr, Dept Pathol, Ft Gordon, GA 30905 USA. Augusta State Univ, Dept Psychol, Augusta, GA USA. US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. Walter Reed Army Inst Res, Dept Clin Trials, Silver Spring, MD USA. RP Waibel, KH (reprint author), Dwight D Eisenhower Army Med Ctr, Dept Med, Allergy & Immunol Serv, 8th Fl,300 Hosp Rd, Ft Gordon, GA 30905 USA. EM kirk.waibel@se.amedd.army.mil NR 24 TC 6 Z9 6 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 FEB 15 PY 2006 VL 42 IS 4 BP E16 EP E20 DI 10.1086/499957 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 004HO UT WOS:000234742800034 PM 16421781 ER PT J AU Stultz, BG Jackson, DG Mortin, MA Yang, X Beachy, PA Hursh, DA AF Stultz, BG Jackson, DG Mortin, MA Yang, X Beachy, PA Hursh, DA TI Transcriptional activation by extradenticle in the Drosophila visceral mesoderm SO DEVELOPMENTAL BIOLOGY LA English DT Article DE Drosophila melanogaster; decapentaplegic (dpp); extradenticle (exd); homothorax (hth); Ultrabithorax (Ubx); transcriptional activation; visceral mesoderm; phosphorylation ID DNA-BINDING SPECIFICITY; HOX PROTEINS; HOMEODOMAIN PROTEINS; NUCLEAR-LOCALIZATION; HOMEOTIC GENES; HOMEOBOX GENES; COOPERATIVE INTERACTIONS; SEGMENTAL EXPRESSION; MIDGUT MORPHOGENESIS; SELECTOR PROTEINS AB decapentaplegic (dpp) is a direct target of Ultrabithorax (Ubx) in parasegment 7 (PS7) of the embryonic visceral mesoderm. We demonstrate that extradenticle (exd) and homothorax (hth) are also required for dpp expression in this location, as well as in PS3, at the site of the developing gastric caecae. A 420 bp element from dpp contains EXD binding sites necessary for expressing a reporter gene in both these locations. Using a specificity swap, we demonstrate that EXD directly activates this element in vivo. Activation does not require Ubx, demonstrating that EXD can activate transcription independently of homeotic proteins. Restoration is restricted to the domains of endogenous dpp expression, despite ubiquitous expression of altered specificity EXD. We demonstrate that nuclear EXD is more extensively phosphorylated than the cytoplasmic form, suggesting that EXD is a target of signal transduction by protein kinases. Published by Elsevier Inc. C1 US FDA, Cellular & Tissue Therapy Branch, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Dept Mol Biol & Genet, Baltimore, MD 21205 USA. NICHHD, Biochem Lab, Natl Canc Inst, NIH, Bethesda, MD 20892 USA. NICHHD, Biochem Lab, Genet Mol Lab, NIH, Bethesda, MD 20892 USA. NCI, Biochem Lab, NIH, Bethesda, MD 20892 USA. RP Hursh, DA (reprint author), US FDA, Cellular & Tissue Therapy Branch, Ctr Biol Evaluat & Res, HFM-730,Bldg 29B,Rm 1E16,8800 Rockville Pike, Bethesda, MD 20892 USA. EM deborah.hursh@fda.hhs.gov RI Mortin, Mark/B-4251-2008 NR 79 TC 11 Z9 11 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 0012-1606 J9 DEV BIOL JI Dev. Biol. PD FEB 15 PY 2006 VL 290 IS 2 BP 482 EP 494 DI 10.1016/j.ydbio.2005.11.041 PG 13 WC Developmental Biology SC Developmental Biology GA 013AR UT WOS:000235382500021 PM 16403493 ER PT J AU Farahani, M Wallace, WE Antonucci, JM Guttman, CM AF Farahani, M Wallace, WE Antonucci, JM Guttman, CM TI Analysis by mass spectrometry of the hydrolysis/condensation reaction of a trialkoxysilane in various dental monomer solutions SO JOURNAL OF APPLIED POLYMER SCIENCE LA English DT Article DE additives; MALDI; mass spectrometry; resins ID SILSESQUIOXANES; CONDENSATION AB 3-Methacryloxypropyltrimethoxysilane (MPTMS) was converted to silsesquioxane oligomers by hydrolysis/condensation in three dental monomer solutions. The molecular mass distribution and molecular structures of these oligomers was studied by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Each dental monomer imparted distinct characteristics on the oligomeric silsesquioxane produced. Ethoxylated bisphenol A dimethacrylate (EBPADMA) produced low-mass oligomer silsesquioxanes that showed complete hydrolysis and a very high degree of intramolecular condensation (i.e., there were no methoxy and few silanol groups remaining on the oligomers). 1,6-Bis(methacryloxy-2-ethoxycarbon-ylamino) 2,4,4-trimethylhexane also produced fully hydrolyzed oligomeric silsesquioxanes but with twice the average molecular mass as the EBPADMA. Finally, triethylene glycol dimethacrylate produced higher mass oligomeric silsesquioxanes than EBPADMA even though it showed incomplete hydrolysis. The degree of hydrolysis increased with increasing mass, as did the degree of intramolecular condensation. Oligomers with degrees of polymerization below 8 were poorly hydrolyzed and showed little if any intramolecular condensation. Those with degrees of polymerization of 9 or greater were almost completely hydrolyzed with a high level of intramolecular condensation. (c) 2005 Wiley Periodicals, Inc. C1 US FDA, Rockville, MD 20855 USA. Natl Inst Stand & Technol, Div Polymers, Gaithersburg, MD 20899 USA. RP Farahani, M (reprint author), US FDA, Rockville, MD 20855 USA. EM farahanim@cder.fda.gov NR 9 TC 10 Z9 11 U1 1 U2 4 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0021-8995 J9 J APPL POLYM SCI JI J. Appl. Polym. Sci. PD FEB 15 PY 2006 VL 99 IS 4 BP 1842 EP 1847 DI 10.1002/app.22190 PG 6 WC Polymer Science SC Polymer Science GA 000DN UT WOS:000234441200064 ER PT J AU Ivanov, AP Dragunsky, EM Chumakov, KM AF Ivanov, AP Dragunsky, EM Chumakov, KM TI 1,25-Dihydroxyvitamin D3 enhances systemic and mucosal immune responses to inactivated poliovirus vaccine in mice SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 13th Meeting of the European-Study-Group-on-the-Molecular-Biology-of-Picornaviruses (Europic 2005) CY MAY 23-29, 2005 CL Lunteren, NETHERLANDS SP European Study Grp Mol Biol Picornaviruses ID IMMUNIZATION; INDUCTION; ANTIBODY AB 1,25-Dihydroxyvitamin D3 (DHVD3) coadministered with monovalent inactivated poliovirus vaccine (IPV) of all 3 serotypes significantly enhances antipoliovirus systemic and mucosal immunity in mice. Although serum immunoglobulin G antibodies are significantly higher in serotypes 2 and 3, and although salivary immunoglobulin A is significantly increased in serotypes 1 and 3, DHVD3 had the most dramatic effect on the level of neutralizing serum antibodies of all 3 IPV serotypes. These findings suggest a possible use of vitamin D3 as an adjuvant for currently used and proposed new Sabin IPVs. C1 US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. RP Ivanov, AP (reprint author), 1401 Rockville Pike,HFM-470, Rockville, MD 20852 USA. EM ivanov@cber.fda.gov NR 12 TC 35 Z9 36 U1 1 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 FEB 15 PY 2006 VL 193 IS 4 BP 598 EP 600 DI 10.1086/499970 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 005NM UT WOS:000234831100016 PM 16425140 ER PT J AU Baim, DS Mehran, R Kereiakes, DJ Gross, TP Simons, M Malenka, D Kaplan, AV AF Baim, DS Mehran, R Kereiakes, DJ Gross, TP Simons, M Malenka, D Kaplan, AV TI Postmarket surveillance for drug-eluting coronary stents - A comprehensive approach SO CIRCULATION LA English DT Article; Proceedings Paper CT 2nd Dartmouth Drug and Device Development Symposium CY OCT 14-15, 2004 CL Woodstock, VT DE angioplasty; coronary disease; postmarket surveillance; regulatory policy; stents ID CLINICAL-OUTCOMES; MEDICAL DEVICE; INTERVENTIONS; REGISTRY; IMPLANTATION; APPROVAL; ERA C1 Dartmouth Coll, Dartmouth Hitchcock Med Ctr, Lebanon, NH 03756 USA. Dartmouth Coll, Dartmouth Med Sci, Cardiol Sect, Lebanon, NH 03756 USA. US FDA, Ctr Devices & Radiol Hlth, Rockville, MD USA. Christ Hosp, Heart Ctr, Lindner Ctr, Cincinnati, OH USA. Columbia Univ, New York, NY USA. Cardiovasc Res Fdn, New York, NY USA. Brigham & Womens Hosp, Cardiol Sect, Boston, MA USA. RP Kaplan, AV (reprint author), Dartmouth Coll, Dartmouth Hitchcock Med Ctr, 1 Med Ctr Dr, Lebanon, NH 03756 USA. EM aaron.v.kaplan@hitchock.org RI Simons, Michael/G-8553-2014 OI Simons, Michael/0000-0003-0348-7734 NR 19 TC 13 Z9 13 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD FEB 14 PY 2006 VL 113 IS 6 BP 891 EP 897 DI 10.1161/CIRCULATIONAHA.105.569657 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 012DU UT WOS:000235319200022 PM 16476863 ER PT J AU Taylor, DR AF Taylor, DR TI Obstacles and advances in SARS vaccine development SO VACCINE LA English DT Review DE severe acute respiratory syndrome; coronavirus; SARS-CoV; animal models; vaccine ID ACUTE-RESPIRATORY-SYNDROME; ANTIBODY-DEPENDENT ENHANCEMENT; FELINE INFECTIOUS PERITONITIS; CORONAVIRUS SPIKE GLYCOPROTEIN; VIRUS-INFECTION; DNA VACCINE; NEUTRALIZING ANTIBODIES; PROTECTIVE IMMUNITY; MONOCLONAL-ANTIBODY; LYMPHOCYTE SUBSETS AB The emergence of the severe acute respiratory syndrome (SARS) that resulted in a pandemic in 2003 spurred a flurry of interest in the development of vaccines to prevent and treat the potentially deadly viral infection. Researchers around the world pooled their scientific resources and shared early data in an unprecedented manner in light of the impending public health crisis. There are still large gaps in knowledge about the pathogenesis of this virus. While significant advances have been made in the development of animal models, the practicality of their use may be hampered by a lack of pathological similarity with human disease. Described here are issues related to progress in vaccine development and the obstacles that lie ahead for both researchers and regulatory agencies. (c) 2005 Elsevier Ltd. All rights reserved. C1 US FDA, CBER, Off Blood Res & Review, Div Emerging & Transfus Transmitted Dis, Bethesda, MD 20892 USA. RP Taylor, DR (reprint author), US FDA, CBER, Off Blood Res & Review, Div Emerging & Transfus Transmitted Dis, 8800 Rockville Pike,HFM-310, Bethesda, MD 20892 USA. EM taylord@cber.fda.gov NR 64 TC 11 Z9 11 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 FEB 13 PY 2006 VL 24 IS 7 BP 863 EP 871 DI 10.1016/j.vaccine.2005.08.102 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 017CT UT WOS:000235672400003 PM 16191455 ER PT J AU Jung, HJ Kim, PI Lee, SK Lee, CW Eu, YJ Lee, DG Earm, YE Kim, JI AF Jung, HJ Kim, PI Lee, SK Lee, CW Eu, YJ Lee, DG Earm, YE Kim, JI TI Lipid membrane interaction and antimicrobial activity of GsMTx-4, an inhibitor of mechanosensitive channel SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE GsMTx-4; mechanosensitive channel; channel inhibitor; antimicrobial peptide ID RELAXATION MATRIX ANALYSIS; GATING MODIFIER TOXINS; DEPENDENT K+ CHANNELS; ESCHERICHIA-COLI; SPIDER VENOM; FUNCTIONAL RECONSTITUTION; CHARYBDOTOXIN BLOCK; ION CHANNELS; VOLTAGE; HANATOXIN AB GsMTx-4, a polypeptide from the spider Grammostola spatulata, is an inhibitor of mechanosensitive channels. It is known to interact with lipid membranes, suggesting it partitions into the membrane to alter the channel gating, but the effect of the membrane charge on GsMTx-4 activity remains unknown. In this study, we found that GsMTx-4 more effectively interacts with anionic lipids than zwitter-ionic ones. The effect of GsMTx-4 on negatively charged membranes was similar to that of the antimicrobial peptide melittin, which led us to assess GsMTx-4's antimicrobial activity. Interestingly, we found that, in contrast to other neurotoxins, GsMTx-4 exhibited antimicrobial properties and was more active against Gram-positive than Gram-negative bacteria. These results suggest that GsMTx-4 exerts its antimicrobial effect by altering the packing of the membrane and/or inhibiting mechanosensitive channels. These findings could point the way towards a new class of antimicrobial peptides. (c) 2005 Elsevier Inc. All rights reserved. C1 Gwangju Inst Sci & Technol, Dept Life Sci, Kwangju 500712, South Korea. US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. Kyungpook Natl Univ, Coll Nat Sci, Sch Life Sci & Biotechnol, Taegu 702701, South Korea. Seoul Natl Univ, Coll Med, Dept Physiol, Seoul 110799, South Korea. RP Kim, JI (reprint author), Gwangju Inst Sci & Technol, Dept Life Sci, Kwangju 500712, South Korea. EM jikim@gist.ac.kr NR 37 TC 17 Z9 21 U1 0 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD FEB 10 PY 2006 VL 340 IS 2 BP 633 EP 638 DI 10.1016/j.bbrc.2005.12.046 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 004DI UT WOS:000234731800040 PM 16376854 ER PT J AU Moore, J Yin, JJ Yu, LL AF Moore, J Yin, JJ Yu, LL TI Novel fluorometric assay for hydroxyl radical scavenging capacity (HOSC) estimation SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE hydroxyl radical; antioxidant; ferric iron; Fenton-like reaction; fluorescein; electron spin resonance ID HYDROGEN-PEROXIDE; ANTIOXIDANT CAPACITY; OXIDATIVE STRESS; DNA-DAMAGE; BIOLOGICAL-SYSTEMS; IN-VITRO; INDUCED CARCINOGENESIS; LIPID-PEROXIDATION; OXYGEN; MECHANISM AB A novel fluorometric method was developed and validated for hydroxyl radical scavenging capacity (HOSC) estimation using fluorescein as the probe. A constant flux of pure hydroxyl radical is generated under physiological pH using a Fenton-like Fe3+/H2O2 reaction. The generation of pure hydroxyl radicals under the experimental conditions was evaluated and confirmed using electron spin resonance with DMPO spin-trapping measurements. The hydroxyl radical scavenging capacity of a selected antioxidant sample is quantified by measuring the area under the fluorescence decay curve with or without the presence of the antioxidant and expressed as Trolox equivalents per unit of the antioxidant. The assay may be performed using a plate reader with a fluorescence detector for high-throughput measurements. The assay was validated for linearity, precision, accuracy, reproducibility, and its correlation with a popular peroxyl radical scavenging capacity assay using selected pure antioxidant compounds and botanical extracts. This method may provide researchers in the food, nutrition, and medical fields an easy to use protocol to evaluate free radical scavenging capacity of pure antioxidants and natural extracts in vitro against the very reactive hydroxyl radical, which may be linked to numerous degenerative diseases and conditions. C1 Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA. US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Yu, LL (reprint author), Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA. EM lyu5@umd.edu RI Yin, Jun Jie /E-5619-2014 NR 66 TC 88 Z9 91 U1 1 U2 29 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 FEB 8 PY 2006 VL 54 IS 3 BP 617 EP 626 DI 10.1021/jf052555p PG 10 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 011EC UT WOS:000235249800003 PM 16448158 ER PT J AU Haffner, ME AF Haffner, ME TI Focus on research - Adopting orphan drugs - Two dozen years of treating rare diseases SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 US FDA, Off Orphan Prod Dev, Rockville, MD 20857 USA. RP Haffner, ME (reprint author), US FDA, Off Orphan Prod Dev, Rockville, MD 20857 USA. NR 1 TC 76 Z9 82 U1 1 U2 8 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 FEB 2 PY 2006 VL 354 IS 5 BP 445 EP 447 DI 10.1056/NEJMp058317 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 008DC UT WOS:000235019400004 PM 16452556 ER PT J AU Wagner, RF AF Wagner, RF TI Toward a strategy for consensus development on a quantitative approach to medical imaging SO ACADEMIC RADIOLOGY LA English DT Editorial Material ID MAMMOGRAPHY C1 US FDA, Ctr Devices & Radiol Hlth, Off Sci & Technol, Rockville, MD 20857 USA. RP Wagner, RF (reprint author), US FDA, Ctr Devices & Radiol Hlth, Off Sci & Technol, HFZ-142,12720 Twinbrook Pkwy,Bldg 1, Rockville, MD 20857 USA. EM robert.wagner@fda-hhs.gov NR 9 TC 2 Z9 2 U1 0 U2 0 PU ASSOC UNIV RADIOLOGISTS PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523-2251 USA SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD FEB PY 2006 VL 13 IS 2 BP 137 EP 139 DI 10.1016/j.acra.2005.11.037 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 009JK UT WOS:000235107800001 PM 16428047 ER PT J AU Badano, A Gallas, BD AF Badano, A Gallas, BD TI Detectability decreases with off-normal viewing in medical liquid crystal displays SO ACADEMIC RADIOLOGY LA English DT Article DE liquid-crystal display; soft-copy display; display contrast; observer study ID LIGHT-EMITTING DEVICES; MULTIREADER; VALIDATION; RADIOLOGY; LUMINANCE; DESIGN AB Rationale and Objectives. To quantify the reduction in detection performance of subtle signals at off-normal viewing directions in medical active-matrix liquid crystal displays (AMLCDs). Materials and Methods. Fifty synthetic image pairs per viewing condition (a total of 350) were used in a two-alternative forced-choice experiment in which 11 trained observers viewed images at 0, 30, and 45 degrees from the display normal, along the diagonal axis of a 5 million pixel in-plane switching monochrome AMLCD. The images were generated using white-noise backgrounds. A Gaussian signal was added to the signal-present set with three different signal amplitudes (4, 8, and 12 gray levels in a 10-bit scale). Results. The average percent correct achieved for a signal of 4 gray levels was 79.6 (95% confidence intervals based on reader and case variability: 71.6-86.9), 63.4 (CI 56.0-71.3), and 55.3 (Cl 48.4-62.0), for 0, 30 and 45 degrees from the display normal, respectively. When the signal amplitude was increased by a factor of two, the performance was 76.9 and 57.0 for 30 and 45 degrees, respectively, and 95.3 and 85.3 when the amplitude was increased by a factor of three. The observers took on average about twice as long and as much as seven times as long to reach decisions in off-normal viewing. Conclusions. Off-normal viewing of diagnostic images in AMLCDs significantly reduces the detection of low-contrast abnormalities. Increased off-normal signal amplitudes were required to regain the detection performance measured for normal viewing. We observed this decrease in detection performance for off-normal viewing even when measured decision times were about twice as long as for normal viewing. C1 US FDA, NIBIB, CDRH, Lab Assessment Med Imaging, Rockville, MD 20857 USA. RP Badano, A (reprint author), US FDA, NIBIB, CDRH, Lab Assessment Med Imaging, 12720 Twinbrook Pkwy,HFZ-142, Rockville, MD 20857 USA. EM aldo.badano@fda.hhs.gov OI Gallas, Brandon/0000-0001-7332-1620; badano, aldo/0000-0003-3712-6670 NR 28 TC 6 Z9 6 U1 0 U2 1 PU ASSOC UNIV RADIOLOGISTS PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523-2251 USA SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD FEB PY 2006 VL 13 IS 2 BP 210 EP 218 DI 10.1016/j.acra.2005.08.015 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 009JK UT WOS:000235107800011 PM 16428057 ER PT J AU Karnaukhova, E Schey, KL Crouch, RK AF Karnaukhova, E Schey, KL Crouch, RK TI Circular dichroism and cross-linking studies of bacteriorhodopsin mutants SO AMINO ACIDS LA English DT Article DE bacteriorhodopsin; mutants; circular dichroism; cross-linking; matrix-assisted laser desorption/ionization mass spectrometry ID PURPLE MEMBRANE; HALOBACTERIUM-HALOBIUM; PROTEIN-INTERACTION; SENSORY RHODOPSIN; MASS-SPECTROMETRY; CD SPECTRUM; CHROMOPHORE; PHOTOCYCLE; MODEL; HETEROGENEITY AB Circular dichroism (CD) spectroscopy was employed for native (wild type, WT) bacteriorhodopsin (bR) and several mutant derivatives: R134K, R134H, R82Q, S35C, L66C, and R134C/E194C. Comparative analysis of the CD spectra in visible range shows that only R134C/E194C exhibits biphasic CD, typical for native bR, the other mutants demonstrate CD spectra with significantly smaller or absent negative band. Since the biphasic CD is a feature of hexagonal lattice structure composed by bR trimers in the purple membrane, these mutants and WT were examined by cross-linking studies, which confirmed the same trend towards trimeric organization. Therefore, a single amino acid substitution may lead to drastically different CD spectra without disruption of bR trimeric organization. Thus, although disruption of bR trimeric crystalline lattice structure (e.g., solubilization with detergents) directly results in the disappearance of characteristic bilobe in visible CD, the lack of the bilobe in the CD alone does not predict the absence of trimers. C1 US FDA, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. Med Univ S Carolina, Dept Pharmacol, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Ophthalmol, Charleston, SC 29425 USA. RP Karnaukhova, E (reprint author), US FDA, Div Hematol, Ctr Biol Evaluat & Res, 8800 Rockville Pike,NIH Bldg 29, Bethesda, MD 20892 USA. FU NEI NIH HHS [EY-14793] NR 49 TC 1 Z9 2 U1 0 U2 2 PU SPRINGER WIEN PI WIEN PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 WIEN, AUSTRIA SN 0939-4451 EI 1438-2199 J9 AMINO ACIDS JI Amino Acids PD FEB PY 2006 VL 30 IS 1 BP 17 EP 23 DI 10.1007/s00726-005-0255-0 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 013YD UT WOS:000235445000002 PM 16477391 ER PT J AU Kim, SJ Kweon, O Freeman, JP Jones, RC Adjei, MD Jhoo, JW Edmondson, RD Cerniglia, CE AF Kim, SJ Kweon, O Freeman, JP Jones, RC Adjei, MD Jhoo, JW Edmondson, RD Cerniglia, CE TI Molecular cloning and expression of genes encoding a novel dioxygenase involved in low- and high-molecular-weight polycyclic aromatic hydrocarbon degradation in Mycobacterium vanbaalenii PYR-1 SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID SP STRAIN PYR-1; RING-HYDROXYLATING DIOXYGENASES; FUNGUS PLEUROTUS-OSTREATUS; ESCHERICHIA-COLI; NAPHTHALENE DIOXYGENASE; DEGRADING MYCOBACTERIUM; NUCLEOTIDE-SEQUENCE; PYRENE DEGRADATION; SP-NOV; METABOLISM AB Mycobacterium vanbaalenii PYR-1 is able to metabolize a wide range of low- and high-molecular-weight (HMW) polycyclic aromatic hydrocarbons (PAHs). A 20-kDa protein was upregulated in PAH-metabolizing M. vanbaalenii PYR-1 cells compared to control cultures. The differentially expressed protein was identified as a P subunit of the terminal dioxygenase using mass spectrometry. PCR with degenerate primers designed based on de novo sequenced peptides and a series of plaque hybridizations were done to screen the M. vanbaalenii PYR-1 genomic library. The genes, designated nidA3B3, encoding the alpha and beta subunits of terminal dioxygenase, were subsequently cloned and sequenced. The deduced enzyme revealed close similarities to the corresponding PAH ring-hydroxylating dioxygenases from Mycobacterium and Rhodococcus spp. but had the highest similarity, 61.9%, to the alpha subunit from Nocardioides sp. strain KP7. The alpha subunit also showed 52% sequence homology with the previously reported NidA from M. vanbaalenii PYR-1. The genes nidA3B3 were subcloned into the expression vector pET-17b, and the enzyme activity in Escherichia coli cells was reconstituted through coexpression with the ferredoxin (PhdC) and ferredoxin reductase (PhdD) genes of the phenanthrene dioxygenase from Nocardioides sp. strain KP7. The recombinant PAH dioxygenase appeared to favor the HMW PAR substrates fluoranthene, pyrene, and phenanthrene. Several other PAHs, including, naphthalene, anthracene, and benz[a]anthracene, were also converted to their corresponding cis-dihydrodiols. The recombinant E. coli, however, did not show any dioxygenation activity for phthalate and biphenyl. The upregulation of nidA3B3 in ill. vanbaalenii PYR-1 induced by PAHs was confirmed by reverse transcription-P(,R analysis. C1 US FDA, Div Microbiol, NCTR, Jefferson, AR 72079 USA. US FDA, Div Biochem Toxicol, NCTR, Jefferson, AR 72079 USA. US FDA, Div Syst Toxicol, NCTR, Jefferson, AR 72079 USA. Kangweon Natl Univ, Dept Food Sci & Technol Anim Resources, Chunchon 200701, South Korea. RP Cerniglia, CE (reprint author), US FDA, Div Microbiol, NCTR, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM CCerniglia@nctr.fda.gov NR 67 TC 68 Z9 75 U1 1 U2 25 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 FEB PY 2006 VL 72 IS 2 BP 1045 EP 1054 DI 10.1128/AEM.72.2.1045-1054.2006 PG 10 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 012QC UT WOS:000235353100011 PM 16461648 ER PT J AU Sharma, SK Ferreira, JL Eblen, BS Whiting, RC AF Sharma, SK Ferreira, JL Eblen, BS Whiting, RC TI Detection of type A, B, E, and F Clostridium botulinum neurotoxins in foods by using an amplified enzyme-linked immunosorbent assay with digoxigenin-labeled antibodies SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID COLORIMETRIC CAPTURE ELISAS; SOLUTION-PHASE COMPLEXES; CURED MEAT SYSTEM; NUCLEOTIDE-SEQUENCE; COAGULATION ASSAY; TETANUS TOXIN; IMMUNOLOGICAL CHARACTERIZATION; ORAL TOXICITIES; PURE CULTURE; BINDING AB An amplified enzyme-linked immunosorbent assay (ELISA) for the detection of Clostridium botulinum complex neurotoxins was evaluated for its ability to detect these toxins in food. The assay was found to be suitable for detecting type A, B, E, and F botulinum neurotoxins in a variety of rood matrices representing liquids, solid, and semisolid food. Specific foods included broccoli, orange juice, bottled water, cola soft drinks, vanilla extract, oregano, potato salad, apple juice, meat products, and dairy foods. The detection sensitivity of the test for these botulinum complex serotypes was found to be 60 pg/ml (1.9 50% lethal dose [LD50]) for botulinum neurotoxin type A (BoNT/A), 176 pg/ml (1.58 LD50) for BoNT/B, 163 pg/ml for BoNT/E (4.5 LD50), and 117 pg/ml for BoNT/F (less than 1 LD50) in casein buffer. The test could also readily detect 2 ng/ml of neurotoxins type A, B, E, and F in a variety of food samples. For specificity studies., the assay was also used to test a large panel of type A C. botulinum, a smaller panel of proteolytic and nonproteolytic type B, E, and F neurotoxin-producing Clostridia, and nontoxigenic organisms using an overnight incubation of toxin production medium. The assay appears to be an effective tool for large-scale screening of the food supply in the event of a botulinum neurotoxin contamination event. C1 US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. Ctr Dis Control & Prevent, Atlanta, GA USA. RP Sharma, SK (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy,HFS-302, College Pk, MD 20740 USA. EM shashi.sharma@cfsan.fda.gov NR 49 TC 81 Z9 90 U1 0 U2 16 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0099-2240 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD FEB PY 2006 VL 72 IS 2 BP 1231 EP 1238 DI 10.1128/AEM.72.2.1231-1238.2006 PG 8 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 012QC UT WOS:000235353100034 PM 16461671 ER PT J AU Szarfman, A Doraiswamy, PM Tonning, JM Levine, JG AF Szarfman, A Doraiswamy, PM Tonning, JM Levine, JG TI Association between pathologic gambling and parkinsonian therapy as detected in the food and drug administration adverse event database SO ARCHIVES OF NEUROLOGY LA English DT Letter C1 US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Szarfman, A (reprint author), US FDA, Ctr Drug Evaluat & Res, HFD-030,Bldg 22,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM szarfman@cder.fda.gov NR 3 TC 32 Z9 34 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD FEB PY 2006 VL 63 IS 2 BP 299 EP 300 DI 10.1001/archneur.63.2.299-b PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 010LH UT WOS:000235195700026 PM 16476828 ER PT J AU Rendon, P Sivinski, J Holler, T Bloem, K Lopez, M Martinez, A Aluja, M AF Rendon, P Sivinski, J Holler, T Bloem, K Lopez, M Martinez, A Aluja, M TI The effects of sterile males and two braconid parasitoids, Fopius arisanus (Sonan) and Diachasmimorpha krausii (Fullaway) (Hymenoptera), on caged populations of Mediterranean fruit flies, Ceratitis capitata (Wied.) (Diptera : Tephritidae) at various sites in Guatemala SO BIOLOGICAL CONTROL LA English DT Article DE Braconidae; augmentative release; sterile insect technique; mass rearing; field-cages ID BIOLOGICAL-CONTROL; PUPAL PARASITOIDS; LARVAL-PUPAL; FLY DIPTERA; ANASTREPHA; DISTRIBUTIONS; SUPPRESSION; HAWAII; MEXICO AB Area-wide control of the Mediterranean fruit fly (=medfly), Ceratitis capitata (Wiedemann), typically involves sterile insect technique (=SIT), and at present the "Temperature Sensitive Lethal" (=TSL) strain is commonly mass-reared for such releases. In theory, and with some experimental support, the augmentative addition of parasitoids to sterile releases can suppress pest populations to a greater extent than either technique alone. The efficacies of TSL males, parasitoids, and TSL males and parasitoids were compared in large field cages erected over coffee grown at four locations and three altitudes (relatively high, medium and low for the crop) in Guatemala. Two species of opiine braconid parasitoids, the larval-pupal parasitoid Diachasmimorpha krausii (Fullaway) and the egg-pupal parasitoid Fopius arisanus (Sonan), were released either together or in combination with sterile males into cages along with fertile medflies. Results of this evaluation were assessed by comparing the number of pupae and adult insects that completed development (F1 generation) as a result of the reproduction of a parental generation released into each field cage. The TSL males significantly suppressed F1 fly populations but only in one of four study sites. However, the inclusion of F. arisanus and D. krausii always provided significant suppression and the effect was frequently substantial. In one site there was a significant interaction between the capacity of sterile males and parasitoids to suppress caged fly populations. There was no effect of host-fruit abundance on the numbers of flies recovered, however, there were significant interactions between maximum and minimum temperatures and the effects of sterile males and parasitoids, respectively. The results suggest that mass-reared sterile medflies and biological control agents should be tested for both consistent sexual-quality and their ability to perform in the various environments in which they will be released. (c) 2005 Elsevier Inc. All rights reserved. C1 USDA ARS, CMAVE, Gainesville, FL 32604 USA. USDA, APHIS, CPHST, Guatemala City, Guatemala. USDA, APHIS, CPHST, FDACS,DPI, Gainesville, FL 32602 USA. Florida A&M Univ, Ctr Biol Control, USDA, APHIS,CPHST, Tallahassee, FL 32307 USA. MOSCAMED, Guatemala City, Guatemala. Inst Ecol, Xalapa 91000, Veracruz, Mexico. RP Sivinski, J (reprint author), USDA ARS, CMAVE, POB 14565, Gainesville, FL 32604 USA. EM jsivinski@gainesville.usda.ufl.edu NR 29 TC 28 Z9 29 U1 3 U2 12 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1049-9644 J9 BIOL CONTROL JI Biol. Control PD FEB PY 2006 VL 36 IS 2 BP 224 EP 231 DI 10.1016/j.biocontrol.2005.10.006 PG 8 WC Biotechnology & Applied Microbiology; Entomology SC Biotechnology & Applied Microbiology; Entomology GA 000CI UT WOS:000234438100013 ER PT J AU Schultz, KR Miklos, DB Fowler, D Cooke, K Shizuru, J Zorn, E Holler, E Ferrara, Y Shulman, H Lee, SY Martin, P Filipovich, AH Flowers, MED Weisdorf, D Couriel, D Lachenbruch, PA Mittleman, B Vogelsang, GB Pavletic, SZ AF Schultz, KR Miklos, DB Fowler, D Cooke, K Shizuru, J Zorn, E Holler, E Ferrara, Y Shulman, H Lee, SY Martin, P Filipovich, AH Flowers, MED Weisdorf, D Couriel, D Lachenbruch, PA Mittleman, B Vogelsang, GB Pavletic, SZ TI Toward biomarkers for chronic graft-versus-host disease: National Institutes of Health Consensus Development Project on criteria for clinical trials in chronic graft-versus-host disease: III. Biomarker working group report SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Review DE graft-versus-host disease; biomarkers ID BONE-MARROW-TRANSPLANTATION; STEM-CELL TRANSPLANTATION; MINOR HISTOCOMPATIBILITY ANTIGEN; CYTOTOXIC T-LYMPHOCYTES; DENDRITIC CELLS; MONOCLONAL-ANTIBODY; GENE POLYMORPHISMS; FEMALE DONORS; LABIAL SALIVA; BLOOD AB Biology-based markers that can be used to confirm the diagnosis of chronic graft-versus-host disease (GVHD) or monitor progression of the disease could help in the evaluation of new therapies. Biomarkers have been defined as any characteristic that is objectively measured and evaluated as an indicator of a normal biologic or pathogenic process, a pharmacologic response to a therapeutic intervention, or a surrogate end point intended to substitute for a clinical end point. The following applications of biomarkers could be useful in chronic GVHD clinical trials or management: (1) predicting response to therapy; (2) measuring disease activity and distinguishing irreversible damage from continued disease activity; (3) predicting the risk of developing chronic GVHD; (4) diagnosing chronic GVHD: (5) predicting the prognosis of chronic GVHD; (6) evaluating the balance between GVHD and graft-versus-leukemia effects (graft-versus-leukemia or GVT); and (7) serving as a surrogate end point for therapeutic response. Such biomarkers can be identified by either hypothesis-driven testing or by high-throughput discovery-based methods. To date, no validated biomarkers have been established for chronic GVHD, although several candidate biomarkers have been identified from limited hypothesis-driven studies. Both approaches have merit and should be pursued. The consistent treatment and standardized documentation needed to support biomarker studies are most likely to be satisfied in prospective clinical trials. (C) 2006 American Society for Blood and Marrow Transplantation. C1 Univ British Columbia, British Columbia Childrens Hosp, Vancouver, BC V6H 3V4, Canada. Stanford Univ, Med Ctr, Stanford, CA 94305 USA. NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Univ Michigan, Med Ctr, Ann Arbor, MI USA. Harvard Univ, Brigham & Womens Hosp, Boston, MA 02115 USA. Univ Regensburg, D-8400 Regensburg, Germany. Univ Washington, Fred Hutchinson Canc Res Ctr, Seattle, WA 98195 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Cincinnati, Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH USA. Univ Minnesota, Minneapolis, MN USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. US FDA, Rockville, MD 20857 USA. NIAMSD, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. RP Schultz, KR (reprint author), Univ British Columbia, British Columbia Childrens Hosp, 4480 Oak St,Room A119, Vancouver, BC V6H 3V4, Canada. EM kschultz@interchange.ubc.ca NR 66 TC 103 Z9 108 U1 0 U2 2 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 FEB PY 2006 VL 12 IS 2 BP 126 EP 137 DI 10.1016/j.bbmt.2005.11.010 PG 12 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 011RD UT WOS:000235284900002 PM 16443511 ER PT J AU Tsong, Y Zhang, J AF Tsong, Y Zhang, J TI Untitled - Reply SO BIOMETRICAL JOURNAL LA English DT Letter DE superiority test; non-inferiority test; switching; simultaneous test C1 US FDA, CDER, Off Biostat, Rockville, MD 20857 USA. RP Tsong, Y (reprint author), US FDA, CDER, Off Biostat, Rockville, MD 20857 USA. EM tsong@cder.fda.gov NR 2 TC 1 Z9 1 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 FEB PY 2006 VL 48 IS 1 BP 176 EP 176 DI 10.1002/bimj.200510203 PG 1 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 018JL UT WOS:000235760400015 ER PT J AU Buck, M Bouguet-Bonnet, S Pastor, RW MacKerell, AD AF Buck, M Bouguet-Bonnet, S Pastor, RW MacKerell, AD TI Importance of the CMAP correction to the CHARMM22 protein force field: Dynamics of hen lysozyme SO BIOPHYSICAL JOURNAL LA English DT Article ID NMR SPIN-RELAXATION; MOLECULAR-DYNAMICS; SIMULATIONS; ACCURACY AB The recently developed CMAP correction to the CHARMM22 force field (C22) is evaluated from 25 ns molecular dynamics simulations on hen lysozyme. Substantial deviations from experimental backbone root mean-square fluctuations and N-H NMR order parameters obtained in the C22 trajectories (especially in the loops) are eliminated by the CMAP correction. Thus, the C22/CMAP force field yields improved dynamical and structural properties of proteins in molecular dynamics simulations. C1 Case Western Reserve Univ, Dept Physiol & Biophys, Sch Med, Cleveland, OH 44106 USA. US FDA, Ctr Biol Evaluat & Res, Biophys Lab, Rockville, MD 20852 USA. Univ Maryland, Sch Pharm, Baltimore, MD 21201 USA. RP Buck, M (reprint author), Case Western Reserve Univ, Dept Physiol & Biophys, Sch Med, Cleveland, OH 44106 USA. EM mxb150@case.edu RI Buck, Matthias/B-2106-2017; OI Buck, Matthias/0000-0002-2958-0403; MacKerell, Alex/0000-0001-8287-6804 NR 11 TC 171 Z9 172 U1 0 U2 15 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2006 VL 90 IS 4 BP L36 EP L38 DI 10.1529/biophysj.105.078154 PG 3 WC Biophysics SC Biophysics GA 007XH UT WOS:000235004200004 PM 16361340 ER PT J AU Menard, C Johann, D Lowenthal, M Muanza, T Sproull, M Ross, S Gulley, J Petricoin, E Coleman, CN Whiteley, G Liotta, L Camphausen, K AF Menard, C Johann, D Lowenthal, M Muanza, T Sproull, M Ross, S Gulley, J Petricoin, E Coleman, CN Whiteley, G Liotta, L Camphausen, K TI Discovering clinical biomarkers of ionizing radiation exposure with serum proteomic analysis SO CANCER RESEARCH LA English DT Article ID TANDEM MASS-SPECTROMETRY; CHROMOSOMAL-ABERRATIONS; BLOOD-LYMPHOCYTES; CANCER; PROTEIN; EXPRESSION; RADIOTHERAPY; PNEUMONITIS; IRRADIATION; BINDING AB In this study, we sought to explore the merit of proteomic profiling strategies in patients with cancer before and during radiotherapy in an effort to discover clinical biomarkers of radiation exposure. Patients with a diagnosis of cancer provided informed consent for enrollment on a study permitting the collection of serum immediately before and during a course of radiation therapy. High-resolution surface-enhanced laser desorption and ionization-time of flight (SELDI-TOF) mass spectrometry (MS) was used to generate high-throughput proteomic profiles of unfractionated serum samples using an immobilized metal ion-affinity chromatography nickel-affinity chip surface. Resultant proteomic profiles were analyzed for unique biomarker signatures using supervised classification techniques. MS-based protein identification was then done on pooled sera in an effort to begin to identify specific protein fragments that are altered with radiation exposure. Sixty-eight patients with a wide range of diagnoses and radiation treatment plans provided serum samples both before and during ionizing radiation exposure. Computer-based analyses of the SELDI protein spectra could distinguish unexposed from radiation-exposed patient samples with 91% to 100% sensitivity and 97% to 100% specificity using Various classifier models. The method also showed an ability to distinguish high from low dose-volume levels of exposure with a sensitivity of 83% to 100% and specificity of 91% to 100%. Using direct identity techniques of albumin-bound peptides, known to underpin the SELDI-TOF fingerprints, 23 protein fragments/peptides were uniquely detected in the radiation exposure group, including an interleukin-6 precursor protein. The composition of proteins in serum seems to change with ionizing radiation exposure. Proteomic analysis for the discovery of clinical biomarkers of radiation exposure warrants further study. C1 NCI, Radiat Oncol Branch, Canc Res Ctr, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NCI, Food & Drug Adm Clin Proteom Program, Pathol Lab, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NCI, Tumor Immunol & Biol Lab, Canc Res Ctr, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NCI, Food & Drug Adm Clin Proteom Program, Off Cellular & Gene Therapy, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. Univ Toronto, Princess Margaret Hosp, Radiat Med Program, Toronto, ON, Canada. McGill Univ, Dept Radiat Oncol, Montreal, PQ H3A 2T5, Canada. NCI, Sci Appl Int Corp Frederick Inc, Clin Proteom Ref Lab, Gaithersburg, MD USA. RP NCI, Radiat Oncol Branch, Canc Res Ctr, NIH,Dept Hlth & Human Serv, Room B3B69,Bldg 10,9000 Rockville Pike, Bethesda, MD 20892 USA. EM camphauk@mail.nih.gov RI Gulley, James/K-4139-2016 OI Gulley, James/0000-0002-6569-2912 NR 36 TC 69 Z9 74 U1 0 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD FEB 1 PY 2006 VL 66 IS 3 BP 1844 EP 1850 DI 10.1158/0008-5472.CAN-05-3466 PG 7 WC Oncology SC Oncology GA 009FD UT WOS:000235095900073 PM 16452246 ER PT J AU Roberts, KP Sobrino, JA Payton, J Mason, LB Turesky, RJ AF Roberts, KP Sobrino, JA Payton, J Mason, LB Turesky, RJ TI Determination of apurinic/apyrimidinic lesions in DNA with high-performance liquid chromatography and tandem mass spectrometry SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID APURINIC APYRIMIDINIC SITES; ALDEHYDIC ABASIC SITE; DIRECT ADDUCTS; GENOMIC DNA; MOUSE SKIN; ASSAY; REPAIR; CELLS; QUANTITATION; TETRACHLOROHYDROQUINONE AB A new method has been developed to accurately measure apurinic and apyrimidinic (AP) DNA damage sites, which are lesions in DNA formed by loss of a nucleobase from oxidative stress or carcinogen adducts. If AP sites are left unrepaired (or if improperly repaired), these sites can lead to DNA mutations that may ultimately result in the formation of cancer. Hence, detection of AP sites may provide a useful indicator of exposure and susceptibility to chemical carcinogens and oxidative stress. AP detection is currently accomplished by immunodetection methods using an aldehyde reactive probe [Nakamura, J., Walker, V. E., Upton, P. B., Chiang, S.-Y., Kow, Y. W., and Swenberg, J. A. (1998) Cancer Res. 58, 222-225; Atamna, H., Cheung, I., and Ames, B. N. (2000) Proc. Natl. Acad. Sci. U.S.A. 97,686-691]; however, these approaches lack the specificity required for unequivocal identification of the AP site. Therefore, we have developed an accurate method based on mass spectrometry detection of AP sites from AP DNA that have been prelabeled with O-4-nitrobenzylhydroxylamine (NBHA). Once labeled and once the excess labeling agent has been removed, enzymatic digestion of DNA to monomeric subunits can be accomplished, followed by isolation and detection with high-performance liquid chromatography coupled to electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS). Optimization and validation of the experimental procedures and detection limits have been established using a model DNA oligomer (11-mer) containing uracil. Enzymatic removal of uracil with uracil glycosylase generates welldefined AP sites in both single- and double-stranded DNA. The addition of NBHA labels the AP site in the oligomer, creating a labeled 11-mer. HPLC-ESI-MS/MS in the negative ionization mode was used to monitor and confirm binding of NBHA to the AP oligomer. The NBHA-tagged oligomer underwent endo- and exonuclease digestion to the 5'-deoxyribose monophosphate (5'-dRp) level, thereby releasing free 5'-dRp-NBHA. The 5'-dRp-NBHA product was partially purified by solid phase extraction and quantified by LC-MS/MS using several transitions of the deprotonated molecule ([M-H](-) at m/z 363) and isotopically labeled 5'-dRp-NBHA as an internal standard. Further experiments with 5',3'-bisphosphatedeoxyribose and heat/acid-treated calf thymus DNA showed similar labeling, digestion, and detection results. Initial results show a quantification limit with 100 mu g of DNA to be 100 fmol (three abasic sites per 10(7) bases). C1 Univ Tulsa, Dept Chem & Biochem, Tulsa, OK 74104 USA. US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Roberts, KP (reprint author), Univ Tulsa, Dept Chem & Biochem, Tulsa, OK 74104 USA. EM kproberts@utulsa.edu RI Bell, Tiffany/F-4403-2010 NR 32 TC 19 Z9 19 U1 0 U2 7 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 FEB PY 2006 VL 19 IS 2 BP 300 EP 309 DI 10.1021/tx0502589 PG 10 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 015XM UT WOS:000235584800014 PM 16485907 ER PT J AU Eder, E Wacker, M Lutz, U Nair, J Fang, X Bartsch, H Beland, FA Schlatter, J Lutz, WK AF Eder, E Wacker, M Lutz, U Nair, J Fang, X Bartsch, H Beland, FA Schlatter, J Lutz, WK TI Oxidative stress related DNA adducts in the liver of female rats fed with sunflower-, rapeseed-, olive- or coconut oil supplemented diets SO CHEMICO-BIOLOGICAL INTERACTIONS LA English DT Article DE DNA adducts; oxidative stress; fatty acids ID POLYUNSATURATED FATTY-ACIDS; WHITE BLOOD-CELLS; 1,N-2-PROPANODEOXYGUANOSINE ADDUCTS; LIPID-PEROXIDATION; FREE-RADICALS; IN-VIVO; CANCER; RISK; MALONDIALDEHYDE; DEOXYGUANOSINE AB Both animal and epidemiological studies support an effect of fatty acid composition in the diet on cancer development, in particular on colon cancer. We investigated the modulating effect of supplementation of the diet of female F344 rats with sunflower-, rapeseed-, olive-, or coconut oil on the formation of the promutagenic, exocyclic DNA adducts in the liver, an organ where major metabolism of fatty acids takes place. 1,N-6-ethenodeoxyadenosine (etheno-dA), 3,N-4-ethenodeoxycytidine (etheno-dC) and 1,N-2-propandodeoxyguanosine from 4-hydroxy-2-nonenal (HNE-dGp) were determined as markers for DNA-damage derived from lipid peroxidation products and markers for oxidative stress. 8-Oxo-deoxyguanosine (8-Oxo-dG) was also measured as direct oxidative stress marker. The body weight of the rats was not influenced by the four diets containing the different vegetable oils during the 4-week feeding period. Highest adduct levels of etheno-dC (430 +/- 181 adducts/10(9) parent bases), HNE-dGp (617 +/- 96 adducts/10(9) parent bases) and 8-Oxo-dG (37.400 +/- 12,200 adducts/10(9) parent bases) were seen in rats on sunflower oil diet (highest linoleic acid content). Highest adducts levels of etheno-dA (133 +/- 113 adducts/10(9) parent bases) were found in coconut oil diet (lowest content of linoleic acid). Weakly positive correlations between linoleic acid content in the four diet groups were only observed for levels of HNE-dGp and 8-Oxo-dG. Neither the diet based on olive oil (which contains mainly oleic acid) nor the diet based on rapeseed oil (containing a-linolenic acid) exerted any significant protective effect against oxidative DNA damage. Our results indicate that a high linoleic acid diet may contribute to oxidative stress in the liver of female rats leading to a marginal increase in oxidative DNA-damage. (c) 2005 Elsevier Ireland Ltd. All rights reserved. C1 Univ Wurzburg, Dept Toxicol, D-97078 Wurzburg, Germany. German Canc Res Ctr, Div Toxicol & Canc Risk Factors, Heidelberg, Germany. US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Swiss Fed Off Publ Hlth, Zurich, Switzerland. RP Eder, E (reprint author), Univ Wurzburg, Dept Toxicol, D-97078 Wurzburg, Germany. EM eder@toxi.uni-wuerzburg.de NR 47 TC 37 Z9 38 U1 0 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0009-2797 J9 CHEM-BIOL INTERACT JI Chem.-Biol. Interact. PD FEB 1 PY 2006 VL 159 IS 2 BP 81 EP 89 DI 10.1016/j.cbi.2005.09.004 PG 9 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology GA 008CD UT WOS:000235016900001 PM 16256967 ER PT J AU Karnaukhova, E Vasileiou, C Wang, A Berova, N Nakanishi, K Borhan, B AF Karnaukhova, E Vasileiou, C Wang, A Berova, N Nakanishi, K Borhan, B TI Circular dichroism of heterochromophoric and partially regenerated purple membrane: Search for exciton coupling SO CHIRALITY LA English DT Article; Proceedings Paper CT 10th International Conference on Circular Dichroism CY AUG 20-25, 2005 CL Sandestin, FL DE purple membrane; bacteriorhodopsin; partial regeneration; heterochromophoric; circular dichroism; exciton-coupled circular dichroism ID POINT-CHARGE MODEL; HALOBACTERIUM-HALOBIUM; RETINAL CHROMOPHORE; MOLECULAR-DYNAMICS; BACTERIORHODOPSIN; PROTEIN; WATER; SPECTROSCOPY; PHOTOCYCLE; PIGMENT AB In order to determine the origin of the bisignate CD spectra of native purple membrane, heterochromophoric analogues containing bacteriorhodopsin regenerated with native all-trans-retinal and retinal analogues were investigated. The data collected for the purple membrane samples containing two different chromophores suggest the additive character of the CD spectra. This conclusion was supported by a series of spectra using 5,6-dihydroretinal and 3-dehydroretinal and by using 33% regenerated PM in buffer and in presence of osmolytes. Our results support the idea of conformational heterogeneity of the chromophores in the bR in the trimer, suggesting that the three bR subunits in the trimer are not conformationally equal, and therefore, the bisignate CD spectrum of bR in the purple membrane occurs rather due to a superposition of the CD spectra from variously distorted bR subunits in the trimer than interchromophoric exciton-coupling interactions. (c) 2005 Wiley-Liss, Inc. C1 Michigan State Univ, Dept Chem, E Lansing, MI 48824 USA. Columbia Univ, Dept Chem, New York, NY 10027 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. RP Borhan, B (reprint author), Michigan State Univ, Dept Chem, E Lansing, MI 48824 USA. EM babak@chemistry.msu.edu FU NIGMS NIH HHS [GM 36564] NR 76 TC 6 Z9 6 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0899-0042 EI 1520-636X J9 CHIRALITY JI Chirality PD FEB PY 2006 VL 18 IS 2 BP 72 EP 83 DI 10.1002/chir.20222 PG 12 WC Chemistry, Medicinal; Chemistry, Analytical; Chemistry, Organic; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 006RP UT WOS:000234915000002 PM 16385624 ER PT J AU Romero-Steiner, S Frasch, CE Carlone, G Fleck, RA Goldblatt, D Nahm, MH AF Romero-Steiner, S Frasch, CE Carlone, G Fleck, RA Goldblatt, D Nahm, MH TI Use of opsonophagocytosis for serological evaluation of pneurnococcal vaccines SO CLINICAL AND VACCINE IMMUNOLOGY LA English DT Review ID PNEUMOCOCCAL CONJUGATE VACCINE; LINKED-IMMUNOSORBENT-ASSAY; STREPTOCOCCUS-PNEUMONIAE; FUNCTIONAL ANTIBODIES; KILLING ASSAY; POLYSACCHARIDES; COLONIES; INFANTS C1 Univ Alabama, Birmingham, AL 35249 USA. Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. US FDA, Bethesda, MD 20892 USA. Natl Inst Biol Stand & Controls, S Mimms, Herts, England. UCL, Inst Child Hlth, London, England. RP Nahm, MH (reprint author), Univ Alabama, Birmingham, AL 35249 USA. EM nahm@uab.edu RI Goldblatt, David/C-5972-2008; OI Goldblatt, David/0000-0002-0769-5242; Romero-Steiner, Sandra/0000-0003-4128-7768; Nahm, Moon/0000-0002-6922-1042 NR 17 TC 91 Z9 96 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1556-6811 J9 CLIN VACCINE IMMUNOL JI Clin. Vaccine Immunol. PD FEB PY 2006 VL 13 IS 2 BP 165 EP 169 DI 10.1128/CVI.13.2.165-169.2006 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 015GG UT WOS:000235539300001 PM 16467321 ER PT J AU Davidson, B Espina, V Steinberg, SM Florenes, VA Liotta, LA Kristensen, GB Trope, CG Berner, A Kohn, EC AF Davidson, B Espina, V Steinberg, SM Florenes, VA Liotta, LA Kristensen, GB Trope, CG Berner, A Kohn, EC TI Proteomic analysis of malignant ovarian cancer effusions as a tool for biologic and prognostic profiling SO CLINICAL CANCER RESEARCH LA English DT Article ID VASCULAR-PERMEABILITY FACTOR; SEROUS EFFUSIONS; CARCINOMA CELLS; PROTEIN MICROARRAYS; CLINICAL PROTEOMICS; MESSENGER-RNA; ASCITES-FLUID; GROWTH; EXPRESSION; PATHWAY AB Purpose: Malignant epithelial ovarian cancer effusions are important in disease dissemination and clinical outcome. The identification of biochemical events active in effusions may improve our identification and application of targeted therapeutics. Experimental Design: Archival effusion samples for which outcome information was known were studied. Clinical variables were comparable between these groups. Two cohorts of patients with malignant effusion were assessed: those with effusion at presentation (Tap1) or at first recurrence (Tap2). Expression and activated fraction of selected signaling proteins were quantitated on serial protein microarrays using validated antibodies. Proteomic results and clinical variables were analyzed by univariate analysis followed by Cox proportional hazards model analysis. Results: Malignant effusions (>80% malignant cells) were distinguished from benign effusions by higher expression of AKT, activated extracellular signal-regulated kinase, activated (P <= 0.001) and total cAMP-responsive element binding protein (P = 0.01), and JNK (P = 0.03). Malignant pleural effusions could not be differentiated from ascites by signaling profiles. Both had signal expression clusters for survival, proliferation and metastasis, and injury pathways. Cox proportional hazards model analysis revealed high p38 and pEGFR/EGFR ratio as jointly associated with poor survival in Tap1 cases (both P <= 0.002). Phospho-JNK quantity was associated with worse outcome in Tap2 patients (P = 0.004), when taking other factors into consideration. Conclusions: Proliferation, survival, and apoptosis signaling dysregulation can be identified in ovarian cancer effusion samples. Biochemical characterization of clinical effusions may provide either predictive and/or correlative information on patient outcome from which to further understand the mechanisms of effusion development and target clinical intervention. C1 NCI, Mol Signaling Sect, Pathol Lab, Bethesda, MD 20892 USA. NCI, US FDA, Clin Prote Grp, Pathol Lab, Bethesda, MD 20892 USA. NCI, Biostat & Data Management Sect, Ctr Canc Res, Bethesda, MD 20892 USA. Univ Oslo, Norwegian Radium Hosp, Dept Pathol, Oslo, Norway. Univ Oslo, Norwegian Radium Hosp, Dept Gynecol Oncol, Oslo, Norway. RP Kohn, EC (reprint author), NCI, Mol Signaling Sect, Pathol Lab, 10 Ctr Dr,MSC-1500, Bethesda, MD 20892 USA. EM ek1b@nih.gov OI Espina, Virginia/0000-0001-5080-5972 NR 49 TC 52 Z9 56 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 FEB 1 PY 2006 VL 12 IS 3 BP 791 EP 799 DI 10.1158/1078-0432.CCR-05-2516 PN 1 PG 9 WC Oncology SC Oncology GA 010NR UT WOS:000235201900015 PM 16467090 ER PT J AU Averbuch, M Katzper, M AF Averbuch, M Katzper, M TI Time to pain relief and degree of drug efficacy rating in acute pain. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT 107th Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics CY MAR 08-11, 2006 CL Baltimore, MD SP Amer Soc Clin Pharmacol & Therapeut C1 Tel Aviv Univ, Med Ctr, IL-69978 Tel Aviv, Israel. US FDA, Ctr Drug Evaluat & Res, Div Analges Antiinflammatory & Ophthalm Drug Prod, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 2006 VL 79 IS 2 SU S BP P59 EP P59 DI 10.1016/j.clpt.2005.12.214 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 012EA UT WOS:000235319800212 ER PT J AU Cantilena, LR Koerner, J Temple, R Throckmorton, DC AF Cantilena, LR Koerner, J Temple, R Throckmorton, DC TI FDA evaluation of cardiac repolarization data for 19 drugs and drug candidates. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT 107th Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics CY MAR 08-11, 2006 CL Baltimore, MD SP Amer Soc Clin Pharmacol & Therapeut C1 Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 2006 VL 79 IS 2 SU S BP P29 EP P29 DI 10.1016/j.clpt.2005.12.106 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 012EA UT WOS:000235319800105 ER PT J AU Huang, SM Reynolds, KS Strong, JM Nallani, SC Lesko, LJ Temple, R Abraham, S Alhabet, S Baweja, R Chung, SM Colangelo, P Collins, JM Frucht, D Green, MD Hepp, P Kavanagh, R Ko, HS Marroum, P Qiu, W Rahman, A Sobel, S Stifano, T Wei, X Yasuda, SU Zhang, L AF Huang, SM Reynolds, KS Strong, JM Nallani, SC Lesko, LJ Temple, R Abraham, S Alhabet, S Baweja, R Chung, SM Colangelo, P Collins, JM Frucht, D Green, MD Hepp, P Kavanagh, R Ko, HS Marroum, P Qiu, W Rahman, A Sobel, S Stifano, T Wei, X Yasuda, SU Zhang, L TI Drug interaction studies - Study design, data analysis, and implications for dosing and labeling: Current opinion. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT 107th Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics CY MAR 08-11, 2006 CL Baltimore, MD SP Amer Soc Clin Pharmacol & Therapeut C1 US FDA, Silver Spring, MD USA. NR 0 TC 1 Z9 1 U1 1 U2 2 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 FEB PY 2006 VL 79 IS 2 SU S BP P7 EP P7 DI 10.1016/j.clpt.2005.12.023 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 012EA UT WOS:000235319800023 ER PT J AU Kim, M Park, J Ortiz, S Jarugula, VR Parekh, A AF Kim, M Park, J Ortiz, S Jarugula, VR Parekh, A TI Comparison of ethinyl estradiol exposure among approved contraceptive products in the US SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT 107th Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics CY MAR 08-11, 2006 CL Baltimore, MD SP Amer Soc Clin Pharmacol & Therapeut C1 US FDA, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 2006 VL 79 IS 2 SU S BP P71 EP P71 DI 10.1016/j.clpt.2005.12.257 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 012EA UT WOS:000235319800255 ER PT J AU Nallani, SC Coles, LD AF Nallani, SC Coles, LD TI A repository of clinical pharmacokinetics data for drugs used in pregnancy and lactation developed at FDA. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT 107th Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics CY MAR 08-11, 2006 CL Baltimore, MD SP Amer Soc Clin Pharmacol & Therapeut C1 Univ Maryland, Coll Pharm, Rockville, MD USA. US FDA, Off Clin Pharmacol & Biopharmaceut, CDER, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 2006 VL 79 IS 2 SU S BP P24 EP P24 DI 10.1016/j.clpt.2005.12.087 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 012EA UT WOS:000235319800087 ER PT J AU Fenical, G AF Fenical, G TI The new EMC directive - Are you ready? SO EE-EVALUATION ENGINEERING LA English DT Article C1 Laird Technol, Delaware Water Gap, PA 18327 USA. US FDA, Rockville, MD 20857 USA. RP Fenical, G (reprint author), Laird Technol, POB 650,Shielding Way, Delaware Water Gap, PA 18327 USA. EM gfenical@lairdtech.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU NELSON PUBLISHING PI NOKOMIS PA 2500 NORTH TAMIAMI TRAIL, NOKOMIS, FL 34275-3482 USA SN 0149-0370 J9 EE-EVAL ENG JI EE-Eval. Eng. PD FEB PY 2006 VL 45 IS 2 BP 52 EP + PG 4 WC Engineering, Electrical & Electronic SC Engineering GA 017AV UT WOS:000235667400007 ER PT J AU Metlay, JP Powers, JH Dudley, MN Christiansen, K Finch, RG AF Metlay, JP Powers, JH Dudley, MN Christiansen, K Finch, RG TI Antimicrobial drug resistance, regulation, and research SO EMERGING INFECTIOUS DISEASES LA English DT Article ID IN-VITRO MODELS; STREPTOCOCCUS-PNEUMONIAE; PHARMACODYNAMICS; PENICILLIN; MOXIFLOXACIN; EMERGENCE; SELECTION; EFFICACY; OUTCOMES; THERAPY AB Innovative regulatory and legislative measures to stimulate and facilitate the development of new antimicrobial drugs are needed. We discuss research approaches that can aid regulatory decision making on the treatment of resistant infections and minimization of resistance selection. We also outline current and future measures that regulatory agencies may employ to help control resistance and promote drug development. Pharmacokinetic/pharmacodynamic research models offer promising approaches to define the determinants of resistance selection and drug doses that optimize efficacy and reduce resistance selection. Internationally, variations exist in how regulators use drug scheduling, subsidy restrictions, central directives, educational guidelines, amendments to prescribing information, and indication review. Recent consultations and collaborations between regulators, academics, and industry are welcome. Efforts to coordinate regulatory measures would benefit from greater levels of international dialogue.. C1 VA Med Ctr, Philadelphia, PA USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. US FDA, Rockville, MD 20857 USA. Diversa Corp, San Diego, CA USA. Royal Perth Hosp, Perth, WA, Australia. City Hosp Nottingham, Nottingham, England. Univ Nottingham, Nottingham NG7 2RD, England. RP Metlay, JP (reprint author), VA Med Ctr, Philadelphia, PA USA. EM jmetlay@cceb.med.upenn.edu NR 37 TC 20 Z9 20 U1 0 U2 2 PU CENTER DISEASE CONTROL PI ATLANTA PA ATLANTA, GA 30333 USA SN 1080-6040 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD FEB PY 2006 VL 12 IS 2 BP 183 EP 190 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 011SC UT WOS:000235287400001 PM 16494740 ER PT J AU Verthelyi, D AF Verthelyi, D TI Female's heightened immune status: Estrogen, T cells, and inducible nitric oxide synthase in the balance SO ENDOCRINOLOGY LA English DT Editorial Material ID DENDRITIC CELLS; 17-BETA-ESTRADIOL; MACROPHAGES; EXPRESSION; TOLL; DIFFERENTIATION; ISCHEMIA; DISEASE; MICE C1 US FDA, Immunol Lab, Div Therapeut Prot, Ctr Drug Evaluat & Review, Bethesda, MD 20892 USA. RP Verthelyi, D (reprint author), US FDA, Immunol Lab, Div Therapeut Prot, Ctr Drug Evaluat & Review, Bldg 29A,Room 3B19,8800 Rockville Pike, Bethesda, MD 20892 USA. EM verthelyi@cber.fda.gov NR 25 TC 21 Z9 25 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD FEB PY 2006 VL 147 IS 2 BP 659 EP 661 DI 10.1210/en.2005-1469 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 005NN UT WOS:000234831200003 PM 16418430 ER PT J AU Albers, PH Klein, PN Green, DE Melancon, MJ Bradley, BP Noguchi, G AF Albers, PH Klein, PN Green, DE Melancon, MJ Bradley, BP Noguchi, G TI Chlorfenapyr and mallard ducks: Overview, study design, macroscopic effects, and analytical chemistry SO ENVIRONMENTAL TOXICOLOGY AND CHEMISTRY LA English DT Article DE chlorfenapyr; insecticide; mallard; chronic exposure; toxic effects ID UNCOUPLING ACTIVITY; PYRROLES AB The first commercial pesticide derived from a class of compounds known as halogenated pyrroles was registered for use in the United States in 2001. Chlorfenapyr degrades slowly in soil, sediment, and water and is highly toxic to birds. Information on biochemical or histological endpoints in birds is lacking; therefore, a two-year study was conducted to provide information needed to develop diagnostic criteria for chlorfenapyr toxicosis. In the first year, male mallard ducks were fed concentrations of 0, 2, 5, or 10 ppm technical chlorfenapyr or 5 ppm of a formulated product in their diet during a 10-week chronic exposure study. Survival, body weight, feed consumption (removal), behavior, and molt progression were monitored. Feed and liver were analyzed for chlorfenapyr and two metabolites. Five of 10 ducks in the 10-ppm group died, and neurotoxic effects were observed in the Sand 10-ppm groups. Feed removal increased for ducks receiving chlorfenapyr and body weights of 5- and 10-ppm ducks were reduced. Loss of body fat, muscle atrophy, and bile retention were suggestive of metabolic disruption or a decreased ability to digest and absorb nutrients. Liver and kidney weights and liver and kidney weight/body weight ratios exhibited a positive response to concentrations of chlorfenapyr in the diet. Emaciation and elevated organ weight/body weight ratios are candidates for a suite of indicators of chronic chlorfenapyr exposure. Liver is the preferred tissue for chemical confirmation of exposure. C1 Beltsville Agr Res Ctr E, US Geol Survey, Patuxent Wildlife Res Ctr, Beltsville Lab, Beltsville, MD 20705 USA. US PHS, US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. Natl Wildlife Hlth Ctr, US Geol Survey, Madison, WI 53711 USA. Univ Maryland Baltimore Cty, Dept Biol Sci, Baltimore, MD 21250 USA. US Fish & Wildlife Serv, Div Environm Qual, Arlington, VA 22203 USA. RP Albers, PH (reprint author), Beltsville Agr Res Ctr E, US Geol Survey, Patuxent Wildlife Res Ctr, Beltsville Lab, 10300 Baltimore Ave,Box 308, Beltsville, MD 20705 USA. EM palbers@usgs.gov NR 19 TC 0 Z9 1 U1 0 U2 1 PU SETAC PI PENSACOLA PA 1010 NORTH 12TH AVE, PENSACOLA, FL 32501-3367 USA SN 0730-7268 J9 ENVIRON TOXICOL CHEM JI Environ. Toxicol. Chem. PD FEB PY 2006 VL 25 IS 2 BP 438 EP 445 DI 10.1897/05-004R.1 PG 8 WC Environmental Sciences; Toxicology SC Environmental Sciences & Ecology; Toxicology GA 004ZS UT WOS:000234792000016 PM 16519304 ER PT J AU D'Ovidio, K Trucksess, M Weaver, C Horn, E McIntosh, M Bean, G AF D'Ovidio, K Trucksess, M Weaver, C Horn, E McIntosh, M Bean, G TI Aflatoxins in ginseng roots SO FOOD ADDITIVES AND CONTAMINANTS PART A-CHEMISTRY ANALYSIS CONTROL EXPOSURE & RISK ASSESSMENT LA English DT Article DE aflatoxins; ginseng root; mycotoxins ID MYCOTOXINS AB Ginseng roots can be infected by molds during growth, harvest and storage and result in contamination with mycotoxins. In this study, an analytical method for the determination of aflatoxins B-1, B-2, G(1) and G(2), a group of structurally similar mycotoxins, in ginseng root was developed. Test samples were extracted with methanol-water (8 + 2), diluted and passed through an immunoaffinity column packed with antibodies specific for aflatoxins. The purified extract was then derivatized with a mixture of water, trifluoroacetic acid and acetic acid. Aflatoxins were then separated and quantified by reverse phase liquid chromatography (LC) with fluorescence detection. Recoveries of total aflatoxins at 2, 4, 8 and 16 ng/g added to toxinfree 4 to 5-year old dried sliced Wisconsin ginseng were 92, 77, 91 and 83% respectively; and relative standard deviations were 3.6, 8.0, 6.9 and 2.0% respectively. A total of 11 wild simulated and 12 cultivated ginseng root samples were analysed for aflatoxins. All cultivated roots were found to be free of aflatoxin contamination. Two of the wild simulated roots contained total aflatoxins B1, B2, G1 and G2 at 15.1 and 15.2 ng/g. One moldy ginseng root purchased from a grocery store was found to be contaminated with aflatoxins at 16 ng/g. C1 Univ Maryland, College Pk, MD 20742 USA. US FDA, College Pk, MD USA. RP Univ Maryland, College Pk, MD 20742 USA. EM mtruckse@cfsan.fda.gov RI McIntosh, Marla/A-3441-2011 OI McIntosh, Marla/0000-0002-4169-8615 NR 7 TC 25 Z9 26 U1 2 U2 8 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND SN 1944-0049 EI 1944-0057 J9 FOOD ADDIT CONTAM A JI Food Addit. Contam. Part A-Chem. PD FEB PY 2006 VL 23 IS 2 BP 174 EP 180 DI 10.1080/02652030500442524 PG 7 WC Chemistry, Applied; Food Science & Technology; Toxicology SC Chemistry; Food Science & Technology; Toxicology GA 007WY UT WOS:000235003300010 PM 16449060 ER PT J AU Collins, TFX Sprando, RL Black, TN Olejnik, N Eppley, RM Shackelford, ME Howard, PC Rorie, JI Bryant, M Ruggles, DI AF Collins, TFX Sprando, RL Black, TN Olejnik, N Eppley, RM Shackelford, ME Howard, PC Rorie, JI Bryant, M Ruggles, DI TI Effects of aminopentol on in utero development in rats SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article DE aminopentol; hydrolyzed fumonisin B1; developmental toxicity ID NEURAL-TUBE DEFECTS; HYDROLYZED FUMONISIN B-1; FUSARIUM-MONILIFORME; ESOPHAGEAL CANCER; CONTAMINATED CORN; PULMONARY-EDEMA; ANIMAL HEALTH; PREGNANT RATS; MYCOTOXINS; TORTILLAS AB Aminopentol (AP1), the backbone and main hydrolysis product of the mycotoxin fumonisin B1 (FB1), is present in corn-based foods which are consumed daily as a substantial part of the diet in some areas of the world. The toxicity of FB1 has been attributed to altered sphingolipid metabolism, but the toxicity of AP1 is less certain. Epidemiological correlations and in vitro studies have suggested that AP1 can increase neural tube defects (NTDs), but no in vivo developmental study of AP1 was done prior to this study. AP1 was given once daily to rats by gavage on gestation days (GD) 3-16 at doses of 0, 15, 30, 60, or 120 mg/kg. Reproductive and developmental parameters were measured at GD 17, one day after the last dose, and on GD 20. In addition, on GD 17, maternal and fetal tissues were analyzed for sphingolipid content. Conclusions: AP1 reduced dam body weight gain, but was less toxic than FB1. AP1 was not teratogenic, did not affect tissue sphingolipid ratios, did not alter reproduction or development of fetuses, and produced no dose-related histopathological effects in dams. (c) 2005 Elsevier Ltd. All rights reserved. C1 US FDA, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Collins, TFX (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 8301 Muirkirk Rd, Laurel, MD 20708 USA. EM tcollins@cfsan.fda.gov NR 47 TC 17 Z9 17 U1 1 U2 4 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 FEB PY 2006 VL 44 IS 2 BP 161 EP 169 DI 10.1016/j.fct.2005.06.009 PG 9 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA 016DB UT WOS:000235599800002 PM 16081197 ER PT J AU Oelbermann, M Voroney, RP Kass, DCL Schlonvoigt, AM AF Oelbermann, M Voroney, RP Kass, DCL Schlonvoigt, AM TI Soil carbon and nitrogen dynamics using stable isotopes in 19-and 10-year-old tropical agroforestry systems SO GEODERMA LA English DT Article DE alley cropping; ground cover; gross soil organic carbon turnover; mulching; multipurpose tree species; residue stabilization efficiency ID NATURAL C-13 ABUNDANCE; ORGANIC-MATTER; CROPPING SYSTEMS; CLIMATE-CHANGE; TURNOVER; MANAGEMENT; TILLAGE; SEQUESTRATION; DECOMPOSITION AB Conversion of forests to agricultural land in the American tropics, through traditional agricultural practices such as shifting cultivation, has not been able to maintain stocks of soil organic carbon (SOC), and increasing population pressure has led to shortened fallow periods, causing further losses of soil fertility. However, land management practices such as agroforestry can provide a sustainable alternative to single cropping because of its ability to maintain or increase the SOC pool. This study quantified SOC and nitrogen (N) pools, gross SOC turnover, residue stabilization efficiency (RSE(AC)) in the alley crop, Soil delta(13)C partitioning, C(3)-C abundance and delta(15)N dynamics in 19- and 10-year Gliricidia sepium and Elythrina poeppigiana alley cropping system. Each system was studied at two fertilizer levels (tree prunings only [-N or -A], and tree prunings plus chicken manure [+N], or Arachis pintoi as a groundcover [+A]), and was compared to a sole crop system. The SOC and N pools were significantly higher (p<0.05) in the 19-year-old alley crop compared to the sole crop, but not significantly different (p<0.05) in the 10-year-old system. Soil C and N (%) showed a similar trend as that of the SOC and N pools in both 19- and 10-year-old systems. Gross SOC turnover, to a 20 cm depth, ranged from 12 to 21 years in the 19-year-old alley crop compared to 50 years in the sole crop, and from 20 to 32 years in the 10-year-old alley crop compared to 106 years in the sole crop. The RSE(AC) ranged from 10% to 58% in the 19-year-old system, and from 3% to 43% in the 10-year-old system. The delta(13)C signature of the soil shifted significantly (p<0.05) towards that of C(3) vegetation in the alley crop due to the greater input of organic residues from tree prunings compared to the sole crop. The proportion of input from tree prunings only in the 19-year-old alley crop ranged from 14% to 20%, and from 9% to 11% in the 10-year-old system to a soil depth of 20 cm. The delta(15)N signature of the soil showed two patterns: that of the 19-year-old system being enriched in delta(15)N, and that of the 10-year-old system being depleted in delta(15)N compared to the sole crop. The addition of manure in the 19-year-old system has enriched the Soil delta(15)N and in the 10-year-old system the soil was depleted due to the N(2)-fixing groundcover A. pintoi. (C) 2005 Elsevier B.V. All rights reserved. C1 Univ Waterloo, Dept Earth Sci, Waterloo, ON N2L 3G1, Canada. Univ Guelph, Dept Land Resource Sci, Guelph, ON N1G 2W1, Canada. US FDA, NE Reg Lab, US Dept HHS, Jamaica, NY 11433 USA. GFA Terra Syst, Latin Amer Div, D-22359 Hamburg, Germany. RP Oelbermann, M (reprint author), Univ Waterloo, Dept Earth Sci, Waterloo, ON N2L 3G1, Canada. EM moelberm@sciborg.uwaterloo.ca RI El Husny, Chafic/G-5410-2012; OI Oelbermann, Maren/0000-0003-0996-4140 NR 46 TC 26 Z9 28 U1 3 U2 25 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0016-7061 J9 GEODERMA JI Geoderma PD FEB PY 2006 VL 130 IS 3-4 BP 356 EP 367 DI 10.1016/j.geoderma.2005.02.009 PG 12 WC Soil Science SC Agriculture GA 006ZI UT WOS:000234936200015 ER PT J AU Chi, B Alston, M Rabin, R AF Chi, B Alston, M Rabin, R TI Respiratory Syncytial Virus (RSV) suppresses CD4 T cell proliferation through IFN-alpha and IFN-lambda SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY MAR 03-07, 2006 CL Miami Beach, FL SP Amer Acad Allergy, Asthma & Immunol C1 US FDA, CBER, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2006 VL 117 IS 2 SU S MA 53 BP S14 EP S14 DI 10.1016/j.jaci.2005.12.057 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 019VR UT WOS:000235865300054 ER PT J AU Raghunandan, R Rudikoff, E Bauer, S AF Raghunandan, R Rudikoff, E Bauer, S TI Cell-cell interactions and cell fate determination: Involvement of Dlk in B cell development and function SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY MAR 03-07, 2006 CL Miami Beach, FL SP Amer Acad Allergy, Asthma & Immunol C1 FDA, CBER, Lab Stem Cell Biol, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2006 VL 117 IS 2 SU S MA 1257 BP S326 EP S326 DI 10.1016/j.jaci.2005.12.1285 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 019VR UT WOS:000235865302335 ER PT J AU Sackesen, C Akdis, M Zumkehr, J Alkan, SS Blaser, K Gursel, I Akdis, CA AF Sackesen, C Akdis, M Zumkehr, J Alkan, SS Blaser, K Gursel, I Akdis, CA TI Suppression of toll-like receptors 3-, 7- and 9-induced B cell activation and antibody production by repetitive oligonucleotides from mammalian telomere SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY MAR 03-07, 2006 CL Miami Beach, FL SP Amer Acad Allergy, Asthma & Immunol C1 Swiss Inst Allergy & Asthma Res, CH-7270 Davos, Switzerland. Univ Hacettepe, Sch Med, Dept Pediat Allergy & Asthma, TR-06100 Ankara, Turkey. 3M Pharmaceut, St Paul, MN USA. US FDA, Sect Retroviral Immunol, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2006 VL 117 IS 2 SU S MA 407 BP S104 EP S104 DI 10.1016/j.jaci.2005.12.418 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 019VR UT WOS:000235865300407 ER PT J AU Wilson, TM Louie, GH Rapkiewicz, AV Foster, B Turner, ML Goldbach-Mansky, R Rabin, RL Prussin, C AF Wilson, TM Louie, GH Rapkiewicz, AV Foster, B Turner, ML Goldbach-Mansky, R Rabin, RL Prussin, C TI Lichenoid drug eruption associated with TNF inhibitors SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY MAR 03-07, 2006 CL Miami Beach, FL SP Amer Acad Allergy, Asthma & Immunol C1 Natl Inst Hlth, Lab Allerg Dis, Bethesda, MD USA. NIAMS, NIH, Bethesda, MD USA. NCI, NIH, Bethesda, MD 20892 USA. FDA, CBER, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2006 VL 117 IS 2 SU S MA 886 BP S229 EP S229 DI 10.1016/j.jaci.2005.12.906 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 019VR UT WOS:000235865301383 ER PT J AU Tankson, JD Fedorka-Cray, PJ Jackson, CR Headrick, M AF Tankson, JD Fedorka-Cray, PJ Jackson, CR Headrick, M TI Genetic relatedness of a rarely isolated Salmonella: Salmonella enterica serotype Niakhar from NARMS animal isolates SO JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY LA English DT Article DE antimicrobial resistance; multiple drug resistance; integrons; PFGE; ribotyping ID FIELD GEL-ELECTROPHORESIS; ANTIBIOTIC-RESISTANCE GENES; ESCHERICHIA-COLI O157-H7; TYPHIMURIUM DT104; UNITED-STATES; ANTIMICROBIAL RESISTANCE; MOLECULAR CHARACTERIZATION; STREPTOCOCCUS-PNEUMONIAE; MULTIDRUG-RESISTANT; LARGE PLASMIDS AB Background: In the United States, Salmonella enterica serotype Niakhar is infrequently isolated. Between 1997 and 2000, the animal arm of the National Antimicrobial Resistance Monitoring System-Enteric Bacteria (NARMS) assayed a total of 22 383 Salmonella isolates from various animal sources (swine, cattle, chickens, turkeys, cats, horses, exotics and dogs) for antimicrobial susceptibility. Isolates originated from diagnostic and non-diagnostic submissions. Objectives: To study the phenotypic and genotypic characteristics of Salmonella Niakhar. Methods and results: Only five (0.02%) of the 22 383 isolates were identified as Salmonella Niakhar. Antimicrobial resistance testing indicated that three isolates were pan-susceptible, one isolate was resistant to ampicillin and one isolate was resistant to ampicillin, chloramphenicol, ciprofloxacin, kanamycin, nalidixic acid, streptomycin, sulfamethoxazole, tetracycline and trimethoprim/sulfamethoxazole. RAPD-PCR analysis, PFGE and ribotyping indicated that two pan-susceptible isolates were genetically similar, whereas the three remaining isolates were genetically different. The one Salmonella Niakhar isolate that was multiresistant harboured a class I integron, intI1 and two large plasmids. Conclusions: This study represents the first report of a ciprofloxacin-resistant Salmonella isolate from the animal arm of NARMS. C1 USDA ARS, Bacterial & Epidemiol Antimicrobial Resistance Re, Athens, GA 30605 USA. US FDA, Ctr Vet Med, Rockville, MD 20855 USA. RP Fedorka-Cray, PJ (reprint author), USDA ARS, Bacterial & Epidemiol Antimicrobial Resistance Re, 950 Coll Stn Rd, Athens, GA 30605 USA. EM pcray@saa.ars.usda.gov NR 65 TC 8 Z9 8 U1 2 U2 3 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 FEB PY 2006 VL 57 IS 2 BP 190 EP 198 DI 10.1093/jac.dki.439 PG 9 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA 007KJ UT WOS:000234967400005 PM 16352736 ER PT J AU Elkins, CA Mullis, LB AF Elkins, CA Mullis, LB TI Mammalian steroid hormones are substrates for the major RND- and MFS-type tripartite multidrug efflux pumps of Escherichia coli SO JOURNAL OF BACTERIOLOGY LA English DT Article ID BILE-SALTS; RESISTANCE; GENES; SYSTEM; ACRB; TYPHIMURIUM; BACTERIA AB A steroid-hormone-dependent growth suppression was observed in Escherichia coli efflux-deficient backgrounds containing mutations in the major RND- and MFS-type tripartite multidrug efflux systems, AcrAB-TolC and EmrAB-TolC, respectively. In addition to their previously known natural steroid spectrum, which includes bile acids, both systems were shown to transport the hormones estradiol and progesterone, whereas hydrocortisone served as a substrate of only AcrAB-TolC. Furthermore, at least two other RND-type pumps, YhiV and AcrD, were capable of transporting such hormones when overexpressed on plasmid vectors (with some demonstrable specificity observed with AcrD). When this activity was examined in a wild-type background, cell-associated estradiol levels remained largely unaffected by competition with exogenous bile acids and hydrocortisone, in contrast to progesterone, which produced a significant modulation in estradiol uptake. C1 US FDA, Div Microbiol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Elkins, CA (reprint author), US FDA, Div Microbiol, Natl Ctr Toxicol Res, 3900 NCTR Dr, Jefferson, AR 72079 USA. EM chris.elkins@fda.hhs.gov NR 25 TC 32 Z9 34 U1 0 U2 7 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 FEB PY 2006 VL 188 IS 3 BP 1191 EP 1195 DI 10.1128/JB.188.3.1191-1195.2006 PG 5 WC Microbiology SC Microbiology GA 005RF UT WOS:000234840800043 PM 16428427 ER PT J AU Mosholder, AD Willy, M AF Mosholder, AD Willy, M TI Suicidal adverse events in pediatric randomized, controlled clinical trials of antidepressant drugs are associated with active drug treatment: A meta-analysis SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Article ID DEPRESSION; RISK; ADOLESCENTS; FLUOXETINE; CHILDREN; PLACEBO; HARM AB Objective: The aim of this study was to compare the incidence of suicidal ideation and behaviors observed with antidepressant drug treatment to the incidence with placebo, in randomized, controlled pediatric clinical trials. Methods: Manufacturers of nine antidepressant drugs identified suicidal adverse events in randomized, placebo-controlled, pediatric clinical trials that they had sponsored. Events were found with an electronic search for adverse event descriptions, including key words suggesting suicidal ideation or self-injury, along with a manual review of all adverse events meeting the standard regulatory definition for seriousness. Incidence rate data for these events supplied by the manufacturers were combined across trials to yield Mantel-Haenszel combined risk estimates. Results: Data from 22 randomized, short-term, placebo-controlled, pediatric trials in various indications, involving nine different antidepressant drugs, were available for analysis. A total of 2298 pediatric subjects were exposed to active drug, and 1952 to placebo. Seventy-eight (78) serious suicidal adverse events occurred in these trials (54 with active drug and 24 with placebo); there were no completed suicides. The combined incidence rate ratio across all trials for serious suicidal adverse events was 1.89 (95% Confidence Interval, 1.18-3.04). Conclusions: In short-term, placebo-controlled, pediatric studies of antidepressants, active drug treatment was associated with a rate of serious suicidal events almost twice that of placebo. C1 US FDA, Off Drug Safety, Div Drug Risk Evaluat, Rockville, MD 20857 USA. RP Mosholder, AD (reprint author), US FDA, Div Drug Risk Evaluat, Off Drug Safety, 10903 New Hampshire Ave,Mail Stop 3411, Silver Spring, MD 20993 USA. EM andrew.mosholder@fda.hhs.gov NR 21 TC 33 Z9 33 U1 3 U2 7 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1044-5463 J9 J CHILD ADOL PSYCHOP JI J. Child Adolesc. Psychopharmacol. PD FEB-APR PY 2006 VL 16 IS 1-2 BP 25 EP 32 DI 10.1089/cap.2006.16.25 PG 8 WC Pediatrics; Pharmacology & Pharmacy; Psychiatry SC Pediatrics; Pharmacology & Pharmacy; Psychiatry GA 030HJ UT WOS:000236624900005 PM 16553526 ER PT J AU Mosholder, AD Pamer, CA AF Mosholder, AD Pamer, CA TI Postmarketing surveillance of suicidal adverse events with pediatric use of antidepressants SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Article AB Objective: The aim of this analysis was to delineate trends in spontaneous postmarketing reporting data with antidepressant drugs for adverse events involving suicidal behaviors in children and adolescents. Methods: The U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (AERS) was searched for postmarketing adverse event reports of suicidal thoughts and behaviors occurring in children and adolescents treated with 10 antidepressant drugs. The search covered the period from market launch of each drug through November 2003. Results: A total of 524 reports were returned by the search. All drugs had reports, and most drugs demonstrated 15 or fewer reports annually, with the following two exceptions. We observed a peak of reporting for fluoxetine in the early 1990s, and another peak of reporting for paroxetine in recent years. Further investigation revealed that the peak in recent paroxetine reporting was accounted for by reports from consumers, whereas reporting by health professionals remained fairly constant. In contrast, the earlier peak in reports for fluoxetine was not accounted for by an increase in consumer reporting. Conclusions: Spontaneous reporting data for suicidal events in pediatric patients treated with antidepressant drugs appears to be highly variable and subject to various influences. The most appropriate method to assess an association of antidepressant drug treatment with suicidal behaviors is examination of systematically collected data with appropriate comparison groups, such as randomized, controlled trial data. C1 US FDA, Div Drug Risk Evaluat, Off Drug Safety, Rockville, MD USA. RP Mosholder, AD (reprint author), US FDA, Div Drug Risk Evaluat, Off Drug Safety, 10903 New Hampshire Ave,Mail Stop 3411, Silver Spring, MD 20993 USA. EM andrew.mosholder@fda.hhs.gov NR 8 TC 9 Z9 9 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1044-5463 J9 J CHILD ADOL PSYCHOP JI J. Child Adolesc. Psychopharmacol. PD FEB-APR PY 2006 VL 16 IS 1-2 BP 33 EP 36 DI 10.1089/cap.2006.16.33 PG 4 WC Pediatrics; Pharmacology & Pharmacy; Psychiatry SC Pediatrics; Pharmacology & Pharmacy; Psychiatry GA 030HJ UT WOS:000236624900006 PM 16553527 ER PT J AU McDermott, PF Bodeis-Jones, SM Fritsche, TR Jones, RN Walker, RD AF McDermott, PF Bodeis-Jones, SM Fritsche, TR Jones, RN Walker, RD CA Campylobacter Susceptibility TI Broth microdilution susceptibility testing of Campylobacter jejuni and the determination of quality control ranges for fourteen antimicrobial agents (vol 43, pg 6136, 2005) SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Correction C1 US FDA, Res Off, Ctr Vet Med, Laurel, MD 20708 USA. JMI Labs, N Liberty, IA 52317 USA. RP McDermott, PF (reprint author), US FDA, Res Off, Ctr Vet Med, 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 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD FEB PY 2006 VL 44 IS 2 BP 677 EP 677 DI 10.1128/JCM.44.2.677.2006 PG 1 WC Microbiology SC Microbiology GA 012MV UT WOS:000235344200078 ER PT J AU Rahman, A White, RM AF Rahman, A White, RM TI Cytotoxic anticancer agents and renal impairment study: The challenge remains SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID MALIGNANT PLEURAL MESOTHELIOMA; CELL LUNG-CANCER; PHASE-II; CHEMOTHERAPY; CISPLATIN C1 US FDA, Silver Spring, MD USA. RP Rahman, A (reprint author), US FDA, Silver Spring, MD USA. NR 23 TC 10 Z9 10 U1 0 U2 1 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 FEB 1 PY 2006 VL 24 IS 4 BP 533 EP 536 DI 10.1200/JCO.2005.03.8299 PG 4 WC Oncology SC Oncology GA 014QT UT WOS:000235495700001 PM 16391294 ER PT J AU Murakami, EG Jackson, L Madsen, K Schickedanz, B AF Murakami, EG Jackson, L Madsen, K Schickedanz, B TI Factors affecting the ultraviolet inactivation of Escherichia coli K12 in apple juice and a model system SO JOURNAL OF FOOD PROCESS ENGINEERING LA English DT Article ID UV DISINFECTION; WASTE-WATER; IRRADIATION; MICROORGANISMS; EFFLUENTS; PLANT AB Ultraviolet (UV) light has been used successfully for years to sterilize water and was recently approved as an acceptable irradiation treatment for the processing of juice. Although there is considerable information on the efficacy of UV processing in the treatment of water, limited data are available on its efficacy in fluid food systems. The objectives of this work were to determine the effects of apple-juice properties on the UV inactivation of Escherichia coli K12 and the interdependence of intensity and time on the efficacy of UV light. Results showed that absorbance (A) and suspended solids (SS) affected UV inactivation, while pH and dissolved solids did not. Concerning the interdependence of intensity and time, intensity levels can only be changed without sacrificing effectiveness at a limited range of intensity and dose levels. This means that the range of the intensity level of the actual UV reactor must be considered in process-parameter determination. C1 Food & Drug Adm, Natl Ctr Food Safety & Technol, Summit Argo, IL 60501 USA. IIT, Natl Ctr Food Safety & Technol, Summit Argo, IL 60501 USA. RP Murakami, EG (reprint author), Food & Drug Adm, Natl Ctr Food Safety & Technol, 6502 S Archer Ave, Summit Argo, IL 60501 USA. EM Edgar.Murakami@fda.hhs.gov NR 24 TC 45 Z9 45 U1 2 U2 13 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-8876 J9 J FOOD PROCESS ENG JI J. Food Process Eng. PD FEB PY 2006 VL 29 IS 1 BP 53 EP 71 DI 10.1111/j.1745-4530.2006.00049.x PG 19 WC Engineering, Chemical; Food Science & Technology SC Engineering; Food Science & Technology GA 014DI UT WOS:000235458600005 ER PT J AU Chen, YH Ross, WH Gray, MJ Wiedmann, M Whiting, RC Scott, VN AF Chen, YH Ross, WH Gray, MJ Wiedmann, M Whiting, RC Scott, VN TI Attributing risk to Listeria monocytogenes subgroups: Dose response in relation to genetic lineages SO JOURNAL OF FOOD PROTECTION LA English DT Article ID FEBRILE GASTROENTERITIS; ENRICHMENT BROTHS; INTERNALIN-A; POPULATIONS; DISTINCT; FOODS; STRAINS; MICE; IDENTIFICATION; EXPRESSION AB The objective of this study was to evaluate the hypothesis that the dose-response relationship for Listeria monocytogenes in humans varies with genotypic lineage or subtype. The linkages between molecular subtyping data and enumeration data for L. monocytogenes subtypes in foods consumed by the at-risk population were examined to test this hypothesis. We applied a conditional probability model to conduct a subtype-specific dose-response analysis, with the focus on invasive listeriosis. L. monocytogenes differed not only in the molecular subtype and lineage but also in the contamination level when isolates of the pathogen occurred in retail samples of ready-to-eat foods. Using the exponential model parameter r-value as a measure (essentially the probability of a single cell causing illness), we found that the virulence varied among L. monocytogenes lineages by several orders of magnitude. Under the assumptions made, for L. monocytogenes lineages I and 11 the consumption of a single cell would result in listeriosis with log average probabilities of -7.88 (equivalent to once in 10(7.78) times) and - 10.3, respectively, as compared with -9.72 for L. monocytogenes independent of subtype. A greater difference in r-values was found for selected ribotypes. The uncertainty about the r-value estimates was small compared with the large differences in the virulence parameters themselves. Thus, for L. monocytogenes both subtype and the number of cells consumed matter, highlighting the usefulness of considering both exposure concentration and subtype prevalence in dose-response analysis. As advances are made in molecular subtyping and quantitative tools for dose-response analysis, further studies integrating genomic data into quantitative risk assessments will enable better attribution of disease risk to L. monocytogenes subtypes. C1 Food Prod Assoc, Washington, DC 20005 USA. Hlth Canada, Food Directorate, Bur Biostat & Comp Applicat, Ottawa, ON K1A 0L2, Canada. Cornell Univ, Dept Food Sci, Ithaca, NY 14853 USA. US FDA, College Pk, MD 20740 USA. RP Chen, YH (reprint author), Food Prod Assoc, 1350 1 St NW,Suite 300, Washington, DC 20005 USA. EM ychen@fpa-food.org RI Wiedmann, Martin/A-9683-2008 OI Wiedmann, Martin/0000-0002-4168-5662 NR 46 TC 46 Z9 49 U1 0 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 FEB PY 2006 VL 69 IS 2 BP 335 EP 344 PG 10 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 011TV UT WOS:000235292100013 PM 16496574 ER PT J AU Grant, MA Hu, JX Jinneman, KC AF Grant, MA Hu, JX Jinneman, KC TI Multiplex real-time PCR detection of heat-labile and heat-stable toxin genes in enterotoxigenic Escherichia coli SO JOURNAL OF FOOD PROTECTION LA English DT Article ID MEXICO AB A multiplex real-time PCR method was developed for detection of heat-labile and heat-stable toxin genes in enterotoxigenic Escherichia coli. Approximately 10 CFU per reaction mixture could be detected in rinsates from produce samples. Several foods representative of varieties previously shown to have caused enterotoxigenic E. coli outbreaks were spiked and enriched for 4 or 6 h. Both heat-labile and heat-stable toxin genes could be detected in the foods tested, with the exception of hot sauce, with threshold cycle values ranging from 25.2 to 41.1. A procedure using membrane filtration which would allow enumeration of the enterotoxigenic E. coli population in a food sample in less than 28 h by real-time PCR analysis of colonies picked from media highly selective for E. coli was also developed. C1 US FDA, Pacif Reg Lab NW, Bothell, WA 98021 USA. US FDA, Seafood Prod Res Ctr, Bothell, WA 98021 USA. Washington State Publ Hlth Lab, Shoreline, WA 98155 USA. RP Grant, MA (reprint author), US FDA, Pacif Reg Lab NW, 22201 23rd Dr SE, Bothell, WA 98021 USA. EM mike.grant@fda.gov NR 15 TC 12 Z9 15 U1 1 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 FEB PY 2006 VL 69 IS 2 BP 412 EP 416 PG 5 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 011TV UT WOS:000235292100023 PM 16496584 ER PT J AU Yao, K Hisada, M Maloney, E Yamano, Y Hanchard, B Wilks, R Rios, M Jacobson, S AF Yao, K Hisada, M Maloney, E Yamano, Y Hanchard, B Wilks, R Rios, M Jacobson, S TI Human T lymphotropic virus types I and II Western blot seroindeterminate status and its association with exposure to prototype HTLV-I SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID MYELOPATHY/TROPICAL SPASTIC PARAPARESIS; CELL LEUKEMIA; NEUROLOGICAL DISEASE; PLASMODIUM-FALCIPARUM; CEREBROSPINAL-FLUID; CENTRAL-AFRICA; CD8(+) CELLS; RISK-FACTORS; SAO-PAULO; FOLLOW-UP AB Human T lymphotropic virus types I and II (HTLV-I/II) Western blot (WB) seroindeterminate status, which is defined as an incomplete banding pattern of HTLV protein Gag (p19 or p24) or Env (GD21 or rgp46), is commonly observed. To investigate the significance of this finding, we examined HTLV-I/II serostatus and HTLV-I proviral load in 2 groups of individuals with WB seroindeterminate status. Low proviral loads were detected in 42% of patients with neurologic symptoms and 44% of voluntary blood donors. These data suggest that a subset of WB seroindeterminate individuals may be infected with prototype HTLV-I. To confirm this hypothesis, we evaluated HTLV-I/II serostatus and proviral load in prospectively collected specimens from 66 WB seronegative patients who had received HTLV-I-infected blood products by transfusion. Eight individuals developed WB seroindeterminate profiles after the transfusion. In addition, using a human leukocyte antigen type A*201-restricted HTLV-I Tax11-19 tetramer, we detected virus-specific CD8(+) T cells in peripheral blood mononuclear cells from WB seroindeterminate patients. These CD8+ T cells were effective at targeting HTLV-I-infected cells. Collectively, the results suggest that HTLV-I/II WB seroindeterminate status may reflect a history of HTLV- I exposure. Our findings warrant further investigation of the possible clinical outcomes associated with WB seroindeterminate status. C1 NINDS, Neuroimmunol Branch, NIH, Viral Immunol Sect, Bethesda, MD 20892 USA. NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA. US FDA, Rockville, MD 20857 USA. Univ W Indies, Mona Kingston, Jamaica. RP Jacobson, S (reprint author), NINDS, Neuroimmunol Branch, NIH, Viral Immunol Sect, 9000 Rockville Pike,Bldg 10,Ste 5N214, Bethesda, MD 20892 USA. EM jacobsons@ninds.nih.gov NR 40 TC 14 Z9 15 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 FEB 1 PY 2006 VL 193 IS 3 BP 427 EP 437 DI 10.1086/499273 PG 11 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 005NL UT WOS:000234831000013 PM 16388491 ER PT J AU Vanderveen, JE AF Vanderveen, JE TI Gap analysis guidelines for assessing acute, chronic, and lifetime exposures to high levels of various nutrients SO JOURNAL OF NUTRITION LA English DT Article; Proceedings Paper CT Workshop on Understanding Tolerable Upper Intake Levels CY APR 23-24, 2003 CL Washington, DC DE nutrient upper levels; nutrition status ID IRON-DEFICIENCY; HEREDITARY HEMOCHROMATOSIS; VITAMIN-A; SUPPLEMENTATION; METABOLISM; THERAPY; RISK AB Twenty-two tolerable upper intake levels (ULs) have been established using data available from research with both humans and animals. No ULs were established for another 10 nutrients for which the existing data were evaluated. Gaps in knowledge on the adverse health effects that may arise as a result of acute, chronic, and lifetime exposures to high levels of many of these nutrients remain. The existence of a UL for a nutrient is not an indication that no gaps in the desired information exist, nor does the absence of a UL suggest that no risk of adverse health effects exists for very high levels of nutrient intake. Finally, it is important to keep in mind the definition of a UL. It is "the highest level of daily nutrient intake that is likely to pose no risk of adverse health effects for almost all individuals in the general population." There are many gaps in knowledge about the levels at which several nutrients cause adverse health effects. As these gaps are filled, the values for ULs will be adjusted as appropriate. C1 US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. RP Vanderveen, JE (reprint author), US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. EM jvanderv@cfsan.fda.gov NR 43 TC 5 Z9 5 U1 0 U2 0 PU AMER SOCIETY NUTRITIONAL SCIENCE PI BETHESDA PA 9650 ROCKVILLE PIKE, RM L-2407A, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD FEB PY 2006 VL 136 IS 2 BP 514S EP 519S PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 006JU UT WOS:000234894600029 PM 16424137 ER PT J AU Derr, J AF Derr, J TI Valid paired data designs: Make full use of the data without "Double-Dipping" SO JOURNAL OF ORTHOPAEDIC & SPORTS PHYSICAL THERAPY LA English DT Editorial Material C1 US FDA, Silver Spring, MD USA. RP Derr, J (reprint author), US FDA, Silver Spring, MD USA. NR 3 TC 8 Z9 8 U1 0 U2 0 PU J O S P T, PI ALEXANDRIA PA 1111 NORTH FAIRFAX ST, STE 100, ALEXANDRIA, VA 22314-1436 USA SN 0190-6011 J9 J ORTHOP SPORT PHYS JI J. Orthop. Sports Phys. Ther. PD FEB PY 2006 VL 36 IS 2 BP 42 EP 44 PG 3 WC Orthopedics; Rehabilitation; Sport Sciences SC Orthopedics; Rehabilitation; Sport Sciences GA 008LR UT WOS:000235042700001 PM 16494071 ER PT J AU Sawant, SP Dnyanmote, AV Mitra, MS Chilakapati, J Warbritton, A Latendresse, JR Mehendale, HM AF Sawant, SP Dnyanmote, AV Mitra, MS Chilakapati, J Warbritton, A Latendresse, JR Mehendale, HM TI Protective effect of type 2 diabetes on acetaminophen-induced hepatotoxicity in male Swiss-Webster mice SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID ANTIMITOTIC AGENT COLCHICINE; TISSUE-REPAIR; THIOACETAMIDE HEPATOTOXICITY; CARBON-TETRACHLORIDE; LIVER-INJURY; MEDIATES PROGRESSION; CYTOCHROME-P450 2E1; HEPATIC-NECROSIS; IN-VIVO; RATS AB Type 2 diabetic (DB) mice exposed to CCl4 (LD50 = 1.25 ml/kg), acetaminophen (LD80 = 600 mg/kg; APAP), and bromobenzene (LD80 = 0.5 ml/kg) i.p. yielded 30, 20, and 20% mortality, respectively, indicating hepatotoxic resistance. Male Swiss-Webster mice were made diabetic by feeding high fat and administrating streptozotocin (120 mg/kg i.p.) on day 60. On day 71, time-course studies after APAP (600 mg/kg) treatment revealed identical initial liver injury in non-DB and DB mice, which progressed only in non-DB mice, resulting in 80% mortality. The hypothesis that decreased APAP bioactivation, altered toxicokinetics, and/or increased tissue repair are the underlying mechanisms was investigated. High-performance liquid chromatography analysis revealed no difference in plasma and urinary APAP or detoxification of APAP via glucuronidation between DB and non-DB mice. Hepatic CYP2E1 protein and activity, glutathione, and [C-14] APAP covalent binding did not differ between DB and non-DB mice, suggesting that lower bioactivation-based injury is not the mechanism of decreased hepatotoxicity in DB mice. Diabetes increased cells in S phase by 8-fold in normally quiescent liver of these mice. Immunohistochemistry revealed overexpression of calpastatin in the newly dividing/divided cells, explaining inhibition of hydrolytic enzyme calpain in perinecrotic areas and lower progression of APAP-initiated injury in the DB mice. Antimitotic intervention of diabetes-associated cell division with colchicine before APAP administration resulted in 70% mortality in APAP-treated colchicine-intervened DB mice. These studies suggest that advancement of cells in the cell division cycle and higher tissue repair protect DB mice by preventing progression of APAP-initiated liver injury that normally leads to mortality. C1 NE Louisiana Univ, Coll Pharm, Dept Toxicol, Monroe, LA 71209 USA. Natl Ctr Toxicol Res, Toxicol Pathol Assoc, Jefferson, AR 72079 USA. RP Mehendale, HM (reprint author), NE Louisiana Univ, Coll Pharm, Dept Toxicol, 700 Univ Ave, Monroe, LA 71209 USA. EM mehendale@ulm.edu RI Latendresse, John/A-9215-2009 NR 40 TC 13 Z9 13 U1 1 U2 1 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD FEB PY 2006 VL 316 IS 2 BP 507 EP 519 DI 10.1124/jpet.105.094326 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 004NH UT WOS:000234759000004 PM 16207833 ER PT J AU Amat, A Rigau, J Waynant, RW Ilev, IK Anders, JJ AF Amat, A Rigau, J Waynant, RW Ilev, IK Anders, JJ TI The electric field induced by light can explain cellular responses to electromagnetic energy: A hypothesis of mechanism SO JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY LA English DT Review DE ATP/ADP ratio; ATP synthesis; Ca2+ regulation; light-induced electric field mitochondria; Na+/K+ ionic pump; photochemistry; ROS ID CYTOCHROME-C-OXIDASE; HELIUM-NEON LASER; LOW-POWER LASER; MITOCHONDRIA IRRADIATED INVITRO; SINGLET OXYGEN PRODUCTION; RAT-LIVER; ATP SYNTHESIS; ADENOSINE-TRIPHOSPHATE; NITRIC-OXIDE; RED-LIGHT AB When cells are irradiated with visible and near-infrared wavelengths a variety of stimulatory effects are observed in their metabolism. To explain the observed light effects, researchers try to identify the chromophores that are involved in the processes. However, the mechanism of light absorption by a chromophore does not explain many of the experimental observations and therefore the primary mechanism for cellular light responses remains unproven. In addition to the ability of photons to produce electronic excitation in chromophores, light induces a wave-like alternating electric field in a medium that is able to interact with polar structures and produce dipole transitions. These dipole transitions are analyzed in the present article at different cellular and biochemical levels, leading to the proposal that the primary mechanism for the observed light effects is related to the light-induced electric field. Published by Elsevier B.V. C1 Univ Rovira & Virgili, Fac Med & Hlth Sci, Histol & Neurobiol Unit, E-43201 Reus, Spain. US FDA, Div Phys, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. Uniformed Serv Univ Hlth Sci, Dept Anat Physiol & Genet, Bethesda, MD 20814 USA. RP Amat, A (reprint author), Univ Rovira & Virgili, Fac Med & Hlth Sci, Histol & Neurobiol Unit, C St Llorenc 21, E-43201 Reus, Spain. EM albert.amat@urv.net NR 79 TC 38 Z9 41 U1 1 U2 3 PU ELSEVIER SCIENCE SA PI LAUSANNE PA PO BOX 564, 1001 LAUSANNE, SWITZERLAND SN 1011-1344 J9 J PHOTOCH PHOTOBIO B JI J. Photochem. Photobiol. B-Biol. PD FEB 1 PY 2006 VL 82 IS 2 BP 152 EP 160 DI 10.1016/j.jphotobiol.2005.10.001 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 007HK UT WOS:000234959400009 PM 16300958 ER PT J AU Konduru, K Kaplan, GG AF Konduru, K Kaplan, GG TI Stable growth of wild-type hepatitis A virus in cell culture SO JOURNAL OF VIROLOGY LA English DT Article ID COMPLETE NUCLEOTIDE-SEQUENCE; RNA TRANSCRIPTS; SERIAL PASSAGE; KIDNEY-CELLS; REPLICATION; PROPAGATION; ADAPTATION; HAV; MUTATIONS; POLYPROTEIN AB Human wild-type (wt) hepatitis A virus (HAV), the causative agent of acute hepatitis, barely grows in cell culture and in the process accumulates attenuating and cell culture-adapting mutations. This genetic instability of wt HAV in cell culture is a major roadblock to studying HAV pathogenesis and producing live vaccines that are not overly attenuated for humans. To develop a robust cell culture system capable of supporting the efficient growth of wt HAV, we transfected different cell lines with in vitro RNA transcripts of wt HAV containing the blasticidin resistance gene. Blasticidin-resistant colonies grew only in transfected Huh7 cells and produced infectious virus. HAV was genetically stable in Huh7 cells for at least nine serial passages and did not accumulate attenuating or cell culture-adapting mutations. Treatment with alpha interferon A/D cured the blasticidin-resistant Huh7 cells of the HAV infection. The cured cells, termed Huh7-A-1 cells, did not contain virus or HAV antigens and were sensitive to blasticidin. Huh7-A-1 cells were more permissive than parental cells for wt HAV infection, including a natural isolate from a human stool sample, and produced 10-fold-more infectious particles. This is the first report of a cell line that allows the genetically stable growth of human wt HAV. The viral vectors and cells described here should allow better insight into the pathogenesis of HAV and the development of attenuated vaccines. The cell lines susceptible to wt HAV growth may also be used to detect and isolate infectious virus from patient and environmental samples. C1 US FDA, Ctr Biol Evaluat & Res, Div Eerging & Transfus Transmitted Dis, Lab Hepatitis & Related Emerging Agents, Bethesda, MD 20892 USA. RP Kaplan, GG (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Eerging & Transfus Transmitted Dis, Lab Hepatitis & Related Emerging Agents, Bethesda, MD 20892 USA. EM GK@Helix.NIH.gov NR 41 TC 25 Z9 27 U1 0 U2 6 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 FEB PY 2006 VL 80 IS 3 BP 1352 EP 1360 DI 10.1128/JVI.80.3.1352-1360.2006 PG 9 WC Virology SC Virology GA 006BZ UT WOS:000234871400029 PM 16415012 ER PT J AU Goyal, N Duncan, R Selvapandiyan, A Debrabant, A Baig, MS Nakhasi, HL AF Goyal, N Duncan, R Selvapandiyan, A Debrabant, A Baig, MS Nakhasi, HL TI Cloning and characterization of angiotensin converting enzyme related dipeptidylcarboxypeptidase from Leishmania donovani SO MOLECULAR AND BIOCHEMICAL PARASITOLOGY LA English DT Article DE kala-azar; Leishmania donovani; dipeptidylcarboxypeptidase; exopeptidases; drug target ID PROTOZOAN PARASITE LEISHMANIA; SALMONELLA-TYPHIMURIUM; DIPEPTIDYL CARBOXYPEPTIDASE; DEFICIENT MUTANTS; SPECTROPHOTOMETRIC ASSAY; CYSTEINE PROTEINASES; NUCLEOTIDE-SEQUENCE; VIRULENCE FACTORS; ESCHERICHIA-COLI; GENE-EXPRESSION AB We report the first identification, gene cloning, recombinant expression and biochemical characterization of an angiotensin converting enzyme (ACE) related dipeptidylcarboxypeptidase (DCP) in a protozoan parasite. The mammalian counterpart of this enzyme, peptidyl dipeptidase A (a carboxyl dipeptidase) also known as ACE leads to the cleavage of angiotensin I to produce a potent vasopressor. The catalytic enzyme activity of its Escherichia coli DCP counter part can be inhibited by the antihypertensive drug captopril, suggesting that this class of enzymes constitutes a novel target for drugs and vaccines. By utilizing a DNA microarray expression profiling approach, we identified a gene encoding a DCP enzyme for the kinetoplast protozoan Leishmania donovani (LdDCP) that was differentially expressed in promastigote and amastigote stages of the parasite life cycle. Both RNA and protein levels of LdDCP are higher in axenic amastigotes compared to promastigotes. Immuno-fluorescence analysis revealed the cytosolic expression of the protein. Primary structure analysis of LdDCP revealed the presence of an active Zn binding site. When expressed in E. coli, the recombinant enzyme showed carboxy-dipeptidase activity with synthetic substrates. Replacement of two histidine and one glutamic acid at positions 466, 470 and 467, respectively, with alanine residues in its active site resulted in loss of enzyme activity. Captopril, an ACE specific inhibitor was able both to reduce significantly LdDCP enzyme activity and to inhibit promastigote growth. Both its cytosolic location and close homology to DCPs from bacterial species suggests a role in parasite nutrition. Further, identification of LdDCP now provides an opportunity to investigate Leishmania peptidases for their potential as drug and vaccine targets. (c) 2005 Elsevier B.V. All rights reserved. C1 Cent Drug Res Inst, Div Biochem, Lucknow 226001, Uttar Pradesh, India. US FDA, Ctr Biol Evaluat & Res, Div Emerging & Transfus Transmitted Dis, Bethesda, MD 20892 USA. RP Goyal, N (reprint author), Cent Drug Res Inst, Div Biochem, Lucknow 226001, Uttar Pradesh, India. EM neenacdri@yahoo.com RI Duncan, Robert/I-8168-2015 OI Duncan, Robert/0000-0001-8409-2501 NR 54 TC 12 Z9 15 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-6851 EI 1872-9428 J9 MOL BIOCHEM PARASIT JI Mol. Biochem. Parasitol. PD FEB PY 2006 VL 145 IS 2 BP 147 EP 157 DI 10.1016/j.molbiopara.2005.09.014 PG 11 WC Biochemistry & Molecular Biology; Parasitology SC Biochemistry & Molecular Biology; Parasitology GA 010XE UT WOS:000235230400002 PM 16257064 ER PT J AU Yoshitomi, KJ Jinneman, KC Weagant, SD AF Yoshitomi, KJ Jinneman, KC Weagant, SD TI Detection of Shiga toxin genes stx1, stx2, and the +93 uidA mutation of E-coli O157 : H7/H-using SYBR (R) Green I in a real-time multiplex PCR SO MOLECULAR AND CELLULAR PROBES LA English DT Article DE SYBR Green I; STEC; E. coli O157 : H7; real-time PCR ID POLYMERASE-CHAIN-REACTION; HEMOLYTIC UREMIC SYNDROME; AMPLICON MELTING ANALYSIS; VIRULENCE FACTORS; RAPID DETECTION; HEMORRHAGIC COLITIS; MOLECULAR BEACONS; DNA AMPLIFICATION; SEROTYPE O157-H7; ASSAY AB Enterohemorrhagic Escherichia coli (EHEC is a major foodbome pathogen capable of causing diarrhea and vomiting, but more serious complications such as hemorrhagic colitis and hemolytic-uremic syndrome (HUS) can result. A real-time PCR method to detect the presence of Shiga toxin producing E. coli(STEC) and E. coli O157:H7 was investigated using SYBR (R) Green I(SG). Primers were designed to target the Shiga toxin genes (stx1 and stx2) and a highly conserved base substitution at +93 of the beta-glucuronidase gene (uidA) unique to E. coli O157:H7. An initial test panel of five E. coli and non-E. coli isolates was tested with individual primer sets (simplex assay) and all primer sets including stx1, stY2, and uidA(multiplex assay). All strains were correctly identified in both assays. Average melt temperatures (T-m's, degrees C) for PCR products were 85.42-stx1, 81.93-stx2 and 88.25-uidA in simplex assays and 85.20-stx1, 81.20-stx2, and 88.16-uidA when multiplexed. Each of the three gene targets in one multiplex reaction could be distinguished by melt curve data with significantly different T-m's. The assay was expanded to a panel of 138 isolates consisting of STEC, E. coli O157, non-toxigenic E. coli, and non-E. coli isolates with melt peaks consistent with those stated above. Published by Elsevier Ltd. C1 US FDA, Seafood Prod Res Ctr, Bothell, WA 98021 USA. US FDA, Pacific Reg Lab NW, Bothell, WA 98021 USA. RP Yoshitomi, KJ (reprint author), US FDA, Seafood Prod Res Ctr, 22201 23rd Dr SE, Bothell, WA 98021 USA. EM ken.yoshitomi@fda.gov NR 47 TC 29 Z9 31 U1 0 U2 7 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 FEB PY 2006 VL 20 IS 1 BP 31 EP 41 DI 10.1016/j.mcp.2005.09.002 PG 11 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Cell Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Cell Biology GA 022JU UT WOS:000236052700007 PM 16271448 ER PT J AU Koehler, KM Lasky, T Fein, SB DeLong, SM Hawkins, MA Rabatsky-Ehr, T Ray, SM Shiferaw, B Swanson, E Vugia, DJ AF Koehler, KM Lasky, T Fein, SB DeLong, SM Hawkins, MA Rabatsky-Ehr, T Ray, SM Shiferaw, B Swanson, E Vugia, DJ CA EIP FoodNet Working Grp TI Population-based incidence of infection with selected bacterial enteric pathogens in children younger than five years of age, 1996-1998 SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Article; Proceedings Paper CT 3rd International Conference on Emerging Infectious Diseases CY MAR 24-27, 2002 CL ATLANTA, GA ID ESCHERICHIA-COLI O157-H7; YERSINIA-ENTEROCOLITICA O-3; HEMOLYTIC-UREMIC SYNDROME; UNITED-STATES; FOODNET SITES; SURVEILLANCE DATA; INFANTS; SALMONELLOSIS; CAMPYLOBACTER; DIARRHEA AB Background: Previous studies of bacterial enteric infections have suggested a disproportionate disease burden for children younger than 5 years of age. Objectives: This study describes population-based incidence of culture-confirmed infections with 6 bacterial enteric pathogens in children younger than 5 years of age in the Foodborne Diseases Active Surveillance Network (FoodNet), 1996-1998. Methods: Cases were ascertained through active laboratory-based surveillance in Minnesota, Oregon and selected counties in California, Connecticut, Georgia, Maryland and New York. Results: Twenty-one percent (5218 of 24,358) of infections were in children younger than 5 years of age, but this age group made up only 7% of the total person-years of observation. Among those younger than 5 years of age, the incidence (cases per 100,000 person-years) for each pathogen was: Salmonella, 55.3; Campylobacter, 43.4; Shigella, 32.7; E. coli O157, 10.3; Yersinia enterocolitica, 7.1; Listeria monocytogenes, 0.7. Incidence varied widely among the 7 FoodNet sites. Conclusions: This study confirmed a disproportionate disease burden in young children. Investigation of risk factors specific to this age group and review and enhancement Of Current prevention and control strategies for children younger than 5 years of age may reduce illness. C1 US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. USDA, Food Safety & Inspect Serv, Washington, DC 20250 USA. Ctr Dis Control & Prevent, Natl Ctr Infect Dis, Foodborne & Diarrheal Dis Branch, Div Bacterial & Mycot Dis, Atlanta, GA USA. Univ Maryland, Sch Med, Baltimore, MD 21201 USA. Yale Univ, Connecticut Emerging Infect Program, New Haven, CT USA. Emory Univ, Sch Med, Atlanta, GA USA. Oregon Dept Human Serv, Portland, OR USA. Minnesota Dept Hlth, Minneapolis, MN USA. Calif Dept Hlth Serv, Richmond, CA USA. RP Koehler, KM (reprint author), US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. NR 48 TC 32 Z9 33 U1 0 U2 1 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 FEB PY 2006 VL 25 IS 2 BP 129 EP 134 DI 10.1097/01.inf.0000199289.62733.d5 PG 6 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA 015QY UT WOS:000235567100006 PM 16462289 ER PT J AU Biernath, KR Reefhuis, J Whitney, CG Mann, EA Costa, P Eichwald, J Boyle, C AF Biernath, KR Reefhuis, J Whitney, CG Mann, EA Costa, P Eichwald, J Boyle, C TI Bacterial meningitis among children with cochlear implants beyond 24 months after implantation SO PEDIATRICS LA English DT Article DE hearing loss; intervention; meningitis; bacterial infections AB BACKGROUND. More than 11 000 children in the United States with severe-to-profound hearing loss have cochlear implants. A 2002 investigation involving pediatric cochlear implant recipients identified meningitis episodes from January 1, 1997, through September 15, 2002. The incidence of pneumococcal meningitis in the cohort was 138.2 cases per 100 000 person-years, > 30 times higher than that for children in the general US population. Children with implants with positioners were at higher risk than children with other implant models. This higher risk of bacterial meningitis continued for up to 24 months after implantation. OBJECTIVE. To evaluate additional reported cases to determine whether the increased rate of bacterial meningitis among children with cochlear implants extended beyond 24 months after implantation. METHODS. Our study population consisted of the cohort of children identified through the 2002 investigation; it included 4265 children who received cochlear implants in the United States between January 1, 1997, and August 6, 2002, and who were < 6 years of age at the time of implantation. We calculated updated incidence rates and incidence according to time since implantation. RESULTS. We identified 12 new episodes of meningitis for 12 children. Eleven of the children had implants with positioners; 2 children died. Six episodes occurred > 24 months after implantation. When cases identified in the 2002 and 2004 investigations were combined, the incidence rate of >= 24-months postimplantation bacterial meningitis among children with positioners was 450 cases per 100 000 person-years, compared with no cases among children without positioners. CONCLUSIONS. Our updated findings support continued monitoring and prompt treatment of bacterial infections by health care providers and parents of children with cochlear implants. This vigilance remains important beyond 2 years after implantation, particularly among children with positioners. The vaccination recommendations for all children with implants, with and without positioners, and all potential recipients of implants continue to apply. C1 Ctr Dis Control & Prevent, Natl Ctr Birth Defects & Dev Disabil, Atlanta, GA 30333 USA. Natl Ctr Infect Dis, Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. US FDA, Rockville, MD 20857 USA. RP Biernath, KR (reprint author), Ctr Dis Control & Prevent, Natl Ctr Birth Defects & Dev Disabil, 1600 Clifton Rd,MS E-88, Atlanta, GA 30333 USA. EM kbiernath@cdc.gov NR 10 TC 52 Z9 55 U1 0 U2 3 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD FEB PY 2006 VL 117 IS 2 BP 284 EP 289 DI 10.1542/peds.2005-0824 PG 6 WC Pediatrics SC Pediatrics GA 014PC UT WOS:000235491100003 PM 16390918 ER PT J AU Faustino, P Chan, CC Carrano, J Gosnell, M Gu, ZQ Maule, A Sigvardson, K Zhang, YF AF Faustino, P Chan, CC Carrano, J Gosnell, M Gu, ZQ Maule, A Sigvardson, K Zhang, YF TI Report on the PQRI impurity characterization and quantification best practices survey SO PHARMACEUTICAL RESEARCH LA English DT Article C1 US FDA, Rockville, MD 20857 USA. Eli Lilly Canada Inc, Toronto, ON, Canada. Wyeth Pharmaceut, Philadelphia, PA USA. Alkermes Inc, Cambridge, MA USA. 3M Pharmaceut, St Paul, MN USA. Schering Plough Res Inst, Kenilworth, NJ USA. Pfizer Inc, New York, NY USA. RP Chan, CC (reprint author), US FDA, Rockville, MD 20857 USA. EM faustinop@cder.fda.gov; chan_chung_c@lilly.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0724-8741 J9 PHARM RES JI Pharm. Res. PD FEB PY 2006 VL 23 IS 2 BP 440 EP 446 DI 10.1007/s11095-005-9646-x PG 7 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 012LN UT WOS:000235340800022 PM 16477396 ER PT J AU Claycamp, HG AF Claycamp, HG TI Rapid benefit-risk assessments: No escape from expert judgments in risk management SO RISK ANALYSIS LA English DT Editorial Material DE benefits assessment; expert judgment; microbial risk assessment; policy making; probalistic risk assessment; quality-adjusted life years ID HUMAN HEALTH-RISKS; ANTIMICROBIAL RESISTANCE; FOOD ANIMALS; VIRGINIAMYCIN; CAUSATION; DIARRHEA; MODELS; IMPACT; TOOLS AB The "human health impacts assessment" described by Cox and Popken (this issue) is intended to be a benefit-risk tool that avoids pitfalls of using expert judgments for policy analysis or during strict application of the precautionary principle in risk management. The proposed benefit-risk calculation uses numerous assumptions and suppositions to calculate a ratio of quality-adjusted life years (QALYs) lost for the number of human illness days prevented by the use of a food-animal antimicrobial drug, to the number of human illness days caused by the use of the antimicrobial drug. Assumptions about data-e.g., expert judgments on the representativeness of parameter estimates-are commonly used in risk assessment and risk management, including Cox and Popken's method. Cox and Popken apply the technique to specific examples of enrofloxacin and macrolides antimicrobial drugs, sometimes used in broiler chickens for human food. Although enthusiastically portrayed as a straightforward calculation of QALYs lost for two decision alternatives, Cox and Popken were silent on the pivotal expert judgment subsumed in their method: quality weights for illnesses caused by antimicrobial-resistant and antimicrobial-sensitive microbes are tacitly assumed to be equal. Yet, the costs in terms of prolonged illness, additional medications, repeat medical visits, and dread of more serious sequelae are expected to differ substantially for antimicrobial-resistant versus antimicrobial-sensitive illnesses. Despite their enthusiasm to the contrary, the "human health impacts assessment" by Cox and Popken is not immune from expert judgments in risk management. 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, 7500 Standish Pl,HFV 102, Rockville, MD 20855 USA. EM hclaycam@cvm.fda.gov NR 48 TC 7 Z9 8 U1 0 U2 5 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0272-4332 J9 RISK ANAL JI Risk Anal. PD FEB PY 2006 VL 26 IS 1 BP 147 EP 156 DI 10.1111/j.1539.6924.2006.00724.x PG 10 WC Public, Environmental & Occupational Health; Mathematics, Interdisciplinary Applications; Social Sciences, Mathematical Methods SC Public, Environmental & Occupational Health; Mathematics; Mathematical Methods In Social Sciences GA 014GQ UT WOS:000235468000018 PM 16492188 ER PT J AU Zhao, Y Staudenmayer, J Coull, BA Wand, MP AF Zhao, Y Staudenmayer, J Coull, BA Wand, MP TI General design Bayesian generalized linear mixed models SO STATISTICAL SCIENCE LA English DT Article DE generalized additive models; hierarchical centering; kriging; Markov chain Monte Carlo; nonparametric regression; penalized splines; spatial count data; WinBUGS ID SPATIAL STATISTICS; ADDITIVE-MODELS; BINARY RESPONSE; BIAS CORRECTION; PRIORS; REGRESSION; INFERENCE; DISPERSION; COMPONENT; ERRORS AB Linear mixed models are able to handle an extraordinary range of complications in regression-type analyses. Their most common use is to account for within-subject correlation in longitudinal data analysis. They are also the standard vehicle for smoothing spatial count data. However, when treated in full generality, mixed models can also handle spline-type smoothing and closely approximate kriging. This allows for nonparametric regression models (e.g., additive models and varying coefficient models) to be handled within the mixed model framework. The key is to allow the random effects design matrix to have general structure; hence our label general design. For continuous response data, particularly when Gaussianity of the response is reasonably assumed, computation is now quite mature and supported by the R, SAS and S-PLUS packages. Such is not the case for binary and count responses, where generalized linear mixed models (GLMMs) are required, but are hindered by the presence of intractable multivariate integrals. Software known to us supports special cases of the GLMM (e.g., PROC NLMIXED in SAS or g1mmML in R) or relies on the sometimes crude Laplace-type approximation of integrals (e.g., the SAS macro glimmix or g1mmPQL in R). This paper describes the fitting of general design generalized linear mixed models. A Bayesian approach is taken and Markov chain Monte Carlo (MCMC) is used for estimation and inference. In this generalized setting, MCMC requires sampling from nonstandard distributions. In this article, we demonstrate that the MCMC package WinBUGS facilitates sound fitting of general design Bayesian generalized linear mixed models in practice. C1 US FDA, Div Biostat, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. Univ Massachusetts, Dept Math & Stat, Amherst, MA 01003 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Univ New S Wales, Sch Math, Dept Stat, Sydney, NSW 2052, Australia. RP Zhao, Y (reprint author), US FDA, Div Biostat, Ctr Devices & Radiol Hlth, 1350 Piccard Dr, Rockville, MD 20850 USA. EM yihua.zhao@fda.hhs.gov; jstauden@math.umass.edu; bcoull@hsph.harvard.edu; wand@maths.unsw.edu.au RI Wand, Matt /F-9413-2012 OI Wand, Matt /0000-0003-2555-896X NR 58 TC 80 Z9 80 U1 0 U2 24 PU INST MATHEMATICAL STATISTICS PI BEACHWOOD PA PO BOX 22718, BEACHWOOD, OH 44122 USA SN 0883-4237 J9 STAT SCI JI Stat. Sci. PD FEB PY 2006 VL 21 IS 1 BP 35 EP 51 DI 10.1214/088342306000000015 PG 17 WC Statistics & Probability SC Mathematics GA 057HF UT WOS:000238586200007 ER PT J AU Orton, SL Stramer, SL Dodd, RY AF Orton, SL Stramer, SL Dodd, RY TI Self-reported symptoms associated with West Nile virus infection in RNA-positive blood donors SO TRANSFUSION LA English DT Article ID UNITED-STATES; NEW-YORK; TRANSMISSION; EPIDEMIC; TRANSFUSION AB BACKGROUND: In 2003, West Nile virus (WNV) nucleic acid amplification testing (NAT) was implemented to detect potentially infected donors. Of more than 5.3 million donations screened prospectively by the American Red Cross during the epidemic periods of 2003 and 2004, 974 were NAT-reactive and 519 confirmed-positive. A subset of both the confirmed-positive and the false-positive groups was assessed for demographic characteristics, symptoms, and symptom reporting relative to date of donation. STUDY DESIGN AND METHODS: All donors with initial WNV NAT-reactive results were invited to participate in a study that included a demographic, symptom, and date-of-symptom questionnaire. WNV confirmed-positive cases were compared to false-positive controls for comparison of frequency of symptom reporting before, on the day of, and after donation. RESULTS: Enrolled cases and controls were similar in all characteristics except cases were more likely to live in rural areas. Symptoms were reported by 61 percent of cases versus 20 percent of controls, with 74 percent of symptoms reported by cases within the 14 days after donation. The frequency of headache and fever reported together in the 7 days before donation was not significantly different between cases and controls; only the individual frequencies of headache, eye pain, and new rash during this time were significantly different. The most commonly reported symptoms, after adjustment for symptom reporting by controls, were headache, new rash, and generalized weakness; these symptoms were reported by 25 percent of cases. CONCLUSIONS: The demographic characteristics of infected donors reflected the rural nature of the 2003 to 2004 WNV epidemics. This study suggests that asking donors about predonation headache and fever had no detectable contribution to blood safety. C1 Amer Red Cross, Gaithersburg, MD 20877 USA. US FDA, Div Blood Applicat, CBER, OBRR, Rockville, MD 20857 USA. RP Stramer, SL (reprint author), Amer Red Cross, Gaithersburg, MD 20877 USA. EM stramers@usa.redcross.org NR 18 TC 34 Z9 36 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0041-1132 J9 TRANSFUSION JI Transfusion PD FEB PY 2006 VL 46 IS 2 BP 272 EP 277 DI 10.1111/j.1537-2995.2006.00710.x PG 6 WC Hematology SC Hematology GA 005WO UT WOS:000234856000019 PM 16441606 ER PT J AU Alvarado-Ramy, F Kuehnert, MJ Alonso-Echanove, J Sledge, L Haley, NR Epstein, J Vostal, J Pearson, ML AF Alvarado-Ramy, F Kuehnert, MJ Alonso-Echanove, J Sledge, L Haley, NR Epstein, J Vostal, J Pearson, ML TI A multistate cluster of red blood cell transfusion reactions associated with use of a leucocyte reduction filter SO TRANSFUSION MEDICINE LA English DT Article DE blood safety; leucocyte reduction; transfusion reactions ID COMPONENTS AB In 2000, the American Red Cross (ARC) received reports of unusual transfusion reactions of unknown aetiology among patients receiving leucocyte-reduced (LR) red blood cell (RBC) units in multiple distribution regions. We evaluated potential risk factors of reactions among patients who received LR-RBC transfusions. A case-patient was defined as any patient with onset of back pain while receiving an LR-RBC transfusion from 1 January to 25 May 2000. Controls were chosen randomly and selected in a 1:3 case : control ratio from healthcare facilities in which case-patients were transfused. Product-specific risk factors of reactions were further determined through nested case-control study, procedural review of blood collection facility and quality-control-testing record review of product processing. Reaction incidence rates were determined through ARC blood product distribution data by region of blood collection and processing. There were 29 reactions detected in patients who received transfusions in 13 healthcare facilities in five states. Eighteen case-patients and 78 controls were included in the case-control study. In univariate analysis, case-patients were more likely than controls to have a haematologic malignancy, to have received the transfusion as an outpatient, to have received an RBC transfusion within the previous 3 months, to have received medication used to prevent reactions or to diminish their intensity upon transfusion (i.e. premedication) or to have received LR-RBC units prepared with the HemaSure r\LS System (TM) (HS) rather than two other filters used. In multivariate analysis limited to recipients of HS-filtered RBC units, transfusion premedication [adjusted odds ratio (AOR) = 7; 95% confidence interval (CI) 1.4-37; P = 0.02] and transfusion as an outpatient (AOR = 5; 95% CI 1.1-20; P = 0.03) were independently associated with reactions. The rate of reported transfusion reactions was 2.0 reactions per 10 000 RBC units distributed. A multistate cluster of transfusion reactions was significantly associated with leucocyte filtration of RBC units prepared with a specific product, the HS filter. The reactions also were independently associated with premedication and transfusion as an outpatient; these may be surrogates for an increased risk of reaction or for greater likelihood of detection. The mechanism for these reactions has not been elucidated. This cluster of reactions underscores the importance of surveillance efforts to detect adverse events after transfusion, particularly when new methods to modify blood products are introduced. C1 Ctr Dis Control & Prevent, Div Healthcare Qual Promot, Natl Ctr Infect Dis, Atlanta, GA 30333 USA. Ctr Dis Control & Prevent, Epidem Intelligence Serv Branch, Div Appl Publ Hlth Training, Epidemiol Program Off, Atlanta, GA 30333 USA. Amer Red Cross, Blood Serv, Arlington, VA USA. US FDA, Ctr Blood Evaluat & Res, Rockville, MD 20857 USA. RP Kuehnert, MJ (reprint author), Ctr Dis Control & Prevent, Div Healthcare Qual Promot, Natl Ctr Infect Dis, 1600 Clifton Rd,MS A-30, Atlanta, GA 30333 USA. EM mkuehnert@cdc.gov NR 13 TC 8 Z9 9 U1 1 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0958-7578 J9 TRANSFUSION MED JI Transfus. Med. PD FEB PY 2006 VL 16 IS 1 BP 41 EP 48 DI 10.1111/j.1365-3148.2006.00646.x PG 8 WC Hematology SC Hematology GA 012SC UT WOS:000235358700005 PM 16480438 ER PT J AU Thorpe, SJ Fox, B Heath, AB Scott, M Haas, M Kochman, S Padilla, A AF Thorpe, SJ Fox, B Heath, AB Scott, M Haas, M Kochman, S Padilla, A TI An International Standard for specifying the minimum potency of anti-D blood-grouping reagents: evaluation of a candidate preparation in an international collaborative study SO VOX SANGUINIS LA English DT Article DE anti-D grouping reagents; International Standard; potency AB Background and Objectives The aim of this study was to evaluate a lyophilized monoclonal immunoglobulin M (IgM) anti-D preparation for use as an International Standard to specify a recommended minimum acceptable potency of anti-D blood-grouping reagents. Materials and Methods The candidate International Standard (99/836) for specifying the minimum potency of anti-D blood-grouping reagents was evaluated against a wide range of commercial anti-D blood-grouping reagents in an international collaborative study involving 20 laboratories in 13 countries. Laboratories titrated reconstituted 99/836, in parallel with as many commercial anti-D blood-grouping reagents as were available to them, in tube tests according to specified haemagglutination methodology for low-protein (e.g. monoclonal IgM) and high-protein (e.g. polyclonal) reagents. The ratios of the mean end-point titres of the reagents to that of 99/836 within each laboratory were calculated. Results The ratios of the mean titres of the low-protein reagents to the mean titre of 99/836 within a laboratory fell between 0.25 and 2 for 43 of the 45 low-protein anti-D reagents tested (i.e. the potencies of the low-protein reagents compared with 99/836 were between a 1 : 4 dilution of 99/836 to twice as potent as 99/836). The ratios of the mean titres of the high-protein reagents to the mean titre of 99/836 within a laboratory fell within 0.125 and 1 for eight out of the 10 high protein reagents tested. Conclusions By international consensus, a 1 : 3 dilution of reconstituted 99/836 was deemed appropriate to define a recommended minimum acceptable potency of low-protein anti-D blood-grouping reagents. A 1 : 8 dilution of reconstituted 99/836 was deemed appropriate to define a recommended minimum acceptable potency of high-protein anti-D blood-grouping reagents. On the basis of the results presented here, 99/836 was established by the World Health Organization as the 1st International Standard for specifying the minimum potency of anti-D blood-grouping reagents, in tube tests. C1 Natl Inst Biol Stand & Controls, Div Haematol, Potters Bar EN6 3QG, Herts, England. Int Blood Grp Reference Lab, Bristol, Avon, England. Sanquin Diagnost Serv, Amsterdam, Netherlands. US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. WHO, CH-1211 Geneva, Switzerland. RP Thorpe, SJ (reprint author), Natl Inst Biol Stand & Controls, Div Haematol, Blanche Lane, Potters Bar EN6 3QG, Herts, England. EM sthorpe@nibsc.ac.uk RI Thorpe, Susan/E-1808-2013; Fox, Bernard/E-2523-2013 NR 7 TC 1 Z9 3 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0042-9007 J9 VOX SANG JI Vox Sang. PD FEB PY 2006 VL 90 IS 2 BP 131 EP 139 DI 10.1111/j.1423-0410.2005.00735.x PG 9 WC Hematology SC Hematology GA 005CW UT WOS:000234801200009 PM 16430672 ER PT J AU Wong-Chew, RM Islas-Romero, R Garcia-Garcia, MDL Beeler, JA Audet, S Santos-Preciado, JI Gans, H Lew-Yasukawa, L Maldonado, YA Arvin, AM Valdespino-Gomez, JL AF Wong-Chew, RM Islas-Romero, R Garcia-Garcia, MDL Beeler, JA Audet, S Santos-Preciado, JI Gans, H Lew-Yasukawa, L Maldonado, YA Arvin, AM Valdespino-Gomez, JL TI Immunogenicity of aerosol measles vaccine given as the primary measles immunization to nine-month-old Mexican children SO VACCINE LA English DT Article; Proceedings Paper CT Annual Meeting of the Infectious-Disease-Society-of-America CY OCT, 2004 CL Boston, MA SP Infectious Dis Soc Amer DE aerosol measles vaccine; cellular and humoral immunity ID ADDITIONAL EVIDENCE; RANDOMIZED-TRIAL; IMMUNE-RESPONSES; DIPLOID-CELL; INFANTS; ANTIBODY; AGE; ROUTES AB Aerosol measles vaccination has been found to be more immunogenic than subcutaneous administration as a booster in school aged children, and immunogenic in 12-month-old children as a primary dose. The objective of the study was to evaluate immunogenicity to aerosol measles vaccine in 9-month-old children. Methods: Nine-months-old infants received Edmonston-Zagreb measles vaccine by aerosol (10(3.58) CCID50/0.1 mL, estimated retained dose 10(2.81) CCID50) or subcutaneous route (10(4.28) CCID50/0.5 rnL); cellular and humoral immunity and adverse events were assessed. Results: Measles-specific T cell proliferative responses developed in 42% of children given aerosolized vaccine compared with 67% of those who received subcutaneous vaccine (p = 0.01); the mean stimulation index (SI) was 4.4 +/- 0.7 Versus 6.9 +/- 1, respectively, (p = 0.05). Seroconversion rates were 33 and 92% after aerosol or subcutaneous immunization (p < 0.001). Arnong infants who developed serologic response,, measles geometric mean titers (GMT; 95% Cl) by neutralizing antibody assay were 215 mIU/mL (115-400) in aerosol vaccine recipients and 411 mIU/mL (345-490) in those given subcutaneous vaccine (p = 0.06). Conclusions: The proportion of 9-month-old infants who developed cellular and/or humoral immunity to measles was lower in the aerosol group but measles antibody and T cell responses were comparable among those who developed measles immunity. Differences in response rates are attributable to the lower aerosol dose. Improving aerosol delivery or increasing the close may enhance immunogenicity of primary aerosol measles vaccination in this age group. (c) 2005 Elsevier Ltd. All rights reserved. C1 Univ Nacl Autonoma Mexico, Fac Med, Dept Expt Med, Mexico City 06726, DF, Mexico. Inst Nacl Salud Publ, Cuernavaca, Morelos, Mexico. Hosp Infantil Mexico Dr Federico Gomez, Mexico City, DF, Mexico. Stanford Univ, Sch Med, Stanford, CA USA. Food & Drug Adm, Rockville, MD USA. RP Wong-Chew, RM (reprint author), Univ Nacl Autonoma Mexico, Fac Med, Dept Expt Med, Dr Balmis 148, Mexico City 06726, DF, Mexico. EM rmwong@correo.unam.mx FU FIC NIH HHS [TW006193]; NIAID NIH HHS [AI37127]; NICHD NIH HHS [HD01310, HD33698] NR 23 TC 41 Z9 42 U1 0 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD JAN 30 PY 2006 VL 24 IS 5 BP 683 EP 690 DI 10.1016/j.vaccine.2005.08.045 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 011NB UT WOS:000235273900017 PM 16154241 ER PT J AU Pogribny, IP Ross, SA Wise, C Pogribna, M Jones, EA Tryndyak, VP James, SJ Dragan, YP Poirier, LA AF Pogribny, IP Ross, SA Wise, C Pogribna, M Jones, EA Tryndyak, VP James, SJ Dragan, YP Poirier, LA TI Irreversible global DNA hypomethylation as a key step in hepatocarcinogenesis induced by dietary methyl deficiency SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article DE methyl-deficient diet; methyl-adequate diet; DNA hypomethylation; rat hepatocarcinogenesis ID RAT-LIVER; HEPATOCELLULAR CARCINOMAS; S-ADENOSYLHOMOCYSTEINE; CELL-PROLIFERATION; TUMOR PROGRESSION; C-MYC; CARCINOGENESIS; CHOLINE; CANCER; PATTERNS AB Dietary methyl group deprivation is now well recognized as a model of hepatocarcinogenesis in rodents. In the present study, we examined the effects of feeding a methyl-deficient diet followed by a methyl-adequate diet on the extent of methylation of liver DNA and on the formation and evolution of altered hepatic foci. Male F344 rats were fed a methyl-deficient diet for 9 18, 24, and 36 weeks, followed by re-feeding a methyl-adequate diet for a total of 54 weeks. Similar to previous findings, the methy I-deficient diet resulted in decreased levels of S-adenosylmethionine (SAM), SAM/SAH ratios, and global DNA hypomethylation. Feeding the rnethyl-adequate diet restored the liver SAM levels and SAM/SAH ratios to control levels in all experimental groups. In contrast, re-feeding the complete diet restored DNA methylation to normal level only in the group that had been fed the methyl-deficient diet for 9 weeks in animals exposed to methyl deprivation longer, the methyl-adequate diet failed to reverse the hypomethylation of DNA. Liver tissue of rats exposed to methyl deficiency for 9, 18, 24, or 36 weeks was characterized by the persistent presence of placental isoform of glutathione-S-transferase (GST pi)-positive lesions despite re-feeding the methyl-adequate diet. The persistence of altered hepatic foci in liver after withdrawal of methyl-deficient diet serves as an indication of the carcinogenic potential of a methyl-deficient diet. Substitution of the methyl-deficient diet with complete diet failed to prevent the expansion of initiated foci and restore DNA methylation in animals exposed to deficiency for 18, 24, or 36 weeks. The association between DNA hypomethylation and expansion of foci suggests that stable DNA hypomethylation is a promoting factor for clonal expansion of initiated cells. These results provide an experimental evidence and a mechanistic basis by which epigenetic alterations may contribute to the initiation and promotion steps of carcinogenesis. Published by Elsevier B.V. C1 Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. NCI, Bethesda, MD USA. Univ Arkansas Med Sci, Little Rock, AR USA. RP Pogribny, IP (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, 3900 NCTR Dr, Jefferson, AR 72079 USA. EM ipogribny@nctr.fda.gov NR 35 TC 99 Z9 103 U1 1 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0027-5107 J9 MUTAT RES-FUND MOL M JI Mutat. Res.-Fundam. Mol. Mech. Mutagen. PD JAN 29 PY 2006 VL 593 IS 1-2 BP 80 EP 87 DI 10.1016/j.mrfmmm.2005.06.028 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 011MI UT WOS:000235272000008 PM 16144704 ER PT J AU Gay, ML Niemann, RA Musser, SA AF Gay, ML Niemann, RA Musser, SA TI An isotopically labeled internal standard liquid chromatography-tandem mass spectrometry method for determination of ephedrine alkaloids and synephrine in dietary supplements SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE ephedrine; synephrine; ephedra alkaloid; dietary supplement; determination; analysis; isotope dilution; mass spectrometry; MS/MS ID CITRUS-AURANTIUM L.; CAPILLARY-ELECTROPHORESIS; ELECTROCHEMICAL DETECTION; ELECTROSPRAY-IONIZATION; GAS-CHROMATOGRAPHY; HERBAL PRODUCTS; FLOW-INJECTION; VAR. AMARA; PSEUDOEPHEDRINE; STEREOISOMERS AB We report a simplified analytical procedure for determination of ephedrine alkaloids and synephrine in dietary supplements. Cleanup by simple filtration, when combined with tandem mass spectrometry (MS/MS) detection, provided results comparable to our published method with solid phase extraction (SPE) cleanup and single-stage MS detection with in-source fragmentation. We also compared three mass spectrometric experimental configurations: electrospray (ESI) and atmospheric pressure chemical ionization (APCI) with MS/MS and APCI-MS with fragmentation provided by increasing cone voltage. Because these methods used one isotopically labeled internal standard to determine several different analytes, quantitation errors may arise from susceptibility to ionization suppression caused by the matrix. We therefore compared the results obtained by ESI and APCI ionization. C1 US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Gay, ML (reprint author), US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. EM mgay@cfsan.fda.gov NR 24 TC 28 Z9 29 U1 0 U2 11 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 JAN 25 PY 2006 VL 54 IS 2 BP 285 EP 291 DI 10.1021/jf051735w PG 7 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 006AL UT WOS:000234867400004 PM 16417281 ER PT J AU Lutterman, DA Fu, PKL Turro, C AF Lutterman, DA Fu, PKL Turro, C TI cis-[Rh-2(mu-O2CCH3)(2)(CH3CN)(6)](2+) as a photoactivated cisplatin analog SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID RH-RH BOND; ELECTRONIC-STRUCTURE; DNA-BINDING; CYTOTOXICITY; CARBOXYLATES; PRODUCTS; ADDUCTS; AGENTS C1 Ohio State Univ, Dept Chem, Columbus, OH 43210 USA. US FDA, College Pk, MD 20740 USA. RP Turro, C (reprint author), Ohio State Univ, Dept Chem, Columbus, OH 43210 USA. EM turro@chemistry.ohio-state.edu RI Turro, Claudia/H-5335-2015 OI Turro, Claudia/0000-0003-3202-5870 NR 22 TC 59 Z9 59 U1 1 U2 18 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 JAN 25 PY 2006 VL 128 IS 3 BP 738 EP 739 DI 10.1021/ja057620q PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 005IE UT WOS:000234815000035 PM 16417361 ER PT J AU O'Connell, KA Wood, JJ Wise, RP Lozier, JN Braun, MM AF O'Connell, KA Wood, JJ Wise, RP Lozier, JN Braun, MM TI Thromboembolic adverse events after use of recombinant human coagulation factor VIIa SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID ACTIVATED FACTOR-VII; DOSE FACTOR VIIA; DEPENDENT COAGULATION; HEMOPHILIA BLOOD; MECHANISM AB Context The US Food and Drug Administration (FDA) licensed recombinant human coagulation factor VIIa (rFVIIa) on March 25, 1999, for bleeding in patients with hemophilia A or B and inhibitors to factors VIII or IX Use in patients without hemophilia has been increasing since licensure. Objective To review serious thromboembolic adverse events (AEs) reported to the FDA's Adverse Event Reporting System (AERS). Design, Setting, and Patients The AERS database was reviewed from March 25, 1999, through December 31, 2004, for thromboembolic AE reports with rFVIIa. The AERS database includes US and non-US spontaneous AE reports from both approved (specific indications for patients with hemophilia) and unlabeled uses. It also includes serious AEs in patients enrolled in postlicensure clinical trials who received rFVIIa. Manufacturer reporting to FDA is mandatory, but primary notification from clinicians and others to FDA or manufacturers is voluntary for spontaneous reports; therefore, AERS underrepresents actual event occurrences. Main Outcome Measure Reported thromboembolic events occurring in patients administered rFVIIa. Results A total of 431 AE reports for rFVIIa were found, of which 168 reports described 185 thromboembolic events. Seventeen events occurred in patients with hemophilia and 59 occurred in patients enrolled in postlicensure trials. Unlabeled indications accounted for 151 of the reports, most with active bleeding (n=115). Reported AEs were thromboembolic cerebrovascular accident (n=39), acute myocardial infarction (n=34), other arterial thromboses (n=26), pulmonary embolism (n=32), other venous thromboses (including deep vein thrombosis) (n=42), and clotted devices (n=10). In 36 (72%) of 50 reported deaths, the probable cause of death was the thromboembolic event. In 144 patients with timing information, 73 events (52%) occurred in, the first 24 hours after the last dose (30 events within 2 hours). Sixty-four reports (38%) noted concomitant use of hemostatic agents. Most reports lacked sufficient information to evaluate potential dosage associations. Conclusions Most reported thromboembolic AEs followed the use of rFVIIa for unlabeled indications and occurred in arterial and venous systems, often resulting in serious morbidity and mortality. Analysis of the relationship between AEs and rFVIIa is hindered by concomitant medications, preexisting medical conditions, confounding by indication, and inherent limitations of passive surveillance. Randomized controlled trials are needed to establish the safety and efficacy of rFVIIa in patients without hemophilia. C1 US FDA, Div Epidemiol, Off Biostat & Epidemiol, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. US FDA, Div Hematol, Off Blood Res & Review, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. RP O'Connell, KA (reprint author), US FDA, Div Epidemiol HFM224, Ctr Biol Evaluat & Res, 1401 Rockville Pike, Rockville, MD 20852 USA. EM oconnellk@cber.fda.gov NR 12 TC 393 Z9 407 U1 0 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JAN 18 PY 2006 VL 295 IS 3 BP 293 EP 298 DI 10.1001/jama.295.3.293 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 003LU UT WOS:000234684500022 PM 16418464 ER PT J AU Kauffman, JF Turner, JM Alabugin, IV Breiner, B Kovalenko, SV Badaeva, EA Masunov, A Tretiak, S AF Kauffman, JF Turner, JM Alabugin, IV Breiner, B Kovalenko, SV Badaeva, EA Masunov, A Tretiak, S TI Two-photon excitation of substituted enediynes SO JOURNAL OF PHYSICAL CHEMISTRY A LA English DT Article ID DENSITY-FUNCTIONAL THEORY; DOUBLE-STRAND CLEAVAGE; ANTITUMOR ANTIBIOTIC DYNEMICIN; THERMAL BERGMAN CYCLIZATION; ABSORPTION CROSS-SECTIONS; AROMATIC NITRO-COMPOUNDS; SILYL ENOL ETHERS; DNA-CLEAVAGE; PHOTOCHEMICAL CYCLOAROMATIZATION; SYNTHETIC EQUIVALENTS AB Electronic spectroscopy of nine benzannelated enediynes and a related fulvene was studied under one-photon and two-photon excitation conditions. We utilize measured absorbance and emission spectra and time-resolved fluorescence decays of these molecules to calculate their radiative lifetimes and fluorescence quantum yields. The fluorescence quantum yields for the other compounds were referenced to the fluorescence quantum yield of compound 3 and used to determine relative two-photon absorption cross-sections. Further insight into experimental studies has been achieved using time-dependent density functional (TD-DFT) computations. The probability of two-photon absorption (TPA) increases noticeably for excitation to the higher excited states. The photophysical properties of benzannelated enediynes are sensitive to substitutions at both the core and the periphery of the enediyne chromophore. Considerably enhanced two-photon absorption is observed in an enediyne with donor substitution in the middle and acceptor substitution at the termini. Excited states with B symmetry are not active in TPA spectra. From a practical point of view, this study extends the range of wavelengths applicable for activation of the enediyne moiety from 350 to 600 nm and provides a rational basis for future studies in this field. Our theoretical computations confirmed that lowest energy TPA in benzannelated enediynes involves different orbitals than lowest energy one-photon absorbance and provided further support to the notion that introduction of donor and acceptor substituents at different ends of a molecule increases TPA. C1 Univ Missouri, Dept Chem, Columbia, MO 65211 USA. Florida State Univ, Dept Chem & Biochem, Tallahassee, FL 32303 USA. New Mexico Highlands Univ, Dept Nat Sci, Las Vegas, NM 87701 USA. Univ Cent Florida, Dept Phys, Orlando, FL 32826 USA. Univ Cent Florida, Inst Chem Dependency, Nanosci Technol Ctr, Orlando, FL 32826 USA. Los Alamos Natl Lab, Div Theoret, Los Alamos, NM 87545 USA. Los Alamos Natl Lab, Ctr Nonlinear Studies, Los Alamos, NM 87545 USA. RP Kauffman, JF (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Pharmaceut Sci, Div Pharmaceut Anal, 1114 Market St, St Louis, MO 63101 USA. EM kauffmanj@cder.fda.gov; alabugin@chem.fsu.edu RI Masunov, Artem/A-1745-2011; Tretiak, Sergei/B-5556-2009; Alabugin, Igor/C-3659-2015 OI Masunov, Artem/0000-0003-4924-3380; Tretiak, Sergei/0000-0001-5547-3647; Alabugin, Igor/0000-0001-9289-3819 NR 95 TC 34 Z9 34 U1 0 U2 13 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1089-5639 J9 J PHYS CHEM A JI J. Phys. Chem. A PD JAN 12 PY 2006 VL 110 IS 1 BP 241 EP 251 DI 10.1021/jp056127y PG 11 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 001FZ UT WOS:000234520300031 PM 16392861 ER PT J AU Chekhun, VF Kulik, GI Yurchenko, OV Tryndyak, VP Todor, IN Luniv, LS Tregubova, NA Pryzimirska, TV Montgomery, B Rusetskaya, NV Pogribny, IP AF Chekhun, VF Kulik, GI Yurchenko, OV Tryndyak, VP Todor, IN Luniv, LS Tregubova, NA Pryzimirska, TV Montgomery, B Rusetskaya, NV Pogribny, IP TI Role of DNA hypomethylation in the development of the resistance to doxorubicin in human MCF-7 breast adenocarcinoma cells SO CANCER LETTERS LA English DT Article DE MCF-7 cells; doxorubicin resistance; DNA hypomethylation ID MULTIDRUG-RESISTANCE; PROMOTER REGION; P-GLYCOPROTEIN; CANCER-CELLS; MDR1 GENE; CHROMATIN-STRUCTURE; DRUG-RESISTANCE; HYPERMETHYLATION; OVEREXPRESSION; DEMETHYLATION AB The resistance of cancer cells to chemotherapeutic agents is a major clinical problem and an important cause of treatment failure in cancer. Mechanisms that have developed to guard cancer cells against anti-cancer drugs are major barriers to successful anti-cancer therapy. Therefore, the identification of novel mechanisms of cellular resistance holds the promise of leading to better treatments for cancer patients. In the present study, we used human MCF-7 breast adenocarcinoma cell line and its doxorubicin-resistant variant MCF-7/R to determine the role of alterations of DNA methylation of chemoresitance-related genes, such as multidrug resistance 1 (MDR1), glutathione-S-transferase (GST pi), O-6-methylguanine DNA methyltransferase (MGMT), and urokinase (Upa), in the development of drug resistance. The promoter regions of MDR1, GST pi, MGMT, and Upa genes were highly methylated in MCF-7 cell line but not in its MCF-7/R drug resistant variant. The hypomethylated status of MDR1 gene was associated with overexpression of P-glycoprotein. We hypothesize that acquirement of doxorubicin resistance of MCF-7 cells is associated with DNA hypomethylation of the promoter regions of the MDR1, GST pi, MGMT, and Upa genes. (c) 2005 Elsevier Ireland Ltd. All rights reserved. C1 Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RE Kavetsky Inst Expt Pathol Oncol & Radiobiol, Dept Mech Anticanc Therapt, Kiev, Ukraine. RP Pogribny, IP (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. EM ipogribny@nctr.fda.gov NR 21 TC 40 Z9 49 U1 0 U2 4 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD JAN 8 PY 2006 VL 231 IS 1 BP 87 EP 93 DI 10.1016/j.canlet.2005.01.038 PG 7 WC Oncology SC Oncology GA 002PD UT WOS:000234622600010 PM 16356834 ER PT J AU Xia, QS Chou, MW Edgar, JA Doerge, DR Fu, PP AF Xia, QS Chou, MW Edgar, JA Doerge, DR Fu, PP TI Formation of DHP-derived DNA adducts from metabolic activation of the prototype heliotridine-type pyrrolizidine alkaloid, lasiocarpine SO CANCER LETTERS LA English DT Article DE lasiocarpine; pyrrolizidine alkaloid; DNA adduct; biomarker ID HUMAN CYTOCHROME-P450; HUMAN LIVER; RIDDELLIINE; INHIBITION; ENZYMES AB Pyrrolizidine alkaloids (PAs) are probably the most common poisonous plants affecting livestock, wildlife, and humans. The PAs that have been found to be tumorigenic in experimental animals belong to the retronecine-, heliotridine-, and otonecine-type PAs. Our recent mechanistic studies indicated that riddelliine, a tumorigenic retronecine-type PA, induced tumors via a genotoxic mechanism mediated by the formation of 6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine (DHP)-derived DNA adducts. The same adducts were formed from clivorine, a tumorigenic otonecine-type PA from metabolism of clivorine by rat liver microsomes in the presence of calf thymus DNA. In this study, we report that metabolism of lasiocarpine, the prototype heliotridine PA, by F344 rat liver microsomes resulted in the formation of DHP. When incubated in the presence of calf thymus DNA, the same DHP-derived DNA adducts were formed. These results suggest that these DHP-derived DNA adducts are potential biomarkers of exposure and tumorigenicity for all types of PAs. Published by Elsevier Ireland Ltd. C1 Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. CSIRO, Geelong, Vic 3220, Australia. RP Fu, PP (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, 3900 NCTR Rd,HFT0-110, Jefferson, AR 72079 USA. EM pfu@nctr.fda.gov NR 20 TC 33 Z9 35 U1 1 U2 6 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD JAN 8 PY 2006 VL 231 IS 1 BP 138 EP 145 DI 10.1016/j.canlet.2005.01.023 PG 8 WC Oncology SC Oncology GA 002PD UT WOS:000234622600016 PM 16356839 ER PT J AU Heller, DN Smith, ML Chiesa, OA AF Heller, DN Smith, ML Chiesa, OA TI LC/MS/MS measurement of penicillin G in bovine plasma, urine, and biopsy samples taken from kidneys of standing animals SO JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES LA English DT Article DE penicillin; liquid chromatography-tandem mass spectrometry; residue analysis; quantification; plasma; urine; kidney ID BETA-LACTAM ANTIBIOTICS; MASS-SPECTROMETRY; LIQUID-CHROMATOGRAPHY; ELECTROSPRAY-IONIZATION; CONFIRMATORY ASSAY; MILK; RESIDUES; STABILITY; TISSUES; STORAGE AB Methods for the measurement of penicillin concentration in bovine plasma, kidney and urine were developed and validated. Detection was based on liquid chromatography/tandem mass spectrometry (LC/MS/MS). Phenethecillin was used as an internal standard. Plasma was extracted with acetonitrile using a method with a calculated limit of quantitation (LOQ) of 12 ng/mL. Kidney samples were homogenized in water and acetonitrile, then cleaned up on C18-bonded silica SPE cartridges. The LOQ of this procedure was 10 ng/g. Urine samples were diluted, filtered, and analyzed directly. The LOQ of this procedure was 63 ng/mL. The overall accuracy for plasma was 103% with coefficient of variation (CV) of 3%; for kidney, 96% and 11%, respectively, and for urine, 98% and 4%, respectively. These methods were applied to the analysis of plasma, urine, and kidney biopsy samples taken from standing animals that had been dosed with penicillin. Published by Elsevier B.V. C1 US FDA, Ctr Vet Med, Laurel, MD USA. RP Heller, DN (reprint author), US FDA, Ctr Vet Med, Laurel, MD USA. EM david.heller@fda.gov NR 19 TC 20 Z9 24 U1 2 U2 13 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1570-0232 J9 J CHROMATOGR B JI J. Chromatogr. B PD JAN 2 PY 2006 VL 830 IS 1 BP 91 EP 99 DI 10.1016/j.jchromb.2005.10.025 PG 9 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 003GM UT WOS:000234669800014 PM 16257590 ER PT B AU Mattei, E Calcagnini, G Triventi, M Censi, F Bartolini, P Kainz, W Bassen, H AF Mattei, E. Calcagnini, G. Triventi, M. Censi, F. Bartolini, P. Kainz, W. Bassen, H. GP IEEE TI MRI induced heating of pacemaker leads: effect of temperature probe positioning and pacemaker placement on lead tip heating and local SAR SO 2006 28TH ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY, VOLS 1-15 LA English DT Proceedings Paper CT 28th Annual International Conference of the IEEE-Engineering-in-Medicine-and-Biology-Society CY AUG 30-SEP 03, 2006 CL New York, NY SP IEEE Engn Med & Biol Soc ID RADIOLOGY WHITE PAPER; IN-VITRO; CARDIAC-PACEMAKERS; SAFETY; VIVO; INTERFERENCE AB The radio frequency field used in Magnetic Resonance Imaging (MRI) procedures leads to temperature and local absorption rate (SAR) increase for patients with implanted pacemakers (PM). In this work a methodological approach for temperature and SAR measurements using fluoroptic probes is presented. Experimental measures show how the position of temperature probes affects the temperature and SAR value measured at the lead tip. The transversal contact between the active portion of the probe and the lead tip is the configuration associated with the highest values for temperature and SAR, whereas other configurations may lead to an underestimation close to 11% and 70% for temperature and SAR, respectively. In addition measurements were performed on a human-shaped phantom inside a real MRI system, in order to investigate the effect of the PM placement and of the lead geometry on heating and local SAR. C1 [Mattei, E.; Calcagnini, G.; Triventi, M.; Censi, F.; Bartolini, P.] Italian Natl Inst Hlth, Dept Technol & Hlth, Rome, Italy. [Kainz, W.; Bassen, H.] Food & Drug Adm, Ctr Devices & Radiol Hlth, Rockville, MD USA. RP Mattei, E (reprint author), Italian Natl Inst Hlth, Dept Technol & Hlth, Rome, Italy. EM eugenio.mattei@studio.unibo.it; eugenio.mattei@studio.unibo.it; eugenio.mattei@studio.unibo.it; eugenio.mattei@studio.unibo.it; eugenio.mattei@studio.unibo.it RI MATTEI, EUGENIO/E-4623-2015 OI MATTEI, EUGENIO/0000-0002-6494-9456 NR 16 TC 0 Z9 0 U1 0 U2 2 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4244-0032-4 PY 2006 BP 4398 EP + PG 2 WC Engineering, Biomedical SC Engineering GA BGI19 UT WOS:000247284705042 ER PT B AU de Pimentel, JCG Tirat-Gefen, YG AF de Pimentel, J. C. G. Tirat-Gefen, Y. G. GP IEEE TI Hardware acceleration for real time simulation of physiological systems SO 2006 28TH ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY, VOLS 1-15 LA English DT Proceedings Paper CT 28th Annual International Conference of the IEEE-Engineering-in-Medicine-and-Biology-Society CY AUG 30-SEP 03, 2006 CL New York, NY SP IEEE Engn Med & Biol Soc ID ELECTROMAGNETIC TRANSIENTS; MODEL AB Testing of medical equipment such as pacemakers is a critical task, because any malfunction may cause patient death or serious and long-lasting health consequences. Thus, device behavior under normal functioning conditions as well as under faulty conditions should be tested as thoroughly as possible under the project's budget. This paper presents a real-time digital simulator (DIRTS) for possible use in testing of medical devices. The simulator runs a model of a physiological system (an organ or a group of organs) in real time and uses A/D and D/A cards to interface the simulation results to real medical equipment. With this simulator, the tests can be made as thorough as needed without much increase in cost. C1 [de Pimentel, J. C. G.] Univ Laval, Dept Elect Engn, Quebec City, PQ G1K 7P4, Canada. [de Pimentel, J. C. G.] Cisco Syst Inc, Kanata, ON, Canada. [Tirat-Gefen, Y. G.] US FDA, OSEL, CDRH, Rockville, MD 20850 USA. [Tirat-Gefen, Y. G.] George Mason Univ, Castel Res Inc, Fairfax, VA 22030 USA. RP de Pimentel, JCG (reprint author), Univ Laval, Dept Elect Engn, Quebec City, PQ G1K 7P4, Canada. EM jpiment@cisco.com; yosefgavriel@computer.org NR 19 TC 0 Z9 0 U1 0 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4244-0032-4 PY 2006 BP 5638 EP + PG 2 WC Engineering, Biomedical SC Engineering GA BGI19 UT WOS:000247284706137 ER PT S AU Kyprianou, IS Paquerault, S Gallas, BD Badano, A Park, S Myers, KJ AF Kyprianou, Iacovos S. Paquerault, Sophie Gallas, Brandon D. Badano, Aldo Park, Subok Myers, Kyle J. GP IEEE TI Framework for determimation of geometric parameters of a cone beam CT scanner for measuring the system response function and improved object reconstruction SO 2006 3RD IEEE INTERNATIONAL SYMPOSIUM ON BIOMEDICAL IMAGING: MACRO TO NANO, VOLS 1-3 SE IEEE International Symposium on Biomedical Imaging LA English DT Proceedings Paper CT 3rd IEEE International Symposium on Biomedical Imaging CY APR 06-09, 2006 CL Arlington, VA SP IEEE AB We present a mathematical framework for image-based geometric calibration of flat-panel, cone-beam, circular-trajectory based Computed-Tomography (CT) scanners. The geometric parameters are used to determine the system response function corrected for misalignment. The system response function includes the shift-variant detector point response, and the location dependent response of the focal-spot. We propose a technique to automatically determine the relative geometric parameters of the scanner by including calibration marks on the object container. These parameters include the relative location and orientation of the detector and location of the focal-spot with respect to the object at each scanner rotation angle. The estimated parameters are used to determine the system response function and perform object reconstruction. Results of the system response function and object reconstruction with misalignment correction are provided, showing relevance of our mathematical framework and proposed technique. C1 [Kyprianou, Iacovos S.; Paquerault, Sophie; Gallas, Brandon D.; Badano, Aldo; Park, Subok; Myers, Kyle J.] US FDA, Lab Assessment Med Imaging Syst, CDRH, NIBIB, Rockville, MD 20857 USA. RP Kyprianou, IS (reprint author), US FDA, Lab Assessment Med Imaging Syst, CDRH, NIBIB, Rockville, MD 20857 USA. EM iacovos.kyprianou@fda.hhs.gov OI Gallas, Brandon/0000-0001-7332-1620; badano, aldo/0000-0003-3712-6670 NR 6 TC 4 Z9 4 U1 0 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1945-7928 BN 978-0-7803-9576-3 J9 I S BIOMED IMAGING PY 2006 BP 1248 EP + PG 2 WC Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BFS91 UT WOS:000244446000315 ER PT S AU Samuelson, FW Petrick, N AF Samuelson, Frank W. Petrick, Nicholas GP IEEE TI Comparing image detection algorithms using resampling SO 2006 3RD IEEE INTERNATIONAL SYMPOSIUM ON BIOMEDICAL IMAGING: MACRO TO NANO, VOLS 1-3 SE IEEE International Symposium on Biomedical Imaging LA English DT Proceedings Paper CT 3rd IEEE International Symposium on Biomedical Imaging CY APR 06-09, 2006 CL Arlington, VA SP IEEE ID PERFORMANCE; OBSERVER; CURVES AB The ability to statistically compare the performance of two computer detection (CD) or computer-aided detection (CAD) algorithms is fundamental for the development and evaluation of medical image analysis tools. Automated detection tools for medical imaging are commonly characterized using free-response receiver operating characteristic (FROC) methods. However, few statistical tools are currently available to estimate statistical significance when comparing two FROC performance curves. In this study, we introduce a permutation and a bootstrap resampling method for the nonparametric estimation of statistical significance of performance metrics when comparing two FROC curves. We then provide an initial validation of the proposed methods using an area under the FROC performance metric and a simulation model for creating CD algorithm prompts. Validation is based on a comparison of the Type I error rate produced by two statistically identical CD algorithms. The results of 104 Monte Carlo trials show that both the permutation and bootstrap methods produced excellent estimates of the expected Type I error rate. C1 [Samuelson, Frank W.; Petrick, Nicholas] US FDA, Ctr Devives & Radiol Hlth, NIBIB CDRH Joint Lab Assessment Med Imaging Syst, HFZ 140,12720 Twinbrook Pkwy, Rockville, MD USA. RP Samuelson, FW (reprint author), US FDA, Ctr Devives & Radiol Hlth, NIBIB CDRH Joint Lab Assessment Med Imaging Syst, HFZ 140,12720 Twinbrook Pkwy, Rockville, MD USA. EM Frank.Samuelson@fda.hhs.gov NR 8 TC 33 Z9 33 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1945-7928 BN 978-0-7803-9576-3 J9 I S BIOMED IMAGING PY 2006 BP 1312 EP + PG 2 WC Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BFS91 UT WOS:000244446000331 ER PT S AU Shamsi, S Wu, DG Chen, J Liu, R Kainz, W AF Shamsi, S. Wu, D. G. Chen, J. Liu, R. Kainz, W. GP IEEE TI SAR evaluation of pregnant woman models in 64 MHz MRI birdcage coil SO 2006 IEEE MTT-S INTERNATIONAL MICROWAVE SYMPOSIUM DIGEST, VOLS 1-5 SE IEEE MTT-S International Microwave Symposium LA English DT Proceedings Paper CT IEEE MTT-S International Microwave Symposium CY JUN 11-16, 2006 CL San Francisco, CA SP IEEE MTTS DE SAR; MRI RF coil; FDTD simulations; pregnant woman model ID EXPOSURE; CHICK AB This study presents numerical SAR evaluation in pregnant woman models exposed to magnetic resonance imaging (MRI) radio frequency (RF) coil at 64 MHz. Nine pregnant woman models, representing different stage of pregnancy, are used for this study. SAR values in and around fetuses at different pregnancy stages are calculated. The investigations show an SAR increase beginning at the fifth month of pregnancy and local fetus SAR values above the IEC limit of 10 W/kg for the first level controlled mode. Based on our results we recommend not to perform MRI procedures for pregnant women in the first level controlled mode. These results can be used towards developing safety standards for pregnant woman undergoing an MRI. C1 [Shamsi, S.; Wu, D. G.; Chen, J.; Liu, R.] Univ Houston, Dept Elect & Comp Engn, Houston, TX USA. [Kainz, W.] US FDA, CDRH, Rockville, MD USA. RP Shamsi, S (reprint author), Univ Houston, Dept Elect & Comp Engn, Houston, TX USA. EM ji.chen@mail.uh.edu; wolfgang.kainz@fda.hhs.gov NR 11 TC 2 Z9 2 U1 0 U2 2 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 0149-645X BN 978-0-7803-9541-1 J9 IEEE MTT S INT MICR PY 2006 BP 225 EP + DI 10.1109/MWSYM.2006.249455 PG 2 WC Engineering, Electrical & Electronic SC Engineering GA BFS69 UT WOS:000244379000055 ER PT B AU Bassen, H Seidman, S Rogul, J Desta, A Wolfgang, S AF Bassen, H. Seidman, S. Rogul, J. Desta, A. Wolfgang, S. GP IEEE TI An exposure system for evaluating. possible effects of RFID on various formulations of drug products SO 2006 INTERNATIONAL SYMPOSIUM ON INDUSTRIAL EMBEDDED SYSTEMS LA English DT Proceedings Paper CT International Symposium on Industrial Embedded Systems CY OCT 18-20, 2006 CL Juan les Pins, FRANCE SP IEEE AB We developed hardware and software to perform exposure studies of the effects of certain radio frequency (RF) electromagnetic fields on solid and liquid pharmaceuticals and biologics. The RF fields generated by our systems are similar to those emitted by radio frequency identification (RFID) readers operating in the USA licensed high frequency (HF) and ultra high frequency (UHF) hands (13.56 and 915 MHz respectively). Our systems can expose drug samples (pharmaceuticals and biologics) to uniform electric (E) and/or magnetic (H) fields at levels that are much higher than those experienced by drugs near "worst-case" readers at a distance of 20 cm. Worst-case readers are defined as those that emit the highest allowable field strengths. Maximum field strengths near these readers were identified by measurements and computations of fields from commercial readers, and are extrapolated to the maximum allowable effective isotropic radiated power or field strength dictated by the U.S. Federal Communications Commission (FCC). The UBF system we developed included a commercially available circularly polarized antenna, a microwave generator with pulse modulation, a high power amplifier, a plastic foam enclosure, and fiber optic temperature monitoring probes placed in the drugs and the surrounding air. The HF system we developed included a specially designed Helmholtz coil pair, an HF signal generator with pulse modulation, an HIT amplifier, an RF impedance matching device, and the same enclosure, and thermometry system as in the UHF system. Exposures can be performed for each drug in both its retail primary package (the smallest container produced with an RFID tag on it, e.g. bottle) and in 54 mm diameter culture dishes. The containers are suitable for exposing a wide variety of formulations of drugs (tablets, liquids, powers, capsules, creams, etc.). Exposures of drugs in culture dishes assure uniform induced electric fields and currents. In contrast, exposures in the primary containers (e.g. vials) allow studies that account for the interactions of RF fields with the packaging materials and container geometry. In our UHF system we can expose drugs to over 20 Watts Effective Isotropic Radiated Power over 5 times the FCC limits. We evaluated H fields emitted by commercially available RFID readers. In our UHF system we can expose drugs to at least 5 times the H field they produce at 20 cm from the reader. We can expose samples to 5 A/m in primary packaging or in special organ culture dishes with an outer concentric ring. The ring has inner and outer diameters of 32 mm and 55 mm respectively. Computer monitoring of power, drug temperature, and air temperature can be performed continuously during exposure. Surrounding air temperature is monitored at all times while in our lab (storage and exposure) and while shipped to drug laboratories for analysis. C1 [Bassen, H.; Seidman, S.; Rogul, J.; Desta, A.; Wolfgang, S.] US FDA, Silver Spring, MD 20993 USA. RP Bassen, H (reprint author), US FDA, Silver Spring, MD 20993 USA. EM howard.bassen@fda.hbs.gov; jonathan.rogul@gmail.com NR 9 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-0-7803-9759-0 PY 2006 BP 191 EP + PG 2 WC Engineering, Electrical & Electronic; Telecommunications SC Engineering; Telecommunications GA BGN06 UT WOS:000248551900027 ER PT S AU Brorson, K AF Brorson, Kurt BE Wirtanen, G Salo, S TI FDA's Process Analytical Technology (PAT) strategy and its implications on sterile product manufacture SO 37th R3-Nordic Contamination Control Symposium SE VTT SYMPOSIA LA English DT Proceedings Paper CT 37th R3-Nordic Contamination Control Symposium CY MAY 29-31, 2006 CL Tampere, FINLAND SP Nord Soc Cleanroom Technol C1 FDA, CDER, HFD-123, Bethesda, MD USA. RP Brorson, K (reprint author), FDA, CDER, HFD-123, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU TECHNICAL RESEARCH CENTRE FINLAND PI ESPOO PA INFORMATION SERVICE, PO BOX 2000, FIN-02044 VT ESPOO, FINLAND SN 0357-9387 BN 951-38-6303-4 J9 VTT SYMP PY 2006 VL 240 BP 87 EP 88 PG 2 WC Engineering, Manufacturing SC Engineering GA BFO07 UT WOS:000243383100062 ER PT J AU Desai, M Stockbridge, N Temple, R AF Desai, M Stockbridge, N Temple, R TI Blood pressure as an example of a biomarker that functions as a surrogate SO AAPS JOURNAL LA English DT Review DE biomarker; surrogate endpoint; blood pressure ID CORONARY-HEART-DISEASE; CONVERTING-ENZYME-INHIBITOR; LIPID-LOWERING TREATMENT; ATTACK TRIAL ALLHAT; CARDIOVASCULAR EVENTS; RANDOMIZED TRIAL; CLINICAL-TRIALS; END-POINTS; WHITE MEN; HYPERTENSION AB There are many important uses of biomarkers in drug development. An area of particular interest is the use of biomarkers as surrogate end points. Only a small minority of biomarkers are established surrogate end points. Blood pressure is an example of a surrogate end point accepted by both clinicians and regulators. It was a plausible surrogate be cause of the large epidemiologic databases demonstrating a correlation between elevated blood pressures and adverse cardiovascular outcomes. That plausibility has been supported, however, by the numerous placebo-controlled outcome studies evaluating several pharmacologically distinct agents that showed an effect on stroke and coronary heart disease outcomes from lowering blood pressure. C1 US FDA, Div Cardiovasc & Renal Prod, Silver Spring, MD 20993 USA. RP Desai, M (reprint author), US FDA, Div Cardiovasc & Renal Prod, HFD-110,Bldg 22,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM desaim@cder.fda.gov NR 35 TC 35 Z9 36 U1 0 U2 3 PU AMER ASSOC PHARMACEUTICAL SCIENTISTS PI ALEXANDRIA PA 1650 KING ST, STE 200, ALEXANDRIA, VA 22314-2747 USA SN 1550-7416 J9 AAPS J PY 2006 VL 8 IS 1 BP E146 EP E152 AR UNSP 17 DI 10.1208/aapsj080117 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 032VT UT WOS:000236804800017 PM 16584122 ER PT J AU Rosenberg, AS AF Rosenberg, Amy S. TI Effects of protein aggregates: An immunologic perspective SO AAPS JOURNAL LA English DT Article; Proceedings Paper CT AAPS Biotechnology Conference Open Fourm on Aggregation of Protein Therapeutics CY JUN 05-08, 2005 CL San Francisco, CA SP AAPS DE aggregates; container closure system; immunogenicity; neutralizing antibody; tolerance ID HUMAN GAMMA-GLOBULIN; FIELD-FLOW FRACTIONATION; RED-CELL APLASIA; IMMUNE-RESPONSE; TRANSGENIC MICE; ANTIBODIES; ANTIGENS; IMMUNOGENICITY; FORMULATIONS; THROMBOPOIETIN AB The capacity of protein aggregates to enhance immune responses to the monomeric form of the protein has been known for over a half-century. Despite the clear connection between protein aggregates and antibody mediated adverse events in treatment with early therapeutic protein products such as intravenous immune globulin ( IVIG) and human growth hormone, surprisingly little is known about the nature of the aggregate species responsible for such effects. This review focuses on a framework for understanding how aggregate species potentially interact with the immune system to enhance immune responses, garnered from basic immunologic research. Thus, protein antigens presented in a highly arrayed structure, such as might be found in large nondenatured aggregate species, are highly potent in inducing antibody responses even in the absence of T-cell help. Their potency may relate to the ability of multivalent protein species to extensively cross-link B-cell receptor, which (1) activates B cells via Bt kinases to proliferate, and (2) targets protein to class II major histocompatability complex (MHC)-loading compartments, efficiently eliciting T-cell help for antibody responses. The review further focuses on protein aggregates as they affect an immunogenicity risk assessment, the use of animal models and studies in uncovering effects of protein aggregates, and changes in product manufacture and packaging that may affect generation of protein aggregates. C1 Ctr Drug Evaluat & Res, Div Therapeut Prot, Food & Drug Adm, Bethesda, MD 20892 USA. RP Rosenberg, AS (reprint author), Ctr Drug Evaluat & Res, Div Therapeut Prot, Food & Drug Adm, Bldg 29A,Room 2D-16,8800 Rockville Pike, Bethesda, MD 20892 USA. EM amy.rosenberg@fda.hhs.gov NR 42 TC 110 Z9 111 U1 7 U2 39 PU AMER ASSOC PHARMACEUTICAL SCIENTISTS PI ARLINGTON PA 2107 WILSON BLVD, STE 700, ARLINGTON, VA 22201-3042 USA SN 1550-7416 J9 AAPS J PY 2006 VL 8 IS 3 BP E501 EP E507 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 097HM UT WOS:000241437900009 ER PT J AU Sammour, OA Hammad, MA Megrab, NA Zidan, AS AF Sammour, Omaima A. Hammad, Mohammed A. Megrab, Nagia A. Zidan, Ahmed S. TI Formulation and optimization of mouth dissolve tablets containing rofecoxib solid dispersion SO AAPS PHARMSCITECH LA English DT Article DE rofecoxib; polyvinyl pyrrolidone K30; solid dispersion; solvent method; mouth dissolve tablets; factorial design ID DISSOLUTION; MANNITOL; SYSTEMS; DRUG AB The purpose of the present investigation was to increase the solubility and dissolution rate of rofecoxib by the preparation of its solid dispersion with polyvinyl pyrrolidone K30 (PVP K30) using solvent evaporation method. Drug-polymer interactions were investigated using differential scanning calorimetry (DSC), x-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FTIR). For the preparation of rofecoxib mouth dissolve tablets, its 1:9 solid dispersion with PVP K30 was used with various disintegrants and sublimable materials. In an attempt to construct a statistical model for the prediction of disintegration time and percentage friability, a 3(2) randomized full and reduced factorial design was used to optimize the influence of the amounts of superdisintegrant and subliming agent. The obtained results showed that dispersion of the drug in the polymer considerably enhanced the dissolution rate. The drug-to-carrier ratio was the controlling factor for dissolution improvement. FTIR spectra revealed no chemical incompatibility between the drug and PVP K30. As indicated from XRD and DSC data, rofecoxib was in the amorphous form, which explains the better dissolution rate of the drug from its solid dispersions. Concerning the optimization study, the multiple regression analysis revealed that an optimum concentration of camphor and a higher percentage of crospovidone are required for obtaining rapidly disintegrating tablets. In conclusion, this investigation demonstrated the potential of experimental design in understanding the effect of the formulation variables on the quality of mouth dissolve tablets containing solid dispersion of a hydrophobic drug. C1 US FDA, CDER, Silver Spring, MD 20903 USA. Howard Univ, Sch Pharm, Washington, DC 20059 USA. Zagazig Univ, Sch Pharm, Zagazig, Egypt. RP Zidan, AS (reprint author), US FDA, CDER, White Oaks Life Sci,Bldg 64,Room 1083,10903 New H, Silver Spring, MD 20903 USA. EM ahmedzidanhendy@hotmail.com RI Zidan, Ahmed/I-1147-2012 NR 21 TC 2 Z9 2 U1 0 U2 1 PU AMER ASSOC PHARMACEUTICAL SCIENTISTS PI ALEXANDRIA PA 1650 KING ST, STE 200, ALEXANDRIA, VA 22314-2747 USA SN 1530-9932 J9 AAPS PHARMSCITECH JI AAPS PharmSciTech PY 2006 VL 7 IS 2 AR 55 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 062WG UT WOS:000238975900024 ER PT J AU Zidan, AS Sammour, OA Hammad, MA Megrab, NA Hussain, MD Khan, MA Habib, MJ AF Zidan, Ahmed S. Sammour, Omaima A. Hammad, Mohammed A. Megrab, Nagia A. Hussain, Muhammad D. Khan, Mansoor A. Habib, Muhammad J. TI Formulation of anastrozole microparticles as biodegradable anticancer drug carriers SO AAPS PHARMSCITECH LA English DT Article DE breast cancer; microencapsulation; biodegradation; anastrozole; PLGA ID IN-VITRO; POLY(D,L-LACTIC-CO-GLYCOLIC ACID); PLGA NANOPARTICLES; MOLECULAR-WEIGHT; VIVO EVALUATION; RELEASE; MICROSPHERES; VARIABLES; SIZE; NANOSPHERES AB The purpose of this study was to develop poly(d, l-lactic-coglycolic acid) (PLGA)-based anastrozole microparticles for treatment of breast cancer. An emulsion/extraction method was used to prepare anastrozole sustained-release PLGA-based biodegradable microspheres. Gas chromatography with mass spectroscopy detection was used for the quantitation of the drug throughout the studies. Microparticles were formulated and characterized in terms of encapsulation efficiency, particle size distribution, surface morphology, and drug release profile. Preparative variables such as concentrations of stabilizer, drug-polymer ratio, polymer viscosity, stirring rate, and ratio of internal to external phases were found to be important factors for the preparation of anastrozole-loaded PLGA microparticles. Fourier transform infrared with attenuated total reflectance (FTIR-ATR) analysis and differential scanning calorimetry (DSC) were employed to determine any interactions between drug and polymer. An attempt was made to fit the data to various dissolution kinetics models for multiparticulate systems, including the zero order, first order, square root of time kinetics, and biphasic models. The FTIR-ATR studies revealed no chemical interaction between the drug and the polymer. DSC results indicated that the anastrozole trapped in the microspheres existed in an amorphous or disordered- crystalline status in the polymer matrix. The highest correlation coefficients were obtained for the Higuchi model, suggesting a diffusion mechanism for the drug release. The results demonstrated that anastrozole microparticles with PLGA could be an alternative delivery method for the long- term treatment of breast cancer. C1 Howard Univ, Sch Pharm, Washington, DC 20059 USA. Zagazig Univ, Fac Pharm, Zagazig, Egypt. US FDA, Div Prod Qual Res, Silver Spring, MD USA. Univ Wyoming, Sch Pharm, Laramie, WY 82071 USA. RP Habib, MJ (reprint author), Howard Univ, Sch Pharm, 2300 4th St NW, Washington, DC 20059 USA. EM mhabib@howard.edu RI Zidan, Ahmed/I-1147-2012 NR 24 TC 3 Z9 3 U1 1 U2 7 PU AMER ASSOC PHARMACEUTICAL SCIENTISTS PI ARLINGTON PA 2107 WILSON BLVD, STE 700, ARLINGTON, VA 22201-3042 USA SN 1530-9932 J9 AAPS PHARMSCITECH JI AAPS PharmSciTech PY 2006 VL 7 IS 3 AR 61 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 097HL UT WOS:000241437800006 ER PT S AU Rollett, AD Campman, R Saylor, D AF Rollett, Anthony D. Campman, Robert Saylor, David BE Poole, WJ Wells, MA Lloyd, DJ TI Three dimensional microstructures: Statistical analysis of second phase particles in AA7075-T651 SO ALUMINIUM ALLOYS 2006, PTS 1 AND 2: RESEARCH THROUGH INNOVATION AND TECHNOLOGY SE MATERIALS SCIENCE FORUM LA English DT Article; Proceedings Paper CT 10th International Conference on Aliminium Alloys (ICAA-10) CY JUL 09-13, 2006 CL Vancouver, CANADA DE 3D Microstructures; statistical reconstruction; constituent particles; aluminum alloys; pair correlation functions ID FATIGUE-CRACK INITIATION; ALUMINUM-ALLOY; COMPOSITES; MICROSCOPY; 7075-T6; GROWTH; SIZE AB This paper describes some aspects of reconstruction of microstructures in three dimensions. A distinction is drawn between tomographic approaches that seek to characterize specific volumes of material, either with or without diffraction, and statistical approaches that focus on particular aspects of microstructure. A specific example of the application of the statistical approach is given for an aerospace aluminum alloy in which the distributions of coarse constituent particles are modeled. Such distributions are useful for modeling fatigue crack initiation and propagation. C1 Carnegie Mellon Univ, Pittsburgh, PA 15213 USA. US FDA, CDRH, OSEL, Rockville, MD 20852 USA. RP Rollett, AD (reprint author), Carnegie Mellon Univ, 5000 Forbes Ave, Pittsburgh, PA 15213 USA. EM rollett@andrew.cmu.edu; campman@andrew.cmu.edu; david.saylor@fda.hhs.gov RI Rollett, Anthony/A-4096-2012 OI Rollett, Anthony/0000-0003-4445-2191 NR 18 TC 14 Z9 14 U1 1 U2 10 PU TRANS TECH PUBLICATIONS LTD PI ZURICH-UETIKON PA BRANDRAIN 6, CH-8707 ZURICH-UETIKON, SWITZERLAND SN 0255-5476 BN 0-87849-408-1 J9 MATER SCI FORUM PY 2006 VL 519-521 BP 1 EP 10 PN 1-2 PG 10 WC Materials Science, Multidisciplinary; Metallurgy & Metallurgical Engineering SC Materials Science; Metallurgy & Metallurgical Engineering GA BEZ41 UT WOS:000240309000001 ER PT J AU Su, ZQ Tong, WD Shi, LM Shao, XG Cai, WS AF Su, ZQ Tong, WD Shi, LM Shao, XG Cai, WS TI A partial least squares-based consensus regression method for the analysis of near-infrared complex spectral data of plant samples SO ANALYTICAL LETTERS LA English DT Article DE near-infrared spectroscopy; partial least squares; consensus modeling; multivariate calibration ID STATE ENSEMBLE; CALIBRATION; PREDICTION; SPECTROSCOPY; ELIMINATION; NIR AB A consensus regression approach based on partial least square (PLS) regression, named as cPLS, for calibrating the NIR data was investigated. In this approach, multiple independent PLS models were developed and integrated into a single consensus model. The utility and merits of the cPLS method were demonstrated by comparing its results with those from a regular PLS method in predicting moisture, oil, protein, and starch contents of corn samples using the NIR spectral data. It was found that cPLS was superior to regular PLS with respect to prediction accuracy and robustness. C1 Univ Sci & Technol China, Dept Chem, Hefei 230026, Anhui, Peoples R China. US FDA, Natl Ctr Toxicol Res, Ctr Toxicoinformat, Jefferson, AR 72079 USA. Nankai Univ, Dept Chem, Tianjin 300071, Peoples R China. RP Cai, WS (reprint author), Univ Sci & Technol China, Dept Chem, Hefei 230026, Anhui, Peoples R China. EM wscai@ustc.edu.cn RI Su, Zhenqiang/H-3914-2012 NR 23 TC 16 Z9 21 U1 1 U2 8 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0003-2719 J9 ANAL LETT JI Anal. Lett. PY 2006 VL 39 IS 9 BP 2073 EP 2083 DI 10.1080/00032710600724088 PG 11 WC Chemistry, Analytical SC Chemistry GA 057AF UT WOS:000238565900024 ER PT J AU Senderowicz, AM Pazdur, R AF Senderowicz, AM Pazdur, R TI Implications for targeted drug development SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 4th International Symposium on Targeted Anticancer Therapies CY MAR 16-18, 2006 CL Amsterdam, NETHERLANDS SP Novartis, AstraZeneca, Bayer HealthCare, Centocor, Johnson & Johnson, Lilly, Merck, MSD, OSI, Schering C1 US FDA, Silver Spring, MD 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 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2006 VL 17 SU 3 BP 22 EP 22 PG 1 WC Oncology SC Oncology GA 046GZ UT WOS:000237800900014 ER PT J AU Dagher, R AF Dagher, Ramzi TI Accelerated approval of oncology drugs: Perspective from the USFDA SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 30th Congress of the European-Society-for-Medical-Oncology CY SEP 29-OCT 03, 2006 CL Istanbul, TURKEY SP European Soc Med Oncol C1 USFDA, DDOP OODP, Silver Spring, MD 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 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2006 VL 17 SU 9 BP 48 EP 48 PG 1 WC Oncology SC Oncology GA 190SH UT WOS:000248078900078 ER PT J AU Siegel, JN Zhen, BG AF Siegel, JN Zhen, BG TI The American College of Rheumatology N (ACR-N) debate: going back into the middle of the tunnel? Comment on the articles by Siegel and Zhen and by Boers - Reply SO ARTHRITIS AND RHEUMATISM LA English DT Letter C1 FDA, Silver Spring, MD USA. RP Siegel, JN (reprint author), FDA, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD JAN PY 2006 VL 54 IS 1 BP 378 EP 378 DI 10.1002/art.21683 PG 1 WC Rheumatology SC Rheumatology GA 002IO UT WOS:000234605200047 ER PT J AU Maher, PD Haffer, M AF Maher, PD Haffer, M TI Orphan drug designation and pharmacogenomics - Options and opportunities SO BIODRUGS LA English DT Article ID SEVERE COMBINED IMMUNODEFICIENCY; GENE-THERAPY; FABRYS-DISEASE; HUMAN-GENOME; MUTAGENESIS; DISORDERS; SHOW AB The rapid increase in characterization and understanding of the human genome has had a major impact on the development of therapies for rare diseases. The "inborn errors of metabolism", which are generally rare diseases, are beginning to realize new therapies based on an understanding of disease processes at the genetic level. Likewise, an understanding of acquired genetic errors, as seen in cancer, is allowing for targeted approaches to therapy that are revolutionizing, in many cases, both standards of care and prognosis. Since its inception, the Office of Orphan Products Development has been privileged to witness many of the successes and also the failures of pharmacogenomics as it relates to rare diseases. This approach, from a regulatory standpoint, often calls into question even basic assumptions about disease classification. Phenotypically homogeneous diseases are more frequently becoming 'subsetted' on the basis of genomics; conversely, overlap of therapeutic mechanisms of action is increasingly seen across seemingly diverse diseases. With the recent completion of sequencing of the human genome, as well as the increasing ease of DNA sequencing, the promise and challenge of the pharmacogenetic approach to treatment will be expected to play an increasingly important role in development of new therapies for both rare and common diseases. C1 US FDA, Off Orphan Prod Dev, Rockville, MD 20857 USA. RP Maher, PD (reprint author), US FDA, Off Orphan Prod Dev, 5600 Fishers Lane, Rockville, MD 20857 USA. EM paul.maher@fda.hhs.gov NR 45 TC 8 Z9 8 U1 0 U2 3 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 1173-8804 J9 BIODRUGS JI Biodrugs PY 2006 VL 20 IS 2 BP 71 EP 79 DI 10.2165/00063030-200620020-00001 PG 9 WC Oncology; Immunology; Pharmacology & Pharmacy SC Oncology; Immunology; Pharmacology & Pharmacy GA 045UJ UT WOS:000237767700001 PM 16626164 ER PT J AU Tan, YX Shi, LM Hussain, SM Xu, J Tong, WD Frazier, JM Wang, C AF Tan, YX Shi, LM Hussain, SM Xu, J Tong, WD Frazier, JM Wang, C TI Integrating time-course microarray gene expression profiles with cytotoxicity for identification of biomarkers in primary rat hepatocytes exposed to cadmium SO BIOINFORMATICS LA English DT Article ID PARTIAL-LEAST-SQUARES; MULTICLASS CANCER CLASSIFICATION; NEMATODE CAENORHABDITIS-ELEGANS; DRUG-METABOLIZING-ENZYMES; OXIDATIVE STRESS; HEAT-SHOCK; DIFFERENTIAL DISPLAY; TUMOR CLASSIFICATION; LINEAR-REGRESSION; INDUCED APOPTOSIS AB Motivation: DNA microarrays can provide information about the expression levels of thousands of genes simultaneously at the transcriptomic level, while conventional cell viability and cytotoxicity measurement methods provide information about the biological functions at the cellular level. Integrating these data at different levels provides a promising approach for evaluating or predicting how cells respond to chemical exposure. It is important to investigate the multi-scale biological system in a systematic way to better understand the gene regulation networks and signal transduction pathways involved in the cellular responses to environmental factors. Results: Primary rat hepatocytes were exposed to cadmium acetate at 0, 1.25 and 2 mu M. mRNA expression profiles at 0, 3, 6, 12 and 24 h were measured using the Affymetrix RatTox U34 GeneChip (R) arrays. Simultaneously, cytotoxicity was assessed by lactase dehydrogenase leakage assay. Gene expression profiles at different time points were used to evaluate cytotoxicity at subsequent time points using partial least squares, and it was found that gene expression profiles at 0 h had the best prediction accuracy for the cytotoxicity observed at 12 h. Some biomarkers whose expression profiles showed strong relationship with cytotoxicity were identified and the underlying pathways were reconstructed to illustrate how hepatocytes respond to cadmium exposure. Permutation studies were also applied to assess the reliability of the predictive models. C1 Cedars Sinai Med Ctr, Cedars Sinai Res Inst, Los Angeles, CA 90048 USA. US FDA, Natl Ctr Toxicol Res, Ctr Toxicoinformat, Jefferson, AR 72079 USA. USAF, Res Lab, Appl Biotechnol Branch, Wright Patterson AFB, OH 45434 USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90048 USA. RP Wang, C (reprint author), Cedars Sinai Med Ctr, Cedars Sinai Res Inst, Los Angeles, CA 90048 USA. EM cwang61@ucla.edu NR 98 TC 22 Z9 23 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD JAN 1 PY 2006 VL 22 IS 1 BP 77 EP 87 DI 10.1093/bioinformatics/bti737 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 000AO UT WOS:000234433500014 PM 16249259 ER PT J AU Klecker, RW Cysyk, RL Collins, JM AF Klecker, RW Cysyk, RL Collins, JM TI Zebularine metabolism by aldehyde oxidase in hepatic cytosol from humans, monkeys, dogs, rats, and mice: Influence of sex and inhibitors SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article DE aldehyde oxidase; zebularine; raloxifene; 5-benzylacyclouridine; hepatic metabolism inhibition ID URIDINE PHOSPHORYLASE INHIBITOR; LIVER; 5-BENZYLACYCLOURIDINE; BENZYLACYCLOURIDINE; PHARMACOKINETICS; RALOXIFENE; 5-FLUOROURACIL; PURIFICATION AB To aid in the clinical evaluation of zebillarine, a potential oral antitumor agent, we initiated Studies on the metabolism of zebularine in liver cytosol from humans and other mammals. Metabolism by aldehyde oxidase (AO, EC 1.2.3.1) was the major catabolic route, Yielding Uridine as the primary metabolite, which was metabolized further to Uracil by Uridine phosphorylase. The inhibition of zebularine metabolism was Studied using raloxifene, a known potent inhibitor of AO, and 5-benzylacyclouridine (BAU), a previously undescribed inhibitor of AO. The Michaelis-Menten kinetics of aldehyde oxidase and its inhibition by raloxifene and BAU were highly variable between species. (c) 2005 Elsevier Ltd. All rights reserved. C1 US FDA, Lab Clin Pharmacol, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. NCI, Mol Therapeut Program, Ctr Canc Res, Bethesda, MD 20892 USA. RP Klecker, RW (reprint author), US FDA, Lab Clin Pharmacol, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. EM klecker@cder.fda.gov NR 23 TC 38 Z9 41 U1 2 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0968-0896 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD JAN 1 PY 2006 VL 14 IS 1 BP 62 EP 66 DI 10.1016/j.bmc.2005.07.053 PG 5 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 989YB UT WOS:000233708900006 PM 16143537 ER PT J AU Schaer, DJ Schaer, CA Buehler, PW Boykins, RA Schoedon, G Alayash, AI Schaffner, A AF Schaer, DJ Schaer, CA Buehler, PW Boykins, RA Schoedon, G Alayash, AI Schaffner, A TI CD163 is the macrophage scavenger receptor for native and chemically modified hemoglobins in the absence of haptoglobin SO BLOOD LA English DT Article ID HUMAN MONOCYTES; DIFFERENTIATION ANTIGEN; ACUTE HEMOLYSIS; DISEASE; BINDING; HEME; HYPOHAPTOGLOBINEMIA; AHAPTOGLOBINEMIA; SUSCEPTIBILITY; IDENTIFICATION AB CD163 mediates the internalization of hemoglobin-haptoglobin (Hb-Hp) complexes by macrophages. Because Hp binding capacity is exhausted during severe hemolysis, an Hp-independent Hb-clearance path. way is presumed to exist. We demonstrate that Hb interacts efficiently with CD163 in the absence of Hp. Not only is Hb internalized into an endosomal compartment by CD163 as a result of active receptor-dependent endocytosis; it also inhibits the uptake of Hb-Hp complexes, suggesting a common receptor-binding site. Free Hb further induces heme oxygenase mRNA expression in CD163(+) HEK293 cells, but not in CD163(-) cells. Additional evidence for Hp-independent Hb-CD163 interaction is provided by the demonstration that CD163 mediates the uptake of alpha alpha-DBBF crosslinked Hb, a chemically modified Hb that forms minimal Hp complexes. Moreover, certain modifications to Hb, such as polymerization or the attachment of specific functional groups (3 lysyl residues) to the beta-Cys93 can reduce or enhance this pathway of uptake. In human macrophages, Hp-complex formation critically enhances Hb uptake at low (11 mu g/mL), but not at high (greater than 100 mu g/mL), ligand concentrations, lending support for a concentration-dependent biphasic model of macrophage Hb-clearance. These results identify CD163 as a scavenger receptor for native Hb and small-molecular-weight Hb-based blood substitutes after Hp depletion. C1 Univ Zurich Hosp, Med Clin B, Res Unit, CH-8091 Zurich, Switzerland. US FDA, Ctr Biol Evaluat & Res, Lab Biochem & Vasc Biol, Bethesda, MD 20014 USA. US FDA, Ctr Biol Evaluat & Res, Biophys Lab, Bethesda, MD 20014 USA. RP Schaer, DJ (reprint author), Univ Zurich Hosp, Med Clin B, Res Unit, CH-8091 Zurich, Switzerland. EM dominik.schaer@usz.ch NR 39 TC 144 Z9 146 U1 2 U2 9 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 JAN 1 PY 2006 VL 107 IS 1 BP 373 EP 380 DI 10.1182/blood-2005-03-1014 PG 8 WC Hematology SC Hematology GA 997HD UT WOS:000234235200061 PM 16189277 ER PT J AU Martin, RCG Ahn, J Nowell, SA Hein, DW Doll, MA Martini, BD Ambrosone, CB AF Martin, Robert C. G. Ahn, Jiyoung Nowell, Susan A. Hein, David W. Doll, Mark A. Martini, Benjamin D. Ambrosone, Christine B. TI Association between manganese superoxide dismutase promoter gene polymorphism and breast cancer survival SO BREAST CANCER RESEARCH LA English DT Article ID GASTRIC-CANCER; TRANSGENIC MICE; EXPRESSION; MNSOD; RISK; ESOPHAGEAL; CHEMOSENSITIVITY; CARDIOMYOPATHY; MITOCHONDRIA; ANTIOXIDANTS AB Background Manganese superoxide dismutase (MnSOD) plays a critical role in the detoxification of mitochondrial reactive oxygen species, constituting a major cellular defense mechanism against agents that induce oxidative stress. A genetic polymorphism in the mitochondrial targeting sequence of this gene has been associated with increased cancer risk and survival in breast cancer. This base pair transition (- 9 T > C) leads to a valine to alanine amino acid change in the mitochondrial targeting sequence. A polymorphism has also been identified in the proximal region of the promoter (- 102 C> T) that alters the recognition sequence of the AP-2 transcription factor, leading to a reduction in transcriptional activity. The aim of our study was to investigate possible associations of the - 102 C> T polymorphism with overall and relapse-free breast cancer survival in a hospital-based case-only study. Materials and methods The relationship between the MnSOD - 102 C> T polymorphism and survival was examined in a cohort of 291 women who received chemotherapy and/or radiotherapy for incident breast cancer. The MnSOD - 102 C> T genotype was determined using a TaqMan allele discrimination assay. Patient survival was evaluated according to the MnSOD genotype using Kaplan-Meier survival functions. Hazard ratios were calculated from adjusted Cox proportional hazards modeling. All statistical tests were two-sided. Results In an evaluation of all women, there was a borderline significant reduction in recurrence-free survival with either one or both variant alleles (CT + TT) when compared with patients with wild-type alleles ( CC) ( odds ratio, 0.65; 95% confidence interval, 0.42 - 1.01). When the analysis was restricted to patients receiving radiation therapy, there was a significant reduction in relapse-free survival in women who were heterozygous for the MnSOD - 102 genotype ( relative risk, 0.40; 95% confidence interval, 0.18 - 0.86). Similarly, when the homozygous and heterozygous variant genotypes were combined, there remained a significant reduction in relapse-free survival in this group ( hazard ratio, 0.42; 95% confidence interval, 0.20 - 0.87). Conclusion The MnSOD - 102 variant allele appears to be associated with an improved recurrence-free survival in all patients, and more dramatically in subjects who received adjuvant radiation therapy. C1 Univ Louisville, Sch Med, Dept Surg, Div Surg Oncol, Louisville, KY 40292 USA. NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD 20892 USA. Roswell Pk Canc Inst, Dept Epidemiol, Buffalo, NY 14263 USA. Natl Ctr Toxicol Res, Div Mol Epidemiol, Jefferson, AR 72079 USA. Univ Louisville, Sch Med, Dept Pharmacol & Toxicol, Louisville, KY 40292 USA. Univ Louisville, Sch Med, James Graham Brown Canc Ctr, Louisville, KY 40292 USA. RP Martin, RCG (reprint author), Univ Louisville, Sch Med, Dept Surg, Div Surg Oncol, Louisville, KY 40292 USA. EM Robert.martin@louisville.edu RI Hein, David/A-9707-2008 FU NCI NIH HHS [CA34627, R01 CA034627, R01 CA034627-21] NR 34 TC 14 Z9 15 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1465-5411 J9 BREAST CANCER RES JI Breast Cancer Res. PY 2006 VL 8 IS 4 AR R45 DI 10.1186/bcr1532 PG 9 WC Oncology SC Oncology GA 087UI UT WOS:000240767500019 PM 16859522 ER PT J AU Sun, DX Chen, G Dellinger, RW Duncan, K Fang, JL Lazarus, P AF Sun, Dongxiao Chen, Gang Dellinger, Ryan W. Duncan, Kimberly Fang, Jia-Long Lazarus, Philip TI Characterization of tamoxifen and 4-hydroxytamoxifen glucuronidation by human UGT1A4 variants SO BREAST CANCER RESEARCH LA English DT Article ID HUMAN LIVER-MICROSOMES; BREAST-CANCER PATIENTS; UDP-GLUCURONOSYLTRANSFERASE 1A4; AMMONIUM-LINKED GLUCURONIDATION; SURGICAL ADJUVANT BREAST; ENDOMETRIAL CANCER; N-GLUCURONIDATION; ACTIVE METABOLITE; THERAPY; RISK AB Introduction Tamoxifen (TAM) is an antiestrogen widely used in the treatment and prevention of breast cancer in women. One of the major mechanisms of metabolism of TAM and one of its major active metabolites, 4-hydroxytamoxifen (4-OH-TAM), is via glucuronidation. In the present study, the glucuronidating activities of three common variant isoforms encoded by the human UDP-glucuronosyltransferase (UGT) 1A4 gene were examined against TAM, trans-4-OH-TAM and cis-4-OH-TAM. Methods HPLC was used to detect glucuronide conjugates in microsomes from UGT1A4-overexpressing HK293 cells. The UGT1A4 wild-type cDNA was synthesized by RT-PCR using normal human liver total RNA. The UGT1A4(24Thr/48Leu) and UGT1A4(24Pro/48Val) variants were generated by site-directed mutagenesis of the pcDNA3.1/V5-His-TOPO plasmid expressing wild-type UGT1A4(24Pro/48Leu). Levels of UGT1A4 expression in UGT-overexpressing cell lines were measured by western blot analysis. Results Microsomes from wild-type UGT1A4(24Pro/48Leu)-overexpressing HK293 cells exhibited significant levels of activity against TAM, trans-4-OH-TAM and cis-4-OH-TAM, forming exclusively the tamoxifen quaternary ammonium glucuronide (TAM-N+-glucuronide) and the 4-hydroxytamoxifen quaternary ammonium glucuronides (trans-4-OH-TAM-N+-glucuronide and cis-4-OH-TAM-N+-glucuronide) with apparent K-m values of 2.0 mu M, 2.2 mu M, and 2.1 mu M, respectively. Higher glucuronidation activities were found by kinetic analysis for microsomes from the variant UGT1A4(24Pro/48Val)-overexpressing cell line as compared with microsomes from wild-type UGT1A4(24Pro/48Leu)-overexpressing cells against TAM and against both the trans and cis isomers of 4-OH-TAM. A significantly ( P < 0.02) lower K-m value (similar to 1.6-fold to 1.8-fold) was observed for both 4-OH-TAM isomers, while a near-significant ( P = 0.053) decrease in K-m was observed for TAM for the UGT1A4(24Pro/48Val) variant as compared with wild-type UGT1A4. The V-max/K-m ratio for the UGT1A4(24Pro/48Val) variant was significantly ( P = 0.005) higher than that observed for the wild-type UGT1A4 isoform for both the trans and cis isomers of 4-OH-TAM after normalization for UGT1A4 expression by western blotting. No significant effect on enzyme kinetics was observed for the UGT1A4(24Thr/48Leu) variant against either isomer of 4- OH-TAM or with TAM. Conclusion These data suggest that the UGT1A4 codon 48 Leu> Val polymorphism significantly alters glucuronidation rates against TAM and its active hydroxylated metabolites, and that this polymorphism may play an important role in individual pharmacological response to TAM therapy. C1 Penn State Univ, Penn State Canc Inst, Coll Med,Canc Prevent & Control Program, Dept Pharmacol,Div Populat Sci & Canc Prevent, Hershey, PA 17033 USA. Penn State Univ, Penn State Canc Inst,Dept Hlth Evaluat Sci, Coll Med,Canc Prevent & Control Program, Div Populat Sci & Canc Prevent, Hershey, PA 17033 USA. Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Lazarus, P (reprint author), Penn State Univ, Penn State Canc Inst, Coll Med,Canc Prevent & Control Program, Dept Pharmacol,Div Populat Sci & Canc Prevent, Hershey, PA 17033 USA. EM plazarus@psu.edu FU NCI NIH HHS [P01 CA068384, P01-CA68384]; NIDCR NIH HHS [R01 DE013158, R01-DE13158] NR 48 TC 63 Z9 66 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1465-5411 J9 BREAST CANCER RES JI Breast Cancer Res. PY 2006 VL 8 IS 4 AR R50 DI 10.1186/bcr1539 PG 11 WC Oncology SC Oncology GA 087UI UT WOS:000240767500024 PM 16884532 ER PT J AU Levine, JG Tonning, JM Szarfman, A AF Levine, JG Tonning, JM Szarfman, A TI Reply: The evaluation of data mining methods for the simultaneous and systematic detection of safety signals in large databases: lessons to be learned SO BRITISH JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Letter ID TRIMETHOPRIM-INDUCED HYPERKALEMIA; ADVERSE DRUG-REACTIONS; RETROSPECTIVE EVALUATION; PHARMACOVIGILANCE TOOL; POTENTIAL UTILITY; ALGORITHMS; PANCREATITIS; SURVEILLANCE C1 US FDA, Ctr Drug Evaluat & Res, Off Pharmacoepidemiol & Stat Sci, Immediate Off, Rockville, MD 20857 USA. US FDA, Off Womens Hlth, Rockville, MD 20857 USA. RP Levine, JG (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Pharmacoepidemiol & Stat Sci, Immediate Off, Rockville, MD 20857 USA. NR 22 TC 9 Z9 9 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0306-5251 J9 BRIT J CLIN PHARMACO JI Br. J. Clin. Pharmacol. PD JAN PY 2006 VL 61 IS 1 BP 105 EP 113 DI 10.1111/j.1365-2125.2005.02510.x PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 991MR UT WOS:000233818600014 PM 16390358 ER PT J AU Tryndyak, VP Kovalchuk, O Pogribny, IP AF Tryndyak, VP Kovalchuk, O Pogribny, IP TI Loss of DNA methylation and histone H4 lysine 20 trimethylation in human breast cancer cells is associated with aberrant expression of DNA methyltransferase 1, Suv4-20h2 histone methyltransferase and methyl-binding proteins SO CANCER BIOLOGY & THERAPY LA English DT Article DE DNA hypomethylation; breast cancer; DNA methyltransferases; histone methylation; histone methyltransferases; tumor progression ID HUMAN-TUMORS; CPG ISLANDS; GLOBAL DNA; HYPOMETHYLATION; EPIGENETICS; INSTABILITY; GENE; HETEROCHROMATIN; CARCINOGENESIS; HYPERMETHYLATION AB Cancer cells are characterized by epigenetic dysregulation, including global genome hypomethylation, regional hypo- and hypermethylation, altered histone modifications, and disturbed genomic imprinting. Despite the long-established fact that global DNA hypomethylation is a common feature of tumors, very little is known about evolution of this and other epigenetic alterations during tumor progression. The present study was undertaken to characterize the status of epigenetic dysregulation in three human breast cancer cell lines (MCF-7, MDA-MB-231 and MDA-MB-231(S30) that represent different stages of human breast cancer. Our data show that breast cancer cells are characterized by significant alterations in cellular epigenetic status compared to non-tumorigenic MCF-10-2A epithelial breast cells. Interestingly, more malignant MDA-MB-231 human breast cancer cells have a more prominent loss of DNA methylation accompanied by altered expression of maintenance DNA methyltransferase DNMT1, methyl-binding proteins MeCP2 and MBD2, decreased trimethylation of lysine 20 of histone H4 and hyperacetylation of histone H4 compared to MCF-7 cells. The decrease in trimethylation of lysine 20 of histone H4 in MDA-MB-231 cells was accompanied by diminished expression of Suv4-20h2 histone methyltransferase. The results of present study demonstrate that MDA-MB-231 cells have more extensive epigenenic alterations than MCF-7. These results demonstrate that human breast cancer cells are characterized by prominent epigenetic alterations which are associated with increased malignant properties of cancer cells. Such epigenetic dysregulation may contribute to and may be indicative of the formation of a more aggressive tumor phenotype during tumor progression. C1 Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. Univ Lethbridge, Dept Biol Sci, Lethbridge, AB T1K 3M4, Canada. RP Pogribny, IP (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM ipogribny@nctr.fda.gov NR 52 TC 70 Z9 77 U1 2 U2 7 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4047 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD JAN PY 2006 VL 5 IS 1 BP 65 EP 70 PG 6 WC Oncology SC Oncology GA 022GW UT WOS:000236044500019 PM 16322686 ER PT J AU King, KE Ponnamperuma, RM Gerdes, MJ Tokino, T Yamashita, T Baker, CC Weinberg, WC AF King, KE Ponnamperuma, RM Gerdes, MJ Tokino, T Yamashita, T Baker, CC Weinberg, WC TI Unique domain functions of p63 isotypes that differentially regulate distinct aspects of epidermal homeostasis SO CARCINOGENESIS LA English DT Article ID SQUAMOUS-CELL CARCINOMAS; HAY-WELLS-SYNDROME; P53 TARGET GENES; COLLAGEN XVII; LUNG-CANCER; SKIN TUMORS; CRABP-II; EXPRESSION; KERATINOCYTES; PROTEIN AB p63 is critical for squamous development and exists as multiple isotypes of two subclasses, TA and Delta N. Delta Np63 isotypes can antagonize transcription by TAp63 and p53, and are highly expressed in squamous cell cancers. Using mouse keratinocytes as a biological model of squamous epithelium, we show that multiple p63 isotypes, Delta N- and TA-containing, are expressed and differentially modulated during in vitro murine keratinocyte differentiation. Delta Np63 alpha declines with Ca2+-induced differentiation, while a smaller Delta N-form, Delta Np63(s), persists, suggesting unique functions of the two Delta N-forms. To investigate the impact of dysregulated p63 expression that is observed in cancers and to define the biological contribution of the different domains of the p63 isotypes, Delta Np63 alpha, Delta Np63(p40), TAp63 alpha, TAp63 gamma or beta-galactosidase were overexpressed in primary murine keratinocytes. Microarray, RT-PCR and western blot analyses revealed that overexpression of Delta Np63(p40), which lacks the entire alpha-tail present in Delta Np63 alpha, permits expression of a full panel of differentiation markers. This is in contrast to overexpression of the full-length Delta Np63 alpha, which blocks induction of keratin 10, loricrin and filaggrin. These findings support a role for the alpha-tail of Delta Np63 alpha in blocking differentiation-specific gene expression. Overexpression of either TAp63 isotype permits keratin 10 and loricrin expression, thus the alpha-terminus requires the cooperation of the Delta N domain in blocking early differentiation. However, both TA isotypes block filaggrin induction. The Delta N-terminus is sufficient to maintain keratinocytes in a proliferative state, as both Delta N forms block Ca2+-mediated p21(WAF1) induction and S-phase arrest, while sustaining elevated PCNA levels. No alteration in cell cycle regulation was observed in keratinocytes overexpressing TAp63 alpha or TAp63 gamma. Clarifying the functional distinctions between p63 isotypes and domains will help to elucidate how their dysregulation impacts tumor biology and may suggest novel therapeutic strategies for modulating behavior of tumor cells with altered expression of p53 family members. C1 US FDA, Ctr Drug Evaluat & Res, Div Monoclonal Antibodies, Off Biotechnol Prod, Bethesda, MD 20892 USA. Sapporo Med Univ, Sch Med, Sapporo, Hokkaido 0608556, Japan. NCI, NIH, Bethesda, MD 20892 USA. RP Weinberg, WC (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Monoclonal Antibodies, Off Biotechnol Prod, 29B Lincoln Dr,HFD-123,Bldg 29B,Room 3NN04, Bethesda, MD 20892 USA. EM weinberg@cber.fda.gov RI Weinberg, Wendy/A-8920-2009 FU Intramural NIH HHS NR 55 TC 38 Z9 39 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 JAN PY 2006 VL 27 IS 1 BP 53 EP 63 DI 10.1093/carcin/bgi200 PG 11 WC Oncology SC Oncology GA 997BF UT WOS:000234219300005 PM 16081516 ER PT S AU Cai, NS McCoy, MT Ladenheim, B Lyles, J Ali, SF Cadet, JL AF Cai, Ning Sheng McCoy, Michael T. Ladenheim, Bruce Lyles, Johnalyn Ali, Syed F. Cadet, Jean Lud BE Ali, SF Fornai, F TI Serial analysis of gene expression in the rat striatum following methamphetamine administration SO CELLULAR AND MOLECULAR MECHANISMS OF DRUGS OF ABUSE AND NEUROTOXICITY: COCAINE, GHB, AND SUBSTITUTED AMPHETAMINES SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Satellite Meeting on Cellular and Molecular Mechanisms of Drugs of Abuse and Neurotoxicity - Cocaine, GHB and Substituted Amphetamines CY AUG 16-19, 2005 CL Venice Int Univ, Venice, ITALY SP Int Soc Neurochem, Neuromed Pozzilli, FDA, Natl Ctr Toxicol Res, Reg Veneto, Prov Venezia HO Venice Int Univ DE METH; SAGE; neurotoxicity; CHOP; carbonic anhydrase ID INDUCED NEUROTOXICITY; NEURONAL APOPTOSIS; TYROSINE-HYDROXYLASE; MOUSE STRIATUM; CDNA ARRAY; ABUSE; MICE; PROTEIN; IDENTIFICATION; CONSEQUENCES AB Methamphetamine (METH), a highly addictive drug, can cause degeneration of monoaminergic terminals and neuronal apoptosis in the mammalian brain. In the present article, we have used serial analysis of gene expression (SAGE) to investigate patterns of gene expression in the striata of rats that were given a neurotoxic dose of the drug. SAGE libraries were generated from animals treated with either saline or METH (40 mg/kg) and sacrificed 2 h later. A total of 315 transcripts were differentially expressed between the two libraries (P < 0.05), with 179 (56%) being upregulated and 136 (44%) being downregulated by the METH injection. Of these, CAATT enhancer-binding protein homologous protein (CHOP)/GADD153 (growth arrest- and DNA damage-inducible gene 153) was found to be upregulated by about threefold. Analysis of the expression of genes downstream of CHOP (DOCs) revealed significant METH-induced increases in their expression. Because DOC1 is an analog of carbonic anhydrase (CA) which is involved in the interconversion between carbon dioxide and the bicarbonate ion, we also measured the effects of METH on the expression of several CAs. These were significantly upregulated by METH in a time-dependent fashion. These results indicate that METH toxicity is mediated, in part, by drug-induced perturbations of physiological processes that are dependent on normal pH and CO2 homeostasis. C1 Natl Inst Drug Abuse, Mol Neuropsychiat Branch, Abuse Intramural Res Program, NIH, Baltimore, MD 21224 USA. US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Neurochem Lab, Jefferson, AR 72079 USA. RP Cadet, JL (reprint author), Natl Inst Drug Abuse, Mol Neuropsychiat Branch, Abuse Intramural Res Program, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM jcadet@intra.nida.nih.gov NR 43 TC 5 Z9 6 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 1-57331-629-6 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2006 VL 1074 BP 13 EP 30 DI 10.1196/annals.1369.002 PG 18 WC Cell Biology; Substance Abuse; Multidisciplinary Sciences; Clinical Neurology; Pharmacology & Pharmacy SC Cell Biology; Substance Abuse; Science & Technology - Other Topics; Neurosciences & Neurology; Pharmacology & Pharmacy GA BFJ04 UT WOS:000242168100002 PM 17105900 ER PT S AU Binienda, ZK Przybyla, BD Robinson, BL Salem, N Virmani, A Amato, A Ali, SF AF Binienda, Zbigniew K. Przybyla, Beata D. Robinson, Bonnie L. Salem, Nadia Virmani, Ashraf Amato, Antonino Ali, Syed F. BE Ali, SF Fornai, F TI Effects of L-carnitine pretreatment in methamphetamine and 3-nitropropionic acid-induced neurotoxicity SO CELLULAR AND MOLECULAR MECHANISMS OF DRUGS OF ABUSE AND NEUROTOXICITY: COCAINE, GHB, AND SUBSTITUTED AMPHETAMINES SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Satellite Meeting on Cellular and Molecular Mechanisms of Drugs of Abuse and Neurotoxicity - Cocaine, GHB and Substituted Amphetamines CY AUG 16-19, 2005 CL Venice Int Univ, Venice, ITALY SP Int Soc Neurochem, Neuromed Pozzilli, FDA, Natl Ctr Toxicol Res, Reg Veneto, Prov Venezia HO Venice Int Univ DE methamphetamine; 3-nitropropionic acid; carnitine; mitochondria; striatum; neuroprotection ID STRIATAL DOPAMINE; SUCCINATE-DEHYDROGENASE; SEROTONIN REDUCTIONS; INDUCED HYPERTHERMIA; RAT-BRAIN; MOUSE; INVOLVEMENT; DYSFUNCTION; HYPOTHERMIA; ANTAGONISTS AB Adult, male Sprague-Dawley rats were injected with 3-nitropropionic acid (3-NPA) at 30 mg/kg or methamphetamine (METH) at 20 mg/kg alone or following pretreatment with L-cartnitine (LC) at 100 mg/kg. Rectal temperature was measured before and 4 h following treatment. Animals were sacrificed at 4 h posttreatment. Monoamine neurotransmitters, dopamine (DA) and serotonin (5-HT), and their metabolites were analyzed in the striatum using high-performance liquid chromatography method coupled with electrochemical detection (HPLC/ED). Transcripts of several genes related to DA metabolism were quantified using real time reverse transciption polymerise chain reaction (RT-PCR). Core temperature decreased significantly after 3-NPA acid and increased in METH-treated rats (P < 0.05). Temperature change at 4 h exhibited a significant LC effect for 3-NPA, preventing hypothermia (P < 0.05) and no effect for METH. Concentration of DA and 5-HT, and their metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA), increased significantly in 3-NPA and decreased in METH-treated rats. An increase in DOPAC/DA turnover and serotonin observed after 3-NPA was abolished in LC-/3-NPA-treated rats. In both 3-NPA- and METH-treated rats, LC prevented an increase in DA receptor D-1 gene expression. It appears that carnitine effect preventing hypothermia after 3-NPA treatments may be related not only to its mitochondriotropic actions but also to inhibitory effect on the DA and 5-HT systems activated after the exposure to 3-NPA. The same effect observed at the transcriptional level, at least for the DA receptor D-1, may account for protection against METH toxicity. C1 US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. Sigmatau Res Inc, Gaithersburg, MD 20877 USA. Signatau Hlth Sci, Res & Dev, I-00040 Pomezia, Italy. RP Binienda, ZK (reprint author), US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, HFT-132, Jefferson, AR 72079 USA. EM zbinienda@nctr.fda.gov NR 25 TC 4 Z9 4 U1 1 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 1-57331-629-6 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2006 VL 1074 BP 74 EP 83 DI 10.1196/annals.1369.006 PG 10 WC Cell Biology; Substance Abuse; Multidisciplinary Sciences; Clinical Neurology; Pharmacology & Pharmacy SC Cell Biology; Substance Abuse; Science & Technology - Other Topics; Neurosciences & Neurology; Pharmacology & Pharmacy GA BFJ04 UT WOS:000242168100006 PM 17105904 ER PT S AU Pereira, FC Lourenco, E Milhazes, N Morgadinho, T Ribeiro, CLF Ali, SF Macedo, TR AF Pereira, Frederico C. Lourenco, Elita Milhazes, Nuno Morgadinho, Teresa Ribeiro, Car-Los F. Ali, Syed F. Macedo, Tice R. BE Ali, SF Fornai, F TI Methamphetamine, morphine, and their combination - Acute changes in striatal dopaminergic transmission evaluated by microdialysis in awake rats SO CELLULAR AND MOLECULAR MECHANISMS OF DRUGS OF ABUSE AND NEUROTOXICITY: COCAINE, GHB, AND SUBSTITUTED AMPHETAMINES SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Satellite Meeting on Cellular and Molecular Mechanisms of Drugs of Abuse and Neurotoxicity - Cocaine, GHB and Substituted Amphetamines CY AUG 16-19, 2005 CL Venice Int Univ, Venice, ITALY SP Int Soc Neurochem, Neuromed Pozzilli, FDA, Natl Ctr Toxicol Res, Reg Veneto, Prov Venezia HO Venice Int Univ DE morphine-methamphetamine combination; caudate putamen; dopamine neurotransmission; microdialysis ID NUCLEUS-ACCUMBENS; LOCOMOTOR-ACTIVITY; OPIOID RECEPTORS; CAUDATE-NUCLEUS; D-AMPHETAMINE; RELEASE; SINGLE; ADDICTION; COCAINE; HEROIN AB The co-administration of methamphetamine (METH) and MOR (MOR)-like compounds is becoming increasingly popular among drug abusers. Recently, it was demonstrated that rats would self-inject METH-heroin combination and that this combination produced a greater rewarding effect than the identical doses of METH alone and it was further suggested that enhanced reward might underlie the popularity of this combination. However, there is null information on the effects of the MOR-METH combination on striatal dopaminergic transmission. In the present article, in vivo brain microdialysis was used to examine the effects of two METH doses (1 and 5 mg/kg, i.p.; [METH1: hyperlocomotion-inducing] and [METH5: stereotypy-inducing], respectively) and MOR (10 mg/kg, i.p. [MOR10]) either alone or in combination on dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC) release in caudate putamen (CPu) in freely moving rats. METH1 evoked a transient threefold increase in DA overflow in only one-third of dosed rats. On the contrary, METH5 elicited a 11-fold increase in the extracellular DA levels 30 min after dosing and stayed significantly (P < 0.05) above control levels up to 1.5 h. On the other hand, MOR10 did not significantly change DA extracellular levels. MOR10-METH1 combination prolonged DA outflow for 1 h in all rats dosed without changing peak effect compared to METH1. On the other hand, MOR10-METH5 combination did not change the peak effect nor the DA outflow profile compared to METH5 alone. Consistently, there is a concentration-dependent decrease in DOPAC efflux evoked by METH: METH1 evoked a smaller decrease in DOPAC outflow showing a tendency for returning to basal values whereas METH5 kept DOPAC extracellular levels reduced throughout the experiment. Again, MOR10 did not significantly change DOPAC extracellular levels. MOR delayed the onset without changing METH effect on the DOPAC output. These findings provide suggestive evidence that MOR potentiated the increase in extracellular DA levels induced by a low dose of METH. Thus, this combination yields a profile of action that might underlie the reinforcing properties sought by drug addicts. C1 Univ Coimbra, Sch Med, Inst Farmacol & Terapeut, P-3004504 Coimbra, Portugal. Univ Porto, Fac Pharm, Dept Organ Chem, CEQOFFUP, P-4050047 Oporto, Portugal. Natl Ctr Toxicol Res, Div Neurotoxicol, Neurochem Lab, Jefferson, AR 72079 USA. RP Pereira, FC (reprint author), Univ Coimbra, Sch Med, Inst Farmacol & Terapeut, Rua Larga, P-3004504 Coimbra, Portugal. EM fredcp@ci.uc.pt OI Fontes Ribeiro, Carlos/0000-0002-9707-4895; Pereira, Frederico/0000-0002-9381-3320; Milhazes, Nuno/0000-0002-5171-0454 NR 36 TC 15 Z9 15 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 1-57331-629-6 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2006 VL 1074 BP 160 EP 173 DI 10.1196/annals.1369.016 PG 14 WC Cell Biology; Substance Abuse; Multidisciplinary Sciences; Clinical Neurology; Pharmacology & Pharmacy SC Cell Biology; Substance Abuse; Science & Technology - Other Topics; Neurosciences & Neurology; Pharmacology & Pharmacy GA BFJ04 UT WOS:000242168100016 PM 17105914 ER PT S AU Sharma, HS Ali, SF AF Sharma, Hari Shanker Ali, Syed F. BE Ali, SF Fornai, F TI Alterations in blood-brain barrier function by morphine and methamphetamine SO CELLULAR AND MOLECULAR MECHANISMS OF DRUGS OF ABUSE AND NEUROTOXICITY: COCAINE, GHB, AND SUBSTITUTED AMPHETAMINES SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Satellite Meeting on Cellular and Molecular Mechanisms of Drugs of Abuse and Neurotoxicity - Cocaine, GHB and Substituted Amphetamines CY AUG 16-19, 2005 CL Venice Int Univ, Venice, ITALY SP Int Soc Neurochem, Neuromed Pozzilli, FDA, Natl Ctr Toxicol Res, Reg Veneto, Prov Venezia HO Venice Int Univ DE morphine; methamphetamine; rats; mice; stress; blood-brain barrier; brain dysfunction; heat shock protein; glial cells; nerve cells; Evans blue; radioiodine ID NORMOTENSIVE YOUNG-RATS; SPINAL-CORD INJURY; SEROTONIN SYNTHESIS INHIBITOR; PITUITARY-ADRENAL RESPONSES; SHOCK-PROTEIN RESPONSE; CENTRAL-NERVOUS-SYSTEM; CHRONIC STRESS; HEAT-STRESS; NITRIC-OXIDE; INDUCED PATHOPHYSIOLOGY AB The possibility that stress associated with morphine and amphetamine administration or withdrawal will influence the blood-brain barrier (BBB) and brain dysfunction was examined in a rodent model. Repeated daily administration of morphine (10 mg/kg, i.p.) resulted in drug dependence in rats on the sixth-day and onwards. Measurement of the BBB permeability to large molecule tracers normally bound to proteins, e.g., Evans blue albumin and radioiodine (([131])Iodine) did not show any leakage on the 12th day of drug dependence. On the other hand, spontaneous withdrawal of morphine on day 1 resulted in profound stress symptoms. These symptoms were much more intense on the second day of morphine withdrawal. Alterations in the BBB to protein tracers were seen in several regions of the brain. This increase in BBB to protein tracers was most pronounced on the second day of morphine withdrawal. These rats also exhibited abnormal neuronal, glial and stress protein, the heat-shock protein 72 kD (HSP-72 kD) response. On the other hand, acute administration of methamphetamine (40 mg/kg, i.p.) in mice resulted in marked extravasation of endogenous serum protein as seen with increased expression of albumin immunohistochemistry. These observations suggest that psychostimulants and associated stress are capable to influence the brain function, probably through modifying the BBB function, not reported earlier. C1 Uppsala Univ, Univ Hosp, Dept Surg Sci Anesthesiol & Intens Care Med, Lab Cerebrovasc Res, SE-75185 Uppsala, Sweden. US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Neurochem Lab, Jefferson, AR 72079 USA. RP Sharma, HS (reprint author), Frodingsgatan 12-28, SE-75421 Uppsala, Sweden. EM Sharma@surgsci.uu.se RI Sharma, Hari/G-4508-2016 NR 58 TC 78 Z9 78 U1 0 U2 8 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 1-57331-629-6 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2006 VL 1074 BP 198 EP 224 DI 10.1196/annals.1369.020 PG 27 WC Cell Biology; Substance Abuse; Multidisciplinary Sciences; Clinical Neurology; Pharmacology & Pharmacy SC Cell Biology; Substance Abuse; Science & Technology - Other Topics; Neurosciences & Neurology; Pharmacology & Pharmacy GA BFJ04 UT WOS:000242168100020 PM 17105918 ER PT S AU Kanthasamy, A Anantharam, V Ali, SF Kanthasamy, AG AF Kanthasamy, Arthi Anantharam, V. Ali, Syed F. Kanthasamy, A. G. BE Ali, SF Fornai, F TI Methamphetamine induces autophagy and apoptosis in a mesencephalic dopaminergic neuronal culture model - Role of cathepsin-D in methamphetamine-induced apoptotic cell death SO CELLULAR AND MOLECULAR MECHANISMS OF DRUGS OF ABUSE AND NEUROTOXICITY: COCAINE, GHB, AND SUBSTITUTED AMPHETAMINES SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Satellite Meeting on Cellular and Molecular Mechanisms of Drugs of Abuse and Neurotoxicity - Cocaine, GHB and Substituted Amphetamines CY AUG 16-19, 2005 CL Venice Int Univ, Venice, ITALY SP Int Soc Neurochem, Neuromed Pozzilli, FDA, Natl Ctr Toxicol Res, Reg Veneto, Prov Venezia HO Venice Int Univ DE methamphetamine; neurotoxicity; autophagy; cathepsin-D; DNA fragmentation ID KINASE-C-DELTA; PROTEOLYTIC ACTIVATION; PARKINSONS-DISEASE; NITRIC-OXIDE; NEUROTOXICITY; DEGENERATION; DAMAGE; BCL-2; PEROXYNITRITE; EXPRESSION AB Autophagy is a phylogenetically conserved process that plays a critical role in the degradation of oxidatively damaged proteins and organelle turnover. The role of oxidative stress and apoptosis in methamphetamine (METH)-induced neurotoxicity is well known; however, the potential contribution of autophagy to METH-induced oxidative damage in dopaminergic neuronal systems remains unclear. The goals of the present article were twofold: (a) to develop an in vitro dopaminergic cell culture model to study cellular and molecular mechanisms underlying METH-induced autophagy and apoptosis, and (b) to determine whether lysosomal protease cathepsin-D activation, resulting from the loss of lysosomal membrane integrity, contributes to METH-induced apoptosis. To accomplish these goals, we characterized morphological and biochemical changes in an immortalized mesencephalic dopaminergic neuronal cell line (N27 cells) following treatment with METH. Exposure of METH (2 mM) to N27 cells resulted in the appearance of cytoplasmic vacuolar structures reminiscent of autophagic vacuoles within 3 h. In order to ascertain the identity of the vacuolar structures that are formed following METH exposure, immunohistochemical staining for markers of autophagy were performed. LAMP 2, a classical marker of autophagolysosomes, revealed an extensive punctuate pattern of distribution on the vacuolar membrane surface, with exclusive localization in the cytoplasm. Additionally, using DNA fragmentation analysis we showed a dose-dependent increase in fragmented DNA in METH treated N27 cells. Since METH-induced autophagy preceded DNA fragmentation, we tested whether dysfunction of the autophagolysosomal system contributes to nuclear damage. Immunofluorescence studies with cathepsin-D demonstrated a granular pattern of staining in untreated cells, whereas an increased cathepsin-D immunoreactivity with a globular pattern of staining was observed in METH-treated cells. Nevertheless, blockade of cathepsin-D activation by pepstatin-A, cathepsin-D inhibitor, failed to alter METH-induced DNA fragmentation. Collectively, these results demonstrate that N27 dopaminergic neuronal cell model may serve as an excellent in vitro model to study the mechanisms of METH-induced autophagy and apoptosis. Furthermore, it is less likely that cathepsin-D may serve as a trigger for the induction of apoptosis subsequent to exposure of N27 dopaminergic neuronal cells to METH. C1 Iowa State Univ, Dept Biomed Sci, Parkinson Disorders Res Lab, Ames, IA 50011 USA. US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Neurochem Lab, Jefferson, AR 72079 USA. RP Kanthasamy, A (reprint author), Iowa State Univ, Dept Biomed Sci, Parkinson Disorders Res Lab, 2062 Vet Med Bldg, Ames, IA 50011 USA. EM arthik@iastate.edu FU NIEHS NIH HHS [ES 10586] NR 31 TC 37 Z9 38 U1 0 U2 6 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 1-57331-629-6 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2006 VL 1074 BP 234 EP 244 DI 10.1196/annals.1369.022 PG 11 WC Cell Biology; Substance Abuse; Multidisciplinary Sciences; Clinical Neurology; Pharmacology & Pharmacy SC Cell Biology; Substance Abuse; Science & Technology - Other Topics; Neurosciences & Neurology; Pharmacology & Pharmacy GA BFJ04 UT WOS:000242168100022 PM 17105920 ER PT S AU Virmani, A Binienda, Z Ali, S Gaetani, F AF Virmani, Ashraf Binienda, Zbigniew Ali, Syed Gaetani, Franco BE Ali, SF Fornai, F TI Links between nutrition, drug abuse, and the metabolic syndrome SO CELLULAR AND MOLECULAR MECHANISMS OF DRUGS OF ABUSE AND NEUROTOXICITY: COCAINE, GHB, AND SUBSTITUTED AMPHETAMINES SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Satellite Meeting on Cellular and Molecular Mechanisms of Drugs of Abuse and Neurotoxicity - Cocaine, GHB and Substituted Amphetamines CY AUG 16-19, 2005 CL Venice Int Univ, Venice, ITALY SP Int Soc Neurochem, Neuromed Pozzilli, FDA, Natl Ctr Toxicol Res, Reg Veneto, Prov Venezia HO Venice Int Univ DE nutrition; drug abuse; metabolic syndrome; L-carnitine; acetyl-L-carnitine; creatine; selenium; cocaine; ecstasy; methamphetamine; alcohol; brain; liver; metabolic compromise; metabolic modifier; glycolysis; free radicals; reactive oxygen species (ROS); vitamins; minerals; zinc; thiamine; supplements; diabetes; metabolic compensation ID L-CARNITINE; VITAMIN-E; MITOCHONDRIAL DYSFUNCTION; DIABETES-MELLITUS; LIVER-CIRRHOSIS; PROTECTIVE ROLE; HUMAN BRAIN; METHAMPHETAMINE; ALCOHOL; COCAINE AB Nutritional deficiency in combination with drug abuse may increase risk of developing the metabolic syndrome by augmenting cell damage, excitotoxicity, reducing energy production, and lowering the antioxidant potential of the cells. We have reviewed here the following points: effects of drugs of abuse on nutrition and brain metabolism; effects of nutrition on actions of the drugs of abuse; drug abuse and probability of developing metabolic syndrome; role of genetic vulnerability in nutrition/drug abuse and brain damage; and the role of neuroprotective supplements in drug abuse. Nutrition education is an essential component of substance abuse treatment programs and can enhance substance abuse treatment outcomes. The strategies available, in particular the nutritional approach to protect the drug abusers from the metabolic syndrome and other diseases are discussed. C1 Sigma Tau Hlth Sci, Res & Dev, I-00040 Pomezia, Italy. US FDA, Neurophysiol Lab, Div Neurotoxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. US FDA, Neurochem Lab, Div Neurotoxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Virmani, A (reprint author), Sigma Tau Hlth Sci, Res & Dev, Via Treviso 4, I-00040 Pomezia, Italy. EM ashraf.virmani@st-hs.it NR 56 TC 14 Z9 16 U1 0 U2 5 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 1-57331-629-6 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2006 VL 1074 BP 303 EP 314 DI 10.1196/annals.1369.027 PG 12 WC Cell Biology; Substance Abuse; Multidisciplinary Sciences; Clinical Neurology; Pharmacology & Pharmacy SC Cell Biology; Substance Abuse; Science & Technology - Other Topics; Neurosciences & Neurology; Pharmacology & Pharmacy GA BFJ04 UT WOS:000242168100028 PM 17105926 ER PT S AU Samantaray, S Ray, SK Ali, SF Banik, NL AF Samantaray, Supriti Ray, Swapan K. Ali, Syed F. Banik, Naren L. BE Ali, SF Fornai, F TI Calpain activation in apoptosis of motoneurons in cell culture models of experimental parkinsonism SO CELLULAR AND MOLECULAR MECHANISMS OF DRUGS OF ABUSE AND NEUROTOXICITY: COCAINE, GHB, AND SUBSTITUTED AMPHETAMINES SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Satellite Meeting on Cellular and Molecular Mechanisms of Drugs of Abuse and Neurotoxicity - Cocaine, GHB and Substituted Amphetamines CY AUG 16-19, 2005 CL Venice Int Univ, Venice, ITALY SP Int Soc Neurochem, Neuromed Pozzilli, FDA, Natl Ctr Toxicol Res, Reg Veneto, Prov Venezia HO Venice Int Univ DE apoptosis; calpain; parkinsonism; METH; MPTP; motoneurons; rotenone; VSC4.1 cells ID SPINAL-CORD; ANIMAL-MODELS; DOPAMINERGIC NEUROTOXICITY; UP-REGULATION; DISEASE; MICE; EXPRESSION; DEATH; CALPASTATIN; ISCHEMIA AB Parkinson's disease (PD) is a movement disorder characterized by progressive degeneration of primarily the dopaminergic neurons in the substantia nigra (SN). The present study briefly describes our findings to support the hypothesis that there is a possibility of degeneration of spinal cord (SC) motoneurons in course of parkinsonism. In cell culture models of experimental parkinsonism, we examined the degeneration of ventral SC motoneuron cell line (VSC4.1) following exposure to two different toxins, such as 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and rotenone. Our studies suggested calpain activation in the apoptosis of VSC4.1 motoneurons due to exposure to these parkinsonian toxins. Furthermore, our study showed the toxic effects of the dopaminergic toxin methamphetamine (METH) on VSC4.1 cells. The results strongly implicated a possible role for calpain in the mechanism of motoneuron apoptosis during parkinsonian degeneration, at large. Hence, we examined the neuroprotective efficacy of calpeptin, a specific inhibitor of calpain, in cell culture model of experimental parkinsonism. C1 Med Univ S Carolina, Dept Neurosci, Div Neurol, Charleston, SC 29425 USA. Natl Ctr Toxicol Res, Neurochem Lab, Div Neurotoxicol, FDA, Jefferson, AR 72079 USA. RP Banik, NL (reprint author), Med Univ S Carolina, Dept Neurosci, Div Neurol, 96 Jonathan Lucas St, Charleston, SC 29425 USA. EM baniknl@musc.edu NR 31 TC 20 Z9 20 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 1-57331-629-6 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2006 VL 1074 BP 349 EP 356 DI 10.1196/annals.1369.034 PG 8 WC Cell Biology; Substance Abuse; Multidisciplinary Sciences; Clinical Neurology; Pharmacology & Pharmacy SC Cell Biology; Substance Abuse; Science & Technology - Other Topics; Neurosciences & Neurology; Pharmacology & Pharmacy GA BFJ04 UT WOS:000242168100034 PM 17105932 ER PT S AU Meyer, JS Brevard, ME Piper, BJ Ali, SF Ferris, CF AF Meyer, Jerrold S. Brevard, Matthew E. Piper, Brian J. Ali, Syed F. Ferris, Craig F. BE Ali, SF Fornai, F TI Neural effects of MDMA as determined by functional magnetic resonance imaging and magnetic resonance spectroscopy in awake marmoset monkeys SO CELLULAR AND MOLECULAR MECHANISMS OF DRUGS OF ABUSE AND NEUROTOXICITY: COCAINE, GHB, AND SUBSTITUTED AMPHETAMINES SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Satellite Meeting on Cellular and Molecular Mechanisms of Drugs of Abuse and Neurotoxicity - Cocaine, GHB and Substituted Amphetamines CY AUG 16-19, 2005 CL Venice Int Univ, Venice, ITALY SP Int Soc Neurochem, Neuromed Pozzilli, FDA, Natl Ctr Toxicol Res, Reg Veneto, Prov Venezia HO Venice Int Univ DE magnetic resonance imaging; magnetic resonance spectroscopy; BOLD; 3,4-methylenedioxymethamphetamine; visual cortex; serotonin; common marmoset ID CEREBRAL-BLOOD-FLOW; ECSTASY MDMA; WORKING-MEMORY; 3,4-METHYLENEDIOXYMETHAMPHETAMINE MDMA; SEROTONIN TRANSPORTER; RECREATIONAL USERS; N-ACETYLASPARTATE; BRAIN; RAT; ACTIVATION AB We used functional magnetic resonance imaging (fMRI) to investigate the acute effects of a recreational dose (1 mg/kg p.o.) of 3,4-methylenedioxymethamphetamine (MDMA) on regional brain activity in awake, restrained marmoset monkeys. In a second study, magnetic resonance spectroscopy (MRS) and postmortem measurements of serotonin transporter (SERT) binding and serotonin (5-HT) concentrations were used to determine the neurotoxic effects of low (4 x 1 mg/kg p.o.) and high (4 x 10 mg/kg i.m.) doses of MDMA. Several brain areas were significantly activated by the low oral dose of MDMA, including the midbrain raphe nuclei, hippocampus, hypothalamus, amygdala, and the corticostriatal circuit composed of the dorsal thalamus, sensory motor cortex, and basal ganglia. MDMA activated the primary visual cortex under baseline conditions and also enhanced the visual cortical response to photic stimulation. The onset of brain activation correlated well with the rise in plasma MDMA concentrations measured in separate monkeys given the same drug treatment. In the second study, the ratio of N-acetylaspartate (NAA; a putative neuronal marker) to creatine was significantly reduced in the hypothalamus following either MDMA treatment regimen, suggesting a particular vulnerability of this structure to MDMA-induced damage. Monkeys given the high-dose regimen also showed prolonged hyperthermia and reductions in 5-HT and SERT in a number of brain areas. These results are the first to identify the pattern of MDMA-induced brain activation in a nonhuman primate model, and they further suggest that even recreational doses of MDMA may, have adverse consequences as indicated by the reduced hypothalamic NAA/creatine ratio. C1 Univ Massachusetts, Dept Psychol, Amherst, MA 01003 USA. Univ Massachusetts, Neurosci & Behav Program, Amherst, MA 01003 USA. Univ Massachusetts, Sch Med, Ctr Comparat Neuroimaging, Worcester, MA 01655 USA. US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Meyer, JS (reprint author), Univ Massachusetts, Dept Psychol, 135 Hicks Way, Amherst, MA 01003 USA. EM jmeyer@psych.umass.edu OI Meyer, Jerrold/0000-0002-8382-7075 FU NIDA NIH HHS [R01 DA0135517, R01 DA019158] NR 47 TC 18 Z9 21 U1 1 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 1-57331-629-6 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2006 VL 1074 BP 365 EP 376 DI 10.1196/annals.1369.036 PG 12 WC Cell Biology; Substance Abuse; Multidisciplinary Sciences; Clinical Neurology; Pharmacology & Pharmacy SC Cell Biology; Substance Abuse; Science & Technology - Other Topics; Neurosciences & Neurology; Pharmacology & Pharmacy GA BFJ04 UT WOS:000242168100036 PM 17105934 ER PT S AU Sharma, HS Lundstedt, T Boman, A Lek, P Seifert, E Wiklund, L Ali, SF AF Sharma, Hari S. Lundstedt, Torbjorn Boman, Arne Lek, Per Seifert, Elisabeth Wiklund, Lars Ali, Syed F. BE Ali, SF Fornai, F TI A potent serotonin-modulating compound AP-267 attenuates morphine withdrawal-induced blood-brain barrier dysfunction in rats SO CELLULAR AND MOLECULAR MECHANISMS OF DRUGS OF ABUSE AND NEUROTOXICITY: COCAINE, GHB, AND SUBSTITUTED AMPHETAMINES SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Satellite Meeting on Cellular and Molecular Mechanisms of Drugs of Abuse and Neurotoxicity - Cocaine, GHB and Substituted Amphetamines CY AUG 16-19, 2005 CL Venice Int Univ, Venice, ITALY SP Int Soc Neurochem, Neuromed Pozzilli, FDA, Natl Ctr Toxicol Res, Reg Veneto, Prov Venezia HO Venice Int Univ DE morphine; withdrawal symptoms; dependence; spontaneous withdrawal; AP-267; serotonin; 5-HT2c receptor; blood-brain barrier; Evans blue; radioiodine ID NORMOTENSIVE YOUNG-RATS; 5-HT3 RECEPTOR ANTAGONISTS; SPINAL-CORD; GUANYLATE-CYCLASE; ADENYLATE-CYCLASE; TRAUMATIC INJURY; CHOROID-PLEXUS; NITRIC-OXIDE; PERMEABILITY; FLOW AB The possibility that a serotonin 5-HT2c receptor-modulating compound, AP-267, will influence spontaneous morphine withdrawal symptoms and the alterations in the brain fluid microenvironment was examined in a rat model. Daily administration of morphine (10 mg/kg, i.p.) for 10 days resulted in dependence of rats as seen by loss of analgesic response. On the 11th day, no morphine administration was given. This resulted in profound withdrawal symptoms 24 h after morphine withdrawal. The magnitude and severity of these symptoms were increased further 48 h after withdrawal. Measurement of the blood-brain barrier (BBB) permeability, a measure of perturbed brain fluid microenvironment showed leakage of Evans blue and radioiodine tracers in several parts of the brain in rats showing withdrawal symptoms. Whereas, rats treated with AP-267 either on the 1st day or 2nd day morphine withdrawal showed much less symptoms and leakage of the BBB. Taken together, these observations suggest that (a) stress associated with the withdrawal symptoms are sufficient enough to induce breakdown of the BBB function, and (b) modulation of serotonin 5-HT2c receptors may have some protective influence on the stress symptoms and the BBB disruption. C1 Uppsala Univ, Univ Hosp, Dept Surg Sci Anaesthesiol & Intens Care Med, Lab Cerebrovasc Res, SE-75185 Uppsala, Sweden. US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Neurochem Lab, Jefferson, AR 72079 USA. Acure Pharma AB, SE-75643 Uppsala, Sweden. Uppsala Univ, Dept Organ & Pharmaceut Chem, SE-74123 Uppsala, Sweden. RP Sharma, HS (reprint author), Uppsala Univ, Univ Hosp, Dept Surg Sci Anaesthesiol & Intens Care Med, Lab Cerebrovasc Res, SE-75185 Uppsala, Sweden. EM Sharma@surgsci.uu.se RI Sharma, Hari/G-4508-2016 NR 61 TC 15 Z9 15 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 1-57331-629-6 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2006 VL 1074 BP 482 EP 496 DI 10.1196/annals.1369.049 PG 15 WC Cell Biology; Substance Abuse; Multidisciplinary Sciences; Clinical Neurology; Pharmacology & Pharmacy SC Cell Biology; Substance Abuse; Science & Technology - Other Topics; Neurosciences & Neurology; Pharmacology & Pharmacy GA BFJ04 UT WOS:000242168100049 PM 17105947 ER PT J AU Equils, O Naiki, Y Shapiro, AM Michelsen, K Lu, D Adams, J Jordan, S AF Equils, O Naiki, Y Shapiro, AM Michelsen, K Lu, D Adams, J Jordan, S TI 1,25-Dihydroxyvitamin D-3 inhibits lipopolysaccharide-induced immune activation in human endothelial cells SO CLINICAL AND EXPERIMENTAL IMMUNOLOGY LA English DT Article DE endothelial cells; IL-6; IL-8; lipopolysaccharide; MD-2; NF-kappa B; RANTES; TLR4; Toll-like receptor; vitamin D ID NF-KAPPA-B; TUMOR-NECROSIS-FACTOR; CD4(+) T-CELLS; VITAMIN-D; 1-ALPHA,25-DIHYDROXYVITAMIN D-3; ALPHA EXPRESSION; GENE-EXPRESSION; DENDRITIC CELLS; DOWN-REGULATION; RECEPTOR 4 AB In addition to its well-known role in mineral and skeletal homeostasis, 1,25-dihydroxyvitamin D-3[1,25-(OH)(2), D-3] regulates the differentiation, growth and function of a broad range of immune system cells, including monocytes, dendritic cells, T and B lymphocytes. Vascular endothelial cells play a major role in the innate immune activation during infections, sepsis and transplant rejection; however, currently there are no data on the effect of 1,25-(OH)(2) D-3 on microbial antigen-induced endothelial cell activation. Here we show that 1,25-(OH)(2) D-3 pretreatment of human microvessel endothelial cells (HMEC) inhibited the enteric Gram-negative bacterial lipopolysaccharide (LPS) activation of transcription factor NF-kappa B and interleukin (IL)-6, IL-8 and regulated upon activation normal T cell exposed and secreted (RANTES) release. The effect of 1,25-(OH)(2) D-3 was not due to increased cell death or inhibition of endothelial cell proliferation. 1,25-(OH)(2) D-3 pretreatment of HMEC did not block MyD88-independent LPS-induced interferon (IFN)-beta promoter activation. 1,25-(OH)(2) D-3 pretreatment of HMEC did not modulate Toll-like receptor 4 (TLR4) or MD-2 expression. These data suggest that 1,25-(OH)(2) D-3 may play a role in LPS-induced immune activation of endothelial cells during Gram-negative bacterial infections, and a suggest a potential role for 1,25-(OH)(2) D-3 and its analogues as an adjuvant in the treatment of Gram-negative sepsis. C1 Univ Calif Los Angeles, Geffen Sch Med,Cedars Sinai Med Ctr, Steven Spielberg Pediat Res Ctr, Burns & Allen Res Inst,Dept Pediat, Los Angeles, CA 90048 USA. Univ Calif Los Angeles, Geffen Sch Med,Cedars Sinai Med Ctr, Steven Spielberg Pediat Res Ctr, Burns & Allen Res Inst,Dept Internal Med, Los Angeles, CA 90048 USA. US FDA, Ctr Drug Evaluat & Res, Div Pediat Drug Dev, Off Counter Terrorism & Pediat Drug Dev, Rockville, MD 20857 USA. RP Equils, O (reprint author), Univ Calif Los Angeles, Geffen Sch Med,Cedars Sinai Med Ctr, Steven Spielberg Pediat Res Ctr, Burns & Allen Res Inst,Dept Pediat, 8700 Beverly Blvd,Room 4221, Los Angeles, CA 90048 USA. EM ozlem.equils@cshs.org RI Adams, John/I-3365-2013 OI Adams, John/0000-0001-9607-5020 FU NIAID NIH HHS [K08 AI051216, KO8 AI51216]; NICHD NIH HHS [K12 HD034610, P30HD34610] NR 55 TC 68 Z9 74 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0009-9104 J9 CLIN EXP IMMUNOL JI Clin. Exp. Immunol. PD JAN PY 2006 VL 143 IS 1 BP 58 EP 64 DI 10.1111/j.1365-2249.2005.02961.x PG 7 WC Immunology SC Immunology GA 988CO UT WOS:000233569200008 PM 16367934 ER PT J AU Mannon, P Fuss, I Groden, C Friend, J Yang, ZQ Yi, CL Dickensheets, H Hornung, R Donnelly, R Strober, W AF Mannon, Peter Fuss, Ivan Groden, Catherine Friend, Julia Yang, Zhiqiong Yi, Chuli Dickensheets, Harold Hornung, Ronald Donnelly, Raymond Strober, Warren TI Decreased IL-13 production by lamina propria mononuclear cells (LPMCS) accompanies ulcerative colitis (UC) remission and clinical response induced by interferon-beta treatment. SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 6th Annual Meeting of the Federation-of-Clinical-Immunology-Societies CY JUN 01-05, 2006 CL San Francisco, CA SP Federat Clin Immunol Soc C1 NIAID, NIH, Bethesda, MD USA. US FDA, CBER, Bethesda, MD USA. SAIC Frederick Inc, Frederick, MD USA. NR 0 TC 0 Z9 0 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. PY 2006 VL 119 SU S BP S33 EP S34 DI 10.1016/j.clim.2006.04.382 PG 2 WC Immunology SC Immunology GA 048CD UT WOS:000237924300078 ER PT J AU Zaidi, MB McDermott, PF Fedorka-Cray, P Leon, V Canche, C Hubert, SK Abbott, J Leon, M Zhao, SH Headrick, M Tollefson, L AF Zaidi, MB McDermott, PF Fedorka-Cray, P Leon, V Canche, C Hubert, SK Abbott, J Leon, M Zhao, SH Headrick, M Tollefson, L TI Nontyphoidal Salmonella from human clinical cases, asymptomatic children, and raw retail meats in Yucatan, Mexico SO CLINICAL INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 42nd Interscience Conference on Antimicrobial Agents and Chemotherapy CY SEP 26-30, 2002 CL SAN DIEGO, CA ID CHILDHOOD DIARRHEA; ANTIMICROBIAL RESISTANCE; CHICKEN; CAMPYLOBACTER; CONTAMINATION; PREVALENCE; SEROTYPE; SPP.; BEEF; ENTEROPATHOGENS AB Background. We report the results of a 3-year Salmonella surveillance study of persons with diarrhea; asymptomatic children; and retail pork, poultry, and beef in Yucatan, Mexico. Methods. Isolates were characterized according to serotype, antimicrobial susceptibility, and genetic relatedness with pulsed-field gel electrophoresis. Results. Salmonella Typhimurium was the most common serotype found in ill humans ( 21.8% of isolates), followed by Salmonella Agona (21% of isolates). Salmonella Enteritidis was a minor serotype (4.2% of isolates). Asymptomatic children carried S. Agona ( 12.1% of isolates), Salmonella Meleagridis (11.6% of isolates), Salmonella Anatum (8% of isolates) and S. Enteritidis (5.8% of isolates). A high percentage of retail meat samples contained Salmonella; it was most commonly found in pork (58.1% of samples), followed by beef (54% of samples) and poultry (39.7% of samples). Resistance to oral drugs used for the treatment of salmonellosis was observed for ampicillin (14.6% of isolates were resistant), chloramphenicol (14.0% of isolates), and trimethoprim-sulfamethoxazole (19.7% of isolates). Resistance to ceftriaxone emerged in 2002 and was limited to the serotype S. Typhimurium. Twenty-seven percent of the isolates were resistant to nalidixic acid, and none were resistant to ciprofloxacin. Multidrug resistance was most common among isolates of serotypes S. Typhimurium and S. Anatum. Pulsed-field gel electrophoresis showed that strains found in retail meats were genetically identical to strains found in both asymptomatic children and ill patients. Conclusions. Our study found a high prevalence of Salmonella in retail meats and persons with enteric infection; many of these isolates were resistant to clinically important antimicrobials. A random selection of isolates from people and retail meat showed genetic relatedness, which suggests that, in Yucatan, considerable transfer of Salmonella occurs through the food chain. C1 Hosp Gen OHoran, Dept Invest, Lab Invest, Merida, Yucatan, Mexico. US FDA, Ctr Vet Med, Rockville, MD 20857 USA. USDA, Russell Res Ctr, Antimicrobial Resistance Res Unit, Athens, GA USA. RP Zaidi, MB (reprint author), Hosp Gen OHoran, Dept Invest, Lab Invest, Av Itzaes X Jacinto Canek, Merida, Yucatan, Mexico. EM mbzaidi@yuc.quik.com FU FDA HHS [FD-U- 001934-03-2] NR 42 TC 45 Z9 50 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 JAN 1 PY 2006 VL 42 IS 1 BP 21 EP 28 DI 10.1086/498508 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 989UH UT WOS:000233698900010 PM 16323087 ER PT J AU Chen, ML AF Chen, Mei-Ling TI Ethnic or racial differences revisited - Impact of dosage regimen and dosage form on pharmacokinetics and pharmacodynamics SO CLINICAL PHARMACOKINETICS LA English DT Article ID MULTIDRUG-RESISTANCE GENE; DRUG-METABOLIZING-ENZYMES; SLOW-RELEASE TABLET; P-GLYCOPROTEIN; OXIDATION POLYMORPHISM; ORAL NIFEDIPINE; PHARMACOLOGICAL RESPONSE; TRANSPLANT RECIPIENTS; MDR1 GENE; IN-VIVO AB Ethnic or racial differences in pharmacokinetics and pharmacodynamics have been attributed to the distinctions in the genetic, physiological and pathological factors between ethnic/racial groups. These pharmacokinetic/pharmacodynamic differences are also known to be influenced by several extrinsic factors such as socioeconomic background, culture, diet and environment. However, it is noted that other factors related to dosage regimen and dosage form have largely been ignored or overlooked when conducting or analysing pharmacokinetic/pharmacodynamic studies in relation to ethnicity/race. Potential interactions can arise between the characteristics of ethnicity/race and a unique feature of dosage regimen or dosage form used in the study, which may partly account for the observed pharmacokinetic/pharmacodynamic differences between ethnic/racial groups. Ethnic/racial differences in pharmacokinetics/pharmacodynamics can occur from drug administration through a specific route that imparts distinct pattern of absorption, distribution, transport, metabolism or excretion. For example, racial differences in the first-pass metabolism of a drug following oral administration may not be relevant when the drug is applied to the skin. On the other hand, ethnic/racial difference in pharmacokineties/pharmacodynamics can also happen via two different routes of drug delivery, with varying levels of dissimilarity between routes. For example, greater ethnic/racial differences were observed in oral clearance than in systemic clearance of some drugs, which might be explained by the pre-systemic factors involved in the oral administration as opposed to the intravenous administration. Similarly, changes in the dose frequency and/or duration may have profound impact on the ethnic/racial differences in pharmacokinetic/pharmacodynamic outcome. Saturation of enzymes, transporters or receptors at high drug concentrations is a possible reason for many observed ethnic/racial discrepancies between single- and multiple-dose regimens, or between low- and high-dose administrations. The presence of genetic polymorphism of enzymes and/or transporters can further complicate the analysis of pharmacokinetic/pharmacodynamic data in ethnic/racial populations. Even within the same dosage regimen, the use of different dosage forms may trigger significantly different pharmacokinetic/pharmacodynamic responses in various ethnic/racial groups, given that different dosage forms may exhibit different rates of drug release, may release the drug at different sites, and/or have different retention times at specific sites of the body. It is thus cautioned that the pharmacokinetic/pharmacodynamic data obtained from different ethnic/racial groups cannot be indiscriminately compared or combined for analysis if there is a lack of homogeneity in the apparent 'extrinsic' factors, including dosage regimen and dosage form. C1 US FDA, Ctr Drug Evaluat & Res, Off Pharmaceut Sci, Rockville, MD 20857 USA. RP Chen, ML (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Pharmaceut Sci, Rockville, MD 20857 USA. EM meiling.dien@fda.hhs.gov NR 75 TC 57 Z9 57 U1 0 U2 5 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 0312-5963 J9 CLIN PHARMACOKINET JI Clin. Pharmacokinet. PY 2006 VL 45 IS 10 BP 957 EP 964 DI 10.2165/00003088-200645100-00001 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 092OB UT WOS:000241105900001 PM 16984210 ER PT J AU Persiani, S D'Amato, M Jakate, A Roy, P Wangsa, J Kapil, R Rovati, LC AF Persiani, Stefano D'Amato, Massimo Jakate, Abhijeet Roy, Partha Wangsa, Julie Kapil, Ram Rovati, Lucio C. TI Pharmacokinetic profile of dexloxiglumide SO CLINICAL PHARMACOKINETICS LA English DT Review ID CHOLECYSTOKININ-1 ANTAGONIST DEXLOXIGLUMIDE; CCK1 RECEPTOR ANTAGONIST; METABOLISM; ABSORPTION; EXCRETION; SINGLE AB Dexloxiglumide is a potent and selective cholecystokinin type I (CCK1) receptor antagonist currently under development in a variety of diseases affecting the gastrointestinal tract such as gastro-oesophageal reflux disease, irritable bowel syndrome (IBS), functional dyspepsia, constipation and gastric emptying disorders. In female patients with constipation-predominant IBS, clinical efficacy has been demonstrated following administration of dexioxiglumide 200mg three times daily. Dexloxiglumide is rapidly and extensively absorbed after single oral administration in humans with an absolute bioavailability of 48%. The incomplete bioavailability is due to both incomplete absorption and hepatic first-pass effect. Following multiple-dose administration of 200mg three times daily, the accumulation is predictable, indicating time-independent pharmacokinetics. In addition, dexloxiglumide pharmacokinetics are dose-independent after both single and repeated oral three-times-daily doses in the dose range 100-400mg. Dexloxiglumide absorption window extends from the jejunum to the colon and the drug is a substrate and a weak inhibitor of P-glycoprotein and multidrug resistance protein 1. Plasma protein binding of dexloxiglumide is 94-98% and the drug has a moderate to low volume of distribution in humans. Systemic clearance of dexloxiglumide is moderate and cytochrome P450 (CYP) 3A4/5 and CYP2C9 have been implicated in the metabolism of dexloxiglumide to produce O-demethyl dexloxiglumide. This metabolite is further oxidised to dexloxiglumide carboxylic acid. These two major metabolites (accounting for up to 50% of dexioxigiumide elimination) have been identified. However, in human plasma the unchanged drug represents the major (up to 91%) component of the metabolic profile. The parent drug is believed to be the major contributor to the efficacy of the compound, since its major metabolites are pharmacologically inactive. In addition, the drug is a single isomer chiral drug (eutomer) that does not undergo chiral inversion into its pharmacologically inactive enantiomer (distomer). After oral administration of C-14-dexloxiglumide, radioactivity is mainly excreted in bile and in faeces (74% of dose) with much lower excretion in urine (20% of dose). Renal excretion of unchanged dexioxiglumide is low (7% of dose in urine and faeces, I % of dose in urine) and is dose-independent in the dose range 100-400mg. As the kidney is a minor contributor to the elimination of dexloxiglumide and/or its metabolites in humans, the pharmacokinetics of the drug should not be affected in patients with renal insufficiency. The pharmacokinetics of dexloxiglumide are also not affected by age, sex and administration with a high-fat breakfast. Mild and moderate liver impairment do not affect the pharmacokinetics of dextoxiglumide but severe liver impairment causes increases in systemic exposure to dexloxiglumide and O-demethyl dexloxiglumide. Thus, the drug should be prescribed with caution in patients with severe hepatic impairment even though no dose adjustment is warranted. The results of different drug interaction studies have indicated that no clinically relevant metabolic and concomitant drug-drug interactions are expected during the clinical use of dexloxiglumide. C1 Rottapharm SpA, Dept Drug Metab Pharmacokinet & Dynam, Rotta Res Lab, I-20052 Monza, Mi, Italy. Rottapharm SpA, Dept Clin Pharmacol, Rotta Res Lab, I-20052 Monza, Mi, Italy. Forester Res Inst Inc, Dept Clin Pharmacol & Drug Dynam, Jersey City, NJ USA. US FDA, Off Clin Pharmacol, Rockville, MD 20857 USA. Forest Res Inst Inc, Dept Bioanalyt & Drug Metab, Farmingdale, NJ USA. RP Persiani, S (reprint author), Rottapharm SpA, Dept Drug Metab Pharmacokinet & Dynam, Rotta Res Lab, Via Valosa Sopra 9, I-20052 Monza, Mi, Italy. EM stefano.persiani@rotta.com NR 19 TC 4 Z9 5 U1 1 U2 4 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 0312-5963 J9 CLIN PHARMACOKINET JI Clin. Pharmacokinet. PY 2006 VL 45 IS 12 BP 1177 EP 1188 DI 10.2165/00003088-200645120-00003 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 116ZN UT WOS:000242842400002 PM 17112294 ER PT J AU Newman, T AF Newman, T TI Do antidepressants cause suicidality in children? A Bayesian meta-analysis - Comment SO CLINICAL TRIALS LA English DT Editorial Material C1 Univ Calif San Francisco, Div Clin Epidemiol, San Francisco, CA 94143 USA. US FDA, Pediat Advisory Comm, Rockville, MD 20857 USA. Phys Social Responsibil, Board Directors, Washington, DC USA. RP Newman, T (reprint author), Univ Calif San Francisco, Div Clin Epidemiol, San Francisco, CA 94143 USA. NR 7 TC 0 Z9 0 U1 0 U2 0 PU HODDER ARNOLD, HODDER HEADLINE PLC PI LONDON PA 338 EUSTON ROAD, LONDON NW1 3BH, ENGLAND SN 1740-7745 J9 CLIN TRIALS JI Clin. Trials PY 2006 VL 3 IS 2 BP 91 EP 92 PG 2 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 051CL UT WOS:000238138000002 ER PT J AU Temple, R Hammad, T Laughren, T Stone, M AF Temple, R Hammad, T Laughren, T Stone, M TI Do antidepressants cause suicidality in children? A Bayesian meta-analysis - Comment SO CLINICAL TRIALS LA English DT Editorial Material C1 US FDA, Off Med Policy, Rockville, MD 20857 USA. US FDA, Off Drug Safety, Rockville, MD 20857 USA. US FDA, Div Psychiat Prod, Rockville, MD 20857 USA. US FDA, Div Neurol Prod, Rockville, MD 20857 USA. RP Temple, R (reprint author), US FDA, Off Med Policy, Rockville, MD 20857 USA. NR 1 TC 0 Z9 0 U1 0 U2 1 PU HODDER ARNOLD, HODDER HEADLINE PLC PI LONDON PA 338 EUSTON ROAD, LONDON NW1 3BH, ENGLAND SN 1740-7745 J9 CLIN TRIALS JI Clin. Trials PY 2006 VL 3 IS 2 BP 94 EP 96 PG 3 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 051CL UT WOS:000238138000005 ER PT J AU Mayer, M AF Mayer, Musa TI Listen to all the voices: an advocate's perspective on early access to investigational therapies SO CLINICAL TRIALS LA English DT Article ID HIGH-DOSE CHEMOTHERAPY; METASTATIC BREAST-CANCER; STEM-CELL RESCUE; CONSOLIDATION THERAPY; MARROW SUPPORT; TRANSPLANTATION AB In this issue of the journal, The Society for Clinical Trials, whose members are clinical investigators and regulators in academia, government and industry, has published the rationale for their opposition to US Senate bill S. 1956, the so-called "ACCESS" act, which would allow the marketing of therapies that have undergone only Phase I studies (dose finding and toxicity testing) in humans, to patients with "serious and life-threatening' disease who have exhausted other treatment options. While this bill reflects the views and efforts or some cancer advocates and their supporters, it does not represent the beliefs of the cancer advocacy community overall. The essay that follows is inspired by the need for other voices from the patient and advocacy communities to be heard in this debate. C1 US FDA, Rockville, MD 20857 USA. RP Mayer, M (reprint author), US FDA, Rockville, MD 20857 USA. NR 22 TC 8 Z9 8 U1 0 U2 1 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1740-7745 EI 1740-7753 J9 CLIN TRIALS JI Clin. Trials PY 2006 VL 3 IS 2 BP 149 EP 153 DI 10.1191/1740774506cn144oa PG 5 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 051CL UT WOS:000238138000012 PM 16773957 ER PT J AU Yang, C Benz, RD Cheeseman, MA AF Yang, C Benz, RD Cheeseman, MA TI Landscape of current toxicity databases and database standards SO CURRENT OPINION IN DRUG DISCOVERY & DEVELOPMENT LA English DT Review DE controlled vocabulary; data exchange; data integration; data model; database standard; toxicity database; QSAR; ToxML ID WEB RESOURCES; SYSTEMS; VOCABULARIES; INTEGRATION; TOXICOLOGY AB Having readily available historical information for modeling toxicity has become important throughout the various stages of research and development. The high cost of late-phase attrition and recent international regulatory legislations have made even more acute the need to be able to mine the fragmented data and information available across diverse databases. In addition, the general trend to accelerate regulatory processes globally makes the effective use of existing data an imperative. To achieve efficient screening, develop profiles and gain the ability to cross reference, databases must be interoperated to allow data exchange and integration. Several database standards and controlled vocabulary initiatives have been used in the development of toxicity data models to transform the current landscape. This review describes the major databases of toxicological information now available, and provides a simple example of standardization that demonstrates the benefits of a toxicity database containing such qualified data. C1 Leadscope Inc, Columbus, OH 43235 USA. US FDA, CFSAN, OFAS, DFCN, Silver Spring, MD 20740 USA. RP Yang, C (reprint author), Leadscope Inc, 1393 Dublin Rd, Columbus, OH 43235 USA. EM cyang@leadscope.com NR 40 TC 37 Z9 37 U1 0 U2 2 PU THOMSON SCIENTIFIC PI LONDON PA 34-42 CLEVELAND STREET, LONDON, W1T 4JE, ENGLAND SN 1367-6733 J9 CURR OPIN DRUG DISC JI Curr. Opin. Drug Discov. Dev. PD JAN PY 2006 VL 9 IS 1 BP 124 EP 133 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 003CT UT WOS:000234659900012 PM 16445125 ER PT J AU Markovic, I AF Markovic, I TI Advances in HIV-1 entry inhibitors: Strategies to interfere with receptor and coreceptor engagement SO CURRENT PHARMACEUTICAL DESIGN LA English DT Review DE viral entry; membrane fusion; CD4; CCR5; CXCR4; coreceptor switch; viral resistance; antiviral therapy ID HUMAN-IMMUNODEFICIENCY-VIRUS; GP120 ENVELOPE GLYCOPROTEIN; PROTEIN-DISULFIDE-ISOMERASE; SELECTIVE ANTI-HIV-1 ACTIVITY; SYNCYTIUM-INDUCING PHENOTYPE; AIDS-RELATED-COMPLEX; T-CELL LINES; CHEMOKINE RECEPTOR; SMALL-MOLECULE; CD4 RECEPTOR AB The present armamentarium of 19 antiretroviral drugs licensed for treatment of HIV-1 infection in the U.S. exemplifics preponderance of scientific evidence, which led to improved understanding of the structural and functional, viral and cellular attributes driving HIV-1 infection. The majority of approved drugs (with exception of enfuvirtide), however, focus on two steps of the viral life cycle: reverse transcription and viral maturation. Therefore, it appears there is ample opportunity for the development of a third drug class that has been extensively researched in recent years known as entry inhibitors. Currently, this class of compounds targets steps involved in virion attachment to CD4 or to an appropriate chemokine receptor on the cell surface as well as subsequent conformational rearrangements induced in the envelope glycoprotein (gp120/gp41; Env). These inhibitors preclude the fusion of the virion envelope with the host cell membrane thereby preventing the release of viral capsid into the cytosol. Antiviral agents interfering with receptor (i.e., CD4) or coreceptor (e.g., CCR5 and/or CXCR4) engagement comprise a special subset of viral entry inhibitors. While drugs targeting viral entry offer certain advantages over other classes of compounds, they also pose specific challenges. This review focuses on compounds blocking viral attachment to CD4, CCR5 or CXCR4, highlights the challenges they present, and attempts to offer possible solutions. C1 US FDA, Ctr Drug Evaluat & Res, Off Biotechnol Prod, Div Therapeut Prot, Bethesda, MD 20892 USA. RP Markovic, I (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Biotechnol Prod, Div Therapeut Prot, Bldg 29A,Room 2D16,29 Lincoln Dr,HFD-122, Bethesda, MD 20892 USA. EM markovic@cber.fda.gov NR 156 TC 19 Z9 19 U1 2 U2 6 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1381-6128 J9 CURR PHARM DESIGN JI Curr. Pharm. Design PY 2006 VL 12 IS 9 BP 1105 EP 1119 DI 10.2174/138161206776055822 PG 15 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 018IT UT WOS:000235758400008 PM 16515489 ER PT J AU Collins, TFX AF Collins, TFX TI History and evolution of reproductive and developmental toxicology guidelines SO CURRENT PHARMACEUTICAL DESIGN LA English DT Review DE guidelines; reproduction; teratology ID TESTING GUIDELINES; FOOD-ADDITIVES; PERSPECTIVES; TERATOLOGY; PREGNANCY; SEMEN; BORN AB Birth defects and other adverse outcomes of pregnancy have been known since before the industrial age, but the need for guidelines to test chemicals to which pregnant women might be exposed was defined by the thalidomide tragedy in the 1950s and early 1960s. During the five decades that followed the tragedy, guidelines were written to test drugs, foods, and environmental contaminants. The guidelines were written to fulfill national needs, and then were expanded to international levels in order to streamline procedures in the expanding global economy. Multiple sets of animal guidelines were written, based on the need to simulate human experience. It was soon realized that the underlying principles were similar for all guidelines. Guidelines gradually evolved in two directions, in complexity and number of endpoints measured and in the expansion of internationally acceptable guidelines. This manuscript reviews, in chronological order, sonic of the milestones in the development of guidelines for animal studies and in the interpretations for safety assessment. Guidelines for long-term and short-term studies are reviewed, followed by a discussion of recently added endpoints and the future integration process for the assessment of reproductive toxicity risk. C1 US FDA, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. RP Collins, TFX (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 8301 Muirkirk Rd, Laurel, MD 20708 USA. EM tcollins@cfsan.fda.gov NR 51 TC 15 Z9 15 U1 4 U2 8 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1381-6128 J9 CURR PHARM DESIGN JI Curr. Pharm. Design PY 2006 VL 12 IS 12 BP 1449 EP 1465 DI 10.2174/138161206776389813 PG 17 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 042QZ UT WOS:000237545200003 PM 16611128 ER PT J AU Babu, US Gaines, DW Lillehoj, H Raybourne, RB AF Babu, Uma S. Gaines, Dennis W. Lillehoj, Hyun Raybourne, Richard B. TI Differential reactive oxygen and nitrogen production and clearance of Salmonella serovars by chicken and mouse macrophages SO DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY LA English DT Article DE Salmonella; chicken macrophages; mouse macrophages; J774A.1; HD11; nitric oxide; superoxide; flow cytometry ID ENTERITIDIS PHAGE TYPE-4; GAMMA-INTERFERON; OXIDATIVE BURST; UNITED-STATES; IFN-GAMMA; MURINE MACROPHAGES; IMMUNE-RESPONSES; MESSENGER-RNA; NADPH OXIDASE; CELL-LINES AB The objective of the present study was to compare the uptake and killing of Salmonella serovars by murine and avian macrophage cell lines. We used Salmonella enterica serovars Enteritidis (SE338) and Typhimurium (SR11) for this study. Uptake of green fluorescent protein-labeled bacteria was measured using flow cytometry. Cell sorting and plating of viable infected macrophages demonstrated that bacterial clearance was significantly better with J774A.1 compared with HD11 cells. HD11 cells produced significantly higher amounts of nitric oxide (NO) than J774A.1 cells upon infection with SE338 and SR11, whereas J774A.1 cells exhibited greater superoxide production with SR11. Treatment of HD11 cells with recombinant chicken interferon gamma in the absence of bacteria enhanced NO production but did not induce increased levels synergistically with bacteria. Interferon treatment did not influence phagocytosis or increase killing by HD11 cells. Published by Elsevier Ltd. C1 US FDA, Immunobiol Branch, Laurel, MD 20708 USA. USDA, Anim & Parasit Dis Lab, Beltsville, MD 20705 USA. RP Raybourne, RB (reprint author), US FDA, Immunobiol Branch, MOD 1,8301 Muirkirk Rd, Laurel, MD 20708 USA. EM rraybour@cfsan.fda.gov NR 51 TC 23 Z9 24 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0145-305X J9 DEV COMP IMMUNOL JI Dev. Comp. Immunol. PY 2006 VL 30 IS 10 BP 942 EP 953 DI 10.1016/j.dci.2005.12.001 PG 12 WC Immunology; Zoology SC Immunology; Zoology GA 079KD UT WOS:000240173900008 PM 16427126 ER PT S AU Petrick, N Myers, KJ Paquerault, S Samuelson, FW Gallas, BD Wagner, RF AF Petrick, Nicholas Myers, Kyle J. Paquerault, Sophie Samuelson, Frank W. Gallas, Brandon D. Wagner, Robert F. BE Astley, SM Brady, M Rose, C Zwiggelaar, R TI Leveraging the Digital Mammography Image Screening Trial (DMIST) data for the evaluation of computer-aided detection (CAD) devices: A proposal SO DIGITAL MAMOGRAPHY, PROCEEDINGS SE LECTURE NOTES IN COMPUTER SCIENCE LA English DT Article; Proceedings Paper CT 8th International Workshop on Digital Mammography CY JUN 18-21, 2006 CL Manchester, ENGLAND AB The availability of the large dataset of screen/film and full-field digital mammograms acquired through the Digital Mammography Imaging Screening Trial (DMIST) presents an extraordinary opportunity for the assessment of CAD devices. The National Cancer Institute and the National Institute of Biomedical Imaging and Bioengineering at the U.S. National Institutes of Health have engaged FDA scientists in the development of a plan to leverage this imaging resource to benchmark the performance of current CAD systems. In this talk, we will present an initial proposal for utilizing the DMIST data to quantitatively assess current CAD systems. It is our goal to engage the IWDM community and other interested groups in the development of a consensus on acceptable study designs for this purpose. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20852 USA. RP Petrick, N (reprint author), US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20852 USA. EM nicholas.petrick@fda.hhs.gov; kyle.myers@fda.hhs.gov; sophie.paquerault@fda.hhs.gov; frank.samuelson@fda.hhs.gov; brandon.gallas@fda.hhs.gov; robert.wagner@fda.hhs.gov NR 6 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 3-540-35625-8 J9 LECT NOTES COMPUT SC PY 2006 VL 4046 BP 565 EP 568 PG 4 WC Computer Science, Interdisciplinary Applications; Computer Science, Theory & Methods; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Radiology, Nuclear Medicine & Medical Imaging GA BET70 UT WOS:000239454900076 ER PT J AU Hundley, SG Sarrif, AM Kennedy, GL AF Hundley, SG Sarrif, AM Kennedy, GL TI Absorption, distribution, and excretion of ammonium perfluorooctanoate (APFO) after oral administration to various species SO DRUG AND CHEMICAL TOXICOLOGY LA English DT Article DE rabbit distribution; mouse distribution; hamster distribution; rat distribution; ammonium perfluorooctanoate (APFO) ID CARBON-CHAIN LENGTH; PERFLUORINATED FATTY-ACIDS; PERFLUOROCARBOXYLIC ACIDS; CYNOMOLGUS MONKEYS; FEMALE RATS; ELIMINATION; TOXICITY AB Male and female mice, rats, hamsters, and rabbits were treated with a single oral dose of C-14-ammonium perfluorooctanoate (APFO), and the excretion and tissue distributions were followed for 120 h (168 h in the rabbit). Substantial sex and species differences in the excretion and disposition of C-14-radioactivity derived from C-14-labeled APFO were observed in this study. The female rat and the male hamster excreted more than 99% of the original C-14 activity by 120 h after dosing; conversely, the male rat and the female hamster excreted only 39% and 60% of the original C-14 activity, respectively, by 120 h postdosing. The male and female rabbits excreted the C-14 activity as rapidly and completely as the female rat and the male hamster, whereas male and female mice excreted only 21% of the original C-14 activity by 120 h postdosing. The rapid excretors (female rat, male hamster, and male and female rabbits) contained negligible amounts of C-14 in organs and tissues at sacrifice. The slow excretors exhibited the highest C-14 concentrations in the blood and liver followed by the kidneys, lungs, and skin. C1 DuPont Co Inc, Haskell Lab Toxicol & Ind Med, Newark, DE 19714 USA. US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Kennedy, GL (reprint author), DuPont Co Inc, Haskell Lab Toxicol & Ind Med, Newark, DE 19714 USA. EM gerald.l.kennedy@usa.dupont.com NR 23 TC 82 Z9 86 U1 2 U2 10 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0148-0545 J9 DRUG CHEM TOXICOL JI Drug Chem. Toxicol. PY 2006 VL 29 IS 2 BP 137 EP 145 DI 10.1080/01480540600561361 PG 9 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy; Toxicology SC Chemistry; Pharmacology & Pharmacy; Toxicology GA 034DU UT WOS:000236908300001 PM 16707323 ER PT J AU Jefferys, D Atkins, D Bufton, A Gutman, S AF Jefferys, D Atkins, D Bufton, A Gutman, S TI Pharmacogenomic testing and regulation: The role of pharmacogenomics in pharmaceutical development and the regulation of pharmacogenetic test as in vitro diagnostics SO DRUG INFORMATION JOURNAL LA English DT Article; Proceedings Paper CT DIA Euro Meeting CY MAR 10-12, 2004 CL Prague, CZECH REPUBLIC SP DIA DE pharmacogenomics; in vitro diagnostics; combination products; pharmacogenetics; conformity assessment; traceability AB This article reviews the current role and future trends of pharmacogenomic testing in pharmaceutical development and postmarketing surd veillance. The regulatory controls operating in Europe and the United States are described and compared. It is suggested that codevelopment of the diagnostic test should be considered as an integral part of the drug development program. The regulatory controls of the pharmacogenetic test and the drug need to be better aligned. Integration of patient and professional information is required. International standards are required for "traceability." C1 Eisai Europe Ltd, London W6 8EE, England. Veridex LLC, Warren, NJ USA. US FDA, Off Vitro Diagnost, Ctr Dis & Radiol Hlth, Rockville, MD 20857 USA. RP Jefferys, D (reprint author), Eisai Europe Ltd, 3 Shortlands, London W6 8EE, England. EM David_Jeffreys@eisai.net NR 13 TC 0 Z9 0 U1 0 U2 0 PU DRUG INFORMATION ASSOCIATION PI HORSHAM PA 800 ENTERPRISE ROAD, SUITE 200, HORSHAM, PA 19044-3595 USA SN 0092-8615 J9 DRUG INF J JI Drug Inf. J. PY 2006 VL 40 IS 1 BP 7 EP 13 PG 7 WC Health Care Sciences & Services; Pharmacology & Pharmacy SC Health Care Sciences & Services; Pharmacology & Pharmacy GA 014QW UT WOS:000235496000002 ER PT J AU McCune, SK Mathis, LL Cochetto, DM Bull, K Rodriguez, W AF McCune, SK Mathis, LL Cochetto, DM Bull, K Rodriguez, W TI Safer, better, more appropriate: Clinical trial design for pediatric drug labels SO DRUG INFORMATION JOURNAL LA English DT Article; Proceedings Paper CT 41st DIA Annual Meeting 2005 CY JUN 26-30, 2005 CL Washington, DC SP DIA DE pediatric drug development; global partnership in drug development; clinical trial design; pediatric regulatory issues; off-label use of drugs ID PLACEBO-CONTROLLED TRIALS; ACTIVE-CONTROL TRIALS; DOUBLE-BLIND; CHILDREN; ENRICHMENT; EFFICACY; ISSUES AB Off-label use of drugs in pediatrics remains a national and international problem. The Ameri can Academy of Pediatrics determined in 1977, and reaffirmed in 1995, that there was a moral imperative to,formally study. drugs in children so they have access to-important medications and receive optimal drug therapy." Congress passed legislation in 1997 that encouraged the study of patent drugs' or those with remaining exclusivity or patent protection, in pediatric patients. Manufacturers of new chemcal entities could earn an incentive (in the form of pediatric exclusivity) for their product if a program of pediatric clinical research that met the requirements of a Written Request from the Drug Administration was completed as scheduled. Such pediatric research must be expected to yield medically valuable information for pediatric patients. Additional legislation, the Best Pharmaceutical for Children Act, which renewed the exclusivity incentive for the "on-patent" drugs and provides a mechanism to facilitate the study of "off-patent drugs", and the Pediatric Research Equity Act address ways to encourage obtaining safety and efficacy data in pediatric patients. Pediatric drug trials require a concerted effort from academia, industry and patient advocacy groups to obtain safety, efficacy, and pharmacokinetic data in placebo-controlled or active-controlled multicenter trials. Because of the unique nature of pediatric patients, data for pediatric drug labeling may need to be derived from creative clinical trial designs and population pharmacokinetic studies, randomized with drawal trials, enrichment studies, as well as the utilization of extrapolation of clinical efficacy when appropriate. These novel approaches to clinical trial design as well as a discussion of more classical clinical trials are discussed in relation to pediatric clinical studies. C1 US FDA, Ctr Drug Evaluat & Res, OCTAP, Silver Spring, MD 20993 USA. US FDA, Ctr Drug Evaluat & Res, Div Pediat Drug Dev, Silver Spring, MD 20993 USA. GlaxoSmithKline Inc, US Regulatory Affairs, Res Triangle Pk, NC USA. Sturge Weber Fdn, Freedom, NJ USA. RP Rodriguez, W (reprint author), US FDA, Ctr Drug Evaluat & Res, OCTAP, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM rodriguezw@cder.fda.gov NR 24 TC 2 Z9 2 U1 0 U2 0 PU DRUG INFORMATION ASSOCIATION PI HORSHAM PA 800 ENTERPRISE ROAD, SUITE 200, HORSHAM, PA 19044-3595 USA SN 0092-8615 J9 DRUG INF J JI Drug Inf. J. PY 2006 VL 40 IS 2 BP 185 EP 195 PG 11 WC Health Care Sciences & Services; Pharmacology & Pharmacy SC Health Care Sciences & Services; Pharmacology & Pharmacy GA 050TU UT WOS:000238112300007 ER PT J AU Ekins, S Fisher, MB Jolivette, L Mahmood, I Testa, B Tucker, GT Benet, LZ Obach, RS AF Ekins, Sean Fisher, Michael B. Jolivette, Larry Mahmood, Iftekhar Testa, Bernard Tucker, Geoffrey T. Benet, Leslie Z. Obach, R. Scott TI Debate: In vivo versus in vitro versus in silico: What is the best way to predict the human pharmacokinetics for new compounds? SO DRUG METABOLISM REVIEWS LA English DT Meeting Abstract CT 14th North American Meeting of the International-Society-for-the-Study-of-Xenobiotics CY OCT 22-26, 2006 CL Rio Grande, PR SP Int Soc Study Xenobiot C1 US FDA, Rockville, MD 20857 USA. Univ Lausanne Hosp, Lausanne, Switzerland. Univ Sheffield, Sheffield, S Yorkshire, England. Univ Calif San Francisco, San Francisco, CA 94143 USA. RI Benet, Leslie/K-8286-2016 NR 0 TC 0 Z9 0 U1 0 U2 1 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. PY 2006 VL 38 SU 2 MA 45 BP 25 EP 26 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 098FO UT WOS:000241506600040 ER PT J AU Goodsaid, F AF Goodsaid, Federico TI Case histories and issues in clinical use of novel safety biomarkers SO DRUG METABOLISM REVIEWS LA English DT Meeting Abstract CT 9th European Meeting of the International-Society-for-the-Study-of-Xenobiotics (ISSX) CY JUN 04-07, 2006 CL Manchester, ENGLAND SP Int Soc Study Xenobiot C1 US FDA, CDER, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0360-2532 J9 DRUG METAB REV JI Drug Metab. Rev. PY 2006 VL 38 SU 1 MA 34 BP 30 EP 30 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 072FL UT WOS:000239659200046 ER PT J AU Uhl, K Cox, E Rogan, R Zeldis, JB Hixon, D Furlong, LA Singer, S Holliman, T Beyer, J Woolever, W AF Uhl, K Cox, E Rogan, R Zeldis, JB Hixon, D Furlong, LA Singer, S Holliman, T Beyer, J Woolever, W TI Thalidomide use in the US - Experience with pregnancy testing in the STEPS (R) programme SO DRUG SAFETY LA English DT Article ID DISEASE AB Introduction: In 1998, thalidomide (Thalomid(R)), a known human teratogen, was approved by the US FDA for the treatment of erythema nodosum leprosum. To prevent fetal exposure to thalidomide, a restricted distribution risk management programme, the System for Thalidomide Education and Prescribing Safety (S.T.E.P.S.(R)), was implemented. All clinicians, pharmacists and patients who prescribe, dispense and receive thalidomide, respectively, are required to enrol in S.T.E.P.S.(R). Sexually active females of childbearing potential must use two methods of birth control before, during and after treatment. These patients must also have a negative pregnancy test within 24 hours before beginning therapy and periodically while on therapy. The objective of this report is to summarise the patterns of thalidomide use and to describe the occurrence of positive pregnancy tests in females of childbearing potential while they were using thalidomide in the S.T.E.P.S.(R) programme in the US. Study design/methods: A retrospective review of patients receiving thalidomide within the S.T.E.P.S.(R) programme from September 1998 to 31 December 2004 to determine the occurrence of positive pregnancy tests whilst on treatment. Results: Approximately 124 000 (43% female) patients were registered within the S.T.E.P.S.(R) programme between September 1998 and 31 December 2004. Approximately 6000 patients were females of childbearing potential, representing 5% of all patients and 11% of all female patients. Between 30 July 2001 and 31 December 2004, >88% of thalidomide use was for oncological conditions. There were 72 females of childbearing potential who had positive pregnancy tests. Sixty-nine of these patients had false positive pregnancy tests. Of the remaining three, one woman was pregnant while on thalidomide. This patient had an initial negative test and received thalidomide. Therapy was stopped when she had a positive pregnancy test. This pregnancy resulted in a miscarriage. Two additional patients were determined to be pregnant before receiving thalidomide. Conclusions: The S.T.E.P.S.(R) programme is critical to managing the risks of thalidomide-associated teratogenicity. Sustained vigilance among healthcare providers and patients receiving thalidomide is essential to its continued success. Healthcare providers should be aware of the occurrence of false-positive pregnancy tests in females of childbearing potential receiving thalidomide. C1 US FDA, Ctr Drug Evaluat & Res, Pregnancy Labeling Task Force, Silver Spring, MD 20993 USA. Celgene Corp, Summit, NJ USA. NIH, Natl Lib Med, Bethesda, MD 20892 USA. RP Uhl, K (reprint author), US FDA, Ctr Drug Evaluat & Res, Pregnancy Labeling Task Force, 10903 New Hampshire Ave,Bldg 22,Room 6460, Silver Spring, MD 20993 USA. EM kathleen.uhl@oc.fda.gov NR 10 TC 29 Z9 29 U1 2 U2 10 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 0114-5916 J9 DRUG SAFETY JI Drug Saf. PY 2006 VL 29 IS 4 BP 321 EP 329 DI 10.2165/00002018-200629040-00003 PG 9 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology GA 033UH UT WOS:000236875000003 PM 16569081 ER PT J AU Moore, MM Honma, M Clements, J Bolcsfoldi, G Burlinson, B Cifone, M Clarke, J Delongchamp, R Durward, R Fellows, M Gollapudi, B Hou, SM Jenkinson, P Lloyd, M Majeska, J Myhr, B O'Donovan, M Omori, T Riach, C San, R Stankowski, LF Thakur, AK Van Goethem, F Wakuri, S Yoshimura, I AF Moore, MM Honma, M Clements, J Bolcsfoldi, G Burlinson, B Cifone, M Clarke, J Delongchamp, R Durward, R Fellows, M Gollapudi, B Hou, SM Jenkinson, P Lloyd, M Majeska, J Myhr, B O'Donovan, M Omori, T Riach, C San, R Stankowski, LF Thakur, AK Van Goethem, F Wakuri, S Yoshimura, I TI Mouse lymphoma thymidine kinase gene mutation assay: Follow-up meeting of the International Workshop on Genotoxicity Testing - Aberdeen, Scotland, 2003 - Assay acceptance criteria, positive controls, and data evaluation SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article DE mouse lymphoma assay; thymidine kinase; gene mutation assay ID WORKGROUP REPORT AB The Mouse Lymphoma Assay (MLA) Workgroup of the International Workshop on Genotoxicity Testing (IWGT), comprised of experts from Japan, Europe, and the United States, met on August 29, 2003, in Aberdeen, Scotland, United Kingdom. This meeting of the MLA Workgroup was devoted to reaching a consensus on the appropriate approach to data evaluation and on acceptance criteria for both the positive and negative/vehicle controls. The Workgroup reached consensus on the acceptance criteria for both the agar and microwell versions of the MLA. Recommendations include acceptable ranges for mutant frequency, cloning efficiency, and suspension growth of the negative/vehicle controls and on criteria to define an acceptable positive control response. The recommendation for the determination of a positive/negative test chemical response includes both the requirement that the response exceeds a defined value [the global evaluation factor (GEF)] and that there also be a positive dose-response (evaluated by an appropriate statistical method). C1 US FDA, Natl Ctr Toxicol Res, DGRT, Jefferson, AR 72079 USA. Natl Inst Hlth Sci, Div Genet & Mutagenesis, Tokyo 158, Japan. Covance Labs Ltd, Harrogate, N Yorkshire, England. AstraZeneca R&D, Safety Assessment, Sodertalje, Sweden. Huntingdon Life Sci, Huntingdon, England. Covance Labs Inc, Vienna, Austria. BioReliance Invitrogen Bioserv, Rockville, MD USA. Safepharm Labs Ltd, Shardlow, Derby, England. AstraZeneca R&D, Safety Assessment, Macclesfield, Cheshire, England. Dow Chem Co USA, TERC, Midland, MI USA. Boehringer Ingelheim Pharmaceut Inc, Ridgefield, CT 06877 USA. Kyoto Univ, Sch Publ Hlth, Kyoto, Japan. Inveresk, Tranent, Scotland. Johnson & Johnson Pharmaceut Res & Dev LLC, Raritan, NJ USA. Johnson & Johnson Pharmaceut Res & Dev, Beerse, Belgium. Food & Drug Safety Ctr, Hatano Res Inst, Kanagawa, Japan. Tokyo Univ Sci, Fac Engn, Shinjuku Ku, Tokyo 162, Japan. RP Moore, MM (reprint author), US FDA, Natl Ctr Toxicol Res, DGRT, HFT-120,3900 NCTR Rd, Jefferson, AR 72079 USA. EM MMMoore@nctr.fda.gov NR 3 TC 63 Z9 66 U1 0 U2 7 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD JAN PY 2006 VL 47 IS 1 BP 1 EP 5 DI 10.1002/em.20159 PG 5 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 010PA UT WOS:000235205400001 PM 15991242 ER PT J AU Manjanatha, MG Aidoo, A Shelton, SD Bishop, ME McDaniel, LP Lyn-Cook, LE Doerge, DR AF Manjanatha, MG Aidoo, A Shelton, SD Bishop, ME McDaniel, LP Lyn-Cook, LE Doerge, DR TI Genotoxicity of acrylamide and its metabolite glycidamide administered in drinking water to male and female Big Blue mice SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article DE acrylamide; glycidamide; Big Blue; cll mutations ID MOUSE GERM-CELLS; TRANSGENIC MICE; N-METHYLOLACRYLAMIDE; HEMOGLOBIN ADDUCTS; INDUCED MUTATIONS; B6C3F(1) MICE; IN-VIVO; DNA; RATS; MUTAGENICITY AB The recent discovery of acrylamide (AA), a probable human carcinogen, in a variety of fried and baked starchy foods has drawn attention to its genotoxicity and carcinogenicity. Evidence suggests that glycidamide (GA), the epoxide metabolite of AA, is responsible for the genotoxic effects of AA. To investigate the in vivo genotoxicity of AA, groups of male and female Big Blue (BB) mice were administered 0, 100, or 500 mg/l of AA or equimolar doses of GA, in drinking water, for 3-4 weeks. Micronucleated reticulocytes (MN-RETs) were assessed in peripheral blood within 24 hr of the lost treatment, and lymphocyte Hprt and liver cll mutagenesis assays were conducted 21 days following the last treatment. Further the types of cll mutations induced by AA and 6 A in the liver were determined by sequence analysis. The frequency of MN-RETs was increased 1.7-3.3-fold in males treated with the high doses of AA and GA (P <= 0.05; control frequency = 0.28%). Both doses of AA and GA produced increased lymphocyte Hprt mutant frequencies (MFs), with the high doses producing responses 16-25-fold higher than that of the respective control (P <= 0.01; control MFs = 1.5 +/- 0.3 x 10(-6) and 2.2 +/- 0.5 x 10(-6) in females and males, respectively). Also, the high doses of AA and GA produced significant 2-2.5-fold increases in liver cll MFs (P <= 0.05; control MFs = 26.5 +/- 3.1 x 10(-6) and 28.4 +/- 4.5 x 10(-6)). Molecular analysis of the mutants indicated that AA and GA produced similar mutation spectra and that these spectra were significantly different from that of control mutants (P <= 0.001). The predominant types of mutations in the liver cll gene from AA- and GA-treated mice were G:C -> T:A transversions and -1/+1 frameshifts in a homopolymeric run of Gs. The results indicate that both AA and GA are genotoxic in mice. The MFs and types of mutations induced by AA and GA in the liver are consistent with AA exerting its genotoxicity in BB mice via metabolism to GA. 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 Manjanatha, MG (reprint author), US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, HFT-120,3900 NCTR Rd, Jefferson, AR 72079 USA. EM Mmanjanatha@nctr.fda.gov NR 45 TC 66 Z9 67 U1 0 U2 8 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD JAN PY 2006 VL 47 IS 1 BP 6 EP 17 DI 10.1002/em.20157 PG 12 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 010PA UT WOS:000235205400002 PM 15957192 ER PT J AU Knudsen, JF Sokol, G AF Knudsen, James F. Sokol, Gerald TI Subcortical manifestation of antiepileptic drugs: Role of carbonic anhydrase SO EPILEPSIA LA English DT Meeting Abstract CT 60th Annual Meeting of the American-Epilepsy-Society CY DEC 01-05, 2006 CL San Diego, CA SP Amer Epilepsy Soc C1 CDER, White Oak Res Facil, Silver Spring, MD USA. Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2006 VL 47 SU 4 BP 162 EP 162 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 096OA UT WOS:000241385500458 ER PT J AU Katz, R AF Katz, R TI FDA update SO EPILEPSY RESEARCH LA English DT Article; Proceedings Paper CT 8th Conference on Antiepileptic Drug Trials CY MAR 17-19, 2005 CL Key Biscayne, FL ID PLACEBO-CONTROLLED TRIALS; ACTIVE-CONTROL TRIALS; ISSUES AB This report addresses: (1) a general update of FDA activity in areas relevant to AED development; (2) an update on issues relevant to the development of AEDs in the pediatric population; and (3) an update on the Agency's approach to the evaluation of AEDs as monotherapy. FDA Actions: Since January 2002, 47 Approval actions for 10 AEDs were issued, but none for a new chemical entity. Nine of the ten Approvable actions taken were relatively minor changes to existing applications. An Approvable letter was issued for Lyrica (pregabalin) for the treatment of post-herpetic neuralgia, painful diabetic neuropathy, and partial seizures in adults. The primary issue to be addressed in the face of post-marketing reports of adverse events is one of causality. The FDA has requested that sponsors search their databases for selected problems under review (e.g.. suicidality). Pediatrics: The Pediatric Research Equity Act (PREA) and the Best Pharmaceuticals for Children Act (BPCA) require studies in pediatric patients for those indications granted for adults that are relevant for the pediatric population. Current FDA policy asks sponsors to undertake a development program in pediatric patients essentially analogous to that for adults. Monotherapy Trials: Establishing the effectiveness of AEDs as monotherapy continues to be desirable, but problematic. Problems include the difficulty of performing monotherapy trials, ethical issues, designation of patients as "newly diagnosed," and endpoints. Historical controls may be acceptable if: (a) there is a consensus that it is essentially impossible to conduct controlled trials designed to demonstrate a difference between treatments; (b) there is an adequate historical database against which the seizure rate seen with the new drug can reasonably be compared; and (c) there is evidence from adequate and well-controlled trials that the treatment is effective as adjunctive therapy. FDA is Agency is reviewing analyses describing historical controls. C1 US FDA, Rockville, MD 20857 USA. RP Katz, R (reprint author), US FDA, Rockville, MD 20857 USA. EM katzr@cder.fda.gov NR 3 TC 18 Z9 18 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-1211 J9 EPILEPSY RES JI Epilepsy Res. PD JAN PY 2006 VL 68 IS 1 BP 85 EP 94 DI 10.1016/j.eplepsyres.2005.09.034 PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA 009SU UT WOS:000235133800022 PM 16377143 ER PT J AU Westphal, CD AF Westphal, Carmen D. BE Maleki, SJ Burks, AW Helm, RM TI Approaches to the Detection of Food Allergens, from a Food Science Perspective SO FOOD ALLERGY LA English DT Article; Book Chapter ID LINKED-IMMUNOSORBENT-ASSAY; POLYMERASE-CHAIN-REACTION; REAL-TIME PCR; INDIRECT COMPETITIVE ELISA; PEANUT ARACHIS-HYPOGAEA; IGE-BINDING EPITOPES; ENZYME-IMMUNOASSAY; SANDWICH-ELISA; PROCESSED FOODS; TRACE AMOUNTS C1 US FDA, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. RP Westphal, CD (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. NR 119 TC 3 Z9 3 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N STREET NW, WASHINGTON, DC 20036-2904 USA BN 978-1-55581-572-1 PY 2006 BP 189 EP 218 PG 30 WC Allergy; Immunology SC Allergy; Immunology GA BPH86 UT WOS:000278889200009 ER PT J AU Gendel, SM AF Gendel, Steven M. BE Maleki, SJ Burks, AW Helm, RM TI Bioinformatics for Predicting Allergenicity SO FOOD ALLERGY LA English DT Article; Book Chapter ID POTENTIAL ALLERGENICITY; FOOD ALLERGY; DATABASES; PROTEINS C1 US FDA, Summit Argo, IL 60501 USA. RP Gendel, SM (reprint author), US FDA, 6502 S Archer Rd, Summit Argo, IL 60501 USA. NR 9 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N STREET NW, WASHINGTON, DC 20036-2904 USA BN 978-1-55581-572-1 PY 2006 BP 249 EP 256 PG 8 WC Allergy; Immunology SC Allergy; Immunology GA BPH86 UT WOS:000278889200011 ER PT J AU Haley, CJ AF Haley, CJ TI The Minor Use and Minor Species Animal Health Act: Past, present, and future SO FOOD AND DRUG LAW JOURNAL LA English DT Article ID ORPHAN DRUG-ACT C1 Pfizer Inc, New York, NY USA. US FDA, CVM, Rockville, MD 20857 USA. RP Haley, CJ (reprint author), Pfizer Inc, New York, NY USA. NR 44 TC 1 Z9 1 U1 0 U2 0 PU FOOD DRUG LAW INST PI WASHINGTON PA 1000 VERMONT AVE NW, SUITE 1200, WASHINGTON, DC 20005-4903 USA SN 1064-590X J9 FOOD DRUG LAW J JI Food Drug Law J. PY 2006 VL 61 IS 1 BP 13 EP 43 PG 31 WC Food Science & Technology; Law; Nutrition & Dietetics; Pharmacology & Pharmacy SC Food Science & Technology; Government & Law; Nutrition & Dietetics; Pharmacology & Pharmacy GA 031TH UT WOS:000236726500002 PM 16838456 ER PT J AU Glavin, MOK AF Glavin, Margaret O' K. TI Enhancing risk management at ORA SO FOOD AND DRUG LAW JOURNAL LA English DT Article; Proceedings Paper CT 49th Annual Conference of the Food-and-Drug-Law-Institutes CY APR 05-06, 2006 CL Washington, DC SP Food & Drug Law Inst C1 US FDA, Off Regulatory Affairs, Rockville, MD 20857 USA. RP Glavin, MOK (reprint author), US FDA, Off Regulatory Affairs, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FOOD DRUG LAW INST PI WASHINGTON PA 1000 VERMONT AVE NW, SUITE 1200, WASHINGTON, DC 20005-4903 USA SN 1064-590X J9 FOOD DRUG LAW J JI Food Drug Law J. PY 2006 VL 61 IS 4 BP 795 EP 798 PG 4 WC Food Science & Technology; Law; Nutrition & Dietetics; Pharmacology & Pharmacy SC Food Science & Technology; Government & Law; Nutrition & Dietetics; Pharmacology & Pharmacy GA 117ZP UT WOS:000242912100007 PM 17180772 ER PT J AU Goswami, BB Kulka, M AF Goswami, B. B. Kulka, M. BE Potter, M TI Pathogenic mechanisms of foodborne viral disease SO FOOD CONSUMPTION AND DISEASE RISK: CONSUMER-PATHOGEN INTERACTIONS LA English DT Article; Book Chapter ID HEPATITIS-A-VIRUS; DOUBLE-STRANDED-RNA; DECAY-ACCELERATING FACTOR; BLOOD GROUP ANTIGENS; NORWALK-LIKE VIRUS; VACCINE-DERIVED POLIOVIRUSES; INDUCED PROTEIN-KINASE; RIBOSOME ENTRY SITE; COXSACKIEVIRUS B3-INDUCED MYOCARDITIS; ANTIBODY-DEPENDENT ENHANCEMENT C1 [Goswami, B. B.; Kulka, M.] US FDA, OARSA, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. RP Goswami, BB (reprint author), US FDA, OARSA, Ctr Food Safety & Appl Nutr, 8301 Muirkirk Rd, Laurel, MD 20708 USA. EM biswendu.goswami@fda.hhs.gov; michael.kulka@fda.hhs.gov NR 345 TC 0 Z9 0 U1 0 U2 0 PU WOODHEAD PUBL LTD PI CAMBRIDGE PA ABINGTON HALL ABINGTON, CAMBRIDGE CB1 6AH, CAMBS, ENGLAND BN 978 1 84569 012 0 PY 2006 BP 343 EP 392 DI 10.1533/9781845692025.3.343 D2 10.1533/9781845692025 PG 50 WC Food Science & Technology; Public, Environmental & Occupational Health SC Food Science & Technology; Public, Environmental & Occupational Health GA BNC40 UT WOS:000274156700015 ER PT J AU Chen, Q Lee, JH Sun, A Zhang, L Espey, M Krishna, M Pooput, C Kirk, K Choyke, P Buettner, G Shacter, E Levine, M AF Chen, Qi Lee, Je-Hyuk Sun, Andrew Zhang, Liqun Espey, Michael Krishna, Murali Pooput, Chaya Kirk, Kenneth Choyke, Peter Buettner, Garry Shacter, Emily Levine, Mark TI Intravenous ascorbic acid as a pro-drug for ascorbate radical and H2O2 delivery to tissues: Implications in cancer treatment SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 13th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine CY NOV 15-19, 2006 CL Denver, CO SP Soc Free Rad Biol & Med C1 NIDDK, NIH, Bethesda, MD 20892 USA. NCI, NIH, Bethesda, MD 20892 USA. Univ Iowa, Iowa City, IA 52242 USA. US FDA, CBER, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2006 VL 41 SU 1 BP S64 EP S64 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 103OC UT WOS:000241895600175 ER PT J AU Moon, H Ahn, H Kodell, RL Lin, CJ Baek, S Chen, JJ AF Moon, Hojin Ahn, Hongshik Kodell, Ralph L. Lin, Chien-Ju Baek, Songjoon Chen, James J. TI Classification methods for the development of genomic signatures from high-dimensional data SO GENOME BIOLOGY LA English DT Article ID GENE-EXPRESSION DATA; BREAST-CANCER; CLASS DISCOVERY; PREDICTION; TREES AB Personalized medicine is defined by the use of genomic signatures of patients to assign effective therapies. We present Classification by Ensembles from Random Partitions ( CERP) for class prediction and apply CERP to genomic data on leukemia patients and to genomic data with several clinical variables on breast cancer patients. CERP performs consistently well compared to the other classification algorithms. The predictive accuracy can be improved by adding some relevant clinical/histopathological measurements to the genomic data. C1 Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, FDA, Jefferson, AR 72079 USA. SUNY Stony Brook, Dept Appl Math & Stat, Stony Brook, NY 11794 USA. RP Moon, H (reprint author), Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, FDA, NCTR Rd, Jefferson, AR 72079 USA. EM hojin.moon@fda.hhs.gov NR 22 TC 10 Z9 10 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1474-760X J9 GENOME BIOL JI Genome Biol. PY 2006 VL 7 IS 12 AR R121 DI 10.1186/gb-2006-7-12-r121 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 132UG UT WOS:000243967100015 PM 17181863 ER PT S AU Ang, CYW Jhoo, JW Cui, Y Hu, L Heinze, TM Lang, Q Wai, CM Mihalov, JJ DiNovi, M Mattia, A AF Ang, CYW Jhoo, JW Cui, Y Hu, L Heinze, TM Lang, Q Wai, CM Mihalov, JJ DiNovi, M Mattia, A BE Wang, M Sang, S Hwang, LS Ho, CT TI Challenges in assessing bioactive botanical ingredients in functional beverages SO HERBS: CHALLENGES IN CHEMISTRY AND BIOLOGY SE ACS SYMPOSIUM SERIES LA English DT Article; Proceedings Paper CT 227th National Meeting of the American-Chemical Society CY MAR 28-APR 01, 2004 CL Anaheim, CA SP Amer Chem Soc ID ST-JOHNS-WORT; PERFORMANCE LIQUID-CHROMATOGRAPHY; HYPERICUM-PERFORATUM L.; LIGHT-SCATTERING DETECTION; PREGNANE X RECEPTOR; GINKGO-BILOBA; PIPER-METHYSTICUM; KAVA LACTONES; MASS-SPECTROMETRY; EXTRACTS AB Bioactive botanicals are used as functional ingredients in conventional foods to be marketed as functional foods. Among these functional foods, teas and non-alcoholic, non-carbonated bottled beverages are especially popular. The analytical assessment of these ingredients in functional foods and beverages presents a new challenge because of low levels of analytes and the matrix complexity. This article summarizes recent development of analytical methods for the determination of bioactive constituents from St. John's wort (SJW; Hypericum perforatum L.), ginkgo (Ginkgo biloba L.) and kava (Piper methysticum, Forst.) in functional beverages. The constituents selected as marker compounds were hyperforin, adhyperforin, hypericin and pseudohypericin for SJW, five terpene trilactones (ginkgolides A, B, C and J, and bilobalide) for ginkgo products, and six kavalactones (methysticin, dihydromethysticin, kavain, dihydrokavain, yangonin and desmethoxyyangonin) for kava products. The methods developed include improved sample preparation, liquid chromatography with ultra violet/photodiode array detection (LC/UV/PDA), LC with evaporative light scattering detection (ELSD) and LC with mass spectrometry (MS). The stability of SJW constituents in non-alcoholic, non-carbonated, fruit-flavored beverages was also discussed. C1 USDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Ang, CYW (reprint author), USDA, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. NR 49 TC 0 Z9 0 U1 2 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 SIXTEENTH ST NW, WASHINGTON, DC 20036 USA SN 0097-6156 BN 0-8412-3930-4 J9 ACS SYM SER PY 2006 VL 925 BP 55 EP 72 PG 18 WC Biochemistry & Molecular Biology; Plant Sciences; Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Plant Sciences; Pharmacology & Pharmacy; Chemistry GA BEC74 UT WOS:000236816500005 ER PT J AU Schmeisser, F Weir, JP AF Schmeisser, F Weir, JP TI Cloning of replication-incompetent herpes simplex viruses as bacterial artificial chromosomes to facilitate development of vectors for gene delivery into differentiated neurons SO HUMAN GENE THERAPY LA English DT Article ID ESCHERICHIA-COLI; MAMMALIAN-CELLS; EXPRESSION; TYPE-1; CONSTRUCTION; GENOME; MUTANTS; DNA; MUTAGENESIS; INFECTION AB We have previously described the adaptation of a tetracycline-regulated system of gene expression for herpes simplex virus ( HSV) vectors and demonstrated that such a system was capable of inducible foreign gene expression in irreversibly differentiated neurons. These studies suggested that such gene delivery vectors would be especially useful for studying the neuron in vitro. Here, we describe the cloning of a replication-incompetent HSV vector as a bacterial artificial chromosome ( BAC) to facilitate vector construction. Using prokaryotic genetic techniques for allele replacement, we demonstrate the ease of manipulation of the BAC-containing vector, including the construction of vector mutations for which there is no simple phenotypic selection. Such constructions include the insertion of a tetracycline-regulated gene cassette into the UL41 gene for regulated gene expression and the mutation of the UL48 gene to reduce vector toxicity. In addition, HSV vectors cloned as BACs can be sequentially modified to make multiple changes to the vector platform. Finally, using the BAC system, we constructed an HSV vector that expressed an inducible human superoxide dismutase-1 ( SOD1) gene for delivery into differentiated human NT-neurons ( cells of the human embryonal carcinoma cell line NT2, which differentiate irreversibly into postmitotic neuron-like cells after treatment with retinoic acid). The results indicated that there is appreciable expression of SOD1 from this HSV vector in the presence of doxycycline and that vector-expressed SOD1 interacts with endogenous SOD1. Thus, the BAC system provides a practicable platform for construction and manipulation of HSV vectors that are suitable for gene delivery into postmitotic neurons in vitro. C1 US FDA, Ctr Biol Evaluat & Res, Lab DNA Viruses, Bethesda, MD 20892 USA. RP Weir, JP (reprint author), Ctr Biol Evaluat & Res, Div Viral Prod, HFM-457,1401 Rockville Pike, Rockville, MD 20852 USA. EM weirj@cber.fda.gov NR 41 TC 1 Z9 1 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD JAN PY 2006 VL 17 IS 1 BP 93 EP 104 DI 10.1089/hum.2006.17.93 PG 12 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 003YY UT WOS:000234720400009 PM 16409128 ER PT S AU Sutherland, JB Rafii, F AF Sutherland, John B. Rafii, Fatemeh BE Wilkins, CL Lay, JO TI CULTURAL, SEROLOGICAL, AND GENETIC METHODS FOR IDENTIFICATION OF BACTERIA SO IDENTIFICATION OF MICROORGANISMS BY MASS SPECTROMETRY SE Chemical Analysis-A Series of Monographs on Analytical Chemistry and Its Applications LA English DT Article; Book Chapter ID POLYMERASE-CHAIN-REACTION; IN-SITU HYBRIDIZATION; 16S RIBOSOMAL-RNA; ANTIBIOTIC-RESISTANCE GENES; EXTRAGENIC PALINDROMIC PCR; ESCHERICHIA-COLI O157-H7; REAL-TIME PCR; RAPID DETECTION; DNA MICROARRAYS; DRINKING-WATER C1 [Sutherland, John B.; Rafii, Fatemeh] US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. RP Sutherland, JB (reprint author), US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. NR 115 TC 5 Z9 5 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND SN 0069-2883 BN 978-0-471-74864-9 J9 CHEM ANAL SERIES MON PY 2006 VL 169 BP 1 EP 21 PG 21 WC Chemistry, Analytical; Microbiology SC Chemistry; Microbiology GA BYG03 UT WOS:000298539200002 ER PT S AU Wilkes, JG Miertschin, G Eschler, T Hosey, L Rafii, F Rushing, L Buzatu, DA Bertrand, MJ AF Wilkes, Jon G. Miertschin, Gary Eschler, Todd Hosey, Les Rafii, Fatemeh Rushing, Larry Buzatu, Dan A. Bertrand, Michel J. BE Wilkins, CL Lay, JO TI METHOD REPRODUCIBILITY AND SPECTRAL LIBRARY ASSEMBLY FOR RAPID BACTERIAL CHARACTERIZATION BY METASTABLE ATOM BOMBARDMENT PYROLYSIS MASS SPECTROMETRY SO IDENTIFICATION OF MICROORGANISMS BY MASS SPECTROMETRY SE Chemical Analysis-A Series of Monographs on Analytical Chemistry and Its Applications LA English DT Article; Book Chapter ID ARTIFICIAL NEURAL-NETWORKS; ASSISTED-LASER-DESORPTION/IONIZATION; QUANTITATIVE-ANALYSIS; NOSOCOMIAL INFECTION; FLOW-CYTOMETRY; ESCHERICHIA-COLI; WHOLE CELLS; DIFFERENTIATION; IDENTIFICATION; IONIZATION C1 [Wilkes, Jon G.; Rafii, Fatemeh] US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. RP Wilkes, JG (reprint author), US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. NR 50 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND SN 0069-2883 BN 978-0-471-74864-9 J9 CHEM ANAL SERIES MON PY 2006 VL 169 BP 91 EP 124 PG 34 WC Chemistry, Analytical; Microbiology SC Chemistry; Microbiology GA BYG03 UT WOS:000298539200006 ER PT S AU Williams, TL Monday, SR Musser, SM AF Williams, Tracie L. Monday, Steven R. Musser, Steven M. BE Wilkins, CL Lay, JO TI BACTERIAL PROTEIN BIOMARKER DISCOVERY: A FOCUSED APPROACH TO DEVELOPING MOLECULAR-BASED IDENTIFICATION SYSTEMS SO IDENTIFICATION OF MICROORGANISMS BY MASS SPECTROMETRY SE Chemical Analysis-A Series of Monographs on Analytical Chemistry and Its Applications LA English DT Article; Book Chapter ID ASSISTED-LASER-DESORPTION/IONIZATION; TERMINAL METHIONINE EXCISION; FLIGHT MASS-SPECTROMETRY; PHASE SEPARATION METHOD; ENTEROBACTER-SAKAZAKII; COMPARATIVE PROTEOMICS; 2-DIMENSIONAL ELECTROPHORESIS; SHOTGUN PROTEOMICS; INFANT FORMULA; LIQUID-CHROMATOGRAPHY C1 [Williams, Tracie L.; Monday, Steven R.; Musser, Steven M.] US FDA, Ctr Food Safety & Nutr, College Pk, MD 20740 USA. RP Williams, TL (reprint author), US FDA, Ctr Food Safety & Nutr, College Pk, MD 20740 USA. NR 72 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND SN 0069-2883 BN 978-0-471-74864-9 J9 CHEM ANAL SERIES MON PY 2006 VL 169 BP 203 EP 227 PG 25 WC Chemistry, Analytical; Microbiology SC Chemistry; Microbiology GA BYG03 UT WOS:000298539200011 ER PT J AU Goon, S Ewing, CP Lorenzo, M Pattarini, D Majam, G Guerry, P AF Goon, S Ewing, CP Lorenzo, M Pattarini, D Majam, G Guerry, P TI A sigma(28)-regulated nonflagella gene contributes to virulence of Campylobacter jejuni 81-176 SO INFECTION AND IMMUNITY LA English DT Article ID EPITHELIAL-CELL CULTURES; INTRACELLULAR SURVIVAL; LEGIONELLA-PNEUMOPHILA; CACO-2 CELLS; HEP-2 CELLS; INVASION; EXPRESSION; FLAGELLIN; MOTILITY; INTERNALIZATION AB A Campylobacter jejuni 81-176 mutant in Cj0977 was fully motile but reduced >3 logs compared to the parent in invasion of intestinal epithelial cells in vitro. The mutant was also attenuated in a ferret diarrheal disease model. Expression of Cj0977 protein was dependent on a minimal flagella structure. C1 Naval Med Res Ctr, Enter Dis Dept, Silver Spring, MD 20910 USA. Food & Drug Adm MOD1, Beltsville, MD USA. RP Guerry, P (reprint author), Naval Med Res Ctr, Enter Dis Dept, 503 Robert Grant Ave, Silver Spring, MD 20910 USA. EM guerryp@nmrc.navy.mil RI Guerry, Patricia/A-8024-2011 FU NIAID NIH HHS [R01 AI 043559, R01 AI043559] NR 37 TC 37 Z9 40 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JAN PY 2006 VL 74 IS 1 BP 769 EP 772 DI 10.1128/IAI.74.1.769-772.2006 PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 997VH UT WOS:000234276400085 PM 16369037 ER PT J AU Parra, M Cadieux, N Pickett, T Dheenadhayalan, V Brennan, MJ AF Parra, M Cadieux, N Pickett, T Dheenadhayalan, V Brennan, MJ TI A PE protein expressed by Mycobacterium avium is an effective T-cell immunogen SO INFECTION AND IMMUNITY LA English DT Article ID TUBERCULOSIS; ANTIGENS; SEQUENCE; GENOMICS; STRAINS; GENES AB Infection of mice with Mycobacterium avium or immunization with a novel PE gene expressed by M. avium (MaPE) showed that a dominant T-cell immune response was elicited. Immunization with an MaPE DNA vaccine protected mice against an aerosol challenge with Mycobacterium tuberculosis, suggesting that mycobacteria express PE antigens with cross-protective T-cell epitopes. C1 US FDA, Off Vaccines Res & Review, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Brennan, MJ (reprint author), US FDA, Off Vaccines Res & Review, Ctr Biol Evaluat & Res, Bldg 29,Rm 503,HFM-431,29 Lincoln Dr, Bethesda, MD 20892 USA. EM Brennan@cber.fda.gov NR 17 TC 15 Z9 15 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JAN PY 2006 VL 74 IS 1 BP 786 EP 789 DI 10.1128/IAI.74.1.786-789.2006 PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 997VH UT WOS:000234276400089 PM 16369041 ER PT S AU Joshi, BH Hogaboam, C Dover, P Husain, SR Puri, RK AF Joshi, Bharat H. Hogaboam, Cory Dover, Pamela Husain, Syed R. Puri, Raj K. BE Litwack, G TI Role of interleukin-13 in cancer, pulmonary fibrosis, and other T(H)2-type diseases SO INTERLEUKINS SE Vitamins and Hormones LA English DT Review; Book Chapter ID RECEPTOR-TARGETED CYTOTOXIN; CARCINOMA CELL-LINES; HUMAN GLIOMA-CELLS; HUMAN B-CELLS; IDIOPATHIC INTERSTITIAL PNEUMONIA; CONVECTION-ENHANCED DELIVERY; RECURRENT MALIGNANT GLIOMA; CHIMERIC FUSION PROTEINS; ALLERGIC AIRWAY DISEASE; COMMON GAMMA-CHAIN AB Interleukin (IL)-13 plays a major role in various inflammatory diseases including cancer, asthma, and allergy. It mediates a variety of different effects on various cell types including B cells, monocytes, natural killer cells, endothelial cells, and fibroblasts. IL-13 binds to two primary receptor chains IL-13R alpha 1 andIL-13R alpha 2. The IL-UR alpha 2 butnotIL-13R alpha 1 chain binds IL-13 with high affinity and is overexpressed in a variety of human cancer cells derived from glioma, squamous cell carcinoma of head and neck, and AIDS-associated Kaposi's sarcoma. We have also demonstrated that IL-13R alpha 2 expression is greatly increased in lung cells when mice were challenged intranasally with bleomycin or Aspergillus fumigatus. In addition, IL-13R alpha 2 increased in surgical lung biopsies from patients with usual interstitial pneumonia, nonspecific interstitial pneumonia, and respiratory bronchiolitic interstitial pneumonia of unknown origin. Based on various studies, it is concluded that IL-13R alpha 2-expressing cells are involved in various pulmonary pathological conditions. In contrast, normal tissues such as brain, lung, endothelial cells, and head and neck tissues express IL-13Ra1 chain, but show only marginal expression of IL-13Ra2 chain. Thus, IL-13Ra2 chain may serve as a novel biomarker for diseased cells such as cancer or fibrosis and a target for receptor-directed therapeutic agents. To target IL-13R, a recombinant fusion protein composed of IL-13 and a derivative of Pseudomonas exotoxin (PE) has been produced. This cytotoxin termed as IL-13PE38QQR or IL-13PE38, or IL-13PE is highly and specifically cytotoxic to a variety of human tumor cell lines. In preclinical models of human glioblastoma, head and neck and AIDS-associated Kaposi's cancer, IL-13PE has been found to have significant antitumor activity at a tolerated dose. Several phase I clinical trials have been completed in patients with recurrent malignant glioma. Recently a phase III clinical trial (PRECISE) in patients with recurrent malignant glioma has been completed recruiting a total of 294 patients. IL-13PE cytotoxin has also shown a significant therapeutic effect in preclinical bleomycin or A. fumigatus or Schistosoma mansoni-induced pulmonary pathology including granulomatous fibrosis in mouse models. A clinical study in these diseases has yet to be initiated. (c) 2006 Elsevier Inc. C1 US FDA, Tumor Vaccines & Biotechnol Branch, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI 48109 USA. RP Joshi, BH (reprint author), US FDA, Tumor Vaccines & Biotechnol Branch, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RI hogaboam, cory /M-3578-2014 NR 126 TC 27 Z9 32 U1 0 U2 2 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0083-6729 BN 0-12-709874-7 J9 VITAM HORM JI Vitam. Horm. PY 2006 VL 74 BP 479 EP 504 DI 10.1016/S0083-6729(06)74019-5 PG 26 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA BFK89 UT WOS:000242541700019 PM 17027527 ER PT J AU Carreon, T Ruder, AM Schulte, PA Hayes, RB Rothman, N Waters, M Grant, DJ Boissy, R Bells, DA Kadlubar, FF Hemstreet, GP Yin, S Lemasters, GK AF Carreon, T Ruder, AM Schulte, PA Hayes, RB Rothman, N Waters, M Grant, DJ Boissy, R Bells, DA Kadlubar, FF Hemstreet, GP Yin, S Lemasters, GK TI NAT2 slow acetylation and bladder cancer in workers exposed to benzidine SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE bladder cancer; benzidine; arylamine N-acetyltransferase; glutathione S-transferase; case-control study ID N-ACETYLTRANSFERASE ACTIVITY; AROMATIC-AMINES; CIGARETTE-SMOKING; MOLECULAR EPIDEMIOLOGY; URINARY METABOLITES; OCCUPATIONAL-CANCER; RISK-FACTORS; DNA-ADDUCTS; HUMAN LIVER; PHENOTYPE AB This study expands a previous study of NAT2 polymorphisms and bladder cancer in male subjects occupationally exposed only to benzidine. The combined analysis of 68 cases and 107 controls from a cohort of production workers in China exposed to benzidine included 30 new cases and 67 controls not previously studied. NAT2 enzymatic activity phenotype was characterized by measuring urinary caffeine metabolite ratios. PCR-based methods identified genotypes for NAT2, NAT1 and GSTM1. NAT2 phenotype and genotype data were consistent. A protective association was observed for the slow NAT2 genotype (bladder cancer OR = 0.3; 95% CI = 0.1 = 1.0) after adjustment for cumulative benzidine exposure and lifetime smoking. Individuals carrying NAT1wt/*10 and NAT1*10/*10 showed higher relative risks of bladder cancer (OR = 2.8,95% CI = 0.8-10.1 and OR = 2.2,95% CI = 0.6-8.3, respectively). No association was found between GSTM1 null and bladder cancer. A metaanalysis risk estimate of case-control studies of NAT2 acetylation and bladder cancer in Asian populations without occupational arylamine exposures showed an increased risk for slow acetylators. The lower limit of the confidence interval (OR = 1.4; 95% 11 = 1.0-2.0) approximated the upper confidence interval for the estimate obtained in our analysis. These results support the earlier finding of a protective association between slow acetylation and bladder cancer in benzidine-exposed workers, in contrast to its established link as a risk factor for bladder cancer in people exposed to 2-naphthylamine and 4-aminobiphenyl. Study findings suggest the existence of key differences in the metabolism of mono- and diarylamines. Published 2005 Wiley-Liss, Inc. C1 NIOSH, Div Surveillance, Hazard Evaluat & Field Studies, Cincinnati, OH 45226 USA. Univ Cincinnati, Med Ctr, Dept Environm Hlth, Cincinnati, OH 45267 USA. NIOSH, Educ & Informat Div, Cincinnati, OH 45226 USA. NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. Natl Inst Environm Hlth Sci, Environm Gen Sect, Res Triangle Pk, NC USA. Natl Ctr Toxicol Res, Div Pharmacogen & Mol Epidemiol, Jefferson, AR 72079 USA. Univ Oklahoma, Hlth Sci Ctr, Dept Urol, Oklahoma City, OK 73104 USA. Chinese Acad Prevent Med, Dept Toxicol, Beijing, Peoples R China. RP Carreon, T (reprint author), NIOSH, Div Surveillance, Hazard Evaluat & Field Studies, 4676 Columbia Pkway,Mailstop R-16, Cincinnati, OH 45226 USA. EM carreota@ucmail.uc.edu RI Carreon, Tania/A-6548-2008; Waters, Martha/B-7441-2011; Ruder, Avima/I-4155-2012; OI Ruder, Avima/0000-0003-0419-6664; Hayes, Richard/0000-0002-0918-661X NR 62 TC 36 Z9 36 U1 1 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JAN 1 PY 2006 VL 118 IS 1 BP 161 EP 168 DI 10.1002/ijc.21308 PG 8 WC Oncology SC Oncology GA 985KJ UT WOS:000233376000021 PM 16003747 ER PT J AU Murphy, S Roberts, R AF Murphy, S Roberts, R TI "Black box" 101: How the Food and Drug Administration evaluates, communicates, and manages drug benefit/risk SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE Food and Drug Administration; adverse drug reactions; MedWatch; "black box" warning; drug labeling; drug benefit/risk; risk management; postmarketing surveillance; drug development ID BLACK-BOX WARNINGS; PRESCRIPTION; SURVEILLANCE; WITHDRAWALS; SAFETY; IMPACT AB A prominently displayed boxed warning, the so-called "black box," is added to the labeling of drugs or drug products by the Food and Drug Administration when serious adverse reactions or special problems occur, particularly those that may lead to death or serious injury. Healthcare providers are often not knowledgeable about the origin, meaning, and implications of these "black box" warnings. In this review, our goal is to provide insight into how the Food and Drug Administration evaluates, communicates, and manages drug benefit/risk. We discuss drug labeling, the emphasis on safety throughout the drug approval process, legislative initiatives for safe use of drugs in children, and postmarketing safety surveillance. In addition, we encourage health care providers to report drug reactions to the Food and Drug Administration's MedWatch program. A discussion of new Food and Drug Administration initiatives to improve drug safety processes and methods to serve the public better are highlighted. C1 US FDA, Ctr Drug Evaluat & Res, Off Counter Terrorism & Pediat Drug Dev, Silver Spring, MD USA. RP Murphy, S (reprint author), 10903 New Hampshire Ave,Bldg 21, Silver Spring, MD 20993 USA. EM murphys@cder.fda.gov NR 14 TC 48 Z9 50 U1 1 U2 4 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 2006 VL 117 IS 1 BP 34 EP 39 DI 10.1016/j.jaci.2005.10.031 PG 6 WC Allergy; Immunology SC Allergy; Immunology GA 017IK UT WOS:000235687100006 PM 16387581 ER PT J AU Wuilloud, RG Altamirano, JC Smichowski, PN Heitkemper, DT AF Wuilloud, Rodolfo G. Altamirano, Jorgelina C. Smichowski, Patricia N. Heitkemper, Douglas T. TI Investigation of arsenic speciation in algae of the Antarctic region by HPLC-ICP-MS and HPLC-ESI-Ion Trap MS SO JOURNAL OF ANALYTICAL ATOMIC SPECTROMETRY LA English DT Article ID ELECTROSPRAY-MASS-SPECTROMETRY; ATOMIC FLUORESCENCE SPECTROMETRY; CHLORELLA-VULGARIS; ENVIRONMENTAL-SAMPLES; RIBOSIDE DERIVATIVES; TERRESTRIAL ORIGIN; NATURAL TISSUES; ARSENOSUGARS; MARINE; CHROMATOGRAPHY AB An investigation into presence and nature of As species in algae originating from the Antarctic region is presented in this work. Arsenic speciation information in Antarctic algae samples was obtained by using anion- and cation- exchange chromatography with on-line detection by inductively coupled plasma spectrometry ( ICP- MS) or electrospray ionization ion trap mass spectrometry (ESI- ITMS). Total arsenic concentrations found by ICP- MS in the Antarctic algae samples ranged from 8.4 to 29.3 mu g As g(-1) ( dry weight). Arsenic species were efficiently extracted ( 83 - 108%) by using an MeOH : H(2)O ( 1 : 1) mixture. Anion- exchange chromatography utilizing gradient elution with 25 mM ammonium bicarbonate adjusted to pH 10 was used to separate the anionic As species present in the algae extracts. Additionally, gradient cation- exchange chromatography was performed using 4 mM pyridine solution adjusted to pH 2.4. This allowed the separation of neutral and cationic As species present in the algae extracts. High volatility of the mobile phases allowed sample introduction compatibility with both ICP- MS and ESI- ITMS detectors. Three arsenosugar species ( arsenosugar - OH, - SO(3), and - PO(4)) previously reported in marine algae samples accounted for similar to 50 - 80% of the total extractable arsenic in 4 of the 5 samples studied. In one algae sample, the presence of a previously unreported arsenic- containing compound in algae samples was con. rmed by ESI- ITMS isolation and fragmentation as 5- dimethylarsinoyl- b- ribofuranose. This compound has been identi. ed previously in marine bivalves but, to our knowledge, not in algae samples. C1 US FDA, Forens Chem Ctr, Cincinnati, OH 45237 USA. Comis Nacl Energia Atom, Unidad Actividad Quim, Ctr Atom Constituyentes, RA-1650 Buenos Aires, DF, Argentina. RP Wuilloud, RG (reprint author), Consejo Nacl Invest Cient & Tecn, Lab Environm Res & Serv Mendoza, LISAMEN, CRICYT, Av Ruiz Leal S-N Parque Gen San Martin,M 5502 IRA, Mendoza, Argentina. EM rwuilloud@lab.cricyt.edu.ar RI Wuilloud, Rodolfo/N-6821-2014 OI Wuilloud, Rodolfo/0000-0002-2962-7718 NR 44 TC 26 Z9 26 U1 1 U2 21 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 0267-9477 J9 J ANAL ATOM SPECTROM JI J. Anal. At. Spectrom. PY 2006 VL 21 IS 11 BP 1214 EP 1223 DI 10.1039/b607203h PG 10 WC Chemistry, Analytical; Spectroscopy SC Chemistry; Spectroscopy GA 099BT UT WOS:000241568200011 ER PT J AU Cherstniakova, SA Garcia, GE Strong, J Bi, DQ Weitz, J Roy, MJ Cantilena, LR AF Cherstniakova, SA Garcia, GE Strong, J Bi, DQ Weitz, J Roy, MJ Cantilena, LR TI Rapid determination of N,N-diethyl-m-toluamide and permethrin in human plasma by gas chromatography-mass spectrometry and pyridostigmine bromide by high-performance liquid chromatography SO JOURNAL OF ANALYTICAL TOXICOLOGY LA English DT Article ID INSECT REPELLENT N,N-DIETHYL-M-TOLUAMIDE; ALTER LOCOMOTOR BEHAVIOR; SOLID-PHASE EXTRACTION; RAT PLASMA; HUMAN URINE; DEET; METABOLITES; TOXICITY; PHARMACOKINETICS; NEUROTOXICITY C1 Uniformed Serv Univ Hlth Sci, Div Clin Pharmacol & Med Toxicol, Bethesda, MD 20814 USA. Walter Reed Army Inst Res, Silver Spring, MD USA. US FDA, Lab Clin Pharmacol, Ctr Drug Evaluat, Rockville, MD 20857 USA. RP Cantilena, LR (reprint author), Uniformed Serv Univ Hlth Sci, Div Clin Pharmacol & Med Toxicol, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM lcantilena@usuhs.mil NR 43 TC 9 Z9 9 U1 1 U2 7 PU PRESTON PUBLICATIONS INC PI NILES PA 7800 MERRIMAC AVE PO BOX 48312, NILES, IL 60648 USA SN 0146-4760 J9 J ANAL TOXICOL JI J. Anal. Toxicol. PD JAN-FEB PY 2006 VL 30 IS 1 BP 21 EP 26 PG 6 WC Chemistry, Analytical; Toxicology SC Chemistry; Toxicology GA 007FQ UT WOS:000234954400004 PM 16620527 ER PT J AU Schlesser, JE Jablonski, JE Mariappagoudar, P AF Schlesser, J. E. Jablonski, J. E. Mariappagoudar, P. TI Partition coefficients for toxic agents in multiple phase foods: Separation of raw whole milk. SO JOURNAL OF ANIMAL SCIENCE LA English DT Meeting Abstract DE aconitine; nicotine; strychnine C1 US FDA, Natl Ctr Food Safety, Summit Argo, IL USA. IIT, Natl Ctr Food Safety, Summit Argo, IL USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC ANIMAL SCIENCE PI SAVOY PA 1111 NORTH DUNLAP AVE, SAVOY, IL 61874 USA SN 0021-8812 J9 J ANIM SCI JI J. Anim. Sci. PY 2006 VL 84 SU 1 BP 174 EP 174 PG 1 WC Agriculture, Dairy & Animal Science SC Agriculture GA 074DS UT WOS:000239793500543 ER PT J AU Cieri, UR AF Cieri, UR TI Determination of phenylephrine hydrochloride, chlorpheniramine maleate, and methscopolamine nitrate in tablets or capsules by liquid chromatography with two UV absorbance detectors in series SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID QUANTITATIVE-DETERMINATION; PRODUCTS AB A procedure is presented for the simultaneous determination of phenylephrine HCI (PE), chlorpheniramine maleate (CM), and methscopolamine nitrate in commercial tablets or capsules by liquid chromatography (LC) with 2 UV absorbance detectors in series. Reference and sample solutions are prepared in methanol. LC separations are performed on a 7.5 cm Novapak silica column. The mobile phase is prepared by mixing 930 mL methanol with 70 mL of a 0.5% aqueous solution of 1-pentanesulfonic acid, sodium salt. The injection volume is 20 mu L; the flow rate is approximately 1 mL/min. Retention times are approximately 1.5 min for PE, 3 min for CM, and 6 min for methscopolamine nitrate. One detector determines the first 2 compounds at 265 nm, but the third compound does not produce a detectable peak. The other detector set at 210 nm generates peaks for all 3 compounds, but only methscopolamine is within the recorder range; the other 2 compounds are exceedingly off scale. If it is not feasible or desirable to arrange 2 UV absorbance detectors in series, separate determinations can be made, one for the first 2 compounds and the other for the third component of the mixture. Two commercial samples of tablets and 2 commercial samples of capsules were analyzed by the proposed method. Recovery studies were also conducted with amounts of the 3 compounds ranging from 80 to 120% of the quantities present in the sample solutions. C1 US FDA, Philadelphia, PA 19106 USA. RP Cieri, UR (reprint author), US FDA, 2nd & Chestnut Sts, Philadelphia, PA 19106 USA. EM ucieri@ora.fda.gov NR 7 TC 6 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 JAN-FEB PY 2006 VL 89 IS 1 BP 53 EP 57 PG 5 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 010GJ UT WOS:000235175000011 PM 16512228 ER PT J AU Blodgett, RJ AF Blodgett, RJ TI Testing deviation for a set of serial dilution most probable numbers from a Poisson-binomial model SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID LISTERIA-MONOCYTOGENES; BACTERIAL; DENSITY AB A serial dilution experiment estimates the microbial concentration in a broth by inoculating several sets of tubes with various amounts of the broth. The estimation uses the Poisson distribution and the number of tubes in each of these sets that show growth. Several factors, such as interfering microbes, toxins, or disaggregation of adhering microbes, may distort the results of a serial dilution experiment. A mild enough distortion may not raise suspicion with a single outcome. The test introduced here judges whether the entire set of serial dilution outcomes appears unusual. This test forms lists of the possible outcomes. The set of outcomes is declared unusual if any occurrence of an observed outcome is on the first list, or more than one is on the first or second list, etc. A similar test can apply when there are only a finite number of possible outcomes, and each outcome has a calculable probability, and few outcomes have tied probabilities. C1 US FDA, College Pk, MD 20740 USA. RP Blodgett, RJ (reprint author), US FDA, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM rblodget@cfsan.fda.gov NR 14 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 JAN-FEB PY 2006 VL 89 IS 1 BP 166 EP 171 PG 6 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 010GJ UT WOS:000235175000026 PM 16512243 ER PT J AU Duvall, RE Eklund, M Tran, TT Hitchins, AD AF Duvall, RE Eklund, M Tran, TT Hitchins, AD TI Improved DNA probe detection of Listeria monocytogenes in enrichment culture after physical-chemical fractionation SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID 16S RIBOSOMAL-RNA; POLYMERASE-CHAIN-REACTION; ACID HYBRIDIZATION ASSAY; INOCULATED FOODS; DAIRY-PRODUCTS; CONFIRMATION; IDENTIFICATION; CELLS AB Bacterial detection in foods by nucleic acid probes is limited by microflora competition during selective enrichment. Probe target concentration by extraction and fractionation of enrichments may diminish this limitation. The 1-h AccuProbe chemiluminescent culture identification test for Listeria monocytogenes was used as a model. Its high detection threshold provides a stringent challenge for evaluating enrichment work-up protocols. Detection of L. monocytogenes, at 1-4 colony-forming units/g food, was not consistently possible in 48 h enrichment cultures using AccuProbe. Concentration by cell sedimentation was occasionally helpful but the volume of co-sedimented food limited concentration to about 10-fold. To improve concentration, enrichment sediments were sonicated or enzymatically lysed to release the probe's target, r-RNA. The RNA was separated from non-RNA material by extraction with phenol and precipitation with ethanol. Enrichments (250 mL) were concentrated 2500-fold, and the limitation was food RNA volume. A strongly competitive Enterococcus faecium food isolate was used to demonstrate the effect of artificial competition on the kit's ability to detect L. monocytogenes in enrichments. High competitor concentrations repressed the level of the target below the detection threshold, but concentration of r-RNA enabled detection of L. monocytogenes. The effectiveness of this enrichment sample work-up was demonstrated with naturally contaminated hummus. C1 US FDA, Ctr food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Hitchins, AD (reprint author), US FDA, Ctr food Safety & Appl Nutr, HFS-516,5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM Anthony.Hitchins@cfsan.fda.gov NR 40 TC 4 Z9 5 U1 0 U2 0 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD JAN-FEB PY 2006 VL 89 IS 1 BP 172 EP 179 PG 8 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 010GJ UT WOS:000235175000027 PM 16512244 ER PT J AU Hammack, TS Johnson, ML Jacobson, AP Andrews, WH AF Hammack, TS Johnson, ML Jacobson, AP Andrews, WH TI Effect of sample preparation and preenrichment media on the recovery of Salmonella from cantaloupes, mangoes, and tomatoes SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID BOARD SURFACES; MICROORGANISMS; RINSES; JUICE; BROTH AB Studies were conducted to determine the relative effectiveness of buffered peptone water (BPW), lactose (LAC) broth, and Universal Preenrichment (UP) broth for the recovery of Salmonella organisms from fruit rinses, whole fruit, and comminuted fruit. In the first phase, the relative effectiveness of the rinse and soak methods for the recovery of Salmonella from surface-contaminated mangoes and tomatoes was examined. Fruits were spot inoculated with single Salmonella serovars and held for 4 days at 2-6 degrees C before analysis was initiated. The contaminated fruit was rinsed in portions of BPW, LAC broth, or UP broth. Portions from each rinse were added to its respective broth (e.g., BPW to BPW). Individual whole fruit, in their remaining broth rinses (soak method), and the fruit rinse/broths (rinse method) were incubated for 24 h at 35 degrees C. The Bacteriological Analytical Manual (BAM) Salmonella culture method was followed thereafter. The soak method produced significantly greater numbers (P < 0.05) of positive test portions than did the rinse method for the analysis of mangoes (93 versus 12) and tomatoes (85 versus 34). The 3 broths were comparable for the recovery of Salmonella for both the soak and the rinse methods for mangoes. For tomatoes, there were no significant differences among the broths for the soak method, but BPW and UP broth were significantly more productive (P < 0.05) than LAC broth by the rinse method. In the second phase, the relative effectiveness of LAC broth, BPW, and UP broth for the recovery of Salmonella from comminuted fruit was examined. Fruits were contaminated with single Salmonella serovars and aged for 4 days at 2-6 degrees C. Twenty 25 g test portions were preenriched in each of the following broths: BPW, LAC broth, and UP broth. The BAM Salmonella culture method was followed thereafter. For cantaloupes, significantly more (P < 0.05) Salmonella-positive test portions were recovered with UP broth (96 Salmonella-positive test portions) and BPW (87 Salmonella-positive test portions) than with LAC broth (57 Salmonella-positive test portions). For mangoes, BPW recovered an arithmetically larger number of Salmonella-positive test portions (27 Salmonellapositive test portions) than did either LAC broth (14 Salmonella-positive test portions) or UP broth (18 Salmonella-positive test portions). For tomatoes, there were no significant differences among the broths: BPW recovered 65 Salmonella-positive test portions, UP broth recovered 62 Salmonella-positive test portions, and LAC broth recovered 60 Salmonella-positive test portions. For the analysis of whole fruit, it is recommended that the soak method be used. For whole fruit analyzed with the soak method, UP broth should be used for tomatoes and BPW should be used for mangoes. It is further recommended that UP broth be used for the analysis of comminuted cantaloupes and that BPW be used for the analysis of comminuted mangoes and tomatoes. C1 US FDA, Ctr Food Safety & Appl Nutr, Div Microbiol Studies, College Pk, MD 20740 USA. RP Hammack, TS (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Div Microbiol Studies, College Pk, MD 20740 USA. EM Thomas.Hammack@fda.hhs.gov NR 22 TC 8 Z9 8 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 JAN-FEB PY 2006 VL 89 IS 1 BP 180 EP 184 PG 5 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 010GJ UT WOS:000235175000028 PM 16512245 ER PT J AU Hepp, NM AF Hepp, NM TI Determination of mercury in carbon black by cold vapor atomic absorption spectrometry SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID PRESERVATION; DIGESTION AB Recently, a new color additive, D&C Black No. 2, a high-purity furnace black in the general category of carbon blacks, was listed as a color subject to batch certification by the U.S. Food and Drug Administration. A simple procedure was developed to determine mercury (Hg) in D&C Black No. 2, which is limited by specification to not more than 1 ppm Hg. The method uses partial acid digestion followed by cold vapor atomic absorption and was developed by modifying a method used for other color additives. The carbon black samples are treated with a mixture of nitric and hydrochloric acids and heated by microwave in sealed Teflon((R)) vessels. The resulting solutions, which are stable to Hg loss for at least 1 week, are diluted and analyzed for Hg using cold vapor atomic absorption spectrometry. Validation was performed by spiking carbon black samples with inorganic Hg (HgNO3) at levels from 0.1 to 1.5 mu g/g, and by analyzing 2 standard reference materials. At the specification level of 1 ppm Hg (1 mu g Hg/g), the 95% confidence interval was +/- 0.01 ppm Hg (0.01 mu g Hg/g). The method developed in this study gave good results for very difficult-to-analyze materials, such as coal standard reference materials and carbon black. By eliminating volatility and adsorption factors through the formation of HgCl4-2 complexes, one can avoid using extremely hazardous acids such as HF and HCLO4. C1 US FDA, Off Cosmet & Colors, College Pk, MD 20740 USA. RP Hepp, NM (reprint author), US FDA, Off Cosmet & Colors, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM nhepp@cfsan.fda.gov NR 13 TC 2 Z9 2 U1 0 U2 0 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD JAN-FEB PY 2006 VL 89 IS 1 BP 192 EP 195 PG 4 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 010GJ UT WOS:000235175000030 PM 16512247 ER PT J AU Schenck, FJ Podhorniak, LV Hobbs, J Casanova, J Donoghue, D AF Schenck, FJ Podhorniak, LV Hobbs, J Casanova, J Donoghue, D TI Liquid chromatographic determination of N-methyl carbamate pesticide residues at low parts-per-billion levels in eggs SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID YOLKS; DRUG; POULTRY; AMPICILLIN; CLEANUP; FEED AB A reversed-phase liquid chromatographic (LC) method is presented for the analysis of N-methyl carbamate pesticide residues and piperonyl butoxide in eggs at levels as low as 2 mu g/kg (ppb). The study was undertaken to provide data for dietary exposure estimates used in risk analysis. The method uses an acetonitrile extraction followed by liquid-liquid partitioning and normal-phase aminopropyl solid-phase extraction column cleanup. Determination of residues is by reversed-phase LC with an inline postcolumn reaction followed by fluorescence detection. The average recoveries of 21 fortified (most at 2.0 and 20.0 ppb) N-methyl carbarnate pesticide residues and the carbarnate metabolite 1-naphthol from eggs ranged from 70 to 107%. Recoveries of the pesticide synergist piperonyl butoxide ranged from 63 to 106%. Single-comb White Leghorn hens were treated with the carbarnate carbaryl, and the eggs subsequently produced were analyzed for carbaryl and 1-naphthol residues. C1 US FDA, SE Reg Lab, Atlanta, GA 30309 USA. US EPA, Off Pesticide Programs, Ft George G Meade, MD 20755 USA. Univ Arkansas, Dept Poultry Sci, Fayetteville, AR 72701 USA. RP Schenck, FJ (reprint author), US FDA, SE Reg Lab, 60 8th St NE, Atlanta, GA 30309 USA. EM fschenck@ora.fda.gov NR 18 TC 3 Z9 4 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 JAN-FEB PY 2006 VL 89 IS 1 BP 196 EP 200 PG 5 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 010GJ UT WOS:000235175000031 PM 16512248 ER PT J AU Hungerford, JM AF Hungerford, JM TI Committee on natural toxins and food allergens - Marine and freshwater toxins SO JOURNAL OF AOAC INTERNATIONAL LA English DT Review ID TANDEM MASS-SPECTROMETRY; ANABAENA-FLOS-AQUAE; PARALYTIC SHELLFISH TOXINS; PERFORMANCE LIQUID-CHROMATOGRAPHY; BLUE-GREEN-ALGAE; PROPOSED AZASPIRACID-1 STRUCTURE; COLLISION-INDUCED DISSOCIATION; FLUOROMETRIC MICROPLATE ASSAY; PHOSPHATASE INHIBITION ASSAY; OYSTER CRASSOSTREA-VIRGINICA C1 US FDA, Seafood Prod Res Ctr, Bothell, WA 98021 USA. RP Hungerford, JM (reprint author), US FDA, Seafood Prod Res Ctr, 22201 23rd Dr SE, Bothell, WA 98021 USA. EM james.Hungerford@fda.gov NR 228 TC 12 Z9 15 U1 0 U2 8 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD JAN-FEB PY 2006 VL 89 IS 1 BP 248 EP 269 PG 22 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 010GJ UT WOS:000235175000039 PM 16512256 ER PT J AU Trucksess, MW AF Trucksess, MW TI Mycotoxins SO JOURNAL OF AOAC INTERNATIONAL LA English DT Review ID TANDEM MASS-SPECTROMETRY; PERFORMANCE LIQUID-CHROMATOGRAPHY; IMMUNOAFFINITY COLUMN CLEANUP; THIN-LAYER-CHROMATOGRAPHY; CORN-BASED PRODUCTS; OCHRATOXIN-A; AFLATOXIN B-1; B TRICHOTHECENES; ASPERGILLUS-FLAVUS; FUMONISIN B-1 C1 US FDA, College Pk, MD 20740 USA. RP Trucksess, MW (reprint author), US FDA, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM mtruckse@cfsan.fda.gov NR 193 TC 9 Z9 9 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 JAN-FEB PY 2006 VL 89 IS 1 BP 270 EP 284 PG 15 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 010GJ UT WOS:000235175000040 PM 16512257 ER PT J AU Andrews, WH Hammack, TS AF Andrews, WH Hammack, TS TI Committee on microbiology and extraneous materials - Food microbiology, nondairy SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article C1 US FDA, College Pk, MD 20740 USA. RP Andrews, WH (reprint author), US FDA, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM wallace.andrews@cfsan.fda.gov; thomas.hammack@cfsan.fda.gov NR 8 TC 0 Z9 0 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 JAN-FEB PY 2006 VL 89 IS 1 BP 304 EP 318 PG 15 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 010GJ UT WOS:000235175000045 PM 16512262 ER PT J AU Ge, B Girard, W Zhao, S Friedman, S Gaines, SA Meng, J AF Ge, B Girard, W Zhao, S Friedman, S Gaines, SA Meng, J TI Genotyping of Campylobacter spp. from retail meats by pulsed-field gel electrophoresis and ribotyping SO JOURNAL OF APPLIED MICROBIOLOGY LA English DT Article DE Campylobacter; genotyping; pulsed-field gel electrophoresis; retail meat; ribotyping ID FRAGMENT-LENGTH-POLYMORPHISM; JEJUNI GENOTYPES; IN-VITRO; POULTRY; COLI; HUMANS; RECOMBINATION; STRAINS; CHICKEN; INFECTIONS AB Aims: To determine the genetic relatedness of Campylobacter spp. from retail meat products, and compare the discriminatory power of pulsed-field gel electrophoresis (PFGE) and automatic ribotyping. Methods and Results: A total of 378 Campylobacter isolates recovered from 159 raw meats (130 chicken, 25 turkey, three pork and one beef) sampled from 50 retail grocery stores of four supermarket chains in the Maryland suburban area from August 1999 to July 2000 were analysed by PFGE with SmaI, 120 isolates of which were also characterized by ribotyping with PstI using RiboPrinter (R) system. A total of 148 unique PFGE patterns were identified, 91 of which were present in multiple Campylobacter isolates and 24 in multiple meat samples. Nineteen Campylobacter clones with identical PFGE patterns recurred frequently (up to nine times) throughout the sampling period. Comparing ribotyping with PFGE, we identified 44 PFGE patterns and 22 RiboGroups among the 120 isolates tested. Multiple PFGE patterns within one RiboGroup were commonly observed, as well as multiple RiboGroups within one PFGE pattern. Conclusions: Although Campylobacter present in retail meats were genetically diverse, certain clones persisted in poultry meats. PFGE had a greater discriminatory power than ribotyping, and the two methods were complementary in genotyping Campylobacter. Significance and Impact of the Study: Genomic DNA fingerprinting of Campylobacter confirmed diverse and recurrent Campylobacter clones in the retail meats, which provides additional data for a better understanding of the epidemiological aspect of Campylobacter infection. C1 Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA. Louisiana State Univ, Dept Food Sci, Baton Rouge, LA 70803 USA. US FDA, Ctr Vet Med, Div Anim & Food Microbiol, Res Off, Laurel, MD USA. RP Meng, J (reprint author), Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA. EM jmeng@umd.edu NR 42 TC 23 Z9 24 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1364-5072 J9 J APPL MICROBIOL JI J. Appl. Microbiol. PD JAN PY 2006 VL 100 IS 1 BP 175 EP 184 DI 10.1111/j.1365-2672.2005.02750.x PG 10 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 001IT UT WOS:000234527500019 PM 16405698 ER PT J AU Hedayat, AS Yan, X Lin, L AF Hedayat, AS Yan, X Lin, L TI Optimal designs in stability studies SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Article DE bracketing design; drug development; fractional factorial; information matrix; matrix design; optimality criterion; power; shelf life; stability studies AB New optimality criteria for stability studies are proposed, and the related optimal designs are investigated. For each optimality criterion, optimal designs are identified within a class of competing designs. The property of the optimal designs for detecting slope differences is discussed. C1 US FDA, Rockville, MD 20850 USA. Univ Illinois, Dept Math Stat & Comp Sci, Chicago, IL 60680 USA. Baxter Healthcare Inc, Round Lake, IL USA. RP Yan, X (reprint author), US FDA, 1350 Piccard Dr HFZ 550, Rockville, MD 20850 USA. EM xxy@cdrh.fda.gov FU NCCIH NIH HHS [P50-AT00155] NR 13 TC 2 Z9 2 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1054-3406 J9 J BIOPHARM STAT JI J. Biopharm. Stat. PD JAN-FEB PY 2006 VL 16 IS 1 BP 35 EP 59 DI 10.1080/10543400500406512 PG 25 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 024YW UT WOS:000236233500004 PM 16440836 ER PT J AU Holford, NHG Gobburu, JVS AF Holford, NHG Gobburu, JVS TI Untitled - Authors' reply SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Letter C1 Univ Auckland, Auckland 1, New Zealand. US FDA, Rockville, MD 20852 USA. RP Holford, NHG (reprint author), Univ Auckland, Auckland 1, New Zealand. OI Holford, Nick/0000-0002-4031-2514 NR 1 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1054-3406 J9 J BIOPHARM STAT JI J. Biopharm. Stat. PD JAN-FEB PY 2006 VL 16 IS 1 BP 125 EP 126 DI 10.1080/10543400500406629 PG 2 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 024YW UT WOS:000236233500010 ER PT J AU Finkelman, MA Lempitski, SJ Slater, JE AF Finkelman, Malcolm A. Lempitski, Steven J. Slater, Jay E. TI beta-Glucans in standardized allergen extracts SO JOURNAL OF ENDOTOXIN RESEARCH LA English DT Article DE beta-glucan; endotoxin; allergen immunotherapy; allergen extracts; allergen standardization ID GRASS-POLLEN IMMUNOTHERAPY; COAGULATION FACTOR-G; IN-HOUSE DUST; CYTOKINE PRODUCTION; MEMBRANE FILTERS; HAY-FEVER; ENDOTOXIN; (1->3)-BETA-D-GLUCAN; ANTIBODIES; ASTHMA AB Background: Allergen extracts contain variable quantities of bacterial endotoxin. Recent studies have suggested that (1 -> 3)-beta-D-glucans (beta-glucans), also microbial cell wall components, may have adjuvant properties that could affect allergen immunotherapy. Objective: To determine the quantities of beta-glucans in standardized allergen extracts. Materials and Methods: Ninety-four lots of 13 standardized allergen extracts were tested for P-glucan content by Glucatell assay, and for endotoxin content by a specific, chromogenic formulation of the Limulus amebocyte lysate test. Results: Standardized allergen extracts contain variable quantities of endotoxins and beta-glucans. As in our previous work, endotoxin activity was greatest in cat pelt and Dermatophagoides farinae, and least in the pollens. There was no correlation between endotoxin and P-glucan levels (r = 0.1887; P = 0.07). beta-Glucan content was highest for grass pollen (median content, 10.6 ng/ml; range, 0.4-41.8 ng/ml), ragweed pollen (32.9 ng/n-d; range, 6.5-41.2 ng/ml), and cat pelt (25.5 ng/ml; range, 16.7-41.1 ng/ml), and lowest for cat hair (4.9 ng/ml; range, 1.2-10.3 ng/ml), D. farinae (1.2 ng/ml; range, 0.4-5.2 ng/ml) and Dermatophagoides pteronyssinus (1.8 ng/ml; range, 0.4-6.7 ng/ml). Conclusions: beta-Glucans are present in standardized allergen extracts. The effects of these quantities of beta-glucans on allergen immunotherapy and allergen skin testing require further study. C1 US FDA, CBER, Rockville, MD 20852 USA. Associates Cape Cod Inc, E Falmouth, MA USA. RP Slater, JE (reprint author), US FDA, CBER, HFM 422,1401 Rockville Pike, Rockville, MD 20852 USA. EM jay.slater@fda.hhs.gov NR 46 TC 12 Z9 14 U1 0 U2 2 PU MANEY PUBLISHING PI LEEDS PA HUDSON RD, LEEDS LS9 7DL, ENGLAND SN 0968-0519 J9 J ENDOTOXIN RES JI J. Endoxtin Res. PY 2006 VL 12 IS 4 BP 241 EP 245 DI 10.1179/096805106X102237 PG 5 WC Biochemistry & Molecular Biology; Immunology; Medicine, Research & Experimental; Microbiology SC Biochemistry & Molecular Biology; Immunology; Research & Experimental Medicine; Microbiology GA 077IL UT WOS:000240022400005 PM 16953976 ER PT J AU Boudreau, MD Beland, FA AF Boudreau, MD Beland, FA TI An evaluation of the biological and toxicological properties of Aloe barbadensis (Miller), Aloe vera SO JOURNAL OF ENVIRONMENTAL SCIENCE AND HEALTH PART C-ENVIRONMENTAL CARCINOGENESIS & ECOTOXICOLOGY REVIEWS LA English DT Review DE acemannan; Aloe vera; Aloe vera gel; Aloe vera latex; anthraquinone; polymannans; toxicological effects ID MACROPHAGE CELL-LINE; RADIATION-INDUCED SUPPRESSION; PERIPHERAL DEFENSE STRATEGY; EMODIN-INDUCED APOPTOSIS; NITRIC-OXIDE PRODUCTION; INDUCED SKIN TOXICITY; SUCCULENT LEAF PARTS; IN-VITRO; ULTRAVIOLET-RADIATION; ALOCTIN-A AB Aloe barbadensis (Miller), Aloe vera, has a long history of use as a topical and oral therapeutic. The plant is the source of two products, gel and latex, which are obtained from its fleshy leaves. Aloe vera products contain multiple constituents with potential biological and toxicological activities, yet the active components elude definition. Ingestion of Aloe vera is associated with diarrhea, electrolyte imbalance, kidney dysfunction, and conventional drug interactions; episodes of contact dermatitis, erythema, and phototoxicity have been reported from topical applications. This review examines the botany, physical and chemical properties, and biological activities of the Aloe vera plant. C1 Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Boudreau, MD (reprint author), Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM mary.boudreau@fda.hhs.gov FU PHS HHS [224-93-0001] NR 254 TC 134 Z9 140 U1 8 U2 57 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1059-0501 J9 J ENVIRON SCI HEAL C JI J. Environ. Sci. Health Pt. C-Environ. Carcinog. Ecotoxicol. Rev. PD JAN-JUN PY 2006 VL 24 IS 1 BP 103 EP 154 DI 10.1080/10590500600614303 PG 52 WC Oncology; Environmental Sciences; Toxicology SC Oncology; Environmental Sciences & Ecology; Toxicology GA 041TN UT WOS:000237478900002 PM 16690538 ER PT J AU Myers, MJ Yancy, HF Araneta, M Armour, J Derr, J Hoostelaere, LAD Farmer, D Jackson, F Kiessling, WM Koch, H Lin, HH Liu, Y Mowlds, G Pinero, D Riter, KL Sedwick, J Shen, YL Wetherington, J Younkins, R AF Myers, MJ Yancy, HF Araneta, M Armour, J Derr, J Hoostelaere, LAD Farmer, D Jackson, F Kiessling, WM Koch, H Lin, HH Liu, Y Mowlds, G Pinero, D Riter, KL Sedwick, J Shen, YL Wetherington, J Younkins, R TI Validation of a PCR-based method for the detection of various rendered materials in feedstuffs using a forensic DNA extraction kit SO JOURNAL OF FOOD PROTECTION LA English DT Article ID BOVINE-DERIVED MATERIALS AB A method trial was initiated to validate the use of a commercial DNA forensic kit to extract DNA from animal feed as part of a PCR-based method. Four different PCR primer pairs (one bovine pair, one porcine pair, one ovine primer pair, and one multispecies pair) were also evaluated. Each laboratory was required to analyze a total of 120 dairy feed samples either not fortified (control, true negative) or fortified with bovine meat and bone meal, porcine meat and bone meal (PMBM), or lamb meal. Feeds were fortified with the animal meals at a concentration of 0.1% (wt/wt). Ten laboratories participated in this trial, and each laboratory was required to evaluate two different primer pairs, i.e., each PCR primer pair was evaluated by five different laboratories. The method was considered to be validated for a given animal source when three or more laboratories achieved at least 97% accuracy (29 correct of 30 samples for 96.7% accuracy, rounded up to 97%) in detecting the fortified samples for that source. Using this criterion, the method was validated for the bovine primer because three laboratories met the criterion, with an average accuracy of 98.9%. The average false-positive rate was 3.0% in these laboratories. A fourth laboratory was 80% accurate in identifying the samples fortified with bovine meat and bone meal. A fifth laboratory was not able to consistently extract the DNA from the feed samples and did not achieve the criterion for accuracy for either the bovine or multispecies PCR primers. For the porcine primers, the method was validated, with four laboratories meeting the criterion for accuracy with an average accuracy of 99.2%. The fifth laboratory had a 93.3% accuracy outcome for the porcine primer. Collectively, these five laboratories had a 1.3% false-positive rate for the porcine primer. No laboratory was able to meet the criterion for accuracy with the ovine primers, most likely because of problems with the synthesis of the primer pair; none of the positive control DNA samples could be detected with the ovine primers. The multispecies primer pair was validated in three laboratories for use with bovine meat and bone meal and lamb meal but not with PMBM. The three laboratories had an average accuracy of 98.9% for bovine meat and bone meal, 97.8% for lamb meal, and 63.3% for PMBM. When examined on an individual laboratory basis, one of these four laboratories could not identify a single feed sample containing PMBM by using the multispecies primer, whereas the other laboratory identified only one PMBM-fortified sample, suggesting that the limit of detection for PMBM with this primer pair is around 0.1% (wt/wt). The results of this study demonstrated that the DNA forensic kit can be used to extract DNA from animal feed, which can then be used for PCR analysis to detect animal-derived protein present in the feed sample. C1 US FDA, Ctr Vet Med, Laurel, MD 20708 USA. US FDA, Off Regulatory Affairs, Pacific Reg Lab SW, Irvine, CA 92612 USA. Canadian Food Inspect Agcy, Ottawa, ON K1A 0C6, Canada. US FDA, Ctr Vet Med, Rockville, MD 20855 USA. US FDA, Off Regulatory Affairs, Div Field Sci, Rockville, MD 20857 USA. US FDA, Off Regulatory Affairs, Denver Reg Lab, Denver, CO 80225 USA. US FDA, Off Regulatory Affairs, Arkansas Reg Lab, Jefferson, AR 72079 USA. US FDA, Off Regulatory Affairs, NE Reg Lab, Jamaica, NY 11433 USA. Off Indiana State Chemist, W Lafayette, IN 47907 USA. Florida State Dept Agr, Tallahassee, FL 32399 USA. US FDA, Off Regulatory Affairs, Pacific Reg Lab NW, Bothell, WA 98021 USA. Eurofins Sci Inc, Des Moines, IA 50313 USA. US FDA, Off Regulatory Affairs, SE Reg Lab, Atlanta, GA 30309 USA. RP Myers, MJ (reprint author), US FDA, Ctr Vet Med, Laurel, MD 20708 USA. EM mmyers@cvm.fda.gov NR 9 TC 15 Z9 15 U1 0 U2 2 PU INT ASSOC FOOD PROTECTION PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD JAN PY 2006 VL 69 IS 1 BP 205 EP 210 PG 6 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 000VG UT WOS:000234489900029 PM 16416920 ER PT J AU Vij, V Ailes, E Wolyniak, C Angulo, FJ Klontz, KC AF Vij, V Ailes, E Wolyniak, C Angulo, FJ Klontz, KC TI Recalls of spices due to bacterial contamination monitored by the US Food and Drug Administration: The predominance of salmonellae SO JOURNAL OF FOOD PROTECTION LA English DT Article ID MICROBIOLOGICAL SURVEY; HERBS AB From 1980 to 2000, the annual per capita consumption of spices in the United States increased by 60% (from 1.0 to 1.6 kg per person per year). Although spices are known to harbor various molds, fungi, and bacteria, relatively few reports have documented this group of foods as the cause of human illness. In recent years, however, the U.S. Food and Drug Administration (FDA) has noted an increased number of recalls of dried spices due to bacterial contamination. Accordingly, we reviewed spice recalls that took place in the United States from fiscal years 1970 to 2003. During the study period, the FDA monitored 21 recalls involving 12 spice types contaminated with bacterial pathogens; in all but one instance, the recalled spices contained Salmonella. Paprika was the spice most often involved in the recalls. A wide variety of countries were the source of the recalled spices. Using data from the Centers for Disease Control and Prevention National Salmonella Surveillance System, we were unable to discern any increases in the reported incidence of laboratory-confirmed salmonellosis in states that received spices contaminated with selected rare Salmonella serotypes. A variety of effective methods exist to disinfect spices, procedures that have attained increased importance given the frequent use of spices in ready-to-eat foods and the potential for contaminated spices to cause widespread outbreaks. C1 US FDA, Ctr Food Safety & Appl Nutr, Bethesda, MD 20814 USA. Atlanta Res & Educ Fdn, Atlanta, GA 30333 USA. Ctr Dis Control & Prevent, Foodborne & Diarrheal Dis Branch, Atlanta, GA 30333 USA. George Washington Univ, Sch Publ Hlth & Hlth Serv, Washington, DC 20052 USA. RP Klontz, KC (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Bethesda, MD 20814 USA. EM karl.klontz@cfsan.fda.gov NR 15 TC 30 Z9 32 U1 0 U2 15 PU INT ASSOC FOOD PROTECTION PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD JAN PY 2006 VL 69 IS 1 BP 233 EP 237 PG 5 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 000VG UT WOS:000234489900035 PM 16416926 ER PT J AU Maximova, OA Taffs, RE Pomeroy, KL Piccardo, P Asher, DM AF Maximova, OA Taffs, RE Pomeroy, KL Piccardo, P Asher, DM TI Computerized morphometric analysis of pathological prion protein deposition in scrapie-infected hamster brain SO JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY LA English DT Article DE digital imaging; hue-saturation-intensity; immunohistochemistry; morphometry; prion disease; scrapie prion protein; transmissible spongiform encephalopathy ID CREUTZFELDT-JAKOB-DISEASE; IMAGE-ANALYSIS; SPONGIFORM ENCEPHALOPATHY; QUANTIFICATION; IMMUNOHISTOCHEMISTRY; EXPRESSION; MICROSCOPY; LESIONS; MODEL; DEER AB Transmissible spongiform encephalopathies (TSEs or prion diseases) are characterized by a constellation of typical though variable pathological changes in the brain. Deposition of disease-associated abnormal prion protein (PrPSc) is the pathological feature of TSEs most consistent and accessible for quantification. However, the evaluation of PrPSc deposits detected by immunohistochemical techniques has been traditionally based on arbitrarily assigned semiquantitative scores. This approach is limited by its subjectivity and bias, yielding considerable variability. In this study, we used MetaMorph 6.1 image analysis software for quantitative analysis of immunostained PrPSc deposits in the CNS of hamsters infected with the 263K strain of scrapie agent. Computerized morphometric analysis (CMA) allowed unambiguous detection of even minimal amounts of immunostained PrPSc. CMA values for intensity of staining and area stained correlated well with semiquantitative scores, providing reproducible quantitative data and objective criteria for analyzing PrPSc deposition. CMA provides a simple and reliable method for improved and consistent diagnosis of TSEs that may also be used to quantify other immunostained biomarkers. C1 US FDA, Lab Bacterial Parasit & Unconvent Agents, Div Emerging & Transfus Transmitted Dis, Off Blood Res & Rev,Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Maximova, OA (reprint author), US FDA, Lab Bacterial Parasit & Unconvent Agents, Div Emerging & Transfus Transmitted Dis, Off Blood Res & Rev,Ctr Biol Evaluat & Res, 1401 Rockville Pike,HFM-313, Rockville, MD 20852 USA. EM maximova@cber.fda.gov NR 36 TC 20 Z9 22 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 JAN PY 2006 VL 54 IS 1 BP 97 EP 107 DI 10.1369/jhc.5A6758.2005 PG 11 WC Cell Biology SC Cell Biology GA 998WZ UT WOS:000234351900012 PM 16148313 ER PT J AU Epstein, SL AF Epstein, SL TI Prior H1N1 influenza infection and susceptibility of Cleveland Family Study participants during the H2N2 pandemic of 1957: An experiment of nature SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT Experimental Biology 2004 Annual Meeting CY APR 17-21, 2004 CL Washington, DC ID A-VIRUS; HETEROTYPIC IMMUNITY; HOUSEHOLD CONTACTS; PROTECTION; VACCINATION; ANTIBODY; CHILDREN; ILLNESS; CD4(+); CD8(+) AB During a pandemic, influenza vaccines that rely on neutralizing antibodies to protect against matched viruses might not be available early enough. Much broader (heterosubtypic) immune protection is seen in animals. Do humans also have cross-subtype immunity? To investigate this issue, archival records from the Cleveland Family Study, which was conducted before and during the 1957 pandemic (during which a shift from subtype H1N1 to H2N2 occurred), were analyzed. Only 5.6% of the adults who had had symptomatic influenza A in earlier study years developed influenza during the pandemic, despite living in households with participants who had influenza. In contrast, 55.2% of the children who had had symptomatic influenza A contracted it again. These findings suggest an impact of accumulated heterosubtypic immunity during a pandemic. Such immunity, as well as its implications for vaccination, should be further investigated. C1 US FDA, Lab Immunol & Dev Biol, Div Cellular & Gene Therapies, Off Cellular Tissue & Gene Therapies,Ctr Biol Eva, Rockville, MD 20857 USA. RP Epstein, SL (reprint author), US FDA, OCTGT, CBER, DCGT, 1401 Rockville Pike,HFM-730, Rockville, MD 20852 USA. EM epsteins@cber.fda.gov NR 23 TC 200 Z9 205 U1 1 U2 7 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 JAN 1 PY 2006 VL 193 IS 1 BP 49 EP 53 DI 10.1086/498980 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 996OF UT WOS:000234182800009 PM 16323131 ER PT J AU Sabharwal, H Michon, F Nelson, D Dong, WL Fuchs, K Manjarrez, RC Sarkar, A Uitz, C Viteri-Jackson, A Suarez, RSR Blake, M Zabriskie, JB AF Sabharwal, H Michon, F Nelson, D Dong, WL Fuchs, K Manjarrez, RC Sarkar, A Uitz, C Viteri-Jackson, A Suarez, RSR Blake, M Zabriskie, JB TI Group A streptococcus (GAS) carbohydrate as an immunogen for protection against GAS infection SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID BETA-D-GLUCOSAMINE; ANTIBODY-RESPONSE; M-PROTEIN; POLYSACCHARIDE; COLONIZATION; PEPTIDES; MIMICRY; ENZYME; SITES; MICE AB Previous studies have shown that human serum containing anti-group A streptococcus carbohydrate ( GAS CHO) antibodies were opsonic for different M protein-carrying serotypes. To investigate the role that anti GAS CHO antibodies play in passive and active protection, mice were immunized subcutaneously or intranasally with GAS CHO conjugated to tetanus toxoid, and mortality and oral colonization were monitored after challenge with live GAS. Compared with control mice, immunized mice were significantly protected against systemic or nasal challenge with GAS. Furthermore, studies of serum samples and throat cultures from Mexican children revealed an inverse relationship between high serum titers of anti-GAS CHO antibodies and the presence of GAS in the throat. Anti-GAS CHO antibodies were also tested for cross-reactivity with human tissues and cytoskeletal proteins. No cross-reactivity was observed in either assay. The present study demonstrates that GAS CHO is both immunogenic and protective against GAS infections. C1 Hosp Special Surg, Div Res, New York, NY 10021 USA. Rockefeller Univ, Lab Clin Microbiol & Immunol, New York, NY 10021 USA. Rockefeller Univ, Lab Microbial Pathogenesis & Immunol, New York, NY 10021 USA. US FDA, Div Bacterial Parasit & Allergen Prod, Lab Bacterial Polysaccharides, Rockville, MD 20857 USA. BioVeris Corp, Gaithersburg, MD USA. Hosp Infantil Mexico Dr Federico Gomez, Dept Internal Med, Mexico City, DF, Mexico. Secretary Hlth, Natl Ctr Hlth Infants & Adolescents, Mexico City, DF, Mexico. RP Sabharwal, H (reprint author), Hosp Special Surg, Div Res, 541 E 71st St, New York, NY 10021 USA. EM sabharwalh@hss.edu RI Nelson, Daniel/I-2198-2012 FU NCRR NIH HHS [C06-RR12538-01] NR 20 TC 45 Z9 47 U1 0 U2 7 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 JAN 1 PY 2006 VL 193 IS 1 BP 129 EP 135 DI 10.1086/498618 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 996OF UT WOS:000234182800019 PM 16323141 ER PT J AU Lee, S Hu, JJ Tang, SX Wood, O Francis, K Machuca, A Rios, M Daniel, S Vockley, C Awazi, B Zekeng, L Hewlett, I AF Lee, Sherwin Hu, Jinjie Tang, Shixing Wood, Owen Francis, Kori Machuca, Ana Rios, Maria Daniel, Sylvester Vockley, Christopher Awazi, Bih Zekeng, Leopold Hewlett, Indira TI Evaluation of FDA licensed HIV assays using plasma from Cameroonian blood donors SO JOURNAL OF MEDICAL VIROLOGY LA English DT Article; Proceedings Paper CT Symposium on HIV Variants and Hepatitis B Virus Surface Antigen (HBsAg) Mutants CY MAY 22-24, 2005 CL Washington, DC SP Abbott Lab DE HIV-1 RNA; NAT; HIV antibodies detection AB Several diagnostic assays for the detection of HIV infection have been approved and licensed by the FDA for blood donor screening. However, the performance of these assays is unknown when testing genetically divergent blood specimens. To evaluate the performance of these assays with diverse HIV strains, we chose to study specimens collected from blood donors in Cameroon where genetic diversity and recombinant variants are prevalent. In this study, we tested 240 human plasma specimens collected from two blood centers in Cameroon. These samples were screened initially in Cameroon for antibody to HIV using a rapid assay. We also performed sequencing to determine subtype. Our evaluation has demonstrated that HIV infection in most HIV plasma samples could be detected by most of the US FDA licensed diagnostic assays. With the exception of a few specimens, HIV-1 p24 antigen was not detected in any of the samples. In addition, some nucleic acid tests (NAT) assays were not able to detect a few serologic reactive samples and all new variants including some CRF02_AG variants. C1 US FDA, Ctr Biol Evaluat & Res, Mol Virol Lab, Div Emerging & Transfus Transmitted Dis, Bethesda, MD 20892 USA. RP Hewlett, I (reprint author), US FDA, Ctr Biol Evaluat & Res, Mol Virol Lab, Div Emerging & Transfus Transmitted Dis, Bldg 29B,Rm 4E16,8800 Rockville Pike, Bethesda, MD 20892 USA. EM hewlett@cber.fda.gov NR 6 TC 5 Z9 5 U1 0 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0146-6615 J9 J MED VIROL JI J. Med. Virol. PY 2006 VL 78 SU 1 BP S22 EP S23 DI 10.1002/jmv.20602 PG 2 WC Virology SC Virology GA 061DX UT WOS:000238852500006 PM 16622873 ER PT J AU Tabor, E AF Tabor, Edward TI Infections by hepatitis B surface antigen gene mutants in Europe and North America SO JOURNAL OF MEDICAL VIROLOGY LA English DT Article; Proceedings Paper CT Symposium on HIV Variants and Hepatitis B Virus Surface Antigen (HBsAg) Mutants CY MAY 22-24, 2005 CL Washington, DC SP Abbott Lab DE hepatitis B virus; mutant; S gene ID LIVER-TRANSPLANT RECIPIENTS; IMMUNE GLOBULIN PROPHYLAXIS; VIRUS MUTANTS; BLOOD-DONOR; S GENE; HBSAG; VACCINATION; POLYMERASE; MUTATIONS; EFFICACY AB Hepatitis B virus (HBV) mutants have usually been studied in patients in Asia because of the wider use of HBV immunization there and the resultant emergence of viral mutants. Nevertheless, HBV surface antigen (S) gene mutants also are found in Europe and North America. In Europe and North America, HBV with mutations in the portion of the S gene coding the "a" determinant of the hepatitis B surface antigen (HBsAg) have been documented in small numbers of infants born to HBV-infected mothers following post-natal HBV vaccine and hepatitis B immune globulin (HBIG) prophylaxis and in many liver transplant recipients who develop HBV re-infection despite HBIG prophylaxis. In some cases, these mutations have included a glycine to arginine substitution at position 145 (G145R), which results in a conformational change and different reactivity to monoclonal antibody reagents than that of the wild-type virus. Mutations in the a determinant (but not G145R) also have been reported in European patients with chronic HBV infection who have not received HBV vaccine or HBIG. However, it appears that such mutations are only responsible for a small proportion of "occult" or "silent" HBV infections, which are characterized by the presence of HBV DNA in serum in the absence of detectable HBsAg. However, some of these mutant forms of HBV in cases of occult HBV may theoretically escape detection and could present a risk to blood safety. C1 US FDA, Off Blood Res & Review, Rockville, MD 20857 USA. RP Tabor, E (reprint author), Quintiles Inc, 1801 Rockville Pike,Suite 300, Rockville, MD 20852 USA. EM edward.tabor@quintiles.com NR 24 TC 36 Z9 41 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0146-6615 J9 J MED VIROL JI J. Med. Virol. PY 2006 VL 78 SU 1 BP S43 EP S47 DI 10.1002/jmv.20606 PG 5 WC Virology SC Virology GA 061DX UT WOS:000238852500010 PM 16622882 ER PT J AU Reeves, JB Delwiche, SR Reeves, VB AF Reeves, J. B., III Delwiche, S. R. Reeves, V. B. TI Least squares means multiple comparison testing of reference versus predicted residuals for evaluation of partial least squares spectral calibrations SO JOURNAL OF NEAR INFRARED SPECTROSCOPY LA English DT Article DE least squares means multiple comparison testing; partial least squares spectral calibrations; ANOVA; pre-treatment; near infrared ID SPECTROSCOPIC ANALYSIS; REFLECTANCE SPECTRA; REGRESSION; PRODUCTS; FORAGES; LIGNIN AB It is common to use data pre-treatments such as scatter correction, derivatives, mean centring and variance scaling prior to the development of near- and mid-infrared spectral calibrations. As a result, it is possible to generate a multitude of calibrations, many of which will have similar statistical properties, as measured by the coefficient of determination (RI) and the residual error. With respect to validation data sets, calibration equations have a tendency to provide the most optimistic modelling statistics on the set of data to which they were developed; however, the pre-treatment that was optimal for one set of samples may not be the best for future samples and, therefore, not the most robust calibration. If several calibrations are found to be statistically the same, then other criteria could be used to determine which one to use (for example, one with fewest partial least squares (PLS) factors or based on past experience) or further investigations could be carried out on the more limited set of calibrations deemed to represent the best of all those originally developed. However, there has been no single accepted statistical procedure for determining which calibrations are statistically the same and which are not from a large group of calibrations. This study describes the use of least squares means multiple comparisons testing of squared reference-versus-predicted residuals for determining the statistical similarity of multiple PLS calibrations. A program has been developed using common commercial statistical software (SAS, Mixed procedure) which computes and summarises comparisons of PLS calibrations. This method is also applicable to other multivariate regression methods as it only requires a list of reference and predicted values from each calibration as input. C1 USDA, ARS, Beltsville Agr Res Ctr, Environm Management & ByProd Utilizat Lab, Beltsville, MD 20705 USA. USDA, ARS, Instrumentat & Sensing Lab, Beltsville, MD 20705 USA. US FDA, CVM, US Dept HHS, Rockville, MD 20855 USA. RP Reeves, JB (reprint author), USDA, ARS, Beltsville Agr Res Ctr, Environm Management & ByProd Utilizat Lab, Bldg 306,BARC E, Beltsville, MD 20705 USA. NR 16 TC 1 Z9 1 U1 1 U2 2 PU N I R PUBLICATIONS PI CHICHESTER PA 6 CHARLTON MILL, CHARLTON, CHICHESTER PO18 0HY, WEST SUSSEX, ENGLAND SN 0967-0335 J9 J NEAR INFRARED SPEC JI J. Near Infrared Spectrosc. PY 2006 VL 14 IS 6 BP 371 EP 377 PG 7 WC Chemistry, Applied; Spectroscopy SC Chemistry; Spectroscopy GA 127LC UT WOS:000243586400005 ER PT J AU Ovanesov, MV Sauder, C Rubin, SA Nath, A Carbone, KM Pletnikov, MV AF Ovanesov, Mikhail V. Sauder, Christian Rubin, Steven A. Nath, Avindra Carbone, Kathryn M. Pletnikov, Mikhail V. TI Borna disease virus infection does not induce activation of microglia in vitro SO JOURNAL OF NEUROVIROLOGY LA English DT Meeting Abstract CT 7th International Symposium on NeuroVirology CY MAY 31-JUN 03, 2006 CL Philadelphia, PA SP NIMH, NINDS, NIDA, Drexel Univ Coll Med, Inst Mol Med Infect Dis, Drexel Univ, Dept Microbiol Immunology, Office Dean, Temple Univ Sch Med, Sbarro Inst Canc Res & Mol Med, Natl Multiple Sclerosis Soc, Journal NeuroVirology C1 Johns Hopkins Univ, Div Neurobiol, Dept Psychiat & Behav Sci, Baltimore, MD USA. US FDA, CBER, Bethesda, MD USA. Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21218 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 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PY 2006 VL 12 SU 1 MA P149 BP 64 EP 64 PG 1 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA 059US UT WOS:000238758300150 ER PT J AU Kalantzi, L Reppas, C Dressman, JB Amidon, GL Junginger, HE Midha, KK Shah, VP Stavchansky, SA Barends, DM AF Kalantzi, L Reppas, C Dressman, JB Amidon, GL Junginger, HE Midha, KK Shah, VP Stavchansky, SA Barends, DM TI Biowaiver monographs for immediate release solid oral dosage forms: Acetaminophen (Paracetamol) - Commentary SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Editorial Material DE absorption; biopharmaceutics classification system (BCS); acetaminophen; paracetamol; permeability; solubility ID BIOPHARMACEUTICS CLASSIFICATION-SYSTEM; IN-VIVO CORRELATION; BCS LITERATURE DATA; SODIUM-BICARBONATE; HEALTHY-VOLUNTEERS; COMPARATIVE BIOAVAILABILITY; INTRAVENOUS PARACETAMOL; INTESTINAL PERMEABILITY; FASTED VOLUNTEERS; ABSORPTION AB Literature data are reviewed on the properties of acetaminophen (paracetamol) related to the biopharmaceutics classification system (BCS). According to the current BCS criteria, acetaminophen is BCS Class III compound. Differences in composition seldom, if ever, have an effect on the extent of absorption. However, some studies show differences in rate of absorption between brands and formulations. In particular, sodium bicarbonate, present in some drug products, was reported to give an increase in the rate of absorption, probably caused by an effect on gastric emptying. In view of Marketing Authorizations (MAs) given in a number of countries to acetaminophen drug products with rapid onset of action, it is concluded that differences in rate of absorption were considered therapeutically not relevant by the Health Authorities. Moreover, in view of its therapeutic use, its wide therapeutic index and its uncomplicated pharmacokinetic properties, in vitro dissolution data collected according to the relevant Guidances can be safely used for declaring bioequivalence (BE) of two acetaminophen formulations. Therefore, accepting a biowaiver for immediate release (IR) acetaminophen solid oral drug products is considered scientifically justified, if the test product contains only those excipients reported in this paper in their usual amounts and the test product is rapidly dissolving, as well as the test product fulfils the criterion of similarity of dissolution profiles to the reference product. (c) 2005 Wiley-Liss, Inc. C1 Natl Inst Publ Hlth & Environm, RIVM, NL-3720 BA Bilthoven, Netherlands. Natl & Kapodistrian Univ Athens, Sch Pharm, Athens, Greece. Univ Frankfurt, D-6000 Frankfurt, Germany. Univ Michigan, Coll Pharm, Ann Arbor, MI 48109 USA. Leiden Univ, Div Pharmaceut Technol, Leiden Amsterdam Ctr Drug Res, Leiden, Netherlands. Univ Saskatchewan, Saskatoon, SK S7N 0W0, Canada. US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. Univ Texas, Coll Pharm, Div Pharmaceut, Austin, TX 78712 USA. RP Barends, DM (reprint author), Natl Inst Publ Hlth & Environm, RIVM, NL-3720 BA Bilthoven, Netherlands. EM dirk.barends@rivm.nl RI Fachbereich14, Dekanat/C-8553-2015 NR 90 TC 57 Z9 58 U1 2 U2 27 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 JAN PY 2006 VL 95 IS 1 BP 4 EP 14 DI 10.1002/jps.20477 PG 11 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 000FE UT WOS:000234445500004 PM 16307451 ER PT J AU Eydelman, MB Drum, B Holladay, J Hilmantel, G Kezirian, G Durrie, D Stulting, RD Sanders, D Wong, B AF Eydelman, MB Drum, B Holladay, J Hilmantel, G Kezirian, G Durrie, D Stulting, RD Sanders, D Wong, B TI Standardized analyses of correction of astigmatism by laser systems that reshape the cornea SO JOURNAL OF REFRACTIVE SURGERY LA English DT Article ID SURGICALLY INDUCED ASTIGMATISM; INDUCED REFRACTIVE CHANGE; ANTERIOR SEGMENT SURGERY; OCULAR SURGERY; CATARACT; VECTORS; ERROR AB PURPOSE: To develop a minimum set of analyses and a format for presentation of outcomes of astigmatism correction by laser systems that reshape the cornea. METHODS: An Astigmatism Project group was created under the auspices of the American National Standards Institute (ANSI) Z80.11 Working Group on Laser Systems for Corneal Reshaping. The Astigmatism Project Group was made up of experts in astigmatism analyses from academia, government, and industry. An extensive literature review was conducted to identify all currently available methodologies for the evaluation of astigmatic outcomes. Project Group members discussed the utility of each method and its specific parameters for evaluating the effectiveness of astigmatism-correcting devices. They gave consideration to unique terminology and analyses required for evaluation of correction of astigmatism by laser systems that reshape the cornea. RESULTS: The Project Group defined a comprehensive list of analysis variables needed for the evaluation of astigmatism-correcting devices and generated a mathematical definition for each term. They developed a minimum set of analyses needed for evaluation of astigmatism treatments by laser systems that reshape the cornea. They established methods for calculating the refractive error analysis variables and constructed recommended table and graph formats for data presentation. CONCLUSIONS: This article contains the recommendations of the Astigmatism Project Group of the American National Standards Institute. We propose it as a standard reference for astigmatic refractive error analyses for the evaluation of safety and effectiveness of laser systems that reshape the cornea. C1 US FDA, CDRH, DOED, Rockville, MD 20850 USA. Baylor Coll Med, Dept Ophthalmol, Houston, TX 77030 USA. SurgiVis Consultants Inc, Scottsdale, AZ USA. Durrie Vis PA, Overland Pk, KS USA. Emory Univ, Dept Ophthalmol, Atlanta, GA 30322 USA. Univ Illinois, Coll Med, Dept Ophthalmol, Chicago, IL USA. Alcon Labs Inc, Orlando, FL USA. RP Eydelman, MB (reprint author), US FDA, CDRH, DOED, 9200 Corp Blvd HFZ 460, Rockville, MD 20850 USA. EM MALVINA.EYDELMAN@FDA.HHS.GOV OI Holladay, Jack T./0000-0002-4609-5522 NR 19 TC 61 Z9 65 U1 0 U2 1 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 1081-597X J9 J REFRACT SURG JI J. Refractive Surg. PD JAN-FEB PY 2006 VL 22 IS 1 BP 81 EP 95 PG 15 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 005SB UT WOS:000234843000016 PM 16447941 ER PT J AU May, JC Del Grosso, A Etz, N Wheeler, R Rey, L AF May, JC Del Grosso, A Etz, N Wheeler, R Rey, L TI Thermogravimetry and vapor pressure moisture - Applications to determination of residual moisture in BCG vaccine SO JOURNAL OF THERMAL ANALYSIS AND CALORIMETRY LA English DT Article; Proceedings Paper CT 32nd Annual Meeting of the North-American-Thermal-Analysis-Society CY OCT 04-06, 2004 CL Williamsburg, VA SP N Amer Thermal Anal Soc DE BCG vaccine; lyophilization; residual moisture; thermogravimetry AB Thermogravimetry (TG), thermogravimetry/mass spectrometry (TG/MS), and loss-on-drying methodology are used to provide residual moisture results for freeze-dried biological products regulated by the US Food and Drug Administration. Residual moisture specifications must be met in order to ensure freeze-dried biological product potency and stability throughout the licensed product's shelf life. TG, TG/MS, loss-on-drying and vapor pressure moisture measurements are compared for a BCG Vaccine. Comparisons are made between residual moisture data for the freeze-dried cake and vapor pressure moisture determinations in the space above the freeze-dried cake in the final container. Vapor pressure moisture precision data is presented for alpha-interferon and BCG vaccine. Impact of residual moisture and vapor pressure moisture upon product stability is presented. C1 US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. Conseiller Sci, CH-1010 Lausanne, Switzerland. RP May, JC (reprint author), US FDA, Ctr Biol Evaluat & Res, 1401 Rockville Pike, Rockville, MD 20852 USA. EM may@cber.fda.gov NR 9 TC 3 Z9 3 U1 0 U2 3 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1388-6150 J9 J THERM ANAL CALORIM JI J. Therm. Anal. Calorim. PY 2006 VL 83 IS 1 BP 31 EP 33 DI 10.1007/s10973-005-7052-6 PG 3 WC Thermodynamics; Chemistry, Analytical; Chemistry, Physical SC Thermodynamics; Chemistry GA 014BA UT WOS:000235452500006 ER PT J AU Caruso, JA Wuilloud, RG Altamirano, JC Harris, WR AF Caruso, JA Wuilloud, RG Altamirano, JC Harris, WR TI Modeling and separation-detection methods to evaluate the speciation of metals for toxicity assessment SO JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART B-CRITICAL REVIEWS LA English DT Review ID PLASMA-MASS-SPECTROMETRY; PERFORMANCE LIQUID-CHROMATOGRAPHY; ISOTOPE-DILUTION ANALYSIS; HEXAPOLE COLLISION CELL; BIOTIC LIGAND MODEL; ANALYSIS ICP-MS; CAPILLARY-ELECTROPHORESIS; GAS-CHROMATOGRAPHY; HUMAN SERUM; ELEMENTAL SPECIATION AB There is an increasing appreciation for the importance of speciation in the assessment of metal toxicity. In this review, two approaches to speciation are discussed, with an emphasis on their application to biological samples. One approach is the direct separation and detection of metal species of toxicological interest. Various "hyphenated" techniques, consisting of a chromatographic system coupled to inductively coupled plasma-mass spectrometry (ICP-MS), are discussed. The chromatographic strategies employed for separation emphasize liquid chromatography (LC), but the increasing use of gas chromatography (GC) and capillary electrophoresis (CE) in speciation analysis is discussed. The second approach to speciation is the use of computer models to calculate the speciation of a metal ion within a complex mixture of ligands. This approach is applicable to systems in which the metal cation exchanges ligands rapidly, so that the sample represents an equilibrium mixture of metal complexes. These computational models are based on the equilibrium constants for the metal complexes and a series of mass balance equations and give the distribution of metal complexes in the original sample. This approach is illustrated using the speciation of Al(III) in serum as an example. C1 Univ Missouri, Dept Chem & Biochem, St Louis, MO 63121 USA. Univ Cincinnati, Cincinnati, OH USA. US FDA, Cincinnati, OH USA. RP Harris, WR (reprint author), Univ Missouri, Dept Chem & Biochem, St Louis, MO 63121 USA. EM wharris@umsl.edu RI Wuilloud, Rodolfo/N-6821-2014 OI Wuilloud, Rodolfo/0000-0002-2962-7718 NR 120 TC 16 Z9 17 U1 0 U2 12 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1093-7404 J9 J TOXICOL ENV HEAL B JI J. Toxicol. Env. Health-Pt b-Crit. Rev. PD JAN-FEB PY 2006 VL 9 IS 1 BP 41 EP 61 DI 10.1080/15287390500196172 PG 21 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 998AO UT WOS:000234290500003 PM 16393869 ER PT J AU Zhang, H Huang, Q Li, L Wang, Y Ranganathan, G Kern, PA Iannaccone, PM Fan, CY AF Zhang, H Huang, Q Li, L Wang, Y Ranganathan, G Kern, PA Iannaccone, PM Fan, CY TI Transgenic mice overexpressing human 8-oxoguanine DNA glycosylase (hOGG) in mitochondria develop obesity, hepatosteatosis and female infertility SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 95th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY FEB 11-17, 2006 CL Atlanta, GA SP US & Canadian Acad Pathol C1 Univ Arkansas Med Sci, Little Rock, AR 72205 USA. City Hope Natl Med Ctr, Duarte, CA 91010 USA. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Northwestern Univ, Sch Med, Chicago, IL 60611 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2006 VL 86 SU 1 MA 1376 BP 296A EP 296A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 996WY UT WOS:000234207602224 ER PT B AU Lewis, SM Ullrey, DE Barnard, DE Knapka, JJ AF Lewis, Sherry M. Ullrey, Duane E. Barnard, Dennis E. Knapka, Joseph J. BE Suckow, MA Weisbroth, SH Franklin, CL TI Nutrition SO LABORATORY RAT, 2ND EDITION SE American College of Laboratory Animal Medicine Series LA English DT Article; Book Chapter ID COPPER-DEFICIENT RATS; SPONTANEOUSLY HYPERTENSIVE-RATS; FATTY-ACID COMPOSITION; VITAMIN-E REQUIREMENT; DIETARY ZINC-DEFICIENCY; CENTRAL-NERVOUS-SYSTEM; THYROID-HORMONE METABOLISM; CARBOHYDRATE-FREE DIETS; SPRAGUE-DAWLEY RATS; FED VARYING LEVELS C1 [Lewis, Sherry M.] Natl Ctr Toxicol Res, Off Sci Coordinat, Jefferson, AR 72079 USA. [Barnard, Dennis E.] NIH, ORS, DIRS, VRP, Bethesda, MD 20892 USA. RP Lewis, SM (reprint author), Natl Ctr Toxicol Res, Off Sci Coordinat, Jefferson, AR 72079 USA. NR 1099 TC 4 Z9 4 U1 1 U2 1 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-045432-0; 978-0-12-074903-4 J9 AM COLL LAB PY 2006 BP 219 EP 301 DI 10.1016/B978-012074903-4/50012-1 PG 83 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA BCT73 UT WOS:000311378400011 ER PT J AU Dutta, A Pal, G Mitra, K Grace, M Ilev, I Gorman, E Waynant, R Romanczk, T Wu, X Chakrabarti, K Anders, J AF Dutta, A Pal, G Mitra, K Grace, M Ilev, I Gorman, E Waynant, R Romanczk, T Wu, X Chakrabarti, K Anders, J TI Fluorescence life time imaging from neurons and subcellular components during low intensity laser therapy using fiber-optic nano-probes SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract CT 26th Annual Meeting of the American-Society-for-Laser-Medicine-and-Surgery CY APR 05-09, 2006 CL Boston, MA SP Amer Soc Laser Med & Surg C1 Florida Tech, Melbourne, FL USA. FDA, Rockville, MD USA. USUHS, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PY 2006 SU 18 MA 31 BP 11 EP 11 PG 1 WC Dermatology; Surgery SC Dermatology; Surgery GA 027JY UT WOS:000236412900032 ER PT J AU Frasch, CE AF Frasch, Carl E. BE Detrick, B Hamilton, RG Folds, JD TI Immune Responses to Polysaccharide and Conjugate Vaccines SO MANUAL OF MOLECULAR AND CLINICAL LABORATORY IMMUNOLOGY, 7TH EDITION LA English DT Article; Book Chapter ID INFLUENZAE TYPE-B; VI-CAPSULAR POLYSACCHARIDE; LINKED-IMMUNOSORBENT-ASSAY; STANDARD REFERENCE SERUM; ACUTE OTITIS-MEDIA; NEISSERIA-MENINGITIDIS; STREPTOCOCCUS-PNEUMONIAE; SALMONELLA-TYPHI; ANTIBODY-RESPONSE; PNEUMOCOCCAL-POLYSACCHARIDE C1 Ctr Biol Evaluat & Res, Lab Bacterial Polysaccharides, Rockville, MD 20852 USA. RP Frasch, CE (reprint author), Ctr Biol Evaluat & Res, Lab Bacterial Polysaccharides, Mailstop HFM 428,1401 Rockville Pike, Rockville, MD 20852 USA. NR 71 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N STREET NW, WASHINGTON, DC 20036-2904 USA BN 978-1-55581-364-2 PY 2006 BP 434 EP 443 PG 10 WC Immunology SC Immunology GA BOX98 UT WOS:000277993100052 ER PT J AU deVore, NC Slater, JE AF deVore, Nicolette C. Slater, Jay E. BE Detrick, B Hamilton, RG Folds, JD TI Quantification and Standardization of Allergens SO MANUAL OF MOLECULAR AND CLINICAL LABORATORY IMMUNOLOGY, 7TH EDITION LA English DT Article; Book Chapter ID INDUCED HISTAMINE-RELEASE; PHARMACIA CAP SYSTEM; RAGWEED POLLEN ANTIGEN; HUMAN BASOPHILS; SKIN-TEST; HYPERSENSITIVITY PHENOMENA; HUMAN LEUKOCYTES; MAST-CELLS; UNITS AU; EXTRACTS C1 [deVore, Nicolette C.; Slater, Jay E.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP deVore, NC (reprint author), US FDA, Ctr Biol Evaluat & Res, 29 Lincoln Dr, Bethesda, MD 20892 USA. NR 51 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N STREET NW, WASHINGTON, DC 20036-2904 USA BN 978-1-55581-364-2 PY 2006 BP 937 EP 946 PG 10 WC Immunology SC Immunology GA BOX98 UT WOS:000277993100106 ER PT J AU Winters, ME Lowenthal, M Feldman, AL Liotta, LA AF Winters, Mary E. Lowenthal, Mark Feldman, Andrew L. Liotta, Lance A. BE Detrick, B Hamilton, RG Folds, JD TI The Future of Cancer Diagnostics: Proteomics, Immunoproteomics, and Beyond SO MANUAL OF MOLECULAR AND CLINICAL LABORATORY IMMUNOLOGY, 7TH EDITION LA English DT Article; Book Chapter ID CATALYZED REPORTER DEPOSITION; RESONANCE MASS-SPECTROMETRY; SIGNAL AMPLIFICATION; CLINICAL PROTEOMICS; PROTEIN MICROARRAYS; MARKERS; ELECTROPHORESIS; TECHNOLOGY; GEL C1 [Winters, Mary E.; Lowenthal, Mark; Feldman, Andrew L.] NCI, Pathol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. [Winters, Mary E.; Lowenthal, Mark; Feldman, Andrew L.] NCI, US FDA, Clin Prote Program, Bethesda, MD 20892 USA. [Liotta, Lance A.] George Mason Univ, Ctr Appl Prote & Mol Med, Manassas, VA 20110 USA. RP Winters, ME (reprint author), NCI, Pathol Lab, Ctr Canc Res, Bldg 10, Bethesda, MD 20892 USA. NR 24 TC 0 Z9 1 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N STREET NW, WASHINGTON, DC 20036-2904 USA BN 978-1-55581-364-2 PY 2006 BP 1183 EP 1192 PG 10 WC Immunology SC Immunology GA BOX98 UT WOS:000277993100135 ER PT S AU Park, S Clarkson, E Barrett, HH Kupinski, MA Myers, KJ AF Park, Subok Clarkson, Eric Barrett, Harrison H. Kupinski, Matthew A. Myers, Kyle J. BA Eckstein, MP BF Eckstein, MP BE Jiang, Y TI Performance of a channelized-ideal observer using Laguerre-Gauss channels for detecting a Gaussian signal at a known location in different lumpy backgrounds - art. no. 61460P SO Medical Imaging 2006: Image Perception, Observer Performance and Technology Assessment SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Medical Imaging 2006 Conference CY FEB 12-14, 2006 CL San Diego, CA SP SPIE DE nonlinear ideal observers; channelized nonlinear-ideal observers; Laguerre-Gauss channels; non-Gaussian distributed lumpy backgrounds AB The Bayesian ideal observer gives a measure for image quality since it uses all available statistical information for a given image data. A channelized-ideal observer (CIO), which reduces the dimensionality of integrals that need to be calculated for the ideal observer, has been introduced in the past. The goal of the CIO is to approximate the performance of the ideal observer in certain detection tasks. In this work, a CIO using Laguerre-Gauss (LG) channels is employed for detecting a rotationally symmetric Gaussian signal at a known location in the non-Gaussian distributed lumpy background. The mean number of lumps in the lumpy background is varied to see the impact of image statistics on the performance of this CIO and a channelized-Hotelling observer (CHO) using the same channels. The width parameter of LG channels is also varied to see its impact on observer performance. A Markov-chain Monte Carlo (MCMC) method is employed to determine the performance of the CIO using large numbers of LG channels. Simulation results show that the CIO is a better observer than the CHO for the task. The results also indicate that the performance of the CIO approaches that of the ideal observer as the mean number of lumps in the lumpy background decreases. This implies that LG channels may be efficient for the CIO to approximate the performance of the ideal observer in tasks using non-Gaussian distributed lumpy backgrounds. C1 US FDA, NIBIB, CDRH, Lab Assessment Med Imaging Syst, Rockville, MD 20857 USA. RP Park, S (reprint author), US FDA, NIBIB, CDRH, Lab Assessment Med Imaging Syst, Rockville, MD 20857 USA. NR 7 TC 4 Z9 4 U1 1 U2 1 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-6425-2 J9 P SOC PHOTO-OPT INS PY 2006 VL 6146 BP P1460 EP P1460 AR 61460P DI 10.1117/12.653931 PG 9 WC Engineering, Biomedical; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BEL81 UT WOS:000238040200022 ER PT S AU Park, S Gallas, B Badano, A Petrick, N Myers, K AF Park, Subok Gallas, Brandon Badano, Aldo Petrick, Nicholas Myers, Kyle BA Eckstein, MP BF Eckstein, MP BE Jiang, Y TI Human efficiency for detecting Gaussian signals in non-Gaussian distributed lumpy backgrounds using different display characteristics and scaling methods. - art. no. 61460Q SO Medical Imaging 2006: Image Perception, Observer Performance and Technology Assessment SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Medical Imaging 2006 Conference CY FEB 12-14, 2006 CL San Diego, CA SP SPIE DE human efficiency; Bayesian ideal observer; non-Gaussian distributed lumpy backgrounds ID HUMAN-OBSERVER; DETECTION PERFORMANCE; NOISE; MAMMOGRAMS; MODEL AB A psychophysical study to measure human efficiency relative to the ideal observer for detecting a Gaussian signal at a known location in a non-Gaussian distributed lumpy background was conducted previously by the author. The study found that human efficiency was less than 2.2% while the ideal observer achieved 0.95 in terms of the area under the receiver operating characteristic curve. In this work, a psychophysical study was conducted with a number of changes that substantially improve upon the previous study design. First, a DICOM-calibrated monitor was used in this study for human-observer performance measurements, whereas an uncalibrated LCD monitor was used in the prior study. Second, two scaling methods to display image values were employed to see how scaling affects human performance for the same task. Third, a random order of image pairs was chosen for each observer to reduce any correlations in human performance that is likely caused by the fixed ordering of the image pairs in the prior study. Human efficiency relative to the ideal observer was found to be less than 3.8% at the same performance level of the ideal observer as above. Our variance analysis indicates that neither scaling nor display made a significant difference in human performance on the tasks in the two studies. That is, we cannot say that either of these factors caused low human efficiency in these studies. Therefore, we conclude that using highly non-Gaussian distributed lumpy backgrounds in the tasks may have been the major source of low human efficiency. C1 US FDA, Ctr Devices & Radiol Hlth, NIBIB,Devis Imaging & Appl Math, CDRH,Lab Assessment Med Imaging Syst, Rockville, MD 20857 USA. RP Park, S (reprint author), US FDA, Ctr Devices & Radiol Hlth, NIBIB,Devis Imaging & Appl Math, CDRH,Lab Assessment Med Imaging Syst, Rockville, MD 20857 USA. OI Gallas, Brandon/0000-0001-7332-1620; badano, aldo/0000-0003-3712-6670 NR 19 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-6425-2 J9 P SOC PHOTO-OPT INS PY 2006 VL 6146 BP Q1460 EP Q1460 AR 61460Q DI 10.1117/12.653902 PG 9 WC Engineering, Biomedical; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BEL81 UT WOS:000238040200023 ER PT S AU Wagner, RF AF Wagner, Robert F. BA Eckstein, MP BF Eckstein, MP BE Jiang, Y TI Recent developments and contemporary issues for diagnostic technology assessment SO MEDICAL IMAGING 2006: IMAGE PERCEPTION, OBSERVER PERFORMANCE AND TECHNOLOGY ASSESSMENT SE Proceedings of SPIE LA English DT Proceedings Paper CT Medical Imaging 2006 Conference CY FEB 12-14, 2006 CL San Diego, CA SP SPIE DE ROC analysis; reader variability; MRMC ROC; ACRIN DMIST; ROC software uprgrades; multiple-blomarkers; cross-validation; bootstrapping; JAFROC ID DORFMAN-BERBAUM-METZ; CROSS-VALIDATION; MAMMOGRAPHY; READERS; POPULATION; VARIANCE; DESIGN; TESTS AB This paper summarizes recent themes of interest to this conference as well as the conferences of the Medical Image Perception Society (MIPS). C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. RP Wagner, RF (reprint author), US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. NR 37 TC 0 Z9 0 U1 0 U2 1 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-6425-2 J9 PROC SPIE PY 2006 VL 6146 AR 614606 DI 10.1117/12.663460 PG 9 WC Engineering, Biomedical; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BEL81 UT WOS:000238040200006 ER PT S AU Gavrielides, MA Petrick, N Myers, KJ AF Gavrielides, Marios A. Petrick, Nicholas Myers, Kyle J. BE Reinhardt, JM Pluim, JPW TI Alignment of full and partial CT thoracic scans using bony structures - art. no. 61443A SO Medical Imaging 2006: Image Processing, Pts 1-3 SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Medical Imaging 2006 Conference CY FEB 12-14, 2006 CL San Diego, CA SP SPIE AB Diagnostic thoracic procedures using computed tomography (CT) often include comparisons of scans acquired with different slice thicknesses. In this manuscript, we investigated the potential for alignment of different CT scans from the same patient using skeletal knowledge of the thoracic region. Skeletal matching was selected because it is expected to be less susceptible to differences associated with patient breath hold, positioning and cardiac motion. Our method utilized the positioning of the ribs relative to the vertebra for matching. It also included matching the scapula when visible in the scans. Rib positioning was described by the angles formed between the vertebra centroid and combinations of pairs of rib centroids visible on each CT slice; this was used as the primary matching mechanism. Scapula morphology was described using a feature based on the local maxima of the distance transform. Since the scapula is not visible in all slices of a full scan, its description was limited to only defining the potential range of slices. A cost function incorporating the difference of features from rib positioning and scapula morphology between two slices was derived and used to match slices. The method was evaluated on an independent set of 10 pairs of full and partial CT scans. Assessment was based on whether or not slices containing known nodules between each pair of scans were overlapping after the alignment procedure. Results showed that the proposed metric correctly aligned 9 out of 10 scans. The preliminary results are encouraging for using this method as a first step towards temporal analysis of lung nodules. C1 US FDA, NIBIB, CDRH, Lab Assessment Med Imaging Syst,Div Imaging & App, Rockville, MD 20852 USA. RP Gavrielides, MA (reprint author), 12720 Twinbrook Pkwy,Bldg 1,Rm 128,HFZ 140, Rockville, MD 20852 USA. NR 4 TC 0 Z9 0 U1 0 U2 1 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-6423-6 J9 P SOC PHOTO-OPT INS PY 2006 VL 6144 BP A1443 EP A1443 AR 61443A DI 10.1117/12.655333 PN 1-3 PG 9 WC Computer Science, Interdisciplinary Applications; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BEL75 UT WOS:000238033301037 ER PT S AU Paquerault, S Petrick, N Sahiner, B Myers, KJ Chan, HP AF Paquerault, S. Petrick, N. Sahiner, B. Myers, K. J. Chan, H. -P. BE Reinhardt, JM Pluim, JPW TI Potential improvement of computerized mass detection on mammograms using a bilateral pairing technique - art. no. 61445N SO Medical Imaging 2006: Image Processing, Pts 1-3 SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Medical Imaging 2006 Conference CY FEB 12-14, 2006 CL San Diego, CA SP SPIE DE mammography; computer-aided diagnosis; bilateral detection technique. ID DIGITAL MAMMOGRAMS; SUBTRACTION; SINGLE; IMAGES AB We are developing a bilateral pairing technique to help reduce false-positives identified by a single-view computer-aided detection (CAD) system for breast masses. In this study, we compare the performance of the proposed bilateral CAD to a single-view CAD. A database of 172 right/left breast pairs containing 205 biopsy-proven masses was used. Single-view CAD was run on each image using a lax selection threshold so that 5 objects per image were retained. The automated bilateral pairing algorithm identified all objects in a left breast mammogram '' matching '' a CAD detected object in the corresponding right breast image and visa-versa. Bilateral pairing was based on geometrical correspondence between objects with a matching score derived from a paired right/left object feature set and a linear discriminant analysis classifier. Leave-one out resampling was used to train/test the technique. We compared the FROC performances of the single-view CAD, the proposed bilateral technique and a modified CAD using manual pairing of bilateral structures. At a per-lesion detection sensitivity of 0.7, there were 3.8 FPs/image for the original CAD, 3.3 for the proposed technique, and 2.2 for the modified CAD using manual matching, a 12.6% and 42.1% reduction, respectively. At an FP rate of 1.0 per image, the sensitivities for the original CAD, the proposed technique and the modified CAD using manual matching were 0.47, 0.51 and 0.60, respectively. Preliminary results show that CAD with bilateral pairing did not achieve a significant FP-reduction. C1 NIBIB, CDRH, Joint Lab Assessment Med Imaging Syst, US FDA, Rockville, MD USA. RP Paquerault, S (reprint author), NIBIB, CDRH, Joint Lab Assessment Med Imaging Syst, US FDA, Rockville, MD USA. NR 13 TC 0 Z9 0 U1 1 U2 1 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-6423-6 J9 P SOC PHOTO-OPT INS PY 2006 VL 6144 BP N1445 EP N1445 AR 61445N DI 10.1117/12.654561 PN 1-3 PG 8 WC Computer Science, Interdisciplinary Applications; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BEL75 UT WOS:000238033302038 ER PT S AU Badano, A Kyprianou, IS Sempau, J AF Badano, Aldo Kyprianou, Iacovos S. Sempau, Josep BE Flynn, MJ Hsieh, J TI Three-dimensional columnar CsI model for x-ray imaging system simulations using MANTIS: validating for noise, blur, and light output - art. no. 61420W SO Medical Imaging 2006: Physics of Medical Imaging, Pts 1-3 SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Medical Imaging 2006 Conference CY FEB 12-14, 2006 CL San Diego, CA SP SPIE DE Monte Carlo simulation; digital imaging; phosphor screen; Cesium Iodide; point response function ID MONTE-CARLO-SIMULATION; POINT-SPREAD FUNCTION; CODE PENELOPE; LEKSELL-GAMMA-KNIFE(R); SCINTILLATORS; COLLECTION; EFFICIENCY; PHOSPHORS; BEAMS; DQE AB In previous work, we and others have focused the validation of detector models for computational simulations of imaging system performance on matching, to a small difference, specific aspects of the detector's performance, i.e., modulation transfer function or light output. In this work, instead, we selected three parameters that, together represent a more complete description of the imaging properties of the phosphor screen to be modeled. The three performance parameters are the information or Swank factor determined from pulse-height spectra, the light output (either in absolute or relative scale), and the point-response function. Using this general methodology, we created screen models that exhibit good agreement with recent experimental measurements available in the literature, over a wide x-ray energy range (18-75 keV), and for front- and back-screen configurations. The models are being used in conjunction with MANTIS, a Monte Carlo code for simulating imaging systems that tracks x rays, electrons, and optical photons in the same geometric model, with x-ray and electron physics models from the PENELOPE package, and optical physics models from DETECT-II. This study allows us to incorporate realistic detector models into a detailed and complete Monte Carlo simulation of the entire imaging system, including the object and its absorbed dose map, and the properties of the imaging acquisition. C1 US FDA, CDRH, Rockville, MD 20857 USA. RP Badano, A (reprint author), US FDA, CDRH, 12720 Twinbrook Pkwy, Rockville, MD 20857 USA. RI Sempau, Josep/J-7834-2013; OI Sempau, Josep/0000-0002-2754-7685; badano, aldo/0000-0003-3712-6670 NR 35 TC 1 Z9 1 U1 0 U2 1 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-6185-7 J9 P SOC PHOTO-OPT INS PY 2006 VL 6142 BP W1420 EP W1420 AR 61420W DI 10.1117/12.653309 PN 1-3 PG 10 WC Engineering, Biomedical; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Optics; Radiology, Nuclear Medicine & Medical Imaging GA BEL88 UT WOS:000238049700030 ER PT S AU Kyprianou, LS Badano, A D Gallas, B Park, S Myers, KJ AF Kyprianou, Lacovos S. Badano, Aldo D Gallas, Brandon Park, Subok Myers, Kyle J. BE Flynn, MJ Hsieh, J TI A practical method for measuring the H matrix of digital x-ray and cone beam CT imaging systems SO MEDICAL IMAGING 2006: PHYSICS OF MEDICAL IMAGING, PTS 1-3 SE Proceedings of SPIE LA English DT Proceedings Paper CT Medical Imaging 2006 Conference CY FEB 12-14, 2006 CL San Diego, CA SP SPIE DE system; matrix; H; cone beam; system evaluation; assessment AB Digital clinical imaging systems designed for radiography or cone-beam computed-tomography are highly shift-variant. The x-ray cone angle of such systems varies between 0 degrees and 15 degrees, resulting in large variations of the focal spot projection across the image field. Additionally, the variable x-ray beam incidence across the detector field creates a location-dependent asymmetric detector response function. In this paper we propose a practical method for the measurement of the angle of incidence dependent two-dimensional presampled detector response function. We also present a method for the measurement of the source radiance at the center of the detector, and provide a geometric transformation for reprojecting given any location in object space. The measurement procedure involves standard, readily available tools such as a focal-spot/pinhole camera, and an edge. Using the measured data and a model based on smooth functions derived from Monte Carlo simulations we obtain the location-dependent detector response function. In this paper we ignore scatter, therefore the resulting location dependent system response is a function of the focal spot and detector response. The system matrix, a representation of the full deterministic point response of the system for all positions in object space, can then be calculated. The eigenvalues and eigenvectors of the system matrix are generated and interpreted. C1 US FDA, NIBIB, CDRH, Lab Assessment Med Imaging Syst, Rockville, MD 20852 USA. RP Kyprianou, LS (reprint author), US FDA, NIBIB, CDRH, Lab Assessment Med Imaging Syst, HFZ-140,12720 Twinbrook Pkwy, Rockville, MD 20852 USA. EM jacovos.kypriwiou@fda.hhs.gov OI badano, aldo/0000-0003-3712-6670 NR 11 TC 1 Z9 1 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-6185-7 J9 PROC SPIE PY 2006 VL 6142 AR 61421U DI 10.1117/12.654374 PN 1-3 PG 12 WC Engineering, Biomedical; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Optics; Radiology, Nuclear Medicine & Medical Imaging GA BEL88 UT WOS:000238049700064 ER PT S AU Kyprianou, IS Thompson, L Banh, DP Pritchard, W Karanian, J Rosen, L Myers, KJ AF Kyprianou, Iacovos S. Thompson, Laura Banh, Diem Phuc Pritchard, William Karanian, John Rosen, Lee Myers, Kyle J. BE Manduca, A Amini, AA TI Gender-specific statistical models of pathological coronary arteries for generating simulated angiograms - art. no. 61432K SO Medical Imaging 2006: Physiology, Function, and Structure from Medical Images Pts 1 and 2 SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Medical Imaging 2006 Conference CY FEB 12-14, 2006 CL San Diego, CA SP SPIE ID SEX-DIFFERENCES; CAROTID-ARTERY; HEART-DISEASE; ANGIOPLASTY; WOMEN; ATHEROSCLEROSIS; MEN; INTERVENTIONS; PLAQUES; AGE AB Cardiovascular disease is considered the leading cause of death in the US, accounting for 38% of all deaths. There are gender differences in the size of coronary arteries and in the character and location of atherosclerotic lesions that affect the detection of coronary artery disease with the medical imaging modalities currently used (e.g. angiography, computed tomography). These differences also affect the safety and effectiveness of image-guided interventions using therapeutic devices. For the optimization of the medical imaging modalities used for this specific task we require the generation of clinically-realistic, gender-specific images of healthy and pathological coronary angiograms. For this purpose we have created a gender-specific statistical model of a pathological coronary artery tree. Starting from "healthy" heart-phantoms created from high resolution CT scans of cadaver hearts of both genders, the model uses prevalence data obtained from clinical studies of patients with significant (> 50% stenosis) coronary artery disease (CAD). The model determines the plaque deposit locations and character (length, percent stenosis) for each case, based on a flow model. These data are then used to generate artificially diseased artery trees, embedded in a gender-specific torso model. Using an x-ray and optical photon Monte-Carlo simulation program, we then generate simulated angiograms exhibiting realistic disease patterns. The severity of each angiogram. is determined from a set of rules that combines the geometrically increasing severity of lesions, the cumulative effects of multiple obstructions, the significance of their locations, the modifying influence of the collaterals, and the size and quality of the distal vessels. The simulated angiograms will consequently be read by model and human observers. The probability of detection derived in combination with the severity score will be used as a figure of merit for the patient- and gender-specific optimization of the imaging modality under investigation. C1 US FDA, NIBIB, CDRH Joint Lab Assessment Med Imaging Syst, Rockville, MD 20857 USA. RP Kyprianou, IS (reprint author), US FDA, NIBIB, CDRH Joint Lab Assessment Med Imaging Syst, Rockville, MD 20857 USA. NR 27 TC 1 Z9 1 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-6186-5 J9 P SOC PHOTO-OPT INS PY 2006 VL 6143 BP K1432 EP K1432 AR 61432K DI 10.1117/12.654383 PN 1-2 PG 11 WC Engineering, Biomedical; Physiology; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Physiology; Radiology, Nuclear Medicine & Medical Imaging GA BEK96 UT WOS:000237637000085 ER PT S AU Liang, H Badano, A AF Liang, Hongye Badano, Aldo BE Cleary, KR Galloway, RL TI Temporal response measurements of medical liquid crystal displays - art. no. 61410U SO Medical Imaging 2006: Visualization, Image-Guided Procedures, and Display SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Medical Imaging 2006 Conference CY FEB 12-14, 2006 CL San Diego, CA SP SPIE DE liquid crystal display; gray level; temporal blur; temporal response; motion artifact ID AAPM/RSNA TUTORIAL; PACS EQUIPMENT; SELECTION AB Liquid crystal displays (LCDs) are fast gaining ground over the cathode ray tube (CRT) displays in the medical display, market. High performing LCDs are considered to have comparable or better performance than CRTs in displaying static images. However. LCDs are inferior to CRTs in displaying moving scenes due to their slow response. The response time provided by display manufacturers is typically measured while switching the LCD from black to white and white to black. This is usually not the longest response time. In reality, the transition time between different gray scales can be many times longer. In this paper we report preliminary work on measuring the gray level response time of LCDs and simulating luminance errors caused by slow transition between some gray levels. We first characterized the measuring system using a fast light-emitting diode (LED) to explore the accuracy and noise-filtering capability of the system. A 256x256 matrix of response time between different gray levels was then measured. Nearly half of the gray level transitions are much longer than the frame time (16.67 ms) of LCD displays. The longest response time was above 100 ms. When driving a display between these gray levels, the targeted gray level can't be achieved until many frame times. To understand how the slow response may affect the display's ability to render the desired image values. we calculated the achieved luminance based on the measured matrix. The results simulate the visual effect of displaying a moving object on the LCD monitors, and providing a reference for determining LCD performance. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Liang, H (reprint author), US FDA, Ctr Devices & Radiol Hlth, 12720 Twinbrook Pkwy, Rockville, MD 20857 USA. OI badano, aldo/0000-0003-3712-6670 NR 14 TC 0 Z9 0 U1 0 U2 1 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-6184-9 J9 P SOC PHOTO-OPT INS PY 2006 VL 6141 BP U1410 EP U1410 AR 61410U DI 10.1117/12.653299 PG 9 WC Engineering, Biomedical; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BEL13 UT WOS:000237688300027 ER PT J AU Gagne, RM Gallas, BD Myers, KJ AF Gagne, RM Gallas, BD Myers, KJ TI Toward objective and quantitative evaluation of imaging systems using images of phantoms SO MEDICAL PHYSICS LA English DT Article DE imaging phantom; image quality; signal detection theory; prewhitening (PW); nonprewhitening (NPW); model observer; digital imaging; signal-to-noise ratio (SNR); bias; "bootstrapping,"; "shuffling" ID OBSERVER PERFORMANCE; HOTELLING-OBSERVER; NOISE MEASUREMENTS; CLASSIFIER DESIGN; COMPUTER-ANALYSIS; SAMPLE-SIZE; SNR; QUALITY; DETECTABILITY; CAMPI AB The use of imaging phantoms is a common method of evaluating image quality in the clinical setting. These evaluations rely on a subjective decision by a human observer with respect to the faintest detectable signal(s) in the image. Because of the variable and subjective nature of the human-observer scores, the evaluations manifest a lack of precision and a potential for bias. The advent of digital imaging systems with their inherent digital data provides the opportunity to use techniques that do not rely on human-observer decisions and thresholds. Using the digital data, signal-detection theory (SDT) provides the basis for more objective and quantitative evaluations which are independent of a human-observer decision threshold. In a SDT framework, the evaluation of imaging phantoms represents a "signal-known-exactly/background-known-exactly" ("SKE/BKE") detection task. In this study, we compute the performance of prewhitening and nonprewhitening model observers in terms of the observer signal-to-noise ratio (SNR) for these "SKE/BKE" tasks. We apply the evaluation methods to a number of imaging systems. For example, we use data from a laboratory implementation of digital radiography and from a full-field digital mammography system in a clinical setting. In addition, we make a comparison of our methods to human-observer scoring of a set of digital images of the CDMAM phantom available from the internet (EUREF-European Reference Organization). In the latter case, we show a significant increase in the precision of the quantitative methods versus the variability in the scores from human observers on the same set of images. As regards bias, the performance of a model observer estimated from a finite data set is known to be biased. In this study, we minimize the bias and estimate the variance of the observer SNR using statistical resampling techniques, namely, "bootstrapping" and "shuffling" of the data sets. Our methods provide objective and quantitative evaluation of imaging systems with increased precision and reduced bias. (c) 2006 American Association of Physicists in Medicine. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Gagne, RM (reprint author), US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. EM rmg4@cdrh.fda.gov OI Gallas, Brandon/0000-0001-7332-1620 NR 35 TC 20 Z9 21 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 JAN PY 2006 VL 33 IS 1 BP 83 EP 95 DI 10.1118/1.2140117 PG 13 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 004SI UT WOS:000234772100012 PM 16485413 ER PT J AU de Oliveira, EJ Kanamura, HY Takei, K Hirata, RDC Nguyen, NY Hirata, MH AF de Oliveira, Edward Jose Kanamura, Herminia Yohko Takei, Kioko Crespo Hirata, Rosario Dominguez Nguyen, Nga Yen Hirata, Mario Hiroyuki TI Application of synthetic peptides in development of a serologic method for laboratory diagnosis of Schistosomiasis mansoni SO MEMORIAS DO INSTITUTO OSWALDO CRUZ LA English DT Article; Proceedings Paper CT 10th International Symposium on Schistosomiasis CY SEP 25-28, 2005 CL Belo Horizonte, BRAZIL DE Schistosoma mansoni; immunodiagnosis; synthetic peptides ID CIRCULATING ANODIC ANTIGEN; PROTEINS; HAMSTER; SM31 AB The immunoreactivity of seven peptides synthesized from Schistosoma mansoni proteins, was evaluated by dotblot and ELISA assays using two different sensitization methodologies. The best results were obtained on wells of the Costar 3590 microplates coated with peptides P1, P2, P3, P6, and P7 using conventional methodology. The signals increased considerably (p < 0.0003) on wells sensitized with P1 to P6 using alternative methodology. In contrast, the well coated with peptide P7 presented lower signal when compared with conventional methodology (p = 0.0019). These results, establish the basis for the application of synthetic peptides for laboratory diagnosis of schistosomiasis mansoni. C1 Univ Sao Paulo, Fac Ciencias Farmaceut, Lab Imunol Clin, BR-05508900 Sao Paulo, Brazil. Univ Taubate, Dept Biol, Taubate, SP, Brazil. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. RP de Oliveira, EJ (reprint author), Univ Sao Paulo, Fac Ciencias Farmaceut, Lab Imunol Clin, Av Prof Lineu Prestes 580,Bloco 17, BR-05508900 Sao Paulo, Brazil. EM edwardjo@usp.br RI Hirata, Rosario/A-7284-2011; Hirata, Mario/C-9718-2013 NR 15 TC 0 Z9 0 U1 0 U2 0 PU FUNDACO OSWALDO CRUZ PI RIO DE JANEIRO, RJ PA AV BRASIL 4365, 21045-900 RIO DE JANEIRO, RJ, BRAZIL SN 0074-0276 J9 MEM I OSWALDO CRUZ JI Mem. Inst. Oswaldo Cruz PY 2006 VL 101 SU 1 BP 355 EP 357 PG 3 WC Parasitology; Tropical Medicine SC Parasitology; Tropical Medicine GA 101KG UT WOS:000241739100057 ER PT J AU Dheenadhayalan, V Delogu, G Brennan, MJ AF Dheenadhayalan, V Delogu, G Brennan, MJ TI Expression of the PE_PGRS 33 protein in Mycobacterium smegmatis triggers necrosis in macrophages and enhanced mycobacterial survival SO MICROBES AND INFECTION LA English DT Article DE Mycobacterium smeginatis; PE_PGRS genes; tuberculosis; tumor necrosis factor ID VIRULENCE GENE-CLUSTER; LUNG EPITHELIAL-CELLS; PE-PGRS PROTEINS; ALPHA TNF-ALPHA; IMMUNE-RESPONSE; HUMAN MONOCYTES; TUBERCULOSIS; INFECTION; SECRETION; FAMILY AB Research on mycobacteria-specific PE_PGRS genes indicates that they code for cell surface proteins that may influence virulence and the infection of host cells by mycobacteria. In the studies presented here, we have expressed the PE_PGRS 33 gene in a non-patho genic fast-growing Mycobacterium smegmatis strain and demonstrated that it survives better in macrophage cultures, in vitro as well as in mice after intraperitoneal administration, than the parental strain containing the vector only or a strain expressing only the PE domain of PE_PGRS 33. In macrophages, enhanced colonization by the M. smegmatis expressing PE PGRS 33 was associated with macrophage aggregation and clearance of macrophage monolayers, visible cell necrosis and significantly greater levels of TNF (TNF-alpha) in the cultures compared with controls. The presence of macrophage cell necrosis was confirmed by measurement of significantly greater levels of lactate dehydrogenase and nucleosomes in the supernatants of the macrophage cultures infected with M. smegmatis expressing PE_PGRS 33. Antibodies directed against TNF partially reduced cytolysis, suggesting that this cytokine is critical but not sufficient for the observed macrophage necrosis and enhanced mycobacterial survival. These results extend earlier observations, which suggested that PE-PGRS proteins may have a role in the pathogenesis of mycobacterial disease and that there may be a specific role for these proteins in influencing host cell responses to infection. (c) 2005 Elsevier SAS. All rights reserved. C1 US FDA, Lab Mycobacterial Dis & Cellular Immunol, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. Univ Sacred Heart, Inst Microbiol, I-00168 Rome, Italy. RP Dheenadhayalan, V (reprint author), US FDA, Lab Mycobacterial Dis & Cellular Immunol, Ctr Biol Evaluat & Res, Bldg 29,Room 503,HFM-431,29 Lincoln Dr, Bethesda, MD 20892 USA. EM Dheenadhayalan@cber.fda.gov; gdelogu@rm.unicatt.it; Brennan@eber.fda.gov RI Delogu, Giovanni/I-3701-2012 OI Delogu, Giovanni/0000-0003-0182-8267 NR 44 TC 65 Z9 70 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1286-4579 J9 MICROBES INFECT JI Microbes Infect. PD JAN PY 2006 VL 8 IS 1 BP 262 EP 272 DI 10.1016/j.micinf.2005.06.021 PG 11 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 013WW UT WOS:000235441700030 PM 16203168 ER PT J AU Zhu, PX Boykins, RA Tsai, CM AF Zhu, PX Boykins, RA Tsai, CM TI Genetic and functional analyses of the IgtH gene, a member of the beta-1,4-galactosyltransferase gene family in the genus Neisseria SO MICROBIOLOGY-SGM LA English DT Article ID MENINGITIDIS SEROGROUP-B; TERMINAL LIPOPOLYSACCHARIDE STRUCTURE; GONORRHOEAE LIPOOLIGOSACCHARIDE; GONOCOCCAL LIPOOLIGOSACCHARIDE; GLYCOSYL TRANSFERASES; VARIABLE EXPRESSION; ANTIGENIC VARIATION; MASS-SPECTROMETRY; CRYSTAL-STRUCTURE; COILED COILS AB Lipooligosaccharide (LOS) is a major virulence factor of the pathogenic Neisseria. Three galactosyltransferase genes, IgtB, IgtE and IgtH, responsible for the biosynthesis of LOS oligosaccharide chains, were analysed in five Neisseria species. The function of IgtH in Neisseria meningitidis 6275 was determined by mutagenesis and chemical characterization of the parent and mutant LOS chains. The chemical characterization included SDS-PAGE, immunoblot, hexose and mass spectrometry analyses. Compared with the parent LOS, the mutant LOS lacked galactose, and its oligosaccharide decreased by three or four sugar units in matrix-assisted laser desorption ionization (MALDI)-MS analysis. The results show that IgtH encodes a beta-1,4-galactosyltransferase, and that the glucose moiety linked to heptose (Hep) in the cc chain is the acceptor site in the biosynthesis of Neisseria LOS. To understand the sequence diversity and relationships of IgtB, IgtE and IgtH, the entire Igt-1 locus was further sequenced in three N. meningitidis strains and three commensal Neisseria strains, and compared with the previously reported Igt genes from Neisseria species. Comparison of the protein sequences of the three enzymes LgtB, LgtE and LgtH showed a conserved N-terminal region, and a highly variable C-terminal region, suggesting functional constraint for substrate and acceptor specificity, respectively. The analyses of allelic variation and evolution of 23 IgtB, 12 IgtE and 14 IgtH sequences revealed a distinct evolutionary history of these genes in Neisseria. For example, the splits graph of IgtE displayed a network evolution, indicating frequent DNA recombination, whereas splits graphs of IgtB and IgtH displayed star-tree-like evolution, indicating the accumulation of point mutations. The data presented here represent examples of the evolution and variation of prokaryotic glycosyltransferase gene families. These imply the existence of multiple enzyme isoforms for biosynthesis of a great diversity of oligosaccharides in nature. C1 US FDA, Div Bacterial Parasit & Allergen Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Zhu, PX (reprint author), Creatv MicroTech Inc, 11609 Lake Potomac Dr, Potomac, MD 20854 USA. EM pzhu@creatvmicrotech.com NR 58 TC 6 Z9 6 U1 0 U2 0 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 1350-0872 J9 MICROBIOL-SGM JI Microbiology-(UK) PD JAN PY 2006 VL 152 BP 123 EP 134 DI 10.1099/mic.0.28327-0 PN 1 PG 12 WC Microbiology SC Microbiology GA 004HA UT WOS:000234741400014 PM 16385122 ER PT J AU Basturk, O Adsay, NV Banerjee, M Newman, L Bouwman, D Doerge, D Djuric, Z Parchment, R Majumdar, A Miller, F Sarkar, F Kucuk, O AF Basturk, O Adsay, NV Banerjee, M Newman, L Bouwman, D Doerge, D Djuric, Z Parchment, R Majumdar, A Miller, F Sarkar, F Kucuk, O TI The value of soy isoflavones in modulating biomarkers of growth and differentiation in breast cancer SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 95th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY FEB 11-17, 2006 CL Atlanta, GA SP US & Canadian Acad Pathol C1 Wayne State Univ, Karmanos Canc Inst, Detroit, MI 48202 USA. Univ Michigan, Ann Arbor, MI 48109 USA. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RI Djuric, Zora/H-5147-2013 OI Djuric, Zora/0000-0002-8886-8853 NR 0 TC 0 Z9 0 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2006 VL 19 SU 1 MA 86 BP 21A EP 21A PG 1 WC Pathology SC Pathology GA 995IR UT WOS:000234094500087 ER PT J AU Zhang, H Huang, Q Li, L Wang, Y Zhou, MW Ranganathan, G Kern, PA Iannaccone, PM Fan, CY AF Zhang, H Huang, Q Li, L Wang, Y Zhou, MW Ranganathan, G Kern, PA Iannaccone, PM Fan, CY TI Transgenic mice overexpressing human 8-oxoguanine DNA glycosylase (hOGG) in mitochondria develop obesity, hepatosteatosis and female infertility SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 95th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY FEB 11-17, 2006 CL Atlanta, GA SP US & Canadian Acad Pathol C1 Univ Arkansas Med Sci, Little Rock, AR 72205 USA. City Hope Natl Med Ctr, Duarte, CA 91010 USA. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Northwestern Univ, Sch Med, Chicago, IL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2006 VL 19 SU 1 MA 1376 BP 296A EP 296A PG 1 WC Pathology SC Pathology GA 995IR UT WOS:000234094502319 ER PT J AU Verma, M Seminara, D Arena, FJ John, C Iwamoto, K Hartmullerl, V AF Verma, M Seminara, D Arena, FJ John, C Iwamoto, K Hartmullerl, V TI Genetic and epigenetic biomarkers in cancer - Improving diagnosis, risk assessment, and disease stratification SO MOLECULAR DIAGNOSIS & THERAPY LA English DT Review ID SQUAMOUS-CELL CARCINOMA; INFLAMMATORY-BOWEL-DISEASE; ABERRANT DNA METHYLATION; TUMOR-SUPPRESSOR GENE; HUMAN COLON-CANCER; COLORECTAL-CANCER; LUNG-CANCER; BREAST-CANCER; PROMOTER METHYLATION; MICROSATELLITE INSTABILITY AB Gene expression patterns change during the initiation, progression, and development of cancer, as a result of both genetic and epigenetic mechanisms. Genetic changes arise due to irreversible changes in the nucleotide sequence, whereas epigenetic changes occur due to changes in chromatin conformation, histone acetylation, and methylation of the CpG islands located primarily in the promoter region of a gene. Both genetic and epigenetic markers can potentially be utilized to identify different stages of tumor development. Several such markers exhibit high sensitivity and specificity for different tumor types and can be assayed in biofluids and other specimens collected by noninvasive technologies. In spite of the availability of large numbers of diagnostic markers, only a few have been clinically validated so far. The current status and the challenges in the field of genetic and epigenetic markers in cancer diagnosis, risk assessment, and disease stratification are discussed. C1 NCI, Analyt Epidemiol Res Branch, Epidemiol & Genet Res Program, Div Canc Control & Populat Sci, Rockville, MD 20852 USA. NCI, Clin Epidemiol & Genet Res Branch, Epidemiol & Genet Res Program, Div Canc Control & Populat Sci, Rockville, MD 20852 USA. US FDA, Rockville, MD 20857 USA. RP Verma, M (reprint author), NCI, Analyt Epidemiol Res Branch, Epidemiol & Genet Res Program, Div Canc Control & Populat Sci, Room EPN 5105,6130 Execut Blvd, Rockville, MD 20852 USA. EM vermam@mail.nih.gov NR 190 TC 19 Z9 20 U1 1 U2 4 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 1177-1062 J9 MOL DIAGN THER JI Mol. Diagn. Ther. PY 2006 VL 10 IS 1 BP 1 EP 15 PG 15 WC Genetics & Heredity; Pharmacology & Pharmacy SC Genetics & Heredity; Pharmacology & Pharmacy GA 050ZJ UT WOS:000238129500001 PM 16646573 ER PT J AU Wu, CG Budhu, A Chen, S Zhou, XL Popescu, NC Valerie, K Wang, XW AF Wu, Chuan-ging Budhu, Anuradha Chen, Sheng Zhou, Xiaoling Popescu, Nicholas C. Valerie, Kristoffer Wang, Xin Wei TI Effect of hepatitis C virus core protein on the molecular profiling of human B lymphocytes SO MOLECULAR MEDICINE LA English DT Article ID CD8(+) T-CELLS; GENE-EXPRESSION; II CRYOGLOBULINEMIA; VILLOUS LYMPHOCYTES; DECREASED FREQUENCY; SPLENIC LYMPHOMA; INFECTION; BLOOD; LEADS; SUPPRESSION AB Hepatitis C virus (HCV) core protein features many intriguing properties and plays a pivotal role in cellular immunity, cell growth, apoptosis, cell transformation, and eventually in tumor development. However, the role of B cells, the primary players in the humoral immune response, during HCV infection is largely unknown. To explore the molecular effects of HCV core on human B cells, we conducted gene expression profiling of serial RNA samples from B cells that were infected with adenovirus harboring full-length HCV core protein and beta-galactosiclase as a reference using a microarray platform containing 22,149 human oligo probes. The entire experiment was performed in duplicate in B lymphocytes that were isolated from two individual donors and incubated for up to 3 days after infection with adenovirus expressing HCV core protein to identify dynamic gene expression patterns. Differential expression of representative genes was validated by quantitative RT-PCR. We found that HCV core significantly inhibited B-lymphocyte apoptosis. We showed a dramatic downregulation of MHC class 11 molecules in B cells expressing HCV core, whereas the expression of immunoglobulin genes was not significantly altered. Moreover, genes associated with leukemia and B-lymphoma were consistently upregulated by HCV core. In contrast, downregulation of caspose-1 and caspose-4 was found to be associated with core's ability to prevent B-lymphocyte apoptosis. In summary, we have identified several clusters of genes that are differentially expressed in human B lymphocytes expressing HCV core, suggesting a potential impairment of antigen processing and presentation, which may provide more insights into HCV infection in B lymphocytes. C1 US FDA, Ctr Biol Evaluat & Res, Div Hematol, Bethesda, MD 20892 USA. NCI, Human Carcinogenesis Lab, NIH, Bethesda, MD USA. Natl Inst Arthritis & Musculoskeletal & Skin Dis, Autoimmun Branch, NIH, Bethesda, MD USA. NCI, Expt Carcinogenesis Lab, NIH, Bethesda, MD USA. Virginia Commonwealth Univ, Med Coll Virginia, Dept Radiat Oncol, Richmond, VA 23298 USA. RP Wu, CG (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Hematol, HFM-345,29 Lincoln Dr, Bethesda, MD 20892 USA. EM wu@cber.fda.gov; xw3u@nih.gov RI Wang, Xin/B-6162-2009 NR 33 TC 16 Z9 18 U1 0 U2 1 PU FEINSTEIN INSTITUTE MED RES PI MANHASSET PA 350 COMMUNITY DRIVE, MANHASSET, NY 11030 USA SN 1076-1551 J9 MOL MED JI Mol. Med. PD JAN-MAR PY 2006 VL 12 IS 1-3 BP 47 EP 53 DI 10.2119/2006-00020.Wu PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 066FX UT WOS:000239216200006 PM 16838065 ER PT J AU Zhang, L Strong, JM Qiu, W Lesko, LJ Huang, SM AF Zhang, Lei Strong, John M. Qiu, Wei Lesko, Lawrence J. Huang, Shiew-Mei TI Scientific perspectives on drug transporters and their role in drug interactions SO MOLECULAR PHARMACEUTICS LA English DT Article DE transporter; drug-drug interaction; regulatory; guidance; new drug application; drug development; exposure-response relationship; labeling; risk management ID ORGANIC CATION TRANSPORTERS; INTESTINAL P-GLYCOPROTEIN; IN-VITRO; EFFLUX TRANSPORTERS; GENE-EXPRESSION; DIGOXIN; MDR1; DISPOSITION; INHIBITION; RECEPTOR AB Recently, increased interest in drug transporters and research in this area has revealed that drug transporters play an important role in modulating drug absorption, distribution, and elimination. Acting alone or in concert with drug metabolizing enzymes they can affect the pharmacokinetics and pharmacodynamics of a drug. This commentary will focus on the potential role that drug transporters may play in drug-drug interactions and what information may be needed during drug development and new drug application (NDA) submissions to address potential drug interactions mediated by transporters. C1 [Zhang, Lei; Strong, John M.; Qiu, Wei; Lesko, Lawrence J.; Huang, Shiew-Mei] CIDER Off 1, Ctr Drug Evaluat & Res Food & Drug Adm, Off Clin Pharmacol & Biopharmaceut, Silver Spring, MD 20993 USA. RP Huang, SM (reprint author), CIDER Off 1, Ctr Drug Evaluat & Res Food & Drug Adm, Off Clin Pharmacol & Biopharmaceut, Bldg 21,Rm 4550,White Oak,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM shiewmei.huang@fda.hhs.gov NR 54 TC 102 Z9 106 U1 0 U2 5 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 JAN-FEB PY 2006 VL 3 IS 1 BP 62 EP 69 DI 10.1021/mp050095h PG 8 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA V52JG UT WOS:000203539200007 PM 16686370 ER PT J AU Manickan, E Smith, JS Tian, J Eggerman, TL Lozier, JN Muller, J Byrnes, AP AF Manickan, E Smith, JS Tian, J Eggerman, TL Lozier, JN Muller, J Byrnes, AP TI Rapid Kupffer cell death after intravenous injection of adenovirus vectors SO MOLECULAR THERAPY LA English DT Article DE Kupffer cells; gene therapy; adenoviridae; genetic vectors; necrosis; electron microscopy; intravenous injections; liver; lung ID MEDIATED GENE-TRANSFER; IN-VIVO; LACTATE-DEHYDROGENASE; FOREIGN PARTICLES; NONHUMAN-PRIMATES; MICE; RESPONSES; LIVER; MACROPHAGES; ACTIVATION AB When adenovirus vectors are injected intravenously, they are quickly taken up by Kupffer cells in the liver. We report that this causes rapid necrosis of Kupffer cells in mice at doses of 10(11) particles/kg or higher. By 10 min after intravenous vector injection, Kupffer cells were permeable to propidium iodide and trypan blue. This coincided with a sharp rise in serum lactate dehydrogenase. Ultrastructural examination showed degeneration of Kupffer cells, including complete disappearance of chromatin by I h. After an initial intravenous injection of vector, dead Kupffer cells were unable to take up a second dose of vector, and hepatic transgene expression from the second dose was augmented. Death of Kupffer cells did not affect serum levels of IL-6 or IL-12. There was no immediate change in the number of Kupffer cells in the liver, but a significant decline was found by 4 h after injection of vector. Interestingly, substantial numbers of vector-containing Kupffer cells were found in pulmonary capillaries, indicating that they had been swept out of the liver. Together these results show that an intravenous injection of adenovirus vector causes synchronous and surprisingly rapid Kupffer cell death. C1 US FDA, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. US FDA, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. NIDDK, NIH, Bethesda, MD 20892 USA. RP Manickan, E (reprint author), US FDA, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, HFM-725, Bethesda, MD 20892 USA. EM byrnesa@cber.fda.gov RI Byrnes, Andrew/D-2808-2013 OI Byrnes, Andrew/0000-0003-1135-2629 NR 38 TC 82 Z9 82 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 1525-0016 J9 MOL THER JI Mol. Ther. PD JAN PY 2006 VL 13 IS 1 BP 108 EP 117 DI 10.1016/j.ymthe.2005.08.007 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 001PK UT WOS:000234548600015 PM 16198149 ER PT J AU Parsons, BL Delongchamp, RR Beland, FA Heflich, RH AF Parsons, BL Delongchamp, RR Beland, FA Heflich, RH TI Levels of H-ras codon 61 CAA to AAA mutation: response to 4-ABP-treatment and Pms2-deficiency SO MUTAGENESIS LA English DT Article ID DNA MISMATCH REPAIR; GENOTYPIC SELECTION; TRANSGENIC MICE; LIVER-TUMORS; PMS2; DEFICIENT; PROTEIN; DAMAGE; CELLS; CISPLATIN AB DNA mismatch repair (MMR) deficiencies result in increased frequencies of spontaneous mutation and tumor formation. In the present study, we tested the hypothesis that a chemically-induced mutational response would be greater in a mouse with an MMR-deficiency than in the MMR-proficient mouse models commonly used to assay for chemical carcinogenicity. To accomplish this, the induction of H-ras codon 61 CAA -> AAA mutation was examined in Pms2 knockout mice (Pms2(-/-), C57BL/6 background) and sibling wild-type mice (Pms2(+/+)). Groups of five or six neonatal male mice were treated with 0.3 mu mol 4-aminobiphenyl (4-ABP) or the vehicle control, dimethylsulfoxide. Eight months after treatment, liver DNAs were isolated and analysed for levels of H-ras codon 61 CAA -> AAA mutation using allele-specific competitive blocker-PCR. In Pms2-proficient and Pms2-deficient mice, 4-ABP treatment caused an increase in mutant fraction (MF) from 1.65 x 10(-5) to 2.91 x 10(-5) and from 3.40 x 10(-5) to 4.70 x 10(-5), respectively. Pooling data from 4-ABP-treated and control mice, the similar to 2-fold increase in MF observed in Pms2-deficient as compared with Pms2-proficient mice was statistically significant (P = 0.0207) and consistent with what has been reported previously in terms of induction of G:C -> T:A mutation in a Pms2-deficient background. Pooling data from both genotypes, the increase in H-ras MF in 4-ABP-treated mice, as compared with control mice, did not reach the 95% confidence level of statistical significance (P = 0.0606). The 4-ABP treatment caused a 1.76-fold and 1.38-fold increase in average H-ras MF in Pms2-proficient and Pms2-deficient mice, respectively. Furthermore, the levels of induced mutation in Pms2-proficient and Pms2-deficient mice were nearly identical (1.26 x 10(-5) and 1.30 x 10(-5), respectively). We conclude that Pms2-deficiency does not result in an amplification of the H-ras codon 61 CAA -> AAA mutational response induced by 4-ABP. C1 Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, USFDA, Jefferson, AR 72079 USA. Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, USFDA, Jefferson, AR 72079 USA. Natl Ctr Toxicol Res, Div Biochem Toxicol, USFDA, Jefferson, AR 72079 USA. RP Parsons, BL (reprint author), Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, USFDA, HFT-120,3900 NCTR Rd, Jefferson, AR 72079 USA. EM bparsons@nctr.fda.gov NR 31 TC 2 Z9 2 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 JAN PY 2006 VL 21 IS 1 BP 29 EP 34 DI 10.1093/mutage/gei066 PG 6 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA 013TE UT WOS:000235431600006 PM 16314341 ER PT J AU Fichtner-Feigl, S Strober, W Kawakami, K Puri, RK Kitani, A AF Fichtner-Feigl, S Strober, W Kawakami, K Puri, RK Kitani, A TI IL-13 signaling through the IL-13 alpha 2 receptor is involved in induction of TGF-beta 1 production and fibrosis SO NATURE MEDICINE LA English DT Article ID GROWTH FACTOR-BETA-1 GENE; NK-T-CELLS; PULMONARY-FIBROSIS; ULCERATIVE-COLITIS; OXAZOLONE COLITIS; TISSUE FIBROSIS; ALPHA-2 CHAIN; IN-VIVO; MICE; INTERLEUKIN-13 AB Interleukin (IL)-13 is a major inducer of fibrosis in many chronic infectious and autoimmune diseases. In studies of the mechanisms underlying such induction, we found that IL-13 induces transforming growth factor (TGF)-beta(1) in macrophages through a two-stage process involving, first, the induction of a receptor formerly considered to function only as a decoy receptor, IL-13R alpha(2). Such induction requires IL-13 (or IL-4) and tumor necrosis factor (TNF)-alpha. Second, it involves IL-13 signaling through IL-13R alpha(2) to activate an AP-1 variant containing c-jun and Fra-2, which then activates the TGFB1 promoter. In vivo, we found that prevention of IL-13R alpha(2) expression reduced production of TGF-beta(1) in oxazolone-induced colitis and that prevention of IL-13Ra2 expression, Il13ra2 gene silencing or blockade of IL-13R alpha(2) signaling led to marked downregulation of TGF-beta(1) production and collagen deposition in bleomycin-induced lung fibrosis. These data suggest that IL-13R alpha(2) signaling during prolonged inflammation is an important therapeutic target for the prevention of TGF-beta(1)-mediated fibrosis. C1 NIAID, NIH, Mucosal Immun Sect, Lab Host Def, Bethesda, MD 20892 USA. Univ Regensburg, Dept Surg, Med Ctr, D-93053 Regensburg, Germany. US FDA, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res,NIH, Bethesda, MD 20892 USA. RP Strober, W (reprint author), NIAID, NIH, Mucosal Immun Sect, Lab Host Def, Bldg 10-CRC 5W3864,10 Ctr Dr, Bethesda, MD 20892 USA. EM wstrober@niaid.nih.gov FU Intramural NIH HHS NR 44 TC 426 Z9 457 U1 3 U2 25 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD JAN PY 2006 VL 12 IS 1 BP 99 EP 106 DI 10.1038/nm1332 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 999VO UT WOS:000234419000058 PM 16327802 ER PT J AU Keller, JE AF Keller, JE TI Recovery from botulinum neurotoxin poisoning in vivo SO NEUROSCIENCE LA English DT Article DE botulism; botulinum neurotoxin; paralysis; recovery; potency assay ID RAT NEUROMUSCULAR-JUNCTION; TOXIN TYPE-A; CLOSTRIDIAL NEUROTOXINS; SKELETAL-MUSCLE; FOODBORNE BOTULISM; CERVICAL DYSTONIA; UNITED-STATES; MOUSE; PARALYSIS; SNAP-25 AB Botulinum neurotoxins cause the disease botulism, which is characterized by prolonged muscle paralysis. In contrast, injections of low doses of purified botulinum neurotoxins do not cause systemic illness but produce localized muscle paralysis that is beneficial for treating several human medical disorders involving uncontrollable muscle contraction. Optimizing the therapeutic efficacy while diminishing adverse reactions requires precise knowledge of toxin potency as well as a clear understanding of how each toxin causes disease. A novel in vivo mouse assay has been used to correlate toxin dosage with the duration of muscle paralysis. Voluntary running activity performed by mice was proportional to the amount of toxin injected into the hind limbs and the subsequent rate of recovery over the ensuing days or weeks was a function of botulinum neurotoxin serotype A or B concentration. Botulinum neurotoxin A produced longer paralysis than botulinum neurotoxin B consistent with human observations. A third serotype, botulinum neurotoxin E, had the shortest duration of action, but unlike the other two toxins, dosage did not influence recovery time. Botulinum neurotoxin A recovery appeared biphasic with the initial phase about two-fold faster than the final phase. Over four weeks, muscle activity had gradually improved following the highest botulinum neurotoxin A dose, reaching about half of the normal running activity. Lower botulinum neurotoxin A doses led to incrementally faster and complete recovery. Persistence of maximum paralysis was exponentially related to botulinum neurotoxin A dosage, with a doubling of the paralysis time occurring with every 25% increase of the toxin concentration. In contrast, the rate of recovery from botulinum neurotoxin B was monophasic relative to toxin dosage and the duration of maximum paralysis was linear relative to dosage. Combinations of botulinum neurotoxin A and B and botulinum neurotoxin A and E were tested and shown to exacerbate paralysis compared with individually administered serotypes. (C) 2006 Published by Elsevier Ltd on behalf of IBRO. C1 US FDA, Lab Bacterial Toxins, Div Bacterial Parasit & Allergen Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Keller, JE (reprint author), US FDA, Lab Bacterial Toxins, Div Bacterial Parasit & Allergen Prod, Ctr Biol Evaluat & Res, 29 Lincoln Dr,HFM 434,Room 122, Bethesda, MD 20892 USA. EM james.keller@fda.hhs.gov NR 57 TC 37 Z9 38 U1 0 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2006 VL 139 IS 2 BP 629 EP 637 DI 10.1016/j.neuroscience.2005.12.029 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 035CC UT WOS:000236976600018 PM 16490322 ER PT J AU Shabalina, SA Ogurtsov, AY Spiridonov, NA AF Shabalina, SA Ogurtsov, AY Spiridonov, NA TI A periodic pattern of mRNA secondary structure created by the genetic code SO NUCLEIC ACIDS RESEARCH LA English DT Article ID FOLDING FREE-ENERGIES; SYNONYMOUS MUTATIONS; SELECTION INTENSITY; SEQUENCE EVOLUTION; TRANSLATION RATE; CODING REGIONS; SILENT SITES; USAGE; EXPRESSION; GENOME AB Single-stranded mRNA molecules form secondary structures through complementary self-interactions. Several hypotheses have been proposed on the relationship between the nucleotide sequence, encoded amino acid sequence and mRNA secondary structure. We performed the first transcriptome-wide in silico analysis of the human and mouse mRNA foldings and found a pronounced periodic pattern of nucleotide involvement in mRNA secondary structure. We show that this pattern is created by the structure of the genetic code, and the dinucleotide relative abundances are important for the maintenance of mRNA secondary structure. Although synonymous codon usage contributes to this pattern, it is intrinsic to the structure of the genetic code and manifests itself even in the absence of synonymous codon usage bias at the 4-fold degenerate sites. While all codon sites are important for the maintenance of mRNA secondary structure, degeneracy of the code allows regulation of stability and periodicity of mRNA secondary structure. We demonstrate that the third degenerate codon sites contribute most strongly to mRNA stability. These results convincingly support the hypothesis that redundancies in the genetic code allow transcripts to satisfy requirements for both protein structure and RNA structure. Our data show that selection may be operating on synonymous codons to maintain a more stable and ordered mRNA secondary structure, which is likely to be important for transcript stability and translation. We also demonstrate that functional domains of the mRNA [5'-untranslated region (5'-UTR), CDS and 3'-UTR] preferentially fold onto themselves, while the start codon and stop codon regions are characterized by relaxed secondary structures, which may facilitate initiation and termination of translation. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. USDA, Ctr Drug Evaluat & Res, Div Therapeut Prot, Bethesda, MD 20892 USA. RP Shabalina, SA (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. EM shabalin@ncbi.nlm.nih.gov RI Shabalina, Svetlana/N-8939-2013; Spiridonov, Nikolay/B-6287-2014 OI Shabalina, Svetlana/0000-0003-2272-7473; FU Intramural NIH HHS NR 55 TC 102 Z9 104 U1 1 U2 9 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PY 2006 VL 34 IS 8 BP 2428 EP 2437 DI 10.1093/nar/gkl287 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 044UD UT WOS:000237697000036 PM 16682450 ER PT J AU Jones, JR Lineback, DM Levine, MJ AF Jones, JR Lineback, DM Levine, MJ TI Dietary reference intakes: Implications for fiber labeling and consumption: A summary of the International Life Sciences Institute North America Fiber Workshop, June 1-2, 2004, Washington, DC SO NUTRITION REVIEWS LA English DT Review ID NUTRITION KNOWLEDGE; FOOD LABELS AB Multiple definitions of dietary fiber have been developed and are in use around the world. The definitions vary as to which substances are considered to be fibers, the analytical methods utilized to identify and measure these fibers, and whether physiological criteria are part of the definition. A workshop entitled "Dietary Reference Intakes: Implications for Fiber Labeling and Consumption" was held by the International Life Sciences Institute North America Technical Committee on Carbohydrates to review the fiber definitions recently published by the Institute of Medicine (IOM) of the National Academies. Presentations and facilitated discussions reviewed the rationale for the IOM definitions of dietary fiber, functional fiber, and total fiber in light of evolving nutritional science. Also discussed were potential analytical, regulatory, and consumer issues involved if the US Food and Drug Administration and/or Health Canada were to implement the IOM's recommendations. Issues, concerns, and questions to be addressed are summarized here. (c) 2006 Intemational Life Sciences Institute. C1 ILSI NA, N Amer Branch, Washington, DC 20005 USA. ILSI NA, Tech Comm Carbohydrates, Washington, DC 20005 USA. Coll St Catherine, Dept Family Consumer & Nutr Sci, Minneapolis, MN USA. Univ Maryland, Joint Inst Food Safety & Appl Nutr, College Pk, MD 20742 USA. RP Levine, MJ (reprint author), ILSI NA, N Amer Branch, 1 Thomas Circle NW,9th Floor, Washington, DC 20005 USA. EM mlevine@ilsi.org NR 21 TC 17 Z9 17 U1 0 U2 4 PU INT LIFE SCIENCES INST NORTH AMERICA PI WASHINGTON PA ONE THOMAS CIRCLE, N W, 9TH FLOOR, WASHINGTON, DC 20005 USA SN 0029-6643 J9 NUTR REV JI Nutr. Rev. PD JAN PY 2006 VL 64 IS 1 BP 31 EP 38 DI 10.1301/nr.2006.jan.31-38 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 009QR UT WOS:000235127800003 PM 16491667 ER PT S AU Klinman, DM Xie, H Ivins, BE AF Klinman, Dennis M. Xie, Hang Ivins, Bruce E. BE Tuschl, T Rossi, J TI CpG oligonucleotides improve the protective immune response induced by the licensed anthrax vaccine SO OLIGONUCLEOTIDE THERAPEUTICS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 1st Annual Meeting of the Oligonucleotide-Therapeutics-Society CY 2005 CL New York, NY SP Oligonucletide Therapeut Soc DE anthrax; vaccine; adjuvant; CpG oligonucleotide; protection ID B SURFACE-ANTIGEN; BACTERIAL-DNA; BACILLUS-ANTHRACIS; SYNTHETIC OLIGODEOXYNUCLEOTIDES; INTERFERON-GAMMA; POTENT ENHANCER; DENDRITIC CELLS; CUTTING EDGE; MOTIFS; INFECTION AB Synthetic oligodeoxynucleotides (ODN) containing unmethylated CpG motifs act as immune adjuvants, improving the response elicited by a coadministered vaccine. Combining CpG ODN with anthrax vaccine adsorbed (AVA, the licensed human vaccine) increases the speed, magnitude, and avidity of the resultant antibody response. IgG Abs against anthrax protective antigen (PA) protect mice, guinuea pigs, and rhesus macaques from infection. C1 US FDA, Sect Retroviral Immunol, CBER, Bethesda, MD 20892 USA. USA, Med Res Inst Infect Dis, Bacteriol Div, Frederick, MD 21702 USA. RP Klinman, DM (reprint author), US FDA, Sect Retroviral Immunol, CBER, Bldg 29A Rm 3 D 10, Bethesda, MD 20892 USA. EM Klinman@CBER.FDA.GOV NR 48 TC 27 Z9 30 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2006 VL 1082 BP 137 EP 150 DI 10.1196/annals.1348.030 PG 14 WC Multidisciplinary Sciences; Pharmacology & Pharmacy SC Science & Technology - Other Topics; Pharmacology & Pharmacy GA BFO50 UT WOS:000243449900018 PM 17145935 ER PT S AU Pfefer, TJ Agrawal, A Drezek, RA AF Pfefer, T. Joshua Agrawal, Anant Drezek, Rebekah A. BE Gannot, I TI Computational modeling of device-tissue interface geometries for time-resolved fluorescence in layered tissue - art. no. 608305 SO Optical Fibers and Sensors for Medical Diagnostics and Treatment Applications VI SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Optical Fibers and Sensors for Medical Diagnostics and Treatment Application VI Conference CY JAN 21-22, 2006 CL San Jose, CA SP SPIE DE time-resolved fluorescence; light-tissue interaction; computational modeling; fiberoptics ID TURBID MEDIA; PROBE DESIGN; SPECTROSCOPY; DEPTH AB Temporal measurements of fluorescence emitted from biological tissue provide information on biochemistry and morphology which may be useful in identifying neoplasia onset. Depth-selective detection of time-resolved fluorescence may enable enhanced discrimination of signals originating from individual tissue layers and thus improve device efficacy. In this study, we investigate how illumination-collection design parameters influence a device's ability to measure fluorophore lifetime and changes in superficial layer thickness. A two-layer, time-resolved Monte Carlo model of fluorescence light propagation in colonic polyps was used to simulate temporal decay curves. Several normal- and oblique-incidence geometries were investigated. Also, the efficacy of a convolution-based, bi-exponential lifetime calculation is compared to a full-width-half-max decay curve metric. Results indicate that interface design has a significant effect on the accuracy of fluorophore lifetime estimates and the ability to discrimnate changes in tissue morphology. This is due to changes in the relative contribution of each tissue layer to the total detected signal. C1 US FDA, Ctr Devices & Radiol Hlth, HFZ 134, Rockville, MD 20857 USA. RP Pfefer, TJ (reprint author), US FDA, Ctr Devices & Radiol Hlth, HFZ 134, 12725 Twinbrook Pkwy, Rockville, MD 20857 USA. NR 18 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-6125-3 J9 P SOC PHOTO-OPT INS PY 2006 VL 6083 BP 8305 EP 8305 AR 608305 DI 10.1117/12.646960 PG 9 WC Engineering, Biomedical; Optics SC Engineering; Optics GA BEF58 UT WOS:000237102500003 ER PT J AU Tomashek, KM Crouse, CJ Iyasu, S Johnson, CH Flowers, LM AF Tomashek, KM Crouse, CJ Iyasu, S Johnson, CH Flowers, LM TI A comparison of morbidity rates attributable to conditions originating in the perinatal period among newborns discharged from United States hospitals, 1989-90 and 1999-2000 SO PAEDIATRIC AND PERINATAL EPIDEMIOLOGY LA English DT Article DE neonatal morbidity; jaundice; birth trauma; intrapartum asphyxia; length of stay; time trends ID BIRTH-WEIGHT INFANTS; CHRONIC LUNG-DISEASE; NEONATAL RESEARCH NETWORK; TERM NEWBORN; READMISSION; MORTALITY; FORCEPS; VACUUM; STAY; HYPERBILIRUBINEMIA AB Perinatal conditions account for 60% of US neonatal deaths, yet little is known about rates of morbidity attributable to these conditions. To estimate these rates, we analysed newborn hospital discharges from the National Hospital Discharge Survey. We used International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) codes to classify discharge diagnoses among a weighted, nationally representative sample of newborns discharged from short-stay, non-federal US hospitals. We compared overall and cause-specific morbidity rates attributable to perinatal conditions (ICD-9-CM 760.0-779.9), as well as the average length of hospital stay among newborn discharges during 1989-90 and 1999-2000. The overall newborn morbidity rate declined from 36.3% in 1989-90 to 33.7% in 1999-2000 (P < 0.01), despite significant increases in high-risk births. The decline can be attributed to significant decreases in the reported rates of jaundice, fetal distress, birth trauma and birth asphyxia. Rates of jaundice decreased from 15.7% to 13.4% (P < 0.01). The average length of stay decreased among newborns with no morbid condition (2.37-2.04 days, P < 0.001) and among those with one perinatal condition (3.11-2.51, P < 0.001), but increased among those with multiple perinatal conditions (8.43-9.98, P < 0.05). Morbidity rates among newborns discharged from US hospitals declined. Shorter newborn hospital stays may have resulted in fewer cases of jaundice being diagnosed before discharge. Stricter diagnostic criteria and changes in obstetric practices may have led to a decline in the rates of fetal distress, birth trauma and birth asphyxia. C1 CDCP, Maternal & Infant Hlth Branch, Div Reprod Hlth, Atlanta, GA 30341 USA. CDCP, Informat Technol Stat & Surveillance Branch, Div Reprod Hlth, Atlanta, GA 30341 USA. US FDA, OCTAP, Div Pediat Drug Dev HFD960, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Tomashek, KM (reprint author), CDCP, Maternal & Infant Hlth Branch, Div Reprod Hlth, Mailstop K-23,Buford Hwy NE, Atlanta, GA 30341 USA. EM kct9@cdc.gov NR 56 TC 12 Z9 13 U1 1 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0269-5022 J9 PAEDIATR PERINAT EP JI Paediatr. Perinat. Epidemiol. PD JAN PY 2006 VL 20 IS 1 BP 24 EP 34 DI 10.1111/j.1365-3016.2006.00690.x PG 11 WC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics SC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics GA 001NL UT WOS:000234543500003 PM 16420338 ER PT J AU Wysowski, DK Governale, LA Swann, J AF Wysowski, DK Governale, LA Swann, J TI Trends in outpatient prescription drug use and related costs in the US - 1998-2003 SO PHARMACOECONOMICS LA English DT Article AB Objective: To present a brief synopsis of trends in the number of prescriptions and retail costs of outpatient drugs dispensed in the US between 1998 and 2003. Methods: Data were extracted from IMS Health, the National Prescription Audit Plus (TM) and the National Disease and Therapeutic Index (TM) databases. Results: In 1998, 2.7 billion outpatient prescriptions were dispensed versus 3.6 billion in 2003. This equates to a 33.3% increase over the 6-year period. Of the top 20 most dispensed drugs by volume, 40% were launched in the 1990s or 2000s. Retail costs for the total market of dispensed outpatient prescription drugs were $US96.1 billion in 1998 and $US196 billion in 2003, a 104% increase. Of the top 20 most dispensed drugs by retail cost, all were tradename drugs and were launched in the 1990s or 2000s. Conclusions: These data indicate a large increase in the US over a short time period in dispensed outpatient prescriptions and their associated retail costs. C1 US FDA, Div Drug Risk Evaluat, Rockville, MD 20857 USA. US FDA, Div Surveillance Res & Commun Support, Rockville, MD 20857 USA. RP Wysowski, DK (reprint author), US FDA, Div Drug Risk Evaluat HFD430, White Oak Campus,Bldg 22,Rm 3424,10903 New Hampsh, Silver Spring, MD 20993 USA. NR 5 TC 17 Z9 17 U1 0 U2 0 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 1170-7690 J9 PHARMACOECONOMICS JI Pharmacoeconomics PY 2006 VL 24 IS 3 BP 233 EP 236 DI 10.2165/00019053-200624030-00003 PG 4 WC Economics; Health Care Sciences & Services; Health Policy & Services; Pharmacology & Pharmacy SC Business & Economics; Health Care Sciences & Services; Pharmacology & Pharmacy GA 026TB UT WOS:000236364100003 PM 16519545 ER PT J AU Vernon, JA AF Vernon, John A. TI Letter from the Commissioner's Office at the US FDA SO PHARMACOECONOMICS LA English DT Editorial Material C1 US FDA, Off Commissioner, Rockville, MD 20857 USA. RP Vernon, JA (reprint author), US FDA, Off Commissioner, Rockville, MD 20857 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 1170-7690 J9 PHARMACOECONOMICS JI Pharmacoeconomics PY 2006 VL 24 IS 12 BP 1179 EP 1179 DI 10.2165/00019053-200624120-00003 PG 1 WC Economics; Health Care Sciences & Services; Health Policy & Services; Pharmacology & Pharmacy SC Business & Economics; Health Care Sciences & Services; Pharmacology & Pharmacy GA 124AS UT WOS:000243339800002 PM 17129073 ER PT J AU Shatin, D Rawson, NSB Curtis, JR Braun, MM Martin, CK Moreland, LW Becker, AF Patkar, NM Allison, JJ Saag, KG AF Shatin, D Rawson, NSB Curtis, JR Braun, MM Martin, CK Moreland, LW Becker, AF Patkar, NM Allison, JJ Saag, KG TI Documented tuberculin skin testing among infliximab users following a multi-modal risk communication interventions SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Article DE rheumatoid arthritis; tuberculin skin testing; infliximab; risk communication ID NECROSIS-FACTOR-ALPHA; RHEUMATOID-ARTHRITIS; CROHNS-DISEASE; MONOCLONAL-ANTIBODY; IMPACT; FDA; METHOTREXATE; PRESCRIPTION; MANAGEMENT; INFECTION AB Purpose Following its licensure, tuberculosis (TB) was reported as a potential adverse effect of infliximab. Subsequently, the product circular was changed to recommend tuberculin skin testing before patients received infliximab, which was reinforced by several risk communication efforts. The aim of this study was to evaluate patterns and predictors of documented tuberculin skin testing in patients before and after manufacturer, federal, and academic risk communications. Methods Patients administered infliximab were identified from 11 health plans located throughout the United States, and claims data were examined to determine whether the patients had received a tuberculin skin test. Patients were divided into three cohorts depending on the timing of their first infliximab treatment in relation to the risk communication efforts. Results The overall tuberculin skin testing rate doubled from 15.4% in the first cohort to 30.9% in the last cohort, while the rate of pre-infliximab treatment testing increased from 0 to 27.7% (Chi-squared test for trend, p < 0.0001 for both). Tuberculin skin testing rates were significantly higher in women, those with a diagnosis of rheumatoid or psoriatic arthritis, and those with a rheumatologist as prescriber. After multivariable analysis, only rheumatologist remained significantly associated with tuberculin skin testing. Conclusions Although the tuberculin skin testing rate was relatively low overall, tuberculin skin testing doubled over 30 months of ongoing risk communication efforts and under ascertainment likely occurred. We also found variation in the tuberculin skin testing rate associated with physician specialty. This study demonstrates a significant change in patient care following risk communication efforts. Copyright (c) 2005 John Wiley & Sons, Ltd. C1 Ctr Hlth Care Policy & Evaluat, Minneapolis, MN USA. Univ Alabama, CERTs Musculoskeletal Disorders, Birmingham, AL USA. US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. RP Saag, KG (reprint author), Univ Alabama, Div Clin Immunol Rheumatol, 820 Fac Off Tower,1530 3rd Ave S, Birmingham, AL 35294 USA. EM ksaag@uab.edu OI Allison, Jeroan/0000-0003-4472-2112 NR 27 TC 4 Z9 4 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD JAN PY 2006 VL 15 IS 1 BP 11 EP 18 DI 10.1002/pds.1132 PG 8 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 006CO UT WOS:000234872900002 PM 16136625 ER PT J AU Itzhak, Y Ali, SF AF Itzhak, Y Ali, SF TI Role of nitrergic system in behavioral and neurotoxic effects of amphetamine analogs SO PHARMACOLOGY & THERAPEUTICS LA English DT Review DE methamphetamine; MDMA (Ecstasy); methylphenidate; fenfluramine; p-chloroamphetamine; cocaine; nitric oxide (NO); sensitization; neurotoxicity; dopamine; serotonin ID NITRIC-OXIDE SYNTHASE; CONDITIONED PLACE PREFERENCE; METHAMPHETAMINE-INDUCED NEUROTOXICITY; INDUCED DOPAMINERGIC NEUROTOXICITY; FREELY MOVING RATS; INDUCED LOCOMOTOR SENSITIZATION; NERVE-TERMINAL DEGENERATION; FIBRILLARY ACIDIC PROTEIN; BRAIN-SEROTONIN NEURONS; IN-VIVO MICRODIALYSIS AB Several amphetamine analogs are potent psychostimulants and major drugs of abuse. In animal models, the psychomotor and reinforcing effects of amphetamine, methamphetamine (METH), 3,4-methylenedioxymethamphetamine (MDMA; Ecstasy), and methylphenidate (MPD; Ritalin) are thought to be dependent on increased extracellular levels of dopamine (DA) in mesocorticolimbic and mesostriatal pathways. However, amphetamine analogs that increase primarily serotonergic, transmission, such as p-chloroamphetamine (PCA) and fenfluramine (FEN), have no potential for abuse. High doses of METH, MDMA, PCA, and FEN produce depletions of dopaminergic and serotonergic nerve terminal markers and are considered as potential neurotoxicants. The first part of this review briefly summarizes the behavioral and neurotoxic effects of amphetamines that have a different spectrum of activity on dopaminergic and serotonergic systems. The second part discusses evidence supporting involvement of the nitrergic system in dopamine-mediated effects of amphetamines. The nitrergic, system in this context corresponds to nitric oxide (NO) produced from neuronal nitric oxide synthase (nNOS) that has roles in nonsynaptic interneuronal communication and excitotoxic neuronal injury. Increasing evidence now suggests cross talk between dopamine, glutamate, and NO. Results from our laboratory indicate that dopamine-dependent psychomotor, reinforcing, and neurotoxic effects of amphetamines are diminished by pharmacological blockade of nNOS or deletion of the nNOS gene. These findings, and evidence supporting the role of NO in synaptic plasticity and neurotoxic insults, suggest that NO functions as a neuronal messenger and a neurotoxicant subsequent to exposure to amphetamine-like psychostimulants. (c) 2005 Elsevier Inc. All rights reserved. C1 Univ Miami, Sch Med, Dept Psychiat & Behav Sci, Miami, FL 33136 USA. US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Neurochem Lab, Jefferson, AR 72079 USA. RP Itzhak, Y (reprint author), Univ Miami, Sch Med, Dept Psychiat & Behav Sci, 1011 NW 15th St Gautier 503, Miami, FL 33136 USA. EM yitzhak@med.miami.edu FU NIDA NIH HHS [DA12867, DA 19107] NR 180 TC 44 Z9 45 U1 3 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0163-7258 J9 PHARMACOL THERAPEUT JI Pharmacol. Ther. PD JAN PY 2006 VL 109 IS 1-2 BP 246 EP 262 DI 10.1016/j.pharmthera.2005.08.004 PG 17 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 996GK UT WOS:000234162200016 PM 16154200 ER PT J AU Mears, D Zimliki, C Chenault, VM AF Mears, D Zimliki, C Chenault, VM TI Electrical signaling in pancreatic beta-cells from Psammomys obesus, an animal model of type 2 diabetes: Implications for glucose homeostasis SO PLACENTA LA English DT Meeting Abstract CT Joint Meeting of the 2nd Latinamerican Symposium on Fetal-Mateanal Interaction and Placenta/19th Annual Meeting of the Chilean-Society-of-Physiological-Sciences CY NOV 06-09, 2005 CL Santiago, CHILE SP Chilean Soc Physiol Sci C1 Univ Chile, Fac Med, ICBM, Santiago, Chile. Uniformed Serv Univ Hlth Sci, Bethesda, MD USA. US FDA, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0143-4004 J9 PLACENTA JI Placenta PD JAN PY 2006 VL 27 IS 1 BP A38 EP A38 PG 1 WC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology SC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology GA 993YM UT WOS:000233996200127 ER PT B AU Li, QH Lagakos, SW AF Li, QH Lagakos, SW BE Nikulin, M Commenges, D Huber, C TI Comparisons of test statistics arising from marginal analyses of multivariate survival data SO Probability, Statistics and Modelling in Public Health LA English DT Proceedings Paper CT Workshop on Probability, Statistics and Modelling in Public Health CY SEP 22-23, 2003 CL Bordeaux, FRANCE SP l IFR-99 Sante Publique DE directional tests; marginal model; multivariate survival data; omnibus test; recurring events ID FAILURE TIME DATA; HUMAN-IMMUNODEFICIENCY-VIRUS; REGRESSION-ANALYSIS; ZIDOVUDINE; DISTRIBUTIONS; 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 [WLW89]. 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 two 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 20855 USA. RP Li, QH (reprint author), US FDA, Ctr Drug Evaluat & Res, HFD-705,7500 Standish Pl, Rockville, MD 20855 USA. NR 18 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 0-387-26022-6 PY 2006 BP 299 EP 318 DI 10.1007/0-387-26023-4_20 PG 20 WC Public, Environmental & Occupational Health; Mathematics, Interdisciplinary Applications; Statistics & Probability SC Public, Environmental & Occupational Health; Mathematics GA BDG73 UT WOS:000233422800020 ER PT B AU Oeller, D Oeller, M AF Oeller, Douglass Oeller, Margaret BE Marx, KL Roston, MA TI FDA briefing: Drug approval, MUMS, compounding, & personal imports SO Proceedings of the 27th Annual Conference on Avian Medicine and Surgery LA English DT Proceedings Paper CT 27th Annual Conference on Avian Medicine and Surgery CY APR 02-04, 2006 CL Virginia Beach, VA SP Mid Atlantic States Assoc Avian Veterinarians AB This presentation discusses the Food and Drug Administration approval process for new animal drugs, the rules for drug usage for Minor Uses and Minor Species (MUMS), rules for drug compounding and policies for personal drug importation. C1 FDA Ctr Vet Med, Off New Anim Drug Evaluat, Div Therapeut Drug Non Food Anim, Rockville, MD USA. RP Oeller, D (reprint author), FDA Ctr Vet Med, Off New Anim Drug Evaluat, Div Therapeut Drug Non Food Anim, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MID-ATLANTIC STATES ASSOC AVIAN VETERINARIANS PI BLACKSBURG PA MEMORIAL BLDG SUITE 291 610 N MAIN STREET, BLACKSBURG, VA 24060-3349 USA PY 2006 BP 93 EP 114 PG 22 WC Ornithology; Veterinary Sciences SC Zoology; Veterinary Sciences GA BES67 UT WOS:000239306900010 ER PT S AU Trucksess, MW Weaver, C Oles, C D'Ovidio, K Rader, JI AF Trucksess, Mary W. Weaver, Carol Oles, Carolyn D'Ovidio, Kathleen Rader, Jeanne I. BE Khan, IA Smillie, TJ Craker, LE Gardner, ZE TI Determination of mycotoxins in botanical roots SO Proceedings of the Fourth International Conference on Quality and Safety Issues Related to Botanicals SE ACTA HORTICULTURAE LA English DT Proceedings Paper CT 4th International Conference on Quality and Safety Issues Related to Botanicals CY AUG 15-18, 2005 CL University, MS DE aflatoxins; Echinacea purpurea; fumonisins; ginger; ginseng; Glycyrrhiza glabra; kava-kava; ochratoxin A; Panax ginseng; Panax quinquefolius; Piper methysticum; Zingiber officinale ID LIQUID-CHROMATOGRAPHY; AFLATOXINS AB Mycotoxins are toxic secondary metabolites produced by certain molds and are common contaminants of many important food crops, such as grains, nuts, and spices. Some mycotoxins are found in fruits, vegetables, and botanical roots. These contaminants have a broad range of toxic effects, including carcinogenicity, immunotoxicity, neurotoxicity, and reproductive and developmental toxicity. The public health concerns related to both acute and chronic effects of mycotoxins in animals have prompted more than 100 countries to establish regulatory limits for some of the well-known mycotoxins such as the aflatoxins (AFL). Our research focused on method development for two of these toxins: AFL and ochratoxin A (OTA) in botanical roots, specifically in ginseng and other selected roots. Methods using an immunoaffinity column (IAC) cleanup, liquid chromatographic separation, and fluorescence detection were modified and evaluated. Two types of JAC were evaluated: JAC for AFL and JAC for both AFL and OTA. Three derivatization techniques to enhance the fluorescence of the AFL were compared: pre-column trifluoroacetic acid, post-column bromination and post-column UV irradiation. No derivatization was needed for OTA. Results for AFL using the single analyte JAC and the three derivatization techniques were all comparable for ginseng and for other roots such as ginger, licorice, and kava-kava. Recoveries of added AFL for ginseng at levels from 2 ng/g to 16 ng/g were about 80%. Recoveries of added AFL for ginger, licorice and kava-kava were about 60%. Recoveries of added AFL for ginseng at 4-16 ng/g using IAC for both AFL and OTA were about 70%. Recoveries of added OTA for ginseng, ginger, and echinacea at 4 ng/g were about 55%. C1 US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. RP Trucksess, MW (reprint author), US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. NR 13 TC 2 Z9 2 U1 0 U2 2 PU INTERNATIONAL SOCIETY HORTICULTURAL SCIENCE PI LEUVEN 1 PA PO BOX 500, 3001 LEUVEN 1, BELGIUM SN 0567-7572 BN 90-6605-629-0 J9 ACTA HORTIC PY 2006 IS 720 BP 103 EP 112 PG 10 WC Plant Sciences; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA BFP09 UT WOS:000243533800010 ER PT S AU Wong, JW Wirtz, MS Hennessy, MK Schenck, FJ Krynitsky, AJ Capar, SG AF Wong, Jon W. Wirtz, Mark S. Hennessy, Michael K. Schenck, Frank J. Krynitsky, Alexander J. Capar, Stephen G. BE Khan, IA Smillie, TJ Craker, LE Gardner, ZE TI Pesticides in botanical dietary supplements SO Proceedings of the Fourth International Conference on Quality and Safety Issues Related to Botanicals SE ACTA HORTICULTURAE LA English DT Proceedings Paper CT 4th International Conference on Quality and Safety Issues Related to Botanicals CY AUG 15-18, 2005 CL University, MS DE Citrus aurantium; Echinacea sp.; ginseng; multiresidue methods; Panax sp. ID TANDEM MASS-SPECTROMETRY; MULTI-RESIDUE METHOD; LIQUID-CHROMATOGRAPHY; GAS-CHROMATOGRAPHY; MULTIRESIDUE DETERMINATION; ORGANOCHLORINE PESTICIDES; MEDICINAL-PLANTS; UNITED-STATES; VEGETABLES; FRUITS AB Current U.S. Food and Drug Administration (FDA) procedures to analyze pesticides in botanical dietary supplements are described. The procedures are from FDA protocols for pesticide analysis in foods, which involve organic solvent extraction (usually with acetonc:water or acetonitrile:water) of the sample, followed by cleanup to remove interfering coextractives, and subsequent analysis primarily by gas chromatography-mass spectrometry. In samples collected in 2004, pesticides were found in 44 out of 87 samples of botanical dietary supplements (the majority of these being ginseng products) suspected of containing pesticides. Over 30 different types of organochlorine, organophosphorus, and organonitrogen pesticide residues were present in these samples, with pentachloroaniline, pentachlorobenzene, and quintozene being the most abundant. A majority of these products contained more than one pesticide; one such sample was found to contain as many as 12 organochlorine compounds. Concentrations of pesticide residues ranged from 0.001 (pentachloroaniline and pentachlorophenyl methyl ester) to 5.57 mg/kg (quintozene). The presence and concentration of pesticides found in dietary supplements indicate the need for increased monitoring. However, current and new procedures need to be validated for pesticides in botanical dietary supplements and expanded to include other pesticide classes. C1 US FDA, Ctr Food Safety & Nutr, College Pk, MD 20740 USA. RP Wong, JW (reprint author), US FDA, Ctr Food Safety & Nutr, 5100 Paint Branch Pkwy,HFS-336, College Pk, MD 20740 USA. NR 30 TC 0 Z9 0 U1 1 U2 3 PU INTERNATIONAL SOCIETY HORTICULTURAL SCIENCE PI LEUVEN 1 PA PO BOX 500, 3001 LEUVEN 1, BELGIUM SN 0567-7572 BN 90-6605-629-0 J9 ACTA HORTIC PY 2006 IS 720 BP 113 EP 128 PG 16 WC Plant Sciences; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA BFP09 UT WOS:000243533800011 ER PT S AU Chen, ST AF Chen, Shaw T. BE Khan, IA Smillie, TJ Craker, LE Gardner, ZE TI Safety evaluation of botanicals as new drugs: A report from CDER botanical team SO Proceedings of the Fourth International Conference on Quality and Safety Issues Related to Botanicals SE ACTA HORTICULTURAE LA English DT Proceedings Paper CT 4th International Conference on Quality and Safety Issues Related to Botanicals CY AUG 15-18, 2005 CL University, MS DE dietary supplements; investigational new drug; medicinal plants; new drug application AB This presentation will summarize the experience of safety evaluation for botanical products to be used as drugs, from the perspective of U.S. Food and Drug Administration (FDA). The current regulatory environment will be reviewed first, with a report on the status of botanical drug applications in FDA's Center for Drug Evaluation and Research (CDER). Regulatory experience and related issues in the safety reviews of botanical applications will then follow. More emphasis will be placed on the safety assessment of botanical INDs (investigational New Drug application); basic principles in safety review of botanical NDAs (New Drug Application for marketing approval) will also be discussed. C1 US FDA, Off Drug Evaluat 1, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Chen, ST (reprint author), US FDA, Off Drug Evaluat 1, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave,Bldg 22,Room 4134, Silver Spring, MD 20993 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU INTERNATIONAL SOCIETY HORTICULTURAL SCIENCE PI LEUVEN 1 PA PO BOX 500, 3001 LEUVEN 1, BELGIUM SN 0567-7572 BN 90-6605-629-0 J9 ACTA HORTIC PY 2006 IS 720 BP 181 EP 184 PG 4 WC Plant Sciences; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA BFP09 UT WOS:000243533800017 ER PT B AU Nano, F Elkins, K AF Nano, Francis Elkins, Karen BE Dworkin, M Falkow, S Rosenberg, E Schleifer, KH Stackebrandt, E TI The Genus Francisella SO PROKARYOTES: A HANDBOOK ON THE BIOLOGY OF BACTERIA, VOL 6, THIRD EDITION: PROTEOBACTERIA: GAMMA SUBCLASS LA English DT Article; Book Chapter ID LIVE VACCINE STRAIN; NECROSIS-FACTOR-ALPHA; FORMERLY YERSINIA-PHILOMIRAGIA; LABORATORY-ACQUIRED TULAREMIA; EXPERIMENTAL MURINE TULAREMIA; INHIBITING ACID-PHOSPHATASE; POLYMERASE CHAIN-REACTION; EARLY PROTECTIVE IMMUNITY; CELL-MEDIATED-IMMUNITY; TULARENSIS LVS C1 [Nano, Francis] Univ Victoria, Dept Biochem & Microbiol, Victoria, BC V8W 3PG, Canada. [Elkins, Karen] US FDA, CDER, Rockville, MD 20852 USA. RP Nano, F (reprint author), Univ Victoria, Dept Biochem & Microbiol, Victoria, BC V8W 3PG, Canada. OI Nano, Francis/0000-0002-9363-7830 NR 120 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-0-387-25496-8 PY 2006 BP 1119 EP 1132 DI 10.1007/0-387-30746-x_44 D2 10.1007/0-387-30746-X PG 14 WC Microbiology SC Microbiology GA BKK09 UT WOS:000268343700044 ER PT J AU Chen, HZ Li, XL Xu, HY Ljungdahl, LG Cerniglia, CE AF Chen, Huizhong Li, Xin-Liang Xu, Haiyan Ljungdahl, Lars G. Cerniglia, Carl E. TI High level expression and characterization of the cyclophilin B gene from the anaerobic fungus Orpinomyces sp strain PC-2 SO PROTEIN AND PEPTIDE LETTERS LA English DT Article DE cyclophilin B; PPIase; Orpinomyces sp strain PC-2; characterization; introns; gene analysis ID PROLYL CIS/TRANS ISOMERASES; CIS-TRANS-ISOMERASE; X-RAY-STRUCTURE; NEOCALLIMASTIX-FRONTALIS; RUMINAL FUNGI; ISOMERIZATION; PROTEINS; ENCODES; FK506; DNA AB Cyclophilins are an evolutionarily conserved family of peptidyl-prolyl cis-trans isomerases (PPIases). A cyclophilin B (cypB) gene from the anaerobic fungus Orpinomyces sp. strain PC-2 was cloned and overexpressed in Escherichia coli. It was expressed as an amino-terminal 6 x His-tagged recombinant protein to facilitate purification. Highly purified protein (26.5 kDa) was isolated by two chromatographic steps involving affinity and gel filtration for biochemical studies of the enzyme. The recombinant CypB displayed PPIase activity with a k(cat)/K(m) of 8.9 x 10(6) m(-1) s(-1) at 10 degrees C and pH 7.8. It was inhibited by cyclosporin A (CsA) with an IC(50) of 23.5 nM, similar to those of the native protein and other cyclophilin B enzymes from animals. Genomic DNA analysis of cypB revealed that it was present as a single copy in Orpinomyces PC-2 and contained two introns, indicating it has a eukaryotic origin. It is one of the most heavily interrupted genes with intron sequences found in anaerobic fungi. The three-dimensional model of Orpinomyces PC-2 CypB was predicted with a homology modeling approach using the Swiss-Model Protein Modeling Server and three dimensional structure of human CypB as a template. The overall architecture of the CypB molecule is very similar to that of human CypB. C1 US FDA, Div Microbiol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. USDA ARS, Natl Ctr Agr Utilizat Res, Fermentat Biotechnol Res Unit, Peoria, IL 61604 USA. Univ Georgia, Dept Biochem & Mol Biol, Athens, GA 30602 USA. Univ Georgia, Ctr Biol Resource Recovery, Athens, GA 30602 USA. RP Chen, HZ (reprint author), US FDA, Div Microbiol, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM huizhong.chen@fda.hhs.gov NR 32 TC 1 Z9 1 U1 0 U2 1 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 0929-8665 J9 PROTEIN PEPTIDE LETT JI Protein Pept. Lett. PY 2006 VL 13 IS 7 BP 727 EP 732 DI 10.2174/092986606777790511 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 060EZ UT WOS:000238786500013 PM 17018017 ER PT J AU Buchalla, R Begley, TH AF Buchalla, R Begley, TH TI Characterization of gamma-irradiated polyethylene terephthalate by liquid-chromatography-mass-spectrometry (LC-MS) with atmospheric-pressure chemical ionization (APCI) SO RADIATION PHYSICS AND CHEMISTRY LA English DT Article DE polyethylene terephthalate; ionizing radiation; radiolysis products; liquid-chromatography-mass-spectrometry ID VOLATILE RADIOLYSIS PRODUCTS; ELECTRON-BEAM IRRADIATION; FOOD-PACKAGING MATERIALS; TRANSFORMATION PRODUCTS; IONIZING-RADIATION; FILM; POLYMERS; IDENTIFICATION; MIGRATION; COLUMNS AB Low-molecular-weight (low-MW) constituents of polyethylene terephthalate (PET), irradiated with Co-60 gamma rays at 25 and 50 kGy. were analvzed by HPLC-MS with atmospheric-pressure chemical ionization (APCI). Consistent with earlier results. the concentrations of the major compounds that are present in the non-irradiated PET do not change perceptibly. However. we find a small but significant increase in terephthalic acid ethylester, from less than 1 mg/kg in the non-irradiated control to ca. 2 mg/kg after 50 kGy, which has not been described before. The finding is important because it gives an impression of the sensitivity of the analytical method. Additionally, it shows that even very radiation-resistant polymers can form measurable amounts of low-MW radiolysis products. The potential and limitations of LC-MS for the analysis of radiolysis products and unidentified migrants are briefly discussed in the context of the question: How can we validate our analytical methods for unknown analytes? (C) 2005 Elsevier Ltd. All rights reserved. C1 US FDA, Div Chem Res & Environm Review, College Pk, MD 20740 USA. RP Buchalla, R (reprint author), Kings Coll London, Dept Pharm, Franklin Wilkins Bldg,150 Stamford St, London SE1 9NH, England. EM rainer.buchalla@kcl.ac.uk NR 25 TC 19 Z9 19 U1 2 U2 11 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 JAN PY 2006 VL 75 IS 1 BP 129 EP 137 DI 10.1016/j.radphyschem.2005.05.012 PG 9 WC Chemistry, Physical; Nuclear Science & Technology; Physics, Atomic, Molecular & Chemical SC Chemistry; Nuclear Science & Technology; Physics GA 994XG UT WOS:000234063900018 ER PT J AU Komolprasert, V Diel, T Sadler, G AF Komolprasert, V Diel, T Sadler, G TI Gamma irradiation of yellow and blue colorants in polystyrene packaging materials SO RADIATION PHYSICS AND CHEMISTRY LA English DT Article DE gamma irradiation; colorant; polystyrene ID FOOD CONTACT MATERIALS; IONIZING-RADIATION; TRANSFORMATION PRODUCTS; TITANIUM-DIOXIDE; ELECTRON-BEAM; POLYETHYLENE; ADDITIVES; MIGRATION; POLYPROPYLENE; PIGMENTS AB The effect of 10- and 20-kGy gamma irradiation was Studied on chromophtal yellow 2RLTS (Yellow 110-2, 3, 4, 5-tetrachloro-6-cyanobenzoic acid) and Irgalite Blue GBP (copper (II) phthalocyanine blue) colorants, which were added to polystyrene (PS) material used to package food prior to irradiation. Analytical results obtained suggest that irradiation did not generate any new chemicals in the PS polymer containing either yellow or blue colorant at a concentration of up to 1% (w/w). Both yellow and blue colorants are relatively stable to gamma irradiation. (C) 2005 Elsevier Ltd. All rights reserved. C1 US FDA, Div Food Proc & Packaging, Summit Argo, IL 60501 USA. IIT, Natl Ctr Food Safety & Technol, Summit Argo, IL 60501 USA. RP Komolprasert, V (reprint author), US FDA, Div Food Proc & Packaging, 6502 S Archer Rd, Summit Argo, IL 60501 USA. EM vanee.komolprasert@cfsan.fda.gov NR 20 TC 6 Z9 7 U1 1 U2 4 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 JAN PY 2006 VL 75 IS 1 BP 149 EP 160 DI 10.1016/j.radphyschem.2005.04.023 PG 12 WC Chemistry, Physical; Nuclear Science & Technology; Physics, Atomic, Molecular & Chemical SC Chemistry; Nuclear Science & Technology; Physics GA 994XG UT WOS:000234063900020 ER PT J AU Heller, DN Smith, ML Chiesa, OA AF Heller, DN Smith, ML Chiesa, OA TI Detection of penicillin residues in bovine oral fluid (saliva) by liquid chromatography/tandem mass spectrometry SO RAPID COMMUNICATIONS IN MASS SPECTROMETRY LA English DT Letter ID PENETRATION; DRUG; QUANTIFICATION; MELATONIN C1 US FDA, Ctr Vet Med, Res Off, Laurel, MD 20708 USA. RP Heller, DN (reprint author), US FDA, Ctr Vet Med, Res Off, 841 Muirkirk Rd, Laurel, MD 20708 USA. EM david.heller@fda.gov NR 19 TC 2 Z9 2 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0951-4198 J9 RAPID COMMUN MASS SP JI Rapid Commun. Mass Spectrom. PY 2006 VL 20 IS 2 BP 321 EP 324 DI 10.1002/rcm.2301 PG 4 WC Chemistry, Analytical; Spectroscopy SC Chemistry; Spectroscopy GA 003PG UT WOS:000234693500036 PM 16345136 ER PT J AU Turnipseed, SB Andersen, WC Karbiwnyk, CM Roybal, JE Miller, KE AF Turnipseed, SB Andersen, WC Karbiwnyk, CM Roybal, JE Miller, KE TI No-discharge atmospheric pressure chemical ionization: evaluation and application to the analysis of animal drug residues in complex matrices SO RAPID COMMUNICATIONS IN MASS SPECTROMETRY LA English DT Article ID CHROMATOGRAPHY MASS-SPECTROMETRY; LIQUID-CHROMATOGRAPHY; MALACHITE GREEN; SPRAY IONIZATION; LC-MS; PHOTOIONIZATION; ELECTROSPRAY; CONFIRMATION; ANTIBIOTICS; METABOLITES AB Alternative ionization methods are increasingly being utilized to increase the versatility and selectivity of liquid chromatography/mass spectrometry (LC/MS). One such technique is the practice of using commercially available atmospheric pressure chemical ionization (APCI) sources with the corona discharge turned off, a process termed no-discharge APCI (ND-APCI). The relative LC/MS responses for several different classes of veterinary drugs were obtained by using ND-APCI, electrospray ionization (ESI), and APCI. While the ND-APCI-MS and -MSn spectra for these compounds were comparable with ESI, ND-APCI provided advantages in sensitivity and selectivity for some compounds. Drugs that were charged in solution as cations or sodium adducts responded particularly well with this technique. Instrumental parameters such as temperatures, gas and liquid flow rates, and source design were investigated to determine their effect on the process of ND-APCI. This paper explores advantages of using ND-APCI for the determination and confirmation of drug residues that might be found in food matrices, including malachite green residues in fish tissue and avermectin residues in milk. Published in 2006 by John Wiley & Sons, Ltd. C1 US FDA, Anim Drugs Res Ctr, Denver Fed Ctr, Denver, CO 80225 USA. Univ Denver, Dept Chem & Biochem, Denver, CO 80208 USA. RP Turnipseed, SB (reprint author), US FDA, Anim Drugs Res Ctr, Denver Fed Ctr, Denver, CO 80225 USA. EM Sherri.turnipseed@fda.hhs.gov NR 29 TC 23 Z9 24 U1 1 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0951-4198 EI 1097-0231 J9 RAPID COMMUN MASS SP JI Rapid Commun. Mass Spectrom. PY 2006 VL 20 IS 8 BP 1231 EP 1239 DI 10.1002/rcm.2438 PG 9 WC Biochemical Research Methods; Chemistry, Analytical; Spectroscopy SC Biochemistry & Molecular Biology; Chemistry; Spectroscopy GA 033MV UT WOS:000236852800010 PM 16541409 ER PT J AU Wilkes, JG Buzatu, DA Dare, DJ Dragan, YP Chiarelli, MP Holland, RD Beaudoin, M Heinze, TM Nayak, R Shvartsburg, AA AF Wilkes, JG Buzatu, DA Dare, DJ Dragan, YP Chiarelli, MP Holland, RD Beaudoin, M Heinze, TM Nayak, R Shvartsburg, AA TI Improved cell typing by charge-state deconvolution of matrix-assisted laser desorption/ionization mass spectra SO RAPID COMMUNICATIONS IN MASS SPECTROMETRY LA English DT Article ID IONIC LIQUID MATRICES; MALDI-TOF; DESORPTION IONIZATION; QUANTITATIVE-ANALYSIS; SAMPLE PREPARATION; SECONDARY-ION; WHOLE CELLS; SPECTROMETRY; TIME; QUANTIFICATION AB Robust, specific, and rapid identification of toxic strains of bacteria and viruses, to guide the mitigation of their adverse health effects and optimum implementation of other response actions, remains a major analytical challenge. This need has driven the development of methods for classification of microorganisms using mass spectrometry, particularly matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS), that allows high-throughput analyses with minimum sample preparation. We describe a novel approach to cell typing based on pattern recognition of MALDI mass spectra, which involves charge-state deconvolution in conjunction with a new correlation analysis procedure. The method is applicable to both prokaryotic and eukaryotic cells. Charge-state deconvolution improves the quantitative reproducibility of spectra because multiply charged ions resulting from the same biomarker attaching a different number of protons are recognized and their abundances are combined. This allows a clearer distinction of bacterial strains or of cancerous and normal liver cells. Improved class distinction provided by charge-state deconvolution was demonstrated by cluster spacing on canonical variate score charts and by correlation analyses. Deconvolution may enhance detection of early disease state or therapy progress markers in various tissues analyzed by MALDI-MS. Published in 2006 by John Wiley & Sons, Ltd. C1 US FDA, Natl Ctr Toxicol Res, Div Syst Toxicol, Jefferson, AR 72079 USA. Manchester Metropolitan Univ, Res Dev Unit, Manchester M15 6BH, Lancs, England. Loyola Univ, Dept Chem, Chicago, IL 60626 USA. ZTech Corp, Jefferson, AR 72079 USA. Pacific NW Natl Lab, Div Biol Sci, Richland, WA 99352 USA. RP Wilkes, JG (reprint author), US FDA, Natl Ctr Toxicol Res, Div Syst Toxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM jon.wilkes@fda.hhs.gov NR 64 TC 6 Z9 6 U1 0 U2 3 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0951-4198 J9 RAPID COMMUN MASS SP JI Rapid Commun. Mass Spectrom. PY 2006 VL 20 IS 10 BP 1595 EP 1603 DI 10.1002/rcm.2475 PG 9 WC Biochemical Research Methods; Chemistry, Analytical; Spectroscopy SC Biochemistry & Molecular Biology; Chemistry; Spectroscopy GA 046EN UT WOS:000237794300019 PM 16628570 ER PT J AU Gratz, SR Gamble, BM Flurer, RA AF Gratz, Samuel R. Gamble, Bryan M. Flurer, Rick A. TI Accurate mass measurement using Fourier transform ion cyclotron resonance mass spectrometry for structure elucidation of designer drug analogs of tadalafil, vardenafil and sildenafil in herbal and pharmaceutical matrices SO RAPID COMMUNICATIONS IN MASS SPECTROMETRY LA English DT Article ID SYNTHETIC PHOSPHODIESTERASE-5 INHIBITORS; PERFORMANCE LIQUID-CHROMATOGRAPHY; DIETARY-SUPPLEMENTS; ELECTROSPRAY-IONIZATION; POTENCY; IDENTIFICATION; PRODUCT AB Phosphodiesterase type 5 (PDE-5) inhibitors are a class of drugs used primarily in the treatment of erectile dysfunction. The Food and Drug Administration (FDA) approved PDE-5 inhibitors include sildenafil citrate, vardenafil hydrochloride and tadalafil. In this study, accurate mass measurements were made by electrospray ionization (ESI) using Fourier transform ion cyclotron resonance mass spectrometry (FTICRMS) to elucidate the structures of sildenafil, tadalafil and vardenafil analogs that were found in products marketed as dietary supplements. Initial detection of these analogs was accomplished through routine screening of suspect samples by liquid chromatography/electrospray ionization multi-stage mass spectrometry (LC/ESI-MS') on a low-resolution ion trap instrument. The chromatographic behavior and mass spectrometric fragmentation patterns observed were often similar to those observed for FDA approved PDE-5 inhibitors. The mass accuracy and resolving power associated with FTICRMS allows for the determination of elemental compositions. Elucidation of the product ion structures for the analogs was accomplished through the use of accurate mass measurements with the aid of Mass Frontier software (version 4.0). Using FTICRMS, accurate masses with measurement errors averaging < 0.4 ppm were achieved, allowing assignment of one possible elemental formula to each fragment ion. The mass measurement errors associated with [M + H](+) for the analogs aminotadalafil, piperidino vardenafil, hydroxyacetildenafil and piperidino acetildenafil were 0.1, 0.0, 0.1 and 0.5 ppm, respectively. Based on the accuracy of the measurements, structural assignments could be made with a high degree of confidence. Published in 2006 by John Wiley & Sons, Ltd. 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 samuel.gratz@fda.hhs.gov NR 14 TC 70 Z9 73 U1 3 U2 14 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0951-4198 J9 RAPID COMMUN MASS SP JI Rapid Commun. Mass Spectrom. PY 2006 VL 20 IS 15 BP 2317 EP 2327 DI 10.1002/rcm.2594 PG 11 WC Chemistry, Analytical; Spectroscopy SC Chemistry; Spectroscopy GA 073HX UT WOS:000239734700012 PM 16817245 ER PT J AU Wilkes, JG Rafii, F Sutherland, JB Rushing, LG Buzatu, DA AF Wilkes, Jon G. Rafii, Fatemeh Sutherland, John B. Rushing, Larry G. Buzatu, Dan A. TI Pyrolysis mass spectrometry for distinguishing potential hoax materials from bioterror agentst SO RAPID COMMUNICATIONS IN MASS SPECTROMETRY LA English DT Article ID RAPID PHENOTYPIC CHARACTERIZATION; REAL-TIME PCR; SURFACE WATERS; SYSTEM; IDENTIFICATION; IONIZATION; POLYMERS; SPORES; ASSAY; DNA AB Pyrolysis mass spectrometry (PyMS) was investigated as a rapid tool to distinguish potential bioterror hoax materials from samples containing pathogenic bacteria. A pyrolysis time-of-flight (TOF) mass spectrometer equipped with an alternative ionization technique, metastable atom bombardment (MAB), was used to produce sample spectra. These spectra were analyzed by principal component and discriminant analysis for pattern recognition. Materials investigated were two strains of Vibrio parahaemolyticus, one of which produced the tdh toxin, two Salmonella enterica serotypes, a biological mosquito control product containing spores of Bacillus thuringiensis, and several white to off-white powders (which could be used as hoax materials), such as flour, corn starch, methyl cellulose, and xanthan gum. PyMS distinguished bacterial samples from hoax materials. Furthermore, pattern analysis differentiated Vibrios from Salmonellae, Salmonella enterica Anatum from S. enterica Heidelberg, and the two V. parahaemolyticus strains from each other. The B. thuringiensis mixture was distinguished from other bacteria and powders, suggesting that PyMS with pattern recognition may differentiate samples containing pathogens, including Bacillus spp., from nonbiological agents and that it can be a rapid method for detection of bacteria. MS data acquisition took only 7 min for each sample. Published in 2006 by John Wiley & Sons, Ltd. C1 US FDA, Natl Ctr Toxicol Res, Div Syst Toxicol, Jefferson, AR 72079 USA. US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. RP Wilkes, JG (reprint author), US FDA, Natl Ctr Toxicol Res, Div Syst Toxicol, Jefferson, AR 72079 USA. EM jon.wilkes@fda.hhs.gov NR 26 TC 5 Z9 6 U1 0 U2 5 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0951-4198 J9 RAPID COMMUN MASS SP JI Rapid Commun. Mass Spectrom. PY 2006 VL 20 IS 16 BP 2383 EP 2386 DI 10.1002/rcm.2604 PG 4 WC Biochemical Research Methods; Chemistry, Analytical; Spectroscopy SC Biochemistry & Molecular Biology; Chemistry; Spectroscopy GA 075ZJ UT WOS:000239926400003 PM 16841357 ER PT J AU Gupta, N Vassell, R Wang, W He, Y Weiss, CD AF Gupta, Nidhi Vassell, Russell Wang, Wei He, Yong Weiss, Carol D. TI Novel resistance mechanism of HIV-1 to peptide fusion inhibitors SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Gupta, Nidhi; Vassell, Russell; Wang, Wei; He, Yong; Weiss, Carol D.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2006 VL 3 SU 1 MA S86 PG 2 WC Virology SC Virology GA V52ZS UT WOS:000203582000087 ER PT J AU Machuca, A Tang, SX Hu, JJ Lee, S Gupta, V Zekeng, L Awazi, B Vockley, C Hewlett, I AF Machuca, Ana Tang, Shixing Hu, Jinjie Lee, Sherwin Gupta, Vutukuri Zekeng, Leopold Awazi, Bih Vockley, Chris Hewlett, Indira TI Genetic diversity and high proportion of intersubtype recombinants of HIV-1 in urban Cameroon SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Machuca, Ana; Tang, Shixing; Hu, Jinjie; Lee, Sherwin; Gupta, Vutukuri; Vockley, Chris; Hewlett, Indira] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2006 VL 3 SU 1 MA P61 PG 1 WC Virology SC Virology GA V52ZS UT WOS:000203582000170 ER PT S AU Gammell, PM Maruvada, S Harris, GR AF Gammell, PM Maruvada, S Harris, GR BE Thompson, DO Chimenti, DE TI A simplified ultrasonic time-delay spectrometry (TDS) system employing digital processing to minimize hardware requirements SO REVIEW OF PROGRESS IN QUANTITATIVE NONDESTRUCTIVE EVALUATION, VOLS 25A AND 25B SE AIP Conference Proceedings LA English DT Proceedings Paper CT 32nd Annual Review of Process in Quantitative Nondestructive Evaluation CY JUL 31-AUG 05, 2005 CL Brunswick, ME DE ultrasonic instrumentation; time delay spectrometry ID 2 MHZ; CALIBRATION AB Time delay spectrometry (TDS) is a swept-frequency technique that has proven useful in several ultrasonic applications. The research systems that have been used depended on features of commercial equipment no longer manufactured; commercial TDS ultrasonic systems are not available. The system described here is easy to replicate with readily available equipment and a digitizer and computer capable of handling audio frequency signals. Two applications are shown to demonstrate the capability of this design. C1 LLC, Gammell Appl Technol, Exmore, VA 23350 USA. Ctr Devices & Radiol Hlth, Food & Drug Adm, Rockville, MD 20852 USA. RP LLC, Gammell Appl Technol, Exmore, VA 23350 USA. EM pgammell@ieee.org NR 7 TC 2 Z9 2 U1 0 U2 0 PU AMER INST PHYSICS PI MELVILLE PA 2 HUNTINGTON QUADRANGLE, STE 1NO1, MELVILLE, NY 11747-4501 USA SN 0094-243X BN 0-7354-0312-0 J9 AIP CONF PROC PY 2006 VL 820 BP 692 EP 699 PG 8 WC Materials Science, Characterization & Testing; Physics, Applied SC Materials Science; Physics GA BDY94 UT WOS:000236275600088 ER PT J AU O'Fallon, WM AF O'Fallon, W. M. (Mike) BA Riffenburgh, RH BF Riffenburgh, RH TI Data, Notation, and Some Basic Terms SO STATISTICS IN MEDICINE, 2ND EDITION LA English DT Article; Book Chapter C1 [O'Fallon, W. M. (Mike)] Mayo Clin, Rochester, MN 55905 USA. [O'Fallon, W. M. (Mike)] NIH, Study Sect, Bethesda, MD 20892 USA. [O'Fallon, W. M. (Mike)] US FDA, Advisory Comm, Rockville, MD 20857 USA. RP O'Fallon, WM (reprint author), Mayo Clin, Rochester, MN 55905 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-054174-7 PY 2006 BP 3 EP + PG 16 WC Mathematical & Computational Biology; Medical Informatics; Statistics & Probability SC Mathematical & Computational Biology; Medical Informatics; Mathematics GA BCT56 UT WOS:000311359400003 ER PT J AU O'Fallon, WM AF O'Fallon, W. M. (Mike) BA Riffenburgh, RH BF Riffenburgh, RH TI Distributions SO STATISTICS IN MEDICINE, 2ND EDITION LA English DT Article; Book Chapter C1 [O'Fallon, W. M. (Mike)] Mayo Clin, Rochester, MN 55905 USA. [O'Fallon, W. M. (Mike)] NIH, Study Sect, Bethesda, MD 20892 USA. [O'Fallon, W. M. (Mike)] US FDA, Advisory Comm, Rockville, MD 20857 USA. RP O'Fallon, WM (reprint author), Mayo Clin, Rochester, MN 55905 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-054174-7 PY 2006 BP 15 EP 35 PG 21 WC Mathematical & Computational Biology; Medical Informatics; Statistics & Probability SC Mathematical & Computational Biology; Medical Informatics; Mathematics GA BCT56 UT WOS:000311359400004 ER PT J AU O'Fallon, WM AF O'Fallon, W. M. (Mike) BA Riffenburgh, RH BF Riffenburgh, RH TI STATISTICS IN MEDICINE Second Edition Foreword to the Second Edition SO STATISTICS IN MEDICINE, 2ND EDITION LA English DT Editorial Material; Book Chapter C1 [O'Fallon, W. M. (Mike)] Mayo Clin, Rochester, MN 55905 USA. [O'Fallon, W. M. (Mike)] NIH, Study Sect, Bethesda, MD 20892 USA. [O'Fallon, W. M. (Mike)] US FDA, Advisory Comm, Rockville, MD 20857 USA. RP O'Fallon, WM (reprint author), Mayo Clin, Rochester, MN 55905 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-054174-7 PY 2006 BP XVII EP XVIII PG 2 WC Mathematical & Computational Biology; Medical Informatics; Statistics & Probability SC Mathematical & Computational Biology; Medical Informatics; Mathematics GA BCT56 UT WOS:000311359400001 ER PT J AU O'Fallon, WM AF O'Fallon, W. M. (Mike) BA Riffenburgh, RH BF Riffenburgh, RH TI STATISTICS IN MEDICINE Second Edition Foreword to the First Edition SO STATISTICS IN MEDICINE, 2ND EDITION LA English DT Editorial Material; Book Chapter C1 [O'Fallon, W. M. (Mike)] Mayo Clin, Rochester, MN 55905 USA. [O'Fallon, W. M. (Mike)] NIH, Study Sect, Bethesda, MD 20892 USA. [O'Fallon, W. M. (Mike)] US FDA, Advisory Comm, Rockville, MD 20857 USA. RP O'Fallon, WM (reprint author), Mayo Clin, Rochester, MN 55905 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-054174-7 PY 2006 BP XIX EP XX PG 2 WC Mathematical & Computational Biology; Medical Informatics; Statistics & Probability SC Mathematical & Computational Biology; Medical Informatics; Mathematics GA BCT56 UT WOS:000311359400002 ER PT J AU O'Fallon, WM AF O'Fallon, W. M. (Mike) BA Riffenburgh, RH BF Riffenburgh, RH TI Summary Statistics SO STATISTICS IN MEDICINE, 2ND EDITION LA English DT Article; Book Chapter C1 [O'Fallon, W. M. (Mike)] Mayo Clin, Rochester, MN 55905 USA. [O'Fallon, W. M. (Mike)] NIH, Study Sect, Bethesda, MD 20892 USA. [O'Fallon, W. M. (Mike)] US FDA, Advisory Comm, Rockville, MD 20857 USA. RP O'Fallon, WM (reprint author), Mayo Clin, Rochester, MN 55905 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-054174-7 PY 2006 BP 37 EP 56 PG 20 WC Mathematical & Computational Biology; Medical Informatics; Statistics & Probability SC Mathematical & Computational Biology; Medical Informatics; Mathematics GA BCT56 UT WOS:000311359400005 ER PT J AU O'Fallon, WM AF O'Fallon, W. M. (Mike) BA Riffenburgh, RH BF Riffenburgh, RH TI Confidence Intervals and Probability SO STATISTICS IN MEDICINE, 2ND EDITION LA English DT Article; Book Chapter C1 [O'Fallon, W. M. (Mike)] Mayo Clin, Rochester, MN 55905 USA. [O'Fallon, W. M. (Mike)] NIH, Study Sect, Bethesda, MD 20892 USA. [O'Fallon, W. M. (Mike)] US FDA, Advisory Comm, Rockville, MD 20857 USA. RP O'Fallon, WM (reprint author), Mayo Clin, Rochester, MN 55905 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-054174-7 PY 2006 BP 57 EP 73 PG 17 WC Mathematical & Computational Biology; Medical Informatics; Statistics & Probability SC Mathematical & Computational Biology; Medical Informatics; Mathematics GA BCT56 UT WOS:000311359400006 ER PT J AU O'Fallon, WM AF O'Fallon, W. M. (Mike) BA Riffenburgh, RH BF Riffenburgh, RH TI Hypothesis Testing: Concept and Practice SO STATISTICS IN MEDICINE, 2ND EDITION LA English DT Article; Book Chapter C1 [O'Fallon, W. M. (Mike)] Mayo Clin, Rochester, MN 55905 USA. [O'Fallon, W. M. (Mike)] NIH, Study Sect, Bethesda, MD 20892 USA. [O'Fallon, W. M. (Mike)] US FDA, Advisory Comm, Rockville, MD 20857 USA. RP O'Fallon, WM (reprint author), Mayo Clin, Rochester, MN 55905 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-054174-7 PY 2006 BP 75 EP 92 PG 18 WC Mathematical & Computational Biology; Medical Informatics; Statistics & Probability SC Mathematical & Computational Biology; Medical Informatics; Mathematics GA BCT56 UT WOS:000311359400007 ER PT J AU O'Fallon, WM AF O'Fallon, W. M. (Mike) BA Riffenburgh, RH BF Riffenburgh, RH TI Statistical Testing, Risks, and Odds in Medical Decisions SO STATISTICS IN MEDICINE, 2ND EDITION LA English DT Article; Book Chapter C1 [O'Fallon, W. M. (Mike)] Mayo Clin, Rochester, MN 55905 USA. [O'Fallon, W. M. (Mike)] NIH, Study Sect, Bethesda, MD 20892 USA. [O'Fallon, W. M. (Mike)] US FDA, Advisory Comm, Rockville, MD 20857 USA. RP O'Fallon, WM (reprint author), Mayo Clin, Rochester, MN 55905 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-054174-7 PY 2006 BP 93 EP 114 PG 22 WC Mathematical & Computational Biology; Medical Informatics; Statistics & Probability SC Mathematical & Computational Biology; Medical Informatics; Mathematics GA BCT56 UT WOS:000311359400008 ER PT J AU O'Fallon, WM AF O'Fallon, W. M. (Mike) BA Riffenburgh, RH BF Riffenburgh, RH TI Sample Size Required for a Study SO STATISTICS IN MEDICINE, 2ND EDITION LA English DT Article; Book Chapter C1 [O'Fallon, W. M. (Mike)] Mayo Clin, Rochester, MN 55905 USA. [O'Fallon, W. M. (Mike)] NIH, Study Sect, Bethesda, MD 20892 USA. [O'Fallon, W. M. (Mike)] US FDA, Advisory Comm, Rockville, MD 20857 USA. RP O'Fallon, WM (reprint author), Mayo Clin, Rochester, MN 55905 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-054174-7 PY 2006 BP 115 EP 123 PG 9 WC Mathematical & Computational Biology; Medical Informatics; Statistics & Probability SC Mathematical & Computational Biology; Medical Informatics; Mathematics GA BCT56 UT WOS:000311359400009 ER PT J AU O'Fallon, WM AF O'Fallon, W. M. (Mike) BA Riffenburgh, RH BF Riffenburgh, RH TI Statistical Prediction SO STATISTICS IN MEDICINE, 2ND EDITION LA English DT Article; Book Chapter C1 [O'Fallon, W. M. (Mike)] Mayo Clin, Rochester, MN 55905 USA. [O'Fallon, W. M. (Mike)] NIH, Study Sect, Bethesda, MD 20892 USA. [O'Fallon, W. M. (Mike)] US FDA, Advisory Comm, Rockville, MD 20857 USA. RP O'Fallon, WM (reprint author), Mayo Clin, Rochester, MN 55905 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-054174-7 PY 2006 BP 125 EP 136 PG 12 WC Mathematical & Computational Biology; Medical Informatics; Statistics & Probability SC Mathematical & Computational Biology; Medical Informatics; Mathematics GA BCT56 UT WOS:000311359400010 ER PT J AU O'Fallon, WM AF O'Fallon, W. M. (Mike) BA Riffenburgh, RH BF Riffenburgh, RH TI Epidemiology SO STATISTICS IN MEDICINE, 2ND EDITION LA English DT Article; Book Chapter C1 [O'Fallon, W. M. (Mike)] Mayo Clin, Rochester, MN 55905 USA. [O'Fallon, W. M. (Mike)] NIH, Study Sect, Bethesda, MD 20892 USA. [O'Fallon, W. M. (Mike)] US FDA, Advisory Comm, Rockville, MD 20857 USA. RP O'Fallon, WM (reprint author), Mayo Clin, Rochester, MN 55905 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-054174-7 PY 2006 BP 137 EP 151 PG 15 WC Mathematical & Computational Biology; Medical Informatics; Statistics & Probability SC Mathematical & Computational Biology; Medical Informatics; Mathematics GA BCT56 UT WOS:000311359400011 ER PT J AU O'Fallon, WM AF O'Fallon, W. M. (Mike) BA Riffenburgh, RH BF Riffenburgh, RH TI Reading Medical Articles SO STATISTICS IN MEDICINE, 2ND EDITION LA English DT Article; Book Chapter C1 [O'Fallon, W. M. (Mike)] Mayo Clin, Rochester, MN 55905 USA. [O'Fallon, W. M. (Mike)] NIH, Study Sect, Bethesda, MD 20892 USA. [O'Fallon, W. M. (Mike)] US FDA, Advisory Comm, Rockville, MD 20857 USA. RP O'Fallon, WM (reprint author), Mayo Clin, Rochester, MN 55905 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-054174-7 PY 2006 BP 153 EP 164 PG 12 WC Mathematical & Computational Biology; Medical Informatics; Statistics & Probability SC Mathematical & Computational Biology; Medical Informatics; Mathematics GA BCT56 UT WOS:000311359400012 ER PT J AU O'Fallon, WM AF O'Fallon, W. M. (Mike) BA Riffenburgh, RH BF Riffenburgh, RH TI Using the Reference Guide SO STATISTICS IN MEDICINE, 2ND EDITION LA English DT Article; Book Chapter C1 [O'Fallon, W. M. (Mike)] Mayo Clin, Rochester, MN 55905 USA. [O'Fallon, W. M. (Mike)] NIH, Study Sect, Bethesda, MD 20892 USA. [O'Fallon, W. M. (Mike)] US FDA, Advisory Comm, Rockville, MD 20857 USA. RP O'Fallon, WM (reprint author), Mayo Clin, Rochester, MN 55905 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-054174-7 PY 2006 BP 187 EP 193 PG 7 WC Mathematical & Computational Biology; Medical Informatics; Statistics & Probability SC Mathematical & Computational Biology; Medical Informatics; Mathematics GA BCT56 UT WOS:000311359400013 ER PT J AU O'Fallon, WM AF O'Fallon, W. M. (Mike) BA Riffenburgh, RH BF Riffenburgh, RH TI Planning Medical Studies SO STATISTICS IN MEDICINE, 2ND EDITION LA English DT Article; Book Chapter C1 [O'Fallon, W. M. (Mike)] Mayo Clin, Rochester, MN 55905 USA. [O'Fallon, W. M. (Mike)] NIH, Study Sect, Bethesda, MD 20892 USA. [O'Fallon, W. M. (Mike)] US FDA, Advisory Comm, Rockville, MD 20857 USA. RP O'Fallon, WM (reprint author), Mayo Clin, Rochester, MN 55905 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-054174-7 PY 2006 BP 195 EP 212 PG 18 WC Mathematical & Computational Biology; Medical Informatics; Statistics & Probability SC Mathematical & Computational Biology; Medical Informatics; Mathematics GA BCT56 UT WOS:000311359400014 ER PT J AU O'Fallon, WM AF O'Fallon, W. M. (Mike) BA Riffenburgh, RH BF Riffenburgh, RH TI Finding Probabilities of Error SO STATISTICS IN MEDICINE, 2ND EDITION LA English DT Article; Book Chapter C1 [O'Fallon, W. M. (Mike)] Mayo Clin, Rochester, MN 55905 USA. [O'Fallon, W. M. (Mike)] NIH, Study Sect, Bethesda, MD 20892 USA. [O'Fallon, W. M. (Mike)] US FDA, Advisory Comm, Rockville, MD 20857 USA. RP O'Fallon, WM (reprint author), Mayo Clin, Rochester, MN 55905 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-054174-7 PY 2006 BP 213 EP 226 PG 14 WC Mathematical & Computational Biology; Medical Informatics; Statistics & Probability SC Mathematical & Computational Biology; Medical Informatics; Mathematics GA BCT56 UT WOS:000311359400015 ER PT J AU O'Fallon, WM AF O'Fallon, W. M. (Mike) BA Riffenburgh, RH BF Riffenburgh, RH TI Confidence Intervals SO STATISTICS IN MEDICINE, 2ND EDITION LA English DT Article; Book Chapter C1 [O'Fallon, W. M. (Mike)] Mayo Clin, Rochester, MN 55905 USA. [O'Fallon, W. M. (Mike)] NIH, Study Sect, Bethesda, MD 20892 USA. [O'Fallon, W. M. (Mike)] US FDA, Advisory Comm, Rockville, MD 20857 USA. RP O'Fallon, WM (reprint author), Mayo Clin, Rochester, MN 55905 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-054174-7 PY 2006 BP 227 EP 240 PG 14 WC Mathematical & Computational Biology; Medical Informatics; Statistics & Probability SC Mathematical & Computational Biology; Medical Informatics; Mathematics GA BCT56 UT WOS:000311359400016 ER PT J AU O'Fallon, WM AF O'Fallon, W. M. (Mike) BA Riffenburgh, RH BF Riffenburgh, RH TI Tests on Categorical Data SO STATISTICS IN MEDICINE, 2ND EDITION LA English DT Article; Book Chapter C1 [O'Fallon, W. M. (Mike)] Mayo Clin, Rochester, MN 55905 USA. [O'Fallon, W. M. (Mike)] NIH, Study Sect, Bethesda, MD 20892 USA. [O'Fallon, W. M. (Mike)] US FDA, Advisory Comm, Rockville, MD 20857 USA. RP O'Fallon, WM (reprint author), Mayo Clin, Rochester, MN 55905 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-054174-7 PY 2006 BP 241 EP 279 PG 39 WC Mathematical & Computational Biology; Medical Informatics; Statistics & Probability SC Mathematical & Computational Biology; Medical Informatics; Mathematics GA BCT56 UT WOS:000311359400017 ER PT J AU O'Fallon, WM AF O'Fallon, W. M. (Mike) BA Riffenburgh, RH BF Riffenburgh, RH TI Tests on Ranked Data SO STATISTICS IN MEDICINE, 2ND EDITION LA English DT Article; Book Chapter C1 [O'Fallon, W. M. (Mike)] Mayo Clin, Rochester, MN 55905 USA. [O'Fallon, W. M. (Mike)] NIH, Study Sect, Bethesda, MD 20892 USA. [O'Fallon, W. M. (Mike)] US FDA, Advisory Comm, Rockville, MD 20857 USA. RP O'Fallon, WM (reprint author), Mayo Clin, Rochester, MN 55905 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-054174-7 PY 2006 BP 281 EP 303 PG 23 WC Mathematical & Computational Biology; Medical Informatics; Statistics & Probability SC Mathematical & Computational Biology; Medical Informatics; Mathematics GA BCT56 UT WOS:000311359400018 ER PT J AU O'Fallon, WM AF O'Fallon, W. M. (Mike) BA Riffenburgh, RH BF Riffenburgh, RH TI Tests on Means of Continuous Data SO STATISTICS IN MEDICINE, 2ND EDITION LA English DT Article; Book Chapter C1 [O'Fallon, W. M. (Mike)] Mayo Clin, Rochester, MN 55905 USA. [O'Fallon, W. M. (Mike)] NIH, Study Sect, Bethesda, MD 20892 USA. [O'Fallon, W. M. (Mike)] US FDA, Advisory Comm, Rockville, MD 20857 USA. RP O'Fallon, WM (reprint author), Mayo Clin, Rochester, MN 55905 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-054174-7 PY 2006 BP 305 EP 329 PG 25 WC Mathematical & Computational Biology; Medical Informatics; Statistics & Probability SC Mathematical & Computational Biology; Medical Informatics; Mathematics GA BCT56 UT WOS:000311359400019 ER PT J AU O'Fallon, WM AF O'Fallon, W. M. (Mike) BA Riffenburgh, RH BF Riffenburgh, RH TI Multifactor Tests on Means of Continuous Data SO STATISTICS IN MEDICINE, 2ND EDITION LA English DT Article; Book Chapter C1 [O'Fallon, W. M. (Mike)] Mayo Clin, Rochester, MN 55905 USA. [O'Fallon, W. M. (Mike)] NIH, Study Sect, Bethesda, MD 20892 USA. [O'Fallon, W. M. (Mike)] US FDA, Advisory Comm, Rockville, MD 20857 USA. RP O'Fallon, WM (reprint author), Mayo Clin, Rochester, MN 55905 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-054174-7 PY 2006 BP 331 EP 354 PG 24 WC Mathematical & Computational Biology; Medical Informatics; Statistics & Probability SC Mathematical & Computational Biology; Medical Informatics; Mathematics GA BCT56 UT WOS:000311359400020 ER PT J AU O'Fallon, WM AF O'Fallon, W. M. (Mike) BA Riffenburgh, RH BF Riffenburgh, RH TI Tests on Variances of Continuous Data SO STATISTICS IN MEDICINE, 2ND EDITION LA English DT Article; Book Chapter C1 [O'Fallon, W. M. (Mike)] Mayo Clin, Rochester, MN 55905 USA. [O'Fallon, W. M. (Mike)] NIH, Study Sect, Bethesda, MD 20892 USA. [O'Fallon, W. M. (Mike)] US FDA, Advisory Comm, Rockville, MD 20857 USA. RP O'Fallon, WM (reprint author), Mayo Clin, Rochester, MN 55905 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-054174-7 PY 2006 BP 355 EP 367 PG 13 WC Mathematical & Computational Biology; Medical Informatics; Statistics & Probability SC Mathematical & Computational Biology; Medical Informatics; Mathematics GA BCT56 UT WOS:000311359400021 ER PT J AU O'Fallon, WM AF O'Fallon, W. M. (Mike) BA Riffenburgh, RH BF Riffenburgh, RH TI Tests on the Distribution Shape of Continuous Data SO STATISTICS IN MEDICINE, 2ND EDITION LA English DT Article; Book Chapter C1 [O'Fallon, W. M. (Mike)] Mayo Clin, Rochester, MN 55905 USA. [O'Fallon, W. M. (Mike)] NIH, Study Sect, Bethesda, MD 20892 USA. [O'Fallon, W. M. (Mike)] US FDA, Advisory Comm, Rockville, MD 20857 USA. RP O'Fallon, WM (reprint author), Mayo Clin, Rochester, MN 55905 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-054174-7 PY 2006 BP 369 EP 386 PG 18 WC Mathematical & Computational Biology; Medical Informatics; Statistics & Probability SC Mathematical & Computational Biology; Medical Informatics; Mathematics GA BCT56 UT WOS:000311359400022 ER PT J AU O'Fallon, WM AF O'Fallon, W. M. (Mike) BA Riffenburgh, RH BF Riffenburgh, RH TI Equivalence Testing SO STATISTICS IN MEDICINE, 2ND EDITION LA English DT Article; Book Chapter C1 [O'Fallon, W. M. (Mike)] Mayo Clin, Rochester, MN 55905 USA. [O'Fallon, W. M. (Mike)] NIH, Study Sect, Bethesda, MD 20892 USA. [O'Fallon, W. M. (Mike)] US FDA, Advisory Comm, Rockville, MD 20857 USA. RP O'Fallon, WM (reprint author), Mayo Clin, Rochester, MN 55905 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-054174-7 PY 2006 BP 387 EP 396 PG 10 WC Mathematical & Computational Biology; Medical Informatics; Statistics & Probability SC Mathematical & Computational Biology; Medical Informatics; Mathematics GA BCT56 UT WOS:000311359400023 ER PT J AU O'Fallon, WM AF O'Fallon, W. M. (Mike) BA Riffenburgh, RH BF Riffenburgh, RH TI Sample Size Required in a Study SO STATISTICS IN MEDICINE, 2ND EDITION LA English DT Article; Book Chapter C1 [O'Fallon, W. M. (Mike)] Mayo Clin, Rochester, MN 55905 USA. [O'Fallon, W. M. (Mike)] NIH, Study Sect, Bethesda, MD 20892 USA. [O'Fallon, W. M. (Mike)] US FDA, Advisory Comm, Rockville, MD 20857 USA. RP O'Fallon, WM (reprint author), Mayo Clin, Rochester, MN 55905 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-054174-7 PY 2006 BP 397 EP 417 PG 21 WC Mathematical & Computational Biology; Medical Informatics; Statistics & Probability SC Mathematical & Computational Biology; Medical Informatics; Mathematics GA BCT56 UT WOS:000311359400024 ER PT J AU O'Fallon, WM AF O'Fallon, W. M. (Mike) BA Riffenburgh, RH BF Riffenburgh, RH TI Modeling and Clinical Decisions SO STATISTICS IN MEDICINE, 2ND EDITION LA English DT Article; Book Chapter C1 [O'Fallon, W. M. (Mike)] Mayo Clin, Rochester, MN 55905 USA. [O'Fallon, W. M. (Mike)] NIH, Study Sect, Bethesda, MD 20892 USA. [O'Fallon, W. M. (Mike)] US FDA, Advisory Comm, Rockville, MD 20857 USA. RP O'Fallon, WM (reprint author), Mayo Clin, Rochester, MN 55905 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-054174-7 PY 2006 BP 419 EP 445 PG 27 WC Mathematical & Computational Biology; Medical Informatics; Statistics & Probability SC Mathematical & Computational Biology; Medical Informatics; Mathematics GA BCT56 UT WOS:000311359400025 ER PT J AU O'Fallon, WM AF O'Fallon, W. M. (Mike) BA Riffenburgh, RH BF Riffenburgh, RH TI Regression and Correlation Methods SO STATISTICS IN MEDICINE, 2ND EDITION LA English DT Article; Book Chapter C1 [O'Fallon, W. M. (Mike)] Mayo Clin, Rochester, MN 55905 USA. [O'Fallon, W. M. (Mike)] NIH, Study Sect, Bethesda, MD 20892 USA. [O'Fallon, W. M. (Mike)] US FDA, Advisory Comm, Rockville, MD 20857 USA. RP O'Fallon, WM (reprint author), Mayo Clin, Rochester, MN 55905 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-054174-7 PY 2006 BP 447 EP 486 PG 40 WC Mathematical & Computational Biology; Medical Informatics; Statistics & Probability SC Mathematical & Computational Biology; Medical Informatics; Mathematics GA BCT56 UT WOS:000311359400026 ER PT J AU O'Fallon, WM AF O'Fallon, W. M. (Mike) BA Riffenburgh, RH BF Riffenburgh, RH TI Survival and Time-Series Analysis SO STATISTICS IN MEDICINE, 2ND EDITION LA English DT Article; Book Chapter C1 [O'Fallon, W. M. (Mike)] Mayo Clin, Rochester, MN 55905 USA. [O'Fallon, W. M. (Mike)] NIH, Study Sect, Bethesda, MD 20892 USA. [O'Fallon, W. M. (Mike)] US FDA, Advisory Comm, Rockville, MD 20857 USA. RP O'Fallon, WM (reprint author), Mayo Clin, Rochester, MN 55905 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-054174-7 PY 2006 BP 487 EP 519 PG 33 WC Mathematical & Computational Biology; Medical Informatics; Statistics & Probability SC Mathematical & Computational Biology; Medical Informatics; Mathematics GA BCT56 UT WOS:000311359400027 ER PT J AU O'Fallon, WM AF O'Fallon, W. M. (Mike) BA Riffenburgh, RH BF Riffenburgh, RH TI Methods You Might Meet, But Not Every Day SO STATISTICS IN MEDICINE, 2ND EDITION LA English DT Article; Book Chapter C1 [O'Fallon, W. M. (Mike)] Mayo Clin, Rochester, MN 55905 USA. [O'Fallon, W. M. (Mike)] NIH, Study Sect, Bethesda, MD 20892 USA. [O'Fallon, W. M. (Mike)] US FDA, Advisory Comm, Rockville, MD 20857 USA. RP O'Fallon, WM (reprint author), Mayo Clin, Rochester, MN 55905 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-054174-7 PY 2006 BP 521 EP 529 PG 9 WC Mathematical & Computational Biology; Medical Informatics; Statistics & Probability SC Mathematical & Computational Biology; Medical Informatics; Mathematics GA BCT56 UT WOS:000311359400028 ER PT S AU Harris, GR AF Harris, Gerald R. BE Clement, GT McDannold, NJ Hynynen, K TI The FDA perspective on pre-clinical testing for high intensity focused ultrasound devices SO Therapeutic Ultrasound SE AIP CONFERENCE PROCEEDINGS LA English DT Proceedings Paper CT 5th International Symposium on Therapeutic Ultrasound CY OCT 27-29, 2005 CL Boston, MA SP Int Soc Therapeut Ultrasound, Acout Soc Amer, Fdn Focused Ultrasound Res DE high intensity focused ultrasound; medical device regulation AB In the U. S., the pre-market review of high intensity focused ultrasound (HIFU) devices is carried out under the authority of the 1976 Medical Device Amendments to the Food, Drug, and Cosmetic Act. Different regulatory mechanisms may apply depending on the complexity of the HIFU device and the indications for use, but in all cases pre-clinical testing is required. This testing typically includes ultrasound field characterization, thermal modeling and measurement and may include demonstrating the accuracy of targeting and monitoring, if applicable. Because there are no guidance documents or standards for these tests at present the U.S. Food and Drug Administration (FDA) welcomes working with interested parties to develop acceptable procedures that can be incorporated into the regulatory review process. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20852 USA. RP Harris, GR (reprint author), US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20852 USA. NR 4 TC 2 Z9 2 U1 0 U2 0 PU AMER INST PHYSICS PI MELVILLE PA 2 HUNTINGTON QUADRANGLE, STE 1NO1, MELVILLE, NY 11747-4501 USA SN 0094-243X BN 0-7354-0321-X J9 AIP CONF PROC PY 2006 VL 829 BP 595 EP 598 PG 4 WC Acoustics; Biophysics; Medicine, General & Internal SC Acoustics; Biophysics; General & Internal Medicine GA BEN61 UT WOS:000238329700117 ER PT S AU Maruvada, S Harris, GR Herman, BA King, RL AF Maruvada, Subha Harris, Gerald R. Herman, Bruce A. King, Randy L. BE Clement, GT McDannold, NJ Hynynen, K TI Analysis of a protocol for measuring ultrasonic power from focused therapeutic ultrasound transducers using radiation force SO THERAPEUTIC ULTRASOUND SE AIP Conference Proceedings LA English DT Proceedings Paper CT 5th International Symposium on Therapeutic Ultrasound CY OCT 27-29, 2005 CL Boston, MA SP Int Soc Therapeut Ultrasound, Acout Soc Amer, Fdn Focused Ultrasound Res DE high intensity focused ultrasound; ultrasound power measurement; radiation force AB To address die challenges associated with measuring the ultrasonic power from high intensity focused ultrasound transducers via radiation force, a protocol based on pulsed measurements was analyzed. Two focused ultrasound transducers were characterized in terms of an effective duty factor, which was then used to calculate the power during the pulse at high drive levels. Two absorbing target designs were used, and both gave accurate, reproducible results and displayed no damage and minimal temperature rise if placed near the transducer and away from the focus. The protocol was accurate up to the maximum power generated of approximately 180 W. C1 [Maruvada, Subha; Harris, Gerald R.; Herman, Bruce A.] Ctr Devices & Radiol Hlth, US FDA, 9200 Corp Blvd,Mail Stop HFZ 170, Rockville, MD 20850 USA. [King, Randy L.] King Acoust Technol LLQ, Washington, DC 20007 USA. RP Maruvada, S (reprint author), Ctr Devices & Radiol Hlth, US FDA, 9200 Corp Blvd,Mail Stop HFZ 170, Rockville, MD 20850 USA. NR 1 TC 0 Z9 0 U1 0 U2 2 PU AMER INST PHYSICS PI MELVILLE PA 2 HUNTINGTON QUADRANGLE, STE 1NO1, MELVILLE, NY 11747-4501 USA SN 0094-243X BN 0-7354-0321-X J9 AIP CONF PROC PY 2006 VL 829 BP 623 EP + PG 2 WC Acoustics; Biophysics; Medicine, General & Internal SC Acoustics; Biophysics; General & Internal Medicine GA BEN61 UT WOS:000238329700123 ER PT S AU May, JC Etz, NM Wang, H Rey, L AF May, J. C. Etz, N. M. Wang, H. Rey, L. BE Dinwiddie, RB White, MA McElroy, DL TI Thermogravimetric methods: Applications to determination of residual moisture in freeze-dried biological products SO Thermal Conductivity 28: Thermal Expansion 16 SE THERMAL CONDUCTIVITY LA English DT Proceedings Paper CT 28th International Thermal Conductivity Conference/16th International Thermal Expansion Symposium CY JUN 26-29, 2005 CL St Andrews, CANADA SP Mathis Instruments Fredericton ID NEAR-INFRARED SPECTROSCOPY; PERTUSSIS-VACCINE; CONTROLLED TRIAL; TG/MS AB Residual moisture specifications set by the US Food and Drug Administration must be met to ensure potency and stability of freeze-dried biological product throughout the product's licensed shelf life. Thermogravimetry, thermogravimetry/mass spectrometry, and Karl Fischer methodology and vapor pressure moisture measurements are used to provide moisture information for freeze-dried biological products. Residual moisture measurements are compared for a Pertussis Vaccine and other freeze dried biological products. Residual moisture data for the freeze-dried cake and vapor pressure moisture determinations in the space above the freeze-dried cake in the final container are discussed in regard to stability. Residual moisture stability data are presented and results for biological products in glass vials with elastomeric container closures are studied and compared to freeze-dried products in flame-sealed glass ampoules. Near-infrared spectroscopy measurements in the OH combination bands region (near 1920 nm) for Pertussis Vaccine incubated at 22, 37 and 50 degrees C indicate moisture migration within the flame-sealed glass ampoule. C1 US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP May, JC (reprint author), US FDA, Ctr Biol Evaluat & Res, 1401 Rockville Pike, Rockville, MD 20852 USA. NR 16 TC 0 Z9 0 U1 0 U2 1 PU DESTECH PUBLICATIONS, INC PI LANCASTER PA 439 DUKE STREET, LANCASTER, PA 17602-4967 USA SN 0163-9005 BN 978-1-932078-59-6 J9 THERM COND PY 2006 VL 28 BP 370 EP 378 PG 9 WC Thermodynamics; Materials Science, Multidisciplinary SC Thermodynamics; Materials Science GA BFY69 UT WOS:000245465900035 ER PT J AU Zhang, J Herman, EH Robertson, DG Reily, MD Knapton, A Ratajczak, HV Rifai, N Honchel, R Blanchard, KT Stoll, RE Sistare, FD AF Zhang, J Herman, EH Robertson, DG Reily, MD Knapton, A Ratajczak, HV Rifai, N Honchel, R Blanchard, KT Stoll, RE Sistare, FD TI Mechanisms and biomarkers of cardiovascular injury induced by phosphodiesterase inhibitor IIISK& F 95654 in the spontaneously hypertensive rat SO TOXICOLOGIC PATHOLOGY LA English DT Article DE cardiac troponin T; CD63; inducible nitric oxide synthase; nitrotyrosine; mast cell degranulation; endothelial cell activation ID NITRIC-OXIDE SYNTHASE; CARDIAC TROPONIN-I; MAST-CELL; ENDOTHELIAL-CELLS; DOXORUBICIN; APOPTOSIS; TOXICITY; LESIONS; EXPRESSION; ICRF-187 AB The cardiovascular injury of the type III selective PDE inhibitor SK&F 95654 was investigated in SHR. Twenty-four hours after a single sc injection of 100 or 200 mg/kg of the drug, rats exhibited cardiomyocyte necrosis and apoptosis, interstitial inflammation, hemorrhage and edema, as well as mesenteric arterial hemorrhage and necrosis, periarteritis, EC and VSMC apoptosis, EC activation, and MC activation and degranulation. Elevated serum levels of cTnT and decreased cTnT immunoperoxidase staining on cardiomyocytes were detected in the drug-treated rats. Serum levels of alpha(2)-macroglobulin and IL-6 were significantly elevated following drug treatment. NMR spectral patterns of urine samples are significantly different between the drug-treated and control rats. These results indicate that measurement of serum cTnT, acute phase proteins, and cytokines as well as metabonomic urine profiles may serve as potential biomarkers for drug-induced cardiovascular injury in rats. Increased expression of CD63 on MC (tissue biomarker of MC), of nitrotyrosine on MC and EC (an indirect indicator of NO in vivo), and of iNOS on MC and EC (source of NO) suggest that NO produced by activated and degranulated MC as well as activated EC play an important role in SK&F 95654-induced mesenteric vascular injury. C1 US FDA, Ctr Drug Evaluat & Res, Div Appl Pharmacol Res, Silver Spring, MD 20993 USA. Pfizer Global Res & Dev, Metabonom Evaluat Grp, Ann Arbor, MI 48105 USA. Boehringer Ingelheim Pharmaceut Inc, Ridgefield, CT 06877 USA. Childrens Hosp, Dept Lab Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Zhang, J (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Appl Pharmacol Res, HFD 910,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM jun.zhang@fda.hhs.gov OI Reily, Michael/0000-0003-1179-1525 NR 52 TC 28 Z9 28 U1 0 U2 3 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PY 2006 VL 34 IS 2 BP 152 EP 163 DI 10.1080/01926230600588562 PG 12 WC Pathology; Toxicology SC Pathology; Toxicology GA 042FG UT WOS:000237512700003 PM 16537294 ER PT J AU Morton, D Kemp, RK Francke-Carroll, S Jensen, K McCartney, J Monticello, TM Perry, R Pulido, O Roome, N Schafer, K Sellers, R Snyder, PW AF Morton, Daniel Kemp, Ramon K. Francke-Carroll, Sabine Jensen, Karl McCartney, Jeffrey Monticello, Thomas M. Perry, Richard Pulido, Olga Roome, Nigel Schafer, Ken Sellers, Rani Snyder, Paul W. TI Best practices for reporting pathology interpretations within GLP toxicology studies SO TOXICOLOGIC PATHOLOGY LA English DT Article C1 Pfizer Inc, Groton, CT 06340 USA. Merck Res Labs, West Point, PA 19586 USA. US FDA, Pathol Branch, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. US EPA, Res Triangle Pk, NC 27711 USA. Charles River Labs, Senneville, PQ H9X 3R3, Canada. Merck & Co Inc, West Point, PA 19486 USA. Wyeth Res, Chazy, NY 12921 USA. Hlth Canada, Ottawa, ON K1A 0L2, Canada. Sanofi Aventis, F-78440 Porcheville, France. Vet Path Serv Inc, Cincinnati, OH 45249 USA. Yeshiva Univ Albert Einstein Coll Med, Bronx, NY 10461 USA. Purdue Univ, W Lafayette, IN 47907 USA. RP Morton, D (reprint author), Pfizer Inc, Eastern Point Rd MS 8274-1345, Groton, CT 06340 USA. EM dan.g.morton@pfizer.com NR 4 TC 24 Z9 25 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PY 2006 VL 34 IS 6 BP 806 EP 809 DI 10.1080/01926230601034624 PG 4 WC Pathology; Toxicology SC Pathology; Toxicology GA 108CL UT WOS:000242217800014 PM 17162539 ER PT J AU Tsuji, JS Maynard, AD Howard, PC James, JT Lam, CW Warheit, DB Santamaria, AB AF Tsuji, JS Maynard, AD Howard, PC James, JT Lam, CW Warheit, DB Santamaria, AB TI Research strategies for safety evaluation of nanomaterials, part IV: Risk assessment of nanoparticles SO TOXICOLOGICAL SCIENCES LA English DT Editorial Material DE nanotechnology; nanoparticles; risk assessment; exposure assessment ID TITANIUM-DIOXIDE PARTICLES; COMPARATIVE PULMONARY TOXICITY; CARBON NANOTUBE MATERIAL; ULTRAFINE PARTICLES; INHALED PARTICLES; OXIDE PARTICLES; TIO2 PARTICLES; INHALATION; LUNG; EXPOSURE AB Nanoparticles are small-scale substances (< 100 nm) with unique properties and, thus, complex exposure and health risk implications. This symposium review summarizes recent findings in exposure and toxicity of nanoparticles and their application for assessing human health risks. Characterization of airborne particles indicates that exposures will depend on particle behavior (e.g., disperse or aggregate) and that accurate, portable, and cost-effective measurement techniques are essential for understanding exposure. Under many conditions, dermal penetration of nanoparticles may be limited for consumer products such as sunscreens, although additional studies are needed on potential photooxidation products, experimental methods, and the effect of skin condition on penetration. Carbon nanotubes apparently have greater pulmonary toxicity (inflammation, granuloma) in mice than fine-scale carbon graphite, and their metal content may affect toxicity. Studies on TiO2 and quartz illustrate the complex relationship between toxicity and particle characteristics, including surface coatings, which make generalizations (e.g., smaller particles are always more toxic) incorrect for some substances. These recent toxicity and exposure data, combined with therapeutic and other related literature, are beginning to shape risk assessments that will be used to regulate the use of nanomaterials in consumer products. C1 Exponent, Bellevue, WA 98007 USA. Woodrow Wilson Int Ctr Scholars, Washington, DC 20004 USA. US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. US FDA, Natl Toxicol Program, Ctr Phototoxicol, Jefferson, AR 72079 USA. NASA, Houston, TX 77058 USA. DuPont Co Inc, Haskell Lab, Newark, DE 19714 USA. Environ Int, Houston, TX 77002 USA. RP Tsuji, JS (reprint author), 15375 SE 30th Pl,Suite 250, Bellevue, WA 98007 USA. EM tsujij@exponent.com RI Maynard, Andrew/D-1076-2010; OI Maynard, Andrew/0000-0003-2117-5128 NR 61 TC 239 Z9 260 U1 9 U2 66 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD JAN PY 2006 VL 89 IS 1 BP 42 EP 50 DI 10.1093/toxsci/kfi339 PG 9 WC Toxicology SC Toxicology GA 993XN UT WOS:000233991000004 PM 16177233 ER PT J AU Holsapple, MP Pitot, HC Cohen, SH Boobis, AR Klaunig, JE Pastoor, T Dellarco, VL Dragan, YP AF Holsapple, MP Pitot, HC Cohen, SH Boobis, AR Klaunig, JE Pastoor, T Dellarco, VL Dragan, YP TI Mode of action in relevance of rodent liver tumors to human cancer risk SO TOXICOLOGICAL SCIENCES LA English DT Editorial Material ID NUCLEAR RECEPTOR CAR; HEPATOCELLULAR-CARCINOMA; CELL-PROLIFERATION; OXIDATIVE STRESS; DRUG-METABOLISM; INDUCTION; PROMOTION; HEPATOCARCINOGENESIS; CARCINOGENESIS; RATS AB Hazard identification and risk assessment paradigms depend on the presumption of the similarity of rodents to humans, yet species specific responses, and the extrapolation of high-dose effects to low-dose exposures can affect the estimation of human risk from rodent data. As a consequence, a human relevance framework concept was developed by the International Programme on Chemical Safety (IPCS) and International Life Sciences Institute (ILSI) Risk Science Institute (RSI) with the central tenet being the identification of a mode of action (MOA). To perform a MOA analysis, the key biochemical, cellular, and molecular events need to first be established, and the temporal and dose-dependent concordance of each of the key events in the MOA can then be determined. The key events can be used to bridge species and dose for a given MOA. The next step in the MOA analysis is the assessment of biological plausibility for determining the relevance of the specified MOA in an animal model for human cancer risk based on kinetic and dynamic parameters. Using the framework approach, a MOA in animals could not be defined for metal overload. The MOA for phenobarbital (PB)-like P450 inducers was determined to be unlikely in humans after kinetic and dynamic factors were considered. In contrast, after these factors were considered with reference to estrogen, the conclusion was drawn that estrogen-induced tumors were plausible in humans. Finally, it was concluded that the induction of rodent liver tumors by porphyrogenic compounds followed a cytotoxic MOA, and that liver tumors formed as a result of sustained cytotoxicity and regenerative proliferation are considered relevant for evaluating human cancer risk if appropriate metabolism occurs in the animal models and in humans. C1 ILSI Hlth & Environm Sci Inst, Washington, DC 20005 USA. Univ Wisconsin, McArdle Lab, Dept Oncol, Madison, WI 53706 USA. Univ Nebraska, Med Ctr, Dept Pathol & Microbiol, Omaha, NE 68198 USA. Univ London Imperial Coll Sci Technol & Med, London W12 0NN, England. Indiana Univ, Sch Med, Indianapolis, IN 46202 USA. Syngenta CropSci, Greensboro, NC 27419 USA. US EPA, Off Pesticides Programs, Washington, DC 20460 USA. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Holsapple, MP (reprint author), ILSI Hlth & Environm Sci Inst, 1 Thomas Circle NW,9th Floor, Washington, DC 20005 USA. EM mholsapple@ilsi.org OI Boobis, Alan/0000-0003-3371-386X NR 41 TC 143 Z9 147 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 JAN PY 2006 VL 89 IS 1 BP 51 EP 56 DI 10.1093/toxsci/kfj001 PG 6 WC Toxicology SC Toxicology GA 993XN UT WOS:000233991000005 PM 16221960 ER PT J AU Xia, QS Chou, MW Yin, JJ Howard, PC Yu, HT Fu, PP AF Xia, QS Chou, MW Yin, JJ Howard, PC Yu, HT Fu, PP TI Photoirradiation of representative polycyclic aromatic hydrocarbons and twelve isomeric methylbenz[a] anthracene with UVA light: formation of lipid peroxidation SO TOXICOLOGY AND INDUSTRIAL HEALTH LA English DT Article DE lipid peroxidation; PAHs; photoirradiation; UVA light ID SINGLET OXYGEN; DNA CLEAVAGE; ULTRAVIOLET; PHOTOTOXICITY; TOXICITY; DAMAGE; PHOTOSENSITIZATION; PHOTOMUTAGENICITY; ACTIVATION; INDUCTION AB Polycyclic aromatic hydrocarbons (PAHs) are widespread genotoxic environmental pollutants, which require metabolic activation in order to exert biological activities, including mutagenicity and carcinogenicity. Photoactivation is another activation pathway that can lead to PAH genotoxicity. In this paper, we demonstrate that photoirradiation of a series of representative PAHs, with and without bearing a methyl substituent, with UVA light in the presence of methyl linoleate resulted in the formation of methyl linoleate hydroperoxides (a lipid peroxide). The lipid peroxide formation was inhibited by dithiothreitol (DTT) (free radical scavenger), NaN3 (singlet oxygen and free radical scavenger), and superoxide dismutase (SOD) (superoxide scavenger), but was enhanced by the presence of deuterium oxide (D2O) (extends singlet oxygen lifetime). These results suggest that photoirradiation of PAHs by UVA light generates reactive oxygen species (ROS), which induce lipid peroxidation. C1 Jackson State Univ, Dept Chem, Jackson, MS 39217 USA. US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Yu, HT (reprint author), Jackson State Univ, Dept Chem, Jackson, MS 39217 USA. EM yu@ccaix.jsums.edu RI Yin, Jun Jie /E-5619-2014 FU NIGMS NIH HHS [S06 GM008047-290048, S06 GM008047, S06 GM08047] NR 39 TC 16 Z9 16 U1 1 U2 6 PU HODDER ARNOLD, HODDER HEADLINE PLC PI LONDON PA 338 EUSTON ROAD, LONDON NW1 3BH, ENGLAND SN 0748-2337 J9 TOXICOL IND HEALTH JI Toxicol. Ind. Health PY 2006 VL 22 IS 4 BP 147 EP 156 DI 10.1191/0748233706th259oa PG 10 WC Public, Environmental & Occupational Health; Toxicology SC Public, Environmental & Occupational Health; Toxicology GA 038LX UT WOS:000237223200001 PM 16786836 ER PT J AU Yan, J Wamer, WG Howard, PC Boudreau, MD Fu, PP AF Yan, J Wamer, WG Howard, PC Boudreau, MD Fu, PP TI Levels of retinyl palmitate and retinol in the stratum corneum, epidermis, and dermis of female SKH-1 mice topically treated with retinyl palmitate SO TOXICOLOGY AND INDUSTRIAL HEALTH LA English DT Article DE mouse skin; retinol; retinyl palmitate ID SKIN IN-VIVO; VITAMIN-A; HUMAN-NUTRITION; ACID AB Retinyl esters are the storage form of vitamin A in skin, and retinyl palmitate (RP) accounts for the majority of the retinyl esters endogenously formed in skin. RP is also obtained exogenously through the topical application of cosmetic and skin care products that contain RP. There is limited information on the penetration and distribution of RP and vitamin A within the stratified layers of the skin. The purpose of these studies was to determine the time course for accumulation and disappearance of RP and retinol in the stratified layers of skin from female SKH-1 mice that received single or repeated topical applications of creams containing 0.5 or 2% of RP. We developed an HPLC method with detection limits of 5.94 and 1.62 ng, to simultaneously quantify the amount of RP and retinol, respectively, in skin samples. Our results showed that RP rapidly diffuses into the stratum corneum and epidermal skin layers within 24 h following the application of RP-containing creams. Of the three skin layers, the highest level of RP and retinol per weight unit (ng/mg) at all time points was found in the epidermis. Levels of RP and retinol were lowest in the dermal layer and intermediate in the stratum corneum. The levels of RP and retinol in the separated skin layers and in the intact skin decreased with time, but levels of RP remained higher than control values for a period of up to 18 days. Our results indicate that the application of RP to mouse skin alters the normal physiological levels of RP and retinol in the skin. C1 US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Fu, PP (reprint author), US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM pfu@nctr.fda.gov NR 16 TC 13 Z9 13 U1 0 U2 4 PU HODDER ARNOLD, HODDER HEADLINE PLC PI LONDON PA 338 EUSTON ROAD, LONDON NW1 3BH, ENGLAND SN 0748-2337 J9 TOXICOL IND HEALTH JI Toxicol. Ind. Health PY 2006 VL 22 IS 4 BP 181 EP 191 DI 10.1191/074233706th253oa PG 11 WC Public, Environmental & Occupational Health; Toxicology SC Public, Environmental & Occupational Health; Toxicology GA 038LX UT WOS:000237223200005 PM 16786840 ER PT J AU Tong, WD Fang, H Xie, Q Hong, HX Shi, LM Perkins, R Scherf, U Goodsaid, F Frueh, F AF Tong, WD Fang, H Xie, Q Hong, HX Shi, LM Perkins, R Scherf, U Goodsaid, F Frueh, F TI Gaining confidence on molecular classification through consensus modeling and validation SO TOXICOLOGY MECHANISMS AND METHODS LA English DT Article DE molecular classification; consensus modeling; validation; decision forest (DF); cross-validation ID GENE-EXPRESSION DATA; SUPPORT VECTOR MACHINES; SELDI-TOF-MS; MICROARRAY DATA; TUMOR CLASSIFICATION; PROTEOMIC PATTERNS; DECISION FOREST; PROGNOSTIC CLASSIFICATION; CANCER CLASSIFICATION; PREDICTION CONFIDENCE AB Current advances in genomics, proteomics, and metabonomics would result in a constellation of benefits in human health. Classification applying supervised learning methods to omics data as one of the molecular classification approaches has enjoyed its growing role in clinical application. However, the utility of a molecular classifier will not be fully appreciated unless its quality is carefully validated. A clinical omics data is usually noisy with the number of independent variables far more than the number of subjects and, possibly, with a skewed subject distribution. Given that, the consensus approach holds an advantage over a single classifier. Thus, the focus of this review is mainly placed on how validating a molecular classifier using Decision Forest (DF), a robust consensus approach. We recommended that a molecular classifier has to be assessed with respect to overall prediction accuracy, prediction confidence and chance correlation, which can be readily achieved in DF. The commonalities and differences between external validation and cross-validation are also discussed for perspective use of these methods to validate a DF classifier. In addition, the advantages of using consensus approaches for identification of potential biomarkers are also rationalized. Although specific DF examples are used in this review, the provided rationales and recommendations should be equally applicable to other consensus methods. C1 ZTech Inc, Div Bioinformat, Jefferson, AR 72079 USA. US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20850 USA. RP Tong, WD (reprint author), US FDA, Ctr Toxicoinformat, NCTR, 3900 NCTR Rd,HFT 020, Jefferson, AR 72079 USA. EM Wtong@nctr.fda.gov NR 53 TC 5 Z9 5 U1 1 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 PY 2006 VL 16 IS 2-3 BP 59 EP 68 DI 10.1080/15376520600558259 PG 10 WC Toxicology SC Toxicology GA 021BO UT WOS:000235957700003 PM 20020998 ER PT J AU Orr, MS AF Orr, MS TI Toxicogenomics and cross-species biomarker discovery: Applications in drug discovery and safety assessment SO TOXICOLOGY MECHANISMS AND METHODS LA English DT Article DE toxicogenomics; cross-species biomarkers ID ALCOHOLIC LIVER-DISEASE; ACTIVATED RECEPTOR-ALPHA; GENE-EXPRESSION; MOLECULAR CLASSIFICATION; PEROXISOME PROLIFERATORS; PREDICTIVE TOXICOLOGY; IDENTIFICATION; MECHANISM; TOXICITY; FIBROSIS AB Toxicogenomics has evolved into a useful technique for providing greater mechanistic insights into adverse effects that will spur the development of novel approaches for identifying and understanding toxicity issues. The ability to capture a snapshot of the transcriptome at any given time during the development of an adverse phenotype allows unprecedented molecular views into the dynamic physiological changes that are occurring on either time or dose continuum for a toxicology study of interest advancing our basic knowledge of adverse events, and providing the necessary scientific framework for developing new strategies and tools for safety assessment programs. The development of an effective subset of cost effective devices for identifying toxicity earlier in the drug development process will help identify the most promising candidate compounds to move forward leading to a reduction in compound attrition due to toxicity. In addition, there is a need in the pharmaceutical industry to develop safety and efficacy biomarkers that are relevant to multiple species such as rat, dog, and human. Genomics provides an opportunity to discover novel cross-species biomarkers for identifying phenotypes such as liver fibrosis, especially if the biomarkers are tissue specific secreted proteins that can be monitored in the serum. This review includes an example of how databases from multiple species, in this case rat and human tissues, can be utilized to identify candidate cross-species diagnostic markers of hepatitis and fibrosis. This study illustrates a genomic approach for identifying candidate cross-species biomarkers of cirrhosis/fibrosis for humans and rats, and a previously known biomarker of fibrosis (APOA1) and a novel candidate biomarker of fibrosis, FETUB were identified. As more "omic" databases are built, a reservoir of molecular information will become available for toxicologist to gain more extensive views on the physiological alterations induced by adverse events, which will inevitably lead to the development of better tools for predicting, identifying, categorizing, and determining cross-species impact of the toxicity and ultimate provide a novel scientific scaffold for improving safety assessment protocols. C1 US FDA, Off Clin Pharmacol & Biopharmaceut, CDER, Silver Spring, MD 20993 USA. RP Orr, MS (reprint author), US FDA, Off Clin Pharmacol & Biopharmaceut, CDER, Bldg 21,Room 4517,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM Michael.Orr@FDA.gov NR 47 TC 4 Z9 5 U1 1 U2 3 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 PY 2006 VL 16 IS 2-3 BP 79 EP 87 DI 10.1080/15376520600558317 PG 9 WC Toxicology SC Toxicology GA 021BO UT WOS:000235957700005 PM 20021000 ER PT J AU Huang, SM Goodsaid, F Rahman, A Frueh, F Lesko, LJ AF Huang, SM Goodsaid, F Rahman, A Frueh, F Lesko, LJ TI Application of pharmacogenomics in clinical pharmacology SO TOXICOLOGY MECHANISMS AND METHODS LA English DT Article DE pharmacogenomics application; clinical pharmacology ID THIOPURINE S-METHYLTRANSFERASE; REGULATORY DECISION-MAKING; MULTIDRUG-RESISTANCE GENE; ADVERSE DRUG-REACTIONS; DATA SUBMISSIONS; PLASMA-CONCENTRATIONS; TRANSPLANT PATIENTS; DOSE REQUIREMENTS; ALLELIC VARIANTS; CYP2D6 ACTIVITY AB Many factors can affect a patient's response to a drug. These include intrinsic factors such as age, gender, race/ethnicity, genetics, disease states, organ dysfunctions, and other physiological changes, including pregnancy, lactation, and extrinsic factors such as smoking, diet ( food, juice, dietary supplements), and concomitant medications (ICH E5, 1998 and 2004). The interplay of genotypes of the enzymes, transporters and receptors, among other factors ( such as concomitant medications and disease states), can affect the risk/benefit ratio for individual patients. This commentary discusses when the genomic information should be obtained during drug development and when it is to be assimilated into labeling and standards of care that can be used to "individualize" drug therapy and become one of the pillars of "personalized medicine." C1 US FDA, Off Clin Pharmacol & Biopharmaceut, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Huang, SM (reprint author), US FDA, Off Clin Pharmacol & Biopharmaceut, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM Shiewmei.huang@fda.hhs.gov NR 91 TC 21 Z9 23 U1 0 U2 0 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1537-6516 J9 TOXICOL MECH METHOD JI Toxicol. Mech. Methods PY 2006 VL 16 IS 2-3 BP 89 EP 99 DI 10.1080/15376520600558333 PG 11 WC Toxicology SC Toxicology GA 021BO UT WOS:000235957700006 PM 20021001 ER PT J AU Mukherjee, A Jackson, SA LeClerc, JE Cebula, TA AF Mukherjee, A Jackson, SA LeClerc, JE Cebula, TA TI Exploring genotypic and phenotypic diversity of microbes using microarray approaches SO TOXICOLOGY MECHANISMS AND METHODS LA English DT Article DE DNA microarray; DNA tiling array; E. coli O157 : H7; phenotypic microarray; microbial diversity ID ESCHERICHIA-COLI K-12; SALMONELLA-ENTERICA; TELLURITE RESISTANCE; GENOME SEQUENCE; HIGH-THROUGHPUT; GENE-TRANSFER; EVOLUTION; BACTERIA; O157-H7; ARRAYS AB Application of genome-scale analysis like DNA microarray technology has revolutionized multiple scientific disciplines. Herein, a next generation of DNA microarrays, a DNA tiling approach that allows high throughput sampling of genomes with single-nucleotide precision, is described. As methods revealing a genomic scale examination of cellular phenotypes offer keen insights for genomic analyses, a high throughput system for whole cell phenotyping is similarly detailed. The merit of these technologies in discriminating pathogenic and commensal strains of microbes is emphasized using the microbe, Escherichia coli, as an example. Deployment of microarray strategies to assess closely-related microbial strains should help address diversity of organisms in their feral settings. C1 US FDA, Off Appl Res & Safety Assessment HFS025, Ctr Food Safety & Appl Nutr, Div Mol Biol HFS025, Laurel, MD 20708 USA. RP Cebula, TA (reprint author), US FDA, Off Appl Res & Safety Assessment HFS025, Ctr Food Safety & Appl Nutr, Div Mol Biol HFS025, Laurel, MD 20708 USA. EM Thomas.Cebula@fda.hhs.gov NR 40 TC 6 Z9 6 U1 0 U2 1 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 PY 2006 VL 16 IS 2-3 BP 121 EP 128 DI 10.1080/15376520600558473 PG 8 WC Toxicology SC Toxicology GA 021BO UT WOS:000235957700008 PM 20021003 ER PT J AU Choudhuri, S AF Choudhuri, S TI Some major landmarks in the path from nuclein to human genome SO TOXICOLOGY MECHANISMS AND METHODS LA English DT Review DE human genome sequencing; nuclein; genomics ID DEPENDENT RNA-POLYMERASE; P21 TRANSFORMING PROTEIN; AVIAN-SARCOMA VIRUSES; ESCHERICHIA-COLI; NUCLEOTIDE-SEQUENCE; DEOXYRIBONUCLEIC ACID; HEMOPHILUS-INFLUENZAE; BACTERIOPHAGE-LAMBDA; DNA-POLYMERASE; MESSENGER-RNA AB The completion of sequencing of the human genome as well as the genomes of other species is a spectacular achievement of 20th-century biology. It is appropriately regarded as a turning point in biology and medicine for the 21st century. Knowledge of the human genome will presumably help us understand the genetic instructions that make us human. By learning about the gene sequences, the functional dynamics of the genome as well as the individual genetic differences, scientists hope to understand the molecular basis of the normal state and the diseased state of life on one hand, and develop ways to individualize medicine and nutrition on the other hand. Thus, the science of genomics that has grown out of this genome sequencing effort is expected to revolutionize the future of biology itself. The present article is an attempt to briefly summarize some major landmarks in the path that began with the discovery of "nuclein" and led to the completion of the human genome sequencing. C1 US FDA, Ctr Food Safety & Appl Nutr, OFAS, DBGNR, College Pk, MD 20740 USA. RP Choudhuri, S (reprint author), US FDA, Ctr Food Safety & Appl Nutr, OFAS, DBGNR, HFS 225 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM Supratim.Choudhuri@cfsan.fda.gov NR 134 TC 2 Z9 2 U1 0 U2 1 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1537-6524 J9 TOXICOL MECH METHOD JI Toxicol. Mech. Methods PY 2006 VL 16 IS 2-3 BP 137 EP 159 DI 10.1080/15376520600558606 PG 23 WC Toxicology SC Toxicology GA 021BO UT WOS:000235957700010 PM 20021005 ER PT J AU Simak, J Gelderman, MP AF Simak, J Gelderman, MP TI Cell membrane microparticles in blood and blood products: Potentially pathogenic agents and diagnostic markers SO TRANSFUSION MEDICINE REVIEWS LA English DT Review ID PLATELET-DERIVED MICROPARTICLES; THROMBOTIC THROMBOCYTOPENIC PURPURA; PLASMA ENDOTHELIAL MICROPARTICLES; ACUTE CORONARY SYNDROMES; CIRCULATING PROCOAGULANT MICROPARTICLES; PAROXYSMAL-NOCTURNAL HEMOGLOBINURIA; ANGIOGENESIS IN-VITRO; ACTIVE TISSUE FACTOR; SMOOTH-MUSCLE-CELLS; DIABETES-MELLITUS AB Cell membrane microparticles (MPs) circulate in the blood of healthy donors, and their elevated counts have been documented in various pathologies. Microparticles are phospholipid microvesicles of 0.05 to 1.5 mu m in size, containing certain membrane proteins of their parental cells. Thus, different phenotypes of MPs derived from platelets, blood cells, endothelial cells, and some other cell types have been identified in plasma. Microparticles are released by various stimuli including shear stress, complement attack, or proapoptotic stimulation. Microparticle release is a highly controlled process and likely independent from metabolic energy. Elevated MPs in various diseases indicate their diagnostic importance, particularly in vascular pathologies. Moreover, MPs in blood possess a broad spectrum of biologic activities. Microparticles; may facilitate cell-to-cell interactions, induce cell signaling, or even transfer receptors between different cell types. The physiological roles of MPs in various tissue defense processes have been suggested and the pathophysiologic implications of MPs in thrombosis, inflammation, cancer metastasis, or response to pathogens have been proposed. This is important for transfusion medicine because MPs are present in both plasma and cellular blood products. Thus, the investigation of potentially pathogenic effects of MPs in blood products and of MP release associated with blood product processing and storage have yet to come. (c) 2006 Elsevier Inc. All rights reserved. C1 US FDA, Ctr Biol Evaluat & Res, Lab Cellular Hematol, Bethesda, MD 20014 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 156 TC 183 Z9 196 U1 1 U2 31 PU W B SAUNDERS CO-ELSEVIER INC 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 JAN PY 2006 VL 20 IS 1 BP 1 EP 26 DI 10.1016/j.tmrv.2005.08.001 PG 26 WC Hematology SC Hematology GA 004VM UT WOS:000234780600001 PM 16373184 ER PT J AU Wear, KA AF Wear, Keith A. TI Fred Lizzi's statistical framework and the interpretation of ultrasound backscatter from bone SO ULTRASONIC IMAGING LA English DT Letter ID FREQUENCY-DEPENDENCE C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Wear, KA (reprint author), US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. EM keith.wear@fda.hhs.gov NR 3 TC 3 Z9 3 U1 0 U2 0 PU DYNAMEDIA INC PI SILVER SPRING PA 2 FULHAM COURT, SILVER SPRING, MD 20902 USA SN 0161-7346 J9 ULTRASONIC IMAGING JI Ultrason. Imaging PD JAN PY 2006 VL 28 IS 1 BP 41 EP 42 PG 2 WC Acoustics; Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 072MR UT WOS:000239678000004 PM 16924881 ER PT S AU Peden, K Sheng, L Pal, A Lewis, A AF Peden, K Sheng, L Pal, A Lewis, A BE Sheets, R Petricciani, J TI Biological activity of residual cell-substrate DNA SO Vaccine Cell Substrates 2004 SE DEVELOPMENTS IN BIOLOGICALS LA English DT Proceedings Paper CT Vaccine Cell Substrates 2004 Symposium CY JUN 29-JUL 01, 2004 CL Rockville, MD SP NIH, NIAID, Int Assoc Biol ID VIRAL-DNA; VIRUS; HAMSTERS; CULTURES; INVIVO AB Vaccines and other biological products manufactured in cells contain contaminating residual DNA derived from that production cell substrate, with the amount and form of this DNA depending mainly on the type of vaccine. The potential risk of this cellular DNA has been debated for over 40 years without resolution. Opinions on residual DNA have varied from it being considered an inert contaminant, and thus its presence should not be deemed to be a risk to vaccine recipients, to it being considered an important risk factor, particularly for vaccines manufactured in certain cell substrates, such as cells derived from tumours or cells that are tumorigenic. We are not of the opinion that DNA can be considered biologically inert, but whether or what risk residual cell-substrate DNA poses remains to be determined. In this paper, we discuss our approaches to address this issue and describe some preliminary work. C1 US FDA, CBER, Div Viral Prod, OVRR, Bethesda, MD 20892 USA. RP Peden, K (reprint author), US FDA, CBER, Div Viral Prod, OVRR, Bldg 29A,Room 3D08,29 Lincoln Dr, Bethesda, MD 20892 USA. NR 15 TC 6 Z9 11 U1 0 U2 0 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 1424-6074 BN 3-8055-7999-3 J9 DEV BIOLOGICALS JI Dev. Biols PY 2006 VL 123 BP 45 EP 53 PG 9 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA BEA67 UT WOS:000236477100006 PM 16566436 ER PT J AU Thorpe, SJ Fox, B Heath, AB Scott, M de Haas, M Kochman, S Padilla, A AF Thorpe, S. J. Fox, B. Heath, A. B. Scott, M. de Haas, M. Kochman, S. Padilla, A. TI International standards for minimum potency of anti-A and anti-B blood grouping reagents: evaluation of candidate preparations in an international collaborative study SO VOX SANGUINIS LA English DT Article DE grouping reagents; potency; safety; specifications; standardization AB Background and Objectives: The aim of the study was to evaluate lyophilized monoclonal IgM anti-A and anti-B preparations for use as international standards (IS) to specify recommended minimum potencies of anti-A and anti-B blood grouping reagents in tube tests. Materials and Methods: The candidate IS for minimum potency of anti-A and anti-B blood grouping reagents, codes 03/188 and 03/164, respectively, were evaluated against a wide range of commercial anti-A and anti-B blood grouping reagents in an international collaborative study involving 16 laboratories in nine countries. Laboratories titrated 03/188 and 03/164 in parallel with as many commercial anti-A and anti-B blood grouping reagents, respectively, as were available to them, in tube tests according to specified haemagglutination methodology. Three of these laboratories and a further laboratory also titrated 03/188 and 03/164 in parallel with currently available reference preparations for anti-A and anti-B. The ratios of the mean endpoint titres of the anti-A and anti-B reagents to those of 03/188 and 03/164, respectively, within each laboratory were calculated. Results: The ratios of the mean titres of the anti-A reagents to the mean titre of 03/188 within a laboratory fell within 0.062 and 4, i.e. the potencies of the anti-A reagents were between a sixteenth to four times as strong as 03/188. The ratios of the mean titres of the anti-B reagents to the mean titre of 03/164 within a laboratory also fell within 0.062 and 4, with one outlier. Conclusions: By international consensus, a 1 in 8 dilution of the candidate IS for anti-A, 03/188, and a 1 in 4 dilution of the candidate IS for anti-B, 03/164, were considered appropriate to define the recommended minimum potencies of anti-A and anti-B blood grouping reagents, respectively, in tube tests. On the basis of these results, preparations 03/188 and 03/164 were established by the World Health Organization as International Standards for Minimum Potency of Anti-A and Anti-B Blood Grouping Reagents respectively, and by the US Food and Drug Administration Center for Biologics Evaluation and Research as Minimum Potency Reference Reagents. C1 Natl Inst Biol Stand & Controls, Biotherapeut Grp, Parenterals Sect, Potters Bar EN6 3QG, Herts, England. Int Blood Grp Reference Lab, Bristol, Avon, England. Sanquin CLB, Amsterdam, Netherlands. US FDA, Ctr Biol Evaluat & Res, Rockville, MD USA. WHO, CH-1211 Geneva, Switzerland. RP Thorpe, SJ (reprint author), Natl Inst Biol Stand & Controls, Biotherapeut Grp, Parenterals Sect, Blanche Lane S Mimms, Potters Bar EN6 3QG, Herts, England. EM sthorpe@nibsc.ac.uk RI Thorpe, Susan/E-1808-2013; Fox, Bernard/E-2523-2013 NR 8 TC 4 Z9 7 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0042-9007 J9 VOX SANG JI Vox Sang. PY 2006 VL 91 IS 4 BP 336 EP 344 DI 10.1111/j.1423-0410.2006.00834.x PG 9 WC Hematology SC Hematology GA 103WD UT WOS:000241917000010 PM 17105610 ER PT J AU Ye, ZP Harmison, GG Ragheb, JA Schubert, M AF Ye, ZP Harmison, GG Ragheb, JA Schubert, M TI Targeted infection of HIV-1 Env expressing cells by HIV(CD4/CXCR4) vectors reveals a potential new rationale for HIV-1 mediated down-modulation of CD4 SO RETROVIROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; TYPE-1 ENVELOPE GLYCOPROTEIN; VESICULAR STOMATITIS-VIRUS; PROTEIN INDUCES DEGRADATION; RECOMBINANT VACCINIA VIRUS; SURFACE CD4; VPU PROTEIN; T-CELLS; CYTOPLASMIC DOMAIN; CELLULAR-PROTEINS AB Background: Efficient targeted gene transfer and cell type specific transgene expression are important for the safe and effective expression of transgenes in vivo. Enveloped viral vectors allow insertion of exogenous membrane proteins into their envelopes, which could potentially aid in the targeted transduction of specific cell types. Our goal was to specifically target cells that express the T cell tropic HIV-1 envelope protein (Env) using the highly specific interaction of Env with its cellular receptor (CD4) inserted into the envelope of an HIV-1-based viral vector. Results: To generate HIV-1-based vectors carrying the CD4 molecule in their envelope, the CD4 ectodomain was fused to diverse membrane anchors and inserted together with the HIV-1 coreceptor CXCR4 into the envelopes of HIV-1 vector particles. Independent of the type of CD4 anchor, all chimeric CD4 proteins inserted into HIV-1 vector envelopes and the resultant HIV(CD4/CXCR4) particles were able to selectively confer neomycin resistance to cells expressing the fusogenic T cell tropic HIV-1 Env protein. Unexpectedly, in the absence of Env on the target cells, all vector particles carrying the CD4 ectodomain anchored in their envelope adhered to various cell types without infecting these cells. This cell adhesion was very avid. It was independent of the presence of Env on the target cell, the type of CD4 anchor or the presence of CXCR4 on the particle. In mixed cell populations with defined ratios of Env(+)/Env(-) cells, the targeted transduction of Env(+) cells by HIV(CD4/CXCR4) particles was diminished in proportion to the number of Env- cells. Conclusion: Vector diversion caused by a strong, non-selective cell binding of CD4(+)-vector particles effectively prevents the targeted transduction of HIV-1 Env expressing cells in mixed cell populations. This Env- independent cell adhesion severely limits the effective use of targeted HIV( CD4/CXCR4) vectors designed to interfere with HIV-1 replication in vivo. Importantly, the existence of this newly described and remarkably strong CD4-dependent cell adhesion suggests that the multiple viral efforts to reduce CD4 cell surface expression may, in part, be to prevent cell adhesion to non-target cells and thereby to increase the infectivity of viral progeny. Preventing CD4 down-modulation by HIV-1 might be an effective component of a multi-faceted antiviral strategy. C1 Natl Inst Neurol Disorders & Stroke, Mol Virol & Neurogenet Sect, NIH, Bethesda, MD 20892 USA. US FDA, Lab Pediat & Resp Viral Dis, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. Natl Inst Neurol Disorders & Stroke, Neurogenet Branch, NIH, Bethesda, MD 20892 USA. NEI, Clin & Mol Immunol Sect, NIH, Bethesda, MD 20892 USA. RP Schubert, M (reprint author), Natl Inst Neurol Disorders & Stroke, Mol Virol & Neurogenet Sect, NIH, Rm 4S-18,5625 Fishers Lane, Bethesda, MD 20892 USA. EM yez@cber.FDA.gov; HarmisoG@ninds.nih.gov; jr50b@nih.gov; schuberm@ninds.nih.gov FU Intramural NIH HHS NR 66 TC 3 Z9 3 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PD DEC 21 PY 2005 VL 2 AR 80 DI 10.1186/1742-4690-2-80 PG 15 WC Virology SC Virology GA 033OP UT WOS:000236858700001 PM 16371160 ER PT J AU Gheorghiade, M Zannad, F Sopko, G Klein, L Pina, IL Konstam, MA Massie, BM Roland, E Targum, S Collins, SP Filippatos, G Tavazzi, L AF Gheorghiade, M Zannad, F Sopko, G Klein, L Pina, IL Konstam, MA Massie, BM Roland, E Targum, S Collins, SP Filippatos, G Tavazzi, L CA Int Working Grp Acute Heart Failur TI Acute heart failure syndromes - Current state and framework for future research SO CIRCULATION LA English DT Article DE heart failure; coronary disease; morbidity; mortality ID RANDOMIZED CONTROLLED-TRIAL; NATIONAL REGISTRY ADHERE; IN-HOSPITAL MORTALITY; QUALITY-OF-CARE; INTRAVENOUS MILRINONE; RECEPTOR ANTAGONIST; RISK STRATIFICATION; SURVEY PROGRAM; RENAL-FUNCTION; OPTIME-CHF C1 Northwestern Univ, Feinberg Sch Med, Div Cardiol, Chicago, IL 60611 USA. CHu Nancy, INSERM, Dommartin Les Toul, France. NHLBI, Bethesda, MD 20892 USA. Univ Hosp Cleveland, Cleveland, OH 44106 USA. Tufts Univ New England Med Ctr, Boston, MA 02111 USA. Vet Affairs Med Ctr, San Francisco, CA 94121 USA. Agence Francaise Secur Sanitaire Prod Sante, Paris, France. US FDA, Rockville, MD 20857 USA. Univ Cincinnati, Cincinnati, OH USA. Univ Athens Hosp Attikon, Athens, Greece. IRCCS Policlin San Matteo, Pavia, Italy. RP Gheorghiade, M (reprint author), Northwestern Univ, Feinberg Sch Med, Div Cardiol, Galter 10-240,201 E Huron St, Chicago, IL 60611 USA. EM m-gheorghiade@northwestern.edu RI Lainscak, Mitja/F-3237-2015 NR 38 TC 347 Z9 372 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD DEC 20 PY 2005 VL 112 IS 25 BP 3958 EP 3968 DI 10.1161/CIRCULATIONAHA.105.590091 PG 11 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 994VB UT WOS:000234058200019 PM 16365214 ER PT J AU Moynahan, M Faris, OP Lewis, BM AF Moynahan, M Faris, OP Lewis, BM TI Cardiac resynchronization devices - The food and drug administration's regulatory considerations SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID HEART-FAILURE; DEFIBRILLATOR AB Cardiac resynchronization therapy (CRT) devices have been studied clinically since 1998, and have been on the U.S. market since the Food and Drug Administration (FDA) approval of the first product in 2001. Since that time, the FDA has approved many different models from three different manufacturers, representing the first and second generations of these products. All of these products have undergone the FDA pre-market approval process, which examines the safety and efectiveness of the devices for their intended use. Over the last several years, the FDA has adapted recommendations for CRT clinical trials based on an evolving understanding of what these devices can achieve. This paper will outline the dynamic nature of the FDA's approval process for CRT devices and briefly review the clinical trial designs for the first generation devices. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Moynahan, M (reprint author), US FDA, Pacing Defibrillators & Leads Branch, Off Device Evaluat, 9200 Corp Blvd,HFZ 450, Rockville, MD 20850 USA. EM megan.moynahan@fda.hhs.gov NR 3 TC 2 Z9 2 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD DEC 20 PY 2005 VL 46 IS 12 BP 2325 EP 2328 DI 10.1016/j.jacc.2005.04.068 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 995HE UT WOS:000234090600025 PM 16360066 ER PT J AU Lague, P Roux, B Pastor, RW AF Lague, P Roux, B Pastor, RW TI Molecular dynamics simulations of the influenza hemagglutinin fusion peptide in micelles and bilayers: Conformational analysis of peptide and lipids SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE viral fusion; hemagglutinin; fusion peptide; peptide-micelle interaction; molecular dynamics ID VIRUS HEMAGGLUTININ; SECONDARY STRUCTURE; MEMBRANE-FUSION; DMPC BILAYER; PROTEIN; NMR; GRAMICIDIN; MELITTIN; ENERGY; ENVIRONMENT AB Molecular dynamics simulations of the influenza hemagglutinin fusion peptide in two differently sized dodecylphosphocholine micelles and a palmitoyl oleoyl phosphatidylcholine bilayer were generated to analyze the influence of the environment. Four independent trajectories (5 ns each for the bilayer, and 2 ns each for the micelles) were generated for each system. The peptide lies at the surface of the micelles, while its N-terminal region inserts deeply in the bilayer. This leads to a substantial increase of the solvation and rigidity of the peptide in micelles as compared to the bilayer. The average structures, nevertheless, are similar in all three systems and agree reasonably with micelle-based NMR structures. When in the bilayer, the peptide increases the chain gauche population and area of adjacent lipids in the same binding leaflet, while it has the opposite effect for the nearby lipids of the other leaflet. These changes, which occur spontaneously to fill voids and defects, cause a decrease in the thickness of the membrane in the neighborhood of the peptide. They would be expected to promote positive curvature, as consistent with the formation of the convex bulge, or "nipple", in the initial stage of membrane fusion. An extension of the classical surfactant theory of Israelachvili based on shapes is proposed to introduce the concept of a "dynamically induced shape" of the membrane lipids by the peptide. (c) 2005 Elsevier Ltd. All rights reserved. C1 US FDA, Ctr Biol Evaluat & Res, Biophys Lab, Rockville, MD 20852 USA. Cornell Univ, Weill Med Coll, Dept Biochem, New York, NY 10021 USA. RP Lague, P (reprint author), Univ Laval, Fac Sci & Genie, CREFSIP, Dept Biochem & Microbiol, Quebec City, PQ, Canada. EM patrick.lague@rsvs.ulaval.ca FU NIGMS NIH HHS [GM-62342] NR 48 TC 53 Z9 54 U1 3 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 DEC 16 PY 2005 VL 354 IS 5 BP 1129 EP 1141 DI 10.1016/j.jmb.2005.10.038 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 995GW UT WOS:000234089800011 PM 16297931 ER PT J AU Fan, YX Wong, LL Johnson, GR AF Fan, YX Wong, LL Johnson, GR TI EGFR kinase possesses a broad specificity for ErbB phosphorylation sites, and ligand increases catalytic-centre activity without affecting substrate binding affinity SO BIOCHEMICAL JOURNAL LA English DT Article DE autophosphorylation; epidermal growth factor receptor (EGFR); ErbB receptor; Michaelis-Menten; receptor tyrosine kinase (RTK) specificity; binding affinity ID EPIDERMAL-GROWTH-FACTOR; RECEPTOR TYROSINE KINASE; AUTOPHOSPHORYLATION SITES; SIGNAL-TRANSDUCTION; GUANIDINE-HYDROCHLORIDE; CRYSTAL-STRUCTURE; PROTEIN-KINASE; IDENTIFICATION; ACTIVATION; DISTINCT AB We previously found that EGF (epidermal growth factor) increases the EGFR (EGF receptor) kinase-binding affinity towards the major tyrosine phosphorylation sites in downstream adaptor proteins such as Gab1 (Grb2-associated binding protein 1) and Shc [Src homology 2 (SH2) domain and collagen containing protein], but not that towards EGFR autophosphorylation sites [Fan, Wong, Deb and Johnson (2004) J. Biol. Chem. 279, 38143-38150]. EGFR activation can also result in transphosphorylation of tyrosine resides in the C-terminal region of the related receptors ErbB2, ErbB3 and ErbB4 in heterodimers which are formed upon ligand stimulation. In the present study, we investigated the specificity of EGFR kinase by comparing the steady state kinetic parameters for peptides derived from all four ErbBs in the absence or presence of EGF. Our results demonstrated that (i) EGFR kinase can efficiently phosphorylate a broad range of diverse peptide sequences representing ErbB sites; (ii) certain ErbB2, ErbB3 and ErbB4 sites had higher specificity constants than any EGFR sequence and (iii) EGF stimulation consistently increases the k(cat) approx. 5-fold, but does not significantly alter the K-m for any ErbB peptides. Furthermore, peptides containing lysine at position - 2 or - 3 N-terminal to the target tyrosine were found to be poor EGFR kinase substrates, and substitution of these lysines with glutamine decreased the K-m and increased the k(cat) for these substrates. We conclude that EGFR kinase-mediated ErbB transphosphorylations are mostly controlled at the level of oligomerization, and not by a preference of the EGFR kinase for phosphorylation sites in any particular ErbB. The results also demonstrated that, unlike phosphorylation sites in select downstream targets, EGF does not regulate the recognition of phosphorylation sites in the C-terminal region of any of the ErbBs. C1 US FDA, Ctr Drug Evaluat & Res, Div Therapeut Prot, Bethesda, MD 20892 USA. RP Fan, YX (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Therapeut Prot, Bldg 29A,Rm 3B-20,8800 Rockville Pike, Bethesda, MD 20892 USA. EM fany@cder.fda.gov; johnsong@cder.fda.gov NR 35 TC 20 Z9 20 U1 0 U2 3 PU PORTLAND PRESS LTD PI LONDON PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD DEC 15 PY 2005 VL 392 BP 417 EP 423 PN 3 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 998YB UT WOS:000234354700001 PM 16122376 ER PT J AU Rubinstein, DB Ziv, R Carmeli, M Leitner, O Wreschner, DH AF Rubinstein, DB Ziv, R Carmeli, M Leitner, O Wreschner, DH TI Immunization with MUC1/X protein enhances cDNA immunization in generating Anti-MUC1 alpha/beta junction antibodies that target cancer cells. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR/NCI/EORTC International Conference on Molecular Targets and Cancer Therapeutics CY NOV 14-18, 2005 CL Philadelphia, PA SP AACR, NCI, EORTC, AMGEN, AstraZeneca, Britol-Myers Squibb Co, Pfizer, Sanofi Aventis, Bayer Hlth Car Pharmaceut, Lilly, Genentech, GSK GlaxoSmithKline, Johnson &Johnson, MERCK, NOVARTIS ONCOL, Centocor, OSI Oncol, Schering-Plough, BTG, Servier, RADPHARM, Cvitkovic & Associes C1 US FDA, Rockville, MA USA. Tel Aviv Univ, Ramat Aviv, Israel. Weizmann Inst Sci, Rehovot, Israel. 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 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 15 PY 2005 VL 11 IS 24 SU S BP 8980S EP 8980S PN 2 PG 1 WC Oncology SC Oncology GA 999IJ UT WOS:000234382700063 ER PT J AU Laassri, M Lottenbach, K Belshe, R Wolff, M Rennels, M Plotkin, S Chumakov, K AF Laassri, M Lottenbach, K Belshe, R Wolff, M Rennels, M Plotkin, S Chumakov, K TI Effect of different vaccination schedules on excretion of oral poliovirus vaccine strains SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 24th Annual Meeting of the American-Society-for-Virology CY JUN 18-22, 2005 CL Penn State Univ, Philadelphia, PA SP Amer Soc Virol HO Penn State Univ ID ENHANCED-POTENCY; VIRUS EXCRETION; POLIOMYELITIS; EVOLUTION; POLIOVACCINE; LIVE; PCR AB Inactivated poliovirus vaccine (IPV) is believed to induce significantly lower mucosal immunity than oral poliovirus vaccine (OPV). Most of the data supporting this were generated before enhanced IPV (eIPV) was introduced. Excretion of poliovirus by OPV recipients can be used to assess intestinal immunity. We studied polymerase chain reaction amplification of viral complementary DNA from the stool of children vaccinated with either OPV alone or eIPV. Of first-time OPV recipients, 92% excreted virus after 1 week, and 81% excreted virus after 3 weeks. Prior vaccination with OPV reduced the number to 22% and shortened the duration of virus excretion (to 5% after 3 weeks). Two doses of IPV reduced the number of poliovirus-positive 1-week samples (to 76%), the duration of shedding (to 37% at 3 weeks), and the quantity of excreted virus. This suggests that IPV-vaccinated communities are partially protected from the spread of poliovirus. Further enhancement of IPV potency may lead to even higher levels of mucosal immunity. C1 US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. EMMES Corp, Rockville, MD USA. Univ Maryland, Sch Med, Baltimore, MD 21201 USA. St Louis Univ, St Louis, MO 63103 USA. Univ Penn, Philadelphia, PA 19104 USA. Sanofi Pasteur, Doylestown, PA USA. RP Chumakov, K (reprint author), US FDA, Ctr Biol Evaluat & Res, 1401 Rockville Pike,HFM 470, Rockville, MD 20852 USA. EM chumakov@cber.fda.gov FU NIAID NIH HHS [N01-AI-45250, N01-AI-45251] NR 29 TC 36 Z9 39 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 DEC 15 PY 2005 VL 192 IS 12 BP 2092 EP 2098 DI 10.1086/498172 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 984QK UT WOS:000233319200010 PM 16288372 ER PT J AU Bi, XL Jones, T Abbasi, F Lee, H Stultz, B Hursh, DA Mortin, MA AF Bi, XL Jones, T Abbasi, F Lee, H Stultz, B Hursh, DA Mortin, MA TI Drosophila caliban, a nuclear export mediator, can function as a tumor suppressor in human lung cancer cells SO ONCOGENE LA English DT Article DE caliban; Sdccag1; tumor suppressor; nuclear export; lung cancer; interference RNA ID PROSPERO GENE; CRM1; LOCALIZATION; HOMOLOG; REVEALS; ENCODES; SIGNALS; PROTEIN; SYSTEM; DOMAIN AB We previously showed that the Drosophila DNA binding homeodomain of Prospero included a 28 amino-acid sequence (HDA) that functions as a nuclear export signal. We describe here the identification of a protein we named Caliban, which can directly interact with the HDA. Caliban is homologous to human Sdccag1, which has been implicated in colon and lung cancer. Here we show that Caliban and Sdccag1 are mediators of nuclear export in fly and human cells, as interference RNA abrogates export of EYFP-HDA in normal fly and human lung cells. Caliban functions as a bipartite mediator nuclear export as the carboxy terminus binds HDA and the amino terminus itself functions as an NES, which directly binds the NES receptor Exportin. Finally, while non-cancerous lung cells have functional Sdccag1, five human lung carcinoma cell lines do not, even though Exportin still functions in these cells. Expression of fly Caliban in these human lung cancer cells restores EYFP-HDA nuclear export, reduces a cell's ability to form colonies on soft agar and reduces cell invasiveness. We suggest that Sdccag1 inactivation contributes to the transformed state of human lung cancer cells and that Caliban should be considered a candidate for use in lung cancer gene therapy. C1 NCI, Biochem Lab, NIH, Bethesda, MD 20892 USA. NICHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Bethesda, MD 20892 USA. RP Mortin, MA (reprint author), NCI, Biochem Lab, NIH, Bethesda, MD 20892 USA. EM mortinm@mail.nih.gov RI Bi, Xiaolin/E-7469-2010; Mortin, Mark/B-4251-2008; Bi, Xiaolin/C-7038-2014 OI Bi, Xiaolin/0000-0002-7172-7851; Bi, Xiaolin/0000-0003-2837-9457 NR 21 TC 12 Z9 16 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD DEC 15 PY 2005 VL 24 IS 56 BP 8229 EP 8239 DI 10.1038/sj.onc.1208962 PG 11 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 993LV UT WOS:000233956500002 PM 16103875 ER PT J AU Santamaria, A Vazquez-Roman, B Perez-De La Cruz, V Gonzalez-Cortes, C Trejo-Solis, MC Galvan-Arzate, S Jara-Prado, A Guevara-Fonseca, J Ali, SF AF Santamaria, A Vazquez-Roman, B Perez-De La Cruz, V Gonzalez-Cortes, C Trejo-Solis, MC Galvan-Arzate, S Jara-Prado, A Guevara-Fonseca, J Ali, SF TI Selenium reduces the proapoptotic signaling associated to NF-kappa B pathway and stimulates glutathione peroxidase activity during excitotoxic damage produced by quinolinate in rat corpus striatum SO SYNAPSE LA English DT Article DE excitotoxicity; antioxidant defense; NMDA receptor; NF-kappa B pathway ID MAMMALIAN THIOREDOXIN REDUCTASE; RADICAL SCAVENGER OPC-14117; INDUCED LIPID-PEROXIDATION; ACID-INDUCED NEUROTOXICITY; IN-VITRO; NEURODEGENERATIVE DISORDERS; OXIDATIVE NEUROTOXICITY; ANTIOXIDANT THERAPY; INDUCED APOPTOSIS; ACTIVATION AB Quinolinate (QUIN) neurotoxicity has been attributed to degenerative events in nerve tissue produced by sustained activation of N-methyl-(D)-aspartate receptor (NMDAr) and oxidative stress. We have recently described the protective effects that selenium (Se), an antioxidant, produces on different markers of QUIN-induced neurotoxicity (Santamaria et al., 2003, J Neurochem 86:479-488.). However, the mechanisms by which Se exerts its protective actions remain unclear. Since some of these events are thought to be related with inhibition of deadly molecular cascades through the activation of antioxidant selenoproteins, in this study we investigated the effects of Se on QUIN-induced cell damage elicited by the nuclear factor kappa B (NF-kappa B) pathway, as well as the time-course response of striatal glutathione peroxidase (GPx) activity. Se (sodium selenite, 0.625 mg/kg/day, i.p.) was administered to rats for 5 days, and 120 min after the last administration, animals received a single striatal injection of QUIN (240 mnol/mu l). Twenty-four hours later, their striata were tested for the expression of I kappa B-alpha (the NF-kappa B cytosolic binding protein), the immunohistochemical expression of NF-kappa B (evidenced as nuclear expression of P65), caspase-3-like activation, and DNA fragmentation. Additional groups were killed at 2, 6, and 24 h for measurement of GPx activity. Se reduced the QUIN-induced decrease in I kappa B-alpha expression, evidencing a reduction in its cytosolic degradation. Se also prevented the QUIN-induced increase in P65-immunoreactive cells, suggesting a reduction of NF-kappa B nuclear translocation. Caspase-3-like activation and DNA fragmentation produced by QUIN were also inhibited by Se. Striatal GPx activity was stimulated by Se at 2 and 6 h, but not, at 24 h postlesion. Altogether, these data suggest that the protective effects exerted by Se on QUIN-induced neurotoxicity are partially mediated by the inhibition of proapoptotic events underlying I kappa B-alpha degradation, NF-kappa B nuclear translocation, and caspase-3-like activation in the rat striatum, probably involving the early activation of GPx. C1 US FDA, Natl Ctr Toxicol Res, Neurochem Lab, Div Neurotoxicol, Jefferson, AR 72079 USA. Inst Nacl Neurol & Neurocirugia Manuel Velasco Su, Lab Aminoacidos Excitadores, Mexico City 14269, DF, Mexico. Inst Nacl Neurol & Neurocirugia Manuel Velasco Su, Dept Neuroinmunol, Mexico City 14269, DF, Mexico. Inst Nacl Neurol & Neurocirugia Manuel Velasco Su, Dept Neuroquim, Mexico City 14269, DF, Mexico. Inst Nacl Neurol & Neurocirugia Manuel Velasco Su, Dept Genet, Mexico City 14269, DF, Mexico. Inst Nacl Neurol & Neurocirugia Manuel Velasco Su, Lab Enfermedades Neurodegenerativas, Mexico City 14269, DF, Mexico. RP Ali, SF (reprint author), US FDA, Natl Ctr Toxicol Res, Neurochem Lab, Div Neurotoxicol, HFT 132, Jefferson, AR 72079 USA. EM sali@nctr.fda.gov NR 53 TC 15 Z9 15 U1 1 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0887-4476 J9 SYNAPSE JI Synapse PD DEC 15 PY 2005 VL 58 IS 4 BP 258 EP 266 DI 10.1002/syn.20206 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 980PO UT WOS:000233030700007 PM 16206188 ER PT J AU Westenberger, BJ Ellison, CD Fussner, AS Jenney, S Kolinski, RE Lipe, TG Lyon, RC Moore, TW Revelle, LK Smith, AP Spencer, JA Story, KD Toler, DY Wokovich, AM Buhse, LF AF Westenberger, BJ Ellison, CD Fussner, AS Jenney, S Kolinski, RE Lipe, TG Lyon, RC Moore, TW Revelle, LK Smith, AP Spencer, JA Story, KD Toler, DY Wokovich, AM Buhse, LF TI Quality assessment of internet pharmaceutical products using traditional and non-traditional analytical techniques SO INTERNATIONAL JOURNAL OF PHARMACEUTICS LA English DT Article DE analytical chemistry; chromatography; chemometrics; dissolution; image analysis; near infrared spectroscopy; thermal analysis AB This work investigated the use of non-traditional analytical methods to evaluate the quality of a variety of pharmaceutical products purchased via internet sites from foreign sources and compared the results with those obtained from conventional quality assurance methods. Traditional analytical techniques employing HPLC for potency, content uniformity, chromatographic purity and drug release profiles were used to evaluate the quality of five selected drug products (fluoxetine hydrochloride, levothyroxine sodium, metformin hydrochloride, phenytoin sodium, and warfarin sodium). Non-traditional techniques, such as near infrared spectroscopy (NIR), NIR imaging and thermogravimetric analysis (TGA), were employed to verify the results and investigate their potential as alternative testing methods. Two of 20 samples failed USP monographs for quality attributes. The additional analytical methods found 11 of 20 samples had different formulations when compared to the U.S. product. Seven of the 20 samples arrived in questionable containers, and 19 of 20 had incomplete labeling. Only 1 of the 20 samples had final packaging similar to the U.S. products. The non-traditional techniques complemented the traditional techniques used and highlighted additional quality issues for the products tested. For example, these methods detected suspect manufacturing issues (such as blending), which were not evident from traditional testing alone. Published by Elsevier B.V. C1 US FDA, Div Pharmaceut Anal, St Louis, MO 63101 USA. US FDA, Div Pharmaceut Anal, Silver Spring, MD USA. US FDA, Div Prod Qual Res, Silver Spring, MD USA. RP Westenberger, BJ (reprint author), US FDA, Div Pharmaceut Anal, 1114 Market St, St Louis, MO 63101 USA. EM westenberger@cder.fda.gov NR 11 TC 58 Z9 58 U1 3 U2 21 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 DEC 8 PY 2005 VL 306 IS 1-2 BP 56 EP 70 DI 10.1016/j.ijpharm.2005.08.027 PG 15 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 994NN UT WOS:000234038600005 PM 16266793 ER PT J AU Zinderman, CE Wise, R Landow, L AF Zinderman, CE Wise, R Landow, L TI Fluid solutions in dengue shock syndrome SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 US FDA, Rockville, MD 20852 USA. RP Zinderman, CE (reprint author), US FDA, Rockville, MD 20852 USA. EM zinderman@cber.fda.gov NR 4 TC 1 Z9 1 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 DEC 8 PY 2005 VL 353 IS 23 BP 2510 EP 2510 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 990OZ UT WOS:000233754400016 PM 16339101 ER PT J AU Izurieta, HS Haber, P Wise, RP Iskander, J Pratt, D Mink, C Chang, SJ Braun, MM Ball, R AF Izurieta, HS Haber, P Wise, RP Iskander, J Pratt, D Mink, C Chang, SJ Braun, MM Ball, R TI Adverse events reported following live, cold-adapted, intranasal influenza vaccine SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID GUILLAIN-BARRE-SYNDROME; CHILDREN; ADOLESCENTS; SYSTEM; SAFETY AB Context In June 2003, the US Food and Drug Administration licensed a trivalent live, attenuated influenza vaccine (LAIV-T) for intranasal administration to healthy persons 5 to 49 years of age. Although prelicensure testing involved 20228 vaccinees, clinical trials were not of sufficient size to detect rare adverse events reliably. Objective To identify adverse events reported following LAIV-T administration after licensure. Design, Setting, and Participants All adverse events reported to the US Vaccine Adverse Event Reporting System (VAERS) during the 2003-2004 and the 2004-2005 influenza seasons. Main Outcome Measures Numbers and proportions of reported adverse events and reporting rates of adverse events per 100 000 vaccinees. Results Approximately 2 500000 persons received LAIV-T during the first 2 post-licensure seasons. As of August 16, 2005, VAERS received 460 adverse event reports for vaccinations received from August 2003 through July 2005. No fatalities were reported. There were 7 reports of possible anaphylaxis, 2 reports of Guillain-Barre syndrome, 1 report of Bell palsy, and 8 reports of asthma exacerbation among individuals with a prior asthma history. Events in individuals for whom the vaccine was not indicated accounted for 73 reports (16%). Conclusions Reports to VAERS in the first 2 seasons of LAIV-T use did not identify any unexpected serious risks with this vaccine when used according to approved indications. Like many vaccines and other medical products, LAIV-T may rarely cause anaphylaxis. Secondary transmission of the vaccine virus merits further investigation. Reports of asthma exacerbations in vaccinees with prior asthma history highlight the risks of vaccine use inconsistent with approved labeling. C1 US FDA, Vaccine Safety Branch, Div Epidemiol, Off Biostat & Epidemiol,Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. Ctr Dis Control & Prevent, Natl Immunizat Off, Off Chief Sci Officer, Atlanta, GA USA. RP Izurieta, HS (reprint author), US FDA, Vaccine Safety Branch, Div Epidemiol, Off Biostat & Epidemiol,Ctr Biol Evaluat & Res, 1401 Rockville Pike,2nd Floor,Suite 200S,HFM-222, Rockville, MD 20852 USA. EM hector.izurieta@fda.hhs.gov NR 18 TC 78 Z9 87 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD DEC 7 PY 2005 VL 294 IS 21 BP 2720 EP 2725 DI 10.1001/jama.294.21.2720 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 990EV UT WOS:000233726900020 PM 16333007 ER PT J AU Jones-Trower, A Garcia, A Meseda, CA He, Y Weiss, C Kumar, A Weir, JP Merchlinsky, M AF Jones-Trower, A Garcia, A Meseda, CA He, Y Weiss, C Kumar, A Weir, JP Merchlinsky, M TI Identification and preliminary characterization of vaccinia virus (Dryvax) antigens recognized by vaccinia immune globulin SO VIROLOGY LA English DT Article DE VIG; dryvax; MVA; humoral response; vaccinia; inclusion body protein ID SMALLPOX VACCINATION; PROTECTS MICE; ANTIBODY-RESPONSES; GAMMA-GLOBULIN; T-CELLS; INFECTION; PROTEINS; THERAPY; COMPLICATIONS; PROPHYLAXIS AB Using vaccinia immune globulin (VIG), a high-titer antibody preparation from immunized subjects, we demonstrate that the humoral immune response in humans is directed against numerous antigens in the Dryvax vaccine strain. Western blot and immunoprecipitation analyses revealed highly antigenic proteins associated with both the extracellular enveloped vir-us and intracellular mature virus forms. The modified vaccinia virus Ankara (MVA), a new generation smallpox vaccine that is attenuated for replication in humans, expresses most, but not all, of the major vaccinia antigens recognized by antibodies in VIG, lacking the highly antigenic protein corresponding to the A-type inclusion body protein. Since new-generation smallpox vaccines such as MVA will require extensive comparison to traditional smallpox vaccines in animal models of immunogenicity and protection, we compared the vaccinia virus antigens recognized by VIG to those recognized by sera from Dryvax and MVA immunized mice. The humoral immune response in immunized mice is qualitatively similar to that in humans. C1 US FDA, Lab DNA Viruses, Div Viral Prod, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Merchlinsky, M (reprint author), US FDA, Lab DNA Viruses, Div Viral Prod, Ctr Biol Evaluat & Res, HFM-457,1401 Rockville Pike, Rockville, MD 20852 USA. EM merchlinsky@cber.fda.gov NR 41 TC 31 Z9 32 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 DEC 5 PY 2005 VL 343 IS 1 BP 128 EP 140 DI 10.1016/j.virol.2005.08.008 PG 13 WC Virology SC Virology GA 993BE UT WOS:000233926900011 PM 16165184 ER PT J AU Steele, AD Warfel, JM D'Agnillo, F AF Steele, AD Warfel, JM D'Agnillo, F TI Anthrax lethal toxin enhances cytokine-induced VCAM-1 expression on human endothelial cells SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE Bacillus anthracis; vasculitis; adhesion molecules; endothelium; lethal factor; RANTES; tumor necrosis factor-alpha; anthrax pathogenesis ID NECROSIS-FACTOR-ALPHA; N-TERMINAL KINASE; INHALATIONAL ANTHRAX; BACILLUS-ANTHRACIS; PATHOLOGY; ACTIVATION; PATHOGENESIS; MACROPHAGES; RELEASE; RANTES AB Vascular endothelial dysfunction is thought to play a prominent role in systemic anthrax pathogenesis. We examined the effect of anthrax lethal toxin (LTx), a key virulence factor of Bacillus anthracis, on the expression of vascular cell adhesion molecule-1 (VCAM-1) on normal and cytokine-stimulated human lung microvascular endothelial cells. Confluent endothelial monolayers were treated with lethal factor (LF), protective antigen (PA), or both (LTx) in the presence or absence of tumor necrosis factor-alpha (TNF alpha). LTx enhanced cytokine-induced VCAM-1 expression and monocyte adhesion. LTx alone had no effect on VCAM-l expression. LF, PA or the combination of a catalytically inactive mutant LF and PA failed to enhance cytokine-induced VCAM-1 expression. Treatment with inhibitors of mitogen-activated protein kinase kinases (MEKs) and mitogen-activated protein kinases did not reproduce the VCAM-l enhancement effect of LTx, a known MEK metalloprotease, suggesting LTx-mediated MEK cleavage may not be a contributing factor. Published by Elsevier Inc. C1 US FDA, Lab Biochem & Vasc Biol, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. RP D'Agnillo, F (reprint author), US FDA, Lab Biochem & Vasc Biol, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. EM dagnillo@cber.fda.gov RI Warfel, Jason/D-2557-2011 FU Intramural NIH HHS NR 28 TC 14 Z9 16 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 DEC 2 PY 2005 VL 337 IS 4 BP 1249 EP 1256 DI 10.1016/j.bbrc.2005.09.180 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 981XF UT WOS:000233120600033 PM 16242117 ER PT J AU Endres, L Fischer, P Jenkins, T Wollet, L Hardman, J Kilpatrick, S Rodvold, K Geller, S Sarto, G Miller, M Fischer, J AF Endres, L Fischer, P Jenkins, T Wollet, L Hardman, J Kilpatrick, S Rodvold, K Geller, S Sarto, G Miller, M Fischer, J TI Influence of body size on labetalol pharmacokinetics during pregnancy SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 26th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 30-FEB 04, 2006 CL Miami Beach, FL SP Soc Maternal Fetal Med C1 Univ Illinois, Dept Obstet & Gynecol, Chicago, IL 60612 USA. Univ Wisconsin, Dept Obstet & Gynecol, Madison, WI 53706 USA. US FDA, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2005 VL 193 IS 6 SU S MA 217 BP S72 EP S72 DI 10.1016/j.ajog.2005.10.257 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 993IM UT WOS:000233947800217 ER PT J AU Raju, BVS Singh, R Sreenivas, G Duncan, R Nakhasi, HL Salotra, P AF Raju, Balaraju Venkat Subba Singh, Ruchi Sreenivas, Gannavaram Duncan, Robert Nakhasi, Hira Lal Salotra, Poonam TI A genomic approach to identify differentially expressed genes in Leishmania donovani isolates from patients of post kala-azar dermal leishmaniasis (PKDC) in comparison with kala-azar (KA) SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract C1 [Raju, Balaraju Venkat Subba; Singh, Ruchi; Sreenivas, Gannavaram; Salotra, Poonam] Inst Pathol ICMR, New Delhi, India. [Duncan, Robert; Nakhasi, Hira Lal] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 DEC PY 2005 VL 73 IS 6 SU S MA 306 BP 101 EP 101 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA V44GA UT WOS:000202990000305 ER PT J AU Curtis, JR Saag, KG Martin, C Patkar, N Shatin, D Kramer, JM Braun, MM AF Curtis, JR Saag, KG Martin, C Patkar, N Shatin, D Kramer, JM Braun, MM TI Validation of claims-identified serious adverse events in rheumatoid arthritis and Crohn's disease patients. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 69th Annual Scientific Meeting of the American-College-of-Rheumatology/40th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 12-17, 2005 CL San Diego, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Univ Alabama, Birmingham, AL USA. Ctr Healthcare Policy & Evaluat, Eden Prairie, MN USA. Duke Univ, Durham, NC USA. US FDA, Rockville, MD 20857 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD DEC PY 2005 VL 52 IS 12 BP 4085 EP 4085 PG 1 WC Rheumatology SC Rheumatology GA 995VC UT WOS:000234131500129 ER PT J AU Moody, JD Freeman, JP Cerniglia, CE AF Moody, JD Freeman, JP Cerniglia, CE TI Degradation of benz[a] anthracene by Mycobacterium vanbaalenii strain PYR-1 SO BIODEGRADATION LA English DT Article DE benz[a] anthracene; degradation; mycobacterium; polycyclic aromatic hydrocarbons ID POLYCYCLIC AROMATIC-HYDROCARBONS; MOLECULAR CHARACTERIZATION; METABOLIZING BACTERIUM; PYRENE; BIODEGRADATION; IDENTIFICATION; SOIL; FLUORANTHENE; OXIDATION; PRODUCTS AB Cultures of Mycobacterium vanbaalenii strain PYR-1 grown in mineral salts medium and nutrients in the presence of benz [ a] anthracene metabolized 15% of the added benz [ a] anthracene after 12 days of incubation. Neutral and acidic ethyl acetate extractable metabolites were isolated and characterized by high performance liquid chromatography ( HPLC) and uv visible absorption, gas chromatography/ mass (GC/MS) and nuclear magnetic resonance (NMR) spectral analysis. Trimethylsilylation of the metabolites followed by GC/MS analysis facilitated identification of metabolites. The characterization of metabolites indicated that M. vanbaalenii initiated attack of benz [ a] anthracene at the C-1,2-, C-5,6-, C-7,12- and C-10,11-positions to form dihydroxylated and methoxylated intermediates. The major site of enzymatic attack was in the C-10, C-11 positions. Subsequent ortho - and meta - cleavage of each of the aromatic rings led to the accumulation of novel ring-fission metabolites in the medium. The major metabolites identified were 3-hydrobenzo [ f] isobenzofuran- 1-one (3.2%), 6- hydrofuran [ 3,4- g] chromene-2,8-dione (1.3%), benzo [ g] chromene-2-one (1.7%), naphtho [2,1-g] chromen-10-one (48.1%), 10-hydroxy-11-methoxybenz [ a] anthracene (9.3%), and 10,11-dimethoxybenz [ a] anthracene (36.4%). Enzymatic attack at the C-7 and C-12 positions resulted in the formation of benz [ a] anthracene-7,12- dione, 1-(2- hydroxybenzoyl) - 2-naphthoic acid, and 1- benzoyl-2-naphthoic acid. A phenyl-naphthyl metabolite, 3-(2- carboxylphenyl) - 2-naphthoic acid, was formed when M. vanbaalenii was incubated with benz [ a] anthracene cis-5,6-dihydrodiol,indicating ortho - cleavage of 5, 6- dihydroxybenz [ a] anthracene. A minor amount of 5,6- dimethoxybenz [ a] anthracene was also formed. The data extend and propose novel pathways for the bacterial metabolism of benz [ a] anthracene. C1 US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. US FDA, Natl Ctr Toxicol Res, Div Chem, Jefferson, AR 72079 USA. RP Cerniglia, CE (reprint author), US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. EM ccerniglia@nctr.fda.gov NR 48 TC 28 Z9 30 U1 4 U2 18 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0923-9820 J9 BIODEGRADATION JI Biodegradation PD DEC PY 2005 VL 16 IS 6 BP 513 EP 526 DI 10.1007/s10532-004-7217-1 PG 14 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 905FY UT WOS:000227555000003 PM 15865344 ER PT J AU Filipovich, AH Weisdorf, D Pavletic, S Socie, G Wingard, JR Lee, SJ Martin, P Chien, J Przepiorka, D Couriel, D Cowen, EW Dinndorf, P Farrell, A Hartzman, R Henslee-Downey, J Jacobsohn, D McDonald, G Mittleman, B Rizzo, JD Robinson, M Schubert, M Schultz, K Shulman, H Turner, M Vogelsang, G Flowers, MED AF Filipovich, AH Weisdorf, D Pavletic, S Socie, G Wingard, JR Lee, SJ Martin, P Chien, J Przepiorka, D Couriel, D Cowen, EW Dinndorf, P Farrell, A Hartzman, R Henslee-Downey, J Jacobsohn, D McDonald, G Mittleman, B Rizzo, JD Robinson, M Schubert, M Schultz, K Shulman, H Turner, M Vogelsang, G Flowers, MED TI National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Review DE chronic graft-versus-host disease; allogeneic hematopoietic cell transplantation; consensus; diagnosis; staging ID BONE-MARROW-TRANSPLANTATION; STEM-CELL TRANSPLANTATION; RISK-FACTORS; PREDICTIVE FACTORS; RECIPIENTS; BLOOD; DONORS; MULTICENTER; MORTALITY; CHILDREN AB This consensus document is intended to serve 3 functions. First, it standardizes the criteria for diagnosis of chronic graft-versus-host disease (GVHD). Second, it proposes a new clinical scoring system (0-3) that describes the extent and severity of chronic GVHD for each organ or site at any given time, taking functional impact into account. Third, it proposes new guidelines for global assessment of chronic GVHD severity that are based on the number of organs or sites involved and the degree of involvement in affected organs (mild, moderate, or severe). Diagnosis of chronic GVHD requires the presence of at least 1 diagnostic clinical sign of chronic GVHD (e.g., poikiloderma or esophageal web) or the presence of at least I distinctive manifestation (e.g., keratoconjunctivitis sicca) confirmed by pertinent biopsy or other relevant tests (e.g., Schirmer test) in the same or another organ. Furthermore, other possible diagnoses for clinical symptoms must be excluded. No time limit is set for the diagnosis of chronic GVHD. The Working Group recognized 2 main categories of GVHD, each with 2 subcategories. The acute GVHD category is defined in the absence of diagnostic or distinctive features of chronic GVHD and includes (1) classic acute GVHD occurring within 100 days after transplantation and (2) persistent, recurrent, or late acute GVHD (features of acute GVHD occurring beyond 100 days, often during withdrawal of immune suppression). The broad category of chronic GVHD includes (1) classic chronic GVHD (without features or characteristics of acute GVHD) and (2) an overlap syndrome in which diagnostic or distinctive features of chronic GVHD and acute GVHD appear together. It is currently recommended that systemic therapy he considered for patients who meet criteria for chronic GVHD of moderate to severe global severity. (c) 2005 American Society for Blood and Marrow Transplantation. C1 Univ Cincinnati, Childrens Hosp, Div Hematol Oncol, Cincinnati, OH 45229 USA. Univ Minnesota, Minneapolis, MN USA. Natl Canc Inst, NIH, Bethesda, MD USA. Hop St Louis, Paris, France. Univ Florida, Shands Cans Ctr, Gainesville, FL USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Washington, Sch Med, Fred Hutchinson Canc Res Ctr, Seattle, WA 98195 USA. Univ Tennessee, Memphis, TN 38163 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. US FDA, Rockville, MD 20857 USA. Naval Med Res Ctr, CW Bill Young Dept Def Marrow Donor Recruitment &, Silver Spring, MD USA. NHLBI, NIH, Bethesda, MD 20892 USA. Northwestern Univ, Childrens Mem Hosp, Sch Med, Chicago, IL 60614 USA. NIAMSD, NIH, Bethesda, MD 20892 USA. Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA. NEI, NIH, Bethesda, MD 20892 USA. Univ British Columbia, British Columbia Childrens Hosp, Vancouver, BC V5Z 1M9, Canada. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. RP Filipovich, AH (reprint author), Univ Cincinnati, Childrens Hosp, Div Hematol Oncol, 333 Burnet Ave,MLC 7015, Cincinnati, OH 45229 USA. EM lisa.filipovich@cchmc.org FU Intramural NIH HHS NR 29 TC 1471 Z9 1526 U1 7 U2 33 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 DEC PY 2005 VL 11 IS 12 BP 945 EP 956 DI 10.1016/j.bbmt.2005.09.004 PG 12 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 995JC UT WOS:000234095600002 PM 16338616 ER PT J AU Hung, HMJ AF Hung, HMJ TI Discussion on "Establishing efficacy of a new experimental treatment in the 'gold standard' design" SO BIOMETRICAL JOURNAL LA English DT Editorial Material DE gold standard design; assay sensitivity; proof of efficacy; relative efficacy; Fieller's confidence interval C1 US FDA, CDER, OB, Div Biometr 1, Silver Spring, MD 20993 USA. RP Hung, HMJ (reprint author), US FDA, CDER, OB, Div Biometr 1, HFD-710,10993 Hampshire Ave,Bldg 22,Rm 4238,Mail, Silver Spring, MD 20993 USA. EM hung@cder.fda.gov NR 3 TC 4 Z9 4 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 2005 VL 47 IS 6 BP 795 EP 796 DI 10.1002/bimj.200510180 PG 2 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 000LW UT WOS:000234464500008 ER PT J AU Skibinsky, A Venable, RM Pastor, RW AF Skibinsky, A Venable, RM Pastor, RW TI A molecular dynamics study of the response of lipid bilayers and monolayers to trehalose SO BIOPHYSICAL JOURNAL LA English DT Article ID PHOSPHATIDYLCHOLINE MODEL MEMBRANES; SURFACE-TENSION; LIQUID/LIQUID INTERFACES; NEUTRON-DIFFRACTION; COMPUTER-SIMULATION; ALKANES; WATER; CONFORMATION; UNDULATIONS; SYSTEM AB Surface tensions evaluated from molecular dynamics simulations of fully hydrated dipalmitoylphosphatidylcholine bilayers and monolayers at surface areas/lipid of 54, 64, and 80 angstrom(2) are uniformly lowered 4 - 8 dyn/ cm upon addition of trehalose in a 1: 2 trehalose/ lipid ratio. Constant surface tension simulations of bilayers yield the complementary result: an increase in surface area consistent with the surface pressure-surface area (pi-A) isotherms. Hydrogen bonding by trehalose, replacement of waters in the headgroup region, and modulation of the dipole potential are all similar in bilayers and monolayers at the same surface area. These results strongly support the assumption that experimental measurements on the interactions of surface active components such as trehalose with monolayers can yield quantitative insight to their effects on bilayers. The simulations also indicate that the 20 - 30 dyn/ cm difference in surface tension of the bilayer lea. et and monolayer arises from differences in the chain regions, not the headgroup/water interfaces. 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, Rockville, MD 20852 USA. EM pastor@cber.fda.gov NR 47 TC 75 Z9 76 U1 1 U2 8 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD DEC PY 2005 VL 89 IS 6 BP 4111 EP 4121 DI 10.1529/biophysj.105.065953 PG 11 WC Biophysics SC Biophysics GA 988JO UT WOS:000233590800048 PM 16183878 ER PT J AU Wouters, KA Kremer, LCM Miller, TL Herman, EH Lipshultz, SE AF Wouters, KA Kremer, LCM Miller, TL Herman, EH Lipshultz, SE TI Protecting against anthracycline-induced myocardial damage: a review of the most promising strategies SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Review DE cancer; anthracyclines; myocardial damage; cardioprotective agents; prevention ID CONGESTIVE-HEART-FAILURE; ACUTE LYMPHOBLASTIC-LEUKEMIA; ADVANCED BREAST-CANCER; DOXORUBICIN-INDUCED CARDIOMYOPATHY; IDIOPATHIC DILATED CARDIOMYOPATHY; LEFT-VENTRICULAR DYSFUNCTION; ADRIAMYCIN-INDUCED CARDIOMYOPATHY; LONG-TERM SURVIVORS; LIPOSOME-ENCAPSULATED DOXORUBICIN; CARDIOPROTECTIVE AGENT ICRF-187 AB Over the last 40 years, great progress has been made in treating childhood and adult cancers. However, this progress has come at an unforeseen cost, in the form of emerging long-term effects of anthracycline treatment. A major complication of anthracycline therapy is its adverse cardiovascular effects. If these cardiac complications could be reduced or prevented, higher doses of anthracyclines could potentially be used, thereby further increasing cancer cure rates. Moreover, as the incidence of cardiac toxicity resulting in congestive heart failure or even heart transplantation dropped, the quality and extent of life for cancer survivors would improve. We review the proposed mechanisms of action of anthracyclines and the consequences associated with anthracycline treatment in children and adults. We summarise the most promising current strategies to limit or prevent anthracycline-induced cardiotoxicity, as well as possible strategies to prevent existing cardiomyopathy from worsening. C1 Vrije Univ Amsterdam, Med Ctr, Div Pediat, Amsterdam, Netherlands. Emma Childrens Hosp, Dept Paediat Oncol, Acad Med Ctr, Amsterdam, Netherlands. Univ Miami, Miller Sch Med, Div Pediat Clin Res, Miami, FL 33152 USA. US FDA, Ctr Drug Evaluat & Res, Div Appl Pharmacol Res, Silver Spring, MD USA. Univ Miami, Jackson Mem Med Ctr, Holtz Childrens Hosp, Miami, FL 33152 USA. Univ Miami, Sylvester Comprehens Canc Ctr, Miami, FL 33152 USA. RP Lipshultz, SE (reprint author), Univ Miami, Miller Sch Med, Dept Pediat, Med Campus MCCD-D820,1601 NW 12th Ave,9th Floor, Miami, FL 33136 USA. EM slipshultz@med.miami.edu NR 204 TC 202 Z9 214 U1 1 U2 16 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD DEC PY 2005 VL 131 IS 5 BP 561 EP 578 DI 10.1111/j.1365-2141.2005.05759.x PG 18 WC Hematology SC Hematology GA 993WQ UT WOS:000233988000001 PM 16351632 ER PT J AU Weinberg, WC Frazier-Jessen, MR Wu, WJ Weir, A Hartsough, M Keegan, P Fuchs, C AF Weinberg, WC Frazier-Jessen, MR Wu, WJ Weir, A Hartsough, M Keegan, P Fuchs, C TI Development and regulation of monoclonal antibody products: Challenges and opportunities SO CANCER AND METASTASIS REVIEWS LA English DT Review DE monoclonal antibodies; Investigational New Drug (IND); cancer therapy; Biologics License Application (BLA); clinical trials; immunogenicity ID IMMUNE-COMPLEXES; POLYMORPHISMS; TRASTUZUMAB; RITUXIMAB AB An increasing number of monoclonal antibodies for cancer diagnosis and treatment are in clinical use and in the development pipeline, with more expected as new molecular targets are identified. As with all drugs, product quality, an appropriate pre-clinical pharmacology-toxicology testing program, and well-designed clinical trials are essential for a successful drug development program. However, protein products such as monoclonal antibodies present unique regulatory concerns. The derivation from biological sources as well as the constantly evolving technologies utilized to develop these products demands continuous appraisal of safety concerns, even while the accumulated experience with these protein products has facilitated their safety evaluations. Because of the complex nature of these products and their inherent heterogeneity, a mechanistic understanding of the mode of action along with careful attention to product design and manufacture are critical to assuring a safe, effective and consistent product. Protein products may be highly species specific, thus pharmacologically relevant animal models are an important component in accurately assessing pre-clinical safety and establishing initial dosing. Furthermore, the immunogenicity of protein products can impact its safety profile, dose exposure, and efficacy. Mechanistic insight should form the basis of biological assays used for monitoring efficacy, safety, lot-to-lot consistency and manufacturing changes. The inherent uniqueness of each product necessitates a flexible case-by-case approach for biologics review that is based on a strong scientific understanding of relative risks. This review will provide an overview of approaches used in the development of antibody-based cancer therapeutics and the scientific basis of regulatory reviews. C1 US FDA, Ctr Biol Evaluat & Res, Div Monoclonal Antibodies, Off Biotechnol Prod,Off Pharmaceut Sci, Bethesda, MD 20014 USA. US FDA, Ctr Drug Evaluat & Res, Div Biol Oncol Prod, Off Oncol ,Off New Drugs, Rockville, MD 20857 USA. RP Frazier-Jessen, MR (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Monoclonal Antibodies, Off Biotechnol Prod,Off Pharmaceut Sci, Bethesda, MD 20014 USA. EM Michelle.Jessen@fda.gov RI Weinberg, Wendy/A-8920-2009 NR 33 TC 38 Z9 38 U1 1 U2 8 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-7659 J9 CANCER METAST REV JI Cancer Metastasis Rev. PD DEC PY 2005 VL 24 IS 4 BP 569 EP 584 DI 10.1007/s10555-005-6196-y PG 16 WC Oncology SC Oncology GA 002FY UT WOS:000234598100007 PM 16408162 ER PT J AU Fricke, MW Zeller, M Sun, H Lai, VWM Cullen, WR Shoemaker, JA Witkowski, MR Creed, JT AF Fricke, MW Zeller, M Sun, H Lai, VWM Cullen, WR Shoemaker, JA Witkowski, MR Creed, JT TI Chromatographic separation and identification of products from the reaction of dimethylarsinic acid with hydrogen sulfide SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID ORGANIC ARSENIC COMPOUNDS; TRIMETHYLARSINE OXIDE; CRYSTAL-STRUCTURE; METABOLITE; GLUTATHIONE; TOXICITY; URINE; RATS; DIMETHYLDITHIOARSINATE; REARRANGEMENT AB The reaction of dimethylarsinic acid (DMA(V)) with hydrogen sulfide (H2S) is of biological significance and may be implicated in the overall toxicity and carcinogenicity of arsenic. The course of the reaction in aqueous phase was monitored, and an initial product, dimethylthioarsinic acid, was observed by using LC-ICP-MS and LC-ESI-MS. Dimethylarsinous acid was observed as a minor product. A second slower-forming product was identified, and the electrospray mass chromatograms for this species produced ions at m/z 275, 171, and 137 in positive mode. To aid in the identification of this slower-forming product, crystalline standards of sodium dimethyldithioarsinate and dimethylarsino dimethyldithioarsinate were prepared and re-characterized by using improved spectroscopic and structural analysis techniques. An aqueous solution of sodium dimethyldithioarsinate produced a single major chromatographic peak that matched the retention time (7.6 min) of the slower-forming product and contained similar molecular ions at m/z 275, 171, and 137 via LC-ESI-MS. The dimethylarsino dimethyldithioarsinate standard produced four aqueous phase species one of which coeluted with the slower forming product. This coeluting peak also produced the identical ESI-MS ions as the slower-forming product of DMA(V) + H2S. ESI-MS/MS experiments conducted on sodium dimethyldithioarsinate in deuterated water produced molecular ions at m/z 276, 173, and 137. Subsequent collisionally activated dissociation (CAD) experiments on m/z 276 did not produce a product ion at m/z 173. These data indicate that two different species are present in solution, while NMR data indicate that only dimethyldithioarsinic acid exists in aqueous solutions. This discrepancy was investigated by conducting NMR studies on the acidic solution of sodium dimethyldithioarsinate after taking this solution to dryness. The resolubilized solution produced a proton NMR signal characteristic of dimethylarsino dimethyldithioarsinate. Therefore, it was concluded that the ESI-MS ion at m/z 275 associated with the slowly forming second reaction product and the sodium dimethyldithioarsinate compound is a product of the ESI desolvation process. C1 US EPA, Natl Exposure Res Lab, Microbiol & Chem Exposure Assessment Res Div, Cincinnati, OH 45268 USA. Youngstown State Univ, Dept Chem, Youngstown, OH 44555 USA. Univ British Columbia, Dept Chem, Vancouver, BC V6T 1Z1, Canada. United States Food & Drug Adm, Vibrat Spect Lab, Forens Chem Ctr, Cincinnati, OH 45237 USA. RP Creed, JT (reprint author), US EPA, Natl Exposure Res Lab, Microbiol & Chem Exposure Assessment Res Div, 26 W Martin Luther King Dr, Cincinnati, OH 45268 USA. EM creedjack@epa.gov RI Creed, John/A-9187-2009; Zeller, Matthias/C-2255-2009 OI Zeller, Matthias/0000-0002-3305-852X NR 44 TC 44 Z9 44 U1 2 U2 16 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 2005 VL 18 IS 12 BP 1821 EP 1829 DI 10.1021/tx050227d PG 9 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 004XY UT WOS:000234787200005 PM 16359172 ER PT J AU Parker, RJ Hartman, NR Roecklein, BA Mortko, H Kupferberg, HJ Stables, J Strong, JM AF Parker, RJ Hartman, NR Roecklein, BA Mortko, H Kupferberg, HJ Stables, J Strong, JM TI Stability and comparative metabolism of selected felbamate metabolites and postulated fluorofelbamate metabolites by postmitochondrial suspensions SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID CARBONYL REDUCTASE; MERCAPTURIC ACIDS; IN-VITRO; CARBAMATE; URINE AB Evidence has been presented suggesting that a reactive metabolite, 2-phenylpropenal (ATPAL), may be responsible for the toxicities observed during therapy with the antiepileptic drug felbamate (FBM). Formation of ATPAL from its unstable immediate precursor, 3-carbamoyl-2-phenylpropionaldedhyde (CBMA) requires the loss of the hydrogen atom at position 2 in the propane chain, and it has been postulated that substitution of this atom with fluorine would prevent the formation of ATPAL. On the basis of this hypothesis, 2-fluoro-2-phenyl-1,3-propanediol dicarbamate (F-FBM) was synthesized and is presently undergoing drug development. To test this hypothesis, we compared the metabolism by human liver post-mitochondrial suspensions (S9) in vitro of selected FBM and postulated F-FBM metabolites leading to formation of CBMA or 3-carbamoyl-2-fluoro-2-phenyl-propionaldehyde (F-CBMA). All S9 incubations included GSH as a trapping agent for any reactive metabolites formed. Our results indicated that, in phosphate buffer, pH 7.4, at 37 degrees C, the half-life for 4-hydroxy5-phenyltetrahydro-1,3-oxazin-2-one (CCMF) was 2.8 and 3.6 h in the presence or absence of GSH, respectively; compared to 4-hydroxy-5-fluoro-5-phenyl-tetrahydro-1,3-oxazin-2-one (FCCMF) which lost only 2.5% or 4.9% over 24 h under the same conditions. When incubated with S9 in the presence of the cofactor, NAD+, 2-phenyl-1,3-propanediol monocarbamate (MCF) was oxidized to CCMF which was further oxidized to 3-carbamoyl-2-phenylpropionic acid (CPPA). 2-Fluoro-2-phenyl-1,3-propanediol monocarbamate (F-MCF) under similar conditions was stable, and no metabolites were observed. When CCMF was incubated with S9 in the presence of NAD+ cofactor, oxidation to CPPA and reduction to MCF were observed. In addition, a new atropic acid GSH adduct (ATPA-GSH) was identified by mass spectrometry. When F-CCMF was incubated under the same conditions as CCMF, both reduced and oxidized metabolites, F-MCF and 3-carbamoyl-2-fluoro-2-phenylpropionic acid (F-CPPA), respectively, were formed but at significantly lower rates, and no GSH conjugates were identified. Our results support the hypothesis that F-FBM and F-CCMF are not metabolized by S9 in vitro to the known reactive FBM metabolite, ATPAL. C1 US FDA, Ctr Drug Evaluat & Res, Lab Clin Pharmacol, Silver Spring, MD 20993 USA. MedPointe Pharmceut, Somerset, NJ 08873 USA. Natl Inst Neurol Dis & Stroke, NIH, Bethesda, MD 20892 USA. RP Strong, JM (reprint author), US FDA, Ctr Drug Evaluat & Res, Lab Clin Pharmacol, 10903 New Hampshire Ave,White Oak Bldg 64, Silver Spring, MD 20993 USA. EM strongj@cder.fda.gov NR 17 TC 14 Z9 14 U1 4 U2 9 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 2005 VL 18 IS 12 BP 1842 EP 1848 DI 10.1021/tx050130r PG 7 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 004XY UT WOS:000234787200007 PM 16359174 ER PT J AU Turesky, RJ LeMaster, D Mcnaughton, L Holland, RD Wu, RW Felton, JS AF Turesky, RJ LeMaster, D Mcnaughton, L Holland, RD Wu, RW Felton, JS TI 2-amino-1,7-dimethylimidazo[4,5-g]quinoxaline (7-MeIgQx): A novel and abundant mutagenic heterocyclic aromatic amine formed in grilled beef. SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Meeting Abstract CT Meeting of the Division of Chemical Toxicology of the American-Chemical-Society held at the 230th National Meeting of the ACS CY AUG 28-SEP 01, 2005 CL Washington, DC SP Amer Chem Soc, Div Chem Toxicol C1 New York State Dept Hlth, Div Environm Dis Prevent, Wadsworth Ctr, Albany, NY 12201 USA. New York State Dept Hlth, Div Biomed Sci, Wadsworth Ctr, Albany, NY 12201 USA. US FDA, NCTR, Div Syst Biol, Rockville, MD 20857 USA. Lawrence Livermore Natl Lab, Biol & Biotechnol Res Program, Livermore, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD DEC PY 2005 VL 18 IS 12 MA 58 BP 1979 EP 1979 PG 1 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 004XY UT WOS:000234787200077 ER PT J AU Fu, PKL Liu, Y Yin, JJ Turro, C AF Fu, PKL Liu, Y Yin, JJ Turro, C TI Mechanistic studies on the photosensitizing activities of 2,3-diaminophenazine, a common contaminant in hair dyes. SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Meeting Abstract CT Meeting of the Division of Chemical Toxicology of the American-Chemical-Society held at the 230th National Meeting of the ACS CY AUG 28-SEP 01, 2005 CL Washington, DC SP Amer Chem Soc, Div Chem Toxicol C1 US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. Ohio State Univ, Dept Chem, Columbus, OH 43210 USA. EM patty.fu@fda.gov RI Yin, Jun Jie /E-5619-2014; Turro, Claudia/H-5335-2015 OI Turro, Claudia/0000-0003-3202-5870 NR 0 TC 0 Z9 0 U1 0 U2 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 DEC PY 2005 VL 18 IS 12 MA 79 BP 1984 EP 1984 PG 1 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 004XY UT WOS:000234787200098 ER PT J AU Wamer, W Fu, PP Falvey, DE AF Wamer, W Fu, PP Falvey, DE TI Photocytotoxicity of retinol and the role of photooxidative damage. SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Meeting Abstract CT Meeting of the Division of Chemical Toxicology of the American-Chemical-Society held at the 230th National Meeting of the ACS CY AUG 28-SEP 01, 2005 CL Washington, DC SP Amer Chem Soc, Div Chem Toxicol C1 US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. Univ Maryland, Dept Chem, College Pk, MD 20742 USA. EM wwamer@cfsan.fda.gov RI Falvey, Daniel/B-7817-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD DEC PY 2005 VL 18 IS 12 MA 80 BP 1984 EP 1984 PG 1 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 004XY UT WOS:000234787200099 ER PT J AU Leighton, J AF Leighton, J TI Incorporation of toxicogenomics into the regulatory process SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Meeting Abstract CT Meeting of the Division of Chemical Toxicology of the American-Chemical-Society held at the 230th National Meeting of the ACS CY AUG 28-SEP 01, 2005 CL Washington, DC SP Amer Chem Soc, Div Chem Toxicol C1 US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20852 USA. EM leightonj@cder.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 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD DEC PY 2005 VL 18 IS 12 MA 103 BP 1989 EP 1989 PG 1 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 004XY UT WOS:000234787200121 ER PT J AU Andersson, T Flockhart, DA Goldstein, DB Huang, SM Kroetz, DL Milos, PM Ratain, MJ Thummel, K AF Andersson, T Flockhart, DA Goldstein, DB Huang, SM Kroetz, DL Milos, PM Ratain, MJ Thummel, K TI Drug-metabolizing enzymes: Evidence for clinical utility of pharmacogenomic tests SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Editorial Material ID RENAL-TRANSPLANT RECIPIENTS; MULTIDRUG-RESISTANCE GENE; HUMAN MDR1 GENE; SINGLE-NUCLEOTIDE POLYMORPHISMS; STEADY-STATE PHARMACOKINETICS; TACROLIMUS DOSE REQUIREMENTS; DUPLICATED CYP2D6 GENES; HUMAN LIVER-MICROSOMES; S-MEPHENYTOIN; P-GLYCOPROTEIN C1 AstraZeneca, Molndal, Sweden. Indiana Univ, Sch Med, Div Clin Pharmacol, Indianapolis, IN 46204 USA. UCL, Dept Biol, Galton Lab, London, England. US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. Univ Calif San Francisco, Sch Pharm, San Francisco, CA 94143 USA. Pfizer Global Res & Dev, Pharmacogenom, Groton, CT USA. Univ Chicago, Chicago, IL 60637 USA. Univ Washington, Seattle, WA 98195 USA. RP Huang, SM (reprint author), US FDA, Off Clin Pharmacol & Biopharmaceut, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM huangs@cder.fda.gov NR 216 TC 78 Z9 81 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD DEC PY 2005 VL 78 IS 6 BP 559 EP 581 DI 10.1016/j.clpt.2005.08.013 PG 23 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 992XD UT WOS:000233916400001 PM 16338273 ER PT J AU Klaschik, S Gursel, I Klinman, DM AF Klaschik, S Gursel, I Klinman, DM TI Gene expression profile analyses of immune cells treated with immunostimulatory DNA SO CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT 35th Critical Care Congress of the Society-of-Critical-Care-Medicine CY JAN 07-11, 2006 CL San Francisco, CA C1 US FDA, CBER, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD DEC PY 2005 VL 33 IS 12 SU S SI SI BP A144 EP A144 DI 10.1097/00003246-200512002-00510 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA 000ZG UT WOS:000234500900505 ER PT J AU Perez-Arellano, JL Luzardo, OP Brito, AP Cabrera, MH Zumbado, M Carranza, C Angel-Moreno, A Dickey, RW Boada, LD AF Perez-Arellano, JL Luzardo, OP Brito, AP Cabrera, MH Zumbado, M Carranza, C Angel-Moreno, A Dickey, RW Boada, LD TI Ciguatera fish poisoning, Canary Islands SO EMERGING INFECTIOUS DISEASES LA English DT Letter ID TOXINS C1 Univ Las Palmas Gran Canaria, Infect Dis & Trop Med Serv, Dept Med & Surg Sci, Fac Hlth Sci, Las Palmas Gran Canaria 35080, Spain. Hosp Univ Insular Gran Canaria, Canary Hlth Serv, Las Palmas Gran Canaria, Spain. Hosp Fuerteventura, Puerto Del Rosario, Spain. Food & Drug Adm, Gulf Coast Seafood Lab, Dauphin Isl, AL USA. RP Perez-Arellano, JL (reprint author), Univ Las Palmas Gran Canaria, Infect Dis & Trop Med Serv, Dept Med & Surg Sci, Fac Hlth Sci, POB 550, Las Palmas Gran Canaria 35080, Spain. EM jlperez@dcmq.ulpgc.es RI Zumbado, Manuel/B-4495-2010; Dominguez-Boada, Luis/L-5577-2015; Carranza, Cristina/K-9578-2016 OI Dominguez-Boada, Luis/0000-0002-0195-4565; NR 10 TC 39 Z9 44 U1 1 U2 9 PU CENTER DISEASE CONTROL PI ATLANTA PA ATLANTA, GA 30333 USA SN 1080-6040 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD DEC PY 2005 VL 11 IS 12 BP 1981 EP 1982 PG 2 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 990UI UT WOS:000233768300040 PM 16485501 ER PT J AU Dearfield, KL Moore, MM AF Dearfield, KL Moore, MM TI Use of genetic toxicology information for risk assessment SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article DE risk assessment; mutagenic mode of action; genetic toxicology ID MOUSE LYMPHOMA-CELLS; SALMONELLA TESTER STRAIN; THYMIDINE KINASE GENE; ASSAY WORKING GROUP; TRANSGENIC MICE; IN-VITRO; PESTICIDE CHEMICALS; TUMOR PROGRESSION; SHUTTLE VECTORS; MUTATION ASSAY AB Genetic toxicology data are used worldwide in regulatory decision-making. On the 25th anniversary of Environmental and Molecular Mutagenesis, we think it is important to provide a brief overview of the currently available genetic toxicity tests and to outline a framework for conducting weight-of-the-evidence (WOE) evaluations that optimize the utility of genetic toxicology information for risk assessment. There are two major types of regulatory decisions made by agencies such as the Environmental Protection Agency (EPA) and the Food and Drug Administration (FDA): (1) the approval and registration of pesticides, pharmaceuticals, medical devices, and medical-use products, and (2) the setting of standards for acceptable exposure levels in air, water, and food. Genetic toxicology data are utilized for both of these regulatory decisions. The current default assumption for regulatory decisions is that chemicals that are shown to be genotoxic in standard tests are, in fact, capable of causing mutations in humans (in somatic and/or germ cells) and that they contribute to adverse health outcomes via a "genotoxic/mutagenic" mode of action (MOA). The new EPA Guidelines for Carcinogen Risk Assessment [Guidelines for Carcinogen Risk Assessment, USEPA, 2005, EPA Publication No. EPA/630/P-03/001 F] emphasize the use of MOA information in risk assessment and provide a framework to help identify a possible mutagenic and/or nonmutagenic MOA for potential adverse effects. An analysis of the available genetic toxicity data is now, more than ever, a key component to consider in the derivation of an MOA for characterizing observed adverse health outcomes such as cancer. We provide our perspective and a two-step strategy for evaluating genotoxicity data for optimal use in regulatory decision-making. The strategy includes integration of all available information and provides, first, for a WOE analysis as to whether a chemical is a mutagen, and second, whether an adverse health outcome is mediated via a mutagenic MOA. C1 US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. US EPA, Off Sci Advisor 8105R, Washington, DC 20460 USA. RP Moore, MM (reprint author), US FDA, Natl Ctr Toxicol Res, 3900 NCTR Rd,HFT-120, Jefferson, AR 72079 USA. EM mmmoore@nctr.fda.gov NR 46 TC 34 Z9 34 U1 0 U2 5 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD DEC PY 2005 VL 46 IS 4 BP 236 EP 245 DI 10.1002/em.20176 PG 10 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 000NL UT WOS:000234468800003 PM 16258925 ER PT J AU Lewis, L Onsongo, M Njapau, H Schurz-Rogers, H Luber, G Kieszak, S Nyamongo, J Backer, L Dahiye, AM Misore, A DeCock, K Rubin, C AF Lewis, L Onsongo, M Njapau, H Schurz-Rogers, H Luber, G Kieszak, S Nyamongo, J Backer, L Dahiye, AM Misore, A DeCock, K Rubin, C CA Kenya Aflatoxicosis Investigation TI Aflatoxin contamination of commercial maize products during an outbreak of acute aflatoxicosis in eastern and central Kenya SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE aflatoxicosis; aflatoxin; corn; food safety; Kenya; maize; mold; mycotoxin ID MYCOTOXINS AB In April 2004, one of the largest aflatoxicosis outbreaks occurred in rural Kenya, resulting in 317 cases and 125 deaths. Aflatoxin-contaminated homegrown maize was the source of the outbreak, but the extent of regional contamination and status of maize in commercial markets (market maize) were unknown. We conducted a cross-sectional survey to assess the extent of market maize contamination and evaluate the relationship between market maize aflatoxin and the aflatoxicosis outbreak. We surveyed 65 markets and 243 maize vendors and collected 350 maize products in the most affected districts. Fifty-five percent of maize products had aflatoxin levels greater than the Kenyan regulatory limit of 20 ppb, 35% had levels >100 ppb, and 7% had levels >1,000 ppb. Makueni, the district with the most aflatoxicosis case-patients, had significantly higher market maize aflatoxin than did Thika, the study district with fewest case-patients (geometric mean aflatoxin=52.91 ppb vs. 7.52 ppb, p=0.0004). Maize obtained from local farms in the affected area was significantly more likely to have aflatoxin levels >20 ppb compared with maize bought from other regions of Kenya or other countries (odds ratio=2.71; 95% confidence interval, 1.12-6.59). Contaminated homegrown maize bought from local farms in the affected area entered the distribution system, resulting in widespread aflatoxin contamination of market maize. Contaminated market maize, purchased by farmers after their homegrown supplies are exhausted, may represent a source of continued exposure to aflatoxin. Efforts to successfully interrupt exposure to aflatoxin during an outbreak must consider the potential role of the market system in sustaining exposure. C1 Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Chamblee, GA 30341 USA. USDA, Foreign Agr Serv, Nairobi, Kenya. US FDA, Off Plant & Dairy Foods, Ctr Food Safety & Appl Nutr, College Pk, MD USA. Kenya Natl Publ Hlth Lab, Nairobi, Kenya. Kenya Minist Hlth, Kenya Field Epidemiol & Lab Training Program, Nairobi, Kenya. Kenya Minist Hlth, Prevent & Promot Hlth, Nairobi, Kenya. Ctr Dis Control & Prevent, Kenya Off, Nairobi, Kenya. RP Lewis, L (reprint author), Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, 4770 Buford Hwy NE,MS F-46, Chamblee, GA 30341 USA. EM lwb6@cdc.gov NR 14 TC 188 Z9 203 U1 6 U2 34 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD DEC PY 2005 VL 113 IS 12 BP 1763 EP 1767 DI 10.1289/ehp.7998 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 989ZP UT WOS:000233713200049 PM 16330360 ER PT J AU Azziz-Baumgartner, E Lindblade, K Gieseker, K Rogers, HS Kieszak, S Njapau, H Schleicher, R McCoy, LF Misore, A DeCock, K Rubin, C Slutsker, L AF Azziz-Baumgartner, E Lindblade, K Gieseker, K Rogers, HS Kieszak, S Njapau, H Schleicher, R McCoy, LF Misore, A DeCock, K Rubin, C Slutsker, L CA Aflatoxin Investigative Grp TI Case-control study of an acute aflatoxicosis outbreak, Kenya, 2004 SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE albumin adducts; aflatoxicosis; aflatoxin; Kenya; lysine; maize ID AFLATOXIN-B1; HEPATITIS; ADDUCT; MYCOTOXINS; EXPOSURE; PLASMA; LIVER AB Objectives: During January-June 2004, an aflatoxicosis outbreak in eastern Kenya resulted in 317 cases and 125 deaths. We conducted a case-control study to identify risk factors for contamination of implicated maize and, for the first time, quantitated biomarkers associated with acute aflatoxicosis. Design: We administered questionnaires regarding maize storage and consumption and obtained maize and blood samples from participants. Participants: We recruited 40 case-patients with aflatoxicosis and 80 randomly selected controls to participate in this study. Evaluations/Measurements: We analyzed maize for total aflatoxins and serum for aflatoxin B-1-lysine albumin adducts and hepatitis B surface antigen. We used regression and survival analyses to explore die relationship between aflatoxins, maize consumption, hepatitis B surface antigen, and case status. Results: Homegrown (not commercial) maize kernels from case households had higher concentrations of aflatoxins than did kernels from control households [geometric mean (GM)=354.53 ppb vs. 44.14 ppb, p=0.04]. Serum adduct concentrations were associated with time from jaundice to death [adjusted hazard ratio=1.3; 95% confidence interval (CI), 1.04-1.6]. Case patients had positive hepatitis B titers [odds ratio (OR)=9.8; 95% CI, 1.5-63.1] more often than controls. Case patients stored wet maize (OR=3.5; 95% CI, 1.2-10.3) inside their homes (OR=12.0; 95% CI, 1.5-95.7) rather than in granaries more often than did controls. Conclusion: Aflatoxin concentrations in maize, serum aflatoxin B-1-lysine adduct concentrations, and positive hepatitis B surface antigen titers were all associated with case status. Relevance: The novel methods and risk factors described may help health officials prevent future outbreaks of aflatoxicosis. C1 Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Atlanta, GA 30341 USA. Ctr Dis Control & Prevent, Natl Ctr Infect Dis, Atlanta, GA 30341 USA. Ctr Dis Control & Prevent, Epidemiol Program Off, Atlanta, GA 30341 USA. US FDA, Washington, DC 20204 USA. Kenya Minist Hlth, Prevent Hlth Serv, Nairobi, Kenya. Kenya Minist Hlth, Promot Hlth Serv, Nairobi, Kenya. Ctr Dis Control & Prevent, Kenya Field Off, Nairobi, Kenya. Ctr Dis Control & Prevent, Kenya Field Off, Kisumu, Kenya. RP Azziz-Baumgartner, E (reprint author), Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Mailstop F46,4770 Buford Hwy NE, Atlanta, GA 30341 USA. EM eha9@cdc.gov NR 26 TC 130 Z9 135 U1 6 U2 30 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD DEC PY 2005 VL 113 IS 12 BP 1779 EP 1783 DI 10.1289/ehp.8384 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 989ZP UT WOS:000233713200052 PM 16330363 ER PT J AU Walker, RI AF Walker, Richard I. TI New vaccines against enteric bacteria for children in less developed countries SO EXPERT REVIEW OF VACCINES LA English DT Article DE developing countries; diarrheal diseases; enteric vaccines; pediatric vaccines ID ENTEROTOXIGENIC ESCHERICHIA-COLI; DIARRHEAL DISEASES; CVD 103-HGR; CHOLERA AB Diarrheal diseases represent a major threat to infant survival in less developed countries. A real opportunity now exists to help alleviate this problem through the development of safe and effective multicomponent whole-bacterial cell vaccine(s) against enterotoxigenic Escherichia coli and Shigella, two important pathogens for which no licensed vaccine exists. What is preventing realization of this achievement is a lack of focus on the unique needs of children in less developed countries, along with committed and sufficient funding directed toward this goal. Live-attenuated and inactivated whole-cell vaccine candidates, some of which have languished too long, are available for testing, which, if performed in a coordinated fashion, can answer key unresolved issues concerning mucosal vaccination against enteric diseases. These candidate vaccines potentially provide a relatively simple intervention which could, if implemented, reduce the impact of these diseases upon the life and productivity of children. C1 US FDA, Div Bacterial Parasit & Allergen Prod, Rockville, MD 20651 USA. RP Walker, RI (reprint author), US FDA, Div Bacterial Parasit & Allergen Prod, 1401 Rockville Pike,HFM-425, Rockville, MD 20651 USA. EM walkerri@cber.fda.gov NR 15 TC 7 Z9 8 U1 0 U2 0 PU FUTURE DRUGS LTD PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1476-0584 J9 EXPERT REV VACCINES JI Expert Rev. Vaccines PD DEC PY 2005 VL 4 IS 6 BP 807 EP 812 DI 10.1586/14760584.4.6.807 PG 6 WC Immunology SC Immunology GA 089ZT UT WOS:000240921100010 PM 16372876 ER PT J AU Blodgett, RJ AF Blodgett, RJ TI Serial dilution with a confirmation step SO FOOD MICROBIOLOGY LA English DT Article DE MPN; most probable number; microbial concentration; plating; selected colonies ID BACTERIOLOGY AB A serial dilution test estimates the concentration of a microbe in a broth by inoculating several tubes with portions of the broth. The test may include both presumptive and confirmation steps. For the confirmation step considered here a portion of the contents of each tube indicating a change in the presumptive step is streaked on a plate. Several colonies are selected and examined to determine if the tube contained the target microbe. A statistical model accounts for the possibility of not selecting the target microbe from a tube that contains it and a similar appearing microbe. Simulations show that this model sometimes gives estimates similar to those currently used, but at other times can make large corrections. Also, a commonness measure helps check the validity of the assumptions of this statistical model. Published by Elsevier Ltd. C1 US FDA, Div Math, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Blodgett, RJ (reprint author), US FDA, Div Math, Ctr Food Safety & Appl Nutr, HFS 705,Rm 2D-011,5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM rblodget@cfsan.fda.gov NR 9 TC 8 Z9 8 U1 0 U2 7 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0740-0020 J9 FOOD MICROBIOL JI Food Microbiol. PD DEC PY 2005 VL 22 IS 6 BP 547 EP 552 DI 10.1016/j.fm.2004.11.017 PG 6 WC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology SC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology GA 931JY UT WOS:000229482800008 ER PT J AU Dubois, J Lewis, EN Fry, FS Calvey, EM AF Dubois, J Lewis, EN Fry, FS Calvey, EM TI Bacterial identification by near-infrared chemical imaging of food-specific cards SO FOOD MICROBIOLOGY LA English DT Article DE NIR imaging; bacteria; food ID MASS-SPECTROMETRY; SPECTROSCOPY; MICROORGANISMS; ACID AB Near-infrared chemical imaging (NIR-CI) is investigated as a tool for the high-throughput analysis of self-contained microbial identification test cards for micro-organisms of concern in food. In this initial work, a NIR-CI system operating in the spectral range 1000-2350 nm was used to acquire NIR chemical images of bacterial cells deposited on a 'card', containing both the calibration and test samples. Results show that some bacteria can be identified from differences observed at unique wavelengths, and that a standard operating procedure can be developed for a particular 'card' to differentiate and hence identify the various organisms it contains using discrete wavelengths. For situations where a particular organism of concern is sought, a PLS chemometric model may offer better performance by accounting for variables that can be incorporated in the calibration without the need to know the taxonomic identity of the complete complement of bacteria present on the 'card'. Overall, the NIR-CI results obtained in this investigation show that this high throughput technique possesses the specificity required to differentiate bacteria on the basis of their NIR spectra. Published by Elsevier Ltd. C1 US FDA, Ctr Food Safety & Appl Nutr, Joint Inst Food Safety & Appl Nutr, College Pk, MD 20740 USA. Spectral Dimens Inc, Olney, MD 20832 USA. Univ Maryland, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Fry, FS (reprint author), Mail Stop HFS 717,Room BE 011,5100 Paint Branch, College Pk, MD 20740 USA. EM frederick.fry@cfsan.fda.gov NR 14 TC 31 Z9 32 U1 1 U2 10 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 DEC PY 2005 VL 22 IS 6 BP 577 EP 583 DI 10.1016/j.fm.2005.01.001 PG 7 WC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology SC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology GA 931JY UT WOS:000229482800012 ER PT J AU Xin, KQ Jounai, N Someya, K Honma, K Mizuguchi, H Naganawa, S Kitamura, K Hayakawa, T Saha, S Takeshita, F Okuda, K Honda, M Klinman, DM Okuda, K AF Xin, KQ Jounai, N Someya, K Honma, K Mizuguchi, H Naganawa, S Kitamura, K Hayakawa, T Saha, S Takeshita, F Okuda, K Honda, M Klinman, DM Okuda, K TI Prime-boost vaccination with plasmid DNA and a chimeric adenovirus type 5 vector with type 35 fiber induces protective immunity against HIV SO GENE THERAPY LA English DT Article DE Ad5/35 vector; HIV; animal model; vaccine; immune response ID HUMAN-IMMUNODEFICIENCY-VIRUS; GENE-TRANSFER VECTOR; RHESUS-MONKEYS; VACCINIA VIRUS; IN-VITRO; VIRAL VECTORS; LIVING MICE; RECOMBINANT; REPLICATION; IMMUNOGENICITY AB Immunization involving a DNA vaccine prime followed by an adenovirus type 5 (Ad5) boost elicited a protective immune response against SHIV challenge in monkeys. However, the hepatocellular tropism of Ad5 limits the safety of this viral vector. This study examines the safety and immunogenicity of a replication-defective chimeric Ad5 vector with the Ad35 fiber (Ad5/35) in BALB/c mice and rhesus monkeys. This novel Ad5/35 vector showed minimal hepatotoxicity after intramuscular administration with the novel Ad5/35 vector. In addition, an Ad5/35 vector expressing HIV Env gp160 protein (Ad5/35-HIV) generated strong HIV-specific immune responses in both animal models. Priming with a DNA vaccine followed by Ad5/35-HIV boosting yielded protection against a gp160-expressing vaccinia virus challenge in BALB/c mice. The Ad5/35-HIV vector was significantly less susceptible to the pre-existing Ad5 immunity than a comparable Ad5 vector. These findings indicate that an Ad5/35 vector-based HIV vaccine may be of considerable value for clinical use. C1 Yokohama City Univ, Grad Sch Med, Dept Mol Biodefense Res, Kanazawa Ku, Yokohama, Kanagawa 2360004, Japan. Natl Inst Infect Dis, AIDS Res Ctr, Tokyo, Japan. Tokyo Dent Coll, Dept Microbiol, Chiba, Japan. Natl Inst Biomed Innovat, Lab Gene Transfer & Regulat, Osaka, Japan. Yokohama City Univ, Grad Sch Med, Dept Publ Hlth, Yokohama, Kanagawa 232, Japan. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. RP Okuda, K (reprint author), Yokohama City Univ, Grad Sch Med, Dept Mol Biodefense Res, Kanazawa Ku, 3-9 Fukuura, Yokohama, Kanagawa 2360004, Japan. NR 51 TC 35 Z9 40 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0969-7128 J9 GENE THER JI Gene Ther. PD DEC PY 2005 VL 12 IS 24 BP 1769 EP 1777 DI 10.1038/sj.gt.3302590 PG 9 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 990MS UT WOS:000233748400005 PM 16079886 ER PT J AU Bassen, H Schaefer, DJ Zaremba, L Bushberg, J Ziskin, M Foster, KR AF Bassen, H Schaefer, DJ Zaremba, L Bushberg, J Ziskin, M Foster, KR TI IEEE Committee on Man and Radiation (COMAR) Technical Information Statement "exposure of medical personnel to electromagnetic fields from open magnetic resonance imaging systems" SO HEALTH PHYSICS LA English DT Article DE magnetic resonance imaging; exposure; radiofrequency; magnetic fields; safety standards ID GUIDELINES; LIMITS AB Open magnetic resonance imaging (MRI) systems enable performing image-guided medical procedures for long periods of time very close to, or inside, the patient imaging area. Medical personnel can be exposed to relatively high static, gradient, and radiofrequency fields compared to most other MRI systems. The Committee on Man and Radiation of the Institute of Electrical and Electronics Engineers calculated or used existing data on magnetic flux densities and field strengths in or near the patient area to assess occupational exposure levels. Potential exposures to each field type were analyzed and compared to relevant values specified in international exposure limits including those of the Institute of Electrical and Electronics Engineers and the International Commission on Nonionizing Radiation Protection. Exposures of the head or torso of a worker to gradient fields near the center of the patient-imaging area can exceed most exposure limits even for times less than a second. Exposures to radiofrequency fields can exceed limits if sustained exposures (minutes or more) occur to parts of the body. Static magnetic fields used by present Opm MRI systems are below exposure limits of all of the standards that address these fields. Overall results of this study suggest that manufacturers and others who program or operate Open MRI systems should take care to ensure that operating parameters produce exposures that comply with the relevant exposure limits. Also, since field levels fall off rapidly with increasing distance, user practices may be implemented that reduce exposures significantly. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20852 USA. Univ Calif Davis, Davis, CA 95616 USA. Temple Univ, Philadelphia, PA 19122 USA. Univ Penn, Philadelphia, PA 19104 USA. RP Bassen, H (reprint author), US FDA, Ctr Devices & Radiol Hlth, 12725 Twinbrook Pkwy, Rockville, MD 20852 USA. EM hib@cdrh.fda.gov NR 10 TC 11 Z9 12 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0017-9078 EI 1538-5159 J9 HEALTH PHYS JI Health Phys. PD DEC PY 2005 VL 89 IS 6 BP 684 EP 689 DI 10.1097/01.HP.0000172545.71238.15 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA 991CI UT WOS:000233789400013 PM 16282801 ER PT J AU Byrnes, AP AF Byrnes, AP TI Challenges and future prospects in gene therapy SO IDRUGS LA English DT Article DE cancer; clinical trials; gene therapy; viral vector AB Gene therapy is a promising technique for treating disease through the modification of gene expression. It is currently being tested not only for correcting genetic defects, but also for treating cancer and other acquired diseases. Although this field is still relatively young, evidence for clinical efficacy has been observed and continued progress seems assured, as clinical trials continue to yield insights into how gene therapy can be applied and improvements are made in gene therapy tools. C1 US FDA, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Byrnes, AP (reprint author), US FDA, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. EM ByrnesA@cber.FDA.gov RI Byrnes, Andrew/D-2808-2013 OI Byrnes, Andrew/0000-0003-1135-2629 NR 5 TC 0 Z9 0 U1 1 U2 2 PU CURRENT DRUGS LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1P 6LB, ENGLAND SN 1369-7056 J9 IDRUGS JI IDrugs PD DEC PY 2005 VL 8 IS 12 BP 993 EP 996 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 992KH UT WOS:000233882300014 PM 16320132 ER PT J AU Jin, ZG Bohach, GA Shiloach, J Norris, SE Freedberg, DI Deobald, C Coxon, B Robbins, JB Schneerson, R AF Jin, ZG Bohach, GA Shiloach, J Norris, SE Freedberg, DI Deobald, C Coxon, B Robbins, JB Schneerson, R TI Conjugates of group A and W135 capsular polysaccharides of Neisseria meningitidis bound to recombinant Staphylococcus aureus enterotoxin C1: Preparation, physicochemical characterization, and immunological properties in mice SO INFECTION AND IMMUNITY LA English DT Article ID MOLECULAR-SIZE ANALYSIS; INFLUENZAE TYPE-B; CAPSULAR POLYSACCHARIDE; O-ACETYLATION; MENINGOCOCCAL MENINGITIS; ESCHERICHIA-COLI; BURKINA-FASO; IMMUNOGENICITY; SEROGROUP; VACCINE AB Neisseria meningitidis groups A (GAM) and W135 capsular polysaccharides (CPs) were bound to recombinant Staphylococcus aureus enterotoxin C1 (rSEC)The CPs were activated with 1-cyano-4-dimethylaminopyridinium tetrafluoroborate and then bound to adipic acid dihydrazide derivatives of rSEC. Syntheses were conducted with native GAM CP (GAMP), W135 CP (W135P), and ultrasonicated or hydrazine-treated W135P at various concentrations of reactants, pHs, and ionic strengths. The conjugates were characterized by compositional and serologic analyses, high-performance size-exclusion chromatography with multi-angle laser light scattering detection, and immunogenicity in 5- to 6-week-old mice. Conjugates injected subcutaneously in phosphate-buffered saline elicited immunoglobulin G (IgG) responses against their respective CPs and rSEC, whereas GAMP and W135P alone did not induce detectable CP antibodies. The O-acetyl content of W135P was low, and its removal had no adverse effect upon the conjugate's immunogenicity. Reduction of the molecular size of W135P by treatment with hydrazine improved the immunogenicity of W135P-rSEC. IgG anti-CP elicited by the conjugates showed complement-dependent bactericidal activity against their respective organisms, and IgG anti-rSEC neutralized the T-cell proliferative activity of native SEC. A bivalent formulation of GAMP-rSEC and W135P-rSEC elicited IgG anti-CP at comparable levels to those induced by the conjugates administered separately. C1 NICHHD, NIH, Bethesda, MD 20892 USA. NIDDK, NIH, Bethesda, MD 20892 USA. Univ Idaho, Dept Microbiol Mol Biol & Biochem, Moscow, ID 83844 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Jin, ZG (reprint author), NICHHD, NIH, Bethesda, MD 20892 USA. EM jinz@mail.nih.gov FU NCRR NIH HHS [P20 RR015587, P20-RR15587]; NIAID NIH HHS [U54AI57141, U54 AI057141] NR 42 TC 5 Z9 8 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD DEC PY 2005 VL 73 IS 12 BP 7887 EP 7893 DI 10.1128/IAI.73.12.7887-7893.2005 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 986WK UT WOS:000233480200012 PM 16299279 ER PT J AU Brzezinski, JL Deka, R Menon, AG Glass, DN Choi, E AF Brzezinski, JL Deka, R Menon, AG Glass, DN Choi, E TI Variability in TRBV haplotype frequency and composition in Caucasian, African American, Western African and Chinese populations SO INTERNATIONAL JOURNAL OF IMMUNOGENETICS LA English DT Article ID T-CELL-RECEPTOR; V-BETA-GENE; JUVENILE RHEUMATOID-ARTHRITIS; LINKAGE DISEQUILIBRIUM; ANTIGEN RECEPTOR; NULL ALLELES; CLASS-II; POLYMORPHISM; HLA; DIVERSITY AB The polymorphic T-cell receptor V beta (TRBV) genes encode much of the variable region of the T-cell receptor beta chain. Analysis of allele frequencies of three closely linked polymorphic TRBV genes, TRBV7-3, TRBV9 and TRBV6-4, was undertaken in several populations. The frequencies of these alleles are not significantly different in populations of Caucasians, African Americans and Western Africans. However, Chinese population is extremely homogenous at all three loci. The current study identifies the existence of haplotypic relationships between alleles of these genes in the Caucasian population. The ORF allele TRBV7-3*A3 is found exclusively on chromosomes bearing TRBV9*A2 and TRBV6-4*A2 in this cohort. In contrast, TRBV7-3*A1 and the null allele TRBV7-3*A2 are associated only with TRBV9*A1 and TRBV6-4*A1. This pattern of linkage disequilibrium (LD) is altered in the African American and Western African populations. In these cohorts, there is a marked reduction in LD between alleles of TRBV7-3 and TRBV9. This study is consistent with previous population genetic studies wherein African-derived samples have a greater level of genetic diversity compared to Caucasians. These data also demonstrate that patterns of LD are not consistent across the entire TRBV locus. C1 Univ Cincinnati, Coll Med, Dept Mol Genet Biochem & Microbiol, Cincinnati, OH 45267 USA. Childrens Hosp, Med Ctr, Dept Pediat, William S Rowe Div Rheumatol, Cincinnati, OH 45229 USA. Univ Cincinnati, Coll Med, Dept Environm Hlth, Cincinnati, OH 45267 USA. RP Brzezinski, JL (reprint author), US FDA, Forens Chem Ctr, 6751 Steger Dr, Cincinnati, OH 45237 USA. EM jennifer.brzezinski@hhs.fda.gov FU NIAMS NIH HHS [AR44059, AR44566] NR 34 TC 2 Z9 2 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1744-3121 J9 INT J IMMUNOGENET JI Int. J. Immunogenet. PD DEC PY 2005 VL 32 IS 6 BP 413 EP 420 DI 10.1111/j.1744-313X.2005.00550.x PG 8 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA 984OL UT WOS:000233314100013 PM 16313308 ER PT J AU Hurst, M Hull, K Nicholls, D Ameratunga, R AF Hurst, M Hull, K Nicholls, D Ameratunga, R TI Hereditary periodic fever syndrome sans fever or distinct periodicity presenting with psychosis SO JCR-JOURNAL OF CLINICAL RHEUMATOLOGY LA English DT Article DE periodic fever syndrome; TRAPS; psychosis; etanercept ID TNF RECEPTOR; MUTATIONS AB The genetic basis for several hereditary periodic fever syndromes has been identified and consequently, the phenotypic spectrum of these disorders has broadened. We describe a young woman with tumor necrosis factor receptor-associated periodic syndrome (TRAPS), proven by mutational analysis, who presented with psychosis but without fever, symptom periodicity, or similar family medical history. This patient represents the first case of TRAPS-associated psychosis. This case illustrates the importance of mutation analysis for this group of disorders in individuals presenting with unexplained inflammatory symptoms and recurrent psychoses. C1 Auckland Hosp, Clin Immunologist, Dept Clin Immunol, Auckland 1001, New Zealand. Middlemore Hosp, Dept Clin Immunol, Auckland, New Zealand. US FDA, CBER, ODE, VI DTBIMP, Rockville, MD USA. RP Ameratunga, R (reprint author), Auckland Hosp, Clin Immunologist, Dept Clin Immunol, Pk Rd, Auckland 1001, New Zealand. EM rohana@adhb.govt.nz RI Nicholls, David/I-8225-2012 NR 5 TC 8 Z9 8 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1076-1608 J9 JCR-J CLIN RHEUMATOL JI JCR-J. Clin. Rheumatol. PD DEC PY 2005 VL 11 IS 6 BP 329 EP 330 DI 10.1097/01.rhu.0000195106.34348.59 PG 2 WC Rheumatology SC Rheumatology GA 998VX UT WOS:000234349100009 PM 16371805 ER PT J AU Valerio, CR Murray, P Arlian, LG Slater, JE AF Valerio, CR Murray, P Arlian, LG Slater, JE TI Bacterial 16S ribosomal DNA in house dust mite cultures SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE allergen extracts; house dust mites; endotoxin; lipopolysaccharide; bacteria; allergen immunotherapy ID BARTONELLA-QUINTANA; LIPOPOLYSACCHARIDE; AMPLIFICATION; HENSELAE; DISEASE; PCR AB Background: Allergen extracts prepared from Dermatophagoides farinae contain significantly more endotoxin than Dermatophagoides pteronyssinus extracts, and extracts from both mite extracts contain more endotoxin than pollen extracts. Attempts to culture bacteria from mite cultures have failed to establish the sources of the endotoxin. Objective: To determine the bacterial sources of endotoxin in mite extracts. Methods: Live mites of both species were obtained from 2 sources, DNA was extracted from the mites, and DNA encoding bacterial 16S ribosomal RNA was amplified by using specific primers. The amount of bacterial DNA in each mite DNA sample was determined by quantitative PCR using an internal standard, and sequence homologies were determined from amplifications performed by using a high-fidelity DNA polymerase. Results: DNA from D farinae appeared to contain between 11-fold and 24-fold more 16S ribosomal gene copies than the genomic DNA from D pteronyssinus (P <= .003). Sequence analysis indicated the dominant presence of at least 3 phylogenetic clusters of Bartonella species (henselae, quintana, vinsonii, and grahamii), as well as uncharacterized alpha-proteobacteria, from both D farinae and D pteronyssinus. In a few clones, sequences from Escherichia coli, Pseudomonas species, and Acinetobacter species were also identified. Conclusion: House dust mite DNA contains evidence of Bartonella and other Gram-negative species. These Gram-negative species are likely to be the sources of the endotoxin found in mite allergenic extracts. C1 Ctr Biol Evaluat & Res, US FDA, Rockville, MD 20852 USA. Natl Inst Hlth, Bethesda, MD USA. Wright State Univ, Dayton, OH 45435 USA. RP Slater, JE (reprint author), Ctr Biol Evaluat & Res, US FDA, HFM 422,1401 Rockville Pike, Rockville, MD 20852 USA. EM slaterj@cber.fda.gov NR 23 TC 46 Z9 47 U1 0 U2 2 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD DEC PY 2005 VL 116 IS 6 BP 1296 EP 1300 DI 10.1016/j.jaci.2005.09.046 PG 5 WC Allergy; Immunology SC Allergy; Immunology GA 017IJ UT WOS:000235687000021 PM 16337462 ER PT J AU Elkins, CA Beenken, KE AF Elkins, CA Beenken, KE TI Modeling the tripartite drug efflux pump archetype: Structural and functional studies of the macromolecular constituents reveal more than their names imply SO JOURNAL OF CHEMOTHERAPY LA English DT Review DE Gram-negative; intrinsic resistance; secondary-active transport; drug efflux; tripartite efflux pumps; resistance nodulation division; porin; membrane fusion protein; Escherichia coli; Pseudomonas aeruginosa ID MEMBRANE-FUSION PROTEIN; GRAM-NEGATIVE BACTERIA; LARGE PERIPLASMIC LOOPS; MULTIDRUG EFFLUX; ESCHERICHIA-COLI; PSEUDOMONAS-AERUGINOSA; SUBSTRATE-SPECIFICITY; CRYSTAL-STRUCTURE; INTRINSIC RESISTANCE; MOLECULAR-CLONING AB It is a remarkable age in molecular biology when one can argue that our current understanding of a process is influenced as much by structural studies as it is by genetic and physiological manipulations. This statement is particularly poignant with membrane proteins for which structural knowledge has been long impeded by the inability to easily obtain crystal structures in a lipid matrix. Thus, several high-resolution structures of the components comprising tripartite multidrug efflux pumps from Escherichia coli and Pseudomonas aeruginosa are now available and were received with much acclaim over ever-evolving crystal structures of soluble, aqueous proteins. These structures, in conjunction with functional mutagenesis studies, have provided insight into substrate capture and binding domains and redefined the potential interactions between individual pump constituents. However, correct assembly of the components is still a matter of debate as is the functional contribution of each to the translocation of drug substrates over long distances spanning the Gram-negative cell envelope. C1 US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. RP Elkins, CA (reprint author), US FDA, Natl Ctr Toxicol Res, Div Microbiol, 3900 NCTR Dr, Jefferson, AR 72079 USA. EM chris.elkins@fda.hhs.gov NR 63 TC 7 Z9 7 U1 0 U2 1 PU E I F T SRL PI FLORENCE PA VIA XX SETTEMBRE 102, 50129 FLORENCE, ITALY SN 1120-009X J9 J CHEMOTHERAPY JI J. Chemother. PD DEC PY 2005 VL 17 IS 6 BP 581 EP 592 PG 12 WC Oncology; Infectious Diseases; Pathology; Pharmacology & Pharmacy SC Oncology; Infectious Diseases; Pathology; Pharmacology & Pharmacy GA 002UQ UT WOS:000234637600001 PM 16433187 ER PT J AU McDermott, PF Bodeis-Jones, SM Fritsche, TR Jones, RN Walker, RD AF McDermott, PF Bodeis-Jones, SM Fritsche, TR Jones, RN Walker, RD CA Campylobacter Susceptibility TI Broth microdilution susceptibility testing of Campylobacter jejuni and the determination of quality control ranges for fourteen antimicrobial agents SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID RESISTANCE; TRENDS AB Quality control ranges were developed for broth microdilution testing of Campylobacter jejuni ATCC 33560 against 14 antimicrobials. Cation-adjusted Mueller-Hinton broth containing 2.5% laked horse blood was the preferred medium, with incubation in a microaerobic atmosphere of 10% CO2, 5% 0(2), and 85% N-2 at 36 degrees C for 48h or 42 degrees C for 24h. C1 US FDA, Ctr Vet Med, Res Off, Laurel, MD 20708 USA. JMI Labs, N Liberty, IA 52317 USA. RP McDermott, PF (reprint author), US FDA, Ctr Vet Med, Res Off, 8401 Muirkirk Rd, Laurel, MD 20708 USA. EM Patrick.McDermott@fda.gov NR 8 TC 27 Z9 27 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD DEC PY 2005 VL 43 IS 12 BP 6136 EP 6138 DI 10.1128/JCM.43.12.6136-6138.2005 PG 3 WC Microbiology SC Microbiology GA 994TZ UT WOS:000234055400050 PM 16333113 ER PT J AU Koonse, B Burkhardt, W Chirtel, S Hoskin, GP AF Koonse, B Burkhardt, W Chirtel, S Hoskin, GP TI Salmonella and the sanitary quality of aquacultured shrimp SO JOURNAL OF FOOD PROTECTION LA English DT Article ID FRESH-WATER SEDIMENTS; VIBRIO-CHOLERAE; PENAEUS-MONODON; UNITED-STATES; SURVEILLANCE; PREVALENCE; SURVIVAL; BACTERIA AB In this study, we examined the prevalence of Salmonella and coliform bacteria on shrimp aquaculture farms to develop guidelines or preventative measures for reducing Salmonella and fecal contamination on products harvested from these farms. The U.S. Food and Drug Administration, in conjunction with foreign government regulatory agencies, the aquaculture industry, and academia affiliates, analyzed 1,234 samples from 103 shrimp aquaculture farms representing six countries between July 2001 and June 2003 for fecal coliforms, Escherichia coli, and Salmonella. A significant relationship was found (P = 0.0342) between the log number of fecal bacteria and the probability that any given sample would contain Salmonella. The likelihood of any given sample containing Salmonella was increased by 1.2 times with each 10-fold increase in either fecal coliform or E coli concentration. The statistical relationship between Salmonella concentration and that of both fecal coliforms and E. coli was highest in grow-out pond water (P = 0.0042 for fecal coliforms and P = 0.0021 for E. coli). The likelihood of finding Salmonella in grow-out pond water increased 2.7 times with each log unit increase in fecal coliform concentration and 3.0 times with each log unit increase in E. coli concentration. Salmonella is not part of the natural flora of the shrimp culture environment nor is it inherently present in shrimp grow-out ponds. The occurrence of Salmonella bacteria in shrimp from aquaculture operations is related to the concentration of fecal bacteria in the source and grow-out pond water. C1 US FDA, Off Seafood, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. US FDA, Div Math, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. US FDA, Off Seafood, Ctr Food Safety & Appl Nutr, Gulf Coast Seafood Lab, Dauphin Isl, AL 36528 USA. RP Koonse, B (reprint author), US FDA, Off Seafood, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. EM brett.koonse@fda.gov NR 25 TC 31 Z9 35 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 DEC PY 2005 VL 68 IS 12 BP 2527 EP 2532 PG 6 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 989US UT WOS:000233700000006 PM 16355822 ER PT J AU Yancy, HF Mohla, A Farrell, DE Myers, MJ AF Yancy, HF Mohla, A Farrell, DE Myers, MJ TI Evaluation of a rapid PCR-based method for the detection of animal material SO JOURNAL OF FOOD PROTECTION LA English DT Article ID BOVINE-DERIVED MATERIALS AB A rapid PCR-based analytical method for detection of animal-derived materials in complete feed was developed. Using a commercially available DNA forensic kit for the extraction of DNA from animal feed, a sensitive method was developed that was capable of detecting as little as 0.03% bovine meat and bone meal in complete feed in under 8 h of total assay time. The reduction in assay time was accomplished by reducing the DNA extraction time to 2 h and using the simpler cleanup procedure of the kit. Assay sensitivity can be increased to 0.006% by increasing the DNA extraction time to an overnight incubation of approximately 16 h. Examination of dairy feed samples containing either bovine meat and bone meal, porcine meat and bone meal, or lamb meal at a level of 0.1% (wt/wt basis) suggested that this method may be suitable for regulatory uses. The adoption of this commercially available kit for use with animal feeds yields an assay that is quicker and simpler to perform than a previously validated assay for the detection of animal proteins in animal feed. C1 US FDA, Ctr Vet Med, Div Anim Res, Laurel, MD 20708 USA. RP Myers, MJ (reprint author), US FDA, Ctr Vet Med, Div Anim Res, 8401 Muirkirk Rd, Laurel, MD 20708 USA. EM mmyers@cvm.fda.gov NR 7 TC 9 Z9 10 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 DEC PY 2005 VL 68 IS 12 BP 2651 EP 2655 PG 5 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 989US UT WOS:000233700000022 PM 16355838 ER PT J AU Baric, I Cuk, M Fumic, K Vugrek, O Allen, RH Glenn, B Maradin, M Pazanin, L Pogribny, I Rados, M Sarnavka, V Schulze, A Stabler, S Wagner, C Zeisel, SH Mudd, SH AF Baric, I Cuk, M Fumic, K Vugrek, O Allen, RH Glenn, B Maradin, M Pazanin, L Pogribny, I Rados, M Sarnavka, V Schulze, A Stabler, S Wagner, C Zeisel, SH Mudd, SH TI S-Adenosylhomocysteine hydrolase deficiency: A second patient, the younger brother of the index patient, and outcomes during therapy SO JOURNAL OF INHERITED METABOLIC DISEASE LA English DT Article ID CYSTATHIONINE BETA-SYNTHASE; MYELIN BASIC-PROTEIN; TOTAL HOMOCYSTEINE; DNA METHYLATION; METHYLTRANSFERASE DEFICIENCY; METHIONINE METABOLISM; MASS-SPECTROMETRY; FOLATE-DEFICIENCY; GLOBAL DNA; ADENOSYLMETHIONINE AB S-Adenosylhomocysteine (AdoHcy) hydrolase deficiency has been proven in a human only once, in a recently described Croatian boy. Here we report the clinical course and biochemical abnormalities of the younger brother of this proband. This younger brother has the same two mutations in the gene encoding AdoHcy hydrolase, and has been monitored since birth. We report, as well, outcomes during therapy for both patients. The information obtained suggests that the disease starts in utero and is characterized primarily by neuromuscular symptomatology (hypotonia, sluggishness, psychomotor delay, absent tendon reflexes, delayed myelination). The laboratory abnormalities are markedly increased creatine kinase and elevated aminotransferases, as well as specific amino acid aberrations that pinpoint the aetiology. The latter include, most importantly, markedly elevated plasma AdoHcy. Plasma S-adenosylmethionine (AdoMet) is also elevated, as is methionine (although the hypermethioninaemia may be absent or nonsignificant in the first weeks of life). The disease seems to be at least to some extent treatable, as shown by improved myelination and psychomotor development during dietary methionine restriction and supplementation with creatine and phosphatidylcholine. C1 Univ Hosp Ctr, Dept Pediat, Zagreb 10000, Croatia. Univ Zagreb, Sch Med, Zagreb 41001, Croatia. Univ Hosp Ctr, Clin Inst Lab Diag, Zagreb 10000, Croatia. Rudjer Boskovic Inst, Dept Mol Med, Zagreb, Croatia. Univ Colorado, Hlth Sci Ctr, Div Hematol, Denver, CO USA. Vanderbilt Univ, Dept Biochem, Nashville, TN 37232 USA. Dept Vet Affairs Med Ctr, Nashville, TN 37212 USA. Univ Hosp Ctr, Dept Neuropathol, Zagreb, Croatia. Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. Univ Hosp Ctr, Dept Radiol, Zagreb 10000, Croatia. Univ Childrens Heidelberg, Heidelberg, Germany. Univ N Carolina, Sch Med, Chapel Hill, NC USA. Univ N Carolina, Sch Publ Hlth, Dept Nutr, Chapel Hill, NC 27599 USA. NIMH, Mol Biol Lab, Bethesda, MD 20892 USA. RP Univ Hosp Ctr, Dept Pediat, Kispaticeva 12, Zagreb 10000, Croatia. EM ibaric@kbc-zagreb.hr FU NCRR NIH HHS [M01 RR000046, M01 RR000046-461213]; NIA NIH HHS [AG-09834, R01 AG009834]; NIDDK NIH HHS [DK56359, 5P30 DK26657, P30 DK056350, R01 DK015289, R01 DK055865, R01 DK055865-05, DK15289, DK55865, P30 DK026657, P30 DK056350-08, R37 DK015289] NR 42 TC 46 Z9 47 U1 0 U2 5 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0141-8955 EI 1573-2665 J9 J INHERIT METAB DIS JI J. Inherit. Metab. Dis. PD DEC PY 2005 VL 28 IS 6 BP 885 EP 902 DI 10.1007/s10545-005-0192-9 PG 18 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 006OR UT WOS:000234907300010 PM 16435181 ER PT J AU Zaitseva, M Romantseva, T Manischewitz, J Wang, J Goucher, D Golding, H AF Zaitseva, M Romantseva, T Manischewitz, J Wang, J Goucher, D Golding, H TI Increased CXCR4-dependent HIV-1 fusion in activated T cells: role of CD4/CXCR4 association SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE chemokine receptors; cell activation ID IMMUNODEFICIENCY-VIRUS TYPE-1; N-LINKED GLYCOSYLATION; CHEMOKINE RECEPTOR; POSTTRANSLATIONAL MODIFICATIONS; SURFACE ASSOCIATION; MULTIVESICULAR-BODY; CORECEPTOR FUNCTION; CXCR4 EXPRESSION; DENDRITIC CELLS; DOWN-REGULATION AB Activation of peripheral CD4(+) T cells resulted in augmented fusion with X4 human immunodeficiency virus type 1 (HIV-1) envelope-expressing cells without parallel increases in the surface expression of CD4 or CXC chemokine receptor 4 (CXCR4). Our study used biochemical methods and biological assays to correlate the increased fusion potential of activated T cells with changes in CXCR4 isoforms and CD4-CXCR4 association. Western blot analyses of CXCR4, precipitated from resting T cells, identified several CXCR4 species with molecular weights of 47, 50, 62, and 98 kDa. After 24 h stimulation with phytohemagglutinin/interleukin-2, a marked reduction was seen in the 47-kDa, with a concomitant increase in the amounts of 50 and 62-64 kDa CXCR4. T cell activation also induced an increase in the coprecipitation of CXCR4 with CD4. The 62-kDa CXCR4 predominantly coprecipitated with CD4 and was shown to be ubiquitinated. Stripping of CD4 from the cell surface with pronase treatment prior to cell lysis only partially reduced coprecipitation of CD4 with the 62-kDa CXCR4, revealing a pool of intracellular CD4-CXCR4 complexes. Coprecipitation of CXCR4 with CD4 was reduced in activated cells treated with Brefeldin A and Monensin, suggesting that late endosomes play a role in intracellular association of CXCR4 with CD4. Confocal microscopy confirmed the colocalization of CD4 and CXCR4 within CD63(+) endocytic compartments. These findings demonstrated a correlation between the enhanced susceptibility of activated T cells to HIV-1 fusion and accumulation of ubiquitinated 62-64 kDa CXCR4 species, which preferentially associated with CD4. The CD4-CXCR4 complexes may shuttle between late endosomes and the cell surface. C1 US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. US FDA, Div Monoclonal Antibodies, Ctr Drug Evaluat & Res, Bethesda, MD 20014 USA. US FDA, Div Therapeut Prot, Ctr Drug Evaluat & Res, Bethesda, MD 20014 USA. RP Zaitseva, M (reprint author), US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Bldg 29B,Room 4NN06,8800 Rockville Pike, Bethesda, MD 20892 USA. EM zaitseva@cber.fda.gov NR 59 TC 12 Z9 15 U1 1 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD DEC PY 2005 VL 78 IS 6 BP 1306 EP 1317 DI 10.1189/jlb.0105043 PG 12 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 992ZE UT WOS:000233921700016 PM 16204649 ER PT J AU Denkin, S Volokhov, D Chizhikov, V Zhang, Y AF Denkin, S Volokhov, D Chizhikov, V Zhang, Y TI Microarray-based pncA genotyping of pyrazinamide-resistant strains of Mycobacterium tuberculosis SO JOURNAL OF MEDICAL MICROBIOLOGY LA English DT Article ID RIFAMPIN RESISTANCE; SPECIES IDENTIFICATION; MUTATIONS; GENE; SUSCEPTIBILITY; EPIDEMIC; ARRAYS AB Drug-resistant Mycobacterium tuberculosis poses a significant threat to the treatment of tuberculosis (TB). The current susceptibility testing for the first-line TB drug pyrazinamide (PZA) is not only time-consuming but also difficult, due to the requirement for acid pH for drug activity. Predominantly, resistance to PZA in M. tuberculosis is caused by mutations in the pncA gene, and the detection of pncA mutations can be an indicator of PZA resistance. In this study, the use of a previously developed microarray method for the rapid detection of PZA-resistant M. tuberculosis based on identifying mutations in the pncA gene was evaluated, Microarray analysis was performed in a blind manner on 33 clinical isolates of M. tuberculosis for which the sequence of the pncA gene had not previously been determined. The results showed that all mutations in PZA-resistant strains identified by DNA sequencing could be unambiguously detected by the microarray method. It is concluded that the microarray method is a valuable tool for the rapid screening and genetic identification of potential PZA-resistant M. tuberculosis strains. C1 Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD 21205 USA. US FDA, Ctr Biol Evaluat & Res, Kensington, MD 20895 USA. RP Zhang, Y (reprint author), Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD 21205 USA. EM yzhang@jhsph.edu FU NIAID NIH HHS [AI44063, AI/HL49485] NR 22 TC 22 Z9 25 U1 0 U2 4 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 0022-2615 J9 J MED MICROBIOL JI J. Med. Microbiol. PD DEC PY 2005 VL 54 IS 12 BP 1127 EP 1131 DI 10.1099/jmm.0.46129-0 PG 5 WC Microbiology SC Microbiology GA 991RJ UT WOS:000233831000002 PM 16278424 ER PT J AU Tang, X Morris, SL Langone, JJ Bockstahler, LE AF Tang, X Morris, SL Langone, JJ Bockstahler, LE TI Microarray and allele specific PCR detection of point mutations in Mycobacterium tuberculosis genes associated with drug resistance SO JOURNAL OF MICROBIOLOGICAL METHODS LA English DT Article DE Mycobacterium tuberculosis; microarray; drug resistance; mutants; mutation; point mutation; point mutation detection; PCR; allele specific PCR ID PRIMER EXTENSION; DNA MICROARRAYS; SINGLE; IDENTIFICATION; STRAINS; TECHNOLOGY; DIAGNOSIS AB Global public health is threatened by the emergence of potentially dangerous antibiotic drug-resistant strains of Mycobacterium tuberculosis. Point mutations in certain M tuberculosis genes are associated with the resistance of M tuberculosis strains to antibiotic drugs. The purpose of this study was to develop a suitable microarray-based protocol for the detection of point mutations in M tuberculosis genes associated with drug resistance. We initially developed a conventional, oligonucleotide microarray protocol and used it to detect and identify on a single microarray slide a number of point mutation-containing rpoB and katG gene target sequences. However, the occurrence of some non-specific hybridization led us to the development of an improved protocol based on allele specific PCR combined with tags/anti-tags and microarrays. This protocol was evaluated by detecting point mutations in M tuberculosis katG and rpoB gene templates produced by recombinant PCR. The methodology allowed sequences containing single point mutations to be readily distinguished from wild type sequences. The data obtained with the improved protocol had strong and specific signals and relatively low amounts of non-specific hybridization. We successfully used this protocol to detect and identify (< 8 h) a number of clinically relevant point mutations in the rpoB, katG and rpsL genes of M tuberculosis clinical isolates. Our allele specific PCR/tags and anti-tags/microarray protocol has several advantages over our conventional oligonucleotide microarray protocol, and it may have broad applications for point mutation detection. (c) 2005 Elsevier B.V. All rights reserved. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Tang, X (reprint author), US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. EM xxt4@cdrh.fda.gov NR 27 TC 29 Z9 33 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-7012 J9 J MICROBIOL METH JI J. Microbiol. Methods PD DEC PY 2005 VL 63 IS 3 BP 318 EP 330 DI 10.1016/j.mimet.2005.04.026 PG 13 WC Biochemical Research Methods; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 987AB UT WOS:000233489700011 PM 15923050 ER PT J AU Su, Y Yu, T Lala, G Francke-Carroll, S Magnuson, B AF Su, Y Yu, T Lala, G Francke-Carroll, S Magnuson, B TI Protection of side effects of 5-flurouracil by anthocyanin-rich extracts. SO JOURNAL OF NUTRITION LA English DT Meeting Abstract CT International Research Conference on Diet, Nutrition and Cancer CY JUL 14-15, 2005 CL Washington, DC SP Amer Inst Canc Res, World Canc Res Fund Int C1 US FDA, Pathol Branch, Washington, DC 20204 USA. Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOCIETY NUTRITIONAL SCIENCE PI BETHESDA PA 9650 ROCKVILLE PIKE, RM L-2407A, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD DEC PY 2005 VL 135 IS 12 SU S BP 3054S EP 3054S PG 1 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 993SS UT WOS:000233975900083 ER PT J AU Eckert, D Williams, O Meseda, CA Merchlinsky, M AF Eckert, D Williams, O Meseda, CA Merchlinsky, M TI Vaccinia virus nicking-joining enzyme is encoded by K4L (VACWR035) SO JOURNAL OF VIROLOGY LA English DT Article ID TEMPERATURE-SENSITIVE MUTANTS; ACID-SPECIFIC NUCLEASE; CONCATEMER JUNCTIONS; POXVIRUS TELOMERES; GENE-EXPRESSION; DNA; RESOLUTION; SEQUENCE; REPLICATION; TERMINI AB Vaccinia virus encodes an enzyme with DNA modifying activity that cleaves and inefficiently cross-links cruciformic DNA. This enzyme is contained within the virion, expressed at late times postinfection, and processes DNA in an energy-independent, Mg2+ ion-independent manner. Viral nuclease activity was measured in extracts from cells infected with well-defined viral mutants. Since some viral extracts lacked nuclease activity, the gene encoding the activity was postulated to be one of the open reading frames absent in the viruses lacking activity. Inducible expression of each candidate open reading frame revealed that only the gene VACWR035, or K4L, was required for nuclease activity. A recombinant virus missing only the open reading frame for K4L lacked nuclease activity. Extracts from a recombinant virus expressing K4L linked to a FLAG polypeptide were able to cleave and cross-link cruciformic DNA. There were no significant differences between the virus lacking K4L and wild-type vaccinia virus WR with respect to infectivity, growth characteristics, or processing of viral replicative intermediate DNA, including both telomeric and cross-linked forms. Purification of the K4L FLAG polypeptide expressed in bacteria yielded protein containing nicking-joining activity, implying that K4L is the only vaccinia virus protein required for the nicking-joining enzymatic activity. C1 US FDA, Lab DNA Viruses, Div Viral Prod, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Merchlinsky, M (reprint author), US FDA, Lab DNA Viruses, Div Viral Prod, Ctr Biol Evaluat & Res, HFM 457,1401 Rockville Pike, Rockville, MD 20852 USA. EM merchlinsky@cber.fda.gov NR 29 TC 13 Z9 14 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 2005 VL 79 IS 24 BP 15084 EP 15090 DI 10.1128/JVI.79.24.15084-15090.2005 PG 7 WC Virology SC Virology GA 997VK UT WOS:000234276700009 PM 16306579 ER PT J AU Aurran-Schleinitz, T Telford, W Perfetto, S Caporaso, N Wilson, W Stetler-Stevenson, MA Zenger, VE Abbasi, F Marti, GE AF Aurran-Schleinitz, T Telford, W Perfetto, S Caporaso, N Wilson, W Stetler-Stevenson, MA Zenger, VE Abbasi, F Marti, GE TI Identification of a new monoclonal B-cell subset in unaffected first-degree relatives in familial chronic lymphocytic leukemia SO LEUKEMIA LA English DT Letter ID LAMBDA-LIGHT CHAIN; DELTA SWITCH; EXPRESS; BLOOD C1 US FDA, Div Cell & Gene Therapies, Off Cellular Tissues & Gene Therapy, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. Inst Paoli Calmettes, Marseille, France. NCI, Flow Cytometry Core Facil, ETIB, NIH, Bethesda, MD 20892 USA. NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. NCI, Genet Epidemiol Branch, NIH, Bethesda, MD USA. NCI, MOCRU, CCR, NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. RP Marti, GE (reprint author), US FDA, Div Cell & Gene Therapies, Off Cellular Tissues & Gene Therapy, Ctr Biol Evaluat & Res, NIH Bldg 29B,Rm 2NN08,8800 Rockville Pike, Bethesda, MD 20014 USA. EM gemarti@helix.nih.gov NR 8 TC 7 Z9 7 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD DEC PY 2005 VL 19 IS 12 BP 2339 EP 2341 DI 10.1038/sj.leu.2403980 PG 3 WC Oncology; Hematology SC Oncology; Hematology GA 986PN UT WOS:000233462300042 PM 16208408 ER PT J AU Kamp, HG Eisenbrand, G Janzowski, C Kiossev, J Latendresse, JR Schlatter, J Turesky, RJ AF Kamp, HG Eisenbrand, G Janzowski, C Kiossev, J Latendresse, JR Schlatter, J Turesky, RJ TI Ochratoxin A induces oxidative DNA damage in liver and kidney after oral dosing to rats SO MOLECULAR NUTRITION & FOOD RESEARCH LA English DT Article DE comet-assay; in vivo; ochratoxin A; oxidative DNA damage; protein oxidation; rat ID PROXIMAL TUBULAR CELLS; CHRONIC INTERSTITIAL NEPHROPATHY; FERRIC NITRILOTRIACETATE; IN-VITRO; LIPID-PEROXIDATION; COMET ASSAY; NANOMOLAR CONCENTRATIONS; OXIDIZED PROTEINS; PLASMA-PROTEINS; NEPHROTOXICITY AB The nephrotoxic/carcinogenic mycotoxin ochratoxin A (OTA) occurs as a contaminant in food and feed and may be linked to human endemic Balkan nephropathy. The mechanism of OTA-derived carcinogenicity is still under debate, since reactive metabolites of OTA and DNA adducts have not been unambiguously identified. Oxidative DNA damage, however, has been observed in vitro after incubation of mammalian cells with OTA. In this study, we investigated whether OTA induces oxidative DNA damage in vivo as well. Male F344 rats were dosed with 0, 0.03, 0.1, 0.3 mg/kg bw per day OTA for 4 wk (gavage, 7 days/wk, five animals per dose group). Subsequently, oxidative DNA damage was determined in liver and kidney by the comet assay (single cell gel electrophoresis) with/without use of the repair enzyme formamido-pyrimidine-DNA-glycosylase (FPG). The administration of OTA had no effect on basic DNA damage (determined without FPG); however, OTA-mediated oxidative damage was detected with FPG treatment in kidney and liver DNA of all dose groups. Since the doses were in a range that had caused kidney tumors in a 2-year carcinogenicity study with rats, the oxidative DNA damage induced by OTA may help to explain its mechanism of carcinogenicity. For the selective induction of tumors in the kidney, increased oxidative stress in connection with severe cytotoxicity and increased cell proliferation might represent driving factors. C1 Univ Kaiserslautern, Dept Chem, Div Food Chem & Environm Toxicol, D-67663 Kaiserslautern, Germany. US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Toxicol Pathol Associates, Jefferson, AR USA. Swiss Fed Off Publ Hlth, Food Toxicol Sect, Zurich, Switzerland. RP Kamp, HG (reprint author), Univ Kaiserslautern, Dept Chem, Div Food Chem & Environm Toxicol, Erwin Schroedinger Str 52, D-67663 Kaiserslautern, Germany. EM hennicke.kamp@basf-ag.de RI Latendresse, John/A-9215-2009 NR 64 TC 62 Z9 64 U1 4 U2 14 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1613-4125 J9 MOL NUTR FOOD RES JI Mol. Nutr. Food Res. PD DEC PY 2005 VL 49 IS 12 BP 1160 EP 1167 DI 10.1002/mnfr.200500124 PG 8 WC Food Science & Technology SC Food Science & Technology GA 995IU UT WOS:000234094800009 PM 16302199 ER PT J AU Linet, MS Freedman, DM Mohan, AK Doody, MM Ron, E Mabuchi, K Alexander, BH Sigurdson, A Hauptmann, M AF Linet, MS Freedman, DM Mohan, AK Doody, MM Ron, E Mabuchi, K Alexander, BH Sigurdson, A Hauptmann, M TI Incidence of haematopoietic malignancies in US radiologic technologists SO OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID ATOMIC-BOMB SURVIVORS; ANKYLOSING-SPONDYLITIS; BRITISH RADIOLOGISTS; RADIATION-EXPOSURE; CANCER RISK; MORTALITY; LEUKEMIA; WORKERS; FOLLOW; RATES AB Background: There are limited data on risks of haematopoietic malignancies associated with protracted low-to-moderate dose radiation. Aims: To contribute the first incidence risk estimates for haematopoietic malignancies in relation to work history, procedures, practices, and protective measures in a large population of mostly female medical radiation workers. Methods: The investigators followed up 71 894 ( 77.9% female) US radiologic technologists, first certified during 1926 - 80, from completion of a baseline questionnaire ( 1983 - 89) to return of a second questionnaire ( 1994 - 98), diagnosis of a first cancer, death, or 31 August 1998 ( 731 306 person-years), whichever occurred first. Cox proportional hazards regression was used to compute risks. Results: Relative risks ( RR) for leukaemias other than chronic lymphocytic leukaemia ( non-CLL, 41 cases) were increased among technologists working five or more years before 1950 ( RR = 6.6, 95% CI 1.0 to 41.9, based on seven cases) or holding patients 50 or more times for x ray examination ( RR = 2.6, 95% CI 1.3 to 5.4). Risks of non-CLL leukaemias were not significantly related to the number of years subjects worked in more recent periods, the year or age first worked, the total years worked, specific procedures or equipment used, or personal radiotherapy. Working as a radiologic technologist was not significantly linked with risk of multiple myeloma ( 28 cases), non-Hodgkin's lymphoma ( 118 cases), Hodgkin's lymphoma ( 31 cases), or chronic lymphocytic leukaemia ( 23 cases). Conclusion: Similar to results for single acute dose and fractionated high dose radiation exposures, there was increased risk for non-CLL leukaemias decades after initial protracted radiation exposure that likely cumulated to low-to-moderate doses. C1 NCI, Radiat Epidemiol Branch, Dept Hlth & Human Serv, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Ctr Biol Evaluat & Res, Off Biostat & Epidemiol, Food & Drug Adm, Rockville, MD USA. Univ Minnesota, Div Occupat & Environm Hlth, Minneapolis, MN USA. RP Linet, MS (reprint author), NCI, Radiat Epidemiol Branch, Dept Hlth & Human Serv, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS Room 7054, Bethesda, MD 20892 USA. EM linetm@mail.nih.gov FU NCI NIH HHS [N01-CP-15673, N02-CP-81005, N02-CP-81121, N01-CP-51016] NR 35 TC 30 Z9 30 U1 2 U2 8 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1351-0711 EI 1470-7926 J9 OCCUP ENVIRON MED JI Occup. Environ. Med. PD DEC PY 2005 VL 62 IS 12 BP 861 EP 867 DI 10.1136/oem.2005.020826 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 985HK UT WOS:000233368000009 PM 16299095 ER PT J AU Yousef, WA Wagner, RF Loew, MH AF Yousef, WA Wagner, RF Loew, MH TI Estimating the uncertainty in the estimated mean area under the ROC curve of a classifier SO PATTERN RECOGNITION LETTERS LA English DT Article DE classification; influence functions; receiver operating characteristic; bootstrap; nonparametric inference ID CROSS-VALIDATION; ERROR AB This article considers the problem of binary classification and its assessment in a distribution-free approach. We estimate the area under the ROC curve (a more general performance metric than the error rate) of a classifier using a bootstrap-based estimator. We then use the method of the influence function to estimate the uncertainty of that estimate from the very same bootstrap samples. Monte Carlo trials show that small-sample estimates can be obtained with little bias. Published by Elsevier B.V. C1 George Washington Univ, Washington, DC 20052 USA. US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. RP Yousef, WA (reprint author), 12720 Twinbrook Pkwy, Rockville, MD 20850 USA. EM wyousef@aucegypt.edu RI Yousef, Waleed/A-9082-2009 NR 23 TC 17 Z9 17 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-8655 J9 PATTERN RECOGN LETT JI Pattern Recognit. Lett. PD DEC PY 2005 VL 26 IS 16 BP 2600 EP 2610 DI 10.1016/j.patrec.2005.06.006 PG 11 WC Computer Science, Artificial Intelligence SC Computer Science GA 984LU UT WOS:000233307200011 ER PT J AU Powers, JH AF Powers, JH TI Microbiologic surrogate end points in infectious diseases: Example of acute clinical trials of otitis media trials SO PHARMACOTHERAPY LA English DT Article DE surrogate end points; acute otitis media; tympanocentesis ID STAPHYLOCOCCUS-AUREUS INFECTIONS; BACTERIAL-MENINGITIS; DOUBLE-BLIND; BACTERIOLOGICAL ERADICATION; CARDIOVASCULAR-DISEASE; ANTIBIOTIC-TREATMENT; CHILDREN; THERAPY; MANAGEMENT; MUPIROCIN AB Clinical outcomes that ineasure how patients feet, function, or survive are the most important and relevant outcomes of therapy in clinical trials and in clinical practice. Surrogate end points, which do not directly measure clinical benefit to the patient, may function as Substitutes for clinical end points in clinical trials. Such surrogates are attractive as they may allow measurement of outcomes earlier in time or with a smaller sample size than with clinical outcomes. Microbiologic biomarkers, such as culture results at a specific time after start of therapy, or pharmacodynamic analyses of the effect of drugs on organisms often are proposed as surrogate end points in clinical trials of therapies for infectious diseases. However, evaluation of biomarkers as surrogate end points poses distinct challenges, and only a few biomarkers have been useful replacements for clinical end points. Evaluation of biomarkers as potential surrogate end points first requires an understanding of the differences among measurements of the cause of a disease, risk factors for Outcome, and measurements Of treatment effects. We will discuss the definitions of clinical and surrogate end points and the reasons why surrogate end points may not predict the true clinical benefit of therapies. We will use the example of the biomarker of microbiologic outcomes from tympanocenteses performed during therapy as the sole measure of clinical effectiveness in clinical trials Of acute otitis media to illustrate the challenges in evaluating biomarkers as Surrogate end points. C1 US FDA, Ctr Drug Evaluat & Res, Off Antimicrobial Prod, Rockville, MD 20857 USA. NIAID, NIH, Bethesda, MD 20892 USA. RP Powers, JH (reprint author), Ctr Drug Evaluat & Res, Antimicrobial Drug Dev & Resistance Initiat, 10903 New Hampshire Ave,Bldg 22,Room 6400, Silver Spring, MD 20993 USA. EM POWERSJOH@cder.fda.gov NR 67 TC 10 Z9 10 U1 1 U2 1 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 DEC PY 2005 VL 25 IS 12 SU S BP 109S EP 123S DI 10.1592/phco.2005.25.12part2.109S PN 2 PG 15 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 993FW UT WOS:000233941000003 PM 16305280 ER PT J AU Contrera, JF Matthews, EJ Kruhlak, NL Benz, RD AF Contrera, JF Matthews, EJ Kruhlak, NL Benz, RD TI In silico screening of chemicals for bacterial mutagenicity using electrotopological E-state indices and MDL QSAR software SO REGULATORY TOXICOLOGY AND PHARMACOLOGY LA English DT Article DE QSAR; E-state indices; electrotopological; mutagenicity; in silico screening; predictive toxicology; drug development; Salmonella; setubal principles ID DRUG DISCOVERY; PREDICTION; GENOTOXICITY; PHARMACEUTICALS; INFORMATION; TOXICITY; DATABASE; (Q)SARS; MODELS; MCASE AB Quantitative structure-activity relationship (QSAR) software offers a rapid, cost effective means of prioritizing the mutagenic potential of chemicals. MDL QSAR models were developed using atom-type E-state indices and non-parametric discriminant analysis. Models were developed for Salmonella typhimurium gene mutation, combining results from strains TA97, TA98, TA100, TA1535, TA1536, TA1537, and TA1538 (n=3228), and Escherichia coli gene mutation tests WP2, WP100, and polA (n=472). Composite microbial mutation models (n=3338) were developed combining all Salmonella, E. coli, and the Bacillus subtilis rec spot test study results. The datasets contained 74% non-pharmaceuticals and 26% pharmaceuticals. Salmonella and microbial mutagenesis external validation studies included a total of 1444 and 1485 compounds, respectively. The average specificity, sensitivity, positive predictivity, concordance, and coverage of Salmonella models was 76, 81, 73, 78, and 98%, respectively, with similar performance for the microbial mutagenesis models. MDL QSAR and discriminant analysis provides rapid and highly automated mutagenicity screening software with good specificity, sensitivity, and coverage that is simpler and requires less user intervention than other similar software. MDL QSAR modules for microbial mutagenicity can provide efficient and cost effective large scale screening of compounds for mutagenic potential for the chemical and pharmaceutical industry. Published by Elsevier Inc. C1 US FDA, CDER, Off Pharmaceut Sci, ICSAS, Rockville, MD 20857 USA. RP Contrera, JF (reprint author), US FDA, CDER, Off Pharmaceut Sci, ICSAS, 5600 Fishers Lane, Rockville, MD 20857 USA. EM contrerajf@eder.fda.gov NR 34 TC 38 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 2005 VL 43 IS 3 BP 313 EP 323 DI 10.1016/j.yrtph.2005.09.001 PG 11 WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology SC Legal Medicine; Pharmacology & Pharmacy; Toxicology GA 986WL UT WOS:000233480300010 PM 16242226 ER PT J AU Chen, JJ Tsai, CA Young, JF Kodell, RL AF Chen, JJ Tsai, CA Young, JF Kodell, RL TI Classification ensembles for unbalanced class sizes in predictive toxicology SO SAR AND QSAR IN ENVIRONMENTAL RESEARCH LA English DT Article DE bagging; cross validation; ensemble classification; imbalanced data; sensitivity; specificity ID EXPRESSION DATA; GENE SELECTION; CANCER; PATTERNS; DATABASE; MODELS; SERUM AB This paper investigates the effects of the ratio of positive-to-negative samples on the sensitivity, specificity, and concordance. When the class sizes in the training samples are not equal, the classification rule derived will favor the majority class and result in a low sensitivity on the minority class prediction. We propose an ensemble classification approach to adjust for differential class sizes in a binary classifier system. An ensemble classifier consists of a set of base classifiers; its prediction rule is based on a summary measure of individual classifications by the base classifiers. Two re-sampling methods, augmentation and abatement, are proposed to generate different bootstrap samples of equal class size to build the base classifiers. The augmentation method balances the two class sizes by bootstrapping additional samples from the minority class, whereas the abatement method balances the two class sizes by sampling only a subset of samples from the majority class. The proposed procedure is applied to a data set to predict estrogen receptor binding activity and to a data set to predict animal liver carcinogenicity using SAR (structure-activity relationship) models as base classifiers. The abatement method appears to perform well in balancing sensitivity and specificity. C1 US FDA, Div Biometry & Risk Assessment, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Acad Sinica, Inst Stat Sci, Taipei 11529, Taiwan. 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 Tsai, Chen-An/0000-0002-7490-4331 NR 26 TC 24 Z9 25 U1 0 U2 3 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1062-936X J9 SAR QSAR ENVIRON RES JI SAR QSAR Environ. Res. PD DEC PY 2005 VL 16 IS 6 BP 517 EP 529 DI 10.1080/10659360500468468 PG 13 WC Chemistry, Multidisciplinary; Computer Science, Interdisciplinary Applications; Environmental Sciences; Mathematical & Computational Biology; Toxicology SC Chemistry; Computer Science; Environmental Sciences & Ecology; Mathematical & Computational Biology; Toxicology GA 011YG UT WOS:000235304800001 PM 16428129 ER PT J AU Ghanayem, BI McDaniel, LP Churchwell, MI Twaddle, NC Snyder, R Fennell, TR Doerge, DR AF Ghanayem, BI McDaniel, LP Churchwell, MI Twaddle, NC Snyder, R Fennell, TR Doerge, DR TI Role of CYP2E1 in the epoxidation of acrylamide to glycidamide and formation of DNA and hemoglobin adducts SO TOXICOLOGICAL SCIENCES LA English DT Article ID WILD-TYPE MICE; LIQUID-CHROMATOGRAPHY; N-METHYLOLACRYLAMIDE; CYTOCHROME-P450 2E1; B6C3F(1) MICE; F344 RATS; METABOLISM; CARCINOGENICITY; ACRYLONITRILE; TOXICITY AB Acrylamide (AA) is an animal carcinogen, neurotoxin, and reproductive toxin. AA is formed in baked and fried carbohydrate-rich foods. Metabolism of AA occurs via epoxidation to glycidamide (GA) or direct conjugation with glutathione. Using CYP2E1-null mice, recent studies in this laboratory demonstrated that induction of somatic and germ cell mutagenicity in AA-treated mice is dependent on CYP2E1. We hypothesized that AA metabolism to GA is a prerequisite for the induction of AA-induced mutagenicity. Current studies were undertaken to assess the role of CYP2E1 in the epoxidation of AA to GA and the formation of DNA and hemoglobin (HGB) adducts. AA was administered to CYP2E1-null or wild-type mice at 50 mg/kg ip. Mice were euthanized 6 h later and blood and tissues were collected. Using LC-ES/MS/MS, AA, GA, and DNA- and HGB-adducts were measured. While the plasma levels of AA and GA were 115 +/- 14.0 and 1.7 +/- 0.31 mu M in CYP2E1-null mice, they were 0.84 +/- 0.80 and 33.0 +/- 6.3 mu M in the plasma of AA-treated wild-type mice. Administration of AA to wild-type mice caused a large increase in N7-GA-Gua and N3-GA-Ade adducts in the liver, lung, and testes. While traces of N7-GA-Gua adducts were measured in the tissues of AA-treated CYP2E1-null mice, these levels were 52- to 66-fold lower than in wild-type mice. Significant elevation of both AA- and GA-HGB adducts was detected in AA-treated wild-type mice. In AA-treated CYP2E1-null mice, levels of AA-HGB adducts were roughly twice as high as those in wild-type mice. In conclusion, current work demonstrated that CYP2E1 is the primary enzyme responsible for the epoxidation of AA to GA, which leads to the formation of GA-DNA and HGB adducts. C1 NIEHS, Lab Pharmacol & Chem, Natl Toxicol Program, NIH, Res Triangle Pk, NC 27709 USA. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RTI Int, Res Triangle Pk, NC 27709 USA. RP Ghanayem, BI (reprint author), NIEHS, Lab Pharmacol & Chem, Natl Toxicol Program, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM ghanayem@niehs.nih.gov RI Fennell, Tim/D-9936-2013 NR 47 TC 88 Z9 95 U1 1 U2 18 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD DEC PY 2005 VL 88 IS 2 BP 311 EP 318 DI 10.1093/toxsci/kfi307 PG 8 WC Toxicology SC Toxicology GA 983FC UT WOS:000233215700005 PM 16141435 ER EF